ACME Computing Facility
| “Advanced Computer for Medical Research

Stanford University pans of Medicine

ANNUAL REPORT
“FY, 1972

Primary support from
Biotechnology Resources Branch ~

National Institutes of Health
NATIONAL INSTITUTES OF HEALTH
DIVISION OF RESEARCH RESOURCES

BIOTECHNOLOGY RESOURCES BRANCH

RESOURCE IDENTIFICATION

 

 

 

 

 

 

 

if
Pe
Report Period: Grant No,
As +e .
From: August 1, 1971 To: July 31, 1972 RR - 311 - 06
“s Date of Report Preparation:
May 1972
Name of Resource Resource Address Resource Telephone No.
Advanced Computer for MEdical | Stanford University (415) 321-1200 ext. 6121
Research (ACME) School of Medicine
Stanford, Calif. 94305
Principal Investigator Title Academic Dept.
Lederberg, Joshua Professor Genetics
Grantee Institution Type of Institution Investigator's
: Telephone No,
Stanford University Private Non-Profit University
School of Medicine (415) 321-1200 ext. 5801

 

 

 

Name of Institution's Biotechnology Resource Advisory Committee:
ACME Policy Committee

Membership of Biotechnology Resource Advisory Committee:

Name Title Department Institution
*Elliott Levinthal Assoc. Dean for Research Genetics SU Med School
Stanley Cohen Assistant Professor Clin. Pharmacology "

Joseph DeGrazia Assistant Professor Nuclear Medicine "

Donald Harrison Associate Professor Cardiology "

Sumner Kalman Professor Pharmacology "

Howard Sussman Assistant Professor Pathology "

*Chariman; has reviewed report.

 

Name and Title of Principal Investigator

 

 

tepesare Date

Name and Title of Grantee Institution Official} Signature ) Date

Joshua Lederberg, Prof. of Genetics

  

 

 

 

 

 
TABLE OF CONTENTS

TMTRODUCTION. a cacscccccccncccccwweccccs ccascassccncesccncccccceel

i.

Ii.

Itt.

IV.

SUMMARY... cece ccc ccc cc cc ncccccccnscccncucececcecccuccacccncd

A. Highlights of Piscal Year, 1972... cccscccccencccecsecesld
Be Goals for Piscal Year, 1973... cccccccccccacccccecescces3
C. Comment on Medical Center Coaputer Planning. ........0.04
D. Overview of Six-Year ACHE Experiment... ....cccccccesccecd
STANFORD MEDICAL CEWTER COMPUTING PLANS. gc cccccccccccccccee?
A. The Sedical Center Scene... .ccccoccccccccccaccacesccecel
Bo ACME FoOllOW-On Grant.ceccccccceccccccrcccscccsccvesesscel
ACME FACILITY ACCOMPLISHMBETS, 197 2eccccccncccencccacccsceed
A. Planning StudieS.....ccccccccccccccccececcccccccccececed
B. ew and Continuing Application Programs......ccceececee ll
C. System Software Improvements... ..cccoenccccasccccesccee t3
D. Hardware Changes... cccsacccccccccccccccacccsccccccccce lt?
E. Operations Report. ccccccccccee cccscccsnccsecscccccccesell
Po. Education and Training. .ccccecceccscccccccccccsccascavela
PLANNED PROGRAM POR 1973.2 cccccccccccccccecccccccccccccess 24
An ODJECCIVES cc reer ecccccccccccccccancccccccccccecacacsces 24
B. Applications Development... ....ccccccccccccccccccccese ltt
Cc. Hardware ACQUISITIONS. oo cere ecewe scene sccceseccceeceee 2
De. System Software... ccc cc ccaccccccccccccccccccccccccse eld

ADMINISTRATIVE ORGANIZATION. ccc cca cccccccecccccncseccesseed3
(ii)

VI. BUDGET 2. ce cc cc cw mec ccc mecca c wc c ccc cece wesc ccececscccesccse JD
Aw. Resource Expenditures. .cwaccccccacccscccrccccseaccccs 39
B. Justification for 1973 Budget. .... cca ccccccccccccecee 36
C. Expenditure Details. ...cseesesccccccsescscaccrccssccee 38
D. Summary of Resource Funding... ccccsccsccccavcccccssees 43
E. Resource Equipment LiStecsccccccccccceccccccccaccccees 44
Fo Income Projection. 2. ccccccscccncccccccccccccscccccccce 4/7
VIL. PROJECT DESCRIPTIONS... cc ccccccc ccs ccccccscccccccccsccccccs 49
A. Core and Collaborative Research... .cccccccccccacsc cece s 49
Bo SeLVice Projects... 2. cece ccc ccc ccccancccccecccccccscsee 56
Cw. Training Project. ence ccccccccccccccccccccccccscessces 18
VIII. UTILIZATION DATA. cc cc cc ccc ccc cccncccc ence cesses asececcess G2
A. Interpreting Utilization Charts... cece cccccaccncccccee 82
B. PatternS Of USC... cc cccccccccc acca nanccsacecsecccccces B3
Cw. Utilization Charts... wc ccccccccccnccnscccccccccccccsce 85
D. Summary of Computer Resource USage...cccccccsccccccece 89
IX. PUBLICATIONS... cc cc cc cc cc cc cc ccc ccswccncascncsaccccesccesecelll
A. Publications in Regularly Scheduled Periodicals.......111
Be Other Publications. .cccsccacccncaccccccacvcccscceceesall2
Cw. Staff Technical Notes... .cccccccaccccccccccccscascces cll]
Appendix A: Summary of Campus/ACME Merger Study......... 223
Appendix B: ACME System Core Timing Results...eccneecece 0l28
Appendix C: Results of Three Compaction Algorithas...... .136
Appendix D: Comparison of Meantime Between Pailures......137

Appendix E: Proposal for Ssall Computer Service......... .138
(iii)

Major portions of this report were prepared
using the Stanford Campus Facility WYLBOR
and ACME Facility text editing prograas.
Final copy was produced on the ACMB systen
printer.
(1)

INTRODUCTION

ACME, Advance Computer for NEdical Research, is about to
conclude its sixth year as a research, development, and service
facility. One year ago, a fifteen month adsinistrative extension
was requested to become effective August 1, 1972. after dis-
cussion with NIH, our fifteen ronth extension reguest was reduced
to twelve aonths.

This annual report describes the accoaplishsents of the

past year and proposes a new work program for the fiscal year
1973. We expect this to be the final year of NIB support for
ACME under this grant. A new competing proposal has been sub-
mitted separately for the creation of a new research resource

at Stanford. The primary task to be accoaplished under the last
year of the ACME grant is preparation for the transition to a
Service facility whose operating costs, hopefully, will be total-
ly recovered from user fees.

During the past several months, a number of faculty seabers
have contributed actively to long term computer planning for
the Medical Center. One question still uader review is a
proposed merger of an academic service-computing facility such
aS ACRE with the Hospital Data Processing facility. A parallel
but separate planning effort is erbodied in a proposal for
“SUMEX" (Stanford University Medical Experizentation Computer
Facility), a new research resource for compater-acience research
on bio-medical problemas. At the university level, planning
has dealt with the interrelationships among Nedical Center,
university administration, and all other caepus coaputing.
A brief description of several of these planning activities is
incorporated in this report.
(2)

I. SUMMARY

A- Highlights of Fiscal Year, 1972

 

The gost significant accomplishment of the past fiscal
year has been the active involvement of the faculty and tech-
nical staff in planning the future of computing at the Stanford
Medical Center. Although the long range-~plans have not been
completed, considerable progress has been sade, resulting in
a far better understanding of our current and future needs.

The long-term viability of ACSE, viewed as a service
facility for the Medical Center, is tied to its ability to
earn income sufficient to cover cost. In mid-April, 1972,
a new rate schedule became effective for ACHE users. Monthly
income in the last three agonths of this fiscal year, is expected
to reach an average of $40,000. This figure includes both
computer service income, which reverts to the grant budget,
and terminal service income, which is handled outside of the
ACME grant. Several major users have developed new systeas on
ACME which will be moved to dedicated Standalone systeas in produc-
tion mode. As soon as these dedicated systeas are available, income
from these sources will drop. On the other hand, one can expect
that new applications will continue to be developed which in
turn will generate new income.

Service on the ACME facility has been parkedly isgproved
in the past fiscal year by the installation of new hardware
and software. New hardware includes faster bulk core, a small
machine interface capable of handling up to 16 satellites,
faster access disk drives, an initial complement for the saail
Bachine equipment pool, a terminal controller that will support
multiple terminal speeds, and new gtaphics hardware. Software
improvements include improveaents to the realtine systen,
extended graphics support, improved text editing, additional]
terminal support, improved small sachine support, file support,
and compiler improvements.

Several new and interesting user projects were implemented
during the past year. Some of the sore interesting new projects
include Dr. Greents activity in Biological Science, Dr. Kadis
in Anethesia, Dr. Tatton in Biological Science, Dr. Lawrence
William in Oncology, and Dr. Jerome Gold in Diagnostic Radiology.
These projects are described in the project descriptions in
Section VII.
(3)

Continuing user projects include the DENDRAL project,
which has connected a new Varian G@ass-spectrometer to the ACHE
System and has used the General Purpose Graphics Terminals
(developed by Dr. Shipton at University of Iowa) to actively
Support spectrometer operatioas. Also, Dr. Stanley Cohen's drug
interaction project has received considerable prograa assistance
during the past year. His project, formerly part of ACHE's
core research activity, received independent funding in
November of 1971. A close cooperation between ACME and the drug
interaction project continues. Dr. James Fries in Inmunology
has continued to develop his time-oriented sedical record
concept. His system has received good acceptance among physicians
an the rheumatic clinics and is being actively considered for
implementation by other departsents (Oncology, Cardiology,
and Hematology). The Oncology Department has recently started
data entry under prograas designed to use the tiaze-coriented
medical record.

Utilization of ACHE has risen only slightly during the past
year. However, this is considered highly satisfactory since
the amount of subsidized usage has decreased markedly while
the amount of paid usage has increased. also, since the basic
service charge is measured as pages of occupied core times sinutes
used, installation of a faster core box necessarily resulted in
more computing accoaplished in a fewer nuaber of pagerinutes.

B. Goals for Fiscal Year, 1973

 

A sugmary listing of objectives for fiscal year 1973
are presented below:

1. Determine a list of new services required under ACHE
to assist in iaproverment of the incosge posture; Then
freeze the system after essential changes are aade.

2. Identify critical planning areas for mounting an inter-
active PL language on the proposed SUSSEX System (a DEC
PDP-10). Improve the documentation of the ACME systea
in those areas that will be required to assist in the
transition.

3. actively support the activities of the Stanford Medical
Center Computer Planning Committee.

4 Improve small sachine support, especially by assist-
ing users in taking advantage of the new small sachine
aultiplexor.
(4)

3. Provide batch services to better utilize the night shift
hours.

6. Assist in coordination of a project to generalize
programs for the time-oriented medical records systen
so that multiple departaents can share in its use.

7. Select commercially available hardware to replace
existing terminals and other peripheral units when
performance improvements can be realized at cost
effective prices. Attempt to make the use of ACME more
cost effective wherever possible.

8. Explore the offering of PL/ACHE services to potential
users at other institutions through comserical
communications systeas such aS TYSNET. Operational
ramifications that might result froma such an offering
will be discussed with Biotechnology Resources Branch.

In summary these objectives call for provision of new
services that will attract added income, the freeze and docunen-
tation of the existing system, the release of staff time to work
on transitions to future systems, and for attracting and assisting
new users.

C. Commpent_on Medical Center Computer Planning

The Stanford Medical Center consists of the Medical School,
Hospital, and Out~Patient Clinics. Computing within the medical
School is handled primarily by the ACME facility plus a nuasber
of dedicated standalone systems, some of which are connected
to ACME. Hospital computing is handled by an adsinistrative
data processing facility operating an IBM 360/40. fhe bulk
of the out-patient clinic computing is currently handled by
the University Administrative Data Processing Facility on an
IBM 370/145. This distribution of the coaputing load has not
proven satisfactory to the user comaunity. A number of
alternatives are being explored.

The role of ACME during the past three years has been to
provide computing services to faculty and staff researchers
in the Medical Center. Earlier the role of ACNE vas to
develop new techniques for offering such services. As the
nueber of users has grown, demand has increased for highly
reliable, stable, and available service. For this reason the
development effort of the ACME facility has shifted to extensions
and improvements to existing facilities rather than radical
(5)

changes which would severely impact availability of routine
Service computing. To provide a research systea which can
tackle probleas associated with high data rate realtine
research is the subject of a separate proposal recently
submitted. This proposal calls for the creation of a dual
processor facility in which one processor and its peripherals
are dedicated to providing service to the aedical comaunity,
while the second processor will be dedicated to a saall nuaber
of research groups.

The organization of the planning effort, current status,
and a brief discussion of sose of the alternatives under con-
sideration are briefly described in Section II.

D. Overview of Six-Year ACHE Experisent

In the past six years, the NIH-sponsored ACHE experizent
has assomplished the following:

1. <A computing system that is remarkably easy to learn and
to use has been designed and built.

2. More than 230 aser projects, exclusive of ACHE staff,
are current users of the systea.

3. The system provides a highly interactive tirze-sharing
Service and realtime data acquisition. The data
collection capabilities are lisited to data rates which,
in light of current technology, appear slow and limited.
Problems of closed loop applications have not been
satisfactorily resolved using the 360/50, primarily
due to its architecture and other inherent lisitations.

4. More than 500 AD's have been trained in the use of this
systea. Sany AD's perforsing research at Stanford now
do their own programaing at an ACHE tersinal.

5S. Small machine support from ACHE is limited but growing.

We have learned in the past six years that cospater science-
type research which can involve frequent hardware adjustaents
and changes, as well as systeas software changes, cannot be
perforaed effectively on a resource which routinely provides
service for the balance of the cosaunity. Conflicts over
resource allocation between research oriented as opposed
to service oriented users lead to coaproaises unacceptable to
one or both groups.
(6)

The rapid advance of small rachines was not anticipated
at the time of the original ACME proposal. This mini revolution
has provided faster, better, more economical systens, including
broader peripheral support, than we envisioned in 1965-66.
Wwe continue to see a role, at least for the next three to five
years, for the large central processor, assuming that its
resources are supplemented with a number of satellite computing
systems to handle special requirements.

A problema which we have been unable to resolve is how to
provide free computing to pilot projects around the Medical
Center. We've observed that a number of the pioneering computer
efforts have been possible only by viture of the free computing
provided under the ACME grant. As the need to provide self-
sufficiency increased, we were able to approve fewer new pilot
projects each year. We strongly urge that NIH waive one of
its policy restrictions for the cosing fiscal year,so that
ACHE can continue to encourage the development of new
concepts on a pilot basis through non-chargeable computing
services. The University in turn aust determine some nethod of
funding such usage when there iS no longer an ACKE grant behind
the service systen.

Computer asers nationwide are learning that the software
costs (both systems and applications) far exceed the hardware
costs in most installations. The significant investment forces
conSideration of major transition costs when converting to new
hardware or software systems. We have learned that we would
like to use manufacturer's supported software whenever possible
to provide maximum exportability to other institutions. We also
observe a trend in which software will become an increasing
percentage of the total computing picture. Therefore, we would
like to see more integration of resources within the Medical
Center so that personnel need not be trained on multiple hard-
ware and software systems, and they will not be required to
reprogram their efforts.
(7)

II. STANFORD MBDICAL CENTER COMPUTING PLANS

4. The Sedical Center Scene

During the past fiscal year, Dr. Clayton Rich, was appoin-
ted Dean of the Medical School: He has expressed concern
for the long-range planning of computing in the Medical Center.
Recently, a new faculty position was created in the Department
of Community Medicine for appointing an M.D. with a
strong interest in problems associated with service computing in
a medical environment. In January, 1972, Dean Rich established
a Medical Center Computer Facilities Planning Committee and
charged it with the responsibility of examining the feasibility
of merging the ACHE facility with the Hospital Data Processing
facility. To date, the Committee has spent the bulk of its
effort examining alternative organizations and configurations and
identifying service requirements. Hopefully, by early fall,
the Committee will be prepared to recommend specific actions to
the Dean. ACME staff merbers vill provide technical support
to the Coamittee's deliberations.

Be. ACNE Follow-on Grant

The SUMEX proposal calls for creating a high data-oriented
resource asing a PDP-10 as the host computer. Dr. Lederberg,
who is Principal Investigator of the new proposal, has
suggested that the service system for the Medical Center
be a hardware configuration similar to the research systea.

In this way, developments occurring on the research systes can

be moved readily to the service system. It also provides a
strong back-up capability for the service systea. One thing
learned at ACME is that Medical Center personnel place a high
value on reliability and availability. Only by having a back-up
System can the kinds of requirements frequently cited here be aet.

The impact of the proposed research systea on ACHE's plans
for the coming year is reflected in the decision to freeze the
ACME system design as soon as possible, tie together the loose
ends through documentation, and move on to efforts that vill
smooth the transition to another hardware system. Other
demonstrations of the impact on our planning are as follows:
Q.

(8)

The current staff will require training on PDP-10
hardware and software systers.

Planning which in the past has been based upon IBM
hardware selection will have to be sodified.

Increasing the income of the service facility requires
development of sore usage and sore users. The creation
of a new research facility will dilute the funding

base to some extent.

A consensus must be reached concerning the long range
plans for the Medical Center so that users of the
existing ACME facility will not be aotivated to develop
dedicated stand-alone systems for all applications.

The Dean of the Medical School will be expected to

make sope firm commitments in order to avoid confusion
and uncertainity over the existence of a large service
center.
(9)

IIIT. ACME FACILITY ACCOMPLISHNENTS, 1972

Accomplishments by staff Operations, Systeas, and Applica-
tions groups and efforts supporting Medical Center planning are
described. User core research progress notes are included in the
section entitled ‘Project Descriptions‘.

Last year's report indicated that two factors were shaping
changes in ACHE. The first was financial and the second involved
a choice between serving special research versus general computer
users. Efforts to solve the financial problem necessitated the
substitution of faster bulk core, which increased our capacity
significantly while only slightly increasing costs. By adding
capacity we have been able to offer services to sore users within
the Stanford sedical community. In addition, rate adjustaents
have been announced which will help us determine the viability of
ACHE in a market situation where prices are set close to actual
cost of providing service.

A. Planning Studies

1. ACME/Campus Merger Study

Last fall, a study was conducted to determine the feasibility
of merging ACME with the Stanford Caapus Pacility. The study
focused on (1) the capacity of the Campus 360/67 to absorb the
ACSE load; (2) an overview of service and cost considerations;
(3) a review of planned changes within the Campus Facility; and
(4) the relative advantages and disadvantages of a serger.

A number of problemas were identified which resalted in

further consideration of saerging Hospital and ACHE cosputing
facilities rather than Caapus and ACHE facilities. Sose

hotes on the ACME/Campus serger study were issued in the fors of
a techaical note, ACM, a copy of which is enclosed as Appendix A.

2. Comparision of Available Tisge-Sharing Systenas

The IBS systeus TSO, CPS, and CALL-OS are under review as
to their possible application to Stanford sedical. coaputinog.
Some specific questions to be answered are the language
differences between the various PL/I subsets, the magnitude
of the conversion problema from PL/ACHE to another PL/I dialect,
hardware regquireaents for approxisgately 50 terainals, and sone
of the specific pros and cons associated with each systen.
(10)

3. Alternative Hardware Proposals

Gio Weiderhold, Tom Rindfleisch and Chuck Dickens were asked
to suggest a limited number of feasible hardware configurations
for consideration by the Medical Center Computer Facilities Plan-
ning Committee. The purpose of this request was to limit the
amount of decision space to be actively considered. The seven
alternatives suggested by the subcommittee included a large IBM
processor, a dual IBM configuration, a large DEC processor with
satellite systems, a highly distributed computing systea, finally
the purchase of essentially all services from outside sources.
The MCCFPC has rejected four of the seven alternatives and con-
tinues to study the remaining three. The new proposal, recently
submitted by J. Lederberg, calls for a dual PDP-10 configuration
in which one machine is primarily a research support machine and
the second machine is a service systen.

There has not been adequate time to date for detailed review
of this topology by the MCCFPC. One of the more significant
problemas envisioned with this topology is the existence
of a large number of second generation programs currently opera-
ting on IsmM hardware supported under DOS. Even if these progrags
were converted to COBOL, it is not clear that the Hospital would
choose to run on hardware other than IBN. However, a fairly small
IBM machine might absorb the load, while coupled to the patient
data base and to a PDP-10. Clearly the MCCFPC has sone
difficult problems to resolve over the next several asonths.

4. Small Machine Support Study

The ACME systeas staff, in cooperation with staff members
of other SCC facilities, formalized current ideas on the
types 9f services required of a large host computer to
adequately support a variety of satellite machines. A
summary of the study was published as ACME Technical sote
PSCS and is included as Appendix E. A few of the salient
features are a ‘front-end’ networking switch, continuous
spooling service, the capability of the satellite computer to
act as a master terminal, and high level language processors.
(11)

B. HNew_and Continuing Application Programs

 

1. DEN DRAL

The ACME facility attempted to support the DENDRAL
project in a number of ways during the past fiscal year. One
approach at supporting DENDRAL has failed... An interactive LISP
compiler was mounted under PL/ACME. Although the coapiler
runs and can be used, it is too slow for the large programs which
the DENDRAL project tend to execute. Furthermore, the coapiler
is not identical to the batch version which igposes limitations
on the user. More successful have been the efforts to support
with hardware and software the 315C General Purpose Graphics
Terminals. Using the tools provided, DENDRAL prograsnmers
have written a rather complete set of operator aids using a
GPGT. In addition, a remote job entry system for overnight
batch jobs has been partially prepared during the month
of May. It is hoped that this service will be offered
routinely in June, and that it will subsequently be iaproved
to be gore flexible in general. Liaited assistance was provided
in planning the long-term needs of the DENDRAL project for
computing. Finally, the DENDRAL staff has been very helpful
to ACME in identifying and solving realtiae support problemas.

2. Drug Interaction Project

The data entry and label printing program was placed into
production in the Hospital Pharmacy last September. Two CRT
devices and two printers are used for entering perscription
information into a central patient file and for subsequent
perscription label printing.

The second phase of the project will isplesent automatic
drug interaction searches and reporting of detected interactions
to the physician. Incorporation of interaction searches into
the production pharmacy system is ianainent.

3. Oncology Time-Oriented Records

Sembers of the ACHE staff have applied the concept of
Dr. James Fries* time-oriented medical records to computerization
of the Department of Oncology patient files. Both narrative and
numerical data are collected and presented in a three-dizensional
form (patient, medical measurements, and tise).
(12)

Initially, four programs have been developed. A patient
record input prograa allows for item entry in either a serial
manner or in an operator-determined sequence. A second program
automates specific item editing on the file. The third and
fourth programs generate letters to referring physicians,
describing the current status of each patient's diagnosis
as determined by the time-dependent visits to the Oncology
Clinic.

Ultimately, we plan to incorporate the data bank analysis
programs of Dr. Fries into this project.

4, New Realtime Projects

Several new realtime users joined us last year. Willian
Tatton, Stanford Department of Biological Sciences (P. I.,
Donald Perkel) is engaged in a study of the characteristics
of neural circuits underlying behavior and sensory information
processing in both mammal and invertebrate nervous systeas. Dr.
Paul Green, also of the Department of Biological Sciences, is ana-
lyzing the growth process of plants. Growth rate is seasured as a
function of step shifts in the turgor pressure. The system
is a gsodel for the study of mechanisms for cessation of growth
in man.

Doctors Walton Roth and Leslie Kadis are both studying EEG
data, but for differing purposes. Dr. Kadis, Department of
Anethesia, was awarded a pilot project for a psycho-physiological
study of tolerance to experimental pain. wWormal college-age
students are subjects for collection of data relevant to an indi-
vidual's pain threshold, response to drugs, etc. Dr. Roth of the
Palo Alto Veterans Administration Hospital, Dept. of Psychiatry,
is processing EEG data for statistical analysis of measures
derived from special purpose machines.

5. CSMNP Design Study

A design specification for inclusion of an interactive
Continuous System Modelling Program (CSMP) in the ACHE syster
has been published as ACME Technical Note CSMPI. Model
definition is accomplished by standard CSMHP language statements
with PL/ACME statements intermixed in the program. Processing
is in three stages: (1) translation of the CSHP sodel to a
PL/ACME program equivalent, (2) compilation of the PL/ACME
program, and (3) execution. Plans for iuplemsentation are in
abeyance at this tine.
(13)

o. Radiation Therapy Programs

An information retrieval program was written for the
Radiation Therapy Department. The data base contains information
On Cancer patients and on the results of various types of
treatment. The information had been collected by the
Department over a 3-year period. The program prints selected
patient information as determined by the interrogating radiologist.

