VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Lederberg, J. Project: GENLIBL Department: Genetics Project Description: This project contains the statistical and miscel- laneous programs used by the Genetics Department. Statistical programs: General statistical analysis for the calculations of sum, mean, standard deviation, the analysis of variance, chisquare and probability of chisquare distribution, correlation and regression analysis, the normal distribution with the same mean and standard deviation for fitting a curve. Plotting programs: Plot bar graph in 100 positions, plot of percentage distribution, plot by function scaled to the range of O to 100, plot of multivalued function allows the choice and supersition of several characters. Flag is inserted on the chart when underflow or overflow occurred, Sorting programs: Sorting a vector in ascending order, sort array and alphabetical informations. Name: Luetscher, J. Project; ‘Slood Pr Department: Medicine - Metabolic Research Project Description: This research project deals with the secretion and metabolism of adrenal hormones. Various steroid hormones, catechola- mines, and trophic hormones are measured under different conditions of sodium loading or sodium depletion. The project attempts to define and relate groups of measurements which assist in the identification of curable forms of hypertension. The ACME system is used in this project in several ways: 1) To assist in the calculation of laboratory data; 2) To interpret the data: (a) Simulation of complex systems, (b) Statistical analysis, (c) Analysis of clinical information. 4) To store information at various stages of a sequential process, and for collection and analysis of the large amount of clinical and laboratory data which accumulates during a long investigation; 4) To aid in research training of fellows and staff, first in principles and techniques of computer use, and subsequently in practical applica- tions. (76) VITL. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Tugzati, L. Project: GRAGSON Department: Pediatrics Project Description: Programs previously utilized for statistical analysis of chromosome measurements in a family with chromosomal abnormalities are now being used for an ongoing study of the morphology of the late replicating X chromosome. Programs are also used for another ongoing study of synchronization of human Lymphocytes in culture. The use of the ACME computer for the study of children with birth defects continues. In addition, a program is now available for the storage of anthropometric data on all patients with congenital defects. A study of anthropometric measurements and dermatoglyphic patterns of sixty children with cleft lip and/or palate, utilizing the data stored in the computer and computer-assisted statistical analysis, has been completed, By using computer information, we have been able to define certain characteristics of body configuration in children with elefts. Further similar studies in other syndromes are now in progress. Name: Melges, F. Project: Mt fe Department: Psychiatry Project Description: This is a study to relate changes in temporal experience to changes in psychopathological symptoms such as depersonalization and delusions. The plan is to discover how aberrations in temporal sequenc- ing and distinquishing memories from perceptions and exoectations relate to the emergence of definable psychopathological processes, The overall notion for a number of sub-projects is: confusing past, vresent, and future underlies the central symptoms of psychosis. Sub-projects involve specific attention to drug-induced psychoses and certain symptoms of psychoses, especially depersonalization, changes in body image, paranoid delusions, end feelings of influence or alien control. Previous work has demonstrated that this approach is highly useful for understanding psychotic processes, (77) VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Nail, L. (P.I.: Farber, E.) Project: PSORIAST Department: Dermatology Project Description: Psoriasis is a chronic, scaling skin disease of un- known etiology, which affects approximately 4% of the general popula- tion, It is a lifetime disorder which does not take life, but indeed destroys it for all age groups. This project involves an investigation of the epidemiology of the disease. A questionnaire survey has been conducted from 1959 to date, Presently, work is being done on Series TI, ITI, and IV of the questionnaire survey. Follow-up studies on the familial incidence of psoriasis and the relationship of psoriasis to other diseases are being done (i.e., arthritis, diabetes, throat infection). The findings from Series are now being handled by ACME's 360/50 computer, Name: Reaven, G. Project: DISPLAY Department: Medicine - Metabolism Project Description: ACME is used for 1) Derivation of a three compartment model describing disappearance of plasma insulin, 2) Evaluation of the dog aS an experimental model for study of insulin distribution in man, and 3) Digital on-line computer display to investigate the structure of metabolic systems. Models of