101
NATIONAL SCIENCE FOUNDATION Dr. John McCarthy Stanford University Stanford, California Dear Dr. McCarthy: WASHINGTON 25, D.C. Oc tober 14, 1965 We ,{Quid appreciate it if you wou ld assist us in the evaluation of the enclosed proposals. Your brief, critical comments on the scientific merits of the proposed projects will be of much value to us in arriving at a decision regarding their support. Your comments, of course , will be treated as confidential. The propo sals and duplicate comment sheets may be retained for your file. The present demands upon our funds and the evolution of the s coring system within our Program have made the numer ical rating scale printed at the bottom of our comment sheet obso lete, Proposals receivin g an average ratin g of 3 "acceptable" are, in fact, usually not supported, our consultants usually use a score of 2.5 to indicate a recommendati on for support at a low prior ity and 2.0 to indicate a good, sound supportable proposal. Some of our consultants li ke to distinguish the better and outstanding proposals by using scores of 1.5 or 1. 0. It would be greatly appreciated if you would return your eValuation to us by October 29. I wish to thank you in advance for your cooperation in this matter, Enclosures Sincerely yours, Herman VI . Lewis Program Director for Genetic Biology

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Page 1: NATIONAL SCIENCE FOUNDATION - Stacksth919jh6519/sc... · 2013. 6. 14. · Oc tober 14, 1965 We ,{Quid appreciate it if you would assist us in the evaluation of the enclosed proposals

NATIONAL SCIENCE FOUNDATION

Dr. John McCarthy Stanford University Stanford, California

Dear Dr. McCarthy:

WASHINGTON 25, D.C.

Oc tober 14, 1965

We ,{Quid appreciate it if you would assist us in the evaluation of the enclosed proposals.

Your brief, critical comments on the scientific merits of the proposed projects will be of much value to us in arriving at a decision regarding their support. Your comments, of course , will be treated as confidential. The proposals and duplicate comment sheets may be retained for your file.

The present demands upon our funds and the evolution of the scoring system within our Program have made the numer ical rating scale printed at the bottom of our comment sheet obsolete, Proposals receiving an average rating of 3 "acceptable" are, in fact, usually not supported, our consultants usually use a score of 2.5 to indicate a recommendat i on for support at a low prior ity and 2.0 to indicate a good, sound supportable proposal. Some of our consultants like to distinguish the better and outstanding proposals by using scores of 1.5 or 1.0 .

It would be greatly appreciated if you would return your eValuation to us by October 29.

I wish to thank you in advance for your cooperation in this matter,

Enclosures

Sincerely yours,

Herman VI. Lewis Program Director for Genetic Biology

Page 2: NATIONAL SCIENCE FOUNDATION - Stacksth919jh6519/sc... · 2013. 6. 14. · Oc tober 14, 1965 We ,{Quid appreciate it if you would assist us in the evaluation of the enclosed proposals

B6 0362 R

Research Proposal

THE FEASIBILITY OF AUTOMATIC MICROSCOPE SCANNING USING REALISTIC INPUTS TO A COMPUTER SIMULATED PERCEPTRON SYSTEM

617-542-5600

Prepared for

National Science Foundation Washington, D. C. 20550

Prepared by

Dr. Peter W. Neurath, Co-Principal Investigator

Kurt Enslein, Co-Principal Investigator

NEW ENGLAND MEDICAL CENTER HOSPITALS Systems/Computer Applications Department

171 Harrison Avenue Boston, Massachusetts 02111

Augusc 16. 1.91D

Page 3: NATIONAL SCIENCE FOUNDATION - Stacksth919jh6519/sc... · 2013. 6. 14. · Oc tober 14, 1965 We ,{Quid appreciate it if you would assist us in the evaluation of the enclosed proposals

.. ~,~ ., . '. : .. , ~

... i

Page 4: NATIONAL SCIENCE FOUNDATION - Stacksth919jh6519/sc... · 2013. 6. 14. · Oc tober 14, 1965 We ,{Quid appreciate it if you would assist us in the evaluation of the enclosed proposals

1.

2.

DESIRED STARTING DATE

It is desired to start this research as soon as possible. In order to allow the customary time for proposal review, the requested starting date is December 1, 1965.

TIME PERIOD

Because this application is for a feasibility study, an initial time period of support for l~ years from December 1, 1965 to May 31, 1967 is requested. If the results are sufficiently prOmising, a proposal may be submitted to build a hardware working system at the end of this feasibility study. Such a proposal ~'7ould be separate and distinct from this work.

3. ABSTRACT OF PROPOSED RESEARCH

It is proposed to study the feasibility of scanning and identifying microscope slides automatically, using human chromosome metaphase spreads as objects to be identified. The most critical conceptual aspect of the problem is the one to be investigated, namely the feasibility of ~ecognizing interesting areas on microscope slides automatically by a method capable of rapid operation in its developed for.m.

The need for rapid methods of examining optical, pictorial data of 411 kinds to find their significant content is urgent in many fields. Automated chromosome analysis is one specific example. Considerable effort is being expended on the automation of counting and analysis - particularly of the chromosomes of each located, good, metaphase cell. However, it is generally as time-consuming to locate worthwhile cells on a slide as it is to analyze them once they are found.

Because of advances in data acquisition methods and in computer pattern recognition we believe we now have sufficiently powerful methods to approach this problem, and that these methods are now at a stage where their actual usefulness can be tested.

It is therefore proposed to train a computer simulated perceptron to distinguish areas encompassing suitable spreads from areas devoid of such. The optical information will be fed into the computer as digitized data from a system such as the one developed and used to analyze single chromosome spreads by Dr. Neurath. The objective will be to find out how feasible this process is, how efficiently it works, and how much it costs, in t~e and money. This information may well pOint the uay to the construction of an automatic slide scanner.

4. DESCRIPTION OF PROPOSED RESEARCH

A. Background

The use of computers for pattern recognition problems is a new and growing field. Although successful applications to date have been few. future extensions appear unlimited. A particular class of patterns

Page 5: NATIONAL SCIENCE FOUNDATION - Stacksth919jh6519/sc... · 2013. 6. 14. · Oc tober 14, 1965 We ,{Quid appreciate it if you would assist us in the evaluation of the enclosed proposals

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Page 2

for recognition are optical ones. One often looks for a particular item or kind of item in one or many photographs. Aerial or satellite surveying are examples of this. Although the human observer is very good and efficient in recognizing particular classes of visual objects, the process may, by the sheer magnitude of the tasks, be t~e-consuming and boring. It may be easy and interesting to look for a hurricane cloud formation among 1000 pictures once, but to look for them on X thousand pictures every day of the year is a different problem.

This sort of problem has become particularly urgent in the matter of chromosome analysis. It would be desirable to analyze the chromosomes of many sections of the population or in fact to analyze everyone's chromosomes at least once. Perhaps one would even like to analyze the chromosomes of people involved with well-knot~ hazards, such as workers exposed to ionizing radiations at regular intervals. For this purpose, several groups in the country, including one of the co-investigators (P. W. Neurath) have been working on pattern recognition programs to computerize toe analysis. A review of the activities in this field was given recently by the participants of the "Yale Conference on Machine Analysis of Chromosomesll

• Most of this information is not yet published. We are including a preprint of our contribution* to this subject which contains the available references as well as an example of chromosome spread pictures. In addition, it describes a data acquisition system similar to one we would use to digitize pictorial information.

From our experience, and from the results reported at this and other meetings, it is clear that the analysis of the selected picture is only part of the problem, and that at least as much time is ordinarily con­sumed in finding under the microscope spreads worth looking at under higher power. On a good average slide, there may be 5 analyzable spreads, and perhaps 10 more which only look good at first glance. To find, therefore, as few as 50 good spreads per person, which is the average number needed for an analYSis, requires a major scanning effort of slides. If a width of 200 microns is scanned at one time with negligible overlap, a 2:5 cm section of a microscope slide will require 125 complete traverses, each containing about 100 complete viewing areas. The 5 spreads per slide are therefore distributed among more than 10,000 possible areas per slide, requiring the operator to look at perhaps 100,000 such distinct areas to pick out all SO good spreads. If the coordinates of the good spreads were known checking them visually would take very little time particularly if a machine to set the coordinates were available. Extensions of this idea to automatic photography of the areas of pro­spective interest are possible but will not be discussed here. We are only aware of one group doing similar work: Dr. K. Preston at Perkin­Elmer, who originally started in conjunction with Dr. M. L. Ingram at the University of Rochester, and more recently is working with Dr. N. Wald at the University of Pittsburgh. Their concept is based on a spatial frequency analyzer using a laser source of coherent light.

It is our opinion that the discriminatory power of such a device to pick out the proper object is very limited while a perceptron, on the other hand, has much higher capabilities.

* "Human Chromosome Analysis by Computer" (to be published in Annals, New York Academy of Sciences). Note that only copies 1 & 2 are com­plete with pictures; copies 3-20 only have the text.

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B.

Page 3

We also feel that we are in a position to check our concept experimentally. Peter W. Neurath et aI, as shol~ in the attached paper titled "Human Chromosome Analysis by Computer," had experience in the· development and use of a method of digitizing optical images for com­puter proce~sing ·which is relatively simple and inexpensive and produces a magnetic tape having the required information whicb can then be processed anywhere, at any time. This has been part of an effort sponsored by the Atomic Energy Commission, Division of Biology and Medicine, which is expected to continue. Similar equipment is becoming available on a commercial rental basis; an example is the Programmed Film Reader of Info~: ation Internatibn41, Inc. in Cambridge, Massachusetts. We propose to uee th method which is most economical at the time the work needs to be done. The budgetary costs are based on current quotations, but this is such a rapidly changing field that something better might become available at the same cost or less within six months. However, at the moment, for the purpose of this discussion, we will assume the use of either the Avco or the I. I., Inc. system, either one of which will give us the required input.

K. Enslein, on the other hand, under a Public Health Service Grant fram NIH, has developed a set of perceptron based pattern recognition programs where the computer and its program replace the actual physical perceptron system. This has the advantage of enabling one to test the ability of a quite generalized and large perceptron to solve a given problem. The attached two expanded abstracts entitled "A Comprebensive Computer Program for Biomedical Pattern Recognition - I. Preprocessing System," and " .. - II. Pattern Recognition System," describe the programs developed by Kurt Enslein as ~ell as perceptrons generally, and give pertinent references.

Proposed Effort

We propose to train a computer simulated perceptron to recognize areas containing good spreads as distinguished from areas containiag . poorer spreads. The pictorial information of an area approximately 100~x 100~in size will be digitized using, for instance, seven grey levels at a resolution based on a raster of 128 x 128 points. This digital data will' form the tnput to the perceptron program; the only additional information will be whether" it contains a reasonably good metaphase spread or not. After a training cycle consisting of interesting and uninteresting areas the perceptron will be tried on a s~ilar number of test patterns not used during the training phase. It is estimated that a total of 30,000 to 100,000 picture presentations will be required.

To obtain a sufficient number of different digitized pictures, con­taining or not containing good metaphase spreads, we propose to use the following schemes. A wide variety of 400 areas containing a good meta­phase spread in one quadrant of the picture (e.g. in the upper left quadrant) will actually be selected and photographed and then will be digitized. We would do this on the Information International, Inc. Fibn Reader, if available, at a resolution of 256 x 256 points and with 7 shades of grey. This gives us four times 400, or 1600 quadrants, each a picture with 128 x 128 points all digitized and on magnetic tape. Four-hundred of

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5.

Page 4

these 1600 contain good metaphase spreads, 1200 do not. Each of these pictures will be given successive small rotations and translations to generate additional similar pictures which the perceptron can use as new inputs. These computer-generated additional digitized "pictures" are far more economical to obtain, by more than an order of magnitude, than the originally digitized data, while still expected to adequately serve the purpose. One reason for this is that one part of the training of the perceptron is to have it recognize good spreads regardless of rotations and translations.

Translations will be accomplished by moving each digitized element of a spread from one area in the core of the computer to a new area, with the proper X and Y offsets, which will remain constant for the entire frame. Rotations of 900 and multiples of 900will be accomplished by transposition and/or "flipping". Rotations by smaller increments will be accomplished by means of an algorithm which computes new element addresses as a function of the desired angle of rotation, the distance of the element in question from the center, and the angular location of the non-rotated element with respect to a reference. It is envisioned that these translations and rotations can be accomplished at fairly high speed in view of the fact that the entire operation will take place within the core storage of the computer with a non-rotated pattern being read into core memory only once, and the output consisting of the trans­lated and rotated patterns on magnetic tape.

If the system can be trained to discr~inate the desired objects efficiently, it would eventually be possible to build a device incorpo­rating the results arrived at by the computer program. Such a perceptron device could work rapidly and "on line" in making the decisions and is envisaged to operate in conjunction with an automatic programmed slide scanner. Automatic focusing might be required at that point, but methods for doing this are available (Dr. G. MOss at Harnwell, England has one such device now). However, the point of the presently proposed work is not to build hardware but to investigate, by computer simulation, the feasibility of the concept.

Although we propose to do this study using human metaphase chromo­some spreads as objects to be recognized, the work clearly has wider applications. The reason for our choice is tl-1o-fold: First, the need for progress on this particular problem, with which Dr. Neurath is par­ticularly concerned, and second, our opinion that suitable metaphase spreads can be distinguished fairly easily with relatively few grey levels and would therefore make the task manageable.