7. Application Prograas for Public Use

Several new prograus were included in the ACHE Public
Library. These include a routine employing the
Cooley-Tukey Fast Fourier Transform Algorithe and AZTEC, a
program for reducing a sequence of observation samples to a list
of horizontal and inclined straight line segaents.

A PL/ACME to PL/I (F-level) translator was written. Most
conversions are performed automatically, but sanual recoding is
still required for conversion of many input and output statesents.

Program PLOTPRIN produces plots on the printer or user's
terminal. The PL/ACAE version of the OPS package is used to
generate the plots. Other programs include a data file copying
routine, an empty file deletion program, and a prograa to print
an alphabetized listing of a project catalog.

C. Systems Software Isprovesents

1. Extended Graphics Support

The Stanford Computation Center Caapus Facility ops
(Overall Plotting Systea) graphics package vas adapted to PL/ACHE
last year. OPS allows the user to plot an entire gtaph by
Siuple calls for grid, grid labels, titles and plotted data.
Any one of ACME‘s various plotting devices aay be specified
as the destination of the plot.

Software support was included in the 1800 system for support
of the 315C General Purpose Graphics Display Terminal.
Both character mode for display of text inforagjation and
the usual graphics mode (where text may be ‘drawn') are provided.
in character mode, line and column control is provided. #odes
may be intermixed within any PL/ACME prograa.

The Calcomp plotting package was revised in a very sinor
manner which surprisingly produced a 20% decrease in execution
time. The change was based upon a known FORTRAN deficiency
in compiling code for symbolic array subscripts.
(14)

2. Additional Realtiae Isprovements

Four projects are to be cited. Additionally, data rates
to and from the 1800/360 were increased by approximately 15%
with the installation of the AMPEX bulk core memory. additional
increases in the 1800 data transfer rate do not appear possible
due to the limitations of the IBM 1800 hardware.

The 18600 disk management routine was redesigned so that
realtime data collected on the disk is not lost as a result of a
failure of the 1800 systen.

A PL/ACME function EVENT was added to the language syntax.
This function allows the user to detect the occurrence of
a data transfer into the 360 and to issue a read command
only after the transfer has completed. The benefits include
Simultaneous processing while waiting on a realtime occurrence
and the ability of a program to respond dynamically to several
realtime input devices. The function has been iapleaented
successfully for both 1800 applications and for the Drug
Interaction Project via the PDP-11.

Operator permission to use realtime lines was eliminated.
Programmed use of devices routed through the PDP~-11 require no
operator permission. A PL/ACME function allows the 1800 user
to enable himself (the PERMIT18 function). The operator is informed
of 1800 status via operator console messages and via the SHOW
DSOPEN command. He may disallow further use of realtiue lines when
data rates for all lines reach the physical maxinua.

ACSE system control is based upon a two-level priority
scheme, The highest level is allocated to the 1800 realtine
user. Changes were incorporated so that the duration of tine
for any realtime user on the high level priority queue is
dynamically variable.

3. Improved Text Editing

ACHE's text editing package was enhanced by the
addition of the LIST and CHANGE commands. LIST outputs lines
on the terminal; CHANGE modifies lines of text without the
requirement of user verification. In both cases, one may edit
according to a specified line range or context criteria.
Terminal output may be suppressed completely or limited to
text only or line numbers only. A by-product of this project
was general improvements to the code for the MODIFY and DELETE
commands. A portion of the Text Editor was written in
Assembler Language to facilitate rapid execution.
(15)

4. Additional Terminal Support

Concomitant with the installation of the Memorex 1270
Terminal Control Unit, software additions recognize a terminal
type and invoke the necessary supporting software. 2741
correspondence code terminals are sore easily specified at
logon time. ASA standard terminalis are supported for both
display and typewriter devices and from al} TCO ports.

5. Satellite Machine Support

Two major efforts for the support of satellite computers are
noteworthy.

Stanford Computation Center Engineering Services has
completed the design of a satellite computer sultiplexor inter-
face to one of our 2701 ports. Supporting software has been
iaplemented for the ACHE systems and for PDP-11 satellites.

The ACHE software resembles the current 1800/PDP-11 support
in many ways. The user interface is nearly identical. all
communications is asynchronously interrupt driven. Differences
in the supporting software do exist, primarily because of proto-
col destinctions and because of an effort to learn frou the 1800/
PDP-11 software iaplerentation.

The SM multiplexor software is in the middle stage of
debugging. We expect to have the project completed by aid-
summer.

A program to simulate the PDP-11 is available for batch
operation and is in the debugging phase for ACHE time-sharing
execution. The Simulator executes in single instruction step
mode. Diagnostic inforgation is returned after the execution
of each instruction of a PDP-11 program. The Siaulator
provides the debugging capabilities of the PDP-11 front
panel as well as the capability to initiate the functions
of DEC's ODT debugging package. A core loader and a core dump
routine are also provided.

6. LISP Additions

Last summer, we added some 32 matheraatical and logical func-
tions to the interactive LISP compiler. This was accoaplished
by interfacing LISP to the corresponding PL/ACNE functions.
(16)

A version of LISP for batch execution, identical to the
SCC 360/67 LISP, has been mounted on ACHE. As of preparation
of this report, the LISP user has a limited method for submitting
OS JCL and ACNE files for overnight batch LISP execution.
Purther efforts on OS RJE submission from ACME are planned for
next year. Upon completion, a batch LISP job may be sore con-
veniently specified and the results more easily retrieved at
a terminal.

7. File Support Improveaents

Several additions to File System support were imple-
mented in the past year. The primary additions are a data
compaction algorithm for reducing disk storage space requirements
and several new catalog management functions.

The characteristics of numeric and character-type data
collected by a program and subsequently stored on disk indicate
that considerable file storage could be saved with sone simple
data compaction algorithms. A study in February, 1972 of
existing numeric data is summarized in Appendix C. Storage
Savings up to 50% are realizable, depending upon the compaction
option's degree of use by the user community. System design
has been completed. Implementation will begin soon.

Batch execution of requests to move user files to and fron
tape and disk was partially automated by the inclusion of public
and operator programs for generation of OS job reguests. On
the overnight operations shift, the operator starts an OS
reader task which reads the job requests from the reserved
disk data set and sends the jobs into the OS job queue.

Two specialized utility routines were written for maintenance
of the job request data set.

Further plans for an ACME BJE interface will automate this
service completely by eliminating any need for operator
intervention. Job requests submitted from a terminal will be
routed directly to a spooled job queue.

Other improvements include two PL/ACMHE functions, BLOCKS
and TYPE, for determining assigned disk block space and the
Storage mode of a file (data or text) respectively, the extension
of the PROTECT statement to prevent a DELETE on a file, and the
new SAVE FILE command. SAVE is similar to CLOSE in that
index and data core buffers are written to disk, but a subsequent
OPEN is not required for continued use of a file. SAVE is a
guarantee against loss of data in the event of a systea crash.
(17)

6. Accounting Software

Software accounting changes included modifications for the
new charging structure, the addition of time-slices accounting to
the system control program, and the inclusion of charges for
printing and punching services. Also, disk file accounting was
removed from the weekly Analyzer program and a new, high-speed
file accounting routine written for rapid collection of file
use charges.

9. PL/ACHE Compiler Iaprovements

The addition of Variable Array Allocation to the PL/ACHE
language extends its flexibility and cost savings features.
Previously, allocation of large arrays were under dynamic
control, but the size of the array was explicitly declared
at compile time. Now, array size definition aay be deferred
until execution time. Furthermore, array size (and the core
requirement of an array) may vary dynamically during a single
execution of a PL/ACME prograa.

10. Deferred Projects

Last year we reported on two systerz projects whose
isplenentation has since been suspended. The ACHE to OS file
conversion project was suspended due to some design deficiencies
and the lack of staff personnel. A design specification has been
completed which builds on the previous effort, buat increases
the flexibility of the anticipated service. Full isplementation
iS expected in the near future.

Extended logon, wherein a user session is controllable
from a device other than one routed through the IBM 2702 (now
Memorex 1270) was suspended when unforeseen design problems
were encountered in the ACME system. This project, its
desirability, and plans for system sodifications to acconsodate
it are further discussed in Section IV.

DO. Hardware Changes

i. Ampex Bulk Core

AMPEX bulk core has replaced 2 megabytes of IBM bulk
core. The Ampex equipment has a cycle time of 2.5 microseconds
versus the 8 microsecond IBM core. Responses of the ACHE
system improved considerably following the installation in
November 1971.
(18)

Core timing studies, conducted during installation of
the AMPEX core, are reported in Technical Note WCTR (See
Appendix B). Execution time of sample PL/ACME prograsgs
improved from 18% to 59% with an average improvement of 36.5%.

2. AMPEX Disk Drives

AMPEX DM312 disk drives (17 spindles) replaced the IBM
2314 disk drives in December 1971. The primary improvement
here is an average head seek time of 32 milliseconds as opposed
to 60 for the IBM drives. The drives were leased as a part
of the contract for the AMPEX bulk core.

3. Memorex 1270

Automatic terminal typing and speed recognition becane
possible when the IBM 2702 transmission Control Unit was
replaced with the Memorex 1270 Terminal Control Unit.
Devices other than a 2741 terminal or Teletype typewriter are
easily supported up to speeds of 1200 bps. Furtheraore, TCU
ports no longer need be dedicated to a specific terminal type.
Any TCU port may recognize and service any terminal, whether
typewriter, display, or computer. ACME views this hardware
modification as a major marketing and user service attribute.
We intend to exploit its poteatial wherever necessary and possible.

4. Development PDP-11 Systea

In last year's report, a small machine equipment pool was
proposed. A development PDP-11 system has been acquired through
purchase on a second-hand basis. This system includes 8k
of core, a printer, a card reader, a fixed-head disk, and an
expansion box. The system is being shared by a number of ACHE
users and is also serving as a test vehicle for small sachine
Support development by the ACHE staff.

5. Satellite Computer Aultiplexor

This is a specialized hardware interface whose purpose
as to allow shared access to the ACME system via one of our
2701 TCU parallel data adaptor ports. fhe multiplexor was
especially designed and built by the Stanford Coaputation Center
Engineering Group for the ACME Facility.
(19)

The design is such that 16 satellite computers share a
Single 2701 port on a block-multiplexed basis. One computer
controls the communications interface from start to completion
of transfer of a data block. At block transfer completion,
control of the interface yields to the next coaputer if necessary.
Data rates up to 250 KB can be sustained. Several designed-in
safety features insure that neither the multiplexor nor the
the satellite computer can disable the ACME systen. Rigid
adherence to a communications protocol and a set of hardware
timeout functions are the primary guarantees.

6. General Purpose Graphics Terminals

Two 315C General Purpose Graphics Terminals were received
in May 1971 from Dr. Harold Shipton and made available to users
in the fall of 1971. The displays are now in use by the Depart-
ment of Genetics and by Abraham Silvers of the Department of
Medicine.

On April 3, 1972, the Stanford Medical Center hosted a
conference on user experience andé@ reaction to the 315C terminal.
The conference was initiated by Dr. Shipton and attended by repre-~
sentatives of eight universities. The general impression was
that the conference was informative and successful.

An evaluation of Stanford's application of the GPGT is
forthcoming to NIH.

7. 2741 Terminal Replacement Stady

Several weeks ago a survey was instituted of available CRT
and hardcopy terminals. We are especially interested in 30 and
120 cps terminals now supportable by the Merorex 1270 Control
Unit. Several demonstration terminals have been tested by the
Staff. Some are acceptable, others not.

We expect to purchase several representative terminals fro
this year's grant funds and from requested funds for next year.

Alphanumeric displays have been used during the past
year as realtime devices by the Drug Interaction Project.
However, the bulk of ACME users have not had access to
CRT terminals primarily due to the speed limitation of
15 characters per second. Wider exposure is now possible (and
desirable) with the installation of the Memorex unit.
(20)

&. Tape Cassette Study

Last year we indicated that we intended to explore the use
of tape cassette attachments for storage of user data. A
survey was conducted of cassette units currently available.
The conclusion was that no unit performed reliably enough
to recoamend its use as a storage backup medius.
Consequently, other alternatives are under consideration.

¥. Planned Acquisitions This Year

Funds remaining in the current budget for hardware acquisi-
tions will be used for purchase of three iteass:

a. A dual DEC tape transport and controller. We wish
to provide DEC tape on our front-end PDP-11 as a
convenient and inexpensive method of reaoving user
files from disk when the files need not be con-
tinuously on-line.

b. One or two 30 character per second thermographic type
terminals. Under consideration are the Anderson-
Jacobson 630 and the Execuport 300.

c. Additional acoustic couplers and wodems for the
higher speed terminals and remote user installations.

E. Qperations Report

1. System Reliability

The Mean time between failure fell last year primarily
because of the higher than normal system instability during the
installation of AMPEX equipment. A chart in Appendix D, cor-
comparing monthly MTBF for the past three years, shows the
pattern vividly. The first of the AMPEX core modules was
delivered in November; the last of the AMPEX disk drives were
installed in January. By the end of February, the new
equipment was stabilized and the MTBF rose draaratically.

Nonetheless, the system failure rate for the year
from all causes is slightly better than last year's record.
This would indicate that failures due to non-hardware systen
components are rare, and that the ACME system software is
extremely stable.
(21)

A chart, summarizing MTBF rates in hours for the past
three years follows.

1 2 3
MTBF (System Crashes) FY70 FY71 FY71 FY?72
Hardware caused 64.3 246.6 218.8 147.7
All reasons 34.4 84.8 80.7 82.2

1
Projected figures reported in last year's report.

2
Actual MTBF for the entire year of 1971.

3
Projected totals for 1972. average of MTBF for AUG71-
APR72 determined estimates for HAY72-JULY72.

2. Hours Change

ACNE service hours were changed to 7:00am-5:30pm and
11:00pm, daily and weekends. The effects of the modification
were to delay the late afternoon system programszer block
by one-half hour (from 5:00 to 5:30) and to extend the late even-
ing service period by one hour (from 10:00 to 11300).

3. Utitity Services

Printing and punching services, performed routinely by
operations for the benefit of the user community, are now
chargeable under the new rate structure. Statistics on
quantities of lines printed/cards punched show that the number
of printed lines in March, 1972, was 50% greater than the figure
for August, 1971. The demand for punching service has remained
relatively low. Of the total printing load in the August to
March period (3,575 * 1000 lines), fully 87% is rechargeable.
(22)

F. Education and Training

1. PL/ACME Classes

During the 12 months ending April 30, 1972, ACHE provided
tormal instruction to 182 persons. Of these, 164 were enrolled
in the PL/ACMNE introductory course and 18 in the advanced
programming course. The format of the courses was changed from
three to four sessions each lasting one and one-half hours.

A questionnaire was used during the past several months to
obtain data on introductory class participants. A total of 49
questionnaires have been collected to date. The limited sample
indicates that:

a. Eighteen of the 49 or 37% expressed specific interest
in realtime applications.

b. Roughly 50% are staff employees, the remainder are
faculty and students.

c. About one-half are from the Medical School, 25%
from the Hospital, and 25% from other departments.

d. Fifteen percent report the PL/ACME course was taken
for use in a new project.

e. Thirty-five percent have a Ph.D. or M.D.
2. Medical Computing Seminars

A seminar series was organized to encourage the dissemination
of information on biomedical computing in the Stanford comsunity.
The first seminar included a talk by Dr. James Fries, Department
of Immunology, on his Time-Oriented Medical Records project,
and a film depicting the patient-oriented medical records systen
developed by Dr. Larry Weed.

For the second seminar, George Swanson of Anesthesia des-
cribed his research activity involving studies of the esophagus.
Dr. Howard Sussman and his staff presented the new Clinical Lab-
oratory Information System in the third seminar. Approximately
fifty people attended each session. ACME will continue to
serve as coordinator for this seminar series.
(23)

3. Consulting

Last Summer, the consultant's office was soved from the ACHE
office area to a partition in the sachine room. The sove was
designed to permit greater accessability of the consultant to the
user community. In January, the systems staff joined the regular
consulting staff in manning the consultant's office. Guaranteed
consulting hours are 9:30-11:30 and 1:30-3:30 daily. Each
SyStems staff member is assigned one two-hour block weekly.

4. Staff Training

Several members of the staff have or are scheduled to attend
IBM and DEC education classes this year. Chargeable classes,
covered by the ACME grant are:

Ying Lew: DEC: PDP-11 School
Charles Granieri: IBM: TP Systeas Control
for Prograssers
Stu Miller: IBS: Advanced Coding
Lee Hundley: IBM: Project Hanagement
Regina Frey: IBM: Project Management.
(24)

TV. PLANNED PROGRAM FOR FY¥1973

A. Objectiv

s

 

The upcoming year will be a period of transition. The
Nedical Center Computing Facilities Planning Committee will
define and establish the nature of computing at the Stanford
Medical Center. Assuming that the grant proposal for the
SUMEX Computer Facility is approved by NIH, we will begin
preliminary efforts on system design, equipment
specification, and training. Specific actions are necessary for
Stabilizing the current ACME System and for increasing the level
of self-sufficiency of the ACNE Facility.

It must be assused that the ACHE System, as currently
constituted, will continue to exist after July 31, 1973
until such time as a blend of the SUNEYX Grant, Sedical Center
computing plans, and Stanford-wide computing produces a viable
alternative. The trends of use in the past year show that the
majority of users depend upon the ACHE systea as a routine
laboratory tool for solution of their own research probleas.
We expect this dependence upon ACME for service computing to
continue,

B. Applications Developrent

1. Digital Filtering Progras

We have contracted with Professor Williaa Gersch of the
University of Hawaii for a sumser project on development of
Several digital filtering, spectral analysis, and time series
analysis programs. They will be designed for application to
to ACME realtime user probleas and vill be publicly available.
fhe availability of these progrags will be an asset to the
System, as some of the techniques to be eaployed have not,
to our knowledge, been attempted elsewhere.
2. Installation of Voice Drus

The voice drum will be interfaced to the production PDP-11

system this summer.

The initial application of this device

will entail retrieval of limited patient data for the

Division of Oncology.

Residents and others will be able to access

limited patient data via touch-tone telephones from throughout

the Medical Center or from their homes.

This project involv-

ing the Oncology Division is in the early planning stage at this
time. (See further notes in Hardware and System Software

Sections.)

3. Stroke Registry Programs

The Stroke Registry Program began over two years ago,
sponsored by the California Regional Medical Program. The
goal of the program is to develop a population base for analysis
of descriptive parameters of stroke and to produce predictive
output for the improvement of care and treatment of patients.

At this tine, first year followup data on surviving

patients is being collected.

A menber of the staff will

develop programs for entry of followup data and for correlation

analysis.

4. Critical Path Analysis

A publicly available computer program for critical path
analysis of a class of multi-segment resource scheduling
problems is scheduled for isplementation soon.

inistration to asedical
j resources. The administra-
ct would benefit greatly froz

rom the Stanford Linear
2 to PL/ACHME.

written the well-known

on text data. This prograrz
ort algorithss examined,
ritten for the Public Library.

Center management, from general adn:
programas and management of computini
tion of any externally funded proje
such a program.

A FORTRAN prograa, available £:
Accelerator Center, may be adaptabli

5. Fast Sort for Text Data

A member of the ACME staff has
SHELL sort algorithms for operation «
will be reviewed, other published s
and a generalized PL/ACME program wi
(26)

6. Bibliographic Data Entry

A number of our users have developed programs for automation
of preprint and bibliographic files. These will be reviewed
and a Suitable program adapted for public use.

7. Time-Oriented Medical Records Support and Other Patient
Data Base Studies

By the fall of 1972, we hope to review all the work per-
formed to date on time-oriented medical records in order to
select the optimal file design, the data entry format, and
retrievable vocabulary for the near term users. Our goai will
be to provide the system tools and the systems or applications
programming that will yield generalized programas which can be
used by many different departments in the Medical Center. we
have found that implementing the system in the Oncology Depart-
ment required some changes from the programs used for the
Immunology Clinic. We have been impressed by physician
acceptance of the time-oriented medical record. Please refer
to the user project descriptions for Drs. Fries and Willian
for additional explanation of the time-oriented medical record
concept.

Additional patient data base studies will be undertaken
with the following goals:

a. Obtain as much information as possible concerning new
tile systems to be supported by IBM and other manufac-
turers. Review the Stanford SPIRES systea as to its
applicability.

b. Monitor carefully the problems encountered at Stanford
in use of the time-oriented medical records.

c. Through literature, search, and travel resain well
informed of work being performed elsewhere.

d. Assign at least one Computer Science department graduate
student (research assistant) to the problem of file
structure design for patient medical records.

The goal of these studies will be to provide a broad
base of information on file systea technology and patient
data base systems that will be used to guide Stanford's
development and implementation of saedical inforzation systeags.
(27)

C. Hardware Acquisition

ee ae — Seen Se ae naan

Rental and purchase funds are included in the FY73
budget for several additional iteas of hardware. A discussion
of each item follows.

1. Terminals

Several 2741 terminals will be released and funds will ke
used to acquire two additional high speed hard copy tersfinals
and four CRT terminals. We are especially interested in
terminals capable of operating at 1200 baud. The choice will
be limited to standard EBCD, Correspondence Code, and ASA
terminals, if at all possible.

2. Public Printer/Plotter

The availability of a relatively fast printer/plotter
device for general use has been requested by our users.
We have been looking at several electrostatic printers,
as such a device provides extremely fast and flexible
printing and plotting. However, electrostatic devices place
a high demand on CPU and channel resources. A further
review of available plotters will be conducted before a decision
1s reached.

3. PDP-11 Equipment

An item is included for purchase of additional core asenory
for both the development PDP-11 and the front-end PDP-11.

Several additional devices (printer/plotter, DEC tape,
voice drum) are to be attached to the front-end PDP-11.
Available core will not be adequate to service these devices.

The current 8k of core on the development PDP-11 is
minimal) for DEC's operating systema. Furthermore, several users
have been unable to perform some operations due to the core
limitation. An additional 8k is required.

4. Ampex Disk Drive
Current 360 disk utilization approaches full capacity.

Addition of a new user pack may be necessary unless significant
savings result from the new file compaction algoriths.
(28)

The disk configuration is eight on one control unit, eight
plus spare on the other. On the first control unit, the eighth
drive serves as a spare since only fifteen disk packs must be
permanently mounted. If we decide to add an additional user pack
(always permanently mounted), rental of a second Spare drive
guarantees better system reliability.

5. Miscellaneous

This category includes interfaces and cabling for the
voice drum and additional acoustic couplers and sodeas (part-
icularly for 1200 baud terminals).

D. System Software

The specific suggestions for syster software tasks are
derived from four criteria:

1. The software should be stabilized as soon as possible.
2. System documentation must be completed.

3. Additional or improved user services should be aimed
toward attracting additional incogze.

4. All changes in the form of additional features should
be disallowed and the system frozen by the end of the
grant year.

Three major modifications (points 5, 6, and 7) are in
direct conflict with rquirements one and four. However, they
are also the primary tasks for achieving reguirement three.

i. System Stabilization and Cleanup

The effort here will concentrate on the elimination of
known inconsistencies and errors in the systema. Wherever
easily possible, attempts will be made to reduce the size of
the software.

2. Docuaentation

A considerable docusentation effort is planned. fhe ains
are to remove incompleteness and redundancies in the current
documentation of the system software. A general paper should
be written explaining the system design, the general functional
flow, and the interactions of the various components. Also,

a comprehensive table of contents and a cross index to each
subject category is useful.
(29)

Cleanup of documentation and the software will benefit any
transfer of the system code to another machine and it will
expedit the maintenance of the system by a reduced staff.

3. Support of Additional Hardware

We anticipate attaching a number of new peripheral devices
to the system. A list of possibilities is discussed in Section
C above.

Additional software will be required in the front-end pPDP-11
system for support of the voice drum, DEC tape (purchased from
this year's grant), and a printeryplotter. Depending upon
the type of printer/plotter selected, we may be able to adapt
manufacturer-supplied software.

