51-01 BIOLOGY (GENERAL)
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Worldwide Population Structure in Cuvier's Beaked Whales: Identification of Units for Conservation
Document ID:
20090001778
Report #:
AD-A490026, NPS-OC-08-006
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dalebout, Merel
Published:
20080901
Source:
New South Wales Univ. (Sydney, Australia)
Pages:
21
Contract #:
MIPR-N6227106MPRR403 MIPR-N62271O7MPRMU01
Abstract:
This report summarizes the research conducted under two contracts from the Southwest Fisheries Science Center, La Jolla, CA, using funding from the Office of Naval Operations (N45), Washington, DC, and the Naval Postgraduate School, Monterey, CA. Small bone samples from over 500 Cuvier's beaked whales (Ziphius cavirostris) representing populations worldwide were collected from museums and other institutions. Genetic analysis of mitochondrial DNA (mtDNA) control region and cytochrome b diversity is underway. These data will be used for a robust statistical assessment of genetic differentiation between populations at regional and ocean basin levels and estimation of rates of dispersal, allowing units for conservation to be identified. Information on the mtDNA haplotype and sex of each specimen will also be provided. Preliminary median-spanning network reconstructions and analyses of molecular variance (AMOVA) for a subset of samples (control region -- 317 base pairs, n = 219; cytochrome b -- 326 base pairs, n = 190) revealed strong differentiation among the three ocean basins (North Atlantic, North Pacific, and Southern Hemisphere) at the haplotype and nucleotide level (p < 0.0001). There also is possible evidence of historical movements of these whales between the Atlantic and Pacific Oceans prior to the closure of the Isthmus of Panama approximately 3 million years ago. DNA extraction and sequencing are ongoing. The final deliverables for these contracts are expected in approximately 6 months' time.
Language:
English
Notes:
Sponsored in part by the Chief of Naval Operations, Washington, DC. Southwest Fisheries Science Center Order Numbers JG133F05SE6342 and JG133F07SE2186. The original document contains color images
Title:
BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex: Candidates for BRCA3
Document ID:
20090001982
Report #:
AD-A486526
Available Online:
http://hdl.handle.net/100.2/ADA486526
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chen, Xiaowei
Published:
20080601
Source:
Fox Chase Cancer Center (Philadelphia, PA United States)
Pages:
66
Contract #:
W81XWH-04-1-0573
Abstract:
Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCA1 and BRCA2 mutation-negative breast cancer-prone families. We hypothesized that other proteins, which have equivalent or complementary functions as BRCA1, may also be involved in the development of breast cancer. We have recently found one such candidate, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors which leads to tumorigenesis in vitro. Furthermore, our studies have defined BRCC36 as a direct regulator of BRCA1 activation and nuclear foci formation in response to IR in a number of breast cancer cell lines. Our results have found that down-regulation of BRCC36 expression impairs homologous recombination repair (HRR). Therefore, our data suggest that DNA repair pathway activated in response to IR and appears to sensitize breast cancer cells to IR-induced apoptosis. Importantly, we found that BRCC36 mutated in the germline of a cancer-prone family and may increase the risk of developing breast cancer. Overall, aberrant expression or mutation of BRCC36 genes in breast tumors may lead to disruption of the normal function of BRCA1 and contribute to the development of breast cancer.
Language:
English
Title:
9th Annual UC Systemwide Bioengineering Symposium
Document ID:
20090001984
Report #:
AD-A486532
Available Online:
http://hdl.handle.net/100.2/ADA486532
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Rodgers, Victor G
Published:
20080801
Source:
California Univ. (Riverside, CA United States)
Pages:
149
Contract #:
W81XWH-08-1-0405
Abstract:
The theme of this conference was to increase the synergistic interaction of the University of California's vast biomedical engineering research expertise with the practical medical and healthcare engineering undertaken by biomedical firms and government agencies. The symposium had 204 attendees representing all ten UC campuses as well as interested corporate and government agencies and individuals in the community. The symposium was supported by seven corporate sponsors and had four partnerships with industrial and government agencies. The symposium had twelve tracks that covered a broad range of topics to represent most research in Bioengineering at the University of California. In all, 48 talks and 49 posters were presented. In addition, five major presentations were given including three keynote speakers and two speakers representing TATRC. Through our generous corporate support, twelve cash awards totaling $5,000 were given to student oral and poster presenters who were judged to be outstanding. Judges were members of the UC, US Army Medical Research ACQ and our corporate sponsors. The program schedule is attached.
Language:
English
Notes:
Conference proceedings of the Annual UC Systemwide Bioengineering Syposium (9th), Riverside, CA on 20-22 Jun 2008
Title:
Identification of Tumor Suppressor Genes by Genetic and Epigenetic Genome-Scanning
Document ID:
20090001988
Report #:
AD-A486546
Available Online:
http://hdl.handle.net/100.2/ADA486546
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yamamoto, Fumiichiro
Published:
20080401
Source:
Burnham Inst. (La Jolla, CA United States)
Pages:
64
Contract #:
W81XWH-05-1-0317
Abstract:
We used systematic multiplex rt-pcr and dna microarray hybridization methods to examine the expression of the genes in the chromosomal regions of 18q21-qter, 8p, and 1p33-pter, which are often decreased in copy number in breast tumors and cell lines derived from breast cancer. We identified dozens of genes in the chromosomal regions whose expression was frequently diminished or lost in breast cancer cell lines that were examined. We confirmed the results by real-time qrt-pcr. We also examined the expression of those genes in the clinical specimens of breast cancer and observed the down-regulation in expression of some of them in the clinical specimens of breast cancer. Those genes included ccbe1, tcf4, np_115536.1, and np_689683.2 in 18q21-qter, and myom2, np_859074, np_001034551, nrg1, phyip (phyhip), q7z2r7, sfrp1, and sox7 in 8p.
Language:
English
Title:
An Essential Protein Repair Enzyme: Investigation of the Molecular Recognition Mechanism of Methionine Sulfoxide Reductase A
Document ID:
20090001993
Report #:
AD-A486576, USNA-TSPR-375
Available Online:
http://hdl.handle.net/100.2/ADA486576
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
So, Joanne D
Published:
20080501
Source:
Naval Academy (Annapolis, MD United States)
Pages:
67
Contract #:
None
Abstract:
The amino acid methionine is particularly sensitive to damage by reactive oxygen species. The enzyme methionine sulfoxide reductase A (MsrA) is capable of repairing oxidized methionines [Met-(O)] found in a wide range of damaged substrates, ultimately protecting cells against oxidative damage. How MsrA reverses oxygen modifications to these damaged proteins is well known, but very little is known about how MsrA recognizes the damaged proteins in the first place. Unlike most enzymes which carry out reactions on a single target molecule, MsrA can repair damage to a single methionine, a peptide, or an entire protein. This study focused on understanding how MsrA is able to recognize, then ultimately repair such a range of oxidatively modified substrates. We propose that MsrA functions as a molecular chaperone, recognizing overall characteristics of unfolded proteins due to oxidative damage. Enzyme-ligand interactions were studied between MsrA of E. coli and four target molecules in their normal and oxidized forms: staphylococcal nuclease, staphylococcal nuclease T62P which has an unfolded structure due to a mutation, a 9-amino acid peptide (KKMVENAKK) derived from staphylococcal nuclease, and the non-steroidal anti-inflammatory drug sulindac. Using the hydrophobic marker 8-anilino-1-naphthalene sulfonic acid (ANS), changes in ANS fluorescence were used to identify changes in the exposed hydrophobic surface area of the protein-ligand complex. The investigation reveals an MsrA target molecule recognition mechanism of weak, but specific hydrophobic interactions enhanced by the presence of a sulfoxide. This study represents the first investigation of the interaction of MsrA with physiologically relevant ligands and has laid the foundation for a novel method of investigating the hydrophobic recognition mechanism of MsrA as a chaperone for oxidatively modified target molecules.
Language:
English
Title:
Identification of Novel Molecular Targets for Pleckstrin Homology (PH) Domains Found in Oncogenes Implicated in Breast Cancer
Document ID:
20090002002
Report #:
AD-A486604
Available Online:
http://hdl.handle.net/100.2/ADA486604
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Keleti, David
Published:
20080301
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
22
Contract #:
W81XWH-04-1-0320
Abstract:
Plecktrin Homology (PH) domains are commonly thought of as membrane-targeting modules involved in signaling pathways that bind phosphoinositides (PPIns) with high affinity and specificity. In a recent study of S. cerevisiae, however, the vast majority demonstrated little affinity or specificity for PPIns (Yu et al, 2004). I show comparable results for selected human PH domains, with one that is high affinity and PPIns-specific, while the remainder are low to moderate affinity and promiscuous for PPIns. I outline two instances where protein-protein and protein-phosphoinositide interactions may account for specific membrane targeting observed in vivo. First, SH3BP-2 PH was identified as highly specific for the membrane lipid PtdIns(3,4)P2, and targets the host protein to the membrane. Second, FAPP1- and OSBP PH domains possess comparable affinities for Golgi- and plama membrane (PM)-enriched PPIns in vitro, although they both localize to the Golgi (not the PM) in vivo, possibly by directly interacting with the Golgi GTPase Arf1. In vitro binding studies suggest that delocalized electrostatic attraction between the basic protein and acidic phospholipids play a prominent role in these interactions. Additionally, I have solved the crystal structure of a related member of this PH domain family in complex with PPIns.
Language:
English
Title:
Effects of Inactivating Ras-Converting Enzyme or Isoprenylcysteine Carboxyl Methyltransferase in the Pathogenesis of Chronic Myelogenous Leukemia
Document ID:
20090002016
Report #:
AD-A486625
Available Online:
http://hdl.handle.net/100.2/ADA486625
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ren, Ruibao
Published:
20080201
Source:
Brandeis Univ. (Waltham, MA United States)
Pages:
6
Contract #:
W81XWH-06-1-0238
Abstract:
The BCR-ABL fusion gene, the hallmark of CML, plays a causal role in the development of CML. The BCR-ABL tyrosine kinase inhibitors have been successfully used to treat patients with CML, but residual disease persists and drug resistance emerges. Although BCR-ABL remains to be an attractive target for developing CML therapies, identifying and targeting additional essential components in the development of CML are important for overcoming resistance to BCR-ABL tyrosine kinase inhibitors and for eradicating leukemic cells. Substantial evidence indicates that Ras and Ras related proteins are critical mediators of BCR-ABL in leukemogenesis. Ras-converting enzyme (Rce1) and isoprenylcysteine carboxyl methyltransferase (Icmt) are two unique enzymes for Ras modifications that are critical for their functions. Targeted inactivation of Rce1 or Icmt is, therefore, an attractive strategy for the treatment of CML. The goal of this project is to determine whether targeted inactivation of Rce1 or Icmt could block BCR-ABL leukemogenesis. In this study, we have found that Icmt plays a critical role in BCR-ABL leukemogenesis and that the role of Rce1 in BCR-ABL leukemogenesis is dosage dependent. We have also found that the mutation affecting the AAX peptide cleavage and methylation of RAS in cis significantly reduces RAS leukemogenesis, suggesting that the AAX peptide cleavage and methylation play an important role for RAS leukemogenesis.
Language:
English
Title:
Regulation of the mTOR Pathway by a Novel Rheb Binding Protein BNIP3
Document ID:
20090002022
Report #:
AD-A486638
Available Online:
http://hdl.handle.net/100.2/ADA486638
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Guan, Kun-Liang
Published:
20080501
Source:
Michigan Univ. (Ann Arbor, MI United States)
Pages:
19
Contract #:
W81XWH-07-1-0179
Abstract:
Uncontrolled mTOR activation is a major contributing factor to the pathogenesis of TSC. mTOR is known to be regulated by a wide range of signals such hypoxia. The major goal of this project is to determine mTOR regulation by hypoxia. We proposed to focus on BNIP3 which is a Rheb interacting protein in mTOR regulation in response to hypoxia. Our goals outlined in the original proposal have been successfully completed. We confirmed that BNIP3 is indeed a Rheb interaction protein under physiological conditions. We demonstrate that BNIP3 plays a critical role in hypoxia-induced mTOR inhibition. Furthermore we found that BNIP3 itself has a growth inhibitory activity and inactivation of BNIP3 promotes cell growth in vitro and tumor growth in vivo. Our observation reveals an important mechanism of cell growth regulation by hypoxia. Our results also indicate potential therapeutic target for TSC disease which has a high level of mTOR and Rheb activation. Activation BNIP3 may inhibit Rheb and mTOR in TSC mutant cells.
Language:
English
Title:
Elucidating the Role of Cks Proteins in Breast Cancer by Combining the Disciplines of Molecular Biology, Pathology, and Biophysics
Document ID:
20090002023
Report #:
AD-A486639
Available Online:
http://hdl.handle.net/100.2/ADA486639
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Rincon, Sonia del
Published:
20080301
Source:
Kimmel (Sidney) Cancer Center (San Diego, CA United States)
Pages:
16
Contract #:
W81XWH-06-1-0344
Abstract:
Breast cancer often occurs when the proteins that regulate normal epithelial cell division become dysregulated. This proposal examines the role of the cell cycle regulatory proteins human cyclin-dependent kinase subunits (Cks1 and Cks2) in human breast cancer. The overexpression of Cks genes in breast tumor tissue and the role of Skp2 in tumorigenesis suggests that Cks and Skp2 levels must be strictly regulated for proper cell cycling. We hypothesize that aberrant Cks protein expression and function contributes to breast carcinogenesis at least in part by its ability to interact with Skp2. In year one of this project we have determined the levels of Cks mRNA and protein in (i) breast cancer cell lines and (ii) normal versus tumor breast tissue. We have also developed breast cancer cell lines that overexpress cksl cks2 or skp2 and cells that co-overexpress cks2 and skp2. In the coming year we will focus on characterizing the breast cancer cell lines developed that stably overexpress the aforementioned cell cycle proteins using both in vitro and in vivo techniques.
Language:
English
Title:
PARK2, a Large Common Fragile Site Gene, is Part of a Stress Response Network in Normal Cells that is Disrupted During the Development of Ovarian Cancer
Document ID:
20090002024
Report #:
AD-A486640
Available Online:
http://hdl.handle.net/100.2/ADA486640
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Smith, David I Zhu, Yu
Published:
20080101
Source:
Mayo Clinic (Rochester, MN United States)
Pages:
18
Contract #:
W81XWH-04-1-0082
Abstract:
PARK2 (Parkin) is a common fragile site (CFS) gene. We examined Parkin in primary ovarian tumors and found that this gene was frequently inactivated. We also found that re-introduction of Parkin is associated with greater sensitivity to apoptotic induction in ovarian cancer cell lines. We also discovered an entire family of very large common fragile site genes. We measured the expression of Parkin and 13 other CFS genes in panels of different cancers. This revealed non-random inactivation of these genes and greater inactivation in cancers that have a poorer clinical prognosis. We then utilized whole genome tiling arrays to characterize all transcripts (not just coding transcripts) and their response to stress. These studies revealed non-coding transcripts within Parkin and other large CFS genes. We discovered a new class of large non-coding transcripts. A sub-set of these were highly evolutionarily conserved; when we examined these transcripts in ovarian and other cancers, we found alterations in their expression. We also found that some of these non-coding transcripts were mutational targets in ovarian and other cancers. Thus, this work has discovered a new group of targets that are altered during the development of ovarian cancer.
Language:
English
Title:
Biomarkers for Amyotrophic Lateral Sclerosis in Active Duty Military (BALSAM)
Document ID:
20090002027
Report #:
AD-A486649
Available Online:
http://hdl.handle.net/100.2/ADA486649
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Milhorn, David E
Published:
20080222
Source:
Cincinnati Univ. (OH United States)
Pages:
55
Contract #:
W81XWH-06-2-0016
Abstract:
Purpose: To compare serum samples from individuals diagnosed with amyotrophic lateral sclerosis (ALS) to serum samples from matched individuals who did not develop ALS. In this study we aim to identify candidate serum biomarkers that are unique for ALS and identify a subset of diagnostic serum biomarkers for early detection of ALS prior to the appearance of overt symptoms. Scope: The significance of a positive identification of protein biomarkers for ALS is indisputably great. However to date no validated clinically relevant biomarkers have been found to allow a more specific diagnosis of ALS at an earlier stage. Previous efforts to identify ALS associated biomarkers have often focused on the identification of genes and proteins characteristic for familial ALS yet validated biomarkers for sporadic ALS which accounts for as much as 90-95% of all ALS cases have yet to be identified. Major Findings: None at this time. Progress: This study received USAMRMC HSSRB approval on 15 Jan 2007. The Durham VA and Univ. of Cincinnati IRB protocols have also been approved. Durham VA IRB began consenting the VA ALS registry members for this study. Model system 2-D gel and mass spectrometry studies have been conducted to develop improved techniques for biomarker identification.
Language:
English
Title:
Molecular Identification of Human Fungal Pathogens
Document ID:
20090002028
Report #:
AD-A486650
Available Online:
http://hdl.handle.net/100.2/ADA486650
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wickes, Brian L
Published:
20080301
Source:
Texas Univ. Health Science Center (San Antonio, TX United States)
Pages:
17
Contract #:
W81XWH-06-1-0234
Abstract:
The focus of the work during this funding period mainly centered around Task 2, which consisted of developing standardized protocols for PCR and sequencing template preparation. The two major subtasks, development of a universal DNA extraction strategy and development of a universal PCR reaction, were initiated during the first funding period and have been completed. These accomplishments now allow us to utilize a standard DNA extraction method and a standard PCR reaction that uses the same primer set, for any unknown fungus. Confirmation of these conclusions has been obtained using a broad range of clinical specimens from both humans and animals, and demonstrates that our standard protocol works across all fungal phyla. In addition to the technical developments, we have now completed the design of the database and have been uploading sequences throughout this second year. During the course of uploading sequences, we have been testing the database since it must perform a number of tasks upon data entry. Debugging issues have been minor and although we will continue to revise the database, we now have a working version that will be used to generate output after searches.
Language:
English
Title:
Characterizing Candidate Oncogenes at 8q21 in Breast Cancer
Document ID:
20090002035
Report #:
AD-A486667
Available Online:
http://hdl.handle.net/100.2/ADA486667
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kao, Jessica Y
Published:
20080301
Source:
Stanford Univ. (Stanford, CA United States)
Pages:
12
Contract #:
W81XWH-06-1-0424
Abstract:
Breast cancer carcinogenesis is caused by molecular genetic changes. These genetic changes ultimately affect the transcriptome. Copy number alterations of the genome is a cardinal feature of cancer and plays an important role in tumor progression by altering the gene expression program. These regions of alteration are associated with oncogenes and tumor suppressor genes of known and unknown identity. Characterization of both CNA's and gene expression profiles have been carried out on breast tumor specimens using microarray technology to gain further insight into the progression of this disease. We comprehensively characterized both DNA copy number changes and captured the gene expression profiles of 50 breast cancer cell lines, widely used model systems for the study of breast cancer. We found that the cell lines could be classified into three main subtypes, Luminal, Basal A, and Basal B by clustering of gene expression. Overall, this is similar to what is seen in the gene expression analysis of the tumors however, distinct differences were found. Analysis of the copy number profile revealed that the cell lines recapitulated the main genetic changes represented in the tumor data set but contained more changes. Finally, caution should be employed with choosing the appropriate cell line model system when studying specific processes in breast cancer.
Language:
English
Title:
Identification of Genes Regulating the Development of Breast Cancer
Document ID:
20090002038
Report #:
AD-A486671
Available Online:
http://hdl.handle.net/100.2/ADA486671
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wang, Hua
Published:
20080401
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
33
Contract #:
W81XWH-06-1-0413
Abstract:
We have identified four different modifiers of Apc(min) that affect mammary tumor number or mammary tumor latency (Mmom1-Mmom4). To further investigate the molecular mechanisms of mammary modifiers, Mmom1 and Mmmom2 congenic mice were produced and tested for the effect on mammary tumor number or mammary tumor latency. The effect of Mmom2 on mammary tumor latency was confirmed in the congenic mice and the region containing Mmom2 was narrowed into a 10cM region. We also show in this report that genetic background can determine the mammary tumor types in Apc(min) mice and we propose a model to explain how mammary modifiers could affect mammary tumor development.
Language:
English
Title:
Developing a Zebrafish Model of NF1 for Structure-Function Analysis and Identification of Modifier Genes
Document ID:
20090002047
Report #:
AD-A486682
Available Online:
http://hdl.handle.net/100.2/ADA486682
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Epstein, Jonathan A
Published:
20080401
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
14
Contract #:
W81XWH-07-1-0228
Abstract:
This progress report summarizes the first year of activity of this project focused on the identification and characterization of the zebrafish orthologs of the neurofibromatosis type 1 genes. This project involves work within the Epstein laboratory and collaboration with the laboratory of Dr. Thomas Look at the Dana Farber Cancer Institute as a sub-contract. This progress report summarized the collaborative work including results from both groups. During the first year, significant progress has been made in the isolation and characterization of two zebrafish orthologs, znf1a and znf1b. The genes have been sequenced and their expression patterns identified. The knockdown phenotypes have been characterized and include overgrowth of glia and cardiovascular abnormalities. Work towards identification of stable mutant fish lines has begun. Manuscripts are in preparation.
Language:
English
Title:
Role of Fetuin-A in Breast Tumor Cell Growth
Document ID:
20090002052
Report #:
AD-A486687
Available Online:
http://hdl.handle.net/100.2/ADA486687
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ochieng, Josiah
Published:
20080330
Source:
Meharry Medical Coll. (Nashville, TN United States)
Pages:
9
Contract #:
W81XWH-07-1-0254
Abstract:
In this report, we have described the breeding protocol we have followed aimed at knocking out the fetuin-A gene in PymT+ transgenic black C57 mice to define the role of fetuin-A in breast cancer carcinogenesis and progression. The central hypothesis of this project is that fetuin-A is a major serum derived growth factor for breast carcinoma cells and creates a favorable environment for the metastatic spread of tumor cells to the lungs. So far we have managed to get PymT+/Fet-/+ heterozygous animals that are significantly protected from breast cancer. We therefore hope that the absence of both alleles in PymT+/Fet-/- mice will result in almost total protection of the animals from developing full blown breast cancer. The results are very encouraging and we hope to complete the critical studies by the end of this year. The main problem we have had is the slow pace of the breeding protocol in that most of the PymT+/Fet+/+ mothers cannibalize their pups and so it takes many attempts before we can move animals to experimental groups.
Language:
English
Title:
Characterization of NF1 Protein Ubiquitination
Document ID:
20090002056
Report #:
AD-A486692
Available Online:
http://hdl.handle.net/100.2/ADA486692
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Murakami, Koko Fried, Victor A
Published:
20080601
Source:
New York Medical Coll. (Valhalla, NY United States)
Pages:
8
Contract #:
W81XWH-07-1-0432
Abstract:
This project aimed at characterization of NF1 protein ubiquitination system by identifying ubiquitination sites and ligases for neurofibromin. We established the method for obtaining ubiquitinated neurofibromin for mass-spectrometric sequencing and identification of ubiquitination sites of neurofibromin. We confirmed neurofibromin ubiquitination and degradation after mitogenic stimulation by serum and LPA. Cbl-Ring finger ubiquitin ligase mediates ubiquitination and degradation of a variety of signaling proteins in the tyrosine kinase receptor signaling pathway. As one of efforts for identifying neurofibromin ubiquitin ligases, we discovered that ubiquitination and degradation of neurofibromin was induced by Cbl which may be responsible for neurofibromin ubiquitination upon activation of tyrosine-kinase receptors.
Language:
English
Title:
The Characterization Of The Kinetics Of Chlamydia Muridarum Infection In Defined Regions Of The Murine Genital Tract
Document ID:
20090002159
Report #:
AD-A486759, CL09-0026
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Eskildsen, Ilea
Published:
20080801
Source:
Texas Univ. (San Antonio, TX United States)
Pages:
63
Contract #:
None
Abstract:
Infection with Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide, and leads to pathological sequelae including pelvic inflammatory disease and infertility. The continued increase in incidence rates of genital chlamydial infection over the last decade underscores a need for comprehensive understanding of the infection kinetics, host immune response, and disease pathogenesis. A mouse model of genital Chlamydia muridarum infection is generally employed in such studies, with most studies relying upon the enumeration of bacterial numbers from vaginal swab material to assess the kinetics of infection. Given the differences in tissue anatomy, hormonal regulation, and immune response among different genital regions, it is possible that kinetics of chlamydial infection as determined by vaginal swabbing may not accurately reflect the kinetics in other regions of the genital tract. In this study, we directly evaluated the kinetics of bacterial ascent into, and clearance from, defined regions of the reproductive tract using highly sensitive quantitative real-time PCR for the detection of Chlamydia genomes. The results of our study show that kinetics of chlamydial infection in different regions of the genital tract are comparable, with high numbers of organisms from day 3 through 18, and subsequent progressive reduction leading to complete clearance of infection around 30 days after challenge. The results also exhibit differences in the numbers of chlamydial organisms between different defined regions. Collectively, the results of this study provide in-depth insight into the kinetics of genital Chlamydia muridarum infection in defined regions of the murine female reproductive tract.
Language:
English
Title:
Regulation of Egr1 Target Genes by the Nurd Chromatin Remodeling Complex
Document ID:
20090002160
Report #:
AD-A486760
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Svaren, John
Published:
20080601
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
20
Contract #:
W81XWH-06-1-0167
Abstract:
Previous work had shown that the EGR1 transactivator is over expressed in prostate cancer, while expression of its corepressor, NAB2, is reduced. Based on our recent characterization of an interaction between NAB2 and the NuRD (Nucleosome remodeling and disruption) chromatin remodeling complex, we have determined if loss of NAB2 expression results in loss of NuRD targeting to EGR1 target genes. In progress thus far, we have shown that repression of some NAB-regulated target genes in prostate cancer cells requires the NuRD chromatin remodeling complex. We have developed novel chromatin immunoprecipitation assays for the NuRD complex in prostate cells to demonstrate the colocalization of the NuRD complex on EGR1-regulated endogenous target genes. In addition, we have shown that recruitment of the NuRD complex to EGR1 target genes is dependent on NAB2. Finally, NuRD-dependent repression of NAB-regulated repression is sensitive to histone deacetylase inhibitors. These results provide the first functional description of one of the major HDACcontaining chromatin remodeling complexes in prostate cancer cells, and elucidate molecular consequences of loss of NAB2 corepressor function in prostate carcinogenesis by analyzing the mechanism of NAB2 corepressor function.
Language:
English
Title:
An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk
Document ID:
20090002164
Report #:
AD-A486764
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Reding, Kerryn W
Published:
20080401
Source:
Hutchinson (Fred) Cancer Research Center (Seattle, WA United States)
Pages:
8
Contract #:
W81XWH-06-1-0312
Abstract:
CHT use has been demonstrated to confer an increased risk of breast cancer. Genetic variation in hormonal pathways may modify the effect of CHT on breast cancer risk. Using 1237 cases and 1015 controls from two population-based case-control studies of breast cancer, we investigated the effect of genetic variation in 7 genes within the progesterone pathway using a tagSNP and functional SNP approach and 5 genes within the catechol estrogen pathway. Within single gene analyses we observed breast cancer risk to be modestly associated with one SNPs in each GSTP1 (rs1695: OR = 1.4 [95% CI: 1.02-1.9] for carriers of A allele); CYP1B1 (rs1056827: OR = 1.7 ]95% CI:1.2-2.5] for T homozygotes); SRD5A1 (rs248793: OR=1.2 [95% CI: 1.02-1.5] for G homozygotes) and PGR (rs492457: OR=1.5 [95% CI: 1.01-2.1] for carriers of the A allele). We found that the breast cancer risk associated with SNPs was particularly strong in long-term CHT users. In a multi-gene model including two genes with single gene effects within the estrogen pathway (CYP1B1*2 and GSTP1), breast cancer risk was 1.6 (95% CI: 1.03-2.4) times higher for carriers of 1 high risk genotype and 2.8 (95% CI: 1.5-5.3) times higher for women with 2 high risk genotypes compared to women with 0 high risk genotypes. The impact of high risk genotypes was stronger in long-term CHT users, particularly in long-term, current CHT users (OR=5.6 [95% CI: 1-5-20.6]). These results suggest that breast cancer risk among CHT users is modified by variation in genes within hormonal pathways.
Language:
English
Title:
Role of GGAP/PIKE-A in Prostate Cancer Progression
Document ID:
20090002167
Report #:
AD-A486770
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ittmann, Michael M
Published:
20080501
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
9
Contract #:
W81XWH-07-1-0023
Abstract:
The clinical behavior of prostate cancer is extremely heterogeneous ranging from indolent disease to aggressive metastatic cancer with rapid mortality. GGAP2 is a GTPase protein with a GTPase activating protein (GAP) domain at the C-terminus. It was reported that GGAP2 or PIKE-A can activate Akt and inhibit apoptosis. The goal of this proposal is characterize the role of GGAP2 in prostate cancer progression. Our results indicate that GGAP2 expression is increased in prostate cancer. In addition GGAP2 is mutated in human prostate cancer. The multiplicity of GGAP2 mutations imply that these mutations may emerge in an environment of the multifocal heterogeneity of prostate cancer tissues. According to our results these mutations can stimulate cancer cell proliferation and enhance GGAP2 activation indicating that they may contribute to increased activity of GGAP2 in prostate cancer. In summary GGAP2 may promote prostate cancer growth and progression via overexpression andlor mutation and as such is an important therapeutic target.
Language:
English
Title:
Advanced Mathematical Modeling of Sonar-Induced Bubble Growth and Coalescence in Humans and Marine Mammals
Document ID:
20090002279
Report #:
AD-A487035
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ilinskii, Yurii A Wilson, Preston S Hamilton, Mark F
Published:
20080901
Source:
Texas Univ. (Austin, TX United States)
Pages:
30
Contract #:
N00014-05-1-0292
Abstract:
For high gas supersaturation levels in liquids, on the order of 300% as predicted in capillaries of marine mammals following a series of dives, standard mathematical models of both static and rectified diffusion are found to underestimate the rate of bubble growth by 10%-20%. The discrepancy is demonstrated by comparing predictions based on existing mathematical models with direct numerical solutions of the differential equations for gas diffusion in the liquid and thermal conditions in the bubble. Underestimation of bubble growth by existing mathematical models is due to the underlying assumption that the gas concentration in the liquid is given by its value for a bubble of constant equilibrium radius. This assumption is violated when high supersaturation causes the bubble to grow too fast in relation to the time scale associated with diffusion. Rapid bubble growth results in an increased gas concentration gradient at the bubble wall, and therefore a growth rate in excess of predictions based on constant equilibrium bubble radius. The effect of gas supersaturation level, excitation frequency, duty cycle and sound pressure level on bubble growth were also studied.
Language:
English
Title:
Seladin-1: A Novel Tumor Suppressor Gene Involved in Breast Cancer?
Document ID:
20090002281
Report #:
AD-A487040
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Galaktionov, Konstantin I
Published:
20080801
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
10
Contract #:
W81XWH-06-1-0650
Abstract:
Seladin-1 maps to the human chromosome region 1p31-1p32 that shows frequent loss of heterozygosity (LOH) in human breast tumors. Publicly available data (Entrez, GEO) also show a significant variability between levels of Seladin-1 expression in breast cancer cell lines and normal breast epithelium. Is Seladin-1 a tumor suppressor on 1p31 -1p32 that is involved in breast cancer? Our concept is that it is. In order to determine if Seladin-1 is a TSG involved in breast cancer we propose to: 1) Identify possible Seladin-1 mutations in primary breast tumors. 2) Investigate the alterations of Seladin-1 expression in breast cancer cells. 3) Perform functional assays on tumor-specific Seladin-1 mutants. Accordingly we amplified Seladin-1 exons from from 60 breast tumor genomic DNA samples (obtained from tissue banks or commercial sources) followed by the sequence analysis of the open reading frames. As a result no missense or nonsense mutations were detected. We found that expression of Seladin-1 significantly varies between different breast cancer cell lines and in one such line MDA-MB-231 is significantly below expression in normal breast epithelium.
Language:
English
Title:
Identifying ECM Mediators of Tumor Cell Dormancy
Document ID:
20090002298
Report #:
AD-A487080
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schedin, Pepper
Published:
20080501
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
16
Contract #:
W81XWH-06-1-0510
Abstract:
Characterize the compositional and functional changes in mammary stroma that result from tamoxifen treatment. Approach and Results: 75 mature female Sprague Dawley rats were randomized into three groups of 25 each; Gp1 nulliparous control, and Gp 2 tamoxifen treated (0.5 mg/tamoxifen per kg body weight, s.c. injection for 30 days)and Gp 3 tamoxifen treated (1.0 mg tamoxifen dose). ECM was harvested from the mammary glands of Gps 1 & 3 for biochemical and functional characterizations. The ECM preparations have been subjected to LCMS and MALDI-TOF mass spec. Due to technical difficulties we have also developed two in vitro models to investigate the effects of tamoxifen on mammary stroma. ECM deposited by primary mammary fibroblasts isolated from control and tamoxifen treated rats, or primary control fibroblasts treated with tamoxifen in culture has been utilized for ECM proteomics method development. Optimized conditions demonstrate fibronectin (FN) is downregulated by tamoxifen, in vitro and in vivo; observations consistent with data demonstrating that FN is upregulated during with MEC proliferation and downregulated at times of MEC loss; suggesting that loss of FN may be integral to a tumor suppressive microenvironment.
Language:
English
Title:
Space Research Fortifies Nutrition Worldwide
Document ID:
20090002510
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002510
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 106-107
Published:
20080901
Source:
Martek Biosciences Corp. (Columbia, MD, United States)
Pages:
2
Contract #:
None
Abstract:
NASA's Controlled Ecological Life Support Systems program attempted to address basic needs of crews, meet stringent payload and power usage restrictions, and minimize space occupancy, by developing living, regenerative ecosystems that would take care of themselves and their inhabitants. An experiment from this program evolved into one of the most widespread NASA spinoffs of all time-a method for manufacturing an algae-based food supplement that provides the nutrients previously only available in breast milk. Martek Biosciences Corporation, in Columbia, Maryland, now manufactures this supplement, and it can be found in over 90 percent of the infant formulas sold in the United States, as well as those sold in over 65 other countries. With such widespread use, the company estimates that over 24 million babies worldwide have consumed its nutritional additives.
Language:
English
Title:
GaN-based sensor nodes for in situ detection of gases
Document ID:
20090002660
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002660
Sales Agency:
CASI Hardcopy A03 No Copyright
Author(s):
Moon, Jeong-Sun Prokopuk, Nicholas Son, Kyung-Ah
Published:
20080722
Source:
California Inst. of Tech. (Pasadena, CA United States)
Pages:
13
Contract #:
None
Abstract:
A system for detecting chemical/biological substances and a detection method. The system comprises a plurality of sensing units or nodes and a radiofrequency link. Each unit has several sensors with different sensing curves. Each sensor is able to transmit information related to the sensed substance on a specific frequency. The sensors preferably comprise AlGaN/GaN high electron mobility transistors.
Language:
English
Notes:
This application claims the benefit of U.S. provisional Patent Application Ser. No. 60/571,713, filed May 17, 2004 by Kyung-Ah Son, Jeong S. Moon and Nicholas Prokopuk and the benefit of U.S. provisional Patent Application Ser. No. 60/592,513, filed Jul. 29, 2004 by Kyung-Ah Son, Jeong S. Moon and Nicholas Prokopuk, the disclosure of all of which is incorporated herein by reference
Title:
Orchestration: The Movement and Vocal Behavior of Free-Ranging Norwegian Killer Whales (Orcinus Orca)
Document ID:
20090003245
Report #:
AD-A487757, MIT/WHOI-2008-08
Available Online:
http://hdl.handle.net/100.2/ADA487757
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Shapiro, Ari D
Published:
20080601
Source:
Massachusetts Inst. of Tech. (Cambridge, MA United States)
Pages:
304
Contract #:
None
Abstract:
Studying the social and cultural transmission of behavior among animals helps to identify patterns and content of interaction. Killer whales likely acquire traits culturally based on their stable social groups, population-specific feeding behaviors, and group-distinctive vocal repertoires. Digital tags were used to record the movements and vocalizations of Norwegian killer whales. These animals carousel feed, corralling herring into a ball before tail slapping, incapacitating and eating the fish. Periods of tail slapping were characterized by elevated movement variability, heightened vocal activity, and call types containing orientation cues. Two types of behavioral sequence preceded the tight circling of carousel feeding. First, the animals swam directionally and in 2 of 3 instances were silent, suggesting that they may have located other foraging groups by eavesdropping. Second, tagged animals made broad horizontal loops as they dove in a manner consistent with corralling. All 4 of these occasions were accompanied by vocal activity, indicating that this and tail slapping may benefit from social communication. Killer whale vocalizations traditionally have been classified into discrete call types. Using human speech processing techniques, the author considered that calls alternatively consist of shared segments that can be recombined to form the stereotyped and variable repertoire. In a classification experiment, the characterization of calls using the whole call, a set of unshared segments, or a set of shared segments yielded equivalent performance. The shared segments required less information to parse the same vocalizations, suggesting a more parsimonious system of representation. This closer examination of the movements and vocalizations of Norwegian killer whales, combined with future work on ontogeny and transmission, will inform our understanding of whether and how culture plays a role in achieving population-specific behaviors in this species.
Language:
English
Title:
Development of Micro-Scale Assays of Mammary Stem and Progenitor Cells
Document ID:
20090003314
Report #:
AD-A488004
Available Online:
http://hdl.handle.net/100.2/ADA488004
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Paguirigan, Amy L
Published:
20080701
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
128
Contract #:
W81XWH-06-1-0487
Abstract:
This portion of the work proposed focused on employing and validating microtechnology for in vitro studies of primary mammary gland cell characteristics. Specific attention has been paid to developing more quantitative methods for analyzing microfluidic cell cultures using In Channel Westerns. Also, understanding how the microfluidic culture platform differs from traditional macro-scale techniques is critical and was explored in more depth than previously done. By thoroughly understanding how this culture platform affects the cellular baseline first, better and more efficient data collection can be performed, thus requiring fewer primary cells.
Language:
English
Title:
Molecular Solutions to Low Injuries Resulting from Battlefield Injuries. Addendum
Document ID:
20090003328
Report #:
AD-A488018
Available Online:
http://hdl.handle.net/100.2/ADA488018
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dartt, Darlene A
Published:
20080501
Source:
Retina Foundation (Boston, MA United States)
Pages:
19
Contract #:
W81XWH-04-2-0008
Abstract:
We hypothesize that targeted molecular intervention can preserve vision threatened by battlefield trauma-induced corneal and retinal inflammation, corneal and retina/optic nerve apoptosis, ocular surface dry eye after refractive surgery, and retinal degeneration. We are studying the consequences of trauma-induced (1) corneal inflammation using a gene therapy approach of providing soluble Fas ligand to the cornea to determine if this ligand can suppress corneal inflammation in mice; (2) retinal inflammation by examining if transforming growth factor-beta, thrombospondin, and somatostatin, in subretinal space, can suppress inflammation within retina secondary to autoimmune uveoretinitis and light-induced damage in mice; (3) corneal cell death by apoptosis and promote regeneration by identifying the anti-apoptotic gene with the greatest capacity to suppress corneal cell apoptosis using mice; (4) retinal cell death and regeneration by using mice to determine if systemic treatment with lithium chloride can prevent collateral damage to retinal neurons and promote optic nerve regeneration; (5) dry eye by determining how to minimize dry eye after LASIK refractive surgery by developing new tests to predict pre-disposition to refractive surgery induced dry eye; and (6) retinal injury by generating stem cell polymer composites.
Language:
English
Title:
A Model System to Investigate the Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and Transformation Potential of the Ovarian Epithelium
Document ID:
20090003369
Report #:
AD-A487180
Available Online:
http://hdl.handle.net/100.2/ADA487180
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Connolly, Denise
Published:
20080501
Source:
Fox Chase Cancer Center (Philadelphia, PA United States)
Pages:
11
Contract #:
W81XWH-07-1-0301
Abstract:
The tumor microenvironment plays an important role in cancer progression. The tumor stroma promotes angiogenesis and is a source of growth factors, chemokincs, and extracellular matrix (ECM) molecules that promotes carcinoma progression. We are investigating the effects of loss of function of BRCAl and Trp53 in the stroma on the growth and neoplastic transformation of epithelial cells using 2-D and 3-D in vitro culture models. Wamcn carrying gerrnline mutations in BRCAl are at high risk for developing ovarian cancer and mutations in pS3 arc frequently detected in ovarim tumors. Further, inactivation of BRCAl in mouse granulosa cells results in the development of benign epithelial neoplasm in the ovary and uterine horn, but the lesions themselves express wild-type BRCAl. Inactivation of BRACl also causes arrest at the G21M transition and significantly increases population doubling times; an effect that is reversed by inactivation of Trp53. 'Therefore, to directly test the hypothesis that stromal cells excrt a ccll-nonautonomous effect on ovarian epithelial cell growth and neoplastic transformation, we will examine the effects of culturing mouse ovarian surface epithelial (MOSE) cells with ECM and conditioned media from stromal calls in which BRACl and Trp53 have been inactivated (alone or in combination).
Language:
English
Title:
Training HBCU Faculty and Students in Prostate Cancer (PC) Research: Signal Transduction and Receptor-Inhibitor Interactions in the Progress of PC
Document ID:
20090003379
Report #:
AD-A487209
Available Online:
http://hdl.handle.net/100.2/ADA487209
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wiese, Thomas E Klassen, R B
Published:
20080301
Source:
Xavier Univ. of Louisiana (New Orleans, LA United States)
Pages:
29
Contract #:
W81XWH-04-1-0252
Abstract:
This program aims to help eradicate prostate cancer (PC) disparity in African Americans through educational and research programs. Our hypothesis is that through PC education and participation in PC research a meaningful number of African Americans will be able to contribute to the elimination of disparity in PC. Our program comprises three Specific Aims. (1) To develop promote and sustain independent competitive research and training programs at Xavier University. Both projects are moving forward presenting data and involving students. (2) To increase the number of Xavier University investigators focused on PC research. One new project has been developed and is involving students. (3) To establish a long-term collaborative relationship between Xavier University and the TCC in PC research. XU faculty in the program are now members of the Tulane Cancer Center and involved in weekly seminars and focus group meetings.
Language:
English
Title:
Bacterial Degradation of Nitrogenous Energetic Compounds (NEC) in Coastal Waters and Sediments
Document ID:
20090003564
Report #:
AD-A487461, NRL/MR/6110-08-9139
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Montgomery, Michael T Walker, S W Boyd, T J Hamdan, L J Osburn, C L
Published:
20080910
Source:
Naval Research Lab. (Washington, DC United States)
Pages:
59
Contract #:
N00014-99-WX-20525
Abstract:
Once released in the environment, either through detonation, casing breakage, or by slow leaks from unexploded ordnance (UXO), nitrogenous energetic compounds (NEC, such as TNT, HMX, RDX) may sorb onto particulates, partition to dissolved organic matter, or remain dissolved in aqueous media. Our hypothesis was that NEC would be transient in coastal ecosystems. This was based primarily on the understanding that microbial grown in these systems is typically nitrogen-limited and there are few examples of nitrogen based organic compounds that are not rapidly metabolized in these environments. During 14 sampling events in coastal waterways from 2002 to 2007, we measured TNT mineralization rates in surface sediment and water samples that were often similar to those of other organic compounds that are transient in natural ecosystems due to their use in bacterial metabolism, such as petroleum hydrocarbons and amino acids.
Language:
English
Notes:
Sponsored in part by Strategic Environmental Research and Development Program (SERDP). The original document contains color images
Title:
Desalination Technology Waste Streams: Impact of pH and Brine on Bacterial Metabolism Among Natural Marine Assemblages
Document ID:
20090003571
Report #:
AD-A487475, NRL/MR/6110--08-9138
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Montgomery, M T Boyd, T J Osburn, C L Plummer, R E Coffin, R B
Published:
20080910
Source:
Naval Research Lab. (Washington, DC United States)
Pages:
16
Contract #:
61-5557-M65
Abstract:
Hydrate formation-based techniques have been proposed as desalination technologies for transforming seawater into potable water. Marine Desalination Systems (MDS) is currently developing new technology in gas hydrate formation to supply potable water using hydrocarbon gas-based hydrate crystals (Kubota et al. 1984). The MDS technology might change the natural bacterial assemblage in primarily two ways: metabolic rate (secondary production) and assemblage composition. This influence on the microbial assemblage can affect ecosystem health with a disruption of the microbial growth efficiency and changes to key elemental cycles. This report focuses on the effect of salinity and pH changes on the rates of bacterial metabolism among natural marine assemblages. When the marine bacterial assemblage is exposed to salinity and pH conditions similar to those expected in MDS system waste streams, heterotrophic production is significantly reduced. However, in the case of salinity, these impacts on overall heterotrophic bacterial metabolism may be transient. Bacterial production inhibition due to decrease in pH is dramatic and appears much less reversible based on the production recovery only after 24 hours. It should be noted that the pH change was three orders of magnitude compared with the two-fold maximum salinity change. The inhibitory effect of 1.5 pH units (from pH 8.0 to 6.5) at 33 PSU was approximately equal to increasing the salinity 27 PSU (from 33 to 60 PSU) at pH 8.0.
Language:
English
Title:
Novel Breast Cancer Therapeutics Based on Bacterial Cupredoxin
Document ID:
20090003586
Report #:
AD-A487517
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wittung-Stafshede, Pernilla
Published:
20080901
Source:
Rice Univ. (Houston, TX United States)
Pages:
61
Contract #:
W81XWH-06-1-0572
Abstract:
The tumor suppressor p53 is a major player in cell growth, genomic stability and cell death. Recent in vivo work suggested that bacterial Pseudomonas aeruginosa azurin can enter cancer cells and interact with p53 promoting cell death. Despite being a novel concept to target cancer, there are no thermodynamic details known for the proposed azurin-p53 complex. This project aims to fill this gap by employing biophysical methods in conjunction with purified proteins in vitro to address four aims. We will reveal (1) which p53 domain interacts with azurin, (2) the molecular mechanism by which azurin increases cellular levels of p53, (3) the region on azurin that interacts with p53 and (4) use the acquired information to propose smaller molecules that retain properties of azurin. We have found that azurin binds to the unstructured N-terminal domain of p53 and a small peptide is able to reproduce part of the azurin interaction. We have also assessed how Cu is metabolized inside cells as well has how the crowdedness of the cell milieu affects proteins. We have made several key discoveries that will aid in the development of azurin-based molecules that can be used as new treatments of cancer.
Language:
English
Title:
Charge Density Quantification and Antimicrobial Efficacy
Document ID:
20090003591
Report #:
AD-A487526, ARL-TR-4530
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Zander, Nicole Leadore, Julia Orlicki, Joshua A
Published:
20080801
Source:
Army Research Lab. (Aberdeen Proving Ground, MD United States)
Pages:
20
Contract #:
None
Abstract:
Emerging threats to soldiers on the battlefield include traditional dangers such as conventional weapons and chemical or biological warfare agents. A less obvious threat is represented by the growing numbers of serious bacterial and fungal infections. Reducing overall warfighter susceptibility to opportunistic infections would improve force readiness in all operational environments. The capability of a material to autonomous decontaminate in situ with an active additive is therefore highly desirable and may increase the warfighter's safety and reduce the logistical burdens associated with decontamination operations. However, to maintain the critical performance characteristics of the coating or fabric, a minimal amount of active material is preferred, reducing the overall impact on bulk physical properties.
Language:
English
Title:
Bioenergetic Approaches and inflammation of MPTP Toxicity
Document ID:
20090003741
Report #:
AD-A490306
Available Online:
http://hdl.handle.net/100.2/ADA490306
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Beal, M F
Published:
20080901
Source:
New York Hospital-Cornell Medical Center (New York, NY United States)
Pages:
13
Contract #:
W81XWH-04-1-0802
Abstract:
We are continuing to examine a number of neuroprotective agents in an MPTP model of PD. We are also continuing to utilize metabolomic profiling to identify novel biomarkers for PD and to investigate whether these occur in animal models of PD. We are continuing to develop and characterize a new animal model of PD by making a knock out of PlNK1, a nuclear encoded kinase localized to mitochondria, and which causes autosomal recessive PD. We have completed a study of the effects of human dopaminergic stem cells in a 6-hydroxy dopamine model of PD.
Language:
English
Title:
A Novel Strategy for Isolation, Molecular and Functional Characterization of Embryonic Mammary Stem Cells Using Molecular Genetics and Microfluidic Sorting
Document ID:
20090003746
Report #:
AD-A490322
Available Online:
http://hdl.handle.net/100.2/ADA490322
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wahl, Geoffrey M
Published:
20080601
Source:
Salk Inst. (La Jolla, CA United States)
Pages:
10
Contract #:
W81XWH-06-1-0331
Abstract:
We developed a genetic system to identify, isolate, and characterize mammary stem cells. Our system consists of an activator component that is dependent on Wnt signaling, which is essential for mammary gland development, and on a doxycycline regulated reporter to toggle the system on and off. The reporter component labels the chromatin of cells for direct visualization. We used a modular design to enable the system to be applied to cancer models and other organs. Over the past year we have targeted mouse embryonic stem cells with our modular transgenic system and validated its Wnt responsiveness. We have also established assays for isolation and characterization of small numbers of viable, fluorescently labeled cells. In parallel, we have determined that embryonic mammary rudiments contain concentrated mammary stem cells and are isolating these structures to obtain stem cell specific expression signatures. The molecular reagents and strategies we are developing have broad applications for studies examining the relationship between normal and cancer stem cells, and determining whether they share the same origin.
