U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SE NATIONAL INSTITUTES OF HEALTH SPECIALRESEARCHRESOURCEANNUALREPORT Grant Number FR-Wll-03 ACME August 1, 1968 toJuly31, 1969 Joshua Lederberg, Ph.D., Principal Investigator Stanford University School of Medicine U. S. DEPARTMENT OF HEALTH, EDIJCATION, AND WELFARE PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH SPECIAL RESEARCH RESOURCE ANNUAL REPORT Report Period; (same as current 12-month Grant No. budget period) From: August 1, 1968 To: July 31, 1969 FR 00311-03 Resource Title Resource Address Resource Tel. No. Stanford University (415) 321-1200 Advanced Computer for School of Medicine Ext. 5818 MEdical Research (ACME) Palo Alto, California Principal Investigator Title Academic Dept. Lederberg, Joshua Professor Genetics Grantee Institution Type of Institution Investigator's Tel. No. Stanford University Private University School of Medicine (415) 321-2300 1 I Ext. 5049 Name of Institution's Special Research Resource Advisory Committee: Computer Policy Committee Membership of Special Research Resource Advisory Committee (Indicate Chairman) Name Title Department Institution see next page Typed Name and Title of Principal Investigator 7 Signature Joshua Lederberg, Professor Typed Name and Title of Grantee Institution Signature Official Date Date 1 Stanford University Advanced Computer for Medical Grant No. FR 00311-03 TABLE OF COWI'ENTS Special Research Resource Annual Report Section I: Resource Operations A. General Description of Resource Operation 4 B. Summary of Resource Usage 27 C. Resource Equipment List 66 D. Summary of Publications 72 Section II: Resource Finances A. Summary of Resource Expenditures B. Summary of Resource Funding C. Expenditure Details - Direct Costs D. Budget Explanation - Justification Section III: Project Descriptions A. Core Research Project Descriptions B. Individual User Project Descriptions 76 77 78 82 85 88 3 Grant No. FR00311-03 Section I-A General Description of Resource Operation Most of this third and final year of the original ACME grant period has been spent implementing changes and adjustments required to make the ACME system a useful and productive unit for the Stanford Medical School. Currently ACME service hours, whenever feasible, are 7:00 a.m. to 5:OO p.m., and 6:30 p.m. until midnight. Hardware reliability since the last report has improved significantly. We are, however, still experiencing an average of two hardware failures a week and are further implementing recovery procedures for all hardware errors where even a minimal chance exists of achieving proper recovery. Changes have been made by IBM in both the 270X and 27OY data-acquisition hardware and in the 1800 subsidiary computer's interface hardware to the 360. The changes, together with a better understanding of the data-acquisition devices, have resulted in a reliability comparable to that of the files and the central processing unit. The current bottleneck in the overall system is the speed of the large-core memories (8 miscrosecond cycle time). This could be improved, without any soft- ware changes by providing more high-speed memory. The shortage of fast-core memory has been aggravated by changing options within the IBM operating system. To obtain greater reliability, we have shifted to the MVT option of os/360. Studies and discussions with IBM have led us to believe we will have fewer errors in using MVT. The last three months of operation of the MVT-based system have proven this judgement to be correct; we have had few failures of OS interrupt processing and partitioning. These are the areas of IBM's operating system upon which we rely most heavily. Our experience with the processors, such as the Fortran compiler under the operating system, are not that favorable. 4 Grant No. FROOTU-03 Section I-A Hardware changes: We added a second 2314 disk unit in December; this second unit is now already 50 per cent filled with user data. This means that our user file capacity has grown from approximately 127 million bytes to 263.6 million bytes with a corresponding--and sometimes too rapid--increase in usage. We also added slowspeed paper tape equipment on the 1800 in order to service instrumentation needs when data rate and duty cycle make an experiment impractical for on-line data acquisction. The 1800 can now timeshare 16 user lines; this is generally sufficient for four to five users' data moving simultaneously over the lines. We are experi- menting to determine how much the load-factor can be increased without affecting our capability to provide reliable service. The 27OY and 2701 service has been successfully provided to remote sites with a 20,000 sample-per-second transmission speed. The data path, that is the size of a sample, on the 1800 and the 2701 is 16 bits wide; the data path on the 27OY is 8 bits wide. More need for 1800 facilities seems to exist and can be handled within the current software design by increasing the amount of core memory storage available in the 1800. Currently a limitation of about 6000 samples per second aggregate net-data rate exists in the communication interface from the 1800 to the 360. Software developments: Implementation of "external procedures". This permits programs and sub- routines tc be shared by users in a modular way and also removes the limit on program size in the ACME system other than that of total hardware core and file size. Of course practical limitations due to the speed of the processor remain. 5 Grant No. FRO0311 -03 Section I-A The direct input/output facility of PL/I has been implemented and enables users to write significant information retrieval and patient-record programs without excessive search time. Organization of these files is a problem for which professional assistance is frequently required. Regina Frey, of the ACME staff, is available to assist with the design and layout of problems of this nature. PROTECT FILE statements have been implemented to provide data-set protection to users who wish it. A non-PL form of file has been implemented-- the text file--which provides for convenient editing of reports, memorandum, and programs themselves under full program control. A number of major internal changes were made to the file system. The first change eliminated the necessity for copying the index of a file into a temporary location on a disk when the file is opened. This saved space on the disks, removed the limitation on the number of files which could be opened simultaneously, and greatly reduced the time required to open and close files. A change to the hardware format of the file blocks allows checking the ownership of a block in the channel program without reading the block into core. As a result the channel time required to write a block was reduced by one-half (see ACME Note FIO appended to this section). The computational facilities of the system have been increased by providing double precision arithmetic. The seven-digit precision of the IBM 360 is generally adequate, but a few'users were seriously hampered by the lack of more precision in the ACNE system. Double precision provides about 16-digit precision for these users. Improvements to the PL/ACME: language include the INITIAL attribute and the capa'bility to write mutiple statements on one line. Both these facilities can decrease program writing time and program compile time. 6 Grant NO. F'RO:JJLL-0~j Section I-A FREE and ALLOCATE statements pertaining to arrays were implemented to give the user program control over the amount of memory he is using. This pro- vides him a tool to minimize charges based on the amount of memory used, yet permits him to take advantage of the very large potential memory capability inherent in the ACME system. A number of new string functions round out the facilities provided in FL/I and some work has been done to speed up the processing of string operators, although much remains to be done in this area. A number of new programs now make it possible to do much file maintenance while the system is on-line without interfering with users. This has enhanced our capability to respond to errors due to either software or hardware problems, We have continued our emphasis on guaranteeing all files stored on disk. File integrity has been maintained through continued use of software redundancy checks and by a number of analyzer and restoration utility programs. Backup files are created by nightly dumps of the disks to tape. Cur backing up of file stopage has proven to be most useful. No loss of data occurred during the last year. Four potentially disastrous failures did happen. Twice loss was prevented by the interlocks in the file system. The other two times the damage was due to operator error, but full recovery was possible from the backup files. Maintenance and development work on the library programs has had to be retrenched, and is now going on at a somewhat lower level than we feel would be benefYcia1 to the Stanford Medical School. A list of the Library routines is appended to this report. Most of these are statistical in nature; a few provide program editing and translation features. Our engineering group has installed and maintains 22 laboratory interfaces. The group is occasionally engaged in the design of specialized instrumentation 7 Grant No. FRG0311-C3 Section I-A to service specific medical requirements. A new terminal switchboard has been installed in the computer room to cope with the iarger frequency of user calls and active terminals. We have been engaged in circuit and software development to make storage displays manufactured by Tektronix and Hewlet t-Packard easily interfaceable for ACME users. A small effort is underway to evaluate the cost and benefits of making a continuous system modelling program (CSMP) available on ACME. It appears that model builders at Stanford would be greatly aided by an interactive facility. Compatibility with batch versions will be important since ACME is not suitable for large simulations. An assembler for the 1800 has been produced with PL/ACME. We expect to cancel the card equipment presently on the 1800 and load the machine through the 360. This assembly concept is being studied to determine the methods and benefits of providing assembler services for small computers that are connected to ACME. This could increase their research duty cycle and make smaller con- figuration feasible. A more unified assembly language could also be an aid in obtaining greater independence from a particular manufacturer by increasing software transparency. A fair amount of effort has gone into the accounting programs in order to prepare for the new recharge policy. Operating Policies and Procedures System reliability has become the primary goal during the last year. This is especially important since some of our users collect instrumentation data on a real-time basis and have no protective backup device. Detailed records are kept of the systems operation. Every failure-software, hardware, or power--is 8 Grant No. FROO311-03 Section S-A logged, analyzed, and discussed in the weekly st*aff meeting in an effort to devise means of preventing recurrence. Five bac'kup systems are kept at all times i.n order to prevent errors being introduced during development of software which mi.ght sffect daily operations. Flexibi!ity is the key to success to operations in a research computer rnvironlrent. This is especially true at ACME. The system is constantly upgraded (both software and hardware --including computer input/output devices and in-house designed and built interface equipment). We have established an enforced system backup to protect user data and system disk packs. All user data packs are dumped to tape three times a week. Two sets of daily tapes are rotated each week; seven weekly' sets are rotated Pve ry month. The first set of weekly tapes each month is saved permanently, and repl.acPit wi!;h a new set, of tapes. All operating procedures are documented by ACME Notes which are distributed ,to the ACME staff. The graph showing hardware-and software downtime is presented on the next pge. This graph shows utilization. Although considerable detail of this ut;ilizati.on is given in Section I-B of this report, it is appropriate at this point to note some of the highlights of utilization of the ACME system. There has been an up'trend ever since the basic software was stabilized enough to present meaningful statistics. After the sharp dips in utilization as the result fJ-,f hardwa.re difficulties toward the end of the previous budget year, the rate '7; inf2re.i.:;2 climbed' more rapidly as the user community gained confidence in the system's reliability. The dip at the end of calendar year 1968 resulted from the announcement of user charges as well as seasonal factors of the end of quarter and year-end holidays. 9 G:an? No. FRM!":: -3: S&iori i-C ACME Note Monthly Usage at ACME Absolute maxima of terminal hours per month: 10,170 (30 !`np.;. 30 days, 1;. 5 hours pr'~ bay:. Absoicte ma*`. . of terminal page minutes per month: 7,866,0@J (380 pages, 30 days. 11 5 I)olii': d:`r day!. Revision of AU-10 dated April 24, 1969. Dist: Staff/All !G Utilization as expressed in page minui;es :c+=pr,'~+,Y an aLI. time high of L - ..bJL^~ ,L 2,260,[596 in the accounting period .April 17, 19: ,p ./ ,)l rough J&3 y 16, I-969 e k1.y .%9,364 page minutes were used by the ACFE staff z~,,i :isErs accounted for almost with :KL.h grants v,l~:ich are presently exs:iq>t from users charges because they have non-compe,ting renewal grants. i;,!)(>`y'i~.J~l oi';, I. ' r:onctar!t, communication with the user is vital, The lightbox on the I,SC'l i : +?~mxll~li,S pro,vide both system and operati.ons information to him. Da i-Ly ;p3cial by)sdcas:;.s announce current system e-fents that may 8ffec-L users. An iilfO~W~.~:`L USf?3r is a !itippy USC?T. I&w features not yet documented in the manual are described in .ACME iJser ii] 0 .[. I" :; " XME hours are from 7:CO a.m. to 5:OC p.m. ar,d 6:30 p.m. to midnight, dail.po i;erjeral. s r- hatern development work.and file maintenance, and four hours a week of Exceptions may be made to use the period from 3:30 to 5:00 p.m. and 1O:OC .p.m. if.i: rnidr;.'_;$tt when urgent system work requires it. `K? L ! I R r'hortsge of terminal lines develops, the following priorities are yj:;e r.;e&: .F ki^s t T)r ior-. ty : Users signed up for realtime experiments. ;~;;:'->:::i x, _ " , rlc!-?:LetJ: Ail other known users, queued in first-in, first-out order. `fp i.rci I-`-f iJ>yity: "~Jn'known" users (i.e., medical student terminals), only ~2' there are free terminal lines. The ACME TV display Gralit &jo . FE:gO", 1 I.-(;" A Section I-A c is scheduled by a separate s ign-up sheet. The operator has control over real-time usage i-c irisure that the required response rates are not impacted by excessive usage, An effort is being made to train our own operators, including recruits frcm the local community. A Sanders 720 graphic display unit. (, nrcvided by the Genetics Department) al-lows the computer operator to obtain a list of users on the system at any ~~;iVWi moment. It has increased our access to user status over the IBM typewriter terminal by a X5-to-l ratio (from 150-second access to 10-second access). Our new switchboard has semi-automated the connecting of user terminals L; ACME . Formerly the user would telephone the computer room and request that ;1 %702 port be connected to his terminal. Our new board requires the user onLy YL ; :r'ess the button on the lightbox. When the operator plugs an available port 5ilto the user's outlet, the indicator lights turn off. ji$g ir;is-e:[*at j ye Changes -_ .II- In this third year of the ACME project Joshua Lederberg, Ph.D., Professor, I :?;2i Chairman, Department of Genetics, continued as Principal Investigator. The A(373 Policy Committee is drawn principally from the community of users in -t'ne Xedic.:al School. ACME is administered technically as a facility of the Stanford !%itlp1tLat;.on Center. During the year covered in this Report, Paul Armer succeeded Edward Feigenbaltifl ;:s i):Lre:tor of the Stanford Computation Center. Professor Feigenbaum is concen- trating on his teaching and research in the Computer Science Department, but `zoiit, il-il;::s z'? sei'de ACME as an advisor for computing techniques. Gio Wiederhold cont~ued as Associate Director of t'ne ACME Facility. !!uri.ng the early months of the current year the trial period of the :;taai'ord Crjnrputetion Cer,ter Campus Facility attempting to market ACME: service 12 Grant No. FRO03 11-03 Section I-A to non-Medical School users at Stanford was complete-l.. Since this service offering did not attract enough utilization to cff:<+t the costs to the Campus Facility, their sharing of ACME costs was reduced substantially at the end of November, 1968. This support was reduce& to the incremental cost of the bilk core for the balance of ACME's third year. This reduced support caused substantial rebudgeting of ACME funds as will b e evFdent in the financial section of this Report. User chargingbased on page minute utilization and file storage was implemented in April, 1969. The users were first notified of the impending charges in the E'all of 1968 arld a first schedule of rates proposed to the Special Research Resource Board in November, but it took until April to work out the details of the charging mechanism. It is too early to assess the full impact of this policy change; but in general the Medical School Researchers are being quite cooperative in coping with the additional paper work necessary to obtain the administrative approvals and to request supplemental funding. As might be expected with the prospect of having to use their own research funds for compu- tation, the asers are devoting considerable attention to improving the efficiency of their program - especially in the use of disc storage. We feel this is important. The users are urged to consult with the ACME staff. With more el'ficient user programs ACE will be able to continue to serve promptly a growing r:umber of users. The following ACME schedule of rates for service was approved by SRRB by Grant No. FR00311.-03 Section I-A Effective Date MARCH 21, 1969 Computer Services: Memory utilization of IBM 360/5C system: 1. Research Service-Real Time, high interaction rate lb per page minute 2. Research Service-routine terminals 2j4 per page minute 3. Administrative and patient care ser- vices, services to non-research users 3+ per page minute File space utilization of IBM 2314 direct Access Storage Facility lO# per block of disk storage per month Consulting and Programming Services-ACME staff no charge ACME Education ACME offers a beginning and an advanced course in PL/ACME programming. 'Ihe beginning course describes the ACME system, the use of the terminal, and the IZ/ACME statements for terminal input and output, calculation, and filing. The advanced course describes variation and options. Real-time (1800) use is not covered. A beginning or advanced course requires three sessions of l-1/2 hours. There are about ten students in a class. Of the 130 beginning students taught since July, 1968, 25 percent have 'been physicians, 30 percent students (medical, graduate, undergraduate, and some high school students), 23 percent lab tec1laicians and secretaries, and 20 percent other researchers, administrators a nd 0 the L'S . Since the teaching program began in 1966, there have been 742 st;!j.dents ( 59'1 beginning, 148 advanced) . `IL !Z t ! ::r rTt1t students generally plan to use ACME for statistical studies r->n iarge g:roups of patients and for processing laboratory data. Most realtime tossers took the course sometime earlier. 14 Grant No. FR00311-03 Section I-A The response to the course is gratif;Cng. Beg>.nners discover that they can use a powerful machine. Many sign up for %,`lie advanced course and recommend the courses to their associates. Even students ' jl;:lrticularly medical students) who do not program after the course feel that tiey nave seen how a computer can help them later in their careers. 