FACILITIES AND SPECIAL ARRANGEMENTS

Dr. Neurath has developed the scanning system at AVCO-RAD, Wilmington, Massachusetts. At the New England Medical Center Hospitals he will continue to use either this or a similar system at Information International, Inc., in Cambridge, Massachusetts, on an hourly rental basis for his work on the proposed program and related areas such as the Neutrophil Area Measurements he is working on with Dr. Sophia Bamford of the New England Medical Center Hospitals. At the New England Medical Center Hospitals there is a fully equipped, active cytogenetic laboratory, under the direction of Dr. Bamford, working on human chromosome problems. Suitable pictures will be obtained in

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6.

Page 5

this laboratory.

The New England Medical Center Hospitals complex is the major training and research institution of Tufts University School of Medicine. Office and laboratory space to perform the contract is available.

Kurt Enslein is located in Rochester, New York, and is not affiliated with any institution on a full-time permanent basis. He is particularly qualified to work on this project, having prepared the perceptron computer programs as an individual investigator under NIH sponsorship. To facilitate the administration of this contract it is proposed that the New England Medical Center Hospitals will employ Kurt Enslein specifically for this project as a Research Associate at a fixed annual rate with a fixed additional amount for secretarial help as shown as a separate item in the budget. Other costs incurred by htm, such as travel, will be handled by New England Medical Center Hospitals in conformance with the proposed budget. K. Enslein will share full responsibility with Dr. P. W. Neurath as co-investigator for the technical direction and performance of the program. In this way maxtmum effectiveness is assured in what is essentially an interdisciplinary problem.

The computer programs are ~~itten in Fortran-63 for the CDC 1604-A and are directly useable on the CDC 3600, the machine that is contemplated for this work. This particular computer is most desitable in this application because the machines available from CDC Data Centers have approx~tely 65 k word core memories, the size essential for a perceptron simulation of this magnitude. New England Medical Center Hospitals bas an IBM 360/30 on order for delivery in May 1966, and some work could possibly be done in-house after that date.

SCIENTIFIC PERSONNEL

A. Principal Co-Investigators

1. Peter W. Neurath, D. Sc., Chief Biophysiciet, New England Medical Center Hospitals, 25%

2. Kurt Enslein, Research ASSOCiate, New England Medical Center Hospitals, (as explained in 5 above), 20%

B. Faculty Associates

1. Medical Advisory Board

Dr. Bertram Selverstone, Chairman Dr. Herbert J. Levine Dr. Douglas J. Marchant Dr. Edward F. Rabe

2. Sophia Bamford, M. D.

C. Research Associates

1. David H. Brand, Director, Systems/Computer Applications Department, New England Medical Center Hospitals

Curricula vita of these key project personnel are included in the Appendix.

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7.

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Page 6

OTHER PERSONNEL

Part time assistance of a laboratory technician to take the metaphase spread pictures and of a secretary are required.

OTHER FINANCIAL ASSISTANCE

The personnel on this contract will be working on other research projects some of 't"hich may be supported by other agencies such as NIH. However, this time will be strictly accounted for according to institutional practice and will not be used to increase the regular salaries of the personnel involved. One of the cO-investigators, P. W. Neurath, has two proposals pending with the Atomic Energy Commission, Division of Biology and Medicine; one is con­cerned with chromosome analysis, as referred to previously, and the other is on biomagnetism. Work on the first would supplement the objectives of this program although directed towards a different phase of the overall chromosome problem. The other co-investigator, K. Enslein, will be working on other perception applications under a current grant and a proposed supplement (NIH grant GM-l20lS-02: "General Purpose Pattern Recognition Program").

BUDGET

Dec. 1, 1965 to Estimated Total Nov. 30, 1966 to May 31. 1967

a. Salaries

Co-Principal Ivesotigator, P. tol. $ 4,245 $ 6,368 Neurath°, Chief Biophysicist, ° New England Me4ical Center Hospitals, 25% °tfme for 12 months at $1415 per month

Co-Principal Investigator, K. 5,000 7,500 Enslein, 42 East Ave., Roches-ter, Ne'(~ York, to be employed by New England Medical Center Hospitals specifically for this project at a flat rate of $5000 per year, to work 20% time

Laboratory Assistant, 50% time 3,000 4,500 for 12 months

Secretary, 25% time for 12 1,125 1,688 months

Reimbursement for K. Enslein 1,200 1,800 secretary (flat amount)

Social Security(4.125% of $8,838.75) 365 518

Total Salaries $14,935 $22,404

b. Supplies

67 reels of computer tape at $45 per $ 2,700 $ 4,000 reel; photographic supplies

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~

~

c.

d.

e.

f.

Travel

Travel for principal investigators to attend scientific meetings and to meet in Rochester and/o~ Boston

Publication Costs: Preparation, page charges and reprints

Other Direct Costs

Communica t ions: Mostly long distance telephone calls, reference books, etc.

Computer Rentals: i. Information International,

Inc., Programmed Film Reader or equivalent, 400 frames

Dec. 1, 1965 to Nov. 30, 1966

$ 2,000

250

200

4,800

ii. CDC 1604-A, $200/hour, 30 hours 4,000 iii. CDC 3600, $425/hour, 15 hours 4,250

Total Direct Costs $33,135

Indirect Costs, 22.4% of total direct 7,422 expenses (U.S.Army Auditor Agency, Trapello Road, l~altham, Nassachusetts, for October 1, 1963 to September 30, 1964)

Total Project Cost $40,557

10. AMOUNT REQUESTED:

Page 7

Estimated Total to May 31, 1967

$ 3,000

250

300

4,800

6,000 6,375

$47,129

10,556

$57,685

The amount requested for the first 12 month period is $40,557.

There are no other sponsors of this project. The institution is sharing the costs of this program since not all of the proposed personnel time is funded by outside projects.

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11.

Page 8

AUTHENTICATION

This proposal is approved for distribution to the National Science Foundation.

P. W. Neurath Principal Co-Investigator

K. Enslein Principal Co-Investigator

D. H. Brand Director, Systems/Computer Applications

R. T. Viguers Administrator

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APPENDIX

A. Curricula Vita of Key Project Personnel

B.

Peter W. Neurath, Co-Investigator Kurt Enslein, Co-Investigator Sophia Bamford, M. D. David H. Brand, Mathematical Analysis/Programming Bertram Selverstone, Chairman, Medical Advisory Board Herbert J. Levine, Medical Advisory Board Douglas J. Marchant, Medical Advisory Board Edward F. Rabe, Medi~al Advisory Board

"A Comprehensive Computer Program for Biomedical Pattern Recognition I. Preprocessing System'

"A Comprehensive Computer Program for Biomedical Pattern Recognition II. Pattern Recognition System'~

"Human Chromosome Analysis by Computer - An Optical Pattern Recognition Problem"

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]'):..!!'.:):.;:;; :'o",':.d -,:;~i ~ i~jf~~~P':'!~ • '" :{~)j::,rl

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CURRICULUM VITAE

~: PETER W. NEURATH, D. Se.

PLACE OF BIRTH: Vienna, Austria

DATE OF BIRTH: August 19, 1923

EDUCATIONAL BACKGROUND:

Institution & Background

University of Toronto, Toronto, Canada

University of Toronto, Toronto, Canada

Carnegie Institute of Technology, Pittsburgh, Pennsylvania

PROFESSIONAL SOCIETIES:

American Physical Society AAAS IEEE RESA Biophysical Society New York Academy of Science

Major Field

Eng. Physics

Physics

Physics

ACADEMIC AND PROFESSIONAL APPOINTMENTS:

Degree ~

B.A.Sc. 1946

M.A. 1947

D.Se. 1950

Chief Biophysicist, New England Medical Center Hospitals, September 1965 to present

Senior Consulting Scientist, Medical Science Depar~ent, AVCO Research and Development Division, 1962-65

Principal Staff Scientist, Materials Research Department, AVCO Research and Development Division, 1959-62

Staff SCientist, Transformer Laboratories, General Electric Co., 1950-59 Westinghouse Fellow, Carnegie Institute of Technology, 1949-50

BIBLIOGRAPHY:

Neurath, P. W., "Creep of Lead at Various Temperatures, II ~ Technical ~ No. 2322, March 1951.

Neurath, P. W., and Koehler, J. S., lithe Plastic Deformation of Pure Single Crystals of Lead and Copper," J. A. P., Volume 22, pp. 62-626, May 1951.

Neurath, P. W., and Waite, R. E., "Elastic and Plastic Strains and Watt Losses in Grain-Oriented 3 Pct Si-Fe," Journal 2!. Metals, Volume 480, March 1955.

Neurath J P. W., "Magnetostriction and Domain Structure of Materials for Use in Low Noise Equipment," Electrical Engineering, November 1954.

Neurath, P. W., "Effect of Plastic and Elastic Stresses on the Losses and the Domain Configurations of Grain-Oriented 3 Pct Si-Fe," Journal of Metals, Volume 1319, October 1956. --

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PETER H. NEURATH, D. Sc. Page 2

Neurath, P. H., "Hhy Present Evaluation Methods for High-Quality ~Iagnetic Strip Materials are Inadequate," AlEE, Conference Proceedings of the 1956 Boston Magnetism Conference.----

Graham, C. D., and Neurath, P. H., "Domain Hall Orientations in Silicon-Iron Crystals," J. A. P., Volume 28, pp. 888-91, August 1957.

Neuroth, P. W., "Study of the So-Called 'Anomalous Losses' in 3 Pct Si-Fe Grain Oriented Strip Material, " Bulletin £f American Physics Society, II Volume 4, p. 109, 1959 (Abstract).

Neurath, P. W., "Hysteresis and Eddy Losses in Silicon Iron as a Function of Sheet Thickness," J. A. P., Volume 30, p. aas, 1959.

Neurath, p. W., "Simple Recording Torque Magnetometer, " J. A. p., Volume 31, p. l84S, 1960.

Neurath, P. W., and Gibbs, T. W., "Arc Cathode Emission Mechanisms at High Currents and Pressure," J. A. P., Volume 34, p. 284, 1963.

Neurath, P. W., "Magnetic Annealing and Directional Ordering," J. A. p., Volume 34, p. 1315, 1963.

Lesensky, L., and Neurath, p. W., "NbZr Superconducting Critical Current Dependence on dI/dt," J. A. P., Volume 34, p. 710, 1963.

Neurath, P. W., and Berliner, M. D., "Theoretical and Experimental Criteria for Biomagnetic Phenomena," Bulletin, American Physical Society, Volume 9, p. 162, February 1964 (Abstract).

Neurath, p. W., Berliner, M. D., Hovnanian, H. P., and LaRochelle, M. F., "The Growth of Fungi Exposed to Static Magnetic Fields," 2nd Inter­national Biomagnetic Symposium, Chicago, Illinois, November 1963 (Proceedings Ahstract).

Falek, A., and Neurath, P. W., "Quicker Chromosome Analysis," Lancet(ii), No. 7320, p. 1277, December 14, 1963.

Neurath, P. W., "Magnetically Produced Translations and Rotations of Red Blood Cells," Bulletin of ~ American Physical Society, Volume 9, p. 681, 1964 (Abstract).

Neurath, P. W., "The Magnetic Translation and Rotation of Fluid Suspensions of Particles Representative to Cells," Biochemical ~ Biophysical Research Communications, Volume 15, p. 536, 1964.

Berliner, M. D., and Neurath, P. 1~., "Effects of Static Magnetic Fields on Basic Microbiological Processes," Aerospace Medicine , Volume 35, p. 259, 1964 (Proceedings Abstract).

Falek, Arthur, Neurath, p. H., and Warms, T., "AnalysiS of Chromosomes by Computer," Mammalian Chromosomes, Volume 15, p. 101, 1965.

Neurath, P. W., at'.c\ Berliner, M. D., "Biological Rhythms," Science, Volume 146, p. 643, 1964.

Berliner, M. D., and Neurath, P. W., "The Band Forming Rhythm of Neurospora Mutants," J. C. & C. Physiology, Volume 65, p. 183, 1965.

Neurath, p. W., and Berliner, M. D., "Biological Rhythm of Fungi," Biophysical Society Abstracts, p. 147, 1965.

Neurath, p. W., "Simple Theoretical Models for Magnetic Interactions with Biological Units," Chapter 2, Biological Effects of Magnetic Fields, Plenum Press, 1965.

Neurath, P. W., and Berliner, M. D., "The Role of Periodic Oscillations in Biophysics," Bulletin of the American Physical Society, II, Volume 10, p. 634, 1965. - -

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PETER W. NEURATH, D. Sc. Page 3

Berliner, M. D., and Neurath, P. tv., "Control of Rhythmic Gro~'1th of a Neurospora Clock Mutant by Sugars," Journal .2! Bacteri.ology, 1965.

Neurath, P. H., Falek, A. Serbagi, R., and Warms, T., "Study of Human Chromosome Analysis By Computer,1f (Scheduled for Annals, New York Academy of Science, 1965).

Berliner, M. D., l\Eurath, P. W., aDd Yankovich, B. M., "The Rhythms of Ascobolus 'Clock' Mutants," Abstract scheduled for Am. J. Bot., 1965.

Neurath, P. tol., and Falek, Arthur, "Optical Pattern Recognition by Com­puter," American Physics Society Bulletin, (Abstract in print).

Berliner, Martha D., and Neurath, P. W., "Use of Lexan Petri Type Long Dishes," Neurospora Newsletter, Volume 7, March 1965.

Berliner, Hartha D., and Neurath, P. W., liThe Rhythms of Three Clock Mutants of Ascobolus Immersus, II lvIycologia, 1965 (in print).

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CURRICULUM VITAE

~: KURT ENSLEIN

DATE OF BIRTH: December 21, 1924

EDUCATIONAL BACKGROUND:

Institution & Location Major Field

Lycee Janson de Sai11y, France Elect. Eng.

