BUDGET - PART D APPLICATIONS OF CARBON(13) NUCLEAR MAGNETIC RESONANCE SPECTROMETRY TO ASSIST IN CHEMICAL STRUCTURE DETERMINATION . . . . . .__"__ --. . . . . ._...-._. .-.. Yb\. I I",. I, .a""<... V. L I . ..a. .."L I "r. "L I -1-C-Y ""YVL I I e%"' SUBSTITUTE PERIOD COVEREO GRANT NUMBER IETAILED BUDGET FOR FIRST 124ONTH PERIOD FR0;,1,74 THROUGH 4130175 PERSONNEL (List all personnel engaged OR pmject) TIME OR AMOUNT REQUESTED (Omit cents) EFFORT NAME (Lest, first, irrltfaf) TITLE OF POSITION X/HRS. TOTAL jerassi, Carl( 1) Ch Principal Investigator or 3 Program Director (2) arhart, Ray Ch Post Doctoral Fellow 100 : nnamed Ch Post.Doc.Res.Assoc. 100 an Antwerp, Craig Ch Research Assistant 50 PART D 1) See budget notes 2) Covers 9/l/74-4/30/75 :.n year 1 TOTAL * s 33,592 CONSULTANT COSTS (Include Fees end TravcO I EQUIPMENT (Itemize) s SUPPLIES I Chemical supplies 900 5 STAFF 0. DOMESTIC 1 east coast trip 5 500 TRAVEL ice Instructions) b. FOREIGN 5 PATIENT COSTS (Separate Inpatient endOutpatient) S ALTERATIONS AND RENOVATIONS s OTHER EXPENSES (Itemize per instructions) Publication costs and reproduction services $ 100 NMR instrument usage (25 hrs/month @ $25/hour) 7,500 Computer usage 10,800 s 18,400 Subtotal - Items 1 thru 8 . $ 53,392 10. TRAINEE EXPENSES 1Sce InstmctionsJ PREDOCTORAL No. Proposed s FOR .a. STIPENDS POSTDOCTORAL No. Proposed s OTHER (Specify) No. Proposed s TRAINING DEPENDENCY ALLOWANCE s GRANTS TOTAL STIPEND EXPENSES _ 5 b. TUITION AND FEES C)NLY s C. TRAINEE TRA?`EL (Describe) s 11. Subtotal - Trainee Expenses + a 2. TOTAL DIRECT COST (Add Subtotals, Ifems 9 and 11. end enter on Pa&e IJ * s 53,392 Substitute Budge? Page S-72 /Q ,`C :. Fn. Fnrmc PHC ?QR nnrl PHC 3400-l GP 0 9 30-79 J SECTION II - PRIVILEGED COMMUNICATION Part L) BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE DIRECT COSTS ONLY (Omit Cents) 1ST PERIOD DESCRIPTION (SAME AS DE. ADDITIONAL YEARS SUPPORT REQUESTED (Thisapplication only) TAILED BUDGET, 2ND YEAR 3FtD YEAR 4-l-H YEAR STH YEAR 6TH YEAR 7TH YEAR PERSONNEL COSTS 33,592 53,178 56,176 CONSULTANT COSTS llnclude fees, travel, etc.) EOUIPMENT SUPPLIES TRAVEL 900 1,000 1,100 DOMESTIC 500 500 500 FOREIGN PATIENT COSTS ALTERATIONS AND RENOVATIONS OTHER EXPENSES 18,400 20,000 22,200 TOTAL DIRECT COSTS 53,392 74,678 79,976 I TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enter on Page 1, /tern 4) - $ 208,046 REMARKS: Justify all costs for the first year for which the need may not be obvious For future years, justify equipment costs, as well asany significant increases in any other category. If a recurring annual increase in personnel costs is requested, give percentage, (Use continuation page if needec.I See attached budget justification notes. Rev. 3-70 COMPOSITE BUDGET - PARTS A + B + C + D `RIVILEGED COMMUNICATION SECTION II SUBSTITUTE THIS PAGE FOR DETAILED BUDGET PAGI SUBSTITUTE PERIOD COVERED 1 GRANT NUMBER DETAILED BUDGET FOR FIRST 12-MONTH PERIOD FR0;,1,74 T HROUGH 4/30/75 AMOUNT REQUESTED (Omit ccnr>) I d on pmjcct) TME OR EFFORT t . PERSONNEL (List all personnel en&s&z NAME (Lest, first, initfal) Lederberg, Joshua G Feigenbaum, Edward cs Djerassi, Carl Ch Buchanan, Bruce cs Duffield, Alan Ch Smith, Dennis Ch Sridharan Natesa cs Hammerum, Steen Ch Pereira, Wilfred Ch Rindfleisch, Thomas E Carhart, Ray ch Summons, Roger ch Unnamed ch See attached sheet I TOTAL TITLE OF POSITION Principal Investigator or Program Director Co-Principal Inves. Co-Principal Inves. Associate Inves. Associate Inves. I?esearch Associate Research Associate Research Associate Research Associate Research Associate Post Doctoral Fello! Post Doctoral Fell01 Post Doc.Res.Assoc. f/HI?% 10 20 3 100 50 100 100 100 50 100 100 100 100 COMPOSITE BUDGET 1 TOTAL * s 302,567 `. CONSULTANT COSTS (Include Fees end Truvel) s 1,100 . EQUIPMENT (Itcmirc) Computer Terminal . SUPPLIES I s 3,000 See attached sheet s 22,000 STAFF 0. DOMESTIC TRAVEL See Instnlclions) b. FOREIGN . PATIENT COSTS (Separate lnpatienf and Outpatient) . ALTERATIONS AND RENOVATIONS Mass spectrometer laboratory air conditioning and power modifications . OTHER EXPENSES (Itemize per instructions) Telephone, data communications, postage, etc. Publication costs $ 1,600 $ 2,500 Mini-computer maintenance contract $ 4,600 NMR Instrument usage Computer terminal rental Computer usage (ACME follow-on, Campus 360/67, and ARPANET) s 2,500 s 152,800 Subtotal - Items 1 thru 8 c s 488,267 10. TRAINEE EXPENSES (See Inslrvcfions) I PREDOCTORAL No. Proposed FOR TRAINING 0. STIPENDS _ POSTDOCTORAL 0 TH ER (Specify) DEPENDENCY ALLOWANCE No. Proposed No. Proposed GRANTS I TOTAL STIPEND EXPENSES -. s ONLY b. TUITION AND FEES 5 S C. TRAINEE TRAVEL (Describe) I 11. Subtotal - Trainee Expenses . S L s 488,267 12. TOTAL DIRECT COST (AddSobtofefs. rtems 9 end II, and enteron ~ege f) iubstiwe Budgat Page 5-72 For Forms PHS 3?8 and PHS 2499-l ,-7. ,`C, .-- CP 0 9 30-791 Continuation page PERSONNEL (Continued) Name Title of Position Veizades, Nicholas Reynolds, Walter Sleed, Ernest Wllite, William Tucker, Robert Reiss, Steve Wegmann, Annemarie Pearson, Dale Hjelmeland, Larry Masinter, Larry Stefik, Mark Farrell, Carl Van Antwerp, Craig Wyche, Margaret DeFrancisci, Richard Wharton, Kathy Larson, Dee Allan, Muriel SUPPLIES E Research Engineer 100 E Research Engineer 20 E Research Engineer 10 CS Computer Programmer 50 CS Computer Programmer 75 CS Computer Programmer 50 Ch Senior Research Assistant 100 E Electronics Technician 60 CS Research Assistant 100 CS Research Assistant 50 CS Research Assistant 50 CS Research Assistant 100 Ch Research Assistant 50 Laboratory Technician 50 Machinist 20 Administrative Assistant 50 Secretary 50 Secretary 25 Time or Effort Office supplies $ 1,450 Chemicals, glassware, and laboratory apparatus 3,400 GC supplies (gases, phases, columns, etc.) 950 Dry ice and liquid nitrogen 1,500 Electronic supplies and parts 3,500 GC/MS data recording media (chart paper, Calcomp, etc.) 2,100 Mini-computer supplies (paper, ribbons, tapes, disks, etc.) 1,500 Mass spectrometer repairs and replacement parts 7,600 $22,000 COMPOSITE - PARTS A, B, C, & D- SECTION II - PRIVILEGE0 COMMUNICATION BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE DIRECT COSTS ONLY (Omit Cents) OESCR IPTION PERSONNEL COSTS 1ST PERIOD ISAME AS DE ;\OOITIONAL YEARS SUPPORT REQUESTED lThisapp/ication only) TAILED UUDCFTI 2ND YEAR 3R0 YEAR 4TH YEAR 5TH YEAR 6TH YEAR 7TH YEAR 302,567 357,613 377,926 CONSULTANT COSTS llnclude fees, travel, etc.1 1,100 1,200 1,300 EQUIPMENT 3,000 3,000 3,000 SUPPLIES 22,000 