U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE

     PUBLIC HEALTH SE

   NATIONAL INSTITUTES OF HEALTH

SPECIALRESEARCHRESOURCEANNUALREPORT

Grant Number FR-Wll-03

     ACME

August 1, 1968 toJuly31, 1969

Joshua Lederberg, Ph.D., Principal Investigator
Stanford University School of Medicine


U. S. DEPARTMENT OF HEALTH, EDIJCATION, AND WELFARE

      PUBLIC HEALTH SERVICE

   NATIONAL INSTITUTES OF HEALTH

SPECIAL RESEARCH RESOURCE ANNUAL REPORT

Report Period; (same as current 12-month    Grant No.
              budget period)
From: August 1, 1968  To: July 31, 1969         FR 00311-03

Resource Title             Resource Address         Resource Tel. No.
                  Stanford University     (415) 321-1200
Advanced Computer for       School of Medicine          Ext. 5818
MEdical Research (ACME)    Palo Alto, California
Principal Investigator      Title              Academic Dept.
Lederberg, Joshua           Professor              Genetics

Grantee Institution       Type of Institution      Investigator's
                                              Tel. No.
Stanford University       Private University
School of Medicine                     (415) 321-2300

              1             I     Ext. 5049
Name of Institution's Special Research Resource Advisory Committee:

Computer Policy Committee

Membership of Special Research Resource Advisory Committee
(Indicate Chairman)

Name            Title

Department

Institution

see next page

Typed Name and Title of Principal Investigator 7 Signature
Joshua Lederberg, Professor
Typed Name and Title of Grantee Institution    Signature
Official

Date



Date

1


Stanford University
Advanced Computer for Medical

Grant No. FR 00311-03

TABLE OF COWI'ENTS

Special Research Resource
   Annual Report

Section I:  Resource Operations

   A.   General Description of Resource Operation       4

    B.   Summary of Resource Usage                 27

    C.   Resource Equipment List                   66

    D.   Summary of Publications                   72

Section II:  Resource Finances


    A.   Summary of Resource Expenditures

    B.   Summary of Resource Funding

    C.   Expenditure Details - Direct Costs

    D.   Budget Explanation - Justification

Section III:  Project Descriptions

   A.   Core Research Project Descriptions

    B.   Individual User Project Descriptions

76

77
78
82

85
88

3



Grant No. FR00311-03
Section I-A

General Description of Resource Operation

  Most of this third and final year of the original ACME grant period has

been spent implementing changes and adjustments required to make the ACME system

a useful and productive unit for the Stanford Medical School.  Currently ACME

service hours, whenever feasible, are 7:00 a.m. to 5:OO p.m., and 6:30 p.m. until

midnight.  Hardware reliability since the last report has improved significantly.

We are, however, still experiencing an average of two hardware failures a week

and are further implementing recovery procedures for all hardware errors where

even a minimal chance exists of achieving proper recovery.  Changes have been

made by IBM in both the 270X and 27OY data-acquisition hardware and in the 1800

subsidiary computer's interface hardware to the 360.  The changes, together with

a better understanding of the data-acquisition devices, have resulted in a

reliability comparable to that of the files and the central processing unit.

The current bottleneck in the overall system is the speed of the large-core
memories (8 miscrosecond cycle time).  This could be improved, without any soft-

ware changes by providing more high-speed memory.  The shortage of fast-core

memory has been aggravated by changing options within the IBM operating system.

To obtain greater reliability, we have shifted to the MVT option of os/360.

Studies and discussions with IBM have led us to believe we will have fewer

errors in using MVT.  The last three months of operation of the MVT-based system

have proven this judgement to be correct; we have had few failures of OS interrupt

processing and partitioning.  These are the areas of IBM's operating system

upon which we rely most heavily.  Our experience with the processors, such as

the Fortran compiler under the operating system, are not that favorable.

4


Grant No. FROOTU-03
Section I-A

   Hardware changes:  We added a second 2314 disk unit in December; this

second unit is now already 50 per cent filled with user data.  This means that

our user file capacity has grown from approximately 127 million bytes to

263.6 million bytes with a corresponding--and sometimes too rapid--increase in

usage.

We also added slowspeed paper tape equipment on the 1800 in order to service

instrumentation needs when data rate and duty cycle make an experiment impractical

for on-line data acquisction.

  The 1800 can now timeshare 16 user lines; this is generally sufficient for

four to five users' data moving simultaneously over the lines.  We are experi-

menting to determine how much the load-factor can be increased without affecting

our capability to provide reliable service.

   The 27OY and 2701 service has been successfully provided to remote sites

with a 20,000 sample-per-second transmission speed.  The data path, that is the

size of a sample, on the 1800 and the 2701 is 16 bits wide; the data path on

the 27OY is 8 bits wide.

   More need for 1800 facilities seems to exist and can be handled within the

current software design by increasing the amount of core memory storage available

in the 1800.  Currently a limitation of about 6000 samples per second aggregate

net-data rate exists in the communication interface from the 1800 to the 360.

Software developments:

   Implementation of "external procedures".  This permits programs and sub-

routines tc be shared by users in a modular way and also removes the limit on

program size in the ACME system other than that of total hardware core and file


size.  Of course practical limitations due to the speed of the processor remain.

5


Grant No. FRO0311 -03
Section I-A

The direct input/output facility of PL/I has been implemented and enables

users to write significant information retrieval and patient-record programs

without excessive search time.  Organization of these files is a problem for

which professional assistance is frequently required.  Regina Frey, of the ACME

staff, is available to assist with the design and layout of problems of this

nature.

PROTECT FILE statements have been implemented to provide data-set protection

to users who wish it.

A non-PL form of file has been implemented-- the text file--which provides

for convenient editing of reports, memorandum,  and programs themselves under

full program control.

  A number of major internal changes were made to the file system. The first

change eliminated the necessity for copying the index of a file into a temporary

location on a disk when the file is opened.  This saved space on the disks, removed

the limitation on the number of files which could be opened simultaneously, and

greatly reduced the time required to open and close files. A change to the

hardware format of the file blocks allows checking the ownership of a block in

the channel program without reading the block into core. As a result the channel

time required to write a block was reduced by one-half (see ACME Note FIO appended

to this section).

The computational facilities of the system have been increased by providing

double precision arithmetic.  The seven-digit precision of the IBM 360 is generally

adequate, but a few'users were seriously hampered by the lack of more precision

in the ACNE system.  Double precision provides about 16-digit precision for

these users.

  Improvements to the PL/ACME: language include the INITIAL attribute and the

capa'bility to write mutiple statements on one line.  Both these facilities can

decrease program writing time and program compile time.

6


Grant NO. F'RO:JJLL-0~j
Section I-A

   FREE and ALLOCATE statements pertaining to arrays were implemented to

give the user program control over the amount of memory he is using. This pro-

vides him a tool to minimize charges based on the amount of memory used, yet

permits him to take advantage of the very large potential memory capability

inherent in the ACME system.

  A number of new string functions round out the facilities provided in FL/I

and some work has been done to speed up the processing of string operators,

although much remains to be done in this area.

   A number of new programs now make it possible to do much file maintenance

while the system is on-line without interfering with users.  This has enhanced

our capability to respond to errors due to either software or hardware problems,

   We have continued our emphasis on guaranteeing all files stored on disk.

File integrity has been maintained through continued use of software redundancy

checks and by a number of analyzer and restoration utility programs.  Backup

files are created by nightly dumps of the disks to tape.

   Cur backing up of file stopage has proven to be most useful. No loss of

data occurred during the last year.  Four potentially disastrous failures did

happen.  Twice loss was prevented by the interlocks in the file system. The other

two times the damage was due to operator error, but full recovery was possible

from the backup files.

  Maintenance and development work on the library programs has had to be

retrenched, and is now going on at a somewhat lower level than we feel would

be benefYcia1 to the Stanford Medical School.  A list of the Library routines

is appended to this report.  Most of these are statistical in nature; a few

provide program editing and translation features.

   Our engineering group has installed and maintains 22 laboratory interfaces.

The group is occasionally engaged in the design of specialized instrumentation

7


Grant No. FRG0311-C3
Section I-A

to service specific medical requirements.  A new terminal switchboard has been

installed in the computer room to cope with the iarger frequency of user calls

and active terminals.

   We have been engaged in circuit and software development to make storage

displays manufactured by Tektronix and Hewlet t-Packard easily interfaceable

for ACME users.

   A small effort is underway to evaluate the cost and benefits of making a

continuous system modelling program (CSMP) available on ACME.  It appears that

model builders at Stanford would be greatly aided by an interactive facility.

Compatibility with batch versions will be important since ACME is not suitable

for large simulations.

  An assembler for the 1800 has been produced with PL/ACME. We expect to

cancel the card equipment presently on the 1800 and load the machine through

the 360.  This assembly concept is being studied to determine the methods and

benefits of providing assembler services for small computers that are connected

to ACME.  This could increase their research duty cycle and make smaller con-

figuration feasible.  A more unified assembly language could also be an aid in

obtaining greater independence from a particular manufacturer by increasing

software transparency.

A fair amount of effort has gone into the accounting programs in order to

prepare for the new recharge policy.

Operating Policies and Procedures

  System reliability has become the primary goal during the last year. This

is especially important since some of our users collect instrumentation data

on a real-time basis and have no protective backup device.  Detailed records

are kept of the systems operation.  Every failure-software, hardware, or power--is

8


Grant No. FROO311-03
Section S-A

logged, analyzed, and discussed in the weekly st*aff meeting in an effort to

devise means of preventing recurrence.  Five bac'kup systems are kept at all times

i.n order to prevent errors being introduced during development of software which

mi.ght sffect daily operations.

   Flexibi!ity is the key to success to operations in a research computer

rnvironlrent.  This is especially true at ACME. The system is constantly upgraded

(both software and hardware --including computer input/output devices and in-house

designed and built interface equipment).

  We have established an enforced system backup to protect user data and

system disk packs.  All user data packs are dumped to tape three times a week.


Two sets of daily tapes are rotated each week; seven weekly' sets are rotated

Pve ry month.  The first set of weekly tapes each month is saved permanently, and

repl.acPit wi!;h a new set, of tapes.

   All operating procedures are documented by ACME Notes which are distributed

,to the ACME staff.

   The graph showing hardware-and software downtime is presented on the next


pge.  This graph shows utilization.  Although considerable detail of this

ut;ilizati.on is given in Section I-B of this report,  it is appropriate at this

point to note some of the highlights of utilization of the ACME system.  There

has been an up'trend ever since the basic software was stabilized enough to

present meaningful statistics.  After the sharp dips in utilization as the result

fJ-,f hardwa.re difficulties toward the end of the previous budget year, the rate

'7; inf2re.i.:;2 climbed' more rapidly as the user community gained confidence in the

system's reliability.  The dip at the end of calendar year 1968 resulted from

the announcement of user charges as well as seasonal factors of the end of

quarter and year-end holidays.

9


G:an? No. FRM!":: -3:
S&iori i-C

ACME Note

Monthly Usage at ACME

Absolute maxima of terminal hours per month: 10,170 (30 !`np.;. 30 days, 1;. 5 hours pr'~ bay:. Absoicte ma*`. .
of terminal page minutes per month: 7,866,0@J (380 pages, 30 days. 11 5 I)olii': d:`r day!.

Revision of AU-10 dated April 24, 1969.
Dist: Staff/All

!G


  Utilization as expressed in page minui;es :c+=pr,'~+,Y an aLI. time high of
                                                   L - ..bJL^~ ,L

2,260,[596 in the accounting period .April 17, 19: ,p ./ ,)l rough J&3 y 16, I-969 e k1.y

.%9,364 page minutes were used by the ACFE staff z~,,i :isErs  accounted for almost

with :KL.h grants v,l~:ich are presently exs:iq>t from users charges because they

have non-compe,ting renewal grants.

i;,!)(>`y'i~.J~l oi';,
I. '       r:onctar!t, communication with the user is vital,  The lightbox on the

I,SC'l i : +?~mxll~li,S pro,vide both system and operati.ons information to him.  Da i-Ly

;p3cial by)sdcas:;.s announce current system e-fents that may 8ffec-L users. An

iilfO~W~.~:`L USf?3r is a !itippy USC?T.

   I&w features not yet documented in the manual are described in .ACME iJser


ii] 0 .[. I" :; "

XME hours are from 7:CO a.m. to 5:OC p.m. ar,d 6:30 p.m. to midnight, dail.po

i;erjeral.  s r-
     hatern development work.and file maintenance, and four hours a week of

Exceptions may be made to use the period from 3:30 to 5:00 p.m. and 1O:OC .p.m.

if.i: rnidr;.'_;$tt when urgent system work requires it.

    `K? L ! I  R r'hortsge of terminal lines develops, the following priorities are


yj:;e r.;e&:

.F ki^s t T)r ior-. ty :  Users signed up for realtime experiments.

;~;;:'->:::i x, _ "
    , rlc!-?:LetJ:  Ail other known users, queued in first-in, first-out
              order.

`fp i.rci I-`-f iJ>yity:  "~Jn'known" users (i.e., medical student terminals), only
            ~2' there are free terminal lines.


The ACME TV display

                                              Gralit &jo . FE:gO", 1 I.-(;" A
                                               Section I-A
                                                                       c


            is scheduled by a separate s ign-up sheet.

   The operator has control over real-time usage i-c irisure that the required

response rates are not impacted by excessive usage,  An effort is being made

to train our own operators,  including recruits frcm the local community.

  A Sanders 720 graphic display unit. (,
                     nrcvided by the Genetics Department)

al-lows the computer operator to obtain a list of users on the system at any

~~;iVWi moment.  It has increased our access to user status over the IBM typewriter

terminal by a X5-to-l ratio (from 150-second access to 10-second access).

   Our new switchboard has semi-automated the connecting of user terminals

L; ACME .  Formerly the user would telephone the computer room and request that

;1 %702 port be connected to his terminal.  Our new board requires the user onLy


YL ; :r'ess the button on the lightbox.  When the operator plugs an available port

5ilto the user's outlet, the indicator lights turn off.



ji$g ir;is-e:[*at j ye Changes
-_ .II-

   In this third year of the ACME project Joshua Lederberg, Ph.D., Professor,

                                   I

:?;2i Chairman, Department of Genetics, continued as Principal Investigator.   The

A(373 Policy Committee is drawn principally from the community of users in -t'ne

Xedic.:al School.  ACME is administered technically as a facility of the Stanford

!%itlp1tLat;.on Center.

   During the year covered in this Report, Paul Armer succeeded Edward Feigenbaltifl

;:s i):Lre:tor of the Stanford Computation Center.  Professor Feigenbaum is concen-

trating on his teaching and research in the Computer Science Department, but

`zoiit, il-il;::s z'? sei'de ACME as an advisor for computing techniques.  Gio Wiederhold


    

cont~ued as Associate Director of t'ne ACME Facility.

  !!uri.ng the early months of the current year the trial period of the

:;taai'ord Crjnrputetion Cer,ter Campus Facility attempting to market ACME: service

12


Grant No. FRO03 11-03
Section I-A

to non-Medical School users at Stanford was complete-l.. Since this service

offering did not attract enough utilization to cff:<+t the costs  to the Campus

Facility, their sharing of ACME costs was reduced substantially at the end

of November, 1968.  This support was reduce& to the incremental cost of the

bilk core for the balance of ACME's third year.  This reduced support caused

substantial rebudgeting of ACME funds as will b e  evFdent in the financial section

of this Report.

   User chargingbased on page minute utilization and file storage was implemented

in April, 1969.  The users were first notified of the impending charges in the

E'all of 1968 arld a first schedule of rates proposed to the Special Research

Resource Board in November, but it took until April to work out the details of

the charging mechanism.  It is too early to assess the full impact of this

policy change; but in general the Medical School Researchers are being quite

cooperative in coping with the additional paper work necessary to obtain the

administrative approvals and to request supplemental funding.  As might be

expected with the prospect of having to use their own research funds for compu-

tation, the asers are devoting considerable attention to improving the efficiency

of their program - especially in the use of disc storage.  We feel this is

important. The users are urged to consult with the ACME staff.  With more

el'ficient user programs ACE will be able to continue to serve promptly a growing


r:umber of users.

The following ACME schedule of rates for service was approved by SRRB by


Grant No. FR00311.-03
Section I-A

Effective Date

MARCH 21, 1969

Computer Services:
Memory utilization of IBM 360/5C system:

1.  Research Service-Real Time, high
   interaction rate              lb per page minute

2.  Research Service-routine terminals    2j4 per page minute

3.  Administrative and patient care ser-
  vices,  services to non-research users   3+ per page minute

File space utilization of IBM 2314 direct
Access Storage Facility           lO# per block of disk storage
                              per month

Consulting and Programming Services-ACME staff     no charge

ACME Education

ACME offers a beginning and an advanced course in PL/ACME programming.

'Ihe beginning course describes the ACME system, the use of the terminal, and the

IZ/ACME statements for terminal input and output, calculation, and filing. The

advanced course describes variation and options.  Real-time (1800) use is not

covered.

A beginning or advanced course requires three sessions of l-1/2 hours.

There are about ten students in a class.  Of the 130 beginning students taught

since July, 1968, 25 percent have 'been physicians, 30 percent students (medical,

graduate, undergraduate, and some high school students),  23 percent lab

tec1laicians and secretaries, and 20 percent other researchers, administrators

a nd 0 the L'S .  Since the teaching program began in 1966, there have been 742

st;!j.dents ( 59'1 beginning, 148 advanced) .

`IL !Z  t ! ::r rTt1t students generally plan to use ACME for statistical studies

r->n iarge g:roups of patients and for processing laboratory data.  Most realtime

tossers took the course sometime earlier.

14


Grant No. FR00311-03
Section I-A

  The response to the course is gratif;Cng.  Beg>.nners discover that they

can use a powerful machine.  Many sign up for %,`lie advanced course and recommend

the courses to their associates. Even students ' jl;:lrticularly medical students)
who do not program after the course feel that tiey nave seen how a computer

can help them later in their careers.