15 Grant No. FR00311-03 Section I-A Appendix A ACME PROGRAM LIBRARY--UN PUBLIC FILE AH-l 8LY- 1 BOC-1 uUA- 1 EAM-4 LAN-4 tAP-3 tr3u-3 tBE-2 f:Bli-1 EBI-3 EBK-3 EBL-2 EBM- 3 tBti-2 EBU-2 EBP-2 * EBQ-4 EBR-3 EUS-2 EBU- I E&V-l tdbJ-2 ACME Program Library HELP: Information on ACME Keywords (G. Sanders) Clay 24, lYti8 Clinic Patient Scheduling (Grouse) June 23, 1967 Questionnaire Program (Sanders) Apr. 15, 1968 Pediatrics Project--Routine No. 1 (brew) Aug. 8, 1967 ACfME Program Library LACKF IT: Test for Linearity of Regression (Schach). Feb. 7, lY6Y ACME Program Library MULT: Multiple Regression (Moore/Schach) Feb. 17, 1969 ACIlE Program Library !JENCORR: Correlation Coefficients--Missing Data (Kraeilier 1 Feb. 7, 1969 ACME Program L i brat-y WE I GTREG: Weirrhted Linear Renressi'on (Schach) Feb. 7, 1969 ACME Program Library LINREG: Linear Regression (Schach/Liere) Feb. 17, 1YbY ACME Program Library ONCALL : Schedu 1 ing Program for Res i dents on Call (Moore) Jan. 8, lYb8 ACtlE Program Library PCPLOT: Frequency Plot (Moore) Feb. 7, 1969 ACME Program Library POLY: Polynomial Regression (Moore) Feb. 7, 1969 ACME Program Library RUNGK-1: Runge-Kutta Solution of First-Order Ordinary Differential Equation (Liebes) Aug. 21, 1968 ACME Prorrram Li brat-v ZEROFIT: Least-Sauares Line throurrh Origin (Schach) Feb. 27,-lY6Y - ACi,IE Program Library BSORT: Sorting (Liere) Sept. 18, 1968 ACME Program Library PEEL: Exponential Curve Fitting (Slirnick/G. Sanders) Feb. 17, 1YbY ACME Program Library KWTEST: Non-Parametric Analysis of Variance-- One-Way (Kraemer) Jan. 12, 1969 ACME Program Library PLOT: Scatter Plotting (Liere) Mar. 27, 1969 ACME Proeram Library SCHUSTER: Schuster Periodoeram (Schach) . Feb. 7, i969 AIXE Program Library RUNGA6: Runge-Kutta Integration (G. Sanders) May 2, 1568 ACME Program Library TIllESER: Spectral Analysis (Schach) June 19, 1968 P.Cf,!E Program Library GOODF IT: Test far Goodness of Fit (Schach) dune 24, 1968 ACME Program Library D I SCRIMZ : Dlscriminant Analysis for Two Groups (Schach 1 Feu. 7, 1969 rs of , a./ pack, cylinder, head, and record number. Space Management When a new storage unit (2316 disk pack) is being added to the file system, an initializing program formats all the blocks in the pack with the proper count and key field information and writes zeros in the data area. Block addresses in the form of block numbers are then stored in the space data sets. When creating new data sets or expanding existing ones, a routine picks up available 'blocks from the space data sets and assigns them. When data sets are deleted, the freed blocks are returned to the space list either on-line or by a stand-alone file analyzer. A block with the avai.lable status has a data set number in its key field equal to the space data set number. An efficient data protection is achieved by testing this information in the channel program prior to writing records in the data field. Input/Output Operations Three types of I/O operations are required in the ACNE file system. Each of them leads to the coding of a different channel program. The operating system handles the positioning of the access mechanism to the proper cylinder on a pack and the selection of ,the desired head. Upon a successful completion of this SEEK command, control Ls passed to the supplied channel program. Its r~rs- c:b,nmand is a search identifier (SEARCH ID): a comparison is made between 5 bytes of data from CPU storage (cyli.nder, head, and record number) and the 5-byte record identifier portion of a count area from the storage unit. Since a track has three data blocks, it may be necessary to reissue this command until a match occurs (Transfer In Channel command). Writing a Block. A WRITE operation is always preceded by a test on the key area (SEARCH KEY EQUAL command). In this case the block must be available and the data set number in its key area reflects this status. If no match occurs an error is signalled and the block is not written. With a successful match, addition>:.1 commands reposition the writing head by disk rotation after the count field and write the key and data area from the user buffer, The data set number in the key -)ieeld is written as the data set number of the data set to which the block is :<.ssigned. Appendix A gives an example of the sequence of commands. Reading a Block. After positioning of the access mechanism, the key end data fields are read into a buffer in the user region. No testing is made on the key field since a data protection on a READ operation is not necessary. A check for vc7.li.d information in the buffer is made before data transmission to the user. Re-,Tritii:g a Block. --.-I- This operation is similar to writing a block except th8t they y kev field of the data record is not modified. Data protection is achieved b;: comparing the key field with the key in the buffer from which the block is rewritten. Appendages These routines art! entered by the I/O Supervisor upon successful completion of a channel program or detection of an error. Grant Nc. FROc?31i-03 Sect j.0; : 1 -k, Appendix F F'z 0-L Page 5 Normal End Appendage. This routine signals a normal completion of an I/O operation to the ACME system posting table. Control can then be given to the user. Abnormal End Appendage, This routine is entered twice whenever an error is detected during execution of a channel program. The first time entered, the file system checks for two types of errors: NO MATCHING KEY which can occur on a WRITE or REWRITE operation, operation. and NO MATCHING ID which can occur during any I/O With other types of errors (DATA CHECK, OVERRUN, etc.) the IBM- supplied error recovery routines attempt to restart the channel program several times. If the error is permanent, the appendage is entered a second time and the ACME system posting table is posted with the pe.rmanent error condition, which is signalled to the user when he receives control. Errors like NO MATCHING KEY can be caused by the ACME system for instance when a block supposedly available is in fact used by a data set. No automatic error recovery is attempted in this case because of the overhead involved; instead sysI:em programmers can patch the damaged information with a file fixer program while the ACME system is in operation. Most of the time required to service an I/O request is spent in mechanical motions. Access time varies from 135 ms for a SEEK between the extreme inner and outer cylinders to 25 ms for a SEEK between adjacent cylinders. Figure 8 shows the minimum and maximum time spent in mechanical motion for a WRITE operation, with 25 ms per disk revolution [2]. The minimum time occurs when the selected read/write head is positioned just before the address marker of the searched record (Figure ga). 1 2 I 3 J -Head position Searched record : 3 Number of rotations for a WRITE Operation : 1 l/3 Firgure 9a: Head Position When Minimum Time is Spent for a WRITE Operation. The maximum time is spent when the head has just passed the address marker: lad position Searched record : 3 Number of rotations for a WRITE Operation : 2 l/S Figure gb: Head Position When Maximum Time is Spent for a WRITE Operation. 23 ms 20 50 100 150 200 tracks Number of Tracks Traveled Figure 8. Mechanical Motion Time for a WRITE Operation. 24 APPENDIX A Channel Program for a WRITE Operation SEARCH ID TIC -x -a SEARCH KEY EQUAL a) TIC * -1.6 b) REND DATA SEARCH ID TIC 9 -8 WRITE KEY and DATA (a) This Transfer In Channel command to another TIC will generate a program check in case no match occurs in comparing the KEY field immediately following the COWI! field of the searched record with the supplied KEY data. The error condition is detected in the Abnornal End Appendage. (b) This is a dummy PEAD required by the control unit operations when SEARCHing on the sa.me track more than once. Grant No. FRO031143 Section I-A Appendix B FIG-1 Page 9 FOOTNOTES 1. Miller, Jerry, "The ACME File System," ACME Note FY-1, February 27, 1969. 2. IBM System 360 Component Descriptions-- 2314 Direct-Access Storage Facility and 2844 Auxiliary Storage Control, A26-3599. 3. Miller, Jerry, "ACME File System--Data Sets," ACME Note FA-5, September 27, 1968. 4. Frey, Regina, "ACME File System--Codes," ACME Note FC-2, August 5, 1968. 5. IBM System/360 Operating System, System Programmer's Guide, ~28-6550. 6. Girardi, Serge, and Jerry Miller, "ACME File System-- Control Block Formats," ACME Note FB-3, March 31, 1969. Did: Prog/All 26 Grant No. FR 0031X-05 Section I-B SUMMARY OF RESOURCE USAGE Month and Days Daily Scheduled Service Account Records Console Hours Pageminutes Apr 21 to May 20 May 21 to June 20 June 21 to July 20 July 21 to Aug 20 Aug 21 to Sept 20 Sept 21 to Ott 20 Ott 21 to Nov 20 Nov 21 to Dee 20 Dee 21 to Jan 20 Jan 21 to Feb 20 Feb 21 to Mar 20 Mar 21 to Apr 20 700-1530 1830-2200 700-1530 1830-2200 700-1530 1830-2200 700-1530 1830-2200 700-1530 1830-2200 700-1700 1a30r2400 70%1700 1830-2400 700-1700 1830-2400 700-1700 1830-2400 700-1700 1830-2400 700-1700 1830-2400 700-1700 1830-2400 2,075 947,000 1,003 1,626 2,761 2,856 3,330 2,262 2,461 1,639 2,521 2,757 4,108 467 > 009 712,514 1,313,940 1>481,671 19955,295 ~28~133 1,1g0,110 738,048 1,213,289 L714,973 2,010,110 27 t- LL -. 0 . h . . c Ir .., I' .,- . . <. c i :: ri .;, 1_ -- .- : - LD . 2 c c c co > c c1 C *. . 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CJ :: 2 . . u I.7 . . ri CP . . 2 ,i ci . . i-- Lil 0.., C-1 K Ln -7 r. P? c ,,.,I 1 ! L'. . " ,:i ,.A . . t t.c u. c 5 .I Grant PJ?. FROCSil-03 Section I-B-l ii r `. p 52 :; Grant No. FR00311-03 Sect!orl I-6-1 -~- -- / I , , 1 `. / Grant No. FR00311-03 Section I-B-l Grant No. FR00311-03 Sec:ion I-B-1 i .i Grant No. FR3031?-03 Sectlon I-B-1 Grn It Nrj `ROO?ll-03 Sxtiori :-B-l :taiit No. FR00311-03 Aection I-E-1 Grant No. FR00311-03 Section !-B-l 62 I -_. Grant No. FRO031 I.-O3 Section i-B-,1 . . . . -. ., n c .+ ,* --' c : ," ," c - . . -4 I. -' .I .I . . . .-I. - I c ,-. -`F ,- : `, ;\ ' i ; i ,- c _ :. ,_ : -. ,. c 1 f ., , .: .' \' 1 . . ." ; ! i 00000000 i-f-r-l-f-r-P-b . . . . . . . . 0rl#-+drlr(00 N(VCU(\I(UNnIcv 00000000 mmlnmuimLnul vi&od&adodc;r; 00000000 f-ll4l-lr-4l-t.-lrlrl 00000000 C\INr\LhlrJWr\lhl 00000000 LnmulmmLnLn~ . . . . . . . ; mcoaJcocoaJmm 00000000 v4dr-l4drlr(rl 00000000 mmmmmmmm QQ4a3coa3coa3~aJ QQQQQQQQQQ \\\\\\\\A\ mmm~d---Q0 -l-ldoooooo~ \\ \\\\\\\\ cIoJ(vmulmmmo~ -s-4-00000-0 i r r ri r' I i f 2. r KKKKKKKKKK wwwwwwwwww I-I-t-t-I-+I-i-t-k r.`-- ._.--._ ..-. --- --__lll_-__( __.- - - -_._ -.. ___ -.__- ACME Note Papers Written by ACME Users This list contains papers voluntarily reported lc.i fiCr,ib.. Bagshaw, Malcolm A., M.D., Harold M. Schneidman, id.;?., Eugene `1. Fari..f.r, !;ILa., ,II~[I Ilenry S. Kaplan, M.D., "Electron Beam Therapy of t,lycosl Fuiygoi~j+s," CPI I!`I/j,l; MEDICINE, 95:292-297, Nov. 1961. tic31 ikian, H., A. Brodie, S. Wi 1 loughby, A. J. Dowdy, (;,iJ. blokes, 1l.ti. ,,iei !-I.;!`: ::`.r ., I/: J.A. Luetscher, "Response of Plasma Aldosterone Cctncer,*,rjtin #ji,j,-,+:i :' , APPLIED SPECTROSCOPY, 1969. tieatr ice, E.S., and U. Glick, "A Direct Reading Polychror~~ator for 11~1i:.t,i I< Spectroscopy, I' APPL I ED SPECTROSCOPY, 1969. Bellville, J.W., J.H. Green, and W.H. Forrest, Jr., "Respira:or> Effect3 OT Etomide and Codeine," CLIN. PHARM. THERAP., vol. 9, pp. 142-151, liiO8. Bellville, J.W., and W.H. Forrest Jr., "Respiratory and Subjective Cifsctb ::* d and 1 Pentazocine," CLIN. PHARM. THERAP., vol. 9, pp. 142-151, 19ub. Bellville, J.W., and J. Seed, "A Comparison of the Respiratory Effects of Dextropropoxyphene and Codeine in Man," CLIN. PHAl?f:. ThCi!&?,, vol. `J, PP. 428-434, lY68. i;ellville, J.W., W.H. Forrest Jr., J. Stevens, and E.G. seer, "The l!ypnotii: tiir.;~.~ of Cthchlorvynol and Secobarbi tal in Man," CLIN. PHA[lE:. THERAP., vc:l, jc PP. 625-530, 1968. Bellville, J.W., L. Escarraga, S. Wallenstein, and R. Houd "The Respiratory Effects of Codeine and Morphine in Man," CLIN. WAl':. THEHAP., vol. 9, pp. 435-441, 1968. Be1 lville, J.W., G. Fleischli, and J.G. Defares, "Respiratory Responses t.0 Varying CO2 Inhalation," COMPUTERS AND BIOMEDICAL RESEARCH, subr,,i tted f13r publication ijellville, J.W., G. Fleischli, and G. Attura, "Servo Control of Inhale<: C,lt-!b..~! oioxide," J. APPL. PHYSIDL., vol. 24, pp. 414-415, 1968. Breitbard, tiary Y., and Gio Wiederhold, "PL/ACME: An Incremental Compiler :I': : Subset of PL/I," lFIP68 CONGRESS PROCEEDINGS, Edinburgh, Scotland, Auquht l'jb8. t:iitler, ii., "bynamics of the Urinary Tract," JOURNAL OF I IiVES ! GATI Vt UTi)l ,,L.I, in preparation. !, I 3 y t 0 n , l(.B., iiETHUbS OF ENZYMOLOGY, STEROLS AND STERCIDS, vol. XV, Aca,:eili~' Press, in preparation. (;ollins, K.u., and G.R. Stark, "Aspartate Transcarbanglase: Studies of the iflt:l I L t 13. ji!burrlt by Ultraviolet Difference Spectroscopy," J. YIOL. CHE!d, Feb. 196'1. "I != c-rouse, Linda, and tiio Wiederhold, "An Advanced Computer System for keal `Iii11~~ ,~t:dical Applications," COMPUTERS AND B IOMED I CAL RESEARCH, to be pub 1 i she;1 about June 19b9. User i ng, C.H., "Cholesterol Side Chain Cleavage Activity in the Adrenal Glanc.. .j: the Young Hat: Development and Responsiveness to Adrenal Cortical Tropic Hormone," ENDOCRINOLOGY, in preparation. -rr\ Englud, P.T., J.A. Huberman, T.M. Jovin, art3 A, IC:):`t-:>r: s. "`Enry:ll;ls..c zk:nt',c,,i . 1 Deoxyribonucleic Acid, XXX, Binding of Tripor,pb,...c:3 :-I !)!;p$ Poly~:e-?se.,`. iiu,. ' t:~.; to J. BIOL. CHEM., 1969. Farber, Eugene M., and Richard P. McClintock, Jr,, il,i;,, "A Lurrcni Re*;it+; ,.f Psor i as i 5, "MEDICAL PROGRESS, 108:440-457, J!..ne I'_ibE. Farber, Eugene M., M.D., and Alvin J. CoxI M.il., "ihe Biology of Psoriasis, "J. I,G investigative dermatology, vol. 49, no. 4, pp. 348-357, 1967. Farber, Eugene, M.D., Ross D. Bright, M.D., and M. Lexi e Ida: 1, M.C., ~?si)r i J., I> - A Questionnaire Survey of 2,144 Patients," ARCH DERRI, vol. 98, pp. 248-251, :,e;~rr `::IJ~ 19b8. Forrest, W.H., Jr., and J.W. Bellville, "The Use of Comptitrrs in Clinica: 11 / j\:,," BHIT. J. ANAESTH., vol. 39, pp. 311-319, 1967. Forrest, W.H., Jr., anti J.W. Bellville, "Respi ratory tf fects of &,l !>hi!i;I.:>\i 1 .jc` I r! Ilan," OBST. AND GYN., vol. 31, pp. 61-68, 1968. Forrest, W.H., Jr., B.W. Brown, and J. Peters, "Manay,emer:t +f :._?upr-rdti~i> ;.lli\b<:.:. Trials," Paper presented at the annual meeting of the Al?t.fi;!:i'* S1AT1.5Tii;5i. ASSOCIATION in Pittsburgh, Pa., on August 20, 1968. Fries, J.F., "Experience Counting in Sequential Computer ;Jiagnc;si5," sub.ll tiec for pub1 ication. Halpern, B., V.A. Close, A. Wegmann, and J.W. Westley, "Gas Ch romd tography rii Alnino Acids as N-Thiocarbonyl Ester Derivatives," TETRAt:Ei)ci;i; LEITERS, v:;l. :O p. 3119, 1968. Henry, W.L., L. Crouse, R.E. Stenson, and D.C. Harrison, "Computer Analybi, ,,I Cardiac Catheterization Data," AM. J. OF CARDIOLOGY, vo:. 22, nurher 5, p. 696-705, Nov. 1968. Kakihana, R., J.C. Butte, and E.P. Noble, "Effects of Goltlthiilg;lsr.!)se 31; Aic `.,,I Consumption in C57BL Mice," LIFE SCIENCES, vol. 7, p. 825, 1969, Kakihana, R., E.P. Noble, and J.C. Butte, "Corticosterone Responsr Co Et.Ildnl.1 ,, Inbred Strains of Mice," NATURE, vol. 218, p. 360, 1963. Kessler, S., "Speed of Mating and Sexual Isolation in Urosphila," llATURil, vol. 220, p. 1044-1045, 1968. Kess 1 er, S., "The Genetics of Drosphila Mating Behavior I. Organizations of llating Speed in Drosphila Pseudoobscura," AN. BEHAV., vol. 16, 1568. Laipis, P.J., "Computer Used Analysis of Sucrose Gradients," R.N.A.S., in prc?ss, !.e./ ter, hir:iee Doir, "Mother-Infant Separation: Effects on Later Maternal Behavior," submitted to SCIENCE, 1969. Lilerr,~:her, J.A., tl.ti. Weinberger, and R.U. Collins, "Oral Contraceptives and Ilvr,ertension: Clinical and Laboratory Observations," METABOLIC EFFECTS Ot GONAUAL HORMONES AND CONTRACEPTIVE STEROIDS," edi ted by D.M. Kipni s, et al, 1 iprl `ublishing Corp., in press. Luctt-ocher J.A., I1.H. Weinberger, A.J. Dowdy, and G.W. Nokes, "Effects of SotI i 4rn LkaJ i ng, Sodium Uepletion and Posture on Plasma Aldosterone Concen- trdtiiin and Kenin Activity in Hypertensive Patients," submitted to .J . L 1. I fd . ENDOCR., 1969. :.orreIl, F., "Neural Coding," NEUROSC I ENCES RESEARCH PRUGRAI: BULLET I h, 19,s. Noble, E.P., S. Si lbergeld, B. Kopell, W. Mckinney, W,.i. L;i itnc?, iinm in Man," J. PSYCHIAT. RES., vol. 6, p. ij%# ,?bg, Pepper, N.A., E.J. Scribner, L.E. Alterton, R.C. i-::i,*i-y, t-5. ~:~-~~t~`:ce, I. ,:i~~~!~~< Bar low, R.C. Rosan, and 0. Glick, "Q-Switcned R:lb: i. ,I 5 e I f a r E r> i 5 s i L: 13 i I- r x , - spectroscopic Elemental Analysis," ANAL. CYEti., by i. .lir, pp. 117$-`113:, 111::. Peters, John, W.H. Forrest, Jr., and B.iu. drown, `!J:e of Cop,outerc ; i: "ia",],::. `"ri ;. i): a Cooperative Study," presented at the 31st Annual ;-ct:rIn:: c.1 ZIP !.i.::`.!?:Tt. ON PROBLEMS OF DRUG DEPENDENCE, Palo Alto, Calif., F,b. 25, I[;nC. Petralli, J.K., S. Wallis, and T.C. Merigan, "A Cor~~::~ter +:ethod icy !I i?i.`,i:; .?IIL of Antibiotic Sensitivity Data and Guidance in Therapv," 1 i:>d. Porter, R.W., M.O. Modebe, and G.R. Stark, "Aspirate I'ra!t~zarbac~y;ili.,: Kinetic Studies of the Catalytic Subunit," JOURNAL nF `)i!ILOCf:.Ii. Cc i...i:?~`, suhmi tted. Reynolds, W., "Computer Control of Mass Analyzers," PR:JCCZ> I t.2: c". iti'. ;i ,.`i;.! II:-, ANtiUAL CONFERENCE ON FlASS SPECTROMETRY AND APPLIED `IZiPiCS, !.a!;TI: Ls*),:,.i ttce : : ,, Pittsburgh, Pa., May 1968. Rousseau, W. F., "A Method for Computing Probabi Ii ties in Complex .;i ;#.a:icnh," Doctoral Uissertation, Stanford University, 1968. Sanajers, IJ.J., G.Y, Breitbard, D.A. Cummins, J.R. Fle;rcr, i;. tl0it.L. .i. f:i ilet, and !io iliederhold, "An Advanced Computer Sys tern for +led; cd 1 Ees:!dr ch, " AFIPS CONFERENCE PROCEEDINGS, ;Jol. 31, 1967. 5olornon, ti.F., S. Levine, and J.K. Kraft, "Early Experience dnd Ifimcrni LY," NATURE, vol. 220, p. X21, Nov. 23, 1968. Solomon, G.F., "Stress and Antibody Response in Rats," IN`i. AKCli. ALLtt;LY -trurer Systeili for initial Psychiatric Inventory," AMER. J. PSYCHIA7.., vol. 125, p. 7, January 19b9. 5 t i 1 ll,lari, Il. c., II. Costell, and D.A. Cummins, "Computer Administered PsychidtriL vc:;l~Iry," presented at AMERICAN PSYCHIATRIC ASSOCIATION annual xeting, !/,ia.,-!i, t iclridd, l,idy 5-J, 1969. :,triri:ianil, K.G., "The Effect of Preduisolone on Gastric Structure a Functisn Ire I !`:n, " l~A3~KOENTEROLOGY, i n press. l'-!,?thachari, Y.T., "X-Ray diffraction Studies on Melanins," PROCEEDINGS OF TIIF. VI 6 IhTERNATlONAL PIGMENT CELL CONFERENCE, Seattle, Wash., 1969. lhti:h~cchat-i, Y.T., and !.I.S. Blois, "Physical Studies on Melanins: X-Ray Uiffrdcf ic,:;,!' 4IOPHYSIZAL JOURNAL, vol. 9, no. 1, pp. 77-89, 1969. . .' j ,, / i? ," ,: : I,.., Thathachari, Y.T., "X-Ray Diffraction Studies CL; `, :.*1~,:5," ;>resc?tr,: ". Fe!.. 2 e, .. 0 : i, 42 Weinberger, M.H., A.J. Dowdy, G.W. Nokes," an< ;.A. icri .`:,-~;,!r, ".;i;ci,alat1ori ::*:iqr:Id ChroiIlatography, Thin-Layer Chromatography and Nuclear PiaEncilc Kesonance Spectrometry," ANAL. CHEM., vol. 40, p. 1888, 196ti- hiederhold, Gio, "A Summary of the ACME System, " PRGCkE1.e i i+(;:; 3C TI!C ,,I CDtlPUTEK AND PSYCHOBIOLOGY CONFERENCE, Monterey, Cal i iorni i'r iiay 17, 19~~. Lliederhold, Gio, "A Summary of the ACME System," PROCkfUINGS OF .THE iti!JVChJi~. TION WITri A 50 CONFERENCE, Argonne National Laboratory, Chical~o, I1 linolb, uct. 31-Nov. 1, 1966. WieJerhold, Gio, "Setting up a General Purpose Data-Acauisi t.ion System," t. `E published in the PROCEEDINGS OF THE IBM SCIENTIFIC COI'PUTING SYI'P:;`;i::;' !j:\ CUllPUTERS IN CHEMISTRY, Yorktown Heights, New York, tict. 9, 13L3. Wiederhold, tiio and L. Hundley, "A Timeshared Data-Acquiji tic,n Sybtc I," iu i)e presented at the IEEE COMPUTER GROUP CONFERENCE ON REAL-Tlh'F SY:-It:,,:r, f.ii nnedpol is, Minnesota, June 17, 1969. Dust: Staff/All Grant No. FRCI"I~~-'I~, -N--c/-.`;;. Secti TT -A Total Resource enditur~ Current Budget Period .___.___" stirnate ext Adget sriod __- -I.- 232,990 $gg 1,300 SUMMARY OF RESOURCE F'i.Z'~!3;i~.;j -- 570,984. I p of -._--- .-._ Time OY Effo 5 0 100 100 100 100 100 -- Salary From SRR Grar 100 ioo 1.00 100 56 l-00 -- 1.00 100 100 35 100 100 100 -- 100 100 100 -I 100 100 100 k!fic.! 1 P i, -"- $> i, > -;.- 'S j 1~3,675 l1.,4GC 10,987 5,250 13,108 --- 2,213 689 2,224 577 554 13,503 4,046 Amount t 8 4,125. 13,675. 