glucose, insulin, and triglyceride kinetics as related to diabetes mellitus and atherosclerosis are being developed. Clinical data obtained from tracer studies are analyzed by the ACME computer through five states of development. The project DISPLAY includes the third and fourth stage. The third stave automatically obtains the parameters for a linear sum of constant coefficients of a system of Linear differential equations. The results are used for the fourth stage. In this phase, the parameters are used for calculation of a theoretical curve which is displayed on a CRT. It is then compared with data which also appears on the CRT. The results of these two stages allow the changing of the parameters until a satisfactory visual fit is obtained. Similar analysis with respect to triglyceride metabolism and extension of the insulin work are now being performed. Stage four is being extended and stage five developed for analysis of non-linear meta- bolic models. VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Stark, G. Project: CHAOS Department: Biochemistry Project Description: ACME serves two primary functions. First, it is used to analyze data generated from steady state kinetic experiments on enzymes, primarily aspartate transcarbamylase from Eschenchia coli. Second, it is used to process chromatograms generated by an amino acid analyzer. It is also used for various research aud educational tasks by graduate students and medical students, such as analyzing the sedimentation velocity of proteins in the ultracentrifuge. Many of the kinetic experiments referred to above could not be done without the services of ACME, since they involve trial and error fitting of several parameters to complex functions. The routine processing of chromatograms on ACME introduces accuracy and dependability not other- wise available. VITI. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Category 4 Name: Enzmann, D. (P.I.: Zboralske, F.) Project: SWALLOW Department: Medical Student Project Description: The ACME computer is being used to assist in the study of both normal and abnormal motions of the humna esophagus during normal and induced swallowing. A series of simultaneous pressure read- ings in various locations in the esophagus are taken by the use of water filled manometers connected to electrical pressure transducers. The electrical voltages representing the pressure data are sampled and converted to digital values 5 times a second, for each of the pressure measurement sources, using the IBM 1800 computer attached to the ACME computer. The data from a swallow is then analyzed as it is obtained and immediate information is provided back to the experimenter, via the terminal, of the properties of the last swallow. Various summary tables are kept during an experimental run regarding the vroverties of all the swallows cbtained, and are available for a final surmary of the experimental data. initially all the data obtained during an ex- perimental run will be saved on data files ts allow divferent methods of analysis of the data to be explored. Name: Earris, R. (P.I.: Melges, F.) Project: PNP Department: Medical Student Project Description: This is a project which attempts to demonstrate correlations between the emotions experienced by subjects and their own appraisals of certain aspects of their environments. The concept is that emotions arise when events in the individual's situation come into certain specified relations with his goals. The study has two parts. The first involves the collection of normative data from normal subjects with respect te six emotions; namely, anger, anxiety, depression, joy, love, and calm. Subjects will be instructed to recall experiences that typify their conception of these states and to describe them on inventories. This data is then used to construct normative profiles of each emotional state and to calculate correlations between different categories of items on the inventories. The second part of the study will employ a number of expectant fathers, who will be tested in the waiting room prior to delivery and again after the birth. This data will be used to determine whether previous normative data is useful in the identification of actual emotional states and to confirm the correlations found in the earlier part of the study. VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Levine, R. (P.I.: Kretchmer, N.) Project: CPS Department: Medical Student Project Description: The purpose of this project is to characterize the control of de novo mammalian pyrimidine biosynthesis. The first two enzymes in the pathway, carbamoyl phosphate synthetase and aspartate transcarbamylase are of special concern. This first enzyme is distinct from an isozyme which provides carbamoyl phosphate for the urea cycle. Consequently the pyrimidine-specific enzyme appears earlier in gesta- tion than that which is urea-specific. ACME has been and continues to be utilized to evaluate and process data obtained during enzyme assays. However this is a relatively rou- tin application. Programs have been devised to study the very compli- cated kinetics of the carbamoyl