ACME Compui ing Facility



Advanced Computer for Medical Research
" Stanford University School of Medicine

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       ANNUAL'REPORT

  Primary support from
Biotechnology Resources Branch m



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National Institutes of Health


NATIONAL INSTITUTES OF HEALTH

DIVISION OF RESEARCH RESOURCES

BIOTECHNOLOGY RESOURCES BRANCH

RESOURCE IDENTIFICATION

                                  r
                            d . ..-
Report Period:                            Grant No.

                    A *'  . . *.
From: August 1, l&l To: July 31, 19'72                RR - 311 - 06


                                     **,     Date of?.Report Preparation:

                                      May 1972
Name of Resource            Resource Address      s Resource Telephone No.
                                                                    I

Advanced Computer for MEdical Stanford University      (415) 321-1200 ext. 6121

  Research (ACME)

Principal Investigator

Lederberg, Joshua

School of Medicine
Stanford. Calif. 94305

Title


Professor

Academic Dept.

Genetics

Grantee Institution

Stanford University
School of Medicine

Type of Institution         Investigator's
                       Telephone No.
Private Non-Profit University
                 (415) 321-1200 ext. 5801

Name of Institution's Biotechnology Resource Advisory Committee:

.

ACME Policy Committee

Membership of Biotechnology Resource Advisory Committee:

Name             Title

*Elliott Levinthal Assoc. Dean for Research
Stanley Cohen     Assistant Professor
Joseph DeGrazia    Assistant Professor
Donald Harrison   Associate Professor
Sumner Kalman     Professor
Howard Sussman    Assistant Professor

Department         Institution

Genetics           SU Med School
Clin. Pharmacology          11
Nuclear Medicine            II

Cardiology                   l`

Pharmacology                l,

Pathology                    II

*Chariman; has reviewed report.

Name and Title of Principal Investigator


TABLE OF COBTEBTS

IITRODUCTIOV ..@.y* ............................................... 1


I.    SU HBAR Y .................................................... 2


    A.  Highlights of Piscal'kar,  1972 ???????????????????????? 2


    B.  Goals for Piscal Year,  1973 ............................ 3


    c.  Comment on Bedical Center Computer Planning ......... ...4


    D.  Overvieu of Six-Year ACM Experfmnt ................. ..S


II.   SXAIWOPD BEDICAL C%ITEE COBOU?IYC PLAllS .................... 7


    h.   The Medical Center  Scene ............................... 7

    B ACHE Pollow-on Grant ???????????????????????????????????? 7

III. ACtiR FACILITY ACCOEPLISHllbDTS, 197Z....q ................ ...9

A.  Planning studies ??????????????????????????????????????? ?


B.  Yew and Continuing ApplicatSoa Progxa88...............11

C.  System Software ImproveDents .......................... 13


D.  Earduare Changes ...................................... 17


E.  Operations Report ..................................... 20


P.  gducation and Training ................................ 22

PLALUYED PROGRAH POB 1973 .................................. 24


h.  Objectives ???????????????????????????????????????????? 24


8.  Applications Development ?????????????????????????????? 24


C.  Hardware Acquisitions ????????????????????????????????? 27


D.  System Software ................ . ....................... 28

ADklItilSTBATIVE ORGARI2ATIOU ............................... 33

IV.

V.


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VI.   BUDGET .................................................... 35


    A.   Resource  Expenditures ................................ 35


     8.  Justificatiohfor -1473 Budget........................*3 6

    C.  Bxpenditure Details .................................. t 38


    D.  Summary of Resource Funding ??????????????????????????? 43


    E.  Resource Equipment  List ............................... 44


    P,  Income Projection ..................................... 47


VII,  PROJRCT DESCEIPTIORS ...................................... 49


    A.   Core and Collaborative Research.......................4 9


    B.  Service Projects ?????????????????????????????????????? 66


    c.  Training Projects ..................................... 78


VIII. UTILIZATXOR DATA ????????????????????????????????????????? 82


    A.  Interpreting Utilization Charts.......................8 2

    9.   Patterns of  Use ....................................... 83


    C.   Utilization Charts .................................... 85


     D.  Summary of Computer Resource Usage .................... 89


IX.   PUBLIC ATIOPS ????????????????????????????????????????????? olll


    A.  Publications in Regularly Scheduled Periodicals......~ll


     0.   Other Publications ................................... J12


    c.   Staff Technical Yotes ................................ ml17

   Appendix A:  Summary of CaBpus/ACRB flerger Study..........12 3

   Appendix B:  ACBB System Core Timing Resnlts..............l2 8

   Appendix C:  Results of Three Compaction Algorithms.......13 6

   Appendix D:  Comparison of Beantine between Pailures,.,.,.l37

   Append ix E:  Proposal for Small Computer Service..........13 8


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Wajor portions of this report uere prepared
using the Stanford Campus Facility lXl.BUR
and ACHE Facility text editing programs.
Final copy was produced on the ACID s/stem
priater.



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IHTRODUCTIOW

   ACHE, Advance Corpater for LlBdical Research, is about to
conclude its sixth year as a research, developueat, and service
facility.  One year ago,  a fifteen month adknistrative extension
was requested to become effective August 1,.:1972.   After dis-
cussion vith EIIH, our fifteen kmth extensiod request was reduced
to tuelve months.

   This annual report describes the accomplishments of the
past year and proposes a neu work program for the fiscal year
1973.  Ye expect this to be the final year of II8 support for
ACHB under this grant.  A neu cmpetiqg proposal has been sub-
mitted separately for the creation of a new research resource
at Stanford.  The primary task to be accomplished under the last
year of the ACBE grant is preparation for the transition to a
service facility uhose operating costs, hopefully, vi11 be total-
ly recovered from user fees.

   During the past several mollths, a nurber of faculty uerbers
have contributed actively to long ters computer planning for
the Hedical Center.  One question still under review is a
proposed merger of an academic service-computing facility such
as ACEliZ with the Hospital Data Processing facility.  A parallel
but separate planning effort is embodied in a praposal for
*sumx"  (Stanford University fledical Brperiaeatatioe Computer
Pacility), a neu research resource for corpoter-ascience research
on bio-medical problems.  At the university level, planning
has dealt uith the interrelationships auong Medical Center,
university admiuistration, and all other campus computing.
A brief description of several of these planaing activities is
incorporated in this report.


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I.   SDHllARY

A.  &@Uhts of Fiscal Year
              ---me           1972
                             a----L-m

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

   The long-term viability of ACaB, viewed as a service
facility for the Fledical Center, is tied to its ability to
earn income sufficient to cover cost.  In mid-April, 1972,
a new rate schedule became effective for ACEB users.  Honthly
income in the last three months of this fiscal year, is expected
to reach an average of 540,000.  This figure includes both
computer service income, uhich reverts to the grant budget,
and terminal service income,  uhich is handled outside of the
ACtlE grant.  Several major users have developed neu systems on
ACClE uhich will be moved to dedicated standalone systems in produc-
tion mode.  As soon as these dedicated systems are available, income
from these sources will drop.  On the otber band, one can expect
that neu applications will continue to be developed uhich in
turn vi11 generate new income.

   Service on the ACME facility has been markedly improved
in the past fiscal year by the installation of neu harduare
and sof tuare.  New harduare includes faster bulk core, a small
machine interface capable of handling up to 16 satellites,
faster access disk drives, an initial complement for the small
machine equipment pool, a terminal controller that will support
multiple terminal speeds, and neu graphics harduare,   Software
improvements include improvements to the realtime system,
extended graphics support, improved text editing, additional
terminal support, improved small machine support, file support,
and compiler iaprovements.

   Several neu and interesting user projects were implemented
during the past year.  Some of the more interesting neu projects
include Dr.  Green*s activity in Biological Science, Dr. Kadis
in bnethesia, Dr. Tatton in Biological Science, Dr. Laurence
William in Oncology, and Dr. Jerome Gold in Diagnostic Radiology.
These proJects are described in the project descripti.ons in
Section VII.


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   Continuing user projects include'the DBPDRAL project,
which has connected a new Varian rass-spectro5eter to the ACME
syste5 and has used the General Purpose Graphics Terminals
(devel:,ped by Dr. Shipton at University of Ioua) to actively
support spectrometer opef'atioes.  &lso, Dr. Stanley Cohen's drug
interaction project has' received considerable program assistance
during the past.year.  His project,  formerly part of ACl_E*s
core research activity, receiwed independeht funding in
November of 1971.  A close cooperatio5 between ACLJE and the drug
interaction project continues.  Dr. James fr$es in Slnunology
has continued to develop his &me-oriented redical record
concept.  His syste5 has received good acceptance araong physicians
in the rheumatic clinics and is being actively considered for
irplementation by other departnents (Oncology, Cardiology,
and Hematology),  The Oncology Department has receetly started
data entry under programs designed to use t&e Use-oriented
medical record.

   Utilization of ACEB ha6 risen only slightly during the past
year.  Eouever, 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 minutes
used, installation of a faster core box necessarily resulted in
more computing accomplished in a fever amber of pageriautes.

B.  Goals fpJ Piscal Ye-1973
     U-P

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

1,  Detemine a list of sew services required under ACi!lB
  to assist in improvement of the incoma pasture; Then
  freeze the system after essential cbaagss are o ade.

2.  Identify critical planniag areas for uounti5g an inter-
  active PL language on the proposed SUlBX S]tstem (a DXC
  PDP-10).  Improve the documentation of the ACERB spste5
  in those areas that vi11 be required to assist in the
   transition.

3.  Actively support the activities of the Stanford Medical
  Center Co5puter Plaani5g Coraittee.

4.  Improve small machine support, especially by assist-
  ing users in taking advantage of the 5eu small machine
  raltiplexor.


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8.

In

Provide batch services to better utilize the night shift
hours.

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

Select couimercially available hardware to replace
existing terminals and other peripberalunits uhen
performance improvements qan be realized at cost
effective prices.  Attempt to make the use of ACCIE more
cost effective wherever possible.

Explore the offering of PL/ACt!lE services to potential
users at other institutions through correrical
communications systems such as TPRIET.  Operational
ramifications that might result from such an offering
will be discussed uith Biotechnology Resources Branch.

summary these objectives call for provision of neu

services that will attract added income, the freeze and docuaen-
tation of the existing system,  the release of staff tine to work
on transitions to future systems, and for attracting and assisting
new users.

C.  Comment on #edi&Center Computer Planninq
     --w--w----      ---

   The Stanford medical Center consists of the Hedical School,
Hospital,  and Out-Patient Clinics.  Computing uithin the medical
School is handled primarily by the ACRE facility plus a number
of dedicated standalone systems,  some of which are connected
to ACr_E,  Hospital computing is handled by an adninistrative
data processing facility operating an IBfi 360/40.  The 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 community.   A number of
alternatives are being explored.

  The role of ACBE during the past three years has been to
provide computing services to faculty and staff researchers
in the lYedica1 Center.  Earlier the role of AChB uas to
develop new techniques for offering such services.   As the
number of users has grown, demand has increased for highly
reliable, stable,  and available service.  Por this reason the
development effort of the ACRB facility has shifted to extensions
and improvements to existing facilities rather than radical


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changes uhich would severely impact availability of routine
service computing.  To provide a research system which can
tackle problem associated with high data rate realtime
research is the subject of a separate proposal recently
subuitted.  This proposalScalls for the creation of a dual
processor facility in which one processor and its peripherals
are dedicated to providing service to the medical commaity,
while the second processor will be dedicate4 to a small number
of research groups.

  The organization of the planning effort, current status,
and a brief discussion of some of the alternatives under COH-
sideration are briefly described in Section 11.