22,850 24,250 DOMESTIC 4,300 4,700 5,100 TRAVEL FOREIGN PATIENT COSTS ALTERATIONS AN0 2,500 - RENOVATIONS OTHER EXPENSES 152,800 168,100 182,150 TOTAL DIRECT COSTS , 488,267 557,463 593,726 TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enteron Page 1, /tern 4) - $ 1,639,456 REMARKS: Justify all costs for the first year for which the need may not be obvious For future years, justify equipment costs, as well as any significant increases in any other category. If a recurring annual increase in personnel ccxts is requested, give percentage, (Use continuation page if needed. ) PHS-398 Rev. J-70 YUDGET ULTAIL AND JUSTIPICATION The bu3gets for the liENbtitAL froject are presented in tour parts, corresponding to the four proposal sections; A, B(i) &nd (ii), C, a113 D, Parts A nnd C represent the portions concern4 with Heuristrc and Heta-DENDHAL; Lart B deals with the datd System dUt3mdtiOn and iIlstrUme~lt maintenance fUnCtiOXls aS Well dS the development aspects of GC/MS analysis of body fluids; .ind Part I? j-5; an extension 01 DENDHAL methodolcqy to Carbon( 13) nuclear- magnetic resonance spectromctry, As a qzneral note, l'rofessor Lederberg will devote a total of 10% ot his time to this research as the principal Investigator. His time is budgeted as follows: 4% on Part -4, 3~ on Part Et, and 3x on i?dL-t i'. The narrative comments on Parts A and t' have been combined below because the personnel anj computer resources overlap to a large extent. BUDGET EXPLAdATION - PAHTS A & C a) The personnel on the DENDHhL stafr constitute its: most valuclble resource. All of tha people listed in the proposal ale now working on the DYhbHAI. Project. ~11 are necessary to support the high level of scientific activity in Chemistry (A. Duffield, b. Smith, 5. Hdmmerum, and L. [IjelmPland) dnd Computer Science (R. Feiqenbsum, B. Buchanan, N. Sridharnn, W. Glhitc?, S. Ueiss, M. :;tefik, L. hasinter, dnd C. rdrrell). fir. l;drk S tefik's statuS will hdve changed to Reseclrch Assistant for Part A from his current strrtus as Computer Programmer on Part B. Mr. s tevk! deiss' salary has been increased in order to properly compensate him for the duties he performs. Recent change; rn drart board policies allow Conscientious Objectors to receive higher compensation to reflect actual job duties. specif.rc University approval has been requested for this increase but has not yet been received. Mr. Larry lrasinter has prevrouslp been pa.id from other Funds, but LS essential to the NIH-teldted work. -L- b) S;lllaty tigures are increased annually by 4% for merit increases and promotions, Fringe benefit:; are budgeted at the stan4ntd University rates of 17% through H/7Li dnd dfe increased annually pi+r University projactions to lti.3X in 9/74, lY.3i irk Y/75, tint! 20.4% in 9/7b,, No new personnel are added in Year 2. However, the salary buciyet inz:reascs by more than the rates rioted above because ail of Dr. Uushanan@s salary is covered (see c) below) dnd Professor Peigennaum returns from his leid), k. i!e:rrerd (A.%), and 2. Sunmons (loll%). PI, Wyzhe provides laboratory ctnd inStKUmE!:it operation support for the low resolution GC/M:; laboratory. rlessc?rs ilindfleisch, VeiLade:;, keynolu;j, and Tucker nrc! *s:;er.ti;il to the d,it(i system devt:lokw?nt effort dnd )JcoviiJo hnrcldd~~ 3nd softwdrc maintenauce suppoK t as well. clr+sse~s ;tindrleiszr, (1OO.h) and Tucker (/5X) dC2 priru;irily L~~5~oIl~SALl6! for the :;3ttware system design, implemcntlition, nno maintenanse. Hr. Vt?izades (1005) i:; primarily concerned dith the hardware maintenance and development aspects of the high resolution ilAT-.I 11 instrument dt11 Mr. He,~rtol:.ls (LOW) with tht! Finniqdn 1~15 low resolution instrument. k+s. A. deylilircn ( IctOX) is ritsponsible for the operation of the high resolution Lt'/fiEIL; instrunient (MAT- 711). hr. Steed (10X) provides necessary Ilasl;vork development dno maintenance, Hr. Pearson (60%) su)~!:arts the fabrication and repair of electronic hardware for both instruments, arl:i i?r. DeFrancisci (Ltl't;) proviciec neccssdr-y mdchinlst support for mechanical repairs dnd fixtures. m:;. All;tn (25%~ provides rwJuire3 secretarid1 :;ukl,ort f_ox t.h\t above Inst.ruluentdtion I{esedrch Laboratory personnel. 'This mdnp>wer complemc!nt is zarried into the future year:; [is shown. Salaries are increase-l bj 5% per yedr and Stdff LeneLiiz are ,:~ppl IZJ. at st.dnddtcl University rate:<. Thf+rie start dt 1 l,& in fiscal yeair- 197U (3/73 - H//q) dnd ~ncrtiC~sC? to 18. 1 ir in 9/`?4, 19.36 in q/71), and 2Q.4X in 3/7b based on University pro jcctions. uur request for nd,litional e.duipment is rsinimal. We budget for t hc purci,a~e of a computer tzrmLna1 in the first ye,ir for f;3,01;0. `This repiai:es a cutrsntlf rented termin int.e:qr il to the (;S/P?:.; data system .in(l saves 65,211O overt the three ye(lr / `- ,`/ .- -t- grant period by purcha:;in;j in stead of con tin:lF+d rental. In the s:?zond year we budget for an C?VC?fit. CountBE rleccss:ir~ for proper e,juLpment maintenance for which YC! are assuming resy)onsibi Lity. We dlr,+ady maintain the binnigan 1C 15 instrument. and will take over the r~A'l'-~ll 1 becciuse of proqr ess ively poorer pizrform3hcz by VRRIAti As:;ocidte?; in maintaining that irrstr-umc?nt 3ver the past. year. This equipment is also naeded to in(,lement axperimental control functions on the ~4~s spectrometer. In the third year, repldC:ent?n t of outdated tLS:;t (27uiF:munt will be r is budgeted for publication c osts and 54,6Oti for mini-co:nputcr maintenancti. This maintenance is an extension of our current conttact with Digital Equipment Corporation and includes the prevailing 10X discount in the Stanford/UK contract. We budget for data re to assume the additional anticipated programming duties. Salaries are increased by 5% rer year and staff benefits are applied at standard Unrversity rates. These start at 17% in fiscdl year 1974 (9/73 - R/74) and increase per University projection; to la.3A iti 9/74, ly.35 in 9/75, and 20.4% in Y/70. SUPPLIES: MC? tluticjct 0900 for chemical supplies for the [Ireparation of test Sdmples. l'RAVKL: We budget. $530 to covef one east coast tr.ip. OTHER EXPENSES: Other exE,enses include I;lUi, for publication and reproduction costs anrl $7,500 for usaqe of th;;! existing NMH instrument in the tiepattment of Chemistry. Thus NMH usa.)a is budgeted ,-rt standard rates cover-in3 15 hours of usage' per month dt 625 per hour. in silditiori, we budget for use of the :;t.dnforii (SC?) 36U/t~7 computer where CN& analysis pro!