Leifer, A. D.
Name: ALEIFER Project: PREMI
Department: Psychiatry

Project Description: Through July 31, 1969, I will use ACME for data analysis
only. Perhaps I will enter permanent data files into ACME during this
period. The data analysis that is planned now will consist of calculation
of means, standard deviations, slopes, correlations, t-tests, and analyses
of variance.

The project for which this data analysis is being done is a long-
term study (five years) of the effects of temporary separation during
the early post-partum period on maternal behavior and subsequent infant
development. The study includes as subjects both premature and fullterm
infants and their mothers and fathers. The data which will be analyzed
under my account is that obtained from time-sampling observations of
mother and infant during routine caretaking at home and in the Stanford
Hospital. Many other measures of the mother, father, and infant are taken
by others involved in the project. Much of this data will also be
analyzed on ACME, but under P. Herbert Leiderman's account. Principal
investigators for this project are P. Herbert Leiderman, Department of
Psychiatry, and Clifford R. Barnett, Departments of Anthropology and of
Pediatrics and Human Development. The project is supported by grants
from NICHD and from the Grant Foundation, New York, New York.

Currently, two reports of the results of the mother-infant observations
are being completed, one for submission to Science and one for presentation
at the March meetings of the Society for Research in Child Development.

Data analysis for these papers was done on ACME, but I do not believe it
accurate to say that the papers are “based on my use of ACME", However,
if you should want more complete titles, etc., please ask for them.

129
a he OVE 2
erany No. PROOSLL-O%4

Section ifl-b

Levine, R. L.
Name: RLLEVINE Project: CPS
Department: Pediatrics - 5352

Project Description: (A complete project description was submitted to the
Medical Scientist Training Program Committee.)

The project, 'Carbamyl Phosphate Synthetase in the Mammaliam
Pyrimidine Pathway’, will hopefully form the basis of a thesis under-
taken as a Medical Scientist Trainee of the NIH. Stipend support comes
from the NTH but leboratory space and research expenses are provided
by my preceptor, Dr. Norman Kretchmer.

Tne purpose of the initisl investigations (in progress six months)
is to isolate and purify the carbamyl phosphate synthetase involved in
fetal pyrimidine synthesis. This enzyme is apparently distinct from
that providing carbamyl phosphate for the urea cycle, whose enzymatic
activities appear later in gestation than the de novo pyrimidine
activities. _

The major work thus far has been on development of a rapid simple
assay for the enzyme. This work will continue, probably to July 31, 1969
and beyond. Lack of an acceptable assay has hampered work in the field
for years. My primary use of ACME hes been to evaluate and process data
obtained during assays. There is no question that without ACME asssitance
the already burdensome assay work would become intolerable.

It is expected that as work with the purification progresses, we
will examine possible regulatory and control mechanisms in which this

enzyme may be important.

I may also become involved in another project with Dr. Kretchmer
which will use ACME services, but probably not until after July 31, 1969.

130
-

venu No. FROOSTL~O4

Section ITI-B

Tevinthal, BE. C.
Name: ELEVINT Project: MM/1L
Department: Genetics

Project Description: We are just initiating efforts to use ACME for photo-
interpretation and enchancement. The direct application is for the
1971 Mars Mariner Orbiter. The photointerpretation techniques will
be applicable to medical research problems as they have already been
at the Jet Propulsion Laboratory.

Liebes, 5S. Jd.
Name: § LIEBES Project: MS
Department: Genetics

Project Description: This project is directed toward the development and
application of techniques of high-spatial-resolution mass spectroscopy
to organic materials of biological interest. The current investigation
involves the use of focused radiation from a pulsed ruby laser to
vaporize portions of solid samples in the ionization chamber of a Bendix
Time-of-lFlight mass spectrometer. The plume of vaporized material is
ionized by electron bombardment and the time evaluation of the mass
spectra of these ions is monitored at a 10-kc/sec repetition rate.

The materials so far studied include amino acids, the nitrogenous
base constituents of DNA, samples of DNA, nucleohistone, lymphocytes,
fibroblasts, and red blood cells. We are moving now to the comparison
of normal versus abnormal blood and tissue samples.

The ACME computer facility serves the following important supportive
functicns:

L. Automation of data acquisition--in the conventional warmed
erucible mode of operation;

2. storage of all derived mass spectral data;

3. Manipulation and comparison of data--certain aspects of these
operations involve extensive use of the interactive television graphic
display;

ay Performance of analytical studies related to the interpretation

of data, the refinement of existing instrumentation, and the development
of new apparatus.