PROFESSIONAL AND HONOR SOCIETIES:

American Men of Science, 1961 Leaders in American Science, 1962 Sigma Xi, Rochester Chapter New York Academy of Sciences IEEE (Senior Member) AAAS ACM

ACADEMIC AND PROFESSIONAL APPOINTMENTS:

Consulting Engineer, January 1963 to present

Degree

B.E.E. 1940

Chairman, Rochester Conferences on Data Acquisition and Processing in Biology and Medicine, 1961-1964

Vice President and Director of Research, Brooks Research, Inc., 1957-1962 Conference Organizer, Symposium on Low-Level Solid State Amplification,

National Electronics Conference, 1961 Consulting Engineer, 1953-1957 Senior Electrical Engineer, Physics Department, University of Rochester,

1951-1957 Instructor of graduate courses in Electronic Circuit Analysis and Computer

Electronics, University of Rochester, 1952-1956 Senior Electrical Engineer, Stromberg-Carlson Company, Rochester, New York,

1948-1951 Project Engineer, Belmont Radio Corporation, Chicago, Illinois, 1946-1948

BIBLIOGRAPHY:

"A Coaxial Cable Driver with Gain," Review 2£. Scientific Instruments, Volume 23, No. 11, pp. 644-645, November 1952.

itA Minimal Noise Preamplifier for Proportional Counters and Similar Applications," Review II Scientific Instruments, Volume 24, No. 10, pp. 916 ff, October 1953.

"Distributed Amplifier for Nuclear Research," ElectroniCS, Volume 27, No.7, pp. 138-141, July 1954.

"The Type 6218 Beam Deflection Tube as a Complex Pulse Generator,1t Review of Scientific Instruments, Volume 25, No.4, pp. 355-58, April 1954.

itA 75 Kw. Magnetic Amplifier, II Proceedings 2! ~ Special Technical Conference 2Q Magnetic Amplifiers, April 1956.

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r ~f..-):t2. ,~.)(:~: 1',' .i ~:'.; '.:-:.)"'.: !'~t.! c. !!1~:·nj·;·-!l(J9l1 ~.#;1 '!-;,:!.~~J .. : ".~ ~tfi_;~~i!.j:i .L 1·:::~.i"J.:::::':., i:~ -:t,."'.:.::::::Z \ ·i: :~:.i ... t ;~'. (: .. r

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KURT ENSLE IN Page 2

"An Amplitude-Stabilized Bridged-T Oscillator," ~ Communication ~ Electronics, Volume 77, No. 35, pp. 75-9, March 1958.

"Silicon-Junction Diodes as Reference DeVices," IRE Transactions on Instrumentation, Volume 1-6, No.2, pp. 105-1a:-June 1957. --

itA Time Scaler for Nuclear Track Width Measurements," Electronic Engineering, Volume 29, pp. 277-81, June 1957.

itA Remotely Controlled Variable Delay Line," Review of Scientific Instruments, Volume 28, No.2, p. 144, March 1957.

"Crossbar Switch Applications," Electrical Manufacturing, Volume 61, No.4, pp. 86-95, p. 139, April 1958.

"High-Speed LOlo1-Level Scanner," IRE Transactions on Instrumentation, Volume 1-8, No.1, pp. 3-7, M~h 1959. --

"Automatic Circuit Analyzer Programs Its Own Test," Electrical Manufacturing, Volume 64, No.5, pp. 106-13, November 1959.

"An Instrumentation Type Crossbar Switch," Proceedings .2! ~ National Electronics Conference, Volume XIV, pp. 565-84, October 1958.

"Study of the Feasibility of a Ferrite Modulation System for an PM Cyclotron," 1M Transactions 2!! Nuclear Science, Volume NS-6, No.1, pp. 14-25, March 1959.

"Two Economical Circuits for High Speed Checking of Contact Closures," ~ Transactions ~ Instrumentation, Volume 1-8, No.2, pp. 51-55, September 1959.

"Magnetic Amplifiers as Magnet Supplies," ~ Special Publication, No. T12l, pp. 245-253.

Colber, D. ~1., and Enslein, Kurt, "A Magnetic Drum Average Response Computer," Digest 21 ~ !2§l International Conference ~ Medical Electronics, p.25.

"Some Approaches to Pattern Recognition," Proceedings 2f!h!. 1961 Rochester Conference 2S ~ Acquisition ~ Processing !a Biology !D£ Medicine, Pergamon Press, New York.

Enslein, K., Editor, Proceedings 2i~!2§l Conference 2n ~ Acquisition ~ Processing in Biology !S& Medicine, Pergamon Press, New York.

"Digital and Analog Computation Considerations for Biomedical Problems," Proceedings 2! ~~ Rochester Conference ~ ~ Acquisition and Processing in Biology ~ Medicine, Pergamon Press, New York.

Enslein, K., Editor, Proceedings.2!~ ~ Rochester Conference ~~ Acquisition !B& ProceSSing in Biology ~ MediCine, Pergamon Press, New York.

"Applications of a Method of Pattern Recognition to Biomedical Problems," ~ Annual Conference 2S Engineering !n Medicine !B& Biology, November 1962.

"A Method of Pattern Recognition and its Application to Medical Problems," Communicator, Volume 2, Section 8, pp. 18-22, September 1962.

"Analog-to-Digital Conversion of Biomedical Data," paper presented at ~ !221 Winter Meeting, January 1963.

Enslein, K., Editor, Proceedings 2i ~!221 Rochester Conference ~~ Acquisition !U Biology ~ Medicine, Pergamon Press, New York.

Enslein, K., Editor, Proceedings 2f~~ Rochester Conference ~~ Acquisition in Biology ~ Medicine, Pergamon Press, New York.

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CURRICULUM VITAE

~: SOPHIA B. BAl-1FORD

PlACE OF BIRTH: Tigna 11, Georgia

DATE OF BIRTH: January 7, 1913

EDUCATIONAL BACKGROUND:

Institution & Location Halor Field

University of Georgia, Athens, Botany-Zoo. Georgia

University of Georgia, Athens, Botany-Zoo. Georgia

Tufts University School of Medicine Medicine, Boston, Massachu-sette

PROFESSIONAL SOCIETIES:

American Society of Cytology Massachusetts Medical Society American Medical Association American Medical Women's Association American Academy for the Advancement of Science Society of Sigma Xi

ACADEMIC AND PROFESSIONAL APPOINTNENTS:

Degree X!!!.

B.S. 1932

M.S. 1933

M.D. 1961

Cytologist, Cytogeneticist, New England Medical Center Hospitals, 1961 to present

Assistant Professor, Obstetrics-Gyneco1ogy(Cyto1ogy), Tufts University School of Medicine, 1963 to present

Consultant Cytologist, St. Margaret's Hospital, Dorchester, Massachusetts, 1961 to present

Consultant Cytogeneticist, St. Margaret's Hospital, Dorchester. Massachusetts, 1965 to present

Cytologist, New England Center Hospital, 1953-61 Instructor, Obstetrics-Gynecology (Cytology), Tufts University School of

Medicine, 1961-63 Assistant, Obstetrics-Gynecology (Cytology), Tufts University School of

Medicine, 1958-61 Cytologist, Medical College Georgia, 1947-52

BIBLIOGRAPHY:

Nieburgs, H. E., and Bamford, S., "The Routine Use of Exfoliative Cytologic Examinations for the Detection of Asymptomatic Cancer of the Cervix Uteri," J. M. A. Ga., July 1950.

}{asdon, S. C., Clarke, B. G., Bamford, S., and Fishman, W. H., "Correlation of Prostatic Exfoliative Cytology with 'Prostatic' Acid Phosphatase and Clinical Findings," Transactions, 1. S. C. C., Volume 2, pp. 102-07, 1954.

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SOPHIA BAMFORD Page 2

!{asdon, S. C., and Bamford, S., "Exfoliative Cytology as a Primary Diagnosis of Carcinoma in Situ of Cervix," Transactions, I. S. C. C., November 1958.

Kasdon, S. C., and Bamford, S., "The Specific Cytology of the In Situ Car­cinoma Cell," Transactions, I. S. C. C., November 1959.

Clarke, B. G., and Bamford, S., "Hydrocele: Studies of Biochemical and Histologic Structure in Relation to Treatment," J. Urol., Volume 82, December 1959.

Clarke, B. G., and Bamford, S., "Cytology of the Prostate Gland in Diagnosis of Cancer," J. A. M. A., Volume 172, pp. 1750-53, April 16, 1960.

!(as don , S. C., and Bamford, S., Atlas 2i !!l ~ Carcinoma g! Cervix, Little­Brown Co., Boston, 1961.

Bamford, S., Cassin, C. M., and Mitchell, B. S., "Sex Chromatin Determinations in Selected Cases of Developmental Sex Abnormalities with an Assessment of Results," Acta-Cytologiea, Volume 7, pp. 151-58, May-June 1963.

Bamford, S. B., Cassin, C. M., Di1ba, D. L., and Mitchell, G. W., "Neutrophil Appendages as Indicators of Sex Chromosome Aberrations," Acta-Cytologica, Volume 8, pp. 323-31, September-October 1964.

Bamford, S. B., Mitchell, G. tol., Bardaw1l, W. A., and Cassin, C. M., "Vaginal Cytology in Polycystic Ovarian Disease," Presented at the Tl'le1fth Annual Meeting of the American Society of Cytology, Pittsburgh, Pennsylvania, 1964.

Bamford, S. B., Mitchell, G. W., Rogers, J., and Woo, A., "Some Cytogenetic Considerations in Polycystic Ovarian Disease," Obstetrics !!!.!! Gynecology, 1964 (Abstract).

Gilfillan, R. F., and Bamford, S. B., "A Mammalian Elastase of Non-Pancreatic Origin," Federal Proceedings, Volume 21, p. 158, 1962.

Gilfillan, R. F., Bamford, S. B. ,Sbarra, A. J., and Bardawil, W. A., "An Elastolytic Proper~y of Human Amnion Cells in Culture," Exp. Cell Res., Volume 27, pp. 58-83, 1962.

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,.'

CURRICULUM VITAE

~: DAVID H. BRAND

PlACE OF BIRTH: Indianapolis, Indiana

DATE OF BIRTH: July 25, 1937

EDUCATIONAL BACKGROUND:

Iustitution & Location

Purdue University, Lafayette, Ind. Ohio State Univ., Columbus, Ohio Ohio State Univ., Columbus, Ohio

Ma10r Field

Eng. Sci. Mathematics Mathematics*

*T!tesis: "Numerical Solutions to Fredholm Integral Equations of the Second Kind"

PROFESSIONAL AND HONOR SOCIETIES:

Phi Eta Sigma, Purdue Univ. Chapter Society of Sigma Xi, Columbus, Ohio Chapter

Degree

B.S. M.S.

Assoc. of Computing Mach., Dayton-Cincinnati Chapter (transferring) DECUS, Dayton Delegate (transferring) Prof. Group of Biomedical Engineers, Dayton Chapter (transferring)

ACADEMIC AND PROFESSIONAL APPOINTMENTS:

1959 1961

Director of Computer Applications, Tufts-New England Medical Center Hospitals, 1965-Present

Director of'Mathematics Division, Systems Research Laboratories, Dayton, Ohio, 1961-1965

Consultant to Miami Valley Hospital and Cox Memorial Heart Inst., Dayton, Ohio, for Medical Applications of Computers, 1962-1964

Instructor and Consultant for Advanced Techniques in Computer Utilization, Ohio, State Univ. Res~lrbb Center, 1960-1961

Undergraduate Mathematics Instructor, Ohio State Univ., 1959-1961

BIBLIOGRAPHY:

Brand, D.H., Colomb, R.M. & Fickes, J .W., "Medical Data Monitor for the PDP-I, II DECl~ Proceedings, Fall, 1964.

Brand, D.B., flClinical Applications of Computers, " Panel Presentation, DECUS Proce edings ,Fall, 1964.

Brand, D.B., Colomb., R.M., & Shirazi, M., A Reference Guide in Biomathematics, Lecture Notes To Be Published from TDR, Contract AF 33(657)-11746, October,1964.

Brand, D.R., flMan-Machine Interaction, Game Theory, and Decision Processes," Chapter 13, Handbook of Multivariate Statistics for Psychologists, Rand-McNally, Spring, 1965.

Brand, D.H. and Fahle, W., "PDP-1 as a V~!satile Research To~l," DECUS Proceedings, Spring, 1963.

Criffis, R. A., Fahle, W. & Brand, D.H., An On-Line PDP-l Computer System for Neurophysiological Experimentation, TDR~ontract AF33(616)-8280, October, 1964.

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DAVID H. BRAND Page 2

Irwin, L., Ostermann, E. & Brand, D.H., A Survey and Extension of Factor Analysis Techniques, TOR, Contract AF30(602)-3300 , February, 1965.

Brand, D.H. & Linhart, R.M., An Integrated Data Collection. Monitoring. and Analysis System for Psychophysiological Research, TDR, Contract AF33(616)-8422, November,l962.

Bachert, R. , Brand, D. & Irwin, L., A New Approach to Computer Command Structures, RADC -TOR-64-135, Contract AF30(602)-274l, September, 1963.

MAJOR FIELD OF INTEREST

Medical applications of computers and mathematics.

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CURRICULUM VITAE

~: BERT~1 SELVERSTONE

PLACE OF BIRTH: Augusta, Georgia

DATE OF BIRTH: March 2, 1917

EDUCATIONAL BACKGROUND:

Institution and Location Major Field

Columbia University, Nel'1 York City, Chemistry Nel'1 York

Harvard University School of Nedi- Medicine cine, C6mbridge, Mass.

PROFESSIONAL AND HONOR SOCIETIES:

Phi Beta Kappa Alpha Omega Alpha Harvey Cushing Society Society of Neurological Surgeons

Degree

B.A.

