BUDGET ~ PART D APPLICATIONS OF CARBON(13) NUCLEAR MAGNETIC RESONANCE SPECTROMETRY TO ASSIST IN CHEMICAL STRUCTURE DETERMINATION PRIVILEGED COMMUNICATION SECTION II SUBSTITUTE THIS PAGE FOR DETAILED BUDGET PAGE PERIOD COVERED GRANT NUMBER SUBSTITUTE DETAILED BUDGET FOR FIRST 12-MONTH PERIOD| ee . 5/1/74 4/30/75 1. PERSONNEL (List all personnel engaged on project) Error AMOUNT REQUESTED (Omit cents) NAME (Last, first, initial) TITLE OF POSITION ”/HRS. TOTAL T . Lurene Djerassi, Carl$ ) Ch | Principal Investigator or 3 9 Program Director Carhart, Ray (2) Ch |}Post Doctoral Fellow 100 nnamed Ch |Post.Doc.Res.Assoc. 100 Van Antwerp, Craig Ch |Research Assistant 50 PART D (1) See budget notes (2) Covers 9/1/74-4/30/75 in year 1 Ce oad TOTAL $ 33,592 2. CONSUL TANT COSTS (Include Fees and Travel) _ $ 3. EQUIPMENT (Itemize) s _ 4. SUPPLIES ‘ Chemical supplies 900 $ STAFF | poMESsi . $ 500 TRAVEL a DoMEsTIC | east coast trip (See Instructions) b. FOREIGN $s 6. PATIENT COSTS (Separate inpatient and Outpatient) 5 - 7, ALTERATIONS AND RENOVATIONS - $ ~_ 8. 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 gs 18,400 9. Subtotal ~ ftems 1 they 8 nnn 1g 53 3 392 10. TRAINEE EXPENSES (See Instructions) PREDOCTORAL No. Proposed $ FOR a. STIPENDS | POSTDOCTORAL No. Proposed $ OTHER (Specify) No. Proposed $ TRAINING DEPENDENCY ALLOWANCE $ GRANTS TOTAL STIPEND EXPENSES =» /§ b., TUITION AND FEES $ ONLY ¢. TRAINEE TRAVEL (Describe) $ VW. Subtotal ~ Trainee Expenses ST nnnnnrnenenonitinn | 12, TOTAL DIRECT COST (Add Subtotals, Items 9 and 11, and enter on Page U Senge | 53 302 > Substitute Budget Page 5-72 Peek. GPO 930-793 For Farme PHS 298 and PHS 2499.1 SECTION tH — PRIVILEGED COMMUNICATION Part D DIRECT COSTS ONLY (Omit Cents) BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE 1ST PERIOD ADDITIONAL YEARS SUPPORT REQUESTED (This application only) DESCRIPTION (SAME AS DE- TAILED BUDGET) | 2ND YEAR 3RD YEAR 4TH YEAR 5TH YEAR 6TH YEAR 7TH YEAR PERSONNEL COSTS 33,592 53,178 56 ,176 CONSULTANT COSTS _ _ _ (include fees, travel, etc.) EQUIPMENT - - - SUPPLIES 900 1,000 1,100 DOMESTIC 500 500 500 TRAVEL FOREIGN PATIENT COSTS - - ~ ALTERATIONS AND RENOVATIONS - - - OTHER EXPENSES 18,400 20,000 22,200 TOTAL DIRECT COSTS 53,392 74,678 | 79,976 TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enter on Page 1, Item 4) ———_—_——_» $ 208,046 page if needec.} See attached budget justification notes. 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 costs is requested, give percentage, (Use continuation L * PHS-398 Rev, 3-70 f-66S COMPOSITE BUDGET - PARTS A+B+C+D PrEGY PRIVILEGED COMMUNICATION SECTION II SUBSTITUTE THIS PAGE FOR DETAILED BUDGET PAGE SUBSTITUTE PERIOD COVERED GRANT NUMBER FROM THROUGH DETAILED BUDGET FOR FIRST 12-MONTH PERIOD 5/1/74 4/30/75 1, PERSONNEL (List all personnel engaged on project) yl aot AMOUNT REQUESTED (Omit cents) NAME (Last, first, initial) TITLE OF POSITION %/ HRS, I TOTAL Lederberg, Joshua G_ | Principal Investigator or 10 Program Director Feigenbaum, Edward CS |Co-Principal Inves. 20 Djerassi, Carl Ch ;Co-Principal Inves. 3} Buchanan, Bruce CS JAssociate Inves, 100 Duffield, Alan Ch |Associate Inves. 50 smith, Dennis Ch |Research Associate 100 COMPOSITE BUDGET Sridharan Natesa CS |Research Associate 100 Hammerum, Steen Ch |Research Associate 100 Pereira, Wilfred Ch |Research Associate 50 Rindfleisch, Thomas E |Research Associate 100 Carhart, Ray Ch |Post Doctoral Fellow 100 Summons, Roger Ch |Post Doctoral Fellow 100 Unnamed Ch {Post Doc.Res.Assoc. 100 See attached sheet TOTAL ————_-—____—-» | § 302,567 2. CONSUL TANT COSTS (Include Fees and Travel) $ 1,100 3. EQUIPMENT (Itemize) Computer Terminal $ 3,000 4. SUPPLIES ‘ See attached sheet s 22,000 STAFF . OMESTIC $ TRAVEL 2° 4 300 (See Instnictions) b. FOREIGN , $ _ 6. PATIENT COSTS (Separate Inpatient and Outpatient) $ 7. ALTERATIONS AND RENOVATIONS J : tga : : $ Mass spectrometer laboratory air conditioning and power modifications 2,500 8. OTHER EXPENSES (Itemize per instructions) Telephone, data communications, postage, etc. $ 1,600 Publication costs $ 2,500 Mini-computer maintenance contract $ 4,600 NMR Instrument usage $ 7,500 Computer terminal rental 4,800 152.800 Computer usage (ACME follow-on, Campus 360/67, and ARPANET) 131,800 s ’ 9, Subtotal — Items 1 they 8 ee 2 488,267 10. TRAINEE EXPENSES (See Instructions) PREDOCTORAL No. Proposed $ FOR o. STIPENDS | POSTDOCTORAL No. Proposed $ OTHER (Specify) No. Proposed $ TRAINING DEPENDENCY ALLOWANCE $ GRANTS TOTAL STIPEND EXPENSES —~————_-_-_» /§ b. TUITION ANO FEES $s ONLY c. TRAINEE TRAVEL (Describe) $s Wa Subtotal ~ Trainee Expenses Sacer |S ~ . , cr 12, TOTAL DIRECT COST (Add Subtotals, Items 9 and 11, end enteron Page 1) $ 488 3267 Substitute Budget Page 5-72 pe ee GPO 930-79) For Forms PHS 398 and PHS 2499-1 DO NOT TYPE IN THIS SPACE-BINDING MARGIN Continuation page ‘ t PERSONNEL (Continued) Name Title of Position Veizades, Nicholas Reynolds, Walter Steed, Ernest White, 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 Office supplies E cS cS cS Ch cS cS cS CS Ch Research Engineer Research Engineer Research Engineer Computer Programmer Computer Programmer Computer Programmer Senior Research Assistant Electronics Technician Research Assistant Research Assistant Research Assistant Research Assistant Research Assistant Laboratory Technician Machinist Administrative Assistant Secretary Secretary Chemicals, glassware, and laboratory apparatus GC supplies (gases, phases, columns, etc.) Dry ice and liquid nitrogen Electronic supplies and parts GC/MS data recording media (chart paper, Calcomp, etc.) Mini-computer supplies (paper, ribbons, tapes, disks, etc.) Mass spectrometer repairs and replacement parts Time or Effort 100 20 10 50 75 50 100 60 100 50 50 100 50 50 20 50 50 25 $ 1,450 3,400 950 1,500 3,500 2,100 1,500 7,600 $22 ,000 PHS -398 Rev. 2-69 Page GPO : 1969 O - 350-360 f-/ G6 COMPOSITE - PARTS A, B, C, & D- SECTION 11 — PRIVILEGEO COMMUNICATION BUDGET ESTIMATES FOR ALL YEARS OF SUPPORT REQUESTED FROM PUBLIC HEALTH SERVICE DIRECT COSTS ONLY (Omit Cents) 1ST PERIOO *ADDITIONAL YEARS SUPPORT REQUESTED (This application only) DESCRIPTION {SAME AS DE- TAILED BUDGET} | 2ND YEAR 3RAD YEAR 4TH YEAR 5TH YEAR 6TH YEAR 7TH YEAR PERSONNEL COSTS 302 ,567 357,613 377,926 CONSULTANT COSTS include fees, travel, etc.) 1,100 1,200 1,300 EQUIPMENT 3,000 3,000 3,000 SUPPLIES 22,000 22,850 24,250 DOMESTIC 4,300 4,700 5,100 TRAVEL FOREIGN - ~ - PATIENT COSTS - - ~ ALTERATIONS AND RENOVATIONS 