15


Grant No. FR00311-03
Section I-A
Appendix A

ACME PROGRAM LIBRARY--UN PUBLIC FILE

AH-l

8LY- 1

BOC-1

uUA- 1

EAM-4

LAN-4


tAP-3

tr3u-3

tBE-2


f:Bli-1

EBI-3

EBK-3

EBL-2

EBM- 3


tBti-2

EBU-2

EBP-2

* EBQ-4

EBR-3


EUS-2


EBU- I


E&V-l


tdbJ-2

ACME Program Library HELP:  Information on ACME Keywords (G. Sanders)
Clay 24, lYti8
Clinic Patient Scheduling (Grouse)
June 23, 1967
Questionnaire Program (Sanders)
Apr. 15, 1968
Pediatrics Project--Routine No. 1 (brew)
Aug. 8, 1967

ACfME Program Library LACKF IT:  Test for Linearity of

Regression (Schach).
Feb.  7, lY6Y
ACME Program Library MULT:  Multiple Regression (Moore/Schach)
Feb.  17, 1969
ACIlE Program Library !JENCORR: Correlation Coefficients--Missing
Data (Kraeilier 1
Feb.  7, 1969
ACME Program L i brat-y WE I GTREG:  Weirrhted Linear Renressi'on (Schach)

Feb. 7, 1969
ACME Program Library LINREG:  Linear Regression (Schach/Liere)
Feb. 17, 1YbY
ACME Program Library ONCALL :  Schedu 1 ing Program for Res i dents
on Call (Moore)
Jan.  8, lYb8
ACtlE Program Library PCPLOT:  Frequency Plot (Moore)
Feb.  7, 1969
ACME Program Library POLY:  Polynomial Regression (Moore)
Feb.  7, 1969
ACME Program Library RUNGK-1:  Runge-Kutta Solution of First-Order Ordinary
Differential Equation (Liebes)
Aug. 21, 1968
ACME Prorrram Li brat-v ZEROFIT:  Least-Sauares Line throurrh Origin (Schach)

Feb. 27,-lY6Y -
ACi,IE Program Library BSORT: Sorting (Liere)
Sept. 18, 1968
ACME Program Library PEEL:  Exponential Curve Fitting (Slirnick/G. Sanders)
Feb. 17, 1YbY
ACME Program Library KWTEST:  Non-Parametric Analysis of Variance--
One-Way (Kraemer)
Jan.  12, 1969
ACME Program Library PLOT:  Scatter Plotting (Liere)
Mar.  27, 1969
ACME Proeram Library SCHUSTER: Schuster Periodoeram (Schach)
                                           .
Feb. 7, i969
AIXE Program Library RUNGA6:  Runge-Kutta Integration (G. Sanders)

May 2, 1568
ACME Program Library TIllESER:  Spectral Analysis (Schach)
June 19, 1968
P.Cf,!E Program Library GOODF IT:  Test far Goodness of Fit (Schach)
dune 24, 1968
ACME Program Library D I SCRIMZ :  Dlscriminant Analysis for Two
Groups (Schach 1
Feu.  7, 1969
r<CME Program Library TSQUARE:  Hotelling's T Square (Schach)
Feb. 7, 19bY
ACI.IE Progra:,l Library CHI-2by2:  Chi-Square Statistic with Continuity
Correction (Schach)
Feb. 7, 19oY
ACME Program Library IAAPIT:  Mapping Bacterial Chromosomes (Nye)
Aug. 5, 1968
HCFiE Program Ll brary UATAPROG:  Writing a Data File Into a
Prograr'i File (Lieref
Sept. 17, 1968

16


Grant No. FR0031i-03
Section I-A
Appendix A

EDC- 1

EDU- 1

EDE-2

ACME Pr'oeram Library FOURIER: Fourier Analvsis (Liere)
Aug. 5, i968
ACME Program Library HEXAR.ITH:  Hexadecimal Arithmetic Routines (Feinberg)
Aug.  3, 1968
ACME Program Library JUST I FY:  Text Justification (E~lons/Liere)

* EDF-2

EDG- 1

EDH- 1

t01-2

EUJ- 1

EUh-2

FDi-I

EDN-2

* EDP-2

tFA-1

tFC- 1

EFD-1

TR-1

Jan.  12, 1969
ACME Program Library RUNGK-2:  Hunge-Kutta Solution of Second-Order
Ordinary Differential Equatidns (Liebes)
Apr. 18, 1969
ACME Program Library POWELL:  Fitting Program for Nonlinear
Functions (G. Sanders)
Jan. 17, 1969
ACME Program Library LISTER:  Listing the User's Program (Liebes)
Sept. 19, 1968
ACME Program Library MATCH:  Matching Donors to Recipients for
Transplants (Bauriedel/Lierel
Feb. 17, 1969
ACME Program Library LINSYS:  Solution of Simultaneous Equations (Jones)
Sept. 13, 1968
ACME Program Library ANOVATIIO:  Two-Way Analysis of Variance--Unequal
Cell Frequencies (Brast)
Feb.  7, 1969
ACME Program Library ,EDITER:  Converting a Program to a Standard
Format (Liebes)
Nov.  14, lYb8
ACI.lE Program Ci brary BALTHREE:  Analysis of Variance for a Balanced
Three-Way Design I Kraemer 1
Feb. 7, 1969
ACME Program Library COPIER:  Reproducing a Complete or Partial
Program Data Set (Bassett)
Jan. 8, 1969
Trans 1 at i ng FORTRAN Progral,ls to PL/ACME Us i ng DATAPROC, UNEKEVAR
and TRANSLATE (Emmons)
Sept. 23, 1968

ACME Program Library UNEKEVAR:  Unique Variables (Emmons)
Sept. 30, 1968
ACME Program Library TRANSLATE:  Translation of FORTRAN Programs to
PL/ACME (Emmons )
Sept. 30, lYb8

Respiratory Project on the 1800 (Hintz)
Mar.  21. 1967

TRA- 1    Interfacing a Packard 3314 Scintillation Counter to ACME (florris)
       Feb. 5, 1958.  Summarized briefly in ACME Note EAE.

W-IX- 1    Text Processing Routines (Wiederhold)
        Not dated.

17


ACME Note

ACME File Input/Output

Grant No. FROC31.1~45
Section L-A
Appendix B

The ACME file system provides in a time-sharing mod e
PL/I language with a few exceptions [l].       all the I/O facilities of the
                         For ease of access and flexibility, the
file is composed of system data sets and user data sets:

(1) System Data Sets

       These data sets are accessed by direct block addressing rather than
using the index facility.  They include system information such as the catalog of
user NAMES and PROJECTS, the available space on each storage unit, and the directory
indices pointing to a directory record for each cataloged data set.

(2) User Data Sets.

       These data sets are composed of the collection of information--data
or programs --manipulated by the users.  Each data set is assigned a qualified
name (User NAME. PROJECT, data set) by the cataloging facility and referenced
through the use of an index and of a directory.

PHYSICAL FILE ORGANIZATION

System and user data sets are currently residing on eleven 2316 disk packs (Two
IBM 2314 units).  The present equipment would provide for 14 disk packs of data
storage.

Disk Organization [2]

The IBM 2316 disk pack is composed af 11 disks and provides 20 surfaces on which
data can be recorded.  It is divided into 203 concentric cylinders numbered from
000 (outermost cylinder) to 202 (innermost cylinder), with 20 tracks per cylinder
(00 to 19).  Tracks in Cylinders 200 through 202 are alternate tracks that can be
used if any tracks in Cylinders 000 through 199 should become defective,

Data Format

Each storage module is divided into fixed-length blocks (2000 bytes), three per
track, except for tracks 0 through 5 of Cylinder 000 which are used by the Operating
System.  A module has e storage capacity of 3,994 tracks or 11,982 blocks, or
23,964,ooo byt:?s.

Track Format

Figure 1 shows the track format.

Data Record

Data Record

Figure 1.  Track Format.

18


Track Format Subfields:

Index Marker:   The beginning of a track is signal.',-'d when the index marker is
detected.  All tracks on a disk pack are synchronized by the same index marker
(there is only one index marker per disk pack).

(G):
Gaps     Gaps separate areas on tracks and contain no data. \';ap lengths vary
depending upon location within a record and the record length. They permit
switching from reading to writing between fields.

.~$gg$  The home address defines the condi.tion 2nd locat.ion

Index     Home
Marker   Address

Flag Byte Cylinder No.
L                   I       GJ\p [;--cTiG{

Figure 2.  Home Address Format.

'Track Descriptor Record (Rn):   This is the first record following the home
address,  on each track.  It is used by IBM programming systems to move the entire
content of a track to alternate tracks if a portion of the primary track becomes
defective.  RC is divided into the same fields as data records except that it is
not preceded by an address marker.  It has a length of 21 bytes.
(';CME data Records (R,-R$,:  These three data blocks are used by ACME data sets;
ail the other fields are initialized and used by IBM programming systems. Figurc-
3 gives the record format.

Index
Marker

A G

Address                                         Address
Marker                                              Marker

Figure 3.  ACME Data Record Format.


Grant No. FROCJll-03
Section I-A
Appendir E

FIO-1
Page 3

Address Marker:  This area indicates the beginning of each record.  It is sup-
plied by the 2314 control unit when the pack is initialized and contains a bit
configuration that can be detected by the 23lG as ti:c area preceding a count fielil.

Count Area (11 bytes):  This field is divided into seven subfields (Figure 4).

RO

Ooto Are0

Record R ,
  A

1, 2     3     4     5    6     7    a     9     10 .

\        /     \
    T                                 t                     /

Address Marker                      Count Area

I

Address

Marker

r-q-J
.O     1

Key Area

Figure 4.  Count Area Format.

Count Area Subfields:

    Flag (1 byte):  Generated by the 2314 control unit as each record is
initialized.  If has information on the record number (odd or even), on the
track condition,  and on overflow records.

    Cylinder (2 bytes):  Byte 1 is set to zero.  Byte 2 has the cylinder
nlJmber from zero to 202.

    Head (2 bytes):  Byte 3 is set to zero.  Byte 4 has the IUZAD/WRITE head
number (0 to 19) for the disk surface on which the record is stored.

Record Number (1 byte):  Sequential number of the record on the track (1 to .:),

    Key Length (1 byte):  Number of bytes excluding cyclic check bytes in
the key area: 8

    Data L!ength (2 bytes):  Number of bytes excluding cyclic check bytes in
the data area* .  2000.

    Cyclic check (2 bytes):  Used for cyclic checking information in the count area,

Key Area (10 bytes):  This field contains part of the count field information
(cylinder, head, record number), the data set number of the data set to which the

                                                                 20


block is assigned, and cyclic check information.  (Fie!?re 5).  This field is

essentially
provided by

used for block identification in addition to the  stendard infciniation
the count field.

count
cl
  area

      I             I

Cylinder     Head     Rec. not

                           no.  used
     I           I
0 12     3  4.5--G 7 8

Figure 5.  Key Area Formzt .

Data Area (2002 bytes):
assigned to a data set.  The data block is the smallestunit of space that can be
            It has a fixed length of 2000 bytes plus 2 bytes of

cyclic information provided by IBM programming systems (Figure 6). Variable-
length header and trailer contain several flags for differentiation purposes
(system or user blocks), a data set number,
Dl, c41.                     a block address, and record length

Figure 6'.  Data Area Format.

ACCESS METHOD

The ACME file I/O system uses the execute channel program (EXCP) macro-instruction
to read or write data blocks [5].  This low-level access method provides the syst:z:m
with greater control over the I/O operations than the standard access methods.
?he EXCP macro-instrubtion uses the Operating System functicns that pro;ride for
scheduling and queuing I/O requests, interruption procedures,
and retry.                               error recognition,
    It passes control information to the I/O supervisor regarding a

rhannel program to be executed.  The file I/O system is only concerned with setting
up a sequence of channel commands for the desired I/O operation

Block Addressing

Reading or writing a data block requires a positioning of the access mechanism
(23111. unit) of the selected pack to the proper cylinder, track, and record on the
track. Each block is assigned a number from 0 to 11,981 (maximum pack capacity),
and in order to locate
(Figure 7).       a block it is only necessary to specify a 32-bit address.

                                           I
        Pack
        Number              Block number

                           L-----l-
byte : 0          1          2      3

21

Figure 7.  Block Address.


From this information a simple conversion gives the hrrdware  ad:Jress in tz::yq>s of
                                                                           , a./
pack, cylinder, head, and record number.

Space Management

When a new storage unit (2316 disk pack) is being added to the file system, an
initializing program formats all the blocks in the pack with the proper count and
key field information and writes zeros in the data area.  Block addresses in the
form of block numbers are then stored in the space data sets. When creating new
data sets or expanding existing ones, a routine picks up available 'blocks from the
space data sets and assigns them.  When data sets are deleted, the freed blocks
are returned to the space list either on-line or by a stand-alone file analyzer.

A block with the avai.lable status has a data set number in its key field equal to
the space data set number.  An efficient data protection is achieved by testing
this information in the channel program prior to writing records in the data field.

Input/Output Operations

Three types of I/O operations are required in the ACNE file system. Each of them
leads to the coding of a different channel program.  The operating system handles
the positioning of the access mechanism to the proper cylinder on a pack and the
selection of ,the desired head.  Upon a successful completion of this SEEK command,
control Ls passed to the supplied channel program.  Its r~rs- c:b,nmand is a search
identifier (SEARCH ID):  a comparison is made between 5 bytes of data from CPU
storage (cyli.nder, head, and record number) and the 5-byte record identifier portion
of a count area from the storage unit.  Since a track has three data blocks, it
may be necessary to reissue this command until a match occurs (Transfer In Channel
command).

     Writing a Block.  A WRITE operation is always preceded by a test on the key
area (SEARCH KEY EQUAL command).  In this case the block must be available and
the data set number in its key area reflects this status.   If no match occurs an
error is signalled and the block is not written.  With a successful match, addition>:.1
commands reposition the writing head by disk rotation after the count field and
write the key and data area from the user buffer,  The data set number in the key
-)ieeld is written as the data set number of the data set to which the block is
:<.ssigned.  Appendix A gives an example of the sequence of commands.

     Reading a Block.  After positioning of the access mechanism, the key
end data fields are read into a buffer in the user region.  No testing is made
on the key field since a data protection on a READ operation is not necessary.
A check for vc7.li.d information in the buffer is made before data transmission to
the user.

     Re-,Tritii:g a Block.
        --.-I-         This operation is similar to writing a block except
th8t they y
       kev field of the data record is not modified.  Data protection is
achieved b;: comparing the key field with the key in the buffer from which the
block is rewritten.

Appendages

These routines art! entered by the I/O Supervisor upon successful completion of
a channel program or detection of an error.


Grant Nc. FROc?31i-03
Sect j.0; :  1 -k,
Appendix F

F'z 0-L
Page 5

  Normal End Appendage. This routine signals a normal completion of an I/O
operation to the ACME system posting table.  Control can then be given to the
user.

  Abnormal End Appendage,  This routine is entered twice whenever an error
is detected during execution of a channel program.  The first time entered, the
file system checks for two types of errors:  NO MATCHING KEY which can occur on
a WRITE or REWRITE operation,
operation.           and NO MATCHING ID which can occur during any I/O
     With other types of errors (DATA CHECK, OVERRUN, etc.) the IBM-
supplied error recovery routines attempt to restart the channel program several
times.  If the error is permanent, the appendage is entered a second time and
the ACME system posting table is posted with the pe.rmanent error condition, which
is signalled to the user when he receives control.  Errors like NO MATCHING KEY
can be caused by the ACME system for instance when a block supposedly available
is in fact used by a data set.  No automatic error recovery is attempted in
this case because of the overhead involved; instead sysI:em programmers can
patch the damaged information with a file fixer program while the ACME system
is in operation.

Most of the time required to service an I/O request is spent in mechanical
motions.  Access time varies from 135 ms for a SEEK between the extreme inner
and outer cylinders to 25 ms for a SEEK between adjacent cylinders.  Figure 8
shows the minimum and maximum time spent in mechanical motion for a WRITE
operation, with 25 ms per disk revolution [2].

The minimum time occurs when the selected read/write head is positioned just before
the address marker of the searched record (Figure ga).

1     2       I   3     J

-Head position
Searched record : 3
Number of rotations for a WRITE
Operation : 1 l/3

Firgure 9a: Head Position When Minimum Time is Spent for a WRITE Operation.

The maximum time is spent when the head has just passed the address marker:

lad position
               Searched record : 3
                Number of rotations for a WRITE
           Operation : 2 l/S

Figure gb:  Head Position When Maximum Time is Spent for a WRITE Operation.

23


ms

20    50

   100       150        200        tracks

Number of Tracks Traveled

Figure 8.  Mechanical Motion Time for a WRITE Operation.

24


APPENDIX A

Channel Program for a WRITE Operation

   SEARCH ID
  TIC -x -a
  SEARCH KEY EQUAL
a) TIC * -1.6
b) REND DATA
   SEARCH ID
  TIC 9 -8
   WRITE KEY and DATA

(a) This Transfer In Channel command to another TIC will generate a program check
in case no match occurs in comparing the KEY field immediately following the COWI!
field of the searched record with the supplied KEY data. The error condition is
detected in the Abnornal End Appendage.

(b) This is a dummy PEAD required by the control unit operations when SEARCHing
on the sa.me track more than once.


Grant No. FRO031143
Section I-A
Appendix B

FIG-1
Page 9

FOOTNOTES

1.  Miller, Jerry, "The ACME File System,"  ACME Note FY-1, February 27, 1969.

2.  IBM System 360 Component Descriptions-- 2314 Direct-Access Storage Facility
  and 2844 Auxiliary Storage Control, A26-3599.

3.  Miller, Jerry, "ACME File System--Data Sets,"  ACME Note FA-5, September 27, 1968.

4.   Frey, Regina, "ACME File System--Codes," ACME Note FC-2, August 5, 1968.

5.  IBM System/360 Operating System, System Programmer's Guide, ~28-6550.

6.   Girardi, Serge, and Jerry Miller,  "ACME File System-- Control Block Formats,"
  ACME Note FB-3, March 31, 1969.

Did:  Prog/All

26


Grant No. FR 0031X-05
Section I-B

SUMMARY OF RESOURCE USAGE

Month and Days

Daily Scheduled
   Service

       Account Records
Console Hours       Pageminutes

Apr 21 to May 20

May 21 to June 20

June 21 to July 20

July 21 to Aug 20

Aug 21 to Sept 20

Sept 21 to Ott 20

Ott 21 to Nov 20

Nov 21 to Dee 20

Dee 21 to Jan 20

Jan 21 to Feb 20

Feb 21 to Mar 20

Mar 21 to Apr 20

700-1530
1830-2200

700-1530
1830-2200

700-1530
1830-2200

700-1530
1830-2200

700-1530
1830-2200

700-1700
1a30r2400

70%1700
1830-2400

700-1700
1830-2400

700-1700
1830-2400

700-1700
1830-2400

700-1700
1830-2400

700-1700
1830-2400

2,075           947,000

1,003

1,626

2,761

2,856

3,330

2,262

2,461

1,639

2,521

2,757

4,108

467 > 009


712,514


1,313,940


1>481,671


19955,295


~28~133


1,1g0,110


738,048


1,213,289


L714,973



2,010,110

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Sectlon I-B-1


Grn It Nrj  `ROO?ll-03
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ACME Note

Papers Written by ACME Users

This list contains papers voluntarily reported lc.i fiCr,ib..

Bagshaw,  Malcolm A., M.D., Harold M. Schneidman, id.;?., Eugene `1. Fari..f.r, !;ILa., ,II~[I
Ilenry S. Kaplan, M.D.,  "Electron Beam Therapy of t,lycosl Fuiygoi~j+s," CPI I!`I/j,l;
MEDICINE,  95:292-297, Nov. 1961.

tic31 ikian, H.,  A. Brodie,  S. Wi 1 loughby, A. J. Dowdy, (;,iJ. blokes, 1l.ti. ,,iei !-I.;!`: ::`.r ., I/:
J.A.  Luetscher,  "Response of Plasma Aldosterone Cctncer,*,rjti<!n i r~ Hy;ic?rr~~f!~, I II"
Patients to Changes in Posture and Sodium Intake," C!it:.RES., vol. Ii, i,? `t-i,

P,t:atrice, E. S., I.  Harding-Barlow, and D. Gl ick,  "Electric S;,ark !:r,:i:-.tr :.' ,_
Ld%er Ilicroprob-Emmission Spectroscopy for Samples Gi l(!--25 !`ier<>n #ji,j,-,+:i :' ,
APPLIED SPECTROSCOPY, 1969.

tieatr ice, E.S., and U. Glick,  "A Direct Reading Polychror~~ator for 11~1i:.t,i I<
Spectroscopy, I' APPL I ED SPECTROSCOPY, 1969.

Bellville, J.W., J.H. Green, and W.H. Forrest, Jr., "Respira:or> Effect3 OT
Etomide and Codeine," CLIN. PHARM. THERAP., vol. 9, pp. 142-151, liiO8.

Bellville, J.W., and W.H. Forrest Jr., "Respiratory and Subjective Cifsctb ::*
d and 1 Pentazocine," CLIN. PHARM. THERAP., vol. 9, pp. 142-151, 19ub.

Bellville, J.W., and J. Seed,  "A Comparison of the Respiratory Effects of
Dextropropoxyphene and Codeine in Man," CLIN. PHAl?f:. ThCi!&?,, vol. `J,
PP.  428-434, lY68.

i;ellville, J.W., W.H. Forrest Jr., J. Stevens, and E.G. seer, "The l!ypnotii: tiir.;~.~
of Cthchlorvynol and Secobarbi tal in Man," CLIN. PHA[lE:. THERAP., vc:l, jc
PP.  625-530, 1968.

Bellville, J.W., L. Escarraga, S. Wallenstein, and R. Houd
"The Respiratory Effects of Codeine and Morphine in Man," CLIN. WAl':.
THEHAP., vol. 9, pp. 435-441, 1968.

Be1 lville, J.W., G. Fleischli, and J.G. Defares, "Respiratory Responses t.0
Varying CO2 Inhalation," COMPUTERS AND BIOMEDICAL RESEARCH, subr,,i tted f13r
publication

ijellville, J.W., G. Fleischli, and G. Attura, "Servo Control of Inhale<: C,lt-!b..~!
oioxide," J. APPL. PHYSIDL., vol. 24, pp. 414-415, 1968.