~c:tn:s, ,:lt the currc:nt level of 3ovelopment, dre run. 'These co;;ts are computed (in th-2 -9- basis of 1.5 hours of usage per month at approximately $bOU per hour. BIOGRAPHIES zz- LEDERBERG, JOSI!UA PLACE OF 61fl :li ICI:Y. StJCd, Ckw~tryl -.- ( FiT,Z I IilIPTHOATE ihfa, try, fr., 7' --uCcls~idr and Execut ivc Head, . i Department of Genetics 5-2 3-25 - PRESENT NATIONALITY (If non-U.S cir~rsn, !SEX lndtcata kind of vim rnd 8xprafIon dare) I INSTITUTION AN0 LO;3ATlGN DEGREE YEAQ SCIEXTIF IC CONFERRED FIELD Columbia College, Sew York B.A. 1944 College of Physicians 6 Surgeons, Columbia University, New York (1944-46 Yale University HONORS 1 Ph.D. I 1947 \i(. 1957 - National Academy of Sciences 1958 - Nobel Prize in Medicine MWOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Molecular Genetics; Artificial Intelligent PRINCIPAL INVESTIGATOR SEE ATTACHMENTS: RESEARCH A&D,08 PROFESSl3NAL EXPERIENCE ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ LtSfall ormost nprs8naav4 publ#w:;ons 30 nor aceed 3 p;ci for och rn&trd.;al.) 1961- Stanforc University i95t-b Director, Prof&sor, Kennedy ,Labqratories .for Molecular Medicine ?'. . . . .:, ,... : ,..._. .., , ,_ Genetics 'and Biology, and Executive Head, Department of Genetics, Stanford University - 1957-1959 University of Wisconsin Chairman, Department of Medical Genetics 1957 Melbourne University, Australia Fullbright Visiting Professor of Bacteriology 1950 University of California, Berkeley Visiting 'Professor of Bacteriology 1947-1959 University of Wisconsin Professor of Genetics 1.946-1947 Yale University. Research Fellow of the Jane Coffin.Childs Fund for: Medical Research 1945-1946 Colunbia University. Research Assistant in Zoology Professional Activities: 196 7- NIMH: National Mental' Health Advisory Council 1961-1962 President (Kennedy)'5 Panel on Hental Retardation 1960- LISA Committees: Lunar and Planetary Missions Board 1958-- National Academy of Sciences: Committees on Space Biology 19500 Prceident's Science Advisory CommFttee panels; National Institutes of Health, National Science Foundation study sections (genetics) RHS3%l Rw. 3-70 RESEARCH SUPPORT SUMMARY FOR JOSHUA LEDERBERG Grant Number Grant Title 1) NASA:NGR-05-020 Cytochemical Studies of Planetary Micro-organisms 2) NIH:AI-05160 Genetics of Bacteria 3) NIH:RR-00311 Advanced Computer for Medical Research (ACME) Stanford Medical School Facility 4) NIH:GM- Genetics Research Center (J. Lederberg,Principal Investigator 5) NIH:RR-00785 Stanford University Medical Experimental Computer Facility (SUMEX) Successor to 83 Current Year Total Award $ 180,000 $3,800,000 60,000 280,000 362,632 2,612,632 (yrs 4-7) 547,035 2,609,383 884,660 5,960,417 6) NIH: Computer Lab- oratory Health Care Resource Program Large Scale Screenin. of Body Fluids for Metabolic Signs of Disease with Computer-managed Gas Chromatographv and Mass Spectrometry 159,881 900,238 7) NIH:GM00295 Training Grant in Genetics 143,964 756,650 Grant Term Budgeted % Time 9160-8173 4% (Future support dubious) 9/68-8173 15% (Renewal pending) 1966-7173 (see F5) 9173-8178 (Pending) 9173-8178 (Pending) 25% 10% 20% 9173-8178 10% (Pending,Program funds impounded) 7169-6173 (Renewal pending) 15% SELECTED LIST OF PUBLICATIONS Lederberg, J., 1959 A View of Genetics Les Prix Nobel en 1958: 170-89. Buchs, A., A. B. Delfino, A. PI. Duffield, C. Djerassi, B. G. Buchanan, E. A. Feigenbaum, and J. Lederberg, 1970. Applications of Artificial Intelligence for Chemical Inference, VI. Approach to a general method of interpreting low resolution mass spectra with a computer. Helvitia Chimica Acta 53 (6): 1394-1417. Feigenbaum, E. A., B. G. Buchanan, J. Lederberg, 1971 On generality and problem solving: a case study using the DENDRAL program in Machine Intelligence 6, (B. Meltzer and D. Michie, eds.), Edinburgh University Press, P. 165-190. Reynolds, W. E., V. A. Bacon, J. C. Bridges, T. C. Coburn, B. Halpern, J. Lederberg, E. C.. Levinthal, E. Steed, R. B. Tucker, 1970 A Computer Operated Mass Spectrometer System. Analvtical Chem. 42:1122-1129, September 1970. Lederberg, J. "Use of Computer to Identify Unknown Compounds: The Automation of Scientific Inference" in Biochemical Applications of Mass Spectrometry (G. R. Waller, ed.). John Wiley & Sons, New York (inpress). 3tLI ION II -PRIVILEGED COMMUNI(:ATION Principal Investigator: Carl Dierassi BIOGRAPHICAL SKETCH (Give the following information for all professional personnel listed on page 3, beginning with the Principal Investigator, Use continuation pages and follow the same genera; format for each parson.) NAME -- TITLE BIRTHDATE f#o., Day, Yr.) Carl DJERASSI Professor of Chemistry October 29, 1923 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY I/f non-U.S. citizen, SEX indicate kind of visa and expfratinn date) Vienna, Austria U.S.A. a Male 0 Female EDUCATION (Begin with baccalaureate training and include postdoctoral) lNSTlTUTlON AND LOCATION DEGREE YEAR SCIENTIFIC CONFERRED FIELD Kenyon College A. B. (summa 1942 cum laude) Chemistry, Biology University of Wisconsin Ph.D. 1945 Organic chemistry, Biochemistrv (minor) HoNoRS Hon. D.Sc., Natl. Univ. of Mexico (1953), Kenyon College (1958), Worcester Polytechnic Institute (1972); Hon. Prof., Fed. Univ. Rio de Janeiro (1969). Member U.S. National Academy of Sciences, American Academy of Arts and Sciences, foreign member, Royal Swedish Academy of Sciences Brazilian Academv of Sciences, (cont. below) ROLE IN PROPOSED PROJECT' Principal Investigator Current Tota I % Time Grant Title Period Year - Budgeted Effort NIH AM 04257 Mass Spectrometry in Organic and Biochemistry 10/l/70 to $56,833 $316,016 10% 9/30/75 NIH GM AM Marine Chemistry with l/l 06840-l 5 special emphasis on steroids / 73 to 112,550 578,180 18% 12 31/77 This is a pending application which, if approved, will represent a renewal of my current NIH Grants No. GM 06840 and No. AMCA-12785, both of which expire in 1973. * RESEARCH ANOKIR PROFESSIONAL EXPERIENCE (Starting withpresentposition,/jst trainingandexperiencerelevant toarea ofproject ListaN or most representative publications. Do not exceed 3 pages for each individual,/ Academic Experience: Protessor ot Chem 1 shy, Stanford University, 1959-present. Associate Professor (1952-1954) and Professor (1954-1959), Wayne State University. Industrial Research Experience: C`b Pharmaceutical Co., Summit, N.J.: Sinyex Corporation Research Chemist, 1942-1943 and 1945-1949. : Associate Director of Chemical Research (Mexico City) 1949-1952, Research Vice President (Mexico City) 