2,500 OTHER EXPENSES 152,800 168,100 182,150 TOTAL DIRECT COSTS 488,267 | 557,463 | 593,726 TOTAL FOR ENTIRE PROPOSED PROJECT PERIOD (Enter on Page 1, {tem 4). ——_——» S$ 4 ,639 ,456 REMARKS: Justify alf 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 costs is requested, give percentage, (Use continuation page if needed.) PHS-398 rr Rev. 3-70 P1607 BUDGET DETALL AND JUSTIFICATION The buiyets for the DENDRAL Froject are presented in tour parts, corresponding to the four proposal sections; 4, B{ij and (ii), C, ani D. Parts A and c represent the portions concerned with Heuristic and Meta-DENDRAL; bart B deals with the data SyStem automation and instrument maintenance functions as well as the development aspects of GC/MS analysis of body fluids; and Part 2 as an extension ot DENDRAL methodoloyy to Carbon (13) nuclear magnetic resonance spectrometry. As a general note, Professor Lederbery will devote a total of 10% of his time to this res2arch as the Principal Investigator. His time is budyated as follows: 4% on Part A, 3a On Part BH, and 3% on Part &. The narrative comments on Parts A and C have been combined below because the personnel ani computer resources overlap to a large extent. BUDGET EXPLAWATION - PARTS A & C PERSONNELS? a) The petsonnel on the DENDRAL staft constitute its most valnable resource. All of the people listed in the proposal are how working on the D&NuRAL Project. All are hecessary to Support the high level of scientific activity in Chemistry (A. Duffield, vb. Smith, S. Hammerum, and L. Ujelmeland) and Computer Science (Ff. Feigenbaum, B. Buchanan, N. Sridharan, WwW. White, S. Kkeiss, M. Stefik, L. Masinter, and C. Farrell). Mr. tark Stefik's status will have changed to Research Assistant for Part A from his current status as Conputer Proglammec on Part B. Mr. Steve deiss' salary has been increased in order to properly compensat2 him for the duties he performs. Recent changes in draft boacu policies allow Conscientious Objectors to receive higher compensation to reflect actual job duties. Specific University approval has been requested for this increase but has not yet been received. Mr. Larcty wasinter has previously been paid from other Eunds, but 18 essential to the NitH-related work. Leet a b) Salary tigures are increased annually by 5% for merit increases and promotions. Fringe benefits are budgeted at the standard University rates of I7% through 8/74 and are increased annually per University projections to 18.3% in 9/74, 19.3% it 9/75, and 20.4% in 9/70. No new personnel are added in Year 2. However, the salary budget incteuses by more than the rates noted above because ail of Pr. Buchanan's salary is tovered (see c) below) and Professor Feigenbaum returns from his leave ot absence (see da) below). c) Beuce Buchanar currently has an NIH Career bevelopment Award through 6/31/76. However, bezause of recent WIH bud jet cutbacks, there is a strong probability that this award will te cancelled before that uate. Dr. Ferguson of NIK stated on 2/e/13 tnat the award could only be guaranteed through s/74, d) As aoted in the Introduction to this proposal, vr. Feigenbaug will be on leave of absence with AKPA tor a period of two yoars. This overlaps the term of this grant application such that no salary is badyeted for Dr. Feigenbaun duriny the first gtant year. His salary is budgeted starting in the second grant year when he will formally return to his position in this research project. KQULP MENT: No equipment purchases are rc2quiced tor Parts A and C, SUPPLi€S AND TRAVEL: Office supplies are budgeted based on our experience over the past year. The trave] budget covers expected costs for attendiny professional meetings and maintaining contact with related work at other locations. Because Artificial Intelligence is a tapidly expanding field, it is essential to Maintain a high deyree of personal interaction in order to assimilat2 new developments, These budget items are increased and roundad at t0% per year. Prey OTHE EXPENSES: Telephone costs include connections and wsage ror conputer terminals, Publication costs are budgeted at a nominal rate based on past experience and are increased by 10% per year. In the catejory of Computer Yerminal Kent, the budget for Part A includes the lease cost of 2 portable Texas Instruments terminals. An additional terminal is added in 5/75 to accommodate increased use of the programs by nersonnel and a larger community of Stanford users. The fart © budyet covers the continued lease of one T.I. terminal and an additional terminal starting in 5/75. Cormpuater time is budgeted according to current rate structures based on dur on-yoing experiance in utilizing the Stanford (SCC) 360/07 and machines available via the AHPAMET. We will hot make use of the AUME follow-on machine (370/158) for Parts A and C beacause of the availability of superior Lise facilities on these other machines. Instrument data will be communicated From the 3/0/158 (see Part B) to the LISP programs for analysis. BUDGET EXPLANATION - PARTS B(i) AwD 8B(ii) Tais budget covers instrumentation maintenance, data syster development, and research into applications of GC/MS analysis ot body fluids as described in Parts B(i) and B(i1l) of this proposal. This budyet represents a significant increase over that Submitted toc Part BR of the DENDRaL grant currently in-proyress (current budyet $60,000 per year). The major reasons for this increase ara twofold: a) Increases in required personnel support because of corresponding decreases in support from other sources and b) The need to implement oar computing support from a source other than the ACME 36u750 for whach NIH funding is terminating. We have ctiyorously attempted to keep these increases to an absolute minimum consistent with Maintaining the viability ot our unaugmented research program, We have previously received substantial support for our GC/MS research from NASA. Hecaase of shifting federal priorities, however, NASA support kas declined Substantially and we project Will terminate in the first year of this renewal. At the sume time, our reseurch has been moving to emphasize more and more heavily GC/MS applications in clinically related aSpects or metabolic indicators of disease. Thus it is reasonable, as well as necessary, that support for this continued research shift to NTH. As waentioned in the Introduction to this proposal, we have an application pending with NIH-G&S for support in applyiny these techniyues to aspects of genetic disease. These