Breitbard, tiary Y., and Gio Wiederhold,  "PL/ACME: An Incremental Compiler :I': :
Subset of PL/I,"  lFIP68 CONGRESS PROCEEDINGS, Edinburgh, Scotland, Auquht
l'jb8.

t:iitler, ii.,  "bynamics of the Urinary Tract,"  JOURNAL OF I IiVES ! GATI Vt UTi)l ,,L.I,
in preparation.

!, I 3 y t 0 n ,  l(.B.,  iiETHUbS OF ENZYMOLOGY,  STEROLS AND STERCIDS, vol. XV, Aca,:eili~'
Press,  in preparation.

(;ollins, K.u., and G.R. Stark,  "Aspartate Transcarbanglase: Studies of the iflt:l I L t 13.
ji!burrlt by Ultraviolet Difference Spectroscopy," J. YIOL. CHE!d, Feb. 196'1.
"I !=
c-rouse, Linda,  and tiio Wiederhold,  "An Advanced Computer System for keal `Iii11~~
,~t:dical Applications,"  COMPUTERS AND B IOMED I CAL RESEARCH, to be pub 1 i she;1
about June 19b9.

User i ng,  C.H.,  "Cholesterol Side Chain Cleavage Activity in the Adrenal Glanc.. .j:
the Young Hat:  Development and Responsiveness to Adrenal Cortical Tropic
Hormone," ENDOCRINOLOGY, in preparation.                                  -rr\


Englud, P.T.,  J.A. Huberman, T.M. Jovin, art3 A, IC:):`t-:>r: s. "`Enry:ll;ls..c zk:nt',c,,i . 1
Deoxyribonucleic Acid, XXX, Binding of Tripor,pb,...c:3 :-I !)!;p$ Poly~:e-?se.,`. iiu,. ' t:~.;
to J.  BIOL. CHEM., 1969.

Farber,  Eugene M.,  and Richard P. McClintock, Jr,, il,i;,, "A Lurrcni Re*;it+; ,.f
Psor i as i 5,  "MEDICAL PROGRESS, 108:440-457, J!..ne I'_ibE.

Farber,  Eugene M., M.D., and Alvin J. CoxI M.il.,  "ihe Biology of Psoriasis, "J. I,G
investigative dermatology, vol. 49, no. 4, pp. 348-357, 1967.

Farber, Eugene, M.D., Ross D. Bright, M.D., and M. Lexi e Ida: 1, M.C., ~?si)r i J., I> -
A Questionnaire Survey of 2,144 Patients," ARCH DERRI, vol. 98, pp. 248-251, :,e;~rr `::IJ~
19b8.

Forrest, W.H., Jr., and J.W. Bellville, "The Use of Comptitrrs in Clinica: 11 / j\:,,"
BHIT. J. ANAESTH., vol. 39, pp. 311-319, 1967.

Forrest, W.H., Jr., anti J.W. Bellville,  "Respi ratory tf fects of &,l !>hi!i;I.:>\i 1 .jc` I r!
Ilan," OBST. AND GYN., vol. 31, pp. 61-68, 1968.

Forrest, W.H., Jr., B.W. Brown, and J. Peters, "Manay,emer:t +f :._?upr-rdti~i> ;.lli\b<:.:.
Trials," Paper presented at the annual meeting of the Al?t.fi;!:i'* S1AT1.5Tii;5i.
ASSOCIATION in Pittsburgh, Pa., on August 20, 1968.

Fries, J.F.,  "Experience Counting in Sequential Computer ;Jiagnc;si5," sub.ll tiec
for pub1 ication.

Halpern, B., V.A. Close, A. Wegmann, and J.W. Westley,  "Gas Ch romd tography rii
Alnino Acids as N-Thiocarbonyl Ester Derivatives," TETRAt:Ei)ci;i; LEITERS, v:;l. :O
p. 3119, 1968.

Henry, W.L., L. Crouse, R.E. Stenson, and D.C. Harrison, "Computer Analybi, ,,I
Cardiac Catheterization Data," AM. J. OF CARDIOLOGY, vo:. 22, nurher 5,
p. 696-705, Nov. 1968.

Kakihana, R., J.C. Butte, and E.P. Noble,  "Effects of Goltlthiilg;lsr.!)se 31; Aic `.,,I
Consumption in C57BL Mice," LIFE SCIENCES, vol. 7, p. 825, 1969,

Kakihana, R., E.P. Noble, and J.C. Butte,  "Corticosterone Responsr Co Et.Ildnl.1 ,,
Inbred Strains of Mice," NATURE, vol. 218, p. 360, 1963.

Kessler, S.,  "Speed of Mating and Sexual Isolation in Urosphila," llATURil,
vol.  220, p. 1044-1045, 1968.

Kess 1 er, S., "The Genetics of Drosphila Mating Behavior I. Organizations of
llating Speed in Drosphila Pseudoobscura," AN. BEHAV., vol. 16, 1568.

Laipis, P.J.,  "Computer Used Analysis of Sucrose Gradients," R.N.A.S., in prc?ss,

!.e./ ter,  hir:iee Doir,  "Mother-Infant Separation: Effects on Later Maternal
Behavior," submitted to SCIENCE, 1969.

Lilerr,~:her, J.A., tl.ti. Weinberger,  and R.U. Collins,  "Oral Contraceptives and
Ilvr,ertension:  Clinical and Laboratory Observations," METABOLIC EFFECTS
Ot GONAUAL HORMONES AND CONTRACEPTIVE STEROIDS," edi ted by D.M. Kipni s, et al,
1 iprl  `ublishing Corp., in press.

Luctt-ocher J.A., I1.H. Weinberger,  A.J. Dowdy, and G.W. Nokes, "Effects of
SotI i 4rn LkaJ i ng,  Sodium Uepletion and Posture on Plasma Aldosterone Concen-
trdtiiin and Kenin Activity in Hypertensive Patients," submitted to
.J .  L 1. I fd .  ENDOCR., 1969.

:.orreIl, F.,  "Neural Coding," NEUROSC I ENCES RESEARCH PRUGRAI: BULLET I h, 19,s.


Noble, E.P.,  S. Si lbergeld, B. Kopell, W. Mckinney, W,.i. L;i itnc?, iin<! J.C., hiri ;rl
"The Effects of Physiologic Doses elf Corticosterni:! `;`;.  CJtC2~01arlti n?! k!taboi t :>m
in Man," J. PSYCHIAT. RES., vol. 6, p. ij%#   ,?bg,

Pepper, N.A.,  E.J. Scribner, L.E. Alterton, R.C. i-::i,*i-y, t-5. ~:~-~~t~`:ce, I. ,:i~~~!~~<
Bar low,  R.C. Rosan, and 0. Glick, "Q-Switcned R:lb:  i. ,I 5 e I  f a r  E r> i 5 s i L: 13  i I- r x , -
spectroscopic Elemental Analysis," ANAL. CYEti., by i. .lir, pp. 117$-`113:, 111::.

Peters, John, W.H. Forrest, Jr., and B.iu. drown, `!J:e of Cop,outerc  ; i: "ia",],::. `"ri ;. i):
a Cooperative Study," presented at the 31st Annual ;-ct:rIn:: c.1 ZIP !.i.::`.!?:Tt.
ON PROBLEMS OF DRUG DEPENDENCE, Palo Alto, Calif., F,b. 25, I[;nC.

Petralli, J.K., S. Wallis, and T.C. Merigan, "A Cor~~::~ter +:ethod icy !I i?i.`,i:; .?IIL
of Antibiotic Sensitivity Data and Guidance in Therapv," 1 i:>d.

Porter, R.W., M.O. Modebe, and G.R. Stark, "Aspirate I'ra!t~zarbac~y;ili.,:
Kinetic Studies of the Catalytic Subunit," JOURNAL nF `)i!ILOCf:.Ii. Cc i...i:?~`,
suhmi tted.

Reynolds, W., "Computer Control of Mass Analyzers," PR:JCCZ> I t.2: c". iti'. ;i ,.`i;.! II:-,
ANtiUAL CONFERENCE ON FlASS SPECTROMETRY AND APPLIED `IZiPiCS, !.a!;TI: Ls*),:,.i ttce : : ,,
Pittsburgh, Pa., May 1968.

Rousseau, W. F.,  "A Method for Computing Probabi Ii ties  in Complex .;i ;#.a:icnh,"
Doctoral Uissertation, Stanford University, 1968.

Sanajers, IJ.J., G.Y, Breitbard, D.A. Cummins, J.R. Fle;rcr, i;. tl0it.L. .i. f:i ilet,
and !io iliederhold,  "An Advanced Computer Sys tern for +led; cd 1 Ees:!dr ch, "
AFIPS CONFERENCE PROCEEDINGS, ;Jol. 31, 1967.

5olornon, ti.F., S. Levine, and J.K. Kraft,  "Early Experience dnd Ifimcrni LY,"
NATURE, vol. 220, p. X21, Nov. 23, 1968.

Solomon, G.F.,  "Stress and Antibody Response in Rats," IN`i. AKCli. ALLtt;LY -tr<L
APPLIED IMMtiNOLOGY, in press.

Starr, A., and J.S. Wet-nick,  "01 ivocochlear Bundle Stimulation:   LtfFcts <Ii!
Spontaneous and lone-Evoked Activities of Single Units in Cat Cochlear
Nucleus," J. NEUROPHYSIOL., vol. 31. pp. 549-564, 1968.

Stenson, R.E.,  Linda Crouse, W.L. Henry, and D.C. Harrison, "A `i isle `.~~~ar~.

Uigital Computer System for On-Line Analysis of Cardiric Catheterization
Data," COMPUTERS AND BIOMEDICAL RESEARCH, vol. 1, number 6, p. GiJ5,
Academic Fress, inc., June 1968.

Stenson, R.E., W.L. Henry, L.P. Grouse, and D.C. Harrison, "Cardiac Cattlett:riiia-
tion Data Analysis," J.A.M.A.,  submitted for pub1 ication,  1969.

St i 1 l,rian,  R.C., d.T. Roth, K.M. Colby, and P. Rosenbaum, "An tin-Line CoVii>urer
Systeili for initial Psychiatric Inventory," AMER. J. PSYCHIA7.., vol. 125,
p. 7, January 19b9.

5 t i 1 ll,lari,  Il. c.,  II. Costell,  and D.A. Cummins,  "Computer Administered PsychidtriL
vc:;l~Iry," presented at AMERICAN PSYCHIATRIC ASSOCIATION annual xeting, !/,ia.,-!i,
t iclridd, l,idy 5-J,  1969.

:,triri:ianil, K.G.,  "The Effect of Preduisolone on Gastric Structure a Functisn Ire
I !`:n, " l~A3~KOENTEROLOGY, i n press.

l'-!,?thachari, Y.T.,  "X-Ray diffraction Studies on Melanins," PROCEEDINGS OF TIIF.
VI 6 IhTERNATlONAL PIGMENT CELL CONFERENCE, Seattle, Wash., 1969.

lhti:h~cchat-i, Y.T., and !.I.S. Blois,  "Physical Studies on Melanins:  X-Ray Uiffrdcf ic,:;,!'
4IOPHYSIZAL JOURNAL, vol. 9, no. 1, pp. 77-89, 1969.


.
.' j ,, / i? ,"
,: : I,..,

Thathachari, Y.T.,  "X-Ray Diffraction Studies CL; `, :.*1~,:5," ;>resc?tr,: <St 1.:`~
BIDPHYSICAL SOCIETY ANNUAL CONFERENCE, Los inge\c , :: >".   Fe!..  2 e, .. 0   : i, 42

Weinberger, M.H., A.J. Dowdy, G.W. Nokes," an< ;.A. icri .`:,-~;,!r, ".;i;ci,alat1ori <II
Plasmas Renin Activity without Increasecl Al;:,.;ter. ~~(2 0.. .!:tjor' drier
Administration of Chlorothiazide to Hypert.er,siv.- 1 `ii-.r~5," .!. iil!~. i',VI I,i
vol.  46, P.  1130, 1967.

Weinberger, M.H., A.J. Dowdy, G.W. Nokes, ani J,a. ' ,:tsrrer, `ik!az, .I :,?nin
Activity and Aldosterone SecretTon in Fypertensive +,tieni5 4urinjz ; :I-II
                                                                  t.
and Low Sodium intake and Administration cf i)iui.i'?;I.." J. CLlid. I'Nbn!.;)..
vol.  28, p. 359, 1968.

Lieinberger, M.H., A. J. Dowdy, G.W. Nokes, and J.R. l.ue:scher,  ":?E:ver :. i `7 1 e
increases in Plasma Renin Activity, Aldosterone Secretion ;, !i dioocl
Pressure in Women Taking Oral Contraceptive Prepardtio!ls," CLIP*. Rr;.,
vol.  16, p.  150, 1968.

Westley, J.W., and B. Halpern,  "The Use of (-)Menthyl ihlor-i ;.;;.iilate : r~ !hr
Uptical Analysis of Asymmetric Amino and Hydroxyl Compounds by GBS
Chro~!Idtography," J. OHG. CHEM., vol. 33, p. 3978, l9h8.

Westley, J.W., V.A. Close, U.N. Nitecki, and 8. Halprrn, "!~r:? ,`r ::!~!i ,r, oi
Steric Purity and Configuration of Diketopiperazines by i,>::*:iqr:Id
ChroiIlatography,  Thin-Layer Chromatography and Nuclear PiaEncilc
Kesonance Spectrometry," ANAL. CHEM., vol. 40, p. 1888, 196ti-

hiederhold, Gio,  "A Summary of the ACME System, "  PRGCkE1.e i i+(;:; 3C  TI!C ,,I
CDtlPUTEK AND PSYCHOBIOLOGY CONFERENCE, Monterey, Cal i iorni i'r iiay 17, 19~~.

Lliederhold, Gio,  "A Summary of the ACME System," PROCkfUINGS OF .THE iti!JVChJi~.
TION WITri A 50 CONFERENCE, Argonne National Laboratory, Chical~o, I1 linolb,
uct.  31-Nov. 1, 1966.

WieJerhold, Gio,  "Setting up a General Purpose Data-Acauisi t.ion System," t. `E
published in the PROCEEDINGS OF THE IBM SCIENTIFIC COI'PUTING SYI'P:;`;i::;' !j:\
CUllPUTERS IN CHEMISTRY, Yorktown Heights, New York, tict. 9, 13L3.

Wiederhold, tiio and L. Hundley,  "A Timeshared Data-Acquiji tic,n Sybtc I," iu i)e
presented at the IEEE COMPUTER GROUP CONFERENCE ON REAL-Tlh'F SY:-It:,,:r,
f.ii nnedpol is,  Minnesota, June 17, 1969.

Dust: Staff/All


Grant No.  FRCI"I~~-'I~,
          -N--c/-.`;;.
Secti TT -A

Total Resource

enditur~

Current
Budget
Period

.___.___"
stirnate
ext
Adget
sriod
__- -I.-

232,990
$gg

1,300


SUMMARY OF RESOURCE F'i.Z'~!3;i~.;j
                           --

570,984.

I


p of       -._--- .-._

Time

OY
Effo

5 0


100


100


100


100


100



--

Salary
From
SRR Grar

100

ioo


1.00


100

56


l-00



--


1.00


100


100

35


100


100


100



--


100


100


100



-I


100


100


100

k!fic.! 1 P i,

-"-

$> i, > -;.- 'S j

1~3,675

l1.,4GC

10,987

5,250

13,108

---

2,213

689

2,224

  577

554

13,503

4,046

Amount
t

8 4,125.

13,675.

11 ,400.

lO,g3y.

9,bO.

13,108.


  ---

hourly 2,213.
I
hourly
  I   689.

hourly 2,224.
  I
hourly 1,670.
I
hourly .
     554


103   13,500.


100   4,&6.

--     e-s

on demand 2,42
I
or! demand575.
I

r):
t
f



         I' %
.       .

  ' /     . :,,i _,. ,
           .L.
  . . _- - . .  . ._ .._. .  

".. -    _Y "_ ;"__

.

.4 of
Time

Or     Amount
Ef'foYt

!.I .,,.         /,-
,. . , ,,.
!
I



i -


y+:`, 540. (3) 284,lU.                   .' ,,;..2 ',          
                                         3 ;-          :' ,,


                           

TOTAL        5 ;-? .-                       


Budget rj,is.t,; 1 i-s ;. i:,:.



   The estimate for the next budget period ref! :P::  I .r `-, :`;'t+,;;   _  [,;l)F "0: 1

%cility paying the full cost of t'ne equipment a~(:     'i  I 7~' L!;C L:l- I~;>:: y =
                                              L :L

'Y'cmporary staff reductions resulting from this yea?:, -.-:,ti-L?<ye';irq i,;i\re FL?F.!.I


r::,;i,ored.  The Macy Grant, which funded a part 1'11 ,-',:,I,' : <:x:;Iet,; :t ..'IY, .!.:I _ ; : :':i,

ko years, has been exhausted; and without the parti-i~:-~i;icr; ol" L!!:`, i'~~rr!; .~n

Facility,the Medical School computing facilit;g will hi:  , ~:,,j.s~ E.9.C :;~L:-d :.',I  ., 1 .!Z'

SET? grant and user charges.

   The present year should be the last in which iate :i:;-.-c-~c.:n;; 0:. YIXI :.:': 1.


.i i c 'ci~rt the cash expenditure for equipment.  As indicated in R  -c.p'- / t:;  / r;

'::.:(.:Lion II-C, the April, May, and June 1968 rental cf' t;h ZiX 'x':
                                                              i ,I\. .L~ ,'. ! i z. i,   1

:lni;j-1. March, 1969.  A freight invoice for part of the oric:i'!al ,-~':::i ii;'!." i..i:-:-.


:,>y,. 7iso invoiced and paid in the clurrect year.  Accou~iti:~g for I&,:  -1 '<> 1-i ;, ,c I ls ;;  -* , .:



<.r,el-: ;j serious problem at Stanford, but the problem has :icw bee:1 ccl*r~?ct~~d a,;\!

i'Cnt;llS are paid on a current basis.

   Curing the year, the partial salaries for ACME tdmi ni~s$rr ki.or, 1-1; CSC:

;kilff members were assumed by the Medical School.  The pyese;lt ch;3rg:: f:,j> t-i.<:si.

I-ir?iuistrative services is low and negotiations will be lielLi sun Y,', tl F` te m-i ; : !

: ;:iore realistic effort distribution 0.' I t,he Stanford Computation aL,mi!li s !.Y,: t Ix, L


i.`.! 'P tind an appropriate distribution of this time bety!Jeen direct    '
                                                       ,C:LG in&lyp(';


~. .-. "
  ,., L,  of the NIH grant supported ACME.  The inaugurrjtion of lzser f~ha~,<;es ,h.:~ :


* ::: i, - Lbuted substantially to the administrative burden.


Detailed Description of Resource Pr?;jects

Core Projects

   As discussed in the Introduction of this Annual Report, the efforts of

the core projects have been directed toward increasing the serviceability, re-

liability, and performance of the system.  Although many of these problems are

not glamorous in the scientific spectrum, the fact that a very advanced computer

facility has come to the point where it can extend its efforts to improving its

reliability and serviceability is certainly significant.  Because of our efforts

to maintain constant communication between users, usage has increased consider-

ably.

   Major efforts went into system measuring and system testing in order to

preserve integrity of the system, even while continuing changes and adjustments

are being made.  In the real-time data-acquisition area we have achieved the

capability to handle multiple users, each with multiple lines doing data acquisi-

<ion and data distribution under routine timeshared operations.  The ability to

handle moderately high data acquisition within an interactive environment alloT/rs

YLodification of the algorithm being employed by the user without loss of data;

as far as we know this capability is unique to ACME.  Continued efforts have been

expended on the compiler and interactive control language development in order to

insure that the system fulfills the needs as expressed by the users.  Here, the

efforts that are being expended are largely in response to request for additional

capabilities that originated from the user community.  System measurement is

part of this activity so that we may predict how and where system changes will

affect total system performance the most.


   A fair amount of resource activity has also gone ii:+0 the file main-

tenance programs which can now be largely run on-line.  Our file reliability

encourages medical users to keep data on line without :\;orrying about back-up.
Daily back-up runs and weekly complete system check ru::s are now an important

part of operational procedures.