Language:
English
Title:
Regulation of the Inflammasome, a Modulator of Caspase-Mediated Cytokine Production
Document ID:
20090003762
Report #:
AD-A490403
Available Online:
http://hdl.handle.net/100.2/ADA490403
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schmitz, Karl R
Published:
20080701
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
11
Contract #:
W81XWH-06-1-0518
Abstract:
Tissue inflammation and inflammatory cytokines can positively affect breast cancer prognosis. By providing a detailed understanding of the mechanism of inflammasome formation and activation, we hope to create the potential for novel inflammation based cancer therapies. The protein, NALP, forms the core of the inflammasome complex. The chief domains of NALP do not express well in bacterial or insect cell expression systems, exhibiting poor expression levels and solubility. The NALP pyrin domain has been successfully produced and purified, and initial crystals of this protein have been produced. Constructs of the adaptor CARDINAL were found to express well, but suffer proteolysis during purification. Full-length constructs of NALP have been produced by baculovirus/SF9 expression; have been observed to exist in monomer/oligomer equilibrium in solution.
Language:
English
Title:
Characterization of the Role of Breast Tumor Kinase (Brk) in Breast Cancer Cells Non-Responsive to EGFR-Targeted Agents
Document ID:
20090003769
Report #:
AD-A490442
Available Online:
http://hdl.handle.net/100.2/ADA490442
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nimnual, Anjaruwee S
Published:
20080701
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
11
Contract #:
W81XWH-05-1-0448
Abstract:
Epidermal growth factor (EGF) receptor tyrosine kinases (erbB family), EGFR (erbB1) and HER2, are highly expressed in breast cancer and are associated with poor prognosis. A number of EGFR and/or HER2-targeted agents are being investigated for breast cancer treatment. Brk (Breast Tumor Kinase) is a nonreceptor tyrosine kinase that has been shown to enhance the mitogenic signaling of EGF, induce phosphorylation of erbB 3 and interact with AKT. In this study, we aim to investigate whether Brk can promote cells to become refractory to EGFR-targeted drugs. Pl-3 kinase/AKT pathway mediates EGF-induced cell growth and survival and is involved in cellular resistance to anti-cancer drugs. Because the P13K/AKT pathway is regulated by multiple activators, downregulation of the EGFR alone may not lead to its inhibition. We will investigate whether Brk promotes growth and survival as well as Pl3K/AKT activity in cells treated with EGFR-targeted agents.
Language:
English
Title:
NKX3.1 Genotype and IGF-1 Interact in Prostate Cancer Risk
Document ID:
20090003772
Report #:
AD-A490467
Available Online:
http://hdl.handle.net/100.2/ADA490467
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Gelmann, Edward P
Published:
20080501
Source:
Columbia Univ. (New York, NY United States)
Pages:
17
Contract #:
W81WXH-07-1-0263
Abstract:
NKX3.1 is a prostate-specific homeobox gene that maps to chromosome 8p21, the most frequent target for loss of heterozygosity in prostate cancer. NKX3.1 is a haploinsufficient tumor suppressor in the prostate. We found that IGFBP-3expression was activated 10-fold by NKX3.1 in cell lines and tissues. IGFBP-3 is an inhibitor of IGF-1, a serum component that when elevated is a risk factor for prostate cancer. NKX3.1 expression inhibits IGFIR signaling and diminishes IRS-1 phosphorylation. Knock down of IGFBP-3 attenuates the growth suppressive effects of NKX3.1. NKX3.1 C154T is a polymorphic allele present in ~10% of the population. The polymorphic allele codes for a variant protein that replaces arginine 52 with cysteine. NXK3.1 C154T confers a minimally increased risk for prostatic enlargement and for prostate cancer. In a cohort of cases and controls with known NKX3.1 genotype we found that the effect of serum IGF-1 on prostate cancer risk was seen only in men with at least one polymorphic NKX3.1allele. Consistent with its apparent interaction with IGF-1 in prostate cancer risk, NKX3.1 R52C protein is attenuated in activation of IGFBP-3. The data therefore show that the two prostate cancer risk factors, NKX3.1 R52C and circulating IGF-1 interact. NKX3.1 R52C activates less IGFBP-3 expression than its wild type counterpart and thereby predisposes prostate epithelial cells to the proliferative and antiapoptotic effects of IGF-1, increasing the risk for prostate cancer.
Language:
English
Title:
Erythropoietin and Breast Cancer
Document ID:
20090003775
Report #:
AD-A490481
Available Online:
http://hdl.handle.net/100.2/ADA490481
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sytkowski, Arthur J
Published:
20080301
Source:
Beth Israel Deaconess Medical Center (Boston, MA United States)
Pages:
12
Contract #:
W81XWH-06-1-0737
Abstract:
Erythropoietin (Epo) is the prime regulator of red blood cell production, principally by mean of "anti-apoptotic" action. Epo also acts on other cells and tissues outside of the hematopoietic system, including endothelium, central nervous system, reproductive system and gut. Epo receptors (EpoR) have also been identified on breast cancer (CaB), and there is an in vitro study suggesting that these EpoR on CaB cell lines may be functional. The presence of functional EpoR on cancer cells is of concern since Epo is used to treat anemia associated with chemotherapy and to improve tumor oxygenation for radiotherapy. This concern was heightened when a trial of Ego in CaB patients was terminated early due to decreased survival in the Epo-treated group. Since CaS patients receive Ego therapy, an anti-apoptotic effect of Ego on CaS cells would have adverse consequences. It is of vital importance to determine the functionality of the EpoR on CaB cells in vivo. We screened CaB lines for Egoo ezpression and used siRNA technology to develop lines that had reduced EgoR. Reduction of EgoR resulted in a significant reduction in cell growth in vitro. These results may have profound implications for the mangement of breast cancer patients.
Language:
English
Title:
Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity
Document ID:
20090003776
Report #:
AD-A490497
Available Online:
http://hdl.handle.net/100.2/ADA490497
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Diamond, Betty
Published:
20080701
Source:
North Shore-Long Island Jewish Research Inst. (Manhasset, NY United States)
Pages:
14
Contract #:
W81XWH-07-1-0327
Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE it is clear that increased or sustained high physiologic levels of estradiol can accelerate onset of disease and exacerbate disease severity. We have shown that estradiol alters B cell maturation in vivo but does so in a genetically restricted fashion. We have also shown that estradiol can act directly on B cells to alter B cell receptor (BCR) signalling strength. This proposal is to understand which estrogen receptors mediate the effects of estradiol on B cell survival maturation and activation in order to assess whether hormonal manipulation has a potential therapeutic role in SLE. The proposal is further designed to ask why estradiol affects B cell function in mice of one genetic background but not another.
Language:
English
Title:
A Search for New Therapeutic Targets: Using Yeast to Find the GEF for Rheb
Document ID:
20090003791
Report #:
AD-A490603
Available Online:
http://hdl.handle.net/100.2/ADA490603
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Leatherwood, Janet
Published:
20080701
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
6
Contract #:
W81XWH-07-1-0358
Abstract:
The Tsc1/2 complex known as Hamartin/Tuberin is mutated in the human disease Tuberous Sclerosis and such mutation predisposes for cancer. Tsc1/2 complex has a clearly established chemical release a GTPase Activating Protein or GAP for the small GTPase Rheb. Rheb in turn regulates TOP. The Tor kinases and associated proteins are large complex units that integrate signals pertaining to nutrients and proliferation potential. Tor promotes growth and proliferation and thus de-regulation of Tor is implicated in carcinogenesis and disease. We have worked toward development of a simple genetically tractable model system for understanding of the Tsc1/2 pathway. Our particular interest is in finding factors that work in opposition to Tsc1/2. Typical GTPases such as the Tsc1/2 target Rheb are controlled by both negative regulators (GAPS) and positive regulators known as guanine nucleotide exchange factors or GEFS. Our most important progress has been to establish functional screens for GEF type activators of the Rheb signalling factor in the simple yeast Schizosaccharomyces pombe.
Language:
English
Title:
Do microRNAs Mediate Estrogen-Dependent Repression of Genes
Document ID:
20090003974
Report #:
AD-A488054
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nakshatri, Harikrishna Collins, Nikail R
Published:
20080801
Source:
Indiana Univ. (Indianapolis, IN United States)
Pages:
24
Contract #:
W81XWH-06-1-0637
Abstract:
Estrogen receptor alpha (ERa) mediates transcriptional effects of estrogen. Estrogen inducible proteins c-Myc and E2F family are required for optimal ERa activity and secondary estrogen response, respectively. The purpose of this study was to investigate whether estrogen regulates its target gene expression through microRNAs. We show that estrogen induces 21 and represses 7 microRNAs, which potentially control 420 estrogen-regulated and 757 non-estrogen regulated mRNAs at post-transcriptional level. Estrogen induced the expression of eight Let-7 family microRNAs, miR-98 and miR-21, which by reducing c-Myc and E2F2 proteins level, may attenuate estrogen response. Consistent with the role of Let-7 in differentiation of cancer stem cells, estrogen reduced ALDH1-positive breast cancer stem subpopulation of MCF-7 cells. The protein kinase AKT reduced estrogen-inducible expression of Let-7 microRNAs and may disrupt attenuation of estrogen response. Significance: Luminal subtype A breast cancers contain functional ERa, are well differentiated and display favorable prognosis. Estrogen:ERa-mediated differentiation pathway in these cancers is yet to be elucidated. We propose that estrogen-regulated Let-7 family microRNAs contribute to differentiated phenotype of ERa-positive breast cancers. The phenotype and the clinical course of ERa-positive breast cancers, particularly response to anti-estrogen therapy, may be dependent on the balance between estrogen-induced tumor suppressor (let-7 family) and oncogenic (miR-21) microRNAs. Our studies also reveal a negative regulatory loop controlling estrogen response through microRNAs and highlights differences in estrogen-induced transcriptome and proteome.
Language:
English
Title:
Genes Involved in Oxidation and Prostate Cancer Progression
Document ID:
20090003977
Report #:
AD-A488057
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Platz, Elizabeth A
Published:
20080101
Source:
Johns Hopkins Univ. (Baltimore, MD United States)
Pages:
11
Contract #:
DAMD17-03-1-0273
Abstract:
We are evaluating whether polymorphisms in genes involved in the genesis of oxidative species, detoxification of oxidative species, or repair of oxidative DNA damage influence risk of prostate cancer progression in men with clinically organ-confined prostate cancer. We identified 524 men with who underwent radical prostatectomy in 1993-2004 and who subsequently experienced biochemical recurrence, development metastases, or died from their prostate cancer. Using incidence-density sampling, we selected 524 men matched on age, race, and pathological stage and grade who had not progressed by the date of the matched case's progression. Noncancer tissue (either unaffected paraffin-embedded lymph nodes or frozen seminal vesicles) was retrieved from the Hopkins pathology archive from which germline DNA was extracted. For 20 men either tissue could be found or DNA extraction was not successful. We attempted several platforms for genotyping, including a SNP chip that included ~1500 SNPs in relevant genes. We selected the Mass Array system (Sequenom) and identified 100 SNPs in relevant genes. We completed genotyping the 524 pairs for 12 of the 100 SNPs. For 33 of the men, genotyping was not successful. A total of 450 of the 524 pairs had genotype data for both members of the pair for at least on SNP. We used conditional logistic regression to estimate the matched ORs of progression for the 12 SNPs; no associations were observed (all p-trend across number of alleles > 0.15). We are awaiting data for the remainder of the 100 SNPs.
Language:
English
Title:
Genetic Dissection of the Role of Heparan Sulfate in Mammary Tumor Progression
Document ID:
20090004007
Report #:
AD-A488128
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yamaguchi, Yu
Published:
20080630
Source:
Burnham Inst. (La Jolla, CA United States)
Pages:
11
Contract #:
W81XWH-07-1-0461
Abstract:
Heparan sulfate (HS) binds growth factors, protein-degrading enzymes, and other bioactive proteins, and to regulate their activities. Many of these proteins have strong implications in human breast cancer. There is also evidence that cellular HS production itself exerts strong influences on tumorigenesis, exemplified by the fact that mutations of Ext1, the gene encoding an HS synthesizing enzyme, cause multiple bone tumors. Furthermore, the level of HS degrading activity correlates with the aggressiveness of the tumor. Despite these long-standing observations, much less is known about the mechanisms by which HS influences the malignant behavior of tumors in vivo. Also important is the fact that HS is produced not only by tumor cells themselves but also by stromal cells that constitute the tumor microenvironment. This project will conduct cohort study using genetic mouse models to address these key questions. The first year of this project was dedicated mainly to establish, expand, and intercross mouse models for generating experimental cohorts. We have also characterized the gene recombination pattern induced by the FSP1-Cre transgenic mouse, which will be used to manipulate the expression of HS in tumor stromal cells.
Language:
English
Title:
Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland
Document ID:
20090004010
Report #:
AD-A488132
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Li, Hua
Published:
20080401
Source:
Dartmouth Coll. (Hanover, NH United States)
Pages:
36
Contract #:
W81XWH-05-1-0350
Abstract:
Delta-N-p63 plays a critical role in making decision to preserve or forfeit mammary stem cells/progenitor cells self-renewal capacity. In embryonic stem cells, some transcription factors including oct3/4, nanog, c-myc and Klf-4 are critical to maintain self-renewal and multi-potential stasis. Our study revealed that these key transcription factors also exist in adult mammary stem cells/progenitor cells as well as breast cell lines such as IMEC, MCF-10A, SUM102 and MCF- 7 cells. Over-expression of ectopic delta-N-p63 could inhibit the proliferation rate of treated cells, and had diverse regulation effects on transcript level of oct3/4, nanog, c-myc and Klf-4 in infected breast cell lines. Retinoic acid treatment also could slow down the growth of treated beast cells, and change the transcript level of these self-renewal related genes. Both of RA treatment and over-expression of delta-N-p63 could increase mammosphere formation capacities in most breast cell lines including IMEC, SUM102 and MCF-7 cells. The mRNA level of oct3/4 and nanog was detectable in mouse mammary stem cells or progenitor cells enriched subpopulation. Additionally, both oct3/4 and nanog transcript level could be regulated by over-expression or removal of delta- N-p63 in mammary stem cells or progenitors fractions, respectively. In human breast cell lines such as SUM102 cells, over-expression of mouse oct3/4 and nanog could increase the mammosphere numbers significantly. On the other hand, removal of delta-N-p63 in MCF-10A cells could decrease the mammosphere formation capacity dramatically. Taken together, all these findings strongly suggested there might be correlation between delta-N-p63 and ES programming genes including oct3/4, nanog, c-myc and Klf-4 to regulate stem cell self-renewal and sustaining of pluripotency in adult mammary gland.
Language:
English
Title:
Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes
Document ID:
20090004017
Report #:
AD-A488140
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Privette, Lisa M
Published:
20080301
Source:
Michigan Univ. (Ann Arbor, MI United States)
Pages:
61
Contract #:
W81XWH-06-1-0332
Abstract:
CHFR is an E3 ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazole and taxanes). Loss of CHFR mRNA expression has been reported in many cancers, including breast cancer, but the relevance of this to tumorigenesis remains unknown. The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics, progression, and genomic stability. As previously reported, nearly 40% of breast cancer show decreased CHFR expression compared to normal cells and tissues and the loss of CHFR expression by RNAi in cell culture models leads to the acquisition of several tumorigenic phenotypes. In particular, MCF10A IHMEC cells transfected with CHFR siRNA, became aneuploid and were analyzed for chromosome segregation defects. We observed increased aneuploidy, misaligned metaphase chromosomes, anaphase bridges, multipolar condensed spindles, multi-nucleated cells, and mislocalization of the mitotic spindle checkpoint proteins MAD2 and BUBR1. CHFR was found to interact with three crucial mitosis proteins, including MAD2 and Aurora A where CHFR loss led to Aurora A oncoprotein over-expression, but no change in MAD2 expression. alpha-tubulin was identified as a novel target for CHFR-mediated ubiquitination after nocodazole treatment and decreased CHFR increased acetylated alpha-tubulin, a mitotic spindle protein implicated in cellular response to taxane treatment. These data indicate that CHFR has tumor suppressive qualities and may be a biomarker for taxane chemo-responsiveness. CHFR also has a previously unrecognized role as a regulator of genomic stability. CHFR may be one of the few proteins that can control the cell cycle, chemotherapeutic response, and genomic stability - processes that go awry in breast cancer.
Language:
English
Title:
Identification of Cytoplasmic Proteins Interacting with the Mammary Cell Transforming Domain of Ese-1
Document ID:
20090004033
Report #:
AD-A488175
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Gutierrez-Hartmann, Arthur
Published:
20080401
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
60
Contract #:
W81XWH-06-1-0502
Abstract:
ETS factors comprise a large transcription factor family known to play a significant role in cellular development, differentiation, and transformation. Emerging evidence reveals that increased mRNA expression of the human Ets factor-1, ESE-1, is associated with breast cancer. Stable expression of ESE-1 transforms MCF-12A immortalized human mammary epithelial cells. However, little is known about ESE-1 protein expression and its role in maintaining the transformed phenotype in human breast cancer cell lines. Here, we used an anti- ESE-1 mouse monoclonal antibody in Western blot and immunofluorescent cell analyses to show that ESE-1 is expressed as a nuclear protein in MCF-7, T47D and ZR-75 transformed, tumorigenic mammary epithelial cell lines, and that it is not expressed in transformed MDAMB- 231 and nontransformed MCF-10A and MCF-12A cells. In addition, specific knockdown of endogenous ESE-1 in the human breast carcinoma ZR-75 and MCF-7 cell lines decreased colony formation and anchorage independent growth. Mechanistically, ESE-1 knockdown decreased cellular proliferation, but had no effect on apoptosis. Finally, serum withdrawal resulted in a time-dependent, ~90% reduction of ESE-1 protein production in MCF-7 cells. These results establish that ESE-1 plays a key role in maintaining the transformed phenotype in breast cancer, thus providing a novel single-point target for breast cancer therapy.
Language:
English
51-02 BIOCHEMISTRY
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex: Candidates for BRCA3
Document ID:
20090001982
Report #:
AD-A486526
Available Online:
http://hdl.handle.net/100.2/ADA486526
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chen, Xiaowei
Published:
20080601
Source:
Fox Chase Cancer Center (Philadelphia, PA United States)
Pages:
66
Contract #:
W81XWH-04-1-0573
Abstract:
Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCA1 and BRCA2 mutation-negative breast cancer-prone families. We hypothesized that other proteins, which have equivalent or complementary functions as BRCA1, may also be involved in the development of breast cancer. We have recently found one such candidate, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors which leads to tumorigenesis in vitro. Furthermore, our studies have defined BRCC36 as a direct regulator of BRCA1 activation and nuclear foci formation in response to IR in a number of breast cancer cell lines. Our results have found that down-regulation of BRCC36 expression impairs homologous recombination repair (HRR). Therefore, our data suggest that DNA repair pathway activated in response to IR and appears to sensitize breast cancer cells to IR-induced apoptosis. Importantly, we found that BRCC36 mutated in the germline of a cancer-prone family and may increase the risk of developing breast cancer. Overall, aberrant expression or mutation of BRCC36 genes in breast tumors may lead to disruption of the normal function of BRCA1 and contribute to the development of breast cancer.
Language:
English
Title:
An Essential Protein Repair Enzyme: Investigation of the Molecular Recognition Mechanism of Methionine Sulfoxide Reductase A
Document ID:
20090001993
Report #:
AD-A486576, USNA-TSPR-375
Available Online:
http://hdl.handle.net/100.2/ADA486576
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
So, Joanne D
Published:
20080501
Source:
Naval Academy (Annapolis, MD United States)
Pages:
67
Contract #:
None
Abstract:
The amino acid methionine is particularly sensitive to damage by reactive oxygen species. The enzyme methionine sulfoxide reductase A (MsrA) is capable of repairing oxidized methionines [Met-(O)] found in a wide range of damaged substrates, ultimately protecting cells against oxidative damage. How MsrA reverses oxygen modifications to these damaged proteins is well known, but very little is known about how MsrA recognizes the damaged proteins in the first place. Unlike most enzymes which carry out reactions on a single target molecule, MsrA can repair damage to a single methionine, a peptide, or an entire protein. This study focused on understanding how MsrA is able to recognize, then ultimately repair such a range of oxidatively modified substrates. We propose that MsrA functions as a molecular chaperone, recognizing overall characteristics of unfolded proteins due to oxidative damage. Enzyme-ligand interactions were studied between MsrA of E. coli and four target molecules in their normal and oxidized forms: staphylococcal nuclease, staphylococcal nuclease T62P which has an unfolded structure due to a mutation, a 9-amino acid peptide (KKMVENAKK) derived from staphylococcal nuclease, and the non-steroidal anti-inflammatory drug sulindac. Using the hydrophobic marker 8-anilino-1-naphthalene sulfonic acid (ANS), changes in ANS fluorescence were used to identify changes in the exposed hydrophobic surface area of the protein-ligand complex. The investigation reveals an MsrA target molecule recognition mechanism of weak, but specific hydrophobic interactions enhanced by the presence of a sulfoxide. This study represents the first investigation of the interaction of MsrA with physiologically relevant ligands and has laid the foundation for a novel method of investigating the hydrophobic recognition mechanism of MsrA as a chaperone for oxidatively modified target molecules.
Language:
English
Title:
Identification of Novel Molecular Targets for Pleckstrin Homology (PH) Domains Found in Oncogenes Implicated in Breast Cancer
Document ID:
20090002002
Report #:
AD-A486604
Available Online:
http://hdl.handle.net/100.2/ADA486604
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Keleti, David
Published:
20080301
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
22
Contract #:
W81XWH-04-1-0320
Abstract:
Plecktrin Homology (PH) domains are commonly thought of as membrane-targeting modules involved in signaling pathways that bind phosphoinositides (PPIns) with high affinity and specificity. In a recent study of S. cerevisiae, however, the vast majority demonstrated little affinity or specificity for PPIns (Yu et al, 2004). I show comparable results for selected human PH domains, with one that is high affinity and PPIns-specific, while the remainder are low to moderate affinity and promiscuous for PPIns. I outline two instances where protein-protein and protein-phosphoinositide interactions may account for specific membrane targeting observed in vivo. First, SH3BP-2 PH was identified as highly specific for the membrane lipid PtdIns(3,4)P2, and targets the host protein to the membrane. Second, FAPP1- and OSBP PH domains possess comparable affinities for Golgi- and plama membrane (PM)-enriched PPIns in vitro, although they both localize to the Golgi (not the PM) in vivo, possibly by directly interacting with the Golgi GTPase Arf1. In vitro binding studies suggest that delocalized electrostatic attraction between the basic protein and acidic phospholipids play a prominent role in these interactions. Additionally, I have solved the crystal structure of a related member of this PH domain family in complex with PPIns.
Language:
English
Title:
Effects of Inactivating Ras-Converting Enzyme or Isoprenylcysteine Carboxyl Methyltransferase in the Pathogenesis of Chronic Myelogenous Leukemia
Document ID:
20090002016
Report #:
AD-A486625
Available Online:
http://hdl.handle.net/100.2/ADA486625
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ren, Ruibao
Published:
20080201
Source:
Brandeis Univ. (Waltham, MA United States)
Pages:
6
Contract #:
W81XWH-06-1-0238
Abstract:
The BCR-ABL fusion gene, the hallmark of CML, plays a causal role in the development of CML. The BCR-ABL tyrosine kinase inhibitors have been successfully used to treat patients with CML, but residual disease persists and drug resistance emerges. Although BCR-ABL remains to be an attractive target for developing CML therapies, identifying and targeting additional essential components in the development of CML are important for overcoming resistance to BCR-ABL tyrosine kinase inhibitors and for eradicating leukemic cells. Substantial evidence indicates that Ras and Ras related proteins are critical mediators of BCR-ABL in leukemogenesis. Ras-converting enzyme (Rce1) and isoprenylcysteine carboxyl methyltransferase (Icmt) are two unique enzymes for Ras modifications that are critical for their functions. Targeted inactivation of Rce1 or Icmt is, therefore, an attractive strategy for the treatment of CML. The goal of this project is to determine whether targeted inactivation of Rce1 or Icmt could block BCR-ABL leukemogenesis. In this study, we have found that Icmt plays a critical role in BCR-ABL leukemogenesis and that the role of Rce1 in BCR-ABL leukemogenesis is dosage dependent. We have also found that the mutation affecting the AAX peptide cleavage and methylation of RAS in cis significantly reduces RAS leukemogenesis, suggesting that the AAX peptide cleavage and methylation play an important role for RAS leukemogenesis.
Language:
English
Title:
GaN-based sensor nodes for in situ detection of gases
Document ID:
20090002660
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002660
Sales Agency:
CASI Hardcopy A03 No Copyright
Author(s):
Moon, Jeong-Sun Prokopuk, Nicholas Son, Kyung-Ah
Published:
20080722
Source:
California Inst. of Tech. (Pasadena, CA United States)
Pages:
13
Contract #:
None
Abstract:
A system for detecting chemical/biological substances and a detection method. The system comprises a plurality of sensing units or nodes and a radiofrequency link. Each unit has several sensors with different sensing curves. Each sensor is able to transmit information related to the sensed substance on a specific frequency. The sensors preferably comprise AlGaN/GaN high electron mobility transistors.
Language:
English
Notes:
This application claims the benefit of U.S. provisional Patent Application Ser. No. 60/571,713, filed May 17, 2004 by Kyung-Ah Son, Jeong S. Moon and Nicholas Prokopuk and the benefit of U.S. provisional Patent Application Ser. No. 60/592,513, filed Jul. 29, 2004 by Kyung-Ah Son, Jeong S. Moon and Nicholas Prokopuk, the disclosure of all of which is incorporated herein by reference
Title:
Regulation of the Inflammasome, a Modulator of Caspase-Mediated Cytokine Production
Document ID:
20090003762
Report #:
AD-A490403
Available Online:
http://hdl.handle.net/100.2/ADA490403
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schmitz, Karl R
Published:
20080701
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
11
Contract #:
W81XWH-06-1-0518
Abstract:
Tissue inflammation and inflammatory cytokines can positively affect breast cancer prognosis. By providing a detailed understanding of the mechanism of inflammasome formation and activation, we hope to create the potential for novel inflammation based cancer therapies. The protein, NALP, forms the core of the inflammasome complex. The chief domains of NALP do not express well in bacterial or insect cell expression systems, exhibiting poor expression levels and solubility. The NALP pyrin domain has been successfully produced and purified, and initial crystals of this protein have been produced. Constructs of the adaptor CARDINAL were found to express well, but suffer proteolysis during purification. Full-length constructs of NALP have been produced by baculovirus/SF9 expression; have been observed to exist in monomer/oligomer equilibrium in solution.
Language:
English
Title:
Characterization of the Role of Breast Tumor Kinase (Brk) in Breast Cancer Cells Non-Responsive to EGFR-Targeted Agents
Document ID:
20090003769
Report #:
AD-A490442
Available Online:
http://hdl.handle.net/100.2/ADA490442
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nimnual, Anjaruwee S
Published:
20080701
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
11
Contract #:
W81XWH-05-1-0448
Abstract:
Epidermal growth factor (EGF) receptor tyrosine kinases (erbB family), EGFR (erbB1) and HER2, are highly expressed in breast cancer and are associated with poor prognosis. A number of EGFR and/or HER2-targeted agents are being investigated for breast cancer treatment. Brk (Breast Tumor Kinase) is a nonreceptor tyrosine kinase that has been shown to enhance the mitogenic signaling of EGF, induce phosphorylation of erbB 3 and interact with AKT. In this study, we aim to investigate whether Brk can promote cells to become refractory to EGFR-targeted drugs. Pl-3 kinase/AKT pathway mediates EGF-induced cell growth and survival and is involved in cellular resistance to anti-cancer drugs. Because the P13K/AKT pathway is regulated by multiple activators, downregulation of the EGFR alone may not lead to its inhibition. We will investigate whether Brk promotes growth and survival as well as Pl3K/AKT activity in cells treated with EGFR-targeted agents.
Language:
English
Title:
A Search for New Therapeutic Targets: Using Yeast to Find the GEF for Rheb
Document ID:
20090003791
Report #:
AD-A490603
Available Online:
http://hdl.handle.net/100.2/ADA490603
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Leatherwood, Janet
Published:
20080701
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
6
Contract #:
W81XWH-07-1-0358
Abstract:
The Tsc1/2 complex known as Hamartin/Tuberin is mutated in the human disease Tuberous Sclerosis and such mutation predisposes for cancer. Tsc1/2 complex has a clearly established chemical release a GTPase Activating Protein or GAP for the small GTPase Rheb. Rheb in turn regulates TOP. The Tor kinases and associated proteins are large complex units that integrate signals pertaining to nutrients and proliferation potential. Tor promotes growth and proliferation and thus de-regulation of Tor is implicated in carcinogenesis and disease. We have worked toward development of a simple genetically tractable model system for understanding of the Tsc1/2 pathway. Our particular interest is in finding factors that work in opposition to Tsc1/2. Typical GTPases such as the Tsc1/2 target Rheb are controlled by both negative regulators (GAPS) and positive regulators known as guanine nucleotide exchange factors or GEFS. Our most important progress has been to establish functional screens for GEF type activators of the Rheb signalling factor in the simple yeast Schizosaccharomyces pombe.
Language:
English
52-01 AEROSPACE MEDICINE
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Ambiguous Tilt and Translation Motion Cues after Space Flight and Otolith Assessment during Post-Flight Re-Adaptation
Document ID:
20090001944
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Wood, Scott J. (NASA Johnson Space Center) Clarke, A. H. (Charite-Universitaetsmedizin) Harm, D. L. (NASA Johnson Space Center) Rupert, A. H. (Army Aeromedical Research Lab.) Clement, G. R. (Centre National de la Recherche Scientifique)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
DLR WB0729
Abstract:
Adaptive changes during space flight in how the brain integrates vestibular cues with other sensory information can lead to impaired movement coordination, vertigo, spatial disorientation and perceptual illusions following Gtransitions. These studies are designed to examine both the physiological basis and operational implications for disorientation and tilt-translation disturbances following short duration space flights.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Robotics Offer Newfound Surgical Capabilities
Document ID:
20090002475
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002475
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 46-47
Published:
20080901
Source:
Barrett Technology, Inc. (Cambridge, MA, United States)
Pages:
2
Contract #:
None
Abstract:
Barrett Technology Inc., of Cambridge, Massachusetts, completed three Phase II Small Business Innovation Research (SBIR) contracts with Johnson Space Center, during which the company developed and commercialized three core technologies: a robotic arm, a hand that functions atop the arm, and a motor driver to operate the robotics. Among many industry uses, recently, an adaptation of the arm has been cleared by the U.S. Food and Drug Administration (FDA) for use in a minimally invasive knee surgery procedure, where its precision control makes it ideal for inserting a very small implant.
Language:
English
Title:
Enhancing Functional Performance using Sensorimotor Adaptability Training Programs
Document ID:
20090002591
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Bloomberg, J. J. (NASA Johnson Space Center) Mulavara, A. P. (Universities Space Research Association) Peters, B. T. (Wyle Life Sciences, Inc.) Brady, R. (Wyle Life Sciences, Inc.) Audas, C. (Wyle Life Sciences, Inc.) Ruttley, T. M. (NASA Johnson Space Center) Cohen, H. S. (Baylor Coll. of Medicine)
Published:
20090202
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
NCC-9-58
Abstract:
During the acute phase of adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform functional tasks. The goal of this project is to develop a sensorimotor adaptability (SA) training program designed to facilitate recovery of functional capabilities when astronauts transition to different gravitational environments. The project conducted a series of studies that investigated the efficacy of treadmill training combined with a variety of sensory challenges designed to increase adaptability including alterations in visual flow, body loading, and support surface stability.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Biosensors for EVA: Muscle Oxygen and pH During Walking, Running and Simulated Reduced Gravity
Document ID:
20090002614
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Lee, S. M. C. (Wyle Labs., Inc.) Ellerby, G. (Massachusetts Univ.) Scott, P. (Massachusetts Univ.) Stroud, L. (Wyle Labs., Inc.) Norcross, J. (Wyle Labs., Inc.) Pesholov, B. (Massachusetts Univ.) Zou, F. (Massachusetts Univ.) Gernhardt, M. (NASA Johnson Space Center) Soller, B. (Massachusetts Univ.)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO2 on the leg during cycling. Our NSBRI-funded project is looking to extend this methodology to examine activities which more appropriately represent EVA activities, such as walking and running and to better understand factors that determine the metabolic cost of exercise in both normal and lunar gravity. Our 4 year project specifically addresses risk: ExMC 4.18: Lack of adequate biomedical monitoring capability for Constellation EVA Suits and EPSP risk: Risk of compromised EVA performance and crew health due to inadequate EVA suit systems.
Language:
English
Title:
Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)
Document ID:
20090002615
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Boyd, Jason L. (Universities Space Research Association) Du, Brian (Wyle Labs., Inc.) Daniels, Vernie (Wyle Labs., Inc.) Simmons, Rita (Naval Aerospace Medical Inst.) Buckey, Jay (Dartmouth-Hitchcock Medical Center) Putcha, Lakshmi (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on duty.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Diving in Space
Document ID:
20090002616
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002616
Sales Agency:
CASI Hardcopy A03 No Copyright
Author(s):
Gernhardt, Michael L. (NASA Johnson Space Center)
Published:
20081218
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
25
Contract #:
None
Abstract:
This viewgraph presentation reviews NASA's extravehicular activity (EVA) procedures and the technological and biomedical issues surrounding EVA.
Language:
English
Notes:
Haldane International Symposium 2008: The Future of Diving: 100 Years of Haldane and Beyond Trondheim 18-19 Dec. 2008
Title:
A History of Space Toxicology Mishaps: Lessons Learned and Risk Management
Document ID:
20090002627
Report #:
None
Sales Agency:
Other Sources No Copyright
Author(s):
James, John T. (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
After several decades of human spaceflight, the community of space-faring nations has accumulated a diverse and sometimes harrowing history of toxicological events that have plagued human space endeavors almost from the very beginning. Lessons have been learned in ground-based test beds and others were discovered the hard way - when human lives were at stake in space. From such lessons one can build a risk-management framework for toxicological events to minimize the probability of a harmful exposure, while recognizing that we cannot foresee all events. Space toxicologists have learned that relatively harmless compounds can be converted by air revitalization systems into compounds that cause serious harm to the crew. Our toxic risk management strategy now includes an assessment of the fate of any compound that might be released into the atmosphere. Propellants are highly toxic compounds, yet we have not always been able to thoroughly isolate the crew from exposure to these toxicants. Leakage of fluids from systems has resulted in hazardous conditions at times, and the behavior of such compounds inside a spacecraft has taught us how to manage potentially harmful escapes should they occur. Potential combustion events are an ever-present threat to the wellbeing of the crew. Such events have been sufficiently common that we have learned that one cannot judge the health threat of a given fire by the magnitude of the event. Management of such risks demands monitoring of combustion products. In the category of unpredictable toxic events, if one assumes that fires are predictable, we can place experience with toxic microbial metabolites, upsets during repair operations, and discharges from filters that have accumulated a substantial load of pollutants in their absorption beds. Management of such events requires a broad-spectrum, real-time analytical capability to discern the identity and concentrations of pollutants if they enter the atmosphere. Adverse events are an integral part of any human activity, and the spacefaring community must learn as much as possible from mistakes and near misses.
Language:
English
Notes:
ICES Meeting Savannah, GA 13-16 Jul. 2009
Title:
Physiological Responses to Exercise-Heat Stress With Prototype Pulsed Microclimate Cooling System
Document ID:
20090003350
Report #:
AD-A487097, USARIEM-TR-T08-12
Available Online:
http://hdl.handle.net/100.2/ADA487097
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Cadarette, Bruce S Chineverse, Troy D Ely, Brett R Goodman, Daniel A Laprise, Brad Teal, Walter Sawka, Michael N
Published:
20080901
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
32
Contract #:
None
Abstract:
This study supported the U.S Army Natick Soldier Research Development and Engineering Center (NSRDEC) effort to develop a lightweight microclimate cooling system (MCCS) for use by dismounted Soldiers. The MCCS evaluated in this study was an early prototype light weight circulating liquid vapor compression MCCS with an integrated skin temperature sensor to trigger on/off cycles The prototype system is based on a USARIEM patent (patent pending) for personalized microclimate cooling that when configured to operate as a skin temperature feedback pulsed cooling (PC) unit should delay heat strain as effectively as constant cooling (CC) during exercise%heat stress while reducing the power requirement by 50% This prototype system could potentially save the U.S Army substantial dollars currently being spent on battery acquisition. Additionally using smaller or fewer batteries would decrease the weight of the system and increase acceptability by dismounted Soldiers This study was designed to evaluate both the prototype MCC system's capability to be controlled by the skin temperature sensor and its ability to sufficiently cool subjects under the given heat stress scenarios.
Language:
English
Title:
The Efficacy of Dextroamphetamine as a Motion Sickness Countermeasure for the Use in Military Operational Environments
Document ID:
20090003614
Report #:
AD-A487648, NAMRL-TR-08-09
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Simmons, Rita G Phillips, Jeffrey B Lawson, Benton D Lojewski, Renee A
Published:
20080709
Source:
Naval Aerospace Medical Research Lab. (Pensacola, FL United States)
Pages:
36
Contract #:
NAVCOMP-2189
Abstract:
Previous research examining pharmacological solutions for motion sickness have reported that dextroamphetamine (d-amphetamine) imparts significant protection against provocative motion without conferring drowsiness or significant side effects. If the purported anti-motion sicknesses properties of d-amphetamine are accurate, the military could utilize a single medication for motion sickness and fatigue prevention. The purpose of this study was to determine the efficacy and side effect profile of this potential motion sickness countermeasure for use in military environments. It was hypothesized that subjects in the oral d-amphetamine condition would tolerate more head movements than subjects in the placebo condition, without performance decrements or significant side effects. Thirty-six aviation candidates were randomized to one of two treatment groups and then exposed to passive Coriolis cross-coupling. Medication efficacy was determined by number of head movements tolerated between groups. Cognitive and medication side-effect profiles for both groups were derived from performance on a computer based cognitive battery, measurements of near-focus visual accommodation (VA), scores on the Karolinska Sleepiness Scale (KSS), and motion sickness questionnaires. Analyses demonstrated that there were no significant differences in the number of head movements tolerated between groups and no treatment effects over time on the cognitive battery, VA, or KSS, p > 0.05.
Language:
English
Title:
Thermoregulatory Responses to Environmental Toxicants: The Interaction of Thermal Stress and Toxicant Exposure
Document ID:
20090003756
Report #:
AD-A490382
Available Online:
http://hdl.handle.net/100.2/ADA490382
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Leon, Lisa R
Published:
20080101
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
17
Contract #:
None
Abstract:
Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment.
Language:
English
Title:
Assessment of Male Anthropometric Trends and the Effects on Simulated Heat Stress Responses
Document ID:
20090003758
Report #:
AD-A490384, USARIEM-M-07-34
Available Online:
http://hdl.handle.net/100.2/ADA490384
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yokota, Miyo Bathalon, Gaston P Berglund, Larry G
Published:
20080101
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
9
Contract #:
None
Abstract:
Assessing temporal changes in anthropometrics and body composition of US Army soldiers is important because these changes may effect fitness, performance, and safety. This study investigated differences in body dimensions(height, weight, percent body fat (%BF)) of US Army male soldiers by comparing 2004- 1988 databases. Anthropometric somatotypes were identified and physiological responses of the different somatotypes to simulated heat stress (35 deg C/50%rh, `550 W work rate, carrying 12 kg load including battle dress uniform and body armor, rest for 30 min and walk for 70 min) using a thermal regulatory model were evaluated.
Language:
English
Title:
A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance
Document ID:
20090003798
Report #:
AD-A490652
Available Online:
http://hdl.handle.net/100.2/ADA490652
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Raskind, Murray Peskind, Elaine McFall, Miles Peterson, Kris Doyle, Michael Engel, Charles
Published:
20080301
Source:
Seattle Inst. for Biomedical Clinical Research (Seattle, WA United States)
Pages:
5
Contract #:
W81XWH-06-2-0014
Abstract:
The primary goal of this proposal is to evaluate the efficacy and tolerability of the alpha-1 adrenergic antagonist prazosin compared to placebo for combat trauma-related nightmares, sleep disturbance and overall function in recently combat-exposed returnees from OIF and OEF. A secondary goal is to evaluate the effects of the SSRI paroxetine on behavioral symptoms and overall function in this population. Specific hypotheses (described below) will be tested in a three parallel arm 12-week randomized controlled trial of prazosin, paroxetine and placebo in combat-exposed troops recently returned from OIF and OEF with combat trauma-related persistent nightmares and sleep disturbance. This will be a two-site study performed in the Seattle/Tacoma area at Madigan AMC and in the Washington DC area at Walter Reed AMC.
Language:
English
Title:
Stress on the Force: Measuring the Impact of Increased Operational Deployments Using Manpower Metrics
Document ID:
20090003810
Report #:
AD-A490695
Available Online:
http://hdl.handle.net/100.2/ADA490695
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Guice, Robert J
Published:
20080101
Source:
Marine Corps Development and Education Command (Quantico, VA United States)
Pages:
32
Contract #:
None
Abstract:
Accurate deployment data, when correlated with manpower metrics such as divorce, separation, and suicide rates, can provide a representative assessment of "stress on the force." The United States Marine Corps (USMC) is involved in a conflict that can potentially last a generation. Given this level of operational commitment, the Marine Corps is sensitive to the ramifications, both long- and short-term, of increased operational tempo. The negative ramifications are commonly referred to as "stress on the force" and can cross most functional boundaries of the Marine Corps. Recognizing and addressing the stress is a challenge for a service that is involved in one of the longest periods of sustained combat in its illustrious history. Identification of measurable stress indicators may facilitate the Marine Corps in maintaining the proper balance between operational deployments and the quality of life of service members and their families. This thesis examines the issues surrounding the measurement of deployment tempo by the Marine Corps Total Force System (MCTFS). The thesis then provides several manpower metrics that can be used as stress indicators. Finally, the author draws conclusions and provides recommendations for improving the Marine Corps' ability to track the health of the force from a manpower perspective. The Marine Corps has the capability to depict the "stress on the force" in near-real time. The breadth of data stored by the MCTFS can be effectively mined via access to the relational database that stores the information. Facilitating the use of manpower metrics to measure "stress on the force" will require a renewed focus on improving the data itself.
Language:
English
Title:
Mindfullness-Based Cognitive Therapy as a Complementary Treatment for Combat/Operational Stress and Combat Post-Traumatic Stress Disorder
Document ID:
20090003881
Report #:
AD-A490935
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dickey, Jr, G W
Published:
20080101
Source:
Marine Corps Development and Education Command (Quantico, VA United States)
Pages:
36
Contract #:
None
Abstract:
Based Cognitive Therapy is a viable complementary treatment to the traditional psychotherapeutic and pharmacological methods used to treat Combat/Operational Stress Reactions and Combat Post-Traumatic Stress Disorder.
Language:
English
Title:
A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel
Document ID:
20090004050
Report #:
AD-A488231, NAMRL-TR-08-10
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Simmons, Rita G Phillips, Jeffrey B Lojewski, Renee A Lawson, Benton D
Published:
20080818
Source:
Naval Aerospace Medical Research Lab. (Pensacola, FL United States)
Pages:
45
Contract #:
None
Abstract:
Results from preliminary studies indicate intranasal scopolamine (IN SCOP) has faster absorption, higher bioavailability, and a more reliable therapeutic index than equivalent oral (PO SCOP). The purpose of this study was to determine and compare the efficacy, side effect profile, and pharmacotherapeutics of IN SCOP and PO SCOP. It was hypothesized that IN SCOP would rapidly achieve therapeutic concentrations at lower doses compared to PO SCOP while minimizing medication-induced performance impairment. Fifty-four aviation candidates were randomized to one of three treatment groups (0.4 mg IN SCOP gel, 0.8 mg PO SCOP or placebo) and then exposed to passive Coriolis cross-coupling. Medication efficacy, pharmacotherapeutics and side-effect profiles were tracked for all groups. Analysis revealed there were no significant differences in efficacy among groups. Pharmacotherapeutic data show increased scopolamine absorption and decreased time to reach maximum salivary concentration with intranasal administration, with no significant treatment side effects detected over time. There was a significant decrease in heart rate over time for IN SCOP and PO SCOP versus placebo, while no clinically significant differences were found for either systolic or diastolic blood pressures. In summary, IN SCOP absorption was significantly greater than PO SCOP with no detrimental impact on performance or side effects.
Language:
English
Title:
ISS Hygiene Activities - Issues and Resolutions
Document ID:
20090004151
Report #:
None
Sales Agency:
Other Sources No Copyright
Author(s):
Prokhorov, Kimberlee S. (NASA Johnson Space Center) Feldman, Brienne (Wyle Labs., Inc.) Walker, Stephanie (Wyle Labs., Inc.) Bruce, Rebekah (Wyle Labs., Inc.)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Hygiene is something that is usually taken for granted by those of us on the Earth. The ability to perform hygiene satisfactorily during long duration space flight is crucial for the crew's ability to function. Besides preserving the basic health of the crew, crew members have expressed that the ability to clean up on-orbit is vital for mental health. Providing this functionality involves more than supplying hygiene items such as soap and toothpaste. On the International Space Station (ISS), the details on where and how to perform hygiene were left to the crew discretion for the first seventeen increments. Without clear guidance, the methods implemented on-orbit have resulted in some unintended consequences to the ISS environment. This paper will outline the issues encountered regarding hygiene activities on-board the ISS, and the lessons that have been learned in addressing those issues. Additionally, the paper will address the resolutions that have been put into place to protect the ISS environment while providing the crew sufficient means to perform hygiene.
Language:
English
Notes:
International Conference on Environmental Systems Savannah, GA 12-16 Jul. 2009
Title:
Physiological Factors Contributing to Postflight Changes in Functional Performance
Document ID:
20090004156
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Bloomberg, J. J. (NASA Johnson Space Center) Feedback, D. L. (NASA Johnson Space Center) Feiverson, A. H. (NASA Johnson Space Center) Lee, S. M. C. (Wyle Integrated Science and Engineering Group) Mulavara, A. P. (Universities Space Research Association) Peters, B. T. (Wyle Integrated Science and Engineering Group) Platts, S. H. (NASA Johnson Space Center) Reschke, M. F. (NASA Johnson Space Center) Ryder, J. (Universities Space Research Association) Spiering, B. A. (Wyle Integrated Science and Engineering Group) Stenger, M. B. (Wyle Integrated Science and Engineering Group) Wood, S. (Universities Space Research Association) Lawrence, E. (Wyle Integrated Science and Engineering Group) Arzeno, N. (Wyle Integrated Science and Engineering Group)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States) NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Astronauts experience alterations in multiple physiological systems due to exposure to the microgravity conditions of space flight. These physiological changes include sensorimotor disturbances, cardiovascular deconditioning and loss of muscle mass and strength. These changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on lunar and Martian surfaces. To date, changes in functional performance have not been systematically studied or correlated with physiological changes. To understand how changes in physiological function impact functional performance an interdisciplinary pre/postflight testing regimen (Functional Task Test, FTT) has been developed that systematically evaluates both astronaut postflight functional performance and related physiological changes. The overall objectives of the FTT are to: Develop a set of functional tasks that represent critical mission tasks for Constellation. Determine the ability to perform these tasks after flight. Identify the key physiological factors that contribute to functional decrements. Use this information to develop targeted countermeasures. The functional test battery was designed to address high priority tasks identified by the Constellation program as critical for mission success. The set of functional tests making up the FTT include the: 1) Seat Egress and Walk Test, 2) Ladder Climb Test, 3) Recovery from Fall/Stand Test, 4) Rock Translation Test, 5) Jump Down Test, 6) Torque Generation Test, and 7) Construction Activity Board Test. Corresponding physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, orthostatic intolerance, upper and lower body muscle strength, power, fatigue, control and neuromuscular drive. Crewmembers will perform both functional and physiological tests before and after short (Shuttle) and long-duration (ISS) space flight. Data will be collected on R+0 (Shuttle only), R+1, R+6 and R+30. Using a multivariate regression model we will identify which physiological systems contribute the most to impaired performance on each functional test. This will allow us to identify the physiological systems that play the largest role in decrement in functional performance. Using this information we can then design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Spaceflight Toxicology
Document ID:
20090004167
Report #:
None
Sales Agency:
CASI Hardcopy A02 Copyright
Author(s):
Meyers, Valerie (NASA Johnson Space Center)
Published:
20081212
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
9
Contract #:
None
Abstract:
This viewgraph presentation provides a review of NASA Johnson Space Center's Toxicology program. The mission of this program is to protect crews from toxic exposures during spaceflight. The presentation reviews some of the health hazards. A toxicological hazard level chart is presented that reviews the rating of hazard level, irritancy, systemic effects and containability. The program also participates in the Lunar Airborne Dust Toxicity Advisory Group.
Language:
English
Notes:
Presentation to freshman chemistry majors, Dec. 2, 2008, College Station, TX
52-02 CLINICAL MEDICINE
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Tocopherol in Elder Self-Neglect
Document ID:
20090001946
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Aung, K. (Texas Univ. Health Science Center) Burnett, J. (Texas Univ. Health Science Center) Dyer, C. (Texas Univ. Health Science Center) Smith, S. M. (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Although elder self-neglect is the most common form of elder mistreatment, its pathophysiology is not well understood. Alpha-tocopherol is a lipid soluble antioxidant required for the preservation of cell membranes. Since the association between tocopherol and cognitive impairment in older adults has been described, we explored the possibility of its role in elder self-neglect. OBJECTIVE: (1) To determine whether serum tocopherol levels are associated with elder self-neglect, and (2) to assess the association of serum tocopherol levels and cognitive function in elder self-neglect. METHODS: Serum tocopherol levels were measured in a cohort of 67 self-neglecting elders and 67 matched controls, recruited for the Consortium for Research in Elder Self-neglect of Texas. Pearson s correlation tests were performed to assess bivariate associations between serum tocopherol levels and cognitive function. RESULTS: Mean serum alpha-tocopherol levels were 10.8 +/- 4.7 ug/mL in self-neglect group and 13.0 +/- 4.9 ug/mL in control group (p = 0.006, unpaired student s t-test). None of the participants from either group had alpha-tocopherol level lower than the reference range. Mean serum gamma-tocopherol levels were 2.0 +/- 1.0 ug/mL in self-neglect group and 2.0 +/- 1.1 in control group (p=0.83). Proportion of the elders with gamma-tocopherol level lower than the reference range were 4.5% (3/66) in self-neglect group and 10.4% (7/67) in control group (p=0.32, Fisher s Exact Test). Among the self-neglecting elders, no association was found between serum alpha-tocopherol levels and the Mini-Mental State Examination (MMSE) or the Wolf-Klein Clock Drawing Test (CDT) scores (r =-0.42, p=0.75 for MMSE; r=0.08, p=0.54 for CDT). No association was found between serum gamma-tocopherol levels and the MMSE or the CDT (r=-0.12, p=0.35 for MMSE; r=0.05, p=0.68 for CDT). CONCLUSION: In our sample, neither alpha-tocopherol nor gamma-tocopherol appears to have a role in pathophysiology of elder self-neglect. Nevertheless, significantly lower serum alpha-tocopherol levels in the self neglect group merits further research.