131
       

rant Na. Peo ug] AC4
poet TTB
Dorenson, M. Y.
Name: MUORENS Profect: REI
Department: Pharmacclogy
Project Description: A portion of the research wor this
laboratory is on the sheep heart enzyme, ase. Investi-

gations are being made on the binding of
the enzyme. It is hoped that from these
on the molecular mechanisms by which this enzyme
metabolism are controlled and regulated in vive.
involved chromatography on G-25 Sephadex columns which
brated with the radioactive ligsnd. Jn order for ¢ cho
large numbers of columns must be run. Statistice’ unelyses

   

Lite
Will ne gained
y oeroohydrate
nel:

    

 

rool radlo-
3} erminatioans

proveln concentrations

 

 

activity present; (2) specific activity of 1.
of units of enzyme activity; (4) determinations
and specific activities; (5) and binding snd the stardard deyvis:ions
‘nvolved. In addition, the date are summarized and related to the
concentrations of unbound ligands. If the computer was not used for these
ealculations, the information to be gained would be difficult to compile
and the research work would be slowed considersbly.

 

 

 

132
ge BN IO" 11-04

Section iii-s

Luetsener, J. A.
Name: JLUBTSC Project: Bloodpr
Department: Medicine - Metabolic Research

Project Description: Our research project, supported by the USPHS (AM-03062) ,
deals with the secretion and metabolism of adrenal hormones. Various
steroid hormones, catecholamines, and trophic hormones are measured under
different conditions of sodium loading or sodium depletion. We attempt
to define and relate groups of measurements, which assist in the identi-
fication of curable forms of hypertension.

The ACME system is used in this project in several ways:

(1) To assist in the calculation of laboratory data, involving
difficult procedures, such as the double isotope derivative method,
which requires solution of simultaneous equations.

(2) Interpretation of data: (a) Simulation of complex systems
(for example, the study of reactions in which substrate and enzyme
concentrations are regulated by different systems and may vary inde-
pendently; or distribution and metabolism of hormones). (b) Statistical
analysis (comparison of means and variance of different groups, or
correlations between different observation). (c) Analysis of clinical
information (the sssociation between different observations, or the
effects of drugs, diets, etc.).

(3) Data files are used to store information at various stages of
a sequential process, and for collection and analysis of the large
amount of clinical and laboratory data which accumulates during a long
investigation.

(4) The computer has been used extensively in research training

of Fellows and staff, first in principles and techniques of computer
used, and subsequently in practical applications.

153
BOCA LL -O%

eSATA.

Section III-B

Lumb 2 J . R °
Name: JLUMB Project: C-TUMOR
Department: Medicine - Micro

Project Description: The purpose of this project is the biochemical charac-
terization of alkaline phosphatase of thymic lymphomas in C57B1 mice.
This enzyme does not occur in normal thymic lymphocytes, These lymphomas
are known to be induced by viruses. This investigation is to determine
whether the information for this enzyme is contained in the virus or
is cellular. This is being done by characterizing the enzyme biochemically
and comparing these results to those found in embryo thymuses and other
normal organs. ACME is used for statistical interpretation of the
results.

Luzzatti, L.
Name: LLUZZAT Project: GRAGSON
Department: Pediatrics

Project Description: The computer has been used to study a family with a
chromosomal mosaicism in % generations. Measurements of involved
chromosome pairs from affected individuals and normal controls were
entered, and means, standard deviations and percentage differences cal-
culated. Distribution curves and three-dimensional histograms to
classify different cell lines were also done by the computer. This
program is now completed and the majority of the files will be deleted.

At present, the computer is used to store information on history,
physical findings and diagnosis on patients with congenital defects.
For each patient, a set of anthropometric measurements and dermatogly-
phic ratterns will also be entered, Our goal is to provide means for
correiation of presence of major or minor congenital defects among
sach other and in relationship to the pregnancy and family histories.
Clustering of certain anomalies in a given patient defines a certain
phenotypic expression or "syndrome". The computer should be able to
provide a "diagnosis" when the eppropriate set of symptoms is presented,
and new syndromes may be further defined by specific clustering of
symptoms. The basic information on patients is already programmed and
stored; the historical data have been programmed but have not been
stored as yet. We are presently developing a program for storage of the
pnysical findings, anthropometry and dermatoglyphics. Information
obtained from this program wiil have a significant educational value for
medical students and house officers in addition to providing clues for
investigation.