With the installation of the Memorex 1270 controller,
session-controlling devices (terminals) and graphics devices
are often Synonymous. A few of the planned projects are:

a. Where necessary, add specialized terminal support. An
example is the inclusion of the Correspondence Code
translation table as developed by the Stanford 360/67
facility for the unique features of the IBM Magnetic Card
Selectric Typewriter terminal (MCST). The new TEKTRONIX
terminals (4010), if selected, will require some special-
ized support.

b. Add a few terminal control commands, such as SET UPPER/
UPLOW and SHOW CASE for specifying upper and lower case
options. Other commands determine the terminal type (ASA
or TTY), and suppress or allow transaission of the ACME
light box characters.

ce. For high-speed displays, incorporate modifications to
the LIST command so that output is suspended every N
lines. This allows the user to scan a page of lines and
use BREAK if he is interested in stopping at that point.

d. Implement page mode output for displays. A full screen
of data is displayed directly froa the user's in-core
atray or variables with a single command. The user may
then modify the contents of the screen and read it back
with another command. Some of the problemas in implemen-
tation of this capability are identical to those discussed
under "Extended Logon’.
(30)

4%. Additional Satellite Machine Support

Satellite aachine support will focus on tasks essential for
a smooth transition to SUMEX and other long range prograas
expected to succeed ACME. In addition, assistance vill be pro-
vided to small machine users wishing to connect to the new small
machine multiplexor.

5. Batch and OS Services

The provision for a user batch service seems necessary
for several reasons:

Current methods for submission of user disk-to-tape
jobs and for submission of LISP overnight work are
inadequate and operationally difficult to control.

Our present method for providing routine printing and
punching services invites some danger to the reliability
of the ACME system. Occasional long delays produce poor
turn-around time.

A number of jobs now routinely executed from an ACHE
terminal need not be run interactively. Scheduling
these jobs for overnight batch frees both the tersinal
and the CPU for additional on-line vork.

Recent hardware monitor tests indicate that the CPD
is busy for 90%-95% of available cycles during peak daytine
hours. Also, there is little free core available during the
same hours.

Consequently, only a small printing/punching utility
region could be supported during the prime shift. Sowever,
sufficient core and cycles are available during evening
and overnight shifts to accoasodate a limited load of user
batch work.

Provision for a batch service requires the completion
of these tasks:

a. An OS-type task which will convert ACHE-type files
to OS files and the converse. The design docusent on
this feature has been completed. Both direct access and
tape data sets will be supported.

b. Incorporation of the HASP system into the OS supervisor.
HASP facilities are preferred over conventional 0S
services for both better operational control and for
its smaller core and disk requirement.
(31)

c. keview of the WYLBUR/HASP interface and its adaptation
to the ACME system, if possible. Otherwise, the
development of a capability to comsunicate with the
HASP in-core reader.

d. Development of a small library of standard 0S
procedures for routine utility operations (printing,
punching, etc.)

e. Adaptation of HASP accounting. Development of a
program to merge HASP accounting with time-sharing
accounting.

6. PL/ACME Object Modules

The ability to save compiled code on a PL/ACME progran
and reload it at a later time has been repeatedly requested.
Unfortunately, we have avoided the subject primarily because
of the lack of a definitive stateszent as to its impact on the
current design of compiled code.

Reloading of compiled code saves user setup time. It
also frees CPU cycles now used for recompilation for sore
productive purposes.

Due to the time constraints of the next year and due to
the uncertainties mentioned above, this project is initially
planned as a two man-sonth study and design specification.
Actual implementation plans will be deferred until the level
of effort is known and until the choice of a computer systen
is determined.

7. &Extended Logon

As the ACME system is currently configured, a user session
can be controlled only by a device routed through the Senorex
1270. References to the desirability of expansion to logon
services are to be found throughout this report.

Specifically, some of the extensions are:

a.~ Allow a satellite computer to function as a terainal,
invoking programs, etc.

b. Allow our front-end PDP-11 to act as a master terminal,
‘logging on‘ users from devices not necessarily
capable of sending and receiving lengthy transactions
(such as touch-tone telephones).
(32)

Cc. Provide a master/slave tersinal concept, so that one
copy of a user program can service aultiple requests
from multiple, geographically separate, users.

d. Page mode support for CRT's reguires extension to the
‘one-line-at-a-time' mode of operation.

The precise technique for implesentation has not been
determined. However, a reorganization of high-level
system control functions is absolutely necessary. Expansions
to the GET/PUT and READ/WRITE statezents of PL/ACHE are a
possibly simple scheme for user comagunications.

We feel that this is the most valuable of all suggestions
tor additions to the ACME system. The considerable design
effort and its impact upon the total structure of the systen
software are wore than justifiable.

8. Miscellaneous

This category contains a nurber of saall projects, none
of which may produce any significant increase in system usage,
but all of which provide gratifying additions to
the current level of service. Cosapared to the level of
effort anticipated for implementation of other proposals in
this section, these projects require very minor manpover
expenditures.

a. A method whereby a user may deteraine his aggregate
monthly charges froa his terminal (SHOW CHARGES coarmand).

b. Extensions to the Text Editor to allow relocation or
duplication of lines of text within a data set (MOVES
COPY commands).

c. Addition of the UNPROTECT command to coaplement the
PROTECT command. This command is necessary if a
user wishes to delete or maintain an existing protected
file.

d. A technique is needed whereby a user can guarantee
sufficient disk file space for writing data to his
data set. A simple impleszentation is to provide
an option wherein the user specifies the nuasber of
disk blocks required at OPEN time. the blocks
are held in reserve for hia (assuming they are
available) until either they are consused or the file
is closed.
(33)

Ve ADMIBISTRATIVE ORGANIZATION

Stanford University has an Associate Provost for Computing anc
reports directly to the Provost and Academic Vice President. The
Provost for Computing and heads the operation of three major
facilities: Campus facility, ACMB facility, and SLAC coaputing
tacility. The current SCC director, Charles Dickens, has made
a number of organizational and procedural changes during the past
year in an effort to find an optimal organization for Stanford's
system programming efforts. One finding was that organizational
rather than functional lines seem to be the most appropriate in
the Stanford setting. For six months we had a single systeas
group manager for all three facilities - SLAC, Campus, and
ACME. Some benefits of the trial period were the creation of a
better reporting system, cross-fertilization of ideas, and auch
more interaction anong the systems programmers. Some of the dis-
advantages were a longer comgpunications chain, travel time between
facilities, and some loss of control by facility directors. The
operations managers of the three facilities were also brought
together in one functional ara of the organization. Cross-
facility training among operations was partially cospleted.
Reporting schemes were unified, and an exchange of ideas was
accomplished. Today, the functional organizations exist for
purposes of communication and coordination. Formal lines of
authority, however, have been returned to individual facility
directors.

We have had a number of meetings in the past year with the
Hospital Data Processing facility director and his staff. A new
era of cooperation and communication between Hospital Data
Processing and ACME has arrived.

The personnel currently on the ACME payroll, their job func-
tion, and percent of full time equivalents are listed below:
CURRENT

NAME

Jamtgaard, &
Wiederhold, G
Rindfleisch, T.
Hundley, L.
Frey, R.
Granieri, C.
Lew, Y.
Miller, S.
Briggs, R.
Stainton, R.
Bassett, k.
Crouse, L.
Whitner, J.
Aranda, M.
Baxter, E.
Class, C.
Cower, R.
Sutter, J.
Matous, J.
fieman, J.
Cannon, D.

Total FTE

(34)

ACME PERSONNEL

SFTE

100
20
50

100

100

100

100

100
20

100

100

100

100

100

100

100

100
80

100
60
50

17.9

JOB TITLE

Director

Consultant

Systeas Analyst
Systeas Programmer
Systems Progragser
Systems Programmer
Systems Programmer
Systeas Programmer
Systems Programmer
Systems Programmer
Scientific Programmer
Scientific Programmer
Scientific Programmer
Secretary
Administrative Asst.
Operations Manager
Computer Operator
Computer Operator
Computer Operator
Computer Operator
Dispatcher
VI.

A. Resource Expenditures

SUMMARY

10.

il.

Personnel:
a. Salaries & Wages
b. Staff Benefits

Subtotal

Consultant Services
Equipment

a. Main Resource-Rented

b. Main Resource-Purchased

e. Supporting Equipment
d. Equipment Maintenance

Subtotal

Supplies

Travel

Engineering Services
Publication Costs
Other

a. Computer Services (1)
b. Other

Subtotal
Subtotal - Direct Costs
Indirect Costs

Total Costs

(35)

BUDGET

Total Resource Expenditures

 

Actual Estimated
Previ ous Current Next
Budget Budget Budget
Period Period Period
239 , 329 248,690 27T 162
32,851 37,505 4h 231
272 ,180 286,195 321,393
912 1,000 1,000
384 542 389 ,458 390 ,596
ho ,848 54,479 50,000
1,951 1,260 1,260
6 145 14 500 18 ,805
433,486 459 ,697 460 ,661
15 ,873 9 ,200 9,700
3,047 4,000 4,000
11,818 30 ,000 31,500
3,031 2,000 2,500
8,272 3,100 7,900
9 531 10 5100 11,200
17,803 13,200 19 ,100
758,150 805 ,292 849 854
141,205 76,600 21,771
899 5355 881 ,892 871,625 (2)

(1) Includes education courses

(2) Assumes $443,976 exempt equipment costs and user
income of $360,000.
(36)

B. Justification for FY1973 Budget

Fiscal year 1973 will be the final year for the ACME Grant. The gross
operating costs will be slightly higher than fiscal year 1972, primarily
due to salary increases, some incremental equipment rent and maintenance,
and some additional programming help for users. The emphasis in this
final year will be one of pulling loose ends together and preparing for a
transition to alternate hardware for research and service computing. In
addition, strong effort will be made to improve the income posture of the
facility so that it can survive in future years without the financial
guarantees provided under the ACME Grant.

The budget for fiscal year 1973 assumes that the staff level achieved

in fiscal year 1972 will be retained. The facility is currently recruiting
a replacement for Gio Wiederhold who has had primary responsibility for
liaison with users and supervision of the consultants. Gio Wiederhold
assumed new responsibilities in the Hospital Data Processing Facility in
March, 1972. ACME continues to pay a fraction of his salary for consulting
on system problems and planning.

An average salary increase of 5% has been included in the budget for fiscal
year 1973.

Equipment rental costs have been budgeted at the current rental rates. The
overall equipment rental budget is slightly higher than fiscal year 1972

due to the installation of Ampex core. Similarly, the hardware maintenance
budget is up slightly due to acquisition of terminals and aging of interface
hardware built during the past six years, and maintenance of the small machine
equipment pool acquired over the past 18 months.

Some miscellaneous budget elements include funds for training of staff on
the PDP-10, acquisition of some terminal service on PDP-10's rum by other
institutions, and some additional communications costs associated with the
move to multiple speed terminal support made in April, 1972.

Capital equipment requested for the new budget period is as follows:

1) Four CRT terminals 12,600
2) Electrostatic Printer/Plotter, or expansion

. . 22 ,000

of small machine equipment pool

3) 8K of core for development PDP-11 5,700
4) 4K of core for production PDP-11 3,300
5) Two 30 character per second typewriter terminals 5,000
6) Acoustic couplers, modems, etc. 1,400

TOTAL $50 ,000
(37)

The CRI's and 30 character per second typewriter terminal will replace
IBM 2741 terminals which have been rented by the facility in the past.
The terminals are less expensive and will provide faster output and a
savings of programmer time. The printer/plotter to be acquired has not
been selected yet. This item is incorporated in the budget because
graphic support continues to attract more users. At the present time
the ACME facility has no plotter to support its users. Three user
groups have plotters attached to ACME and they find the provision of
service to miscellaneous users more than a trivial nuisance. Provision
of good interactive graphics support on the ACME system will demand

that the facility offer plotting to its users. Another problem which
we have had is the slow turnaround on print jobs caused by the speed of
our printer and the system degradation caused by use of the printer while
PL/ACME is running. This latter problem is induced by IBM hardware and
software constraints which cannot be fixed without a very sizable expen-
diture of effort.

The core for the Development PDP-1l and Production PDP-11 systems will
permit use of the DEC Fortran compiler on the development system and
will remove the limitation which has hampered the efforts of several
development groups. The added core for the production PDP-1l will be
needed only if several additional user devices or services are inter-
faced through the PDP~1l. We have barely enough core to mount the
voice drum at the present time. We assume that additional special
devices will be needed.

Funds for acoustic couplers modems, etc., will be needed to effectively
use the new terminals from remote locations. Also, a number of medical
school groups are being moved to space adjacent to but outside of the
current Medical Center buildings. For such users, telephone service
for terminals is a must. This requires expansion of the communication
equipment available. Users pay for their own terminals and acoustic
couplers but the facility helps to respond to their temporary require-
ments or new requirements pending delivery of new equipment.
(38)

C. Expenditure Details

DIRECT COSTS ONLY

August 1, 1971- August 1, 1972-

 

July 31, 1972 July 31, 1973
1. Personnel

Director's Office 32 ,929 23,582
Systems Analysis 4 5633 10 ,600
Systems Programmers 9h , 306 97 ,960
Applications Programmers 39 ,ohe 63,470
Research Assistants 9 852 7,150
Operations 52,430 58,680
Secretarial & Administrative 15,498 15,720

Subtotal, Salaries 248 ,690 277,162
Staff Benefits 37 505 4h 231

TOTAL PERSONNEL 286 ,195 321,393

2. Consultant Services 1,000 1,000
(39)

C. Expenditure Details
DIRECT COSTS ONLY

August 1, 1971- August 1, 1972-

 

July 31, 1972 July 31, 1973
3. Equipment
Major Equipment

1052 Console Typewriter 635 635
1403 Printer 600 LPM 8,397 8,397
2050 Additional CPU (F) 99 ,955 101 ,817
2314 #1 Dir. Acess Storage 21,466 a
2314 #2 Dir. Acess Storage 19,988 em
2361 Core Storage 27,29. ee
2401 Mag. Tape Unit 3,377 3,377
2403 Mag. Tape Unit Control 8,971 8,971
2540 Card Reader Punch 6 947 7,157
2701 Data Adapter Unit 10,561 10,728
2702 Transmission Control 16,834 en
2821 Control Unit 10 ,937 10 ,937
Ampex DC 314 20 ,068 36 304
Ampex DC 314 22,243 36 5304
Ampex ECM-50 TT 949 119 ,922
Memorex 1270 meee 16,248
Subtotal 355 ,619 360 ,842
Disk Packs (IBM 2316/3) (25) 2,114 (25) 2,100
Terminals (2741) (11) 11,763 (4) 4 109

IBM 1800 add. units
1y4e 2,638 2,671
1826 7,691 7,691
1856 1,701 1,701
Subtotal, 1800 12,030 12,063
Unit Record 029 1,192 1 259

TOTAL, RENTALS 382 ,718 380 ,373
(40)

C. Expenditure Details

DIRECT COSTS ONLY

August 1, 1971- August 1, 1972-

 

 

July 31, 1972 July 31, 1973
Purchased Equipment
RPQ's for Beehive Terminals 381
PDP-11 System 38,466
DEC Dual Tape System 8,700
1200 Baud Modems (2+
Power Supply) 130
Computer Terminals (2) 6 ,182
Four CRT Terminals 12 ,600
Electrostatic Printer/Plotter,
22 000
or expansion of small
machine equipment pool
8K of core for development 5,700
PDP-11
4K of core for production
PDP-11 3,300
Two 30 character per second 5,000
typewriter terminals >
Acoustic couplers, modems, etc. 1,400
5h U79 50 ,000
Data Set and Line Rentals 8,000 8,400
Maintenance (Under outside contract )14,500 14,805

Total Equipment 4O5 ,218 403,578
C.

(41)

Expenditure Details

DIRECT COSTS ONLY

August 1, 1971-
July 31, 1972

Consumable Supplies
Office
Computer

Subtotal, Consumable Supplies
Travel

Frey -U. of Missouri Comp.
Ctr., 8/6/71

-SHARE, New York, 8/9-12
-Automated Health Sys.,
Wakefield, Mass., 8/13
Nozaki -WESCON, S.F., 8/25
Wiederhold-SIGPLAN Symp., Purdue
Univ. , 10/24-26
Jamtgaard -MUMPS Sys., Boston Gen.
Hosp., 11/28-30
Jamtgaard -Conference, S.F., 1/19-
1/21/72

3,700
22200
9,200

77
9

359
426
78

Wiederhold-Conference, 8.F., 1/19-21 78

Wiederhold-Conference, Washington,
D.C. , 1/28-29

Granieri -~SHARE, S.F., 3/6-10

Wiederhold-SHARE, S.F., 3/6-10

364
20
Th

Granieri -IBM Class, S.F., 4/12-14 33

Class -SJCC, Atlantic City &
DEC, Boston 5/15-18
All Other Travel

Subtotal, Travel
Engineering Services
Publication Costs

Computer Services
360/67
PDP-10 and Line Charges
Staff Training

Subtotal, Computer Services

925
1,257
4,000

30 ,000

2 ,000

2500

600
3,100

August 1, 1972-

3,700
_6 ,000
9,700

4,000
31,500
2,500

2 500
3,000

_2,,400
7,900
(42)

C. Expenditure Details
DIRECT COSTS ONLY

August 1, 1971- August 1, 1972-

 

July 31, 1972 July 31, 1973
9. Other Expenditures
Audio-Visual Presentation re 700
Books and Periodicals 200 200
Postage and Freight 2,000 2,000
Telephone 7,000 7,000
Physical Plant 100 300
Technical Services 800 1,000
Subtotal, Other 10 ,100 11,200

GRAND TOTAL -- DIRECT costs 805 ,292 849 ,854
(43)

D. Summary of Resource Funding

BUDGET PERIODS

 

 

 

 

Actual Estimated
Previous Current Next
Budget Budget Budget
Period Period Period
Source of Funds
Computer Equipment - Service 170 ,596 270 ,000 360 ,000
Biotech. Resources Branch Support
Amount of Current Award:
Line (5) of Award Statement 675,747 573,755 511,625
Adjustment from Prior Periods:
1. Line (4) of Current Award 76,459 273275
<27 5275>
2. Balance of 270 x/y Proceeds 5,292
Total BR Support Tek ,931 606 , 322 511 ,625

TOTAL FUNDING 895 ,527 876 , 322 871 ,625
(44)

 

 

 

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F. Income Projection:

A revised rate structure was implemented effective April 16, 1972. In
general, rates for use of ACME were increased by 25% to 30%. Some users
computing bills were doubled as a result of the new increase. Actual
income for the month ending May 15, 1972 amounted to $31,500. Some users
will reduce their utilization due to the higher rates. A conservative
estimate of income for fiscal year 1973 is $360,000. This figure does
not include the terminal service fees which cover terminal rent plus
other services to the ACME user community which could not be covered by
the current funding level of the ACME grant. Some major users of the
current system will be transferring loads to dedicated small computer
systems in the next 1l2-month period. One such user is Dr. Stanley
Cohen whose Drug Interaction Program should be running on a dedicated
PDP-1l by early 1973. Another such user is Dr. Howard Sussman in the
Clinical Laboratory; programs are being written now for use of the
newly acquired Sigma 3 by the Clinical Laboratory. Both Drs. Cohen

and Sussman will continue to make some use of ACME for data analysis
but the income from these two sources will be much reduced over current
jevels. On the next page you will see a table which shows the monthly
income collected by ACME for the past nine months. Based upon this
experience and the estimated impact of the higher rates, it is felt
that the $360,000 is a reasonable estimate of next fiscal year's income
from computer service fees.
(48)

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(49)
VII. PROJECT DESCRIPTIONS

CORE RESEARCH PROJECT DESCRIPTIONS

 

Staff

Core research and development projects carried on by the ACME staff during
Fiscal 1972 have already been discussed in previous sections of this report.

Principal Investigator

Joshua Lederberg maintains one account for the purpose of system development
and testing and another as a utility file for demonstration programs. These
projects, PILOT1 and PILOT2, are listed in Category 6 of the Summary of
Computer Resource Usage.

Users
During portions of Fiscal 1972, two user projects had core research status:
DENDRAL and the Drug Interaction Project. Since both began to be charged for

their usage during Fiscal 1972, they are listed below as a combination of core
and collaborative research.

CORE AND COLLABORATIVE RESEARCH PROJECT DESCRIPTIONS

Investigator: Edward Feigenbaum, Project: DENDRAL
Joshua Lederberg, and Carl Realtime
Djerassi. Chargeable use began May 1971

Dept. of Chemistry, Computer
Science, and Genetics
Project Began 1970

The DENDRAL project involves collaboration between the Instrumentation Re-
search Laboratory operating under NASA grant NGR-05-020-004, investigators
operating under NIH grant RR 00612-02, and ACME.

The emphasis of the DENDRAL-ACME efforts is computer science, while that of
IRL~ACME endeavors is data acquisition and computer-instrument control.

The DENDRAL project aims at emulating in a computer program the inductive
behavior of the scientist in an important but sharply limited area of science:
organic chemistry. Most of the work is addressed to the following problem:
given the data of the mass spectrum of an unknown compound, infer a workable
number of plausible solutions, that is, a small list of candidate molecular
structures. In order to complete the task, the DENDRAL program then deduces
the mass spectrum predicted by the theory of mass spectrometry for each of

the candidates and selects the most productive hypothesis, i.e., the struc-
ture whose predicted spectrum most closely matches the data.
(50)
Core and Collaborative Research Project Descriptions (cont'd.)

The project has designed, engineered, and demonstrated a computer program
that manifests many aspects of human problem solving techniques. It also
works faster than human intelligence in solving problems chosen from an
appropriately limited domain of types of compounds, as illustrated in the
cited publications.

Some of the essential features of the DENDRAL program include:

Conceptualizing organic chemistry in terms of topological graph
theory, i.e., a general theory of ways of combining atoms.

Embodying this approach in an exhaustive HYPOTHESIS GENERATOR.
This is a program which is capable, in principle, of "imagining"
every conceivable molecular structure.

Organizing the GENERATOR so that it avoids duplication and irrele-
vancy, and moves from structure to structure in an orderly and pre-
dictable way.

The key concept is that induction becomes a process of efficient selection
from the domain of all possible structures. Heuristic search and evalua-
tion are used to implement this "efficient selection."

Most of the ingenuity in the program is devoted to heuristic modifications
of the GENERATOR. Some of these modifications result in early pruning of
unproductive or implausible branches of the search tree. Other modifica-
tions require that the program consult the data for cues (pattern analysis)
that can be used by the GENERATOR as a plan for a more effective order of
priorities during hypothesis generation. The program incorporates a memory
of solved sub-problems that can be consulted to look up a result rather than
compute it over and over again. The program is aimed at facilitating the
entry of new ideas by the chemist when discrepancies are perceived between
the actual functioning of the program and his expectation of it.

The DENDRAL research effort has continued to develop along several dimen-
sions during Fiscal 1972. The mass spectra of some previously uninvestiga-
ted compounds were recorded. The computer program has been extended to
analyze the mass spectra of a more complex class of compounds, using new
kinds of data. The artificial intelligence work on theory formation and
program generality has also progressed.

Many mass spectra were taken to gather more data for the DENDRAL program.
The analysis of the mass spectra of a variety of functional groups provided
general mass spectrometry rules for the computer program. The spectra of
many estrogenic steroids were taken to elucidate the mass spectrometry of
this class of steroids and to provide data for a problem area new to DEN-
DRAL.

The estrogenic steroid problem is new in several respects:

(1) dn working with steroids, the program deals with much more con-
plex molecules than ever before;

(2) the computer program uses element maps from high resolution data
to resolve ambiguities; and
(51)
Core and Collaborative Research Project Descriptions (cont'd.)

(3) ‘the program uses metastable peaks to determine parent-daughter
relationships between ions and thus to distinguish molecular
fons and their primary fragments.

Programming for the analysis of spectra has been completed. The program and
results are described in a forthcoming article:

Smith, D.H., et al., “Applications of Artificial Intelligence for
Chemical Inference:VIII: An Approach to the Computer Interpretation
of the High Resolution Mass Spectra of Complex Molecules. Structure
Elucidation of Estrogenic Steroids," Journal of American Chemical
Society, in press.

Analysis of the mass spectra of pregnanes will be the next task for the com-
puter program. Work is under way to collect the data from several preg-
nane samples and to allow the program to use a less well-defined theory for
this class than for estrogens.

The artificial intelligence interests of the DENDRAL groups are reflected

in work in program generality, partly described in reference (A), and in the
program called meta~DENDRAL described in reference (C), which will infer
mass spectrometry rules from collections of data. Parts of the meta-DENDRAL
program have been written which codify observations about mass spectrometry,
and work has started on the succeeding phase of the program which will gener-
alize these observations into tentative rules.