Language:
English
Notes:
American Geriatrics Society Annual Meeting Chicago, IL 29 Apr. - 3 May 2009
Title:
Increases in Tricare Costs: Background and Options for Congress
Document ID:
20090001960
Report #:
AD-A486432
Available Online:
http://hdl.handle.net/100.2/ADA486432
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Best, Richard Jansen, Don J
Published:
20080815
Source:
Library of Congress (Washington, DC United States)
Pages:
7
Contract #:
None
Abstract:
In its FY2007, 2008, and 2009 budget submissions, the Department of Defense (DOD) proposed increases in Tricare enrollment fees, deductibles, and pharmacy copayments for retired beneficiaries not yet eligible for Medicare. The raises were justified by DOD as necessary to constrain the growth of health care spending as a proportion of the overall defense budget in the next decade. Many beneficiaries argued that the proposed hikes were unfair and unnecessary. The proposed increases found favor in neither chamber and Congress passed legislation to prohibit such increases. The FY2007 Defense Authorization Act (P.L. 109-364) prohibited increases in premiums, deductibles and co-payments prior to September 30, 2007. For FY2008, the Administration based its budget submission on the assumption of fee increases but the FY2008 National Defense Authorization Act (P.L. 110-181) extended the prohibition of increases in co-payments and enrollment fee until October 2008. For FY2009, the Administration's budget submission assumed fee increases linked to recommendations made by the Task Force on the Future of Military Health Care. However, both House and Senate versions (H.R. 5658/S. 3001) of the defense authorization bill contain provisions to prohibit fee increases in 2009. In July 2008, the Tenth Quadrennial Review of Military Compensation recommended new fees linked to Medicare Part B premiums. This report will be updated as necessary.
Language:
English
Notes:
CRS Report for Congress
Title:
Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer
Document ID:
20090001976
Report #:
AD-A486515
Available Online:
http://hdl.handle.net/100.2/ADA486515
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Fathers, Kelly E
Published:
20080301
Source:
McGill Univ. (Montreal, Quebec Canada)
Pages:
51
Contract #:
W81XWH-06-1-0381
Abstract:
The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion. Targeting CrkI and CrkII in breast cancer cell lines by RNA interference demonstrated that loss of Crk expression corresponded with a significant decrease in cell migration and invasion. This implies that Crk adaptor proteins play an important role in integrating signals for migration and invasion of highly malignant cancer cell lines. As migration and invasion are important components of the metastatic cascade, future work includes performing in vivo metastasis assays using cells with stably knocked down expression of Crk proteins. Furthermore, mouse models over-expressing CrkI/II result in delayed ductal outgrowth. MMTV-CrkII mice display enhanced branching and leads to tumour development. This has important implications as we have shown elevated levels of Crk are observed in human breast cancer. This project may provide information, which could be used to develop effective treatments for breast cancer, as well as other cancer types.
Language:
English
Title:
Iraqi Civilian Deaths Estimates
Document ID:
20090001979
Report #:
AD-A486521, CRS-RS22537
Available Online:
http://hdl.handle.net/100.2/ADA486521
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Fischer, Hannah
Published:
20080827
Source:
Library of Congress (Washington, DC United States)
Pages:
6
Contract #:
None
Abstract:
This report presents various governmental and non-governmental estimates of Iraqi civilian deaths. The Department of Defense (DoD) regularly updates total U.S. military deaths statistics from Operation Iraqi Freedom (OIF), as reflected in CRS Report RS21578, "Iraq: U.S. Casualties." However, no Iraqi or U.S. government office regularly releases publicly available statistics on Iraqi civilian deaths. Statistics on Iraqi civilian deaths are sometimes available through alternative sources, such as nonprofit organizations, or through statements made by officials to the press. Because these estimates are based on varying time periods and have been created using differing methodologies, readers should exercise caution when using these statistics and should look on them as guideposts rather than as statements of fact. See also CRS Report RS22532, "Iraqi Police and Security Forces Deaths Estimates." This report will be updated as needed.
Language:
English
Notes:
CRS Report for Congress
Title:
BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex: Candidates for BRCA3
Document ID:
20090001982
Report #:
AD-A486526
Available Online:
http://hdl.handle.net/100.2/ADA486526
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chen, Xiaowei
Published:
20080601
Source:
Fox Chase Cancer Center (Philadelphia, PA United States)
Pages:
66
Contract #:
W81XWH-04-1-0573
Abstract:
Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCA1 and BRCA2 mutation-negative breast cancer-prone families. We hypothesized that other proteins, which have equivalent or complementary functions as BRCA1, may also be involved in the development of breast cancer. We have recently found one such candidate, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors which leads to tumorigenesis in vitro. Furthermore, our studies have defined BRCC36 as a direct regulator of BRCA1 activation and nuclear foci formation in response to IR in a number of breast cancer cell lines. Our results have found that down-regulation of BRCC36 expression impairs homologous recombination repair (HRR). Therefore, our data suggest that DNA repair pathway activated in response to IR and appears to sensitize breast cancer cells to IR-induced apoptosis. Importantly, we found that BRCC36 mutated in the germline of a cancer-prone family and may increase the risk of developing breast cancer. Overall, aberrant expression or mutation of BRCC36 genes in breast tumors may lead to disruption of the normal function of BRCA1 and contribute to the development of breast cancer.
Language:
English
Title:
Legubicin a Tumor-activated Prodrug for Breast Cancer Therapy
Document ID:
20090001983
Report #:
AD-A486531
Available Online:
http://hdl.handle.net/100.2/ADA486531
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Liu, Cheng
Published:
20080401
Source:
Scripps Research Inst. (La Jolla, CA United States)
Pages:
81
Contract #:
W81XWH-05-1-0318
Abstract:
Legumain is a recently discovered and only known asparaginyl endopeptidase that is well conserved throughout the biologic kingdoms. We have demonstrated that legumain is highly and inappropriately expressed in 100% human breast cancer specimens as well as murine breast cancer models. We demonstrated that an inactive prototype doxorubicin derived prodrug incorporating a succinyl blocked substrate peptide removable by legumain was effectively activated and tumoricidal in human breast cancer models. We designated this prodrug legubicin. Legubicin is not cytotoxic until activated by legumain due to reduced ability to enter cells and blocked binding to DNA. These properties led to increased tumor exposure and much reduced drug accumulation in normal tissues when administered in vivo. It has markedly reduced cardiac and myelosuppressive toxicities compare to doxorubicin. In this grant application we propose to further develop this prodrug strategy as a potential treatment for breast cancer.
Language:
English
Title:
9th Annual UC Systemwide Bioengineering Symposium
Document ID:
20090001984
Report #:
AD-A486532
Available Online:
http://hdl.handle.net/100.2/ADA486532
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Rodgers, Victor G
Published:
20080801
Source:
California Univ. (Riverside, CA United States)
Pages:
149
Contract #:
W81XWH-08-1-0405
Abstract:
The theme of this conference was to increase the synergistic interaction of the University of California's vast biomedical engineering research expertise with the practical medical and healthcare engineering undertaken by biomedical firms and government agencies. The symposium had 204 attendees representing all ten UC campuses as well as interested corporate and government agencies and individuals in the community. The symposium was supported by seven corporate sponsors and had four partnerships with industrial and government agencies. The symposium had twelve tracks that covered a broad range of topics to represent most research in Bioengineering at the University of California. In all, 48 talks and 49 posters were presented. In addition, five major presentations were given including three keynote speakers and two speakers representing TATRC. Through our generous corporate support, twelve cash awards totaling $5,000 were given to student oral and poster presenters who were judged to be outstanding. Judges were members of the UC, US Army Medical Research ACQ and our corporate sponsors. The program schedule is attached.
Language:
English
Notes:
Conference proceedings of the Annual UC Systemwide Bioengineering Syposium (9th), Riverside, CA on 20-22 Jun 2008
Title:
Identification of Novel Molecular Targets for Pleckstrin Homology (PH) Domains Found in Oncogenes Implicated in Breast Cancer
Document ID:
20090002002
Report #:
AD-A486604
Available Online:
http://hdl.handle.net/100.2/ADA486604
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Keleti, David
Published:
20080301
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
22
Contract #:
W81XWH-04-1-0320
Abstract:
Plecktrin Homology (PH) domains are commonly thought of as membrane-targeting modules involved in signaling pathways that bind phosphoinositides (PPIns) with high affinity and specificity. In a recent study of S. cerevisiae, however, the vast majority demonstrated little affinity or specificity for PPIns (Yu et al, 2004). I show comparable results for selected human PH domains, with one that is high affinity and PPIns-specific, while the remainder are low to moderate affinity and promiscuous for PPIns. I outline two instances where protein-protein and protein-phosphoinositide interactions may account for specific membrane targeting observed in vivo. First, SH3BP-2 PH was identified as highly specific for the membrane lipid PtdIns(3,4)P2, and targets the host protein to the membrane. Second, FAPP1- and OSBP PH domains possess comparable affinities for Golgi- and plama membrane (PM)-enriched PPIns in vitro, although they both localize to the Golgi (not the PM) in vivo, possibly by directly interacting with the Golgi GTPase Arf1. In vitro binding studies suggest that delocalized electrostatic attraction between the basic protein and acidic phospholipids play a prominent role in these interactions. Additionally, I have solved the crystal structure of a related member of this PH domain family in complex with PPIns.
Language:
English
Title:
Bioavailability of TGF-Beta in Breast Cancer
Document ID:
20090002003
Report #:
AD-A486606
Available Online:
http://hdl.handle.net/100.2/ADA486606
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Bochaca, Irineu I Barcellos-Hoff, Mary H
Published:
20080301
Source:
California Univ. (Berkeley, CA United States)
Pages:
11
Contract #:
DAMD17-03-1-0488
Abstract:
The Transforming Growth Factor beta (TGF-) superfamily includes three isoforms designated TGF-1, 2 and 3. All three isoforms are secreted as latent complex where the TGF- cytokine is non-covalently associated with an isoform specific latency-associated peptide (LAP). Mature cytokine binds cell surface receptors only after release from its LAP making extracellular activation a critical regulatory point for TGF- bioavailability. Proposed activation mechanisms include proteolysis and conformational changes. Previous work from our laboratory showed that latent TGF-1 (LTGF-1) is efficiently activated upon exposure to reactive oxygen species (ROS). ROS activation is restricted to the LTGF-1 isoform. Because of the amino acid sequence differences between the three LAPs, we postulate that the specificity of this activation mechanism lies within the LAP. Furthermore, we hypothesize that the presence of a metal in the latent complex could provide a redox active center for this process. Redox mediated activation provides a novel mechanism for TGF- participation in tissues undergoing oxidative stress. Moreover, this would allow TGF-1 to act both as a sensor of oxidative stress within tissues as well as a transducer of that signal by binding to its cellular receptors.
Language:
English
Title:
Short-Term Exercise and Prostate Cancer Prevention in African American Men
Document ID:
20090002008
Report #:
AD-A486612
Available Online:
http://hdl.handle.net/100.2/ADA486612
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Taylor, Teletia R
Published:
20080401
Source:
Howard Univ. (Washington, DC United States)
Pages:
12
Contract #:
W81XWH-05-1-0366
Abstract:
This study seeks to examine the impact of exercise on serum factors related to prostate cancer in African-American men. Aims and Objectives: 1. To recruit 40 African-American men between the ages of 40 and 70 who are at increased risk for developing prostate cancer and randomize them into an exercise intervention or control group. 2. To examine the effect of 12 days of aerobic exercise over 4 weeks on PSA levels in African-American men who have PSA levels under 4.0 ng/ml. 3. To examine the effect of 12 days of aerobic exercise on free and total testosterone, insulin, IGF1, and SHBG levels in African-American men. A total of 40 African-American men between the ages of 40 70 yrs, from the Howard University Cancer Center prostate screening program that have a PSA under 4.0 ng/ml, a BMI > 25 and < 35 kg/m2, <375 pounds, and have been sedentary for at least 6 months (not exercising for more than 20 minutes 2 days a week). The men will be randomized into 2 groups 12 days of aerobic exercise (20 participants), or a control group (20 participants). The 12 days of exercise will consist of 30 minutes of walking on a treadmill at 50 60% of maximal heart rate reserve (HRR). Free testosterone, lipids, glucose, insulin, SHBG, psychosocial measures, body weight, BMI and body fat, anthropometric measurements, height, and weight will be measured before and after the study.
Language:
English
Title:
Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics
Document ID:
20090002012
Report #:
AD-A486620
Available Online:
http://hdl.handle.net/100.2/ADA486620
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ko, Mei-Chuan
Published:
20080501
Source:
Michigan Univ. (Ann Arbor, MI United States)
Pages:
20
Contract #:
W81XWH-07-1-0-0162
Abstract:
These experiments demonstrated that (1) intrathecal N/OFQ did not produced hyperalgesia-like effects as reported in rodents, (2) systemic Ro 64-6198 produced antinociceptive effects that are independent from mu opioid receptors, and (3) activation of NOP receptors produced antinociception without reinforcing/abuse liability in monkeys. Ro 64-6198 has only been studied in rodent species. This is the first functional study to investigate the behavioral effects of Ro 64-6198 in primates. More importantly, Ro 64-6198 produces antinociception like alfentanil, a commonly used mu opioid analgesic in the clinic, in two primate nociceptive models, but Ro 64-6198 does not produce reinforcing effects /abuse liability like mu receptor opioid analgesics. These findings may indicate that NOP receptor agonists may be a new generation of novel analgesics without abuse liability.
Language:
English
Title:
Systemic and Gene Modified Mesenchymal Stem Cell Therapy for Metastatic Prostate Cancer
Document ID:
20090002014
Report #:
AD-A486623
Available Online:
http://hdl.handle.net/100.2/ADA486623
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ponnazhagan, Selvarangan
Published:
20080501
Source:
Alabama Univ. (Birmingham, AL United States)
Pages:
7
Contract #:
W81XWH-06-1-0069
Abstract:
Bone is the frequent metastatic site for human prostate cancer resulting in significant morbidity and mortality in patients with advanced disease. The type of bone defect encountered in prostate cancer bone metastasis is osteoblast lesions resulting in excess bone. However, initiation of osteoclastogenesis is first aided by osteolysis, mediated by osteoclasts. The areas provided as source for osteoblast accumulation later leads to thickening of the bone. In this proposal, we planned to address arresting both the events of osteolysis and osteoblastogeneis by biological inhibitors of these two events. Osteoprotegerin (OPG) is a decoy receptor that competes with RANK for RANKL, thus, modulating the effects of RANKL. Thus, OPG remains an effective molecule for future therapies for bone metastasis. We sought to achieve sustained effects of OPG combining cell therapy and gene therapy approaches. Similarly, for inhibiting osteoblast activity we chose noggin, capable of arresting osteoblast formation. The aims were to determine therapeutic effects of OPG and noggin expression by rAAV gene therapy in a murine model of prostate cancer bone metastasis. So far, we produced high-titer recombinant AAV vectors encoding osteoprotegerin, and noggin and currently testing the feasibility of MSC therapy for reducing bone burden initiated by cancer growth. Continuation of the ongoing studies in to next year will provide valuable information on therapeutic effects of this therapy for prostate cancer bone metastasis.
Language:
English
Title:
Early Life Processes, Endocrine Mediators and Number of Susceptible Cells in Relation to Breast Cancer Risk
Document ID:
20090002015
Report #:
AD-A486624
Available Online:
http://hdl.handle.net/100.2/ADA486624
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Trichopoulos, Dimitrios
Published:
20080401
Source:
Harvard Univ. (Cambridge, MA United States)
Pages:
47
Contract #:
W81XWH-05-1-0314
Abstract:
To investigate the role of early life processes, endocrine mediators and number of susceptible cells on adult life breast cancer risk. Five interlinked component projects covering the spectrum from endometrial to adult life. Progress report: Component projects 1 to 4 were officially launched July 2005. Component projects 5a and 5b were officially launched July 18, 2006. Tasks and subtasks to be performed were described in the submitted Statement of Work (SOW). Subtasks 1a, 1b, 2a, 2b, 3a, 3b, 3c, 4a, 4b, 4c, 5a, 5b have been completed. Subtasks 1c, 2c, 2d, 3d, 4d, 5c, 5d are ongoing. Subtasks 3e, 4e, 5f and 5g have been initiated. Subtasks 6a, 6b and 6c are being implemented. (a) No substantial main effect of ESR1 and EGF on breast cancer risk, so that interaction with early life influences is unlikely (CP3) (b) Differences in the estradiol serum concentrations between the Boston and Shanghai pregnant women have been found to persist even after adjusting for proxies of plasma volume expansion (CP4). (c) Androgen levels have been found to be higher in cord blood samples from Chinese compared to Caucasian women, suggesting that elevated prenatal androgen exposure could mediate reductions in breast cancer risk (CP4). (d) Collagen I substrate has been found to be essential for the formation of mammospheres from epithelial cells found in cord blood (CP5). (e) Among term newborns with a normal-to-high birth weight, birth weight was found to be significantly positively associated with stem cell measurements, supporting a role of stem cell pool on cancer risk (CP5).
Language:
English
Title:
Effects of Inactivating Ras-Converting Enzyme or Isoprenylcysteine Carboxyl Methyltransferase in the Pathogenesis of Chronic Myelogenous Leukemia
Document ID:
20090002016
Report #:
AD-A486625
Available Online:
http://hdl.handle.net/100.2/ADA486625
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ren, Ruibao
Published:
20080201
Source:
Brandeis Univ. (Waltham, MA United States)
Pages:
6
Contract #:
W81XWH-06-1-0238
Abstract:
The BCR-ABL fusion gene, the hallmark of CML, plays a causal role in the development of CML. The BCR-ABL tyrosine kinase inhibitors have been successfully used to treat patients with CML, but residual disease persists and drug resistance emerges. Although BCR-ABL remains to be an attractive target for developing CML therapies, identifying and targeting additional essential components in the development of CML are important for overcoming resistance to BCR-ABL tyrosine kinase inhibitors and for eradicating leukemic cells. Substantial evidence indicates that Ras and Ras related proteins are critical mediators of BCR-ABL in leukemogenesis. Ras-converting enzyme (Rce1) and isoprenylcysteine carboxyl methyltransferase (Icmt) are two unique enzymes for Ras modifications that are critical for their functions. Targeted inactivation of Rce1 or Icmt is, therefore, an attractive strategy for the treatment of CML. The goal of this project is to determine whether targeted inactivation of Rce1 or Icmt could block BCR-ABL leukemogenesis. In this study, we have found that Icmt plays a critical role in BCR-ABL leukemogenesis and that the role of Rce1 in BCR-ABL leukemogenesis is dosage dependent. We have also found that the mutation affecting the AAX peptide cleavage and methylation of RAS in cis significantly reduces RAS leukemogenesis, suggesting that the AAX peptide cleavage and methylation play an important role for RAS leukemogenesis.
Language:
English
Title:
Family Maltreatment, Substance Problems, and Suicidality: Randomized Prevention Effectiveness Trial
Document ID:
20090002019
Report #:
AD-A486633
Available Online:
http://hdl.handle.net/100.2/ADA486633
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Heyman, Richard E Slep, Amy M
Published:
20080201
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
47
Contract #:
W81XWH-06-1-0165
Abstract:
This study aims to enhance the ability of base major command (MAJCOM) and Air Staff IDSs to reduce death, injury, and degraded force readiness through (a) dissemination of base MAJCOM and AF prevalences of secretive problems; (b) provision of base-level information to identify and prioritize risk and protective factors (c) assistance in bases selecting and implementing empirically supported interventions and (d) evaluation of whether prevalences were lowered.
Language:
English
Title:
Regulation of the mTOR Pathway by a Novel Rheb Binding Protein BNIP3
Document ID:
20090002022
Report #:
AD-A486638
Available Online:
http://hdl.handle.net/100.2/ADA486638
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Guan, Kun-Liang
Published:
20080501
Source:
Michigan Univ. (Ann Arbor, MI United States)
Pages:
19
Contract #:
W81XWH-07-1-0179
Abstract:
Uncontrolled mTOR activation is a major contributing factor to the pathogenesis of TSC. mTOR is known to be regulated by a wide range of signals such hypoxia. The major goal of this project is to determine mTOR regulation by hypoxia. We proposed to focus on BNIP3 which is a Rheb interacting protein in mTOR regulation in response to hypoxia. Our goals outlined in the original proposal have been successfully completed. We confirmed that BNIP3 is indeed a Rheb interaction protein under physiological conditions. We demonstrate that BNIP3 plays a critical role in hypoxia-induced mTOR inhibition. Furthermore we found that BNIP3 itself has a growth inhibitory activity and inactivation of BNIP3 promotes cell growth in vitro and tumor growth in vivo. Our observation reveals an important mechanism of cell growth regulation by hypoxia. Our results also indicate potential therapeutic target for TSC disease which has a high level of mTOR and Rheb activation. Activation BNIP3 may inhibit Rheb and mTOR in TSC mutant cells.
Language:
English
Title:
Elucidating the Role of Cks Proteins in Breast Cancer by Combining the Disciplines of Molecular Biology, Pathology, and Biophysics
Document ID:
20090002023
Report #:
AD-A486639
Available Online:
http://hdl.handle.net/100.2/ADA486639
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Rincon, Sonia del
Published:
20080301
Source:
Kimmel (Sidney) Cancer Center (San Diego, CA United States)
Pages:
16
Contract #:
W81XWH-06-1-0344
Abstract:
Breast cancer often occurs when the proteins that regulate normal epithelial cell division become dysregulated. This proposal examines the role of the cell cycle regulatory proteins human cyclin-dependent kinase subunits (Cks1 and Cks2) in human breast cancer. The overexpression of Cks genes in breast tumor tissue and the role of Skp2 in tumorigenesis suggests that Cks and Skp2 levels must be strictly regulated for proper cell cycling. We hypothesize that aberrant Cks protein expression and function contributes to breast carcinogenesis at least in part by its ability to interact with Skp2. In year one of this project we have determined the levels of Cks mRNA and protein in (i) breast cancer cell lines and (ii) normal versus tumor breast tissue. We have also developed breast cancer cell lines that overexpress cksl cks2 or skp2 and cells that co-overexpress cks2 and skp2. In the coming year we will focus on characterizing the breast cancer cell lines developed that stably overexpress the aforementioned cell cycle proteins using both in vitro and in vivo techniques.
Language:
English
Title:
PARK2, a Large Common Fragile Site Gene, is Part of a Stress Response Network in Normal Cells that is Disrupted During the Development of Ovarian Cancer
Document ID:
20090002024
Report #:
AD-A486640
Available Online:
http://hdl.handle.net/100.2/ADA486640
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Smith, David I Zhu, Yu
Published:
20080101
Source:
Mayo Clinic (Rochester, MN United States)
Pages:
18
Contract #:
W81XWH-04-1-0082
Abstract:
PARK2 (Parkin) is a common fragile site (CFS) gene. We examined Parkin in primary ovarian tumors and found that this gene was frequently inactivated. We also found that re-introduction of Parkin is associated with greater sensitivity to apoptotic induction in ovarian cancer cell lines. We also discovered an entire family of very large common fragile site genes. We measured the expression of Parkin and 13 other CFS genes in panels of different cancers. This revealed non-random inactivation of these genes and greater inactivation in cancers that have a poorer clinical prognosis. We then utilized whole genome tiling arrays to characterize all transcripts (not just coding transcripts) and their response to stress. These studies revealed non-coding transcripts within Parkin and other large CFS genes. We discovered a new class of large non-coding transcripts. A sub-set of these were highly evolutionarily conserved; when we examined these transcripts in ovarian and other cancers, we found alterations in their expression. We also found that some of these non-coding transcripts were mutational targets in ovarian and other cancers. Thus, this work has discovered a new group of targets that are altered during the development of ovarian cancer.
Language:
English
Title:
Preventing Epilepsy After Traumatic Brain Injury
Document ID:
20090002026
Report #:
AD-A486647
Available Online:
http://hdl.handle.net/100.2/ADA486647
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dichter, Marc A
Published:
20080201
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
9
Contract #:
W81XWH-05-1-0020
Abstract:
The purpose of this study is to determine the safety and tolerability of topiramate (TPM) in the treatment of early seizures following traumatic brain injury (TBI) and to compare the efficacy of TPM to prevent early seizures to the standard of care (phenytoin). A secondary objective is to obtain the data necessary to design a randomized clinical trial to determine if TPM can prevent epilepsy and improve neurological outcome after TBI. In the first two years of the study we formulated the protocol and all documents required by regulatory bodies. These were approved by the IRB at the University of Pennsylvania HRPO at the US Army and the FDA. The infrastructure for the study was established relevant personnel were hired and the patient recruitment methods interactions with the trauma center neurosurgical services EEG laboratory pharmacy etc. were organized. Subject recruitment began. Initial subject recruitment was very slow and the protocol was revised to eliminate several major obstacles. We have enrolled 5 subjects into the study; two in the phenytoin arm one in the short term topiramate one in the 3 month topiramate arm; one subject was withdrawn after testing positive for illicit drug use. We have also organized a NINDS-sponsored workshop on Biomarkers for Epileptogenesis and a program to assist TBI veterans.
Language:
English
Title:
Molecular Identification of Human Fungal Pathogens
Document ID:
20090002028
Report #:
AD-A486650
Available Online:
http://hdl.handle.net/100.2/ADA486650
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wickes, Brian L
Published:
20080301
Source:
Texas Univ. Health Science Center (San Antonio, TX United States)
Pages:
17
Contract #:
W81XWH-06-1-0234
Abstract:
The focus of the work during this funding period mainly centered around Task 2, which consisted of developing standardized protocols for PCR and sequencing template preparation. The two major subtasks, development of a universal DNA extraction strategy and development of a universal PCR reaction, were initiated during the first funding period and have been completed. These accomplishments now allow us to utilize a standard DNA extraction method and a standard PCR reaction that uses the same primer set, for any unknown fungus. Confirmation of these conclusions has been obtained using a broad range of clinical specimens from both humans and animals, and demonstrates that our standard protocol works across all fungal phyla. In addition to the technical developments, we have now completed the design of the database and have been uploading sequences throughout this second year. During the course of uploading sequences, we have been testing the database since it must perform a number of tasks upon data entry. Debugging issues have been minor and although we will continue to revise the database, we now have a working version that will be used to generate output after searches.
Language:
English
Title:
The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis
Document ID:
20090002033
Report #:
AD-A486664
Available Online:
http://hdl.handle.net/100.2/ADA486664
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Fereshteh, Mark P
Published:
20080301
Source:
Georgetown Univ. (Washington, DC United States)
Pages:
13
Contract #:
W81XWH-06-1-0350
Abstract:
AIBI (Amplified In Breast Cancer I) is a nuclear receptor coactivator whose gene is amplified in 5-10% of breast cancers and both the mRNA and protein are overexpressed in 30% of breast tumors. In vitro studies show that AIBI plays a significant role in estrogen and IGF-1-induced cell proliferation. Germline knockout of the AIBI gene leads to reduced somatic growth abnormal reproductive function and reduced mammary gland development. Knockout of AIBI expression also abrogates Ras-induced tumorigenesis. Furthermore patients with tumors expressing high levels of the growth factor HER2/Neu in addition to AIBI often develop anti-estrogen resistance to tamoxifen therapy. These findings imply that AIBI plays a fundamental role in the development of hormone-independent breast cancer through growth factor mediated pathways. Nonetheless the underlying mechanism of AIBI regulation of growth factor mediated mammary neoplasia is unknown. In this invesbgation I will utilize the MMTV-Neu mouse model (develop mammary gland tumors in 7-9 months) to elucidate the specific role of AIBI in growth factor-induced mammary tumorigenesis.
Language:
English
Title:
Characterizing Candidate Oncogenes at 8q21 in Breast Cancer
Document ID:
20090002035
Report #:
AD-A486667
Available Online:
http://hdl.handle.net/100.2/ADA486667
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kao, Jessica Y
Published:
20080301
Source:
Stanford Univ. (Stanford, CA United States)
Pages:
12
Contract #:
W81XWH-06-1-0424
Abstract:
Breast cancer carcinogenesis is caused by molecular genetic changes. These genetic changes ultimately affect the transcriptome. Copy number alterations of the genome is a cardinal feature of cancer and plays an important role in tumor progression by altering the gene expression program. These regions of alteration are associated with oncogenes and tumor suppressor genes of known and unknown identity. Characterization of both CNA's and gene expression profiles have been carried out on breast tumor specimens using microarray technology to gain further insight into the progression of this disease. We comprehensively characterized both DNA copy number changes and captured the gene expression profiles of 50 breast cancer cell lines, widely used model systems for the study of breast cancer. We found that the cell lines could be classified into three main subtypes, Luminal, Basal A, and Basal B by clustering of gene expression. Overall, this is similar to what is seen in the gene expression analysis of the tumors however, distinct differences were found. Analysis of the copy number profile revealed that the cell lines recapitulated the main genetic changes represented in the tumor data set but contained more changes. Finally, caution should be employed with choosing the appropriate cell line model system when studying specific processes in breast cancer.
Language:
English
Title:
Identification of Genes Regulating the Development of Breast Cancer
Document ID:
20090002038
Report #:
AD-A486671
Available Online:
http://hdl.handle.net/100.2/ADA486671
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wang, Hua
Published:
20080401
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
33
Contract #:
W81XWH-06-1-0413
Abstract:
We have identified four different modifiers of Apc(min) that affect mammary tumor number or mammary tumor latency (Mmom1-Mmom4). To further investigate the molecular mechanisms of mammary modifiers, Mmom1 and Mmmom2 congenic mice were produced and tested for the effect on mammary tumor number or mammary tumor latency. The effect of Mmom2 on mammary tumor latency was confirmed in the congenic mice and the region containing Mmom2 was narrowed into a 10cM region. We also show in this report that genetic background can determine the mammary tumor types in Apc(min) mice and we propose a model to explain how mammary modifiers could affect mammary tumor development.
Language:
English
Title:
Prairie View A&M/Baylor College of Medicine SMART Summer Undergraduate Prostate Cancer Research Project
Document ID:
20090002040
Report #:
AD-A486674
Available Online:
http://hdl.handle.net/100.2/ADA486674
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Weigel, Nancy L Slaughter, B G
Published:
20080401
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
7
Contract #:
W81XWH-06-1-0391
Abstract:
The goal of this project is to encourage undergraduates to enter careers in prostate cancer research. This project involves BCM faculty presentations at Prairie View A & M University and a 9 week summer prostate cancer research experience at BCM for up to 5 undergraduates/year from PVAMU (4 participated in 2007; 5 or 6 will be recruited for 2007.) Participants attended a weekly research discussion group focused on prostate cancer. Students make PowerPoint presentations on their work at the end of the program. The participants are co-registered in the SMART Program at Baylor College of Medicine (www.bcm.tmc.edu/smart) and have access to elements of the SMART Program including a interdisciplinary seminar series, career development activities and career counseling and the SMART GRE Prep Course. Four students participated in the 2007 program. One student showed that a CYP24 inhibitor potentiated vitamin D mediated growth inhibition, another examined combination treatments in prostate cancer cells, a third studies transition to myofibroblasts, and the fourth studied actions in dendritic cells. Student made multiple presentations. Participants reported significant gains in knowledge and skills.
Language:
English
Title:
Self Managing the Consequences of Major Limb Trauma
Document ID:
20090002042
Report #:
AD-A486676
Available Online:
http://hdl.handle.net/100.2/ADA486676
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
MacKenzie, Ellen J
Published:
20080301
Source:
Johns Hopkins Univ. (Baltimore, MD United States)
Pages:
15
Contract #:
W81XWH-06-1-0343
Abstract:
The objective of this research is to develop and evaluate the efficacy of a computer-based self management program (heretofore referred to as NextSteps Program) for reducing secondary conditions and improving function following major lower limb trauma. The intervention will build on widely accepted self-management programs developed for persons with arthritis as well as components of a face-to-face self-management program for civilians with long-standing limb loss. It will be necessary, however, to tailor the content and delivery of these programs to better accommodate the needs of a young, acutely injured population. Specific needs not typically addressed in the existing programs include the management of acute anxiety and post-traumatic stress disorder (PTSD), and the maintenance or acquisition of employment or return to active duty. If shown to be efficacious, computer based self management programs for the acutely injured will provide a much-needed adjunct to the orthopedic care now available and contribute to a comprehensive trauma management program to improve long-term outcomes and quality of life. The military version of SM program will provide injured soldiers with an ongoing mechanism of support as they transition from inpatient rehabilitation to the community -- whether that be in the military or civilian sectors.
Language:
English
Title:
Evolution in a Test Tube: Exploring the Structure and Function of RNA Probes
Document ID:
20090002044
Report #:
AD-A486679, USNA-TSPR-376
Available Online:
http://hdl.handle.net/100.2/ADA486679
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Vandenengel, Jeffrey E
Published:
20080502
Source:
Naval Academy (Annapolis, MD United States)
Pages:
48
Contract #:
None
Abstract:
This Trident project used the new in vitro selection strategy to explore the structure and function of one of the tobramycin beacon aptamers. The question addressed was the following: What are the sequence/structure constraints on a functional tobramycin beacon aptamer? The sequence of the RNA was partially randomized in order to produce a large number of variants related to the original aptamer. Then, the selection for functional molecules was repeated. The function and the sequences of the RNA molecules were monitored during the course of the selection process. The function of the RNA pools improved after each round of selection until, after nine rounds, the newly selected molecules functioned nearly as well as the original RNA molecules did. An additional five rounds of selection did not result in further improvement. RNAs present at various stages of selection were randomly chosen and sequenced. Many sequence variants remained at the end of the selection, suggesting that there are multiple solutions to the problem of constructing a tobramycin beacon aptamer. The sequence variants were analyzed for clues about structural requirements. Analysis of the sequences variants provided evidence that supports a hypothetical secondary structure. Evidence for additional interactions begins to outline the tertiary structure of the molecule. In addition to increasing our understanding of RNA structure/function relationships, the results of these experiments will aide in the design of future in vitro selection strategies.
Language:
English
Title:
Inhibition of the Protein Tyrosine Phosphatase, SHP-1, in Dendritic Cells to Enhance their Efficacy as Cell-Based Prostate Cancer Vaccines
Document ID:
20090002046
Report #:
AD-A486681
Available Online:
http://hdl.handle.net/100.2/ADA486681
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Levitt, Jonathan M
Published:
20080501
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
15
Contract #:
W81XWH-07-1-0025
Abstract:
Early preclinical and clinical trials suggest that dendritic cell (DC)-based tumor vaccines are both feasible and safe. However, to date clinical trials of DC-based vaccines have demonstrated only limited efficacy in causing tumor regression despite eliciting measurable systemic T cell responses against prostate cancer. In an effort to enhance the effectiveness of DC-based vaccines against prostate cancer, we have tested the hypothesis that the Src homology region 2 domain-containing phosphatase-1 (SHP-1), is a global inhibitor of DC activation and that by blocking SHP-1 in DC would induce stronger anti-tumor immunity. Our results demonstrate that inhibition of SHP-1 enhances DC activation, survival and migration in vitro. Further, using in vivo mouse models, we show that SHP-1 inhibition in DC enhances the generation of CD8+ effector T cells and skews the CD4+ T cell compartment to a Th1 phenotype while inhibiting the induction of T regulatory cells. These observations suggest that SHP-1 is a pleiotropic inhibitor of DC function and that its inhibition in DCs enhances the strength of immune responses. Finally, using 2 ectopic mouse tumor models (B16 melanoma and TRAMP prostate tumors), we show that SHP-1 inhibition in DC-based vaccines significantly inhibits tumor growth. The implication of these data in concert, is that SHP-1 signaling is a feasible protein to target in the design and implementation of DC-based vaccines against tumors and potentially against other infectious diseases.
Language:
English
Title:
Dietary Influences on Alpha-Methylacyl-CoA Racemase (AMACR) Expression in the Prostate
Document ID:
20090002048
Report #:
AD-A486683
Available Online:
http://hdl.handle.net/100.2/ADA486683
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ananthanarayanan, Vijayalakshmi
Published:
20080401
Source:
Illinois Univ. (Chicago, IL United States)
Pages:
57
Contract #:
W81XWH-06-1-0414
Abstract:
daAlpha Methyl Acyl CoA Racemase (AMACR) a peroxisomal and mitochondrial enzyme is up regulated in majority of prostate cancers (PCa). This enzyme is involved in the breakdown of phytanic & pristanic acids which are derived primarily through the ingestion of dairy and red meat products. There are no studies done so far that have examined the relationship of this enzyme with red meat and dairy intake and therefore PCa risk. The current research focuses on examining the relationships between AMACR expression in the prostate and phytanicipristanic acid levels in the blood and prostate. So far 19 patients with Pca have been recruited in the study. Research staff has been trained to obtain dietary information as well as process tissue and blood samples from participants. Protocols for processing biological samples have been established. Preliminary optimization of laboratory assays including assays for quantifying AMACR using automated image analysis tools have been developed.
Language:
English
Title:
The Impact of the 6:3 Polyunsaturated Fatty Acid Ratio on Intermediate Markers of Breast Cancer
Document ID:
20090002050
Report #:
AD-A486685
Available Online:
http://hdl.handle.net/100.2/ADA486685
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Hudson, Alana
Published:
20080501
Source:
Pittsburgh Univ. (Pittsburgh, PA United States)
Pages:
45
Contract #:
W81XWH-06-1-0532
Abstract:
Evidence suggests omega-6 (n-6) polyunsaturated fatty acids (PUFAs) promote breast cancer whereas omega-3 (n-3) PUFAs inhibit breast cancer growth. These fatty acids may influence breast cancer development by impacting prostaglandin E2 (PGE2) formation and consequently estradiol synthesis. We sought to establish the relationship between erythrocyte n-6 and n-3 PUFAs with serum estradiol and breast density, two hormonally-related breast cancer risk factors. We hypothesized the n-6 PUFA's and the 6:3 PUFA ratio are positively related and n-3 PUFAs negatively related to both risk factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) also inhibit PGE2 formation, therefore were further hypothesized that estradiollevels would be lower among NSAID users. Participants (n=260) were eligible for these analyses if they were cancer-free, postmenopausal and not taking exogenous hormones. Estradiol levels were significantly lower among current users of NSAIDs as compared to non-users of NSAIDs. Further, estradiol concentration decreased with increasing total n-3 PUFAs and rose with increasing total n-6 PUFAs and the 6:3 PUFA ratio; however, this was noted only among non-users of NSAIDs. No relationship was observed between any fatty acid measure and breast density. In summary, lowering n-6 intake, increasing n-3 intake, or taking a NSAID may result in reduced estradiol synthesis and potentially breast cancer risk.
Language:
English
Title:
Novel Methods for Imaging PET Biomarkers and Gene Therapy of Cancer
Document ID:
20090002051
Report #:
AD-A486686
Available Online:
http://hdl.handle.net/100.2/ADA486686
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Tigyi, Gabor
Published:
20080501
Source:
Tennessee Univ. (Memphis, TN United States)
Pages:
10
Contract #:
W81XWH-07-1-0248
Abstract:
Cancer mortality in the USA ranks Tennessee number 43 in incidence and 5th in the nation in mortality both numbers suggesting much work to be done. Altogether, there are over 660,000 citizens with active military or veteran status in our state constituting over 15% of the general population. Therefore, the poor cancer mortality statistics negatively affects not only the state's general population but also military and veteran families living in the state. A self-evaluation of the strengths and weaknesses of our state-wide University of Tennessee Cancer Institute programs revealed two major weaknesses impairing progress toward advancing translational research into the detection and treatment of cancer patients in Tennessee. Both are deficiencies in infrastructure: the first, is the lack of a core diagnostic and prognostic imaging facility and the second, is the lack of a core facility for investigational and therapeutic viral vector production and development. Congress agreed with our self analysis and recognized deficiencies in cancer research infrastructure in our state with its impact on the poor mortality ranking and earmarked funds to bolster our abilities to fight cancer through research into state-of-the-art cancer diagnostics and experimental therapies. In line with the congressional mandate, here we propose to set up two core facilities at the University of Tennessee Cancer Institute: one for the generation of PET biomarkers using microfluidic chemistry and validate their effectiveness for PET/CT-based monitoring of conventional and novel anticancer therapy in animal models and non-small cell lung cancer patients at UT Knoxville; the other a viral vector core for the generation of investigational tools for anticancer therapies at UT Health Science Center Memphis. These cores will work in highly coordinated interactive manner on three interlinked projects.
Language:
English
Title:
Role of Fetuin-A in Breast Tumor Cell Growth
Document ID:
20090002052
Report #:
AD-A486687
Available Online:
http://hdl.handle.net/100.2/ADA486687
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ochieng, Josiah
Published:
20080330
Source:
Meharry Medical Coll. (Nashville, TN United States)
Pages:
9
Contract #:
W81XWH-07-1-0254
Abstract:
In this report, we have described the breeding protocol we have followed aimed at knocking out the fetuin-A gene in PymT+ transgenic black C57 mice to define the role of fetuin-A in breast cancer carcinogenesis and progression. The central hypothesis of this project is that fetuin-A is a major serum derived growth factor for breast carcinoma cells and creates a favorable environment for the metastatic spread of tumor cells to the lungs. So far we have managed to get PymT+/Fet-/+ heterozygous animals that are significantly protected from breast cancer. We therefore hope that the absence of both alleles in PymT+/Fet-/- mice will result in almost total protection of the animals from developing full blown breast cancer. The results are very encouraging and we hope to complete the critical studies by the end of this year. The main problem we have had is the slow pace of the breeding protocol in that most of the PymT+/Fet+/+ mothers cannibalize their pups and so it takes many attempts before we can move animals to experimental groups.
Language:
English
Title:
Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC-1alpha
Document ID:
20090002137
Report #:
AD-A486720
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Puigserver, Pere
Published:
20080201
Source:
Dana Farber Cancer Inst. (Boston, MA United States)
Pages:
12
Contract #:
W81XWH-06-1-0214
Abstract:
The main purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by GCN5 and associated proteins, Pc3 and WDR18, is a key regulatory modification that controls hepatic glucose production. The major findings of this Research Technical Report are in tasks 1, 2 and 3. In task 1, we have further validated siRNAs for Pc3 and WDR18. In task 2, we have identified how WDR18 specifically interacts with GCN5 and does not interfere with the formation of the PGC-1alpha transcriptional protein complex. In Task 3, in order to identify what specific lysines are important for the PGC-1alpha function, we have also mapped the PGC-1beta lysines that are acetylated by GCN5. These experiments have pointed out to specific sites on PGC-1alpha that are also acetylated and might control hepatic glucose output. We will continue to complete the proposed tasks to understand how PGC-1alpha acetylation controls hepatic glucose production through the GCN5 complex.
Language:
English
Title:
The Characterization Of The Kinetics Of Chlamydia Muridarum Infection In Defined Regions Of The Murine Genital Tract
Document ID:
20090002159
Report #:
AD-A486759, CL09-0026
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Eskildsen, Ilea
Published:
20080801
Source:
Texas Univ. (San Antonio, TX United States)
Pages:
63
Contract #:
None
Abstract:
Infection with Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide, and leads to pathological sequelae including pelvic inflammatory disease and infertility. The continued increase in incidence rates of genital chlamydial infection over the last decade underscores a need for comprehensive understanding of the infection kinetics, host immune response, and disease pathogenesis. A mouse model of genital Chlamydia muridarum infection is generally employed in such studies, with most studies relying upon the enumeration of bacterial numbers from vaginal swab material to assess the kinetics of infection. Given the differences in tissue anatomy, hormonal regulation, and immune response among different genital regions, it is possible that kinetics of chlamydial infection as determined by vaginal swabbing may not accurately reflect the kinetics in other regions of the genital tract. In this study, we directly evaluated the kinetics of bacterial ascent into, and clearance from, defined regions of the reproductive tract using highly sensitive quantitative real-time PCR for the detection of Chlamydia genomes. The results of our study show that kinetics of chlamydial infection in different regions of the genital tract are comparable, with high numbers of organisms from day 3 through 18, and subsequent progressive reduction leading to complete clearance of infection around 30 days after challenge. The results also exhibit differences in the numbers of chlamydial organisms between different defined regions. Collectively, the results of this study provide in-depth insight into the kinetics of genital Chlamydia muridarum infection in defined regions of the murine female reproductive tract.
Language:
English
Title:
Regulation of Egr1 Target Genes by the Nurd Chromatin Remodeling Complex
Document ID:
20090002160
Report #:
AD-A486760
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Svaren, John
Published:
20080601
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
20
Contract #:
W81XWH-06-1-0167
Abstract:
Previous work had shown that the EGR1 transactivator is over expressed in prostate cancer, while expression of its corepressor, NAB2, is reduced. Based on our recent characterization of an interaction between NAB2 and the NuRD (Nucleosome remodeling and disruption) chromatin remodeling complex, we have determined if loss of NAB2 expression results in loss of NuRD targeting to EGR1 target genes. In progress thus far, we have shown that repression of some NAB-regulated target genes in prostate cancer cells requires the NuRD chromatin remodeling complex. We have developed novel chromatin immunoprecipitation assays for the NuRD complex in prostate cells to demonstrate the colocalization of the NuRD complex on EGR1-regulated endogenous target genes. In addition, we have shown that recruitment of the NuRD complex to EGR1 target genes is dependent on NAB2. Finally, NuRD-dependent repression of NAB-regulated repression is sensitive to histone deacetylase inhibitors. These results provide the first functional description of one of the major HDACcontaining chromatin remodeling complexes in prostate cancer cells, and elucidate molecular consequences of loss of NAB2 corepressor function in prostate carcinogenesis by analyzing the mechanism of NAB2 corepressor function.
Language:
English
Title:
Advances in Breast Cancer Therapy (IBRP)
Document ID:
20090002162
Report #:
AD-A486762
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Gallion, Holly
Published:
20080501
Source:
Precision Therapeutics, Inc. (Pittsburgh, PA United States)
Pages:
5
Contract #:
W81XWH-06-2-0021
Abstract:
Therapeutics, Inc. 1) wrote and gained approval for the data safety monitoring plan for this protocol; 2) identified and contracted a medical monitor for this protocol; 3) revised the protocol, informed consent and case report forms, and obtained approval by the USAMRMC ORP HRPO; 4) submitted the protocol and informed consent form to the Western IRB for approval; 5) is collaborating with Windber Research Institute in the preparation of the protocol for the gene chip analysis; 6) secured the vendor for the specimen kits; and negotiated a contract with vendor to provide the electronic data collection, management, and reporting system used for this protocol; and, 7) contracted a medical science liaison for the identification of qualified participating investigators and sites.
Language:
English
Title:
Phenotype and Function of Bone Marrow Infiltrating Lymphocytes in Chronic Myelogenous Leukemia
Document ID:
20090002163
Report #:
AD-A486763
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Pullarkat, Vinod
Published:
20080201
Source:
City of Hope Medical Center (Duarte, CA United States)
Pages:
31
Contract #:
W81XWH-06-1-0277
Abstract:
The aims of this project are to determine the phenotype and antileukemic activity of activated bone marrow infiltrating leukemia (MIL) and compare them to activated peripheral blood lymphocytes from patients with chronic myelogenous leukemia (CML) on imatinib or other tyrosine kinase inhibitor therapy. Bone marrow and peripheral blood specimens were obtained from CML patients who had at least a minor cytogenetic response. The phenotype of MILs and peripheral blood lymphocytes (PBL) was analyzed by flow cytometry. MILs and PBLs were expanded and activated with anti CD3/CD28 magnetic beads in culture for 10 days. Activated MILs and PBLs were characterized by flow cytometry and tested for antileukematic activity in a colony suppression assay by coculture with CD34+ bone marrow progenitors at varying CD3:CD34 ratios in methycullulose medium. Analysis of the phenotype of MILs from four patients showed that MILs are predominantly comprised of effector memory T cells. These MILs could be expanded effectively without change in phenotype. MILs as well as activated PBLs showed ability to suppress CML progenitor growth in vitro.
Language:
English
Title:
An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk
Document ID:
20090002164
Report #:
AD-A486764
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Reding, Kerryn W
Published:
20080401
Source:
Hutchinson (Fred) Cancer Research Center (Seattle, WA United States)
Pages:
8
Contract #:
W81XWH-06-1-0312
Abstract:
CHT use has been demonstrated to confer an increased risk of breast cancer. Genetic variation in hormonal pathways may modify the effect of CHT on breast cancer risk. Using 1237 cases and 1015 controls from two population-based case-control studies of breast cancer, we investigated the effect of genetic variation in 7 genes within the progesterone pathway using a tagSNP and functional SNP approach and 5 genes within the catechol estrogen pathway. Within single gene analyses we observed breast cancer risk to be modestly associated with one SNPs in each GSTP1 (rs1695: OR = 1.4 [95% CI: 1.02-1.9] for carriers of A allele); CYP1B1 (rs1056827: OR = 1.7 ]95% CI:1.2-2.5] for T homozygotes); SRD5A1 (rs248793: OR=1.2 [95% CI: 1.02-1.5] for G homozygotes) and PGR (rs492457: OR=1.5 [95% CI: 1.01-2.1] for carriers of the A allele). We found that the breast cancer risk associated with SNPs was particularly strong in long-term CHT users. In a multi-gene model including two genes with single gene effects within the estrogen pathway (CYP1B1*2 and GSTP1), breast cancer risk was 1.6 (95% CI: 1.03-2.4) times higher for carriers of 1 high risk genotype and 2.8 (95% CI: 1.5-5.3) times higher for women with 2 high risk genotypes compared to women with 0 high risk genotypes. The impact of high risk genotypes was stronger in long-term CHT users, particularly in long-term, current CHT users (OR=5.6 [95% CI: 1-5-20.6]). These results suggest that breast cancer risk among CHT users is modified by variation in genes within hormonal pathways.