Proposals are complementacy in goals and it is assumed in this budyet that the Genetics Center proposal will provide support for a Major fraction (approximately 50%) of tne low cesolution GC/HS laboratory (Finnigan 1015 instrument) aincludiny personnel, Supplies, atc. There is, howevar, a small amount of operational manpower overlap between the two proposed efforts. If both proposals ate funded, a savings will result through common Operational support which will be negotiated with NIH at the appropriate time. AS discussed under future plans tor Part B(i) of this proposal, w2 have had to plan an alternative source of computing to support this research because NIH subsidy of the ACME tacility terminates in July 1973. We have chosen to use the stanford-sronsored follow-on to ACME, mounted on an Lupe 375/155, Since out computer programs will operate with a minimum of modification. This facility will operate on a tee-tor-service basis. Whetaas its rate structure is still evolving, we have estinated, on the basis of available information, the cost of transferting our computing to that facility as reflected in our budget (%64,u00 per year). It should be noted that this rate Structure dyes not include indirect charges at this time. as the Tate structure becomes better tefined, the indirect cost may be full -49- ancluded in the usage rates. Tais would necessitate a slight modification of the budyet as will be negotiated with NIH as appropriata, Tice following gives a detailed description ot the various components 91 the bart # budget: PRESONNELS: The ,ercsonnel budgeted for GT/MsS applications, laboratory operations, and data system development are necessary to achieve our research quals and are Currently active in the SC/MS plrojtams, Chemistry support for the interpretation of body fluii analyses in cooperation with our clinical collaborators include prs. A. Duffield (29%), Ww. Periera (20%), and 2. Summons (10U%). M. Wyche provides laboratory and instcument operation support for the low resolution GCS/N5 laboratory. Messers vindfleisch, Veizades, keynolas, and Tucker are essertial to the data systea development effort and prooviue hardware and software maintenance Support aS well. dessers Kinditleiscu (1004) and Tucker (/5%) are pligartly cesponsitle for the sottware system design, implerentation, alu maintenance. Hr. Veizades (100%) is primarily concerned «aith the hatdware maintenance and development aspects of the hiyh resolution MAT-711 instrument ani Mr. Reynolds (20a) with the Finnigan 1415 low resolution instrument. Fs. A. wWeywann (1004) is reSponsible for the operation of the high resolution GC/MS instrument (MAT-711). br. Steed (104) provides necessary jlasswock development ana maintenance, Mc. Pearson (60%) Supports the fabrication and repair of electronic hardware for both instruments, and #c. NeFrancisci (4U%) provides necessary machinist support tor mechanical repairs and fixtures. fs. Allan (254) provides reyuired secretarial Support tor the above Instcuwentation kesearch Laboratory personnel. This manpower complement is sarried into the future Yeadls as Shown. Salaries are increased by 54 per year and staff Lenerits are applied at standaca University cates. These start at I/7k in fiscal year 1974 (9/773 - 8/74) and increase to 16.3% in 4/74, 19.34 in 9775, and 20.4% in 9/76 based on University projections. OCUIPMENT: Vur request for additional eyuipment is minimal. we budget tor the purchase of a computer tarminal in the first year tor $3,000. This replaces u currantly rented terminal integral to the Oty: data system and saves $5,280 over the three year -6- jtant period by purchasing instead of continued rental. In the sscond year we budget for an event counter necessary tor proper equipment maintenance for which we are assubbing responsibility. we already maintain the Finniyan 1615 instrument and will take over the mAT-711 because of progressively poorer pertormance by VARLAN ASsociates in maintaining that instrument over the past year. This equipment is also needed to implement experimental control functions on the mass spectrometer. In the third year, replacemant of outdated test egjaipment will be required, $3,090 are budgeted for this purpose. SUPPLIES: Supplies are budgeted based on our actual Operating experience and are minimized consistent with a viable research effort. Office supplies include stationery supplies, postage, reproduction services, etc. and are budjeted at $63 per month. The budget for chemicals, glassware, and laboratory appacatus ($2,900) provides the necessary materials for derivatizing and analyzing body fluid sumples. GU supplies ($950) and dry ice and liquid nitroyen ($1,500) are necessary tor instrument Operation and are based on past experience. The largest part ot the liguid nitrojen pudget is used for the high cvesolution instrument, Electronics supplies and parts (83,599) inclade Circuit boards, semi-conductors, etc. needed for mass spectroaeter control electronics such as tot the metastable acquisition system as well as for maintaining out existing test equipment (oscilloscopes, voltmeters, power supplies, etic.). GC/Ms cata Lecorcing media (82,190) include chart ana Calcomp plotter papers of vatious types (includiny UV-sersitive Paper for the war-711) for tne purvose of Lecotding mass Spectromet:1 and yaS chromatograph effluent uata. The budjeted amount reflects our usaje over the past year. Similarly, wini-computer supplies (1,500) include Teletype and line printer paper and ribbons, magnetic tapes (DEC tape and Lun cotpatible tape), aru disk cartridges based on previous usage history. The budget for MmaSS Spectrometer repairs ani replacement parts (37,600) covels our maintenance of these instruments based in part on predictable replacsments (tilamonts, multipliers, etc.) and in part on an estimate tron previous experience of unscheduled problemas (power supplies, valves, pumps, etc.). fhe supplies budjet tor future years covers tiese same thems with 6% added for increased usaye and intlation. TRAVEL: We have budgeted for travel to attend plotessional meetings and to visit other GU/NS laboratolics on the basis Of § @ast coust trip (6500), 1 mid-west trip (6350), and | owost coast trip ($155) . ALTENAITONS AND KUNOVAPIONS: We have had problems with thermal overloads on the high resolution fass spectrometer instrument and associated electronics during the summer months. In addition, because ot the moditied computing configuration Cequired by the ACME