A. Feigenbaum, E.A., Buchanan, B.G., and Lederberg, J. "On Gener~
ality and Problem Solving: A Case Study Using the DENDRAL Pro-
gram", in Machine Intelligence 6, B. Meltzer and D. Michie (eds),
Edinburgh University Press, 1971.

B. Buchanan, B.G., and Lederberg, J. "The Heuristic DENDRAL Program
for Explaining Empirical Data", presented at the 1971 Congress
of the International Federation of Information Processing Society
(August, 1971) and published by North Holland Publishing Co.

Cc. Buchanan, B.G., Feigenbaum, E.A., and Lederberg, J. "Beyond Heur-
istic DENDRAL", presented at the International Joint Conference
on Artificial Intelligence (September, 1971) and published in the

Proceedings.

This system plans to incorporate a high degree of computer control. The goal
of the instrumentation project will be to combine the analysis of the DENDRAL
computer program with the data acquisition and control capability of the com-
puter. It is planned to do a fast preliminary data acquisition, let the DEN-
DRAL program determine what additional data and data mode is desirable, have
the computer control the instrument mode and data scan, and return the perti-
nent data to the DENDRAL program. Further iterations of this cycle can be
repeated as long as the sample persists.

A GLC (gas chromatograph) has been connected to one inlet of the mass spec-
trometer. The persistence of a given sample is determined by the duration of
the GLC peak, a few seconds to half a minute. We have the type of mass spec-
trometer which usefully takes data in many modes: low, high, ultra-high, reso-
lution and meta stables, high or low ionization potential, etc. It cannot
(52)

Core and Collaborative Research Project Descriptions (cont'd.)

 

acquire all this data in the time span allowed by a single GLC peak. Hence
it is desirable that the computer determine, during the limited sampling
time, the most useful mode of operation, and then implement this optimum mode,

Dispersed Computer for Instrumentation

During Fiscal 1972, support was given to the development of the "HIQ" remote
smart terminal. This was in cooperation with Professor Melvin Schwartz of the
Physics Department, with joint NASA support and Air Force support under con~
tract AF F 44620 67C 0070.

This cooperation did develop a unique Direct Memory Access unit for the PDP-1l.
This portion of the project is concluded. The experience and concepts of

that joint effort are now integrated with the realization and future planning
of the instrumentation for the DENDRAL project.

This PDP-11 is now being used as a satellite computer to the IBM 360/50 in the
data acquisition from the mass spectrometers. As such it is used to prepro-
cess data streams from the mass spectrometers.

The general pattern for system development is to use the larger resources of
the ACME 360/50 to develop algorithms. Program techniques may be tried and
proved either on real data streams or on files of data from prior instrument
runs. After an algorithm has been thus proven, it can be encoded into the
less flexible local computer code.

This experience and experiments with this master satellite system are proving
invaluable to the economical and adequate selection of the next generation of
DENDRAL requirements. (Considerations for this next generation have ranged
from a re-dedication of the present hardware to an all new system with a new
master and satellite chains of small computers. No firm decision has yet
been made.)

In the Summary of Computer Resource Usage, DENDRAL usage is listed under the
following names and projects.

Bob Berns LISP
Larry Hjelmeland DENDRAL
Walter Reynolds DENDRAL
DREAMS
Tom Rindfleisch DENDRAL
Robert Ross CHEM
DENDRAL
Mark Stefik DENDRAL
Robert Stillman DENDRAL
DREAMS

The following two pages list some of the publications which have resulted from
the DENDRAL research project.
(53)

REFERENCES

1.

7b.

Te.

7d.

Je.

For pertinent reviews see: C. G. Hammar, B. Holmstedt, J. E. Lindgren
and R. Tham, Advan. Pharma Col. Chemother., 7, 53, (1969); J. A. Vollmin
and M. Muller, Enzymol. Biol. Clin., 10 _, 458 (1969)

 

J. R. Althans, K. Biemann, J. Biller, P. F. Donaghue, D. A. Evans,
H. J. Forster, H. S. Hertz, C. E. Hignite, R. C. Murphy, G. Petrie and
V. Reinhold, Experientia, 26, 714 (1970).

H. Fales, G. Milne and N. Law, reported in Medical World News, February
19, 1971.

E. Jellum, 0. Stokke and L. Eldjarn, The Scandinavian Journal of Clinical
and Laboratory Investigation, 27, 273 (1971).

 

A. L. Burlingame and G. A. Johanson, Anal. Chem. , 44, 337R (1972).

H. S. Hertz, R. A. Hites and K. Biemann, Analytical Chemistry, 43, 681
(1971), S. L. Grotch, ibid., 43, 1362 (1971).

 

Applications of Artificial Intelligence for Chemical Inference. I. The
Number of Possible Organic Compounds: Acyclic Structures Containing C,
H, O and N.

J. Am. Chem. Soc., 91, 2973 (1969)
By J. Lederberg, G. L. Sutherland, B. G. Buchanan, E. A. Feigenbaum,
A. V. Robertson, A. M. Duffield and C. Djerassi.

Applications of Artificial Intelligence for Chemical Inference. II.
Interpretation of Low Resolution Mas Spectra of Ketones
J. Am. Chem. Soc., 91, 2977 (1969)
By A. M. Duffield, A.V. Robertson, C. Djerassi, B. G. Buchanan,
G. L. Sutherland, E. A. Feigenbaum and J. Lederberg

Applications of ARtificial Intelligence for Chemical Inference. III. Al-
iphatic Ethers Diagnosed by Their Low Resolution Mass Spectra and NMR
Data.

J. Am. Chem. Soc., 91, 7440 (1969)
By G. Schroll, A. M. Duffield, C. Djerassi, B. G. Buchanan,
G. L. Sutherland, E. A. Feigenbaum and J. Lederberg

Applications of Artificial Intelligence for Chemical Inference. IV.
Saturated Amines Diagnosed by Their Low Resolution Mass Spectra and
Nuclear Magnetic Resonance Spectra.

J. Am. Chem. Soc., 92, 6831 (1970)
By A. Buchs, A. M. Duffield, G. Schroll, C. Djerassi, A. B. Delfino,
B. G. Buchanan, G. L. Sutherland, E. A. Feigenbaum and J. Lederberg

Applications of Artificial Intelligence for Chemical Inference. V. An
Approach to the Computer Generation of Cyclic Structures. Differentiation

between all the Possible Isomeric Ketones of Composition CEH 90:
7f.

7g.

7h.

7i.

(54)

Org. Mass Spectr., 4, 493 (1970)

By Y. M. Sheikh, A. Buchs, A. B. Delfino, G. Schroll, A. M. Duffield,
C. Djerassi, B. G. Buchanan, G. L. Sutherland, E. A. Feigenbaum and
J. Lederberg

Applications of Artificial Intelligence for Chemical Inference. VI. An
Approach to a General Method of Interpreting Low Resolution Mass Spectra
with a Computer.

Helv. Chim. Acta., 53, 1394 (1970)
By A. Buchs, A. B. Delfino, A. M. Duffield, C. Djerassi, B. G. Buch-
anan, E. A. Feigenbaum and J. Lederberg

The Application of Artificial Intelligence in the Interpretation of Low
Resolution Mass Spectra.
Advances in Mass Spectrometry, 5, 314, (1970)
By A. Buchs, A. B. Delfino, C. Djerassi, A. M. Duffield, B. G. Buch-
anan, E. A. Feigenbaum, J. Lederberg, G. Schroll and G. L. Sutherland.

Applications of Artificial Intelligence forChemical Inference. VIII.
An Approach to the Computer Interpretation of the High Resolution Mass
Spectra of Complex Molecules. Structure Elucidation of Estrogenic Steroids.
J. Amer. Chem. Soc.,
By D. H. Smith, B. G. Buchanan, R. S. Englemore, A. M. Duffield,
A. Yeo, E. A. Feigenbaum, J. Lederberg and C. Djerassi

An Application of Artificial Intelligence to the Interpretation of
Mass Spectrometry.
By B. G. Buchanan, A. M. Duffield and A. V. Robertson,
Mass Spectrometry, B. W. G. Milne, Editor, John Wiley and Sons,
New York, 1971. pp. 121-178.

D. H. Smith, A. M. Duffield - d C. Djerassi, Org. Mass Spectrom.,
Submitted for publication.

Anal. Chem., 42, 1122 (1970); W. E. Reynolds, V. A. Bacon, J. C. Bridges,
T. C. Cobum, B. Halpern, J. Lederberg, E. Levinthal, E. C. Steed,
and R. B. Tucker.
(55)

Core and Collaborative Research Project Descriptions (cont'd.)

Investigator: Stan Cohen Project: SNCOHEN. DRUGALRT
Dept. of Medicine, Div. of Clinical Non-Realtime
Pharmacology Chargeable Use Began December 1971

Project Began October 1969

The project involves the establishment of a computer-based program aimed at
preventing undesirable drug interactions and reducing drug toxicity at the
Stanford University Medical Center. A data bank dealing with drug interac-
tions of clinical significance will be compiled utilizing already available
information present in the pharmacological literature. When prescriptions
are filled by the Stanford pharmacists, the pharmacists will type the name of
the drug and the dosage regimen into a terminal located in the Hospital phar-
macy. When a new drug added to a patient's regimen interacts with any one of
the several drugs the patient may already be receiving, the computer will
print out an appropriate drug interaction alert accompanied by a literature
reference, which will then be sent to the nursing unit by the pharmacist--
together with the drug. Prior to administering a drug accompanied by such an
"alert", the nurse will contact the physician in charge, who will retain the
prerogative of deciding whether or not the drug should be administered. This
program will provide considerable teaching benefits to students and house
staff, in addition to providing benefits of major importance to patient care.
In addition, it will be possible to assess the impact of providing physicians
with drug interaction information, and also to learn in a prospective way
about the clinical consequences of drug interactions.

Initial operation of the system began in September 1971. Since it was anti-
cipated that production of drug interaction warnings would influence the pre-
scription writing habits of physicians, it was desirable to obtain baseline
information on drug use, duration of hospitalization and other parameters

in various diseases at Stanford University prior to generation of interaction
reports. Moreover, in the initial stages of the project, it was desirable to
evaluate the ability of the pharmacist to rapidly enter the additional pre-
scription information the system requires without disrupting normal pharmacy
routines, and to determine whether an on-line interactive video display unit
and label printing program would function effectively in a busy in-patient
hospital pharmacy. At the present time, accumulation of baseline information
on drug utilization is continuing, and routine interaction reports are not yet
being issued.

In the future, it is anticipated that the program will be extended to other
hospitals, and a modified version is currently under development that will be
usable in community out-patient pharmacies. It is also expected that the pro-
gram will interface with the laboratory test program which has recently been
developed by Dr. Howard Sussman. Once this interface has been accomplished,
it will be possible to utilize prescription information in evaluating labora-
tory test results. Thus, laboratory evidence of inadequate renal function
might serve to alert the physician not to administer usual doses of a drug
that is excreted entirely by the kidney. Conversely, the artifactual effects
of certain drugs on laboratory test results can be detected and appropriate
warnings provided in the clinical laboratory.
(56)

COLLABORATIVE RESEARCH PROJECTS

 

Investigator: Christos Constantinou Project: C_CONSTA. UROL
Dept. of Surgery, Div. of Urology Realtime
Project Began November 1969

Studies are being done to improve the clinical appraisal, follow-up and manage~
ment of patients with neurogenic bladder dysfunction secondary to spinal cord
injury or disease. In particular, we are trying to determine the feasibility
of utilizing computer~based techniques of information data storage, processing
and retrieval in this patient population.

Of particular interest is the mechanism of initiation of peristaltic waves

and the quantitative description of the process through which continuous urine
flow at the kidney is transformed to discrete peristaltic waves. The signifi-
cance of this transformation lies in the rhythmic properties of the output
sequence of peristaltic waves, and the stroke volume of each wave. These two
variables alone provide the most convenient measures for ureteral function
evaluation. A hypothetical model has been developed to simulate the genera-
tion of peristaltic wave trains with the objective of developing a manageable
description of their temporal sequence. Spike train analysis traditionally
employed in statistics has been used for this purpose. It is expected that

in the course of development of the mathematical model, a better understand-
ing of what is responsible for the observed process will result. As a con-
sequence, it will be possible to make inference as to whether the ureteral
system is driven by a neuronal pacemaker or is myogenic.

ACME is being used for real-time data acquisition and feedback, and for
analysis. Analog data collected from anesthetized animals in surgery is
transmitted via the interface box to the 1800 and 2741 output received in
the operating room during the experiment.

 

Investigator: Eugene Dong Project: E DONG. LAB
Dept. of Surgery, Div. of Cardiovascular Realtime
Surgery

Project Began November 1970

The primary purpose of the project was to study the principles of mammalian
heart rate control, with particular emphasis on the sino-atrial node--the
controlled pacemaker which governs heart rate. Since understanding the pace-
maker requires a mathematical description of its behavior, a concomitant
obiective was to quantify observed heart rate data.

The contributions of this research should be helpful in interpreting the
functional status of the central nervous system from observed heart rate data.
They are basic to understanding respiratory sinus arrhythmia and ventriculo-
phasic arrhythmia and are also pertinent to establishing control criteria for
artificial heart assist and replacement devices.
(57)
Collaborative Research Project Descriptions (cont'd.)

The control of mammalian heart rate was studied by first eliminating normal
central nervous control to the heart and then artificially evoking impulses
in the nerves leading to the heart. The work was restricted to an analysis

of the effect that vagal nerve impulses have on resulting decreases in heart
rate,

In these experiments, the heart was placed in an autonomous state by severing
both cervical vagal nerves and administering the beta adrenergic blocking
agent propranolol. Heart rate responses were then elicited in 14 anesthetized
dogs by electrical stimulation of the cut end of the right vagal nerve. Each
stimulation was varied in intensity and in time relative to the heart cycle.

Computer controlled stimulations yielded reproducible temporal sequences of
heart periods for the two testing schedules employed. For one schedule, the
. system was impulsively perturbed by one stimulation. For the other, a train
of stimulations reproducibly forced the system to a second state, where it
was either perturbed further by one stimulation or permitted to relax to the
autonomous state. The new measurements obtained demonstrated that existing
mathematical models of heart rate control functions are incomplete.

A model consisting of coupled, first-order, nonlinear differential equations
was formulated to predict the heart period first lengthened by one stimula-

tion; the measured periods ranged to three times the autonomous period. For .
es - sacecu tue Gependaence Of heart period «

the stimulation. The model supports |

Po

on the intensity and relative timing of
-he hypotheses that

(1) after one stimulation, the <
at the heart's pacemaker ris
tially decreases with a 400
total time for the pacemaker
except for an uncontrollable
each heart cycle, heart rate

-oncentration of the neurotransmitter
ses in negligible time and then exponen-
msec half-life time--one~twentieth the
' to relax to the autonomous rate; and (2)
2, 175 msec period prior to the end of

» is continuously controlled.

A second model, a first-order nonline:
temporal sequence of time delays betwe
a class of injection-locked relaxatior
conditions on the nonlinear term are 2
output when they are of similar fundan
cal results are shown to be applicable
served under repetitive, constant freq

ir difference equation, describes the
en the input and output pulse trains of
. oscillators. Necessary and sufficient
iven for synchronization of input and
ental frequency. The derived analyti-
/ to the analysis of heart rate data ob-
uency, vagal nerve stimulations.
Other extensions to previous research

are as follows:

(1) large increases in heart rat

e above the autonomous rate which are paradoxically produced by va

gal nerve stimulation are reported; (2) quantitative analysis is mad
following the cessation of stimulations; (3) measurements are made of the

smallest observable time for a stimula~
d the dependence of this time on the
h;
nsiveness to a stimulation is shown to

tion to affect heart rate an
unaffected heart cycle lengt
(4) the decrease in system respo
(58)
Collaborative Research Project Descriptions (cont'd.)

be dependent upon the short term past history of stimulations;

(5) measurement is made of the recovery of responsiveness that occurs
following the cessation of stimulations; and

(6) the time required for complete recovery of responsiveness is shown
to exceed the total time required for heart rate to return to the
autonomous rate.

During the latter part of this fiscal year, a part-time ACME programmer has
developed additional graphics tools for this project. Scatter plotting of
experimental parameters, and historical plotting of treatments are included.

 

Investigator: Eugene Dong Project: E DONG. PATIENT
Dept. of Surgery, Div. of Cardiovascular Realtime
Surgery

Project Began July 1970

ACME has been used to enter and store data from over 1800 cardiac surgery
patients. Data includes age, diagnosis, admission data, operation date,
discharge date, and operation description.

Using this data base, weekly and monthly operating schedules are generated.
Survival tables are produced for the transplant patients, and some correla-
tion work is done with the entire data base. Tables of patient data (ordered
by hospital number and last name) are also generated.

 

Investigator: Alan Duffield Project: VABACON. GAME
Dept. of Genetics Realtime
Project Began December 1968

In this "on-line" application, the decision-making capabilities of the com-
puter are coupled with those of an operator to direct the operation of a
Finnigan 1015 quadrupole mass spectrometer.

The computer is used to actively direct the operation of the mass spectrometer
by controlling the mass filtering system of the instrument. It is used to
recognize and control the voltage changes which define mass peaks and enable
the rapid collection and presentation of data.

The computer traces out peak shapes of the known masses in a reference gas
allowing the operator to determine correct mass positions, and to enter any
shifts in calibration into the computer register for compensation automati-
cally.

While taking data, the information may be displayed on an oscilloscope or re-
corded on magnetic tape. Once data is acquired, the structural identification
of organic compounds is made from orthogonal coordinate or spiral base plots
(59)

Collaborative Research Project Descriptions (cont'd.)

of mass spectra made by computer direction of a CALCOMP plotter. The system
is also used to analyze Gas Liquid Chromatograph effluent, permitting the
structural identification of mixtures of organic compounds. This last appli-
cation has important uses in the analysis of organic compounds from biologi-
cal sources.

 

Investigator: James Fries Project: J FRIES. DATABANK
Dept. of Medicine, Div. of Immunology Non-Realtime
Project Began July 1969

This project involves a primary clinical information retrieval system which
interrogates computer-stored accumulated patient experience and obtains data
for direct answers to clinical and research questions.

The present non-indexed disorganized methods of maintaining medical records
represent an obstacle to good patient care, a hindrance to medical education
and a limit on the quality of medical research. This project attempts to re-
move these obstacles by implementation of a structured method of data col-
lection and entry of the structured data into a computer databank. Search
programs operating on the databank provide prompt, accurate recall of past
experience and correlations with new developments. The databank is contri-
buted to and used by physicians in private practice as well as those of the
university center. The structure of the computer file is designed to maxi-
mize "search" efficiency and a library of output program allows the immediate
answering of many millions of possible clinical questions by retrieval, tabu-
lation, and statistical manipulation of primary patient data.

A systematic method of recording serial clinical and laboratory information
has been developed and clinically tested. The method has two important fea-
tures:

(1) As a “"time-oriented record" it displays changes in parameters with
respect to time so that the entire past course of the patient can
be quickly analyzed by the physician.

(2) It replaces rather than adds to present records.

These features improve physician acceptance as well as scientific validity.
The chart reduces redundancy and decreases total "paper work" by the physi-
cian.

Factual clinical information is displayed in a two-dimensional time-oriented
format, listing parameters on the vertical axis and time on the horizontal.
Time is represented by successive "patient-visits" in which each encounter
of a patient and a physician is considered a data-gathering point and forms
one column of the chart. Laboratory data and the therapeutic program are
similarly entered on the record.

If the course of a patient may be displayed in two dimensions, then a com-
puter databank may be considered a three-dimensional array of data. Data
(60)
Collaborative Research Project Descriptions (cont'd.)

thus arranged may be located directly by the use of three coordinates, and
search procedures may be operated on the parameter axis, the time axis, or
the patient axis with equal ease. A search may be addressed to various para~
meters of one patient, to changes with time, or to findings in groups of
patients. Interrelationships of parameters are easily investigated, and
questions involving the time axis, such as prognostic importance of varia-
bles or response to therapy, may be answered.

In our system, information is entered into an IBM 360/50 digital computer
by use of a typewriter terminal. Ten new patients, fifty patient visits,
and about 20,000 pieces of data are entered each week. Three hundred and
fifty-two entries are made for each patient visit. Daily search procedures
acting on the databank provide research data, support individual clinical
decisions, and develop experience-based data for clinical teaching.

Our computer is frequently consulted instead of a traditional medical-lib-
rary-based review of the literature, as the databank often contains a series
which is larger, more recent, more accurate, and more directly applicable to
our patient population. Moreover, if expenditure of physician time is con-
sidered, consultation with the computer is generally less expensive than
utilization of the library.

Computer storage of detailed clinical information has been feasible, desir-
able, and useful in our clinic, and by extension, should have wide applica-
tion within medicine. The clinical databank is a powerful tool which can
serve as the central focus for teaching, research, and patient-care activi-
ties. By development of improved methods of handling and analyzing patient
data the clinician and the clinical researcher may be able to effectively
utilize the increasing flow of biological information from our laboratories.
Design of improved clinical charts, methods of computer file organization,
formats which output data should assume, and potential interchange of
clinical information between institutions are crucial medical questions,
and evolving answers to these questions will play an important part in
determining the quality of future health delivery systems.

 

Investigator: Jerome Gold Project: J GOLD. SWALLOW
Dept. of Radiology, Div. of Diagnostic Realtime
Radiology

Project Began October 1969

This project involves the study of esophageal blood flow.

One study compared the esophageal blood flow of normal subjects and subjects
affected with a connective tissue disease (CTD). Such diseases are character-
ized by esophageal motility abnormalities. The hypothesis was that these ab-
normalities were related to impaired blood flow. The blood flow was indirect-—
ly assessed by measuring the time for intraluminal esophageal temperature to
rise to normal following ingestion of 5 ml. swallows of 0.5° C. ice water.
With the subject sitting, 2 small thermistors were inserted into the esopha-
(61)

Collaborative Research Project Descriptions (cont'd.)

 

gus, one located in the distal 1/3 and the other in the proximal 1/3 near the
junctional zone of smooth and striated muscle. Thermistor rewarming curves
were recorded and the amplified signals collected by ACME through the 1800
for storage and analysis. Thermistor curves were analyzed (deg/sec) for
several portions of the rewarming time. A significant difference existed
between the slopes of the first half rewarming in CTD patients and normals in
the lower esophagus. Although of lesser magnitude, a significant difference
also existed between the slopes of the first half rewarming in the upper
esophagus. Preliminary evaluation suggests that the time for first half re-
warming may also be significantly different between the two groups. These
data provide additional support for the hypothesis that esophageal blood flow
is decreased in some CTD and may be related to their manifest motor dysfunc-
tion.

A second study, utilizing laboratory animals, measured esophageal blood flow
with injections of radioactive material. A catheter-type semi-conductor beta
radiation detector system (catelix) was used. A detector was passed into the
distal esophagus. Two millicuries of 86Rb were injected intravenously, and
ACME made continuous recordings of the Catelix counts per unit time over a
ten-minute period. After ten minutes, another 2 mCi of 86Rb were injected
and counts again recorded. After serial determination, a final 2 mCi of 6Rb
were injected and the animal sacrificed 60 seconds later. The esophagus was
removed. Counts were then recorded at different levels in the esophagus and
correlated with the amount of 86rp per gram as determined by counting the
tissue in a well-type scintillation counter. The data will be subjected to
statistical analysis to evaluate the linearity of count rate with dose of
administered isotope. The area under the curve generated by changing count
rate after the isotope is administered may be used to calculate cardiac out-
put.

By substituting another isotope and different dosages, serial determinations
of esophageal blood flow are feasible in humans.

 

Investigator: Donald Harrison Project: DCHARRIS. CATH LAB
Dept. of Medicine, Div. of Cardiology Realtime
Project Began 1968

Fourier analysis is being performed on left ventricular pressure curves. Their
component points are stored for frequency spectrum quantitation. This study

is done to determine the frequency response which the equipment must have in
order to represent the data accurately. The results are applied to hemodynamic
studies in both patients and experimental animals.

ACME is used for data handling for cardiology research on dogs. Normal dogs
and dogs which have undergone various surgical procedures are involved in the
study. Numerous hemodynamic values collected under a variety of experimental
conditions are filed for each dog. These files provide a convenient source of
reference and comparison for a number of cardiology researchers.
(62)
Collaborative Research Project Descriptions (cont'd.)