11 ,400. lO,g3y. 9,bO. 13,108. --- hourly 2,213. I hourly I 689. hourly 2,224. I hourly 1,670. I hourly . 554 103 13,500. 100 4,&6. -- e-s on demand 2,42 I or! demand575. I r): t f I' % . . ' / . :,,i _,. , .L. . . _- - . . . ._ .._. . ".. - _Y "_ ;"__ . .4 of Time Or Amount Ef'foYt !.I .,,. /,- ,. . , ,,. ! I i - y+:`, 540. (3) 284,lU. .' ,,;..2 ', 3 ;- :' ,, TOTAL 5 ;-? .- Budget rj,is.t,; 1 i-s ;. i:,:. The estimate for the next budget period ref! :P:: I .r `-, :`;'t+,;; _ [,;l)F "0: 1 %cility paying the full cost of t'ne equipment a~(: 'i I 7~' L!;C L:l- I~;>:: y = L :L 'Y'cmporary staff reductions resulting from this yea?:, -.-:,ti-L?y,. 7iso invoiced and paid in the clurrect year. Accou~iti:~g for I&,: -1 '<> 1-i ;, ,c I ls ;; -* , .: <.r,el-: ;j serious problem at Stanford, but the problem has :icw bee:1 ccl*r~?ct~~d a,;\! i'Cnt;llS are paid on a current basis. Curing the year, the partial salaries for ACME tdmi ni~s$rr ki.or, 1-1; CSC: ;kilff members were assumed by the Medical School. The pyese;lt ch;3rg:: f:,j> t-i.<:si. I-ir?iuistrative services is low and negotiations will be lielLi sun Y,', tl F` te m-i ; : ! : ;:iore realistic effort distribution 0.' I t,he Stanford Computation aL,mi!li s !.Y,: t Ix, L i.`.! 'P tind an appropriate distribution of this time bety!Jeen direct ' ,C:LG in&lyp('; ~. .-. " ,., L, of the NIH grant supported ACME. The inaugurrjtion of lzser f~ha~,<;es ,h.:~ : * ::: i, - Lbuted substantially to the administrative burden. Detailed Description of Resource Pr?;jects Core Projects As discussed in the Introduction of this Annual Report, the efforts of the core projects have been directed toward increasing the serviceability, re- liability, and performance of the system. Although many of these problems are not glamorous in the scientific spectrum, the fact that a very advanced computer facility has come to the point where it can extend its efforts to improving its reliability and serviceability is certainly significant. Because of our efforts to maintain constant communication between users, usage has increased consider- ably. Major efforts went into system measuring and system testing in order to preserve integrity of the system, even while continuing changes and adjustments are being made. In the real-time data-acquisition area we have achieved the capability to handle multiple users, each with multiple lines doing data acquisi- i, use of ACME for the data collection, presentation, and a.neiysis. Tk ;: 3 : will have a general title of "D-ynamics of :;i:e urinary ix-a~';." Cam, 1;. M. Department: Pediatrics Fho cormunities on the east shore of tne l.ake are b~',ng s5:jdied a:;d ~$1~ are about to initiate studies in another India:1 La>:? sl.or? coy:rllurlity. A pilot project icvoiving 300 inhabitacts of two L?dlan cOT&r.inimties on the south shore of the lake was conpleted prior to under:;akcnfi the preset,*- .~ investigation. De,pal~:~!li?nt : Psychiatry Pr ,oje?t Descrlptione The purpose of our project is to determine the effec~tz of steroids and hormones of RNA activity on the brain, We inject live rates with radioactive tritriated uridine. The rats are then killed and processed In the re&ar histological procedure. Radioactive element reduces silver grains and slides are made frown which the grains LD t,hP braln cell are count,ed, From the number of grains, we determine the area of RNA ineorporatlon In the brain, the brain cell, and 21 i',-.c t,issues. The level of RNA incorporation is also determined. Expz~imer!:;a and contra! groups are compared by ACME. Our d.at,a analysis time is ::,rerz,i-.:) I' duced by :;slng ACME. Coilins, K. D. Department : Biochemistry Pl`Oj ect Description: This file (KIM COLLINS, AT Case) 1s used for three purposes: First, it is used in a variety of ways as a research t.ooi. It has .been used to compute the dissociation constants for an enzyme (AT Case) and some of its inhibitors (see Journal Biological Chemistry, approximately February 1969; "Aspartate Transcarbenglase: St-udies of +'!ne Catalyt.ic S-ubumt by Ultraviolet Difference Spectroscopy," by Yim D, ;Sollins and George R. Stark). It will be used in the fr;t-ux to I; emulate d.iI'ference from model compounds and compare these spectra :%:I: ii ' +I? experimental spectra. It will aLso be -used i.n the futu.re to ar,aly~i,r dat,a from equilibrium dialysis studies of AT Case and its s~:1-~stra*,es and i nhibi: / ct`,r,. Second, it is used as a data processing facili.ty for research- ,Tcrlt>r-ated data. 'It is extensively and routinely used t,o process chromatograme from an amino acid analyzer; a long program stored in :j.CVIE provides a variety of different procedures that may be used on the !.!ata (See p.revious ACME' write-up). Third, it is used as an education device, For instance, this i`:le has been used to process data from a laboratory course in ultraeentrl- rugat ion ( Riochemfs~~ry 214) , DepalXLment : Genetics - ZRL Project Description: DATA COLLECTION, STORAGE, ANALYSIS FROM FI!@J:GAX 1015 MASS SPECTROMETER. In this "on line" application, the decision making capabilities of the computer are coupLed with those of an operator to direct the operation of a Finnigan 1015 quadrupole mass speetrome'.er. The computer is used to actively direct the operat?on of +hpj mass spectrometer by controlling the mass filtering system of the Uris+ :1rn!'ls' It is used to recognize and control the voltage changes which aei !tne mass peaks and enable the rapid collection and presentation of da+~a. The computer traces out peak shapes of the known masses LII a reference gas allowing the operator to det'ermine correct mass posi-tiol:s, and to enter any shifts in calibration into the comput~er register fo? compensation automatically. While taking data the information may be displayed on an oscriLoacope or recorded on magnetic tape. Once data is acquired the str-uctural identification of organic compounds is made from orthogcnal coordrnate or spiral base plots of mass spectra made by computer direction of a caicomp plotter. The system is also used to analyze Gas Liquid Chroma.:ograph effluenf, permitting the structural identification of mixtures of' orpan;.c compounds. Stored data offer the future possibility of spectra ma.+cniing of -unknown compounds. Publlcatlons using this system of computer [Jpsrat ~(~`1 of the mass spectrometer are: B. HaLpern, V. A. Close, A. Wegmann, J. W. Westley, "'lass Chr:~mato- ,~".:i:ihy of Amino Acids as IX-Thiocarbonyl Ester Derivar ives", 'lc+,:`ahedron Let,ters 27, 3119 CL$8), - J. W. Westley and E. Halpern, 'The Use of (-)-Methyl Chloroformate in the Optical Analysis o f Asymmetric Amino and Hydr0xy.i Compounds by Gas Chromatography" J. Org. Chem. 33, 3978 (1968). j, W. Westley, V. A. C:lose, D. N. Nitecki, and B, Haipern, "Determination of Steric Purity and Configuration of Diketopi- perazines by Gas-Liquid Chromatography, Thin-Layer Chromatography, and Nuclear Magne+.lc Resonance Spectrometry Anal. Chem. 40, 1888 g_- i1gG8). Department: Psychiatry Project Description: There are approximately 15 individ,zals in this Laboratory directly involved 1n experimentation relating neluroendoerzne function to behavior0 Information from animal testing chambers will soor: be recorded on a hfgh-speed paper-tape punch, The data on the paper- tapes will be dumped directly into ACME data files through 2 PDP8 inter- face, or listed by the PDT8 for iieyboard terminal input to AcMi:. -11 either case, a program in the permanent ACME files will be ~rl~er; -c sort the data from the several. experiments recorded simultaneously on the paper-tape0 Appropriate programs for the analysis of data from ,:pec X1(. ~~xperiments wili also be maintained in the permanent ;~I-,~~- -':j~ files 0 in addition, we plan to use ACME facilities to reduce and a;:;I-l)~c data derived from experimenta +,ion which does not involve use of our paper-tape recording system, cO$", adrenocortical steroid levels of sni.mals under various conditions and ACTH bioassay data, Cooper, J0 M0 Name: JMCSOPER Project: SEXG;TjT DC '1.: rtment : Psychiatry Pr.8 lject Description: At present I am using ACME for t,wo purposes only: (I) comparison of 2 sets of data by means of the t-test, and (2; caL:YLaT jon qf sample radioactivity together wit.h standard deviation thereof. r do o-t envisage expansion of this work, Such use is not mainstream to my project, in that the calculations (, &J -cc-l performed manually" My project lies essentlslly in investigation of biochemical correlait jr' neonatal sercual differentlstion in rats: such as androgen meta~boiis~~. !j?ught;ers, G. T. Department: Medical Research ar~::c- (MedI-al) i 1 t i 1 i a 9 t L <-' :, . A comparisoc of membership and doctor sr.isii-.z, '.,: :.-, I,ora7,0ry wo 17i;, etc . , 01' the same population under two differer:? insurance plans is being m-de. Studies of costs to the patient iacl:ordirq ~,o disgncsis) arc also being made on the same group, for the two diff'eren? plans. The results should be of vide interest tc e?n-:Lcye:,s, i:isLrers, hospital planners, etc. 101 1 :. 's, G. T. Name : G-DAUGHI Department: Bioengineering and Phys i0 UY Project Description: This project is purely educational in nature, It is desirable to make a knowledge of a high-level scientific computer language one of the standard tools of today's research scientist. P:L/AiI\E is such a language, and being FORTRAN based, is useful wherever a machlne with a FORTRAN compiler is found. The availability of a machine as large as ACME'S 360/50 is a definite asset in learning how to use a compLIT,er on scientific problems, since storage space is almost never exceeded, (ind programs can be very straightforward, The Palo Alto Medical Research Foundation has active training i8rngran' (one supported by N.I.H,) in Molecular Genetics, Allergy, Immunology, Infectious Diseases, and Bioengineering. There are currently several post-doctoral fellows in training at the Foundation, and members of the Foundation staff hold faculty appointments at Stanford University and i,he University of Santa Clara. Those of us at the Foundation who are relatively competent in the ACME language have been giving informal instruction to members of our staff who have taken an interest in using the computer as a research tool, and the terminal sees almost full-time use only a month after inst.aiiation in a facility where only two people had had any previous computer t,raining. Project: XENONl:,' Department: Nuclear Medicine Porject Description: This project involves the use of radioactive methods to assess the regional distribution of ventilation and pulmonary blood flow in normal subjects and subjects with disease. A scintillation camera and special purpose computer are used to generate positimal and quantitive information for subjegnent processing by ACME. Studies in upright man have revealed that the distribution of ventilation is determined by the pre-inspiratory and inspiratory volumes. We propose to study pulmonary embolism with these radioactive methods and compare the results with those obtained from conventional pulmonary function studies. Name: CHDOERIN Project: DESMOL&: Department: Psychiatry Project Description: CONNECTIONS TO LABORATORY INSTRUMJXCS, E.G., LIQUID SCINTILLATION COUNTER. We have studied the development.of an enzyme system in the rat adrenal gland which is involved in the response to stress. In the newborn rat, there is a brief period of poor response to stress by the adrenal gland, As one parameter, we are measuring the capacity of the adrenal gland to synthesize steroid hormones. We prepare an enzyme system that catalyzes the conversion of cholesterol to pregnenolone. The rste of this conversion is an indicator of the amount of enzyme present in the glands. We follow the rate of conversion by using cholesterollabeledwith two different radioactive isotopes and calculating the change in isotope ratio. From each incubation more than ten samples are withdrawn, counted in duplicate for the two isotopes and recounted with a radioactive standard. Thus, about 100 different counts are generated with each incubation, We use ACME to compute the ratio of the two isotopes for each sample (by averaging duplicate counts and correcting for overlapping counts) and to store these results along with other information about the incubation. Various other programs are used to work on the information stored in the data file and to proudce the rate of enzymatic conversion by fitting the best line through the experimental points and by determining the slope.and its confidence interval. All this derived information is stored in another data file. The date over 150 incubations ranging over the ages of 1 to 46 days have been carried out and treated in this manner. !he project was started in October 1967. All the information of a set of similar experiments has been retrieved, dnd a significant pattern of development of the enzyme system has been ,iscerned. Another program analyzes the entire set of experiments and c?lerates a mathematical function that describes the pattern of devehopmer: 2his development pattern of the enzyme system was found to correlate closely with the pattern of stress responsiveness described for the idrenal gland of the neonatal rat. Two reports of this work have been .;ubmitted for publication in Endocrinology. Some aspects of the work on the rat adrenal capacity to produce hormones will continue, At the same time we will use the above method to study genetic differences of this capacity in different strains of micea The use of ACME will be very similar to the past. 104 Name: RADOHERT Project: SEXCHJTF.: Department: Pediatrics Project Description: I am currently using ACME for: 1) statistical evaluation of experimental data, and 2) calculation of random fields to obtain random sampling of cells dispersed on microscope slides. Sex chromatin body counts are being obtained on the random cell sample by visual search. Dong, E. Name EDONG Project: heart Department: Surgery Project Description: Study effects of heart transplantation. Collecting data on blood volume, heart rate, rhythm and blood pressures., Also: developing the relationship between white cell types. Correlations and negative correlations. Name: EDONG Project: MARGl Department: Stanford Electronics Laboratory Project Description: The purpose of our project is to develop a controller for an artificial heart, We are attempting to do this by using a transfer function between arterial pressure and heart rate. The project is a joint concern between the Department of Cardiovascular Surgery and Stanford Electronics Laboratory, It is funded by a grant from NIH and is to be completed September 1969, At present time we are recording 3 channels of analog data from an auto transplanted dog, This data is processed using the 1800-360/50 ACME sy;;tem, The data are converted to digital data using the 1800 and stored in the 360/50. It is then processed and 6 channels of data are calculated, The digital data is then converted to analog signals using the 1800 and printed out on an offner strip chart in the laboratory. We also have a PDP-8-360/5c interface which we use to store PDP-8 data on the ACME system, Duffield, A, M. Iv;> yw : ADUFFIE Project: CHEM Dryartment: Chemistry l'r>niect Description: This project can be summarized as follows: (A) The zaking of high rate data transmission to write experimental analysis ;)rogrems so as to develop programs for the routine analysis and finished output of mass spectra. The transmission is through the 27OY-270X channel, The project plans to develop this interface to service three !,ass spectrometers (ALTAS CHb, AEI MS9, and 8 FINIGAN 1015 quadropole). ~'ne taken spectra are then to be fed to the Artificial Intelligence group Alder the supervision of Jo Lederberg and E. Feigenbaum to be used in their dendral investigations, (B) Another use of data transmission -Irollgh the 27OY is to take spectropolorimeter measurements and then ., r:lalysize these spectra for form, bandwidths and similarities between derivitives for theoretical projections, (C) This project also includes a battery of utility programs for metastable analysis, chemical rate analysis, Cl3 substitution ratios and other routine analysis that the Chemists wished programmed, 106 Name: TDURBRl Project: ROOT Department: Pathology Project Description: (1) Statis,tics: Using ACME subroutines, programs, and minimal own coding will compute statistics for S.V.H. research projects, (A) only when requested, and (B) only if researcher will foot the bill. Hopefully, I will not be doing too much of this. (2) Pathologese Snop Translation: Working with Derek Enlander on the same problems. I am transferring the files to d-enland cases, and deleting this aspect of ROOT. Name: D EDWARD Project: STRESS Department: Medical Student Project Description: Using ACME to conduct research on the effects of hormones on the alpha rhythm and temporal perception, D&a relevant to these experiments are reduced statistically using ACME., In addition, specific programs are used to: (I) generate time intervals to minimize search time for the two-flash threshold, (2) to convert evoked potential amplitude measurements into micro volts, (3) to identify the two-flash threshold on the basis of a linearization assumption, (4) to prepare and justify manuscripts. In the near future, specific programs will be employed (with the 1800) to identify hormone-indured changes in the EEG on the basis of Fourier and spectical analysis of recorded EEG's. 11 Vii d-cn Land Project: cases Uf, ;i; ;*tment: Pathology I it: Description: I am endeavoring to devise a system whereby medical diagnoses can be filed in disc storage in coded form, The coding is automatically derived from a thesaurus file by matching key words, which will conserve both file space and enable synonymous diagnoses to be retrieved efficiently" T'he basic thesaurus and code is based on the common S.N.O.P. (Standard Nomenclature of Pathology) on account of its wide usage and comprehensive modern terminology, 1.07 Name; d enland Project: snop - Department: Pathology Project Description: I am endeavoring to devise a system whereby medical diagnoses can be filed in disc storage in coded form. The coding is automatically derived from a thesaurus file by matching key words, which will converse both file space and enable synonymous diagnoses to be retrieved efficiently, The basic thesaurus and code is based on the common S.N.O.P, (Standard Nomenclature of Pathology) on account of its wide usage and comprehensive modern terminology* Enlander, D, Name: d enland - Project: PIPIC Department: Pathology Project Description: I am endeavoring to devise a system where'by medical diagnoses can be filed- in disc storage in coded form. The coding is automatically derived from a thesaurus file by matching key words, which will conserve both file space and enable synonymous diagnoses to be retrieved efficiently. The basic thesaurus and code is based on the common S.N.O.P, (Standard Nomenclature of Pathology) on account of its wide usage and comphrehensive modern terminology. 