Language:
English
Title:
Role of GGAP/PIKE-A in Prostate Cancer Progression
Document ID:
20090002167
Report #:
AD-A486770
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ittmann, Michael M
Published:
20080501
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
9
Contract #:
W81XWH-07-1-0023
Abstract:
The clinical behavior of prostate cancer is extremely heterogeneous ranging from indolent disease to aggressive metastatic cancer with rapid mortality. GGAP2 is a GTPase protein with a GTPase activating protein (GAP) domain at the C-terminus. It was reported that GGAP2 or PIKE-A can activate Akt and inhibit apoptosis. The goal of this proposal is characterize the role of GGAP2 in prostate cancer progression. Our results indicate that GGAP2 expression is increased in prostate cancer. In addition GGAP2 is mutated in human prostate cancer. The multiplicity of GGAP2 mutations imply that these mutations may emerge in an environment of the multifocal heterogeneity of prostate cancer tissues. According to our results these mutations can stimulate cancer cell proliferation and enhance GGAP2 activation indicating that they may contribute to increased activity of GGAP2 in prostate cancer. In summary GGAP2 may promote prostate cancer growth and progression via overexpression andlor mutation and as such is an important therapeutic target.
Language:
English
Title:
Comparative Kinetics and Distribution to Target Tissues of Organophosphates Using Physiologically - Based Pharmacokinetic Modeling
Document ID:
20090002221
Report #:
AD-A486878, AFIT/GEM/ENV/08-M20
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Vermillion, Rick E
Published:
20080301
Source:
Air Force Inst. of Tech. (Wright-Patterson AFB, OH United States)
Pages:
214
Contract #:
None
Abstract:
A physiologically-based pharmacokinetic model has been developed to examine the effects of organophosphates on the levels of acetylcholine in different tissues throughout the mammalian body. Many organophosphate-like chemical and kinetic characteristics are tested without reference to a specific chemical. Characteristics include partition coefficients, metabolic constants, the inhibition coefficient, the aging rate, and the regeneration rate. Two separate exposure scenarios are tested and compared against a baseline. The baseline consists of a direct inhalation exposure. The first exposure scenario examines the effects of bronchial scrubbing (via inhalation) and the second scenario is a study of dermal exposures and compares the levels of ACh in the different tissues with those in the inhalation (baseline) tests. Organophosphates that are absorbed directly into the bronchial tissue exhibit little variation on the levels of ACh buildup in any of the tissue groups tested when compared to the inhalation exposures. No matter what the scrubbing coefficient used, or the combination of the parameters (partition coefficients, inhibition coefficient, aging rate, and regeneration rate) values, the change in ACh was minimal. The results showed different behavior between inhalation and dermal exposures. The dermal results suggest that an individual may have additional time to don protective equipment before the levels of ACh are high enough to render the person incapable of doing so.
Language:
English
Title:
Automated Patient Positioning Guided by Cone-Beam CT for Prostate Radiotherapy
Document ID:
20090002269
Report #:
AD-A487020
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chao, Ming
Published:
20080101
Source:
Stanford Univ. (Stanford, CA United States)
Pages:
95
Contract #:
W81XWH-06-1-0235
Abstract:
Modern radiotherapy equipment is capable of delivering high precision conformal dose distributions to the target. However the target localization especially for soft-tissue target such as prostate is an issue because of its possible non-rigid internal motion relative to bony structures or external landmarks. Recently a new technology of kV cone-beam CT (CBCT) has been integrated onboard with the linear accelerator. The prostate target localization could be potentially done more accurately with the aid of the on-board CBCT imager. In this project the PI group developed a novel technique of automatic patient positioning for prostate cancer radiation therapy. A few important milestones have been achieved toward the goal of the project. These include: (i) Established a novel technique to enhance on-board cone-beam CT and to effectively reduce the radiation dose incurred in the scanning process; (ii) Developed a robust registration model with improved metric function; (iii) Developed an innovative narrow shell technique for better target localization and model the critical structure; (iv) Established the method for auto-propagation of contours from planning CT to CBCT based on feature based spline deformable registration. With more evaluations the automatic patient positioning technique and relevant research outcomes will soon be part of routine practice at Stanford University Hospital. The data and experiences we accumulated in this project are well documented and server as a good reference for effectively utilizing CBCT imager and will definitely enhance the outlook of the onboard CBCT in guiding radiation therapy as a whole.
Language:
English
Title:
Barriers to Breast Cancer Screening Among Latinas in the U.S.-Mexico Border Region
Document ID:
20090002271
Report #:
AD-A487024
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Pagan, Jose A
Published:
20080501
Source:
Texas-Pan American Univ. (Edinburg, TX United States)
Pages:
12
Contract #:
W81XWH-06-1-0334
Abstract:
The purpose of this project is to establish a research and training collaborative partnership between the Institute for Population Health Policy (IPHP) at the University of Texas-Pan American (UTPA) and the Leonard Davis Institute of Health Economics (LDI) at the University of Pennsylvania (Penn). Our objectives and scope are: to develop a competitive and successful breast cancer research program that focuses in cancer control and population sciences at UTPA; to develop and complete a research project on barriers to breast cancer screening among Latinas in the U.S.-Mexico border region; to develop the research infrastructure that will enable UTPA investigators to submit competitive breast cancer research proposals. The key accomplishments during the second year of the project are: the collection of most of the survey data on mammography screening practices; acceptance in a peer reviewed journal of a manuscript on health insurance coverage and mammography screening; and securing a federal grant to further develop health services research at UTPA in collaboration with Penn.
Language:
English
Title:
DNA Repair and Ethnic Differences in Prostate Cancer Risk
Document ID:
20090002274
Report #:
AD-A487027
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Goldman, Radoslav
Published:
20080301
Source:
Georgetown Univ. (Washington, DC United States)
Pages:
124
Contract #:
W81XWH-04-1-0294
Abstract:
Prostate cancer is the most common lethal tumor among US males and is particularly high in African Americans. This study evaluates DNA repair in a study of 240 prostate cancer patients and 240 healthy controls matched on age and race in a 50% African American population. Low DNA repair correlates with increased risk of certain cancers but prostate cancer was not yet examined. We hypothesize that low DNA repair especially in African American men contributes to increased risk of having prostate cancer. To evaluate this hypothesis we quantify DNA repair capacity in blood cells using comet assay and evaluate how this repair capacity is related to genetic variants in OGG1 and XRCC1 DNA repair genes. Genetic variants of OGG1 and XRCC1 with a decreased DNA repair capacity were previously identified. This means that a portion of the general population carrying the `at risk variant might be at higher risk of developing prostate cancer. This pilot study is expected to fill important gaps in our understanding of prostate cancer etiology produce new hypotheses which can be tested in an expanded prostate cancer study focus prostate cancer prevention in a new direction and help design better cancer prevention and treatment strategies.
Language:
English
Title:
Information Technology: DOD and VA Have Increased Their Sharing of Health Information, but Further Actions Are Needed
Document ID:
20090002275
Report #:
AD-A487028, GAO-08-1158T
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Melvin, Valerie C
Published:
20080924
Source:
General Accounting Office (Washington, DC United States)
Pages:
30
Contract #:
None
Abstract:
The National Defense Authorization Act for Fiscal Year 2008 required the Department of Defense (DOD) and the Department of Veterans Affairs (VA) to accelerate the exchange of health information between the departments and to develop systems or capabilities that allow for full interoperability (generally, the ability of systems to use data that are exchanged) and that are compliant with federal standards. The act also established an interagency program office to function as a single point of accountability for the effort and whose role is to implement such systems or capabilities by September 30, 2009. Further, the act required that GAO semi-annually report on the progress made in achieving these goals; its first report was issued in July 2008. In that report, GAO described the departments' progress in sharing electronic health information, developing electronic health records that comply with federal standards, and establishing the interagency program office. In this testimony, GAO discusses its July 2008 report and updated information obtained from the departments. In the report covered by this testimony, GAO made recommendations that the departments give priority to fully establishing the interagency program office and finalizing the implementation plan. DOD and VA concurred with GAO's recommendations.
Language:
English
Notes:
Testimony before the Senate Committee on Veterans' Affairs
Title:
Endogenous 6-Hydroxymelatonin Excretion and Subsequent Risk of Breast Cancer: A Prospective Study
Document ID:
20090002276
Report #:
AD-A487029
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Muti, Paola C
Published:
20080301
Source:
Italian National Cancer Inst. (Rome, Italy)
Pages:
45
Contract #:
W81XWH-04-1-0195
Abstract:
The prevalence of breast cancer is greatest in industrialized regions and exposure to light at night has been proposed as a potential risk factor. Modulation of melatonin secretion by light has been implicated in the causal pathway linking exposure to light and breast cancer risk. Recent evidence indicates that melatonin is a natural oncostatic agent capable of functioning through a variety of anti-proliferative, anti-oxidative, and immunostimulatory mechanisms. We conducted a study to investigate the association of prediagnostic melatonin production and subsequent breast cancer risk in a prospective cohort study, the Italian ORDET study. Thus, prediagnostic melatonin production was measured as urine levels of the 6-hydroxymelatonin sulphate (6-OHMS), its primary enzymatic metabolite, in 12-hour urine (overnight) collection. The study was conducted as a nested case-control study. We included XXX breast cancer cases among cohort members during the 17 year-follow-up period. Four controls were matched to each case on age, menopausal status, recruitment center and time of recruitment.
Language:
English
Title:
Vaccination of High-Risk Breast Cancer Patients with Carbohydrate Mimicking Peptides
Document ID:
20090002278
Report #:
AD-A487032
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kieber-Emmons, Thomas
Published:
20080501
Source:
Arkansas Univ. for Medical Sciences (Little Rock, AR United States)
Pages:
111
Contract #:
W81XWH-06-1-0542
Abstract:
The expression of the Tumor Associated Carbohydrate Antigens such as the neolactoseries antigen Lewis Y (LeY) and gangliosides such as GM2 and GD2/GD3 are amplified on breast cancer cells and is linked to poor prognosis and high risk of disease relapse. Immunotherapy to direct responses to TACA is, therefore, perceived to be of clinical benefit. To overcome this deficiency, we developed mimotopes of TACA to induce more robust cross-reactive and tumor-specific responses. In preclinical studies, immunization with these mimotopes reduce tumor burden and inhibited metastatic outgrowth of murine tumor cells expressing TACA structural homologues. Thus, peptide mimotopes of TACA represent a new and very promising tool to induce a strong immune response to TACA expressed on Breast Cancer cells. Based on encouraging preclinical results, our objectives are for the current funding period (years 1 and 2) are to develop the necessary preclinical data required by the Food and Drug Administration (FDA) for filing an Investigational New Drug (IND). In this context we: 1.) Developed the necessary procedures for the required Good Laboratory Practice (GLP) studies; 2.) Defined problems in scale up of the manufactured mimotope vaccines; 3.) Identified alternative mimotopes of TACA that circumvent the scale up problems.
Language:
English
Title:
Seladin-1: A Novel Tumor Suppressor Gene Involved in Breast Cancer?
Document ID:
20090002281
Report #:
AD-A487040
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Galaktionov, Konstantin I
Published:
20080801
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
10
Contract #:
W81XWH-06-1-0650
Abstract:
Seladin-1 maps to the human chromosome region 1p31-1p32 that shows frequent loss of heterozygosity (LOH) in human breast tumors. Publicly available data (Entrez, GEO) also show a significant variability between levels of Seladin-1 expression in breast cancer cell lines and normal breast epithelium. Is Seladin-1 a tumor suppressor on 1p31 -1p32 that is involved in breast cancer? Our concept is that it is. In order to determine if Seladin-1 is a TSG involved in breast cancer we propose to: 1) Identify possible Seladin-1 mutations in primary breast tumors. 2) Investigate the alterations of Seladin-1 expression in breast cancer cells. 3) Perform functional assays on tumor-specific Seladin-1 mutants. Accordingly we amplified Seladin-1 exons from from 60 breast tumor genomic DNA samples (obtained from tissue banks or commercial sources) followed by the sequence analysis of the open reading frames. As a result no missense or nonsense mutations were detected. We found that expression of Seladin-1 significantly varies between different breast cancer cell lines and in one such line MDA-MB-231 is significantly below expression in normal breast epithelium.
Language:
English
Title:
Military Disability System: Increased Supports for Servicemembers and Better Pilot Planning Could Improve the Disability Evaluation Process
Document ID:
20090002292
Report #:
AD-A487068, GAO-08-1137
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Bertoni, Daniel Grgich, Michele Green, Joel Rogowski, Bryan Steel-Lowney, Barbara Whitney, Greg Vance, Walter Gilbert, Cindy Anderson, Bonnie Beale, Rebecca
Published:
20080901
Source:
General Accounting Office (Washington, DC United States)
Pages:
55
Contract #:
None
Abstract:
The Army has taken a number of steps to help service members navigate the disability evaluation process through additional supports and streamlining efforts, but it faces challenges in meeting internal goals and demonstrating impact. Most significantly, the Army has expanded support to service members by hiring more staff, such as board liaisons to help service members navigate the process and legal personnel to counsel them during the process. Furthermore, the Army established internal staff-to service member goals for board liaisons as well as for board physicians who are responsible for documenting service members conditions. However, the Army has not met its internal staffing goals for board liaisons and physicians, and it continues to face shortages in legal personnel. The Army has also struggled to meet timeliness goals for case processing and has even experienced negative trends over the last year, despite streamlining initiatives such as reducing forms, increasing automation in the process, and deploying a unit of mobile medical staff to help address caseload surges at certain locations. According to Army officials and data, longer case processing times have resulted, in part, from increases in the number and complexity of disability cases, as exemplified by the growing incidence of conditions that require psychiatric evaluation.
Language:
English
Title:
Phase II Study of a HER-2/neu (HER2) Intracellular Domain (ICD) Peptide-Based Vaccine Administered to Stage IIIB and IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab Monotherapy
Document ID:
20090002293
Report #:
AD-A487069
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Disis, Mary L
Published:
20080501
Source:
Washington Univ. (Seattle, WA United States)
Pages:
16
Contract #:
W81XWH-04-1-0561
Abstract:
The primary purpose of this grant is to determine the overall survival (OS) benefit in Stage IIIB and IV HER2 positive breast cancer patients vaccinated with a HER2 intracellular domain (ICD) peptide-based vaccine while receiving maintenance trastuzumab. Patients enrolled will be HER2 overexpressing stage IIIB and IV breast cancer patients who have been treated to a clinical complete response remission or have stable bone only disease and are within 6 months of starting maintenance trastuzumab. The scope of the work includes a Phase II, nonrandomized, single arm study of a HER2 ICD peptide-based vaccine given concurrently with trastuzumab. Ten subjects have been enrolled during the last reporting period. All adverse events reported for these ten subjects are grades 1 and 2. There have been no major findings to date.
Language:
English
Title:
Crosstalk between Leptin Receptor and Igf-Ir in Breast Cancer: A Potential Mediator of Chemoresistance
Document ID:
20090002297
Report #:
AD-A487078
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nahta, Rita
Published:
20080401
Source:
Emory Univ. (Atlanta, GA United States)
Pages:
19
Contract #:
W81XWH-06-1-0452
Abstract:
Obesity is a major risk factor for breast cancer, and is associated with reduced treatment response and reduced overall survival. The obesity-associated hormones IGF-I and leptin and their receptors, IGF-IR and leptin receptor (Ob-R), are elevated in breast cancer. Co-immunoprecipitation and immunoblotting demonstrated that IGF-IR and Ob-R interact in the breast cancer cell lines MDA-MB-231, MCF7, BT474, and SKBR3. Stimulation of cells with IGF-I promoted Ob-R phosphorylation, which was blocked by IGF-IR kinase inhibition. In addition, IGF-I activated downstream signaling molecules in the leptin receptor and IGF-IR pathways. In contrast to IGF-I, leptin did not induce phosphorylation of IGF-IR, indicating that receptor cross signaling is unidirectional, occurring from IGF-IR to Ob-R. Our results demonstrate for the first time a novel interaction and cross talk between the IGF-I and leptin receptors in human breast cancer cells. Our ongoing studies will examine this cross talk in more detail by determining the biological and molecular effects of inhibition of these growth factor receptors. We will then examine the influence of this cross talk on response to taxane-based chemotherapy.
Language:
English
Title:
Identifying ECM Mediators of Tumor Cell Dormancy
Document ID:
20090002298
Report #:
AD-A487080
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schedin, Pepper
Published:
20080501
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
16
Contract #:
W81XWH-06-1-0510
Abstract:
Characterize the compositional and functional changes in mammary stroma that result from tamoxifen treatment. Approach and Results: 75 mature female Sprague Dawley rats were randomized into three groups of 25 each; Gp1 nulliparous control, and Gp 2 tamoxifen treated (0.5 mg/tamoxifen per kg body weight, s.c. injection for 30 days)and Gp 3 tamoxifen treated (1.0 mg tamoxifen dose). ECM was harvested from the mammary glands of Gps 1 & 3 for biochemical and functional characterizations. The ECM preparations have been subjected to LCMS and MALDI-TOF mass spec. Due to technical difficulties we have also developed two in vitro models to investigate the effects of tamoxifen on mammary stroma. ECM deposited by primary mammary fibroblasts isolated from control and tamoxifen treated rats, or primary control fibroblasts treated with tamoxifen in culture has been utilized for ECM proteomics method development. Optimized conditions demonstrate fibronectin (FN) is downregulated by tamoxifen, in vitro and in vivo; observations consistent with data demonstrating that FN is upregulated during with MEC proliferation and downregulated at times of MEC loss; suggesting that loss of FN may be integral to a tumor suppressive microenvironment.
Language:
English
Title:
Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance
Document ID:
20090002300
Report #:
AD-A487082
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Siclari, Valerie A
Published:
20080501
Source:
Virginia Univ. (Charlottesville, VA United States)
Pages:
38
Contract #:
W81XWH-06-1-0512
Abstract:
The majority of patients with advanced breast cancer develop bone metastases, which are incurable. Recently, tumor-secreted factors have shown promise as targets for the treatment of bone metastasis. Adrenomedullin (AM) is a breast cancer-secreted peptide that is pro-proliferative, anti-apoptotic, pro-angiogenic, and stimulates new bone formation. AM overexpression increases bone metastases while AM knockdown decreases bone metastases in mouse models of prostate and lung cancer respectively. The objective of this project is to validate AM as an important target for the treatment of breast cancer bone metastasis. I hypothesize that AM expression increases bone metastases and resistance to chemotherapy. Specific Aims: (1) To determine if AM expression by breast cancer cells increases bone lesion formation in bone metastasis mouse models. (2) To determine the role of AM in breast cancer cells. Key Research Accomplishments: (1) MDA-MB-231 clones that overexpress AM were produced. (2) Stable AM shRNA knockdown MDA-MB-231 breast cancer cell clones were produced. (3) Decreasing AM in breast cancer cells increased bone lesion formation but decreased mammary fat pad tumor-take and growth in mice. Relevance: Currently no treatments improve overall survival for breast cancer bone metastasis patients. Inhibitors of certain tumor-secreted factors have decreased bone metastases in mice. My results indicate that inhibitors of the tumor-secreted factor AM would not be a good treatment for breast cancer bone metastases.
Language:
English
Title:
Scavenger Receptors and Resistance to Inhaled Allergens
Document ID:
20090002403
Report #:
AD-A486143
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kobzik, Lester
Published:
20080201
Source:
Harvard School of Public Health (Boston, MA United States)
Pages:
6
Contract #:
W81XWH-06-1-0289
Abstract:
After OVA sensitization and aerosol challenge, SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyperresponsiveness compared to wild-type mice. A role for simple SRA-mediated antigen clearance ('scavenging') by lung macrophages was excluded by observation of comparable uptake of fluorescent OVA by wild-type and SRA-deficient lung Mgammas and DCs. In contrast, airway instillation of fluorescent antigen revealed significantly higher traffic of labelled DCs to thoracic lymph nodes in SRA-deficient mice than in controls. The increased migration of SRA-deficient DCs was accompanied by enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SRAs expressed on lung DCs in down-regulation of specific immune responses to aero-allergens by reduction of DC migration from the site of antigen uptake to the draining lymph nodes.
Language:
English
Title:
Polymer Coats Leads on Implantable Medical Device
Document ID:
20090002469
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002469
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 52-53
Published:
20080901
Source:
Medtronic, Inc. (Minneapolis, MN, United States)
Pages:
1
Contract #:
None
Abstract:
Langley Research Center s Soluble Imide (LaRC-SI) was discovered by accident. While researching resins and adhesives for advanced composites for high-speed aircraft, Robert Bryant, a Langley engineer, noticed that one of the polymers he was working with did not behave as predicted. After putting the compound through a two-stage controlled chemical reaction, expecting it to precipitate as a powder after the second stage, he was surprised to see that the compound remained soluble. This novel characteristic ended up making this polymer a very significant finding, eventually leading Bryant and his team to win several NASA technology awards, and an "R&D 100" award. The unique feature of this compound is the way that it lends itself to easy processing. Most polyimides (members of a group of remarkably strong and incredibly heat- and chemical-resistant polymers) require complex curing cycles before they are usable. LaRC-SI remains soluble in its final form, so no further chemical processing is required to produce final materials, like thin films and varnishes. Since producing LaRC-SI does not require complex manufacturing techniques, it has been processed into useful forms for a variety of applications, including mechanical parts, magnetic components, ceramics, adhesives, composites, flexible circuits, multilayer printed circuits, and coatings on fiber optics, wires, and metals. Bryant s team was, at the time, heavily involved with the aircraft polymer project and could not afford to further develop the polymer resin. Believing it was worth further exploration, though, he developed a plan for funding development and submitted it to Langley s chief scientist, who endorsed the experimentation. Bryant then left the high-speed civil transport project to develop LaRC-SI. The result is an extremely tough, lightweight thermoplastic that is not only solvent-resistant, but also has the ability to withstand temperature ranges from cryogenic levels to above 200 C. The thermoplastic s unique characteristics lend it to many commercial applications; uses that Bryant believed would ultimately benefit industry and the Nation. "LaRC-SI," he explains, "is a product created in a government laboratory, funded with money from the tax-paying public. What we discovered helps further the economic competitiveness of the United States, and it was our goal to initiate the technology transfer process to ensure that our work benefited the widest range of people." Several NASA centers, including Langley, have explored methods for using LaRC-SI in a number of applications from radiation shielding and as an adhesive to uses involving replacement of conventional rigid circuit boards. In the commercial realm, LaRC-SI can now be found in several commercial products, including the thin-layer composite unimorph ferroelectric driver and sensor (THUNDER) piezoelectric actuator, another "R&D 100" award winner (Spinoff 2005).
Language:
English
Title:
Robotics Offer Newfound Surgical Capabilities
Document ID:
20090002475
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002475
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 46-47
Published:
20080901
Source:
Barrett Technology, Inc. (Cambridge, MA, United States)
Pages:
2
Contract #:
None
Abstract:
Barrett Technology Inc., of Cambridge, Massachusetts, completed three Phase II Small Business Innovation Research (SBIR) contracts with Johnson Space Center, during which the company developed and commercialized three core technologies: a robotic arm, a hand that functions atop the arm, and a motor driver to operate the robotics. Among many industry uses, recently, an adaptation of the arm has been cleared by the U.S. Food and Drug Administration (FDA) for use in a minimally invasive knee surgery procedure, where its precision control makes it ideal for inserting a very small implant.
Language:
English
Title:
Photorefraction Screens Millions for Vision Disorders
Document ID:
20090002481
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002481
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 58-59
Published:
20080901
Source:
Vision Research Corp. (Birmingham, AL, United States)
Pages:
2
Contract #:
None
Abstract:
Who would have thought that stargazing in the 1980s would lead to hundreds of thousands of schoolchildren seeing more clearly today? Collaborating with research ophthalmologists and optometrists, Marshall Space Flight Center scientists Joe Kerr and the late John Richardson adapted optics technology for eye screening methods using a process called photorefraction. Photorefraction consists of delivering a light beam into the eyes where it bends in the ocular media, hits the retina, and then reflects as an image back to a camera. A series of refinements and formal clinical studies followed their highly successful initial tests in the 1980s. Evaluating over 5,000 subjects in field tests, Kerr and Richardson used a camera system prototype with a specifically angled telephoto lens and flash to photograph a subject s eye. They then analyzed the image, the cornea and pupil in particular, for irregular reflective patterns. Early tests of the system with 1,657 Alabama children revealed that, while only 111 failed the traditional chart test, Kerr and Richardson s screening system found 507 abnormalities.
Language:
English
Title:
Robotic Joints Support Horses and Humans
Document ID:
20090002485
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002485
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 56-57
Published:
20080901
Source:
Walter Reed Army Medical Center (Washington, DC, United States)
Pages:
2
Contract #:
None
Abstract:
A rehabilitative device first featured in Spinoff 2003 is not only helping human patients regain the ability to walk, but is now helping our four-legged friends as well. The late James Kerley, a prominent Goddard Space Flight Center researcher, developed cable-compliant mechanisms in the 1980s to enable sounding rocket assemblies and robots to grip or join objects. In cable-compliant joints (CCJs), short segments of cable connect structural elements, allowing for six directions of movement, twisting, alignment, and energy damping. Kerley later worked with Goddard s Wayne Eklund and Allen Crane to incorporate the cable-compliant mechanisms into a walker for human patients to support the pelvis and imitate hip joint movement.
Language:
English
Title:
Periodontal Probe Improves Exams, Alleviates Pain
Document ID:
20090002486
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002486
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 60-61
Published:
20080901
Source:
Visual Programs, Inc. (Richmond, VA, United States)
Pages:
2
Contract #:
None
Abstract:
Dentists, comedian Bill Cosby memorably mused, tell you not to pick your teeth with any sharp metal object. Then you sit in their chair, and the first thing they grab is an iron hook!" Conventional periodontal probing is indeed invasive, uncomfortable for the patient, and the results can vary greatly between dentists and even for repeated measurements by the same dentist. It is a necessary procedure, though, as periodontal disease is the most common dental disease, involving the loss of teeth by the gradual destruction of ligaments that hold teeth in their sockets in the jawbone. The disease usually results from an increased concentration of bacteria in the pocket, or sulcus, between the gums and teeth. These bacteria produce acids and other byproducts, which enlarge the sulcus by eroding the gums and the periodontal ligaments. The sulcus normally has a depth of 1 to 2 millimeters, but in patients with early stages of periodontal disease, it has a depth of 3 to 5 millimeters. By measuring the depth of the sulcus, periodontists can have a good assessment of the disease s progress. Presently, there are no reliable clinical indicators of periodontal disease activity, and the best available diagnostic aid, periodontal probing, can only measure what has already been lost. A method for detecting small increments of periodontal ligament breakdown would permit earlier diagnosis and intervention with less costly and time-consuming therapy, while overcoming the problems associated with conventional probing. The painful, conventional method for probing may be destined for the archives of dental history, thanks to the development of ultrasound probing technologies. The roots of ultrasound probes are in an ultrasound-based time-of-flight technique routinely used to measure material thickness and length in the Nondestructive Evaluation Sciences Laboratory at Langley Research Center. The primary applications of that technology have been for corrosion detection and bolt tension measurements (Spinoff 2005). This ultrasound measurement system was adapted to the Periodontal Structures Mapping System, invented at Langley by John A. Companion, under the supervision of Dr. Joseph S. Heyman. Support of the research and development that led to this invention was provided by NASA s Technology Applications Engineering Program and by the Naval Institute for Dental and Biomedical Research, in Great Lakes, Illinois.
Language:
English
Title:
LED Device Illuminates New Path to Healing
Document ID:
20090002502
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002502
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 50-51
Published:
20080901
Source:
Quantum Devices, Inc. (Barneveld, WI, United States)
Pages:
1
Contract #:
None
Abstract:
Among NASA s research goals is increased understanding of factors affecting plant growth, including the effects of microgravity. Impeding such studies, traditional light sources used to grow plants on Earth are difficult to adapt to space flight, as they require considerable amounts of power and produce relatively large amounts of heat. As such, an optimized experimental system requires much less energy and reduces temperature variance without negatively affecting plant growth results. Ronald W. Ignatius, founder and chairman of the board at Quantum Devices Inc. (QDI), of Barneveld, Wisconsin, proposed using light-emitting diodes (LEDs) as the photon source for plant growth experiments in space. This proposition was made at a meeting held by the Wisconsin Center for Space Automation and Robotics, a NASA-sponsored research center that facilitates the commercialization of robotics, automation, and other advanced technologies. The Wisconsin group teamed with QDI to determine whether an LED system could provide the necessary wavelengths and intensities for photosynthesis, and the resultant system proved successful. The center then produced the Astroculture3, a plant growth chamber that successfully incorporated this LED light source, which has now flown on several space shuttle missions. NASA subsequently identified another need that could be addressed with the use of LEDs: astronaut health. A central concern in astronaut health is maintaining healthy growth of cells, including preventing bone and muscle loss and boosting the body s ability to heal wounds all adversely affected by prolonged weightlessness. Thus, having determined that LEDs can be used to grow plants in space, NASA decided to investigate whether LEDs might be used for photobiomodulation therapy (PBMT).
Language:
English
Title:
Experiments Advance Gardening at Home and in Space
Document ID:
20090002504
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002504
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 94-95
Published:
20080901
Source:
BioServe Space Technologies (United States) Agrihouse Inc (Berthoud, CO, United States)
Pages:
2
Contract #:
None
Abstract:
Aeroponics, the process of growing plants suspended in air without soil or media, provides clean, efficient, and rapid food production. Crops can be planted and harvested year-round without interruption, and without contamination from soil, pesticides, and residue. Aeroponic systems also reduce water usage by 98 percent, fertilizer usage by 60 percent, and eliminate pesticide usage altogether. Plants grown in aeroponic systems have been shown to absorb more minerals and vitamins, making the plants healthier and potentially more nutritious. The suspended system also has other advantages. Since the growing environment can be kept clean and sterile, the chances of spreading plant diseases and infections commonly found in soil and other growing media are greatly reduced. Also, seedlings do not stretch or wilt while their roots are forming, and once the roots are developed, the plants can be easily moved into any type of growing media without the risk of transplant shock. Lastly, plants tend to grow faster in a regulated aeroponic environment, and the subsequent ease of transplant to a natural medium means a higher annual crop yield. For example, tomatoes are traditionally started in pots and transplanted to the ground at least 28 days later; growers using an aeroponic system can transplant them just 10 days after starting the plants in the growing chamber. This accelerated cycle produces six tomato crops per year, rather than the traditional one to two crop cycles. These benefits, along with the great reduction in weight by eliminating soil and much of the water required for plant growth, illustrate why this technique has found such enthusiastic support from NASA. Successful long-term missions into deep space will require crews to grow some of their own food during flight. Aeroponic crops are also a potential source of fresh oxygen and clean drinking water, and every ounce of food produced and water conserved aboard a spacecraft reduces payload weight, decreasing launch costs and freeing room for other cargo.
Language:
English
Title:
Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)
Document ID:
20090002615
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Boyd, Jason L. (Universities Space Research Association) Du, Brian (Wyle Labs., Inc.) Daniels, Vernie (Wyle Labs., Inc.) Simmons, Rita (Naval Aerospace Medical Inst.) Buckey, Jay (Dartmouth-Hitchcock Medical Center) Putcha, Lakshmi (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on duty.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Three Papers in International Health Policy: Modeling the Links between Economics and Epidemiology
Document ID:
20090003253
Report #:
AD-A487787
Available Online:
http://hdl.handle.net/100.2/ADA487787
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dutta, Arindam
Published:
20080401
Source:
RAND Corp. (Santa Monica, CA United States)
Pages:
188
Contract #:
None
Abstract:
Paper I establishes the benefits of linking epidemiological modeling with international health resource allocation decisions, reviewing the recent modeling literature on pandemic influenza control. The review indicates that outbreaks in resource poor settings are controllable with moderate resource intensity and complexity of effort for viral strains of moderate infectiousness. However, very high resource allocations for preparedness in industrialized nations -- at low geographic risk for the pandemic -- are predicated on containment failure in countries at higher risk of outbreaks. Without assuming the infectiousness of a future flu virus, a redistribution of resources to the developing countries at primary risk reduces overall systemic risk of containment failure. The payoffs in terms of reduced global mortality and morbidity are higher with increased infectiousness. The two other papers are associated with implementing the experimental desktop models for the context of India. Paper II first constructs a scenario based a nonepidemiological model of pandemic influenza introduction to, and subsequent spread within, India under various assumptions. The model uses published data on attack rates in Asia during previous pandemics as well as seasonal influenza. The model exploits geographical risk variations across provinces of India as well as the provinces' demographics, transport networks, and rural urban settings. Paper III reestimates the estimates of people living with HIV/AIDS (PLWHA) in India by combining the available prevalence data from the latest sero-surveillance data as well as the National Family Health Survey (NFHS-3) of 2005-2006. The paper continues to comprehensively analyze antiretroviral (ARV) policy in India, beginning with the estimation of total costs of utilization under public and private market rates for first line ART. A cohort simulation is conducted using a desktop model of disease progress in the population without access to ARVs.
Language:
English
Title:
Structural Characterization and Determinants of Specificity of Single-Chain Antibody Inhibitors of Membrane-Type Serine Protease 1
Document ID:
20090003279
Report #:
AD-A487918
Available Online:
http://hdl.handle.net/100.2/ADA487918
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Farady, Christopher J
Published:
20080301
Source:
California Univ. (San Francisco, CA United States)
Pages:
35
Contract #:
W81XWH-05-1-0300
Abstract:
Membrane-type serine protease 1 (MT-SP1) is a cancer-associated serine protease implicated in the tumorogenesis and metastasis of breast cancer. Inhibition of MT-SP1 activity has been shown to decrease metastatic potential. We have developed a number of potent and specific single-chain (scFv) antibody inhibitors to MT-SP1, and have begun to characterize their mechanism of inhibition. Through kinetic characterization and site-directed mutagenesis experiments, it has been determined that three potent inhibitors have separate and novel mechanisms of inhibition which do not mimic either biologically or pharmaceutically relevant protease inhibitors. These novel modes of binding and inhibition are the basis for their specificity, and suggest these inhibitors will have less cross-reactivity and toxicity problems when used in vivo to further dissect the role of MT-SP1 in breast cancer.
Language:
English
Title:
Mesenchymal Stem Cell as Targeted-Delivery Vehicle in Breast Cancer
Document ID:
20090003305
Report #:
AD-A487984
Available Online:
http://hdl.handle.net/100.2/ADA487984
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chen, Xiaoyuan
Published:
20080601
Source:
Stanford Univ. (Stanford, CA United States)
Pages:
17
Contract #:
W81XWH-07-1-0374
Abstract:
Mesenchymal stem cells (MSCs) have been proposed to be cellular vehicles for the targeted delivery and local production of biological agents in tumors. In this proposal we will stably transfect mesenchymal stem cells with a lentiviral vector containing a therapeutic gene and dual reporter gene mrfp-ttk. Specific Aims: 1) We will monitor breast cancer tropism of mesenchymal stem cells by multimodality imaging techniques; 2) We will demonstrate the ability of mesenchymal stem cells to target delivery of gene therapeutics to breast cancer in vitro; 3) We will determine the effect of mesenchymal stem cell to target delivery of gene therapeutics to breast cancer lung metastasis. Major findings from year 1 studies: 1) MSCs home to both subcutaneous breast cancer and its lung metastasis; 2) MSCs home to both premature and well-established breast cancer lung metastasis; 3) MSCs proliferate at tumor site; 4) MSCs show dissimilar differentiation potential at lung tumor and subcutaneous tumor niches; 5) lung tumor microenvironment upregulates BMP-2 and Noggin transcription, which favor MSCs osteoblastogenic differentiation.
Language:
English
Title:
Quantitative in Situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-in-Pentetreotide. Addendum
Document ID:
20090003306
Report #:
AD-A487987
Available Online:
http://hdl.handle.net/100.2/ADA487987
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chung, Gina G Rimm, David
Published:
20080501
Source:
Yale Univ. (New Haven, CT United States)
Pages:
41
Contract #:
W81XWH-04-1-0277
Abstract:
Somatostatin (SST) is a peptide hormone implicated in the growth and progression of cancers and SSTR2 is the predominant receptor subtype expressed in breast cancer. We hope to study the pattern of expression and clinical significance of SSTR2 levels in breast cancer. We have developed an algorithm called AQUA that can assess protein expression on tissue microarrays (TMA) based on molecular co-localization techniques. Our results show that SSTR2 is localized predominantly to the malignant cells although also in vessel/lymphatic elements. Although expression was not significantly correlated with survival on our TMA it did appear to be overexpressed compared with benign breast tissue. A vessel compartment has been developed using a multiplexing protocol for co-localization of SSTR2 to tumor and endothelium concurrently. Cell line controls have also been developed to generate a reference standard curve and to use as a normalization feature. Whole sections analysis with SSTR2 also show that while heterogeneity of expression is present it is modest.
Language:
English
Title:
Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk
Document ID:
20090003312
Report #:
AD-A488001
Available Online:
http://hdl.handle.net/100.2/ADA488001
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Hartmann, Lynn C
Published:
20080601
Source:
Mayo Clinic (Rochester, MN United States)
Pages:
17
Contract #:
DAMD17-02-1-0473
Abstract:
Optimal early detection and prevention strategies for breast cancer are predicated on our ability to identify individuals at significantly increased risk for this disease. The purpose of this Center is to bring molecular risk prediction for breast cancer into the clinical area. This will require progress on three fronts of scientific endeavor:(i) Establishment of a tissue repository of benign breast disease; (ii) Assessment of potential biomarkers of risk in this tissue set and (iii) Discovery of new, potentially relevant biomarkers of risk. We have made significant progress on these aims. Our cohort is comprised of 9,376 women, 758 (8%) of whom have been diagnosed with breast cancer since the time of their benign biopsy. We established our tissue repository of benign breast tissue and have collected the subsequent breast cancer tissue. We assessed the significance of benign histology in predicting risk of future breast cancer, examining in detail the role of proliferative disease, atypia, papillomas, radial scars and involution. We explored the link between centrosome amplification, COX-2 expression and breast cancer outcomes and are currently exploring the significance of p16, ER and Ki67. We are working with Wayne State to characterize the histopathology in a cohort of African American women. Our focus in 2008-2009 will be on the Wayne State cohort.
Language:
English
Title:
The Hygiene Hypothesis and Breast Cancer: A Novel Application of an Etiologic Theory for Allergies, Asthma, and Other Immune Disorders
Document ID:
20090003313
Report #:
AD-A488003
Available Online:
http://hdl.handle.net/100.2/ADA488003
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Clarke, Christina A
Published:
20080501
Source:
Northern California Cancer Center (Fremont, CA United States)
Pages:
12
Contract #:
W81XWH-05-1-0283
Abstract:
The hygiene hypothesis , the idea that reduced exposure to important microbes, especially in childhood, impacts development of asthma and allergies, may have application to breast cancer. This research project aims to explore the hygiene hypothesis as it might relate to breast cancer development, thereby assessing its utility for more comprehensive future research. This research project aimed to interview a population-based series of Californian women recently diagnosed with breast cancer and a matched set of healthy control women as regards age-specific experiences relevant to microbial exposures. This project is currently at the end of Year 3, with an approved one-year no-cost extension. To date, we have interviewed over 350 study subjects and carried new control ascertainment procedures using mailing list sampling methods. Of n=743 cases identified, we have successfully interviewed 51% (n=379). 9% were deemed ineligible to participate on the basis of being deceased, ill or unable to communicate due to senility or language. Regardless, proportions of cases refusing to participate in the study are higher than our original estimates, including 19% hard-refusing and 31% passively or soft refusing to participate.
Language:
English
Title:
Development of Micro-Scale Assays of Mammary Stem and Progenitor Cells
Document ID:
20090003314
Report #:
AD-A488004
Available Online:
http://hdl.handle.net/100.2/ADA488004
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Paguirigan, Amy L
Published:
20080701
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
128
Contract #:
W81XWH-06-1-0487
Abstract:
This portion of the work proposed focused on employing and validating microtechnology for in vitro studies of primary mammary gland cell characteristics. Specific attention has been paid to developing more quantitative methods for analyzing microfluidic cell cultures using In Channel Westerns. Also, understanding how the microfluidic culture platform differs from traditional macro-scale techniques is critical and was explored in more depth than previously done. By thoroughly understanding how this culture platform affects the cellular baseline first, better and more efficient data collection can be performed, thus requiring fewer primary cells.
Language:
English
Title:
Targeting Sirna Missiles to Her2+ Breast Cancer
Document ID:
20090003315
Report #:
AD-A488005
Available Online:
http://hdl.handle.net/100.2/ADA488005
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Medina-Kauwe, Lali K
Published:
20080601
Source:
Cedars-Sinai Medical Center (Los Angeles, CA United States)
Pages:
10
Contract #:
W81XWH-06-1-0549
Abstract:
The most significant findings here are that HerPBK10-siRNA complexes retain stability in whole serum and evade serum nuclease mediated degradation of the siRNA, thus providing an encouraging prediction that the complex will be stable in vivo. We also show that HerPBK10- siRNA complexes induce targeted cell death to HER2+ but not HER2- cells in culture, suggesting that in vivo tumor targeting and cell death, as anticipated in the third year of this project, will be feasible. We show that the complex induces IFN-alpha secretion from HER2+ but not HER2- cells, which likely contributes to the mechanism of targeted cell death by these complexes. Interestingly, we also found that the HerPBK10 protein alone also induced a similar pattern of IFN-alpha secretion, and will be examining the contribution of the carrier protein and siRNA toward the targeted cell death observed here. Finally, we show that the siRNA carrier, HerPBK10, undergoes tumor-preferential accumulation in tumor-bearing mice, and preferentially avoids of normal tissues and organs.
Language:
English
Title:
Characterization of Gene Expression in Human Breast Tumor Endothelium
Document ID:
20090003316
Report #:
AD-A488006
Available Online:
http://hdl.handle.net/100.2/ADA488006
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Klauber-DeMore, Nancy
Published:
20080501
Source:
North Carolina Univ. (Chapel Hill, NC United States)
Pages:
15
Contract #:
W81XWH-04-1-0434
Abstract:
Angiogenesis is the growth of new capillary blood vessels, and is a critical component of solid tumor growth. We characterized molecular changes between human breast tumor vessels and normal vessels to identify genes that may serve as therapeutic targets. We developed a method for rapid immunohistochemistry (IHC) and laser capture microdissection (LCM) of vascular cells from frozen human breast tumors and normal breast tissue for genomic analysis. We found SFRP2 to have 6 fold increased mRNA expression in breast tumor vessels, and confirmed localization of SFRP2 to endothelium using IHC with antibodies to SFRP2 on paraffin-embedded breast tumors. SFRP2 protein expression in endothelium was significantly higher in breast tumors than normal (13/15 or 87% versus 4/10 or 40%, p=0.03). We found that SFRP2 stimulates angiogenesis ex vivo and in vitro through a calcineurin/ NFAT pathway. A polyclonal antibody to SFRP2 inhibited malignant endothelial tube formation, demonstrating the contribution of SFRP2 to angiogenesis. We found that tacrolimus, a calcineurin/ NFAT inhibitor inhibits SFRP2 induced endothelial tube formation, and inhibited malignant endothelial tumor growth in mice. Based on its expression and function, we have discovered that SFRP2 is a novel therapeutic target for the treatment of breast cancer.
Language:
English
Title:
Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study
Document ID:
20090003318
Report #:
AD-A488008
Available Online:
http://hdl.handle.net/100.2/ADA488008
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Munshi, Medha
Published:
20080601
Source:
Joslin Diabetes Center (Boston, MA United States)
Pages:
10
Contract #:
W81XWH-07-1-0282
Abstract:
During this research period, we have identified patients over age 70 with diabetes and poor glycemic control as defied by A1c>8%, and randomized them to either geriatric diabetes intervention team (GDT) or attention control group. Subjects in GD group underwent comprehensive geriatric assessment and have individualized intervention plan formed. The interventions are now being implemented with help of a geriatric life specialist (GLS). Intervention by GDT includes focused strategies to overcome barriers in the areas of clinical care, education, social environment, and finances. In addition, study subjects in GDTarm also underwent cerebral blood flow study. At the end of 6 months of intervention, goal is to develop support network that will empower patients to sustain improvements seen during the intervention. The subjects in the control group will have similar contact time as GDT group with research diabetes team without geriatric expertise. Clinical functional, quality of life and economical outcome measures in both groups are assessed at baseline and will be compared at 6 and 12 months intervals. These time points (0, 6 and 12 months) patients will also be evaluated for effect of improved glycemic control on change in the cerebral perfusion. The first patient was recruited on January 8, 2008, and there are no findings at this time.
Language:
English
Title:
Biologic and Computational Modeling of Mammographic Density and Stromal Patterning
Document ID:
20090003319
Report #:
AD-A488009
Available Online:
http://hdl.handle.net/100.2/ADA488009
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Seewaldt, Victoria Lo, Joseph
Published:
20080701
Source:
Duke Univ. (Durham, NC United States)
Pages:
13
Contract #:
W81XWH-07-1-0393
Abstract:
The goals of this synergistic grant proposal are to develop computational and biological tools to investigate the relationship between mammographic density and short-term breast cancer risk. Here we have worked to correlate computational models of mammographic and stromal patterning with clinical outcome leading to the construction of multi-disciplinary tools for the classification of breast cancer risk and response to prevention strategies. To this end we have currently evaluated mammographic density in 25 women taking tamoxifen chemoprevention and 25 high-risk women who elected not to take tamoxifen using pattern analysis of 1) serial mammograms, 2) serial breast Magnetic Resonance Imaging, and 3) Random Periareolar Fine Needle Aspiration (RPFNA). We observe no correlation between the presence or absence of atypia after tamoxifen prevention and changes in mammographic density. Two women developed breast cancer while taking tamoxifen who had a progressive decrease in mammographic density. These findings demonstrate the viability of using RPFNA to assess prevention response.
Language:
English
Title:
Annexin II-Dependent Mechanism of Breast Cancer Progression
Document ID:
20090003320
Report #:
AD-A488010
Available Online:
http://hdl.handle.net/100.2/ADA488010
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sharma, Mahesh C
Published:
20080601
Source:
Drexel Univ. (Philadelphia, PA United States)
Pages:
9
Contract #:
W81XWH-07-1-0424
Abstract:
Angiogenesis and metastasis are two processes that are central to the progression of cancer. As such, they have become important targets for the development of anti-cancer agents. Invasive and metastatic cancers of the breast are distinguished by their propensity of newly formed blood vessels (neoangiogenesis). Neoangiogenesis is a significant independent prognostic indicator in early stage breast cancer (1). Delineating the molecular mechanism(s) of neoangiogenesis may provide new insights into the biology of breast cancer progression and metastasis and may provide novel prognostic and therapeutic tools. Recently, the plasminogen (PLG)/plasmin (PL) system was demonstrated to play an important role in breast cancer progression and metastasis. Experimental studies in animal models combined with extensive clinicopathological data provide a compelling case indicating that proteins of PLG/PL pathways play a key role in breast cancer progression and metastasis(2). In this context, enzymes of the PLG/PL pathway have been reported to have prognostic value in breast cancer and are associated with poor prognosis both for overall and disease free survival(2). In fact these molecules have been associated with a high rate of relapse for patients with breast cancer Preliminary studies in animal model demonstrated that PLG gene deficient mice (PLG-/-) display inhibition of tumor invasion, lymph node metastasis and angiogenesis supporting the idea that PL is required for angiogenesis, tumor growth and metastasis(3). Despite established role in tumor angiogenesis, growth and metastasis it is still unclear.
Language:
English
Title:
Design of an NF-kB Activation-Coupled Apoptotic Molecule for Prostate Cancer Therapy
Document ID:
20090003321
Report #:
AD-A488011
Available Online:
http://hdl.handle.net/100.2/ADA488011
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yang, Wannian
Published:
20080731
Source:
Geisinger Medical Center (Danville, PA United States)
Pages:
23
Contract #:
W81XWH-07-1-0084
Abstract:
This proposal is to establish an effective and selective gene therapy technique for prostate cancer. The main idea is to create an NF-kB/Caspase-3 fusion protein, designated as NF-kB activation-coupled apoptotic molecule (NACAM), that couples activation of NF-kB to activation of Caspase-3, thus to apoptosis. During the eighteen months, we constructed 32 plasmids for testing the function of NACAM and determined the expression of the plasmids in HEK293 cells. We further tested the function of NACAM by examining the caspase activity of NACAM and interaction of NF-kB/Caspase-3 fusion proteins. We found that p65-L-SS and p65-L-LS are capable of forming active caspase-3. However, because NF-kB/Caspase-3 fusion proteins form homo-dimers, NF-kB/Caspase-3 subunit fusion proteins have only small portion to form NACAM. Nevertheless, our work provided a preliminary study for creating an NF-kB activation-coupled apoptosis molecule. In addition to NACAM, we continued our research on development of mitogenesis-coupled apoptosis molecular device (MCAMD). The first-phase research of MCAMD was funded by DOD-PCRP concept award (W81XWH-05-1-0178) and completed in June of 2006. Because MCAMD is technically related to NACAM, we further developed MCAMD with this funding support and successfully established MCAMD system in HEK293 cells. We have observed that mitogenic conditions induced cellular apoptosis through MCAMD, providing preliminary data for application of MCAMD to prostate cancer therapy. This work is in preparation of manuscript for publication and in process of application for a patent. Future studies will include: (a) to further characterize and improve NACAM; and (b) to test the function of MCAMD for killing cancer cells in a prostate cancer cell system and a prostate cancer cellxenografted mouse model.