transition, we will locate a disk and fCinter equipment in the same laboratory to support the mini-~computer interfacing the MAT-/11. These conditions require an auyghentation to existing air-conditioning and power facilities in the laboratory estimated at $2,564. OTHER EXPENSES: We budget for telephone and data communications service based On out curcent experience (5100 per month). In addition, $81, .9 is budgeted for publication zosts and $4,600 for mini-comnputer maintetance. This maintenance is an extension of our current contract with Digital Equipment Corporation and includes the prevailing 10% discount in the Stanford/vEC contract. We budget for data reduction and storage computing costs on the ACME tollaow-on machine (370/158) as follows, based on our ACN experienc? and current information on the follow-on System rate Structuce. We consume approximately 300,000 pajge-Minutes of computing per month on ACME for development and production computing. At a rate of $4.02 per paje-minute, this comes to $6,900 per month. In addition, we use approximately 82,000 per month for data storaye (29,096 ulocks at #10 per wlock pec month). This gives a total of 896,000 per year and applying a projected 30% discount rate for hijgh volume usage, leaves an estimated net cost of $64,900 per year. These estimates are increasel by 64 in succeeding years for increased usage and inflation. /- vt ~ BUDGET EXPLANATION - PART D This cudget covers the portion of the research program which extends the DENDRAL methodology to Carbon(13) suclear Magnetic Resonance Spectrometry. DERSONNEL: The personnel budget includes a salary tor Dr. &. Carhart after the expiration of his SIH Fellowship in 6/74, one Post voctoral kesearch Associate (to ba adied to the staft), and one half-tim2 Research Assistant (Mr. Van Antwerp). No funding is requested for Dr. Carl Djerassi's time (3%). A Computer Programmer (to be added to the staff) is budgeted in 1975 to assume tha additional anticipated programming duties. Salaries are increased by 5% per year and staff benefits are applied at standard University rates. These start at 17% in fiscal year 1974 (9/73 - 8/74) and increase per University projections to 16.3% in 9/74, 19.3% in 9/75, and 20.4% in G/7To. SUPPLIES: We budget 9900 for chemical supplies for the preparation ot test samples. TRAVELS: Wwe budyet $5090 to cover one 2ast coast trip. OTHER EXPENSES: Other expenses include $100 for publication and reproduction costs and $7,500 for usage of the existing NMR instrument in the bepattment of Chemistry. This NMR usaje is budgeted at Standard cates covering 25 hours of usage per month at 525 per hour. {fn addition, we budget tor use of the Stanford (5C7) 360/o7 computer where CM& analysis proyrams, at the current level of jevelopment, are run. these costs are computed on the f- he -9- basis of 1.5 hours of usage per month at approximately $000 per hour. frttk, BIOGRAPHIES Pte 7 Aare Tit BIRTHOATE (Ma, Gay, 7; Professur and Executive Head, LEDERBERG, JOSHUA Department of Genetics 5=2 3-25 PLACE OF BIRTH (City, State, Counvy! PRESENT NATIGNALITY (If non-US citizen, DEX Indicate kind of visa and expiration date) Montetair, Now Jersey U.S.A, [TY Male (77 Female ECUCATION (Sujfa with boccalaureate traming und include postdoctoral} ~ YEAR | SCIENTIFIC INSTITUTION ANDO LOCATION OEGREE CONFERRED FIELO Columbia College, New York B.A. 1944 College of Physicians & Surgeons, Columbia University, New York (1944-46) Yale University Ph.D. 1947 Microbiglozy HONORS 1957 - National Academy of Sciences 1958 ~ Nobel Prize in Medicine MAJOR RESEARCH INTEREST ROLE tN PROPOSED PROJECT Molecular Genetics; Artificial Intelligence PRINCIPAL INVESTIGATOR RESEARCH SUPPOAT (See in Sruczons} SEE ATTACHMENTS: RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, ist trainiog end experience relevant io area of project, List ail Of most representaove pudlication:s Oa not exceed 2 pazes for earch individual.) . . 1961- —1959- 1957-1959 1957 1950 1947-1959 1946-1947 1945-1946 Stanforc University Director, Kennedy Laboratories. for Molecular Medicine ... ._ Professor, Genetics and Biology, and Executive Head, Department of Genetics, Stanford University University of Wisconsin Chairman, Department of Medical Genetics Melbourne University, Australia Fullbright Visiting Professor of Bacteriology University of California, Berkeley Visiting Professor of Bacteriology University of Wisconsin Professor of Genetics Yale University. Research Fellow of the Jane Coffin. Childs Fund for. Medical Research Columbia University. Research Assistant in Zoology Professional Activities: 1967- NIMH: National Mental Health Advisory Council 1961-1962 President (Kennedy)'s Panel on Mental Retardation 1960- NASA Committees: Lunar and Planetary Missions Board 1958-" National Academy of Sciences: Committees on Space Biology 1950-. President's Science Advisory Committee panels: National Institutes of Health, National Science Foundation Study sections (genetics) RHS-398 Rev. 3-70 1) 2) 3) 4) 5) 6) 7) Grant Number NAS A:NGR-05-020 NIH: AIT-05160 NIH: RR-00311 NIH: GM- NIH: RR-00785 NIH: Computer Lab- oratory Health Care Resource Program NIH:GM00295 RESEARCH SUPPORT SUMMARY FOR JOSHUA LEDERBERG Grant Title Cytochemical Studies of Planetary Micro-organisms Genetics of Bacteria Advanced Computer for Medical Research (ACME) Stanford Medical School Facility Genetics Research Center (J. Lederberg,Principal Investigator Stanford University Medical Experimental Computer Facility (SUMEX) Successor to #3 Large Scale Screening of Body Fluids for Metabolic Signs of Disease with Computer-managed Gas Chromatographv and Mass Spectrometry Training Grant in Genetics Current Year $ 180,000 60,000 362 ,632 547,035 884 ,660 159,881 143,964 Total Award $3,800,000 280 ,000 2,612 ,632 (yrs 4-7) 2,609 , 383 5,960,417 900 ,238 756,650 Grant Term Budgeted 4 Time 9/60-8/73 4% (Future support dubious) 9/68-8/73 15% (Renewal pending) 1966-7/73 25% (see #5) 9/73-8/78 10% (Pending) 9/73-8/78 20% (Pending) 9/73-8/78 10% (Pending, Program funds impounded) 7/69-6/73 15% (Renewal pending) SELECTED LIST OF PUBLICATIONS Lederberg, J., 1959 A View of Genetics Les Prix Nobel en 1958: 170-89. Buchs, A., A. B. Delfino, A. M, 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. Analytical 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 (in press). DELIION Ht ~ PRIVILEGED COMMUNICATION Principal Investigator: Carl Djerassi BIOGRAPHICAL SKETCH (Give the following information for all Professional personnel listed on page 3, beginning with the Principal Investigator. se continuation pages and follow the same generai format for each person.) NAME TITLE BIRTHDATE (Mo., Day, Yr.