108 Name : BFOLK Project: GFS Department: Biochemistry Project Description: My ACME use will primarily involve the calculation of rough data dealing with work 7. am doing on mitants of Ecali having altered activating enzymes (amino acyl TRNA synthetasesj, -The calculations will primarily be of an arithmetical nature - taking data from sanhillahran co.unting and laboratory assays and computing various varfables from this data., We are presently writing two papers in which ACME facilities have been used. Forrest, W, H. Name: W FORRES Project: DATA - Department: Anesthesia F'-reject Description: We use the 360/50 time sharing real-time system to research the management and statistical application of methods to the Cooperative Study. Problems of pilot studies, data validity, quality, cost of clinical trials and useful reduction of data for active sane management are constantly evaluated and updated, The plan is to develop an inexpensive system of quality and quantity control of large masses of clinical data from several sources so that data diarr-hea and "gigo" are diagnosed properly and treated prophylactically rather than symtomatically. b'nrn:st, W, H. Tj,i I I:: r.i,ment : Anesthesia '- .::t Description: We use the 360/50 time sharing real-time system to research the management and statistical application of methods to the Cooperative Study. Problems of pilot studies, data validity, quality, cost of clinical trials and useful reduction of data for active sane management are constantly evaluated and updated, The plan is to develop an inexpensive system of qualIt,y and qflantity control of Large masses of clintcal data from several sotirces so that data diarrhea and "gigo" are diagnosed properly and treated prophylact,ically rather than symtomatfcally, Name: JFRIES Project: DXARTH Department: Medicine Project Description: Present projects involving computer diagnosis of rheumatic disease are, in addition, p artly designed to increase our familiarity with the system0 (Experience Counting in Sequential Computer Diagnosis, J. F!. Fries, 1969, (submitted for publication). Beginning in late Spring 1969 we will begin work on a large- scale data file entry, storage, retrieval system for clinical information about Rheumatic Diseases. This system has exciting possibilities for improving quality of clinical research, quality of medical care, accuracy of di.ai-i.los:s, extension of the medical school influence into the community. and so forth, Methods of supporting clerical, software, and hardware needs are currently being explored in several areas. During early development, we will request 10% support for hardware costs through the ACME System, Fung, 9. Name: D FUNG- - Project: RESPUNIT h-a rtment: Anesthesia ;'roject Description: Ob,jective: To determine the response of the pulmonary circulation to changes in inspired gas composition and intra-treacheal pressure, Progress to Date: Apparatus has been set up for measuring pulmonary 'blood flow from exhaled gas composition and a program is :ilready available to compute the results, Current Work: (1) Refinements are 'being made to improve the accuracy of the pulmonary blood flow mea St: !`?!ii?nt,, and (2) A pilot study is being started to observe the ,:l'ft-c.t elf' a change in inspired gas composition on pulmonary artery :;';:ssure6 Intended Computer Use: Computation results from data (a) Lalibration curves are computed, (b) Data is converted, (c) Results are computed, (d) Statistical parameters are calculated. No data files will be used, 110 ITme: WGERSCfi Project: smms r Department: Neurology Project Description: The project 1s a research investigation to examine the extent to which the interreiationship between a variety of electrophysio- logical data records can be modified by a linear relatfonship. Examples of previous and ongoing computations include: I, Computation of the coherence between macropotqentials and intra- cellular slow waves (human data provided by Dr. F. Morrell and animal data now being gathered in coll,aboration with Dr. Morrell - preliminary researcn res-tilts reported at a Neurosciences Research Program Work Session on "Ne-dral Coding" February 1968 to be described in a forthcoming N.R.P. bulletin, 2, Determination of transfer function and a study of the causality :.:slati.onship between averaged evoked potential and post stimulus time histograms on experimental data provided by Dr. K, L, Chow taken in cat, lateral geniculate with light stimulation and by Cr. A, Starr in cat cochlear nucleus with sound stimulation. 3. Determination of tne evolution of a transfer function between macropotentials during the evoLut,ion (over a period of weeks) of epilepsy in cats. Computations performed on data supplied by Dr. G. Goddard. 111 !X:!-: i:, 'I'. J, Name : T-GLATTK Project: ENG Department: EJXC (Surgery) Project Description: Use cf the ACME facility through July 31, 1969, is anticipated in two research areas: Auditory physiology: We are collecting data on an almost-daily basis from a group of preparations with electrodes implanted in the auditory nervous system. Generally, the recorded activity is processed and stored briefly with a small general-purpose computer. Use of ACME in this work would seem desirable for numerical analysis incorporating ACME, but since the sample sizes are modest, use of ACME for analyses requiring many replications of an operation (e.g., in auto- correlation) is advantageous. Clinical research: Over the next few months, we anticipate attempting a feasibility study to determine if ACME would be useful for patient categorization. Our general thinking is that files containing coded history and test findings would be updated on a daily basis, so that these might be available for a trend analysis. (For example, the audiological examination on a given patient may incorporate as many as a half-dozen tests, Patient selection for a given course of treatment or additional special testing would seem to be enchanced by the availability of such trend analyses.) Gleason, C, A, r\Jrir,e : CGLEASO Project: CORmAS DrTpartment : Medical Student - Graduate *t Description: This user project is being used in connection with my .,2redoctoral research fellowship. To date the various researchers in the Neurology department have been sharing the costs for the ACME terminals hilt +l?,>:"n _ has been no provision in their budgets for computer time. Their ,rojected budgets do not provide for computer time and my predoctoral 71lowshi.p does not provide funds either. While my use of ACME has not lIeen extensive I have been using it primarily in an educational way to learn how computers can be used in electro-physiological research. I would like to continue using ACME and storing programs on a 100% rebate basis through the summer at which time my predoctoral program is to be completed. 112 Name : D-GLICK Project: LASER Departments Pathology, Histochemistry Project Description: The ACME facility is needed to provide the computational requirements of the laser microprobe analytical system which we have designed, and are continuing to develop, for elemental analysis of micro- scopic 'biological samples down to the single cell and very small volumes of fluids. The applications of the system to biological and medical research and clinical medicine obviously have impressive potential. ACME is involved in data calculation for definition of sample size as well as content and concentration of elements. Statistical evaluations include calculation of F-ratio, ,I'-test, U-test, population means and variariz: n , and also linear regressions , graphical interpolations and curve fitting. A second system is now being built so that one can be devoted to applications and the other to continued technological develop- ment, This will, of course, at least double our need for use of ACME. Eventually we expect to a-utomate the system, which would further increase our ACME-dependence. Papers completed this year of work in which ACME was involved are: Pepper, N, A,, Scribner, E. I,, Alter-ton, L, E., Honey, R0 C., Beatrice, E, S,, Harding-Barlow, I., Rosan, R. C, and Glick, D. Q-switched ruby laser for emission microspectroscopic elemental analysis. Anal, Chem> t-0:1178-1182 (1968). Beatrice, E. S., Harding-Barlow, I and Glick, D, Electric spark cross- excitation in laser microprobe-emission spectroscopy for samples of lo-25 micron diameter. In preparation. Beatrice, E, S. and Glick, D. A direct reading polychromator for emission spectroscopy. In preparation. Nitme t DGODWIN Project: ADRENAL De!-,` ;-tment : Surgery Project Description: Clinical cancer research record protocols and data for storage and analysis, Next step will be display routines. 11-3 Name : JHACKNE Project: PHN Department: Pharmacology Project Description: User works with Goldstein who is on leave until September 1, 1969. Project is not being used now, but want to keep in abeyance for now. Hahn, G. M. Name : G-HAGN Project: RADIATE Department: Radiology Project Description: There are various programs used in graphics of experimental data, e,g,, survival curves of x-irradiated mammalion cells; output of planchet counter, etc, 114 Harrison, D. C. Name : DCHARRIS Project: CATH LAB - Department: Cardiology Project Description: An extensive cardiac catheterization data analysis program has been developed (1, 2, 3), Statistical analysis of the results obtained by a computer justify routinely using such a program on a day by day basis for calculation of the results of cardiac catheterization. This would greatly decrease the amount of time a physician need spend after the catheterization in analysis of the data. Because of the time required to complete a catheterization, the large size of the program and the fact that it is resident in core while data is being collected, serious consideration is now being given to the use of digitally coded magnetic tapes which may be played back after the completion of the catheterization, This would result in decreased computational cost. In addition, other catheterization laboratories in the area may then be in a position to utilize such a program. Given the necessary computer reliability to routinely analyze catheterization data, a program is available to automatically transfer the results of computation to a patient record in a data file. Forms are available which will be used to obtain clinical, X-ray, EKG and surgical followup data permitting statistical correlations on a large group of patients, The computer facility is also being used to develop a program for recognition of abnormal EKG complexes. In the near future we hope to be able to use such a program in a computer devoted to monitoring of Coronary Care Unit patients. References 1. Stenson, R. E,, Crouse, L,, Henry, W. L., Harrison, D. C. A time shared Digital Computer System for On-Line Analysis of Cardiac Catheterization Data. Computers and Biomedical Research, Vol. 1, Number 6 P, 605 June 1968. 2 . Henry, W. L., Crouse, L., Stenson, R., Harrison, D. C. Computer Analysis of Cardiac Catheterization Data. Am. J. of Cardiology, Vol. 22, Number 5, p. 696, Nov. 1968. 3. Stenson, R. E., Henry, W. L., Crouse, L., Harrison, D. C. Cardiac Catheterization Data Analysis. J.A.M,A, - Submitted for publication. 1-15 Hari-is, R. F. Name : RHARRIS Project: PNP Department: Medical Student Project Description: Our project is an attempt to demonstrate correlations between the emotions experienced by subjects and their own appraisals of certain aspects of their environments. Our concept is that emotions arise when events in the individual's situation come into certain specified relations with his goals, For example, if an individual perceives such events as facilitating rather than hindering his potential achievement of the goal, then he will experience a positive emotion rather than a negative one. Similarly, other dimensions, such as the extent to which the individual feels in control of the situation, the extent to which he is explicitly pursuing a goal within the situation, and the degree of certainty with which events in the situation affect his potential achievement of the goal, are also hypothesized to be important in determining which of a number of different emotions the individual will experience in any situation, The emotional state consequent to such appraisals is thought to have physical and cognitive effects specific to it. Cognitive effects include changes in the per- ception of time. For example, different emotional states may be associated with different focus of attention with respect to past, present, or future events in the life of the individual. By physical effects we mean the individual's sensations of changes occurring within his body as part of the emotional state. We are developing standard inventories for obtaining objective measures of these subjective variables. The study will have two parts. The first involves the collection of normative data from normal subjects with respect to six emotions, namely, anger, anxiety, depression, joy, love, and calm. Subjects will be instructed to recall experiences that typify their conception of these states and to describe them on our inventories. We will use this data to construct normative profiles of each emotional state, and to calculate correlations between different categories of items on our inventories. The second part of the study will employ a number of expectant fathers, who will be tested in the waiting room prior to delivery and again after the birth. This data will be used to determine whether our previous normative data is useful in the identification of actual emotional states and to confirm the correlations found in the earlier part of the study. We plan to collect the data for the first part of the project by the end of February and to process this data at that time. Data from the second part of the study will be collected by the end of April and processed then. 116 Harris, R. F. (cont.) Name : RHARRIS Project: PNP Department: Medical Student Project Description: If successful, the study could have important theoretical and methodological implications. Theoretically, we hope to demonstrate that an individual's subjective appraisal of events in relation to his goals are important determinants of his emotional state. Methodologically, we hope to show that certain forms of inventories yield replicable descriptions of subjective events. Normative profiles such as I have mentioned could thus be constructed and employed as operational definitions of emotional states in a number of experimental contexts. StudTies in the physiological correlates of emotions are but one class of examples. Helikson, M. A. Name : MHELIKS Project: LBF Department: Medical Student Project Description: E?JALUATION OF LIVER BLOOD FLOW WITH RADIOACTIVE ISOTOPES. Use of ACME facility: storage of data, statistical analysis, evaluation of curves into exponential components. We are using radioactive Xenon-133 to evaluate the hepatic-arterial and portal-venous contributions to hepatic blood flow in dogs. It is our objective to develope a relatively quick and technically easy method for determining blood flow in humans on a screening basis and in pathologic states, 117 HerL:z::iberg, L. A, Name : LHERZEN Project: LAB Department: Genetics Project Description: Cur studies in immunology, genetics and maternal fetal immunologic relationship's in the mouse require the colation of many experimental observations on a given serum sample or individual. Since such data is accumulated over long periods of time, frequent interim reviews must be made to determine new directions, etc. Currently, most data colation in our laboratory is done by hand incompletely, inadequately and infrequently, thus hampering the process of the research. To over- come these difficulties we have begun the process of changing our data storage procedures to utilize the ACME capabilities, For example, all breeding records for the inbred nucleus of our mouse colony are stored in ACME, Approximately once a momth ACME is called upon to draw updated pedigree charges, so that breeding decisions may be made. Presently we are working on programs to colate multiple immunoglobulin level determinations done on individual serum samples, returning histories of immunoglobulin level changes with time in treated animals. Eventually we hope also to be able to use ACME to store data and direct antiserum production in the laboratory, In addition to the data storage aspects of ACME, the computer is used in this laboratory for a number of routine calculations on data sets, e,g., per cent antigen precipitated, geometric means of plaque events, etc, / :"I nberg, L, A. Name: LHERZEN Project: STORE Dt 122. tment: Genetics Pro,) .ct Description: Same project description as for project LAB, Her::onberg, L. A, Name : LHERZEN Project: PIGGY Department: Genetics Project Description: Same project description as for project LAB. 118 Hilf? F. D. Name : FHILF Project: BLACKBOX Department: Psychiatry Project Description: This project, which is virtually complete, involves pathological tests using a new technique of "non-contingent reinforce- ment" of paranoid and non-paranoid patients. The raw data obtained by an electronic apparatus was analyzed by ACME as were the clinical behavioral ratings of patients. Other statistical techniques were used involving analysis of variance to obtain level of significance of results. This project is virtually complete and I anticipate placing my files on tape or deleting this altogether, Hilf, F. D, Name : FHILF Project: TESTA Department: Psychiatry Project Description: This project involves psychological testing of psychiatric patients using on-line interactive techniques in which the patient sits at the terminal and is asked questions and he gives the answers and is rei~nforced by the computer. A bravity procedure is also incorporated in this program. The main purpose is to determine if paranoid psychiatric patients respond to feedback differently than a control group of other VA psychiatric patients. 119 Hodges, D. Name : DHODGES Project: SWALLOW Department: Radiology Project Description: The ACME camp-uter is being used to assist in the study of both normal and abnormal motions of the human esophagus during normal and induced swallowing. A series of simultaneous pressure readings in various locations in the esophagus are taken by the use of water filled manometers connected to electrical pressure transducers. The electrical voltages representing the pressure data are sampled and converted to digital values 5 times a second, for each of the pressure measurement sources, using in the IBM 1800 computer attached to the ACME computer system, It is planned to have the ACME computer analyze the data from a swallow as it is obtained and provide immediate information back to the experimenter, via the terminal, of the properties of the last swallow, Various summary tables are kept during an experimental run regarding the properties of all the swallows obtained so far, and are available for a final summary of the experimental data. Initially all the data obtained during an experimental run will be saved on the ACME data files to allow different methods of analysis of the data to be explored. Huberman, JQ A. Nme : JHUBERM Project: TEMPLATE Department: Biochemistry Pro4ect Description: I am using ACME to perform the lengthy and tedious calculations required to reduce the raw data obtained in equilibrium dialysis experiments to a meaningful form. I am performing equilibrium dialysis experiments with the enzyme, DNA polymerase, and various nucleztide substrates, in order to get a better understanding of the active site of the enzyme, Using equilibrium dialysis, it is possible to answer such questions as-- What kinds of molecules bind to DNA polymerase? How strongly do they bind? How many binding sites does each enzyme molecule have? The answers to these questions help in understanding the stlructure of the active site of DNA polymerase and its mechanism of action. So far we have produced one p-ublication based on experiments aided by ACME's calculations; Englud, P, I',, Huberman, J. A,, Jovin, T. M,, and Kornberg, A., Enzymatic Synthesis of Deoxyribonucleic Acid, XXX., Binding of Tri- phosphates to DNA Polymerase., J, Biol, Chem. Submitted for publication. 