Language:
English
Title:
Functional Analysis of the Beclin-1 Tumor Suppressor Interaction with hVps34 (Type-III P13'-kinase) in Breast Cancer Cells
Document ID:
20090003322
Report #:
AD-A488012
Available Online:
http://hdl.handle.net/100.2/ADA488012
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Maltese, William A
Published:
20080601
Source:
Toledo Univ. (OH United States)
Pages:
15
Contract #:
W81XWH-04-1-0493
Abstract:
Macroautophagy plays a pivotal role in type II programmed cell death. Beclin 1 regulates macroautophagy. Over expression of Beclin has been reported to promote autophagy and inhibit tumorigenesis in breast carcinoma cells, and conversely, heterozygous disruption of the Beclin gene can promote tumorigenesis in mice. In Year-1 we established that Beclin associates with the human type-III phosphatidylinositol 3-kinase (PI3K), hVps34. The lipid product of Vps34, PI(3)P, is required not only for autophagy, but also for assembly of proteins involved in endocytosis and trafficking of enzymes from the trans-Golgi network to the lysosomes. Our studies indicated that Beclin is required for hVps34 to function in autophagy, but is dispensable for hVps34 to function in endocytosis. In Year-2 we generated stable MCF7 breast cancer cells with expression of FLAG-tagged Beclin under the control of an inducible promoter. Using this cell line, we purified the FLAG-Beclin-Vps34 complex and performed mass spectrometry to identify other protein components in the complex. We established that p150, a regulatory subunit of type-III PI3K, and associates with Beclin. In Year-3 we generated stable Beclin knockdown cell lines in ZR-75 and MCF7 breast cancer lines. During the extension year we have used these lines to explore the relationship of autophagy to cell death in breast cancer cells treated with tamoxifen and rottlerin. These studies have revealed that Beclin is not required for initiation of autophagic cell death in breast cancer cells and that under some circumstances autophagy can occur independent of Beclin-1. These studies challenge the accepted notion that Beclin is an essential regulator of autophagy in breast cancer.
Language:
English
Title:
Role of Stat5a in Differentiation of Human Breast Cancer
Document ID:
20090003323
Report #:
AD-A488013
Available Online:
http://hdl.handle.net/100.2/ADA488013
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ryder, Amy
Published:
20080601
Source:
Thomas Jefferson Univ. (Philadelphia, PA United States)
Pages:
8
Contract #:
W81XWH-06-1-0554
Abstract:
The Prolactin (PRL)-Jak2-Stat5 pathway has been described as a key regulator in the normal growth, development, and differentiation of human breast epithelia. Recent evidence from our lab and others has suggested that active Stat5 is a positive predictive marker of prognosis in breast cancer patients and the loss of active Stat5 correlates with a more aggressive disease state. Further, in vitro expression of Stat5 increased differentiation characteristics of human breast cancer cell lines and was able to inhibit invasive characteristics in human breast cancer cell lines. The specific aims of this proposal were designed to further investigate the role of Stat5 in breast cancer progression and metastasis. We hypothesize that active Stat5a suppresses invasion and metastasis of human breast cancer by promoting upregulation of differentiation markers, increasing homotypic adhesion, and inhibiting growth. We aim to test this hypothesis in human breast cancer cell lines both in vitro and in vivo using a novel constitutively active Stat5a construct. We have constructed constitutively active Stat5 mutants and generated adenoviral, lentiviral, and tetracycline-inducible expression systems. We have also generated stable cell lines expressing these constructs. Stable expression of Stat5 in mesenchymal MDA-MB- 231 breast cancer cells does not yield consistent results with those seen in transient expression systems, and it is likely that we are not using an appropriate cell line to study Stat5 signaling. We are in the process of optimizing cell lines and assays to measure Stat5 differentiation in a more relevant setting where Stat5 intracellular regulators are more likely to be present and functioning.
Language:
English
Title:
High-Content FRET-FLIM Screening in Inhibitors of Oncogenic Transcription by c-myc in Breast Cancer
Document ID:
20090003325
Report #:
AD-A488015
Available Online:
http://hdl.handle.net/100.2/ADA488015
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Andrews, David
Published:
20080601
Source:
McMaster Univ. (Hamilton, Ontario Canada)
Pages:
19
Contract #:
W81XWH-07-1-0333
Abstract:
There is an urgent need for novel anti-breast cancer therapeutics. Our hypothesis is that by identifying small molecules that target the Myc oncogene, we will develop an effective therapeutic that will improve breast cancer patient care and contribute to the eradication of disease. Our OBJECTIVE is to identify compounds that can be used to selectively inhibit the oncogenic activity of Myc by inhibiting its interaction with one of its key binding partners TRRAP. To this end, we aim to 1) develop a novel high content screen to identify inhibitors that block Myc:TRRAP interaction; 2) determine the transcriptional signatures of Myc:TRRAP target genes; 3) screen drug and chemical libraries to identify compounds that disrupt Myc:TRRAP interaction; and, 4) validate lead compounds that disrupt Myc:TRRAP interaction and block the transformation potential of breast cancer cells. In the first year of this grant we have constructed several fluorescent fusion protein constructs of Myc and TRRAP, and evaluated their ability to bind and engage in fluorescence resonance energy transfer (FRET) in vivo. We have identified FRET pairs that are functional and established methodology using novel instrumentation that will enable the high throughput screening of chemical libraries. In the course of our work, we have shown that the cell systems we were aiming to use are unfortunately sensitive to expression of the fusion proteins. To overcome this unexpected issue, we are evaluating additional cell systems, as well as new expression constructs that will enable stable cell lines to be developed that constitutively and conditionally express the Myc and TRRAP fusion proteins, respectively. We have completed all tasks that we aimed to achieve in the first year of the grant and we are well positioned to fulfill the objectives of our proposal by the end of the second year of this grant.
Language:
English
Title:
CXCL5 is a Novel Mediator of Prostate Cancer Proliferation and Migration/Invasion
Document ID:
20090003326
Report #:
AD-A488016
Available Online:
http://hdl.handle.net/100.2/ADA488016
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Macoska, Jill A
Published:
20080601
Source:
Michigan Univ. (Ann Arbor, MI United States)
Pages:
19
Contract #:
W81XWH-07-1-0385
Abstract:
The primary concept driving this proposal is that CXCL5 may provide a link between aging and the development of malignant proliferative prostatic disease, and may act as a previously unrecognized growth factor that promotes prostate cancer cell proliferation and migration/invasion. The major findings of these studies are that CXCL5 protein expression levels are significantly elevated in primary and metastatic prostate tumors, that CXCL5 induces prostate cancer cell proliferation, migration and invasion in vitro, and that CXCL5 activates both MAPK and PI3K signaling and stimulates gene transcription in both nontransformed and transformed prostate epithelial cells. These findings suggest that CXCL5 works at many levels to promote prostate tumor progression and metastasis. Moreover, CXCL5 may provide a non-steroidal therapeutic target useful towards the treatment of hormone refractory prostate cancers.
Language:
English
Title:
Molecular Solutions to Low Injuries Resulting from Battlefield Injuries. Addendum
Document ID:
20090003328
Report #:
AD-A488018
Available Online:
http://hdl.handle.net/100.2/ADA488018
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dartt, Darlene A
Published:
20080501
Source:
Retina Foundation (Boston, MA United States)
Pages:
19
Contract #:
W81XWH-04-2-0008
Abstract:
We hypothesize that targeted molecular intervention can preserve vision threatened by battlefield trauma-induced corneal and retinal inflammation, corneal and retina/optic nerve apoptosis, ocular surface dry eye after refractive surgery, and retinal degeneration. We are studying the consequences of trauma-induced (1) corneal inflammation using a gene therapy approach of providing soluble Fas ligand to the cornea to determine if this ligand can suppress corneal inflammation in mice; (2) retinal inflammation by examining if transforming growth factor-beta, thrombospondin, and somatostatin, in subretinal space, can suppress inflammation within retina secondary to autoimmune uveoretinitis and light-induced damage in mice; (3) corneal cell death by apoptosis and promote regeneration by identifying the anti-apoptotic gene with the greatest capacity to suppress corneal cell apoptosis using mice; (4) retinal cell death and regeneration by using mice to determine if systemic treatment with lithium chloride can prevent collateral damage to retinal neurons and promote optic nerve regeneration; (5) dry eye by determining how to minimize dry eye after LASIK refractive surgery by developing new tests to predict pre-disposition to refractive surgery induced dry eye; and (6) retinal injury by generating stem cell polymer composites.
Language:
English
Title:
ER/PR Status of the Originating Cell of ER-Negative Breast Cancer
Document ID:
20090003330
Report #:
AD-A488026
Available Online:
http://hdl.handle.net/100.2/ADA488026
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Li, Yi
Published:
20080401
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
6
Contract #:
W81XWH-07-1-0293
Abstract:
The goal of this study is to test whether ER breast cancers arise from ER or ER+ mammary cells. We specifically hypothesize that ER is absent in the originating cell of ER-negative breast cancer. Although until now it has been technically difficult to test it, we have developed a unique mouse model based on the RCASTVA technology that allows us to trace the ER status of the cancer-originating cell. It is now possible to test this hypothesis in experimental mice.
Language:
English
Title:
Diagnosed Eating Disorders in the U.S. Military: A Nine Year Review
Document ID:
20090003357
Report #:
AD-A487117, USARIEM-M08-17
Available Online:
http://hdl.handle.net/100.2/ADA487117
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Antczak, Amanda J Brininger, Teresa L
Published:
20080901
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
16
Contract #:
None
Abstract:
The objective of this study was to determine the incidence of three types of eating disorders (ED) -- anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified (EDNOS) -- diagnosed in the U.S. Military. Diagnosed cases of ED were obtained from the Defense Medical Epidemiology Database for all Service Members (SM) from 1998-2006. The percentage per year of SM with an ED diagnosis was .30%. Eating disorders were diagnosed significantly more in 2006 (.41%) compared to 1998 (.23%) (p < .001). Females were diagnosed significantly more than males (p < .001). The majority of AN cases (66%) were in the Marines. This is the first known study to investigate the incidence of ED in SM using medical record data. Service Members diagnosed with ED have increased. Females, specifically White females, have higher incidence of ED. The reported incidence of diagnosed ED in SM was lower compared to previous research.
Language:
English
Title:
A Model System to Investigate the Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and Transformation Potential of the Ovarian Epithelium
Document ID:
20090003369
Report #:
AD-A487180
Available Online:
http://hdl.handle.net/100.2/ADA487180
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Connolly, Denise
Published:
20080501
Source:
Fox Chase Cancer Center (Philadelphia, PA United States)
Pages:
11
Contract #:
W81XWH-07-1-0301
Abstract:
The tumor microenvironment plays an important role in cancer progression. The tumor stroma promotes angiogenesis and is a source of growth factors, chemokincs, and extracellular matrix (ECM) molecules that promotes carcinoma progression. We are investigating the effects of loss of function of BRCAl and Trp53 in the stroma on the growth and neoplastic transformation of epithelial cells using 2-D and 3-D in vitro culture models. Wamcn carrying gerrnline mutations in BRCAl are at high risk for developing ovarian cancer and mutations in pS3 arc frequently detected in ovarim tumors. Further, inactivation of BRCAl in mouse granulosa cells results in the development of benign epithelial neoplasm in the ovary and uterine horn, but the lesions themselves express wild-type BRCAl. Inactivation of BRACl also causes arrest at the G21M transition and significantly increases population doubling times; an effect that is reversed by inactivation of Trp53. 'Therefore, to directly test the hypothesis that stromal cells excrt a ccll-nonautonomous effect on ovarian epithelial cell growth and neoplastic transformation, we will examine the effects of culturing mouse ovarian surface epithelial (MOSE) cells with ECM and conditioned media from stromal calls in which BRACl and Trp53 have been inactivated (alone or in combination).
Language:
English
Title:
Innovative Microsystems: Novel Nanostructures to Capture Circulating Breast Cancer Cells
Document ID:
20090003375
Report #:
AD-A487203
Available Online:
http://hdl.handle.net/100.2/ADA487203
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Zohar, Yitshak
Published:
20080501
Source:
Arizona Univ. (Tucson, AZ United States)
Pages:
23
Contract #:
W81XWH-07-1-0305
Abstract:
The goal of this project is to develop a microsystem for sorting metastatic breast cancer cells from a heterogeneous suspension of cells circulating in the blood stream. Conceptually, the technique requires the transformation of a distinguishing biochemical characteristic of the target cells, such as up-regulated cadherin phenotype, into a mechanical or electrical that makes it possible to selectively manipulate the cells on the microscale. The project includes developments of a model system of cells to evaluate cadherin-mediated cell sorting and an integrated bio-functional microfluidic system to capture target cells from heterogeneous suspensions of cells. We have succeeded in the transfection of MDA-MB-231 cells with an N-cadherin expression vector deriving a homogeneous population. An anti-N-cad functionalized surface has been shown to capture N-cad expressing prostate cancer cells (PC3N) with high degree of selectivity. An assay to characterize and a technique to control the amount of immobilized anti-N-cad antibodies on surfaces have been developed to maximize the cell capture efficiency. Microchannels with anti-N-cad functionalized surfaces have been fabricated. Under flow conditions, the capture rate is poor; however, after 15min of incubation time, the capture rate is high. Once captured, the cell/surface adhesion bond is strong enough to sustain high flow-induced shears stress.
Language:
English
Title:
Investigation of Metastatic Breast Tumor Heterogeneity and Progression Using Dual Optical/SPECT Imaging. Addendum
Document ID:
20090003377
Report #:
AD-A487206
Available Online:
http://hdl.handle.net/100.2/ADA487206
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Antich, Peter P
Published:
20080501
Source:
Texas Univ. (Dallas, TX United States)
Pages:
65
Contract #:
W81XWH-04-1-0551
Abstract:
The goal of our project was to develop methods to image the processes that occur during tumor growth and metastatic spread or regression including the fate of minimal residual disease. The key to this was through the development of a dual modality imaging system capable of performing both optical and SPECT imaging in mice. To do so it is necessary to test the limits of sensitivity of newly developed techniques: our technical goal is to develop integrated light emission and single photon emission tomography. We have made substantial progress in our techniques for the detection of metastases. We have demonstrated our capability to detect millimeter or sub-millimeter metastases in mice by light emission. To this end we have used Light Emission Tomography (LET) a technique based on bioluminescence of cancer cells transfected with lucifernse to detect metastases in the lung bones and head. We have begun assessment of perfusion using fluorescence imaging. In addibon our technological focus is on the simultaneous use of Single-photon Emission Computed Tomography (SPECT) and to this end we have developed a new form of micro-SPECT based on cooled electron-multiplied Charge-Coupled Devices (EMCCDs).
Language:
English
Title:
Treatment of PTSD-Related Anger in Troops Returning From Hazardous Deployments
Document ID:
20090003378
Report #:
AD-A487207
Available Online:
http://hdl.handle.net/100.2/ADA487207
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Shea, M T
Published:
20080301
Source:
Brown Univ. (Providence, RI United States)
Pages:
6
Contract #:
W81XWH-05-1-0171
Abstract:
Objective: The long-term goal of the research is to provide an effective intervention for the prevention of secondary and escalating effects of poor anger control associated with trauma-related anger problems. The specific objectives are to adapt an existing evidenced-based cognitive-behavioral intervention (CBI) for the treatment of anger to specific needs of military personnel returning from hazardous deployments, and to conduct a pilot study providing preliminary data on the adapted intervention. Design: There are two phases in this project. In Phase 1, protocol therapists gained experience with the cognitive-behavioral intervention (CBI) for anger control, and the manual adapted to the needs of the population. In Phase 2, participants are randomly assigned to CBI or a Supportive Therapy Control (supportive intervention, SI) condition. Each condition includes a maximum of 14 sessions, 75 minutes in length. Progress: Phase I of the study has been completed with 14 participants (12 in CBI and 2 in SI) entering treatment. Of the 12 starting CBI treatment, 8 completed all sessions. Of the 251 participants, 1 completed and 1 did not. Termination and 3 months follow up assessments have been completed for phase I completers. Phase II is in progress. Fifteen subjects have been assessed, 13 have been randomized, 12 started treatment (6 CBI and 6 SI). Of the 6 CBI subjects, 4 have completed and 2 are in progress. Of the 6 SI subjects, 3 have completed, one dropped after 5 sessions, and 2 are in progress. Termination and 3 month follow-up assessments are completed as they are due. Findings: Phase I CBI participants who completed treatment showed significant improvement on the four anger indices. Although very preliminary, findings are encouraging for the efficacy of CBI for the treatment of anger symptoms following deployment related trauma.
Language:
English
Title:
Training HBCU Faculty and Students in Prostate Cancer (PC) Research: Signal Transduction and Receptor-Inhibitor Interactions in the Progress of PC
Document ID:
20090003379
Report #:
AD-A487209
Available Online:
http://hdl.handle.net/100.2/ADA487209
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wiese, Thomas E Klassen, R B
Published:
20080301
Source:
Xavier Univ. of Louisiana (New Orleans, LA United States)
Pages:
29
Contract #:
W81XWH-04-1-0252
Abstract:
This program aims to help eradicate prostate cancer (PC) disparity in African Americans through educational and research programs. Our hypothesis is that through PC education and participation in PC research a meaningful number of African Americans will be able to contribute to the elimination of disparity in PC. Our program comprises three Specific Aims. (1) To develop promote and sustain independent competitive research and training programs at Xavier University. Both projects are moving forward presenting data and involving students. (2) To increase the number of Xavier University investigators focused on PC research. One new project has been developed and is involving students. (3) To establish a long-term collaborative relationship between Xavier University and the TCC in PC research. XU faculty in the program are now members of the Tulane Cancer Center and involved in weekly seminars and focus group meetings.
Language:
English
Title:
Prostate Cancer Research Training Program
Document ID:
20090003384
Report #:
AD-A487221
Available Online:
http://hdl.handle.net/100.2/ADA487221
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Lubaroff, David M
Published:
20080201
Source:
Iowa Univ. (Iowa City, IA United States)
Pages:
9
Contract #:
W81XWH-06-1-0266
Abstract:
The HBCU Summer Research Training Program accepted a total of eight students from Lincoln University for the eight week session in the summer of 2007. Five of the students were supported by this grant and three of the students were supported by the second grant awarded in 2007. At the last minute one student withdrew leaving seven students for the summer. Each student was assigned to a laboratory of a participating mentor and also paired with a member of the mentor's laboratory. This laboratory member assisted with day to day aspects of the research project. During the summer the students worked diligently on their research project, participated in meetings of the mentor's laboratory, attended workshops and seminars associated with our and other summer programs, and attended a special course in prostate cancer. We integrated the Lincoln students into social programs held throughout the campus for summer interns and they attended and participated in the CIC Conference at Purdue University. At the end of the summer session the students presented a poster of the research results from the summer experience. They also presented the results of their research in the fall at Lincoln University and some presented at the DOD's IMPaCT meeting in the Fall of 2007. Of the seven students, three have graduated and four are in their junior year at Lincoln University. Of the three graduates, two are in graduate school and one currently working and applying to graduate schools.
Language:
English
Title:
MINDS - Medical Information Network Decision Support System
Document ID:
20090003385
Report #:
AD-A487222
Available Online:
http://hdl.handle.net/100.2/ADA487222
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Armenian, H K
Published:
20080601
Source:
TechFinity, Inc (Calabasas, CA United States)
Pages:
19
Contract #:
W81XWH-07-2-0052
Abstract:
Advances in medical knowledge and technology have created new opportunities for disease specific diagnosis and treatment. The increase in and complexity of medical data at various levels of resolution has increased the need for system level advancements in clinical decision support systems that provide computer-aided analysis for diagnostics and treatment. In order to facilitate a more rapid and systematic transfer of new medical knowledge and capabilities into mainstream clinical practice, a new Medical Information Network Decision Support (MINDS) system is proposed. This system is intended to be a platform for storing and fusing medical data across all levels (e.g. from low-level genomic and proteomic data to higher level clinical data) in a standardized way, and provide probabilistic diagnostic and treatment decisions to assist doctors and medical researchers in understanding and treating disease. This tools is viewed as complementary to the many other information technologies that are streamlining the health care administration processes and empowering patients through web-based informational tools. The pilot application will be targeted to breast cancer diagnosis and treatment, and later expanded to other diseases. The system will build upon the information fusion and decision architecture technology that is currently being developed in the Missile Defense community and apply it to the medical science of identification, tracking, and treatment of disease. It will provide initial diagnostic and treatment models for breast cancer, and refine those models using validated, state-of-the-art research techniques applied to clinical data, medical imaging data, experimental proteomics data, and cell-based experimental data. The ultimate goal is to provide a rapid and systematic introduction of the latest medical knowledge and techniques into mainstream medical practice throughout the medical community and within large national systems.
Language:
English
Title:
Efficacy of Adjunctive Sleep Interventions for PTSD
Document ID:
20090003387
Report #:
AD-A487226
Available Online:
http://hdl.handle.net/100.2/ADA487226
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Germain, SaAnne Nofzinger, Eric A
Published:
20080301
Source:
Pittsburgh Univ. (Pittsburgh, PA United States)
Pages:
19
Contract #:
W81XWH-06-1-0257
Abstract:
Since the last report we have successfully achieved all goals initially set in our statement of work and task timeline for the first 24 months of the award. Recruitment has been delayed and accrued at a slower pace than initially anticipated for clinician-initiated referrals. However we have rapidly changed our recruitment strategy and continue to seek opportunities to collaborate effective with our colleagues at the VAPHS to facilitate and enhance recruitment of military veterans with sleep disturbances to our research program. This award has also significantly contributed to other reportable outcomes including several presentations and provided preliminary data for 2 successful applications for federal funding by the PI.
Language:
English
Title:
Antigens for a Vaccine that Prevents Severe Malaria
Document ID:
20090003388
Report #:
AD-A487227
Available Online:
http://hdl.handle.net/100.2/ADA487227
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Duffy, Patrick E
Published:
20080301
Source:
Seattle Biomedical Research Inst. (Seattle, WA United States)
Pages:
97
Contract #:
W81XWH-05-2-0014
Abstract:
Malaria is the primary infectious disease threat facing the U.S. soldier and is the leading cause of all causalities during tropical deployments. The long-term objective of this project is to identify and prepare the malaria parasite forms causing severe anemia and then apply functional genomics and bioformatics tools to identify 15 to 30 proteins that could form the basis for an effective vaccine at both the pre-erythrocytic and blood stages of malaria infection. The project will then evaluate these lead candidates for their recognition by sera collected from immune individuals in order to identify the leading 3 to 5 candidates for a blood stage vaccine that prevents severe malaria anemia.
Language:
English
Title:
Center of Excellence for Individualization of Therapy for Breast Cancer
Document ID:
20090003389
Report #:
AD-A487228
Available Online:
http://hdl.handle.net/100.2/ADA487228
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sledge, George W
Published:
20080401
Source:
Indiana Univ. (Indianapolis, IN United States)
Pages:
52
Contract #:
W81XWH-04-1-0468
Abstract:
The report submitted herein includes reports from subcontractors involved in the COE, which explain in detail the efforts of the COE during the past year. This report will highlight the overall progress made by the Center of Excellence. As discussed in a recent teleconference between the COE team and DOD representatives, the past year has seen a significant change in our overall approach to the Center of Excellence for Therapeutic Individualization for Breast Cancer. Our initial approach, as originally set out, involved obtaining frozen tissue samples for all women entering the trial. Obtaining these tissues in a timely fashion proved more difficult than we initially predicted, due to regulatory issues that delayed trial participation and due to accrual problems at clinical sites. Simultaneously, changes in technology have made it possible to perform high-quality analyses on formalin- fixed, paraffin-embedded tissues. We therefore shifted the focus of clinical trial material from fresh frozen tissues to formalin-fixed, paraffin-embedded tissues (FFPET). This shift in focus has had important consequences for trial performance, accrual, and technology. From a trial performance standpoint, we inaugurated during the past year our COE05 trial. This trial, our "Retrospective-Prospective" trial, has obtained FFPET samples from women who have died of metastatic breast cancer and on whom clinical response and time to treatment failure data were available. To date samples from over 60 patients have been obtained. Because patients may have been exposed to more than one chemotherapy regimen during the course of their disease, patients can provide informative data for multiple agents. We are also currently in negotiation with a prominent medical oncology consortium in Poland (headed by Dr. Jacek Jassem) to obtain additional specimens for COE05; at present this consortium has identified 200 patients who are case-eligible for COE05.
Language:
English
Title:
Alcohol Intoxication Impact on Outcome from Traumatic Injury
Document ID:
20090003391
Report #:
AD-A487242
Available Online:
http://hdl.handle.net/100.2/ADA487242
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Molina, Patricia
Published:
20080501
Source:
Louisiana State Univ. (New Orleans, LA United States)
Pages:
9
Contract #:
W81XWH-06-1-0236
Abstract:
Acute alcohol intoxication (AAI) impairs the hemodynamic counteregulatory response to trauma and hemorrhagic shock (HS), blunts the pressor response to fluid resuscitation (FR), suppresses the HS-induced neuroendocrine response, impairs pro-inflammatory cytokine expression and increases mortality from infection during recovery Studies conducted during this funding period examined a) whether the attenuated neuroendocrine response, particularly reduced sympathetic nervous system (SNS) activation, is the principal mechanism responsible for the hemodynamic instability seen in AAI+ HS and b) what the impact of AAI was on the integrity of host defense mechanisms during the immediate and delayed recovery from HS. We determined whether SMS activation can be restored by central (intracerebroventricular; IC") neostigmine administration and whether this in turn is capable of improving the hemodynamic counteregulatory response to HS in AAI. Our results show that ICV neostigmine stimulates SNS activation and improves the recovery of blood pressure following hemorrhagic shock. Furthermore, our results indicate that this in part mediated by arginine vasopressin Interestingly while the presser response to phenylephrine in vitro appears to be blunted by alcohol, the in vivo response to a presser with a different mechanism of action appears to be preserved,
Language:
English
Title:
Telemedicine Based Ultrasound for Detecting Neonatal Heart Disease in Babies at Remote Military or Native American Health Care Facilities
Document ID:
20090003400
Report #:
AD-A487267
Available Online:
http://hdl.handle.net/100.2/ADA487267
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sahn, David J Kinney, James Puntel, Robert
Published:
20080901
Source:
Oregon Health Sciences Univ. (Portland, OR United States)
Pages:
14
Contract #:
DAMD17-03-1-0109
Abstract:
Our partnership of investigators from Madigan Army Medical Center at Fort Lewis Washington and Oregon Health & Science University in Portland will test the hypothesis that trained primary care practitioners or nurses can with telemedicine supervision perform cardiac ultrasound exams on neonates at risk for heart disease and thereby impact time to diagnosis and outcomes. This study is targeted at Military Medical Facilities within TRICARE West and Western Regional Medial Command. It will also include two large Alaska Native Health Care Centers. Echocardiography has had major impact in the management of neonates suspected of having congenital heart disease. The expensive specialized equipment and significant expertise to adequately perform and interpret these studies usually is present only in tertiary level medical centers with a pediatric cardiologist on staff. Initial results of a National Multicenter Neonatal Telemedicine Echo Outcomes Study developed by the Principal Investigator suggest that telemedicine-implemented diagnosis positively affects outcomes in infants suspected of having congenital heart disease. Our partnership has trained 33 non cardiologists to perform neonatal echo and has installed a high bandwidth telecommunications link using the military version of Internet2, NIPRNET. By spring of 20077 we will be overseeing neonatal echo exams from 3 military installations in the NW and in Alaska, as well as a large Alaska Native Health Center in Anchorage. We have also arranged to upgrade the scanners used in our network to the latest architecture from Sonosite(Registered): the fully digital phased array hand held ultrasound scanner, the MicroMaxx(Registered).
Language:
English
Title:
Evaluation of Purine Salvage as a Chemotherapeutic Target in the Plasmodium yoelii Rodent Model
Document ID:
20090003401
Report #:
AD-A487269
Available Online:
http://hdl.handle.net/100.2/ADA487269
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kim, Kami
Published:
20080301
Source:
Albert Einstein Coll. of Medicine (Bronx, NY United States)
Pages:
35
Contract #:
W81XWH-05-2-0025
Abstract:
Because resistance to current antimalarials is widespread new targets for malaria chemotherapy are needed to protect military personnel stationed in developing countries. Malaria parasites cannot make purines needed for RNA and DNA and must salvage purines from their host. We are investigating whether the malaria purine salvage pathway can be exploited to develop specific treatments for malaria that will be effective but not toxic. We perform our studies in Plasmodium yoelii a rodent malaria. We have genetically disrupted purine salvage enzyme purine nucleoside phosphorylase (PNP) and have shown that these P .yoelii parasites are attenuated and confer protective immunity to subsequent lethal challenge. We have also mapped residues in PNP responsible for the unique methylthiopurine activity. New protocols for transfection have been developed and we now have succeeded in attempts to disrupt adenosine deaminase (ADA). Both PNP and ADA deficient parasites are unable to form oocysts in the mosquito. We have developed GFP and GFP-luciferase reporter P. yoelii parasite lines that are able to complete the entire life cycle in mosquito and rodent hosts. The GFP-luciferase reporter parasites can be visualized in vivo by detection of bioluminescence both during intrahepatic and erythrocytic development. Initial studies suggest that we can use these parasites to test efficacy of drugs against exoerythrocytic malaria forms. We hope these experiments will lead to the development of new effective and nontoxic agents that can protect our military personnel from the lethal effects of malaria infection.
Language:
English
Title:
Gene-Environment Interaction and Breast Cancer on Long Island, NY
Document ID:
20090003550
Report #:
AD-A487438
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Teitelbaum, Susan L
Published:
20080501
Source:
Mount Sinai School of Medicine (New York, NY United States)
Pages:
31
Contract #:
W81XWH-04-1-0507
Abstract:
This research project will build upon the Long Island Breast Cancer Study Project (LIBCSP), a large population-based, case-control study of the environment and breast cancer. Participants completed an in-person interviewer-administered interview, donated blood and urine samples and had home environment samples (dust, soil and water) collected. For this study, 200 cases and 200 controls who donated urine samples will be selected and their urine samples will be analyzed for a panel of EE biomarkers. In addition, these same women will be screened for polymorphisms in both the estrogen receptor alpha and beta genes. Breast cancer risk in relation to the combination of these multiple EE exposures and gene-environment interaction will be investigated using sophisticated statistical methods such as hierarchical regression models and factor analysis. Additionally, a pilot investigation of the correlation between EE levels in house dust and urinary biomarker levels will be conducted. Currently, samples for this study have been selected and the laboratory analyses are underway. Results of the proposed research project will be of enormous public health relevance since they may advance our knowledge of modifiable breast cancer risk factors and newly identified EEs, thereby providing information that is essential for primary prevention.
Language:
English
Title:
Studies on Axonal Transport in an Animal Model for Gulf War Syndrome
Document ID:
20090003551
Report #:
AD-A487439
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Baas, Peter W
Published:
20080701
Source:
Drexel Univ. Coll. of Medicine (Philadelphia, PA United States)
Pages:
44
Contract #:
W81XWH-07-1-0466
Abstract:
Gulf War Veterans are more prone to neurodegeneration, presumably due to a combination of toxins to which they were exposed together with stress. The hypothesis of the project was that these toxins might adversely affect the transport of subcellular elements called microtubules within the nerves, and that potential therapies could be developed accordingly. The one year of work did not resolve the issue, but progress was made toward refining the best experimental paradigm in which to test the hypothesis, and progress was made toward refining therapies based on novel tools that target a microtubule-based motor protein called kinesin-5 and microtubule-severing proteins called katanin and spastin.
Language:
English
Title:
Test Operations Procedure (TOP) 1-1-003 Cold Regions Personnel Effects
Document ID:
20090003554
Report #:
AD-A487444, TOP-1-1-003
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
(Author(s) Not Available)
Published:
20080915
Source:
Army Cold Regions Test Center (Fort Greely, AK United States)
Pages:
13
Contract #:
None
Abstract:
This Test Operations Procedure (TOP) provides background information on physiological and psychological effects of cold on the human. It is an overview TOP and is organized to provide information on some of the problems associated with conducting operations, training, testing, and living in a cold environment. Rather than test procedures, it provides needed knowledge to safely conduct tests in the cold environment.
Language:
English
Title:
Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer
Document ID:
20090003557
Report #:
AD-A487448
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Behbakht, Kian
Published:
20080430
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
9
Contract #:
W81XWH-07-1-0268
Abstract:
Ovarian cancer is the leading cause of death from gynecologic cancers in the developed world. Most ovarian cancers are diagnosed late and current treatment results only in a 20% 5-year survival in advanced disease. More effective therapies are urgently needed. One of the most promising therapies in development for ovarian cancer is the use of either the Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL) or agonistic antibodies that activate the receptors for TRAIL. Both these strategies are designed to induce apoptosis in ovarian cancer cells. TRAIL therapies are particularly exciting because TRAIL reverses chemoresistance to standard chemotherapy as well as having a direct growth inhibitory effect on ovarian cancer cells, while sparing normal ovarian cells. However, the characteristics of ovarian tumor cells that determine whether TRAIL pathway agonists will be effective are poorly understood. For this reason, we currently do not have a rational basis for selecting patients who will benefit most from drugs that target this pathway or for improving the clinical response in those patients whose tumors are refractory to TRAIL pathway activators. We have identified a homeobox gene, Six1, which is over-expressed in ovarian cancers as compared to normal ovarian surface epithelium. Expression of Six1 is correlated with poor clinical prognosis and confers resistance to TRAIL, possibly via upregulation of a decoy receptor. If this is the case, tumor cells would be expected to be resistant to TRAIL, but not to TRAIL agonistic antibodies. We hypothesize that Six1 expression in ovarian cell lines and primary tumor cells results in resistance to TRAIL-induced apoptosis through activation of the DcR1 decoy receptor.
Language:
English
Title:
Breast Cancer Lymphatic Dissemination - Influence of Estrogen and Progesterone
Document ID:
20090003565
Report #:
AD-A487462
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Harrell, Joshua C
Published:
20080301
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
30
Contract #:
W81XWH-06-1-0314
Abstract:
Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. We developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors were tracked in living mice by whole-body imaging, and macrometastases or micrometastases were detected by intravital imaging or fluorescence microscopy. Tumor growth was estrogen dependent. To determine if the LN microenvironment alters estrogen-dependent gene expression, we developed a unique model to identify estradiol regulated genes in ER+ breast tumors and LN metastases. Fluorescent ER+ MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and PR induction were deficient in LN metastases, indicating that ER transcriptional activity was altered in the LN. Cancer cells from estradiol treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and contributes to antiestrogen resistance.
Language:
English
Title:
Detection of Prostate Cancer Progression by Serum DNA Integrity
Document ID:
20090003566
Report #:
AD-A487467
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Hoon, Dave S
Published:
20080401
Source:
John Wayne Inst. for Cancer Treatment and Research (Santa Monica, CA United States)
Pages:
12
Contract #:
W81XWH-07-1-0144
Abstract:
The main objective/hypothesis for this proposal is that additional diagnostic and prognostic insight can be obtained through analysis of tumor-related DNA integrity and methylation in patient serum. Additionally, DNA biomarkers will be assessed for their usefulness in predicting early disease recurrence and progression in patients during PCa treatment. The scope of the studies is to optimize and validate Alu, LINE1 and uLINE1 assays for assessment of prostate cancer (PCa) patient serum targeted for clinical utility. For the first year, we have put in place specimen procurement and processing protocols and optimized assays for Alu qRT and LINE1 qRT. The uLINE1 AQAMA (absolute quantitative allele methylation assay) assay is also near optimal. We have utilized prostate cell lines and tumor specimens for the initial assay optimization and validation. In the coming year, more PCA patients will be accrued as well as further accrual of serum at defined treatment intervals. Assays for the markers will be carried out once we have obtained statistically meaningful numbers of serum sets of PCa patients in treatment. We are also continuing our efforts in discovering additional clinically relevant DNA biomarkers.
Language:
English
Title:
Internet-Based Cervical Cancer Screening Program
Document ID:
20090003568
Report #:
AD-A487470
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wilbur, David C Crothers, Barbara A Eichhorn, John H Ro, Min S Gelfand, Jeffrey A
Published:
20080501
Source:
Massachusetts General Hospital (Boston, MA United States)
Pages:
23
Contract #:
W81XWH-04-C-0083
Abstract:
This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet. The project is in 3 phases: 1) hardware/software and interface development and end user training with a 200 case pilot study; 2) a 500 case prospective pilot study with hardware/software adjustment with the development of clinically applicable specimen triage and management guidelines; and 3) a 5000 case prospective clinical trial of the completed system with report and development of a training and operation manual. During this report pedod phase 2 patient accrual was completed at the Massachusetts General and Walter Reed sites. Modifications to the image acquisition and reading/reporting software have been completed. All phase 2 patients have been entered into the system and are ready for reading (which will take place by July 2008). Preliminary planning for phase 3 is near complete with IRB submissions planned for summer 2008.
Language:
English
Title:
Targeted Zinc Delivery: A Novel Treatment for Prostate Cancer
Document ID:
20090003570
Report #:
AD-A487473
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Baldassare, Joseph J
Published:
20080601
Source:
Saint Louis Univ. (MO United States)
Pages:
8
Contract #:
W81XWH-07-1-0289
Abstract:
At present, treatment for patients with advanced metastatic prostate disease or who progress to metastatic disease is limited. We proposed to initiate studies to develop and comprehensively evaluate targeted zinc loaded liposomes as a therapeutic for the treatment of men refractory to current treatment options. In the past year we have evaluated a number of zinc compounds and have shown that zinc acetate is suitable for entrapment into transferrin targeted liposomes. We have also developed a human xenograft model and have shown that intratumor injection of zinc solutions arrest the growth of the subcutaneous PC-derived tumors. This result is exciting and shows the potential of zinc as a prostate cancer therapeutic.
Language:
English
Title:
Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting an Engineered Tumor-Specific Immunotoxin
Document ID:
20090003585
Report #:
AD-A487516
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Patricia, Yotnda
Published:
20080601
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
10
Contract #:
W81XWH-07-1-0284
Abstract:
In this project we propose to use tumor-specific T cells to produce an immunotoxin (IT) targeting tumor cells only when these T cells are specifically activated by the tumor. We use lentiviral vectors to modify tumor specific T cells with our immunotoxin. PEA based immunotoxins affect cell viability by ADP ribozilation of their elongation factor-2. To produce high titer of vector encoding the IT we needed to generate a producer cell line resistant to PEA toxin. Several methods including the use of two mutated elongation factors drug and peptides blocking PEA effect were used to protect the producer cells from the lethal activity of the toxin thus increasing the production of proteins by these cells. We have established stable cell lines of PEA-resistant producer cells and showed that cells protected against PEA produced a significant higher amount of IT. Using these stable cell lines we will produce a high titer of IT-lentivirus preparation. We have also generated vectors encoding survival genes to further protect the producer cells as well as the IT-modified tumor-specific T cells.
Language:
English
Title:
Novel Breast Cancer Therapeutics Based on Bacterial Cupredoxin
Document ID:
20090003586
Report #:
AD-A487517
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Wittung-Stafshede, Pernilla
Published:
20080901
Source:
Rice Univ. (Houston, TX United States)
Pages:
61
Contract #:
W81XWH-06-1-0572
Abstract:
The tumor suppressor p53 is a major player in cell growth, genomic stability and cell death. Recent in vivo work suggested that bacterial Pseudomonas aeruginosa azurin can enter cancer cells and interact with p53 promoting cell death. Despite being a novel concept to target cancer, there are no thermodynamic details known for the proposed azurin-p53 complex. This project aims to fill this gap by employing biophysical methods in conjunction with purified proteins in vitro to address four aims. We will reveal (1) which p53 domain interacts with azurin, (2) the molecular mechanism by which azurin increases cellular levels of p53, (3) the region on azurin that interacts with p53 and (4) use the acquired information to propose smaller molecules that retain properties of azurin. We have found that azurin binds to the unstructured N-terminal domain of p53 and a small peptide is able to reproduce part of the azurin interaction. We have also assessed how Cu is metabolized inside cells as well has how the crowdedness of the cell milieu affects proteins. We have made several key discoveries that will aid in the development of azurin-based molecules that can be used as new treatments of cancer.
Language:
English
Title:
The Effect of Hypotensive Resuscitation and Fluid Type on Mortality, Bleeding, Coagulation and Dysfunctional Inflammation in a Swine Grade V Liver Injury Model
Document ID:
20090003589
Report #:
AD-A487524
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schreiber, Martin A
Published:
20080101
Source:
Oregon Health Sciences Univ. (Portland, OR United States)
Pages:
20
Contract #:
W81XWH-04-1-0104
Abstract:
To determine the optimal fluid resuscitation and anesthetic regimen for swine undergoing uncontrolled hemorrhage. Methods: 1. 37 swine at 3 institutions underwent femur fracture, controlled hemorrhage, hypothermia and resuscitation with normal saline and Grade V liver injury followed by 30 minutes of hemorrhagic shock without resuscitation. Animals were then randomized to controls, shams, whole blood, 1:1 PRBC:FFP, FFP alone and Hextend. Physiologic measurements and coagulation assays were compared between the 3 institutions. 2. 40 swine were randomized to receive midazolam and buprenorphine with either 1-3% isoflurane or IV ketamine (TIVA). Animals underwent a Grade V liver injury followed by 30 minutes of uncontrolled hemorrhagic shock and LR resuscitation to achieve and maintain a MAP of 65mmHg. Physiologic and inflammatory parameters were compared between groups. Results: 1. There was excellent reproducibility in all parameters measured between the 3 centers. Resuscitation with 1:1 FFP:PRBCs and whole blood resulted in significantly lower end of study lactate levels. End of study coagulation parameters were similar in all groups except the Hextend group which was significantly more coagulopathic than the other groups. 2. Mortality was significantly higher in animals receiving TIVA. Dysfunctional inflammation was significantly greater in animals receiving TIVA.
Language:
English
Title:
Charge Density Quantification and Antimicrobial Efficacy
Document ID:
20090003591
Report #:
AD-A487526, ARL-TR-4530
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Zander, Nicole Leadore, Julia Orlicki, Joshua A
Published:
20080801
Source:
Army Research Lab. (Aberdeen Proving Ground, MD United States)
Pages:
20
Contract #:
None
Abstract:
Emerging threats to soldiers on the battlefield include traditional dangers such as conventional weapons and chemical or biological warfare agents. A less obvious threat is represented by the growing numbers of serious bacterial and fungal infections. Reducing overall warfighter susceptibility to opportunistic infections would improve force readiness in all operational environments. The capability of a material to autonomous decontaminate in situ with an active additive is therefore highly desirable and may increase the warfighter's safety and reduce the logistical burdens associated with decontamination operations. However, to maintain the critical performance characteristics of the coating or fabric, a minimal amount of active material is preferred, reducing the overall impact on bulk physical properties.
Language:
English
Title:
EPR Assembly of Microgel for FRET Imaging of Breast Cancer
Document ID:
20090003601
Report #:
AD-A487569
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Stein, Stanley
Published:
20080401
Source:
Rutgers - The State Univ. (New Brunswick, NJ United States)
Pages:
14
Contract #:
W81XWH-05-1-0342
Abstract:
The purpose of this project is to develop a method to detect breast cancer with greatest possible accuracy at smallest possible size. The method should give least stress and inconvenience to the patient. We have proposed to combine different techniques into a three-step process to accomplish this goal. 1) The first goal is to place a marker on tumor. For this purpose, we will use the enhanced permeability and retention (EPR) effect1-3, which might be universal for all tumors. The markers developed herein will be optimized for their ability to accumulate in tumor but not in normal tissues. We propose to use polymer-5 -PNA (peptide nucleic acid)(4-6) conjugates that will accumulates in tumors due to the EPR effect. 2) The second goal is target the signaling moiety selectively to the tumors. This is to be accomplished by using dye-labeled complementary PNA sequence. This complementary sequence will have minimal retention in the body or tumors on account of its smaller size. However, in this case, the dye-labeled PNA conjugates will be retained in tumors because of the Watson-Crick base pairing between the complementary PNA sequences. The specific base pairing between the complementary sequences will link the signaling (dye) moiety to polymer-PNA:complementary-PNA-dye complex. 3) The third goal is to detect the signal non-invasively.
Language:
English
Title:
Estrogen Metabolism and Prostate Cancer Risk: A Prospective Study
Document ID:
20090003603
Report #:
AD-A487572
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Muti, Paola
Published:
20080501
Source:
Istituto Superiore di Sanita (Rome, Italy)
Pages:
33
Contract #:
DAMD17-03-1-0315
Abstract:
Prostate cancer is the most common cancer among men in the United States (IARC 1995) and the second most common in the European Community (IARC 1995). The causes of prostate cancer however remain largely unknown with age race and family history being the only established risk factors (Nomura et al. 1997). The prostate gland has historically been considered the prototype of an androgen-dependent organ. However there is evidence that estrogens may induce mitosis of prostatic epithelial cells in many species including humans (Leave et al. 1978; Schulze et al. 1987). This report analyzes the association between prostate cancer and estrogen metabolism investigated in a case-control study. In particular we tested the hypothesis that the pathway favoring 2-hydroxylation over 160-hydroxylation may be associated with a decrease in prostate cancer risk. This is the final report for the study. During the final year of activity we completed determinations of the estrogen metabolites using gas-chromatography and carried out statistical analysis. We have also prepared an article for publication of the results.
Language:
English
Title:
Inhibition of Rac GTPases in the Therapy of Chronic Myelogenous Leukemia
Document ID:
20090003608
Report #:
AD-A487594
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Cancelas, Jose
Published:
20080401
Source:
Children's Hospital Medical Center (Cincinnati, OH United States)
Pages:
77
Contract #:
W81XWH-07-1-0297
Abstract:
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) characterized by the expression of the p210-BCR/ABL fusion gene [1]. This gene is produced by the reciprocal translocation (9; 22) (q34; q11) that juxtaposes the 3 end of Abelson leukemia virus (ABL) gene with the 5 end of the breakpoint cluster region (Bcr) gene on chromosome 22. The transcript formed as a result encodes for the BCR/ABL fusion protein with constitutively active tyrosine kinase activity [2-6]. Recent studies with inducible BCR/ABL transgenic mice showed that expression of BCR/ABL in hematopoietic stem cells and progenitors (HSC/P) is required and is sufficient to induce MPD [7]. If untreated, chronic phase (CP) CML patients progress to a poor-prognosis myeloid or lymphoid blastic phase (BP). The only curative treatment for CML is allogeneic HSC transplantation. The long-term survival rate for this procedure is approximately 65%, however, the procedure is only available to a minority of CML patients due to a lack of compatible donors and age [8-10]. Imatinib is an ABL kinase inhibitor that shows significant activity in CP CML and Ph-positive acute leukemias [11]. By selective induction of apoptosis of BCR/ABL-positive cells [12-14], it provides an effective treatment in CML and has rejuvenated the field of rationalized drug design. The selective inhibitory activity of imatinib toward BCR/ABL has been associated with three problems: the emergence of BCR/ABL mutants in the kinase domain that confer resistance to imatinib; the evidence that CML stem cells are the least vulnerable to ABL-targeted therapy and may serve as reservoirs for occult CML progression; and the relatively low impact of imatinib therapy on the outcome of BP CML patients. Resistance to imatinib has an incidence of 4% annually.
Language:
English
Title:
The Efficacy of Dextroamphetamine as a Motion Sickness Countermeasure for the Use in Military Operational Environments
Document ID:
20090003614
Report #:
AD-A487648, NAMRL-TR-08-09
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Simmons, Rita G Phillips, Jeffrey B Lawson, Benton D Lojewski, Renee A
Published:
20080709
Source:
Naval Aerospace Medical Research Lab. (Pensacola, FL United States)
Pages:
36
Contract #:
NAVCOMP-2189
Abstract:
Previous research examining pharmacological solutions for motion sickness have reported that dextroamphetamine (d-amphetamine) imparts significant protection against provocative motion without conferring drowsiness or significant side effects. If the purported anti-motion sicknesses properties of d-amphetamine are accurate, the military could utilize a single medication for motion sickness and fatigue prevention. The purpose of this study was to determine the efficacy and side effect profile of this potential motion sickness countermeasure for use in military environments. It was hypothesized that subjects in the oral d-amphetamine condition would tolerate more head movements than subjects in the placebo condition, without performance decrements or significant side effects. Thirty-six aviation candidates were randomized to one of two treatment groups and then exposed to passive Coriolis cross-coupling. Medication efficacy was determined by number of head movements tolerated between groups. Cognitive and medication side-effect profiles for both groups were derived from performance on a computer based cognitive battery, measurements of near-focus visual accommodation (VA), scores on the Karolinska Sleepiness Scale (KSS), and motion sickness questionnaires. Analyses demonstrated that there were no significant differences in the number of head movements tolerated between groups and no treatment effects over time on the cognitive battery, VA, or KSS, p > 0.05.
Language:
English
Title:
Bioenergetic Approaches and inflammation of MPTP Toxicity
Document ID:
20090003741
Report #:
AD-A490306
Available Online:
http://hdl.handle.net/100.2/ADA490306
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Beal, M F
Published:
20080901
Source:
New York Hospital-Cornell Medical Center (New York, NY United States)
Pages:
13
Contract #:
W81XWH-04-1-0802
Abstract:
We are continuing to examine a number of neuroprotective agents in an MPTP model of PD. We are also continuing to utilize metabolomic profiling to identify novel biomarkers for PD and to investigate whether these occur in animal models of PD. We are continuing to develop and characterize a new animal model of PD by making a knock out of PlNK1, a nuclear encoded kinase localized to mitochondria, and which causes autosomal recessive PD. We have completed a study of the effects of human dopaminergic stem cells in a 6-hydroxy dopamine model of PD.