Investigator: Leslie Kadis Project: L_KADIS. VISAEP
Dept. of Anesthesia Realtime
Project Began July 1971

The purpose of this project is to develop a model for experimental pain that
will be clinically applicable. The model, based on the gate control theory
of pain proposed by Melzack and Wall, will be tested in man and in animals.

Sensory information from painful stimuli travels from peripheral receptors

to synapse with second order neurons ("T" cells) in the substantia gelatinosa
in the spinal cord over both large, fast conducting fibers, and small, slow
conducting fibers. Melzack and Wall proposed that transmission to the T cell
in the spinal cord depends on the balance between large and small fiber acti-
vity. For example, when large fiber activity predominates, the threshold for
excitability of the T cell is raised, or, in other words, the gate is closed.
Transmission of information about painful stimuli is then impaired. We will
study the role of disorganization of sensory information (change in the bal-
ance between large and small fiber activity) on transmission of neural im-
pulses in the spinal cord in cats. We also will assess the modification of
spinal cord activity by narcotics.

Another aspect of the Melzack and Wall hypothesis is that there is a separate
pathway for rapid transmission of sensory information directly to higher cen-
ters with feedback to the "Gate” to change the threshold for excitability of
the T cell. The averaged evoked cortical response (AER) to somesthetic stimu-
lation reflects both transmission at the spinal cord level and central pro-
cessing, and it is our hypothesis that individual responsivity to painful
stimuli can be predicted from the pattern of response of AER to graded
intensity stimuli. We plan to develop quantitative methods to test this
hypothesis using experimental pain in man.

We also plan to evaluate psychophysiologic aspects of experimental pain in
man, as well, and relate these to the pattern of response of the AER. We
know, for example, that individuals whose perceptual style is such that they
require perceptual clues from the external world, or who, in their interper-
sonal relationships are extroverts, or who have little anxiety, are most
tolerant of pain. The project will assess some aspects of personality (the
introversion - extroversion parameter) as well as cognitive and affective
variables and relate these to patterns of response of AER to graded intensity
stimuli.

Finally, the project will utilize the methods developed above and assess the
relationship between clinical and experimental pain in patients who are suf-
fering from cancer and who have metastases to bone. In this homogenous group
of patients we will correlate patterns of AER with clinical pain, response

to drugs, and methods of coping with illness to assess the relative importance
of these variables.
(63)
Collaborative Research Project Descriptions (cont'd.)

Investigators: Larry William and Project: S ROSENB. MEDONCOL
Saul Rosenberg Non~Realtime

Dept. of Medicine, Div. of Oncology

Project Began 1972

The Division of Oncology has recently begun to experience an increasing need
for a versatile medical record data processing system to serve both patient
care and research requirements. To achieve these goals we are currently
attempting to modify a computer-based time-oriented medical record system
developed by the Division of Immunology.

Specifically, we are using a versatile input program to store approximately
450 different patient care parameters for each clinic visit. Thus, we are
currently inputting most of the hard data from the clinical charts of our
patients. Once a suitable data base has been established, we hope to be
able to obtain a variety of outputs. For example, we hope to nimbly re-
trieve, compare and display actuarial survival curves of patients treated
with competing therapies; search for laboratory tests which are of prog-
nostic significance; find patient subsets with uniquely good or bad respon-
ses to treatment, etc.

Initially we are exploring the advantages of this record keeping system on
the patients in the medical oncology clinic. If it proves feasible, we hope
to expand and generalize the programs so devised to apply to other problems
in oncology and general medicine.

A new time-oriented medical chart is an essential and unique feature of our
current system. Information is recorded in an efficient, basically flow-
sheet mode in the most objective fashion possible. Then this material is
input via the typewriter terminal into the 360/50 computer. The chart serves
as a hard copy of the patients' record and satisfies all medical-legal re-
quirements.

 

Investigator: Howard Sussman Projects: H_SUSSMA. LABSYSO
Dept: Stanford Univ. Hosp. H_SUSSMA. LAB PAT

Clinical Lab Pathology H_SUSSMA. c1050937
Project Began November 1969 Realtime and Non-Realtime

Over time, the work load of the Clinical Laboratory has steadily increased.
At present, in the Chemistry and Hematology areas of the Clinical Laboratory,
over 2000 tests per day are performed on approximately 400 specimens. The
increased work load has put such a strain on the manual system that serious
problems have developed in specimen handling, and the gathering and dissem-
ination of information.

A Clinical Laboratory Information System has been developed at Stanford Hos-
pital using the ACME system. Mark-sensed card input to the patient data
(64)

Collaborative Research Project Descriptions (cont'd.)

Investigator: Gerald Reaven Projects: G_REAVEN. PAT DATA
Dept. of Medicine, Div. of Metabolic G_REAVEN, DISPLAY
Diseases and Endocrinology Non-Realtime

Project Began January 1969

We are involved in studies of the relationship of risk factors such as choles-
terol, etc., to coronary heart disaase in the community. This study involves
the use of ACME in three major ways:

(1) We utilize ACME's data storage and retrieval capabilities. The
data collected consists of variables describing the demographic.
medical and behavioral characteristics of the subjects in the
study. Our first major study was just recently published and
the ACME facility was used almost exclusively.

(2) We use the library of statistical programs in conjunction with the
retrieval capabilities of ACME to analyze community data.

(3) We have used the graphic capabilities of ACME to develop an inter-
active graphic pattern recognition procedure which describes the
underlying distribution of the data obtained from the community.
It also is an exploratory mechanism to determine if the distribu-
tion may consist of sub-component populations. We are also capa-
ble of estimating in another graphic subroutine the parameters of
the resulting component populations if they are bivariate Gaussian.

A second major research activity consists of developing mathematical, phy-
siological and computer models describing the production, distribution and
removal of certain metabolites important in the study of diabetes mellitus
and atherosclerosis. In the past, we have developed and updated a model
describing the distribution and degradation of insulin in man and dog. We
have, in conjunction, developed graphic computer techniques to aid us in this
model building. The distribution and uptake of glucose in man has also been
considered and a paper is forthcoming describing a comparative study of the
dynamics of the glucose and insulin systems. A prior paper described the
efficiency of glucose uptake in normal and diabetic man and has utilized both
the graphic and statistical capabilities of ACME.

We are now developing models that describe the mechanisms of insulin pro-
duction in man and dog and the effect of glucose on this secretory system.

Another important aspect of our work concerns inpatient metabolic problems,
and we are at present involved in establishing a data file on ACME for two
specialty clinics. We hope to use ACME's storage, retrieval and statistical
capabilities to analyze this data in order to explain various mechanisms that
may be responsible for some of the etiology of maturity onset diabetes and
atherosclerosis.

We are also involved in the development of a nationwide clinical trial to test
the "lipid hypothesis" and are utilizing ACME to develop statistical models
which can explain the interrelationship of the parameters associated with

this clinical trial.
(65)

Collaborative Research Project Descriptions (cont'd.)

files is provided using a mark-sensed card reader tied into the IBM 1800 at
ACME. The system prints worklists for the technicians and monitors the status
of the tests which have been ordered. At the end of each day, the patient
results are printed in a form suitable for chart copies or lab files.

A multiple analyzer, the SMA 12/60, has been interfaced to the IBM 1800 to
provide an efficient way of inputting test results to the patient files. In
the future, more instruments will be interfaced.

At present, the Clinical Laboratory Information System is in pilot production
mode at the Hoover Pavilion, a small hospital adjacent to Stanford. Using
the lessons learned from operations there, the system will eventually come
into production for the whole of Stanford Hospital.

 

Investigator: George Swanson Project: G_SWANSO. THESIS
Dept. of Anesthesia Realtime
Project Began September 1969

The respiratory laboratory in the Department of Anesthesia has been in-
volved in the investigation of dynamic experimental techniques for the study
of the human respiratory control system. Our goal has been to develop non-
invasive experimental techniques in which we can assess human respiratory
drug effects in terms of specific physiologic mechanisms which contribute

to respiratory control.

The classical steady state and rebreathing experimental methods are restric-
ted to assessing drugs in terms of an integrated respiratory effect. Our
experimental approach uses the temporal aspects of a ventilatory response to
an end-tidal C09-02 stimulus to observe and isolate the contribution of
specific mechanisms such as the central chemoreceptor, cerebral blood flow,
carotid body and lung to brain circulation time.

For the past year we have been involved in a theoretical study of dynamic
experimental design. We have developed a dynamic end-tidal forcing tech-
nique. The basic idea is that the end-tidal time histories of C09 and 0,
can be selected for model discrimination and for minimizing the uncertainty
in a model parameter estimate.

The design of experiments depends upon computer simulation of alternative
models. We have implemented a descriptive computer simulation of the respi-
ratory system. The simulation is general enough to encompass alternative con-
figurations of interest. We have also validated via computer simulation, a
theoretical method of selecting the end-tidal C0 2-0, forcing function for
minimizing the variance of estimated model parameter.

The experimental design is enhanced through man-computer interaction. This
concept was explored on ACME using the Tectronix display scope. Alternative
forcing functions were generated and evaluated.
(66)

SERVICE PROJECTS

Investigator: Malcolm Bagshaw Project: M _BAGSHA. SUMMARY

Dept. of Radiology, Div. Radia- Non~Realtime
tion Therapy

Project Began December 1968

The project contains datasets for four general purposes, listed below in the
order of disk storage space occupied.

The purpose of the first two groups of files and programs is to allow the
medical staff to conduct research on various forms of cancer and make com-
parisons of various methods of treatment,

(1) Files of records of general data on all patients of the Radiotherapy
Division are kept from about 1968 to the present with the necessary
programs for input and retrieval of the data. The retrieval pro~
grams are designed to allow the radiologist himself to select pa-
tients based on any desired criterion, print out desired informa-
tion about each, or create a subset of these patients for further
analysis.

(2) Another set of files contains records of detailed data on all pa-
tients with Hodgkin's Disease, along with the necessary programs
for input and retrieval of the data. The retrieval programs will
choose records of patients selected on any combination of desired
criteria, print out desired information about each, and perform
survival or remission analysis on the selected group.

(3) Mathematical programs have been developed for use by the radiologic
physicists for calculations concerning beam characteristics, depth
dose tables, analysis of curves, etc.

(4) Statistical programs are available to obtain Berkson-Gage or Kaplan-
Meier survival tables from data input by the user.

 

Investigator: Walter Bodmer Project: W_BODMER. POPGEN
Dept. of Genetics Non-Realtime
Project Began December 1968

Since the original discovery of sera with isoantibodies directed against
human white cell antigens, the use of statistical techniques has played a
major role in the discovery and analysis of human white cell antigen systems.
Stanford's Department of Genetics has long been involved with the development
of statistical analysis. The computer has always been one of our most basic
tools.

White cell antigens are now known to constitute the major human histocompa-
tability system, called HL-A. They form the basis for tissue typing for
clinical transplantation. Recent data has also shown significant correlation
between the HL-A system and certain diseases, notably Hodgkins disease. It
is also related to certain other cancers and to autoimmune diseases.
(67)
Service Project Descriptions (cont'd. )

The analysis of 2 x 2 associations between serum reactions for the definition
of antigens in the HL-A system was pioneered in 1962 by Van Rood and has been
further developed and extended by ourselves and others. It has been the basis
for the definition of most of the presently known antigens of the HL-A system.
The main principle involved is the recognition of groups of associated sera
which share antibodies and can therefore be used to define the corresponding
antigen. In addition, the analysis of association between antigens in popula-
tions has proved an important adjunct to understanding the genetic control of
the HL-A antigens.

The improvement of serological techniques for the detection of white cell
antigens has greatly helped in their definition. However, in order to have a
basis for the original identification of new antigens and characterizations of
sera, we find that it is still necessary to use the same statistical procedures
which were originally essential for the definition of the antigens. Over the
years, considerable effort has been invested in developing a library of pro-
grams for the analysis of serological data. This set of programs deals with
all aspects of our work:

(1) input and organization of data

(2) characterization of sera

(3) assignment of antigen phenotypes

(4) calculation of population frequencies with respect to complex
combinations of phenotypes

(5) fitting of complex genetic models to the phenotypic frequencies.

There is no doubt that the availability of the time-sharing system has greatly
increased our ability to handle and analyze the large bodies of data involved
in our research. Programs are designed for use by people who have no detailed
programming knowledge. They include appropriate prompts for every stage of
data input. During input, the data is monitored in various ways to verify
that the input corresponds to expectations. Then the data is put into a
standard format for subsequent ease of analysis. The computer is used at
every stage of data analysis and interpretation. Examples are: the selec-
tion of subjects of a given phenotype to use for absorption, and the assign-
ment of antigen phenogypes based on complex patterns of reaction to defined
sets of sera. We have also developed programs for displaying population data
on complex patterns of phenotypes and for the analysis of family data.

 

Investigator: Edward Bunnenberg Project: E_BUNNEN. CHEM
Dept. of Chemistry Realtime
Project Began December 1970

The main goal of this project is to achieve an effective interactive computer-
assisted operation of a highly specialized type of spectrophotometer--a mag-
netic circular dichrometer. The utilization of organic chemical and especial-
ly biochemical applications of magnetic circular dichroism will allow the
following:

(1) an increase in the operational sensitivity of the instrument
(68)
Service Project Descriptions (cont'd.)

through the application of digital averaging and smoothing tech-
niques. This is especially important for this instrument because
of its inherent single-beam operation;

(2) the measurement of compounds having relatively strong signals much
more rapidly;

(3) the extraction of quantitatively meaningful spectroscopic para-
meters from the magnetic circular dichroism spectra. This is of
crucial importance for much of the work and requires the implemen-
tation of generalized curve deconvolution and fitting programs.

The first objective was demonstrated in the use of the MCD instrument with
on-line computer connection to analyze lunar soil extracts for metallopor-
phyrins.

Preliminary experiments indicate that the time required to scan through the
MCD spectrum of a routine sample, i.e., one in which the signals are rela-~
tively strong, can be materially decreased through on-line computer operation
of the MCD instrument.

Significant progress has been made in connection with the third objective,
the extraction of quantitatively meaningful spectroscopic parameters from MCD
spectra, although fund limitations have necessitated this accomplishment by
off-line (curve tracer) rather than on-line computer assisted operation.

 

Investigator: Howard Cann Project: H_CANN. GUAT
Dept. of Pediatrics Non-Realtime
Project Began December 1968

This project is an investigation of factors which affect frequencies of genes
controlling various human heritable characters. The extent to which selec-
tion, genetic drift, and migration affect frequencies of certain human genes
is being assessed and specific selective factors are being sought. Environ-
mental, cultural, and historical conditions favorable for this type of study
have been found in settlements of Mayan Indian descendants in the Lake
Atitlan Basin of southwest Guatemala. The local microgeography and mating
patterns appear to enforce a high degree of genetic isolation for each of a
number of Indian towns and villages ringing Lake Atitlan. These high mortal-
ity populations provide the opportunity to study selection on human genetic
polymorphisms.

The ACME system stores demographic, clinical and socioeconomic data collected
from large samples of inhabitants of each of eight isolated Indian villages.

A master file for each village has been developed to link laboratory, demo-
graphic, and anthropological information on each individual. An indexing
system allows quick retrieval of each bit of data collected on a given indi-
vidual, as well as a means of linking him into a family unit, thereby retriev-
ing similar data from other members of his nuclear family. Using the various
data collected for and generated by this project, the ACME computer is now
being employed for the final analyses which will include maximum likelihood
(69)

Service Project Descriptions (cont'd.)

 

estimation of gene frequencies, analysis of variation in gene frequency dis-
tributions, estimation of coefficient of kinship from pedigrees, segregation
analysis of polymorphisms, comparison of fertility and mortality by genotypes
and association of clinical, epidemiologic and socioeconomic variables with
genotypes.

This project will also contribute information on the genetic taxonomy of the
American Indian. Families of large size, characteristic of the study popula-
tion, will afford excellent opportunities for medical genetic investigation
of inherited diseases encountered in our field activities and for studies of
genetic linkage.

 

Investigator: Luca Cavalli-Sforza Projects: L_CAVALL. PAVIA
Dept. of Genetics L_CAVALL. JUDY
Project Began March 1971 L_CAVALL. KEN

L_CAVALL. LAURA
L_CAVALL. MARK
Non-Realtime

The Evolutionary Rate in Man

 

Models have been developed for the reconstruction of phylogenetic trees.
These trees are developed to indicate not only relationships between and
among populations, but also to indicate the amount of time elapsed since the
separation of populations. Simulation is used (particularly in the determi-
nation of the amount of expected error in phylogenetic tree reconstruction).
Computer analysis is necessary in the construction and analysis of migration
matrices, genetic distance matrices, and gene frequency data.

Changes in Man's Genetic Composition Brought About By the Spread of The Neo-
lithic

 

The Neolithic revolution has undoubtedly brought about some changes in the
genetic composition of man. The rate of spread and mode of spread have been
analyzed. Geographic maps with isochrones of the spread were drawn by the
computer, fitting the radiocarbon data to a surface. Analysis of the rela-
tion between radiocarbon time with the more accurate tree time is now being
carried out with polynomial fitting and search for periodicities. The
genetic effects will now be studied using the gene frequencies of various
polymorphisms, anthropometric measures, etc. In addition, simulations have
been set up to test the validity of the methods of analysis used.

Patterns of Inheritance in Behavioral Traits Such as Schizophrenia

 

Models have been developed, mainly using computer simulations, to throw light
on the possible modes of inheritance of such traits as schizophrenia. It is
hoped that such factors as penetrance, polygenic or single gene inheritance
can be brought into their proper relative perspectives.
(70)
Service Project Descriptions (cont'd.)

The Analysis of Record Linkage Data and Pedigree Information Based on Material
Available from Parish Books, Census Data, Etc.

There is an on-going program of analysis of data, particularly from the Parma
Valley of Italy. This data is obtained from parish books and from municipal
records, as well as from Italian censuses. Such information as degree of
inbreeding in the population, amount of migration, changes in life expectancy,
family size, isonymy, etc. will be obtained from this study.

 

Investigator: Avram Goldstein Project: A GOLDST. OFFSTUFF
Dept. of Pharmacology Non-Realtime
Project Began August 1970

The computer is used for filing and analyzing data from a clinical study on
the use of methadone in the treatment of heroin addiction. The study is de-
signed to answer questions about the efficacy of methadone in stopping heroin
use and rehabilitating heroin addicts, to determine if there is an optimal
dosage stabilization level for most patients, and to discover just what that
dosage level is.

The subjects of this study are patients of the Santa Clara County Methadone
Program and of several "sister" programs in this region. Data from several
hundred patients is collected, in order to obtain a statistically valid
sample, and the subjects are monitored in several ways:

(1) Urine samples are obtained on a random basis with a basic frequency
of once in five days from each person. These samples are tested
for the presence of morphine (heroin) and other drugs (barbiturates
and amphetamines), and thus provide concrete evidence of the pa-
tient's progress or lack of progress, as measured by his continued
use of heroin. ACME is used to file and analyze the results of
the urine test, and also to generate the lists of random numbers
which determine which patients give urine samples on which days,
maintaining the desired frequency.

(2) Progress questionnaires (30 items, multiple choice) are adminis-
tered to each patient at the time of admission to the methadone
program and at regular intervals thereafter. These questionnaires
provide data on physical symptoms while on methadone, current use
of heroin, criminal activities, and occupation. This information
is stored and analyzed statistically by ACME to discover correla-
tions between success on the program and other characteristics,
such as current dosage, age, sex, holding a job, etc.

(3) Symptom questionnaires are various short questionnaires (4-11 items)
which deal primarily with physical symptoms and which are used to
measure the patients' comfort on a particular dosage level or
schedule. These questionnaires are administered more often than
the progress questionnaire, usually weekly or daily, and have pro-
vided data for studies on determining the ideal dosage stabiliza-
tion level, and on comparing once-daily and twice-daily administra-
(71)
Service Project Descriptions (cont'd.)

tion of methadone. This type of questionnaire will also be used
in an upcoming study comparing the action of methadone and long-
acting methadone (levorotatory-q-acetylmethadol, abbreviated as
LAM). One hundred patients will be involved in this study (in-
cluding control subjects) and ACME will again be used for per-
forming a variety of statistical analyses.

No conclusions have been reached as yet concerning the best medication (meth-
adone or LAM) since the study is still in the planning stages. The investi-
gations as to the best dosage level and dosage schedules of methadone have
given conclusive results, however. It has been shown that a dose of 50 ng
per day is adequate for most patients, and that administering the entire
dose once a day is best in terms of patient comfort.

There is a great mass of data involved in these studies, due to the number of
questions being investigated and the large number of subjects about whom data
is being collected. (The large number of subjects is necessary in a clinical
trial of a drug to avoid having results biased by individual idiosyncrasies.)
To record this mass of data by hand would require a great many man-hours; per-
forming the complex and selective computations for the statistical analyses
without the use of a computer would probably be impossible. In addition to
its speed, ACME's interactive capability gives much-needed flexibility in the
use and handling of data.

Since the methadone program is an ongoing treatment facility, using a drug
and treating a disease about which there are still many unanswered questions,
the need and opportunity for further study can be expected to continue for
several years. Continued availability of the ACME facility will be vital to
the success of such studies.

 

Investigator: Scott Grant Project: 5S GRANT. CORNEA
Dept. of Surgery, Div. of Ophthalmology Non-Realtime
Project Began October 1971

The endothelial membrane of the cornea is being studied. This membrane is
responsible for maintaining the proper hydration of the cornea via an active
pumping process. One way of attacking the problem of ynderstanding this pump
is by the use of radioactive isotopes of Na and Cl. These tracers are used

in perfusion studies of the endothelium. The amount of data gathered from
each experiment is copious. The analysis of the results would require approx-
imately six hours of uninterrupted manual calculation. Due to the delicacy
and sensitivity of the mounted corneas, it has been necessary to repeat the
experiments quite often to obtain statistically relevant results. The use of
ACME in data analysis has allowed a job that once took six hours to be reduced
to a fifteen to twenty minute period for data entry. More experiments can be
carried out per week. Most important, the accuracy of the calculations is now
unchallenged. This work has proceeded smoothly, providing further insight
into this difficult problem.
(72)

Service Project Descriptions (cont'd.)

 

Further work has been initiated using ACME in the realm of mathematical
modeling. One of the still unanswered questions about the cornea is why it
is transparent. Electron micrographs are used to provide data on the ultra-
structure of the cornea. This information is applied by the computer to
evaluate the electromagnetic scattering of the cornea. An analysis of this
sort is impossible without the assistance of ACME due to the several thousand
data points of input.

 

Investigator: Paul Green Project: P GREEN. AVENA
Dept. of Biosciences Realtime
Project Began September 1971

Biological Significance

 

The growth of plants is governed by a number of hormones each of which is a
low-molecular-weight compound of known structure. These molecules are "keys"
but the lock into which they fit is obscure. We treat the growing plant-
object of choice, the oat (Avena) coleoptile, as a "black box" which we study
by observing output (growth rate) as a function of step shifts in the driving
force (turgor pressure). It can be shown that the growth process contains a
governor or feedback system, with the feedback term coupled to the braking or
deceleration component of the governor. The action of the hormone appears to
involve a resetting of the coupling, giving less braking action, hence higher
rate. A detailed characterization of the actual responses allows the descrip-
tion of a chemo~mechanical model for the growth process.

Computer Use

The analysis requires very accurate information of growth rate (accuracy of
one part in 80,000, per minute). This is achieved by feeding voltage from

a linear displacement transducer into a digital voltmeter (4 1/2 places).

The information is then converted to paper tape using a teletype. As the
experiments run for 12 hours, with a reading being taken every minute, this
method keeps the information in the laboratory until the experiment is over
and judged worthy of analysis. If so, the tape is read in, and length, rate,
rate of change of rate, In rate, etc. are computed. The change in various
parameters allows us to characterize the action of ageing of the tissue,
turgor pressure, and hormone action in abstract, but measurable terms.

Pertinence to Man

The system is a model for the study of the mechanisms for the cessation of
growth (ageing). It also allows study of the action of a hormone of known
chemical composition (indole acetic acid) on a biophysical system where the
physical components (turgor pressure and wall parameters) are relatively well
understood.
(73)
Service Project Descriptions (cont'd.)

Investigator: Samuel Kountz Project: SLKOUNTZ. KIDNEY

Univ. of California Medical Center, San Non-Realtime
Francisco, Dept. of Surgery

Project Began December 1968

The Transplant Service at the University of California uses ACME in the
selection of recipients for renal homotransplantation. The computer has been
programmed to include data from over 100 patients who are on chronic hemo-
dialysis awaiting a cadaver transplant. When a cadaver kidney becomes avail-
able, similar data is obtained about the donor's body. The computer matches
donor information with recipient information. Matched recipients are then
brought into the hospital for transplantation.