120 Hmng, J. Name : JBWANG Department: Genetics Project: GENL1B.l Project Description: This project contains the statistical and miscellaneous programs used by the Genetics Department. Statistical programs: General statistical analysis for the calculations of sun, mean, standard deviation, the analysis of variance, chisquareand probability of chisquare distribution, correlation and regression analysis, the normal distribution with the same mean and standard deviation for fitting a curve. Plotting programs: Plot bar graph in 100 positions, plot of percentage distribution, plot by function scaled to the range of 0 to 100, plot of multivalued function allows the choice and supersition of several characters, Flag is inserted on the chart when underflow or overflow occured, Sorting programs: Sorting a vector in ascending order, sort array and alphabetical informations, Hwang, J. Name : JHWANG Project: BWTSTUDY Department: Genetics 'C ject Description: Study of birth weight and IQ in relation to sex, parents, education, race, income, 121 Ingels, N. B. Name : NiNGELS Project: ASMSE~06 Department; Bioengineering and Physiology Project Description: This project is a study of the dynamics of the myocardium, utilizing stereo stop motion photogrammetric methods on an open-chest canine preparation, This study is being done with full N.I,H. support, on grant number HE 11739-01, Data from two stereo cameras (in the form of a stereo pair of negatives) is reduced by the computer to present the investigator with various length-velocity-load-time relationships. Since this work is of a "pioneering" nature, it is necessary to be able to interact quickly with the computer in order to change the program, certain data, etc. The size of the data reduction problem in these studies can be gleaned from the fact that the programs necessary could only be run at S.C,C, at night due to the core size limitations. The grant includes some funds for computer -Lime, but at the rate which it was being used at the Stanford Computation Center, the study could not have been completed, The availability of ACME services at little or no cost is of paramount importance to the studies being presently done under this grant, and to those suggested by our present studies, The TV dis.piay at ALOE is also of great importance, since the graphics routines therein are exceedingly fast in comparison to the Calcomp Hard-copy plotting routines used at the S,C,C. It is estimated that the availability of ACME has cut computation costs (assuming the 85% rebate rate) by about a factor of ten. The funds originally committed to computer time are being used to dc,fray the cost of terminal rental, I\: __ e : W JAN - - Department: Medical Student Project: WOMAN Project Description: RJn various statistical tests on data from laboratory experiments? Do ?!ext editing, 122 Jones, H, E, Name : DJONES Project: FLU Department: Biochemistry Project Description: Work with ACME centers around a nanosecond fluormeter designed by Stryer, et, al, which measures kinetics of fluorescence as a function of time directly, Data acquisition is accomplished through the 1800, and subsequent data reduction is carried out in the 360 proper, The instrument as a whole has been used to determine 1) excited state lifetimes of various organic fluorescent compounds; 2) rotational relaxation times of various proteins, using fluorescent labels to determine rotatIona behavior of the protein in both natural and denatural states; 3) excited state proton-transfer reactions. Kakihana, R. Y. Name : RKAKIHA Project: ETFANC:, Department: Psychiatry Project Description: We have been studying the effects of alcohol on the central nervous system of rodents, This study is supported by MH 14599 from the NIMH, A study of alcohol's effect on the pituitary adrenal system is being studied in various inbred mouse strains, We are also studying the effects of central nervous system lesions on alcohol preference phenomenon in mice. Finally, the mechanism of central nervous system adaptation to alcohol and other stressors is being considered. It is our plan to continue the use of ACME facilities for the period to July 31, 1969e Tnis service has been extremely valuable and has resulted in three publications based on its use. 1. Kakihana, R., Butte, J, C. and Noble, E, P., 1968. Effects of goldthioglucose on alcohol consumption in C57BL mice, Life Sciences 7: 825. 2. Kakihana, R., Noble, E, P, and Butte, J. C,, 1968, Corticosterone response to ethanol in inbred strains of mice. Nature, 218: 360. 3* Noble, E. P., Silbergeld, S,, Kopell, B., McKinney, W., Wittner, W. K., and Butte, J. CO, 1968, The effects of physiologic doses of cortico- steroid on catecholamine metabolism in man. J, Psychiat. Res., 6: 1593 124 Kanla!!, B. E. L Name: BKAPLAN Project: PSYCHOPIi Department: Psychiatry Project Description: The general nature of the project is the investigation of the relation of automatic nervous system (ANS) responses to attentional sets (thin'king and environmental observation). In a recently completed study, which examined ANS changes as a function of verbalization and environmental attention and rejection, the computer was used to obtain heart rate and skin conductance values from raw data. This physiological data was then analyzed, using analysis of variance and other parametric statistical procedures. In addition, ACME was used for obtaining correlations between the physiological responses and personality variables. Future work will look at ANS responses in lactating and non-lactating human females and will investigate ANS correlates of attention and infor- mation processing. ACME will be used for transformation of the raw physiological data into meaningful units and the statistical analysis of this data. Kessler, S. Name : SKESSLE Project: MATSPEED Department: Psychiatry Project Description: Mill be analyzing mating speed experiments as previously, including use of linear regression and analysis of variance programs. I'ublications: Kessler, S. 1968. Nature, 220: 1044-1045. Kessler, S. 1968. An. Behac 16: 7 e - 125 Koran. L. M. Name: L KORAN Project: SEX - Department: Psychiatry Project Description: We plan to use ACME to complete one, two and three way analyses of variance on tes t, scores made by one thousand students. We wish to explore the relation of these scores to a number of variabies including sex9 class of college, size of home, major field, religion and other demographic informat3ion0 After completing the analysis of the data we plan to write two articles on the relation of the students identifying characteristics to their knowledge as measured by the exam. Kount;z, S. Li Name: SKOUNTZ Project: TRANSPLA Department: Medical Student Project Description: The ACME compuf,er is used by the Transplant Service at the University of California in two areas. The first area is the selection of recipients for renal homotransplantation, and the storage and analysis of data of the follow-up on the degree of renal function in an effort to predict the onset of rejection crisis. The computer has been programmed to include sixty or more patients in the Bay Area who are on cronic hemo- dialysis awaiting a cadaver transplant0 Their ABO blood groups and their HL-A antigens are stored in the computer. When a cadaver kidney becomes available, similar tests are performed on the donor; the lfidneys are pre- served and the information on the donor is fed into the computer and the ..atched recipients are then selected and brought into the hospital for ,.ransplantation, The second area is to measure and calculate hemodynamic changes in transplant patients as a means to detect early incipient -eject,inc., Renal function is measured by the single injection of radio- ,-totapes and the disappearance curves are analyzed by the computer and )mpared with previous determinations- This has provided a very accurate :,iethod of following patients and detecting early incipient rejection. In ..he future we hope to feed all this information into the computer and jlalyze it in terms of survival in an effort to pick out which HL-A antigens or other factors might be playing a significant role in rejection as well as survival. Although we have a limited amount of funds on an N.IOH. grant to study the pathophysiology of renal transplantation in man, our grant does not include funds for computer analysis, 126 Kraemer, H. CC Name: HKRAFJME Project: PSYSTAT Department: Psychiatry Project Description: The work done in PSYTAT is that of developing statistical programs and evaluating set s of data coming from research where output is not extensive enough to zustify opening a separate file. Kriss, J. P0 Name: J-KRISS Project: BLDVOLl Department: Radioiogy Project Description: The program is being used to calculate plasma volume, blood volume and red cell mass in patients who receive radioactive tracer material, The determination is useful in the evaluat.ion of patients with anemia and polycythemiaO Kriss, J. P. Name: J-KRISS Project: ASSAY Deportment: Radiology Project Description: This program is used to calculate the results of a bioassay for the long-acting thyroid stimulator, to calculate the statistical significance of these results, and to calculate the results of a radioactive iodine assay for TSH, These data are being acquired as part of a study on the pathogenesis of Graves' disease and on the effec",:r of X-ray therapy upon thyroid f-unction, 127 Laipjs,, P, ,J. Name: PLAIPIS Project: LIGASE Department: Genetics Project Description: T'ne computer is being used for statistical and mathe- matical reduction of data from experiments connected with my graduate research, principly those experiments involving sucrose and cesium chloride gradients in the ultracentrifuge, The computer is also used for other simple opera-tions too complex for a desk calculator, i.e., least-squares line fitting, Use will be sporadic and of short duration. The computer was used in the analysis of sucrose gradients presented in Laipis, Olivera, and Ganesan, P,N,A.S. (in press). 'iamb, E. J0 Name: EJM Project: EMPIRE Depajxtment: Gynecology - Obstetrics Project Description; Calculation of relative potency and confidence limits for total gonadotropin bioassay. Used primarily for research but will also be used (C_ 1 assay per momth; 1 for calculations involved in service work--even these assays may be used in a research project. T,c,derberg, J. :fsme 1 JLEDERB Project: DENDRAL L,. :ir,tment : Genetics 1 ' *I x Description* Y This project is used to do a limited generating chemical .:tructur,es and display on sanders 720 by interfacing0 128 Leiier, A, DO Name: ALEIFER Project: PREMI Department: Psychiatry Project Description: Through July 31, 1969, I will use ACME for data analysis only. Perhaps I will enterpermanent data files into ACME during this period. The data analysis that is planned now will consist of calculation of means, standard deviations, slopes, correlations, t-tests, and analyses of variance, The project for which this data analysis is being done is a long- term study (five years) of the effects of temporary separation during the early post-pertum period on maternal behavior and subsequent infant development D The study includes as subjects both premature and fullterm infants and their mothers and fathers, The data which will be analyzed under my account is that obtained from time-sampling observations of mother and infant during routine caretaking at home and in the Stanford Hospital. Many other measures of the mother, father, and infant are taken by others involved in the project. Much of this data will also be analyzed on ACME, but under P, Herbert Leiderman's account. Principal investigators for this project are P. Herbert Leiderman, Department of Psychiatry, and Clifford R. Barnett, Departments of ,4nthropology and of Pediatrics and Human Development* The project is supported by grants from NICHD and from the Grant Foundation, New York, New York. Currently, two reports of the results of the mother-infant observations are being completed, one for submission to Science and one for presentation at t`he March meetings of the Society for Research in Child Development. Data analysis for these papers was done on ACME, but I do not believe it accurate to say that the papers are "based on my use of ACMEi'O However, if you should want more complete titles, etc., please ask for them. 129 Levihe, R. I,. Name: RLLEVINE Project: CPS Department: Pediatrics - al532 Project Description: (A complete project description was submitted to the Medical Scientist Training Program Committee.) The project, 'Carbamyl Phosphate Synthetase in the Mammaliam Pyrimidine Pathway', will 'hopefully form the basis of a thesis under- taken as a Medical Scientist Trainee of the NIH, Stipend support comes from the NTH but laboratory space and research expenses are provided by my preceptor, Dr. Norman Kre-tchmer. T:;e purpose of tne initial investigations (in progress six months) is to isolate and purify the carbamyi phosphate synthetase involved in fetal pyrimidine synthesis. This enzyme is apparently distinct from that providing carbsmyl phosphate for the urea cycle, whose enzymatic activities appear later in gestation than the de novo pyrimidine -- activities. The major work thus far has been on development of a rapid simple assay for the enzyme. T.his work will continue , probably to July 31, 1969 and beyond, Lack of an accepta`bie assay has hampered work in the field for years. My primary use of ACME has been to evaluate and process data obtained during assays, There is no question that without ACME asssitance the already burdensome assay w-or'k would become intolerable. It is expected tnat as war%, with the purification progresses, we will examine possible regulatory and control mechanisms in which this enzyme may be important, I may also become involved in another project with Dr. Kretchmer which will use ACME services, but proba-bly not until after ,suiy 31, 1969. 130 z. cn., :\.:. k :rr;'Gz, 1, y. -(>7 Section III-B T,evin:-hsl, E a CD Name: ELEVINT Project: MI471 Department: Genetics Project Description: We are just initiating efforts to use ACME for photo- interpretation and enchancement. The direct application is for the 1971 Mars Mariner Orbiter. The photointerpretation techniques will be applicable to medical research problems as they have already been at the Jet Prop-ulslon Labsoratory. Liebes, S. J. Name: S-LIEBES Project: MS Department: Genetics Project Description: This project is directed toward the development and application of techniques of high-spatial-resolution mass spectroscopy to organic materials of biological interest. The current investigation involves the use of focused radiation from a pulsed ruby laser to vaporize portions of solid samples in the ionization chamber of a Bendix Time-of-1Flight mass spectrometer. The plume of vaporized material is ionized by electron bombardment and the time evaluation of the mass spectra of these ions is monitored at a lo-kc/see repetition rate. The materials so far studied include amino acids, the nitrogenous base constituents of DIVA, sampies of DNA, nucleohistone, lymphocytes, fibroblasts, and red blood cells. We are moving now to the comparison of normal versus abnormal 'blood and tissue samples. The ACME computer facility serves the following important supportive func+ I -"!s: 1. Automation of data acquisition--in the conventional warmed (crucible mode of' operation; 2. Storage of all derived mass spectral data; 3. Manipulation and comparison of data --certain aspects of these operations involve extensive use of the interactive television graphic display; 4. Performance of analytical studies related to the interpretation of data, the refinement of existing instrumentation, and the development of new apparatus. 131 Name : M;,ORENS * _/.8' 1. !~`ic: j TIepsrtment: Pharmacology 132 Luetscner,, J. A. Name: JLUETSC Project : Bloodpr Department: Medicine - Metacoiic Research Project Description: 0u.r research project, supported by the USPHS (AM-030621, deals with the secretion and metabolism of adrenal hormones. Various steroid hormones, catecholamines, and trophic hormones are measured under different conditions of sodium loading or sodium depletion. We attempt to define and relate groups of measurements, which assist in the identi- fication of curable forms of hypertension, The ACME system is used In this project in several ways: ( 1) To CJSSlst in the calculation of laboratory data, involving difficult procedures, such as the double isotope derivative method, which requires solution of simultaneous equations. (2) Interpretation of data: (a) Simulation of complex systems (for example, the study of reactions in which substrate and enzyme concentrations are regulated by different systems and may vary lnde- pendently; or distrYbution and metabolism of hormones). (b) Statistical analysis (comparison of means and variance of different groups, or correlations between different observation). (c) Analysis of clinical information (th e association 'between different observatfons, or the effects of drugs, diets, etc,). (J) Data f.l- 1 es are used to store information at various stages of a sequential process, and for collection and anaiysis of the large amount of clinical dnd La borstory data which accumulates during a long lnvestigatlon, (4) The computer has been used extensively in research training of Fl-iIlows and staff, first in principles and techniques of computer USCCi, a:id subsequently in practical applications. 1-33 Name: JLUME Project: 17 - TW!i>E Department: Medicine - Micro Project Description: The purpose of this project is the biochemical charac- terization of alkaline phosphatase of thymic lymphomas in C57Bl mice. This enzyme does not, occur in normal thymic lymphocytes, These lymphomas are known to 'be induced by viruses, This investigation is to determine whether the information for this enzyme is contained in the virus or is cellular0 This is be!ing done by characterizing the enzyme biochemical and comparing these results to those found in embryo thymuses and other normal organs. ACME is used for statistical interpretation of the results. Luzzatti, L. Name: LLUZZAT Project: GRAGS ON Department: Pediatrics Pro,ject Description: The computer has been used to study a family with a chromosomal mosaicism in 3 generatlons, Measurements of involved chromosome pairs from affected individuals and normal controls were entered, and means, standard deviations and percentage differences cal- culated, Distribution curves and three-dimensional histograms to clsssify different cell lines were also done by the computer, This program is now compieted and the majority of the files will be deleted, At present, the computer is used to store information on history, physical findings and diagnosis on patients with congenital defects. For each patient, a set of anthropometric measurements and dermatogly- phic natterns will also be entered, Our goal is to provide means for correiat.ion of presence of major or minor congenital defects among -:ach other and in relationship to the pregnancy and family histories, Clustering of certain anomalies in a given patient defines a certain phenotypic expression or YYsyndrome"O The computer should be able to llrovide a "diagnosis" when the appropriate set of symptoms is presented, and new syndromes may be further defined by specific clustering of symptoms, The basic information on patients is already programmed and stored; the historical data have been programmed but have not been stored as yet. We are presently developing a program for storage of the physical findings, anthropometry and dermatoglyphics. Information obtained from thus program will have a significant educational value for medical sfudents and house officers in addition to providing clues for investigation, 134 MacPherson , La Name: LMACPHE Project: META Department: Psychiatry (Ve+erans Administration) Project Description: PROPOSAL AND MEXHOD OF STUDY. We plan to investigate the significance of the CN\T and aspects of the MP studying their similarities, differences, interrelationships, and relationships to mental states such as selective attention and expectancy. Healthy college student volunteers will serve as subjects, No drugs will be given and no risk to participants will accrue. We will proceed in an explorative fashion with pilot studies, hoping that as possible avenues of investigation are outlined, more difinitive experiments with larger population samples will tske shape. We plan to start with the following study, Ss' AEP wiii be obtained under the following experimental conditions. Short auditory stimulus presented repetitively and timed randoiiy. (T o obtain AFP evoked by the auditory stimulus.) 2. S presses button randomly whenever he desires. (To obtain MP associated witn muscle contraction,) tone.?.(l" S presses button immediately after hearing randomly presented o obtain averaged EEG produced in combination by the AEP to the tone and the MP when S attends to an autside command.) 4. S presses 'button randomly whenever he desires. This produces a tone. (To obtain EEG as in condition #3 except that S is not paying attention to any outside commands.) 5" S hears a tone (conditional stimulus) and when two seconds lateI- another tone appears (imperative stimulus), S presses button clulckl.