   Due to the establishment of recharge rates, efforts ha-ve also gone into

producing an accounting system with a proper audit trail which still runs at

minimum overhead to the system itself,

   Laboratory support, development, and testing have resulted in direct bene-

fits to users who had greater need of computing assistance than the ~lvc~ge user,

   Development projects that have required a much smaller fraction of the core

resource use are the display support for storage scope, the testing of algorithms

for continuous system modelling programs, and the development of the assemblers
for the 1800 computer part of the system which can operate inside the 360/59.

   Usage of the ACME system is also made by our own staff while engaged in con-

sultation for the medical school faculty and staff.  A prolduct of this work is

the public EKG program which can be used to mark cardiology data acquired on-line.

Statistical routines for users are developed by our staff and then made available

on the PUBLIC files.

   Internal usage of the system is also made for editing of the PL/ACME Manual

and editing and preparing indexes for the ACME Notes.  Other internal usage has

been for teaching and demonstration of the system to visitors.

   The bulk of this section of the annual report is devoted to usage that our

users are making of the system.  However, we do not feel capable of evaluating the

scientific merit of these applications.  In an organization serving well over 200


medical research projects, no single person would 3ar`e cJal?late ali these
projects for their scientific merit, or place them ir tk proper perspective

relative to each other.  The allocation of the resource that is available at

the Stanford Medical School for computation will .be cankrolled in the f'uture
through the individual institutes themselves, by all?c?tLng grant monies to

be used for research computer support.  The individual progress reports are
ordered alphabetically by the name of the researcher who requested the usage

of the computer facility.  Since the projects are described in the medical

researcher's own wording, some inconsistencies in terminology--especiaIlg as
t'r,ey pertain to the description of the computer-oriented aspects of the nro-

ject itself--will have to be excused.


Grant No. E'ROC313.-C3
Section III-B

ACME INDIVIDUAL USER PROJECTS

Angel, R. W.

Name :  RWANGEL                             Project:  ERCOREXT

Department:  Neurology (Veterans Administration Medical Center)

Project Description:  Data reduction and statistical analysis of movement patterns,
  limb displacement, limb velocity, and electromyography in relation to both
  normal subjects and neurologically impaired patients.

  Between now and July 1969 further data will be collected for both
dissertation research (unsupported) and medical (neurology) research. Two
publications are pending completion of research now underway.

Aronow, L.

Name :  LARONOW

Project: LCEL

Department:  Pharmacology

Project Description:  Routine laboratory calculations, including statistical
  tests of significance, in studies relating to the mechanism of action of
  anti-cancer drugs.

Atkinson, M.

Name :  MATKINS

Project: FLYHIGH

Department: Neurology

Project Description:  We use ACME for Neurology research to help process data
  that our Line-8 cannot easily handle. We send data down to ACME via the
   interface , perform several statistical operations on the data and then
  return the data to the Lint-8 via the interface.

  Our data consists of digitized position, velocity, and EMG traces
for a specific arm movement.  Since the number of data points used is too
great in some cases for our Lint-8, we use ACME.

  Our plans to July 31, 1969 are to continue to use ACME for statistical
manipulations of BMG traces.

  No publications as of yet on our use of ACME, although one now being
prepared.

88


Grant No.  FRC?C)31 l-03
Section III-~

Baldwin, R. L.

Name: RLBALDm

Froject:  OLIGOMER

Department:  Biochemistry

Project Description: The project is charact-rization and helix -- forming
  properties (both kinetic and equilibr',.um properties) of short DNA helices
   formed by dAT oligomers of defined \chair, of lengths.  dAT oliogomers have
   the repeating and self-complementary b&se sequence . ..kTfiT... .

   They may form either hairpig helices or dimmer helices, depending
on conditions.

   The aims of the project are:  (1) characterization of loops in DNA
helices; (2) measurement of the parameters controlling the cooperativity
of DNA melting, and (3) measurement of the rates ol' the elementary steps
of base pair opening and dosing in DNA nelices.

Kaplan, W. S.

Name :  GBAUSEK                              Project:  HODPAT

Department: Radiology

Project Description:  Lymphoma Data Program (LDP). The radiotherapeutic
  treatment of lymphomas, particularly Hodgkin's disease, has been shown
  to be the most effective way of achieving high cure rates.  However,
  many aspects of these malignancies are still puzzling.  For example, in
   addition to the obvious truth that we are still in the dark regarding the
  origin of lymphatic cancer, there appear to be significant differences
  between the lymphomas in their methods of progression, both in the presence
   and absence of treatment.  The LDP has as its initial goal the accumulation
  in readily retrievable form, of data on many aspects of lymphoma patients.
   Items of importance are:  results of physical exams of new patients,
  background information such as records of malignancies in the patients'
   families, early symptoms of the disease, laboratory data, method of
  treatment, and follow-up data (recurrence, retreatment, etc.).

  From the analysis of such stored information, it is anticipated that
inference can be drawn regarding optimun treatment scheduling and, hopefully,
regarding the possible causes of these diseases.


Grant No. FROO311-03
Section III-B

Beard, R. R.

Name :  R-BEARD-

Project: PBEVMED

Department:  Preventive Medicine

Project Description:  We are making correlation computations.  Anal) zing behavioral
  responses and influences of inhaling carbon monoxide.  An example:  correlation
   cf carbon monoxide in the breat,h with athletic performance.

Bellville, J. W.

N`ame :  JBELLVI                               Project:  PROBABIL

Department :  Anesthesia

Project Description:  This study is of the pharmacology of anesthetics and
   related agents.  Statistical programs are stored in the 360/50, so that
  with the 2741 terminal on cue, the data are entered.  Various procedures
     are  carried out.  For instance, the relative potency of a biologic compound
  and its associated 95% confidence limits are computed.  Lambda, a measure
   of efficiency of the assay, is also computed.  Standard statistical procedures
   are stored under this project, and carried out by research fellows or the
   principal investigator.

Bellville, J. W.

Name :  JBELLVI                              Project: RESPIRfYT

Department:  Anesthesia

Project Description:  This project involves the use of a special purpose analog
   computer that preprocesses data,
   1800.              which is then entered into 360/50 via the
       In addition, the 1800 interacts with the experiment to generate
  sinusoidally varying carbon dioxide which is administered to the subject.
   Thus, we are doing research not only on the basic physiologic mechanisms
  involved with the control of respiration, but on the use of digital computers
  on-line in the ccntrol of experiments in the acceptance of data from special
  purpose analog domputers and the storage, analysis, retrieval, and display
   of tr-ese data.  This represents an entirely new approach to the study of
  respiratory control mechanisms,  and could not be carried out without the
   ACME facility.

90


Bernfield, M. R.

Department:   Pediatrics


.;.. ,: :       -"

r ,: :_ .~

Brast, N. B.

Pi


Bri, 3;,r ,  1,' , R.

] , : ,p . .
  ,J    ,   !.I:1 * .,`; .,`,; i 


Brodey, W. R.

Name :  BBRQDY

Dc.pa.Fcmz tit :  Biochemistry


Buchanan, B. G.

Name :  B-BUCHAN

Department:  Computer Science Depa:~-t!",,11?,.'1'~1:. '.

Bunnenberg, E.

Name :  EBUN-NEN

Department:  Chemistry


Butler, E. D.

Department:  Surgery (Urologyj

  Microscopic analysis is made of item (i) bfi' iin:' -::I ,;,e e.ffezi <,I
drugs on the waveform which necessitates us:? of ti-e !?V .-',j S-[,:: a:,-  :3r,r: SC:; .-~ .
Digital filtering, histogram plotting, :&',.a / .r q.;. p,;yy II  t:,:jQ. ~~.~-;3^orl'e11a:.:lo;-, -1 .;
performed.  Data files are kept of the re.duced dkia, poirt-",:,.   SC, vi:rfi:1 CJ-'
the standard statistical subroutines are used, ':.:z.,  ,j;~-;y-jyr  aq c4 7 -:c- -: c
                                                              I LLJ Cl,-)
spectral analysis, frequency plots.   k Se:I`I..S  <iA li f5-;." p!q~,?';< &J-C~ ir, p?"--
paration to be published in the "Journal of ~p~~~p~'~<p~ti~;e u~.c,lcl;;;,r" iii
early 1969 concerning work and techniques -~sr,ablished. ea+ire;l;,-  0 n -t l>i,
use of ACME for the data collection, presentation, and a.neiysis.   Tk ;: 3 :
will have a general title of "D-ynamics of :;i:e urinary ix-a~';."


Cam, 1;. M.

Department:   Pediatrics

  Fho cormunities on the east shore of tne l.ake are b~',ng s5:jdied a:;d
~$1~ are about to initiate studies in another India:1 La>:? sl.or? coy:rllurlity.
A pilot project icvoiving 300 inhabitacts of two L?dlan cOT&r.inimties on
the south shore of the lake was conpleted prior to under:;akcnfi the preset,*-
                                                                    .~
investigation.


De,pal~:~!li?nt :  Psychiatry

Pr

,oje?t Descrlptione  The purpose of our project is to determine the effec~tz
of steroids and hormones of RNA activity on the brain,  We inject live
  rates with radioactive tritriated uridine.  The rats are then killed
  and processed In the re&ar histological procedure.  Radioactive
element reduces silver grains and slides are made frown which the grains
  LD t,hP braln cell are count,ed,  From the number of grains, we determine
the area of RNA ineorporatlon In the brain, the brain cell, and 21 i',-.c
  t,issues.  The level of RNA incorporation is also determined.  Expz~imer!:;a
  and contra! groups are compared by ACME.  Our d.at,a analysis time is
  ::,rerz,i-.:) I' duced by :;slng ACME.

Coilins, K. D.

Department :  Biochemistry

Pl`Oj

ect Description:  This file (KIM COLLINS, AT Case) 1s used for three
purposes:  First, it is used in a variety of ways as a research t.ooi.
It has .been used to compute the dissociation constants for an enzyme
(AT Case) and some of its inhibitors (see Journal Biological Chemistry,
approximately February 1969; "Aspartate Transcarbenglase:   St-udies of
+'!ne Catalyt.ic S-ubumt by Ultraviolet Difference Spectroscopy," by
Yim D, ;Sollins and George R. Stark).  It will be used in the fr;t-ux to

I; emulate d.iI'ference from model compounds and compare these spectra :%:I: ii
' +I? experimental spectra.  It will aLso be -used i.n the futu.re to ar,aly~i,r
dat,a from equilibrium dialysis studies of AT Case and its s~:1-~stra*,es and
i nhibi: / ct`,r,.

   Second, it is used as a data processing facili.ty for research-
,Tcrlt>r-ated data.  'It is extensively and routinely used t,o process
chromatograme from an amino acid analyzer; a long program stored in
:j.CVIE provides a variety of different procedures that may be used on the
!.!ata (See p.revious ACME' write-up).

   Third,  it is used as an education device,  For instance, this i`:le
has been used to process data from a laboratory course in ultraeentrl-
rugat ion ( Riochemfs~~ry 214) ,


DepalXLment :  Genetics - ZRL

Project Description:  DATA COLLECTION, STORAGE, ANALYSIS FROM FI!@J:GAX 1015
   MASS SPECTROMETER.   In this "on line" application, the decision making
   capabilities of the computer are coupLed with those of an operator
   to direct the operation of a Finnigan 1015 quadrupole mass speetrome'.er.

   The computer is used to actively direct the operat?on of +hpj mass
spectrometer by controlling the mass filtering system of the Uris+ :1rn!'ls'
It is used to recognize and control the voltage changes which aei !tne
mass peaks and enable the rapid collection and presentation of da+~a.

   The computer traces out peak shapes of the known masses LII a
reference gas allowing the operator to det'ermine correct mass posi-tiol:s,
and to enter any shifts in calibration into the comput~er register fo?
compensation automatically.

   While taking data the information may be displayed on an oscriLoacope
or recorded on magnetic tape.  Once data is acquired the str-uctural
identification of organic compounds is made from orthogcnal coordrnate or
spiral base plots of mass spectra made by computer direction of a caicomp
plotter.  The system is also used to analyze Gas Liquid Chroma.:ograph
effluenf, permitting the structural identification of mixtures of' orpan;.c
compounds.

   Stored data offer the future possibility of spectra ma.+cniing of
-unknown compounds.  Publlcatlons using this system of computer [Jpsrat ~(~`1
of the mass spectrometer are:

B. HaLpern, V. A. Close, A. Wegmann, J. W. Westley, "'lass Chr:~mato-
,~".:i:ihy of Amino Acids as IX-Thiocarbonyl Ester Derivar ives",
'lc+,:`ahedron Let,ters 27, 3119 CL$8),
-

J. W. Westley and E. Halpern, 'The Use of (-)-Methyl Chloroformate
in the Optical Analysis  o f Asymmetric Amino and Hydr0xy.i Compounds
by Gas Chromatography" J. Org. Chem. 33, 3978 (1968).

j, W. Westley, V. A. C:lose, D. N. Nitecki, and B, Haipern,
"Determination of Steric Purity and Configuration of Diketopi-
perazines by Gas-Liquid Chromatography, Thin-Layer Chromatography,
and Nuclear Magne+.lc Resonance Spectrometry Anal. Chem. 40, 1888
                                                g_-
i1gG8).


Department:  Psychiatry

Project Description:  There are approximately 15 individ,zals in this
   Laboratory directly involved 1n experimentation relating neluroendoerzne
   function to behavior0  Information from animal testing chambers will soor:
  be recorded on a hfgh-speed paper-tape punch,  The data on the paper-
   tapes will be dumped directly into ACME data files through 2 PDP8 inter-
   face, or listed by the PDT8 for iieyboard terminal input to AcMi:.   -11
   either case, a program in the permanent ACME files will be ~rl~er; -c
   sort the data from the several. experiments recorded simultaneously on
   the paper-tape0  Appropriate programs for the analysis of data from
   ,:pec X1(. ~~xperiments wili also be maintained in the permanent ;~I-,~~- -':j~
    files 0  in addition, we plan to use ACME facilities to reduce and a;:;I-l)~c
   data derived from experimenta +,ion which does not involve use of our
  paper-tape recording system, cO$", adrenocortical steroid levels of
    sni.mals under various conditions and ACTH bioassay data,

Cooper, J0 M0

Name:   JMCSOPER                             Project:   SEXG;TjT

DC '1.: rtment :  Psychiatry

Pr.8 lject Description:  At present I am using ACME for t,wo purposes only:
  (I) comparison of 2 sets of data by means of the t-test, and (2; caL:YLaT jon
  qf sample radioactivity together wit.h standard deviation thereof.   r do
   o-t envisage expansion of this work,

  Such use is not mainstream to my project,  in that the calculations
(, &J -cc-l performed manually"

  My project lies essentlslly in investigation of biochemical correlait
jr' neonatal sercual differentlstion in rats:  such as androgen meta~boiis~~.


!j?ught;ers, G. T.

Department:  Medical Research <Palo Alto)

Project Description:  This project is a study 21' I~r,,~>ar~::c- (MedI-al)  i 1 t i 1 i a 9 t L <-' :, .
  A comparisoc of membership and doctor sr.isii-.z, '.,:
                                         :.-, I,ora7,0ry wo 17i;, etc . , 01'
  the same population under two differer:? insurance plans is being m-de.

  Studies of costs to the patient iacl:ordirq ~,o disgncsis) arc also
being made on the same group, for the two diff'eren? plans.

  The results should be of vide interest tc e?n-:Lcye:,s,  i:isLrers,
hospital planners, etc.

101


1 :.    's, G. T.


Name :  G-DAUGHI

Department:  Bioengineering and Phys

i0

UY

Project Description:  This project is purely educational in nature,   It is
   desirable to make a knowledge of a high-level scientific computer
  language one of the standard tools of today's research scientist.  P:L/AiI\E
   is such a language, and being FORTRAN based,  is useful wherever a machlne
   with a FORTRAN compiler is found.  The availability of a machine as large
  as ACME'S 360/50 is a definite asset in learning how to use a compLIT,er on
   scientific problems,  since storage space is almost never exceeded, (ind
   programs can be very straightforward,

   The Palo Alto Medical Research Foundation has active training i8rngran'
(one supported by N.I.H,) in Molecular Genetics, Allergy, Immunology,
Infectious Diseases, and Bioengineering.  There are currently several
post-doctoral fellows in training at the Foundation, and members of the
Foundation staff hold faculty appointments at Stanford University and
i,he University of Santa Clara.

   Those of us at the Foundation who are relatively competent in the
ACME language have been giving informal instruction to members of our
staff who have taken an interest in using the computer as a research tool,
and the terminal sees almost full-time use only a month after inst.aiiation
in a facility where only two people had had any previous computer t,raining.


Project: XENONl:,'

Department:  Nuclear Medicine

Porject Description:  This project involves the use of radioactive methods to
  assess the regional distribution of ventilation and pulmonary blood
  flow in normal subjects and subjects with disease.  A scintillation camera
  and special purpose computer are used to generate positimal and quantitive
  information for subjegnent processing by ACME.  Studies in upright man
  have revealed that the distribution of ventilation is determined by the
  pre-inspiratory and inspiratory volumes.

  We propose to study pulmonary embolism with these radioactive methods
and compare the results with those obtained from conventional pulmonary
function studies.



Name:   CHDOERIN

Project:  DESMOL&:

Department:  Psychiatry

Project Description:  CONNECTIONS TO LABORATORY INSTRUMJXCS, E.G., LIQUID
   SCINTILLATION COUNTER.  We have studied the development.of an enzyme
   system in the rat adrenal gland which is involved in the response to
    stress.  In the newborn rat, there is a brief period of poor response
   to stress by the adrenal gland, As one parameter, we are measuring
   the capacity of the adrenal gland to synthesize steroid hormones.

   We prepare an enzyme system that catalyzes the conversion of
cholesterol to pregnenolone.  The rste of this conversion is an indicator
of the amount of enzyme present in the glands.  We follow the rate of
conversion by using cholesterollabeledwith two different radioactive
isotopes and calculating the change in isotope ratio.  From each
incubation more than ten samples are withdrawn, counted in duplicate
for the two isotopes and recounted with a radioactive standard.  Thus,
about 100 different counts are generated with each incubation,

   We use ACME to compute the ratio of the two isotopes for each sample
(by averaging duplicate counts and correcting for overlapping counts)
and to store these results along with other information about the
incubation.  Various other programs are used to work on the information
stored in the data file and to proudce the rate of enzymatic conversion
by fitting the best line through the experimental points and by determining
the slope.and its confidence interval.  All this derived information is
stored in another data file.  The date over 150 incubations ranging over
the ages of 1 to 46 days have been carried out and treated in this manner.
!he project was started in October 1967.

  All the information of a set of similar experiments has been retrieved,
dnd a significant pattern of development of the enzyme system has been
,iscerned.  Another program analyzes the entire set of experiments and
c?lerates a mathematical function that describes the pattern of devehopmer:
2his development pattern of the enzyme system was found to correlate
closely with the pattern of stress responsiveness described for the
idrenal gland of the neonatal rat.  Two reports of this work have been
.;ubmitted for publication in Endocrinology.

   Some aspects of the work on the rat adrenal capacity to produce
hormones will continue,  At the same time we will use the above method
to study genetic differences of this capacity in different strains of
micea  The use of ACME will be very similar to the past.

104


Name:   RADOHERT

Project:   SEXCHJTF.:

Department:  Pediatrics

Project Description:  I am currently using ACME for:  1) statistical evaluation
   of experimental data, and 2) calculation of random fields to obtain
   random sampling of cells dispersed on microscope slides.  Sex chromatin
  body counts are being obtained on the random cell sample by visual search.

Dong, E.

Name  EDONG                              Project:   heart

Department:  Surgery

Project Description:  Study effects of heart transplantation.  Collecting
   data on blood volume, heart rate, rhythm and blood pressures.,  Also:
  developing the relationship between white cell types.   Correlations
   and negative correlations.