1957-1960; (Palo Alto, California) 1960-1968, President, Syntex Research 1968-present. Editorial Boards: Current) Journal of the American Chemical Society, Steroids, Tetrahedron, Organic Mass Spectrometry. (continued on next page) Honors (cont.) Mexican Academy for Scientific Investigation. Hon. Fellow of Phi Lambda Upsilon. Amer. Academy of Pharmaceutical Sciences, British Chemical Society and Mexican Chemical Society, Phi Beta Kappa. Numerous hon. lectureships including 1964 Centenary Lecturer (The British Chemical Society) and 1969 Annual Chemistry Lecturer, Royal Swedish Academy of Engineering. American Chemical Society Award in Pure Chemistry (1958), Baekeland Medal (1959), Fritzsche Award (1960). Intra-Science Research Foundation Award (1969). Freedman Patent Award of American Institute of Chemists (1971). Foreign Member, Royal Swedish Academy of Sciences (1972). D.Sc. (hon.), Worcester Polytechnic Institute (1972). Scheele-Lecturer, Pharmaceutical Society of Sweden (1972); American Chemical et-IS-398 Soctety's Award t or Creatrve Inventron Rev. 3-70 ESEARCH AND/OR PROFESSIONAL EXPERIENCE (cont.) BIOGRAPHICAL SKETCH (C. Djerassi) Continuation page Principal Investigator:Carl Djerassi R~ iv T k 0 a P lisce I laneous: hairman of the AAAS Gordon Research Conferences on Steroids and Natural Products (1952-1954); lember of American Pugwash Committee (1968 to present); Chairman of Latin America Science Boarc f National Academy of Sciences (1966-1968); Ch nd Technology for International Development. airman of National Academy's Board on Science UBLICATIONS d Author or co-author of 750 publications and six books. Approximately 150 papers and one book eal with various applications of chiroptical methods in organic and biochemistry. SECTION II -PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for all professional personnel listed on page 3, buginning with the Principal Investigator. Use continuation pages and follow the same general format for each person.1 NAME TITLE Principal Investigator, BIRTHDATE (MO.. Day, Yr.l Feigenbaum, Edward A. DENDRAL Project l-20-36 PIACE OF BIRTH ICiry, Stare, Country) PRESENT NATIONALITY i/f non-U.S citizen, indicate kind of visa and expiration date) SEX Weehawken, New Jersey U.S. Citizen a Male 0 Female EDUCATION (Begin with baccalaurea@ training and include postdocroral) INSTlTUTlON AND LOCATION Carnegie Institute of Technology Pittsburgh, Pennsylvania DEGREE B.S. Ph.D. YEAR SCIENTIFIC CONFERRED FIELD 19% Electrical Engineering 1959 Behavioral Sciences. HoNoRS and memberships: American Psychological Association; Association for Computing Machinery (Member of the National Council 1966-68); Am erican Association for the Advancement of Science. blAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Artificial Intelligence RESEARCH SUPPORT (See instructions) Principal Investigator kESEARCH ANDIOR PROFESSIONAL EXPERIENCE (Starting withpresentposition. list traininqandexperience relevant to area ofproject List all or most representative publications. Do not exceed 3 pages for each individual.) 1965- Stanford University, Computer Science Department Faculty 1965-1968 Stanford University, Director, Computation Center 1963 Summer Research Training Institute in Computer Simulation of Cognitive Processes (National Science Foundation) 1962 Carnegie Corporation. Sumner Research Training Institute in Heuristic Programming. Faculty member. 1960-1964 University of California, Berkeley Research-Center for Research in Management Science, 1960-1964 Research-Center for Human Learning, 1961-1964 Assistant and Associate Professor, School of Business Administration, 1960-64 1957-1960 The RAND Corporation, Santa Monica, California 19% IBM Scientific Computing Center, New York Selected Publications: "Applications of Artificial Intelligence for Chemical Inference 1. The Number of Possible Organic Compounds. Acyclic Structures Containing C, H, 0 and N", J. Am. Chem. Sot., 91, 2973 (1969). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference II. Interpretation of Low Resolution Mass Spectra of Ketones", J. Am. Chem. Sot., 91, 2977 (1969). (Co-Author). R HS-398 Rev. 3-70 Publications of Edward Feigenbaum "Applications of Artificial Intelligence for Chemical Inference III. Aliphatic Ethers Diagnosed by thctir Low Resolution Mass Spectra and Nuclear Magnetic Rcsonancr:", .T. Am. (!hern. :;oc. , 31, '7111'0 (1363). (Co-Author). "Heuristic DISNDNAL: A I'rogram for Generating l~:xpla.natory Il.ypoI,he::e:: in Organic Chemistry", in Machine Intelligence 4, Edinburgh University Press, 1969. (Co-Author). "Toward an Understanding of Information Processes of Scientific Inference in the Context of Organic Chemistry", in Machine Intelligence 5, Edinburgh University Press, 1970. (Co-Author). "A Heuristic Program for Solving a Scientific Inference Problem: Summary of Motivation and Implementation", Stanford Artificial Intelligence Project Memo No. 104, November 1969. (Co-Author). "Applications of Artificial Intelligence For Chemical Inference IV. Saturated Amines Diagnosed by Their Low Resolution Mass Spectra and Nuclear Magnetic Resonance Spectra", Journal of the American Chemical Society, 92, 6831 (1970). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference V. An Approach to the Computer Generation of Cyclic Structures. Differentiation Between All the Possible Isomeric Ketones of Composition C6HlOO", Organic Mass Spectrometry, 4, 493 (1970). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference VI. Approach to a General Method of Interpreting Low Resolution Mass Spectra with a Computer", Chem. Acta Helvetica, 53, 1394 (1970). (Co-Author). "On Generality and Problem Solving: A Case Study Using the DENDRAL Program", in Machine Intelligence 6, Edinburgh University Press (1971). (Co-Author). "A Heuristic Programming Study of Theory Formation in Science", in proceedings of the Second International Joint Conference on Artificial Intelligence, Imperial College, London (September 1971). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference VIII. An Approach to the Computer Interpretation of the High Resolution Mass Spectra of Complex Molecules. Structure Elucidation of Estrogenic Steroids", Journal of the American Chemical Society, 94, 5962-5971 (1972). (Co-Author). "Heuristic Theory Formation: Data Interpretation and Rule Formation", in M&chine Intelligence 7, Edinburgh University Press (1972). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference X. Datsum. A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids", to be submitted. (Co-Author). SECTION II -PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for al/professional personnel listed on page 3, beginning with the Principal Investigator. Use continuation pages and follow the same general format for each person.) NAME TITLE BIRTHDATE (MO., Day, Yr./ Buchanan, Bruce G. Research Computer Scientist 7-7-40 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY I/f non-U.S citizen, SEX indicate kind of visa and expiration date) St. Louis, Missouri U.S.Citizen m Male 0 Female EDUCATION lBco;n wirh 6accaL~raare trainmo dnd include Dostdoctorall INSTITUTION AND LOCATION Ohio Wesleyan University Tlichigan State University DEGREE YEAR SCIENTIFIC CONFERRED FIELD B.A. 1961 Mathema%ics M.A., Ph.D. 1966 Philosophy HONORS Recipient of National Institutes of Health Career Development Award (1971-1976) Invited Speaker at 1972 National Institutes of Health Symposium on Numerical Methods F:; Chemistry (Washington) MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Associate Investigator RESEARCH SUPPORT /See instructions) RESEARCH AND/OR PROFESSIONAL EXPERIENCE lStart.ing with present position, list training and experience relevant to area of project List a// or most representative publications. Do not exceed 3 pages for each individual.) 1?72-present Research Computer Scientist, Stanford University 1966-1971 Research Associate, Stanford Artificial Intelligence Project Publications: lrOn the Design of Inductive Systems: Some Philosophical Problems". British Journal for the Philosophy of Science 20 (1969), 311-323. (Co-Author), "Applications of Artificial Intelligence for Chemical Inference II. Interpretation of Low Resolution Mass Spectra of Ketones". Journal of the American Chemical Society, 91, 2977-2981 (1969). (CorAuthor). "Applications of Artificial Intelligence for Chemical Inference I. The Number of Possible Organic Compounds: Acyclic Structures Containing C, II, 0 and N". *Journal of -ihe American Chemical Society, 91, 2973-2976 (1969). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference III. Aliphatic Ethers Diagnosed by Their Low Resolution Mass Spectra and NMR Data". Journal of the American Chemical Society, 91, 7440-45 (1969). (Co-Author). "Heuristic DENDRAL: A Program for Generating Explanatory Hypotheses in Organic Chemistry". Machine Intelligence 4, Edinburgh University Press (1969). (Co-Author). RI-IS-398 Rev. 3-70 Publications of Bruce Buchanan: "Toward an Understanding of Information Processes of Scientific Inference in the Context of Organic Chemistry". Machine Intelligence 5, Edinburgh University Press (1969). (Co-Author). "On Generality and Problem Solving: A Case Study Using the DENDRAL Program". T~lachine Intelligence 6, Edinburgh University Press (1969). (Co-Author). sze Speculation About Artificial Intelligence and Legal Reasoning". Stanford Law Review, Vol. 23, No. 1, November 1970. (Co-Author). "hpplieations of Artificial Intelligence for Chemical Inference VI. Approach ts a General Method of Interpreting Low Resolution Mass Spectra with a Computer". Chemica Acta Helvetica, 53, 1394 (1970). (Co-Author). "An Application of Artificial Intelligence to the Interpretation of Mass Spectra". Ilass Spectrometry Techniques and Appliances (1970). "Applications of Artificial Intelligence for Chemical Inference IV. Saturated Pmines Diagnosed by Their Low Resolution Mass Spectra and Nuclear Magnetic Resonance Spectra". Journal of the American Chemical Society, 93, 6831 (1970). (Co-Author). "The Heuristic DENDRAL Program for Explaining Empirical Data". Proceedings of IFIP Congress 1971, Ljubljana, Yugoslavia. (Co-Author). "A Heuristic Programming Study of Theory Formation in Science". Proceedings of second International Joint Conference on Artificial Intelligence, Imperial College, London (1971). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference VIII. An Approach to the Computer Interpretation of the High Resolution Mass Spectra of Complex !blolecules. Structure Elucidation of Estrogenic Steroids". Journal of the American Chemical Society, 1972. (Co-Author). "Heuristic Theory Formation: Data Interpretation and Rule Formation". Machine Intelligence 7, Edinburgh University Press (1972). (Co-Author). llReview of Hubert Dreyfus' 'What Computers Can't Do: A Critique of Artificial Reason"', Computing Reviews (January, 1973). "Applications of Artificial Intelligence for Chemical Inference IX. Analysis of Mixtures Without Prior Separation as Illustrated for Estrogens". Submitted to the Journal of the American Chemical Society. (Co-Author). "Applications of Artificial Intelligence for Chemical Inference X. Datsum. A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids". To be submitted. (Co--Author). Memberships Association for Computing Machinery (ACM) Philosophy of Science Association American Association for Advancement of Science (AA&S) PLACE OF 8iRTH (ClCV. Stdte, Counuy/ PHESENT ?uATIONALlTY /l/non-U,S c,rizcn, indicate kind of viu and uxpirJt,on &tc} Perth, Western Australia EDUC,\T:O`. I.;..: INSTITUTION AND LOCATION University of Western Autralia University of Western Australia DEGREE YEA3 SCIE'JTIFIC CONiEr?RED FiE'-5 B. Sc(lst Class Hons) 1958 Organic C:rez=istrjl Ph.D. 1962 Organic CteEsitry MAJOR RESEARCH INTEREST ROLF IN PROPOSED PROJECT Applications of mass spectrosletry to Piolow and Biomedccal Problems Organic Chemist/mass spectroscop?st RESENICn SW?ORT (Scarnscructions~ N/A 1970 - 3esearch Associate, Department of Genetics, Stanford ijniversity School 0:` 2Zedici.39 1969 - Sead of the ikss S?ectroxetry Laboratory, Chexistry Depztmer,; 1965 - 69 St3nford L!;Tniversity .?cZcsrck Associate, 1963 - 65 2eTartment of Chenlstry, S Zanford ':civa,-sl:y 1962 - 63 P'os'tioctorai Fellow, Department ofnChemistry, S'kanforci lJnive,-sity ?~~~doctoral Fellow, Department of Biochemistry, Stanford University . . School of Medicine. - - --- --. - -- . PUBLICATIONS SIFCE-1971 Mass S?ect:a. ne, td., JUICES vvllGy and Sons, 1. An Application of Artificial Intel!isznce to t!;e l~~erpr~tfti;;:~~ Moss Spectrometry, B.W. G. Mil A I New York, 1971, PF,. 1;1-178 8y B . G 3!Jchoncn, A. M. Duffieid and A. V. Robertson 2. Mass Spectrometry in Structural x.3 Stereochemical Problems. CCIV. ,ze,,tr3 of Hydantoins.11. Electron Impact Induced Fragmentation of some Subsiituteti Hydantoins. Org. Mass Spectr., 2, 551 (1971) By R. A. Corral, 0. 