Language:
English
Title:
Copine-I: Modulator of NF-kappa B Transcription and Prostate Cancer Survival
Document ID:
20090003745
Report #:
AD-A490321
Available Online:
http://hdl.handle.net/100.2/ADA490321
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Mayo, Marty W Creutz, Carl
Published:
20080101
Source:
Virginia Univ. (Charlottesville, VA United States)
Pages:
73
Contract #:
W81XWH-06-1-0186
Abstract:
The purpose of our studies is to elucidate how Copine-I antagonizes NF-.B transcription. Nuclear factor-.B (NF-.B) is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. Identifying regulators that control the half-life of NF-.B is important to understanding molecular processes that control the duration of transcriptional responses. In this study we identify Copine-I, a calcium phospholipid-binding protein, as a novel repressor that physically interacts with p65 to inhibit NF-.B transcription. Knockdown of Copine-I by siRNA increases tumor necrosis factor a-stimulated NF-.B transcription, while Copine-I expression blocks endogenous transcription. Copine-I abolishes NF-.B transcription by inducing endoprotease processing of the N-terminus of p65, a process antagonized by I.Ba. Copine-I stimulates endoproteolysis of p65 within a conserved region that is required for base-specific contact with DNA. p65 proteins lacking the N-terminus fail to bind to DNA and act as dominant-negative molecules that inhibit NF-.B transcription. Our work provides evidence that Copine-I regulates the half-life of NF-.B transcriptional responses through a novel mechanism that involves endoproteolysis of the p65 protein. Copine has significance as a potential biomarker for therapeutic intervention in prostate cancer.
Language:
English
Title:
Alcohol-Related Aviation Accidents Involving Pilots With Previous Alcohol Offenses
Document ID:
20090003748
Report #:
AD-A490324, DOT/FAA/AM-08/22
Available Online:
http://hdl.handle.net/100.2/ADA490324
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Botch, Sabra R Johnson, Robert D
Published:
20081001
Source:
Federal Aviation Administration (Oklahoma City, OK United States)
Pages:
14
Contract #:
None
Abstract:
The Federal Aviation Administration (FAA) requires airmen to report legal actions involving ethanol and/or other drugs, including driving while impaired by or while under the influence of alcohol. Pilots are also required to report any administrative action resulting in denial, suspension, cancellation, or revocation of driving privileges or mandatory attendance at an educational or rehabilitation program. The purpose of this study was to evaluate fatal civil aviation accidents between the years 2000 and 2007 in which ethanol was present in the pilot, and the pilot had previously documented drug and/or alcohol offenses and/or dependence. Toxicological and aeromedical findings from pilots were collected for an 8-year period, 2000 - 2007. Case histories, accident information, and the probable cause of the accidents were obtained from the National Transportation Safety Board. Toxicological information was obtained from the Civil Aerospace Medical Institute's Forensic Toxicology Research Laboratory. During the examined time period, 215 pilots (9%) of the 2,391 received for analysis had documented alcohol- or drug-related offenses. Of the 215 pilots, 23 (11%) had consumed ethanol prior to the fatal incident. Of these 23 pilots, 16 (~70%) had ethanol concentrations above the FAA's legal limit of 40 mg/dL and 7 (~30%) between 20 and 40 mg/dL. Providing more detailed documentation to aviation medical examiners would aid in the determination of eligibility for medical certification and could potentially save pilots as well as their passengers' lives. Identifying pilots with substance abuse problems is paramount for providing a safe environment to fly but also benefits the pilots who may not have addressed these issues.
Language:
English
Title:
Development of Nanomechanical Sensors for Breast Cancer Biomarkers
Document ID:
20090003750
Report #:
AD-A490342
Available Online:
http://hdl.handle.net/100.2/ADA490342
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Erramilli, Shyamsunder
Published:
20080601
Source:
Boston Univ. (Boston, MA United States)
Pages:
22
Contract #:
W81XWH-04-1-0578
Abstract:
Nanotechnology has the potential to develop silicon-based arrays for sensing biomarkers associated with breast cancer. In order to develop patient-specific therapy tailored for each individual parallel detection of a large number (`103-104) biomarkers may be required. The experience of the semiconductor industry in developing large scale integrated circuits at very lost cost can lead to similar breakthroughs in array sensors for biomolecules of interest to the breast cancer community. Nanotechnology can meet the need for high throughput sensitive methods for rapidly recording biomarker profiles of tumors in individual patients. We report results on the development of arrays of conductance sensors of biofunctionalized silicon nanowires. The fractional change is greatest for the smallest sensors due to the increased surface-to-volume ratio. The fabrication of arrays of conductance based sensors has now been done and the nanosensors have been characterized using model systems. This work sets the path for translation of the fabricated sensors to breast cancer clinical practice.
Language:
English
Title:
Wave Reflection and Central Aortic Pressure Are Increased in Response to Static and Dynamic Muscle Contraction at Comparable Workloads
Document ID:
20090003754
Report #:
AD-A490380, USARIEM-M-07-29
Available Online:
http://hdl.handle.net/100.2/ADA490380
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Edwards, David G Mastin, Corey R Kenefick, Robert W
Published:
20080201
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
8
Contract #:
None
Abstract:
Wave reflection and central aortic pressure are increased in response to static and dynamic muscle contraction at comparable workloads. We determined the effects of static and dynamic muscle contraction at equivalent workloads on central aortic pressure and wave reflection. At random, 14 healthy men and women (23 +/- 5 yr of age) performed a static handgrip forearm contraction [90 s at 30% of maximal voluntary contraction (MVC)], dynamic handgrip contractions (1 contraction/s for 180 s at 30% MVC), and a control trial.
Language:
English
Title:
CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer
Document ID:
20090003757
Report #:
AD-A490383
Available Online:
http://hdl.handle.net/100.2/ADA490383
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Tanaka, Yuichiro
Published:
20080601
Source:
Northern California Inst. for Research and Education (San Francisco, CA United States)
Pages:
16
Contract #:
W81XWH-04-1-0579
Abstract:
We utilized 97 healthy, 77 benign prostatic hyperplasia (BPH) and 156 prostate cancer (PC) samples that are pre-existing from African-American and Caucasian patients. Due to human subjects issues, the project has been on hold from Dec 2005 till Jan 2008 and thus, results reported are based on a period of approximately two years. In the first hypothesis, we have determined CYP1B1 protein to belocalized to the cytoplasm of PC cells, with levels being much higher in PC than BPH. In the second hypothesis, single nucleotide polymorphisms (SNPs) of CYP1B1 have been evaluated to determine if they are risk factors for race-related PC. Racial differences are observed in allele frequencies as the variant at codons 119 and 432 are greater among Blacks (P<0.001) whereas the 453 variant is predominant in Whites (P<0.001). Within race, a case-control study show the variant at codon 453 plays a protective role for PC among Blacks (P<0.05). Interestingly, SNPs at codons 432 and 449 are determined to be linked and the 432G-449C haplotype was observed to be a risk for PC (P<0.05). In a sampling of cases, no differences were observed between stages (<T2c vs >T2c) and grades (<7 vs >7) of PC in either race. A no-cost extension has been submitted for the 3rd year for which continuation of SNP studies with additional samples to be collected; as well as further experimentation with aim #1 to be performed.
Language:
English
Title:
The Role of the Co-Chaperone, CHIP, in Androgen Independent Prostate Cancer
Document ID:
20090003761
Report #:
AD-A490397
Available Online:
http://hdl.handle.net/100.2/ADA490397
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Hassen, Waleed A
Published:
20080201
Source:
Mount Sinai School of Medicine (New York, NY United States)
Pages:
10
Contract #:
W81XWH-06-1-0285
Abstract:
Expression of Chip, a Co-Chaperone Which Interacts with the Androgen Receptor, Results in Loss of AR Expression and Growth Inhibition of Prostate Cancer Cells Waleed Hassen, Xiaoyoung Zheng, Antonio Otero, Erwin Wang, Yuancheng Wang, Sherwin Zargaroff, Jian Pu, Mary Kunjappu, Avrom Caplan and Simon Hall Mount Sinai School of Medicine, New York Introduction and Objectives: Earlier studies in our laboratory and others have demonstrated that over-expression of a co-chaperone, CHIP, an E3 ligase which interacts with HSP-70/90, results in degradation of the androgen receptor (AR) (Cardozo et al, Arch Biochem Biophy, 2003 and He et al, JBC, 2004) Furthermore, it has been shown that CHIP binds directly to a highly conserved sequence on the AR to facilitate degradation. Mutations in this sequence are commonly identified in hormone refractory cancers from TRAMP mice (He et al, JBC, 2004), which result in prostate cancers when over-expressed in a transgenic model (Han et al, PNAS 2005). This suggests that CHIP may have important functions in the homeostatic mechanisms underlying AR function in prostate cancer. These studies explored the outcomes of CHIP over-expression in prostate cancer cells. Methods: CHIP over-expression was achieved by either lipofectamine or adenovirus mediated transduction; the latter contained a tetracycline control mechanism (tet-off). Studies first focused on AR levels by Western blot and effects on growth by either cell counts or MTT assays. Reduction in AR function was addressed by hormone binding studies, while the mechanism of growth suppression was detected by ascertaining cell cycle status via proprium iodide and FACS analysis. Results: By either method, CHIP over-expression resulted in both reduced levels of AR and growth suppression of only AR-expressing cells. Hormone binding studies in AR expressing cells noted reduced levels of hormone binding following CHIP over-expression, correlating with the reduced levels noted by Western blot.
Language:
English
Title:
Regulation of the Inflammasome, a Modulator of Caspase-Mediated Cytokine Production
Document ID:
20090003762
Report #:
AD-A490403
Available Online:
http://hdl.handle.net/100.2/ADA490403
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schmitz, Karl R
Published:
20080701
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
11
Contract #:
W81XWH-06-1-0518
Abstract:
Tissue inflammation and inflammatory cytokines can positively affect breast cancer prognosis. By providing a detailed understanding of the mechanism of inflammasome formation and activation, we hope to create the potential for novel inflammation based cancer therapies. The protein, NALP, forms the core of the inflammasome complex. The chief domains of NALP do not express well in bacterial or insect cell expression systems, exhibiting poor expression levels and solubility. The NALP pyrin domain has been successfully produced and purified, and initial crystals of this protein have been produced. Constructs of the adaptor CARDINAL were found to express well, but suffer proteolysis during purification. Full-length constructs of NALP have been produced by baculovirus/SF9 expression; have been observed to exist in monomer/oligomer equilibrium in solution.
Language:
English
Title:
Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy
Document ID:
20090003764
Report #:
AD-A490413, W81XWH-05-1-0566
Available Online:
http://hdl.handle.net/100.2/ADA490413
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Huang, Chung-Ying
Published:
20080901
Source:
Hutchinson (Fred) Cancer Research Center (Seattle, WA United States)
Pages:
22
Contract #:
None
Abstract:
Patients with high-risk localized prostate cancer have a high recurrence rate following primary therapy. Neoadjuvant chemotherapy has been shown to be beneficial in reducing recurrence rates in some tumor types, but has yet to be of proven benefit in prostate cancer. We utilized tissue resources from a phase II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone in patients with high-risk localized prostate cancer to identify molecular alterations after chemotherapy, and correlated these alterations with clinical indicators of tumor response. A chemotherapy-induced profile was generated by a direct comparison of expression changes between pre-treatment and post-treatment cancerous epithelia from prostate. After excluding genes previously shown to be influenced by the radical prostatectomy procedure, we identified 51 genes with significant transcript level alterations following chemotherapy. This group included several cytokines including GDF15, IL8, CXCL10, IL1B, and CCL2. In vitro analyses confirmed overexpression of GDF15 may confer resistance to chemotherapy in prostate cancer cells. Gene expression changes after chemotherapy were further correlated with clinical outcomes including percentage of PSA decline and PSA-relapse free survival. Several chemokines and chemokine pathways were found to be associated with the percentage of PSA decline. Expression changes of IL8 and CXCL10 measured by qRT-PCR were significantly and negatively associated with the percentage of PSA decline. Further, in vitro tests showed only IL1B influenced chemosensitivity of prostate cancer cells. When correlating expression profiles with PSA-relapse free survival, we found patients with a positive post-chemotherapy change in the expression of monoamine oxidase A (MAOA) have higher risk to have a PSA relapse compared with patients with negative post-chemotherapy MAOA expression change.
Language:
English
Title:
Multifunctional Nanocomposites for Breast Cancer Imaging and Therapy
Document ID:
20090003765
Report #:
AD-A490418
Available Online:
http://hdl.handle.net/100.2/ADA490418
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Gayen, Swapan K Balogh-Nair, Valeria
Published:
20080701
Source:
City Univ. of New York (NY United States)
Pages:
17
Contract #:
W81XWH-06-1-0620
Abstract:
The objective of the research was to explore the feasibility of concomitant detection and of breast cancer through the development of multifunctional nanocomposites that will enable early detection of breast tumors, visualization of dormant metastatic cells and prevent their spread. Fluorescent nanocomposites consisting of CdS and PbS quantum dots (QDs) encapsulated in dendrimers, a class of organic macromolecules, were synthesized, and their optical absorption spectra, emission spectra, and fluorescence lifetime were measured. The CdS-based nanocomposites fluoresced in the visible, and PbS-based nanocomposites fluoresced in the near-infrared spectral regions. Optical imaging experiments demonstrated the potential for using these nanocomposites as contrast agents. Three chemokine mimics were synthesized and a toxicity study carried out under a collaborative arrangement showed that none of the mimics to be toxic to MDA MB 468 breast cancer cell lines. Attempts were made to conjugate a chemokine to PbS-dendrimer nanocomposite surface.
Language:
English
Title:
Novel Serum Inflammatory Biomarkers for Early Detection of Breast Cancer
Document ID:
20090003766
Report #:
AD-A490428
Available Online:
http://hdl.handle.net/100.2/ADA490428
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Brown, Thomas R
Published:
20080601
Source:
Oxford Biomedical Research, Inc. (Rochester Hills, MI United States)
Pages:
10
Contract #:
W81XWH-06-1-0711
Abstract:
Proteins that are post-translationally modified by reactive oxygen and nitrogen species (ROS/RNS) have relevance to disease including cancer however, their study as a source of cancer biomarkers is still at a relatively early stage. Identifying these biomarkers in serum presents a difficult task given the vast range of protein concentrations. To alleviate this problem two enrichment strategies that precede analysis are emerging. The first is removal of high abundance proteins and the second, enrichment of the adducted proteins using immunopurification with antibodies developed against specific protein adducts. Using the latter approach, we isolated and identified four NT-containing proteins unique to the serum of breast cancer patients: obscurin, nucleoprotein, fibrinogen gar and fibrinogen bet. The potential impact of this work is that first, it provides a methodological template for the purification and further study of post-translationally-modified proteins and secondly, through the development of assays to monitor these biomarkers in the serum of cancer patients, it has the potential to present the physician an opportunity for more timely therapeutic intervention by providing improved diagnostic capability with use of early disease biomarkers. This should result in improving long term survival which is highly relevant to the goals of the Era of Hope.
Language:
English
Title:
Sonic Hedgehog Signaling in Normal Prostate Stem Cells and Prostate Cancer Stem Cells
Document ID:
20090003768
Report #:
AD-A490432
Available Online:
http://hdl.handle.net/100.2/ADA490432
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Levine, Charles
Published:
20080101
Source:
New York Univ. (New York, NY United States)
Pages:
19
Contract #:
W81XWH-07-1-0123
Abstract:
As an approach to identify potential Shh-responding stem cells in the mouse prostate, we used Genetic Inducible Fate Mapping (GIFM) to follow the fate of Shh-responding cells both during prostate development and during androgen-mediated regeneration of the gland in the adult, two processes that are driven by stem or progenitor cell expansion. As Gli1 expression is a sensitive readout of Shh signaling, we used a Gli1CreER allele and Rosa26 reporter to fate map Shh-responding cells. We show that Shh-responding cells do not expand over time in the normal homoeostatic prostate, but these same cells do expand massively after androgen-mediated regeneration, indicating that Shh-responding cells are normally quiescent, but retain the ability to expand in the adult prostate. The expansion of cells is confined to stromal fibroblasts and smooth muscle cells; no glandular epithelial cells are marked. These results indicate that Gli1 either specifically marks stromal stem cells that expand during regeneration to give rise to the two stromal cell types, or that fibroblasts and smooth muscle cells in general have a high capacity for proliferation even in the adult prostate. To determine whether the marked Shh-responding cells have the capacity for selfrenewal, we subjected Gli1CreER ; Rosa26 mice to eight cycles of prostate involution and regeneration. Cells marked before castration expand after 8 cycles of involution/regeneration, indicating that the initially marked Shh-responding cells are self-renewing. Additionally, using Gli1 null mutant mice, we demonstrate that Gli1 is required to drive stromal expansion during prostate regeneration. Based on our results, we propose a model wherein Shh is expressed in adult prostate epithelial cells, the signal is received by the adjacent stroma, which responds by expressing critical genes, including the transcription factor Gli1, that result in expansion of the two stromal cell types.
Language:
English
Title:
Characterization of the Role of Breast Tumor Kinase (Brk) in Breast Cancer Cells Non-Responsive to EGFR-Targeted Agents
Document ID:
20090003769
Report #:
AD-A490442
Available Online:
http://hdl.handle.net/100.2/ADA490442
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nimnual, Anjaruwee S
Published:
20080701
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
11
Contract #:
W81XWH-05-1-0448
Abstract:
Epidermal growth factor (EGF) receptor tyrosine kinases (erbB family), EGFR (erbB1) and HER2, are highly expressed in breast cancer and are associated with poor prognosis. A number of EGFR and/or HER2-targeted agents are being investigated for breast cancer treatment. Brk (Breast Tumor Kinase) is a nonreceptor tyrosine kinase that has been shown to enhance the mitogenic signaling of EGF, induce phosphorylation of erbB 3 and interact with AKT. In this study, we aim to investigate whether Brk can promote cells to become refractory to EGFR-targeted drugs. Pl-3 kinase/AKT pathway mediates EGF-induced cell growth and survival and is involved in cellular resistance to anti-cancer drugs. Because the P13K/AKT pathway is regulated by multiple activators, downregulation of the EGFR alone may not lead to its inhibition. We will investigate whether Brk promotes growth and survival as well as Pl3K/AKT activity in cells treated with EGFR-targeted agents.
Language:
English
Title:
NKX3.1 Genotype and IGF-1 Interact in Prostate Cancer Risk
Document ID:
20090003772
Report #:
AD-A490467
Available Online:
http://hdl.handle.net/100.2/ADA490467
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Gelmann, Edward P
Published:
20080501
Source:
Columbia Univ. (New York, NY United States)
Pages:
17
Contract #:
W81WXH-07-1-0263
Abstract:
NKX3.1 is a prostate-specific homeobox gene that maps to chromosome 8p21, the most frequent target for loss of heterozygosity in prostate cancer. NKX3.1 is a haploinsufficient tumor suppressor in the prostate. We found that IGFBP-3expression was activated 10-fold by NKX3.1 in cell lines and tissues. IGFBP-3 is an inhibitor of IGF-1, a serum component that when elevated is a risk factor for prostate cancer. NKX3.1 expression inhibits IGFIR signaling and diminishes IRS-1 phosphorylation. Knock down of IGFBP-3 attenuates the growth suppressive effects of NKX3.1. NKX3.1 C154T is a polymorphic allele present in ~10% of the population. The polymorphic allele codes for a variant protein that replaces arginine 52 with cysteine. NXK3.1 C154T confers a minimally increased risk for prostatic enlargement and for prostate cancer. In a cohort of cases and controls with known NKX3.1 genotype we found that the effect of serum IGF-1 on prostate cancer risk was seen only in men with at least one polymorphic NKX3.1allele. Consistent with its apparent interaction with IGF-1 in prostate cancer risk, NKX3.1 R52C protein is attenuated in activation of IGFBP-3. The data therefore show that the two prostate cancer risk factors, NKX3.1 R52C and circulating IGF-1 interact. NKX3.1 R52C activates less IGFBP-3 expression than its wild type counterpart and thereby predisposes prostate epithelial cells to the proliferative and antiapoptotic effects of IGF-1, increasing the risk for prostate cancer.
Language:
English
Title:
Cell Therapy to Obtain Spinal Fusion
Document ID:
20090003773
Report #:
AD-A490469
Available Online:
http://hdl.handle.net/100.2/ADA490469
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Olmsted-Davis, Elizabeth A Davis, Alan R Heggeness, Michael Gannon, Francis Dickinson, Mary Hipp, John West, Jennifer
Published:
20080701
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
18
Contract #:
W81XWH-07-1-0281
Abstract:
Surgery of the spine to fuse the vertebral bones is one of the most commonly performed operations with an estimated 350,000 Americans undergoing this surgery annually with estimated costs of $60 billion. Current procedures are highly invasive with limited success. The goal of this study is to develop a safe efficacious system for inducing spine fusion which will eliminate the need for invasive surgery. We have currently developed a cell based gene therapy system that can induce rapid bone formation at a targeted location which is independent of immune status of the model. This system relies on adenovirus transduced cells expressing bone morphogenetic protein 2 to induce bone formation leading to vertebral fusion after delivery into the paraspinous musculature. To prolong cell survival and insure cells are maintained at the target site, we have encapsulated them in a non-degradable hydrogel material. This provides additional safety by eliminating direct injection of the virus through cell delivery, and prevention of cell diffusion, through encapsulation. Here we provide preliminary data; demonstrating spine fusion using this system at 6 weeks after induction. This is the first step in demonstrating efficacy, a critical component of preclinical testing. Thus with validation of our hypothesis, this approach can now be developed as a safe and efficacious gene therapy system for spine fusion, thus circumventing the need for costly invasive surgery.
Language:
English
Title:
The Cadherin Interaction as a Rate Limiting Step in Breast Cancer Metastasis to the Liver
Document ID:
20090003774
Report #:
AD-A490478
Available Online:
http://hdl.handle.net/100.2/ADA490478
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chao, Yvonne
Published:
20080301
Source:
Pittsburgh Univ. (Pittsburgh, PA United States)
Pages:
10
Contract #:
W81XWH-06-1-0403
Abstract:
Our overall objective is to identify molecular elements that enable breast cancer cells to establish metastatic growths. Finding rationale approaches to inhibit rate-limiting events of the metastatic growth is preferable to using systemic therapeutics that are cytotoxic on a systemic level. Cadherins make up a family of adhesion molecules that mediate Ca2+-dependent cell-cell adhesion at points of cell-cell adhesion. Epithelial-cadherin (E-cadherin), the prototype classical cadherin present on the surface of most epithelial cells, has a cytoplasmic domain that anchors the cell adhesion molecule to the actin cytoskeleton via catenin-based complexes. It is generally considered that E-cadherin directs homotypic binding, organizing cells of the same lineage into a functional tissue during morphogenesis. Thus, E-cadherin is central to epithelial cell differentiation and suppress ion of proliferation and migration. Finding E-cadherin downregulated or even lost in invasive and metastatic carcinomas buttressed this role of E-cadherin in modulating the epithelial phenotype [3]. It has been hypothesized that loss of E-cadherin allows individual tumor cells to break from the primary tumor mass at the same time as enabling autocrine pro-proliferative and migratory signaling to ensue from receptors and ligands physiologically separated by cell polarity and the E-cadherin-based tight junctions. This was supported experimentally when poorly differentiated and invasive carcinoma cells could be made less so by transfection with E-cadherin cDNA, with well-differentiated carcinomas becoming more aggressive when antibodies blocked. This supported a designation as a tumor suppressor, even placing E-cadherin at the apex of a tumor suppressor system. More recent reports of E-cadherin being expressed at the site of metastatic foci in the liver, lung and lymph nodes have caused reconsideration of E-cadherin downregulation as required for tumor dissemination.
Language:
English
Title:
Erythropoietin and Breast Cancer
Document ID:
20090003775
Report #:
AD-A490481
Available Online:
http://hdl.handle.net/100.2/ADA490481
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sytkowski, Arthur J
Published:
20080301
Source:
Beth Israel Deaconess Medical Center (Boston, MA United States)
Pages:
12
Contract #:
W81XWH-06-1-0737
Abstract:
Erythropoietin (Epo) is the prime regulator of red blood cell production, principally by mean of "anti-apoptotic" action. Epo also acts on other cells and tissues outside of the hematopoietic system, including endothelium, central nervous system, reproductive system and gut. Epo receptors (EpoR) have also been identified on breast cancer (CaB), and there is an in vitro study suggesting that these EpoR on CaB cell lines may be functional. The presence of functional EpoR on cancer cells is of concern since Epo is used to treat anemia associated with chemotherapy and to improve tumor oxygenation for radiotherapy. This concern was heightened when a trial of Ego in CaB patients was terminated early due to decreased survival in the Epo-treated group. Since CaS patients receive Ego therapy, an anti-apoptotic effect of Ego on CaS cells would have adverse consequences. It is of vital importance to determine the functionality of the EpoR on CaB cells in vivo. We screened CaB lines for Egoo ezpression and used siRNA technology to develop lines that had reduced EgoR. Reduction of EgoR resulted in a significant reduction in cell growth in vitro. These results may have profound implications for the mangement of breast cancer patients.
Language:
English
Title:
Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity
Document ID:
20090003776
Report #:
AD-A490497
Available Online:
http://hdl.handle.net/100.2/ADA490497
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Diamond, Betty
Published:
20080701
Source:
North Shore-Long Island Jewish Research Inst. (Manhasset, NY United States)
Pages:
14
Contract #:
W81XWH-07-1-0327
Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE it is clear that increased or sustained high physiologic levels of estradiol can accelerate onset of disease and exacerbate disease severity. We have shown that estradiol alters B cell maturation in vivo but does so in a genetically restricted fashion. We have also shown that estradiol can act directly on B cells to alter B cell receptor (BCR) signalling strength. This proposal is to understand which estrogen receptors mediate the effects of estradiol on B cell survival maturation and activation in order to assess whether hormonal manipulation has a potential therapeutic role in SLE. The proposal is further designed to ask why estradiol affects B cell function in mice of one genetic background but not another.
Language:
English
Title:
Immune Function During and After 60 min of Moderate Exercise Wearing Protective Clothing
Document ID:
20090003778
Report #:
AD-A490511, USARIEM/TMMD-M08-21
Available Online:
http://hdl.handle.net/100.2/ADA490511
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Jimenez, Chantal Mathieu, Jacques Peinnequin, Andre Carter, III, Robert Alonso, Antonia Melin, Bruno
Published:
20080601
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
8
Contract #:
None
Abstract:
As exercise while wearing protective clothing exacerbates body heat storage, compared to exercise in the heat, and as exercise alters immune responses, it appeared interesting to examine immune and stress responses while wearing protective clothing during moderate exercise. Methods: Eight subjects completed two bouts of exercise at 45% VO2 max in a thermo neutral environment: once while wearing shorts only (Control trial, CON) and again while wearing protective clothing (PRO). Venous blood samples were taken to analyze TNF-a mRNA by RT-PCR in LPS simulated blood, plasma catecholamines, and cortisol. Blood cell count was analyzed by flow cytometry. Rectal temperature (Tre) was monitored continuously.
Language:
English
Title:
Simulations to Evaluate Accuracy and Patient Dose in Neutron-Stimulated, Emission-Computed Tomography (NSECT) for Diagnosis of Breast Cancer
Document ID:
20090003788
Report #:
AD-A490591
Available Online:
http://hdl.handle.net/100.2/ADA490591
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kapadia, Anuj J
Published:
20080401
Source:
Duke Univ. (Durham, NC United States)
Pages:
100
Contract #:
W81XWH-06-1-0484
Abstract:
We are developing a tomographic technique called Neutron Stimulated Emission Computed Tomography (NSECT) for early detection of breast cancer. NSECT is sensitive to metabolic changes in trace element concentrations that are seen in tumors at very early stages of development. Detecting and measuring these element concentrations has the potential to detect breast cancer very early. Using neutrons as the imaging radiation leads to significant concerns about patient dose due to their higher weighting factor. While preliminary experiments show that it is possible to perform NSECT scans with patient dose comparable to mammography, one of the key aspects of successful clinical translation is to deliver the minimum dose possible. This project aims at evaluating the effects of NSECT dose-reduction techniques on the accuracy of detecting breast cancer. Four dose-reduction techniques are under evaluation: reducing neutron flux; reducing spatial projections; reducing angular positions; and using multiple detectors. As separate evaluation of each factor using experimental studies is prohibitively time consuming, these evaluations are performed using Monte-Carlo simulations as a feasible alternative. In the first year of the study, we developed a Monte Carlo simulation of the NSECT tomographic scanning system in GEANT4 along with phantoms of benign and malignant breast tissue. The simulated system has now been used to generate simulated data from NSECT scans of the benign and malignant breast. The simulations have been tested and validated against experimentally acquired data from several different types of phantoms. Tomographic images are reconstructed using a maximum-likelihood algorithm, which has been used to generate diagnostic images of a single-element disease model based on iron distribution. These results demonstrate that NSECT has the ability to detect cancer-marking elements in the breast at reasonable levels of patient dose.
Language:
English
Title:
A Search for New Therapeutic Targets: Using Yeast to Find the GEF for Rheb
Document ID:
20090003791
Report #:
AD-A490603
Available Online:
http://hdl.handle.net/100.2/ADA490603
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Leatherwood, Janet
Published:
20080701
Source:
State Univ. of New York (Stony Brook, NY United States)
Pages:
6
Contract #:
W81XWH-07-1-0358
Abstract:
The Tsc1/2 complex known as Hamartin/Tuberin is mutated in the human disease Tuberous Sclerosis and such mutation predisposes for cancer. Tsc1/2 complex has a clearly established chemical release a GTPase Activating Protein or GAP for the small GTPase Rheb. Rheb in turn regulates TOP. The Tor kinases and associated proteins are large complex units that integrate signals pertaining to nutrients and proliferation potential. Tor promotes growth and proliferation and thus de-regulation of Tor is implicated in carcinogenesis and disease. We have worked toward development of a simple genetically tractable model system for understanding of the Tsc1/2 pathway. Our particular interest is in finding factors that work in opposition to Tsc1/2. Typical GTPases such as the Tsc1/2 target Rheb are controlled by both negative regulators (GAPS) and positive regulators known as guanine nucleotide exchange factors or GEFS. Our most important progress has been to establish functional screens for GEF type activators of the Rheb signalling factor in the simple yeast Schizosaccharomyces pombe.
Language:
English
Title:
The Loss of Pin1 Deregulates Cell Cycle Progression and Promotes the Development of Breast Cancer
Document ID:
20090003795
Report #:
AD-A490639
Available Online:
http://hdl.handle.net/100.2/ADA490639
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Lew, Brian
Published:
20080701
Source:
Duke Univ. (Durham, NC United States)
Pages:
11
Contract #:
W81XWH-06-1-0442
Abstract:
Pin1 regulates many factors that are relevant to breast cancer, such as c-Jun, c-Myc, cyclin D1, and cyclin E. However the function of Pin1 in a normal cell is still poorly understood. Thus the role of Pin1 in G0/G1 to S-phase progression of the cell cycle was examined in this research project. The most significant finding was that Pin1 appears to be a novel regulator of the Rb signaling pathway.
Language:
English
Title:
A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced PTSD Nightmares and Sleep Disturbance
Document ID:
20090003798
Report #:
AD-A490652
Available Online:
http://hdl.handle.net/100.2/ADA490652
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Raskind, Murray Peskind, Elaine McFall, Miles Peterson, Kris Doyle, Michael Engel, Charles
Published:
20080301
Source:
Seattle Inst. for Biomedical Clinical Research (Seattle, WA United States)
Pages:
5
Contract #:
W81XWH-06-2-0014
Abstract:
The primary goal of this proposal is to evaluate the efficacy and tolerability of the alpha-1 adrenergic antagonist prazosin compared to placebo for combat trauma-related nightmares, sleep disturbance and overall function in recently combat-exposed returnees from OIF and OEF. A secondary goal is to evaluate the effects of the SSRI paroxetine on behavioral symptoms and overall function in this population. Specific hypotheses (described below) will be tested in a three parallel arm 12-week randomized controlled trial of prazosin, paroxetine and placebo in combat-exposed troops recently returned from OIF and OEF with combat trauma-related persistent nightmares and sleep disturbance. This will be a two-site study performed in the Seattle/Tacoma area at Madigan AMC and in the Washington DC area at Walter Reed AMC.
Language:
English
Title:
Prostate Specific Antigen-Triggered Prodrug of S-Trityl-L-Cysteine, an Eg5 Kinesin Inhibitor and Antimitosis Agent with Low Neurotoxicity
Document ID:
20090003800
Report #:
AD-A490654
Available Online:
http://hdl.handle.net/100.2/ADA490654
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Mitchell, Miguel O
Published:
20080801
Source:
Salisbury Univ. (Salisbury, MD United States)
Pages:
9
Contract #:
W81XWH-07-1-0118
Abstract:
A tripartate prodrug of S-trityl-L-cysteine was synthesized and investigated for antiprostatic potency versus the free anticancer agent (S-trityl- L-cysteine) in PSA-secreting cells (LNCap) and non-PSA-secreting cells (PC3). The prodrug did not inhibit cell growth as much as S-trityl-Lcysteine itself was not selective for PSA-secreting cells, and did not release S-trityl-L-cysteine when treated with cell-free PSA. Interestingly, S-trityl-L-cysteine itself selectively inhibited the growth of LNCap versus PC3 cells.
Language:
English
Title:
Assessing a Drosophila Metastasis Model in Mouse and Human Breast Cancer
Document ID:
20090003801
Report #:
AD-A490655
Available Online:
http://hdl.handle.net/100.2/ADA490655
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Weilbaecher, Katherine Cagan, Ross
Published:
20080501
Source:
Washington Univ. (Saint Louis, MO United States)
Pages:
8
Contract #:
W81XWH-07-1-0360
Abstract:
We propose to combine our expertise to target a process that is critical to breast cancer metastasis that is likely conserved in flies, mice and humans. The advantages of addressing the question of metastasis through the combined expertise of the Cagan and Weilbaecher labs is that we will use the powerful genetic tools provided by Drosophila that will identify key genetic pathways critical to tumor cell migration and metastasis that can be rapidly and rigorously tested. This a real time, in vivo dynamic screen that occurs in a whole organism. Tumors develop in the epithelial layer of the wing and the genetics of tumor cell invasion and migration throughout the organism can be modeled in real time, and genetically manipulated in large scale genetic screens. Dr. Weilbaecher's laboratory will take advantage of the genetic knowledge gained from the Drosophila metastasis models in the development of an improved breast cancer metastasis mouse model. Dr. Cagan's laboratory will be provided with mammalian human and murine breast cancers to validate their genetic and pharmacologic anti-metastasis strategies. Jointly, Drs. Cagan and Weilbaecher propose to develop novel therapeutics targeted to the metastatic process. In year one, we have identified 6 compounds that decrease metastasis in Drosophila metastasis model and decrease viability of mammalian breast cancer cells in vitro. We have validated the compound Cyclopamine, a hedgehog inhibitor, to block lung metastases in murine breast cancer xenograft and will use this as a template for testing other candidate therapeutic compounds from fly to mouse. Finally, we have uncovered a previously unknown and important connection between Src and Hedgehog signaling in mediating metastasis.
Language:
English
Title:
Mechanisms Underlying the Breast Cancer Susceptibility Locus Mcs5a
Document ID:
20090003802
Report #:
AD-A490656
Available Online:
http://hdl.handle.net/100.2/ADA490656
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Smits, Bart M
Published:
20080701
Source:
Wisconsin Univ. (Madison, WI United States)
Pages:
13
Contract #:
W81XWH-07-1-0404
Abstract:
For low-penetrance breast cancer risk alleles it is currently unknown how they lead to predisposition. Here, we study the Mcs5a locus that is associated with breast cancer risk in rats and humans. In our rat model we show that the presence of the resistant genotype of two components of the locus (Mcs5a1, Mcs5a2) down regulates the expression of the Fbxo10 gene in the T cells and that this reduced expression is associated with reduced mammary tumor multiplicity. We show that genetic elements in Mcs5a1 and Mcs5a2 are physically close to each other in the nuclear space. The spatial organization of the locus in primary T cells is conserved between rat and human. We present a model that begins to explain how the Fbxo10 gene could be regulated in T cells.
Language:
English
Title:
A Combined Nutritional and Immunological Intervention to Activate Natural Cytotoxicity Against Breast Cancer Cells In Vitro and In Vivo
Document ID:
20090003803
Report #:
AD-A490657
Available Online:
http://hdl.handle.net/100.2/ADA490657
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Ross, A C
Published:
20080701
Source:
Pennsylvania State Univ. (University Park, PA United States)
Pages:
11
Contract #:
W81XWH-07-1-0478
Abstract:
The central hypothesis of this Idea Award is that a combination of nutritional and immunological treatments may work together to stimulate the body's natural immune defenses against breast cancer. We are testing treatment with 3 agents, retinoic acid (RA), a metabolite of the essential nutrient vitamin A, with immune stimulation using alpha-galactosylceramide (<-GalCer, a synthetic lipid known to alter immune function and to display antitumorigenic activity in vivo; and poly-I:C (PIC), an inducer of type I and type II interferons (IFN). Our research has shown that RA induces CD1d expression and, as a consequence, iNKT cell activation is altered. Research in year 1 has shown that RA potentiates )-GalCer-induced mouse spleen cell proliferation, and alters the balance of NKT1 to NKT2 cytokines by reducing the former type and increasing the latter type. This was also shown be testing the intracellular cytokine mRNA expression in NKT cells (NK1.1-positive CD3-positive spleen cells) detected by flow cytometry. Our studies showed that B cells play a significant role as CD1d expressing cells. B cells are antigen-presenting cells, and thus this cell population should be further considered in the hypothesis we are testing.
Language:
English
Title:
The Inflammatory Milieu Permits Metastasis in Pregnancy-Associated Breast Cancer
Document ID:
20090003805
Report #:
AD-A490666
Available Online:
http://hdl.handle.net/100.2/ADA490666
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schedin, Pepper
Published:
20080701
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
19
Contract #:
W81XWH-07-1-0487
Abstract:
Background and Hypothesis: Pregnancy associated breast cancer (PABC) has higher metastatic potential. We propose that the process of mammary gland involution following pregnancy co-opts programs of wound healing and this pro-inflammatory milieu promotes metastasis. The following aims are proposed. Aim 1. Validate in human breast tissue that breast involution has a pro-inflammatory component. Results: CD45 and CD68 positive cells are increased in human involuting brnasts consistent with a pro-inflammatory program. Aim 2. Investigate the hypothesis that PABC in women will be characterized by expression of negative prognostic stromal markers (desmoplasia) and correlate with clinical data and outcomes. Results: work to begin year 2. Aim 3. Using animal models for human PABC determine whether mammary tumors that develop in the context of involution have increased desmoplasia and metastases. Results: Four new models for PABC are in development with promising preliminary results. Impact on Breast Cancer Research and Patients: The identification of mammary gland involution as the mediator of PABC metastasis identifies a new window for targeted therapies directed at decreasing the pro-inflammatory milieu of the involuting breast.
Language:
English
Title:
Early Support of Intracranial Perfusion
Document ID:
20090003806
Report #:
AD-A490671
Available Online:
http://hdl.handle.net/100.2/ADA490671
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Scalea, Thomas
Published:
20081001
Source:
Maryland Univ. (Baltimore, MD United States)
Pages:
19
Contract #:
W81XWH-07-2-0118
Abstract:
This report represents the first year in a multi-year effort to improve outcomes in patients with traumatic brain injury (TBI). This project will utilize human and animal models in an effort first to identify what factors are most important in determining outcome from TBI and secondly to test new techniques in patient care. Year 1 focused on development of an infrastructure for assessment of TBI patients, development of a protocol to advance our understanding of the inflammatory process which follows TBI and creation of a basic science model of penetrating brain trauma. Hiring and assignment of staff purchase and development of need equipment, and protocol and database development were the primary focus of efforts. Work was initiated on the development of the Brain Resuscitation Registry to provide structure and linkage capabilities for data collection and outcome reporting. Three sub-projects were also developed, two human uses and one animal model. By the close of Year 1, institutional review board approval for all three sub-projects had been obtained and subject recruitment and data collection initiated for the human use sub-projects.
Language:
English
Title:
U.S. Army Medical Department Journal, April-June 2008
Document ID:
20090003857
Report #:
AD-A490746, PB-8-08-4/5/6
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Aldridge, Don Aquino, Janet
Published:
20080601
Source:
Army Medical Dept. Center and School (Fort Sam Houston, TX United States)
Pages:
84
Contract #:
None
Abstract:
Partial contents: Perspective,Chemical Defense Against Blood-Feeding Arthropods 4 by Disruption of Biting Behavior,The Deployed Warfighter Protection Research Program: 9 Finding New Methods to Vanquish Old Foes, Support of Far-Forward Disease Surveillance Operations with Deployable, 21 Real-Time Vector-Borne Disease Agent Analytic Capability, Level III Preventive Medicine in a Counterinsurgency Environment, Preparing the Force for the Chemical, Biological, Radiological, and 36 High Yield Explosives Battlefield; Today and Tomorrow, The Army Preventive Medicine Specialist in the Medical Education and Training Campus Era, Malaria Risk Assessment for the Republic of Korea Based on Models of Mosquito Distribution, The US Air Force Aerial Spray Unit: A History of Large Area Disease Vector Control Operations, WW2 Through Katrina, Evolution of the Army Hearing Program, Perspectives of Malaria and Japanese Encephalitis in the Republic of Korea, Health Implications of Occupational Environmental Health Sampling.
Language:
English
Title:
Mindfullness-Based Cognitive Therapy as a Complementary Treatment for Combat/Operational Stress and Combat Post-Traumatic Stress Disorder
Document ID:
20090003881
Report #:
AD-A490935
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dickey, Jr, G W
Published:
20080101
Source:
Marine Corps Development and Education Command (Quantico, VA United States)
Pages:
36
Contract #:
None
Abstract:
Based Cognitive Therapy is a viable complementary treatment to the traditional psychotherapeutic and pharmacological methods used to treat Combat/Operational Stress Reactions and Combat Post-Traumatic Stress Disorder.
Language:
English
Title:
Behavioral and Mental Healthcare: Total Warrior Care Commitment. U.S. Army Medical Department Journal, July-September 2008
Document ID:
20090003883
Report #:
AD-A490967
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Aldridge, Don
Published:
20080901
Source:
Army Medical Dept. Center and School (Fort Sam Houston, TX United States)
Pages:
81
Contract #:
None
Abstract:
Clinical and non-clinical professional information designed to keep U.S. Army Medical Department personnel informed of health care, research, and combat and doctrine development information.
Language:
English
Title:
Concurrent MR-NIR Imaging for Breast Cancer Diagnosis
Document ID:
20090003969
Report #:
AD-A488046
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yazici, Birsen
Published:
20080601
Source:
Rensselaer Polytechnic Inst. (Troy, NY United States)
Pages:
71
Contract #:
W81XWH-04-1-0559
Abstract:
The primary objective of this research program is to investigate concurrent near infrared (NIR) optical and magnetic resonance (MR) imaging for breast cancer diagnosis. The NIR diffuse optical imaging offers novel criteria for cancer differentiation with the ability to measure (in vivo) oxygenation and vascularization state, the uptake and release of contrast agents and chromophore concentrations with high sensitivity. However, NIR diffuse optical tomography is inherently a low spatial resolution imaging modality due to diffuse nature of light photons. Alternatively, MRI provides high spatial resolution with excellent tissue discrimination, but has limited ability to monitor hemoglobin dynamics and other contrast mechanisms that optical imaging provides. Therefore, concurrent MRI-NIR optical imaging brings together the most advantageous aspects of the two imaging modalities for breast cancer diagnosis.
Language:
English
Title:
A Proteomic Approach to Identify Phosphorylation-Dependent Targets of BRCT Domains
Document ID:
20090003971
Report #:
AD-A488051
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Songyang, Zhou
Published:
20080301
Source:
Baylor Coll. of Medicine (Houston, TX United States)
Pages:
9
Contract #:
W81XWH-05-1-0233
Abstract:
BRCA1 C-terminal (BRCT) domains are novel phosphopeptide binding modules. Cancer-associated missense and deletion mutations have been found in the BRCT repeat regions of BRCA1, suggesting an essential role of BRCT domains in regulating BRCA1activity. In addition, BRCT domains are found in many proteins that regulate DNA damage repair, cell cycle, and genome stability, implying a more global role of BRCT domains in genome stability surveillance. These results suggest that the BRCT domain acts as a sensor to protein phosphorylation in response to DNA damage, recruits phosphorylated cellular targets, and mediates signaling complex formation. However, the identities of the in vivo BRCT domain targets are largely unknown. In order to understand the role of phosphorylation in protein-protein interactions, we developed several approaches utilizing peptide libraries and peptide arrays. We propose to use these methods to systematically identify phosphorproteins that can interact with BRCT domains. In addition to potential new regulators of genome stability, the approaches can identify phosphorylated sequences on proteins that are important for DNA damage responses and cell cycle. Such information should prove valuable, especially for the development of new screening strategies, drug targets, and treatment for breast cancer.
Language:
English
Title:
Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant
Document ID:
20090003972
Report #:
AD-A488052
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Cooper, Laurence Young, Rita
Published:
20080501
Source:
Texas Univ. (Houston, TX United States)
Pages:
33
Contract #:
W81XWH-07-1-0250
Abstract:
To develop T-cell therapies for B-cell malignancies we have developed a chimeric antigen receptor (CAR) which when expressed on the cell surface redirects T-cell specificity for CD19, a B-lineage cell-surface antigen. We have undertaken a series of systematic experiments to improve the ability of these CAR+ T cells to persist after adoptive transfer based on conditional expression of interleukin-2 (IL-2) which is a potent cytokine that can prolong T-cell persistence. Firstly, we have combined T-cell therapy with antibody therapy directing both immunotherapies to B-cell antigens. To improve CD19-specific T-cell survival we combined a CD20-specific antibody with IL-2 which deposits IL-2 in the tumor microenvironment and is a surrogate for T-cell help (TH). Secondly, we have developed a gene transfer platform to propagate CD19-specific CAR+ CD4+ T cells that provide TH to CD8+ T cells. Thirdly, we have re-engineered the CD19-specific CAR itself so that it can signal for endogenous production of IL-2 through chimeric CD28. These technologies will now be evaluated in animal models in preparation for deciding which to take forward to a clinical trial.
Language:
English
Title:
Estrogen and the Dietary Phytoestrogen Tesveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Research
Document ID:
20090003973
Report #:
AD-A488053
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Dharmawardhane, Suranganie
Published:
20080601
Source:
Universidad Central del Caribe (Bayamon, Puerto Rico)
Pages:
16
Contract #:
W81XWH-07-1-0330
Abstract:
This award proposed to test the hypothesis that estrogen (E2) and low concentrations of resveratrol promote breast cancer invasion and metastasis while high concentrations of resveratrol prevent breast cancer metastasis via regulation of the signaling protein Rac. Specific Aim1 was to test the effect of varying concentrations of E2, resveratrol, or a small molecule Rac-specific inhibitor NSC23766 on cell migration, invasion, and Rac activity of metastatic breast cancer cells. Aim 2 was to test the effect of these compounds on breast cancer progression in immunocompromised nude mice from mammary tumors established from fluorescent protein-tagged breast cancer cells. This first year report shows that at low concentrations, resveratrol acted similar to E2 and activated while at high concentrations resveratrol inhibited Rac and breast cancer cell migration. As proposed, we tested the efficiency of the commercially available Rac inhibitor NSC23766 in breast cancer cells. However, NSC23766 had only a modest inhibitory effect on Rac activity or cell migration of breast cancer cell lines. Therefore, we developed and tested novel more efficacious NSC23766 derivatives that will be used for the proposed study. For Aim 2, the effect of treatment with vehicle or resveratrol on mice with GFP-MDA-MB-435 mammary tumors was determined. Primary breast cancer progression and distant metastases as analyzed by whole body and microscopic fluorescence image analysis demonstrated that resveratrol reduced lung and liver metastases. Therefore, these experiments support our hypothesis that E2 and low concentrations of resveratrol promote while high concentrations of resveratrol inhibit breast cancer progression.
Language:
English
Title:
Do microRNAs Mediate Estrogen-Dependent Repression of Genes
Document ID:
20090003974
Report #:
AD-A488054
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nakshatri, Harikrishna Collins, Nikail R
Published:
20080801
Source:
Indiana Univ. (Indianapolis, IN United States)
Pages:
24
Contract #:
W81XWH-06-1-0637
Abstract:
Estrogen receptor alpha (ERa) mediates transcriptional effects of estrogen. Estrogen inducible proteins c-Myc and E2F family are required for optimal ERa activity and secondary estrogen response, respectively. The purpose of this study was to investigate whether estrogen regulates its target gene expression through microRNAs. We show that estrogen induces 21 and represses 7 microRNAs, which potentially control 420 estrogen-regulated and 757 non-estrogen regulated mRNAs at post-transcriptional level. Estrogen induced the expression of eight Let-7 family microRNAs, miR-98 and miR-21, which by reducing c-Myc and E2F2 proteins level, may attenuate estrogen response. Consistent with the role of Let-7 in differentiation of cancer stem cells, estrogen reduced ALDH1-positive breast cancer stem subpopulation of MCF-7 cells. The protein kinase AKT reduced estrogen-inducible expression of Let-7 microRNAs and may disrupt attenuation of estrogen response. Significance: Luminal subtype A breast cancers contain functional ERa, are well differentiated and display favorable prognosis. Estrogen:ERa-mediated differentiation pathway in these cancers is yet to be elucidated. We propose that estrogen-regulated Let-7 family microRNAs contribute to differentiated phenotype of ERa-positive breast cancers. The phenotype and the clinical course of ERa-positive breast cancers, particularly response to anti-estrogen therapy, may be dependent on the balance between estrogen-induced tumor suppressor (let-7 family) and oncogenic (miR-21) microRNAs. Our studies also reveal a negative regulatory loop controlling estrogen response through microRNAs and highlights differences in estrogen-induced transcriptome and proteome.