134
Soane’ ac, FROCGLL-0%

Section iTIT-5

MacPherson, L.

Name:

LMAC PHE Project: META

Department: Psychiatry (Veterans Administration)

Project Description: PROPOSAL AND METHOD OF STUDY. We plan to investigate

the significance of the CNV and aspects of the MP studying their
similarities, differences, interrelationships, and relationships to
mental states such as selective attention and expectancy. Healthy
college student volunteers will serve as subjects. No drugs will be
given and no risk to participants will accrue. We will proceed in

an explorative fashion with pilot studies, hoping that as possible
avenues of investigation sre outlined, more difinitive experiments with
larger population samples will take shape. We plan to start with the
following study.

Ss! AEP will be obteined under the following experimental conditions.

1. Short auditory stimulus presented repetitively and timed
randomly. (To obtein AEP evoked by the auditory stimulus.)

2. S presses button randomly whenever he desires. (To obtain
MP associated with muscle contraction.)

3.6 S presses button immediately after hearing randomly presented
tone. (To obtain averaged EEG produced in combination by the AEP to
the tone and the MP when S attends to an autside command. )

4, S presses button randomly whenever he desires. This produces
a tone. (To obtain FEG as in condition #3 except that S is not paying
attention to any outside commands.)

5. § hears a tone (conditional stimulus) and when two seconds
later another tone appears (imperative stimulus), S presses button
quickiy. (To obtain the type of CNV that was reported by Walter.)

The averaged EEG potentials of these conditions will be analyzed
and compared with eech other in order to ascertain which stimuli produce
which potential changes under which conditions and in order to elucidate
whether and how the CNV reported in the literature is related to the MP.

IMPLICATIONS. The importance of the proposed work of larger scope
lies in development of techniques for the concrete electrophysiologic
measurement of psychologic states of the mind. Already such related
methods have demonstrated surprising corresondence between cerebral
ARP findings and mental states of attention, expectancy, conditioning,
habituation, meaningfulness, and levels of certainty. The experiment

135
Srant fo. FEOO*1]
L-B

bi
ht

Section

MacPherson, L. (cont.)

LMAC PHE Project: META

Department: Psychiatry (Veterans Administration)

Project Description: described in more detail could clarify the relationship

betwen the MP and the CNV. Since muscle activity (e.g., pressing of
switches) is widely used as an indicator of S's intent or state of mind,
elucidation of the relationship between CNV and MP is needed.

REFERENCES

1. Caspers, H., in The Nature of Sleep (Churchill, London, 1961).

Cs Gilden, L. et. al., Electroenceph. Clin. Neurophysiol.,

20:433-438, 1966.

 

Be Rowland, V. and Goldstone, M., Electroenceph. Clin.
Neurophysiol. (1963).

yy Rusinov, V. S., Electroenceph. Clin. Neurophysiol., Supp
No. 13, 1960.

De Shvets, T. B., Conf. Electrophysiclogy of Higher Nervous
Activity, Moscow, 1958.

6. Walter, W. G., Nature, 203:380-384, 1964.

maPety, RH,

RMAFFLY Project: Code

norptment: Medicine (Veterans Administration)

+. Description: Under study is active sodium transport by the toad
bladder. We correlate three variables: short circuit current, CQs
production and ClYoOo proudction. The computer is used to calculate
the variables and to interrelate them, and to perform statistical
analyses,

At the V.A. Hospital I plan to collect date on all patients with
elevation of blood urea nitrogen and all with decreased serum sodium
concentration and to usé the computer to find out the predictive value
of s variety of test and procedures and laboratory data.

136
oven. fe. BROOTT1-0%
Section T1I-B

Mesel., E.
Name: EMESEL Project: DOGLAP
Department: Pediatrics

Project Description: One of the parameters to be derived from indicator
dilution measurements of pulmonary blood flow is the “impulse response",
which is essentially the distribution of transit times of particles
through the lungs. If ci(t) represents the dye concentrations in the
right heart following injection of a bolus of dye at t=O and Co(t)
represents the concentration in the left heart, then the impulse
response h(t) is described by the equation:

Replacing the integral with a summation over equally spaced intervals
of time:

n

Co(n) = )° h(i)ci(n-i)

L=O0

Thus a program can be written for a digital computer which solves
for the function h(t) when given the values for Ci(t) and Co(t)

However, a simple straightforward solution yields an impulse
response which is hopelessly disrupted by artifacts in the collected
data. A technique must be employed which somehow filters the data.
Several possible methods are known; one has in fact been successfully
used. The program was executed on the Burroughs 5500, a machine which
has twelve significant figures in regular precision and twenty-four
with double precision. A similar program attempted in ACME accumulated
so mech error during execution that it proved useless. Thus if we are
to acheive our goal using ACME, we must somehow obtain greater precision
than ig now available. Our current efforts are directed at this
problem of insufficient precision.