   In the past six years, the MI&!-sponsored ACIIB experiment
has assomplished the following:

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

2.  Bore than 230 user projects, exclusive of ACllE staff,
  are current users of the system,

3.  The system provides a highly interactive time-sharing
  service and realtime data acquisition.   The data
  collection capabilities are lirited to data rates uhich,
  in light of current technology, appear slow and limited.
  Problem of closed loop applications have not been
  satisfactorily resolved usilpg the 360/50, prirarily
  due to its architecture and other inbeteut liritations.

4.  tiore than 500 ND's have been trained in the use of this
  system.  many fib's performing research at Stan%ord nou
  do their oun prograD8iag at aa:ACIB tettinal.

5.  Small machine support from ACElE is limited but grouing,

  We have learned in the past sir years that computer science-
type research which can involve frequent hardware adjustments
and changes, as vell as systems softuare changes, cannot be
performed effectively on a resource rhich routinely provides
service for the balance of the comvunity.  Coaf licts oper
resource allocation between research oriented as opposed
to service oriented users lead to compromises unacceptable to
one or both groups.

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

   A problea which we have been unable to resolve is how to
provide free computing to pilot projects around the Wedical
Center.  Ye've observed that a number of the pioneering computer
efforts have been possible only by viture of the free computing
provided under the ACdB grant.  As the need to provide self-
sufficiency increased, ue were able to approve fever new pilot
projects each year.  We strongly urge that BIB uaive one of
its policy restrictions for the coming fiscal year,so that
ACWE can continue to encourage the development of neu
concepts on a pilot basis through non-chargeable computing
services.  The University in turn must determine some method of
funding such usage when there i$ no longer an ACBB grant behind
the service system.

   Computer users 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 ue would
like to use O anufacturer1s supported softvare whenever possible
to provide maxiaufn exportability to other institutions.   Ue also
observe a trend in vhich softuare vi11 become an increasing
percentage of the total computing picture.  Therefore, ue 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 vi11 not be required to
reprogram their efforts.


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II.   STAIPOBD flEDSCAL CBIATBA? COBPUTIIPG PLAllS

A.  The bed$.cal Center Sm
     ---

   During the past fiscal year, Dr. Claytoa Rich, uas appoin-
ted Dean of the Medical Schooll  He has expressed concern
for the long-range planning of computing in the Medical Center.
Decently, a new faculty position was created in the Department
of Community Medicine for appointing an I.D. uitb a
strong interest in problems associated with service computing in
a aedical env%ronment,  In January,  1972, Dean Rich established
a Bedical Center Corputer facilities Planning Corrittee and
charged it uith the responsibility of erauiniag the feasibility
of merging the ACllB facility with the Eospital Data Processing
facility.  To date, the Committee has spent the bulk of its
effort examining alternative organiratiom and conffgurations and
identifying service regairements.  Ropefully, by early fall,
the Committee vi11 be prepared to recosmead specific actions to
the Dean.  ACRE staff *embers will, provide technical support
to the Coanittee*s deliberatioos.

H.  A&BE Pouou-on  Grant
     ---

   The SUJEIEX proposal calls for creating a high data-oriented
resource using a PDP-10 as the host co8pster.  Dr. tederberg,
vho is Principal Investigator of the new proposal, has
suggested that the service system for the Cledical Center
be a hardware configuration similar to the research system.
In this uay, developments occurring on the research system can
be moved readily to the service system,  It also provides a
strong back-up capability for the service system.  One thing
learned at ACHE is t&at Medical Center persoanel place a high
value on reliability and availability.  Only by having a back-up
system can the kinds of requirements frequently cited here be vet,

   The impact of the proposed research syste8 OR ACCIB's plans
for the coming year is reflected in the decision to freeze the
ACRE system design as soon as possible, t&e together the loose
ends through documentation,  and aove on to efforts that will
smooth the transition to another harduare system.   Other
demonstrations of the impact on our planning are as follows:


1.  The current staff vi11 require training on PDP-10
  hardvare and sof tvare systems.

2.  Planning which in the past has been based upon IEM
  hardware selection will have to be rodified,

3.  Increasing the income of the service facility requires
  development of more usage and more users.   The creation
  of a neu research facility will dilute the funding
   base to some extent.

4.  A consensus must be reached concerning the long range
  plans for the hedical Center so that users of the
  existing AC&E facility vi11 not be motivated to develop
  dedicated stand-alone systems for all applications.
  The Dean of the Medical School will be expected to
  make soae firm commitments in order to avoid confusion
  and uncertainity over the existence of a large service
   center.


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III,  ACBE FACILITY ACCOf!PLISHBBYTS, 1972

  AccomplishBents by staff Operations, System, and Applica-
tions groups and efforts Supporting aedical Center planning are
described,  US~X core research progress nOt8S are included in the
section entitled *Project Descriptions'.

  Last year's report indicated that tuo factors uere shaping
changes in ACHE.  The first was financial aad th8 second inoolved
d choice between serving special research versus general computer
users.  Efforts to solve the financial problem necessitated the
substitution of faster bulk core, uhich iocreased our capacity
significantly Uhil8 only slightly increasing costs.  By adding
capacity ue hare been able to offer s8rvices to more users within
the Stanford medical comuaity,  In addition, rate adjnstaents
have been aAnOUACed uhich vi11 h8lp ns det8r8in8 t&e viability of
ACBB ia a market situation Uh8r8 prices 8r8 set ~10~8 to aCtUa1
cost of providing service.

A.  Banninq Studies

1.  ACfiE/Caapus Herger Study

  Last fall, a study was conducted to determine the feasibility
of aerging ACBB with the Stanford Caapus Pacility.  The study
focused on (1) the capacity of the Campus 360/67 to absorb the
ACflB load;  (2) an overview of service and cost coasiderations;
(3) a review of planned changes within the Ca8pus Facility; and
(4) the relatiwe advantages and disadvantages of a rerger.
A nnaber of problems were identifi8a which rcsmlted in
further consideration of merging Hospital and ACHB computing
facilities rather than Campus and ACIB facilities.   Soae
notes on the ACME/Campus 8erger study were iSSQ8d in the form of
a techrical note, ACB, a copy of uhich is enclosed as Appendix A.

2,  Co8parision of Available Tire-Sharing Systems

  The IFM systems TSO, CPS, and CALL-OS are under review as
to their possible application to Stanford medical computing.
Some specific questions to be answered are the language
differences between the various PL/I subsets. th8 Bagnitade
of the conversion prObl'8R from PL/ACHB to another PA/I dialect,
hardware requirements for approximately SO ter&i&als, and some
of the specific pros and cons associated uith each system.


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3.  Alternative Hardware Proposals

   Gio Weiderhold, Tom Eindfleisch and Chuck Dickens were asked
to suggest a limited number of feasible harduare 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 sewen
alternatives suggested by the subcommittee inciuded a large IBB
processor, a dual LBH configuration, a large DEC processor with
satellite systems,  a highly distributed computing system, finally
the purchase of essentially all services from outside sources.
The HCCFPC has rejected four of the seven alternatives and con-
tinues to study the reuaining 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 SeCOAd maChiA8 iS a service system.

   There has not been adequate time to date for detailed review
of this topology by the LJCCPPC.  One of the more sigaificant
problems envisioned with this topology is the existence
of a large number of second generation programs currently opera-
ting on IBH harduare supported under DOS.  EV8A if these programs
were converted to COBOL, it is not clear that the Hospital would
choose to run on hardware other than IBB,  Rowever, a fairly small
IBH machine might absorb the load, uhile coupled to the patient
data base and to a PDP-10.  Clearly the f!lCCPPC has sole
difficult problems to resolve over the next several month,

4.  Small Bachine Support Study

  The ACHE systems staff,  in cooperation uith staff members
of other XC facilities,  formalized current ideas on the
types of services required of a large host computer to
adequately support a variety of satellite o achi8es. A
summary of the study was published as AChB Technical Mote
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.


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fl.  hew and Cont&nuinq AJ&ication Proqraos
     --w--w---

1.   DElJDRAL

   The ACRE facility attempted to support the DBBDRAL
project in a number of ways during the past fiscal year.   One
approach at supporting DEblDBAL has failed.   An interactive LISP
compiler uas mounted under PL/ACHE.  blthough the compiler
runs and can be used, it is too slow for the large program uhic'n
the DEIDBAL project tend to execute.  Furthermore, the coslpiler
is not identical to the batch version which inrrposes limitations
on the user.  Bore successful have been the efforts to support
vith hardware and software the 31% General Purpose Graphics
Terminals.  Using the tools provided, DEBDRAL programmers
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 Flay.  It is hoped that this service will be offered
routinely in June, and that it will subsequently be iaproved
to be more flexible in general.  Limited assistance vas provided
in planning the long-term needs of the DBBIDEAL project for
computing,  Pinally, the DBYDBAL staff has been very helpful
to ACHE in identifying and solving realtime support problems.

2.  Drug Interaction Project

   The data entry and label printing program was placed into
production in the Eospital Pharmacy last Septerber.   Two CRT
devices aad tro printers are used for entering perscriptioa
information into a central. patient file and for subsequent
perscription label printing.

   The second phase of the project will iaplement autorsatic
drug interaction searches and reporting of detected interactions
to the physician.  Incorporation of interaction searches into
the production pharmacy system is imminent.

3.  Oncology Time-Oriented Records

   flembers of the ACBE staff have applied the concept of
Dr,  James fries' time-oriented medical records to computerization
of the Departaent of Oncology patient files.   Both narrative and
numerical data are collected and presented in a three-dimensional
form (patient, medical measurements, and time).


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   Initially, four programs have been developed.  A patient
record input program 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 bg the time-dependent visits to the Oncology
Clinic.

   Ul tinately, ue plan to incorporate the data bank analysis
programs of Dr. Fries into this project.

4.  tieu Realtime Projects

   Several new realtime users joined us last year.   Uilliam
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 systems. Dr.
Paul Green, also of the Department of Biological Sciences, is ana-
lyzing the growth process of plants.   Growth rate is measured as a
function of step shifts in the turgor pressure.  The system
is a model for the study of mechanisms for cessation of growth
in man.

   Doctors Walton Roth and Leslie Kadis are both studying BEG
data, but for differing purposes. Dr. Kadis, Depart8ent of
Anethesia, was awarded a pilot project for a psycho-physfological
study of tolerance to experimental pain.  normal 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.  CSHP Design Study

   A design specification for inclusion of an interactive
Continuous System flodelling Program (CSHP) im the ACMB system
has been published as ACME Technical Kote CSHPI.   Model
definition is accomplished by standard CSBP language statements
uith PL/ACHB statements intermixed in the progra8.  Processing
is in three stages:   (1) translation of the CSBP model to a
PL/ACHE program equivalent,  (2) compilation of the PL/ACKB
program, and (3) execution.  Plans for implementation are in
abeyance at this time.


0.  Radiation Therapy Programs

   hn information retrieval program was written for the
tiadiation 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 Prograss for Public Use

   Several new programs uere included in the ACti% Public
Library.  These include a routine employing the
Cooler-Tukey Past Pourier Transform Algorithm and AZTEC, a
program for reducing a sequence of observation samples to a list
of horizontal and inclined straight line segxetrts.

   A PLIACHE to PL/I (P-level) translator was urittea.   Host
conversions are performed automatically, but manual recoding is
still required for conversion of 8aay input and output atatesents,

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

C.  atea Software Imnrore8ents
         w-m-

l.  Extended Graphics Support

   The Stanford Computation Center Caapns Pacility OPS
(Overall Plotting System) graphics package was adapted to PL/ACBE
last year.  OPS allous the user to plot an entire graph by
simple calls for grid, grid labels, titles and plotted data.
Any one of ACI!lEas various plotting devices may 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 information and
the usual graphics mode (where text may be *draun*) are provided,
In character mode, line and column control is provided.   Modes
may be intermixed within any PL/ACtiI program.

   The Calcomp plotting package was revised in a very minor
manner which surprisingly produced a 20X decrease in execution
tiae.  The change was based upon a known FOBTRAP deficiency
in compiling code for symbolic array subscripts.