Name:  EDONG                              Project:  MARGl

Department:  Stanford Electronics Laboratory

Project Description:  The purpose of our project is to develop a controller
   for an artificial heart,  We are attempting to do this by using a
  transfer function between arterial pressure and heart rate. The project
  is a joint concern between the Department of Cardiovascular Surgery and
   Stanford Electronics Laboratory,  It is funded by a grant from NIH and
  is to be completed September 1969,

  At present time we are recording 3 channels of analog data from an
auto transplanted dog,  This data is processed using the 1800-360/50
ACME sy;;tem,  The data are converted to digital data using the 1800
and stored in the 360/50.  It is then processed and 6 channels of data
are calculated,  The digital data is then converted to analog signals
using the 1800 and printed out on an offner strip chart in the laboratory.

  We also have a PDP-8-360/5c interface which we use to store PDP-8
data on the ACME system,

Duffield, A, M.

Iv;> yw :  ADUFFIE                             Project:   CHEM

Dryartment:  Chemistry

l'r>niect Description:  This project can be summarized as follows:  (A) The
  zaking of high rate data transmission to write experimental analysis
  ;)rogrems so as to develop programs for the routine analysis and finished
   output of mass spectra.  The transmission is through the 27OY-270X
    channel,  The project plans to develop this interface to service three
  !,ass spectrometers (ALTAS CHb, AEI MS9, and 8 FINIGAN 1015 quadropole).
  ~'ne taken spectra are then to be fed to the Artificial Intelligence group
  Alder the supervision of Jo Lederberg and E. Feigenbaum to be used
   in their dendral investigations, (B) Another use of data transmission
   -Irollgh the 27OY is to take spectropolorimeter measurements and then
     .,
   r:lalysize these spectra for form, bandwidths and similarities between
  derivitives for theoretical projections, (C) This project also includes
  a battery of utility programs for metastable analysis, chemical rate
  analysis, Cl3 substitution ratios and other routine analysis that the
  Chemists wished programmed,

106


Name:  TDURBRl                            Project: ROOT

Department:  Pathology

Project Description: (1) Statis,tics: Using ACME subroutines, programs, and
  minimal own coding will compute statistics for S.V.H. research projects,
  (A) only when requested, and (B) only if researcher will foot the bill.
  Hopefully, I will not be doing too much of this.  (2) Pathologese Snop
    Translation:  Working with Derek Enlander on the same problems. I
  am transferring the files to d-enland cases, and deleting this aspect
   of ROOT.

Name:  D EDWARD

Project:  STRESS

Department:  Medical Student

Project Description:  Using ACME to conduct research on the effects of
  hormones on the alpha rhythm and temporal perception,  D&a relevant
  to these experiments are reduced statistically using ACME.,  In addition,
   specific programs are used to:  (I) generate time intervals to minimize
   search time for the two-flash threshold, (2) to convert evoked potential
  amplitude measurements into micro volts, (3) to identify the two-flash
  threshold on the basis of a linearization assumption, (4) to prepare
   and justify manuscripts.  In the near future, specific programs will be
  employed (with the 1800) to identify hormone-indured changes in the EEG
  on the basis of Fourier and spectical analysis of recorded EEG's.

11  Vii   d-cn Land                            Project:   cases

Uf, ;i; ;*tment:  Pathology

I  it: Description:  I am endeavoring to devise a system whereby medical
  diagnoses can be filed in disc storage in coded form,  The coding is
  automatically derived from a thesaurus file by matching key words,
  which will conserve both file space and enable synonymous diagnoses to
  be retrieved efficiently"

   T'he basic thesaurus and code is based on the common S.N.O.P.
(Standard Nomenclature of Pathology) on account of its wide usage
and comprehensive modern terminology,

1.07


Name;  d enland                            Project:   snop
        -

Department:  Pathology

Project Description:  I am endeavoring to devise a system whereby medical
  diagnoses can be filed in disc storage in coded form.  The coding is
  automatically derived from a thesaurus file by matching key words,
  which will converse both file space and enable synonymous diagnoses to
   be retrieved efficiently,

   The basic thesaurus and code is based on the common S.N.O.P,
(Standard Nomenclature of Pathology) on account of its wide usage and
comprehensive modern terminology*

Enlander, D,

Name:  d enland
        -

Project:  PIPIC

Department:  Pathology

Project Description:  I am endeavoring to devise a system where'by medical
  diagnoses can be filed- in disc storage in coded form.  The coding is
  automatically derived from a thesaurus file by matching key words,
  which will conserve both file space and enable synonymous diagnoses
   to be retrieved efficiently.

   The basic thesaurus and code is based on the common S.N.O.P,
(Standard Nomenclature of Pathology) on account of its wide usage and
comphrehensive modern terminology.

108


Name :  BFOLK                               Project:   GFS

Department:  Biochemistry

Project Description:  My ACME use will primarily involve the calculation of
  rough data dealing with work 7. am doing on mitants of Ecali having
  altered activating enzymes (amino acyl TRNA synthetasesj,
                                  -The calculations
   will primarily be of an arithmetical nature - taking data from sanhillahran
  co.unting and laboratory assays and computing various varfables from
   this data.,

  We are presently writing two papers in which ACME facilities have
been used.

Forrest, W, H.

Name:  W FORRES                             Project:  DATA
        -

Department:   Anesthesia

F'-reject Description:  We use the 360/50 time sharing real-time system to research
  the management and statistical application of methods to the Cooperative
   Study.  Problems of pilot studies, data validity, quality, cost of clinical
  trials and useful reduction of data for active sane management are constantly
   evaluated and updated,  The plan is to develop an inexpensive system of
  quality and quantity control of large masses of clinical data from several
  sources so that data diarr-hea and "gigo" are diagnosed properly and treated
  prophylactically rather than symtomatically.

b'nrn:st, W, H.

Tj,i I I:: r.i,ment :   Anesthesia

'- .::t Description:  We use the 360/50 time sharing real-time system to research
the management and statistical application of methods to the Cooperative
Study.  Problems of pilot studies, data validity, quality, cost of clinical
trials and useful reduction of data for active sane management are constantly
evaluated and updated,  The plan is to develop an inexpensive system of
qualIt,y and qflantity control of Large masses of clintcal data from several
sotirces so that data diarrhea and "gigo" are diagnosed properly and treated
prophylact,ically rather than symtomatfcally,


Name:  JFRIES

Project:  DXARTH

Department:  Medicine

Project Description:  Present projects involving computer diagnosis of
   rheumatic disease are, in addition,  p artly designed to increase our
  familiarity with the system0 (Experience Counting in Sequential
  Computer Diagnosis, J. F!. Fries, 1969, (submitted for publication).

  Beginning in late Spring 1969 we will begin work on a large-
scale data file entry, storage, retrieval system for clinical information
about Rheumatic Diseases.  This system has exciting possibilities for
improving quality of clinical research, quality of medical care, accuracy
of di.ai-i.los:s, extension of the medical school influence into the community.
and so forth,  Methods of supporting clerical, software, and hardware
needs are currently being explored in several areas.  During early
development, we will request 10% support for hardware costs through the
ACME System,

Fung, 9.

Name:  D FUNG-
        -

Project:  RESPUNIT

h-a rtment:  Anesthesia

;'roject Description:  Ob,jective:  To determine the response of the pulmonary
   circulation to changes in inspired gas composition and intra-treacheal
    pressure,  Progress to Date:  Apparatus has been set up for measuring
   pulmonary 'blood flow from exhaled gas composition and a program is
   :ilready available to compute the results,   Current Work:  (1) Refinements
   are 'being made to improve the accuracy of the pulmonary blood flow
   mea St: !`?!ii?nt,, and (2) A pilot study is being started to observe the
   ,:l'ft-c.t elf' a change in inspired gas composition on pulmonary artery
      :;';:ssure6  Intended Computer Use:  Computation results from data (a)
  Lalibration curves are computed, (b) Data is converted, (c) Results
  are computed, (d) Statistical parameters are calculated.

No data files will be used,

110


ITme:   WGERSCfi                              Project:   smms r

Department:  Neurology

Project Description:  The project 1s a research investigation to examine the
   extent to which the interreiationship between a variety of electrophysio-
   logical data records can be modified by a linear relatfonship.

Examples of previous and ongoing computations include:

    I,  Computation of the coherence between macropotqentials and intra-
cellular slow waves (human data provided by Dr. F. Morrell and animal
data now being gathered in coll,aboration with Dr. Morrell - preliminary
researcn res-tilts reported at a Neurosciences Research Program Work
Session on "Ne-dral Coding" February 1968 to be described in a forthcoming
N.R.P. bulletin,

    2,  Determination of transfer function and a study of the causality
:.:slati.onship between averaged evoked potential and post stimulus time
histograms on experimental data provided by Dr. K, L, Chow taken in cat,
lateral geniculate with light stimulation and by Cr. A, Starr in cat
cochlear nucleus with sound stimulation.

   3.   Determination of tne evolution of a transfer function between
macropotentials during the evoLut,ion (over a period of weeks) of epilepsy
in cats.  Computations performed on data supplied by Dr. G. Goddard.

111


!X:!-: i:, 'I'. J,

Name :  T-GLATTK                            Project:  ENG

Department:  EJXC (Surgery)

Project Description:  Use cf the ACME facility through July 31, 1969, is
   anticipated in two research areas:  Auditory physiology: We are collecting
   data on an almost-daily basis from a group of preparations with electrodes
   implanted in the auditory nervous system.  Generally, the recorded activity
   is processed and stored briefly with a small general-purpose computer.
   Use of ACME in this work would seem desirable for numerical analysis
   incorporating ACME, but since the sample sizes are modest, use of ACME
  for analyses requiring many replications of an operation (e.g., in auto-
  correlation) is advantageous.   Clinical research:   Over the next few
   months, we anticipate attempting a feasibility study to determine if ACME
   would be useful for patient categorization.  Our general thinking is that
   files containing coded history and test findings would be updated on a
   daily basis, so that these might be available for a trend analysis.  (For
   example, the audiological examination on a given patient may incorporate as
    many as  a half-dozen tests,  Patient selection for a given course of
   treatment or additional special testing would seem to be enchanced by the
  availability of such trend analyses.)

Gleason, C, A,

r\Jrir,e :  CGLEASO                             Project:  CORmAS

DrTpartment :  Medical Student - Graduate

*t Description:  This user project is being used in connection with my
.,2redoctoral research fellowship.  To date the various researchers in the
Neurology department have been sharing the costs for the ACME terminals
hilt +l?,>:"n _ has been no provision in their budgets for computer time.   Their
,rojected budgets do not provide for computer time and my predoctoral
71lowshi.p does not provide funds either.  While my use of ACME has not
lIeen extensive I have been using it primarily in an educational way to
learn how computers can be used in electro-physiological research.

  I would like to continue using ACME and storing programs on a 100%
rebate basis through the summer at which time my predoctoral program is
to be completed.

112


Name :  D-GLICK                             Project:  LASER

Departments  Pathology, Histochemistry

Project Description:  The ACME facility is needed to provide the computational
  requirements of the laser microprobe analytical system which we have
   designed, and are continuing to develop, for elemental analysis of micro-
   scopic 'biological samples down to the single cell and very small volumes
    of fluids.  The applications of the system to biological and medical
   research and clinical medicine obviously have impressive potential.
   ACME is involved in data calculation for definition of sample size as
   well as content and concentration of elements.  Statistical evaluations
   include calculation of F-ratio, ,I'-test, U-test, population means and
   variariz: n , and also linear regressions , graphical interpolations and
   curve fitting.  A second system is now being built so that one can be
  devoted to applications and the other to continued technological develop-
    ment,  This will, of course,  at least double our need for use of ACME.
  Eventually we expect to a-utomate the system, which would further increase
   our ACME-dependence.  Papers completed this year of work in which ACME
    was involved are:

Pepper, N, A,, Scribner, E. I,, Alter-ton, L, E., Honey, R0 C., Beatrice,
   E, S,, Harding-Barlow, I., Rosan, R. C, and Glick, D.  Q-switched
  ruby laser for emission microspectroscopic elemental analysis.
  Anal, Chem> t-0:1178-1182 (1968).

Beatrice, E. S., Harding-Barlow, I and Glick, D,  Electric spark cross-
  excitation in laser microprobe-emission spectroscopy for samples of
   lo-25 micron diameter.  In preparation.

Beatrice, E, S. and Glick, D.  A direct reading polychromator for
   emission spectroscopy.  In preparation.

Nitme t  DGODWIN                              Project:  ADRENAL

De!-,` ;-tment :  Surgery

Project Description:  Clinical cancer research record protocols and data for
   storage and analysis,  Next step will be display routines.

11-3


Name :  JHACKNE                            Project:  PHN

Department:  Pharmacology

Project Description:  User works with Goldstein who is on leave until
  September 1, 1969.  Project is not being used now, but want to keep
   in abeyance for now.

Hahn, G. M.

Name :  G-HAGN                             Project:  RADIATE

Department:  Radiology

Project Description:  There are various programs used in graphics of
   experimental data, e,g,,  survival curves of x-irradiated mammalion
   cells; output of planchet counter, etc,

114


Harrison, D. C.

Name :  DCHARRIS                           Project:  CATH LAB
                                                                           -

Department:  Cardiology

Project Description:  An extensive cardiac catheterization data analysis
  program has been developed (1, 2, 3),  Statistical analysis of the
   results obtained by a computer justify routinely using such a program
   on a day by day basis for calculation of the results of cardiac
    catheterization.  This would greatly decrease the amount of time a
   physician need spend after the catheterization in analysis of the data.
   Because of the time required to complete a catheterization, the large
   size of the program and the fact that it is resident in core while data
   is being collected,  serious consideration is now being given to the use
   of digitally coded magnetic tapes which may be played back after the
   completion of the catheterization,   This would result in decreased
   computational cost.  In addition, other catheterization laboratories in
   the area may then be in a position to utilize such a program.

   Given the necessary computer reliability to routinely analyze
catheterization data, a program is available to automatically transfer
the results of computation to a patient record in a data file.   Forms
are available which will be used to obtain clinical, X-ray, EKG and
surgical followup data permitting statistical correlations on a large
group of patients,

   The computer facility is also being used to develop a program for
recognition of abnormal EKG complexes.  In the near future we hope to
be able to use such a program in a computer devoted to monitoring of
Coronary Care Unit patients.

References

1.   Stenson, R. E,, Crouse, L,, Henry, W. L., Harrison, D. C.  A time
   shared Digital Computer System for On-Line Analysis of Cardiac
    Catheterization Data.  Computers and Biomedical Research, Vol. 1,
  Number 6 P, 605 June 1968.

2 .   Henry, W. L., Crouse, L., Stenson, R., Harrison, D. C.  Computer
   Analysis of Cardiac Catheterization Data. Am. J. of Cardiology,
  Vol. 22, Number 5, p. 696, Nov. 1968.

3.   Stenson, R. E., Henry, W. L., Crouse, L., Harrison, D. C.   Cardiac
   Catheterization Data Analysis.   J.A.M,A,  - Submitted for publication.

1-15


Hari-is, R. F.

Name :   RHARRIS

Project:   PNP

Department:  Medical Student

Project Description:  Our project is an attempt to demonstrate correlations
  between the emotions experienced by subjects and their own appraisals of
   certain aspects of their environments.  Our concept is that emotions
   arise when events in the individual's situation come into certain
   specified relations with his goals,  For example,  if an individual
   perceives such events as facilitating rather than hindering his potential
   achievement of the goal, then he will experience a positive emotion
   rather than a negative one.  Similarly, other dimensions, such as the
   extent to which the individual feels in control of the situation, the
   extent to which he is explicitly pursuing a goal within the situation,
   and the degree of certainty with which events in the situation affect
   his potential achievement of the goal, are also hypothesized to be
   important in determining which of a number of different emotions the
   individual will experience in any situation,  The emotional state
   consequent to such appraisals is thought to have physical and cognitive
   effects specific to it.  Cognitive effects include changes in the per-
   ception of time.  For example, different emotional states may be
   associated with different focus of attention with respect to past, present,
    or future events in the life of the individual.  By physical effects we
   mean the individual's sensations of changes occurring within his body
   as part of the emotional state.  We are developing standard inventories
   for obtaining objective measures of these subjective variables.

   The study will have two parts.  The first involves the collection
of normative data from normal subjects with respect to six emotions,
namely, anger, anxiety, depression, joy, love, and calm.  Subjects will
be instructed to recall experiences that typify their conception of
these states and to describe them on our inventories. We will use this
data to construct normative profiles of each emotional state, and to
calculate correlations between different categories of items on our
inventories.  The second part of the study will employ a number of
expectant fathers, who will be tested in the waiting room prior to
delivery and again after the birth.  This data will be used to determine
whether our previous normative data is useful in the identification of
actual emotional states and to confirm the correlations found in the
earlier part of the study.  We plan to collect the data for the first
part of the project by the end of February and to process this data at
that time.  Data from the second part of the study will be collected
by the end of April and processed then.

116


Harris, R. F. (cont.)

Name :  RHARRIS                              Project:  PNP

Department:  Medical Student

Project Description:  If successful, the study could have important theoretical
   and methodological implications.  Theoretically, we hope to demonstrate
  that an individual's subjective appraisal of events in relation to his
  goals are important determinants of his emotional state. Methodologically,
  we hope to show that certain forms of inventories yield replicable
   descriptions of subjective events.  Normative profiles such as I have
   mentioned could thus be constructed and employed as operational definitions
   of emotional states in a number of experimental contexts.   StudTies in the
  physiological correlates of emotions are but one class of examples.

Helikson, M. A.

Name :  MHELIKS                             Project:   LBF

Department:  Medical Student

Project Description:  E?JALUATION OF LIVER BLOOD FLOW WITH RADIOACTIVE ISOTOPES.
   Use of ACME facility:  storage of data, statistical analysis, evaluation
   of curves into exponential components.  We are using radioactive Xenon-133
   to evaluate the hepatic-arterial and portal-venous contributions to
   hepatic blood flow in dogs.  It is our objective to develope a relatively
   quick and technically easy method for determining blood flow in humans
   on a screening basis and in pathologic states,

117


HerL:z::iberg, L. A,

Name :   LHERZEN                             Project:  LAB

Department:  Genetics

Project Description:  Cur studies in immunology, genetics and maternal fetal
   immunologic relationship's in the mouse require the colation of many
   experimental observations on a given serum sample or individual.   Since
   such data is accumulated over long periods of time, frequent interim
   reviews must be made to determine new directions, etc.  Currently, most
   data colation in our laboratory is done by hand incompletely, inadequately
   and infrequently, thus hampering the process of the research.   To over-
   come these difficulties we have begun the process of changing our data
   storage procedures to utilize the ACME capabilities,  For example, all
   breeding records for the inbred nucleus of our mouse colony are stored
    in ACME,  Approximately once a momth ACME is called upon to draw updated
   pedigree charges, so that breeding decisions may be made.

   Presently we are working on programs to colate multiple immunoglobulin
level determinations done on individual serum samples, returning histories
of immunoglobulin level changes with time in treated animals.  Eventually
we hope also to be able to use ACME to store data and direct antiserum
production in the laboratory,

   In addition to the data storage aspects of ACME, the computer is
used in this laboratory for a number of routine calculations on data
sets, e,g., per cent antigen precipitated, geometric means of plaque
events, etc,


/ :"I nberg, L, A.

Name:   LHERZEN                             Project:  STORE

Dt 122. tment:  Genetics

Pro,) .ct Description:  Same project description as for project LAB,

Her::onberg, L. A,

Name :   LHERZEN                            Project:  PIGGY

Department:  Genetics

Project Description:  Same project description as for project LAB.

118


Hilf? F. D.

Name :   FHILF

Project:   BLACKBOX

Department:  Psychiatry

Project Description:  This project, which is virtually complete, involves
  pathological tests using a new technique of "non-contingent reinforce-
   ment" of paranoid and non-paranoid patients.  The raw data obtained by
   an electronic apparatus was analyzed by ACME as were the clinical
   behavioral ratings of patients.

   Other statistical techniques were used involving analysis of variance
to obtain level of significance of results.

   This project is virtually complete and I anticipate placing my
files on tape or deleting this altogether,

Hilf, F. D,

Name :   FHILF                              Project:   TESTA

Department:  Psychiatry

Project Description:  This project involves psychological testing of
   psychiatric patients using on-line interactive techniques in which
   the patient sits at the terminal and is asked questions and he gives the
   answers and is rei~nforced by the computer.  A bravity procedure is
   also incorporated in this program.  The main purpose is to determine
   if paranoid psychiatric patients respond to feedback differently than
   a control group of other VA psychiatric patients.