137
cran. No. £ROO1L1-04
Section III-B

Mesel, E.
Name: EMESEL Project: VSD
Department: Pediatrics

Project Description: Project VSD is concerned with blood flow through
ventricular septal defects (VSD) surgically produced in dogs. Two
major sets of comparisons are made: the pattern of flow through the
VSD is compared with the pattern of differential pressure between the
left and right ventricles and with the electrocardiogram (ecg); and
and flow measured by an electromagnetic flow probe (which we consider
a primary standard) is compared with flow measured by other techniques
used on people (Fick, dye dilution).

During the experiment, VSD flow, left and right ventricular pressures,
and the ecg are recorded on tape. The more interesting data are selected

for A to D conversion and for computation of the differential pressure

by program WORKHORSE. Program LISTING lists digitized data, which, when

graphed, permits comparison of the pattern of flow with the pattern of
differential pressure. As might be expected, we have found that these
patterns are very similar even under varying conditions (e.g., ectopic
beats), with flow slightly delayed with respect to pressure. Program
eathlog produces a file which summarizes all our VSD experiments.

Future effort will be directed towards the incorporation and use

of programs developed in project carcat for pattern recognition of
pressure and flow contours.

138
erent No. FRCOZ10,.-05

Section ITI-B

Mesel, E.
Name: EMESEL Project: CLINIC
Department: Pediatrics

Project Description: The object of this project was to store patient identi-
fication information, and disgnoses obtained at each step in the course
of illmess (clinical - OPD or IPD, cardiac catheterization, surgery,
autopsy) in ACME files. This work was patient-service oriented but had
several experimental aspects such as the structuring of the filing
schemes to permit rapid access (while conserving the amount of file
space utilized), and the utilization of the stored information for
hospital planning purpose, evaluation of patient survival with different
modes of therapy, etc. Plans are to discontinue this project until
such time as adequate clerical assistance is available to implement the
filing system.

Mesel, E.

Name: EMESEL Project: CARCAT

Department: Pediatrics

Project Description: Project “carcat" analyzes cardiac catheterization
pressure tracings in children. From catheters in the right and left
heart, pressure tracings to determine atrial, ventricular, arterial,
venous and wedge pressures. Currently the values in millimeter of
mercury are calculated for the a and wu waves, x and y troughs,
and mean pressures in the artia and great veins, for systolic and end-
diastolic pressures in the ventricles, for systolic, diastolic and
mean pressures in the great arteries, and for mean pressures for the
wedge positions. These values ere calculated immediately and printed
out ci the computer terminal in the catheterization room.

At this time, efforts are under way to improve and ascertain the
accuracy of the algorithms used in pattern recognition for atrial and
ventricular pressure tracings.

The basic data acquisition and analysis system that has been set
up will also be used to store data acquisition and analysis system that
has been set up will also be used to store data for additional calcu-
lations and for the preparation of reports. As data is accumulated in
storage from cardiac catheterizations and from other sources of clinical
information, it will be possible to analyze large amounts in elinical
data rapidly using the ACME computer. Research into methods of storing
and recalling data for analysis of clinical information will be an
important part of our future efforts.

159
want No. FROOSL2 -O3

Section III -5b
Milier, R. P.
Name: R_MILLER Project: TOSTAT

Department: Preventive Medicine

Project Description: The Division of Biostatistics, Department of Preventive
Medicine, provides biostatistical consulting to persons doing medical
research in the Stanford Medical Center and occasionally elsewhere, such
as Presbyterian Hospital in San Francisco. Some of the people who have
consulted us in the past years have been Dr. Ken Gardner, Dr. Yule,

Dr. Maffly, Dr. Hart of Infectuous Diseases.

The Division also trains postdoctoral fellows and some graduate
students in Statistics in biostatistical consulting. Investigations
of statistical methods may also be done by the staff, postdoctoral
fellows, or graduate students.

The computer is used in all these activities.

Monnin, L. M.

Name: L MONNIN Project: DISCRIM

Department: Speech and Hearing Sciences

Project Description: A study of the relationship of articulation and identi-
fication abilities of normal speaking and speech defective children.