(14)

2.  Additional Realtime Improvements

   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 AWPBX 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 1800 disk management routine vas redesigned so that
realtime data collected on the disk is not lost as a result of a
failure of the 1800 system.

   A PL/ACHE function EVEBIT 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 uaiting on a realtime occurrence
and the ability of a program to respond dynamically to several
realtime input devices,  The function has been implemented
successfully for both 1800 applications and for the Drug
Interaction Project via the PDP-11.

   Operdtor permission to use realtime lines was eliminated,
Programmed use of devices routed through the PDP-II require no
operator permission.  A PL/ACflB function allovs the 1800 user
to enable himself (the PBEBITl8 function).  The operator is informed
of 1800 status via operator console messages aad via the SHOW
DSOPBN command.  He may disallov further use of realtime lines uhen
data rates for all lines reach the physical maxinan.

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

3.  Improved Text Editing

   ACCJE*s text editing package was enhanced by the
addition of the LIST and CHANGE coxsands.  LIST outputs lines
on the terminal;  CHAYGE 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 HODIFY and DBLBTE
commands.  A portion of the Text Bditor was uritten in
Assembler Language to facilitate rapid execution.


4.  Additional Terminal Support

    Concomitant with the installation of the Wemorex 1270
Terminal Control Unit, softuare additions recogaize a terminal
eype and invoke the necessary supporting softuare.   274 1
correspondence code terminals are lore easily specified at
logon time.  ASA standard terminals are supported for both
display and typevriter devices and from all TCU ports.

5.  Satellite nachine Support

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

   Stanford Computation Center Engineering Services has
completed the design of a satellite computer multiplexor inter-
face to one of our 2701 ports.  Supporting softuare has been
implemented for the ACEB system and for PDP-11 eatellites.

   The ACHB software resembles the current 18OO/PDP-11 support
in many ways.  The user interface is nearly identical.   All
couaunications is asynchronously interrupt driven.  Differences
in the supporting softuare do exist, primarily because of proto-
col destinctions and because of an effort to learn from the 1800/
PDP-11 softvare implementation,

   The SH xultiplexor softuare is in the o iddle stage of
debugging.  He expect to have the project completed by nid-
suaver.

   A program to simulate the PDP-11 is available for batch
operation and is in the debugging phase for AC8B time-sharing
execution.  The Simulator executes in single instruction step
mode.  Diagnostic information is returned after the execution
of each instruction of a PDP- 11 program.  The Simulator
provides the debugging capabilities of the PDP- 11 front
panel as vell 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 sumer, ve added some 32 mathematical and logical func-
tions to the interactive LISP compiler.  This vas accomplished
by interfacing LISP to the corresponding PL/ACf_E functions.


(16)

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

.7 .  File Support Improvements

   Several additions to File System support vere imple-
mented in the past year.  The primary additions are a data
compaction algorithm for reducing disk storage space requirements
and several nev 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 vith some simple
data compaction algorithms.  A study in February, 1972 of
existing numeric data is summarized in Appendix C.  Storage
savings up to 501 are realizable, depending upon the compaction
option*s degree of use by the user comaunity.  System design
has been co mple ted.  Implementation will begin soon.

   Batch execution of requests to move user files to and from
tape and disk was partially automated by the inclusion of public
and operator programs for generation of OS job requests. On
the overnight operations shift,  tbe 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 vere vritten for maintenance
of the job request data set.

   Further plans for an ACHE EJB interface will automate this
service completely by eliminating any need for operator
intervention.  Job requests submitted from a terminal vi11 be
routed directly to a spooled job queue.

   Other improvements include tuo PL/ACHE functions, BLOCKS
and TYPE, for determining assigned disk block space aad the
storage mode of a file (data or text) respectively, the extension
of the PROTECT statement to prevent a DBLBTB on a file, and the
nev SAVE PILE command.   SAVE is similar to CLOSE in that
index and data core buffers are vritten to disk, but a subsequent
OPEN is not required for continued use of a file.   SAVB is a
guarantee against loss of data in the event of a system crash,


(171

8.  Accounting Software

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

3.  PL/ACBE Corapiler Improvements

   The addition of Variable Array Allocation to the PL/ACBE
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.  ltOY, array size definition map be deferred
until execution time,  Purtheraore, array size (and the core
requirement of an array) may vary dynamically daring a single
execution of a PL/ACLJB program.

10.  Deferred Projects

   Last year we reported on tuo system projects uhose
implementation has since been suspended.  The ACBB to OS file
conversion project uas suspended due to some design deficiencies
and the lack of staff personnel.  A design specification has been
corspleted which builds on the previous effort, but increases
the flexibility of the anticipated service.  Pull irplerentation
is expected in the near future.

   Extended logon,  wherein a user session is controllable
from a device other than one routed through the IB8 2702 (now
nemorex 1270) was suspended uhen unforeseen design problems
were encountered in the ACUB system.  This project, its
desirability, and plans for system modifications to accommodate
it are further discussed in Section IV.

D.  Hardware Chap4ea
     --m--v

1.  Ampex Bulk Core

   AMPEX bulk core has replaced 2 megabytes of IBH bulk
core.  The Ampex equipment has a cycle time of 2.5 microseconds
versus the 8 microsecond IB1( core.  Responses of the ACIIIB
system improved considerably following the installation in
November 7971.


`33)

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

2.   AHPEX Disk Drives

  AMPEX Dh312 disk drives (17 spindles) replaced the IBFI
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 ABPEX bulk core,

3.   Wemorex 1270

  Automatic terminal typing and speed recognition became
possible uhen the IBH 2702 transmission Control Unit oas
replaced with the Hemorex 1270 Terminal Control Unit.
Devices other than a 2741 terminal or Teletype typewriter are
easily supported up to speeds of 1200 bps.  Furthermore, 'PC0
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.  ACflE vievs this hardvare
modification as a major marketing and user service attribute.
We intend to exploit its potential wherever necessary and possible.

4.  Development PDP-11 System

   In last year's report, a small machine equipment pool uas
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 bp a number of ACBE
users and is also serving as a test vehicle for saall machine
support development by the ACHE staff.

5.  Satellite Computer Multiplexor

  This is a specialized hardware interface whose purpose
AS to allow shared access to the ACIlE system via one of our
2701 TCU parallel data adaptor ports.  The nultiplexor was
especially designed and built by the Stanford Corputation Center
Engineering Group for the ACBE Facility,


(19)

   The design is such that 16 satellite computers share a
single 27Gl 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 computer 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 ACBE system.  Rigid
adherence to a communications protocol and a set of harduare
timeout functions are the primary guarantees.

6.  General Purpose Graphics Terminals

   Two 31% General Purpose Graphics Terminals uere received
in Bay 1971 from Dr. Harold Shipton and made available to users
in the fall of 1971,  The displays are DOW in use by the Depart-
ment of Genetics and by Abraha8 Silvers of the Department of
Hedicine.

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

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

7,  2741 Terminal Beplacement Study

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

   We expect to purchase several representative terminals from
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 AC8E users have not had access to
CBT terminals primarily due to the speed limitation of
15 characters per second.  Rider exposure is now possible (and
desirable) with the installation of the Uerorex unit.


(20)

8.  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 uas that no unit performed reliably enough
to recommend its use as a storage backup medium,
Consequently,  other alternatives are under consideration.

9.  Planned Acquisitions This Year

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

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 uhen 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 Bxecuport 300.

C.  Additional acoustic couplers and modems for the
  higher speed terminals and remote user installations.

E.  aerations Report
       e-e---- -

1.  System Reliability

   The Hean time between failure fell last year primarily
because of the higher than normal system instability during the
installation of AHPEX equipment.  A chart in Appendix D, com-
comparing monthly RTBF for the past three years, shous the
pattern vividly.   The first of the AdPEX core modules was
delivered in November;  the last of the AHPEX disk drives were
installed in January.  By the end of February, the neu
equipment was stabilized and the MTBP rose dramatically.

   Nonetheless, the system failure rate for the year
from all causes is slightly better than last year's record.
This uould indicate that failures due to non-hardware system
components are rare,  and that the ACNE system softuare is
extremely stable.


(21)

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

                             1        2        3
BTBP (System Crashes)    PY70     FY71     PP71     PY72

Hardware caused          64.3     246.6    214.8    147.7
All reasons             34,4     84.8     80.7     82.2

1

Projected figures reported in last year's report.

2

Actual HTBF for the entire year of 1971,

3

Projected totals for 1972.  Average of l!!TBf for AUG71-
aPBy2 determined estimates for lliY72-JULY72,

2.  Hours Change

   ACME service hours were changed to 7:00am-5:30pr and
ll:OOpn, daily and weekends.  The effects of the modification
uere to delay the late afternoon system programmer block
by one-half hour (from 5:OO to 5:30) and to extend the late even-
ing service period by one hour (from 10:00 to 1l:OO).

3.  Utitity Services

   Printing and punching services, performed routinely by
operations for the benefit of the user community, are nou
chargeable under the neu rate structure.  Statistics on
quantities of lines printed/cards punched show that the number
of printed lines in &arch,  1972, uas 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
Harch period (3,575 * 1000 lines), fully 87% is rechargeable.


(22)

F.  Education and Training
     -------m----s---

1.   PL/ACBE Classes

  During the 12 months ending April 30, 1972, ACHE provided
formal instruction to 182 persons.  Of these,  164 uere enrolled
in the PL/ACIJE 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.  tloughly 50% are staff employees, the remainder are
  raculty 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/AC?iE course was taken
  for use in a new project.

e.  Thirty-five percent have a Ph.D. or B.D.

2.  medical Computing Seminars

  A seminar series was organized to encourage the dissemination
of information on biomedical computing in the Stanford community.
The first seminar included a talk by Dr. James Pries, Department
of Immunology, on his Time-Oriented Iedical Records project,
and a film depicting the patient-oriented medical records system
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.   ACM3 will continue to
serve as coordinator for this seminar series,


(23)

3.  Consulting

    Last Sumner,  the consultant8s office was moved from the ACIS
office area to a partition in the machine room.   The move 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 coosultaatts office.   Guaranteed
consulting hours are 9:30-11:30 and 1:30-3:30 daily.   Bach
systeas staff member is assigned one tuo-hour block weekly.

4,  Staff Training

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

Ying Lev:          DEC: PDP-I1 School
Charles Granieri;  IBM: TP Systems Control
                for Programmers
Stu Hiller:      n3g: Advanced coding
Lee Hundley:      IBB: Project Ilanagement
Regina Frey:      IELI: Project flanagemeat,


(24)

IV*   PLANWED PROGBAII FOB FYI973

A.  Objectives
     - ---

   The upcoming year will be a period of transition.   The
bedical Center Computing Facilities Planning Committee will
define and establish the nature of computing at the Stanford
Bedical Center.  Assuming that the grant proposal fox the
SUHEX Colaputer Facility is approved by NIB, we uil3 begin
preliminary efforts on system design, equipseat
specification, and training.  Specific actions are necessary for
stabilizing the current ACHE syste8 and for increasing the level
of self-sufficiency of the ACRE Pacility.

   It must be assumed that the ACM system, as currently
constituted, will continue to exist after July 31, 1973
until such time as a blend of the SUIBX Grant, ledical 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 ACLIB system as a routine
laboratory tool for solution of their own research problems.
We expect this dependence upon ACHE for service computing to
continue.

B.  -1icationm)eent
         ----              --

1.  Digital Filtering Program

    We have contracted with Professor William Gersch of the
University of Hawaii for a summer project on development of
several digital filtering, spectral analysis, and time series
analysis programs.  They vi11 be designed for application to
to ACHE realtime user problems and will be publicly available.
The availability of these programs will be an asset to the
system, as some of the techniques to be employed have not,
to our knowledge,  been attempted elserhere,


(25)

2.   Installation of Voice Drum

   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 Harduare and System Software
Sections.)