ACME is also used as a follow-up tool to predict the onset of rejection crisis
by monitoring renal function and hemodynamic changes. Renal function is
measured by the single injection of radioisotopes. The disappearance curves
are analyzed by the computer and compared with previous determinations. This
has provided a very accurate method of following patients and detecting

early incipient rejection.

Using all of the available data on transplant patients, ACME generates survi-
val statistics. These are analyzed with the aim of finding factors signifi-
cant to rejection and survival.

 

Investigator: P. Herbert Leiderman Project: PHLEIDER. PREMIE
Dept. of Psychiatry Non-Realtime
Project Began December 1968

Studies of maternal behavior in non-human mammals have suggested that the de-
gree of interaction permitted between mother and infant in the postpartum
period will influence later maternal attachment and infant development. The
hypotheses raised by these studies can be explored with human mothers and
infants through manipulation of care procedures of mothers and newborns in
the immediate postpartum period.

Assessments of each mother and her infant are made periodically during the
time the infant is hospitalized and during the first two years at home.
Three major areas are included in these assessments:

(1) maternal attitudes regarding her relationship with the child as
reflected in responses to interviews and questionnaires;

(2) maternal behavior observed during routine caretaking of the infant;
and

(3) the behavioral development of the infant.

A pilot study was conducted to determine the feasibility of changing premature
care procedures in order to study the effects of interactional deprivation in
the neonatal period on maternal attitudes and behavior. Forty-one mothers
(74)

Service Project Descriptions (cont'd.)

 

were permitted to enter the nursery and touch or handle their premature in-
fants in incubators as early as the second day after birth. The feasibility
of admitting mothers to the premature nursery without increasing the risk or
occurrence of infection, or disrupting the organization of the care of the
infants, was demonstrated.

We are now conducting a long-term study based on this pilot model to delin-
eate the differences in commitment, feelings of competence, and behavior in
the two differentially treated groups of mothers and to relate their behavior
to the motor and mental development of the infants.

 

Investigator: Harden McConnell Project: H_MCCONN. ABSORB
Dept. of Chemistry Realtime
Project Began February 1971

ACME is used for analysis of experimental paramagnetic resonance spectra and
calculation of theoretical spectra. These paramagnetic resonance spectra
arise from the application of the "spin label" technique to problems involv-
ing biological macromolecules. Biological problems which are currently being
studied include cooperative oxygen binding to the protein hemoglobin, the
relation of molecular orientation and motion to function in biological mem-
branes and membrane model systems, and development of quantitation assay
techniques using spin labels.

The paramagnetic resonance spectra that are obtained in spin label studies
are recorded as the first derivative of an absorption curve. The area under
the absorption curve is proportional to the number of spin labels giving rise
to the signal. Also, spin label spectra give information on changes in con-
formation or motion of a macromolecule. Frequently, these changes are de-
tected as a small change in the paramagnetic resonance spectrum. Quantita-
tive measurement of spectral changes requires normalization of spectra from
a series of experiments. ACME is used to compute the double integral of the
experimental spectrum and then to regenerate a normalized spectrum. Sub-
traction and addition of spectra are used to analyze experimental data. In
addition, experimental spectra are often analyzed by comparison with theo-
retical spectra which are calculated using ACME.

Interfacing Electronparamagnetic Resonance Spectrometers to the Computer

 

Models E-4 and E-12 of the Varian EPR Spectrometer have been interfaced to
ACME for purposes of real time data acquisition and data reduction. Analog
data from the spectrometer is sent to the 360/50 via a subsidiary computer,
the IBM 1800, at a rate determined by the user. A 16-bit analog-to-digital
converter converts the analog data to 10,000 digital values per scan for use
in the 360. Processed data is displayed on the spectrometers by the reverse
process.

The software for the system was designed for the following applications:

(a) correction of spectra for baseline drift and systematic base-
(75)

Service Project Descriptions (cont'd.)

line irregularities,

(b) calculation of relative concentrations of paramagnetic species
in the sample (value of the double integral),

(c) normalization of different spectra to the same relative con-
centrations,

(d) simulation of complex spectra by appropriate addition of com-
posite spectra,

(e) output of computer-calculated spectra to the EPR recorder for
comparison with experimental spectra, and

(£) long term storage of and ready access to spectra.

Research Projects Involving Computing Capability

(1)

(2)

(3)

Studies of the protein hemoglobin have led to a model which accounts
for the binding of oxygen to normal human hemoglobin as well as the
abnormal binding to mutant hemoglobins. Continued study of abnor-
mal hemoglobins is in progress.

Many of the observations which led to the model resulted from ac-
curate measurement of small deviations among experimental spectra.
Both normalization of spectra and spectral addition have been used
in this project. Many small programs have also been used to ana-
lyze data points (least squares, etc.).

Investigation of the structure of biological membranes has led to
characterization of a wide range of motions that contribute to the
characteristic fluidity of such membranes. We are making quanti-
tative measurements of the extent of fluid regions in membranes and
of the rates of motion of membrane components. The studies are
directed toward an understanding of such problems as virus attack
on cell membranes, biosynthesis of membranes, and surface proper-
ties of transformed tumor cells.

ACME is used to normalize spectra so that differences between two
states of a membrane may be determined. Also, many details of
membrane motion have been deduced from theoretical analysis (per-
formed on ACME) of the line shapes of the magnetic resonance
spectra. For example, a set of reference spectra have been added,
in proportions dictated by solutions to the diffusion equation, in
order to simulate a series of experimental spectra which are depen-
dent on the rate of lateral diffusion of membrane components. The
observed rapid lateral diffusion of membrane components has impor-
tant biological implications in such areas as membrane biogenesis
and structural arrangement of membrane components.

Electrochemical potentials are an essential feature of living cells.
We are developing "molecular indicators" of both trans-membrane
potentials and localized surface potentials in membranes. In

these studies, we design spin labels so that their spectra depend
on whether the label is outside or inside the membrane, or inside
of the membrane-enclosed volume. In general, the spectra of the
two species of spin labels are overlapping and must be separated
for quantitative analysis. A general procedure is to use ACME to
calculate the total integrated area of both spectra and then compare
(76)

Service Project Descriptions (cont'd.)

 

this with the measured height of some portion of the composite
resonance spectra..

 

Investigator: M. Lexie Nall Project: L_NALL. PSORIASI
Dept. of Dermatology Non~Realtime
Project Began April 1969

The computer is used to perform calculations in connection with a study of

the genetics of psoriasis. A questionnaire requesting information on presence
or absence of the disease in relatives was sent to almost 700 psoriasis suf-
ferers and to 100 controls. A statistically significant familial concentra-
tion of the disease has been demonstrated which, together with twin studies,
supports the concept that hereditary factors contribute to the etiology of
psoriasis.

Pedigree analysis and frequencies of psoriasis among siblings of sufferers
were not consistent with inheritance of genetic differences at a single auto-
somal or x-linked locus, even with decreased penetrance due to delayed age

of onset. These findings, plus further analysis, suggested that psoriasis

is determined by multifactorial inheritance.

Application of the twin method to this study is still in process. The sample
of monozygotic and dizygotic twins (one or both members affected) was drawn
from the United States.

The questionnaire used in this study has been translated into several lan-
guages. An international information exchange and coordination center is
being set up in the Department of Dermatology.

 

Investigator: John Petralli Project: J _PETRAL. MED DATA
Stanford Univ. Hospital Clinical J_PETRAL. INFCON

Lab. - Infectious Disease J_PETRAL. PROGRESS
Project Began January 1969 Non-Realtime

Antibiotic-sensitivity testing gives physicians important information about
treatment of specific infections. To improve the quality of antibiotic-sen-
sitivity 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 into the ACME computer each
day. As the information is given to the computer, the quality-control program
immediately detects and challenges unusual results and directs the laboratory
technicians to appropriate restudy of the organism in question. This system
converts zone sizes to resistant, intermediate, or sensitive and prints final
reports from its memory. These final results are generated three days to eight
weeks after the specimen enters the lab. Reports for "routine" specimens are
printed for distribution to the nursing units. Antibiotic sensitivity test
(77)

Service Project Descriptions (cont'd.)

 

results are compared to previous results and unusual values are flagged for
further study before release to the physician. Results which pass this screen-
ing are interpreted for the physician. Previous results are analyzed every

six months to allow updating of acceptable criteria and to provide the fellows
and residents of Infectious Diseases with patterns of antibiotic susceptibility
for approximately fifty organisms. The results for rare organisms are accumu-
lated until sufficient data is present to include them in the daily quality
control program.

Decreased potency of an antibiotic disc is detected by comparison of periodi-
cally 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.

Knowledge of antibiotic sensitivities of organisms isolated from a specific
site such as blood or urine will help to guide the selection of antibiotics
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 sensi-
tivity patterns obtained will give information about major trends and suggest
appropriate changes in treatment of various infections.

Currently the project is testing the feasibility of automatically generating
patient charges from the specimen identification data entered into ACME.

This would hopefully decrease the paperwork for the lab personnel, facilitate
data control and practically eliminate keypunching from charge slips. This
also involves automatic routing of charges, depending on whether the patient
made an in-house, clinic, or other outpatient visit.

There are plans to use ACME to provide physicians with preliminary results

on a daily basis. Such a system would be adaptable to a hospital information
system to provide instant preliminary and final results at nursing units as
they are generated. This system should be running on a small scale within
the near future,

Another plan involves using ACME to study the possibility of routinely iden-
tifying bacteria with gas chromatography.

This summer we will begin parallel testing of an automated sensitivity test-
ing instrument for approximately four months. The machine will provide
sensitivity results twenty hours sooner than conventional methods.

In addition to improving the accuracy of laboratory results for the benefit
of patients, the computer has proved valuable in checking the work of labora-
tory technicians and students in training.
(78)

TRAINING PROJECTS

Investigator: James Calvert Project: J_CALVER. TEXT
Medical Student Non-Realtime
Project Began November 1969

The computer is used for calculations involving the economics of investment
in biomedical research. Given some fraction of the gross national product as
appropriate for the total national expenditure on health, national investment
policy can be made more explicit and rational by considering for each major
disease category:

(1) medical care costs and lost income per year,

(2) yearly probability of premature death or continued disability,
(3) fraction of the health budget allocated to research,

(4) discount (interest) rate for patient lives saved or improved,

(5) the maximum number of years allowed to complete cure or
prevention of the particular disease.

A second study investigates the economics of effectiveness and efficiency in
patient care. Effective patient care simultaneously focuses on the patient's
visit, the current illness, the patient's year, and the patient's lifetime.
Schedules for effective care are integrated by a simultaneous analysis of
policies relating investments of professionals and facilities to benefits of
patient care at each of the four time foci. Optimal schedules can then be
derived for the care of individual patients within the national population by
a weighting matrix of investment policies.

Efficient utilization of invested professionals and facilities is markedly
influenced by such human capital factors as:

(1) degree of specialization and rate of ongoing improvement,
(2) flexibility of allocation, and

(3) overall state of the technical art.

 

Investigator: Glenn Funk Project: GAFUNK. RHINO
Medical Student Non-Realtime
Project Began June 1971

The intent of this project is to stu.y rhinovirus defectiveness from three
approaches:
(1) an attempt to derive a subgenomic "defective interfering"
(DI) rhinovirion by rapid passage at high multiplicity of
infection.
(79)
Training Project Descriptions (cont'd)

 

(2) study of the kinetics of viral RNA production at permissive and non-
permissive temperatures, and

(3) study of the intracellular development of rhinovirions under both
temperature conditions using an electron microscope.

In addition, an attempt will be made to determine a particle-to-PFU-ratio as an
indicator of the degree of defectiveness of a viral suspension.

 

Investigator: Rodney Levine Project: RLLEVINE. CPS
Medical Student Non-Realtime
Project Began December 1968

The project was undertaken to clarify some of the mechanisms of pyrimidine
synthesis in mammals, and the relationship of that synthesis to the control

of cellular proliferation. The computer is used for data analysis and statis-
tical evaluation. It greatly accelerates the pace of the experiments.

As the work has progressed into an examination of enzyme kinetics, the comput er
has been used for theoretical curve fitting. Important properties of the
enzyme system have been deduced, and theoretical equations have led to the
conclusion that an allosteric enzyme is involved.

The computer has been an indispensable aid in calculation related to predic-
tion of enzyme preparation behavior in a sucrose gradient centrifugation.

 

Investigator: D. Craig Miller Project: C MILLER. CAB
Medical Student Non-Realtime
Project Began February 1972

This project is an attempt to define concrete risk/benefit guidelines for the
new saphenous vein - coronary artery bypass surgery.
Method:

1. Collection of 15 significant pre-operative parameters on 400 patients
who have undergone the surgery at Stanford.

2. Collection of follow-up clinical and angiographic data on as many of
the 400 patients as possible.

3. Collection of 5 operative parameters.

4. Using computer and non-parametric multivariable biostatistical methods,
attempt to find correlations among the parameters collected.
(80)

Training Project Descriptions (cont'd)

 

5. Report Stanford's results and formulate pre-operative risk/benefit
guidelines from the above data.

6. Report on subpopulations of patients with unique pre-op or post-op

 

courses.
Investigator: Larry Nestor Project: L NESTOR. DIFFDX
Medical Student Non-Realtime

Project Began January 1970

This project has developed a program to aid in diagnosis. Its original purpose
was to provide a teaching aid for students. The program would output differen-
tial diagnoses with probability-like values associated with them, in response
to a given set of symptoms.

Clinical practitioners can also make use of the program in an effort to avoid
overlooking an obscure diagnosis. By asking the program what other diseases
can show a given set of symptoms, the number of missed diagnoses can be reduced.

 

Investigator: Marc Nuwer Project: MRNUWER. NEURON
Medical Student Non-Realtime
Project Began February 1971

The computer is used for modeling of neurons and groups of neurons. Arrays are
constructed which simulate the temporal and spatial relationships of electrical
activity on neuron surfaces, using an array for the soma, and a set of arrays
for dendrites. In this manner, the interactions of “slow potential" gradients
on neurons can be matched; inputs can interact with both spatial and temporal
summation.

Plans have been formulated to order the modeling to fit the parameters of
known neuron types (e.g. pyramidal cells, stellate cells, etc.).

Array values will be changed to simulate the properties of the neuron membranes
in a way which will simulate learning and memory, principally as proposed in a
holographic memory model.

 

Investigator: William Rosenthal Project: W_ROSENT. RESEARCH
Medical Student Non-Realtime
Project Began December 1968

This project investigates speech and language pathology and normal speech
perception, utilizing studies of language-deviant children. ACME is used for
(81)
Training Project Descriptions (cont'd)

statistical data reduction of auditory processing of these children and for
longitudinal study and follow-up.

The project includes research into the effectiveness of stuttering therapy,

speech and auditory perception in aphasic children, and normal speech percep-
tion in adults and children.
(82)

VIII. UTILIZATION DATA

A. Interpreting Utilization Charts

 

The teras used to discuss ACME utilization involve charging
units and categories of users.

1. Charging Units
Last year, the computer service charge units were:

page minutes

terminal connect tire
blacks of disk storage
terminal service charge

In April, 1972, our rate structure was revised and charge
units for batch execution, CPU time slices, and tape sounts vere
added. However, due to their recent incorporation in the rate
structure, no data is included for thea.

A pageminute is defined as occupancy of 4096 bytes of
core for one minute. Terminal connect time is the total
nuaber of minutes that a terminal is connected to the syster
in a logged-on condition. a block of disk storage is a fixed
length block of 2000 bytes of 2314-type disk storage. The
terminal service charge covers sonthly terminal rent plus other
services offered by the ACME staff. This service charge is
handled by the University independent of the ACHE grant.

2. User Categories

This table shows the category identifier, rate, and
definition of each user category. The rate charged per pagenrinute
varies by user categories and some categories are subsidized
100% by the ACME Grant. An asterisk next to the category
identifier (*4) designates those so subsidized. All other
categories are paying. There is a distinction between real-
time and non-realtime users. Realtime users ase the 1800
processor or 2701 data adapter for data collection or process
control functions.
(83)

PAGE-MINUTE CHARGE TABLE

Cateyory cents/pagemsinute
Pre-April,72 Post-April,72

1. Realtime User - Sponsored Research -50 1.00
2. Non-Realtime User - Sponsored Research 1.00 1.70
3. Non-Stanford Medical 2.00 2.50
*4u. Medical Students 1.00 2.00
*5. Realtime User - Core Research 250 2.00
*6. Non-Realtime User - Core Research 1.00 2.00
*7. ACME Staff 1.00 2.00
8. Hospital Data Processing 1.25 1.70
9. Non-Medical - Stanford and Non-Stanforda 2.50 2.00
*10. Realtime - Pilot and Pending Proposal 50 2.C0
*11. Non-Realtime - Pilot and Pending Proposal 1.00 2.00
*12. Realtime —- Extended Non-Funded 50 2.00
*13. Non-kealtime - Extended Non-Funded 1.00 2.00
16. Negotiated Rates - Combination of Core 25 1.20

Research and Medical Administration
*No cash charges, i.e., absorbed by the ACME project budget.

The four graphs in Section C show atilization since February,
1970 by user-supplied income, pageminutes of use, block storage,
and number of terminal connect time hours. An additional table
in Section C summarizes ACME utilization by Department. Section D
sugmarizes computer resource usage by charge category and primary
investi gator.

B. Patterns of Use

buting fiscal year 1972, a noticeable shift has occurred
from a preponderance of program development to execution.
Approximately two years ago, it was norsal to find 50% of
logged-on users in execution with another 50%
performing data entry functions or prograg development. One
year ago, approximately 2/3 of those logged-on to the systen
were found to be in execution during normal daytime hours.
More recently it appears that 75% of the users logged-on
to the system are in program execution. The effect of this trend
is that more cycles per user hour are absorbed than was the case
two years ago. It also indicates that a certain amount of work
performed on the system is now more or less routine or operates
in a "production" mode. Much of this so-called production-
type work is used to support research in the Medical Center.
Bxamples of this are the realtime data collection fros spectro-
meters and the data collection phase of the Drug Interaction
Program.
(84)

During the past year, approximately 75%-85% of the available
disk storage for users has been used. Prequentiy we have run
out of space on individual packs during the norsal operating
hours. This has caused considerable inconvenience to all
users, especially those who attempt to create very large files.
Next gonth a number of data compression routines will be made
available to all users. These routines will permit a con-
Siderable reduction in the amount of space used for individual
files. We expect that our users will quickly adopt these
techniques to reduce their disk storage charges.
Yass

INCOME

Total Income Incl. Terminal Service —— — —Computer Servic

e

 

 

 

 

 

 

 

 

 

   

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

$40 ,000 ~ $40,000
$30,000), 30,000
TOTAL
$20,000}, | 20,000
%., ~‘ o an, a
“ ni TERMINAL SERVICE INCOM ~_-F-~ ~
~ 4
~ ON ”
~ ~17
$10,000}. 40,000
Ampex
Rate Core
Decrease COMPUTER SERVICE INCOME Added
_— _
Feb 70 May Aug Nov Feb May Aug Nov Feb
Mar Jun Sep Dec Mar Jun Sep Dec Mar
Apr Jul Oct Jan 71 = Apr Jul Oct Jan 72 Apr
PAGEMINUTES
Total ——~— — Chargeable +4+++-Total Excl. Staff & Pharmacy
3,000,000 5,000,000
2,000,000] NE™ ,000 ,000
eet tt Lee Z
ds
1,000, 0004 aoK. Zs B,,000 ,000
\ “oo ie”
~ a a
a Ampex
Rate Core
Decrease Added
- -_-
Feb70 May Aug Nov Feb May Aug Nov Feb
Mar Juri Sep Dec Mar Jun Sep Dec Mar
Apr Jul Oct Jan 7| = Apr Jul Oct Jan 72 Apr
(86)

BLOCK STORAGE

oo Pot

1a, 000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

camnnanprammetlargeable | 120,000
bn
90,000 J. - eh 70,008
a“
”
Lo
60,000 IN ’ 4 60,006
— ~ ” _
s - q4~—_——
“ -
~ a
~ ~— —- -
30,000} ah 30,000
Ampex
Rate Core
Decreask Added
_— -
Feb 70 May Aug Nov Feb May Aug Nov Feb
Mar Jun Sep Dec Mar Jun Sep Dec Mar
Apr Jul Oct Jan 71 Apr Jul Oct Jan 72 Apr
TERMINAL HOURS
———_—s Total ~~ «oe Chargeable \
4,00 4,000
3,001 ab3 ,000
4
4
4
2,001. sf abe 050
oT. 7
+ 7 ~Y
Lae a
~~ ~ ”
1,009 “abe Ampex [1,000
“TF Rate Core
Decrease Added
- -
Feb 70 ay Aug Nov Feb May Aug Nov Feb
Mar Jun Sep Dec Mar Jun Sep Dec Mar

Apr Jul Oct Jan 71 Apr Jul Oct Jan 72 Apr
(87)

 

 

 

 

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(111)
IX. PUBLICATIONS

A. = - .
Published in Regularly Scheduled Periodicals During Fiscal 1972

Ammerman, A., and L.L. Cavalli-Sforza, "Measuring the Rate of Spread of
Early Farming in Europe," MAN, Vol. 6, pp. 674-688, December 1971.

Chester, T., P. DeClercq, and T. Merigan, "PolyrI, PolyrC and Antibody,
Interferon, and Phagcytosis," INFECTION AND IMMUNITY, April 1971.

Glaze, H.J., Jr., and E. Dong, "Vagal Control of Heart Rate," in Abstracts
of the American Heart Association, 44th Scientific Sessions, Supplement II
to CIRCULATION, Vol. XLIV, October 1971.

Glick, D., K. Marich, J. Orenberg, P. Carr, and D. Miller, "Effect of
Atmosphere on Spectral Emission from Plasmas Generated by the Laser
Microprobe," ANALYTICAL CHEMISTRY, Vol. 43, pp. 1452-1456, September 1971.

Ingels, N.B., Jr., G.T. Daughters, II, S.R. Davies, and I.B. MacDonald,
"Stereo Photogrammetric Studies on the Dynamic Geometry of the Canine
Left Ventricular Epicardium," J. BIOMECHANICS, Vol. 4, pp. 541-550, 1971.

Kaplan, B.E., J.C. Corby, and P.H. Leiderman, "Attention and
Verbalization: Differential Responsivity of Cardiovascular and
Electrodermal Systems," JOURNAL OF PSYCHOSOMATIC RESEARCH, Vol. 15, pp.
323-328, 1971.

Levine, R. and N. Kretchmer, "Conversion of Carbamyl Phosphate to
Hydroxyurea: An Assay for Carbamyl Phosphate Synthetase," ANALYTICAL
BIOCHEMISTRY, Vol. 42, No. 2, pp. 324-337, August 1971.

Levine, R., N. Hoogenroad, and N. Kretchmer, “Copurification of Carbamoy]
Phosphate Synthetase and Aspartate Transcarbamoylase from Mouse Spleen, "
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol. 44, pp. 981-988,
1971.

Levine, R., N. Hoogenroad, and N. Kretchmer, “Regulation of Activity of
Carbamoy] Phosphate Synthetase from Mouse Spleen," BIOCHEMISTRY, Vol. 10,
No. 20, pp. 3694-3699, 1971.

Melges, F.T., R.E. Anderson, H.C. Kraemer, J.R. Tinklenberg,
and A.E. Weisz, "The Personal Future and Self-Esteem," ARCHIVES OF GENERAL
PSYCHIATRY, Vol. 25, pp. 494-497, December 1971.

Morris, S., H. Ralston, and . Shooter, "Studies on the Turnover of Mouse
Brain Synaptosomal Proteins," J. NEUROCHEM., Vol. 18, pp. 2279-2290,
1971.

Nola, G., et al., "Action of Acetystrophanthidin on Experimental
Myocardial Infarction," AMER. J. PHYSIOL., Vol. 222, pp. 265-71, February
1972.

Pauling, L., A.R. Robinson, R. Teranishi, and P. Cary, "Quantitative
Analysis of Urine Vapor and Breath by Gas - Liquid Partition
Chromatography," PROC. NAT. ACAD. SCI. USA, Vol. 68, No. 10, pp.
2374-2376, October 1971.
(112)

Silbergeld, S., N. Brast, and E. Noble, “The Menstrual Cycle: A
Double-Blind Study of Symptoms, Mood, and Behavior, and Biochemical
Variables Using Enovid and Placebo," PSYCHOSOMATIC MEDICINE, Vol. 33, p.
411, 1971.