~~-. (To o.btain the type of CIVJ that was reported by Walter.) The averaged EEG potentials of these conditions will be analyzed and compared with each other in order to ascertain which stimuli produce which potential changes under which conditions and in order to elucidate whether and how the CWT reported in the literature is related to the MP. IMPLICATIONS= The importance of the proposed work of larger scope lies in development of techniques for the concrete electrophysiologic measurement of psychologic states of the mind. Already such related methods have demonstrated surprising corresondence between cerebral AEP findings and mental states of attention, expectancy, conditioning, habituation, meaningftilness, and levels of certainty. The experiment 135 M-7CPilerSOT: , L. (corit,) Name: LMACPHF Project: META Department: Psychiatry (Veterans Administration) Project Description: described In more detail could clarify the relationship betwen the MP and the CNV, Since muscle activity (e.gO, pressing of switches) is widely used as an indicator of S's intent or state of mind, elucidation of -the relationship between CNV and MP is needed. REFERENCES 1. Caspers, H., in The Nature of Sleep (Churchill, London, 1961). c: 1 Gflden, LL, et, al,, Electroenceph, Clln, Neurophysiol., 20:4.13-438, 1966. - - V. and Goldstone, M., Electroenceph, Clin. Neurozhysi?1a;:b6j) e 4. Rusinov, V. S., Electroenceph, Clin. Neurophysiol., No. 13, 1960. SUPP 50 Shvets, T0 B., Conf, Electrophysiology of Higher Nervous Activity, Moscow, 1958. 60 Walter, W. G., Nature, 203:380-384, 1964, lv:rliiE : RMAFFLY Project: CO2 I):-I rt,ment . Medicine (Veterans Administration) z~L Description: Under study is active sodium transport by the toad bladder. We correlate three variables: short circuit current, CO2 product,ion and ClYO2 proudction. The computer is used to calculate the variables and to interrelate them, and to perform statistical analyses, At the V.A, Hospital I plan to collect data on all patients with elevation of blood urea nitrogen and all with decreased serum sodium concentration and to use the computer to find out the predictive value of a variety of test and procedures and laboratory data. 136 Mesel, E. Name: EMESEL Project: DOGLAF Department: Pediatrfcs Project Description: One of the parameters to be derived from indicator dilution measurements of pulmonary blood flow is the "impulse response", which is essentially the distribution of transit times of particles through the lungs. If Ci(t) represents the dye concentrations in the right heart following injection of a bolus of dye at t=O and Co(t) represents the concentration in the left heart, then the impulse response h( t> is described by tihe equation: s=t Co(t) + s h(s)Ci(t-s)ds szo Replacing the of time: integral with a summation over equal ly spaced interva IS Co(n) = 2 h(i)Ci(n-i) i Z~I Thus a program can be written for a digital computer which solves for the function h(t) when given the values for Ci(t) and Co(t) However, a simple straightforward solution yields an impulse response which IS hopelessly disrupted by artifacts in the collected data. A technique must be employed which somehow filters the data. Several possible methods are known; one has in fact been successfully used. The program was executed on the Burroughs 5500, a machine which has twelve significant figures in regular precision and twenty-four with double precision. A similar program attempted in ACME accumulated so m--'-h error during execution that it proved useless. Thus if we are to acheive o.ur goal using ACME, we must somehow o.btain greater precision than is now available. Our current efforts are directed at this problem of insufficient precision. 1-37 Mesel, E. Name: EMESEL Project: VSD Department: Pediatrics Project Description: Project VSD is concerned with blood flow through ventricular septal defects (VSD) surgically produced in dogs. Two major sets of comparisons are made: the pattern of flow through the VSD is compared with the pattern of differential pressure between the left and right ventricles and with the electrocardiogram (ecg); and and flow measured by an electromagnetic flow probe (which we consider a primary standard) is compared with flow measured by other techniques used on people (Fick, dye dilution). During the experiment, VSD flow, left and right ventricular pressures, and the ecg are recorded on tape. The more interesting data are selected for A to D conversion and for computation of the differential pressure by program WORK!ZORSE. Program LISTING lists digitized data, which, when graphed, permits comparison of the pattern of flow with the pattern of differential pressure. As might be expected, we have found that these patterns are very similar even under varying conditions (e.g., ectopic beats), with flow slightly delayed with respect to pressure. Program cathlog produces a file which summarizes all our VSD experiments. Future effort will be directed towards the incorporation and use of programs developed in project carcat for pattern recognition of pressure and flow contours. Mesel., E. Name: EMESEL Project: CLINIC Department: Pediatrics Project Description: The object of this project was to store patient identi- fication information, and diagnoses obtained at each step in the course of illness (clinical - OPD or IPD, cardiac catheterization, surgery, autopsy) in ACME files, This work was patient-service oriented but had several experimental aspects such as the structuring of the filing schemes to permit rapid access (while conserving the amount of file space utilized), and the uti.liz.atlon of the stored information for hospital planning purpose, evaluation of patient survival with different modes of therapy, etc, Plans are to discontinue this project until such trme as adequate clerical assistance is available to implement the filing system, Mesel, E0 Name: EMESEL< Project: CARCAT Department: Pediatrics Project Description: Project "carcat" analyzes cardiac catheterization pressure tracings in children. From catheters in the right and left heart, pressure tracings to determine atrial, ventricular, arterial, venous and wedge pressures. Currently the values in millimeter of mercury are calculated for the a and u waves, x and y troughs, and mean pressures in the ar-t,ia and great veins, for systolic and end- diastolic pressures in the ventricles, for systolic, diastolic and mean pressures in the great arteries, and for mean pressures for the wedge positions, These values are calculated immediately and printed out f-i, t;he computer terminal in the catheterization room. At this time, efforts are under way to improve and ascertain the accuracy of the algorithms used in pattern recognition for atria1 and ventricular pressure tracings, The basic data acquisition and analysis system that has been set up will also be used to store data acquisition and analysis system that has been set up will also be used to store data for additional calcu- lations and for the preparation of reports, As data is accumulated in storage from cardiac catheterizations and from other sources of clinical information, it will be possible to analyze large amounts in clinical data rapidly using the ACHE computer, Research into methods of storing and recalling data for analysis of clinical information will be an important part of our future efforts, 139 Miller, R. P. Name: R MILLER Project: BICSTAT - Department: Preventive Medicine PI yoject Description: The Division of Biostatistics, Department of Preventive Medicine , provides biostatistical consulting to persons doing medical research in the Stanford Medical Center and occasionally elsewhere, such as Presbyterian Hospital in San Francisco. Some of the people who have consulted us in the past years have been Dr. Ken Gardner, Dr. Yule, Dr. Maffly, Dr. Hart of Infectuous Diseases. . The Division also trains postdoctoral fellows and some graduate students in Statistics in biostatistical consulting. Investigations of statistical methods may also be done by the stsff, postdoctoral fellows, or graduate students. The computer is used in all these activities. Monnin, L. M. Name: L MONNIN Project: DISCRIM Department: Speech and Hearing Sciences P-r,oject Description: A study of the relationship of articulation and identi- fication abilities of normal speaking and speech defective children. Distorted speech stimuli will be presented to the subjects so that an identification threshold can be estimated. 140 Morris, S. J. Name: SMORRIS Project: EXFI'4 Department: Genetics Project Description: I am using the 1800 to interface a Packard liquid scintillation counter to the 360. This allows me to feed raw data directly into the 360 where it can later be retrieved and digested. The original interfacing work was done in lieu of a language requirement -- for my PhD. The system will be used to analyze the incorporation of radiolabeled amino acids into brain proteins. See ACME Note TRA-1 for a full discription of the system. 141 Name: _ _ L NALL Project: PSORIASI Department: Dermatology Project Description: Psoriasis is a chronic, scaling skin disease of unknown etiology, which affects approximately 4% of the general population (no accurate figures are available)O It is a lifetime disorder which does not take life, but indeed destroys it for all age groups. The Department of Dermatology of the Stanford Medical School is a world center for both clinical and laboratory investigations on psoriasis. As one phase of the over-all Psoriasis Research Program, the Department is engaged in a continuing investigation of the epidemiology of the disease. A questionaire survey has been conducted from 1959 to date. Presently, the Department is conducting Series I.I, III, and IV of its questionnaire survey; doing follow-up studies on the familial incidence of psoriasis and the relationship of psoriasis to other diseases, i.e., arthritis, diabetes, throat infection (The findings from Series I, which had been computerized on the 7090 are now being handled by the 360/50 and 67-) o We have applied to the National Research Council to participate in their Twin Registry of Veterans, in order to utiiize the twin method in our study of the etiology of psoriasis. In addition, we are applying to utilize their registry of veterans in a large scale epidemiology investigation, Hopefully, 'both will be financed by an NlH grant. The application of ACME to the computerized phase of our findings has been indicated in all grant protocols. 142 Nali, ?I. L, Name: I, NALL Project: MYCOSIS - - Department: Dermatology Project Description: Mycosis fungoides is a fatal skin disease of unknown etiology, Various chemotherapeutic agents (i.e,, nitrogen mustard, steroids, etc,) have been utilized to abate this disease, but the x-ray and elctron beam are the only techniques that have proven effective in producing remissions. The Stanford School of Medicine and the Massachusetts General Hospital are the only facilities in this country, who have applied the beam in treating mycosis fungoldcs; although recently the Ovarian Company has developed smaller accelerators which vi11 be used in other hospitals. Drs, Harold Schneidman and William Watson of the Dermatology Department conducted a retrospective study on the effect of the electron beam in comparison to other methods of treatment. In a pilot study of 51 mycosis patients (treated at the Stanford Medical Center in the !:adiology Department), the investigators developed a data gathering form. The coded information was keypunched and read into A_'!@ as a data file, which was computed via a number of input-output programs, Although no paper has been published as yet (since the study is in progress), the results of the pilot study were presented by Drs. Schneidman and Watson at the annual Meeting of the American Academy of Dermatology in Chicago :n December, Tne investigators were able to learn from their preliminary study that by applying the electron beam at an early stage of the mycosis that longer periods of remission will result. This information is a pioneering fact; albeit, more detailed st,udies will be forthcoming to yubstantiste this early data. Dr, Schneidman has supported this effort from nis personal funds ;ind plans to continue to do so. Thus, we are concerned in keeping our , 3!L? ~'YTS~C` at a minimal level. 143 Noble7 E. P. Name: EPNOBLE Pro2ectr ALCGHO - Department: Psychiairy Project Description: central nervous from the NIGH. system is being We have been studying the effects of alcohol on the system of rodents. This study is supported by MH 14599 A study of alcohol's effect on the pituitary adrenal studied in various inbred mouse strains, We are also studying the effects of central nervous system lesions on alcohol preference phenomenon in mice0 Finally, the mechanism of central nervous system adaptation to alcohol and other stressors is being considered. It is our plan to continue the use of ACME facilities for the period to July 31, ~969. This service has been extremely valuable and has resulted in three publications based on its use. 1. Kakihana, R., Butte, J, C. and Noble, E. P., 1968. Effects of goldthioglucose on alcohol consumption in C57BD mice. Life Sciences 7: 825. 2. Kakihana, F., Noble, E. P. and Butte, J. C., 1968. Corticosterone response to ethanol in inbred strains of mice0 Nature, 218: 360. 3. Noble, E. P., Silbergeld, S., Kopell, B., MeKinney, W., Wittner, W. K., and Butte, J, C., 1968. The effects of physiologic doses of corticosteroid on catecholamine metabolism in man. J. Psychiat. Res,, 6: 159 - - - "J?rnP : WNYE Project" STUDENT 1-t,- ,\; 1. 7ment : Medicine - Micro E)w ;.-c:t Description: Under this tiser name, several people in this department have ,used this project for statistical calculations and bibliography ompilations y Several of the users have been graduate students of the department or postdoctoral fellows, The bibliography compilation will probably be published in the new Biochemistry Handbook by Dr. Kirschbaum. 144 `*l'd I, t >$o I F1;00:,, -;. j -CT: Section III-B Payne, R. 0. Name: _ R PAYNE Project: SERNAL Department: Medicine - Hermatology Project Description: The research is concerned with extending the classi- fication of leukocyte and/or tissue antigens by serologic and genetic analysis of specific human antisera. In the computer programs, 1) donor-recipient pairs of individuals are selected for deliberate immuni- zation to produce antisera and 2) the antisera are analyzed by comparing their reactions with test cells in 2 x 2 tables for associations between them, The significant associations are calculated, and the frequency of positive reactions are determined. Pearson, M. Lo Name: MPEARSO Project: CTCOR Department: Biochemistry Project Description: The program is used to compute normaliz4ed chromatographic elution profiles of viral SRNA. We have found that induction of lysogenic bacteria results in the formation of a set of small molecular weight ordered RNA's coded by phage X DNA. These RNA's have physical character- istics similar to transfer RNA and may be intimately involved in genetic control, The set of viral RNA's can be fractionated on benzoylated deae columns. The computer normalizes the elution profiles of viral RNA's to a constant total output RNA, allowing comparison of the relative amount of each viral RNA from one column run to the next. It is anticipated that future programs will be used to calculate quench-corrected values of radioisotope activity in double-label exper-iments, using data from a liquid scintillation counter0 145 Petralii, J. K. Name: JPETRAL Project: MET;-DATA Department: Infectious Diseases Project Description: A COMPUTER METHOD FOR IMPROVEMEI'~ OF ANTIBIOTIC SENSI- TIVITY DATA AND GUIDANCE IN THERAPY. J. K, Petralli*, S. Wallis*, T. C. Merigan, Department of Medicine, Stanford University, School of Medicine, Palo Alto, California. To improve the quality of antibiotic sensitivity data (high potency single disc method) and to guide the interpretation of results and antibiotic selection a computer program has been developed. Clinical information and zone sizes are entered each day on the IBM 360 time sharing computer (which allows on-line continuous data generation). Each zone size is compared with limits based on previous results and unusual values are challenged for further study. This system rapidly detects unusual organisms or laboratory error. The computer converts zone sizes to resistant, intermediate, or sensitive and prints final reports Orom its memory, Decreased potency of antibiotic disc is detected by comparison of periodically determined mean zone sizes. Limits of confidence of a single reading are established by review of zone sizes observed with a standard organism tested on different occasions. Know- ledge of antibiotic sensitivities of organisms isolated from a specific site such as blood or urine will heip to guide the selection of anti- `biotics before specific sensitivities are known. Such information is of value in selection of antibiotics in treating rarely encountered organisms with less well known sensitivity patterns or in selection of alternate antibiotics when ,the first choice drug is hazardous. Yearly comparison of antibiotic sensitivity patterns obtained will give infor- mation about major trends and suggest appropriate changes in treatment of various infections, 146 porter, R. w. Name: RWPORTER Project:. ATT KT"J Department: Biochemistry Project Description: Project ATC KIN has been ,used for data processing in the investigation of the steady-state kinetics of the enzyme, aspartate transcarbamylase. The programs were written for curve-fitting the data from different types of kinetics experiments. For example, program "DataFit" employs a simple linear least squares fit to calculate the initial rate of reaction from the raw data, measured as amount of radioactivity versus time of reaction, and converts the result to standard units of specific enzyme activity, using units of concentration. Other programs calculate the kinetic parameters using a linear least squares fit for the reciprocal transformation, due to Lineweaver and Burke, of the Michaelis-Menten equation. Another program, "Hyper- Fftts, was written to fit the non-linear, hyperbolic function of the original Michaelis-Menten equation. The program employs a reiterative procedure of trial-and-error testing for optimal fit. Trial values for the two parameters of the Michaelis-Menten equation are tested for minimizing the residual, and the procedure is reiterated to give a close approximation of the best values, This computational procedure was refined and optimized for speed, and the program will compute the best values for the two parameters, to an accuracy exceeding that of the data, in less than ten seconds of computer time in 3 time-sharing environment. This approach proved to be so successful that, It was adapted for curve-fitting other, more complex non-linear kinetic equations with more parameters. For example, the non-linear equation describing substrate inhibition, with three parameters, which does not give a simple linear reciprocal transformation, has been employed directly, using this trial-and-error technique. ln addition, the family of hyperbolic curves described by the equation for competitive inhibition, with three parameters, has been employed ;,lccessfully. The greatest success of this technique has been the use of equations ,rith four parameters for curve-fitting, such as the equations describing non-competitive inhibition and parabolic competitive inhibition. With correspondingly longer times for calculation, these programs have pro- vided quantitative support for the existence of certain reaction inter- mediates in the pathway of this enzyme mechanism. 147 Porb?r, R. W. (cont.) Name: RWPORTER Project: ATC-KT?i Department: Biochemistry Project Description: These programs make special use of the on-line communication available with the ACME system, especially through the use of options and operator-controlled branchpoints in the programs. The results of these kinetic studies have been reported to The Journel of Biological Chemistry, where they will be published in March, The manuscript for this report was prepared making extensive use of the manuscript editing facrlities of ACME. The authors of the report are Robert W. Porter, Michael 0 Modebe, and George R. Stark, and the title is "Aspartate Transcarbamylase: Kinetic St-udies of the Catalytic Subunit". 