M.D.

Neurological Society of America (Treasurer 1956-64) Society of British Neurological Surgeons (Honorary Member)

1937

1941

N£w England Neurological Society (Secretary-Treasurer, 1953-56; President, 1961-62)

Congress of Neurological Surgeons Executive Committee World Federation Neurosurgical Societies (1957 to date) American College of Surgeons (Fe1Io'{'7) Royal Society of Medicine (Fello"('l, Section of Neurology) Association for Research in Nervous and Hental Disease Boston Society of Psychiatry and Neurology (President, 1963) Boston Surgical Society American Federation for Clinical Research U. S. Committee of t-lorld Medical Association Lat'1-Sc ience Academy American Medical Association American Association for the Advancement of Science New York Academy of Science rledical Foundation (Board of Directors and Executive Committee, 1956-64,

Research Allocations Committee, 1956 to date, Chairman 1962-64) Advisory Committee M. I. T. Reactor

ACADEMIC AND PROFESSIONAL APPOINTNENTS:

Neurosurgeon-in-Chief, Nel-l England Center Hospital, January 1954 to present Chief of Neurosurgery, Boston Dispensary, January 1952 to present Neurosurgeon, Boston Floating Hospital, September 1951 to present Professor of Neurosurgery, Tufts University School of Medicine,

September 1951 to present Instructor in Neuropathology, Harvard Medical School, July 1951 to present Consultant in Neurosurgery, Jewish Memorial Hospital, July 1955 to present Consultant in Neurosurgery, Nt. Auburn Hospital, December 1962 to present Consultant in Neurosurgery, Veterans Administration Hospital, June 1964

to present

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BERTRAM SELVERSTO~m Page 2

Clinical Associate - Neurosurgery, Massachusetts General Hospital, July 1951 - June 1961

Chief of Neurosurgical Service, New England Center Hospital, July 1951 -January 1954

Neurosurgeon, Net-' England Center Hospital, July 1949 - June 1951 Associate in Surgery, Harvard Medical School, July 1949 - June 1951 Assistant in Neurosurgery, Massachusetts General Hospital, July 1949 -

June 1951 Assistant Neurosurgeon, Boston Floating Hospital, September 1949 -

June 1951 Visiting Neurosurgeon, Manchester Royal Infirmary, August 1950 Senior Fellow in Neurology, The National Research Council; Research

Fellot-1 in Surgery, Harvard Medical School, July 19lJ.8 - June 1949 Clinical Assistant and Research Fellow in Neurcsurgery, Massachusetts

General Hospital, January 1948 - June 1949 Assistant in Surgery, Harvard Medical School, October 1946 - July 1948 Resident in Neurosurgery, Massachusetts General Hospital, October 1946 -

December 1947 Assistant Chief, Neurosurgical Service, Letterman General Hospital (Army)

June 1944 - January 1946 Hard Officer, Neurosurgery, {-la1ter Reed General Hospital (Army), March -

May 1944 Intern and Assistant Resident, Surgery, Medicine and Neurosurgery,

McGill University Hospitals, July 1941 - December 1943

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BERTRM1 SELVERSTONE

BIBLIOGRAPHY:

The follolTling is a list of published articles from 1956 to 1963. Twenty-nine articles from 1942 to 1955 have not been included.

Page 3

Se1verstone, Bertram, Yaun, R. H. P., and Robinson, C. V., "Improved Syringe for Angiography," Journal .9! Neurosurgery, Volume 13, pp. 303-4, 1956.

Selverstone, Bertram, "Craniotomy," Chapter 7, ~ Principles !!!2. Practices of Sur~ery, The Department of Surgery, Tufts University School of Medicine, pp. 28-30, 1956.

White, James C., and Selverstone, Bertram, "Pain and Related Phenomena, Including Causalgia," Chapter 6, Peripheral Nerve Regeneration, Veterans Administration monograph, pp. 311-40, June 1956.

Selverstone, Bertram, and White, James C., "Autonomic Recovery," Chapter 7, Peripheral Nerve Regeneration, Veterans Administration monograph, pp. 341-7, June 1956.

Selverstone, Bertram, and Moulton, Mildred Jewett, "The Phosphorus Metabolism of Gliomas: a Study "lith Radioactive Isotopes," Brain, Volume 80, pp. 362-375, 1957.

Robinson, Charles V., and Selverstone, Bertram, "Localization of Brain Tumors at Operation with Radioactive Phosphorus: an Improved TechM nique using a Proportional Counter," Journal of Neurosurgery, Volume 15, pp. 76-83, 1958.

Se1verstone, Bertram and Ronis, Norman, "Coating and Reinforcement of Intracranial aneurysms l-lith Synthetic Resins," Bulletin of Tufts ~ England Medical Center, Volume 4, pp. 8-12, January -March 1958.

Selverstone, Bertram, "Studies of the Formation and Absorption of the Cerebrospinal Fluid using Radioactive Isotopes: A Critical Evaluation of Data and Conclusions," Ciba Foundation Symposium on the Cerebro­spinal Fluid, Production, Circulation and Absorption, pp. 147-167, 1958.

Selverstone, Bertram, and Robinson, Charles V., IIRadioactive Isotopes: Localization of Brain Tumors with Beta-emitting Isotopes," Medical PhYSiCS, Volume 3, pp. 328-32, 1960.

Selverstone, Bertram, ''Vascular Reinforcement with Adherent Plastics," ~ England Cardiovascular Society Proceedings, Volume 19, p. 37, 1960-61.

Selverstone, Bertram, and Cooper, David R., "Astrocytomas and ABO Blood Groups," Journal of Neurosurgery, Volume 18, pp. 602-4, September 1961.

Selverstone, Bertram, "Reinforcement of Intracranial Aneurysms with Adherent PlastiCS," Proceedings of Society of British Neurological Surgeons, Journal 2£ Neurology, Neurosurgery ~ Psychiatry, Volume 24, p. 24, February 1961.

Selverstone, Bertram, "Treatment of Intracranial Aneurysms with Adherent Plastics," Proceedings of the Boston Society of Psychiatry and Neurology, ~ England Journal 2! Medicine, Volume 265, p. 100, July 13, 1961.

Selverstone, Bertram, Dehghan, R., Ronis, N., Deterling, R. A. Jr., and Calloll, A. D., "Adherent Synthetic Resins in Experimental Surgery," Archives £! Surgery, Volume 84, pp. 80-84, January 1962.

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BERT~l SELVERSTONE Page 4

Callow, A. D., Deter1ing, R. A., Jr., Selverstone, B., and Dehghan, R., "Reinforcement of Arterial Anastomoses and Aneurysms with Adherent Synthetic Resins," Bulletin ~.!!. Societe Internationale ~ Chirurgie, Volume 21, pp. 104-111, March-April 1962.

Se1verstone, Bertram, "Aneurysms at Middle Cerebral 'Trifurcation': Treatment l-1ith Adherent Plastics," Journal ~ Neurosurgery, Volume 19, pp.884-8, 1962. -

Se1verstone, Bertram, "Treatment of Intracranial Aneurysms ~1ith Adherent Plastics," Clinical Neurosurgerv, Volume 9, pp. 201-13, 1963.

Se1verstone, Bertram, and Gillespie, Garrett G., "Localization of Brain Tumors with Radioactive Mercury," Presented at Tufts University Surgical Research Forum, May 18, 1963, Tufts Folia Medica, Volume 9, pp. 77-82, July-September 1963.

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CURRICULUM VITAE

NAME: HERBERT J. LEVINE

PLACE OF BIRTH: Boston, Massachusetts

DATE OF BIRTH: July 22, 1928

EDUCATIONAL BACKGROUND:

Institution & Location Major Field

Harvard College, Cambridge, Mass. Chemical Sci. John Hopkins Medical School, Medicine

Baltimore, Maryland

PROFESSIONAL AND HONOR SOCIETIES:

American Federation for Clinical Research Phi Beta Kappa Alpha Omega Alpha

ACADEMIC AND PROFESSIONAL APPOINTMENTS:

Degree ~

B.A. 1950 M.D. 1954

Assistant Professor, Tufts University Medical School, 1963 to present Assistant Physician, New England Center Hospital, 1961 to present Senior Instructor, Tufts University Medical School, 1961-63 Assistant in Medicine, Peter Bent Brigham Hospital, 1959-61 Research Fellow in Medicine, Harvard Medical School, 1959-61 Senior Assistant Resident in Medicine, Peter Bent Brigham Hospital,

1958-59 Assistant Resident in Medicine, Massachusetts General Hospital, 1957-58 Clinical Associate, National Cancer Institute (Endocrinology Branch)

National Institutes of Health, 1955-57 Intern in Medicine, Peter Bent Brigham Hospital, 1954-55

BIBLIOGRAPHY:

Gorlin, R., Messer, J. B., Levine, H., Neill, W. A., and {'lagman, R. J., "Coronary Circulation in Health and Disease," Medical Clinics £! North America, Volume 44, p. 1181, 1960.

Levine, H. J., and t'lagman, It. J., "Energetics of the Human Heart, If American Journal £! Cardiology, Volume 9, p. 372, March 1962.

Neill, W. A., Levine, H. J., Wagman, F. J., Messer, J. V., Krasnow, N., and Gorlin, R., "Left Ventricular Heart Production Measured by Coronary Flot-l and Temperative Gradient, II Journal 2! Applied Physiology, Volume 16, p. 833, 1961.

Levine, H. J., Neill, W.'A., Wagman, R. J., Krasno't'1, N., and Gorlin, R., "Effect of Exercise on the Mean Left Ventricular Ejection Rate in Man," Journal of Clinical Investigation, May 1962.

Wagman, R. J., Messer, J. V., Levine, H. J., Neill, W. A., and Gorlin R., "Coronary Insufficiency in ~mn: The Physiologic and Electrocardiograph Correlation," American Journal .2! Cardiology, Volume 9, March 1962.

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HERBERT J. LEVINE Page 2

Birt"lell, t>l. C., Soroff, H. S., Wall, M., Bisberg, A •. ~ Levine, H. J., and Deterling, R. A., DAssisted Circulation: I. An Improved Method For Counterpulsation," .Tournal American Society !2!. Artificial Internal Organs, Volume VIII, p. 35, 1962.

Soroff, H. S., Levine H. J., Sachs, B. F., Birtwel1, w. e., and Deter1ing, R. A., "Assisted Circulation: II. The Effects of Counterpulsation on Left Ventricular Oxygen Consumption and Hemodynamics,lI Circulation, Volume 27, April 1963.

Soroff, H. S., Birt-C;-1ell, H. C., Levine, H. J., Bellas, A. E., and Deter1ing, R. A., liThe Effect of Counterpulsation Upon the Myocardial Oxygen Consumption and Heart Work," Surgical Forum, Volume 13, 1962.

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CURRICULUM VITAE

~: DOUGlAS J. MARCHANT

PLACE OF BIRTH: Malden, Massachusetts

DATE OF BIRTH: December 31, 1925

EDUCATIONAL BACKGROUND:

Institution & Location

Tufts University, Medford, Mass. Nassachusetts Institute of Tech­

nology, Cambridge, Mass. Tufts University Medical School,

Boston, Mass. Harvard Medical School, Cambridge,

Mass.

PROFESSIONAL AND HONOR SOCIETIES:

American Medical Association ~~ssachusetts Medical Society St. Luke's Guild

Major Field

Biochemistry Aero. Eng.

Medicine

Postgraduate, Gyn. Patho1.

Net-1 England Obstetrics and Gynecology Society Obstetrical Society of Boston American Society for the Study of Sterility American College of Obstetricians and Gynecologists American Board of Obstetrics and Gynecology Boston Surgical Society American College of Surgeons

Degree

B.S.

M.D.

Association of Professors of Obstetrics and Gynecology Sigma Xi Canadian Society for Study of Fertility

ACADE~lIC AND PROFESSIONAL APPOINTMENTS

1947

1951

1957

Associate Professor, Tufts University School of Medicine, 1965 to present

Gynecologist, New England Medical Center Hospitals, December 1960 to present.

Surgeon, Boston Dispensary Gynecology and Tumor Clinic, January 1959 to present

Assistant Surgeon (GYN) Boston Floating Hospital, April 1959 to present Associate Director, OBS-GYN, Boston City Hospital, July 1965 to present Surgeon in Chief, Gynecology Tumor Clinic, Boston City Hospital, July 1965

to present Assistant Professor, Tufts University School of Medicine, July 1961 - 1965 Senior Instructor, Tufts University School of Medicine, September 1960 -

July 1961 Instructor, OBS-GYN, Tufts University School of MediCine, July 1955 -

September 1960

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DOUGIAS J. l.fARCHANT

Assistant Gynecologist, Ne ... ·, England Center Hospital, July 1956 -December 1960

Assistant Surgeon, Boston Dispensary Gynecology and Tumor Clinic, January 1956 - 1958

Page 2

Clinical Assistant, OBS-GYN, Boston City Hospital, August 1957 - January 1958

Associate Visiting Surgeon, OBS-GYN, Boston City Hospital, January 1958 Assistant Gynecologist, Boston Floating Hospital, August 1955 - 1956 Fellow in Gynecology, New England Center Hospital, July 1955 - June 1956 J.A.R., OBS, Boston City Hospital, July 1955 - June 1956 Teaching Fello~·" OBS-GYN, Tufts University School of Medicine, October

1954 - June 1955 Resident in Gynecology, New England Center Hospital, July 1952 - June 1954 Assistant Resident in Surgery, New England Center Hospital, July 1952 -

June 1954 Intern in Surgery, Ne't'7 England Center Hospital, July 1951 - June 1952

BIBLIOGRAPHY:

S~'1ensen, Orvar, and Marchant, Douglas, "Ureteropelvic Obstruction in Infants and Children: Clinical, Radiological and Experimental Studies on Eleven Patients," ~ Journal of yrology, Volume 73, No.6, June 1955.