phosphate synthetase. Physical inter- pretations have been drawn from ACME-derived functions and the control mechanism of the enzyme has been greatly clarified. It is hoped that a TV screen will become available so that our kinetic analysis programs can have a visual interaction with the investigator, C2 ta Name: Odell, R. (P.I.: Krahl, M.) Project: Department: Medical Student Project Description: The field of investigation is neuroendocrine bio- logical control. Research is being done on the interaction of hormonal and neurel events which could act as signals in transient and steady-state operation of physiological systems. The data used is based on experiments with dogs. An attempt is being made to understand biological communication systems and their signals in order to unravel physiological basis of behavior. Name: Rosenfeld, R. (P.I.: Miller, wW.) Projeet: CCUPSYCA / Department: Medical Student Project Description: This is a research project on the psychophysiological adaptation of male patients to the Coronary Care Unit. The goals of the research are to try to establish some relationships between psycho- logical variables and physiological variables, particularly as these latter affect the morbidity and mortality of patients with acute myocardial infarctions. The patients on the Coronary Care Linit are under constant daily observation and have a large number of physiologi- cal functions monitored, The study will provide a huge amount of data daily on each patient. The ACME computer will be used to store this data and make a number of statistical manipulations of the data. (81) VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Sachs, D. (P.I.: Lederberg, J.) Project: POPCIT Department: Medical Student Project Description: ACME is being used as a text editing system. Research is being done on population growth rates in various nations, and the resulting data is then correlated with natural resource use in those nations. The purpose is to understand medicine's role in alleviating problems posed by environmental deterioration. ACME's contribution to the project is that of storing text files on the data that has been collected, VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Category 11 Name: Belt, D. Project: HSA Department: Speech and Hearing Project Description: This project constitutes a program in large scale hearing and vision sereening testing. A professionally staffed mobile test laboratory has been collecting the results of hearing and vision tests performed on elementary school children, Data, which has been taken from four counties in the Bay Area, is being stored on mark-sense or punch cards for about twenty-thousand children and adults. Subse- quently, the sample will be enlared to about sixty-thousand in order to provide a broad base for the analysis of the data, The need for survey data on the incidence of hearing and vision loss is admitted with Public Health surveys dating back to 1957. It is because of this need that ACME has been employed in processing the results of these hearing and vision tests. VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Bunnenberg, E. Project: CHEM Department: Chemistry Project Description: The main goal of this project is to achieve an effective interactive computer-assisted operation of a highly specialized type of spectrophotometer -- a magnetic circular dichrometer. The utilization of organic chemical and especially biochemical applications of magnetic circular dichroism will allow the following: 1) An inerease in the operational sensitivity of the instrument through the application of digital averaging and smoothing techniques. This is especially important for this instrument because of its inherent single- beam operation; 2) The measurement of compounds having relatively strong signals much more rapidly; %) The extraction of quantitatively meaningful spectroscopic parameters from the magnetic circular dichroism spectra. This is of crucial impor- tance for much of the work and requires the implementation of generalized curve deconvolution and fitting programs, To date, the first goal (1) has been accomplished. The instrument was used to analyze lunar soil extracts for metalloporphyrins. The second goal has been partially realized. In particular, a provisional conclusion was reached: (a) Computer operation greatly decreased the time required to sean through the MD spectrum of a routine sample and (b) computer operation on a routine basis is in fact economical. This second goal, it is anticipated, will be quite useful in increasing the efficiency of measuring MCD spectra and in permitting the application of various mathematical operations to the stored spectra. This should increase the utility of MCD spectrometry to a variety of biochemical probiems, VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Cavalli, L. Project: PAVIA Department: Genetics Project Description: The purpose of this project is the simulation of populations. This simulation will be used for making predictions about evolutionary processes. Very often these processes are too complicated for standard analytical