148 Reaven, G. M. Name: _ G REAVEN Froject: DISPLAY Department: Medicine Project Description: We are interested in developing models of glucose, insulin and triglyceride kinetics as related to diabetes mellitus and atherosclerosis. Clinical data obtained from tracer studies are analyzed by the ACME computer through five stages of development. The project display includes the third and fourth stage. In the third stage, the program PEEL automatically obtains the parameters for a linear sum of exponentials and the program SKINNER obtains parameters which are the constant coefficients of a system of linear differential equations. The results are used for the fourth stage. In this phase, the parameters are used for calculation of a theoretical curve which is displayed on a CRT. It is then compared with data which also appears on the CRT. The results of PEEL and SKINNER get us into the "ball park" and we change parameters until we obtain a satisfactory visual fit. In this phase we use the programs RUNGCURV, DATA, TDATA and berman. We are in the process of preparing two manuscripts in which the results are based on the above program support, The first paper is a mathematical model of insulin distriibution in man in vivo and the second paper is a description of the use of on line display procedure for determiping physiological models of metabolic processes. We are now perform&g similar analysis with respect to triglyceride metabolism and are extending the insulin work. We expect to use the above procedures the entire year and expect to extend stage 4 and develop stage 5 for analysis of nonlinear metabolic models. Name: G-REAVEN Project: FIT Department: Medicine Project Description: (See d iscussion in Project DISPLAY,) The final phase is at the present being developed. The results of simulation in stage 4 is to be statistically evaluated to see if the parameters obtained do not violate the statistical limitations of the data. At the moment, we are doing this is a crude manner at the Computation Center. However, the most satisfactory results are obtained if the statistical evaluation is coupled to stage 4. We plan to use nonlinear regression techniques to evaluate these parameters. We have developed four programs for this procedure; they are RUNGPCW, sPOWELL, COVARE and EXPCPCW. Reaven, G. M. Name: G REAVEN - Project: PAT DATA Department: Medicine Ercjject Description: (' bee discussion in Project DISPLAY.) This project includes Stage 1 and Stage 2. Stage 1 and Stage 2 are support programs for Stages 3, 4, and 5* In Stage 1, serum endogenous insulin is bio- logically assayed by the program INSULIN. The program TGCONRAD determines triglyceride concentration and the program DOUBLE estimates counts from double label experiments., The final program in this phase WEIGHT estimates weights of data points for future statihical analysis. The second stage -onsists of statistical support programs for evaluation of the results .P Stage 1, The programs used in this phase are TEATEST, RAT, NOVA, CORL, :,nd REGRESS. c 11 :esearch activities also include procedures to determine weight -*.tterns of patients, The programs involved in this aspect are BODYCOMP 3-1 BODYFAT. Name: J REITAN - Department: Anesthesia Project: INDIRECT Project Description: We are processing cardiac internal timings collected by non-invasive, indirect techniques in order t.o monitor the contractile state of the heart tinder varying loads and drugs. 150 Reyncids, W. E. Name: WEREYNOL Project: soo'i Department: Genetics Project Description: This project supports the basic development of automation in computer-mass spectrometer instrumentation systems. This worker is an instrumentation engineer, hence the remarks about the biological aspects will be brief, The mass spectrometer has become a powerful tool in the elucidation of organic molecules. This is of great interest in the biochemistry field and in the case of DNA and related structures to the Genetics Department. Since the basic principles involved are common to at least the Genetics Department ?nd Organic Chemistry, the physical instruments and location are sometimes shared, This is the case for this project. Hence the efforts of this project span over 5 mass spectrometers in 3 diverse loca- tions on the Stanford campus. The technical development consists in the origination of instrumenta- tion concepts, and realization, in both hardware and software, complete operating systems. These systems are intended to automate ,the mass spectrometer (low resolution Bendix t-o-f, Finnigan quadrupoles, Atlas CH-4 and a high resolution AEI MS-9) to provide the following benefits to the biological user-researcher: Savings of the researcher's time in instrument operation and data reduction, Improve the quality of the data. .:ap?*ove the presentation of the data, Foster computer files of pertinent data. ,`,!?i s is being accomplished by basic research and development in the ,plic?tion of computers, both dedicated and time shared to the field of computer-instrument integration, The ACME system is being used by this user both as the final computer in the automated system and as an engineering design aid to achieve the final sys+.ems e 1-51 .,.:..t !.:,. YE&C'31 1 -43 section III-B Reynolds, W, E. (cont.") Name: WEREYNOL project: so07 Department: Genetics Project Description: Publication - COMPUTER CONTROL OF MASS ANALYZERS. A paper given, and published in the proceedings of, The Sixteenth Annual Conference on Mass Spectrometry and Allied Topfcs. (May l968, Pittsburg, Pa.) (ASTM Committee E-14). Reynolds, W. E., Name: WEREYNOL Project: TEXTS Department: Genetics Project Description: This 1s a text management project to support general engineering efforts in instrumentation. The project supported is: W.E.REYNOLDS,S007. "TEXTS ff contains commercial technical data and information retrieval programs. Robertson, W. y~:.i:TiF : W ROBERT Project: UGAG - t:i: iartment : Pediatrics Project Description: (1) D.t a a on urinary analyses of glycosaminoglycsns ,;oth on patients and normal individuals will be entered. The curve relating concentrations to age in normal children will be developed. The vsiues of groups of children with different diseases will then be compared .dith normals to discover which diseases lead to abnormal excretion. (2) Analytical data on immunoglobulin concentrations in sera from jtients with a variety of immunologic diseases will be entered and -orrelations developed with the clfnical state of the patient and therapy. (3) Data on the binding of ligands to macromolecules, e.g., cortisol to hyaluronic acid will be used to determine association constants. 152 Rosenberg, L,. T, Name: L-ROSENB Project: ALEXINE Department: Medicine - Micro Project Description: We are studying levels of serum complement in mice using ACME to carry out the appropriate statistical analyses and calculations. We rare storing accumulated data on large numbers of mice of diverse pedigree. Using ACME facilitates data retrieval. Rosenthal, W. S, Name: W ROSENT Project: RESEARCH Department: Medical Student - Speech and Hearing Science Project Description: I am using the computer essentfa'lly for statistical analysis of data in connection with various experimental studies in speech and language pathology and normal speech perception. These studies include research in effectiveness of stuttering therapy, speech and a-uditory perception in aphasic children, and normal speech perception in adults and children. Plans through July 31, 1969 include continuation of above usage as well as possible use of the computer in a language perception simulation program, 153 .,.a~it idp. FROO3'.' -0" Section III-B Ross, K. Go Name: R-ROSS Project: CHEM - Department: Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experi- mental analysis programs so as to develop programs for the routine analysis and finsihed output of mass spectra. The transmission is through the 27OY-270X channel. The project plans to develop this interface to service three mass spectrometers (ALTAS CH4, AEI MS9, and a FINIGAN 1015 quadro- pole) o The talier, spectrs are then to be fed to the Artificial Intelligence group under the supervision of J. Lederberg and E. Feigenbaum to be used in their dendral investigations, (B) Another use of data transmission through the 27OY is to take spectropolorimeter measurements and then analyze these spectra for form, 'bandwidths and similarities between derivatives for theoretical projections, (C) The project mentioned also includesa `battery of utility programs for metastable analysis, chemical rate analysis, Cl3 substit-&ion ratios and other routine analysis that the Chemists wished programmed, l?otkl, w. To Name: W ROTH ,- - Project: COMP i.,i"~~rtment: Psychiatry !'roject Description: For the period prior to January 1, 1969 I have submitted two papers for publication based on using the ACME system for the analysis of electroencephalograms (EEG's) and the statistical processing of the results, T will. be at Stanford unt,il June, 1969. During the next 5 months : will be doing a project involving the computer analysis of habituation f the evoked response and EEG desynchronization. Also an attempt will me made to distinguish states of arousal produced by emotional stim-uli. 4nalysis methods include spectral density calculations based on the "fast" I ourier transform, p eriod analysis (Burch), and response averaging to 'mprove the signal-to-noise ratio. Since 90+$ of the grant goes to stipends of four residents in psychistry, faculty salaries, and other expenses such as tuition, Dr. Moos feels that the 95% support level is most appropriate at the present time0 154 ,. :.11rt .Jr. . F'Eiw:, .I 1 -0" Section III-B Saunders, A. MO Name: AMSAUNDE Project: MASTCELL Department: Pathology Project Description: Multiple numerical parameters are determined for single cells under varying conditions of staining and animal pre-treatment. Analysis of results lead to conclusions on the type and quantity of poly- anion in the mast cells under study (once thought to be just hepanin). Hence the pr0jec.t involves the chemistry of Hepanin type substances at the single cell level, the maturation and biology of the mast cell in rats and people, and development of methodology, mostly centering on fluoresence microscopy. Saunders, A. M. Name: AMSAUNDERS Project: SPHEPES Department: Pathology (Genetics) Project Description: Cells measured by a rapid sensor system. Data collected on tape and records will be transformed from a LINK to ACME for storage and analysis. Sal,isgeau, M. A. NRT? : M SAVAGEAU Project: KINET - De;:,,rrment: Cardiology ~'LI~:~L. t Description: I am concerned with the kinetic behavior of systems of 'lzyme catalyzed reactions. During the coming year I expect to use the T4X computer in three ways. First, I will use it to store and process xperimental data from enzyme systems. Second, a nonlinear curve fitting qrocedure will be implemented to estimate the kinetic parameters for the \:hanisms yielding the experimental data. Third, the solution of the ;;ystem of differential equations will be simulated to obtain the temporal behavior of these enzyme systems. 155 Cavalli-Sforza, L:. L, Name: L SFORZA Project: PAVIA - Department: Genetics Project Description: Programs on storage were mostly developed for simulation of population genetics studies. One of them was developed for the I.C.R.O. course, and is still being used for research purposes. It deals with genetic drift in a human population and takes care of the effects of age structure. Another simulates nutrition,drift and selection in a haploid population, or in a diploid population with additive selection. Others simulate the propagation of hemoglobin mutants in Africa., I will have to use these programs in the coming year, but it is difficult at present to estimate actual use - except for hoping that. it will be less intensive. It will be perhaps 2% of what it was in the period for which sample billing may be carried out. I am also planning to use ACME for a course for medical students, to teach computer use in simulation experiments that may illustrate the meaning of major statistical methods, and some special use of statistics in medical research. 156 Smallwood, R. D. Name: R SMALLW - Project: MUjIP:~:'::! Department: Engineering - Economic Systems Project Description: The Stanford Medical Facilities Planning Group is engaged in a system planning study for the design of the new Stanford Medical Care Facilities. The primary goal of this group is the develop- ment of systematic quantitative procedures for evaluating the relative utility of alternative plans for the new facilities, Because of the emphasis on quantitative analyses and because of the magnitude of the problem, much of our work will be directed at large scale computer simulations that will aid in the evaluation of alternative macro organization strategy for the facilities. At the present time we are completing the development of several of the computer programs that will serve as intrinsic components to the overall simulation system. We have also nearly completed the task of gathering the data that is necessary for estimating the parameters of the simulation, Current plans are to complete the integration of these components by the spring of 1969, to use this tool in the actual evaluation of alternative plans, and to write up the results by June. Smith, N. T. pz c 1 r.n+e : NTSMITH Project: BABOONS T!epartment: Anesthesia -ct Description: This particular project (BABOONS) simply involves transfer of manually obtained and calculated data into ACME files. Multiple regres- sion and correlation analyses are then performed on these data. Data obtai'ned b:,r destructive methods (thoracotomy, catheter placement, etc.) are compared to those obtained by nondestructive methods (microphones, !3celerometers, etc.). It is hoped to replace the former with the Latter. We have an enormous amount of data which we are preprocessing with our analog computer. We would like to transfer this data directly to ACME for analysis. However, because of limited funds, need for pro- gramming assistance, and difficulties with ACME, this will not be possible in the forseeable future, Smith, N. T. Name: NTSMITH Project: MAC Department: Anesthesia Project Description: This project involves calculation of cardiovascular data from variables obtained in normal volunteer subjects and patients. No statistical analyses are performed through this program; rather they are performed separately using standard programs. Project: PREMIES Name: p-smith Department: Pediatrics Project Description: This data will be used in any study involving pre- mature or sick newborn infants cared for in the Stanford nurseries. Such items as 'birth weight, gestational age, system desease, etc., will be correlated by pairs, For further information, contact the Smith, P. Premature Research Center. . a vent1 Smith, P. h3me : p-smith Project Department: Anesthesia ect Description: This project (ventl) is to find out if any \ parameter of mechanical ventilation (rate, pressure vt, i.e., ratio) influences pa02 in newborn infants with respiratory failure.. So far ACME has been used to store the measured variables and perform statisticalmaneu- vers such as correlation coefficient calculations, A program for estimation of venous lung shunt is included. 158 Smith, R. C. Name: RCSMITH Project: FAMIL" Department: Medical Student Project Description: I am a medical student who has been using the ACME Project for my own research, I am a medical student pursuing an M.D.-PhD. program at Stanford. Funds for my own research have been supplied through the Dean's Office, the General Research Support Fund. The ACME file has been used to store analysis data from an experi- mental study of family structure which I conducted during the past year. The project contains one data file (SDM) and a number of program files to analyze the data. Most of the analysis has been completed during the past year, but some still remains to be done. I have also done some socio-physiological studies of Kidney transplant patients, data which I will be entering in the near future. I plan to make inter- mittent use of ACME for further analysis of data from these projects during the next six months. However, because my clinical responsibilities will become heavy after January, I plan to put the major file (SFDM) on disc or tape storage, to be recalled when I have more time for further detailed analysis of raw data. Two papers are currently being prepared from the family research described above. If specific NIH grant support for use of ACME should be listed in publications, please send me data on and acco,unt number of the grants. 159 Stewart, L. Ti, Name: _ L STEWAR Department: C. J, Jung Institute (San Francisco) Project: DREPJ4 Project Description: The research aims of the Institute is the establishment of an archive of classified psychological information centering around such primary dat'a as dreams, and other unconscious material. Also included will be psychological test, data, clinical assessments, and systematic demographic information. These archives will be valuable in extending our understanding of unconscious material; i.e., dreams and fantasies, and will enhance our comprehension of the relationships between the ego and the unconscious. Methods for the rapid collation and analysis of data are being considered. This includes techniques for the indexing and preparation of concordances of clinical material drawn from history, archaeology, mythology, comparative religion, and other sources0 Such techniques will facilitate the search seeking the connection between themes from historical and cultural sources mentioned above. The availability of such data will be of immense value in the training of analysts, in the general practice of analytical psychotherapy, and in extending the frontiers of o?lr present knowledge of the human psyche. ;:tillman, R. Name: R STILLM - Project: PSYGAPE :; 2rtment: Psychiatry Project Description: Our project involves the use of an interactive system for the: interviewing and testing of psychiatric patients. The work has'appeared as a presentation to The American Psychiatric Association's annual meeting and as a publication in the January 1969 issue of the American Journal of Psychiatry. We are attempting to use the computer and a peripheral CRT display for anticipated psychological testing. This includes terms from standard psychological tests, and novel tests which the computer is especially suited for., 161 Stillman, R0 A. Name: RASTILLM Project: DRPF Department: Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental analysis programs so as to develop programs for the routine analysis and finished output of mass spectra., The transmission is through the 27OY-270X channel. The project plans to develop this inter- face to service three mass spectrometers (ALTAS CH4, AEI MS9, and a FINIGAN 1015 quadropole). The taken spectra are then to be fed to the Artificial Tntelligence group under the supervision of J. Lederberg and E, Feigenbaum to -be used in their dendral investigations. (B) Another use of data transmission through the 27OY is to take spectro- polorimeter measurements and then analyze these spectra for form, band- widths and similarities between derivatives for theoretical projections. (C) The project mentioned also includesa battery of utility programs for metastable analysis, chemical rate analysis, Cl3 substitution ratios and other routine analysis that the Chemists wished programmed, S:.il.lman, R. A. Name: RASTILLM 1 je 1-1~3 rtment : Chemistry : Ser pro ject description for DRAFT. Project: DREAMS Project: GASTRIC ?