119


Hodges, D.

Name :  DHODGES                            Project:  SWALLOW

Department:  Radiology

Project Description:  The ACME camp-uter is being used to assist in the study
   of both normal and abnormal motions of the human esophagus during normal
   and induced swallowing.  A series of simultaneous pressure readings in
   various locations in the esophagus are taken by the use of water filled
   manometers connected to electrical pressure transducers.  The electrical
   voltages representing the pressure data are sampled and converted to
   digital values 5 times a second, for each of the pressure measurement
    sources, using in the IBM 1800 computer attached to the ACME computer
   system,  It is planned to have the ACME computer analyze the data from
    a swallow as it is obtained and provide immediate information back to the
   experimenter, via the terminal, of the properties of the last swallow,
   Various summary tables are kept during an experimental run regarding the
   properties of all the swallows obtained so far, and are available for
   a final summary of the experimental data.  Initially all the data obtained
   during an experimental run will be saved on the ACME data files to allow
   different methods of analysis of the data to be explored.

Huberman, JQ A.

Nme :   JHUBERM                             Project:  TEMPLATE

Department:  Biochemistry

Pro4ect Description:  I am using ACME to perform the lengthy and tedious
   calculations required to reduce the raw data obtained in equilibrium
   dialysis experiments to a meaningful form.  I am performing equilibrium
   dialysis experiments with the enzyme, DNA polymerase, and various
   nucleztide substrates, in order to get a better understanding of the
   active site of the enzyme,  Using equilibrium dialysis, it is possible
   to answer such questions as-- What kinds of molecules bind to DNA
   polymerase?  How strongly do they bind?  How many binding sites does
   each enzyme molecule have?  The answers to these questions help in
   understanding the stlructure of the active site of DNA polymerase and
    its mechanism of action.

   So far we have produced one p-ublication based on experiments aided
by ACME's calculations;

Englud, P, I',, Huberman, J. A,, Jovin, T. M,, and Kornberg, A.,
Enzymatic Synthesis of Deoxyribonucleic Acid, XXX.,  Binding of Tri-
phosphates to DNA Polymerase., J, Biol, Chem.  Submitted for publication.

120


Hmng, J.


Name :  JBWANG

Department:  Genetics

Project:  GENL1B.l

Project Description:  This project contains the statistical and miscellaneous
   programs used by the Genetics Department.

   Statistical programs:  General statistical analysis for the
calculations of sun, mean, standard deviation, the analysis of variance,
chisquareand probability of chisquare distribution, correlation and
regression analysis, the normal distribution with the same mean and
standard deviation for fitting a curve.

   Plotting programs:  Plot bar graph in 100 positions, plot of
percentage distribution, plot by function scaled to the range of 0
to 100, plot of multivalued function allows the choice and supersition
of several characters,  Flag is inserted on the chart when underflow
or overflow occured,

   Sorting programs:  Sorting a vector in ascending order, sort array
and alphabetical informations,

Hwang, J.


Name :  JHWANG                             Project:  BWTSTUDY

Department:  Genetics

'C ject Description:  Study of birth weight and IQ in relation to sex,
   parents, education, race, income,

121


Ingels, N. B.

Name :  NiNGELS                             Project:  ASMSE~06

Department;  Bioengineering and Physiology

Project Description:  This project is a study of the dynamics of the
   myocardium, utilizing stereo stop motion photogrammetric methods on
   an open-chest canine preparation,  This study is being done with full
   N.I,H. support, on grant number HE 11739-01,

  Data from two stereo cameras (in the form of a stereo pair of
negatives) is reduced by the computer to present the investigator
with various length-velocity-load-time relationships.   Since this
work is of a "pioneering" nature, it is necessary to be able to interact
quickly with the computer in order to change the program, certain
data, etc.

   The size of the data reduction problem in these studies can be
gleaned from the fact that the programs necessary could only be run
at S.C,C, at night due to the core size limitations.

   The grant includes some funds for computer -Lime, but at the rate
which it was being used at the Stanford Computation Center, the study
could not have been completed,  The availability of ACME services at
little or no cost is of paramount importance to the studies being
presently done under this grant, and to those suggested by our present
studies,  The TV dis.piay at ALOE is also of great importance, since
the graphics routines therein are exceedingly fast in comparison to the
Calcomp Hard-copy plotting routines used at the S,C,C.  It is estimated
that the availability of ACME has cut computation costs (assuming the
85% rebate rate) by about a factor of ten.

   The funds originally committed to computer time are being used
to dc,fray the cost of terminal rental,

I\: __ e :  W JAN
        - -

Department:  Medical Student

Project:  WOMAN

Project Description:  RJn various statistical tests on data from laboratory
   experiments?

Do ?!ext editing,

122


Jones, H, E,

Name :  DJONES                             Project:   FLU

Department: Biochemistry

Project Description:  Work with ACME centers around a nanosecond fluormeter
  designed by Stryer, et, al, which measures kinetics of fluorescence as
   a function of time directly,  Data acquisition is accomplished through
  the 1800, and subsequent data reduction is carried out in the 360
    proper,   The instrument as a whole has been used to determine 1)
  excited state lifetimes of various organic fluorescent compounds;
  2) rotational relaxation times of various proteins, using fluorescent
  labels to determine rotatIona behavior of the protein in both natural
   and denatural states; 3) excited state proton-transfer reactions.


Kakihana, R. Y.

Name :   RKAKIHA                               Project:   ETFANC:,

Department:  Psychiatry

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

   It is our plan to continue the use of ACME facilities for the period
to July 31, 1969e  Tnis service has been extremely valuable and has
resulted in three publications based on its use.

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

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

3*   Noble, E. P., Silbergeld, S,, Kopell, B., McKinney, W., Wittner, W. K.,
  and Butte, J. CO, 1968,  The effects of physiologic doses of cortico-
    steroid on catecholamine metabolism in man.  J, Psychiat. Res., 6:
   1593

124


Kanla!!, B. E.
  L

Name:  BKAPLAN

Project:  PSYCHOPIi

Department:  Psychiatry

Project Description:  The general nature of the project is the investigation
  of the relation of automatic nervous system (ANS) responses to attentional
  sets (thin'king and environmental observation).  In a recently completed
   study, which examined ANS changes as a function of verbalization and
  environmental attention and rejection, the computer was used to obtain
   heart rate and skin conductance values from raw data.  This physiological
   data was then analyzed, using analysis of variance and other parametric
   statistical procedures.  In addition, ACME was used for obtaining
  correlations between the physiological responses and personality variables.

  Future work will look at ANS responses in lactating and non-lactating
human females and will investigate ANS correlates of attention and infor-
mation processing.  ACME will be used for transformation of the raw
physiological data into meaningful units and the statistical analysis of
this data.

Kessler, S.

Name :  SKESSLE

Project:  MATSPEED

Department:  Psychiatry

Project Description:  Mill be analyzing mating speed experiments as previously,
  including use of linear regression and analysis of variance programs.

I'ublications:  Kessler,  S.  1968.  Nature, 220: 1044-1045.
         Kessler,  S.  1968.  An. Behac 16: 7 e
                                                    -

125


Koran. L. M.

Name:   L KORAN                               Project:   SEX
        -

Department:  Psychiatry

Project Description:  We plan to use ACME to complete one, two and three way
   analyses of variance on tes t, scores made by one thousand students. We
   wish to explore the relation of these scores to a number of variabies
   including sex9 class of college, size of home, major field, religion
   and other demographic informat3ion0  After completing the analysis of the
   data we plan to write two articles on the relation of the students
   identifying characteristics to their knowledge as measured by the exam.

Kount;z, S. Li

Name:   SKOUNTZ                              Project:  TRANSPLA

Department:  Medical Student

Project Description:  The ACME compuf,er is used by the Transplant Service at
   the University of California in two areas.  The first area is the selection
   of recipients for renal homotransplantation,  and the storage and analysis
   of data of the follow-up on the degree of renal function in an effort to
   predict the onset of rejection crisis.  The computer has been programmed
   to include sixty or more patients in the Bay Area who are on cronic hemo-
   dialysis awaiting a cadaver transplant0  Their ABO blood groups and their
   HL-A antigens are stored in the computer.  When a cadaver kidney becomes
   available,  similar tests are performed on the donor; the lfidneys are pre-
   served and the information on the donor is fed into the computer and the
   ..atched recipients are then selected and brought into the hospital for
   ,.ransplantation,  The second area is to measure and calculate hemodynamic
   changes in transplant patients as a means to detect early incipient
   -eject,inc.,  Renal function is measured by the single injection of radio-
   ,-totapes and the disappearance curves are analyzed by the computer and
    )mpared with previous determinations-  This has provided a very accurate
   :,iethod of following patients and detecting early incipient rejection. In
   ..he future we hope to feed all this information into the computer and
   jlalyze it in terms of survival in an effort to pick out which HL-A
   antigens or other factors might be playing a significant role in rejection
    as well as survival.  Although we have a limited amount of funds on an
   N.IOH. grant to study the pathophysiology of renal transplantation in man,
   our grant does not include funds for computer analysis,

126


Kraemer, H. CC

Name:  HKRAFJME                               Project:   PSYSTAT

Department:  Psychiatry

Project Description:  The work done in PSYTAT is that of developing statistical
   programs and evaluating set s of data coming from research where output is
   not extensive enough to zustify opening a separate file.

Kriss, J. P0

Name:  J-KRISS

Project:   BLDVOLl

Department:  Radioiogy

Project Description:  The program is being used to calculate plasma volume,
   blood volume and red cell mass in patients who receive radioactive tracer
   material,  The determination is useful in the evaluat.ion of patients with
   anemia and polycythemiaO

Kriss, J. P.

Name:  J-KRISS                               Project:  ASSAY

Deportment:  Radiology

Project Description:  This program is used to calculate the results of a
   bioassay for the long-acting thyroid stimulator, to calculate the
   statistical significance of these results, and to calculate the results
   of a radioactive iodine assay for TSH,  These data are being acquired
   as part of a study on the pathogenesis of Graves' disease and on the
   effec",:r of X-ray therapy upon thyroid f-unction,

127


Laipjs,, P, ,J.

Name:   PLAIPIS                            Project:  LIGASE

Department:  Genetics

Project Description:  T'ne computer is being used for statistical and mathe-
   matical reduction of data from experiments connected with my graduate
   research, principly those experiments involving sucrose and cesium
   chloride gradients in the ultracentrifuge,  The computer is also used
   for other simple opera-tions too complex for a desk calculator, i.e.,
   least-squares line fitting,  Use will be sporadic and of short duration.
   The computer was used in the analysis of sucrose gradients presented in
   Laipis, Olivera, and Ganesan, P,N,A.S. (in press).

'iamb, E. J0

Name:  EJM                             Project:  EMPIRE

Depajxtment:  Gynecology - Obstetrics

Project Description;  Calculation of relative potency and confidence limits
   for total gonadotropin bioassay.  Used primarily for research but will
  also be used (C_ 1 assay per momth; 1 for calculations involved in service
   work--even these assays may be used in a research project.

T,c,derberg, J.

:fsme 1   JLEDERB                             Project:  DENDRAL

L,. :ir,tment :   Genetics



1 ' *I  x Description* Y  This project is used to do a limited generating chemical
   .:tructur,es and display on sanders 720 by interfacing0

128



Leiier, A, DO

Name:   ALEIFER

Project:  PREMI

Department:  Psychiatry

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

  The project for which this data analysis is being done is a long-
term study (five years) of the effects of temporary separation during
the early post-pertum period on maternal behavior and subsequent infant
development D  The study includes as subjects both premature and fullterm
infants and their mothers and fathers,  The data which will be analyzed
under my account is that obtained from time-sampling observations of
mother and infant during routine caretaking at home and in the Stanford
Hospital.  Many other measures of the mother, father, and infant are taken
by others involved in the project.  Much of this data will also be
analyzed on ACME, but under P, Herbert Leiderman's account.  Principal
investigators for this project are P. Herbert Leiderman, Department of
Psychiatry,  and Clifford R. Barnett, Departments of ,4nthropology and of
Pediatrics and Human Development*  The project is supported by grants
from NICHD and from the Grant Foundation, New York, New York.

  Currently, two reports of the results of the mother-infant observations
are being completed, one for submission to Science and one for presentation
at t`he March meetings of the Society for Research in Child Development.
Data analysis for these papers was done on ACME, but I do not believe it
accurate to say that the papers are "based on my use of ACMEi'O  However,
if you should want more complete titles, etc., please ask for them.

129


Levihe, R. I,.

Name:   RLLEVINE                             Project: CPS

Department:  Pediatrics - al532

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

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

  T:;e purpose of tne initial investigations (in progress six months)
is to isolate and purify the carbamyi phosphate synthetase involved in
fetal pyrimidine synthesis.  This enzyme is apparently distinct from
that providing carbsmyl phosphate for the urea cycle, whose enzymatic
activities appear later in gestation than the de novo pyrimidine
                                                   --
activities.

  The major work thus far has been on development of a rapid simple
assay for the enzyme.  T.his work will continue , probably to July 31, 1969
and beyond,  Lack of an accepta`bie assay has hampered work in the field
for years.  My primary use of ACME has been to evaluate and process data
obtained during assays,  There is no question that without ACME asssitance
the already burdensome assay w-or'k would become intolerable.

  It is expected tnat as war%, with the purification progresses, we
will examine possible regulatory and control mechanisms in which this
enzyme may be important,

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

130


z. cn., :\.:.  k :rr;'Gz, 1, y. -(>7
Section III-B

T,evin:-hsl, E a CD

Name:   ELEVINT                             Project: MI471

Department:  Genetics

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

Liebes, S. J.

Name:  S-LIEBES                            Project: MS

Department:   Genetics

Project Description:  This project is directed toward the development and
   application of techniques of high-spatial-resolution mass spectroscopy
   to organic materials of biological interest.  The current investigation
    involves the use of focused radiation from a pulsed ruby laser to
   vaporize portions of solid samples in the ionization chamber of a Bendix
   Time-of-1Flight mass spectrometer.  The plume of vaporized material is
   ionized by electron bombardment and the time evaluation of the mass
   spectra of these ions is monitored at a lo-kc/see repetition rate.

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

   The ACME computer facility serves the following important supportive
func+ I -"!s:

    1.  Automation of data acquisition--in the conventional warmed
(crucible mode of' operation;

2.   Storage of all derived mass spectral data;

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

   4.   Performance of analytical studies related to the interpretation
of data, the refinement of existing instrumentation, and the development
of new apparatus.

131


Name :   M;,ORENS                                                         *
                                                                _/.8' 1.   !~`ic: j

TIepsrtment:  Pharmacology

132


Luetscner,, J. A.

Name:   JLUETSC                               Project :  Bloodpr

Department:  Medicine  - Metacoiic Research

Project Description:  0u.r research project, supported by the USPHS (AM-030621,
   deals with the secretion and metabolism of adrenal hormones. Various
   steroid hormones, catecholamines, and trophic hormones are measured under
   different conditions of sodium loading or sodium depletion. We attempt
   to define and relate groups of measurements, which assist in the identi-
   fication of curable forms of hypertension,

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

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

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

  (J) Data f.l-
         1 es are used to store information at various stages of
a sequential process, and for collection and anaiysis of the large
amount of clinical dnd La borstory data which accumulates during a long
lnvestigatlon,

  (4) The computer has been used extensively in research training
of Fl-iIlows and staff, first in principles and techniques of computer
USCCi,  a:id subsequently in practical applications.

1-33


Name:   JLUME                               Project:    17 - TW!i>E

Department:  Medicine - Micro

Project Description:  The purpose of this project is the biochemical charac-
   terization of alkaline phosphatase of thymic lymphomas in C57Bl mice.
   This enzyme does not, occur in normal thymic lymphocytes,  These lymphomas
    are known to 'be induced by viruses,  This investigation is to determine
   whether the information for this enzyme is contained in the virus or
     is cellular0  This is be!ing done by characterizing the enzyme biochemical
    and comparing these results to those found in embryo thymuses and other
   normal organs.  ACME is used for statistical interpretation of the
     results.

Luzzatti, L.

Name:   LLUZZAT

Project:   GRAGS ON

Department:   Pediatrics

Pro,ject Description:  The computer has been used to study a family with a
   chromosomal mosaicism in 3 generatlons,  Measurements of involved
    chromosome pairs from affected individuals and normal controls were
   entered,  and means,  standard deviations and percentage differences cal-
    culated,  Distribution curves and three-dimensional histograms to
   clsssify different cell lines were also done by the computer,  This
   program is now compieted and the majority of the files will be deleted,

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

134


MacPherson , La

Name:  LMACPHE                             Project:   META

Department:  Psychiatry (Ve+erans Administration)

Project Description:  PROPOSAL AND MEXHOD OF STUDY. We plan to investigate
  the significance of the CN\T and aspects of the MP studying their
  similarities, differences, interrelationships, and relationships to
   mental states such as selective attention and expectancy.  Healthy
   college student volunteers will serve as subjects,  No drugs will be
  given and no risk to participants will accrue. We will proceed in
  an explorative fashion with pilot studies, hoping that as possible
   avenues of investigation are outlined, more difinitive experiments with
  larger population samples will tske shape. We plan to start with the
    following study,

Ss' AEP wiii be obtained under the following experimental conditions.

    Short auditory stimulus presented repetitively and timed
randoiiy. (T o obtain AFP evoked by the auditory stimulus.)

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

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

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

   5"  S hears a tone (conditional stimulus) and when two seconds
lateI- another tone appears (imperative stimulus), S presses button
clulckl.~~-.  (To o.btain the type of CIVJ that was reported by Walter.)

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

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

135


M-7CPilerSOT: , L. (corit,)

Name:   LMACPHF                               Project:  META

Department:  Psychiatry (Veterans Administration)

Project Description:  described In more detail could clarify the relationship
    betwen the MP and the CNV,  Since muscle activity (e.gO, pressing of
  switches) is widely used as an indicator of S's intent or state of mind,
   elucidation of -the relationship between CNV and MP is needed.

REFERENCES

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

     c: 1  Gflden, LL, et, al,, Electroenceph, Clln, Neurophysiol.,
20:4.13-438, 1966. -
-

          V. and Goldstone, M., Electroenceph, Clin.
Neurozhysi?1a;:b6j) e

   4.  Rusinov, V. S., Electroenceph, Clin. Neurophysiol.,
No. 13, 1960.

SUPP

   50   Shvets, T0 B., Conf, Electrophysiology of Higher Nervous
Activity, Moscow, 1958.

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

lv:rliiE :   RMAFFLY                            Project: CO2

I):-I rt,ment .  Medicine (Veterans Administration)


   z~L Description:  Under study is active sodium transport by the toad
    bladder.  We correlate three variables:  short circuit current, CO2
   product,ion and ClYO2 proudction.  The computer is used to calculate
   the variables and to interrelate them, and to perform statistical
   analyses,

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

136


Mesel, E.

Name:  EMESEL                              Project:  DOGLAF

Department:  Pediatrfcs

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

represents the concentration in the left heart, then the impulse
response  h( t>  is described by tihe equation:

                              s=t

Co(t) + s h(s)Ci(t-s)ds
       szo

Replacing the
of time:

integral with a summation over equal ly spaced interva IS

Co(n) = 2 h(i)Ci(n-i)
       i Z~I

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

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

1-37


Mesel, E.

Name:  EMESEL                              Project:  VSD

Department:  Pediatrics

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

  During the experiment, VSD flow, left and right ventricular pressures,
and the ecg are recorded on tape.  The more interesting data are selected
for A to D conversion and for computation of the differential pressure
by program WORK!ZORSE.  Program LISTING lists digitized data, which, when
graphed, permits comparison of the pattern of flow with the pattern of
differential pressure. As might be expected, we have found that these
patterns are very similar even under varying conditions (e.g., ectopic
beats), with flow slightly delayed with respect to pressure.  Program
cathlog produces a file which summarizes all our VSD experiments.

   Future effort will be directed towards the incorporation and use
of programs developed in project carcat for pattern recognition of
pressure and flow contours.


Mesel., E.