procedures; on the other hand, these simulations may indicate ways of recognizing the unimportant variables, and perhaps also indicate ways of simplifying the analyti- cal treatment of populations. At the moment the problem of the re- lationship between the intensity of selection on a phenotypic character and the effect on the genes that contribute to it is under study, Programs are also being developed for the statistical analysis for such processes and of a variety of genetic, epidemiological and other types of problems which often require the fitting of complex functions for which we must use the computer. These programs are generally sufficiently different from standard programs to warrant developing. Name: Costell, R. (P.I.: Wittner, W.) Project: AHSO Department: Psychiatry Project Description: Ninety-five randomly selected, incarcerated sex offenders completed a questionnaire containing relevant demographic data, history of sexual activity, etc. The computer is used for tabulation, analysis and statistical testing of factors of signifi- cance in the sexual histories and activities of this population. Results may yield new information relevant to the pathogenesis of these deviations, and establish the validity of this method of data collection and analysis. (85) VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Eddy, D. (P.I.: Shumway, N.) Project: NIFTY Department: Cardiovascular Surgery Project Description: The purpose of this project is to develop an optimization technique for control of infectious diseases. Currently the individuals faced with controlling an epidemic have at their disposal a wide range of control measures. These vary from acute treatment of active cases, through public health programs, to immuni- zation programs, A decision must be made as to how much of each mode of control should be applied to minimize morbidity and mortality while not exceeding available resources. Furthermore, the optimal mixture of preventive and curative programs is dynamic and varies as the disease progresses through a population. The multitude of control measures available, the interrelationships between the control variables and the behavior of the disease, and the constraints of Limited resources and time present a problem far too complex for the individual mind. This project will use a mathematical programming technique to find the optimal mixture of control methods to minimize morbidity and mortality while concurrently minimizing the demand for monetary and manpower resources. To demonstrate the technique, the disease Cholera has been chosen as an example. To date, two steps have been accomplished. A mathematical model of the disease has been constructed, and an algorithm which will find the proper weightings of the various control measures has been developed. The third step, which is the purpose of this project, is to implement the program on the ACME computer. Name: Goldstein, A, Project: OFFSTUF? Department: Pharmacology Project Description: ACME is being used for periodic data summation, statistical tests, and tabular output of results of research in methadone maintenance programs in Santa Clara County. The purpose of this research is to determine the importance of the use of methadone in treating heroin addicts. Name: Leiderman, P. Project: KENYA Department: Psychiatry Project Description: This project involves the analysis of data collected in a village in Kenya on physical, psychological, and social growth of infants during their first year of life. T-tests, Anova, Cluster analysis, Regression analysis, curve fitting are all being used., The importance of the work lies in changing family life in the underdeveloped world, nutrition, and factors influencing social relationships. (86) VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Category 12 Name; Constantinou, C. (P.I.: Govan, D.) Project: UROL Department: Urology Project Description: Studies are being done to improve the clinical appraisal follow-up and management of patients with nevrogenic bladder dysfunction secondary to spinal cord injury or disease. In particular, we are trying to determine the feasibility of utilizing computer-based techniques of information data storage, processing and retrieval in this patient popu- lation. 3 ACME is being used for real-time data acquisition and feedback, and for analysis. Analog data collected from anesthetized animals in surgery is transmitted via the interface box to the 1800 and 271 output received’ in the operating room during the experiment, There are six input channels used simultaneously for action potentials from ureteral smooth muscle, peristaltic pressure waves, urine flow rate, EKG and blood pressure. The analog output is used for driving the xY plotter and providing a reference for servomechanical pump. During experiments, data files are written from the analog inputs for long-term storage and also for short term (up to two weeks) before data reduction. ACME is also used for statistical analysis of the experimental results utilizing repression, correlation, and convolution subroutines available in the system library. The digital