Distorted speech stimuli will be presented to the subjects so that an
identification threshold can be estimated.

140
vant Ho. FROOZL1-03
Section Jil-B

Morris, 4S. Jd.
Name: SMORRIS Project: EXPT4
Department: Genetics

Project Description: I am using the 1800 to interface a Packard liquid
scintillation counter to the 360. This allows me to feed raw data
directly into the 360 where it can later be retrieved and digested. The
original interfacing work was done in lieu of a language requirement
for my PhD. The system will be used to analyze the incorporation of
radiolabeled amino acids into brain proteins.

 

See ACME Note TRA-1 for a full discription of the system.

VAL
cart No. FRCOZ1L1-03
Section JI1T-B8

Nall, M. L.
Name: L_NALL Project: PSORIASL
Department: Dermatology

Project Description: Psoriasis is a chronic, scaling skin disease of unknown
etiology, which affects approximately ug of the general population (no
accurate figures are available). It is a lifetime disorder which does
not take life, but indeed destroys it for all age groups.

The Department of Dermatology of the Stanford Medical School is a
world center for both clinical and laboratory investigations on psoriasis.
As one phase of the over-all Psoriasis Research Program, the Department is
engaged in a continuing investigation of the epidemiology of the disease.
A questionaire survey has been conducted from 1959 to date.

Presently, the Department is conducting Series IT, III, and IV of
its questionnaire survey; doing follow-up studies on the familial incidence
of psoriasis and the relationship of psoriasis to other diseases, i.e.,
arthritis, diabetes, throat infection (The findings from Series I, which
nad or) computerized on the 709O are now being handled by the 360/50
and 67.}.

We have applied to the National Research Council to participate in
their Twin Registry of Veterans, in order to utilize the twin method in
our study of the eticlogy of psoriasis. In addition, we are applying
to utilize their registry of veterans in a large scale epidemiology
investigation. Hopefully, both will be financed by an NIH grant. The
application of ACME to the computerized phase of our findings has been
indicated in all grant protocols.

Lye
cont Ho. FROOZ) 1-03
Section LiI-B

Nali, M. L.
Name: L_NALL Project: MYCOSIS
Department: Dermatology

Project, Description: Mycosis fungoides is a fatal skin disease of unknown
etiology. Various chemotherapeutic agents (i.e., nitrogen mustard,
steroids, etc.) have been utilized to abate this disease, but the x-ray
and elctron beam are the only techniques that have proven effective in
producing remissions. The Stanford School of Medicine and the
Massachusetts General Hospital are the only facilities in this country,
who have appLied the beam in treating mycosis fungoides; although
recently the Varian Company has developed smaller accelerators which
will be used in other hospitals. ,

Drs. Harold Schneidman and Williem Watson of the Dermatology
Department conducted a retrospective study on the effect of the electron
beam in comparison to other methods of treatment. In a pilot study of
51 mycosis patients (treated at the Stanford Medical Center in the
Radiology Department) , the investigators developed a data gathering form.
The coded information was keypunched and read into ACME as a data file,
which was computed via a number of input-output programs. Although no
paper has been published as yet (since the study is in progress), the
results of the pilot study were presented by Drs. Schneidman and Watson
at the annual Meeting of the American Academy of Dermatology in Chicago
in December. The investigators were able to learn from their preliminary
study that by applying the electron beam at an early stage of the mycosis
that longer periods of remission will result. This information is a
pioneering fact; albeit, more detailed studies will be forthcoming to
cubstantiste this early data.

Dr. Schneidman has supported this effort from his personal funds
and plans to continue to do so. Thus, we are concerned in keeping our
CME costs st a minimal level.

144
rrant No. FROOS?1 -0%
Section I1i-B

Noble, E. P.

Name:

EPNOBLE _ Project: ALCOHOT

Department: Psychiatry

Project Description: We have been studying the effects of alcohol on the

Name:

De Ne

Proje

central nervous system of rodents. This study is supported by MH 14599
from the NIMH. A study of alcohol's effect on the pituitary adrenal
system is being studied in various inbred mouse strains. We are also
studying the effects of central nervous system lesions on alcohol
preference phenomenon in mice. Finally, the mechanism of central nervous
system adaptation to alcohol and other stressors is being considered.

Tt is our plan to continue the use of ACME facilities for the
period to July 41, 1969. This service has been extremely valuable and
has resulted in three publications based on its use.

Ll. Kakihana, R., Butte, J. C. and Noble, E. P., 1968. Effects of
goldthioglucose on alcohol consumption in C57BL mice. Life
Sciences 7: 825.