Language:
English
Title:
Crosstalk Between Cancer Cells and Bones Via the Hedgehog Pathway Determines Bone Metastasis of Breast Cancer
Document ID:
20090003975
Report #:
AD-A488055
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Shevde-Samant, Lalita
Published:
20080601
Source:
University of South Alabama (Mobile, AL United States)
Pages:
21
Contract #:
W81XWH-07-1-0400
Abstract:
The Hh pathway has been extensively studied in development and recently has also been shown to be activated in a variety of cancer types thus making it a putative therapeutic target. Our preliminary data indicated that OPN is a transcriptional target of Gli1 = Gli1 is a transcription factor of the Hedgehog (Hh) pathway. Research in our laboratory indicates that OPN is under direct control of the Hh pathway as seen by the effect of agonistic Hh pathway ligands and the Hh pathway inhibitor cyclopamine. Moreover we find that the Hh ligands Shh and lhh can stimulate differentiation of osteoblasts. The OPN-containing conditioned medium from the MDA-MB-435 cells is also able to potentiate differentiation of osteoblasts.
Language:
English
Title:
Genes Involved in Oxidation and Prostate Cancer Progression
Document ID:
20090003977
Report #:
AD-A488057
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Platz, Elizabeth A
Published:
20080101
Source:
Johns Hopkins Univ. (Baltimore, MD United States)
Pages:
11
Contract #:
DAMD17-03-1-0273
Abstract:
We are evaluating whether polymorphisms in genes involved in the genesis of oxidative species, detoxification of oxidative species, or repair of oxidative DNA damage influence risk of prostate cancer progression in men with clinically organ-confined prostate cancer. We identified 524 men with who underwent radical prostatectomy in 1993-2004 and who subsequently experienced biochemical recurrence, development metastases, or died from their prostate cancer. Using incidence-density sampling, we selected 524 men matched on age, race, and pathological stage and grade who had not progressed by the date of the matched case's progression. Noncancer tissue (either unaffected paraffin-embedded lymph nodes or frozen seminal vesicles) was retrieved from the Hopkins pathology archive from which germline DNA was extracted. For 20 men either tissue could be found or DNA extraction was not successful. We attempted several platforms for genotyping, including a SNP chip that included ~1500 SNPs in relevant genes. We selected the Mass Array system (Sequenom) and identified 100 SNPs in relevant genes. We completed genotyping the 524 pairs for 12 of the 100 SNPs. For 33 of the men, genotyping was not successful. A total of 450 of the 524 pairs had genotype data for both members of the pair for at least on SNP. We used conditional logistic regression to estimate the matched ORs of progression for the 12 SNPs; no associations were observed (all p-trend across number of alleles > 0.15). We are awaiting data for the remainder of the 100 SNPs.
Language:
English
Title:
Establishment of an 'In Vitro Cell-Based System' to Assay Radiation Sensitivity in Breast Cancer
Document ID:
20090003978
Report #:
AD-A488058
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Langland, Gregory
Published:
20080531
Source:
California Univ. (Berkeley, CA United States)
Pages:
12
Contract #:
W81XWH-06-1-0527
Abstract:
The purpose of this proposal is to develop an 'in vitro cell-based system' to study radioresistance in sporadic breast cancer. By performing colony formation assays in response to X-ray treatment we have shown that there is a wide range of sensitivities to this form of treatment. Interestingly, we have also observed that p53 status does not accurately predict response to radiation treatment. Using correlation studies, we have identified novel predictors of IR resistance/sensitivity. We have sensitized two breast cancer cell lines to X-ray treatment by using RNAi-based technology to inhibit Artemis function. In the future, these observations may have a significant clinical impact on the way radiation oncologists treat breast cancer patients.
Language:
English
Title:
Exercise to Counteract Loss of Bone and Muscle during Androgen Deprivation Therapy in Men with Prostate Cancer
Document ID:
20090003979
Report #:
AD-A488062
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kohrt, Wendy M Glode, L M Schwartz, Robert S Barry, Daniel W
Published:
20080801
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
11
Contract #:
DAMD17-03-1-0276
Abstract:
The original objective was to determine whether a 1-year intensive resistance exercise training (RT) program is more effective than a moderate-intensity walking program in ameliorating the effects on body composition of androgen deprivation therapy (ADT) in men with prostate cancer. It was postulated that: 1) RT will attenuate the declines in bone mineral density (BMD) and fat-free mass (FFM) to a greater extent than walking; and 2) both RT and walking will prevent an increase in fat mass. Primary outcomes are lumbar spine BMD and FFM. Secondary outcomes are: total body and hip BMD; fat mass; markers of bone turnover; serum sex hormones; physical functional performance; quality of life, and risk factors for cardiovascular disease (blood lipids, glucose tolerance, arterial stiffness). Because of the inability to enroll the projected number of participants, the study protocol was modified at the time of the 2006 annual IRB review to focus only on the intensive resistance training intervention.
Language:
English
Title:
Exploiting for Breast Cancer Control a Proposed Unified Mechanism for Reduction of Human Breast Cancer Risk by the Hormones of Pregnancy
Document ID:
20090003981
Report #:
AD-A488067
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Jacobson, Herbert Andersen, Thomas T Bennett, James A
Published:
20080501
Source:
Albany Medical Coll. (NY United States)
Pages:
18
Contract #:
W81XWH-04-1-0486
Abstract:
Results in the third grant year further support the Unified Mechanism Hypothesis in that: (1) Giving pregnancy associated hormones or hCG to virgin female rats either before or after MNU treatment elicits persistent serum AFP levels, thereby explaining why breast cancer appearance is inhibited when employing either treatment sequence; (2) Giving hCG to estrogenized SCID mice bearing human breast cancer xenografts inhibits the cancer growth, apparently by action of murine AFP that the treatment has elicited from the mouse liver as an inform with low avidity for our available anti mAFP antibody. We are able to detect mAFP in mouse serum by western blot when it is present in the very high concentration that is elicited by injection of the animals with high E3 doses. (3) In an all-human in vitro system, hCG elicits hAFP from cultured HepG2 human liver cancer cells, addition of the hAFP-containing supernate to cultures of MCF7 human breast cancer cells blocks their growth, and that adding anti hAFP antibody to that system prevents the inhibition. hAFP is thus confirmed as the proximal inhibitor.
Language:
English
Title:
Criterion-Based Training to Reduce Surgical Errors
Document ID:
20090003993
Report #:
AD-A488101
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Fried, Marvin P
Published:
20080901
Source:
Montefiore Medical Center (Bronx, NY United States)
Pages:
5
Contract #:
W81XWH-05-1-0577
Abstract:
Technical skill is at the core of surgery. Surgical training typically lasts for a specified time period or number of procedures. This approach produces surgeons with considerably variable skill levels. Also training on patients is becoming unacceptable for patient safety. In contrast pilots and other non-medical personnel are trained to criteria on simulators to ensure skill proficiency in their MOS prior to reporting for duty. Proficiency levels are objectively established by experienced practitioners and the trainee is required to consistently demonstrate that level of proficiency before progressing. We propose to use a surgical simulator (the ES3) to train surgical residents to criterion performance levels and to investigate whether criterion-based training is superior to training for a fixed number of trials. Twenty-four otolaryngology residents will serve as subjects. Eight attending otolaryngologists will establish performance criteria and will serve as comparators for infra-operative assessment. Subjects will complete a battery of validated objective tests to assess visuospatial perceptual and psychomotor abilities. An experimental group will be trained to criterion on the simulator and then perform a procedure on a patient. A control group will train by repeatedly performing the same procedure on patients with no simulator training. All procedures will be videotaped and objectively assessed for explicitly defined metrics. We hypothesize that prior training to established criteria will reduce surgical errors and provide evidence for training on simulators before ever operating upon a patient.
Language:
English
Title:
Targeting Signal Transducers and Activators of Transcription-3 (Stat3) As a Novel Strategy In Sensitizing Breast Cancer To Egfr-Targeted Therapy
Document ID:
20090003998
Report #:
AD-A488113
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Lo, Hui-Wen
Published:
20080601
Source:
Duke Univ. (Durham, NC United States)
Pages:
23
Contract #:
W81XWH-07-1-0390
Abstract:
We have performed proposed studies to test the hypothesis that deregulated EGFR and STAT3 pathways synergistically contribute to the malignant biology of breast cancer and that combined uses of anti-EGFR and anti-STAT3 treatments result in significantly increased breast cancer cell death compared to single agent treatments. Analysis of a panel of human breast cancer cell lines and primary breast carcinoma specimens revealed that EGFR and constitutively activated STAT3 (p-STAT3) are frequent and concurrent. EGFR and STAT3 cooperate to induce epithelial mesenchymal transition by activating expression of TWIST, an E-cadherin repressor. In breast cancer cells with high levels of EGFR and p-STAT3, forced expression of dominant-negative STAT3 significantly suppresses cell proliferation. Importantly, dominant-negative STAT3 sensitizes breast cancer cells with high EGFR/p-STAT3 to anti-EGFR agent, Iressa. In contrast, transfection of constitutively active STAT3 into these cells does not increase cell proliferation nor induces resistance to Iressa, suggesting the endogenous p-STAT3 is sufficient in facilitating cell survival. Consistently, breast cancer cells with no or low EGFR expression do not respond to Iressa treatments. Together, the findings to date point to significant in vivo and in vitro interactions between EGFR and STAT3 oncoproteins in breast cancer as well as a role of STAT3 constitutive activation may play in the resistance of these tumors to anti-EGFR therapy.
Language:
English
Title:
A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant Cmls
Document ID:
20090004001
Report #:
AD-A488118
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Reddy, E P
Published:
20080501
Source:
Temple Univ. (Philadelphia, PA United States)
Pages:
33
Contract #:
W81XWH-06-1-0267
Abstract:
We have developed several novel small molecule inhibitors of BCR-ABL that inhibit the proliferation and induce apoptosis of CML cell lines that express the WT or the T315I mutant form of BCR-ABL. These compounds readily induced the downregulation of BCR-ABL auto-phosphorylation and STAT-5 phosphorylation. Using ON044580 as the lead compound, we have carried out chemical modification of the compound to facilitate the oral bio-availability of the compound. This resulted in the derivation of two compounds, ONO45260 and ON044690 which retained the BCR-ABL inhibitory activity of the parent compound. They also retained the ability to inhibit kinase activities of WT and V617F mutant forms of JAK2 and induce apoptosis of leukemic cell lines that express the V617F mutant form of JAK2. We show that ON044850 destroys the Bcr- Abl/Jak2 protein Network, which is a large multi-component signaling structure maintained in an active state by members of the HSP90 chaperone complex. ON044850 causes reduction of STAT3 levels leading to reduced expression of HSP90.
Language:
English
Title:
Genetic Dissection of the Role of Heparan Sulfate in Mammary Tumor Progression
Document ID:
20090004007
Report #:
AD-A488128
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yamaguchi, Yu
Published:
20080630
Source:
Burnham Inst. (La Jolla, CA United States)
Pages:
11
Contract #:
W81XWH-07-1-0461
Abstract:
Heparan sulfate (HS) binds growth factors, protein-degrading enzymes, and other bioactive proteins, and to regulate their activities. Many of these proteins have strong implications in human breast cancer. There is also evidence that cellular HS production itself exerts strong influences on tumorigenesis, exemplified by the fact that mutations of Ext1, the gene encoding an HS synthesizing enzyme, cause multiple bone tumors. Furthermore, the level of HS degrading activity correlates with the aggressiveness of the tumor. Despite these long-standing observations, much less is known about the mechanisms by which HS influences the malignant behavior of tumors in vivo. Also important is the fact that HS is produced not only by tumor cells themselves but also by stromal cells that constitute the tumor microenvironment. This project will conduct cohort study using genetic mouse models to address these key questions. The first year of this project was dedicated mainly to establish, expand, and intercross mouse models for generating experimental cohorts. We have also characterized the gene recombination pattern induced by the FSP1-Cre transgenic mouse, which will be used to manipulate the expression of HS in tumor stromal cells.
Language:
English
Title:
Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland
Document ID:
20090004010
Report #:
AD-A488132
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Li, Hua
Published:
20080401
Source:
Dartmouth Coll. (Hanover, NH United States)
Pages:
36
Contract #:
W81XWH-05-1-0350
Abstract:
Delta-N-p63 plays a critical role in making decision to preserve or forfeit mammary stem cells/progenitor cells self-renewal capacity. In embryonic stem cells, some transcription factors including oct3/4, nanog, c-myc and Klf-4 are critical to maintain self-renewal and multi-potential stasis. Our study revealed that these key transcription factors also exist in adult mammary stem cells/progenitor cells as well as breast cell lines such as IMEC, MCF-10A, SUM102 and MCF- 7 cells. Over-expression of ectopic delta-N-p63 could inhibit the proliferation rate of treated cells, and had diverse regulation effects on transcript level of oct3/4, nanog, c-myc and Klf-4 in infected breast cell lines. Retinoic acid treatment also could slow down the growth of treated beast cells, and change the transcript level of these self-renewal related genes. Both of RA treatment and over-expression of delta-N-p63 could increase mammosphere formation capacities in most breast cell lines including IMEC, SUM102 and MCF-7 cells. The mRNA level of oct3/4 and nanog was detectable in mouse mammary stem cells or progenitor cells enriched subpopulation. Additionally, both oct3/4 and nanog transcript level could be regulated by over-expression or removal of delta- N-p63 in mammary stem cells or progenitors fractions, respectively. In human breast cell lines such as SUM102 cells, over-expression of mouse oct3/4 and nanog could increase the mammosphere numbers significantly. On the other hand, removal of delta-N-p63 in MCF-10A cells could decrease the mammosphere formation capacity dramatically. Taken together, all these findings strongly suggested there might be correlation between delta-N-p63 and ES programming genes including oct3/4, nanog, c-myc and Klf-4 to regulate stem cell self-renewal and sustaining of pluripotency in adult mammary gland.
Language:
English
Title:
Enhancing the Efficacy of Chemotherapeutic Breast Cancer Treatment with Nonanticoagulant Heparins
Document ID:
20090004011
Report #:
AD-A488133
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Mousa, Shaker A
Published:
20080501
Source:
Albany Coll. of Pharmacy (Albany, NY United States)
Pages:
10
Contract #:
W81XWH-07-1-0344
Abstract:
A mouse model of breast cancer with human breast cancer cell lines MCF7 (wild type) or MCF7-doxorubicin resistant (MCF7-R) cells was used evaluate the efficacy of low molecular weight heparins (LMWH) either alone or in combination with doxorubicin to prevent tumor growth. Tumor volume measurements were performed at intervals throughout the course of treatment. LMWH compounds (Enoxaparin or non-anticoagulant heparin NACH) given together with chemotherapeutic agent doxorubicin decreased tumor growth rate and prolong survival in animals bearing MCF7 wild-type tumors. These agents appeared to be less effective in animals bearing doxorubicin-resistant tumors. Bleeding times determined on animals in all treatment groups showed that there were no statistically significant differences among the groups. However, animals in ENOX groups showed increased bruising at the sites of injection. These studies will be repeated, and studies with alpha v beta 3-targeted nanoparticle formulations will be performed to compare the efficacies of non-targeted and targeted therapies.
Language:
English
Title:
Magnetic Nanoparticle-Based Imaging of RNA Transcripts in Breast Cancer Cells
Document ID:
20090004016
Report #:
AD-A488139
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Tsourkas, Andrew
Published:
20080630
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
17
Contract #:
W81XWH-07-1-0457
Abstract:
We have developed a novel approach to detect RNA transcripts via magnetic resonance by taking advantage of the decrease in the spin-spin (i.e. T2) relaxation time that results from the self-assembly of superparamagnetic iron oxide nanoparticles (NPs). Specifically, two unique NP-oligonucleotide (ON) conjugates were designed to recognize adjacent sites on nucleic acid targets. Thus, upon hybridization to complementary targets the NP-ON conjugate pairs were brought into close proximity, which resulted in a detectable reduction in the T2 relaxation time. This mechanism of switching from a high T2-relaxation time to a low T2-relaxation time is generally referred to as magnetic relaxation switching (MRSw). In the presence of target nucleic acids, we measured as much as a 40% decrease in T2 signal due to aggregate formation, with reliable detection of target at levels as low as 10 pmoles. We have also prepared NPs with sizes ranging from ~20 nm to 1 um and identified that positively charged NPs <200 nm are taken up by cells much more effectively than larger NPs. Therefore, we plan to use NPs in this size range when attempting to detect RNA in cells.
Language:
English
Title:
Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes
Document ID:
20090004017
Report #:
AD-A488140
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Privette, Lisa M
Published:
20080301
Source:
Michigan Univ. (Ann Arbor, MI United States)
Pages:
61
Contract #:
W81XWH-06-1-0332
Abstract:
CHFR is an E3 ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazole and taxanes). Loss of CHFR mRNA expression has been reported in many cancers, including breast cancer, but the relevance of this to tumorigenesis remains unknown. The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics, progression, and genomic stability. As previously reported, nearly 40% of breast cancer show decreased CHFR expression compared to normal cells and tissues and the loss of CHFR expression by RNAi in cell culture models leads to the acquisition of several tumorigenic phenotypes. In particular, MCF10A IHMEC cells transfected with CHFR siRNA, became aneuploid and were analyzed for chromosome segregation defects. We observed increased aneuploidy, misaligned metaphase chromosomes, anaphase bridges, multipolar condensed spindles, multi-nucleated cells, and mislocalization of the mitotic spindle checkpoint proteins MAD2 and BUBR1. CHFR was found to interact with three crucial mitosis proteins, including MAD2 and Aurora A where CHFR loss led to Aurora A oncoprotein over-expression, but no change in MAD2 expression. alpha-tubulin was identified as a novel target for CHFR-mediated ubiquitination after nocodazole treatment and decreased CHFR increased acetylated alpha-tubulin, a mitotic spindle protein implicated in cellular response to taxane treatment. These data indicate that CHFR has tumor suppressive qualities and may be a biomarker for taxane chemo-responsiveness. CHFR also has a previously unrecognized role as a regulator of genomic stability. CHFR may be one of the few proteins that can control the cell cycle, chemotherapeutic response, and genomic stability - processes that go awry in breast cancer.
Language:
English
Title:
Harnessing Novel Secreted Inhibitors of EGF Receptor Signaling for Breast Cancer Treatment
Document ID:
20090004031
Report #:
AD-A488172
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Lemmon, Mark A
Published:
20080401
Source:
Pennsylvania Univ. (Philadelphia, PA United States)
Pages:
64
Contract #:
WW81XWH-05-1-0289
Abstract:
We aim to develop protein therapeutics that neutralizes growth factors that activate EGF receptor family members in breast cancer. Rather than targeting receptors themselves (as do Herceptin, Iressa, etc), we propose to target the activating ligands. Our model is Argos from Drosophila, which we showed naturally, inhibits EGF receptor signaling in fruit flies by inactivating the ligand. We hope to effectively humanize Argos - making it bind human EGFR ligands and/or to use human protein scaffolds for this. In the past year, we crystallized a complex between the minimal functional fragment of Argos and its target (Spitz), and are about to complete structure determination which will provide critical information for therapeutic design. We also established an experimental approach for screening libraries of Argos variants for those that bind human EGF-like ligands (our therapeutic aim). This approach employs yeast surface (rather than phage) display. We are now poised to combine our technical position and new structural information to identify Argos (and Dkk) variants that bind human EGFs and represent starting points for developing new therapeutics.
Language:
English
Title:
Identification of Cytoplasmic Proteins Interacting with the Mammary Cell Transforming Domain of Ese-1
Document ID:
20090004033
Report #:
AD-A488175
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Gutierrez-Hartmann, Arthur
Published:
20080401
Source:
Colorado Univ. (Aurora, CO United States)
Pages:
60
Contract #:
W81XWH-06-1-0502
Abstract:
ETS factors comprise a large transcription factor family known to play a significant role in cellular development, differentiation, and transformation. Emerging evidence reveals that increased mRNA expression of the human Ets factor-1, ESE-1, is associated with breast cancer. Stable expression of ESE-1 transforms MCF-12A immortalized human mammary epithelial cells. However, little is known about ESE-1 protein expression and its role in maintaining the transformed phenotype in human breast cancer cell lines. Here, we used an anti- ESE-1 mouse monoclonal antibody in Western blot and immunofluorescent cell analyses to show that ESE-1 is expressed as a nuclear protein in MCF-7, T47D and ZR-75 transformed, tumorigenic mammary epithelial cell lines, and that it is not expressed in transformed MDAMB- 231 and nontransformed MCF-10A and MCF-12A cells. In addition, specific knockdown of endogenous ESE-1 in the human breast carcinoma ZR-75 and MCF-7 cell lines decreased colony formation and anchorage independent growth. Mechanistically, ESE-1 knockdown decreased cellular proliferation, but had no effect on apoptosis. Finally, serum withdrawal resulted in a time-dependent, ~90% reduction of ESE-1 protein production in MCF-7 cells. These results establish that ESE-1 plays a key role in maintaining the transformed phenotype in breast cancer, thus providing a novel single-point target for breast cancer therapy.
Language:
English
Title:
Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax
Document ID:
20090004036
Report #:
AD-A488183, TR-08-042
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Heine, H S> Bassett, J Miller, L Bassett, A Ivins, B E Lehous, D Arhin, F F Parr, Jr , T R Moeck, G
Published:
20080621
Source:
Army Medical Research Inst. of Infectious Diseases (Fort Detrick, MD United States)
Pages:
9
Contract #:
None
Abstract:
The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. The potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against B. anthracis (MIC against Ames strain, 0.015 microg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. In postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of oritavancin of 5, 15, or 50 mg/kg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100% proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90% of control animals receiving ciprofloxacin at 30 mg/kg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development; a single i.v. dose of 50 mg/kg administered 42 h after challenge provided 56% proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mg/kg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20% of mice at 30 days; mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models.
Language:
English
Notes:
Sponsored in part by Defense Threat Reduction Agency, project no. 02-4-2c-013
Title:
A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel
Document ID:
20090004050
Report #:
AD-A488231, NAMRL-TR-08-10
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Simmons, Rita G Phillips, Jeffrey B Lojewski, Renee A Lawson, Benton D
Published:
20080818
Source:
Naval Aerospace Medical Research Lab. (Pensacola, FL United States)
Pages:
45
Contract #:
None
Abstract:
Results from preliminary studies indicate intranasal scopolamine (IN SCOP) has faster absorption, higher bioavailability, and a more reliable therapeutic index than equivalent oral (PO SCOP). The purpose of this study was to determine and compare the efficacy, side effect profile, and pharmacotherapeutics of IN SCOP and PO SCOP. It was hypothesized that IN SCOP would rapidly achieve therapeutic concentrations at lower doses compared to PO SCOP while minimizing medication-induced performance impairment. Fifty-four aviation candidates were randomized to one of three treatment groups (0.4 mg IN SCOP gel, 0.8 mg PO SCOP or placebo) and then exposed to passive Coriolis cross-coupling. Medication efficacy, pharmacotherapeutics and side-effect profiles were tracked for all groups. Analysis revealed there were no significant differences in efficacy among groups. Pharmacotherapeutic data show increased scopolamine absorption and decreased time to reach maximum salivary concentration with intranasal administration, with no significant treatment side effects detected over time. There was a significant decrease in heart rate over time for IN SCOP and PO SCOP versus placebo, while no clinically significant differences were found for either systolic or diastolic blood pressures. In summary, IN SCOP absorption was significantly greater than PO SCOP with no detrimental impact on performance or side effects.
Language:
English
Title:
Fentanyl, 2003-2006. National Forensic Laboratory Information System (NFLIS) Special Report
Document ID:
20090004207
Report #:
PB2009-103358
Sales Agency:
National Technical Information Service (NTIS) No Copyright
Author(s):
(Author(s) Not Available)
Published:
20080101
Source:
Drug Enforcement Administration (Washington, DC, United States)
Pages:
8
Contract #:
None
Abstract:
The National Forensic Laboratory Information System (NFLIS) is a program sponsored by the Drug Enforcement Administration (DEA) Office of Diversion Control that systematically collects drug identification results and associated information from drug cases analyzed by federal, state, and local forensic laboratories. These laboratories analyze substances secured in law enforcement operations across the country and represent an important resource in monitoring drug abuse and trafficking. This NFLIS Special Report presents findings on fentanyl drug items. Fentanyl is a powerful synthetic opiate approximately 50 times more potent than heroin and 100 times more powerful than morphine. It is typically prescribed to treat severe or chronic pain. In recent years, clandestinely produced fentanyl in combination with heroin or cocaine has been linked to hundreds of deaths and overdoses. Because fentanyl is an opiate and specialized testing is required to detect it in biological samples, many fentanyl overdoses were initially classified as heroin overdoses.
Language:
English
52-03 PHYSIOLOGICAL FACTORS
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Scavenger Receptors and Resistance to Inhaled Allergens
Document ID:
20090002403
Report #:
AD-A486143
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Kobzik, Lester
Published:
20080201
Source:
Harvard School of Public Health (Boston, MA United States)
Pages:
6
Contract #:
W81XWH-06-1-0289
Abstract:
After OVA sensitization and aerosol challenge, SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyperresponsiveness compared to wild-type mice. A role for simple SRA-mediated antigen clearance ('scavenging') by lung macrophages was excluded by observation of comparable uptake of fluorescent OVA by wild-type and SRA-deficient lung Mgammas and DCs. In contrast, airway instillation of fluorescent antigen revealed significantly higher traffic of labelled DCs to thoracic lymph nodes in SRA-deficient mice than in controls. The increased migration of SRA-deficient DCs was accompanied by enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SRAs expressed on lung DCs in down-regulation of specific immune responses to aero-allergens by reduction of DC migration from the site of antigen uptake to the draining lymph nodes.
Language:
English
Title:
Biosensors for EVA: Muscle Oxygen and pH During Walking, Running and Simulated Reduced Gravity
Document ID:
20090002614
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Lee, S. M. C. (Wyle Labs., Inc.) Ellerby, G. (Massachusetts Univ.) Scott, P. (Massachusetts Univ.) Stroud, L. (Wyle Labs., Inc.) Norcross, J. (Wyle Labs., Inc.) Pesholov, B. (Massachusetts Univ.) Zou, F. (Massachusetts Univ.) Gernhardt, M. (NASA Johnson Space Center) Soller, B. (Massachusetts Univ.)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO2 on the leg during cycling. Our NSBRI-funded project is looking to extend this methodology to examine activities which more appropriately represent EVA activities, such as walking and running and to better understand factors that determine the metabolic cost of exercise in both normal and lunar gravity. Our 4 year project specifically addresses risk: ExMC 4.18: Lack of adequate biomedical monitoring capability for Constellation EVA Suits and EPSP risk: Risk of compromised EVA performance and crew health due to inadequate EVA suit systems.
Language:
English
Title:
Physiological Responses to Exercise-Heat Stress With Prototype Pulsed Microclimate Cooling System
Document ID:
20090003350
Report #:
AD-A487097, USARIEM-TR-T08-12
Available Online:
http://hdl.handle.net/100.2/ADA487097
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Cadarette, Bruce S Chineverse, Troy D Ely, Brett R Goodman, Daniel A Laprise, Brad Teal, Walter Sawka, Michael N
Published:
20080901
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
32
Contract #:
None
Abstract:
This study supported the U.S Army Natick Soldier Research Development and Engineering Center (NSRDEC) effort to develop a lightweight microclimate cooling system (MCCS) for use by dismounted Soldiers. The MCCS evaluated in this study was an early prototype light weight circulating liquid vapor compression MCCS with an integrated skin temperature sensor to trigger on/off cycles The prototype system is based on a USARIEM patent (patent pending) for personalized microclimate cooling that when configured to operate as a skin temperature feedback pulsed cooling (PC) unit should delay heat strain as effectively as constant cooling (CC) during exercise%heat stress while reducing the power requirement by 50% This prototype system could potentially save the U.S Army substantial dollars currently being spent on battery acquisition. Additionally using smaller or fewer batteries would decrease the weight of the system and increase acceptability by dismounted Soldiers This study was designed to evaluate both the prototype MCC system's capability to be controlled by the skin temperature sensor and its ability to sufficiently cool subjects under the given heat stress scenarios.
Language:
English
Title:
Test Operations Procedure (TOP) 1-1-003 Cold Regions Personnel Effects
Document ID:
20090003554
Report #:
AD-A487444, TOP-1-1-003
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
(Author(s) Not Available)
Published:
20080915
Source:
Army Cold Regions Test Center (Fort Greely, AK United States)
Pages:
13
Contract #:
None
Abstract:
This Test Operations Procedure (TOP) provides background information on physiological and psychological effects of cold on the human. It is an overview TOP and is organized to provide information on some of the problems associated with conducting operations, training, testing, and living in a cold environment. Rather than test procedures, it provides needed knowledge to safely conduct tests in the cold environment.
Language:
English
Title:
Carbohydrate Supplementation and Immune Responses After Acute Exhaustive Resistance Exercise
Document ID:
20090003751
Report #:
AD-A490343, USARIEM-M-07-46
Available Online:
http://hdl.handle.net/100.2/ADA490343
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Carlson, Lara A Headley, Samuel DeBruin, Jason Tuckow, Alex P Koch, Alexander J Kenefick, Robert W
Published:
20080101
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
14
Contract #:
None
Abstract:
This investigation sought to study changes in leukocyte subsets after an acute bout of resistance exercise (ARE) and to determine whether ingestion of carbohydrate (CHO) could attenuate those immune responses.
Language:
English
Notes:
International Journal of Sport Nutrition and Exercise Metabolism, v18 p247-259, 2008
Title:
Thermoregulatory Responses to Environmental Toxicants: The Interaction of Thermal Stress and Toxicant Exposure
Document ID:
20090003756
Report #:
AD-A490382
Available Online:
http://hdl.handle.net/100.2/ADA490382
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Leon, Lisa R
Published:
20080101
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
17
Contract #:
None
Abstract:
Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment.
Language:
English
Title:
A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol
Document ID:
20090004013
Report #:
AD-A488136
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Pitman, Roger K
Published:
20080601
Source:
General Hospital Corp. (Boston, MA United States)
Pages:
5
Contract #:
W81XWH-07-1-0440
Abstract:
The objective of this project is to test whether the beta-adrenergic blocker propranolol, given following combat memory reactivation, results in a significantly greater weakening of traumatic memories than propranolol alone, supporting the proposition that this weakening is due to pharmacological blockade of memory reconsolidation, rather than non-specific actions of propranolol. We hypothesize that subjects who undergo script preparation for the combat event(s) that caused their PTSD, followed by (post-reactivation) propranolol, will show significantly smaller psychophysiologic responses during script-driven imagery testing a week later, indicative of weakening of the emotional memory, compared to those who receive (non-reactivation) propranolol two days prior to combat script preparation. Subjects will be randomly assigned to one of two groups: post-reactivation propranolol or non-reactivation propranolol. Subjects randomized to the non-reactivation propranolol group will receive a "test" dose of propranolol, whereas subjects randomized to the post-reactivation propranolol group will receive placebo. Two days later, all subjects will return for an approximate 15-30 minute "script preparation" session, at which flme they will describe the details of their traumatic combat event(s). Subjects randomized to the post-reactivation propranolol group will then receive propranolol, whereas subjects randomized to the non-reactivation propranolol group will receive placebo. Scripts will be composed portraying each subject's personal combat events in their own words. Subjects will return to the psychophysiology laboratory one week and six months later. During each of these visits, heart rate, skin conductance, and corrugator electromyogram responses during will be recorded during script-driven imagery of personal combat events.
Language:
English
Title:
Physiological Factors Contributing to Postflight Changes in Functional Performance
Document ID:
20090004156
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Bloomberg, J. J. (NASA Johnson Space Center) Feedback, D. L. (NASA Johnson Space Center) Feiverson, A. H. (NASA Johnson Space Center) Lee, S. M. C. (Wyle Integrated Science and Engineering Group) Mulavara, A. P. (Universities Space Research Association) Peters, B. T. (Wyle Integrated Science and Engineering Group) Platts, S. H. (NASA Johnson Space Center) Reschke, M. F. (NASA Johnson Space Center) Ryder, J. (Universities Space Research Association) Spiering, B. A. (Wyle Integrated Science and Engineering Group) Stenger, M. B. (Wyle Integrated Science and Engineering Group) Wood, S. (Universities Space Research Association) Lawrence, E. (Wyle Integrated Science and Engineering Group) Arzeno, N. (Wyle Integrated Science and Engineering Group)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States) NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Astronauts experience alterations in multiple physiological systems due to exposure to the microgravity conditions of space flight. These physiological changes include sensorimotor disturbances, cardiovascular deconditioning and loss of muscle mass and strength. These changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on lunar and Martian surfaces. To date, changes in functional performance have not been systematically studied or correlated with physiological changes. To understand how changes in physiological function impact functional performance an interdisciplinary pre/postflight testing regimen (Functional Task Test, FTT) has been developed that systematically evaluates both astronaut postflight functional performance and related physiological changes. The overall objectives of the FTT are to: Develop a set of functional tasks that represent critical mission tasks for Constellation. Determine the ability to perform these tasks after flight. Identify the key physiological factors that contribute to functional decrements. Use this information to develop targeted countermeasures. The functional test battery was designed to address high priority tasks identified by the Constellation program as critical for mission success. The set of functional tests making up the FTT include the: 1) Seat Egress and Walk Test, 2) Ladder Climb Test, 3) Recovery from Fall/Stand Test, 4) Rock Translation Test, 5) Jump Down Test, 6) Torque Generation Test, and 7) Construction Activity Board Test. Corresponding physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, orthostatic intolerance, upper and lower body muscle strength, power, fatigue, control and neuromuscular drive. Crewmembers will perform both functional and physiological tests before and after short (Shuttle) and long-duration (ISS) space flight. Data will be collected on R+0 (Shuttle only), R+1, R+6 and R+30. Using a multivariate regression model we will identify which physiological systems contribute the most to impaired performance on each functional test. This will allow us to identify the physiological systems that play the largest role in decrement in functional performance. Using this information we can then design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
52-04 BIOLOGICAL RADIATION EFFECTS
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Automated Patient Positioning Guided by Cone-Beam CT for Prostate Radiotherapy
Document ID:
20090002269
Report #:
AD-A487020
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Chao, Ming
Published:
20080101
Source:
Stanford Univ. (Stanford, CA United States)
Pages:
95
Contract #:
W81XWH-06-1-0235
Abstract:
Modern radiotherapy equipment is capable of delivering high precision conformal dose distributions to the target. However the target localization especially for soft-tissue target such as prostate is an issue because of its possible non-rigid internal motion relative to bony structures or external landmarks. Recently a new technology of kV cone-beam CT (CBCT) has been integrated onboard with the linear accelerator. The prostate target localization could be potentially done more accurately with the aid of the on-board CBCT imager. In this project the PI group developed a novel technique of automatic patient positioning for prostate cancer radiation therapy. A few important milestones have been achieved toward the goal of the project. These include: (i) Established a novel technique to enhance on-board cone-beam CT and to effectively reduce the radiation dose incurred in the scanning process; (ii) Developed a robust registration model with improved metric function; (iii) Developed an innovative narrow shell technique for better target localization and model the critical structure; (iv) Established the method for auto-propagation of contours from planning CT to CBCT based on feature based spline deformable registration. With more evaluations the automatic patient positioning technique and relevant research outcomes will soon be part of routine practice at Stanford University Hospital. The data and experiences we accumulated in this project are well documented and server as a good reference for effectively utilizing CBCT imager and will definitely enhance the outlook of the onboard CBCT in guiding radiation therapy as a whole.
Language:
English
Title:
Polymer Coats Leads on Implantable Medical Device
Document ID:
20090002469
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002469
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 52-53
Published:
20080901
Source:
Medtronic, Inc. (Minneapolis, MN, United States)
Pages:
1
Contract #:
None
Abstract:
Langley Research Center s Soluble Imide (LaRC-SI) was discovered by accident. While researching resins and adhesives for advanced composites for high-speed aircraft, Robert Bryant, a Langley engineer, noticed that one of the polymers he was working with did not behave as predicted. After putting the compound through a two-stage controlled chemical reaction, expecting it to precipitate as a powder after the second stage, he was surprised to see that the compound remained soluble. This novel characteristic ended up making this polymer a very significant finding, eventually leading Bryant and his team to win several NASA technology awards, and an "R&D 100" award. The unique feature of this compound is the way that it lends itself to easy processing. Most polyimides (members of a group of remarkably strong and incredibly heat- and chemical-resistant polymers) require complex curing cycles before they are usable. LaRC-SI remains soluble in its final form, so no further chemical processing is required to produce final materials, like thin films and varnishes. Since producing LaRC-SI does not require complex manufacturing techniques, it has been processed into useful forms for a variety of applications, including mechanical parts, magnetic components, ceramics, adhesives, composites, flexible circuits, multilayer printed circuits, and coatings on fiber optics, wires, and metals. Bryant s team was, at the time, heavily involved with the aircraft polymer project and could not afford to further develop the polymer resin. Believing it was worth further exploration, though, he developed a plan for funding development and submitted it to Langley s chief scientist, who endorsed the experimentation. Bryant then left the high-speed civil transport project to develop LaRC-SI. The result is an extremely tough, lightweight thermoplastic that is not only solvent-resistant, but also has the ability to withstand temperature ranges from cryogenic levels to above 200 C. The thermoplastic s unique characteristics lend it to many commercial applications; uses that Bryant believed would ultimately benefit industry and the Nation. "LaRC-SI," he explains, "is a product created in a government laboratory, funded with money from the tax-paying public. What we discovered helps further the economic competitiveness of the United States, and it was our goal to initiate the technology transfer process to ensure that our work benefited the widest range of people." Several NASA centers, including Langley, have explored methods for using LaRC-SI in a number of applications from radiation shielding and as an adhesive to uses involving replacement of conventional rigid circuit boards. In the commercial realm, LaRC-SI can now be found in several commercial products, including the thin-layer composite unimorph ferroelectric driver and sensor (THUNDER) piezoelectric actuator, another "R&D 100" award winner (Spinoff 2005).
Language:
English
Title:
Concurrent MR-NIR Imaging for Breast Cancer Diagnosis
Document ID:
20090003969
Report #:
AD-A488046
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yazici, Birsen
Published:
20080601
Source:
Rensselaer Polytechnic Inst. (Troy, NY United States)
Pages:
71
Contract #:
W81XWH-04-1-0559
Abstract:
The primary objective of this research program is to investigate concurrent near infrared (NIR) optical and magnetic resonance (MR) imaging for breast cancer diagnosis. The NIR diffuse optical imaging offers novel criteria for cancer differentiation with the ability to measure (in vivo) oxygenation and vascularization state, the uptake and release of contrast agents and chromophore concentrations with high sensitivity. However, NIR diffuse optical tomography is inherently a low spatial resolution imaging modality due to diffuse nature of light photons. Alternatively, MRI provides high spatial resolution with excellent tissue discrimination, but has limited ability to monitor hemoglobin dynamics and other contrast mechanisms that optical imaging provides. Therefore, concurrent MRI-NIR optical imaging brings together the most advantageous aspects of the two imaging modalities for breast cancer diagnosis.
Language:
English
Title:
Establishment of an 'In Vitro Cell-Based System' to Assay Radiation Sensitivity in Breast Cancer
Document ID:
20090003978
Report #:
AD-A488058
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Langland, Gregory
Published:
20080531
Source:
California Univ. (Berkeley, CA United States)
Pages:
12
Contract #:
W81XWH-06-1-0527
Abstract:
The purpose of this proposal is to develop an 'in vitro cell-based system' to study radioresistance in sporadic breast cancer. By performing colony formation assays in response to X-ray treatment we have shown that there is a wide range of sensitivities to this form of treatment. Interestingly, we have also observed that p53 status does not accurately predict response to radiation treatment. Using correlation studies, we have identified novel predictors of IR resistance/sensitivity. We have sensitized two breast cancer cell lines to X-ray treatment by using RNAi-based technology to inhibit Artemis function. In the future, these observations may have a significant clinical impact on the way radiation oncologists treat breast cancer patients.
Language:
English
53-01 PSYCHOLOGICAL FACTORS
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Tocopherol in Elder Self-Neglect
Document ID:
20090001946
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Aung, K. (Texas Univ. Health Science Center) Burnett, J. (Texas Univ. Health Science Center) Dyer, C. (Texas Univ. Health Science Center) Smith, S. M. (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Although elder self-neglect is the most common form of elder mistreatment, its pathophysiology is not well understood. Alpha-tocopherol is a lipid soluble antioxidant required for the preservation of cell membranes. Since the association between tocopherol and cognitive impairment in older adults has been described, we explored the possibility of its role in elder self-neglect. OBJECTIVE: (1) To determine whether serum tocopherol levels are associated with elder self-neglect, and (2) to assess the association of serum tocopherol levels and cognitive function in elder self-neglect. METHODS: Serum tocopherol levels were measured in a cohort of 67 self-neglecting elders and 67 matched controls, recruited for the Consortium for Research in Elder Self-neglect of Texas. Pearson s correlation tests were performed to assess bivariate associations between serum tocopherol levels and cognitive function. RESULTS: Mean serum alpha-tocopherol levels were 10.8 +/- 4.7 ug/mL in self-neglect group and 13.0 +/- 4.9 ug/mL in control group (p = 0.006, unpaired student s t-test). None of the participants from either group had alpha-tocopherol level lower than the reference range. Mean serum gamma-tocopherol levels were 2.0 +/- 1.0 ug/mL in self-neglect group and 2.0 +/- 1.1 in control group (p=0.83). Proportion of the elders with gamma-tocopherol level lower than the reference range were 4.5% (3/66) in self-neglect group and 10.4% (7/67) in control group (p=0.32, Fisher s Exact Test). Among the self-neglecting elders, no association was found between serum alpha-tocopherol levels and the Mini-Mental State Examination (MMSE) or the Wolf-Klein Clock Drawing Test (CDT) scores (r =-0.42, p=0.75 for MMSE; r=0.08, p=0.54 for CDT). No association was found between serum gamma-tocopherol levels and the MMSE or the CDT (r=-0.12, p=0.35 for MMSE; r=0.05, p=0.68 for CDT). CONCLUSION: In our sample, neither alpha-tocopherol nor gamma-tocopherol appears to have a role in pathophysiology of elder self-neglect. Nevertheless, significantly lower serum alpha-tocopherol levels in the self neglect group merits further research.
Language:
English
Notes:
American Geriatrics Society Annual Meeting Chicago, IL 29 Apr. - 3 May 2009
Title:
IMPRINT Analysis of an Unmanned Air System Geospatial Information Process
Document ID:
20090002045
Report #:
AD-A486680, ARL-TR-4513
Available Online:
http://hdl.handle.net/100.2/ADA486680
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Hunn, Bruce P Schweitzer, Kristin M Cahir, John A Finch, Mary M
Published:
20080701
Source:
Army Research Lab. (Aberdeen Proving Ground, MD United States)
Pages:
44
Contract #:
None
Abstract:
This study evaluated the streaming video analysis portion of the geospatial intelligence process associated with an unmanned aircraft system, which provides information to a four-person, military intelligence, geospatial analysis cell. The Improved Performance Research Integration Tool (IMPRINT) modeling program was used to understand this process and to assess crew workload during several test scenarios. Based on the use of IMPRINT, recommendations are made regarding the level of staffing for this type of system, based on crew workload characteristics discovered. This initial model was the first segment of a more comprehensive model to be developed to look at full mission conditions for a 12-hour shift.
Language:
English
Title:
Effects of Visual Communication Tool and Separable Status Display on Team Performance and Subjective Workload in Air Battle Management
Document ID:
20090002146
Report #:
AD-A486735
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Schwartz, Daniel Knott, Benjamin A Galster, Scott M
Published:
20080601
Source:
Air Force Research Lab. (Wright-Patterson AFB, OH United States)
Pages:
19
Contract #:
None
Abstract:
Tactical Air Battle Managers, such as AWACS Weapons Directors (WDs), perform as a team to effect command and control (C2) of assigned forces by planning, organizing, and directing operations. Specifically, AWACS WDs must coordinate offensive counter-air, defensive counter-air, and air refueling operations. AWACS WD teams accomplish their C2 function through networked collaboration that is typically supported by monitoring multiple radio communications channels under conditions of moderate to high ambient cabin noise while performing several visual and manual tasks. The purpose of this study is to compare team performance and subjective workload on a simulated AWACS scenario, for two conditions of communication (Voice-only, and Voice augmented with a Visual Communication Tool), and using two supplementary display conditions (Separable Status Display and No-Separable Status Display). Team performance measures on the AWACS scenario include (1) the percentage of enemy targets that were allowed to penetrate friendly airspace, (2) the percentage of high value assets destroyed (i.e., the air base, infantry units, and tanker aircraft), (3) the percentage of fighter assets that were lost due to fuel depletion or enemy attack, (4) the average time of enemy target prosecution.
Language:
English
Notes:
Presented at the International Command and Control Research and Technology Symposium (13th), held in Seattle, WA, on 17-19 June 2008. The original document contains color images
Title:
Designing to Support Command and Control in Urban Firefighting
Document ID:
20090002192
Report #:
AD-A486810
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Trent, Stoney Voshell, Martin Fern, Lisa Stephens, Robert
Published:
20080601
Source:
Military Academy (West Point, NY United States)
Pages:
15
Contract #:
DAAD19-01-2-0009
Abstract:
Recent fire disasters (e.g. 2000 Fireworks Factory, Enschede, NL; 2001 World Trade Center Attacks, NYC; 2007 Airline crashed into fuel warehouse, Sao Paolo, BR) have highlighted the need for support to incident commanders in emergency response situations. Contrary to technologists who introduce designs which are often clumsy and do not support critical tasks, human factors engineers take a problem-centered approach. This research and design project begins with a functional analysis of firefighting based on observations, interviews, doctrinal literature reviews, accident analysis, and simulations. The functional analysis then provides the design requirements for systems to support command and control for urban firefighters. These systems include personal tracking/alerting/communication devices, an interface for incident commanders, vehicular interfaces for fire companies, and an overarching architecture to support cross-echelon and interagency coordination. Recommendations are also made for improving Emergency Operations Centers. Findings from this project will provide unique insight for military command and control and inform decision makers about a design approach that applies to the development of future complex human-machine systems.
Language:
English
Notes:
Presented at the International Command and Control Research and Technology Symposium (13th) (ICCRTS 2008) held in Seattle, WA on 17-19 Jun 2008. The original document contains color images
Title:
Efficacy of Adjunctive Sleep Interventions for PTSD
Document ID:
20090003387
Report #:
AD-A487226
Available Online:
http://hdl.handle.net/100.2/ADA487226
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Germain, SaAnne Nofzinger, Eric A
Published:
20080301
Source:
Pittsburgh Univ. (Pittsburgh, PA United States)
Pages:
19
Contract #:
W81XWH-06-1-0257
Abstract:
Since the last report we have successfully achieved all goals initially set in our statement of work and task timeline for the first 24 months of the award. Recruitment has been delayed and accrued at a slower pace than initially anticipated for clinician-initiated referrals. However we have rapidly changed our recruitment strategy and continue to seek opportunities to collaborate effective with our colleagues at the VAPHS to facilitate and enhance recruitment of military veterans with sleep disturbances to our research program. This award has also significantly contributed to other reportable outcomes including several presentations and provided preliminary data for 2 successful applications for federal funding by the PI.
Language:
English
Title:
Test Operations Procedure (TOP) 1-1-003 Cold Regions Personnel Effects
Document ID:
20090003554
Report #:
AD-A487444, TOP-1-1-003
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
(Author(s) Not Available)
Published:
20080915
Source:
Army Cold Regions Test Center (Fort Greely, AK United States)
Pages:
13
Contract #:
None
Abstract:
This Test Operations Procedure (TOP) provides background information on physiological and psychological effects of cold on the human. It is an overview TOP and is organized to provide information on some of the problems associated with conducting operations, training, testing, and living in a cold environment. Rather than test procedures, it provides needed knowledge to safely conduct tests in the cold environment.
Language:
English
Title:
Cooperative Engagements and Levels of Interoperability (CELI) between Unmanned Aircraft Systems and the AH-64D Longbow
Document ID:
20090003740
Report #:
AD-A489364, DSE-TR-0806
Available Online:
http://hdl.handle.net/100.2/ADA489364
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sperling, Brian Kewley, Jr, Robert H
Published:
20080901
Source:
Military Academy (West Point, NY United States)
Pages:
35
Contract #:
None
Abstract:
This study outlines efforts to look into some of the considerations for integrating UAS video into the Apache cockpit in order to support cooperative engagements between UAS and attack helicopters. In these cooperative engagements, the UAS initially detects the target. A tactical operations center then does coordination with pre-planned or dynamically re-tasked aviation assets to move to the target area and engage the target. As the UAS hands off the target, the ability to view the UAS video inside the Apache cockpit supports a faster and more reliable target acquisition with greater situation awareness of the target area. This study addresses concerns about the cognitive workload this additional video places on the pilots. It also addresses some of the factors associated with overall success of cooperative engagements. This second portion of the study included a deployment into Iraq and Afghanistan to do detailed stakeholder analysis and functional analysis in order to better understand cooperative engagements and the potential challenges they pose for all elements of this systems of systems integration.