Clarke, B. G., and ~1archant, Douglas, "Urinary Tract Disease in Females," Bulletin 52i Tufts-Ne't'l England Medical Center, Volume V, No.3, October-December, 1959.

Marchant, Douglas, and Hobika, J. H., "Acute Blood Loss Requiring Ninety-five TransfuSions," Journal .2£. ~ American Medical Association, Volume 171, No. 17, December 26, 1959.

Marchant, Douglas J., "Medical Records," American Journal of Obstetrics !B& Gynecology, Volume 81, No.1, January 1961.

Marchant, Douglas J., "Hemangioma of the Cervix," Obstetiics and Gyne­cology, Volume 17, No.2, February 1961.

Barda't'lil, t·l. A., Mitchell, G. ~1., McKeogh, R. P., and Marchant, D. J., "Behavior of Skin Homografts in Human Pregnancy," American Journal of Obstetrics !n& Gynecology, Volume 84, No. 10, November 1962.

Harchant, D. J., Bardawil, W. A., Mitchell, G. H., Carey, E., "Observations on the Behavior of Skin Homografts in Human Pregnancy,1t Fertilitv ~ Sterility, Volume 15, No.3, May-June 1964.

Marchant, Douglas, J., "Urinary Diversion, Historical Revie't'1," Obs tetrics and Gynecology Survey, Volume 19, No.3, June 1964.

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CURRICULUN VITAE

~: EDl'IARD F. RABE

PLACE OF BIRTH: t-Jatsonto,·m, Pennsylvania

DATE OF BIRTH: November 7, 1918

EDUCATIONAL BACKGROUND:

Institution & Location Major Field Degree Year

BuclQle11 University, Lewisburg, Biology B.S. 1939 Pennsylvania Yale University School of Medicine Medicine M.D. 1943 New Haven, Connecticut

PROFESSIONAL AND HONOR SOCIETIES:

Executive Committee, Pennsylvania Heart Association Pediatric Society of Northern Pennsylvania American Academy of Pediatrics American Medical Association Philadelphia Pediatric Society Pennsylvania Chapter of the American Academy of Pediatrics Massachusetts Chapter of the iunerican Academy of Pediatrics Member, Committee on the Handicapped Child, 1964 Massachusetts Medical Society Member, New England Pediatric Society Sigma Xi Society for Pediatric Research Eastern Association of Ele ctroencephalographers American Academy of Neurology

ACADEHIC AND PROFESSIONAL APPOINTMENTS:

Pediatric Neurologist, Boston Floating Hospital, July 1961 to present Associate Professor of Pediatrics (Neurology), Tufts University

School of Medicine, July 1962 to present Neurological Consultant, Paul A. Dever State School, July 1963 to

present Assistant Professor of Pediatrics (Neurology), Tufts University

School of Medicine, July 1961 - June 1962 Chief, State Seizure Clinic, Pennsylvania Department of Health,

September 1957 - July 1958 Chief, Montour County Child Health Conference, Pennsylvania Dept. of

Health, January 1956 - July 1958 Chief, Department of Electroencephalography, George F. Geisinger

Memorial Hospital and Foss Clinic, September 1954 - July 1958 Cllief, Department of Pediatrics, George F. Geisinger Memorial

Hospital and Foss Clinic, January 1951 - July 1958 Assistant Professor of Pediatrics, University of Kansas Medical

School, June 1949 - June 1950 Instructor of Pediatrics, University of Kansas Medical School, June

1949 - June 1950 Research Fellow in Poliomyelitis, University of Kansas Medical School,

June 1949 - January 1951

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EDWARD F. RABE

Instructor in Pediatrics, Yale University School of Medicine, June 1947 - June 1949

Page 2

National Institute of Health Special Fellow in Pediatric Neurology, Massachusetts General Hospital, July 1958 - June 1961

Resident in Pediatrics, New Haven Community Hospital, July 1944 -July 1945

Intern, Ear, Nose and Throat Department, New Haven Community Hospital, January 1944 - July 1944

Intern in Pediatrics, Neu Haven Community Hospital, April 1943 -January 1944

BIBLIOGRA!!1X.:

Rabe, Edlolard F., Infectious Group I, "Etiology, II Pediatrics, Volume 2, p.225, 1948.

Rabe, Edl07ard F., Infectious Group II, "Virus Group," Pediatrics, Volume 2, p. 415, 1948.

Rabe, Edward F., Infectious Group III, "Hemophilus Influenzas, Type B Group," Pediatrics, Volume 2, p. 559, 1948.

Rabe, Edl07ard F., "Agglutinating Substances for Homologous Coliform Organisms, Occurrence in the Serum and Feces of Infants,"American Journal of Diseases of Children, Volume 78, p. 717, 1949.

Rabe, Edl'lardF., If Occurrence of Lysozyme in the Cerebrospinal Fluid and Serum of Children in Health and Disease," Journal .2! Pediatrics, Volume 38, p. 147, 1951.

Rabe, Edl·lard F., and Henner, H., "Immunologic Classification of Polio­myelitis Viruses: Results Obtained with the Method of Neutralization with Prototype Sera," American Journal .Q£. Hygiene, Volume 54, p. 243, 1951.

Rabe, Edl·lard F., and l-lenner, H., "The Recovery of Virus from Regional Lymph Nodes of Fatal Human Cases of Poliomyelitis," American Journal of Medical Science, Volume 222, p. 292, 1951.

Rabe, Edl07ard F., Spicer, l·I., "An Evaluation of the Middlebrook-Dubos Hemagglutination Test,lt Journal .Q£. Laboratory ~ Clinical Medicine, Volume 41, p. 98, 1951.

Rabe, Edl'lard F., "Streptococcosis, If Bulletin of ~ Geisinger Memorial Hospital !B& f2!! Clinic, Volume 3, p. 109, 1951.

Rabe, Edvlard F., rtHemolytic Disease of the Newborn," Bulletin .2i the Geisinger Memorial Hospital !E& ~ Clinic, Volume 5, p. 3, 1953.

Rabe, Edl'lard F., and Hilliams, John L., ItHegacolon in Infants and Children." Bulletin of ~ Geisinger Memorial Hospital !!!2. f2!! Clinic, Volume 1, p. 3, 1954.

Rabe, Edlo1ard F., "Salmonellosis in Children," Pediatrics, Volume 13, p. 247, 1954.

Rabe, Edl'1ard F., "Orthopedic Problems in Children, If Pennsylvania Medical Journal, Volume 57, p. 339, 1954.

Rabe, Edward F., "The Antibody Response to Gram Negative Organisms: An Explanation of the Difference betl-1een Bacterial and Hemog­glutinating Antibody Titers," Pediatrics, Volume 14, p. 351, 1954.

Rabe, Edlo1ard F., "The Treatment of Salmonellosis with Massive Doses of Penicillin: A Comparison 'olith other Methods of Therapy," Pediatrics, Volume 16, p. 590, 1955.

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'. ~ . . ~,·:,!~~"V ~. ~;'lj ~ 1 !~,:t ,.: -)_:. 4 .; ;~.:~'::~ ~;{.!

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EDt-1ARD F. RABE Page 3

Rabe, EdHard F., "Evidence of Pyridoxine Hydrochloride (Vitamin H6) Need in Infants and Children "lith Anemia, Convulsive, and Acute Infections,1I American Journal ~ Diseases ~ Children, Volume 92, p. 582, 1956.

Rabe, Edl'lard F., liThe Use of Electroencephalography in a General Hospital,lI Bulletin of Geisinger Memorial Hospital !!!2. ~ Clinic, Volume 8,p. 3, 1956. .

Rabe, Ed,~ard l., Smull, Christine, and Oplinger, Nancy, lithe Incidence of Meningococci in the Nasopharynx of Hospitalized Children in a Rural Area, II Bulletin .Q£. ~ Geisinger Memorial Hospital !!t<! ~ CliniC, Volume 8, p. 53.

Rabe, Ed,~ard F., IIAcute Inflammatory Disorders of the Larynx and Laryngotracheal Area,1I Pediatric Clinics of North America, February, 1957.

Rabe, Ed,~ard F., IIPresent Day Problems in Salmonellosis, a Pennsylvania Medical Journal, Volume 61, p. 209, 1958.

Rabe, Ed,~ard F., and Greerman, George H., IIStaphylococcal Bacteremia in Children Under One Year of Age,lI Bulletin ~ ~he Geisinger Memorial Hospital ~ ~ Clinic, Volume 9, p. 106, 1957.

Rabe, Edward F., "Exchange Transfusions in Babies with Erythroblastosis Fetalis: Its Effect Upon the Total Serum Bilirubin Concentration," Bulletin 2! ~ Geisinger MEDorial Hospital ~ !2!! Clinic, Volume 9, p. 140, 1957.

Rabe, Ed"lard F., Fletcher, Thomas F., Morrison, Samuel S., and Helper, Thomas H., "Erythroblastosis Fetalis: A Survey of the Clinical and Laboratory Picture ~lith Special Reference to Indications for Exchange Transfusion," Pennsylvania Medical Journal, Volume 61, p. 752, 1958.

Rabe, Ed"lard F., Flynn, R. E., and Dodge, P. R., " A Study of Subdural Effusions in an Infant: With Particular Reference to the Mechanisms of their Persistence,1I Neurology, Volume 12, p. 79, 1962.

Rabe, Edt-lard F., and Castleman, B. F., DToxoplasmosis in an Infant, II CPC, Massachusetts General Hospital, New England Journal 2! Medicine, Volume 269, p. 369, 1963.

Rabe, Ed"lard F., II The Hpotonic Infant, A Review," Journal 2i Pediatrics, Volume 64, pp. 422-440, 1964.

Rabe, Edl-lard F., Young, G. E., and Dodge, P. R., liThe Distrbution of Subdurally Instilled Labelled Serum Albumin in Infants with Chronic Subdural EffUSions," Neurologv, Volume 14, p. 1020, 1964.

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/

EXPANDED ABSTRACT OF A PAPER TO BE PRESENTED AT THE PHILADELPHIA 18TH ACEMB, NOVEMBER 10-12, 1965

NOT FOR PUB L I CAT ION .

A COMPREHENSIVE COMPUTER PROGRAM FOR BIOMEDICAL PATTERN RECOGNITION*

I. Preprocessing System

Kurt Enslein, Rochester, New York

A. Introduction

This note is a progress report on our efforts to construct a com-

prehensive set of digital computer programs to implement generalized

Pattern Recognition techniques for application to biology and medi-

cine. The main body of the programs is based on various versions

of the perceptron. This technique permits classification of objects

as well as delinearization of the important features of objects.

The system includes a comprehensive set of data preprocessing rou-

tines. The individual routines will eventually be imbedded in a

~ super-compiler which will have the function of accepting simple

specification statements of the perceptrons to be simulated and of

the preprocessing operations to be performed, and from these state-

ments, produce Fortran statements which can in turn be compiled on

the object computer.

This first of two papers will deal with the preprocessing system. A

companion paper (1) describes the pattern recognition routines.

These programs are written in Fortran-63 which is an overset

of Fortran-IV and Fortran-II, and are arranged in such a way

* This project was supported by Public Health Service Grant No. GH12015 from the National Institutes of Health.

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that they can be easily converted to other versions of Fortran

and recompiled on most modern computers having Fortran

capability.

The presently, either active or planned, applications for this

technique are as follows:

1. Unidimensional Patterns

Patterns of diagnostic signs, symptoms and measurements

(congenital heart disease, electrophoretic patterns,

especially disc electrophoresis, antropomorphic measure­

ments, etc.>, sampled waveforms such as EKG, PCG, and EEG.

2. Multidimensional Patterns

~ Chest x-rays

Chromosomes

Facial features (physiographs)

Transformed waveforms such as contourograms

Spectral phonocardiograms

In some instances, combinations of unidimensional and

multidimensional patterns are used in a single application.

B. Overall Purpose

The purpose of the preprocessing system is to accept non-standard

format input data, operate on it in various ways, and then

produce an output in standardized but changeable (as desired)

- 2 -

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- ----

format on either cards or tapes. The operations performed on

the data (which will be outlined in Section D) are such that

this preprocessing system is useful for other than Pattern

Recognition applications. For example, it can be readily

used as input to clustering techniques, to generate distribu­

tions, and quite generally, to perform relatively simple but

extensive manipulations on data.

C. Input Command Format

One on the features of this system is to make the input control

requirements relatively simple. While what is explained below

is not the ultimate of what we intend to produce, it is at

least a step in the right direction. In Figure I, we show the

listing of a typical control deck.

In this listing, artificial spacing has been introduced between

certain sections in order to make the output more legible.

This particular run had as an object the production of ternary

tape records. Each variable was classified into a range, and

an one-out-of-N ternary representation for a variable made

up a word. The assembly of these words then made up one

pattern. Each pattern thus generated, is also preceeded by

an identification record.

The first card, thus. shows that the length of the ternary

record must not exceed 300 bits, that there are 17 integer

variables, 3 floating-point variables. and that B types of

subroutines are being used.