Zo Kakihana, R., Noble, E. P. and Butte, J. C., 1968. Corticosterone
response to ethanol in inbred strains of mice. Nature, 218: 360.

Be Noble, E. P., Silbergeld, S., Kopell, B., McKinney, W., Wittner,
W. K., and Butte, J. C., 1968. The effects of physiologic doses of

corticosteroid on catecholamine metabolism in man. J. Psychiat.
Res., 6: 159.

wW. N.

WNYE Project: STUDENT

-~rment: Medicine - Micro

et Description: Under this user name, several people in this department
have used this project for statistical calculations and bibliography
compilations. Several of the users have been graduate students of the
department or postdoctoral fellows. The bibliography compilation will
probably be published in the new Biochemistry Handbook by Dr. Kirschbaum.

144
Grant No. FROOSLL-0%
Section III-B

Payne, R. O.
Name: R_PAYNE Project: SERNAL
Department: Medicine - Hermatology

Project Description: The research is concerned with extending the classi-
fication of leukocyte and/or tissue antigens by serologic and genetic
analysis of specific human antisera. In the computer programs, 1)
donor-recipient pairs of individuals are selected for deliberate immuni-
zation to produce antisera and 2) the antisera are analyzed by comparing
their reactions with test cells in 2 x @ tables for associations between
them. The significant associations are calculated, and the frequency

of positive reactions are determined.

Pearson, M. L.
Name: MPEARSO Project: CTCOR
Department: Biochemistry

Project Description: The program is used to compute normalized chromatographic
elution profiles of viral SRNA. We have found that induction of lysogenic
bacteria results in the formation of a set of small molecular weight
ordered RNA'ts coded by phage A DNA. These RNA's have physical character-
istics similar to transfer RNA and may be intimately involved in genetic
control. The set of viral RNA's can be fractionated on benzoylated deae
columns. The computer normalizes the elution profiles of viral RNA's
to a constant total output RNA, allowing comparison of the relative amount
of each viral RNA from one column run to the next.

It is anticipated that future programs will be used to calculate

quench-corrected values of radioisotope activity in double-label
experiments, using data from a liquid scintillation counter.

145
rar. No. FROO3? 1-03
Section ITI-B
Petralli, J. K.
Name: JPETRAL Project: MED DATA
Department: Infectious Diseases
Project Description: A COMPUTER METHOD FOR IMPROVEMENT OF ANTIBIOTIC SENSI-
TIVITY DATA AND GUIDANCE IN THERAPY. J. K. Petralli*, 5. Wallis*®,

T. C. Merigan. Department of Medicine, Stanford University, School of
Medicine, Palo Alto, California.

 

To improve the quality of antibiotic sensitivity data (high potency
single disc method) and to guide the interpretation of results and
antibiotic selection a computer program has been developed. Clinical
information and zone sizes are entered each day on the IBM 360 time
sharing computer (which allows on-line continuous data generation). Each
zone size is compared with limits based on previous results and unusual
values are challenged for further study. This system rapidly detects
unusual organisms or Llatoratory error. The computer converts zone
sizes to resistant, intermediate, or sensitive and prints final reports
from its memory, Decreased potency of antibiotic disc is detected by
comparison of periodically determined mean zone sizes. Limits of
confidence of a single reading are established by review of zone sizes
observed with a standard organism tested on different occasions. Know-
ledge of antibiotic sensitivities of organisms isolated from a specific
site such as blood or urine will help to guide the selection of anti-
piotics before specific sensitivities are known. Such information is
of value in selection of antibiotics in treating rarely encountered
organisms with less well known sensitivity patterns or in selection
of alternate antibiotics when the first choice drug is hazardous. Yearly
comparison of antibiotic sensitivity patterns obtained will give infor-
mation about major trends and suggest appropriate changes in treatment
of various infections.

146
Grant Wo. FROCS1i-04
Section III-B

Porter, R. W.
Name: RWPORTER Project: ATC KIN
Department: Biochemistry

Project Description: Project ATC_KIN has been used for data processing in
the investigation of the steady-state kinetics of the enzyme, aspartate
transcarbamylase. The programs were written for curve-fitting the data
from different types of kinetics experiments. For example, program
"DataFit" employs a simple linear least squares fit to calculate the
initiel rate of reaction from the raw data, measured as amount of
radioactivity versus time of reaction, and converts the result to
standard units of specific enzyme activity, using units of concentration.