0. Orazi, A. M. Duffield and C. Djerassi 3. Electron Impact Induced Hydrogen Scrambling in Cyclohexanol and Isoczric Methylcyclohexanols. Org. Mass Spectr., 5, 383 (1971) By R. H. Shapiro, S. P. Levine and A. M. Duffield 4. Derivatives of 2-Biphenylcarboxylic Acid. Rev. Roumain. Chem., 16, 1095 (1971) By A. T. Balaban and KM. Duffield 5. Alkaloide aus Evonymus europaea L. Helv. Chim. Acta, 54, 2144 (1971) By A. Kldsek, T. Rzchstein, A. M. Duffield and F. Santa* 6. Studies on Indian Medicinal Plarts. XXVIII. Sesquiterpene Lactones cf Enhydrc Fluctuans Lour. Structure? of Enhydrin, Fluctuanin and Fluctuadin. Tetrahedron, 2-8) 3as5- ci37.0 By E, Ali, P. P. Ghosh Dastidar, S. C. Pakrashi, L. J. Durham and A. M. Duffield 7. The Electron Impact Promoted Fragmentation of Aurone Epoxides. Or2 . Mass Spectr., 2, 199 Ci972j By B. A. Brady, W. I. O'Sullivan and A. M. Duffield 8. The Determination of Cyclohexylamine in Aqueous Solutions of Sodium Cyclsmste by Electron Capture Gas Chromatography. Anal. Letters, ', 3C1 (19?1) By b!. D. Soloman, g. E. Pereira and A. M. Duffield 9. Computer ?.ecognition of Yetastabie Ions. Nineteenth Annual Ccnference CT. Mass Spectrometry, Atianta, 1971, p. 63 By A. M. Duffield, 'N. Z. Reynolds, D. A. Anderson, R. A. Stillsan, Jr. and C. E. Carroll 10. Spectrometrie de Masse. VI. Fragmentation de Dimethyl-2,2-dioxolanes-l,3- Insatures. Org. Mass Spectr., 5, 1409 (1971) By J. Kossanyi, J. Chuche and A. M. Duffield 11, Chlorpromazine ?I~tabolism in Sheep. II. In vitro Metabolism and Preparatien of 3H-7-Hydroxychlorpromazine. -- Journees D'Agressologie, 12 By L. G. Brooks, M. A. Ho&$ 333 Cl9711 , I. S. Forrest, V. A. Bacon, A. M. Duffield and M. D. Solomon 12., Mass Spectrometry in Structural and Stereochemical Problems. CCXVII. Electron Impact Promoted Fragmentation of O-Methyl Oximes of Some a,B-Unsaturated Ketones and Methyl Substituted Cyclohexanones. Canadia;; J. Chem., 50, 2776 (1972) By Y. M. Sheikh, R.?. Liedtke, A. M. Duffield and C. Djerassi Wilfred E. PEREIRA Research Associate June 23 lC36 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (Ifnon-U.S crtizen. SEX indicate kind of vim and expirarion dare) Madras, S. India Indian, Permanent Resident ImmiFrant Visa @ Male 1 Fe---,,+ EDUCATION (Em/n with baccalaure3:e tralnm and rnclude ~o.~tdoctwa1J INSTITUTION AND LOCATION DEGREE Madras Medical College, Madras, India Saugar Univ. Madhya Pradesh, India U.C. Med. Center, San Francisco, Calif B. Pharm M. Pharm Ph.D. HONORS YEAR SCIENTIFIC CONFERRED FIELD 1960 Pharmaceutical 'kezistry 1962 Pharm. Chem & Chec of :;a:.;: 1968 harm. Chem & ?harvrq3:C.T2* h-&c MAJOR RESEARCH INTEREST Identification of Metabolites t drug metabolites in Biological fluids RESEARCH SUPPORT lSeeinstructionsl ROL' IN PROPOSED PROJECT Organic chemist RESIZA.RC~ ~~30 CR ?~QZESSIONAL ExpEqlExCE is;JT;/rq ;r,i~ 0~35~"~ oosition, /ist r+ninqand expermcereIsnt toarea 3fUrOlecI L:j: j 4 or mcp represenQf?ove pbti1c3t1ons 1906 Do no: exceed 3 pages for edch mdivmual.1 - l?!O Fost Doctoral Fellow, Cept. 1970 of Genetics Stanford University Med. School - present Research Associate same institution During: these four years I have been involved with peptide synthesis, amino acid analysis and synthetic organic chemistry. I helped develop methods for the separation of diasterioisomers by gas chromatography and have been involved with the routine use of gas chromatography @ass spectrometry for the identification of urinary metabolites in normal and pathological urine and serum samples. t@ applications of mass spectrometrg have iccluded the deveolsment of mass fragrnentography for the determination of the amino acid contents of soil and plksrnmly serum. My present project involves the screening of urine kOm leukemic patients for abnormal metabolites and to investigate the metabolic fate of anti-leukemic chemotherapeutic agents in the body. PUBLICATIONS 1. TransesterificatiOn with an Anion-exchange Resin; w, Pereira, V. Close, W, Patton and B. Halpern, J, Org. Chem. 2:2032 (1969)- 2. Alcoholysis of the Merrifield-type Peptide-polymer Bond with an hion Exchange Resin; W. Pereira, V. A. Close, E. Jelly, W. Patton and B. Halpern, Australian Ji of Chem. 22:1337 (1969). ..z: " .-.. . . . _A__*?-; Publications 13. 14. 15. 16. 17. 18. 19. 20. El. 22. Thermal Fragmentation of Quinoline and Isoquinoline N-Oxides in the IO:; Source of a Mass Spectrometer. Acta Chem. Stand., 26, 2423 (1972). By A. M. Duffield and 0. Buchardt Applications of Artificial Intelligence for Chemical Inference. ','I:. .;:. Approach to the Computer Interpretation of the High Resolution I.!ass C----r= -iz- -- I of Complex Molecules. Structure Elucidation of Estrogenic Steroids. - J. Amer. Chem. Sot., 94, 5962 (1972) By D. H. Smith, B. G. Buchanan, R. S. Englemore, A. M. Duffield, A. Yeo, E. A. Feigenbaum, J. Lederberg and C. Djerassi Mass Spectrometry in Structural and Stereochemical Problems. CCXIX. Identification of a Unidirectional Quadruple Hydrogen Trmsfer Process in 7-Phenyl-hept-3-en-2-one O-Methyl Oxime Ether. Org. Mass Spectr., $1271 (1972). By R. J. Liedtke, Y. H. Sheikh, A. M. Duffield and C. Djerassi An Automated Gas Chromatographic Analysis of Phenylalanine in Serum. Clinical Biochem., 5 166 (1972) By E. Steed, ;J. PerZ!ra, a. Halpern, M. D. Solcmcn a.nd A. M. Duffield Pyrrolizidine Alkaloids. XIX. Structure of the Alkaloid Erucifoline. Coil. Czech. Chern. Cc?xmun., (1972) By P. Sedmera, A. Klasek, A. :4. Duffield and F, SantaG. Mass Spectronetry in Struc,u, + -al and Stereocfiemical ?rcSle;?s, CCXKI. Delineation of Cczpeting ?a,Fentation Pathways of COF.~~??~ `.Iol?.:'-lGS from a Study of I?etastable Ion Trznxitinns nf DeuterateS Zerivz:L:es. Org. Mass Soectr., L, (1973) , By D. H. Smith, A. 14. Duffield and C. Djerassi Chlorination Studies I. The Reaction of Aqueous Hypochlorous Acid with Cytosine. Biochem. Biophys. lies. CorxTun., 48, 880 (19721 By W. Pattcn, 'I. Bacon, A. !4. DuEield, B. Halpern, Y. Xoyano, Y. Pereira and J. Lederberg A Study of the Elec tron InDact Fragmentation of Pronazine SUl;hCXide and Promazine using Specifically Deuterated Analogues. . Austral. J. C'nem., 26, (1973). By M. D. Solcnon, R. Summons, W. Pereira and A. M. Duffield Spectrometric de Masse. VIII. Elimination d'eau Induite par Impact Electronique dans le Tetrhydro-1,2,3,4-naphtalenediol-1,2. Org. Mass. Spectrom., 7 (1973). By P. Perros, J. P. Morizui, J. Kossanyi and A. M. Duffield The Determination of Phenylalanine in Serum by Mass Fragmentography Clinical Biochem., submitted for publication (1973). By w, E. Per-ira, V. A. Bacon, Y. Hoyano, R. Summons and A. y. Duffield 3. The Action of Ritrosyl Chloride on Enenylalanine Peptides; W. Patton, E, Jellum, D. Xitecki, W. Pereira and B. Halpern, Australian J. of Chem. 22:2709 (1969). 