3.  Stroke Registry Programs

   The Stroke Registry Program began over two years ago,
sponsored by the California Regional Hedical 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 patieets,

   At this time, first year follouup data on surviving
patients is being collected.  A member of the staff will
develop programs for entry of follovup 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 implementation soon.

inistration to medical
g resources.  The administra-
ct would benefit greatly from

Center management, from general adm:
programs and management of computinl
tion of any externally funded projel
such a program.

COB the Stanford Linear                       A FORTRAR program, available fl
a to PL/AC!!lB.                         Accelerator Center, may be adaptablr

S.   Fast Sort for Text Data

written the well-knoun
an text data.  This program
3rt algorithms examined,
ritten for the Public Library.

    A member of the ACHE staff has
SHELL sort algorithm for operation (
vi.11 be reviewed, other published s(
and a generalized PL/ACtlB program WI



(26)

6.  Bibliographic Data Entry

   A number of our users have developed program6 for automation

of preprint and bibliographic files.  These vi11 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 tine-oriented medical records in order to
select the optimal file desiga, the data entry foraat, and
retrievable wocabulary for the near term usem.  Our goal will
be to provide the system tools and the systems or applications
programming that will yield generalized programs which can be
used by many different departments in the fledical Center, Ue
have found that impleaenting the system in the Oncology Depart-
ment required some changes froa the programs used for the
Immunology Clinic.  Ue have been impressed by physician
acceptance of the time-oriented medical record.   Please refer
to the user project descriptions for Drs. Pkies and Slilliaa
for additional explanation of the time-oriented medical record
concept.

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

a.

b.

C.

d.

Obtain as such information as possible concerning new
file systems to be supported by IB8 and other aanufac-
turers.  Review the Stanford SPIBBS spstea as to its
applicability.

Honitor carefully the problems encountered at Stanford
ia use of the time-oriented medical records.

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

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 vi11 be to provide a broad
base of information on file system technology and patient
data base systems that vi11 be used to guide Stanfordas
development and implementation of medical information systems,


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C.  Harduare Acusitions
     w---w--     -1a-1

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

1.   Terminals

    Several 2741 terminals will be released and funds will be
used to acquire tvo additional high speed hard copy terminals
and four CBT terminals.  Ye are especially interested in
terminals capable of operating at 1200 baud.  The choice vi11
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.   Hovever,  electrostatic devices place
a high demand on CPU and channel resources.   A further
review of available plotters vi11 be conducted before a decision
is reached.

3.  PDP- 11 Equipment

   An item is included for purchase of additional core memory
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 systen.  Purtherrore,  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 algorithm.


(28)

   The disk configuration is eight on one control unit, eight
ylus 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.

I-
3.   Riscellaneous

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

D.  Listen Softuare
         -w--Y-

   The specific suggestions for system softuate 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 income.

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 rguirenents one and four.  tiowever, they
dre also the prinarp tasks for achieving requirement three.

1.  System Stabilization and Cleanup

    The effort here vi11 concentrate on the elimination of
known inconsistencies and errors in the system.   Yherever
easily possible, attempts will be made to reduce the size of
the software.

2.   Dot unen ta tion

   A considerable docnseatation effort is planned,   The aims
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 softuare 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 PDP-11
system for support of the voice drum,
this year's grant),              DEC tape (purchased from
            and a printer/plotter.  Depending upon
the type of printer/plotter selected, we may be able to adapt
manufacturer-supplied software.

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

a.

b.

C.

d.

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

Add a few terminal control commands, such as SET UPPEB/
UPLOW and SHOW CASE for specifying upper and lover case
options.
or TTY),  Other commands determine the terminal type (ASA
     and suppress or allov transmission of the ACHE

light box characters.

For high-speed displays, incorporate modifications to
the LIST command so that output is suspended every I4
lines.  This allows the user to scan a page of lines and
use BREAK if he is interested in stopping at that point.

Implement page mode output for displays.   A full screen
of data is displayed directly from the user's in-core
array 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 problems in implemen-
tation of this capability are identical to those discussed
under 'Extended Logon'.


(30)

4.  Additional Satellite Hachine Support

   Satellite machine support will focus on tasks essential for
a smooth transition to SUIiEX and other long range programs
expected to succeed ACHE.  Ia addition, assistance vi11 be pro-
vided to small machine users wishing to connect to the neu 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 routfne 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 fro@ an AC&lB
terminal need not be run interactively.  Scheduling
these jobs for overnight batch frees both the terminal
and the CPU for additional on-line work.

   Recent hardware monitor tests indicate that the CPU
is busy for 90%-95X of available cycles during peak daytime
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.  Bowever,
sufficient core and cycles are available during evening
and overnight shifts to accommodate 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 ACfM-type files
   to OS files and the converse.  The design document on
  this feature has been completed.  Both direct access and
  tape data sets vi11 be supported.

b,  Incorporation of the HASP system into the OS supervisor.
  HASP facilities are preferred over conventional OS
  services for both better operational contlcol and for
  its smaller core and disk requirement.


(31)

C.  kevieu of the WYLBUB/EASP interface and its adaptation
  to the ACHE system, if possible.  Otherwise, the
  developaent of a capability to communicate uith the
   HASP in-core reader.

d.  Development of a small library of standard OS
  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/ACHE Object nodules

  The ability to save compiled code on a PL/ACHP program
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 statement 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 more
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-month study and design specification.
Actual isplenentation plans will be deferred until the level
of effort is known and until the choice of a computer system
is determined.

7.  Extended Logon

  As the ACClE system is currently configured, a user session
can be controlled only by a device routed through the Flenorex
1270.  Beferences 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 terminal,
  invoking programs, etc.

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


02)

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

d.  Page mode support for CRT's requires extension to the
  'one-line-at-a-tiue' node of operation.

   The precise technique for implementation has not been
determined.  However, a reorganization of high-level
system control functions is absolutely necessary,  Bxpansions
to the GET/PUT and READ/HRITB stateaents of PL/ACHB are a
possibly simple scheme for user commnications,

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

8.   Miscellaneous

  This category contains a number of small projects, none
of which may produce any signif icant increase in system usage,
but all of which provide gratifying additions to
the current level of service.  Compared to the level of
effort anticipated for implementation of other proposals in
this section, these projects require very minor * anpouer
expenditures.

a.  A method whereby a user may determine his aggregate
  monthly charges from his terminal (SHOU CHARGBS cormand).

b,  Extensions to the Text Editor to allow relocation or
  duplication of lines of text within a data set (HOVE/
  COPP commands).

c.  Addition of the UNPEOTECT command to corplement the
   PROTECT command.  This command is necessary if a
  user vishes 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 implementation is to provide
  an option wherein the user specifies the nuaber of
  disk blocks required at OPE# time.   The blocks
  are held in reserve for him (assuming they are
  available) until either they are consumed or the file
   is closed.


(33)

v.    AD~IIISTRATIBB OBCAPXZATIO1

   Stanford University has an Associate Provost for Computing anl
reports directly to the Provost and Academic vice President.   The
Provost for Computing and heads the operation of three major
facilities:  Campus facility, ACBE facility, and SLAC computing
racility.  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 uas that organizational
rather than functional lines seen to be the most appropriate in
the Stanford setting.  For six months ue had a single systems
group manager for all three facilities - SLAC, Campus, and
ACBE.  Soae benefits of the trial period were the creation of a
better reporting system, cross-fertilization of ideas. and much
more interaction among the systems programmers.   Some of the dis-
advantages were a longer communications chain, travel time between
facilities,  and some loss of control by facility directors.   The
operations managers of the three facilities mere also brought
together in one functional arm of the organieation.   Cross-
facility training among operations was partially completed.
Reporting schemes were unified,  and an exchange of ideas nas
accomplished.  Today, the functional organizations exist for
purposes of communication and coordination.   Pormal lines of
authority, houever, 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 ACBE payroll, their job func-
tion, and percent of full time equivalents are listed below:


(34)

CURRENT ACAE PERSONNEL

NAflE

Jamtgaard, R
Wiederhold, G
Rindfleisch, T.
Hundley, L.
Prey, R.
Granieri, C.
Len, Y,
Riller, S.
Briggs, R.
Stainton, R.
Bassett, H.
Crouse, L.
Whitner, J.
Aranda, H.
Baxter, E,
Class, C.
Cower, R.
Sutter, J.
Hatous, J.
Rieman, J.
Cannon, D.

XPTE

100         Director
20         Consultant
50       Systems Analyst
100        Systems Programmer
100        Systems Programmer
100        Systems Programreer
100        Systems Programmer
100        Systeas Programmer
20        Systems Programmer
100        Systems Programmer
100       Scientific Programmer
100       Scientific Programmer
100       Scientific Programmer
100        Secretary
100         Administrative Asst,
100       Operations Manager
100        Computer Operator
80        Computer Operator
100        Computer Operator
60       Computer Operator
50       Dispatcher

JOB TITLE

Total FTE

17.9


(35)

VI.  BUDGET

A.  Resource Expenditures

SUMMARY

Total Resource Expenditures

1.

2.


3.

4.


5.

6.


7.

a.

9.


10.


11.

Actual
Previous
Budget
Period

Personnel:

a.  Salaries & Wages
b.  Staff Benefits

Subtotal

239,329
32,851
272,180

Consultant Services             912

Equipment
a.  Main Resource-Rented
b.  Main Resource-Purchased

C.  Supporting Equipment
d.  Equipment Maintenance

Subtotal

384,542
40,848
1,951
6,145
433,486

Supplies                15,873

Travel                 3,047

Engineering Services         11,818

Publication Costs            3,031

Other

a.  Computer Services (l)
b.  Other

Subtotal

8,272
9,531
17,803

Subtotal -  Direct Costs       758,150

Indirect Costs           141,205

Total Costs              899,355

(1) Includes education courses
(2) Assumes $443,976 exempt equipment costs and user
  income of $360,000.

Current
Budget
Period

Estimated
Next
Budget
Period

248,690   277,162
37,505    44,231
286,195    321,393

1,000     1,000

389,458    390,596
54,479     50,000
1,260     1,260
14,500   18,805
459,697   460,661

9,200     9,700

4,000     4,000

30,000     31,500

2,000     2,500

3,100     7,900
10,100     11,200

13,200     19,100

805,292    849,854

76,600     21,771

881,892   871,625 (2)


(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 run 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
2) Electrostatic Printer/Plotter, or expansion
  of smsLL1 machine equipment pool

u.,600

22,000

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 CRT'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-11 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-11 will be
needed only if several additional user devices or services are inter-
faced through the PDP-11.  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.  Kxpenditure Details

DIRECT COSTS ONLY

1.   Personnel


     Director's Office

    Systems Analysis

    Systems Programmers

    Applications Programmers

     Research Assistants

    Operations

     Secretarial & Administrative

       Subtotal, Salaries


     Staff Benefits


         TOTAL PERSONNEL


2.   Consultant Services

August 1, 1971-   August 1, 1972-
July 31, 1972    July 31, 1973

32,929        23,582

4,633       10,600

94,306       97,960

39,042       63,470

9,852         7,150

52,430       58,680

15,498        15,720

248,690

37,505

277,162

44,231

2% ,195

1,000

321,393

1,000


09)

C.  Expenditure Details

DIRECT COSTS ONLY

3.  Equipment

    Major Equipment

1052
1403
2050
2314 #l
2314 #2
2361
2401
2403
2540
2701
2702
2821

Subtotal

August 1, 1971-   August 1, 1972-
July 31, 1972    July 31, 1973

Console Typewriter
Printer 600 LPM
Additionsl CPU (F)
Dir. Acess Storage
Dir. Acess Storage
Core Storage
Mag. Tape Unit
Mag.Tape Unit Control
Card Reader Punch
Data Adapter Unit
Transmission Control
Control Unit
Ampex DC 314
Ampex DC 314
Ampex ECM-50
Memorex 1270

Disk Packs (IBM 2316/3) (25)

Terminals (2741)      (11)

    IBM 1800 add. units

   1442
   1826
   1856
Subtotal, 1800

    Unit Record 029             1,192         1,259

TOTAL, RENTALS              382,718       380,373

635
8,397
92: E
19 h8
27,291
3,377
8,971
6,947
10,561
16,834
10,937
20,068
22,243
77,949
-mm--

  635
8,wi
101,817
  -w--m

-s--m

355,619

2,114

11,763

  --mm-
3,377
8,971
7,157
10,728
  --M-m
10,937
36,304
36,304
119,922
16,248
360,842

(25)   2,100

(4)   4,109

2,638        2,671
7,691        7,691
1,701         1,701

12,030       12,063


(40)

C.  Expenditure Details

DIRECT COSTS ONLY

Purchased Equipment

August 1, lg`i'l-   August 1, 1972-
July 31, 1972    July 31, 1973

RPQ's for Beehive Terminals       381

PDP-11 System            38,466
DEC Dual Tape System         8,700
1200 Baud Modems (2+
Power Supply)                750
Computer Terminals (2)        6,182
Four CRT Terminals
Electrostatic Printer/Plotter,
or expansion of small
machine equipment pool
8K of core for development
PDP-11
4K of core for production
PDP-11
Two 30 character per second
typewriter terminals
Acoustic couplers, modems, etc.