TV and particularly the storage oscilloscope on periodic loan from ACME is used for the rapid display and examination of results. VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Gersch, W. (P.I.: Tharp, B.) Project: SYNTHEST Department: Neurology Project Description: The application of time series methods to problems in neurophysiology and medicine is being studied. Specifically, research is being done in the following areas: 1) Development and application of new multidimensional autoregressive representation methods of spectral analysis to EEG analysis; 2) Development and application of a time series analysis technique to locate anatomical site of epileptic focus from human EEG data taken from scalp electrodes and implanted bipolar depth electrodes during generalized seizure activity; 3) Research on modeling feedback paths in the cat's visual system. Experimental data taken in the laboratory of Dr. K.L. Chow; 4) A critical computer analysis of a long standing model of vagus control of heart rate; 5) Development of a novel Markov chain-symbol pattern recognition procedure applied to recognition of cardiac arrhythmias using R-R interval data. The evaluation of the electroencephalographic activity during seizures in three patients has been completed and is being compiled for publi- cation. The major emphasis of this rather unique analysis method depends entirely on the facility available at ACME since there was no outside funding support. Name: Glaze, H. (P.I.: Shumway, N.) Project: MODEL Department: Cardiovascular Surgery Project Deseription: ACME real-time experiments have been devised to characterize a subset of the time-varying, non-linear, and memory properties of the mammalian vagal-cardiac rate control system. Heart rate data from 20 anesthetized vagotomized dogs have been acquired on-line and programs have been written for quantitation of this data. A mathematical model has subsequently been developed and standard curve fitting techniques used for quantitation of this data. The project was used to complete development of the mathematical model and to obtain hard-copy plots of the results. (88) VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Name: Thathachari, Y. (P.I.: Blois, M.) Project: DOPA Department: Dermatology Project Description: This is a study of the structure of melanins. Melanin is a polymeric pigment widely distributed throughout the plant and animal kingdoms, It has unusual physical and chemical properties. Using ACME as a real-time terminal, models of the molecular structure of melanins were generated starting with the known shape of the subunits and using various criteria for the link- ing of adjacent units. By watching the output periodically, the flow of the computation could be directed at will. For these genere- ted models, various measurable physical data were computed and compared with the experimentally derived values. Programs were espe- cially written for these calculations and were found to be very promising and fruitful. Radioactive tracer techniques for the detection and therapy of melanomas are being studied. An attempt is being made to improve on the conventional scanning techniques, making more efficient use of observations with a real-time feed back between the collection of data and their processing. Simulated experiments using ACME are under way to make a choice between alternate techniques. When the choice is made, the project will commission the equipment and the interfacing with ACME. VIII. REPRESENTATIVE SAMPLE OF USER PROJECT DESCRIPTIONS Category 13 Name: Cann, H. Project: GUAT Department: Pediatrics Project Description: This project is an investigation of factors which affect frequencies of genes controlling various human heritable characters. The extent to which selection, genetic drift, and migration affect frequencies of certain human genes is being assessed and specific selective factors are being sought. Environmental, cultural, and historical conditions favorable for this type of study have been found in settlements of Mayan Indian descendents in the Lake Atitlan Basin of southwest Guatemala. The local microgeography and mating patterns appear to enforce a high degree of genetic isolation for each of a number of Indian towns and villages ringing Lake Atitlan. These high mortality populations provide the opvor- tunity to study selection on human genetic polymorphisms. Studies of gene frequencies, segregation analysis of polymorphisms and demographic charac- terization of these sub-populations are being undertaken. This project will also contribute information on the genetic taxonomy of the American Indian. Families of large size, characteristic of the study population, will afford excellent opportunities for medical genetic inves- tigation of inherited diseases encountered in our field activities and for studies of genetic linkage. Over 2500 Indians in seven communities on the shores cf Lake Atitian are being studied for heritable blood characteristics, fertility, mortality, and other demographic indicators and socioeconomic variables. 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