-.ent : Medicine - Gas+,ro-Intestinal Division I ,-:-It Description: I am involved in clinical research projects relating to a;;tric secretory function tests and have used the ACME Computation ('enter over the past, year for filing of data collected from these projects and for statistically analyzing the results obtained. I plan to continue these usages through July 1969. Cne publication, 'The Effect of Preduisolane on Gastric Structure ,-jnd 'r'unct,lon in Man', has been accepted and wil 1 be appearing shortly in Q,S :'I;;;`F I\l"E,EC:~&Y i -1.1 D Other p;bLicat,lons have either been submitted or are in preparation now. 162 Stocker, B. Name: R STOCKER - Project: stm Department: Medicine - Micro Project Description: My main project concerns genetics and physiology of Salmonella typhimurium - in particular somatic lipopolysacchsride, flagella and motility, and plasmids, especially R and colicine factors. I am co-investigator in Dr.. E. Lederberg's project, which concerns mainly recombination-deficient mutants in the same organism. Main ACME usage so far has been in statistical analysis of data from experiments concerning pathogenicity of lipopolysaccharide mutants (estimations of LD50, rate constant for clearance of bacteria from blood stream, harmonic mean times-to-death, significance tests, etc.). I expect to continue such usage. Ii' my grant is renewed and if I can hire s-citable help, I expect to use ACME also for storage and analysis of extensive stock- culture data concerning strains with numerous genetic markers, and for participation in a co-operative scheme for exchange of such data for several Salmonella stock collections. 163 Stryer, L. Name: _ L, STRmR Project: NANOS Department: Biochemistry Project Description: The principal aims of the research are: 0) t 0 acquire an understanding of mechanisms of electronic excitation energy transfer; (2) to develop novel fluorescence and phosphorescence methods which can provide detailed information concerning the structure and dynamics of biological macromolecules; and (3) to apply these optical techniques to obtain insight into aspects of the structure and function of selected proteins. The experimental approach which is used in these studies involves: (1) the synthesis of model compounds which serve to define relationships between o.bservable emission parameters and structure; (2) the synthesis of fluorescent and phosphorescent labeling reagents which have appropriate spectral properties and can be specifically attached to defined sites on proteins, and (3) the development of optical instrumentation for kinetic iaeasurements in the nanosecond time range and for the detection of fluor- escence and phosphorescence emission from membranes and cells. Stuedeman, D, L. Project: ADMIN Dcgartment: Genetics 1, : xt Description: I keep an inventory of IRL capital equipment, update it :ccasionally, use the computer to locate items, sort by room or whatever IS required, It can be used for preparing reports to sponsors and pre- forming; listings in various forms. I also apply the ACME sys,tem on r,r;ous r~athematical calculations used in my work, including a study of >:e University's retirement insurance program. NaIQc . WTSUMJGR Project: BIOCHEM Department: Dermatalogy Pro.;ect Description: T o stlJdy biochemical control of collagen formation via proline/hydroxjproLine (ratios). 164 Thathachari, Y. TO Name: YTTHATFA Project: DOPA Department: Dermatology Project Description: Structure of melanins. Melanin is a polymeric pigment widely distributed throughout the plant and animal kingdoms. It has unusual physical and chemical properties, Using ACME as a real time terminal models of the molecular structure of melanins were generated starting wihh the known shape of the subunits and using various criteria for the linking of adjacent units. By watching the output periodically the flow of the computation could 'be directed at will. For these generated models various measurable physical data were computed and com- pared with tne experimentally derived values. Programs were especially written for these calculations and were found to be very promising and fruitful, Some of the results have been published and presented in conferences and more publications are under way. In view of the success of the techniques the work is being continued. . . 4 Radioactive tracer zechnse!'s vor the detection and therapy of melanomas suggested .by Blois). Improvement on the conventional scanning techniques making more efficient use of observations with a real time feed back between the collection of data and their processing. Simulated experiments using ACME as a real time terminal are under way to make a choice between alternate techniques, When this decision is made we plan to commission the equipment and the interfacing with ACME. References: ?-ray diffraction studies on melanins paper containing some of the pre- liminary results presented at the Annual American Crystallographic Conference at, Buffalo, New York during August 1968. Jhysical-&i 'dies on melanin paper containing the results of the Monte Carlo techniques on the structure of melanin - to appear in the January 1969 issue of the Biophysical Journal, '<-ray diffraction studies on melanins paper describing the inversion of the high precision X-ray diffraction data as a radial distribution function presented to the annual blophysical society meeting to be held in Los Angeles, California in February, 1969. 165 Tickiier, E. G. Name: EGTICK%E Project: ?+lYuwmRS Department: Palo Alto Medical Research Foundation Project Description: We intend to perform spectral analysis of murmurs recorded with intracardiac microphones in experimental animals before and after making cronic inplants of known sizes. We hope to correlate the onsetofmurmurs and their characteristics with the instaneous flow rate. Trudell, J. R. Name: J TBL'sEI;L Project: MASS SPE - Department: Chemistry Project Description: I am working on computerized interpretation of mass spectroscopy. At present information is visually taken from strip chart recordings and entered into the computer through a keyboard terminal. The computer then assimilates the data and presents the results in tsbular form. In the near future the data will be acquired on-line using the 270X-Y system. 'l'tlcker, R. B. ; ] F _ RBTUCKER Project: MS Department: Genetics I'!~~~-'~ ':i Description: The project consists primarily of developing a computer rstem for the control of a mass spectrometer-GLC! apparatus and the ollection, analysis, and presentation of the resulting data. Presently this work takes on two forms: developing a set of ACME/PLl programs :ich control the apparatus utilizing a LINC computer as an I/O buffer, .jnd investignting the capabilities of the ACME 1800 computer persuant to using it (in a time-shared mode) in place of the LINC. When replacing the LINC with the 1800 it will be necessary to build additional hardware to perform certain timing and logic functionsnow performed by the LINC. It is therefore essentia 1 that the operating parameters of the 1800 be accurately known, 166 Warrick, G. Name: G-WARRIC Project: ST'EROTD Department: Psychiatry Project Description: The present research in our psychophysiological labora- tory revol\res around the "averaged evoked response." We record a con- tinuous EEG on magnet,ic Lape when presenting selected stimuli. After- wards it is necessary to take out fhe EEG from the recording for certain time periods after each stimulus and average from 25 to 100 curves. When more than one kind of si;imulus is shown the EEG must be distributed according to specific stimuli and several averages calculated simultan- eously. ACME supply us with 3 analog Input lines for reading of the EEG and corresponding signals. Our sampling rate -is 4 msec and by reading 100 curves for 500 msec or 25 curves for 4 see we use a storage space of 25000. After the curves are selected and averaged, they are returned through an analog output line and plotLed con cur X-Y plot,ter. The curves are also stored in digital form In t.he ACME file system. We are presently having a second output line installed to give us a time base for the x-axis on the plotter. The two output lines wili be connected for more syst,ematic results. 167 Weissman, I. Name: _ I WEXSSM Project: TFlIYMLE Department: Pathology Project Description: Our use of ACME has been limited to developing methods of applying statistical subroutines to our particular data needs. This has proved most valuable in handling volumes of data which required statistical analysis, but, which was simply not feas.ible using ordinary calculators. For example, in the past year we have modified the chisquare and bastat; subrout,lnes to be able to compare 6 standard 'bits of data with up to 200 test items, g iving the exact (p) values for each item. This has been incorporated into a paper which has been submitted for publication. The data analyzed in that paper had been obtained in 1963 and 1954. We have also studied the feasibility of setting up a program to analyze raw 1iquLd scintillation spectrometry data from tissue samples, requiring analysis of 3 channels counting simultaneously within different "windowsE'. Channels-ratios must, then be obtained and compared to a plot of counting efficiency vs. channels ration, in order to obtain the actual cXsintegrations/minute/sample. Specific activities and fractional input activities must then be calculated, subtracting physical background counts (solution, bottles, filters) and control organ background counts. Until such programs are developed, and interfaced between ACME and our scintillation counters, we cannot properly study quantitative aspects of in viva cellular migration streams in the --- lymphoid system. 168 Whitcher, C. Name : C-WHITCH Project: ONCALL~ Department: Anesthesia Project Description: Computerization of the anesthesia call schedule is necessary because the present manual method has proved unsatisfactory. Scheduling is complex, excessive errors have occurred despite due care, and the time required to writ,e schedules is cost$.Ly in terms of profess-, ional and secretaria; time. The anesthesia consitltarit staf'f includes 1 t.ci 3 research f'ell.ows, and 1'2 to 14 full-t.ime faculty physicians. Dutf i es > responsibilities, and need5 I-)? these 13 to 17 lndivlduals are diverse, including teaching, research, I'urt,her train lng, a.s well as the administration of operat.ing room3 obstetrical and other forms of clinfcal anesthesia. Nfght) week- ends and holiday coverage musu + be scheduled t,o cover the various anesthetizing locat.~ons as well as vacations, s.Lcknessj and out-of-t&wn meetings. Schedules are regular.ly prepared at, monthly intervals. However, changes of plans frequent,ly I;Iccur, calling for schedule revision, at, additional expend'i ture of staff and secretarial effort. Arrangement of schedule for' night, weekend, holiday, and emergency coverage is filled with many problems and difficulties. For exampie, twc nights on call in a row (excep,t on weekends) is undes ira.ble and each st,aff member has certain nights and weekends when he prefers net, to cover. These reserved n.ights and weekends vary from week tc week. Fur t.hermore, call is rarely, if ever, popular. Each s+.af"f merrlber willingly accept.s his share, but none wf.l.l.ingly accept.s more t,han his share. It is important for pur,- poses of good morale to be sure that t,his relat,lvely undesirable work 1;: evenly dist,ributed and proper.Ly credIted. At. . . . ..a51. 10 dlffsrent t,ypes of zight, call work have to be tallied ,ind evenly divided, incl;Ading firs-t call with o.bstetrics on business lJ.ys, first ca.Ll without cbstetrics on business days., first call on .;eekends with and without obst,et,rrcs, second call on weekends, second -:?I1 cn. ho:Lidays, and third ca.l.1 Saturdays to accomodate Saturday scheduling. Such schedules would be compiex enough if they cou1.d be assigned in simple riJ:ation3 and this might `be done if the number of staff were CCrlStanT; throughour, the year. However) t,he number of staff varies; and the fewer t,he staff, t,he more frequent t,he call. This :`Yctor is considered in t,al.Lying the ca..lls. Gross tallying errors which have cccasionally occurred tave incited staff members t,o count. up their week- ends on obstetrical or i:,+,her caL.Ls, &ith t.he fInding +,hat they have received .rm?re t,han their =.hare, and understandably nave asked, "How come? 169 Whitcher, C!. (Cont. ) Name : C WHITCH - Project: ONCALL Department: Anesthesia Project Description: The ccmput.er program already worked out offers several advantages. A running tally is accurate and immediately available. Schedule revisions required by the staff will be rapidly available and ~111 require a minimum amount of professional and secretarial staff time. Finally, the estimated savings in staff time should be noted: 12 hours per month secretarial and an equal amount of anesthetist's time which could `be more profitably spent in other duties such as income-producing clinical work. The Department cf Anesthesia hopes that ACME will support this important clinical project,. Whitcher, C. Name : c whitch - Department: Anesthesia Project: Spctrm Project Description: Spectral analysts of blood pressure sounds. Determine why 'blood pressure sounds are difficult to hear under adverse circum- stances. The pilot project shows that part of the reason lies in their energy distribution. This work should be extended to verify this. 170 if ale;. Xc. $ hOi';.! i- c?5 Section III-B Wittner, W. Name: W_WITTrE Project: KR.oGIR? :; Department: Psychia+,ry Project Description: (AROGTJESS) 'The Influence of Correctly and Incorrectly Guessed Visual Patterns on Visual Averaged Evoked Response. This study deals with changes in the elect~roencephalogram (EEG) of human subjects under conditions of various "mental states". The EEG associated with certain visual stimuli in certain "mental states" will be averaged to obtain the so- called averaged evc'ked response (AER). The shape of the AER waveform reflect,s bra.Ln activity beyond the purely sensory-receptive component. For instance, the AER is influenced 'by such variables as attentic,n, condit,ioning, an.d habit,uation. In this study, young healthy males will be present,ed with a sequence of two types of visual stimuli which will alternate randomly. One presentation will consist of a cueing flash, an arrow pointing left, and a test fLash. The other visual stimulus presentation will consist, of a cueing flash, an arrow pointing right, and a test flash. Prior to each presentation, the subject will make a guess as t,c the type of upcoming presentation by pressing either a left-handed or a right-,handed button. On the basis of results of related studies by other investigators, it is assumed that the e?xked response to correctly guessed arrows will differ from that evoked by incorrectly guessed arrows. One purpose of the study will be t,O ascer+,ain whether .indeed this is SO. Furthermore, it is hypothesized that, the AER induced by flashes fol.Lowing incorrectly guessed arrows will differ in shape from the AER averaged on flashes following correctly guessed arrows. The assumption is made that guess- ing correctly produces a different "state of minds' than guessing in- c~.rrectly and that. this "state of mind" persists long enough to alter the 4ER to a rapidly following neutral light stimulus. The various As?.;: >l'i 1 be differentially averaged to prove or disprove the stated hypotheses. 'The averaging of the EEG to obtain the AER will be done by the use of ACME computers. Our laboratory at the V.A. Hospital is connected with AC,ME by appropriate lines for the transmission of analog data. Once the various AERs are averaged, they will be analyzed and compared with each other, again 'by use of ACME facilities. Should the hypotheses prove to be correct,, further research will be conduct,ed to lnvest,lgate the effects of hormones on these parameters. Ec:r this reast>n this r,esearch is supported by Dr. David A. Hamburg's NIM "st,eroid grant". DrO Hamburg and Dr. Bert S. Kopell are involved in this research as ,my preceptors. 171 Wit trier, W. (Cont.) Name: W-WITTNE Project: AROGUE Department: Psychiatry Project Description: My plans for computer use between now and July 1969: The actual collection of dat,a has been accomplished. Data are stored on magnetic tape. ACME: facilities will. be used for data reduction as soon as technical difficulties with the transmission lines are solved, hopefulLy before July 1969. Wong, F. Name : F 'WONG Project: MEDONCOL - Department: Medfcine/Cncology Pr~o;~ect Description: Patient and disease analysis - primarily to correlate drug responsiveness in cancer patients for educational and research purposes. Wang, F. :$, me : F-WONG Project: PLAN Department: Radiology ,,,ject Description: The research is still under way. We hope soon that we can use the computer to provide the radiation therapists with: 1. External beam treatment, planning 2. Interstitial and intracavitary dose calculaticn 3. Data accession and retrieval 172 L-ra;?i pie. FROO?:J .! --CT Section III-B Wang, F. Name: _ F WCNG Project: S TIMMAR .5- Department: Radiology Project Description: The project is designed for retrieval of cases and classification of cases from the tumor registration. The ACME is used: 1. To gather the case histories and follow-up information of patients with t,umors treated by radiation therapy. 2. To quickly generate reliable data for the therapist's use In either research work or patient treatment. 1-73 Yguersbide, J. Name: J-YGUERA Project: LUM Department: Biochemistry Project Description: The principal aims of the research are: (1) to acquire an understanding of mechanisms of electronic excitation energy transfer; (2) to develop novel fluorescence and phosphorescence methods which can provide detailed information concerning the structure and dynamics of biological macromolecules; and (3) to apply these optical techniques to obtain insight into aspects of the structure and function of selected proteins. The experimental approach which is used in these studies involves: (1) the synthesis of model compounds which serve to define relationships 'between observable emission parameters and structure; (2) the synthesis of fluorescent and phosphorescent labeling reagents which have appropriate spectral properties and can be specifically attached to defined sites on proteins; and (3) the development of optical instrumentation for kinetic measurements in the nanosecond time range and for the detection of fluor- escence and phosphorescence emission from membranes and cells. Zackheim, H. S. N: r,ir" : H ZACKEE _ Project: PSORIASI 1.Ifapartment : Dermatology F'-=-;cct Description: The present study is a determination of serum copper and ceruloplasmin levels in patients with psoriasis as compared to other skin diseases and healthy controls. I anticipate at least 60 determinations. 7: will want the mean, range, and standard deviation on this data. 174 Zwick, M. Name: _ M ZWICK Project: CRYSTAT Department: Biochemistry Project Description: This project concerns the development of new theoretical techniques for the solution of protein crystal structures. The method currently used, r'isomorphous replacement," generally requires a team of scientists working for a number of years with no guarantee of success. This method has the surprising feature that it makes virtually no use of a great deal of a priori stereochemical information about proteins: e.g., the bond distances and angles of the repeating pephile unit in the protein backbone or on the amino acid side-chains. Hence it is very plausible that new improved methods might be developed which utilize such information and which can solve protein structures much more rapidly and easily. In this project, attempts are being made to define a new set of variables which can specify the protein structure, which is much smaller and hence more easily determinable than the set of atomic coordinates. This new set of variables might conceivably be determinable simply from the X-ray intensities of the native crystal, i.e., isomorphous derivative may not be required, The new set of structure variables are designed to implicitly include the fact that a protein is a linear polymer folded up in some manner in three dimensions, and that this polymer has a set of well known bond distances and angles in its repeating unit and in its branching side chains. 175