- 3 -

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r7F Bit sIN T! -N~:t'L----lIINl-\ul-lmD-bt\.@e~r , Output Integer Floating of

-_______ h~eeord ______ Variah.l...as variable s Subs

FIGURE 1 ~----- ---_._----_.-=====- .. _------- ---- ---.-

~ ~ ~ ~ 300 17 3 8

Var Nr Var Name Format Mode Sub to be U~ed Lowll. Ifts. Classes :- 1

2 ----t---------f-:-':--TI......:~-RA-M-E-_ --I-1~-.:::.-.8----.l--~~~&~~~~·-~~- . ~- -----.- - -- --

~ YFAR 12 INTFG!::R NONE --. - -.--- ----- ----- ------------------

4 MONT~ J? no NON~ c:; nAY 12 no ~O~E

6 I\G~'~OC-. 12 ['~ J'!TCLASS 8 CHFCOM.P 6Al ALPHA F'IL>FIELL)

~ 9

h 1 0

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SHRTB~F 6AI DO FNOFIELD .... 1 3 til

CYANo~rS6Ar DO F~DFJf-LD

CD 14 SPELLS 5At DO F~DFI~LD

o

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-1-' .- -- --.-

10 6

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6

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._-AGPAR -f?-------- ---f)-C)' TF.r~NF ILL . -- ------ .-

;:>0 PATCLASS 12 DO NONE 20

7 AGEYRS F~.O FLOATIN( RLCLASS 1.0 1.0 10 17 BJRFWATE F5.0 FLOATING ~I...CLA~':; 2.0 0.2~ 20 19 'P~ES'''''ATt F:='.O FLOATING T'IJU~PACt: 1 7 .. :H.>l,.·'!Tol..J 1 .

____ L ______ -.:.-~-.: ~:: ~ ::-,::-==.-:;:=:._ -::::-.. ::. __ -===-=-.=-:-:.::. -:":. -.;:-:~-: -..:, -----. -.;:=-=---~-=-=.:: .;::.:-:.-:-.:, ---:-~-=-.:.-..:.:------INTCLASS INTSP~CE

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9.5 10. 1 10.8 1 1 .5 -_.-----_ .. _- --- 12.4

15.d 1 1 .2 13.0 14.6 ----16.6

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The next section of 17 cards describes the integer variables

and how these are to be treated. One notes that each of

these cards carries the name of the variable, its format, its

mode, what subroutine should be used to process it, as well

as subsidiary information when this is needed, that is, the

number of classes, the names of tables that should be used

in the classification process, etc.

The next set of 3 cards carries the same information for the

floating-point variables. The next section of eight cards

contains the names of the subroutines used in the program.

The last set of cards contains various tables and constants

needed in this particular run.

Note that the action of the program is almost completely de­

fined by the variable specification cards. Note also that

it is not necessary to feed control flags and similar data

into this program. Most of the control is performed by the

mnemonics, which closely resemble natural language.

Even this form of input is not considered ideal from an appli­

cation standpoint. It is planned that the specification cards

will have a freer format, that the names of the available sub­

routines need not be fed in as data, but, rather, will be

already stored, that specification cards for different type

- 4 -

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variables can be intermixed, and that cleaner partitioning of

constants and variables will be effected.

D. Major Preprocessing Routines

1. Classification Routines - These consistof three general

types:

a) Classification of an integer or real variable into

one out of N classes, using an equal increment comb.

These routines are often used for classification of

age, height, and similar antropomorphic data.

b) Classification of an integer or real variable into

one out of N classes using an arbitrary increment

comb. In these routines, we can use non-linear scales

which are often useful for such items as temperature

and pressure; in general, measured physiologic variables.

c) Two-dimensional classification of a real variable. An

example of this is the calculation of the percentile

group into which a person of a given height at a given

age falls.

d) Classification of an alphanumeric variable into one

~ut of N classes. This type of routine is useful for

the classification of such things as sex, race, and

other characteristics which are more conveniently des­

cribed by a word or mnemonic rather than by the assig­

nation of numbers.

- 5 -

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e) Calculation of the index number of a mark in a field.

Typically, these routines are used in multiple-choice

cases where one wishes to discover which of the N

choices has (or have) been selected.

2. Pattern Assembly Routines - These consist basically of

two types:

a) Routines to convert a class number to a one-out-of-N

binary or ternary representation, generate the binary

or ternary word and insert this word in the proper.

position of the binary or ternary output record, and

b) Routines to assemble identification and data records

into a standard format.

3. Augmenting Vectors

This routine (under development at this writing), the

justification for which is found in (2), is used to gen­

erate an augmented pattern from each basic pattern. The

augmented pattern consists of the original variables,

their squares and their cross-products. It has been

proven by Koford that such augmented vectors possess a

much higher chance of being classified properly than the

original vectors.

4. Data Compression - These routines (projected for the

future) will take advantage of the algorithms developed

- 6 -

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by Specht, Drapkin, and Weber (3 and 4) to compress

digitally-sampled waveforms such as EKG, EEG, and peG,

to the minimum number of required samples as a function

of the information content of the data.

5. Feature and Measurement Extraction - These routines (also

planned for the future) will attempt to abstract from raw

input patterns the more "significant" measurements, that

is, those which lead to a higher probability of correct

classification, and those combinations of measurements,

that is, features, which achieve the same objective. A

substantial amount of theoretical work has proceeded in

recent past in this area which work needs to be put to

use.

E. Program Output

The output from the preprocessing system consists of three

types: the properly formatted output patterns, informative

messages as to the action of the program, and error messages.

1. Pattern Output - Routines are available for output of

patterns in standardized format on cards or tape with pro­

visions for multiple tapes, parity errors, etc., etc.

The output data can be in binary, ternary, integer, or

real form or any mixture of these. The Pattern Recognition

routines proper can utilize any mixture of input data as

well. Thus, it is not necessary in this preprocessing

- 7 -

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system to use the classification routines if they are not

desired.

Binary Qutputs are generated from packed binary variables

(1).

2. Informative Messages - These provide such information as

what patterns have been worked on, which routines are

being used, etc., etc. Much of this output can be sup­

pressed if it is not desired.

3. Error Messages - A multitude of these have been provided.

Such items as exceeding the specified record length,

looking for a subroutine that has not been provided, im­

proper field specifications, etc., etc., produce messages

which effectively check the input control card and many

other quirks that could occur within the running of a

program.

F. Plans for the Future

In addition to the points mentioned throughout this discussion,

it is planned to immerse the entire system in a list processor

(SLIP) in order to be able to use free-form statements at the

input and remove several other input requir~ments. Also, we

plan to elaborate the use of these routines to make them some­

what less bounded in application than they now are.

- 8 -

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Finally, in order to make the system compatible with smaller

machines, a super-compiler, also based on SLIP, will be used

to assemble into a Fortran source package only those subroutines

and those parameters that are needed for a specific problem.

G. Comments

Many auxiliary methods can be fruitfully used in connection

with these preprocessing programs. Generally, these would be

clustering programs based on various distance measures. We

have not dwelled on the use of these routines in this paper

in view of the fact that they really form a separate topic

that will be more properly covered in a different note.

- 9 -

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REFERENCES

1. Enslein, K. - "A Comprehensive Computer Program for Biomedical

Pattern Recognition", II Pattern Recognition Systems - This

volume, p. ___ •

2. Cover, T. M. - "Classification and Generalization Capabilities

of Linear Threshold Units", Report RACD-TDR-6~-32, Information

Processing Branch, Rome Air Development Center - p. 10.

3. Specht, D. F. and Drapkin, P. E. - "Biomedical Data Compression"

Internal Report, Lockheed Missiles and Space Co •• Sunnyvale,

California.

4. Weber, D. R. - "A Synopsis on Data Compression" - Internal

Report 5-13-65-6, Lockheed Missiles and Space Co •• Sunnyvale,

California.

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EXPANDED ABSTRACT OF A PAPER TO BE PRESENTED AT THE PHILADELPHIA 18TH ACEMB, NOVEMBER 10-12, 1965

NOT FOR PUB L I CAT ION

A COMPREHENSIVE COMPUTER PROGRAM FOR BIOMEDICAL PATTERN RECOGNITION*

II. Pattern Recognition System

Kurt Enslein, Rochester, New York

A. Introduction

Certain details of this paper will be better understood by reference

to the companion paper appearing in this volume (1). The purpose of

the research to be reported is to mechanize the major presently more

workable and proven perceptron techniques, including two, three, four

and higher level systems with a concentration of the effort being on

the four-level organization (2, 3), mostly because it has been dem-

onstrated in recent past that this organization appears to be sub-

stantially more powerful than most others investigated up to the

present (4, 5).

Generally speaking, perceptrons are physical devices or computer

simulations of such devices capable of classifying objects into one

out of N classes. Perceptrons usually operate in a training (or

organizing) mode followed by a recognition mode. In the training

mode, the perceptron connections are organized both as to terminals

and weights, with known objects. At the recognition phase, an un-

known object is presented to the system and the question is asked:

into which class does this object fall? The results obtained from

perceptron simulation can be the organization of the system, the

values of the connecting weights, and, after training, the class

into which a particular object falls.

* This project was supported by Public Health Service Grant No. GM12015 &omthe National Institutes of Health.

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~ B. Organization

Figure 1 is a simple sketch of a four-level perceptron.

s A2 R

In such a system. the programs under discussion have the

ability to effect the following actions:

1. Organize any of the connections between layers according

to a variety of rules such as: connect K randomly se-

~ lected S terminals to each of L units in the Al layer;

or. connect a random number not exceeding J S terminals

to L Al units with the fol19wing constraint •••• Thus. one

can specify the maximum number of units in the originating

layer. the number of units in the next layer. the number

of inhibiting and enabling connections per unit in this

next layer. and the weights of these connections whether

they be random (with an upper bound). assigned according

to some other algorithms. binary, ternary, integer. or

real. In other words. we believe that most. if not all.

the known connection rules are mechanized in this fashion.

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2. Reorganization - Change a given fraction of the connections

and/or weights between two layers according to an algorithm

or on a random basis. This covers such cases as selecting

different S units to be connected to the Al level in order,

for example. to improve the measurement set. It also in-

cludes the A2 to R weight changes which are the result of

a number of training methods to be detailed in Section C.

In general, then. this set of routines permits the reorgan­

ization of connections between units and/or the weights

of these connections.

3. The mode of the connections between units is optimized,

depending upon the need in order to conserve computing

~ time and memory space. Thus, in most four-level organ­

izations, the Al to A2 connections are strictly binary and

packed logical variables are used for this purpose (see

Section D below).

C. Training Methods

Various investigators have proposed a number of training

algorithms, at least for three-level perceptrons. We have

found that these algorithms can be equated by means of

Iq. (I) ,below.

g(k+l) = g(k) + XiCD (1)

where g(k) is the kth weight vector

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g(k+l) is the (k+l)th weight vector

Xi is the ith pattern vector

C and D are defined in Table 1

n is the number of patterns used

Parameters C and D can be calculated as shown in Table 1.

TABLE 1

Training Method Parameters

C D

May's Modified Relaxation (6) 'If :t l-Xi·g(k) n+l

Koford's Single-Pattern LMS (7) 2u :t l-Xi,g(k)

May's Increment (6) 8 :t 1 ii+r

Forced Training ( 8) a :t 1

In this Table, the references from which the several training al-

gorithms were obtained are shown. Thus, by means of a single

training routine for which the C and D parameters are calculated

according to the rules shown in Table 1, it is possible to imple-

ment most of the known training rules, Please note that the most

current versions of these training rules are used, All of them,

of course, in one way or another find their origin in the work of

Rosenblatt or Widrow.

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There are many more optimization procedures which might result

in fa$ter convergence of the perceptron routines. At the pre­

sent time, we have not implemented these but hope to do so in

the next few years.

D. Methods

In this section we will describe a few of the methods which

we believe relevant or unique.

1. In2ut Command Structure - The only items which need to be

specified to the system are the various parameters of the

perceptrons to be simulated, layer by layer, and output

formats. The input data is already in standard form as a

result of the preprocessing routines described in (1).

While a rather stringent order of these parameters is

necessary at this time, it is the intention to remove this

limitation when the SLIP list-processing features are

added to this program. Nevertheless, the control parameters

are relatively easy to specify eyen at this time.

2. Sequence Control - The sequence of operations to be per­

formed, that is, which subroutines are to be called at what

stage, is specified by a control array made up of cards

similar to the specification cards of (1). The control

array is read in as an initialization step. The informa­

tion in this array specifies the index of a computed GO TO.

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This GO TO determines the branch that the program will

execute with its index. In addition, the number of times

that this branch should be taken as a result of this par­

ticular step in the program is specified on each control

card. Other subsidiary information such as conditional

branches, etc., etc., are also specified on these cards.

After the execution of a subroutine, the sequence con­

trol returns to this computed GO TO.

In this manner, it is possible to specify at each execu­

tion just how the system is to operate. In other words,

it is extremely simple to change from 2 to 3 to 4 or

higher level organizations or from one training method to

another or from one decision method to another, or the num­

ber of iterations at various steps, or the reorganization

techniques, by simply specifying this information on the

control cards.

This method of control also provides a simple link for the

imbedding of this sytem in a super-compiler which will

simplify the control of the system as well as assemble only

those Fortran statements needed for a particular simulation.

3. Structure of Organization Lists - When perceptrons with

large numbers of terminals are to be simulated, the number of

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interconnections becomes rather large. For example, if there

are 1,000 S terminals and 2,000 Al terminals, the number of

possible connections becomes 2 x 10 6 • While this problem may

not be as severe if only binary connections are used, it be-

comes of paramount importance if the weights can have real or

integer values. In the case cited above, 2,000,000 words of

memory would be needed just to store the S to Al organization.

Most of the time, only a small fraction (between 0.001 to 0.02)

of the possible interconnections are used. For the example

under consideration, this means between 2,000 and 40,000.