Language:
English
Title:
Documentation of Sensory Information in the Operation of Unmanned Aircraft Systems
Document ID:
20090003749
Report #:
AD-A490325, DOT/FAA/AM-08/23
Available Online:
http://hdl.handle.net/100.2/ADA490325
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Williams, Kevin W
Published:
20081001
Source:
Federal Aviation Administration (Oklahoma City, OK United States)
Pages:
60
Contract #:
None
Abstract:
The Federal Aviation Administration (FAA) requires airmen to report legal actions involving ethanol and/or other drugs, including driving while impaired by or while under the influence of alcohol. Pilots are also required to report any administrative action resulting in denial, suspension, cancellation, or revocation of driving privileges or mandatory attendance at an educational or rehabilitation program. The purpose of this study was to evaluate fatal civil aviation accidents between the years 2000 and 2007 in which ethanol was present in the pilot, and the pilot had previously documented drug and/or alcohol offenses and/or dependence. Toxicological and aeromedical findings from pilots were collected for an 8-year period, 2000 - 2007. Case histories, accident information, and the probable cause of the accidents were obtained from the National Transportation Safety Board. Toxicological information was obtained from the Civil Aerospace Medical Institute's Forensic Toxicology Research Laboratory. During the examined time period, 215 pilots (9%) of the 2,391 received for analysis had documented alcohol- or drug-related offenses. Of the 215 pilots, 23 (11%) had consumed ethanol prior to the fatal incident. Of these 23 pilots, 16 (~70%) had ethanol concentrations above the FAA's legal limit of 40 mg/dL and 7 (~30%) between 20 and 40 mg/dL. Providing more detailed documentation to aviation medical examiners would aid in the determination of eligibility for medical certification and could potentially save pilots as well as their passengers' lives. Identifying pilots with substance abuse problems is paramount for providing a safe environment to fly but also benefits the pilots who may not have addressed these issues.
Language:
English
Title:
Wave Reflection and Central Aortic Pressure Are Increased in Response to Static and Dynamic Muscle Contraction at Comparable Workloads
Document ID:
20090003754
Report #:
AD-A490380, USARIEM-M-07-29
Available Online:
http://hdl.handle.net/100.2/ADA490380
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Edwards, David G Mastin, Corey R Kenefick, Robert W
Published:
20080201
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
8
Contract #:
None
Abstract:
Wave reflection and central aortic pressure are increased in response to static and dynamic muscle contraction at comparable workloads. We determined the effects of static and dynamic muscle contraction at equivalent workloads on central aortic pressure and wave reflection. At random, 14 healthy men and women (23 +/- 5 yr of age) performed a static handgrip forearm contraction [90 s at 30% of maximal voluntary contraction (MVC)], dynamic handgrip contractions (1 contraction/s for 180 s at 30% MVC), and a control trial.
Language:
English
Title:
Behavioral and Mental Healthcare: Total Warrior Care Commitment. U.S. Army Medical Department Journal, July-September 2008
Document ID:
20090003883
Report #:
AD-A490967
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Aldridge, Don
Published:
20080901
Source:
Army Medical Dept. Center and School (Fort Sam Houston, TX United States)
Pages:
81
Contract #:
None
Abstract:
Clinical and non-clinical professional information designed to keep U.S. Army Medical Department personnel informed of health care, research, and combat and doctrine development information.
Language:
English
Title:
Structural and Mechanistic Analyses of TSC1/2 and Rheb 1/2-Mediated Regulation of the mTORC Pathway
Document ID:
20090003997
Report #:
AD-A488112
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sabatini, David
Published:
20080731
Source:
Whitehead Inst. for Biomedical Research (Cambridge, MA United States)
Pages:
12
Contract #:
W81XWH-07-1-0448
Abstract:
The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. In particular, the mTOR pathway is hyperactive in Tuberous Sclerosis Complex (TSC), a mental retardation and cancer-prone syndrome affecting 1 in 6,000 people in the United States. With the long-term goal of developing anti-cancer therapeutics based on the mTORC1 regulatory mechanism, we recently found that the Rag proteins, a family of four related small GTPases, interact with mTORC1 in an amino acid sensitive manner and are necessary for the activation of the mTORC1 pathway by amino acids. The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb. In addition, our structural analysis of mTORC1 generated preliminary cryo-EM reconstructions of the mTORC1 dimer and Raptor at resolutions of 25 and 30 , respectively.
Language:
English
Title:
A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol
Document ID:
20090004013
Report #:
AD-A488136
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Pitman, Roger K
Published:
20080601
Source:
General Hospital Corp. (Boston, MA United States)
Pages:
5
Contract #:
W81XWH-07-1-0440
Abstract:
The objective of this project is to test whether the beta-adrenergic blocker propranolol, given following combat memory reactivation, results in a significantly greater weakening of traumatic memories than propranolol alone, supporting the proposition that this weakening is due to pharmacological blockade of memory reconsolidation, rather than non-specific actions of propranolol. We hypothesize that subjects who undergo script preparation for the combat event(s) that caused their PTSD, followed by (post-reactivation) propranolol, will show significantly smaller psychophysiologic responses during script-driven imagery testing a week later, indicative of weakening of the emotional memory, compared to those who receive (non-reactivation) propranolol two days prior to combat script preparation. Subjects will be randomly assigned to one of two groups: post-reactivation propranolol or non-reactivation propranolol. Subjects randomized to the non-reactivation propranolol group will receive a "test" dose of propranolol, whereas subjects randomized to the post-reactivation propranolol group will receive placebo. Two days later, all subjects will return for an approximate 15-30 minute "script preparation" session, at which flme they will describe the details of their traumatic combat event(s). Subjects randomized to the post-reactivation propranolol group will then receive propranolol, whereas subjects randomized to the non-reactivation propranolol group will receive placebo. Scripts will be composed portraying each subject's personal combat events in their own words. Subjects will return to the psychophysiology laboratory one week and six months later. During each of these visits, heart rate, skin conductance, and corrugator electromyogram responses during will be recorded during script-driven imagery of personal combat events.
Language:
English
54-02 CREW SAFETY AND PROTECTIVE CLOTHING
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
No records are available for this topic on this date.
54-03 HUMAN ENGINEERING
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Human Error Quantification Using Performance Shaping Factors in the SPAR-H Method. 52nd Annual Meeting of the Human Factors and Ergonomics Society (Preprint)
Document ID:
20090001926
Report #:
DE2008-940041, INL/CON-08-14386
Sales Agency:
Department of Energy Information Bridge No Copyright
Author(s):
Blackman, H. S. Gertman, D. I. Boring, R. L.
Published:
20080901
Source:
Idaho National Lab. (Idaho Falls, ID, United States)
Pages:
6
Contract #:
None
Abstract:
This paper describes a cognitively based human reliability analysis (HRA) quantification technique for estimating the human error probabilities (HEPs) associated with operator and crew actions at nuclear power plants. The method described here, Standardized Plant Analysis Risk-Human Reliability Analysis (SPAR-H) method, was developed to aid in characterizing and quantifying human performance at nuclear power plants. The intent was to develop a defensible method that would consider all factors that may influence performance. In the SPAR-H approach, calculation of HEP rates is especially straightforward, starting with pre-defined nominal error rates for cognitive vs. action-oriented tasks, and incorporating performance shaping factor multipliers upon those nominal error rates.
Language:
English
Title:
The Development and Validation of a Human Systems Integration (HSI) Program for the Canadian Department of National Defence (DND)
Document ID:
20090002441
Report #:
AD-A486675, DRDC-CR-2008-005
Available Online:
http://hdl.handle.net/100.2/ADA486675
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Greenley, Mike Scipione, Andrea Brooks, Jeremy Salwaycott, Alice Dyck, Walter Shaw, Carolyn M
Published:
20080901
Source:
CAE Professional Services (Kanata, Ontario Canada)
Pages:
403
Contract #:
None
Abstract:
From 2000 to 2004, Defence Research and Development Canada conducted multi-year Research and Development (R&D) activities under contract to develop, demonstrate and validate a Human Systems Integration (HSI) approach for the Canadian Department of National Defence (DND) with the aim to transition this approach to an operational program within the DND's Material Acquisition and Support community. The foundation of an HSI Program was applied to 31 Defence acquisition projects from 2001-2004. Various components of the HSI Program were researched, developed, demonstrated, and iteratively improved. A cost benefit analysis derived from this effort was used to determine whether a permanent HSI Program within the DND would be worthwhile. $3,331,000.00 was spent on exercising a full or partial HSI process. This resulted in $3,515,000.00 in immediate savings based on observed data, providing a 106% payback. The cost of HSI application compared with immediate savings plus at least $133,000,000.00 in extrapolated savings (based on the impact the application of HSI had on projected life cycle costs) resulted in a 4000% payback, suggesting that HSI is a worthwhile investment. The possibility in hundreds of millions of dollars in further downstream savings based on lives saved or re-engineering costs avoided also existed but was not calculated. This study found that HSI costs ranged from 4 20% of a project's engineering budget and that Canada's integrated approach to HSI, whereby analyses are shared between HSI domains, can save up to 25% of HSI costs. This R&D effort developed and validated the Canadian HSI approach and supports the implementation of a formalized and enhanced HSI program within the Canadian DND.
Language:
English
Title:
Space Suit Technologies Protect Deep-Sea Divers
Document ID:
20090002470
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002470
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 80-81
Published:
20080901
Source:
Paragon Space Development Corp. (AZ, United States)
Pages:
1
Contract #:
None
Abstract:
Working on NASA missions allows engineers and scientists to hone their skills. Creating devices for the high-stress rigors of space travel pushes designers to their limits, and the results often far exceed the original concepts. The technologies developed for the extreme environment of space are often applicable here on Earth. Some of these NASA technologies, for example, have been applied to the breathing apparatuses worn by firefighters, the fire-resistant suits worn by racecar crews, and, most recently, the deep-sea gear worn by U.S. Navy divers.
Language:
English
Title:
Software Simulates Sight: Flat Panel Mura Detection
Document ID:
20090002490
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002490
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 136-137
Published:
20080901
Source:
Radiant Images, Inc. (Duvall, WA, United States)
Pages:
2
Contract #:
None
Abstract:
In the increasingly sophisticated world of high-definition flat screen monitors and television screens, image clarity and the elimination of distortion are paramount concerns. As the devices that reproduce images become more and more sophisticated, so do the technologies that verify their accuracy. By simulating the manner in which a human eye perceives and interprets a visual stimulus, NASA scientists have found ways to automatically and accurately test new monitors and displays. The Spatial Standard Observer (SSO) software metric, developed by Dr. Andrew B. Watson at Ames Research Center, measures visibility and defects in screens, displays, and interfaces. In the design of such a software tool, a central challenge is determining which aspects of visual function to include while accuracy and generality are important, relative simplicity of the software module is also a key virtue. Based on data collected in ModelFest, a large cooperative multi-lab project hosted by the Optical Society of America, the SSO simulates a simplified model of human spatial vision, operating on a pair of images that are viewed at a specific viewing distance with pixels having a known relation to luminance. The SSO measures the visibility of foveal spatial patterns, or the discriminability of two patterns, by incorporating only a few essential components of vision. These components include local contrast transformation, a contrast sensitivity function, local masking, and local pooling. By this construction, the SSO provides output in units of "just noticeable differences" (JND) a unit of measure based on the assumed smallest difference of sensory input detectable by a human being. Herein is the truly amazing ability of the SSO, while conventional methods can manipulate images, the SSO models human perception. This set of equations actually defines a mathematical way of working with an image that accurately reflects the way in which the human eye and mind behold a stimulus. The SSO is intended for a wide variety of applications, such as evaluating vision from unmanned aerial vehicles, measuring visibility of damage to aircraft and to the space shuttles, predicting outcomes of corrective laser eye surgery, inspecting displays during the manufacturing process, estimating the quality of compressed digital video, evaluating legibility of text, and predicting discriminability of icons or symbols in a graphical user interface.
Language:
English
Title:
Virtual Reality System Offers a Wide Perspective
Document ID:
20090002505
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002505
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 134-135
Published:
20080901
Source:
Sensics, Inc. (Baltimore, MD, United States)
Pages:
2
Contract #:
None
Abstract:
Robot Systems Technology Branch engineers at Johnson Space Center created the remotely controlled Robonaut for use as an additional "set of hands" in extravehicular activities (EVAs) and to allow exploration of environments that would be too dangerous or difficult for humans. One of the problems Robonaut developers encountered was that the robot s interface offered an extremely limited field of vision. Johnson robotics engineer, Darby Magruder, explained that the 40-degree field-of-view (FOV) in initial robotic prototypes provided very narrow tunnel vision, which posed difficulties for Robonaut operators trying to see the robot s surroundings. Because of the narrow FOV, NASA decided to reach out to the private sector for assistance. In addition to a wider FOV, NASA also desired higher resolution in a head-mounted display (HMD) with the added ability to capture and display video.
Language:
English
Title:
Determination of Ergonomic and Thermal Load Tests and Assessment of Reference Values with Light Weight Bomb Disposal Suits
Document ID:
20090002579
Report #:
TD2008-0073, TNO-DV 2008 A1 88
Sales Agency:
Other Sources Copyright
Author(s):
Kistemaker, J. A. (Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek)
Published:
20080501
Source:
Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (Soesterberg, Netherlands)
Pages:
28
Contract #:
None
Abstract:
A third series of tests were performed with light weight explosive ordnance disposal suits to get reference data about ergonomics and heat load. The results can be used for future tenders of light weight explosive ordnance disposal suits.
Language:
Dutch
Title:
Sensorimotor Adaptations Following Exposure to Ambiguous Inertial Motion Cues
Document ID:
20090002612
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Wood, S. J. (NASA Johnson Space Center) Harm, D. L. (NASA Johnson Space Center) Reschke, M. F. (NASA Johnson Space Center) Rupert, A. H. (Army Aeromedical Research Lab.) Clement, G. R. (Centre National de la Recherche Scientifique)
Published:
20090204
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
NCC9-58
Abstract:
The central nervous system must resolve the ambiguity of inertial motion sensory cues in order to derive accurate spatial orientation awareness. We hypothesize that multi-sensory integration will be adaptively optimized in altered gravity environments based on the dynamics of other sensory information available, with greater changes in otolith-mediated responses in the mid-frequency range where there is a crossover of tilt and translation responses. The primary goals of this ground-based research investigation are to explore physiological mechanisms and operational implications of tilt-translation disturbances during and following re-entry, and to evaluate a tactile prosthesis as a countermeasure for improving control of whole-body orientation.
Language:
English
Notes:
Human Research program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Biosensors for EVA: Muscle Oxygen and pH During Walking, Running and Simulated Reduced Gravity
Document ID:
20090002614
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Lee, S. M. C. (Wyle Labs., Inc.) Ellerby, G. (Massachusetts Univ.) Scott, P. (Massachusetts Univ.) Stroud, L. (Wyle Labs., Inc.) Norcross, J. (Wyle Labs., Inc.) Pesholov, B. (Massachusetts Univ.) Zou, F. (Massachusetts Univ.) Gernhardt, M. (NASA Johnson Space Center) Soller, B. (Massachusetts Univ.)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO2 on the leg during cycling. Our NSBRI-funded project is looking to extend this methodology to examine activities which more appropriately represent EVA activities, such as walking and running and to better understand factors that determine the metabolic cost of exercise in both normal and lunar gravity. Our 4 year project specifically addresses risk: ExMC 4.18: Lack of adequate biomedical monitoring capability for Constellation EVA Suits and EPSP risk: Risk of compromised EVA performance and crew health due to inadequate EVA suit systems.
Language:
English
Title:
Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)
Document ID:
20090002615
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Boyd, Jason L. (Universities Space Research Association) Du, Brian (Wyle Labs., Inc.) Daniels, Vernie (Wyle Labs., Inc.) Simmons, Rita (Naval Aerospace Medical Inst.) Buckey, Jay (Dartmouth-Hitchcock Medical Center) Putcha, Lakshmi (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on duty.
Language:
English
Notes:
Human Research Program Investigators' Workshop League City, TX 2-4 Feb. 2009
Title:
Diving in Space
Document ID:
20090002616
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002616
Sales Agency:
CASI Hardcopy A03 No Copyright
Author(s):
Gernhardt, Michael L. (NASA Johnson Space Center)
Published:
20081218
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
25
Contract #:
None
Abstract:
This viewgraph presentation reviews NASA's extravehicular activity (EVA) procedures and the technological and biomedical issues surrounding EVA.
Language:
English
Notes:
Haldane International Symposium 2008: The Future of Diving: 100 Years of Haldane and Beyond Trondheim 18-19 Dec. 2008
Title:
Cooperative Engagements and Levels of Interoperability (CELI) between Unmanned Aircraft Systems and the AH-64D Longbow
Document ID:
20090003740
Report #:
AD-A489364, DSE-TR-0806
Available Online:
http://hdl.handle.net/100.2/ADA489364
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sperling, Brian Kewley, Jr, Robert H
Published:
20080901
Source:
Military Academy (West Point, NY United States)
Pages:
35
Contract #:
None
Abstract:
This study outlines efforts to look into some of the considerations for integrating UAS video into the Apache cockpit in order to support cooperative engagements between UAS and attack helicopters. In these cooperative engagements, the UAS initially detects the target. A tactical operations center then does coordination with pre-planned or dynamically re-tasked aviation assets to move to the target area and engage the target. As the UAS hands off the target, the ability to view the UAS video inside the Apache cockpit supports a faster and more reliable target acquisition with greater situation awareness of the target area. This study addresses concerns about the cognitive workload this additional video places on the pilots. It also addresses some of the factors associated with overall success of cooperative engagements. This second portion of the study included a deployment into Iraq and Afghanistan to do detailed stakeholder analysis and functional analysis in order to better understand cooperative engagements and the potential challenges they pose for all elements of this systems of systems integration.
Language:
English
Title:
Assessment of Male Anthropometric Trends and the Effects on Simulated Heat Stress Responses
Document ID:
20090003758
Report #:
AD-A490384, USARIEM-M-07-34
Available Online:
http://hdl.handle.net/100.2/ADA490384
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yokota, Miyo Bathalon, Gaston P Berglund, Larry G
Published:
20080101
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
9
Contract #:
None
Abstract:
Assessing temporal changes in anthropometrics and body composition of US Army soldiers is important because these changes may effect fitness, performance, and safety. This study investigated differences in body dimensions(height, weight, percent body fat (%BF)) of US Army male soldiers by comparing 2004- 1988 databases. Anthropometric somatotypes were identified and physiological responses of the different somatotypes to simulated heat stress (35 deg C/50%rh, `550 W work rate, carrying 12 kg load including battle dress uniform and body armor, rest for 30 min and walk for 70 min) using a thermal regulatory model were evaluated.
Language:
English
Title:
Herontwerp Ballistisch vest voor Vrouwen: Fase 1 (Redesign Ballistic Vest for Women: Phase 1)
Document ID:
20090003980
Report #:
AD-A488066, TNO-DV-2008-A323
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Koerhuis, C L Weghorst, M G
Published:
20080901
Source:
Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (Soesterberg, Netherlands)
Pages:
28
Contract #:
None
Abstract:
In this study, an investigation was made about the experiences with the current ballistic vest. A questionnaire was filled out by fourteen female soldiers consisting of questions about complaints, characteristics of the ballistic vest and the mobility of the combat soldier wearing the ballistic vest. Most of the respondents experienced discomfort in the arm-pit, followed by discomfort in the lower back, the shoulders and on the busts. For the different characteristics of the ballistic vest, the worst score was given for comfort, followed by mobility and thermal strain. The worst mobility wearing the ballistic vest was experienced during sneaking, followed by climbing over obstacles. Optimization of ergonomical aspects of the ballistic vest is expected to result in a reduced detriment in physical performance of female soldiers performing operational tasks and will therefore be recommended.
Language:
Dutch
Title:
Suit Port Aft Bulkhead Mockup Test Results and Lessons Learned
Document ID:
20090004153
Report #:
None
Sales Agency:
Other Sources No Copyright
Author(s):
Romig, Barbara A. (NASA Johnson Space Center) Allton, Charles (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
The Small Pressurized Rover (SPR) is currently being carried as an integral part of the current Lunar Surface Architectures under consideration in the Constellation program. One element of the SPR is the suit port, the means by which the crew performs Extravehicular Activities (EVAs). Two suit port deliverables were produced in fiscal year 2008: an aft bulkhead mockup for functional integrated testing with the 1-G SPR mockup and a functional and pressurizable engineering unit. This paper focuses on the test results and lessons learned on the aft bulkhead mockup. The suit port aft bulkhead mockup was integrated with the mockup of the SPR cabin and chassis. It is located on the aft bulkhead of the SPR cabin structure and includes hatches, a locking mechanism, seals, interior and exterior suit don/doff aids, and exterior platforms to accommodate different crewmember heights. A lightweight mockup of the Mark III suit was tested with the suit port aft bulkhead mockup. There are several limitations to the suit port and mockup suits, and results of the suit port evaluation are presented and interpreted within the context of the limitations.
Language:
English
Notes:
39th International Conference on Environmental Systems Savannah, GA 12-16 Jul. 2009
Title:
Proposed Schematics and Modeling Results for a Lunar Portable Life Support System
Document ID:
20090004154
Report #:
None
Sales Agency:
Other Sources Copyright
Author(s):
Conger, Bruce (Jacobs Technologies Engineering Science Contract Group) Chullen, Cinda (NASA Johnson Space Center)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
The Constellation Space Suit Element (CSSE) is an integrated assembly made up of primarily a Pressure Garment System (PGS) and a Portable Life Support System (PLSS). The PLSS is further composed of an oxygen (O2) subsystem, a ventilation subsystem, and a thermal subsystem. This paper baselines a detailed schematic of the CSSE PLSS to provide a basis for current and future CSSE PLSS development efforts. Both context diagrams and detailed schematics describe the hardware components and overall functions for all three of the PLSS subsystems. Additionally, PLSS functions are presented for multiple operational scenarios as follows: 1) Nominal Extravehicular Activity (EVA) Mode; 2) Umbilical Modes; a) No Recharge, b) With Recharge; 3) Decompression Sickness (DCS) Treatment Mode; 4) Buddy Mode; 5) Secondary O2 Modes; a) Helmet Purge; b) Suit Purge; c) Operational; and 5) PLSS Removed Umbilical Mode. A performance modeling effort is being performed to provide a preliminary confirmation of this layout and the current state of the thermal hydraulic modeling efforts being conducted for the PLSS is presented. The goal of these efforts is to provide realistic simulations of the PLSS under various modes of operation. Modeling approaches and assumptions are discussed as well as component model descriptions. Results from the models are included that show PLSS operations at steady-state and transient conditions. Finally, conclusions and recommendations are offered that summarize results, identify PLSS design weaknesses uncovered during review of the analysis results, and propose areas for improvement to increase model fidelity and accuracy.
Language:
English
Notes:
39th International Conference on Environmental Systems Savannah, GA 12-16 Jul. 2009
54-04 MAN-MACHINE SYSTEMS
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Improved Decision Making in an Environment of Extreme Uncertainty through the Application of Augmented Cognition
Document ID:
20090002156
Report #:
AD-A486753
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Lenahan, Jack Nash, Mike Charles, Phil
Published:
20080601
Source:
Space and Naval Warfare Systems Command (Charleston, SC United States)
Pages:
25
Contract #:
None
Abstract:
The hypothesis of this paper is as follows: Uncertainty and inconsistency during complex endeavors can be reduced through the application of augmented cognition. An analysis of the genealogy of modern decision aides leads one to conclude that we should only be discussing the capability spectrum of intelligent software agents. We believe that this represents a limited view of the field of automated decision aides and assisted cognition. Instead of asking how smart the software agents can become, we would like to propose the following question: Can we make the human being smarter? Is it possible to improve cognitive functions inside the mind resulting in better selections of decision alternatives and interpretations of events? Is it possible to radically alter human training, development, and education to optimize the potential of every individual? The authors believe that the processes and tools being developed in the emerging field of augmented cognition can be exploited to provide a novel fusion of more capable human beings and exotic software agents. This fusion should result in breakthrough levels of situational awareness and superior decision making in environments of extreme uncertainty.
Language:
English
Notes:
Presented at the International Command and Control Research and Technology Symposium (13th) (ICCRTS 2008) held in Seattle, WA on 17-19 Jun 2008. Document includes briefing charts (13 slides, title same as paper). The original document contains color images
Title:
Future Combat Systems (FCS) Small Unmanned Ground Vehicle (SUGV) Teleoperation Experiment Results
Document ID:
20090003858
Report #:
AD-A490748, ARL-TR-4660
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
O'Brien, Barry Kovach, Jesse
Published:
20081201
Source:
Army Research Lab. (Aberdeen Proving Ground, MD United States)
Pages:
30
Contract #:
None
Abstract:
As part of the Army's Future Combat Systems (FCS) transformation effort, the newly redesigned Small Unmanned Ground Vehicle (SUGV) is required to use a common radio for communication between the SUGV s operator and the FCS network environment. FCS has proposed using the Joint Tactical Radio System (JTRS) Soldier-level Integrated Communications Environment (SLICE) radio operating with the Soldier Radio Waveform (SRW) as the SUGV radio solution. In the 2007 Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance (C4ISR) On-The-Move experiment, the FCS Network Analysis and Integration Laboratory (NAIL) conducted initial experiments to simulate the teleoperation of a SUGV-class platform using an implementation of this radio system called the Wearable Soldier Radio Terminal (WSRT). Working with NAIL representatives, U.S. Army Research Laboratory (ARL) engineers integrated the WSRT radios onto an ARL-modified PackBot system so that relevant real-world data could be collected. This report examines the integration effort that took place to allow the WSRT to control the ARL PackBot system, including the hardware and software used, and focuses on performance results, comparisons with the existing ARL radio solution, and initial conclusions.
Language:
English
54-05 BIOINSTRUMENTATION
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
9th Annual UC Systemwide Bioengineering Symposium
Document ID:
20090001984
Report #:
AD-A486532
Available Online:
http://hdl.handle.net/100.2/ADA486532
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Rodgers, Victor G
Published:
20080801
Source:
California Univ. (Riverside, CA United States)
Pages:
149
Contract #:
W81XWH-08-1-0405
Abstract:
The theme of this conference was to increase the synergistic interaction of the University of California's vast biomedical engineering research expertise with the practical medical and healthcare engineering undertaken by biomedical firms and government agencies. The symposium had 204 attendees representing all ten UC campuses as well as interested corporate and government agencies and individuals in the community. The symposium was supported by seven corporate sponsors and had four partnerships with industrial and government agencies. The symposium had twelve tracks that covered a broad range of topics to represent most research in Bioengineering at the University of California. In all, 48 talks and 49 posters were presented. In addition, five major presentations were given including three keynote speakers and two speakers representing TATRC. Through our generous corporate support, twelve cash awards totaling $5,000 were given to student oral and poster presenters who were judged to be outstanding. Judges were members of the UC, US Army Medical Research ACQ and our corporate sponsors. The program schedule is attached.
Language:
English
Notes:
Conference proceedings of the Annual UC Systemwide Bioengineering Syposium (9th), Riverside, CA on 20-22 Jun 2008
Title:
Biosensors for EVA: Muscle Oxygen and pH During Walking, Running and Simulated Reduced Gravity
Document ID:
20090002614
Report #:
None
Sales Agency:
CASI Hardcopy A01 Copyright
Author(s):
Lee, S. M. C. (Wyle Labs., Inc.) Ellerby, G. (Massachusetts Univ.) Scott, P. (Massachusetts Univ.) Stroud, L. (Wyle Labs., Inc.) Norcross, J. (Wyle Labs., Inc.) Pesholov, B. (Massachusetts Univ.) Zou, F. (Massachusetts Univ.) Gernhardt, M. (NASA Johnson Space Center) Soller, B. (Massachusetts Univ.)
Published:
20090101
Source:
NASA Johnson Space Center (Houston, TX, United States)
Pages:
1
Contract #:
None
Abstract:
During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO2 on the leg during cycling. Our NSBRI-funded project is looking to extend this methodology to examine activities which more appropriately represent EVA activities, such as walking and running and to better understand factors that determine the metabolic cost of exercise in both normal and lunar gravity. Our 4 year project specifically addresses risk: ExMC 4.18: Lack of adequate biomedical monitoring capability for Constellation EVA Suits and EPSP risk: Risk of compromised EVA performance and crew health due to inadequate EVA suit systems.
Language:
English
Title:
Directional microwave applicator and methods
Document ID:
20090002665
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002665
Sales Agency:
CASI Hardcopy A03 No Copyright
Author(s):
Fink, Patrick W. Lin, Greg Y. Chu, Andrew W. Dobbins, Justin A. Arndt, G. Dickey Ngo, Phong H.
Published:
20080812
Source:
NASA (Washington, DC United States)
Pages:
22
Contract #:
None
Abstract:
A miniature microwave antenna is disclosed which may be utilized for biomedical applications such as, for example, radiation induced hyperthermia through catheter systems. One feature of the antenna is that it possesses azimuthal directionality despite its small size. This directionality permits targeting of certain tissues while limiting thermal exposure of adjacent tissue. One embodiment has an outer diameter of about 0.095'' (2.4 mm) but the design permits for smaller diameters.
Language:
English
Title:
Telemedicine Based Ultrasound for Detecting Neonatal Heart Disease in Babies at Remote Military or Native American Health Care Facilities
Document ID:
20090003400
Report #:
AD-A487267
Available Online:
http://hdl.handle.net/100.2/ADA487267
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Sahn, David J Kinney, James Puntel, Robert
Published:
20080901
Source:
Oregon Health Sciences Univ. (Portland, OR United States)
Pages:
14
Contract #:
DAMD17-03-1-0109
Abstract:
Our partnership of investigators from Madigan Army Medical Center at Fort Lewis Washington and Oregon Health & Science University in Portland will test the hypothesis that trained primary care practitioners or nurses can with telemedicine supervision perform cardiac ultrasound exams on neonates at risk for heart disease and thereby impact time to diagnosis and outcomes. This study is targeted at Military Medical Facilities within TRICARE West and Western Regional Medial Command. It will also include two large Alaska Native Health Care Centers. Echocardiography has had major impact in the management of neonates suspected of having congenital heart disease. The expensive specialized equipment and significant expertise to adequately perform and interpret these studies usually is present only in tertiary level medical centers with a pediatric cardiologist on staff. Initial results of a National Multicenter Neonatal Telemedicine Echo Outcomes Study developed by the Principal Investigator suggest that telemedicine-implemented diagnosis positively affects outcomes in infants suspected of having congenital heart disease. Our partnership has trained 33 non cardiologists to perform neonatal echo and has installed a high bandwidth telecommunications link using the military version of Internet2, NIPRNET. By spring of 20077 we will be overseeing neonatal echo exams from 3 military installations in the NW and in Alaska, as well as a large Alaska Native Health Center in Anchorage. We have also arranged to upgrade the scanners used in our network to the latest architecture from Sonosite(Registered): the fully digital phased array hand held ultrasound scanner, the MicroMaxx(Registered).
Language:
English
Title:
Spring 2008 Industry Study: Biotechnology Industry
Document ID:
20090003594
Report #:
AD-A487542
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Anttonen, John Darnauer, Trish Douglas, Tim Ferrari, John Zimdahl, Jennifer Hall, Ian M King, William Klotzsche, Carl Miller, Doug Packard, Doug Renegar, Mike Rimback, Ed Rogers, Gordon Schnedar, Chris Sekulovski, Zoran
Published:
20080101
Source:
Industrial Coll. of the Armed Forces (Washington, DC United States)
Pages:
41
Contract #:
None
Abstract:
Defined broadly as the manipulation of genetic material in living organisms or the derivatives thereof, biotechnology represents a veritable gold mine of possibilities for improving the human condition. Society tends to focus on the glamorous; the success of the Human Genome Project and its modern miracle of unraveling the composition of human deoxyribonucleic acid (DNA). However, biotechnology is much more than genetics. It twines the developments in understanding the building blocks of life with their characteristics and uses in organic systems. In short, biotechnology is a multifaceted science that supports all manner of micro and macro interactions within the life sciences. This paper addresses three specific industries within the rubric of biotechnology - bio-fuels, agriculture, and medicine and offers broad policy recommendations designed to foster discussion and debate among senior leadership in order to leverage the applications of biotechnology for the good of the nation. In addition, the paper provides the reader with three essays that provide greater depth and breadth on significant current biotechnology issues. Continued development and implementation of governmental policies and funding that aggressively promote continued scientific discovery and breakthroughs in this diverse industry offer unprecedented opportunities to increase mankind's quality of life by reducing dependence on fossil fuels, significantly reducing greenhouse gas emissions, increasing production and distribution of food, improving resistance to disease, and developing personalized medicine. The question is not if this will occur, but when and how to ensure that it takes place in an ethical, reasonable manner that benefits America and the rest of the world.
Language:
English
Title:
Assessment of Male Anthropometric Trends and the Effects on Simulated Heat Stress Responses
Document ID:
20090003758
Report #:
AD-A490384, USARIEM-M-07-34
Available Online:
http://hdl.handle.net/100.2/ADA490384
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Yokota, Miyo Bathalon, Gaston P Berglund, Larry G
Published:
20080101
Source:
Army Research Inst. of Environmental Medicine (Natick, MA United States)
Pages:
9
Contract #:
None
Abstract:
Assessing temporal changes in anthropometrics and body composition of US Army soldiers is important because these changes may effect fitness, performance, and safety. This study investigated differences in body dimensions(height, weight, percent body fat (%BF)) of US Army male soldiers by comparing 2004- 1988 databases. Anthropometric somatotypes were identified and physiological responses of the different somatotypes to simulated heat stress (35 deg C/50%rh, `550 W work rate, carrying 12 kg load including battle dress uniform and body armor, rest for 30 min and walk for 70 min) using a thermal regulatory model were evaluated.
Language:
English
Title:
A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol
Document ID:
20090004013
Report #:
AD-A488136
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Pitman, Roger K
Published:
20080601
Source:
General Hospital Corp. (Boston, MA United States)
Pages:
5
Contract #:
W81XWH-07-1-0440
Abstract:
The objective of this project is to test whether the beta-adrenergic blocker propranolol, given following combat memory reactivation, results in a significantly greater weakening of traumatic memories than propranolol alone, supporting the proposition that this weakening is due to pharmacological blockade of memory reconsolidation, rather than non-specific actions of propranolol. We hypothesize that subjects who undergo script preparation for the combat event(s) that caused their PTSD, followed by (post-reactivation) propranolol, will show significantly smaller psychophysiologic responses during script-driven imagery testing a week later, indicative of weakening of the emotional memory, compared to those who receive (non-reactivation) propranolol two days prior to combat script preparation. Subjects will be randomly assigned to one of two groups: post-reactivation propranolol or non-reactivation propranolol. Subjects randomized to the non-reactivation propranolol group will receive a "test" dose of propranolol, whereas subjects randomized to the post-reactivation propranolol group will receive placebo. Two days later, all subjects will return for an approximate 15-30 minute "script preparation" session, at which flme they will describe the details of their traumatic combat event(s). Subjects randomized to the post-reactivation propranolol group will then receive propranolol, whereas subjects randomized to the non-reactivation propranolol group will receive placebo. Scripts will be composed portraying each subject's personal combat events in their own words. Subjects will return to the psychophysiology laboratory one week and six months later. During each of these visits, heart rate, skin conductance, and corrugator electromyogram responses during will be recorded during script-driven imagery of personal combat events.
Language:
English
54-06 ROBOTICS
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
Title:
Capability Driven Robotic Swarms in Reconnaissance-Based Operations
Document ID:
20090002142
Report #:
AD-A486727, USNA-TSPR-363, USNA-1531-2
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Barnes, Evan A
Published:
20080502
Source:
Naval Academy (Annapolis, MD United States)
Pages:
152
Contract #:
None
Abstract:
While 21st century surveillance techniques have started to utilize unmanned robotic platforms to gradually relieve many of the dangers and pressures placed on a human being, there is still a significant cost issue when addressing the overall effectiveness and efficiency. It is obvious that the unmanned robotic vehicle's ability to carry out surveillance missions is unparalleled by any human due to technological advances in electronic sensors. However, a single autonomous robot faces many limitations which decrease its cost efficiency and prevent it from being the best choice for various missions. On the other hand, a group of robots working together can remove many of the limitations imposed on one single unit. However, controlling a group of robots is inherently more complex than controlling just one. Initial controllers focused on the swarms mean position and variance in order to control its individual members and direct the entire swarm. This approach was successful in directing a swarm to a certain location; however, the swarm units were not always in the best position to use their individual capabilities. Since there is no way to control each individual unit's position without specific coding, the swarm may be in the correct location but some of the units may be rendered useless due to their position to the target point. This is one of the major concerns for using a mean/variance based controller in reconnaissance operations. This standard controller is better used for formation control of relative unit position based operations. This project developed new methodologies for optimizing the performance of a heterogeneous swarm in reconnaissance based operations.
Language:
English
Title:
The Safety of Unmanned Systems: The Development of Safety Precepts for Unmanned Systems (UMS)
Document ID:
20090002153
Report #:
AD-A486748
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
English, Thomas P Shampine, David J Adams, Julie A Muniak, Charles G Kratovil, Edward W
Published:
20080601
Source:
Naval Surface Warfare Center (Panama City, FL United States)
Pages:
52
Contract #:
None
Abstract:
In October 2005, the Defense Safety Oversight Council (DSOC), Acquisition and Technology Programs Task Force (ATP TF) established an initiative to help ensure the safety of unmanned systems (UMS). This initiative was established in response to the proliferation of UMS within the Department of Defense (DoD), and a concern for safety when these systems, primarily unmanned air vehicles, were operated over populated areas, or in proximity to other aircraft, both military and civilian, and when configured with weapons or ordnance items. This paper discusses the process that was followed in developing the UMS safety precepts and the associated DoD UMS safety guidelines document. It will also discuss the environment in which UMS are currently employed, the safety concerns with those operational environments and designs, UMS guide objectives, and conclude with an example of a Command and Control/Situational Awareness precept.
Language:
English
Title:
C2 of Unmanned Systems in Distributed ISR Operations
Document ID:
20090002194
Report #:
AD-A486817
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Bowman, Elizabeth K Thomas, Jeffrey A
Published:
20080601
Source:
Army Research Lab. (Aberdeen Proving Ground, MD United States)
Pages:
36
Contract #:
None
Abstract:
This paper describes a series of experiments to investigate issues of human-robot teaming and network centric operations. Experiment objectives were coordinated to address issues within and among the physical, communications, information, and human (cognitive/social) domain layers of the network. Objectives spanned the cognitive, social, and physical domains of the network. In the cognitive domain, researchers tested a predictive performance tool for robotic operators and measured operator situational awareness and workload during missions as these conditions related to reliance upon unmanned surveillance technologies. In the social domain, we documented the ad hoc development of social, task, and knowledge networks during missions. These human dimensions of the network were juxtaposed to the agile computing infrastructure operating over a Future Force surrogate network and an 802.11 network. Results show that many challenges exist across the layers of the network domain architecture. Primary among these is to develop a mobile ad hoc network (MANET) to support mobile and extended vehicle/dismount ranges in a variety of terrain conditions. In the cognitive/social domain, we need to understand what information Soldiers need from a network, when this information is of maximum use, and what form the information should take for maximum situational awareness and decision making.
Language:
English
Notes:
Presented at the International Command and Control Research and Technology Symposium (ICCRTS 2008) (13th), held in Seattle, WA, on 17-19 June 2008. Document includes briefing charts in addition to text. The original document contains color images
Title:
Triple Helix
Document ID:
20090002421
Report #:
AD-A486058
Available Online:
http://hdl.handle.net/100.2/ADA486058
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
(Author(s) Not Available)
Published:
20080801
Source:
Newport News Public School District (VA United States)
Pages:
11
Contract #:
W911NF-07-1-0663
Abstract:
FIRST(For Inspiration and Recognition of Science and Technology) was founded by inventor Dean Kamen to inspire an appreciation of science and technology in young people. Based in Manchester, New Hampshire, the 501.3(c) not-for-profit organization designs accessible, innovative programs to build self-confidence, knowledge, and life skills while motivating young people to pursue opportunities in science, technology, and engineering. One such program is the FIRST Robotics Competition for high school students. In 2008, the FIRST Robotics Competition challenged over 37,000 high-school-aged young people on more than 1,500 teams worldwide to work with 18,000 mentors and 2,000 sponsoring companies to design, construct, and test a robot during an intense, six-week season. This six-week season, in which teams must advance from initial design to final product, creates a real world engineering experience that includes critical technical analysis, acquisition and application of engineering knowledge, technical fabrication, systems engineering and integration, time management, resource allotment, teamwork, and many other life skills that combine to help students focus on technology as a possible career choice. In September 2007, Menchville High School in Newport News, Virginia, with the assistance of a Department of the Army grant and contributions by other non-government entities, established a FIRST Robotics Competition (FRC) team. The Menchville Robotics Team, also known as Triple Helix, had an outstanding first year. The highlight of the year was participating in the FIRST NASA/Virginia Commonwealth University Regional competition held in Richmond, Virginia, March 6-8, 2008. Although placing only 58th out of 64 teams, Triple Helix was awarded with the FIRST Rookie Inspiration Award for outstanding success in technology education.
Language:
English
Title:
Robotics Offer Newfound Surgical Capabilities
Document ID:
20090002475
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002475
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 46-47
Published:
20080901
Source:
Barrett Technology, Inc. (Cambridge, MA, United States)
Pages:
2
Contract #:
None
Abstract:
Barrett Technology Inc., of Cambridge, Massachusetts, completed three Phase II Small Business Innovation Research (SBIR) contracts with Johnson Space Center, during which the company developed and commercialized three core technologies: a robotic arm, a hand that functions atop the arm, and a motor driver to operate the robotics. Among many industry uses, recently, an adaptation of the arm has been cleared by the U.S. Food and Drug Administration (FDA) for use in a minimally invasive knee surgery procedure, where its precision control makes it ideal for inserting a very small implant.
Language:
English
Title:
Mars Mapping Technology Brings Main Street to Life
Document ID:
20090002482
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002482
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 140-141
Published:
20080901
Source:
Earthmine, Inc. (Berkeley, CA, United States)
Pages:
2
Contract #:
None
Abstract:
The Red Planet has long held a particular hold on the human psyche. From the Roman god of war to Orson Welles infamous Halloween broadcast, our nearest planetary neighbor has been viewed with curiosity, suspicion, and awe. Pictures of Mars from 1965 to the present reveal familiar landscapes while also challenging our perceptions and revising our understanding of the processes at work in planets. Frequent discoveries have forced significant revisions to previous theories. Although Mars shares many familiar features with Earth, such as mountains, plains, valleys, and polar ice, the conditions on Mars can vary wildly from those with which we are familiar. The apparently cold, rocky, and dusty wasteland seen through the eyes of spacecraft and Martian probes hints at a dynamic past of volcanic activity, cataclysmic meteors, and raging waters. New discoveries continue to revise our view of our next-door neighbor, and further exploration is now paving the way for a human sortie to the fourth stone from the Sun. NASA s Mars Exploration Program, a long-term effort of robotic exploration, utilizes wide-angle stereo cameras mounted on NASA s twin robot geologists, the Mars Exploration Rovers (MERs), launched in 2003. The rovers, named "Spirit" and "Opportunity," celebrated 4 Earth years of exploration on January 3, 2008, and have sent back a wealth of information on the terrain and composition of the Martian surface. Their marathon performance has far outlasted the intended 90 days of operation, and the two intrepid explorers promise more images and data.
Language:
English
Title:
Robotic Joints Support Horses and Humans
Document ID:
20090002485
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002485
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 56-57
Published:
20080901
Source:
Walter Reed Army Medical Center (Washington, DC, United States)
Pages:
2
Contract #:
None
Abstract:
A rehabilitative device first featured in Spinoff 2003 is not only helping human patients regain the ability to walk, but is now helping our four-legged friends as well. The late James Kerley, a prominent Goddard Space Flight Center researcher, developed cable-compliant mechanisms in the 1980s to enable sounding rocket assemblies and robots to grip or join objects. In cable-compliant joints (CCJs), short segments of cable connect structural elements, allowing for six directions of movement, twisting, alignment, and energy damping. Kerley later worked with Goddard s Wayne Eklund and Allen Crane to incorporate the cable-compliant mechanisms into a walker for human patients to support the pelvis and imitate hip joint movement.
Language:
English
Title:
Robots Explore the Farthest Reaches of Earth and Space
Document ID:
20090002503
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002503
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 116-117
Published:
20080901
Source:
Deep Ocean Engineering, Inc. (San Leandro, CA, United States)
Pages:
2
Contract #:
None
Abstract:
"We were the first that ever burst/Into that silent sea," the title character recounts in Samuel Taylor Coleridge s opus Rime of the Ancient Mariner. This famous couplet is equally applicable to undersea exploration today as surface voyages then, and has recently been applied to space travel in the title of a chronicle of the early years of human space flight ("Into That Silent Sea: Trailblazers of the Space Era, 1961-1965"), companion to the +n the Shadow of the Moon book and movie. The parallel is certainly fitting, considering both fields explore unknown, harsh, and tantalizingly inhospitable environments. For starters, exploring the Briny Deep and the Final Frontier requires special vehicles, and the most economical and safest means for each employ remotely operated vehicles (ROVs). ROVs have proven the tool of choice for exploring remote locations, allowing scientists to explore the deepest part of the sea and the furthest reaches of the solar system with the least weight penalty, the most flexibility and specialization of design, and without the need to provide for sustaining human life, or the risk of jeopardizing that life. Most NASA probes, including the historic Voyager I and II spacecraft and especially the Mars rovers, Spirit and Opportunity, feature remote operation, but new missions and new planetary environments will demand new capabilities from the robotic explorers of the future. NASA has an acute interest in the development of specialized ROVs, as new lessons learned on Earth can be applied to new environments and increasingly complex missions in the future of space exploration.
Language:
English
Title:
Virtual Reality System Offers a Wide Perspective
Document ID:
20090002505
Report #:
None
Available Online:
http://hdl.handle.net/2060/20090002505
Sales Agency:
CASI Hardcopy A01 No Copyright
Author(s):
(Author(s) Not Available)
Journal:
Spinoff 2008: 50 Years of NASA-Derived Technologies (1958-2008), Page: 134-135
Published:
20080901
Source:
Sensics, Inc. (Baltimore, MD, United States)
Pages:
2
Contract #:
None
Abstract:
Robot Systems Technology Branch engineers at Johnson Space Center created the remotely controlled Robonaut for use as an additional "set of hands" in extravehicular activities (EVAs) and to allow exploration of environments that would be too dangerous or difficult for humans. One of the problems Robonaut developers encountered was that the robot s interface offered an extremely limited field of vision. Johnson robotics engineer, Darby Magruder, explained that the 40-degree field-of-view (FOV) in initial robotic prototypes provided very narrow tunnel vision, which posed difficulties for Robonaut operators trying to see the robot s surroundings. Because of the narrow FOV, NASA decided to reach out to the private sector for assistance. In addition to a wider FOV, NASA also desired higher resolution in a head-mounted display (HMD) with the added ability to capture and display video.
Language:
English
Title:
Initial Set of Use Cases for High-Fidelity Synthetic Environment/Virtial Autonomous Navigation Environment Development Tied to Unmanned Ground Vehicle Capability Gaps
Document ID:
20090003343
Report #:
AD-A486602, DSE-TR-0912
Available Online:
http://hdl.handle.net/100.2/ADA486602
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
Nagle, Joyce A Goerger, Niki C DeLong, Suzanne M
Published:
20080901
Source:
Army Engineer Research and Development Center (Vicksburg, MS United States)
Pages:
34
Contract #:
None
Abstract:
To help guide alternative assessments and experiments for the development of a high fidelity synthetic environment (HFSE), an initial set of Use Cases was developed based on Capability Gaps identified in the U.S. Army/U.S. Marine Corps Ground Robotics Master Plan (Robotics Systems Joint Project Office (RS JPO), 2007). Four specific scenarios were developed in which an unmanned ground vehicle (UGV) is employed to contribute to a mission. The Use Cases are narrative descriptions of a sequence of actions a Warfighter equipped with a UGV, would undertake to accomplish a goal. The Use Cases do not identify requirements, but rather imply them in the stories they tell, leaving it up to an analyst to identify the requirements. The Use Cases avoid identifying or describing specific platforms, but rather create opportunities for analysts to identify capabilities. The Use Cases developed will provide the structure in which we can analyze both the HFSE and the UGV performance in the HFSE.
Language:
English
Notes:
Sponsored by the Office of the Under Secretary of Defense for Acquisition, Technology and Logistics/Portfolio Systems Acquisition, Land Warfare and Munitions, Joint Ground Robotics Enterprise
Title:
Future Combat Systems (FCS) Small Unmanned Ground Vehicle (SUGV) Teleoperation Experiment Results
Document ID:
20090003858
Report #:
AD-A490748, ARL-TR-4660
Sales Agency:
Defense Technical Information Center (DTIC) No Copyright
Author(s):
O'Brien, Barry Kovach, Jesse
Published:
20081201
Source:
Army Research Lab. (Aberdeen Proving Ground, MD United States)
Pages:
30
Contract #:
None
Abstract:
As part of the Army's Future Combat Systems (FCS) transformation effort, the newly redesigned Small Unmanned Ground Vehicle (SUGV) is required to use a common radio for communication between the SUGV s operator and the FCS network environment. FCS has proposed using the Joint Tactical Radio System (JTRS) Soldier-level Integrated Communications Environment (SLICE) radio operating with the Soldier Radio Waveform (SRW) as the SUGV radio solution. In the 2007 Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance (C4ISR) On-The-Move experiment, the FCS Network Analysis and Integration Laboratory (NAIL) conducted initial experiments to simulate the teleoperation of a SUGV-class platform using an implementation of this radio system called the Wearable Soldier Radio Terminal (WSRT). Working with NAIL representatives, U.S. Army Research Laboratory (ARL) engineers integrated the WSRT radios onto an ARL-modified PackBot system so that relevant real-world data could be collected. This report examines the integration effort that took place to allow the WSRT to control the ARL PackBot system, including the hardware and software used, and focuses on performance results, comparisons with the existing ARL radio solution, and initial conclusions.
Language:
English
55-01 EXTRATERRESTRIAL LIFE
Feb 1, 2009 -- Additions to the NASA scientific and technical information knowledge base
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