Swanson, G., T. Carpenter, D. Snider, and J. Bellville, "An On-Line
Hybrid Computing System for Dynamic Respiratory Response Studies",
COMPUTERS AND BIOMEDICAL RESEARCH, Vol. 4, pp. 205-215, April 1971.

Teranishi, R., T.R. Mon, A.B. Robinson, P. Cary, and L. Pauling, “Gas
Chromatography of Volatiles from Breath and Urine," ANALYTICAL CHEMISTRY,
Vol. 44, p. 18, January, 1972.

Thoman, E., C. Barnett, and P. Leiderman, "Feeding Behaviors of Newborn
Infants as a Function of Parity of the Mother," CHILD DEVELOPMENT, Vol.
42, pp. 1471-1483, 1971.

Thoman, E., J. Olson, and P. Leiderman, "Neonate-Mother Interaction During
Breast-Feeding," DEVELOPMENTAL PSYCHOLOGY, Vol. 6, No. 1, pp. 110-118,
1972.

Thoman, E. and A. Korner, "Effects of Vestibular Stimulation on Behavior
and Development of Infant Rats," DEVELOPMENTAL PSYCHOLOGY, Vol. 5, No. 1,
pp. 92-98, 1971.

Watson, W., H.M. Cann, E.M. Farber, and M.L. Nall, "The Genetics of
Psoriasis," ARCH. DERM., Vol. 105, pp. 197-207, February 1972.

B.
Other Publications

Ammerman, A., and L.L. Cavalli-Sforza, "A Population Model for the
Diffusion of Early Farming in Europe," Proceedings of the Research Seminar
in Archaeology and Related Subjects, Sheffield, December 1971.

Barth, G., R.E. Linder, E. Bunnenberg, and C. Djerassi, "The Magnetic
Circular Dichroism of Porphyrin Dications," presented at the April 3, 1972
Porphyric Conference sponsored by the New York Academy of Sciences, to be
published in the ANN. N.Y. ACAD. SCI. (spring 1972).

Bernfield, M., "Chromatographic Properties of Pyrrolidone
Carboxylate-tRNA," submitted to J. BIOLOGICAL CHEM. (spring 1972).

Bernfield, M., "Characterization of Pyrrolidone Carboxylate-RNA from Rat
Liver," in preparation (spring 1972).

Bodmer, W.F., and L.L. Cavalli-Sforza, "Variation in Fitness and Molecular
Evolution," PROCEEDINGS OF THE SIXTH BERKELEY SYMPOSIUM ON MATHEMATICAL
STATISTICS AND PROBABILITY, CONFERENCE ON EVOLUTION, April 1971.

Bodmer, W.F., and L.L. Cavalli-Sforza, "Migration Matrices," IV INT.
CONGR. HUMAN GENETICS PROCEEDINGS, in press (spring 1972)
(113)

Bodmer, W., and L. Cavalli-Sforza, THE GENETICS OF HUMAN POPULATIONS,
Freeman and Company, 1971.

Buchanan, B.G., D.H. Smith, R.S. Engelmore, A.M. Duffield, A. Yeo, E.A.
Feigenbaum, J. Lederberg, and C. Djerassi, "Applications of Artificial
Intelligence for Chemical Inference," submitted to J. AM. CHEM. SOC.
(spring 1972).

Buchanan, B.G., E.A. Feigenbaum, and J. Lederberg, "A Heuristic
Programming Study of Theory Formation in Science," Stanford Artificial
Intelligence Project, Memo AIM-145, Computer Science Department Report CS
221, June 1971.

Buchanan, B.G., and J. Lederberg, "The Heuristic DENDRAL Program for
Explaining Empirical Data," presented at the 1971 Congress of the
International Federation of Information Processing Society (August 1971)
and published by North Holland Publishing Co.

Buchanan, B.G., £.A. Feigenbaum, and J. Lederberg, "Beyond Heuristic
DENDRAL," presented at the International Joint Conference on Artificial
Intelligence (September 1971) and published in the Proceedings.

Calvert, J.L. and J.H. Frenster, "Economics of Effectiveness and
Efficiency in Patient Care," CLINICAL RESEARCH, Vol. 19, p. 501, 1971
(abstract).

Calvert, J.L. and J.H. Frenster, "Economics of Investment in Biomedical
Research and Current Patient Care," CLINICAL RESEARCH, Vol. 19, p. 499,
1971 (abstract).

Cavalli-Sforza, L.L., "Pygmies, an Example of Hunters-Gatherers, and
Genetic Consequences for Man of Domestication of Plants and Animals," IV
INT. CONGR. HUMAN GENETICS, PROCEEDINGS, in press (spring 1972).

Cavalli-Sforza, L.L., and K. Kidd, "Considerations on Genetic Models of
oe NEUROSCIENCES RESEARCH PROGRAM BULLETIN, in press (spring
1972).

Chester, T., P. DeClercq, R. Newer, and T. Merigan, “Release of Interferon
by Cycloheximide," INFECTION AND IMMUNITY, in press (spring 1972).

Constantinou, C., and E. Butler, "Medical Application of Computer Displays
in the Rapid Examination of Developing Abnormality Patterns in the
Kidney," PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM OF THE SOCIETY OF
INFORMATION DISPLAY, Philadelphia, May 1971.

Constantinou, C., E. Briggs, R. Dale, and D. Govan, "Real-Time Digital
Computer System for Ureteral Physiology Investigation," URODYNAMICS,
Chap. 33, Academic Press, New York, 1971.

Constantinou, C., J. Sands, and D. Govan, "Computer Monitoring and Control
Instrumentation in Urology Research," PROCEEDINGS OF THE 6TH ANNUAL
BIOENGINEERING SYMPOSIUM, Fort Collins, Colo., May 1971.
(114)

Corby, James C., and B.S. Kopell, "Differential Contribution of Blinks and
Vertical Eye Movements as Artifacts in EEG Recording," PSYCHOPHYSIOLOGY,
in press (spring 1972).

Corby, J.C., and B.S. Kopell, "The Effect of Predictability on Evoked
Response Enhancement in Selective Attention," submitted to
PSYCHOPHYSIOLOGY (spring 1972),

DeGrazia, J.A., and MR. MacLaury, “Radioressirometry Studies of the
Effects of L-dopa and ™K486 Therapy -- A Mcdei Application of Carbon
Isotopes to the in vivo Evaluation of Intermediary Metabolism During
Clinical Drug Trials," accepted for publication by the AEC (spring 1972).

Dong, E., and G.C.M. Wiederhold, "The Use of a General-Purpose Time~Shared
Computer in Physiology Research," to be published in the PROCEEDINGS OF
THE NATIONAL CONFERENCE ON RESEARCH ANIMALS IN MEDICINE (spring 1972).

Farber, E.M., "Genetics of Psoriasis: Twin Study," in PSORIASIS:
PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM, STANFORD UNIVERSITY, 1971,
E.M. Farber and A.J. Cox (eds.), Stanford Press, 1971,

Feigenbaum, E.A., B.G. Buchanan, and J. Lederberg, "On Generality and
Problem Solving: A Case Study Using the DENDRAL Program," in MACHINE
INTELLIGENCE, B. Mellzer and D. Michie (eds.), Edinburgh Press, 1971.

Fries, J., "Time-Oriented Patient Records and a Computer Databank, "
presented at American Fed. for Clinical Res. Annual Meeting, Atlantic
City, May 1971.

Fries, J., "“Time-Oriented Patient Records and a Computer Databank, JAMA,
in press (spring 1972).

Fries, J., "Questions for the Computer," a demonstration to the National
Meeting of the American Rheumatism Association, San Diego, December 1971.

Fries, J., “The Effect of Ice Water on Esophageal Rewarming in Connective
Tissue Diseases (CTD)," abstract submitted to GASTROENTEROLOGY (spring
1972),

Glaze, H.J., Jr., and £. Dong, "Mathematical Analysis of the Impulse
Response of the Vagal Nerve - Heart Pacemaker System," in PROCEEDINGS OF
THE 24TH ANNUAL CONFERENCE ON ENGINEERING IN MEDICINE AND BIOLOGY, Vol.
13, 1971.

Glick, D., "Cytochemical Ane: :..5 by Laser Microprobe - Emission
Spectroscopy," RECENT ADVANCES IN QUANTITATIVE HISTO- AND CYTOCHEMISTRY,
pp. 192-193, 1971.

Gold, J. A., G.S. Harrell, B.R. Bradley, and F.F. Zboralske, "Sequential
Esophageal Blood Flow Determination," submitted ta GASTROENTEROLOGY
(spring 1972).
(115)

Gordon, L., "Completely Separating Groups in Subsampling," submitted to
ANNALS OF MATH STATIST., (spring 1972).

Gordon, L., “Efficiency in Subsampling," submitted to J. AMER. STATIST.
ASSN., (spring 1972).

Hillman, R., "The Teaching of Psychotherapy Problems by Computer,"
ARCHIVES OF GENERAL PSYCHIATRY, in press.

Kidd, K., P. Astolfi, and L.L. Cavalli-Sforza, "Error in the
Reconstruction of Evolutionary Trees," GENETIC DISTANCE, J.F. Crow (ed.),
in press (spring 1972)

Kidd, K., and L.L. Cavalli-Sforza, "An Analysis of the Genetics of
Schizophrenia," IV INT. CONGR. HUMAN GENETICS, PROCEEDINGS, in press
(spring 1972).

Kidd, K.K., and L.L. Cavalli-Sforza, "Number of Characters Examined and
Error in Reconstruction of Evolutionary Trees," in MATHEMATICS IN THE
ARCHAEOLOGICAL AND HISTORICAL SCIENCES, F.R. Hodson, D.G. Kendall, and P.
Tautu (eds.), Edinburgh University Press, pp. 335-346, 1971.

Leiderman, P.H., "African Infant Precocity: Some Social Influences during
the Fist Year," submitted to SCIENCE (spring 1972).

Leifer, A.D., P.H. Leiderman, C.R. Barnett, and J.A. Williams, "Effects of
Mother-Infant Separation on Maternal Attachment Behavior," CHILD
DEVELOPMENT, in press (spring 1972).

Luzzatti, L. and H. Pryor, "Body Proportions and Dermatoglyphic Patterns
in oye with Cleft Lip and/or Palate," submitted to PEDIATRICS (spring
1972).

Luzzatti, L., and L. Knight, "The Replication Pattern of the X and Y

Chromosomes in Partially Synchronized Lymphocyte Cultures, submitted to
CHROMOSOMA (spring 1972).

Luzzatti, L. and L. Knight, "“Intrapair and Interpair Chromosome Distance
at Metaphase in Human Lymphocytes," in preparation (spring 1972).

McConnell, H.M., and P. Devaux, "Lateral Diffusion in Spin Labeled
ro Choline Multilayers," J. AM. CHEM. SOC. in press (spring
1972).

Mesel, E. and M.J. Gelfand, "An Automated Data Analysis and Acquisition
System for a Cardiac Catheterization Laboratory," COMPUTERS IN BIOLOGY AND
MEDICINE, in press.

Raybin, D.M., L.L. Bertsch, and A. Kornberg, "A Phospholipase in
Bacillus Megaterrum Unique to Spores and Sporangia," to be published in
BIOCHEMISTRY, (spring 1972).

Reynolds, W., "Biochemical Applications of Mass Spectrometry," Chapter

III, (ed. by Waller), to be published by John Wiley & Sons, New York
(spring 1972).
(116)

Rosenthal, W.S., "Auditory Threshhold-Duration Functions in Aphasic
Subjects: Implications for the Interaction of Linguistic and Auditory
Processing in Aphasia," paper delivered at the 47th Annual Convention for
the American Speech and Hearing Association, Chicago, November 1971.

Rosenthal, W.S., and J. Eisenson, "Auditory Temporal Order in Aphasic
Children as a Function of Selected Stimulus Features," JOURNAL OF SPEECH
AND HEARING RESEARCH, to be published (spring 1972).

Rosenthal, W.S., and J. Eisenson, "Longitudinal Studies of Linguistically
Deviant Children," Final Report, Grant NSO7514, National Institute of
Neurological Diseases and Stroke, April 1972.

Sachs, D.P. and D.M. Rubin, "Mass Media and the Environment," Volumes I,
Il, and III, Stanford, 1971.

Seashore, M.J., A.D. Leifer, C.R. Barnett, and P.H. Leiderman, "The
Effects of Denial of Early Mother Infant Interaction on Maternal
Self-Confidence,” JOURNAL OF PERSONALTIY AND SOCIAL PSYCHOLOGY, in press
(spring 1972).

Skolnick, M.R., A. Moroni, and L.L. Cavalli-Sforza, "The Population
Structure of the Parma Valley, Italy," IV INT. CONGR. HUMAN GENETICS,
PROCEEDINGS, in press (spring 1972).

Smith, D.H., et al., "Applications of Artificial Intelligence for Chemical
Inference: VIII: An Approach to the Computer Interpretation of the High
Resolution Mass Spectra of Complex Molecules. Structure Elucidation of
Estrogenic Steroids," JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, in press
(spring 1972).

Zei, G., A. Moroni, and L.L. Cavalli-Sforza, “Age of Consanguineous
Marriages," in GENETIQUE ET POPULATIONS. HOMMAGE A JEAN SUTTER, Institut
National d'Etudes Demographiques. Travaux et Documents. Cahier No. 60,
Presses Universitaires de France, pp. 147-153, 1971.
(117)

C. Staff Technical Notes

AAC-1

AAD-1

ACH- 1

ADDA-1

AFORT-1

AG-1

AORG~-1

APAGE-1

APAGEX~- 1

ARATE-~1

BASS-1

BGOLD-1

ACHE User Accounting -- Update & Listing (Bassett,
C. Miller) AUG 13, 1971

APUB --
AUG 13,

Update & Listing
1971

(PlaschysC. Miller)

Summary
NOV 30,

of Campus/ACME Serger Study (Jastgaard)
1971

Additions to ACME Software Suggested by Users
(Jamtgaard) APE 20, 1972

Implementing a Tise-Shared/Realtise Systea in
FORTRAN (Frey) APB 23, 1971

Usage of the ACHE System (Wiederhold)
To be published in Statistik an Dokusentation in der
Medicine, NOV 15, 1971

ACME Organization Chart (Baxter)
MAR 6, 1972

ACME Service Rates (Jantgaard)
APR 16, 1972

Description of ACHE Service Rates (Jaatgaard)
APR 13, 1972

Revised Rate Structure for ACHE Facility Services
(Subpitted to NIH) (Jamtgaard) APR 16, 1972

An Assessment of Current Developrents in Coaputer
Technology and their Significance for Developrent
at the Stanford Medical Center (Wiederhold)

MAY 1, 1972

Beyond LISP (Wiederhold) MAR 29, 1972

ACME Program Library PLA_PLi: Converting
a PL/ACSE Program into an Equivalent PL/1 Progras
(Berman) JUN 16, 1971

Programs for Processing of Temperature Data in
SCLERODERMA (J. Gold/Wiederhold) DEC 30, 1971
bSPD-1

CONS-2

CRASH-1

CSMP-1

CSMPI-1

CTP-1

DEC-1

DP-1

DSLL-1

EDQ- 1

EEW-1

nFFT- 1

EG-1

EIRP-1

EOPS- 1

EPP-2

(118)
Sharing Patient Data Files (Wiederhold)
MAR 29, 1972

Consulting Schedule (Wiederhold)
FEB 2, 1972

Recovery from Cisk Failures (Frey)
SEP 24, 1971

Design Considerations for a Digital Analog Simulator
on ACME (Hjelmeland) OCT 15, 1971

Interactive Continuous System Modelling Program

‘(J. Hu) APR 16, 1972

Communication Port/Terminal Protection (Wiederhold)
MAR 6, 1972

Decimal Arithmetic in ACME (Wiederhold)
FEB 14, 1972

Proposal for Decimal Arithmetic in ACME (Wiederhold)
FEB 14, 1972

315C (Loma Linda) Display Terminals ({Freret)
OCT 28, 1971

ACME Program Library DATACOPY: Reproducing a
Complete or Partial Data Pile (Wiederhold)
NCV 15, 1971

Accuracy of ACME Statistical Subroutines (Whitner)
AUG 9, 1971

ACME Subprograms FFT and FFTD: Fast Fourier
Transforms (Whitner) MAR 10, 1972

ACME Subprogram GRAPHH: Creates Display and Plotter
Output (Hale) MAK 22, 1971

Information Retrieval Program (Radiation Therapy
Dept.) (J. Hu) NOV 18, 1971

Versatile Plotting System {Hale)
JUN 15, 1971

ACME Subprogram PLOTPRIN: Flots Graphs and Prints on
Line Printer or Terminal (J. Hu)
FEB 16, 1972
FPKR-2

FRM-1

FSEC-1

FSTAT-1

FUTIL-1

HAC~-1

HBE-1

HBS~1

HEPR-1

HHOG-1

HLP-1

HPWR-1

HSCI-1

HWEA-~1

J33

(119)

Restoring Blocks Onto Disk From Tape (Lew)
FEB 29, 1972

File Utility Restore and Move Programs (Frey)
JAN 12, 1972

File Security (G. Wiederhold)
FEB 25, 1971

File System Statistical Summary (J. Hu)
AUG 9, 1971

Pile System Utility Library (Frey)
JUN 9, 1971

Log@a Linda Terminal/ACME 1800 Link (Matheson)
BUNO57 OCT 11, 1971

Beehive CRT Display Terminal to PDP-11 Interface
(Stubbs) JAN 3, 1972

Bioscience/ACME 1800 Digital-Analog Link (M. Hu)
EUNO46 SEP 1, 1971

Varian EPR Recorder to IBM 1800 Interface
(M. Hu/Matheson) JUL 20, 1971

Cable Voltage Levels for the Sanders (Cower)
JUL 9, 1971

Litton Printer to PDP-11 Interface (Stubbs)
JAN 3, 1972

A Proposed Method of Protecting Computing Machinery
from Power Surges (Hundley)
JAN 31, 1972

Scan Converter Interface (Stukbs)
JUN 18, 1971

Summary of Western Electric (Telephone Cospany)
Analog Modems (Stainton)
JAN 17, 1972

User Note: ACME Keywords,Conversion Progras
PLA_PL1,Truth Tests in ACME,

Computer Room Modifications (Staff)

MAY 25, 1971
J34

J35

J36

J37

J38

J39

J4&0

J4i

KBEE-1

(120)

User Note: Consulting Schedule,Progragr JOBTAKER
PUBLIC,Graphics Package OPS (Staff)
JUL 20, 1971

User Note: Special Announcement, Hardware
Substitutions, Bulk Core, Disk CDPrives,
Small Machine Intertace (Jamtgaard)

OCT 22, 1971

User Note: New Bulk Core and Cisks, PLCTPRIN, Loma
Linda Graphics, New Commands in PL/ACME (Staff)
NOV 5, 1971

User Note: Performance Tests cn New Bulk Core, New
Text Editing Features, LATACOEY, EVENT,

User Tape Services, New Character String Function,
New [Information on LOGOFF (Staff)

NOV 18, 1971

User note: Holiday Schedule, Fermitting of Real Time
Lines, User Services, Consulting Service Schedule,
Clean Up Your Files! (Staff)

DEC 21, 1971

User note: Seminar on Time-Oriented Medical Records,
Small Machine Multiplexor, Medical Center Computer
Facility Planning Committee,

Printing and Punching Services, Double Precision
Argument Bug, New Show Command: SHOW CSOPEN (Staff)
FEB 7, 1972

User note: Revised Operating Hours, Medical
Computing Seminars, PL/1 versus PL/ACME
Compatibility, Small Machine Multiplexor Interface,
System Errors 226 and 237({File System), Program
CATALCG PUBLIC, Fast Fourier Transforms,

Antilogs (Staff) FEB 28, 1972

User Note: Revised Rates for ACME Service, New
Terminal Support (Memorex), Medical Computing Seminars,
Reassignment of Gio Wiederhold, New ACME Note Index,
New LISTAKER/JOBTAKER Feature, Bug: Character string
Variable and Title Cption, Card and Paper recyling,
Acknowledging ACME in Puklications (Staff)

APR 10, 1972

Using the Beehive Terminals on ACHE (Wiederhold)
NOV 30, 1971
KON-1

KPERA~2

KTB-1

KTBA-1

LM-5

PEFF-1

PLC-2

PLCH-1

PPa-1

PPLO-1

Pscs-1

RSY-1

UEI-1

UEVT-1

ULA- 1

(121)

Comaunication Development (Wiederhold)
JAN 4, 1972

PERAIT18 Function - User Perait on 1800 (Granieri)
DEC 13, 1971

Character Translations for Teletype and Beehive
Terminals (Wiederhold)
FEB 14, 1972

Changes to TTY Translation Takles (Stainton)
MAY 17, 1972

Edit Commands (Berman)
NOV 18, 1971

Proposal to Aid in More Efficient Usage of Disk
(Wiederhold) DEC 30, 1971

Compatibility Requiresents for PL/ACAE Programs to
Use IBM‘s PL/1 (Wiederhold,sFrey)
MAR 8, 1972

A Choice of Language to Support Medical Research
(Wiederhold)

Position paper for a panel discussion on "Coaputer
Language for Medicine," to be held at the 1972

ACM Conference, Boston MAR 6, 1972

ACME/LISP Internal Documentation (Berns)
JOL 14, 1971

Proposal: Interactive Prograass for Pile Bditing and
Data Plotting (Weyl) APR 20, 1972

Proposal for Small Computer Service By ACBE
(Stainton) MAR 21, 1972

Proposal to Allow Release of Sysbol-Table pages in
Production Jobs (Wiederhold) NOV 23, 1971

ACNE Realtize Library Program IRON: Smoothing by
TRONing with an Exponential Decreasing Window
(Wiederhold) DEC 13, 1971

Realtime EVENT Function (Frey)
NOV 4, 1971

ACHE Real Time Program Library AZTEC: Data Reduction
for a Sequence of Sasples (Wiederhold)
NOV 23, 1971
ULC-1

UPDP- |

WCTR-1

WDERM-1

WPDP-1

WPDPA~1

WPDPB-1

WPDPC-1

WSVC-1

XPL-1

YDEBE-1

£u-1

L4PICK-2

é6YL-1

(122)

ACME Realtime Library CUADRO: Smoothing Using a
Square Window (Wiederhold) FEB 17, 1972

PDP-11 Hanging the 360 Channel (Briggs)
MAB 1, 1972

ACME System Core Timing Results (AMPEX vs. 18M)
(Frey) NOV 29, 1971

Terminal In and Output for 3270 Displays
(Wiederhold) DEC 30, 1971

Disk Monitor for the PDP-11 (triggs)
JUN 21, 1971

Index for PDP-11 Software Hinder in the Computer
Room (Briggs) AUG 9, 1971

Using the Litton Printer On ACME Through the PDP-11
(Briggs) AUG 13, 1971

bisk Monitor Utility Program for the PDP-11 (Briggs)
AUG 16, 1971

ACME Written SVCs (Frey)
SEP 1, 1971

Inferred Syntax and Semantics of PL/S
(WiederholdyEhrman) OCT 15, 1971

NVTDEBE ~ OS/360 Multi-Purpose Utility (Frey)
DEC 7, 1971

Flow Chart for ACME System Program MODIFY (Berman)
JAN 10, 1972

PICK Flowchart and Tables (Berman)
JAN 10, 1972

Flow of Light Logic in YIELD (Wiederhold)
DEC 15, 1971
(123)

APPENDIX A

Summary of Campus/ACME Merger Study
(124)
ACME Note ACM]
Ron Jamtyaard
Summary of Campus/ ACME Merger Study November 30, LOY 1

The study of this potential merger has been limited to five specific areas:
- The capacity of the 360/67 to absorb the ACME load;
* An overview of services and cost considerations;
* A brief statement of the planned changes to the Campus Facility;
A list of relative advantages and disadvantages of such a merger; and
Comments on cost comparisons.
There follows a summary of considerations in these five areas.