Name:  EMESEL                             Project:  CLINIC

Department:  Pediatrics

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

Mesel, E0

Name:  EMESEL<

Project:  CARCAT

Department:  Pediatrics

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

   At this time, efforts are under way to improve and ascertain the
accuracy of the algorithms used in pattern recognition for atria1 and
ventricular pressure tracings,

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

139


Miller, R. P.

Name:  R MILLER                            Project:  BICSTAT
        -

Department:  Preventive Medicine

PI

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

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

The computer is used in all these activities.

Monnin, L. M.

Name:  L MONNIN                           Project: DISCRIM

Department:  Speech and Hearing Sciences

P-r,oject Description:  A study of the relationship of articulation and identi-
  fication abilities of normal speaking and speech defective children.
  Distorted speech stimuli will be presented to the subjects so that an
   identification threshold can be estimated.

140


Morris, S. J.

Name:  SMORRIS                              Project:  EXFI'4

Department:  Genetics

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

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

141


Name: _ _
     L NALL                              Project:   PSORIASI

Department:  Dermatology

Project Description:  Psoriasis is a chronic,  scaling skin disease of unknown
   etiology, which affects approximately 4% of the general population (no
  accurate figures are available)O  It is a lifetime disorder which does
   not take life, but indeed destroys it for all age groups.

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

   Presently, the Department is conducting Series I.I, III, and IV of
its questionnaire survey; doing follow-up studies on the familial incidence
of psoriasis and the relationship of psoriasis to other diseases, i.e.,
arthritis, diabetes, throat infection (The findings from Series I, which
had been computerized on the 7090 are now being handled by the 360/50
and 67-) o

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

142


Nali, ?I. L,

Name:  I, NALL                              Project:   MYCOSIS
        -     -

Department:  Dermatology

Project Description:  Mycosis fungoides is a fatal skin disease of unknown
   etiology,  Various chemotherapeutic agents (i.e,, nitrogen mustard,
   steroids, etc,) have been utilized to abate this disease, but the x-ray
  and elctron beam are the only techniques that have proven effective in
   producing remissions.  The Stanford School of Medicine and the
   Massachusetts General Hospital are the only facilities in this country,
  who have applied the beam in treating mycosis fungoldcs; although
  recently the Ovarian Company has developed smaller accelerators which
   vi11 be used in other hospitals.

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

   Dr, Schneidman has supported this effort from nis personal funds
;ind plans to continue to do so.  Thus, we are concerned in keeping our
, 3!L? ~'YTS~C` at a minimal level.

143


Noble7 E. P.

Name:  EPNOBLE                             Pro2ectr  ALCGHO
               -

Department:  Psychiairy

Project Description:
    central nervous
   from the NIGH.
   system is being

We have been studying the effects of alcohol on the
system of rodents.  This study is supported by MH 14599
A study of alcohol's effect on the pituitary adrenal
studied in various inbred mouse strains,  We are also

studying the effects of central nervous system lesions on alcohol
preference phenomenon in mice0  Finally, the mechanism of central nervous
system adaptation to alcohol and other stressors is being considered.

  It is our plan to continue the use of ACME facilities for the
period to July 31, ~969.  This service has been extremely valuable and
has resulted in three publications based on its use.

1.  Kakihana, R., Butte, J, C. and Noble, E. P., 1968.  Effects of
  goldthioglucose on alcohol consumption in C57BD mice.  Life
  Sciences 7: 825.

2.  Kakihana, F., Noble, E. P. and Butte, J. C., 1968.  Corticosterone
  response to ethanol in inbred strains of mice0  Nature, 218: 360.

3.  Noble, E. P., Silbergeld, S., Kopell, B., MeKinney, W., Wittner,
   W. K., and Butte, J, C., 1968.  The effects of physiologic doses of
   corticosteroid on catecholamine metabolism in man.  J. Psychiat.
   Res,, 6:  159 -
     - -

"J?rnP :  WNYE                               Project"  STUDENT

1-t,- ,\;
1.    7ment :  Medicine - Micro

E)w ;.-c:t Description:  Under this tiser name, several people in this department
  have ,used this project for statistical calculations and bibliography
   ompilations y  Several of the users have been graduate students of the
  department or postdoctoral fellows,  The bibliography compilation will
  probably be published in the new Biochemistry Handbook by Dr. Kirschbaum.

144


`*l'd I, t >$o I F1;00:,, -;. j -CT:
Section III-B

Payne, R. 0.

Name: _
     R PAYNE                              Project:  SERNAL

Department: Medicine - Hermatology

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

Pearson, M. Lo

Name:  MPEARSO                              Project:  CTCOR

Department:  Biochemistry

Project Description:  The program is used to compute normaliz4ed chromatographic
   elution profiles of viral SRNA.  We have found that induction of lysogenic
  bacteria results in the formation of a set of small molecular weight
   ordered RNA's coded by phage X DNA.  These RNA's have physical character-
   istics similar to transfer RNA and may be intimately involved in genetic
    control,  The set of viral RNA's can be fractionated on benzoylated deae
    columns.  The computer normalizes the elution profiles of viral RNA's
   to a constant total output RNA, allowing comparison of the relative amount
   of each viral RNA from one column run to the next.

  It is anticipated that future programs will be used to calculate
quench-corrected values of radioisotope activity in double-label
exper-iments,  using data from a liquid scintillation counter0

145


Petralii, J. K.

Name:  JPETRAL                          Project: MET;-DATA

Department:  Infectious Diseases

Project Description:  A COMPUTER METHOD FOR IMPROVEMEI'~ OF ANTIBIOTIC SENSI-
   TIVITY DATA AND GUIDANCE IN THERAPY. J. K, Petralli*, S. Wallis*,
  T. C. Merigan,  Department of Medicine, Stanford University, School of
   Medicine, Palo Alto, California.

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

146


porter, R. w.

Name:   RWPORTER                             Project:.  ATT KT"J

Department:  Biochemistry

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

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

   This computational procedure was refined and optimized for speed,
and the program will compute the best values for the two parameters, to
an accuracy exceeding that of the data, in less than ten seconds of
computer time in 3 time-sharing environment.  This approach proved to
be so successful that, It was adapted for curve-fitting other, more
complex non-linear kinetic equations with more parameters.  For example,
the non-linear equation describing substrate inhibition, with three
parameters, which does not give a simple linear reciprocal transformation,
has been employed directly, using this trial-and-error technique. ln
addition,  the family of hyperbolic curves described by the equation for
competitive inhibition, with three parameters, has been employed
;,lccessfully.

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

147


Porb?r, R. W. (cont.)

Name:   RWPORTER                         Project: ATC-KT?i

Department:  Biochemistry

Project Description:  These programs make special use of the on-line
   communication available with the ACME system,  especially through the use
   of options and operator-controlled branchpoints in the programs.  The
   results of these kinetic studies have been reported to The Journel of
   Biological Chemistry, where they will be published in March,  The
   manuscript for this report was prepared making extensive use of the
   manuscript editing facrlities of ACME.  The authors of the report are
   Robert W. Porter, Michael 0 Modebe, and George R. Stark, and the title
   is "Aspartate Transcarbamylase:  Kinetic St-udies of the Catalytic
   Subunit".

148


Reaven, G. M.

Name: _
     G REAVEN                           Froject:  DISPLAY

Department:  Medicine

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

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


Name:  G-REAVEN

Project:   FIT

Department:  Medicine

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

Reaven, G. M.

Name:   G REAVEN
        -

Project:   PAT DATA

Department:  Medicine

Ercjject Description: ('
            bee discussion in Project DISPLAY.) This project
   includes Stage 1 and Stage 2.  Stage 1 and Stage 2 are support programs
   for Stages 3, 4, and 5* In Stage 1,  serum endogenous insulin is bio-
   logically assayed by the program INSULIN.  The program TGCONRAD determines
   triglyceride concentration and the program DOUBLE estimates counts from
   double label experiments.,  The final program in this phase WEIGHT estimates
   weights of data points for future statihical analysis.  The second stage
   -onsists of statistical support programs for evaluation of the results
    .P Stage 1,  The programs used in this phase are TEATEST, RAT, NOVA, CORL,
    :,nd REGRESS.

    c 11 :esearch activities also include procedures to determine weight
-*.tterns of patients,  The programs involved in this aspect are BODYCOMP
3-1 BODYFAT.

Name:   J REITAN
        -

Department:  Anesthesia

Project:   INDIRECT

Project Description:  We are processing cardiac internal timings collected
   by non-invasive,  indirect techniques in order t.o monitor the contractile
   state of the heart tinder varying loads and drugs.

150


Reyncids, W. E.

Name:  WEREYNOL

Project:  soo'i

Department:  Genetics

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

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

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

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

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

Improve the quality of the data.

.:ap?*ove the presentation of the data,

Foster computer files of pertinent data.

,`,!?i s is being accomplished by basic research and development in the
,plic?tion of computers, both dedicated and time shared to the field
of computer-instrument integration,

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

1-51


.,.:..t !.:,. YE&C'31 1 -43
section III-B

Reynolds, W, E. (cont.")

Name:  WEREYNOL                           project:  so07

Department:  Genetics

Project Description:  Publication - COMPUTER CONTROL OF MASS ANALYZERS. A
   paper given, and published in the proceedings of, The Sixteenth Annual
  Conference on Mass Spectrometry and Allied Topfcs.  (May l968, Pittsburg,
  Pa.) (ASTM Committee E-14).

Reynolds, W. E.,

Name:  WEREYNOL

Project:  TEXTS

Department:  Genetics

Project Description:  This 1s a text management project to support general
  engineering efforts in instrumentation.  The project supported is:
   W.E.REYNOLDS,S007.  "TEXTS ff contains commercial technical data and
   information retrieval programs.

Robertson, W.

y~:.i:TiF :   W ROBERT                            Project:  UGAG
        -

t:i: iartment :  Pediatrics

Project Description: (1) D.t
                              a  a on urinary analyses of glycosaminoglycsns
  ,;oth on patients and normal individuals will be entered.  The curve
  relating concentrations to age in normal children will be developed.  The
  vsiues of groups of children with different diseases will then be compared
   .dith normals to discover which diseases lead to abnormal excretion.

  (2) Analytical data on immunoglobulin concentrations in sera from
jtients with a variety of immunologic diseases will be entered and
-orrelations developed with the clfnical state of the patient and therapy.

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

152


Rosenberg, L,. T,

Name:  L-ROSENB                            Project:  ALEXINE

Department: Medicine - Micro

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

Rosenthal, W. S,

Name:  W ROSENT                            Project:  RESEARCH

Department:   Medical Student - Speech and Hearing Science

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

153



.,.a~it idp. FROO3'.' -0"
Section III-B

Ross, K. Go

Name:  R-ROSS                              Project:   CHEM
              -

Department:  Chemistry

Project Description:  The purpose of this project can be summarized as
    follows:  (A) The taking of high rate data transmission to write experi-
  mental analysis programs so as to develop programs for the routine analysis
   and finsihed output of mass spectra.  The transmission is through the
   27OY-270X channel.  The project plans to develop this interface to service
  three mass spectrometers (ALTAS CH4, AEI MS9, and a FINIGAN 1015 quadro-
  pole) o  The talier, spectrs are then to be fed to the Artificial Intelligence
  group under the supervision of J. Lederberg and E. Feigenbaum to be used
   in their dendral investigations,  (B) Another use of data transmission
  through the 27OY is to take spectropolorimeter measurements and then
   analyze these spectra for form,  'bandwidths and similarities between
   derivatives for theoretical projections,  (C) The project mentioned also
   includesa `battery of utility programs for metastable analysis, chemical
  rate analysis, Cl3 substit-&ion ratios and other routine analysis that
   the Chemists wished programmed,

l?otkl, w. To

Name:  W ROTH
        ,-     -

Project:   COMP

i.,i"~~rtment:  Psychiatry

!'roject Description:  For the period prior to January 1, 1969 I have submitted
  two papers for publication based on using the ACME system for the analysis
  of electroencephalograms (EEG's) and the statistical processing of the
    results,

  T will. be at Stanford unt,il June, 1969.  During the next 5 months
: will be doing a project involving the computer analysis of habituation
f the evoked response and EEG desynchronization.  Also an attempt will
me made to distinguish states of arousal produced by emotional stim-uli.
4nalysis methods include spectral density calculations based on the "fast"
I ourier transform,  p eriod analysis (Burch), and response averaging to
'mprove the signal-to-noise ratio.

  Since 90+$ of the grant goes to stipends of four residents in
psychistry, faculty salaries,  and other expenses such as tuition, Dr.
Moos feels that the 95% support level is most appropriate at the present
time0

154


,. :.11rt .Jr. .  F'Eiw:, .I 1 -0"
Section III-B

Saunders, A. MO

Name:  AMSAUNDE                            Project:  MASTCELL

Department:  Pathology

Project Description:  Multiple numerical parameters are determined for single
  cells under varying conditions of staining and animal pre-treatment.
  Analysis of results lead to conclusions on the type and quantity of poly-
  anion in the mast cells under study (once thought to be just hepanin).

  Hence the pr0jec.t involves the chemistry of Hepanin type substances
at the single cell level, the maturation and biology of the mast cell in
rats and people, and development of methodology, mostly centering on
fluoresence microscopy.

Saunders, A. M.

Name:  AMSAUNDERS                           Project:  SPHEPES

Department:  Pathology (Genetics)

Project Description:  Cells measured by a rapid sensor system.  Data collected
   on tape and records will be transformed from a LINK to ACME for storage
   and analysis.

Sal,isgeau, M. A.

NRT? :  M SAVAGEAU                           Project:  KINET
        -

De;:,,rrment:  Cardiology

~'LI~:~L. t Description:  I am concerned with the kinetic behavior of systems of
    'lzyme catalyzed reactions.  During the coming year I expect to use the
    T4X computer in three ways.  First, I will use it to store and process
   xperimental data from enzyme systems.  Second,  a nonlinear curve fitting
   qrocedure will be implemented to estimate the kinetic parameters for the
    \:hanisms  yielding the experimental data.  Third, the solution of the
   ;;ystem of differential equations will be simulated to obtain the temporal
   behavior of these enzyme systems.

155


Cavalli-Sforza, L:. L,

Name:  L SFORZA                            Project:  PAVIA
        -

Department:  Genetics

Project Description:  Programs on storage were mostly developed for simulation
   of population genetics studies.  One of them was developed for the I.C.R.O.
    course,  and is still being used for research purposes.  It deals with
   genetic drift in a human population and takes care of the effects of age
    structure.  Another simulates nutrition,drift and selection in a haploid
   population,  or in a diploid population with additive selection.   Others
   simulate the propagation of hemoglobin  mutants in Africa.,  I will have
   to use these programs in the coming year, but it is difficult at present
   to estimate actual use - except for hoping that. it will be less intensive.
  It will be perhaps 2% of what it was in the period for which sample billing
   may be carried out.

   I am also planning to use ACME for a course for medical students, to
teach computer use in simulation experiments that may illustrate the
meaning of major statistical methods,  and some special use of statistics
in medical research.

156


Smallwood, R. D.

Name:  R SMALLW
        -                                Project:   MUjIP:~:'::!

Department:  Engineering - Economic Systems

Project Description:  The Stanford Medical Facilities Planning Group is
  engaged in a system planning study for the design of the new Stanford
   Medical Care Facilities.  The primary goal of this group is the develop-
  ment of systematic quantitative procedures for evaluating the relative
  utility of alternative plans for the new facilities,  Because of the
  emphasis on quantitative analyses and because of the magnitude of the
  problem, much of our work will be directed at large scale computer
   simulations that will aid in the evaluation of alternative macro
   organization strategy for the facilities.

  At the present time we are completing the development of several
of the computer programs that will serve as intrinsic components to the
overall simulation system.  We have also nearly completed the task of
gathering the data that is necessary for estimating the parameters of
the simulation,  Current plans are to complete the integration of these
components by the spring of 1969, to use this tool in the actual
evaluation of alternative plans, and to write up the results by June.

Smith, N. T.

pz c 1 r.n+e :  NTSMITH                             Project:  BABOONS

T!epartment:  Anesthesia

-ct Description:  This particular project (BABOONS) simply involves transfer
of manually obtained and calculated data into ACME files.  Multiple regres-
sion and correlation analyses are then performed on these data.   Data
obtai'ned b:,r destructive methods (thoracotomy, catheter placement, etc.)
are compared to those obtained by nondestructive methods (microphones,
!3celerometers, etc.).  It is hoped to replace the former with the
Latter.

  We have an enormous amount of data which we are preprocessing with
our analog computer.  We would like to transfer this data directly to
ACME for analysis.  However, because of limited funds, need for pro-
gramming assistance, and difficulties with ACME, this will not be
possible in the forseeable future,


Smith, N. T.

Name:   NTSMITH                           Project: MAC

Department:  Anesthesia

Project Description:  This project involves calculation of cardiovascular
  data from variables obtained in normal volunteer subjects and patients.
  No statistical analyses are performed through this program; rather they
   are performed separately using standard programs.

Project:  PREMIES

Name:  p-smith

Department:  Pediatrics

Project Description:  This data will be used in any study involving pre-
   mature or sick newborn infants cared for in the Stanford nurseries.
  Such items as 'birth weight, gestational age, system desease, etc.,
   will be correlated by pairs,  For further information, contact the

Smith, P.

Premature Research Center.

.
a  vent1

Smith, P.


h3me :  p-smith                              Project

Department:  Anesthesia

  ect Description:  This project (ventl)  is to find out if any
                                                                     \

parameter

of mechanical ventilation (rate, pressure vt, i.e., ratio) influences
pa02 in newborn infants with respiratory failure..  So far ACME has
been used to store the measured variables and perform statisticalmaneu-
vers   such as correlation coefficient calculations,  A program for
estimation of venous lung shunt is included.

158


Smith, R. C.

Name:   RCSMITH

Project:   FAMIL"

Department:  Medical Student

Project Description:  I am a medical student who has been using the ACME
   Project for my own research,  I am a medical student pursuing an
   M.D.-PhD. program at Stanford.  Funds for my own research have been
  supplied through the Dean's Office, the General Research Support Fund.

  The ACME file has been used to store analysis data from an experi-
mental study of family structure which I conducted during the past
year.  The project contains one data file (SDM) and a number of program
files to analyze the data.  Most of the analysis has been completed
during the past year, but some still remains to be done.   I have also
done some socio-physiological studies of Kidney transplant patients,
data which I will be entering in the near future.  I plan to make inter-
mittent use of ACME for further analysis of data from these projects
during the next six months.  However, because my clinical responsibilities
will become heavy after January, I plan to put the major file (SFDM)
on disc or tape storage, to be recalled when I have more time for further
detailed analysis of raw data.

  Two papers are currently being prepared from the family research
described above.  If specific NIH grant support for use of ACME should
be listed in publications, please send me data on and acco,unt number
of the grants.

159



Stewart, L. Ti,

Name: _
     L STEWAR

Department:  C. J, Jung Institute (San Francisco)

Project:  DREPJ4

Project Description:  The research aims of the Institute is the establishment
   of an archive of classified psychological information centering around
   such primary dat'a as dreams,  and other unconscious material.   Also
   included will be psychological test, data, clinical assessments, and
   systematic demographic information.

   These archives will be valuable in extending our understanding
of unconscious material; i.e., dreams and fantasies, and will enhance
our comprehension of the relationships between the ego and the unconscious.

   Methods for the rapid collation and analysis of data are being
considered.  This includes techniques for the indexing and preparation
of concordances of clinical material drawn from history, archaeology,
mythology,  comparative religion, and other sources0  Such techniques
will facilitate the search seeking the connection between themes from
historical and cultural sources mentioned above.  The availability of
such data will be of immense value in the training of analysts, in
the general practice of analytical psychotherapy, and in extending the
frontiers of o?lr present knowledge of the human psyche.

;:tillman, R.

Name:   R STILLM
        -

Project:   PSYGAPE

:; 2rtment:  Psychiatry

Project Description:  Our project involves the use of an interactive system
   for the: interviewing and testing of psychiatric patients.

   The work has'appeared as a presentation to The American Psychiatric
Association's annual meeting and as a publication in the January 1969
issue of the American Journal of Psychiatry.

   We are attempting to use the computer and a peripheral CRT display
for anticipated psychological testing.   This includes terms from
standard psychological tests,  and novel tests which the computer is
especially suited for.,

161


Stillman, R0 A.