Other programs calculate the kinetic parameters using a linear
least squares fit for the reciprocal transformation, due to Lineweaver
and Burke, of the Michaelis-Menten equation. Another program, “Hyper-
Fit", was written to fit the non-linear, hyperbolic function of the
original Michaelis-Menten equation. The program employs a reiterative
procedure of trial-and-error testing for optimal fit. Trial values
for the two parameters of the Michaelis-Menten equation are tested for
minimizing the residual, and the procedure is reiterated to give a close
approximation of the best values.

This computational procedure was refined and optimized for speed,
and the program will compute the best values for the two parameters, to
an accuracy exceeding that of the data, in less than ten seconds of
computer time in a time-sharing environment. This approach proved to
be so successful that it was adapted for curve-fitting other, more
complex non-linear kinetic equations with more parameters. For example,
the non-linear equation describing substrate inhibition, with three
parameters, which does not give a simple linear reciprocal transformation,
has been employed directly, using this trial-and-error technique. In
addition, the family of hyperbolic curves described by the equation for
competitive inhibition, with three parameters, has been employed
suecessfully.

The greatest success of this technique has been the use of equations
sith four perameters for curve-fitting, such as the equations describing
non-competitive inhibition and parabolic competitive inhibition. With
correspondingly longer times for calculation, these programs have pro-
vided quantitative support for the existence of certain reaction inter-
mediates in the pathway of this enzyme mechanism.

147
grant No. FROGS) -0%
Section III-B

Porter, R. W. (cont.)

Name: RWPORTER

Project: ATC_KIN

Department: Biochemistry

Project Description: These programs make special use of the on-Line
communication available with the ACME system, especially through the use

of options
results of
Biological
manuscript
manuscript

and operator-controlled branchpoints in the programs. The
these kinetic studies have been reported to The Journal of
Chemistry, where they will be published in Merch. The

for this report was prepared making extensive use of the
editing facilities of ACME. The authors of the report are

Robert W. Porter, Michael O Modebe, and George R. Stark, and the title
is "Aspartate Transcarbamylase: Kinetic Studies of the Catalytic

Subunic"™.

148
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Section III-B

Reaven, G. M.
Name: G_REAVEN Project: DISPLAY
Department: Medicine

Project Description: We are interested in developing models of glucose,
insulin and triglyceride kinetics as related to diabetes mellitus and
atherosclerosis. Clinical data obtained from tracer studies are analyzed
by the ACME computer through five stages of development. The project
display includes the third and fourth stage. In the third stage, the
program PEEL automatically obtains the parameters for a linear sum of
exponentials and the program SKINNER obtains parameters which are the
constant coefficients of a system of linear differential equations. The
results are used for the fourth stage. In this phase, the parameters
are used for calculation of a theoretical curve which is displayed on a
CRT. It is then compared with data which also appears on the CRI. The
results of PEEL and SKINNER get us into the "ball park" and we change
parameters until we obtain a satisfactory visual fit. In this phase
we use the programs RUNGCURV, DATA, TDATA and berman.

We are in the process of preparing two manuscripts in which the
results are based on the above program support. The first paper is a
mathematical model of insulin distribution in man in vivo and the second
paper is a description of the use of on Line display procedure for
determining physiological models of metabolic processes. We are now
perforntee. similar analysis with respect to triglyceride metabolism and
are extending the insulin work. We expect to use the above procedures
the entire year and expect to extend stage 4 and develop stage 5 for
analysis of nonlinear metabolic models.

 

 

149
want No. PROO3L.-0%

Section TIT-B

Reaven, G. M.
Name: G_REAVEN Project: FIT
Department: Medicine

Project Description: (See discussion in Project DISPLAY.) The final phase
is at the present being developed. The results of simulation in stage
4 is to be statistically evaluated to see if the parameters obtained do
not violate the statistical limitations of the data. At the moment,
we are doing this is a crude manner at the Computation Center. However,
the most satisfactory results are obtained if the statistical evaluation
is coupled to stage 4. We plan to use nonlinear regression techniques to
evaluate these parameters. We have developed four programs for this
procedure; they are RUNGPOW, sPOWELL, COVARE and EXPOPOW.

Reaven, G. M.