4. Abnormal Circular Dichroism of d -Amino Acid Esters; J. Cymerman Craig and W. E. Pereira, Tet. Let. g:1563 (1970). 5. The Use of (+)-2,22-Trifluoro-l-Phenylethylhydrazine in the Optical Analysis of Asymmetric Ketones by Gas Chromatography; W. E. Pereira, M. Solomon and B. Halpern, Australian J. of Chem.&:1103 (1971). 6. The Microsomal Oxygenation of Ethyl Benzene. Isotopic, Stereochemical, and Induction Studies; R. E. McMahon, H. R. Sullivan, J. Cymerman Craig and W. E. Pereira, Arch. Biochem. Biophys. 132:575 (1969). 7. The Steric Analysis of Aliphatic Amines with Two Asymmetric Centers by Gas-liquid Chromatography of Diastereoisomeric Amties, W. E. Pereira and B. Halpern, Australian J. Chem. 25:667 (1972). 8, Optical Rotatory Dispersion and Absolute Configuration -XVII, d-Alkylphenylacetic Acids; J, Cymerman Craig, W. E. Pereira, B. Halpern and J. W. Westley, Tetrahedron 27:1173 (1971). 9. The Optical Rotary Dispersion and Circ dar Dichroism of d-Anino and b-Hydroxy Acids; J. Cymerman Craig and W. E. Pereira Tetrahedron g:3457 (1970). 10. The Determination of Cyclohexylamine in Aqueous Solutions of Sodium Cyclamate by Eiectron-capture Gas Chromatography; M. D. Solomon, W. E, Pereira and A. M. Duffield, Anal. Let. k:301 (1971). ?ublics:ions continued- 11. 12. 13. 14, 15. 16. 17. 18. 19. 20. Chlorination Studies. I. The Reaction of Aqueous Hypochlorous Acid with Cytosine; *cc,, W. Patton, V. Brwn, A. M. Duffield, B. Halpern, Y. Hoyano, W. Pereira and J. Lederberg, Biochem. Biophys. Res. Commun. 48:880 (1972). The Use of R-(+)-1-Phenylethylisocyanate in the Optical Analysis of Asymmetric Secondary Alcohols by Gas Chromatography; W. Pereira, V. A. Bacon, W. Patton, B. Halpern, and G. E, Pollock, Anal, Let. 3:23 (1970). A Rapid and Quantitative Gas Chromatographic Analysis for Phenylalanine in Serum; B. Halpern, W. E. Pereira, M. D. Solomon and E, Steed, Anal. Biochem. 39:1.56 (1971), EkCtrOn-impact Promoted Fragmentation of Alkyl-N-(1-Phenylethyl)- Carbamates cf Primary, Secondary and Tertiary Alcohols; W, E, Pereira, B. Halpern, M. D. Solomon and A. M. Duffield, Org. Mass Spectrometry 5:157 (197?). Peptide Sequencing by Low Resolution Mass Spectrometry; V. Bacon, E. Jellum, W. Patton, W. Pereira and B. Halpern, Biochem. Biophys. Res. Commun. 3'J:878 (1969). A Gas Liquid Chromatographic Method for the Determination of Phenylalanine in Serum; E. Jellum, V. A. Close, W. Patton, W. Pereira and B. Halpern, Anal, Biochem. 2:227 (19691, Quantitative Determination of Biologically Important Thiols and Disulfides by Gas Liquid Chrosatography; E. Jellum, W. Patton, '4. A, Bacon, W, E. Pereira and B. Halpern, Anal. Biochem. 2;339 (1969). A Study of the Electron Impact-promoted Fragmentation of Promazine Sulfoxide and Prorzazine Using Specifically Deuterated Analogues; M. D. Solomon, R. Summons, W. ?ereira and A. M. Duffield, Australian J. Chem. (1973, in press). The Determination of Phenylalanine in Serum by Mass Fragmentography; W. Yereira, V. A. Bacon, Y. Hoyano, R. Summons and A. M. Duffield, Clin. Biochem. (In press). Chlorination Studies II. The Reaction of Aqueous Hypochlorous Acid with A-Amino Acids and Dipeptides; W. E. Pcreira, Y. Hoyano, R. Summons, V. A. Bacon and A, M. Duffield, Biochem.et Biophys. Acta (In press), ---..-_ _._ _. m BlOGFirli~;{IcAL SKETCH PLACE OF EJIRTH Khty, State. Country1 PRESEhrT NATIONALITY l/f non-U.S citizen, indicate kind of vire and axpiration detoJ Oohkosh, Wisconsin, USA INSTITUTION AN0 LOCATION Purdue University, Lafayette, Ind. California Institute of Technology, Pnsndcna, CA B.S M.S Ph.D 7; T `ncludo ~ostdoctoraI/ YEAR SClt'dTIF IC CONFERRED FIELD 1962 1965 Thesis to b course work completed. Physics . ' Physics completed. All znd examinations Purdue University, Graduated with Highest Honors, Sigma xi. t.!AdOR t:i-SEkRCri IhTEAEST Space scienseP, computer science and image processing HOLE IN PROPOSED Pfl0JEC-r Technical Support RESEARCH ANDX)R PAOFESS:ONAL EX?EFlli:;CE lS~?mry n~rh~riGsntpozition,~afldrxprn'ancerelsvant roared ofpro,xCf ixta.`/ OfmOlt r&prcssntrOrrpublica;~ons, Do not rxceod 3 ~3~~)s for mch individ&.) 1971-Present Stanford University ?!edical School, Department of Genetics, Stanford, CA. Research Associate - P'ass Spectronetry, Instruaentation research. 1962-1971 Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA. Relevant Experience: 1969-1971: Supervisor of Image Processing Development and Applications Group. 1968-1969: ,Xariner Xars 1969 Cognizant Engineer for Image Processing 1962-1968: Engineer - design and implement image processing computer software. 1. Rindfleisch, T. and Willingham, D., "A Figure of Merit Measuring Picture Resolution," JPL Technical Report 32-666, September 1, 1965. 2, Rfndflcisch, T. and Willinghan, D'., "A Figure of Merit Measuring Picture Resolution," Advances in Electronics and Electron Physics, Volume 22A, Photo-Electronic Iagc Devicts, Acodcnic Press, 1966. Thomas C. Mndileisch PUBLICATIONS (cont'd) 3. 4. 5. 6. 7. 8, 9, Rindfleiech, T., "A Photometric Yethod for Deriving Lunar Topographic Information," JPL Technical Report 32-786, September 15, 1945. Rindfleisch, T., "Photometric Method for Lunar Topography, " Photo- grammetric Engineering, &arch 1966. . I Rindfleisch, T., "Generalizations and Limitations of Photoclinometry," JPL Space Science Summary Volume III, 1967. Rindfleisch, T., "The Digital Removal of h'oise from Imagery," JPL Space Science Summary 37-62 Volume III, 1970. Rindfleisch, T., "Digital Image Processing for the Rectification of Television Carnero Distortions," Astronomical Use of Television-Type Ircage Sensors, USA Special Publicstion SP-256, 1971. Rindfleioch, T., Dunne, J., Frieden, H., Stromberg, W., and Ruiz, R,, "Digital Processing of the >!zriner 6 and 7 Pictures," Jourr.al of Geophysical Research, VoluL;e 76, Xcmber 2, January 1971. Rindf leisch, T., "Digital Image Processing," To be published, IEEE Special Issue, July 1972. SCCrlCN II -PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information For all profcssiondf pcrsonncl fisted on page 3, beginning with the Principal Investigator. Use continuation paga and iollow the same general format for each person.] NAME TITLE BIRTHDATE (MO.. Day, Yr.) Dennis H. Smith Research Associate 11/12/42 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (ff non4.S citizen, SEX indicate kind of visa and expiration date) New York USA b Male 0 Female EDUCATION (Begin with baccalaureafe training and include posrdocrorall INSTITUTION AND LOCATION ?yassachusetts Inst. of Technology Cambridge, Mass. University of California, Berkeley Berkeley, California HONORS Alfred P. Sloan Foundation Scholarship ,"U'ASA Predoctoral Traineeship Phi Lambda Upsilon, Sigma Xi DEGREE S.B. Ph.D. YEAR SCiENTlFlC CONFERRED FIELD 1964 Chemistry 1967 Chemistry MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT xass Spectrometry and A.I. in Chemistry Research Associate RESEARCH SUPPORT (See instructionsl X/A I GESEAACH AND/OR PROFESSIONAL EXPERIENCE (Starting withpresentposition, list traininqandexperiencerelevant toarea ofproject List all or most representative publications, 00 not exceed 3 pages for each individual.) 