Name:   RASTILLM                              Project:  DRPF

Department:  Chemistry

Project Description:  The purpose of this project can be summarized as
    follows:  (A) The taking of high rate data transmission to write
  experimental analysis programs so as to develop programs for the routine
   analysis and finished output of mass spectra.,  The transmission is
   through the 27OY-270X channel.  The project plans to develop this inter-
    face to service three mass spectrometers (ALTAS CH4, AEI MS9, and a
  FINIGAN 1015 quadropole).  The taken spectra are then to be fed to the
  Artificial Tntelligence group under the supervision of J. Lederberg
    and E, Feigenbaum to -be used in their dendral investigations. (B)
  Another use of data transmission through the 27OY is to take spectro-
  polorimeter measurements and then analyze these spectra for form, band-
  widths and similarities between derivatives for theoretical projections.
  (C) The project  mentioned also includesa battery of utility programs
  for metastable analysis, chemical rate analysis,  Cl3 substitution ratios
   and other routine analysis that the Chemists wished programmed,

S:.il.lman, R. A.


Name:   RASTILLM


1 je 1-1~3 rtment :  Chemistry

             : Ser pro

ject description for DRAFT.

Project:  DREAMS

Project:  GASTRIC

?-.ent :   Medicine  - Gas+,ro-Intestinal Division

I   ,-:-It Description:  I am involved in clinical research projects relating to
   a;;tric secretory function tests and have used the ACME Computation
  ('enter over the past, year for filing of data collected from these projects
  and for statistically analyzing the results obtained.  I plan to continue
  these usages through July 1969.

   Cne publication,  'The Effect of Preduisolane on Gastric Structure
,-jnd 'r'unct,lon in Man', has been accepted and wil 1 be appearing shortly in
Q,S :'I;;;`F I\l"E,EC:~&Y
     i -1.1         D  Other p;bLicat,lons have either been submitted or are
in preparation now.

162


Stocker, B.

Name:   R STOCKER
        -

Project:   stm

Department:  Medicine - Micro

Project Description:  My main project concerns genetics and physiology of

Salmonella typhimurium - in particular somatic lipopolysacchsride,
flagella and motility, and plasmids,  especially R and colicine factors.

I am co-investigator in Dr.. E. Lederberg's project, which concerns mainly
recombination-deficient mutants in the same organism.  Main ACME usage so
far has been in statistical analysis of data from experiments concerning
pathogenicity of lipopolysaccharide mutants (estimations of LD50, rate
constant for clearance of bacteria from blood stream, harmonic mean
times-to-death, significance tests, etc.).  I expect to continue such
usage.  Ii' my grant is renewed and if I can hire s-citable help, I
expect to use ACME also for storage and analysis of extensive stock-
culture data concerning strains with numerous genetic markers, and for
participation in a co-operative scheme for exchange of such data for
several Salmonella stock collections.

163


Stryer, L.

Name: _
     L, STRmR

Project:  NANOS

Department:  Biochemistry

Project Description:  The principal aims of the research are:  0) t 0 acquire
  an understanding of mechanisms of electronic excitation energy transfer;
  (2) to develop novel fluorescence and phosphorescence methods which can
  provide detailed information concerning the structure and dynamics of
   biological macromolecules; and (3) to apply these optical techniques to
  obtain insight into aspects of the structure and function of selected
   proteins.

  The experimental approach which is used in these studies involves:
(1) the synthesis of model compounds which serve to define relationships
between o.bservable emission parameters and structure; (2) the synthesis
of fluorescent and phosphorescent labeling reagents which have appropriate
spectral properties and can be specifically attached to defined sites on
proteins, and (3) the development of optical instrumentation for kinetic
iaeasurements in the nanosecond time range and for the detection of fluor-
escence and phosphorescence emission from membranes and cells.

Stuedeman, D, L.

Project:  ADMIN

Dcgartment:  Genetics

1, :  xt Description:  I keep an inventory of IRL capital equipment, update it
   :ccasionally, use the computer to locate items, sort by room or whatever
   IS required,  It can be used for preparing reports to sponsors and pre-
   forming; listings in various forms.  I also apply the ACME sys,tem on
  r,r;ous r~athematical calculations used in my work, including a study of
   >:e University's retirement insurance program.

NaIQc .   WTSUMJGR                             Project:  BIOCHEM

Department:  Dermatalogy

Pro.;ect Description:   T o stlJdy biochemical control of collagen formation via
  proline/hydroxjproLine (ratios).

164


Thathachari, Y. TO

Name:  YTTHATFA                             Project:  DOPA

Department:  Dermatology

Project Description:  Structure of melanins.  Melanin is a polymeric pigment
  widely distributed throughout the plant and animal kingdoms.   It has
  unusual physical and chemical properties,  Using ACME as a real time
   terminal models of the molecular structure of melanins were generated
  starting wihh the known shape of the subunits and using various criteria
   for the linking of adjacent units.  By watching the output periodically
   the flow of the computation could 'be directed at will.  For these
  generated models various measurable physical data were computed and com-
  pared with tne experimentally derived values.  Programs were especially
  written for these calculations and were found to be very promising and
    fruitful,  Some of the results have been published and presented in
   conferences and more publications are under way.   In view of the success
  of the techniques the work is being continued.

. . 4

  Radioactive tracer zechnse!'s vor the detection and therapy of
melanomas  suggested .by Blois).  Improvement on the conventional scanning
techniques making more efficient use of observations with a real time
feed back between the collection of data and their processing.  Simulated
experiments using ACME as a real time terminal are under way to make a
choice between alternate techniques,  When this decision is made we plan
to commission the equipment and the interfacing with ACME.

References:

?-ray diffraction studies on melanins paper containing some of the pre-
  liminary results presented at the Annual American Crystallographic
   Conference at, Buffalo, New York during August 1968.

Jhysical-&i 'dies on melanin paper containing the results of the Monte
  Carlo techniques on the structure of melanin - to appear in the
  January 1969 issue of the Biophysical Journal,

'<-ray diffraction studies on melanins paper describing the inversion of
  the high precision X-ray diffraction data as a radial distribution
  function presented to the annual blophysical society meeting to
  be held in Los Angeles, California in February, 1969.

165


Tickiier, E. G.

Name:  EGTICK%E                            Project:  ?+lYuwmRS

Department:  Palo Alto Medical Research Foundation

Project Description:  We intend to perform spectral analysis of murmurs
   recorded with intracardiac microphones in experimental animals before
   and after making cronic inplants of known sizes.  We hope to correlate
   the onsetofmurmurs and their characteristics with the instaneous flow
    rate.

Trudell, J. R.

Name:   J TBL'sEI;L                            Project:  MASS SPE
        -

Department:  Chemistry

Project Description:  I am working on computerized interpretation of mass
   spectroscopy.  At present information is visually taken from strip chart
   recordings and entered into the computer through a keyboard terminal.
   The computer then assimilates the data and presents the results in
    tsbular form.

   In the near future the data will be acquired on-line using the 270X-Y
system.

'l'tlcker, R. B.

; ] F   _   RBTUCKER

Project: MS

Department:   Genetics

I'!~~~-'~ ':i Description:  The project consists primarily of developing a computer
    rstem for the control of a mass spectrometer-GLC! apparatus and the
   ollection, analysis, and presentation of the resulting data.  Presently
    this work takes on two forms:  developing a set of ACME/PLl programs
  :ich control the apparatus utilizing a LINC computer as an I/O buffer,
  .jnd investignting the capabilities of the ACME 1800 computer persuant
  to using it (in a time-shared mode) in place of the LINC.  When replacing
  the LINC with the 1800 it will be necessary to build additional hardware
   to perform certain timing and logic functionsnow performed by the LINC.
    It is therefore  essentia 1 that the operating parameters of the 1800 be
   accurately known,

166


Warrick, G.

Name:  G-WARRIC                              Project:   ST'EROTD

Department:  Psychiatry

Project Description:  The present research in our psychophysiological labora-
   tory revol\res around the "averaged evoked response."  We record a con-
  tinuous EEG on magnet,ic Lape when presenting selected stimuli.   After-
   wards it is necessary to take out fhe EEG from the recording for certain
   time periods after each stimulus and average from 25 to 100 curves.  When
   more than one kind of si;imulus is shown the EEG must be distributed
  according to specific stimuli and several averages calculated simultan-
   eously.

  ACME supply us with 3 analog Input lines for reading of the EEG and
corresponding signals.  Our sampling rate -is 4 msec and by reading 100
curves for 500 msec or 25 curves for 4 see we use a storage space of 25000.
After the curves are selected and averaged, they are returned through an
analog output line and plotLed con cur X-Y plot,ter.   The curves are also
stored in digital form In t.he ACME file system.

  We are presently having a second output line installed to give us a
time base for the x-axis on the plotter.

The two output lines wili be connected for more syst,ematic results.

167


Weissman, I.

Name: _
     I WEXSSM                             Project:  TFlIYMLE

Department:  Pathology

Project Description:  Our use of ACME has been limited to developing methods
  of applying statistical subroutines to our particular data needs.   This
  has proved most valuable in handling volumes of data which required
  statistical analysis, but, which was simply not feas.ible using ordinary
    calculators.  For example, in the past year we have modified the
  chisquare and bastat; subrout,lnes to be able to compare 6 standard 'bits
   of data with up to 200 test items,  g iving the exact (p) values for each
    item.  This has been incorporated into a paper which has been submitted
   for publication.  The data analyzed in that paper had been obtained in
  1963 and 1954.  We have also studied the feasibility of setting up a
  program to analyze raw 1iquLd scintillation spectrometry data from
   tissue samples, requiring analysis of 3 channels counting simultaneously
   within different "windowsE'.  Channels-ratios must, then be obtained and
  compared to a plot of counting efficiency vs. channels ration, in order
  to obtain the actual cXsintegrations/minute/sample.  Specific activities
   and fractional input activities must then be calculated, subtracting
  physical background counts (solution, bottles, filters) and control organ
   background counts.  Until such programs are developed, and interfaced
   between ACME and our scintillation counters, we cannot properly study
  quantitative aspects of in viva cellular migration streams in the
                                ---
   lymphoid system.

168


Whitcher, C.

Name :  C-WHITCH                            Project:  ONCALL~

Department:  Anesthesia

Project Description:  Computerization of the anesthesia call schedule is
  necessary because the present manual method has proved unsatisfactory.
   Scheduling is complex, excessive errors have occurred despite due care,
  and the time required to writ,e schedules is cost$.Ly in terms of profess-,
   ional and secretaria; time.

   The anesthesia consitltarit staf'f includes 1 t.ci 3 research f'ell.ows,
and 1'2 to 14 full-t.ime faculty physicians.  Dutf i es > responsibilities,
and need5 I-)? these 13 to 17 lndivlduals are diverse, including teaching,
research,  I'urt,her train lng, a.s well as the administration of operat.ing
room3 obstetrical and other forms of clinfcal anesthesia.  Nfght) week-
ends and holiday coverage musu + be scheduled t,o cover the various
anesthetizing locat.~ons as well as vacations, s.Lcknessj and out-of-t&wn
meetings.

  Schedules are regular.ly prepared at, monthly intervals.  However,
changes of plans frequent,ly I;Iccur, calling for schedule revision, at,
additional expend'i ture of staff and secretarial effort.  Arrangement of
schedule for' night, weekend, holiday, and emergency coverage is filled
with many problems and difficulties.  For exampie, twc nights on call in
a row (excep,t on weekends) is undes ira.ble and each st,aff member has
certain nights and weekends when he prefers net, to cover.   These reserved
n.ights and weekends vary from week tc week.  Fur t.hermore, call is rarely,
if ever, popular.  Each s+.af"f merrlber willingly accept.s his share, but
none wf.l.l.ingly accept.s more t,han his share.   It is important for pur,-
poses of good morale to be sure that t,his relat,lvely undesirable work
1;: evenly dist,ributed and proper.Ly credIted.

    At.  . . . ..a51. 10 dlffsrent t,ypes of zight, call work have to be tallied
,ind evenly divided, incl;Ading firs-t call with o.bstetrics on business
lJ.ys, first ca.Ll without cbstetrics on business days., first call on
.;eekends with and without obst,et,rrcs, second call on weekends, second
-:?I1 cn. ho:Lidays, and third ca.l.1 Saturdays to accomodate Saturday
scheduling.  Such schedules would be compiex enough if they cou1.d be
assigned in simple riJ:ation3 and this might `be done if the number of
staff were CCrlStanT; throughour, the year.  However)  t,he number of staff
varies; and the fewer t,he staff, t,he more frequent t,he call.   This :`Yctor
is considered in t,al.Lying the ca..lls.  Gross tallying errors which have
cccasionally occurred tave incited staff members t,o count. up their week-
ends on obstetrical or i:,+,her caL.Ls, &ith t.he fInding +,hat they have
received .rm?re t,han their =.hare, and understandably nave asked, "How
come?

169


Whitcher, C!.  (Cont. )

Name :   C WHITCH
        -

Project:   ONCALL

Department: Anesthesia

Project Description:  The ccmput.er program already worked out offers several
   advantages.  A running tally is accurate and immediately available.
  Schedule revisions required by the staff will be rapidly available and
   ~111 require a minimum amount of professional and secretarial staff time.
   Finally, the estimated savings in staff time should be noted:   12 hours
   per month secretarial and an equal amount of anesthetist's time which
   could `be more profitably spent in other duties such as income-producing
    clinical work.

  The Department cf Anesthesia hopes that ACME will support this
important clinical project,.

Whitcher, C.

Name :   c whitch
        -

Department:  Anesthesia

Project:  Spctrm

Project Description:  Spectral analysts of blood pressure sounds.   Determine
   why 'blood pressure sounds are difficult to hear under adverse circum-
    stances.  The pilot project shows that part of the reason lies in
   their energy distribution.  This work should be extended to verify this.

170


if ale;. Xc.  $ hOi';.! i- c?5
Section III-B

Wittner, W.

Name:  W_WITTrE                              Project:  KR.oGIR? :;

Department:  Psychia+,ry

Project Description: (AROGTJESS) 'The Influence of Correctly and Incorrectly
  Guessed Visual Patterns on Visual Averaged Evoked Response.  This study
  deals with changes in the elect~roencephalogram (EEG) of human subjects
under conditions of various "mental states".  The EEG associated with certain
visual stimuli in certain "mental states" will be averaged to obtain the so-
  called averaged evc'ked response (AER).  The shape of the AER waveform
  reflect,s bra.Ln activity beyond the purely sensory-receptive component.
   For instance, the AER is influenced 'by such variables as attentic,n,
   condit,ioning,  an.d habit,uation.

  In this study, young healthy males will be present,ed with a sequence
of two types of visual stimuli which will alternate randomly.   One
presentation will consist of a cueing flash, an arrow pointing left, and
a test fLash.  The other visual stimulus presentation will consist, of a
cueing flash, an arrow pointing right, and a test flash.  Prior to each
presentation, the subject will make a guess as t,c the type of upcoming
presentation by pressing either a left-handed or a right-,handed button.

   On the basis of results of related studies by other investigators,
it is assumed that the e?xked response to correctly guessed arrows will
differ from that evoked by incorrectly guessed arrows.  One purpose of
the study will be t,O ascer+,ain whether .indeed this is SO.  Furthermore,
it is hypothesized that, the AER induced by flashes fol.Lowing incorrectly
guessed arrows will differ in shape from the AER averaged on flashes
following correctly guessed arrows.  The assumption is made that guess-
ing correctly produces a different "state of minds' than guessing in-
c~.rrectly and that. this "state of mind" persists long enough to alter
the 4ER to a rapidly following neutral light stimulus.   The various
As?.;: >l'i 1 be differentially averaged to prove or disprove the stated
hypotheses.

  'The averaging of the EEG to obtain the AER will be done by the use
of ACME computers.  Our laboratory at the V.A. Hospital is connected
with AC,ME by appropriate lines for the transmission of analog data.
Once the various AERs are averaged, they will be analyzed and compared
with each other, again 'by use of ACME facilities.

  Should the hypotheses prove to be correct,, further research will
be conduct,ed to lnvest,lgate the effects of hormones on these parameters.
Ec:r this reast>n this r,esearch is supported by Dr. David A. Hamburg's
NIM "st,eroid grant".  DrO Hamburg and Dr. Bert S. Kopell are involved
in this research as ,my preceptors.

171


Wit trier, W. (Cont.)

Name: W-WITTNE                            Project: AROGUE

Department:  Psychiatry

Project Description:  My plans for computer use between now and July 1969:
   The actual collection of dat,a has been accomplished.  Data are stored
   on magnetic tape.  ACME: facilities will. be used for data reduction as
   soon as technical difficulties with the transmission lines are solved,
  hopefulLy before July 1969.

Wong, F.

Name :  F 'WONG                             Project:  MEDONCOL
        -

Department:  Medfcine/Cncology

Pr~o;~ect Description:  Patient and disease analysis - primarily to correlate
   drug responsiveness in cancer patients for educational and research
    purposes.

Wang, F.

:$, me :  F-WONG                             Project: PLAN

Department:  Radiology

,,,ject Description:  The research is still under way. We hope soon that
  we can use the computer to provide the radiation therapists with:

1.   External beam treatment, planning

2.   Interstitial and intracavitary dose calculaticn

3.   Data accession and retrieval

172


L-ra;?i pie. FROO?:J .! --CT
Section III-B

Wang, F.

Name: _
     F WCNG

Project:  S TIMMAR .5-

Department: Radiology

Project Description:  The project is designed for retrieval of cases and
   classification of cases from the tumor registration.  The ACME is
    used:

1.  To gather the case histories and follow-up information of
  patients with t,umors treated by radiation therapy.

2.  To quickly generate reliable data for the therapist's use
   In either research work or patient treatment.

1-73


Yguersbide, J.

Name:  J-YGUERA                            Project:   LUM

Department:  Biochemistry

Project Description:  The principal aims of the research are:  (1) to acquire
  an understanding of mechanisms of electronic excitation energy transfer;
  (2) to develop novel fluorescence and phosphorescence methods which can
  provide detailed information concerning the structure and dynamics of
  biological macromolecules; and (3) to apply these optical techniques to
  obtain insight into aspects of the structure and function of selected
   proteins.

  The experimental approach which is used in these studies involves:
(1) the synthesis of model compounds which serve to define relationships
'between observable emission parameters and structure; (2) the synthesis
of fluorescent and phosphorescent labeling reagents which have appropriate
spectral properties and can be specifically attached to defined sites on
proteins; and (3) the development of optical instrumentation for kinetic
measurements in the nanosecond time range and for the detection of fluor-
escence and phosphorescence emission from membranes and cells.

Zackheim, H. S.

N: r,ir" :   H ZACKEE
        _                               Project:   PSORIASI

1.Ifapartment :  Dermatology

F'-=-;cct Description:  The present study is a determination of serum copper and
  ceruloplasmin levels in patients with psoriasis as compared to other
  skin diseases and healthy controls.  I anticipate at least 60 determinations.
  7: will want the mean, range, and standard deviation on this data.

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Zwick, M.

Name: _
      M ZWICK

Project:   CRYSTAT

Department:  Biochemistry

Project Description:  This project concerns the development of new theoretical
   techniques for the solution of protein crystal structures.  The method
   currently used, r'isomorphous replacement," generally requires a team
   of scientists working for a number of years with no guarantee of success.
  This method has the surprising feature that it makes virtually no use
  of a great deal of a priori stereochemical information about proteins:
  e.g., the bond distances and angles of the repeating pephile unit in the
   protein backbone or on the amino acid side-chains.  Hence it is very
  plausible that new improved methods might be developed which utilize such
   information and which can solve protein structures much more rapidly
   and easily.  In this project, attempts are being made to define a new
   set of variables which can specify the protein structure, which is much
   smaller and hence more easily determinable than the set of atomic
    coordinates.  This new set of variables might conceivably be determinable
   simply from the X-ray intensities of the native crystal, i.e., isomorphous
   derivative may not be required,  The new set of structure variables are
   designed to implicitly include the fact that a protein is a linear polymer
   folded up in some manner in three dimensions, and that this polymer has
   a set of well known bond distances and angles in its repeating unit and
   in its branching side chains.

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