} Carl DJERASS! Professor of Chemistry October 29, 1923 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY f/f non-US citizen, SEX indicate kind of visa and expiration date} Vienna, Austria U.S.A, Bl Matle (Female EDUCATION (Begin with baccalaureate training and include postdoctoral) * YEAR SCIENTIFIC (NSTI N TUTION AND LOCATION DEGREE CONFERRED FIELD Kenyon College A.B. (summa 1942 Chemistry, Biology cum laude) University of Wisconsin Ph.D. 1945 Organic chemistry, Biochemistry (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 f a ienti leopoldina), Brazilian Academy of Sciences, (cont, below) MAJOR RESEARCH INTEREST Kigt, prod, chemist _|ROLE IN PROPOSED PROJECT res} and (steroids, alkaloids, terpenoids, antibiot . . chem, applicgtions of physical methods (mass Principal Investigator ec,, Optical rotatory dispersion, circular AESeAd CH SUPeORT (See instructions] dichrotsm), Current Total % Time Grant Title Period Year Budgeted Effort NIH AM 04257 Mass Spectrometry in 10/1/70 to $56,833 $316,016 10% Organic and Biochemistry 9/30/75 NIH GM AM Marine Chemistry with 1/1/73 to 112,550 578,180 18% 06840-15 special emphasis on steroids 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 AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area of project. List all Or most representative publications, Do not exceed 3 pages for each individual, } Academic Experience: Professor of Chemistry, Stanford University, 1959-present. Associate Professor (1952-1954) and Professor (1954-1959), Wayne State University. Industrial Research Experience: Ciba Pharmaceutical Co., Summit, N.J.: Research Chemist, 1942-1943 and 1945-1949, Syntex Corporation: 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 RHS-398 Society's Award for Creative Invention Gos Rev. 3-70 : age 5 U.S. GOVERNMENT PRINTING OFFICE : 1971 O - 451-736 DO NOT TYPE IN THIS SPACE-BINDING MARGIN BIOGRAPHICAL SKETCH (C. Djerassi) Continuation page Principal Investigator:Carl Djerassi RESEARCH AND/OR PROFESSIONAL EXPERIENCE (cont.) Miscellaneous: Chairman of the AAAS Gordon Research Conferences on Steroids and Natural Products (1952-1954); Member of American Pugwash Committee (1968 to present); Chairman of Latin America Science Board of National Academy of Sciences (1966-1968); Chairman of National Academy's Board on Science and Technology for International Development. PUBLICATIONS Author or co-author of 750 publications and six books. Approximately 150 papers and one book | deal with various applications of chiroptical methods in organic and biochemistry. PNS-398 Page Rev. 2-69 GPO ; 1969 © - 380-360 SECTION 1! — PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for all Professional personnel listed on page 3, beginning with the Principal Investigator. Use continuation pages and foltow the same general format for each person.} NAME TITLE BIRTHDATE (Mo., Day, Yr.) Principal Investigator, Feigenbaum, Edward A. DENDRAL Project 1-20-36 PLACE OF BIRTH (City, State, Country] PRESENT NATIONALITY (/f non-US, citizen, SEX indicate kind of visa and expiration date) Weehawken, New Jers U.S. Citi eehawken, New Jersey S. Citizen G9 Mate} Female EOUCATION (Begin with baccalaureate training and include postdoctoral) YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELD Carnegie Institute of Technology Pittsburgh, Pennsylvania B.S. 1956 Electrical Engineering Ph.D, 1959 Behavioral Sciences. HONORS and memberships: American Psychological Association; Association for Computing Machinery (Member of the National Council 1966-68); American Association for the Advancement of Science, . MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Artificial Intelligence Principal Investigator RESEARCH SUPPORT (See instructions} RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area of project. 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. Summer Research Training Institute in Heuristic Programming. Faculty member. 1960-1964 University of California, Berkeley Research-Center for Research in Management Science, 1960-196) 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 1956 IBM Scientific Computing Center, New York Selected Publications: "Applications of Artificial Intelligence for Chemical Inference I. The Number of Possible Organic Compounds. Acyclic Structures Containing C, H, O ana N", J. Am. Chem. Soe., 91, 2973 (1969). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference II. Interpretation of Low Resolution Mass Spectra of Ketones", J. Am. Chem. Soc., 91, 2977 (1969). ' (Co-Author). RHS-398 Rev. 3-70 Publications of Edward Feigenbaum "Applications of Artificial Intelligence for Chemical Inference III. Aliphatic Ethers Diagnosed by their Low Resolution Mass Spectra and Nuclear Magnetic Resonance", J. Am. Chem. Soc., 91, 740 (1969). (Co-Author). “Heuristic DENDRAL: A Program for Generating hxplanatory Ulypotheses in Organic Chemistry", in Machine Intelligence h, 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 C6H100", Organic Mass Spectrometry, 4, 493 (1970). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference VI. Avproach 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 Mechine Intelligence 7, Edinburgh University Press (1972). (Co-Author). "Applications of Artificial Intelligence for Chemical Inference X. Datsun. A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids", to be submitted. (Co-Author). SECTION I! — PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for alf Professional personne! listed on page 32, 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 7-7-0 PLACE OF BIRTH (City, State, Country} PRESENT NATIONALITY (/f non-US citizen, SEX indicate kind of visa and expiration date) St. Louis, Missouri U.S.Citizen . AZ) Mate (_] Female EDUCATION (Begin with baccalaureate training and include pastdoctoral) YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELD Ohio Wesleyan University B.A. 1961 Mathematics Michigan State University 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 in Chemistry (Washington) MAJOR RESEARCH INTEREST . ROLE IN PROPOSED PROJECT Associate Investigator RESEARCH SUPPORT (See instructions) RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area of project. List alf or most representative publications, Do not exceed 3 pages for each individual.) 