300/67 Capacity:

In July a test was conducted to determine whether the 360/67 timesharing
monitor called ORVYL could handle its current load plus ACME's current load
plus the anticipated load associated with the new information retrieval system
called SPIRES. The test indicated that the 360/67 had adequate cycles and
performance capability to handle the anticipated SPIRES load plus a substantial
ACMI; load based on current ACME usage levels. The 360/67 has considerable
unused capacity today. The test of ORVYL capacity demonstrated that a
considerably heavier load could be handled with acceptable degradation and
response times to the user. The test did tax the capability of the system with
respect to its paging system on the drums; but this was fully expected. The
ACMI portion of the test appeared to consume approximately 79 per cent of the
460/67 eycles. The simulation of the ACME load consisted of a series of
WORTRAN routines which would require cycles corresponding to approximately 15 users
in execublion on the current ACMM hardware (560/50 with ? megabytes of 8 micro-
second bulk core).

Overview of Service and Cost ConsideraLtions:

 

The Campus Facility provides the following services: production batch service,
quick partition batch service, timesharing in at least three languages, text editing,
(one of the best found anywhere), plotting, and remote job entry. Many languages
are supported in the preduction batch partition. Rates for use of the system
have been designed tc remove administrative fiat with respect to scheduling of
resource utilization. Thus, priority can be obtained by any user who is willing
to pay a fee. No realtime support services are offered at the present time,
although there is limited small machine support through the PDP-9.

Card readers are handled by both computer operators and users. Fast printing
service is available and normally the turn around time is extremely good (a few
minutes). Terminal services are normally offered between 8 a.m. and 1:00 a.m.
except. for brief periods of system staff time from 5 to 8 p.m. three days per
week, plus some system time on weekends.
(125) ACM-1
Page 2

Comments On Planned Changes:

 

The Campus Facility is likely to acquire some new hardware by January 1973.
The new hardware could either replace existing systems or could supplement them.
For example, a fast batch engine could be acquired to support the current 360/67
services, It is essential that any potential hardware changes in the Campus
Facility be capable of demonstrating cost effectiveness. Operations over the
past 4 years have led to an approximate $600,000 deficit. It is hoped thet user
fees and cost reductions over the next couple of years can remove the deficit.
The Campus Facility anticipates having the SPIRES Information Retrieval System
operating for users within the next year. This new service will fill a major
need. The library automation system BALLOTS developed in the environment pro-
vided by SPIRES and ORVYL is being developed and has the University Large Lib-
rary Commitment. Some of the planned changes on the 360/67 entail optimizing
the systems which are presently run there. A major new service to be offered by
the Campus Facility will be an interactive version of a subset of the PL/1 lang-
uage. This will be especially interesting to users of the current ACME system.

Advantages of Potential Merger:

 

1) Availability of an increased range of services to the Medical School
users, including batch service and additional languages;

2) Participation in the system which the University is committed to support
would increase the financial support available for computing. The University
Computing Fund used for unsponsored research and student computing has been
running approximately $700,000 per year. The Medical School use of such funding
has been limited to approximately $15,000 per year, primarily due to the avail-
ability of ACME. The University's Computing funds have been declared to be
unavailable for use on the ACME system since the primary focus of the University
must rest with the support of a central system;

3) Data bases could be easily shared among various disciplines within the
University;

4) The new SPIRES Information Retrieval facility would be available to
medical users;

5) The service center would not be totally dependent upon one source of
funding such as NIH with respect to medical funding. Thus it would be less sen-
sitive to use by a single group of users;

6) There may be long term advantages associated with economy of scale with
respect to hardware, staffing, and physical plant;

7) The Medical School would not have to assume full financial responsibili-
ty for a sizable computing facility such as ACME; the risk would be shared among
all schools within the University for a central facility.

Disadvantages of the Potential Merger:

 

1) The realtime services which already exist on the ACME system do not
exist on the Campus Facility. ACME is currently attempting to develop a real
time support system which would be host-machine independent. Campus Facility
may add it as a service,

2) ACME type service has a strong personal relationship quality which may
be more difficult to attain in a system shared by several thousand users;
(126) ACM-1
Page 3

3) The Campus Facility is located more than a quarter mile from the Medical
School. Although this distance may sound small, it is a physical obstacle which

does present potential interaction problems, despite the terminal service available;

4) Current disk rates and the ORVYL file system will make disk storage more
expensive for medical users that the current ACME rates. See the subsequent
section on Cost Considerations;

5) <A large facility serving several thousand users may have less flexibility
in terms of changing its systems than a smaller facility serving approximately
300 user projects;

6) ACMF users would have to translate their programs to the form of
interactive Pl,/1 mounted on the Campus Facility. Hopefully the conversion cost
can be minimized with translation aids prepared by the facility.

Comments on Cost Comparisons between Campus and ACME Services:

Cost comparisons have been difficult to draw between Campus and ACME Facili-
ties due to the disparate nature of the facilities and the accounting algorithms.
Three of the FORTRAN programs used in the ORVYL capacity study were translated
into PL/ACME. The three were of different types: A matrix multiplier which is
heavily compute-bound, a file writing program, and a psuedo parser which is pri-
marily a string manipulator with a great deal of 2741 output. Considering only
the charges for CPU time and terminal access time under both systems, the compute-
bound job would cost 42% less on Campus Facility than on ACME assuming that ACME
is used during hours of heavy activity. The other two programs (which were heavi-
ly dependent on output speeds) provided roughly equal costs at Campus and ACME.
These cost statements assume that ACME is charged at 2-1/2¢ per pageminute plus
$45.75 per terminal hour on the old 8 microsecond bulk core. The Campus rates
were the standsrd $10 per CPU minute on ORVYL, plus $3.50 per terminal hour.

One factor which is difficult to evalunte is the extent to which the CPU plus
terminal aceoesn at Campus: reflects the total cost of the job. Averaging all
user charges for Tinenl year 1971 at the Campus Facility, a total of 68% was de-
rived from CPU usage and terminal secess., This means that another 45% of the in-
cone wit derived fron disk storage, printing, card punching, card reading, off-
Line plotting, and use of the WYLBUR text editor. The point is that 32% of the
income comes from sources other than those used in the above comparison.

At ACME the charges to users other than pageminutes and terminal access
cover disk storage and terminal rental service. ACME's terminal rental service
includes an add-on to cover general services to the community whereas the Cam-
pus Facility terminal rental rate covers only costs. The rate is $135 per month
plus $4 to $13 for telephone lines on the Campus Facility versus $225 per month
on ACME for a private 2741 terminal. The disk storage rate at ACME is 1¢ per
track per day versus Campus Facility rate recently announced of 2¢ per track per
day. Since ACME has moved to a faster bulk core, it can now provide more comput-
ing per dollar than the old 2 1/2¢ per pageminute rate permitted; the effect of
the new core will vary by types of use. Cycle intensive users will use 50” to
70° of the pageminute usage encountered with the slower bulk core. Data input
via terminals and program development will require about the same number of
pogeminutes: on the new core.
ACM-1
(127) Page 4

The cost comparisons are difficult to make. It is clear that compute-bound
jobs can be executed more efficiently on the Campus Facility than on the ACME
configuration, 1/o bound jobs tend to run at roughly comparable costs on each
facility. On the basis of these findings, it appears that short term economics
should not be the basis for any decision with respect to merger or lack of merger.

Dist: Staff/All
(128)

APPENDIX B

ACME System Core Timing Results
(AMPEX vs. IBM)
(129)

ACME Note WCTR-1
Regina Frey
ACMI; bystem Core Timing Resulvus (AMPRXY vs, TpM) November 79, LO71L

 

Tntroduction:

A set of programs were collected for the purpose of measuring the effect
on the ACME system of substituting AMPEX 2.5 microsecond core for IBM's
& microsecond Large Capacity Storage.

hssentially, these programs were selected to answer three questions:

1. Whether the AMPEX core boxes do indeed have a 2.5 microsecond
cycle time.

“. The performance improvement on a hopefully representative set of
PL/ ACME programs.

3. Whether the core substitution would have any effect on the
maximum possible transmission rate between the 1800 and the 360.

Comparative Core Timings:

 

An 05 batch program was written in assembler language which measured the
true cycle times of the TBM °050 'fast' core, the IBM 2361 LCS, and the
AMPEX core boxes. The time required in each case to perform a series of
fixed and floating point operations was measured.

The results are given in Table 1. The program contains four Loops. The
first measures true cycle time; the last three time loops containing

fixed point arithmetic, short floating point arithmetic, and long floating
point arithmetic instructions.

That each core box performed according to specification was proved in the
first operation. The operation consisted of little more than ten million
Sfore instructions. Each ST requires 2 core cycles for completion, Thus
if the core cycle is ® ps, then each ST will require 4 ws, ten million of
them require 4 x 10 x 10° us or 4O seconds.
(130) WCTR~1

 

 

Page 2
Table 1. Core Timing Results (Seconds)
Core
IBM IBM AMPEX 2050
Operation 2050 AMPEX 2301 2361 AMPEX
(Fast Core) (Bulk Core) (Bulk Core) (%) (%)
Fixed
point 40.29 50.46 161.65 31 80
Store
Fixed
point 111.10 121,11 220.17 55 91
arithmetic
Short
floating 118.14 128.15 21h, 36 60 92
arithmetic
Long,
floating 287.16 302.19 4LO,25 69 95
arithmetic

 

Notes on Table 1:

1. The AMPEX times are the averages of two runs.

2. All figures include overhead time for instruction loop control and
fetch/conversion of the interval timer.

3. Time intervals were calculated to the nearest one-hundredth of a second.
The TIME SVC was used to obtain the contents of the hardware timer.

4, The operations performed in each loop were:
a) Fixed point store: 10x 10° $T instructions.
b) Fixed point arithmetic: 2 x 10° sequences of L, M, A, S, D.
c) Short floating arithmetic: 2 x 10° sequences of LE, ME, AE, SE, DE.
ad) Long floating arithmetic: 2 x 10° sequences of LD, MD, AD, SD, DD.

5. No index register was used in any of the instructions.
(131)
WCTR- 1
Page 4

Representative PL/ ACM rrograms:

 

sever pL/ACME prosyrams were run with the IBM #361 core and the AMPEX
core. All of these programs were written by the ACME staff.

Ali. runs were executed in single user mode. Module TEN], written on
11/4 and 11/11, was used. The differences between the two versions of the
module do not affect the results.

The program attributes are given below; the timing results are in Table 2.
The performance improvement was calculated as the difference between
TBM time and AMPEX time over the original IBM time.

Program Attributes

CONVERS Ts PDP-ll assembler. No terminal output. Moderate disk file
T/O. Heavy string operations,

CM] Matrix multiplier. No I/O operations, no strings. Totally
compute-bound.,

ioLime Disk file read and write sequential operations. ‘Time was
measured for reading and writing 100 records of one block
each, ‘The loop was repeated 10 times each run. Little
computation. No terminal output.

Lisptest LISP test program. Light file and terminal activity. The
program did not complete due to an error in the LISP garbage
collector, Time was measured by eyeballing the machine room
clock,

PLA Viel The PL/ ACME to Pi/L translator. Heavy file and string activity.
he prorram produced a page of terminal output and required
Pour cne-character terminal responses.

PLOT] WW plotting proemram. No file or terminal activity. Light
mathematical calculations. Heavily dependent upon the speed
of the display.

randfile Random disk file operations. Light computations; no terminal
output. The program consists of three sequences: Write
direct of “O records with randomly assigned keys, each record
1200 words long; Read sequentially each of the randomly
written records; Read randomly the 20 records 5 times for a
total of 100 reads.
(132)

 

 

WCTR-1
Page 4
Table 2. PL/ACME Program Timing Results
Core
Perform.
TBM Performance
Program 2361 AMPEX Improvement (%)
CONVERSE 5.7 min. 3.2 min. 46.9
CML 6.1 min. 2.5 min. 59.0
lisptest 4.75 min. 3,0 min. 36.8
PLA_PL1 23.8 min. 17.4 min. 24.8
PLOT1 4,9 min. 4,0 min. 18.1
iotime:
100 reads 13.2 sec 9.5 sec 28.0
100 writes 19.8 sec 14.4 sec 27.3
randfile:
20 write direct] 23.0 sec 15.8 sec 31.3
20 read seq. 71.7 sec 34.2 sec 52.3
100 read direct | 49.1 sec 29.1 sec 4O.7

 

Average 36.5
(133)
WCTR- 1

c

Page 5

The rather unexpected gains in the execution speeds of 'lotime' and
‘randfile' require discussion. While they were included primarily for

determining a base against which to measure the impending AMPEX disk
drives, the results of this test provide some interesting information
regarding the nature of the ACME file system.

Unfortunately, ‘ilotime' was executed only once with the TBM core, so while
the times listed are the averages for 1000 operations (100 read/writes
repeated 10 times), they may not in fact represent true average results.
This statement is based on two facts: The times for the 10 repetitions
did not vary greatly, but the differences between the AMPEX runs were
considerable,

‘iotjme' was executed 4 times with the AMPEX core. The time required
for 100 reads varied from 7.2 seconds to 14.7 seconds. For 100 writes,
the variance was from 143 seconds to 17.4 seconds.

These broad ranges are due to the variability of the required disk head
seek time (from near zero to a maximum of 130 milliseconds. )

Because of the ascendingly ordered nature of the ACME Space List, the
averarze seek time should not be 60 ms, but 25 ms (time to seek to next
contifuous cylinder). Total 1/0 time for an average read is 25 ms plus
ih.5 ms disk rotation time or 37.5 ms, For a write operation, an
additional complete rotational period of 25 ms must be added for an
averarse time of 62.5 ms.

Subtracting these figures from the average times for a single read or
write, we get these software overhead values:

 

 

TBM AMPEX
read LS 95
37.5 - af.
OWLS ins 57.5 ms
write 198 14h
- 62.5 - 62.5
145.5 ms 81.5 ms

The values are somewhat inflated since the times required to update the
index and to type the time on the terminal have not been subtracted. But
clearly the unexpected savings while performing disk I/O have been
explained, and equally clearly the file system software could be optimized.

'randfile' was executed twice with the IBM core, four times with the AMPEX
core, Ail comments on ‘iotime' apply as well to 'randfile' except that
the results of the individual runs were not as variable.

The phenomenal savings on the read sequential operation can be explained
by the fact that the record keys were distributed randomly throughout the
(134)

WCTR-L
Page 6

Tile index and consequently a considerable amount of in-core index
searching was necessary for finding the next sequential record.

1800 Communications:

Little improvement was expected in the 1800 communications transmission rate
since the essential routines (EIGHING@, RW18¢¢, YIELD) were already located
in the 2,0 us core,

To test the hypothesis, one of Lee Hundley's 1800 test routines (READALOT)
was executed before and after the core switch. The purpose of the tests
was to establish the conditions under which data overruns (data arriving
too soon for the 360 to process) would occur,

READALOT accepts as parameters the number of 1800 input lines (N), the
sample interval in milliseconds (TIME), and the number of 360 buffers
assigned to each line (BUFS). Buffer size was fixed at the maximum
permitted, 250 points. After experimentation, we decided to leave BUFS
at its maximum value (20) and to vary only N and TIME,

The following information was gathered from the IBM 2361 test:

1. N=8 and TIME=1 (8000 points/sec) will crash the 1800.
2. N=7 and TIME=1 (7000 points/sec) will cause data overruns.
3. N=lé and TIME=2 (6000 points/sec) will not cause data overruns.

Running as a single user and performing no calculations on the collected
data, the only significant overhead was the time required for YIELD to
service the commutator (i.e., look for another user and ultimately

return to the only active one). Therefore, to determine the approximate
amount in excess of 6000 points/sec at which overruns would occur, we
inserted DELAY(O) statements in the program following each CALL READ

(One DELAY(O) forces one yield to the commutator and wastes one time slice),
With N=12 and TIME=2, two DELAY(O) statements resulted in overruns.

The same program, executed in AMPEX core, gave these results:

1. N=7 and TIME=1 (7000 points/sec) will not result in overruns.

2. N=? and TIME=1 with two DELAY(O) statements will result in
overruns.

Thus the maximum possible data rate was increased by approximately 1000
points per second or roughly 15%,

The second experiment was concerned with the question of whether
EIGHTNZS could execute properly in 2.5 ps core. About six months ago,
EIGHTINGS was moved from the 8 us core to 2 us core when it was discovered
that the channel commands contained within EIGHTN@¢% could not be decoded
(135) WCTR- L

Page 7

fasl enough and channel data chaining checks occurred. This condition
prevailed only if the buffer size was extremely small.

A special link edit off TEN] placed WIGHTN@Z in 2.5 ps core. Tests on
this module save these results:

1. A buffer size of one no longer caused data chaining checks, but
overruns consistently occurred, even at low data rates. At
1000 points/see on the line, the 1800 will crash.

2. A buffer size of two points or greater will execute properly.

However, it is not recommended that EIGHTN@S be moved out of our fast core.
AMPFX performance at its best is still 80% of the maximum on a Model 50.
Moving EIGHTNDY would decrease our maximum possible transmission rate

(has not been tested).

Summary :

It has been confirmed that the AMPEX core does run with a 2.5 microsecond
cycle time, Fixed point operations execute 2 to } times faster; floating
point operations roughly 1 1/2 times faster than in 8 microsecond core.

Total time savings is heavily dependent upon the nature of a PL/ACME pro-
gram. Terminal-bound or otherwise T/O dependent programs will see lit-
tle increase in execution speed. Compute-bound programs may execute as
much as 2 1/2 times faster.

The time slice allocated to each executing program remains as before.
Thus, terminal response time will in many cases be the same, but since
more computation is possible within each time slice, total execution time
for a program will decrease. A sample of PL/ ACME programs executes from
18 to 60% faster. The average was 46.5%.

While some improvement is realized for disk file operations, the gain may
be unnoticed due to the yield to the commutator (other users) at the start
of each T/o operation and the resultant wait by a user until his turn again
arrives.

The maximum 1800 /360 transmission rate has increased by about 15%. A
greater increase was not expected since the 4360 communications program
had already been located in 2 microsecond core.

Dist: Prog/All/D. Phillips/C. Dickens
(136)

APPENDIX C

Results of Three Compaction Algorithas
The test was performed during a File System Analyzer run
on all user data sets, February 28, 1972.
CODINGS USED BY EACH COMPRESSION ALGORITHN TO BUILT BITSTRING*

COMPAC?i COMPAC2 COBPAC3

WORD IS ZERO 00 00 =
WORD IS UNDEFINED 01 01 -
WORD HAS VALUE 1 10 0
WORD IS REPEAT OF LAST WORD - V1 1

TOTAL NON-NUMERIC WORDS = 16,532, 183
TOTAL EMPTY (zero) WORDS = 5,184,105

The resultant savings from the application of each algoritha
is stated below. Percentage figures were computed as the total
storage requirement after application of the algorithm over
the current storage requirement. TOTAL WORDS WHEN LESS refers
to the inclusion of a file only when its ‘compacted! size is
less than the original size.

TOTAL WORDS IN ALL ACME NUMERIC DATA FILES 7,783,794

TOTAL WORDS USING COMPAC1 ON ALL FILES 4,395,400 ( 56%)
TOTAL WORDS USING COMPAC1? ONLY WHEN LESS 4,314,484 ( 55%)
TOTAL WORDS USING COMPAC2 ON ALL FILES 3,661,950 { 47%)
TOTAL WORDS USING COMPAC2 ONLY WHBH LESS 3,612,031 ( 46%)
TOTAL WORDS USING COMPAC3 ON ALL FILES 3,818,520 ( 49%)
TOTAL WORDS USING COMPAC3 OHLY WHEN LESS 3,783,314 ( 48%)

*The bitstring describes the characteristics of the values ina
numeric array. It is stored on disk along with sufficient data
to reconstruct the array. Repeated, undefined, or zero data is
omitted from storage.
(137)

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APPENDIX E

Proposal for Small Computer Service by ACME
(139)

ACME Note PSCS-1
Bob Stainton
Proposal for Small Computer Service by ACME March 21, 1972

 

The rapid decline in the price of mini-computers has led to an incrense
in the number of these computers installed at the Medical Center. This
memo describes the services which could be provided to these computers
by the ACME facility.

The service is summarized as follows:

1. Spooling service-~-
A. Accept data - GO hours a2 day
B. Send data (or processing modules) - 20 hours a day

“, On line service (while the user is actually logged on to ACME)-~=
A. Retrieve data from the spool
B. Write data (or processing modules) to the spool for later
use by the mini-computer
C. Read and write directly to the mini-computer

NN

All services of an ACME typewriter terminal.

4. High level language processors.

spooling Service

“pooling (Simultaneous Peripheral Operation) refers to a procedure which
has become popular with large-scale third generation computers. It is
exemplified by s card reader which is always ready to accept cards, even
though these cards may not be processed by a user program until severnl
hours have passed.

Our early experience with “741 terminals has shown that their usefulness
takes a quantum jump as soon as a computer system is installed which is
continuously avcilable to “answer the telephone”.

Our proposal is to provise a computer system which is always (20 hours a
duy) available to take dota from the user's mini-computer. Our defini-
tion of mini-computer is any device which is able to conform to the re-
quirements of the communications protocol. The data will be held on a
special disk system, and retrieved when the user “logs-on"” to the ACME
system and runs a program. In this way a research scientist may set up
an experiment which may run for several hours during the night. The
next morning he may “log-on” and run a program which processes the data
generated by that experiment.

Ancther service of the spooling system is the ability to provide storage
for “processing modules” which can be called by the mini-computer. The
relntionship betwern the mini-computer and the ACME system in this in-
stance can best be described by an analysis of the classic ‘pen tracking
problem".
(140)
PSCS-1

Page 2

In order to draw a line by means of a "light pen", a tracking cross is
displayed on the screen of a cathode ray tube at the location where the
“pen” is pointing. As the "pen" moves, the cross is no longer in the
center of vision of the pen, and a computer interrupt takes place. The
computer now re-establishes the cross in a new location.

To accomplish this smoothly requires a fast response and a large amount
of data transfer. The response must be fast, or the cross will appear to
drag as through a viscous fluid. The constant re-writing of the display
requires the transfer of a large amount of data.

The conventional solution to this problem would be to use a very high
speed communications line between a large central processor and the re-
mote screen. This would ask the communications line to do that which it
is least able to do, namely, provide fast response with large volumes of
data.

A better solution is to employ a local mini-computer at the screen which
produces the rapid response necessary to accomplish the “pen tracking”.
In this solution, a low speed communications line is used, and only the
location of the tracking cross is sent to the large central computer.
This information may be saved for later analysis or processed for a real
time response.

In the medical research environment, the local mini-computer would con-
tain that part of the software necessary to provide immediate reaction to
the stimulus of the experiment. This software is contained in a replace-
able "processing module” which also directs the sending of partially
processed data to the ACME system for storage and statistical computation.

The replaceable "processing module” may be changed for individual experi-
ments, or a new module may be loaded dynamically as the life of an ex-
periment progresses.

These "processing modules" may be compiled inthe ACME system and saved on
the spooling system for later call by the mini-computer. A list of ex-
perimental parameters may also be stored on the spool and played back as
data over an extended period of time.

On Line Service

The ACME user wouldbe able to access data which has been previously placed
on the spool by using a special "OPEN FILE" statement. The data may then
be accessed with "READ FILE" statements as a sequential data file, Simi-
lar "WRITE FILE" statements may be used to write data (or processing mod-
ules) to the spool system for later use by the mini-computer.

An option would also be provided to bypass the spooling system and com-
municate directly with a running ACME program, using the current directory
mechanism. This allows the same real time interactive service which has
been available in the past.
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WN yu

reryvies of an ACME Terminal

 

As a convenience, it is realized that the “teletype” console of a mini-
computer should be able to act as if it were an ACME terminal, so that
the user need not use a separate 2741 terminal in order to use the ACME
system, The user would also be able to "log-on" and run programs auto-
matically, under control of a program in his mini-computer.

High Level Language Processors

 

We will attempt to provide a hardware-independent language for writing
"processing modules". Translators for this language to produce object
code for the most popular mini-computers would be produced. This would
provide an ease of programming not found on stand-alone systems, as well
as a medium for sharing programs among individual researchers.

Implementation

Implementation would require several loosely related projects:

lL. The spooling system, housed in a separate mini-computer so that
it can operate during maintenance hours for the large central
computer.

nN

- A switching system, for attaching a given user to an ACME port,
a real time data port, or the spooling system. As a by-product,
we hope to allow any mini-computer in the system to communicate
with any other mini in the system.

45. A communication system to transport the data and verify its
correct receipt, with as little effort on the part of the mini-
computer program as possible. We hope to provide a parallel,
demand-response interface to the mini-computer, which appears
to its program as 1 device similar to a tape drive.

4, Ihgh-level processors to provide an easy way of writing prograus
for the mini-computer.

Dist: Staff/All