54,479

Data Set and Line Rentals

8,000

Maintenance (Under outside contract)14,500

12,600

22,000

5,700

3,300

5,000
1,400

50,000

a ,400

14,805

Total Equipment     405,218       403,578


(41)

C.  Expenditure Details

DIRECT COSTS ONLY

4.  Consumable Supplies
     Office
    Computer
  Subtotal, Consumable Supplies

August 1, 1971-   August 1, 1972-
July 31, 1972    July 31, 1973

3,700          3,700
5,500        6,000
9,200         9,700

5.   Travel
    Frey    -U. of Missouri Comp.
              8/G/71
    -h%&, New York 8/9-12
      -Automated Health Sys.,
         Wakefield, Mass., 8/13
     Nozeki   -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., l/19-
          1/21/72
   Wiederhold-Conference, S.F., l/19-21
   Wiederhold-Conference, Washington,
           D.C., l/28-29
     Grsnieri  -SHARE, S.F., 3/6-10
   Wiederhold-SHARE, S.F., 3/6-10
     Granieri  -IBM Class, S.F., b/12-14
     Class    -SJCC, Atlantic City &
          DEC, Boston 5/15-18

777
9

359

426

78
78

364
;t
33

525

All Other Travel          1,;57

  Subtotal, Travel              4,000

6.  Engineering Services             30,000

7.  Publication Costs                2,000

a.  Computer Services
    360/67                    2,500
    PDP-10 and Line Charges                 ----
    Staff Training                 600
  Subtotal, Computer Services         3,100

4,000

31,500

2,500

2,500
3,000
2,400
7,900


(42)

C.  Expenditure Details

DIRECT COSTS ONLY

9.  Other Expenditures
     Audio-Visual Presentation
     Books and Periodicals
    Postage and Freight
    Telephone
    Physical Plant
     Technical Services

Subtotal, Other

August 1, 1971-   August 1, 1972-
Lull 31, 1972    July 31, 1973

----
200
2,000
7,000
100
800

10,100

  700
  200
2,000
7,000
  300
1,000

11,200

GRAND TOTAL --    DIRECT COSTS   805,292       849,854


(43)

D.  Summary of Resource Funding

BUDGET PERIODS

Source of Funds

Computer Equipment - Service

Biotech. Resources Branch Support

  Amount of Current Award:
   Line (5) of Award Statement

Adjustment from Prior Periods:
1.  Line (4) of Current Award

2.  Balance of 270 x/y Proceeds

Total BR Support

TOTAL FUNDING

Actual
Previous
Budget
Period

170,596

675,747

76,459
~27,275'

724,931

895,527

Current
Budget
Period

270,000

573,755

27,275

5,292

606,322

876,322

Estimated
Next
Budget
Period

360,000

511,625

511,625

871,625


(44)

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(46)

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(47)

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 12-month period.  One such user is Dr. Stanley
Cohen whose Drug Interaction Program should be running on a dedicated
PDP-11 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
levels.  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)

f


          (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,
Joshua Lederberg, and Carl
Djerassi.
Dept. of Chemistry, Computer
Science,  and Genetics
Project Began 1970

       Project: DENDRAL
                Realtime
Chargeable use began May 1971

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) 3.n working with steroids, the program deals with much more com-
  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
  ions 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 1nference: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.
C.   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


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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-11.
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 chdins 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
Larry Hjelmeland
Walter Reynolds

Tom Rindfleisch
Robert Ross


Mark Stefik
Robert Stillman

LISP
DENDRAL
DENDRAL
DREAMS
DENDRAL
CHEM
DENDRAL
DENDRAL
DENDRAL
DREAMS

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


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REFERENCES

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

2.  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).

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

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

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

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

7a.  Applications of Artificial Intelligence for Chemical Inference. I. The
   Number of Possible Organic Compounds:  Acyclic Structures Containing C,
   H, 0 and N.

J. Am. Chem. Sot., 9l, 2973 (1969)
By J. Lederberg, G. L. Sutherland, B. G. Buchanan, E. A. Feigenbaum,
A. V. Robertson, A. M. Duffield and C, Djerassi.

7b.  Applications of Artificial Intelligence for Chemical Inference. II.
   Interpretation of Low Resolution Mas Spectra of Ketones
     J. Am. Chem. Sot., 9l, 2977 (1969)
      By A. M. Duffield, A.V. Robertson, C. Djerassi, B. G. Buchanan,
      G. L. Sutherland, E. A. Feigenbaum and J. Lederberg

7c.  Applications of ARtificial Intelligence for Chemical Inference. III. Al-
   iphatic Ethers Diagnosed by Their Low Resolution Mass Spectra and NMR
    Data.

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

7d.  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. Sot., 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

7e.  Applications of Artificial Intelligence for Chemical Inference. V. An
   Approach to the Computer Generation of Cyclic Structures.  Differentiation
  between all the Possible Isomeric Ketones of Composition C6H100*


7f








7g








711

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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. Sot.,

By D. H. Smith, B. G. Buchanan, R. S. Englemore, A. M. Duffield,
A. Yeo, E. A. Feigenbaum, J. Lederberg and C. Djerassi

7i.  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.

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

9.  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.

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

Investigator:  Stan Cohen
Dept. of Medicine, Div. of Clinical
  Pharmacology
Project Began October 1969

    Project:  SNCOHEN. DRUGALRT
               Non-Realtime
Chargeable Use Began December 1971

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.


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COLLABORATIVE Rl%ARCH PROJECTS

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

Project:  C-CONSTA. UROL
            Realtime

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
Dept. of Surgery, Div. of Cardiovascular
Surgery
Project Began November 1970

Project: _
        E DONG.  LAB
         Realtime

The primary purpose of the project was to study the principles of mammalian
heart rate control, with particular emphasis on the sino-atria1 node--the
controlled pacemaker which governs heart rate.  Since understanding the pace-
maker requires a mathematical description of its behavior, a concomitant
objective 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.


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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  eriod.  For
                 Ih__^- -= ---- 1        .-- -            LLQLCU LIE uepena nce or heart period (
                                        ii
In the intensity and relative timing of                   the stimulation.
the hypotheses that                                     The model supports 1

                                          (1)
zoncentration of the neurotransmitter                      after one stimulation, the c

ses in negligible time and then exponen-                   at the heart's pacemaker ris

msec half-life time--one-twentieth the                     tially decreases with a 400

: to relax to the autonomous rate; and                     total time for the pacemaker

!, 175 msec period prior to the end of                    (2)  except for an uncontrollable

: is continuously controlled.                          each heart cycle, heart rate


II: difference equation, describes the                A second model, a first-order nonlinea

!en the input and output pulse trains of             temporal sequence of time delays betwe

1 oscillators.  Necessary and sufficient              a class of injection-locked relaxation

liven for synchronization of input and              conditions on the nonlinear term are g

lental frequency.  The derived analyti-               output when they are of similar fundax

I to the analysis of heart rate data ob-             cal results are shown to be applicable

,uency, vagal nerve stimulations.                 served under repetitive, constant freq


are as follows:                           Other extensions to previous research


e above the autonomous rate which are                 (1) large increases in heart rat

gal nerve stimulation are reported;                      paradoxically produced by va

e of the transient relaxation of heart                 (2) quantitative analysis is mad
                                                   rate to the autonomous rate
following the cessation of stimulations;                  (3)  measurements are made of the
smallest observable time for a stimula-                        tion to affect heart rate an
d the dependence of this time on the
h;                                        unaffected heart cycle lengt

nsiveness to a stimulation is shown to                (4) the decrease in system respo:


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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 %CXE programmer has
developed additional graphics tools for this project.  Scatter plotting of
experimental parameters, and historical plotting of treatments are included.

Investigator:  Eugene Dong
Dept. of Surgery, Div. of Cardiovascular
Surgery
Project Began July 1970

Project:  E-DONG. PATIENT
             Realtime

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
Dept.  of Genetics
Project Began December 1968

Project:  VABACON. GAME
           Realtime

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


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Collaborative Research Project Descriptions (cont'd.1

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
Dept. of Medicine, Div. of Immunology
Project Began July 1969

Project:  J-FRIES. DATABANK
           Non-Realtime

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


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Collaborative Research Proiect 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
Dept. of Radiology, Div. of Diagnostic
Radiology
Project Began October 1969

Project: _
        J GOLD.  SWALLOW
             Realtime

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 0.5O C. ice water.
With the subject sitting, 2 small thermistors were inserted into the esopha-


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Collaborative Research Project Descriptions (cont'd.)

ws , one located in the distal l/3 and the other in the proximal l/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 injecte
and counts again recorded.  After serial determination, a final 2 mCi of fl 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 86Rb 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
Dept. of Medicine, Div. of Cardiology
Project Began 1968

Project:  DCHARRIS. CATH LAB
           RealTime

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.


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Collaborative Research Project Descriptions (cont'd.)

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

Project: _
        L KADIS.  VISAEP
             Realtime

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 ('IT" 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.


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Collaborative Researc,h Project Descriptions (cont'd.)

Investigators:  Larry William and
Saul Rosenberg
Dept. of Medicine, Div. of Oncology
Project Began 1972

Project: _
       S ROSENB.  MEDONCOL
            Non-Realtime

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 ?%SSMA. cl055937
Project Began November 1969               Realtimeand 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


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Collaborative Research Project Descriptions (cont'd.)

Investigator:  Gerald Reaven
Dept. of Medicine, Div. of Metabolic
Diseases and Endocrinology
Project Began January 1969

Projects:  G-REAVEN. PAT-DATA
       G-REAVEN. DISPLAY
             Non-Realtime

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

(1) We utilize ACXE'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 ACHE'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.


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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 Siti U/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
Dept. of Anesthesia
Project Began September 1969

Project:  G-SWANSO. THESIS
              Realtime

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 CO2-02 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 CO2 and O2
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 CO2-O2 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.


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SERVICE PROJECTS

Investigator:  Malcolm Bagshaw
Dept. of Radiology, Div. Radia-
tion Therapy
Project Began December 1968

Project: _
        M BAGSHA.  SUMMARY
           Non-Realtime

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

   (1)

(2)






(3)


(4)

of various methods of treatment,

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.
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.
Mathematical programs have been developed for use by the radiologic
physicists for calculations concerning beam characteristics, depth
dose tables, analysis of curves, etc.
Statistical programs are available to obtain Berkson-Gage or Kaplan-
Meier survival tables from data input by the user.