1972-present Research Computer Seientist, Stanford University 1966-1971 Research Associate, Stanford Artificial Intelligence Project Publications: "On 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 IT. 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, H, O and N". Journal of the 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, 7440-5 (1969). (Co-Author). "Heuristic DENDRAL: A Program for Generating Explanatory Hypotheses in Organic Chemistry". Machine Intelligence 4, Edinburgh University Press (1969). (Co-Author). RHS-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 Generaiity and Problem Solving: A Case Study Using the DENDRAL Program". Machine Intelligence 6, Edinburgh University Press (1969). (Co-Author). "Some Speculation About Artificial Intelligence and Legal Reasoning". Stanford Law Review, Vol. 23, No. 1, November 1970. (Co-Author). "Applications of Artificial Intelligence for Chemical Inference VI. Approach t+ @ 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", Mass Spectrometry Techniques and Appliances (1970). "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, 93, 6831 (1970). (Co-Author). "The Heuristic DENDRAL Program for Explaining Empirical Data". Proceedings of :FIP 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 Molecules. 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). "Review 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 (AAAS) aotre gy er Loe, Bde cm fom mm . a foe wn nae “ +t wre CON AES Sop sat for awe it ara geeeral format for ech person | NAME . TITLE . BATE GATE (Yarra ae, Alan M. DUFFIELD Research Associate Vvecemncér 672555 PLACE OF BIRTH (City, State, Country] PRESENT NATIONALITY (/f non-US citizen, SEK indicate kind of visa and expiration date) Perth, Western Australia Australian, Permanent resident Termipcrant Vian Cot Male T Fay a EDNUCATION (Sera wrt oucculiureate treme sd include Qovtductoral) INSTITUTION AND LOCATION YEAR SCIENTIFIC OEGREE CONFERRED FIELS University of Western Australia B. Sc(lst Clhss Hons ) 1958 Organic Chemistry University of Western Australia Ph.D. 1962 Organic Chemsitry HONORS - wo MAJOR RESEARCH INTEREST ROLT IN PROPOSED PROJECT Applications of mass spectrometry to Organic Chemist/mass spectroscopist Piology and Biomedical Problems RESEARCH SUPPORT (See instructions) N/A RESEARCH AND/OR PROFESS, ONAL EXPER EN CE (Starurg with present cosigon, {ist {raining and experience reievant (0 area Of prs,est wisldn OF most representauve pubucations, Oo notexceed 3 Gages for each individual.) . we fet, Sete te het Research Associate, Department of Genetics, Stanford University 1970 School of Medicine 1969 - Head of the Mass Spectrometry Laboratory, Chemistry Department Stanford University . 1965 - 69 “esearch Associate, Department of Chemistry, Stanford University 1963 - 65 Posidoctoral Fellow, Department of Chemistry, Stantord University 1962 - 63 Postdoctoral Fellow, Department of Biochemistry, Stanford University . . School of Medicine. a PUBLICATIONS SINCE 1971 . . £ ¢} r 1. An Apolicetion of Artificial Intelligence to the Interpretation of Mass spectra. Mass Spectrometry, _B.W.G. Milne, Ed., John Wiley and Sons, i New York, 1971, pp, 121-178 . By B. G. duchanane A. M. Duffield and A. V. Robertson Any Bev. 3-79 10, il, 12, Mass Spectrometry in Structural ard Stereochemical Problems. CCIV. Spectra of Hydantoins.II. Electron Impact Induced Fragmentation of some Substituted Hydantoins. Org. Mass Spectr., 5, 551 (1971) By R. A. Corral, 0. 0. Orazi, A. M. Duffield and C. Djerassi Electron Impact Induced Hydrogen Scrambling in Cyclohexanol and Isomeric Methylcyclohexanols. Org. Mass Spectr., 5, 383 (1971) By R. H. Shapiro, S. P. Levine and A. M. Duffield Derivatives of 2-Biphenylcarboxylic Acid. Rev. Roumain. Chem., 16, 1095 (1971) By A. T. Balaban and A. M. Duffield Alkalcide aus Evonymus europaea L. Helv. Chim. Acta, S4&, 2144 (1971) By A. Kldsek, T. Reichstein, A. M. Duffield and F. Santavy Studies on Indian Medicinal Plarts. XXVIII. Sesquiterpene Lactones of Enhyura Fluctuans Lour. Structures of Enhydrin, Fluctuanin and Fluctuadin. Tetrahedron, 28, 2239 (1972). By E. Ali, P. P. Ghosh Dastidar, S. C. Pakrashi, L. J. Durham and A. M. Duffield The Electron Impact Promoted Fragmentation of Aurone Epoxides. Org. Mass Spectr., 6, 199 (1972) By B. A. Brady, W. I. O'Sullivan and A. M. Duffield The Determination of Cyclohexylanine in Aqueous Solutions of Sodium Cyclamate by Electron Capture Gas Chromatography. Anal. Letters, 4, 3C1 (2971) By M. D. Soloman, W. E. Pereira and A. M. Duffield Computer Recognition of Metastable Ions. Nineteenth Annual Conference cn Mass Spectrometry, Atlanta, 1971, p. 63 To By A. M. Duffield, W. £. Reynolds, D. A. Anderson, R. A. Stillman, Jr. and C. E. Carroll Spectrometrie de Masse. VI. Fragmentation de Dimethy1-2 ,2-dioxolanes-1,2- Insatures. Org. Mass Spectr., 5, 1409 (1971) By J. Kossanyi, J. Chuche and A. M. Duffield Chlorpromazine Metabolism in Sheep. II. In vitro Metabolism and Preparation of 3H-7-Hydroxychlorpromazine. ~ Journees D'Agressologie, 12 , 333 (1971) By L. G. Brooks, M. A. Holmes, I. S. Forrest, V. A. Bacon, A. M. Duffield and M. D. Solomon Mass Spectrometry in Structural and Stereochemical Problems. CCXVII. Electron Impact Promoted Fragmentation of O-Methyl Oximes of Some a,8-Unsaturated Ketones and Methyl Substituted Cyclonhexanones. Canadiau J. Chem., 50, 2776 (1972) By Y. M. Sheikh, R. J. Liedtke, A. M. Duffield and c. Djerassi PL ie eT an Ae Ud lor US2 CONE NUaHON 25-8 FOI fay the ame general tormat for each person. | NAME Wilfred E, PEREIRA TITLE BIRTHDATE (313., Sav, rr) Research Associate June 23 1976 PLACE OF BIRTH (City, State, Country} Madras, S, India PRESENT NATIONALITY f/f non-US crtizen, SEX indicate kind of visa and expiration @ste} Indian, Permanent Resident Immigrant Visa Gel Male Femsi2 EDUCATION (Begin with baccalaureate training and include postdoctoral} YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELD Madras Medical College, Madras, India |B, Pharm 1960 Pharmaceutical Cheristry Saugar Univ, Madhya Pradesh, India M. Pharm 1962 Pharm. Chem & Cherm of Natu: U.C. Med. Center, San Francisco, Calif | Ph.D. 1968 Pharm. Chem & Pharmacoloey HONORS MAJOR RESEARCH INTEREST Identification of Metabolites & drug metabolites in Biological fluids ROLT IN PROPOSED PROJECT Organic chemist RESEARCH SUPPORT (See instructions) RESEARCH AND CR PROFESSIONAL EXPERIENCE (Starting with oresent position, fist training and experience relevant to area of projecte Listas or mgst representatve pubications, Do not