Moreover, when the number of possible interconnections is

large, one often finds that a less richly connected matrix is

quite adequate. For this reason, the system has been organized

to utilize a list structure for the interconnections. For

non-binary interconnections, a two-column list is established,

the number of lines in the list equaling the number of connec-

tions plus the number of receptor units. For example, for a

S to Al structure, we have the following organization:

LADDRESS

(Ai> (NR of 1st Al Unit) + LACONST

S-layer address of an Al connection 1

S-layer address of an Al connection 1

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VALUE

Threshold for this Al unit

t Weight of this Al connection 1

t Weight of this Al connection 1

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LADDRESS V.ALUE

d f h • 1 • Last S-layer a d. or t 1S Al un1t We ight

(NR of 2nd Al unit) + LACONST Threshold for this Al unit

1 S-A2 connection Weight

Thus, a constant is added to LADDRESS to identify the be-

ginning of the next Al unit.

Below is shown an example with the following assumptio~s:

100 S units, 3 units in the Al layer, LACONST=lO.OOO. and

3. 4. 5 connections I Al unit respectively, and a threshold

of n-2, i.e., I, 2, 3. respectively.

LADDRESS VALUE LADDRESS VALUE

10001 1.0 99 10.8 21 3.0 10003 3.0 63 1.9 15 12.0 12 6.6 19 4.1

10002 2.0 77 9.6 17 2.3 80 6.0 84 4.7 90 12.3 87 9.9

In this fashion. a very substantial amount of storage space

is saved. The additional computation required to identify

each cell in this list turns out to be relatively small. For

binary connection cases, the value column is omitted.

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4. Packing of Logical Arrays - Another me~ory-space saving

feature is the facility of Fortran-S3 to pack logical var­

iables into arrays, 32 bits per computer word. Through the

proper use of EQUIVALENCE statements and TYPE LOGICAL and

INTEGER, it becomes possible to operate on binary variables

such as interconneetions, either I bit at a time or 32 bits

at a time. This also turns out to be a time-saving feature.

5. Historical Output - The running of this system is copiously

documented by means of historical output on tape units which

are listed by means of a comprehensive set of routines. Only

a small object-time price is paid for this feature in view of

the fact that Fortran-53 through BUFFER-OUT permits overlap

of input/output and computations with interrupts. This is

another reason we are using this particular language.

The historical output can consist of the weights after each

update, the organization after each change, the error func­

tions at various steps, etc., etc. Just what historical in­

formation is kept is once more a function of the previously

explained control array.

E. Plans for the Future

It might be well to summarize at this point what additional

work needs to be performed to make the system still more use­

ful and comprehensive. In addition to imbedding the system in a

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super-compiler as mentioned above and simplifying the control

input requirements. exhaustive testing of these routines is

required. While it is manifestly impossible to try all the

possible combinations, at least a larger set than has been

tried up to now must be investigated. A larger set of con­

vergence procedures must be programmed and tested. In this

connection, the various possibilities for updating, training,

reorganization, etc., must be tested with common and with

various types of data so that one can obtain a better know­

ledge of which types of organizations are more fruitful for

certain problems.

The problem of selection of variables already referred to in

the companion paper, is of major importance and must receive

a comprehensive attack in that the theory in this area is still

in its infancy.

Finally, it is our hope, that through cooperation with invest­

igators needing classification routines, a thorough test of

the utility of perceptron simulation can be achieved.

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REFERENCES

1. Enslein, K. - "A Comprehensive Computer Program for Biomedical

Pattern Recognition", I. Preprocessing System; This Volume,

p. -'

2. Rosenblatt, F. - "Principles of Neurodynamics" - Spartan Books,

Washington, D. C. - 1962.

3. Widrow, B. - "Generalization and Information Storage in Net-

works of Adaline "Neurons"", - Self-Organizing Systems, 1962 -

Spartan B~oks, Washington, D. C. - pp. 435-461.

4. Rosenblatt. F. - "A Comparison of Several Perceptron Models",

5.

Self-Organizing Systems, 1962 - Spartan Books, Washington,

D. C. - pp. 463-484.

Rosenblatt, F. - Editor, "Collected Technical Papers, Vol.

July 1963, Cognitive Systems Research Program - Cornell

University - Ithaca, New York.

2" ,

6. Mays, C. H. - "Adaptive Threshold Logic" - Technical Report

No. 1557-1, April 1963 - Solid State Electronics Lab. - Stanford d

Electronics Lab.~ - Stanford, California.

7. Koford, J. S. - "Adaptive Pattern Dichotomization" - Technical

Report No. 6201-1, May 1964 - Systems Theory Lab. - Stanford

Electronics Laboratories - Stanford, Calfornia.

8. Goerner, J. and Gerhardt, L. - "Analysis of Training Algorithms

for a Class of Self-Organizing Systems", NEe Proceedings, 1964 -

Chicago - pp. 631-636.

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Human Chromosome Analysis by Computer -

An Optical Pattern Recognition Problem

Peter W. Neurath, Arthur Falekt.c , Barkev L. Bablouzian, Tom H. Warms

and Russell C. Serbagi

Medical Science Department, Avco Corporation, Wilmington, Mass. and

*Department of Medical Genetics, N. Y. State Psychiatric Institute,

Columbia University, New York, N. Y.

By means of cytogenetic techniques human chromosomes can be

observed and analyzed. Under the microscope the chromosomes are visible

as dark structures approximately one micron to eight mic ron in overall

length and less than one micron in width (1). Cells of normal persons contain

22 pairs of autosomes and one pair of sex chromosomes classified by group

and number (2).

Consistent chromosome abnormalities are found to occur in association

with specific congenital disorders (3). The two types of observed chromosomal

aberrations are: (A) chromosome complements with abnormal numbers of

chromosomes and (Bl disturbances in the structure of the chromosome rather

than in number.

In addition to congenital defects chromosome abnormalities are reported

in persons with a diagnos.is of cancer (4,5,6) and chromosome damage is

found in individuals after irradiation (7,8, 9). Chemical muta.ena a8 well have

produced chromosome apreaCls with aberrations (la, 11).

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Les s is known about chromosomal variations in the general population.

Due in part to the time consuming work involved in karyotyping the chromosome

spreads, only about 100 cases can be analyzed in one year by a laboratory

having a senior scientist and a highly trained technician. This rate is not

only insufficient to meet existing demands for clinical evaluation, but quite

inadequate for l~rge scale studies of radiation induced chromosome damage

particularly at low dosage levels, or for the investigation of specific

chromosome polymorphism in populations.

Computer techniques of pattern recognition appeared to be of value for

the specific task of chromos orne analysis. Our results to date are promosing

and have general applicability although our procedure differs in approach from

other work in this area (12, 13, 14, 15, 16).

Outline of System

The system of computer aided processing of chromosomes is shown in

the block diagram of Figure 1. In this figure, the heavily outlined rectangles

represents pieces of equipment, while the thin rectangles are the inputs to

and outputs from this equipment. The vis ual information at the start is either

in the form of a photographic print or an image formed through a microscope.

A scanner is used to convert this visual information into an electrical signal.

In our case the scanner is a slow-scan TV camera syst em which will be

described in greater detail below. The output from this scanner is an analog

signal which has t~! be converted into an IBM compatible digital record on

magnetic tape, a task performed by an analog to digital (A to D) converter.

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The resulting "raw" digital tape contains a great deal of unnecessary

information and is therefore re-processed as the first step in the digital

computer program. The digital computer then analyzes this "prepared" tape

in terms of chromosome counting and characterization. The final information

is furnished in pictorial form, numbered and identified by a graphic computer

output device, the SC -4020 photographic plotter.

Results of this process are presented in Figure 2a, 2b, and 2c. They

illustrate the extent of the computer's ability to count and classify "perfect"

spreads, as well as some of the limitat~ons which need to be overcome. A

more detailed consideTation of the scanning and computing process will make

clear the achievements as well as the shortcomings.

Scanner and A to D Converter

The information to be put into the computer consists of all the

coordinate points of a square raster or grid which covers the picture area

of interest ~ith the proper grey level for each such point. Although the human

eye and brain has a rather more elaborate system, this type of breakdown of

a picture is the usual approach taken when visual data are handled electrically.

In our program we use a slow-scan TV system shown schematically

in Figure 3. This slow-scan Vidicon is an IT & T Videx Camera NV -700. The

chromosome spread is focused on its face plate at a magnification such as to

cover most of the available picture tube area and at a proper light intensity.

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The image of the chromosome spread is obtained from the monocular

tube of the microscope using the TV camera lens focused at infinity. In this

way., the infinity corrected objective of the microscope produces the image on

the vidicon face plate parfocal with the visual image in the binocular eyepiece

system.

Alternatively an enlarged photograph is suitably illuminated, focused

and magnified to the correct size with the vidicon zoom lens.

The output from the vidicon, an analog signal, can be viewed on the

IT & T monito,r at the same time the video signal is taken to Avco's Astrodata

A to D converter, where the signal is digitized and recorded. Figure 4 shows

the microscope-TV system and Figure 5 gives a view of the A to D converter

and tape unit.

The lines of the TV -scan represent one set of vertical grid lines, xl'

xz' x3- •••• , •...••.••• ~ and the samples for digitizing taken at equal and

corresponding time intervals during each line scan represent horizontal

grid lines Yl, yz' y3.····.····· ·Ym. By choosing the time intervals ~ ,

properly, we can make the effective spatial distances for the X and y grid lines

equal and thus get a square grid. For a 40-second scan per complete picture,

at 100 milliseconds per scan line, the required sampling rate turns out to be

3500 samples per second. The analog output of the slow scan TV system is

shown schematically in Figure 6. A picture, filling the TV screen has 400

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-5-

vertical lines, each divided into 350 samples and the A to D converter

records on magnetic tape all these 400 x 350 samples, or fewer if we choose

not to record the whole field of view. The grey level of each sample is

recorded as a three decimal digit number between -5.00 and +5. 00 volts in

8-1-2-1 BCD code with 12 bits plus sign. As the actual voltage difference

from black to white is approximately 2. 00 volts, this means that the A to D

converter is recording a completely unrealistic figure of 200 shades of grey.

Initial Data Processing

The resulting raw digital tape thus has a great deal of unnecessary

information, while not explicitedly listing some desirable items. From the

cost point of view it is important that this redundant information not be fed

into the IBM 7094. The first step in the digital computation, is therefore, to

reprocess the information in preparation for the 7094 computer run. At

the beginning of each scan there is a synch pulse, an oscillating voltage

of high opposite polarity. No actual useful visual scanning is done during

this time, equivalent to approxirnately 20 of our samples of interval d . Therefore the first 25 samples starting with the first " negative" one are dropped,

leaving 325 samples per scan. line; in place of the synch pulse, each scan line

is nu,mbered in sequence, and the number entered into the record.

The second step is to convert the 3-digit voltage levels into not more

than 14 shades of grey. That is, instead of describing the shade of grey by any

number between -5.00 and +5. 00 we group these 1000 possibilities into 14

intervals labelled 1 to 14. As the actual resolving power of the TV camera

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above noise is only about 7 or 8 shades of grey at best, and as even better

available cameras would hardly distinguish more than 10 shades, the 14

shade limit is most generous. It reduces the amount of information on the tape

by a factor of about 70.

At this point an additional question arises: how to select the 14

intervals. Because of non-linearity in eye and camera, a division into equal

voltage intervals between the extremes of white and black would be quite

inappropriate. Under one set of conditions white to black may represent

o to 2 volts, under another 0 to 1 volts. Equal steps of photograJhic density

in the latter interval may be about 0.2 volts apart in the range between 0.2 and

0.8 volts, but less than 0.05 volts apart near the ends of the scale. This makes

a simple standardized choice inadequate.

In the course of programming, it became obvious that the selection

of grey levels was an important and even curcial step. In fact we found that

our approach depended considerably on the exact choice of grey level. This

is not surprising, because in our further programming we want to represent

the chromosomes in outline by a contour-line of equal grey level. Everything

lighter than this level is to be considered "white" background and everything

darker rrblack" chromosome.

We thought that for many spreads such a representation would be

adequate. This in fact turns out not to be the case. Fixing and staining of

the chromosomes by the usual methods results in spreads which are not only

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unevenly "black" from chromosome to chromosome but the color intensity

also differs widely within each chromosome. The centromere often does

not stain IIblackll at all. Therefore, only in very few spreads can all of

the individual chromosomes be represented satisfactorily by their "equal

greyness" and even for these few spreads the choice of grey level has to

be carefully determined.

Fortunately, it is possible to check this choice in our system when

first viewing the spread. Instead of tape recording the A to D converter output

one can select a digital limit and view the result on the TV monitor: on the

monitor everything with an intensity below this selected limit will look black

and everything above will look white. Therefore, the chromosomes become

dark shapes w40se outlines are determined by their "equal grey contour

level" equal to th~s digital limit. Figure 7 presents some of the results and

illustrates the problem. By this visual check it is possible to select a

nearby optimum grey level at which the equal grey contour lines will give

a fair representation of the chr0mosomes in the spread, and to select spreads

which will be worth processing by this method. The 14 grey levels are then

chosen to cover in equal voltage steps a narrow interval centered about the

visually determined optimum and the computer print-outs of all of these

can then be used to determine the actual optimum grey discrimination level.

In this way, we have been able to demonstrate what kind of computer

processing of chromosome outlines is possible, with the programs described

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-8-

below. A more elaborate "description" of the outline of each chromosome

than the equal grey contour level at one grey level for the entire spread

will certainly be required in the future. To determine specifically the kind

of programming needed and to evaluate it step by step, it was necessary to

program actual "real" data and to find a relatively simple method for doing

this.

TV Resolving Power

Before proceeding to the description of our program a short discussion

of the resolving power of the TV system is in order. Nominally, its resolution

is 330 lines, and visually this is true, but only because the eye is able to

reconstruct, out of noise, signals such as straight lines.