Investigator:  Walter Bodmer
Dept.  of Genetics
Project Began December 1968

Project: _
        W BODMER.  POPGEN
           Non-Realtime

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.


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Service Project Descriptions (cont'd.)

The analysis of 2 x 2 associations between serum reactions for the definition
of antigens in the HI-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 HZ-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 HI-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
Dept. of Chemistry
Project Began December 1970

Project:  E-BUNNEN. CHEM
            Realtime

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


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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
Dept.  of Pediatrics
Project Began December 1968

Project:  H CANN. GUAT
     Non-Realtime

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


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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
Dept.  of Genetics
Project Began March 1971

Projects:  L-CAVALL. PAVIA
      L-CAVALL. JUDY
       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.


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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
Dept. of Pharmacology
Project Began August 1970

Project:  A-GOLDST. OFFSTUFF
            Non-Realtime

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-


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Service Project Des,criptions (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-o-acetylmethadol, abbreviated as
LAN '  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 I&l) 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 mg
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
Dept. of Surgery, Div. of Ophthalmology
Project Began October 1971

Project:  S-GRANT. CORNEA
         Non-Realtime

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.-understanding 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.


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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
Dept.  of Biosciences
Project Began September 1971

Project: _
        P GREEN.  AVENA
            Realtime

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 l/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.


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Service Project DescriDtions (cont'd.)

Investigator:  Samuel Kountz
Univ. of California Medical Center, San
Francisco, Dept. of Surgery
Project Began December 1968

Project:  SLKOUNTZ. KIDNEY
          Non-Realtime

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
Dept. of Psychiatry
Project Began December 1968

Project:  PHLEIDER. PREMIE
          Non-Realtime

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


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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
Dept. of Chemistry
Project Began February 1971

Project: _
        H MCCONN.  ABSORB
              Realtime

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-


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Service Project Descriptions (cont'd.)

  line irregularities,
(b)  calculati.on of relative concentrations of paramagnetic species
  in the sample (value of the double integral),
cc>  normalization of different spectra to the same relative con-
   centrations,
Cd)  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
(f) long term storage of and ready access to spectra.

Research Projects Involving Computing Capability

(1)  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.

(2)

(3)

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 Nail
Dept. of Dermatology
Project Began April 1969

Project:  L-NALL. PSORIASI
          Non-Realtime

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. I&CON
Lab. -  Infectious Disease               J-PFTRAL. 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
Medical Student
Project Began November 1969

Project:  J CALVER. TEXT
      -Non-Realtime

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
Medical Student
Project Began June 1971

Project:  GAFUNK. RHINO
        Non-Realtime

The intent of this project is to stucy 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
Medical Student
Project Began December 1968

Project:  RLLEVINE. CPS
        Non-Realtime

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 computer
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
Medical Student
Project Began February 1972

Project:  C-MILLER. CAB
        Non-Realtime

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
Medical Student
Project Began January 1970

Project: _
       L NESTOR.  DIFFDX
          Non-Realtime

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
Medical Student
Project Began February 1971

Project:  MRNUWER. NEURON
          Non-Realtime

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
Medical Student
Project Began December 1968

Project:  W-ROSENT. RESEARCH
            Non-Realtime

This project investigates speech and language pathology and normal speech
perception, utilizing studies of language-deviant children.  ACME is used for


                         031)
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.  QttretinA Utiliaat&n Chm

   The terns used to discuss ACflE utilization involve charging
units and categories of users.

1.  Charging Units

Last year, the computer service charge units uere:

page minutes
terminal connect time
blocks of disk storage
terminal service charge

   In April,  1972, our rate structure was revised and charge
units for batch executiou, CPD ti6e slices, and tape mouats uere
added.  However. due to their recent incorporation in the rate
structure,  no data is included for them.

   A pageainute is defined as occupancy of 4096 bytes of
core for one minute.  Terminal connect time is the total
nauber of minutes that a terminal is connected to the spstex
in a logged-on condition.  A block of disk storage is a fired
length block of 2000 bytes of 2314-type disk storage.   The
termiaal service charge covers monthly terminal rent plus other
services offered by the ACHE staff,  This service charge is
handled by the University independent of the ACM% grant.

2.  User Categories

   This table shows the category identifier, rate, and
definition of each user category. The rate charged per pageminute
varies by user categories and some categories are subsidized
100% by the ACIE Grant.  An asterisk next to the category
identifier (+4) de6ignateS those so subsidized.  All other
categories are paying.  There is a distinction between real-
time and non-realtime users.  Realtixe users use the 1800
processor or 2701 data adapter for data collection or process
control functions.


(831

PAGE-FlIlUTE CHARGE TABLE

1.
2.
3.
*4.
*5.
*6.
47.
0.
9.
*10.
*11.
412.
*13.
16.

Cateyory

   ceats/pagerinute
Pre-April,72  Post-April,72

Realtime User - sponsored Research         .50
Non-Realtime User - Sponsored Research    1.00
Ron-Stanford Hedical                    2.00
Medical Students                        1.00
Realtime User  - Core Research             *50
Non-Realtine User - Core Research         1.00
ACME Staff                             1.00
Hospital Data Processing                1.25
Non-Medical -  Stanford and Ron-Stanford   2.50
Realtime - Pilot and Pending Proposal       -50
Non-Realtime - Pilot and Pending Proposal   1.00
Realtime -  Extended Non-Funded             .50
Non-Realtime -  Extended Ron-Funded         1.00
Negotiated Rates  - Combination of Core      -25
Research and nedical Administration

1.00
1.70
2.50
2.00
2.00
2.00
2.00
1.70
2.00
2,co
2.00
2.00
2.00
1.20

*No cash charges, i.e., absorbed by the ACHE project budget.

   The four graphs in Section C show utilization 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 ACRE utilization by Department.   Section D
summarizes computer resource usage by charge category and primary
investigator.

B.   Patterns of Use
     -----------

   During fiscal year 1972,  a noticeable shift has occurred
from a preponderance of program development to execution.
Approximately two years ago, it vas normal to find 509 of
logged-on users in execution with another 50%
performiny data entry functions or program development.   One
year ago, approximately 2/3 of those logged-on to the system
vere foUAd to be in execution during normal daytime hours,
Hare recently it appears that 75% of the users logged-on
to the system are in prograa 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 nov more or less routine or operates
in a "production" mode.  Auch of this so-called production-
type work is used to support research in the Hedical Center.
tixamples of this are the realtime data collection from spectro-
meters and the data collection phase of the Drug interaction
Yrogram,


(84)

   During the past year, approximately 75%-851 of the available
disk storage for users has been used.  Frequently we baoe run
out of space on individual packs during the normal operating
hours.   This has caused considerable inconoenience to all
users, especially those who attempt to create very large files.
lext month a number of data compression roqtiaes vi11 be made
available to all users.  These routines uill permit a con-
siderable reduction in the amount of space used for individual
files.  Ye expect that our users uill quickly adopt these
techniques to reduce their disk storage charges.


\"dJ
INCOME

- - - -Computer  Servic

Total Income  Incl.  Terminal Service

b
ir

TOTAL

Ampex
Core
Added
6%

TERMINAL SERVICE INCOM


                  0
   - NW/ /

   ecrease     COMPLTER SERVICE INCO



Feb 70  May   A'4     Nov    Feb     Mi
Mar ( Jun    Sw     Dee    Mar     Jurf
Apr     Jul    Ott     Jan 71   Apr     Jul

-el
MZ

3     Dee

Jan 72 Apr

PAGEMINUTES

Total --- - Chargeable *Total Excl. Staff & Pharmacy

3,000,








2,000,

`,000,000

`,000,000

,,ooo,ooo

3
r

000 k

\
"c,




.\
    \

000,. ) c \
    e

Rate
Decrease
c-

--        \ / /
                          /

                   0 \
          ----  /
-- -+                          Ampex
                                     Core
                                    Added
                                                  I--

`cl tp L        b     F  3Y      `cl
               r cI  n       `P
:t    Jan 71   APr     Jul     Ott

1,000,

Apr     Jul


(86)
BLOCK STORAGE

--

- Cha
TT

  0'
/









9

;`O ,000





go,oiis





60,COC






30,000

.
0

AmpCC
COI-e
Added

1 .









`as

--

Feb70
Mar     J un
Av     JUI

19
Itp

1"
1C    Mar
n 72 Apr

71

TERMINALHOURS

- Total

---- Chi

tble

/

1'
//

4UpX
:0I-I?
ldded

,000






,000






,000







,000

\









.C-

\








. .

.
.

xr
r

0
0

.
-.

4
w
ct I

71

3
r

`Y
n
I

I"
C
n 72


(87)

6
.


8   8888 8 8 8
r-i   l-i N-i Pi #-i r-: l-i ri




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(93)


(94)

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(96)

*



(98)






(102)


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(104)

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(105)


(106)

1
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.
F2




(109)


   (110'
' I 1


    (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 Carbamoyl
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
Carbamoyl 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
Chromatbgraphy 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 CHEF?. (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, 3. 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., E.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,"
(abstract).          CLINICAL RESEARCH, Vol. 19, p. 501, 1971

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

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
Schizophrenia,"
1972).     NEUROSCIENCES RESEARCH PROGRAM BULLETIN, in press (spring

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,
Instrumentation in Urology Research,"   "Computer Monitoring and Control
                      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 M.R. MacLaury, "Radioresr-!rometry Studies of the
Effects of L-dopa and iqK486 Therapy -- A Mode.1 Application of Carbon
Isotopes to the in vivo Evaluation of Interrnedi.3ry 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),"
1972).          abstract submitted to GASTROENTEROLOGY (spring

Glaze, H.J., Jr., and E. 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 Ana; '.,A by Laser Microprobe - Emission
Spectroscopy," RECENT ADVANCES I;; QUANTITATIVE HISTO- AND CYTOCHEMISTRY,
pp. 192-193, 1971.

Gold, 3. A., G.S. Harrell, B.R. Bradley, and F.F. Zboralske, "Sequential
Esophageal Blood Flow Determination," submitted `:o 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 Children 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
Phosphatidyl 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 Hearinq 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 NS07514, National Institute of
Neurological Diseases and Stroke, April 1972.