exceed 3 pages far each individual.) : 4 190 - 1970 1970 ~ present Research Associate During these four years I have been and synthetic organic chemistry. Post Doctoral Fellow, Dept. of Genetics Stanford University Med. School same institution LD involved with peptide synthesis, amino acid analysis 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 and pathological urine and serum samples, for the identification of urinary metabolites in normal My applications of mass Spectrometry have included the deveoloment of mass fragmentography for the determination of the amino acid contents of soil and PXLARMAX serum. My present project involves the screening of urine from leukemic patients for abnormal metabolites and to investigate the metabolic fate of anti-leukemic chemotheropeutic agents i. 2. in the body. PUBLICATIONS Transesterification with an Anion-exchange Resin: W. Pereira, V. Close, W, Patton and B. Halpern, J. Org. Chem. 34:2032 (1969). Alcoholysis of the Merrifield-type Peptide-polymer Bond with an Anion Exchange Resin; W. Pereira, Ve Ay Close, E, Jellum, W, Patton and 8B. Halpern, Australian J. of Chem. 22:1337 (1969). AnS98 Rev. 370 13. 14. 15. 16. 1?. 18. 19, 20, Publications Thermal Fragmentation of Quinoline and Isoquinoline N-Oxides in the loz Source of a Mass Spectrometer. : Acta Chem. Scand., 26, 2423 (1972). By A. M. Duffield and 0. Buchardt Applications of Artificial Intellisence for Chemical Inference. VIZ. An Approach to the Computer Interpretation of the High Resolution Mass Spectra of Complex Molecules. Structure Elucidation of Estrogenic Steroi¢s. J. Amer. Chem. Soc., 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 Transfer Process in 7-Phenyl-hept-3-en-2-one O-Methyl Oxime Ether. Org. Mass Spectr., 6,1271 (1972). By R. J. Liedtke, Y. M. Sheikh, A. M. Duffield and c. Djerassi An Automated Gas Chromatographic Analysis of Phenylalanine in Serun. Clinical Biochem. , 5, 166 (1972) | By E. Steed, W. Peraira, 3B. Halpern, M. D. Solemen and A. M. Duffield Pyrrolizidine Alkaloids. XIX. Structure of the Alkaloid Erucifoline, Coll. Czech. Chem. Commun., (1972) . By P. Sedmera, A. Klasek, A. M. Duffield and F, Santavy. Mass Spectrometry in Structural and Stereochemical Problems, COMNIZ, Delineation of Ccmpeting Frasmentation Pathways of Comzlex Molecule from a Study of Metastable Ion Transitions of Deuterated lerivarive Org. Mass Spectr., 7, (1973) By D. H. Smith, A. M. Duffield and C. Djerassi L w Chlorination Studies I. The Reaction of Aqueous Hypoch lorous Acid with Cytosine. Biochem. Biophys. Res. Commun., 48, 880 (1972) By W. Patten, V. Bacon, A. M. Duffield, B. Halpern, Y. Hoyano, “%. Pereira and J. Lederberg A Study of the Electron Impact Fragmentation of Promazine Sulshoxide and Promazine using Specifically Deuterated Analogues. Austral. J. Chem., 26, (1973). By M. D. Solomon, 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. Pereira, V. A. Bacon, Y. Hoyano, R. Summons and A. M. Duffield 36 56 T. 9. 10. the Action of Nitrosyl Chloride on Faenylalanine Peptides; W. Patton, E, Jellum, D. Nitecki, W. Pereira and B. Halpern, Australian J. of Chem, 22:2709 (1969). Abnormal Circular Dichroism of & «Amino Acid Esters; J. Cymerman Craig and W. E. Pereira, Tet. Let. 18:1563 (1970). The Use of (+)-2,22-Trifluoro-1-Phenylethylhydrazine in the Optical Analysis of Asymmetric Ketones by Gas Chromatography ; W. E. Pereira, M. Solomon and B. Halpern, Australian J. of Chem.24:1103 (1971). The Microsomal Oxygenation of Ethyl Benzene. Isotopic, Stereochemical, and Induction Studies; R. E, McMehon, H. R. Sullivan, J. Cymerman Craig and W. E. Pereira, Arch. Biochem. Biophys. 132:575 (1969). The Steric Analysis of Aliphatic Amines with Two Asymmetric Centers by Gas-liquid Chromatography of Diastereoisomeric Amides, W. E. Pereira and B. Halpern, Australian J. Chem. 25:667 (1972). Optical Rotatory Dispersion and Absolute Configuration -XVII, A -Alkylphenylacetic Acids; J. Cymerman Craig, W. E. Pereira, B. Halpern and J. W. Westley, Tetrahedron 27:1173 (1971). The Optical Rotary Dispersion and Cire dar Dichroism of o-Amino and A-Hydroxy Acids; J. Cymerman Craig and W. E. Pereira Tetrahedron 26:3457 (1970) . The Determination of Cyclohexylamine in Aqueous Solutions of Sodium Cyclamate by Electron-capture Gas Chromatography; M. D. Solomon, W, E, Pereira and A. M. Duffield, Anal, Let. 4:301 (1971). Publications continued- ll. le. 13. 14, 15. 16. iT. 18, 19. 20. Chlorination Studies. I. The Reaction of Aqueous Hypochlorous Acid with Cytosine; acca W. Patton, V. Brown, 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. 39:156 (1971). Electron-impact Promoted Fragmentation of Alkyl-N-(1-Phenylethyl)- Carbamates of Primary, Secondary and Tertiary Alcohols; W. E. Pereira, B, Halpern, M. D. Solomon and A. M. Duffield, Org. Mass Spectrometry 5:157 (1972). Peptide Sequencing by Low Resolution Mass Spectrometry; V. Bacon, E. Jellum, W. Patton, W. Pereira and B, Halpern, Biochem. Biophys. Res. Commun. 37:878 (1969). A Gas Liquid Chromatographic Method for the Determination of Phenylalanine in Serun; E, Jellum, V. A. Close, W. Patton, W. Pereira and B, Halpern, Anal. Biochem, 31:227 (1969). Quantitative Determination of Biologically Important Thiols and Disulfides by Gas Liquid Chromatography} E. Jellum, W. Patton, V. A. Bacon, W. E. Pereira and B. Halpern, Anal, Biochem, 31;339 (1969). . A Study of the Electron Impact-promoted Fragmentation of Promazine Sulfoxide and Promazine Using Specifically Deuterated Analogues; M. D. Solomon, R. Summons, W, Pereira and A. M, Duffield, Australian J. Chem. (1973, in press). The Determination of Phenylalanine in Serum by Mass Fragmentography; + Pereira, 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 ~-Amino Acids and Dipeptides; W. E. Pereira, Y. Hoyano, R. Summons, V. A. Bacon and A, M, Duffield, Biochem.et Biophys. Acta (In press), BIOGRAFAICAL SKETCH (Give the following information for a'!l profissioral cerscnr 4 listed on pase 3, beginning with the Principal {nvastigstor, Use continuation pes and follow the same general format for eech person, } NAME TITLE BIRTHDATE (da, Osy, ¥r) Thomas C. Rindfleisch Research Associate 12-10-41 PLACE OF BIATH (City, State, Country] PRESENT NATIONALITY (/f non-U.