1971-Present Research Associate, Stanford University, Stanford,Ca. 1970-1971 Visiting Scientist, University of Bristol, Bristol, England 1967-1970 Assistant Research Chemist, University of Calif.at Berkeley, Berkeley, Ca. 1965-1967 NASA Pre-Doctoral Traineeship, University of Calif.at Berkeley,Eerkeley, Ca. Publications: See attached list. RI-IS-358 Rev. 3-70 Continuation oaoe Pub 1. 2. 3. 4. 5. 6. 7. a. 9. 0. 1. 2. 3. lications: H. G. Langer, R. S. Gohlke, and D. H. Smith, "Mass Spectrometric Differential Thermal Analysis," Anal. Chem., 37, 433 (1965). -- S. M. Kupchan, J. M. Cassady, J. E. Kelsey, H. K. Schnoes, D. H. Smith, and A. L. Burlingame, "Structural Elucidation and High Resolution Mass Spectrometry of Gaillardin, a New Cytotoxic Sesquiterpene Lactone," J. Amer. Chem. Sot. ---- 88, 5292 (1966). D. H. Smith, Ph.D. Thesis, "High Resolution Mass Spectrometry: Techniques and Applications to Molecular Structure Problems," Dept. of Chemistry, University of California, Berkeley, California (1967). H. K. Schnoes, D. H. Smith, A. L. Burlingame, P. W. Jeffs, and W. DElpke, "Mass Spectra of Amaryllidaceae Alkaloids: The Lycorenine Series," Tetrahedron, 24, 2825 (1968). A. L. Burlingame, D. H. Smith, and R. W. Olsen, "High Resolution Mass Spectrometry in Molecular Structure Studies, XIV. Real-time Data Acquisition, Processing and Display of High Resolution Mass Spectral Data," Anal. Chem,, -- 40, 13 (1968). A. L. Burlingame and D. H. Smith, "High Resolution Mass Spectrometry in Molecular Structure Studies II. Automated Heteroatomic Plotting as an Aid to the Presentation and Interpretaiton of High Resolution Mass Spectra Data," Tetrahedron, 24, 5749 (1968). W. J. Richter, B. R. Simoneit, D. H. Smith, and A. L. Burlingame, "Detection and Identification of Oxocarboxylic and Dicarboxylic Acids in Complex Mixtures by Reductive Silylation and Computer-Aided Analysis of High Resolution Mass Spectra Data," Anal. Chem., -- 41, 1392 (1969). The Lunar Sample Preliminary Examination Team, "Preliminary Examination of Lunar Samples from Apollo 11," Science, 165, 1211 (1969). S. M. Kupchan, W. K. Anderson, P. Bollinger, R. W. Doskotch, R. M. Smith, J. A. Saenz Renauld, H. K. Schnoes, A. L. Burlingame, and D. H. Smith, "Tumor Inhibitors, XxX1X. Active Principles of Acnistus arborescens. Isolation and Structural and Spectral Studies of Withaferin A and Withacnistin," 2. Org. Chem., 34, 3858 (1969). A. L. Burlingame, D. H. Smith, T. 0. Merren, and R. W. Olsen, "Real-time High Resolution Mass Spectrometry," in Computers in Analytical Chemistry (Vol. 4 in Progress in Analytical Chemistry series), C. H. Orr and J. Norris, Eds., Plenum Press, New York, 1970, pp. 17-38. The Lunar Sample Preliminary Examination Team, "Preliminary Examination of Lunar Samples from Apollo 12," Science, 167, 1325 (1970). D. H. Smith, R. W. Olsen, F. C. Walls, and A. L. Burlingame, "Real-Time Mass Spectrometry: LOGOS--A Generalized Mass Spectrometry Computer System for High and Low Resolution, GC/MS and Closed-Loop Applications," Anal. Chem., 43, -- 1796 (1971). A. L. Burlingame, J. S. Hauser, B. R. Simoneit, D. H. Smith, K. Biemann, N. Mancuso, R. Murphy, D. A. Flory, and M. A. Reynolds, "Preliminary Organic An- alysis of the Apollo 12 Cores," Proceedings of the Apollo 12 Lunar Science Conference, E. Levinson, Ed., M.I.T.?ress, Cambridge, Mass. 1971, p. 1891. s.398 Y. ?-69 Page Continuation page - 1 1 1 1 1 1 2 2 2 4. 5. 6. 7. 8. 9. 0. 1. 2. D. H. Smith, "A Compound Classifier Based on Computer Analysis of Low Resolution Mass Spectral Data," Anal. Chem., 44, 536 (1972). -- D. H. Smith and G. Eglinton, "Compound Classification by Computer Treatment of Low Resolution Mass Spectra-Application to Geochemical and Environmental Problems,"Nature, 235, 325 (1972). D. H. Smith, N. A. B. Gray, C. T. Dillinger, B. J. Kimble, and G. Eglinton, "Complex Mixture Analysis - Geochemical and Environmental Applications of a Compound Classifier Based on Computer Analysis of Low Resolution Mass Spectra," "Advances in Organic Geochemistry 1971," M. R. v.Gaertner and M. Weher, Ed., Pergammon Press, Oxford, New York, Toronto, Sydney and Braunschweig, 1972, p.249 D. H. Smith, B. G. Buchanan, R. S. Engelmore, A. M. Duffield, A. Yeo, E. A. Feigenbaum, J. Lederberg, and C. Djerassi, "Applications of Artificial Intelligence for Chemical Inference, VIII. An Approach to the Computer Interpre- tation of the High Resolution Mass Spectra of Complex Molecules. Structure Elucidation of Estrogenic Steroids," J. Amer. Chem. Sot., 94, 5962 (1972). ---__ D. H. Smith, A. M. Duffield, and C. Djerassi, "Mass Spectrometry in Structural and Stereochemical Problems, CCXXII. Delineation of Competing Fragmentation Pathways of Complex Molecules from a Study of Metastable Ion Transitions of Deuterated Derivatives," a. Mass. Spectrom., in press. B. R. Simoneit, D. H. Smith, G. Eglinton, and A. L. Burlingame, "Applications of Real-Time Mass Spectrometric Techniques to Environmental Organic Geochemistry, II. San Francisco Bay Area Waters," Arch. Env. Contam. -- and Tox., in press. -- D. H. Smith, B. G. Buchanan, R. S. Engelmore, H. Adlercreutz, and C. Djerassi, "Applications of Artificial Intelligence for Chemical Inference, IX. Analysis of Mixtures Without Prior Separation as Illustrated for Estrogens," J. Amer. -- Chem. Sot., - - submitted for publication. D. H. Smith, B. G. Buchanan, W. C. White, E. A. Feigenbaum, J. Lederberg, and C. Djerassi, "Applications of Artificial Intelligence for Chemical Inference X, INTSIJM. A Data Interpretation and Summary Program as Applied to the Collected Mass Spectra of Estrogenic Steroids," Tetrahedron, submitted. I I D. H. Smith, "Mass Spectrometry," Chapter X in Guide to Modern Methods of t --- --- .- Instrumentac Analysis, T. H. Gouw, Ed., Wiley-Interscience, New Ycrk, l?iZ. I SECTION II -PRIVILEGED COMMUNICATION - BIOGRAPHICAL SI