Sachs, D.P. and D.M. Rubin, "Mass Media and the Environment," Volumes I,
II, 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,"
(spring 1972).   JOURNAL OF PERSONALTIY AND SOCIA,L PSYCHOLOGY, in press

Skolnick, M.R., A. Moroni, and L.L. Cavalli-Sforza, "The Population
Structure of the Parma Valley, Italy," IV IFIT. 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,"
(spring 1972).     JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, in press

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 Technjcal  Uotes
     -s-m---      ---

AAC- 1    ACME User Accounting -- Update 8 Listing (Rassett/
         c.  Riller) AUG 13, 1971

AAD-      APUB -- Update & Listing (Plasch/C. fliller)
       AUG 13, 1971

AC&- 1    Summary of Caepus/ACdE Berger Study (Jaatgaard)
       uov 30, 1971

ADDA-   Additions to AC!lB Software Suggested by Users
       (Jantgaard) APE 20, 1972

AFORT-   Iapl'eaenting a Time-Shared/Realtime System in
       FORTRAW (Frey) APB 23, 1971

AG- 1

Usage of the ACflE Systen (Yiederhold)
To be published in Statistik an Dokunentation in der
Cledicine,  IOV 15, 1971

BORG-1    ACME Organization Chart (Baxter)
       HAR 6, 1972

APAGE-   ACRB Service Rates (Jartgaard)
       APB 16, 1972

APAGBX- 1  Description of ACM Service Rates (Jartgaard)
       APB 13, 1972

ARATB-1   Revised Rate Structure for ACflE Facility Services
      (Submitted to IJIB) (3amtgaard) APP 16, 1972

BASS-1   An Assessaent of Current Developments in Corputer
      Technology and their Significance for Development
      at the Stanford fledical Center (Yiederhold)
       MAX 1, 1972

BDEN-1    Beyond LISP (Wiederhold) HAR 29, 1972

t+ER- 1    ACnE Program Library PLA-PL1:  Converting
      a PL/ACBE Program into an Bquiraleat PL/l Program
       [Berman) JUR 16, 1971

BGOLD-1   Programs for Processing of Temperature Data in
      SCLERODERBA (J. Gold/Piederbold) DEC 30, 1971


(118)

nSPD-1



CONS-2



CRASH-1



CSMP-1



CSMPI-1

CTY- 1



DEC-1

DP-1

DSLL-1



ED@1

EEW- 1



tiFFT-1



EC,- 1



KIHP-1



EOPS- 1




r;PP-2

Sharing Patient Data Files (Wiederhold)
MAR 29, 1972

Consulting Schedule (Wiederhold)
FEB 2, lY72

Recovery from Cisk Failures (Frey)
SEP 24, 1971

Design Considerations for a Digital Analog Simulator
on ACHE (Hjelmeland) OCT IS, 197.1

Interactive Continuous System Elodelling Program
'(il.  Hu) APE 16, 1972

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

Decimal Arithmetic in ACME (Wiederhold)
FEa 14, 1972

Proposal for Decimal Arithmetic in ACHE (Yiederbold)
FEB 14, 1972

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

ACME Program Library DATACOPY: Reproducing a
Complete or Partial Data File (wiederbold)
NOV 15, 1971

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

ACHE Subprograms PPT and FPTD: Fast Fourier
Transforms (Whitner) HAA? 10, 1972

ACHE Subprogram GRAPHH: Creates Display and Platter
Output (Hale) n&n L2, 1971

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

Versatile Plotting System (Elale)
JUN 15, 1971

ACHE Subprogram PLOTPRIN:  Plots Graphs and Prints an
Line Priater or Terminal (J, Hu)
FBB 16, 1972


(119)

PPKR-2

FBI'!-1

PSEC- 1

PSTAT-1

PUTIL-1

HAC- 1

HBE-1

NBS- 1

HEPR-1

HHOG-I

HLP-1

HPWR-1

HSCI-1

HWEA-1

333

Restoring Blocks Onto Disk From Tape (Leu)
PBB 29, 1972

Pile Utility Restore and Wove Program (Prey)
Jbl 12, 1972

File Security (G. Wiederhold)
FEB 25, 1971

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

File System Utility Library (Prey)
JUN 9, 1971

Loea Linda Terainal/ACtlB 1800 Link (l4atheson)
BUN057 OCT 11, 1971

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

BiosciencejACHR 1800 Digital-Analog Link (I_, Ru)
EON046 SEP 1, 1971

Varian EPB Recorder to IBfl 1800 Interface
(!I. Hu/Uatheson) JUL 20, 1971

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

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

A Proposed Method of Protecting Computing I!Iachinery
from Pouer Surges (Bandley)
JAI 31, 1972

Scan Converter Interface (Stutbs)
JUN 18, 1971

Summary of Western Electric (Telephone Co8pang)
Analog Bodeas (Stainton)
JAB 17, 1972

User Note: ACHE Keywords,Conversion Program
PLA-PLl,Truth Tests in ACti&,
Computer Room dodifications (Staff)
BAY 25, 1971


(120)

534

JJ5

536

537

J38

J39

340

541

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

User Note: Special Announcement, Hardware
Substitutions, Bulk Core, Bisk Crives,
Small Machine Interrace (Jdmtgaard)
OCT 22, 1971

User Note: Nev Bulk Core and Cisks, PLCTPBIN, Loea
Linda Graphics, Nev Commands in PL/ACflE [Staff)
NOV 5, 1971

User Note: Performance Tests cn New Bulk Core, New
Text Editing Features, CATACOFY, EVENT,
User Tape Services, New Character String Function,
New Information on LOGOEF (Staff)
NCV 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 Ccmputer
Facility Planning Committee,
Printing and Punching Services, Double Precision
Argument Bug,  New Show Command:  SHOW CSOPEN (Staff)
PEB 7, 1972

User note: Revised Operating HOUIS, Medical
Computing Seminars, PL/l versus PL/ACME
Compatibility, Small Machine Multiplexor Interface,
System Errors 226 and 237(Pile System), Program
CATALOG PUBLIC,  Fast Fourier Transforms,
Antilogs (Staff) FEB 28, 1972

User Note: Revised Bates for ACME Service, Neu
Terminal Support (Memorex), Redical Computing Seminars,
Reassignment of Gio Wiederhold, Nev ACME Note Index,
New LISTAKER/JOBTAKER Feature, Bug:  Character string
Variable and Title Option, Card and Paper recgling,
Acknovledginq ACME in Publications (Staff)
APR 10, 1972

KBEE-1   Using the Beehive Terminals on ACME (Wiederhold)
       NOV 30, 1971


(121)

KOH-1

KPERH-2

KTB-1

KTBA-1

Ll!l-5



PBPF-1



PLC-2

PLCH-1

PPA-1



PPLO-1



PSCS-1



RSY-1



UEI- 1

UEVT-1



ULA- 1

Coaannication Development (Uiederhold)
JILlI 4, 1972

PERflXT18 Function - User Permit on 1800 (Graaieri)
DBC 13, 1971

Character Translations for Teletype and Beehive
Terasiaals (Wiederhold)
FEE 14, 1972

Changes to TTY Translation Tables (Stainton)
HAY 17, 1972

Edit Commands (Berman)
MOV 18, 1971

Proposal to Aid in Bore Efficient Usage of Disk
(Wiederhold) DBC 30, 1971

Compatibility Beqairerents for PL/ACfiB Programs to
Use IBH@s PL/l (Uiederhold/Prey)
UAR 8, 1972

A Choice of Language to Support Uedical Research
(Yiederhold)
Position paper for a panel discussion on "Computer
Language for medicine, m to be held at the 1972
ACM Conference, Boston l_AR 6, 1972

ACHE/LISP Internal Documentation (Baas)
JOL 14, 1971

Proposal:  Interactive Programs for Pile Bditiaq and
Data Plotting (Eleyl) APB 20, 1972

Proposal for Small Computer Service Bp ACBE
(Stainton) DAR 21, 1972

Proposal to Allow Release of Symbol-Table pages in
Production Jobs (Uiederhold) DOV 23, 1971

ACHE Bealtiae Library Program IROU: Smoothing by
IBOling with an Exponential Decreasing Uiadou
(Wiederhold) DBC 13, 1971

Realtime EVENT Function (Pre?)
MOV 4, 1971

ACME Real Time Program Library ALTBC: Data Reduction
for a Sequence of Samples (Uiederhold}
MOV 23, 1971


(122)

ULC-1    ACME Redltirae Library CUADBO: Smoothing Using a
      Square Window (Wiederhold) PEE! 17, 1972

UPDP-I   PDP-11 Hcinging the 360 Channel (Briggs)
       MAR 1, 1972

IJCTR-1   ACHE System Core Timing Results (AMPEX vs. IBH)
       (Frey) NOV 29, 1971

liDERM- 1   Terminal In and Output for 3270 Displays
       (Wiederhold) DEC 30, 1971

WPDP-1   Disk Monitor for the PDP-11 (briygs)
       JUN 21, 1971

MPDPA-1   Index for PDP-11 Software Binder in the CornFuter
      Room (Briggs) AUG 9, 1971

YPDPB-1   Using the Litton Printer On ACRE Through the PDP-11
      (Briggs) AUG 13, 1971

WPDPC-1   Disk Monitor Utility Program for the PDP-11 (Briggs)
       AUG 16, 1971

wsvc-1    ACHE Written SVCs (Frey)
       SEP 1, 1971

YPL-1    Inferred Syntax and Semantics of PL/S
       (Wiederhold/Ehrnan) OCT 15, 1971

YDEBE-1    MVTDEBE - OS/360 Multi-Purpose Utility (Frey)
       DEC 7, 1971

XM-1     Plow Chart for ACflE System Prcgram flODIFY (Berman)
       JAN 10, 1972

ZPICK-2   PICK Flowchart and Tables (Berman)
      JAN 10, 1972

LYL-1    Flow of Light Logic in PIELD (Wiederhold)
       DEC 15, 1971


(123)

APPENDIX A

Summary of Campus/ACME Merger Study


          A\clM-:l
  Ron <I nmt,il;anr!!
November 30, 19'9

The  st,utly 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
s Comments on cost comparisons.

There follows a summary of considerations in these five areas.

360/67 Capacity:

  In July a test was conducted to determine whether the 360/67 timesharing
monitor called ORVYI, could handle its current load plus ACME's current load
plus the anticipated load associated with the new information retrieval system
called SPIRXS.  The test indicated that the 360/67 had adequate cycles and
perf'ormance capability to handle the anticipated SPIRES load plus a substantial
ACME load based on current ACMF usage levels.  The 360/67 has considerable
unused capacity today.  The test of ORVYL capacity demonstrated that a
considerably heavjer load could be handled with acceptable degradation and
response -times to the user.  The test did tax the capability of the system with
-rcspcr*t 1.0 its paging system on the drums; but this was fully expected.   The
ACFII~I port ion 01' the test appeared to consume approximately 2'1 per cent of the
~ji)i)/ijj C.yc.1 C2.  '7%~ simillal,ion of the ACME load consisted of a series of
P'ORTRAN rout-i nc':: which woul (i require cycl es corresponding to approx~imately I', llser::
itI c~xc~c:~~l.io~~ orI Llle i%\lrrcnt .ACMl~I hardware ($O/!jO w-ith ii mec;ab,ytes of' 8 micro-
k:cc-otIcI 1,1r I I< f73rc) .

   `r'tle c:ampus P'acility 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 production batch partition.  Rates for use of the system
have been designed to 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. and1:OO a.m.
except for br-icf periods of system staff time from 5 to 8 p.m. three days per
weel-:, plus some system time on weekends.


025)

ACM-l
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 that 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/l 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 ccanputing 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
expensivo 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) ACM? users would have to translate their programs to the form of
interactive I'],/1 mounted on the Campus Facility.  Hopefully the conversion cost
can be m.iriimized 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 42ql 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 clepenrlent on output speeds) provided roughly equal costs at Campus and ACME.
These cost statements assume that ACME is charged at 2-l/24 per pageminute plus
.$i.'i"j per terminal hour on the old 8 microsecond bulk core.  The Campus rates
w('rr the ::t:rnli:lrd $10 pr'r CPU minute on ORVYL, plus $3.50 per terminal hour.
Ont> fnc-tor which is difficult to evalu:\te is the extent to which the CPU plus
tc>-r-m i.n:t L :ic'oc:::: at Campus. rc.flcctz the total cost of the *job. Averaging all
ll::('r c~ll:rryr`:: f'r)r fY::c;tl yc-:~r lV(l :k khc CarnTu:: F:lcility, a total. of 68$ wa:: de-
T'i vcb11 Tr0l11 Clll Il:::~f~y~ :rnll tt??Tlini11 :tf:cv::::.  'ribi:: rn('an:: th:lt, another $I,$ of th, in-
~'Olll(' w:1:: ~I(\r*-ivcarI fYan di;:l< :;torafl;c, printing, card punching, card reading, off'-
I inr plott;i.ng,  and use of the WYLWR text editg?r.  The point is that 32s of the
in(:orrle 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 ccver 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 teiephone lines on the Campus Facility versus $225 per month
on ACME for a private 2741 terminal.  The disk storage rate at ACME is 14 per
track per day versus Campus Facility rate recently announced of 24 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 l/2+ per pageminute rate permitted; the effect of
the new core will vary by types of use.
70"                     Cycle intensive users will use 50"' to
  of the pageminute usage encountered with the slower bulk core.  Data input
via terminal:: and program development will require about the same number of
p:lr;ctninutc:: on the new core.