Name: G_REAVEN Project: PAT DATA

Department: Medicine

Project Description: (See discussion in Project DISPLAY.) This project

includes Stage 1 and Stage 2. Stage 1 and Stage 2 are support programs
for Stages 3, 4, and 5. In Stage 1, serum endogenous insulin is bio-
logically assayed by the program INSULIN. The program TGCONRAD determines
triglyceride concentration and the program DOUBLE estimates counts from
double label experiments. The final program in this phase WEIGHT estimates
weights of date points for future statistical analysis. The second stage
consists of statistical support programs for evaluation of the results

£ Stage 1. The programs used in this phase are TEATEST, RAT, NOVA, CORL,
und REGRESS.

Qar research activities also include procedures to determine weight
“.tterns of patients. The programs involved in this aspect are BODYCOMP

ad BODYFAT.
Re.be a, J. As
Name: J_RBEITAN Project: INDIRECT

Department: Anesthesia
Project Description: We are processing cardiac internal timings collected

by non-invasive, indirect techniques in order to monitor the contractile
state of the heart under varying Loads and drugs.

150
aeknt No. PROCS] 1-04
Section III-B

Reynolds, W. E.
Name: WEREYNOL Project: $007
Department: Genetics

Project Description: This project supports the basic development of automation
in computer-mass spectrometer instrumentation systems. This worker is
an instrumentation engineer, hence the remarks about the biological aspects
will be brief.

The mass spectrometer has become a powerful tool in the elucidation
of organic molecules. This is of great interest in the biochemistry field
and in the case of DNA and related structures to the Genetics Department.
Since the basic principles involved are common to at least the Genetics
Department and Organic Chemistry, the physical instruments and location
are sometimes shered. This is the case for this project. Hence the
efforts of this project span over 5 mass spectrometers in 3 diverse loca-
tions on the Stanford campus.

The technical development consists in the origination of instrumenta-
tion concepts, and realization, in both hardware and software, complete
operating systems.

These systems are intended to automate the mass spectrometer (low
resolution Bendix t-o-f, Finnigen quadrupoles, Atlas CH-4 and a high
resolution AEI MS-9) to provide the following benefits to the biological
user-researcher:

Savings of the researcher's time in instrument operation and
data reduction.

Improve the quality of the data.

Dyprove the presentation of the data.

Foster computer files of pertinent data.
This is being accomplished by basic research and development in the
-yplication of computers, both dedicated and time shared to the field

of computer-instrument integration.

The ACME system is being used by this user both as the final computer
in the automated system and as an engineering design aid to achieve the
final systems.

L51
vest Mo. FROOS11-03
section ITI-B
Reynoids, W. E. (cont.)
Name: WEREYNOL Project: S007
Department: Genetics
Project Description: Publication - COMPUTER CONTROL OF MASS ANALYZERS. A
paper given, and published in the proceedings of, The Sixteenth Annual
Conference on Mass Spectrometry and Allied Topics. (May 1968, Pittsburg,
Pa.) (ASTM Committee E-14).
Reynolds, W. E.
Name: WEREYNOL Project: TEXTS
Department: Genetics
Project Description: This is a text management project to support general
engineering efforts in instrumentation. The project supported is:
W.E.REYNOLDS.S007. "TEXTS contains commercial technical data end
information retrieval programs.
Robertson, W.
Name: W_ROBERT Project: UGAG
Department: Pediatrics
Project Description: (1) Data on urinary analyses of glycosaminoglycans
soth on patients and normal individuals will be entered. The curve
relating concentrations to age in normal children will be developed. The
values of groups of children with different diseases will then be compared
aith normals to discover which diseases lead to abnormal excretion.
(2) Analytical data on immunoglobulin concentrations in sera from
atients with a variety of immunologic diseases will be entered and

correlations developed with the clinical state of the patient and therapy.

(3) Data on the binding of ligands to macromolecules, e.g., cortisol
to hyaluronic acid will be used to determine association constants.

152
vant Neo. FROO311-04
Section JTiI-B

Rosenberg, L. T.
Name: LL ROSENB Project: ALEXINE
Department: Medicine - Micro

Project Description: We are studying levels of serum complement in mice using
ACME to carry out the appropriate statistical analyses and calculations.
We are storing accumulated data on large numbers of mice of diverse pedigree.
Using ACME facilitates data retrieval.

Rosenthal, W. S.
Name: W_ROSENT Project: RESEARCH
Department: Medical Student - Speech and Hearing Science

Project Description: I am using the computer essentially for statistical
analysis of data in connection with various experimental studies in
speech and language pathology and normal speech perception. These
studies include research in effectiveness of stuttering therapy, speech
and auditory perception in aphasic children, and normal speech perception
in adults and children. Plans through July 31, 1969 include continuation
of above usage as well as possible use of the computer in a language
perception simulation program.

155