Of concern is the fact that if the electrical signals for every two

adjacent raster points are equated to their proper grey value on a voltage

versus grey level scale, the resolution is effectively reduced to approximately

one half. The exact resolution depends on the gradient of the voltage or

grey level, as well. Our. sy~tem, therefore, is certainly not as good as the

monitor screen indicates visually. While greater resolution would have

improved our results, particularly on the smaller chromosomes, the main

conclusions would not be altered.

Digital Computer Program

The computer program* is outlined in Figure 8. Up to this point,

*The complete program is available at Avco Corporation, RAD

Division, Wilmington, Mas~. and copies have also been submitted to the U. s.

Atomic Energy Commiss:.on, Division of Biology and Medicine, Washington, D. C.

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-9-

we have obtained the vis ual data as electrical signals, put them into

computer form in the most compact way and decided at what shade of grey

the chromosome boundary should be drawn. This information is on the

"prepared" mag'netic tape. The computer pictorial print-out device can

reproduce this information as a picture. In fact, by a suitable choice of

grey levels the reproduced picture can be made to resemble in great detail,

and to all appearances, the original picture. But all that would be achieved

is an ingenious and expensive method of "photographing" chromosome spreads.

The next required step is a separation of the total spread into components,

each of which is one individual chromosome, no more, no less. Only then

can further classification proceed. To accomplish this task the computer

program has been developed to perform several functions in order.

A. Counting the Number of Chromosomes in a Spread.

The Vidicon scans the complete raster or grid, line by line; when

it reaches a point "darker" than the pre-selected threshold grey level for

the outline contour, it stops this progressive scan and instead starts to

search the eight nearest neighboring points systematically one by one, in a

clockwise sequence until it finds the next "dark" point. It then repeats this

systematic search, always going clockwise. In this way, it completely

traces the outline of the "dark" area, going clockwise around the boundary.

As it identifies each boundary point, it labels it as such in the computer

memory. This procedure is illustrated in Figure 9A. Criteria for rejections

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-10-

of outlines which are too short, or too Jong are incorporated in the program.

After the first completely closed outline meeting all the proper criteria

has been obtained, it is labelled chromosome outline #1 and the line by

line scan is resumed. Previously identified and labelled outlines and the

points "inside" the already identified outline are omitted, using the inter­

section criteria shown in Figure 9B. The process is continued, and by a

suitable rejection logic indicated in Figure 9B, previously identified points

are discarded, until all chromosome outlines have been established and

numbered. The output from this completed step of our program is an

outline drawing of the original chromosome spread, with each chromosome

numbered consecutively as was shown in Figure 2B. It should be noted that

the number of points making up the outlines of all the chromosomes is a

small·fraction of all raster points, only a few percent in fact, making further

computations much more economical.

If a count were all that is required of the computer system, one could

perhaps stop here. However, as illustrated previously in Figure 7, the

usefulness of this approach is limited because one cannot c·ount properly unless

there is also a degree of recognition; otherwise a chromosome may be divided

into several parts, or two chromosomes adjacent to each other may be counted

as one. Additional criteria of a "classification" sort may be needed to obtain

the correct chromosome count at this stage.

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-11-

B. Classification by Chromosome Length

After the chromosome outlines are established and counted, the next

step has been to:

(a) find the "length" of each chromosome outline. In this procedure

successive rectangles are circumscribed about the outline; each time the

rectangle sides are rotated 100 • The rectangle having the min imum area

fits the chromos orne outline best and its long s ide is taken to be the "length"

of the chromosome (see Figure 7).

(b) The whole chromosome outline is then rotated in such a way

that the longest side of the circumscribed minimum area rectangle is

vertical. This rotation produces the "erect outline. II

(c) All the erect chromosome outlines are finally lined up in neat

rows, in descending order of their lengths as shown in Figure 2C.

The number which each chromosome had in the spread is retained

with each chromosome to facilitate referral to the spread. A print-out

of the chromosome outlines, now erect and arranged similar to a karyotype

can be obtained at this stage, but two further classification criteria, chromosome

area and arm length ratio are calculated first, t,y two additional steps in

our program.

C. Calculation of Area

The area within each chromos orne outline is easily obtained by

counting the number of raster points belonging to the outline and interior of

each chromosome.

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-lZ-

As a sole criterion this area does not arrange the chromosome

nearly as well as the "lengthsll criterion, At this stage in our work we

therefore simply record the area as a percentage of that of the largest

chromosome. This percentage area, A, a number not larger than 100,

is printed next to each chromos ome outline. At the next stage of refinement

this number Gould be combined with all the other criteria, given proper

weight in the evaluation, and all the chromosomes could then be reordered

accordingly.

D. Determination of Arm Ratio

In the idealized "general" chromosome shown in Figure 10, the

arm length of the short arms is labelled AI' that of the long arms is

labelled A Z while the total length is labelled L. One' can therefore define

a percentage arm ration R :: (All AZ) x 100. For a so-called "·median"

chromosome for which Al = AZ

' R = 100; for an acrocentric chromosome

R will approach zero while, in general, it can take any value in between.

For the computer to determine R, it needs to find the position of the

line XXI. This is done by checking the number of intersections a hor~ zontal

line makes with the erect chromosome outline as the line is traversed from

top to bottom. For the typical case shown, the number of intersections goes

through the following sequence at the points marked a to k, as ~hown in

Table I. The line XXI. the center of the centromere is taken to lie mid-way

between the points e and g and found in this way. The ratio R is then calculated.

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~13~

TABLE I

Sequence of Boundary Intersections for Typical Chromosome

Point

a

b

c

d

e

£

g

h

i

j

k

Number of Intersections with Boundary

1

2

3

4

3

2

3

4

3

2

1

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-14-

Pictorial Print-Out

It is desirable to extract all the information obtained by the computer

in an easily readable form. As the information wanted is in large part,

pictorial, a graphic output device is most advantageous. Therefore, we

print out our results on two pages of ordinary size paper per spread by

means of the Stromberg-Carlson SC-4020. The first page is the reproduction

of ' the spread without rearrangement, but with the chromosomes represented

by their computer-determined outlines and numbered consecutively, which

is us eful for quick reference to the original material. As shown in Figure 2B

the location numbers appear just above each chromosome outline.

The complete count of the outlined chromosomes appears with the

outline located at the bottom of the page. If there has been no error, this

hi.ghest figure will be the number of chromosomes in the spread.

The second page, Figure 2C, presents the computer karyotype. It

shows all the " erect" outlines, in order of their length, L. Up to four sets

of numbers accompany each chromosome outline on its right side. The

bottom number identi1je~ the chromosome on the spread; A indicates the

-relative area of the chromosome and, where computable, R, the ar,m ratio,

is shown. The top number on the larger, well resolved chromos omes is the

manually arrived classification number of the chromosome, as shown in Figure

2D.

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-15-

When, with more sophisticated programming, better values of

length, (L), area (A) and arm ratio (R) become available for a representative

number of spreads, the sequence in which the chromosomes will be printed

out would not be in the order of their length but in the order of the magnitude

of a function S of L, A, and R, for instance the function

in which W l' W 2' and W 3 are weighting factors to be determined from

comparison with manually prepared karyotypes.

Even in their present size .. determined sequence the agreement between

the computer and the manually assigned classification numbers of the

larger chromosomes is excellelit. This can be seen by examining Figure 2C

which is typical of several spreads processed in this way.

Cost and Time

The IBM 7094 running time required to process a complete spread

was approximately one minute. No attempt was made during this initial

trial and error stage to minimize this running time, because most of the

computer cost is in the program development. At the commercial rate of the

7094 equIpment, one minute, representing a cost of $10 per "computer

karyotype" is a most encouraging factor.

Conclusions

The applicability of a pictorial pattern recognition program. to

chromosome analysis at moderate cost and without the construction of

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-16-

specialized equipment has been demonstrated. Computer analysis of chromo­

some spreads presented some unforeseen problems because of the non-uniform

staining of the material, but considerable progress has been made in

developing parts of a workable program as well as in identifying existing

problems in terms of computer processing.

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IIfA ~

~."""" ~

BIBLIOGRAPHY

1. Chu, E. H. Y. andN. M. Giles. 1959. Human chromosome complements

in normal somatic cells in culture. Am. J. Hum. Genet. 11:63.

2. Human Chromosome Study Group (Denver). 1960. A proposed standard of

nomenclature of human mitotic chromosomes. Lancet. 2: 1063.

3. Ford, C. E. 1964. Autosomal abnormalities. In: Second International

Conference on Congenital Malformations (Ed. M. Fishbein). International

Medical Congres,s. New York.

4. Nowell, P. C. and D. A. Hungerford. 1960. A minute chromosome in

human chronic granulocytic leukemia. Science. 132: 1497.

5. Tough,!. M.,K. B. Buckton, A. G. Baikee, and E. R. D. Williamson.

1963. Cytogenetic studies on bone -marrow in chronic myeloid leukemia.

Lancet. 1:844.

6. Socolow, E. L., E. Engel, L. Mantooth, and J. B. Stanbury. 1964. Chromo-

somes of human thyroid tumors. 3: 394.

7. Tough, 1. M., K. D. Buckton, A. G. Baikie, and W. M. Court-Brown. 1960.

X-ray induced chromosome damage in man. Lancet. 2:849.

8. Evans, J. H. 1962. Chromosome aberrations induced by ionizing radiations.

Int. Rev. Cytol. 13: 221.

9. Engel, E., J. M. Flexner, L. Mireille, E. de Montmollin, and H. E. Frank.

1964. Blood and skin chromosomal alterations of clonal type in a leukemic

man previous1 irradiated for lung carcinoma. Cytogenetics. 3: 228.

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10. Boyd, E., W. W. Buchanan, and B. Lennox. 1961. Damage to chromosomes

by therapeutic doses of radioiodine. Lancet 1: 977.

11. Elves, M. W., A. S. Buttoo, M. C. G. Israels, andJ. F. Wilkinson.

1963. Chromosome changes caused by 6-azauridine during treatment of

acute mye10blactic leukemia. Brit. Med. J. 1: 156.

12. Falek, A. and P. W. Neurath. 1963. Quicker chromosome analysis. Lancet

No. 7320. p. 1277.

13. Falek, A., P. W. N eurath, and T. W ar~s . 1965. Anal ys is of chromos orne s

by computer, Mammalian Chromosomes 15: 101.

14. Mendelsohn, M. J., W. A. Kolman, and R. C. Bostrom. 1964. Initial

approaches to the computer analysis of cytophotometric fields. Annals,

New York Academy Sci. 115:998-1009.

15. Butler, J. W., M. K. Butler, and A. Stroud. 1964. Automatic classification

of chromosomes. In: Data Acquisition and Processing in .Biology and

Medicine. Vol. 3, K. Enslein, Ed. 261-275. Pergamon Press.

16. Ledley, R. S. 1964. High-speed automatic analysis of biomedical pictures.

Science 146: 216-223.

Acknowledgements

Supported in part by the U. S. Atomic Energy Commission of Biology and

Medicine. Contracts #AT-3381 and AT-3400. The supply of rare samples

of nearly "ideal" slides, negatives, or prints initially by Dr. H. Punnett

and subsequently by Drs. A. Morishima, L. Razavi, Sajiro Makino,

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F. Sergovich and M. Shaw were extremely helpful in the development of

our approach and are gratefully acknowledged, as is the technical

assistance of Miss Jean Nolan.

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· . '

Figure 1 -

Figure 2 -

Figure 3 -

Figure 4 -

Figure 5 -

Figure 6 ~.

Figure 7 -

List of Figure Captions

Complete block diagram of computer chromosome processing:

heavy outline s for" equipment, light outlines for input and output items.

Complete exarr1p!e of computer processing of normal, male, 46-XY

chromost~me sp!'~ad: (A) print of spread, (B) computer determined

chromosome outli::::'.es of equal grey level, identified by being numbered

corl.secuti·vely, 1 to 46, (C) computer array of the outlines shown in

B, with thei:r identification number, the percent area "A, II the arm

ratio uR, II as defi:'f!ed in the text, and their corresponding manually

determined class~£:cation for comparison, (D) manual karyotype.

Block diag:L'am of s cann~ r and analog to digital computer and tape

:r'ecorde:~.

ComplE:!te mi(:.:"oscope - TV system.

High spef: d analog tu digHal converter with tape unit.

T"fF~-Ca~ a:r.~alog g:~.g:':lal i:-om. TV camera. Two ~can lines, 1 and 2 are

s.l:lo-~!.l.; 100 m:~.~~:se~('''ld s';Neep time, 6 millisecond synch pulse.

Voltage m.agr..itude and zero level can be modified arbitrarily by the

use of a ::H::·.tablc a~pl::.fie!".

Criteria of equal g:~ey level, pictures taken from the slow-scan TV

monitor: (A) good p:r'int of chromosome spread, reproduced as analog

signal in all shades of g:t"ey; note light grey centromere IILI!;

(B) same spread as A, recorded digitally on b :k and white only;

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Figure 8 -

." l"/ ~ . ,

': :',.J' . . ~

-2-

discrimination level - 165. Note broken chromosome L, simultaneous ~

with lack of sepa:r:l.tio~ of arms of other chromosome, T; (A 1) identical

to A, but print has been retouched to darken light grey areas; (D) same

sp!"ead as AI, recorded digitally, as black and white only; discrimina-

tion level - 190. All chromosomes properly outlined.

Block diagram of digital computation.

Figure 9A - Schematic representation of method of boundary search_

Figure 9B - Some possible bo~nda!"y intersections with previously located

chromos ome •

Figure 10 - GeneraHzed chromosome outline and a circumscribed rectangle of

length L. The ch:to:mosome arm ratio R :.-: 100 Al/AZ-