(127)

ACM-l
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.  I/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)

APPENJlIX B

ACME System Core Timing Results
     (AMPEXVS. IBM)


(129)

Introduction:

A set of pro,n;ramS were collected for the purpose of measuring .the effect
on the ACME system of substituting AMPT1:X 2.5 microsecond core for IBM's
8 microsecond Large Capacity Storage.

Fssentially, these programs were selected to answer three questions:

1.  Whether the AMPEX core boxes do indeed have a 3.5 microsecond
  cycle time.

'2
I.  The performance improvement on a hopefully representative set of
  PL/AC!MF programs.

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

maximum possible

transmiss

        WCTR-1
   R[=gina Frey
November 29, lq71

("onlpa~~ative Core Timiy,s:

At1 0:: batch program was written in assembler language which measured the
t.rue cycle times of t;le IBM 2050 'fast' core, the IBM 2361 LCS, and the

   ,/
AMPi',X COYC boxes.  'The time required in each cage to perform a series of
fixeti 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 poirit 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
STore instructions.  Each ST requires 2 core cycles for completion.   Thus
if the core cycle is 2 PS, then each ST will require 4 ps,   ten million of
them req]Jire 4 x10 x106 p.s or &O seconds.


   Core
\
Operation

Fixed
point
STore

Fixed
point
arithmetic

Short
floating
arithmetic

Long
floating
arithmetic

(130)

Table 1.  Core Timing Results (Seconds)

WCTR-1
Page 2

  IBM                      IBM         AMPEX    2050
  2050         AMPEX
-(Fast Core)               2361      2361      AMPEX
        (Bulk Core)   (Bulk Core)        0     (F)

40.29      50.46      161.65     31      80

111.10

121.ll

220.17      55      91

118.14     128.15      214.36     60      92

287.16      302.19      440.25     69      95

Notes on Table 1:

1.  The AMPEX times are


2.  All figures include
  fetch/conversion of

the averages of two runs.

overhead time for instruction loop control and
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:  10 x lG* ST instructions.
  b) Fixed point arithmetic:  2 x lo6 sequences of L, M, A, S, D.
  c)  Short floating arithmetic:  2 x 10" sequences of LE, ME, AE, SE, DE.
  d) Long floating arithmetic:  2 x lo6 sequences of LD, MD, AD, SD, DD.

5. No index register was used in any of the instructions.


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WCTR- 1
Pa@' 5

:;cvcrl Pi,/ACbiI; pro;;rams were run with the .iBI? ::$l core <and the AMPF:)!
c:oru.  All of ihese programs were written by the ACME staff.


XL1 y'U.IlS  were executed in single user mode.
11/l+ and 11/U, was used.             Module TEN& written on
                   i'he 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

IBM time

CM1

lispi.est

l'l,A I'i,I
   -





I'T,OT 1

randi'ilc

and AMPEX time over the original IBM time.

Attributes

PDP-II assembler .  No t,erminal output.   Moderate disk file
T/O.  Hrtavy string operations.

Matrix mllltiplier.  No I/O operations, no strings.  Totally
compute-bound.

Disk file read and write sequential operations.   'Cime was
measured for reading and writing 100 records of one block
each.  'i'he loop was repeated 10 times each run.  1.ittl.e
computation.  IJo terminal output.

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
Cl.OCk.

'i'V p1.r)IA.i ~i:r prcbiram.  No file or !,errflinaIL activit,y.  1,i phi,
mathematical c,alculations.  Heavily dependent upon the speed
of the display,

Random disk file operations.  Light computations; no termi-nal
output.  The program consists of three sequences:   Write
direct of 20 records with randomly assigned keys, each record
1200 words long; Read sequentially each of the randordy
written records; Read randomly the "0 records 5 times for a
total of 100 reads.


     Core
\
      Perform

Program     \



CONVERSE

IBM
2361

AMPEX

5.7 min.

3.2 min.

CM1          6.1 min.           2.5 min.

lisptest

4.75 min.

3.0 min.

PLA PLl
   -

PLOT1

23.8 min.         17.4 min.

4.9 min.

4.0 min.

iotime:
100 reads
100 writes

13.2 set           9.5 set         28.0
19.8 set          14.4 set          27.3

randfile:
20 write direc
20 read seq.
100 read direct

23.0 set          15.8 set          31.3
71.7 set          34.2 set          52.3
49.1 set           29.1 set         40.7

032)

Table 2.  PL/ACME Program Timing Results

WCTR-1
Page 4

Performance
Improvement('%)

Average   36.5

46.9

59.0

36.8

24.8

18.1


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The rattler unexpected gains in the execution speeds of  'iotime' and
' rant1 f i 1-e'  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
regardin{: the nature of the ACME file system.

Unfortunately,  ' iotime' was executed only once with the IBM 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.

' iol;ime' was executed )C times with the AMPEX core.  The time req-uired
for 100 reads varied from 7.2 seconds to 14.7 seconds.  For 100 writes,
tile variance was from 13 seconds to 17.4 seconds.

`I'hcsc broach range:; 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
avera;:e seek time should not be 60 ms, but 25 ms (time to seek to next
con-C i {:ilOUS cylinder).  Total I/O time for an average read is 25 ms plus
l'i.5 ms disk rotation time or 37.5 ms.   For a write operation, an
add~it,ional complete rotational period of 25 ms must be added for an
avera::e time of 62.5 ms.

Slibtracting these figures from the average times for a single read or
write,  we {:et these software overhead values:

write

198           144
- 6;:. 5
1.35.5 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.  411 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


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WCTR-1
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file 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 (EIGHTN$$$RWl8&$,YIELD) were already located
in the 2.0 ps 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/set) will crash the 1800.

2.  N=7 and TIME=1 (7000 points/set) will cause data overruns.
3.  N=12 and TIME=2 (6000 points/set) 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/set 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=lZ and TIME=Z, 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/set) will not result in overruns.

2.  N=7 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
EIGHTN$$ could execute properly in 2.5 fls core.  About six months ago,
EIGHTN@ was moved from the 8 ps core to 2 ps core when it was discovered
that the channel commands contained within EIGHTN@ could not be decoded


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WCTR-1
Page 7

t'asl, enough and channel data chainin{: checks occurred.   This  condition
prevni~.ecl nnly -If the buffer size was extremely small.

A spcvial link edit ofk' TEN1 placed l~:l!;HTN$@ in 2.5 1~s core. Tests on
illi:: module i:ave i,hese results:

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

.1
L. .  A buffer size of two points or greater will execute properly.

IIowever,it is not recommended that EIGHTNJd@ be moved out of our fast core.
AMPEX performance at its best is still 80% of the maximum on a Model 50.
Moving EIGHTN/i$! would decrease our maximum possible transmission rate
(has not been tested).

::ummary:

It ha:-: been confirmed that the AMPEX core does run with a 2.5 microsecond
yfclc time.  Fixed point opcrationc execute 2 to 1 times faster; floating
point operations roughly 1 l/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 I/O dependent programs will see lit-
tle increase in execution speed.  Compute-bound programs may execute as
much as 2 l/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
111 or 6` -amputation is possible within each time slice, totpi execution time
for 3 program will decrease.  A s:mple of PL/ACME programs executes from
li3 to 60d fa-ter
         /* .I     .  The average was jh.5$.

Whi. I (' some improvement is realized for disk file operations, thv gain may
bc unnoticed due to the yield to the commutator (other users) at the start
of each I/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 360 communications program
had already been located in 2 microsecond core.

Dist:  Prog/All/D. Phillips/C. Dickens


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APPEEDIX C

Results of Three Compaction Algorithms

  The test uas performed during a Pile System Analyzer run
on all user data sets, February 28, 1972.

CODIRGS USED BY EACB COBPEESSIOR ALGORITHR TO BUXLT BITSTRING*

WORD  IS  ZERO
WORD  IS  UYDBPIPED
WORD  HAS  VALUE
WORD IS REPEAT OF LAST HORD

COWPACI COBPACZ   COBPAC3
  00       00
  01       01
    1       10        0
          11        1

TOTAL NON-RUXERIC WORDS = 16,532,183

TOTAL EHPTX (zero) WORDS = 5,184,105

  The resultant savings frora the application of each algorithm
is stated below.  Percentage figures were coaputed as the total
storage requirement after application of the algorithm over
the cur rent storage requirement.  TOTAL UORDS URElY LESS refers
to the inclusion of a file only uhen its *compactwIg size is
less than the original size.

TOTAL WORDS IN ALL ACI5E HUHERIC DATA PILES   7.783.794

TOTAL WORDS USING COBPACl ON ALL PILES     4,395,400 ( 56%)
TOTAL WORDS USING CORPACI ONLY flEElO LESS    4,314,484 ( 55%)

TOTAL WORDS USING COMPAC2 ON ALL PILBS     3,661,950 ( 47%)
TOTAL WORDS USING COBPAC2 ORLY UHBR LESS    3,612,031 ( 46%)

TOTAL WORDS USING CORPAC3 ON ALL PILES     3,818,520 ( 49X)
TOTAL WORDS USING COHPAC3 ORLX UBBR LESS    3,783,314 ( 481)

*The bitstring describes the characteristics of the values in a
numric array.  It is stored on disk along with sufficient data
to reconstruct the array.  Repeated,  undefined,  or zero data is
omitted f ram storage.


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U38)

APPENDIX E

Proposal for Small Computer Service by ACME


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AcPm Note

Proposal for ,Sm,~ll Computer Service bv ACME

       PSCS-1
Bob Stainton
March 21, 19'12

The rapid ciecline in the price of mini-computers has led to an incre:lse
in the number of tl!esil 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 - 29 hours a 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
R. Write data (or processing modules) to the spool for later
   use by the mini-computer

C. Read and write directly to the mini-computer

3.  All services of an ACME typewriter terminal.

4.  High level language processors.

,;pooling Service

::pooling (Simultaneous Peripheral Operation) refers to a procedure which
lla:: become popular with large-scale third generation computers.   It is
exemplified by :1 card reader whit:? is always ready to accept cards, even
though these cards may not be processeG by a user program until sever:11
hour:; have passeri.

Our early t>xperience with -741 terminals has shown that their usefulness
takc:`s :j quantum <jump as soon as a computer system is installed which is
continuou::ly av::ilable to "answer the telephone".

Our proposal is to provic!e a computer s:ystem which is always (20 hours a
d:ly) available to take r3:;ta from the user's mini-computer.   Our defini-
tion of mini-computer is any device which is able to conform to the re-
cluirements of the communications protocol.  The data will be hP1d on a
special clisk 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 fiata
generate<1 by that experiment.

Another service of the spooling system is the ability to provide storage
for "processing modules" which can be called by the mini-computer.   The
rel,ltionship bc,twe~n the mini-computer and the ACME system in this in-
st:!nce can best be described by an analysis of the classic "pen tracking
problem".


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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 forstorage 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 in&e 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 ACMEuser wouldbeable 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 realtime interactive service which has
been available in the past.


041)

PSCS-1
Page ',

A:: a (:onv~~ni~~ric~*, it i.:: rca!~izeil that, the "teletype" console of a mini-
i~oi!~i~utcr :;houl~G b(> :tblc to act as if it were an ACME! tr>rminal, so that
tllc u:cr neel! not use n separate "1741 terminal in order to use the ACMJS
::y stem.  The user would also be able to "log-on" and run programs auto-
rriatic:!lly, untler 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.

Im~~~emcntntion woulil require several loosely related projects:

1. .  'nlc~ ;:pooling sy;;tem, housed in a separate mini-computer so that
  it can operate (luring maintenance hours for the large central
  computer.

2.  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 alloh) any mini-computer in the system to communicate
  with any other mini in the system.

5.  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,
  clemand-response interface to the mini-computer, which appears
  to its program as. n device similar to a tape drive.

)I .  IliglkLevel proce:::: or:; to provide an easy way of writing progrc-?;ns
  for the mini-computer.

!!ist:  Staff/All