& citizen, SEX 7 indicate kind of visa and expiration date} J c Oshkosh, Wisconsin, USA USA XS male ems EDUCATION (egin with baccalaureate traming end includo postdoctoral] YEAR SCIENTIFIC { NSTITUTION AND LOCATION DEGREE CONFERRED FIELD Purdue University, Lafayette, Ind. B.S 1962 Physics California Institute of Technology, _ M.S 1965 Physics Pasadena, CA Ph.D Thesis to bd completed. All course work jand examinations completed. HONORS Purdue University, Graduated with Highest Honors, Sigma xi. MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Space scilencee, computer science and imaze processing Technical Support HESEAKCH SUPPORT (Soe fastrucuons) RESEARCH ANO/OR PROFESSIONAL EXPERIENCE (Starting with presant position, dist training end experience retevant Co ares Of project Listas Of Most representative publication, Do not exceed 3 popes for esch individwal.} 1971-Present Stanford University Medical School, Department of Genetics, Stanford, CA. / Research Associate - Mass spectrometry, Instrumentation 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: Mariner Mars 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. Rindfleisch, T. and Willinghan, D., "A Figure of Merit Measuring Picture Resolution," Advances in Electronics and Electron Physics, Volume 22A, Photo~Electronic Image Devices, Academic Press, 1966. USS ame Thomas C. Rindfleisch PUBLICATIONS (cont'd) 3. 4, 5. 8, 9, Rindfleisch, T., "A Photometric Method for Deriving Lunar Topographic Information," JPL Technical Report 32-786, September 15, 1965. Rindfleisch, T., "Photometric Method for Lunar Topography," Photo- grammetric Engineering, March 1966, : Rindfleisch, T., "Generalizations and Limitations of Photoclinometry,” JPL Space Science Summary Volume III, 1967. Rindfleisch, T., "The Digital Removal of Noise fron Imagery," JPL Space Science Summary 37-62 Volune III, 1970. Rindfleisch, T., "Digital Image Processing for the Rectification of Television Camera Distortions," Astronomical Use of Television-Type Image Sensors, NASA Special Publication SP-256, 1971. Rindfleiech, T., Dunne, J., Frieden, H., Stromberg, W., and Ruiz, R., “Digital Processing of the Mariner 6 and 7 Pictures,” Journal of Geophysical Research, Voluze 76, Number 2, January 1971, Rindfleisch, T., "Digital Image Processing," To be published, IEEE Special Issue, July 1972. ° SECTION UW — PRIVILEGED COMMUNICATION 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 general format for each person.) NAME : TITLE Dennis H. Smith Research Associate BIRTHDATE (Mo., Day, Yr} 11/12/42 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (ff non-U.& citizen, SEX indicate kind of visa and expiration date) New York USA aa Male (J Female EDUCATION (Begin with baccalaureate training and include postdocteral) YEAR SCIENTIFIC INSTITUTION ANDO LOCATION DEGREE CONFERRED FIELD Massachusetts Inst. of Technology Cambridge, Mass. S.B. 1964 Chemistry University of California, Berkeley Berkeley, California Ph.D. 1967 Chemistry HONORS Alfred P. Sloan Foundation Scholarship NASA Predoctoral Traineeship Phi Lambda Upsilon, Sigma Xi MAJOR RESEARCH INTEREST Mass Spectrometry and A.1I. in Chemistry RESEARCH SUPPORT (See instructions) N/A ROLE iN PROPOSED PROJECT Research Associate RESEA RCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area of project, List all Or most representative publications. Do 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,Berkeley, Ca. Publications: See attached list. RHS-358 Rev. 3-70 DO NOT TYPE IN THIS SPACE-BINDING MARGIN Continuation page l. 10. ll. 12. 13. Publications: 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. Soc. 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. DUupke, "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 bv Reductive Silylation and Computer-Aided Analysis of High Resolution Mass Spectral 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, XXXIX. Active Principles of Acnistus arborescens. Isolation and Structural and Spectral Studies of Withaferin A and Withacnistin," J. 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.1.T.Press, Cambridge, Mass. 1971, p. 1891. PHS-398 Page Rev. 2-69 GPO : 1969 © - 350-360 DO NOT TYPE IN THIS SPACE-BINDING MARGIN Continuation page 14, 15. 16. 17. 18. 19. 20. 21. 22. D. H. Smith, "A Compound Classifier Based on Computer Analysis of Low Resolution Mass Spectral Data," Anal. Chen., 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. Soc., 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," Org. 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. Analvsis of Mixtures Without Prior Separation as Illustrated for Estrogens," J. Amer. Chem. Soc., 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, INTSUM. A Data Interpretation and Summary Program as Applied to the Collected Mass Spectra of Estrogenic Steroids," Tetrahedron, submitted. D. H. Smith, "Mass Spectrometry," Chapter X in Guide to Modern Methods of Instrumentatl Analysis, T. H. Gouw, Ed., Wiley-Interscience, New Yerl, 1972. PHS -398 Page Rev. 2-69 GPO: 1964 0 350.460 SECTION I! — PRIVILEGED COMMUNICATION 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 general format for each person.) NAME TITLE BIRTHDATE (Mo., Day, Yr.) Sridharan, Natesa S. Research Associate 10~2-h6 PLACE OF BIRTH (City, State, Country) PRESENT NATIONALITY (If non-U.S. citizen, SEX indicate kind of visa and expiration date) Madras, India India; pending permanent residerlce YX] Mate (Female EOUCATION (Begin with baccalaureate training and include postdoctoral} YEAR SCIENTIFIC INSTITUTION AND LOCATION DEGREE CONFERRED FIELD Indian Institute of Technology, Madras, Bachelor of India Technology 1967 Electrical Engineering State University of New York, Stony Brook | M.S. 1969 Computer Science Ph.D. 1971 Computer Science HONORS University Fellow 1968-1971 SUNY Stony Brook Graduate Assistant 1967-1968 SUNY Stony Brook emens'Award (awarded for top rank . An in Eisctrigal Engineering 1967 ITT Madras yoerens, Merit Sehoal arship- { MAJOR RESEARCH INTEREST ROLE IN PROBS SED PROJECT Computer Applications in Chemistry Research Associate and Medicine RESEARCH SUPPORT (See instructions) RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting with present position, list training and experience relevant to area of project List alf or most representative publications, Do not exceed 3 pages for each individual.) i97l-present Research Associate, Heuristic Programming Project, Stanford University 1970-1971 Consultant, IAC Computer Company, Long Island, N.Y. "Heuristic Theory Formation: Data Interpretation and Rule Formation". Machine Intelligence, Volume VII, 1972. (Co-Author). "An Application of Artificial Intelligence to Organic Chemical Synthesis” Doctoral Dissertation, SUNY StonyBrook, August, 1971. RHS-398 Rev. 3-7C