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Biomedical subjects

D Zipser

Publications and source records attributed to D Zipser.

At least 19 recordsLinked to original sources
PubMed1992

Identification models of the nervous system.

It has been widely observed that when artificial neural networks are trained by supervised learning to do computations that also occur in the nervous system, the behavior of the model neurons often closely resembles that of the real neurons involved in the task. It is not immediately clear why this should be the case or what use can be made of models generated by supervised learning. Here, recent developments are reviewed and analysed in an attempt to clarify these issues. This analysis is facilitated by treating supervised learning models of the brain as a special case of system identification, a general and well-studied modeling paradigm. The neural systems identification paradigm provides a systematic way to generate realistic models starting with a high-level description of a hypothesized computation and some architectural and physiological constraints about the area being modeled. There is no inherent limitation to the realism that can be incorporated into identification models. This approach eliminates the need to find neural implementation algorithms by ad hoc means and provides neuroscientists with a convenient way to build models that account for observed data.

Algorithms↗
PubMed1988

A back-propagation programmed network that simulates response properties of a subset of posterior parietal neurons.

Neurons in area 7a of the posterior parietal cortex of monkeys respond to both the retinal location of a visual stimulus and the position of the eyes and by combining these signals represent the spatial location of external objects. A neural network model, programmed using back-propagation learning, can decode this spatial information from area 7a neurons and accounts for their observed response properties.

Animals↗
PubMed1988

The role of the teacher in learning-based models of parietal area 7a.

The back-propagation learning procedure can be used to train simulated neural networks to compute arbitrary functions. We have recently shown that when such a network is trained to carry out the transformation of stimulus location to head-centered coordinates that occurs in parietal area 7a, the response properties of certain units in the network closely resemble neurons found in area 7a. The back-propagation procedure requires the use of a teacher. Here we examine the effect of using different kinds of teachers. As long as the teacher represents information about stimulus location in head-centered coordinates, the trained network contains units of the kind found in area 7a. Differences in teacher format only effect the quantitative distribution of the different unit types. When the teacher does not represent stimulus location explicitly, the network does not contain units of the required kind.

Computer Simulation↗
PubMed1988

Learning the hidden structure of speech.

In the work described here, the backpropagation neural network learning procedure is applied to the analysis and recognition of speech. This procedure takes a set of input/output pattern pairs and attempts to learn their functional relationship; it develops the necessary representational features during the course of learning. A series of computer simulation studies was carried out to assess the ability of these networks to accurately label sounds, to learn to recognize sounds without labels, and to learn feature representations of continuous speech. These studies demonstrated that the networks can learn to label presegmented test tokens with accuracies of up to 95%. Networks trained on segmented sounds using a strategy that requires no external labels were able to recognize and delineate sounds in continuous speech. These networks developed rich internal representations that included units which corresponded to such traditional distinctions as vowels and consonants, as well as units that were sensitive to novel and nonstandard features. Networks trained on a large corpus of unsegmented, continuous speech without labels also developed interesting feature representations, which may be useful in both segmentation and label learning. The results of these studies, while preliminary, demonstrate that backpropagation learning can be used with complex, natural data to identify a feature structure that can serve as the basis for both analysis and nontrivial pattern recognition.

Computer Simulation↗
PubMed1988

The role of the posterior parietal cortex in coordinate transformations for visual-motor integration.

Lesion to the posterior parietal cortex in monkeys and humans produces spatial deficits in movement and perception. In recording experiments from area 7a, a cortical subdivision in the posterior parietal cortex in monkeys, we have found neurons whose responses are a function of both the retinal location of visual stimuli and the position of the eyes in the orbits. By combining these signals area 7 a neurons code the location of visual stimuli with respect to the head. However, these cells respond over only limited ranges of eye positions (eye-position-dependent coding). To code location in craniotopic space at all eye positions (eye-position-independent coding) an additional step in neural processing is required that uses information distributed across populations of area 7a neurons. We describe here a neural network model, based on back-propagation learning, that both demonstrates how spatial location could be derived from the population response of area 7a neurons and accurately accounts for the observed response properties of these neurons.

Animals↗
PubMed1986

A model of hippocampal learning during classical conditioning.

During classical conditioning of the rabbit blink reflex, a large fraction of the hippocampal pyramidal neurons are recruited to respond to the conditioned stimulus. The summed response of these neurons comes to match the whole time-amplitude profile of nictitating membrane movement, whereas some individual neurons respond only to part of this profile. A model is described which accounts for these data. The model proposes a learning rule to explain neuron recruitment and uses a tapped delay line to account for the temporal learning properties of the system and the spectrum of individual unit responses.

Animals↗
PubMed1985

A computational model of hippocampal place fields.

There are neurons in the hippocampus that become active only when an animal is near a particular location in a specific environment. The activity of some of these units is known to be governed by the configuration of a small set of discrete landmarks. In order to respond in this fashion, these neurons must, in effect, be able to recognize particular locations. A model of this recognition process is described which is able to make quantitative predictions about how the response of these place-field units varies as properties of the environmental landmarks are manipulated. Computer simulations of the model show that it is consistent with the available quantitative data. These simulations also predict large, characteristic changes in place-field location and size with manipulations of the environmental landmarks. Comparison of this kind of prediction with actual experiments will serve as a test of the validity of the model.

Hippocampus↗
PubMed1983

Isolation and preliminary characterization of the Chinese hamster thymidine kinase gene.

The Chinese hamster thymidine kinase (TK) gene has been isolated from a recombinant phage library constructed with genomic DNA from mouse Ltk- cells transformed to Tk+ by transfection with Chinese hamster genomic DNA. The phage library was screened by the Benton-Davis plaque hybridization technique, using as probes, subclones of recombinant phage that were isolated from mouse Ltk+ transformants by the tRNA suppressor rescue method. The Chinese hamster TK gene is contained within 13.2 kilobases of genomic DNA in the isolate designated lambda 34S4. This gene, defined by restriction enzyme sensitivity experiments, homology studies with the chicken TK gene, and mRNA blotting experiments, may extend over 8.5 kilobases. Subclones of the lambda 34S4 isolate used as hybridization probes identified a 1,400-nucleotide polyadenylated RNA as the hamster TK mRNA. The abundance of this mRNA varies dramatically in Chinese hamster cells cultured under various growth conditions, providing direct evidence that the growth dependence of TK activity may be regulated in an important way at the level of cytoplasmic TK mRNA.

Animals↗
PubMed1983

Mutational analysis of the cloned chicken thymidine kinase gene.

We have analyzed the transcription and coding unit of the chicken thymidine kinase (tk) gene. We have constructed a library of mutant chicken tk genes by the in vitro linker insertion method of Heffron et al. A total of 125 mutations within a 3.0 kbp HindIII fragment containing the gene were isolated and mapped. The effect of each mutation upon the thymidine kinase gene was determined by measurement of the transfection efficiency in mouse Ltk- cells. The chicken tk mRNA is about 2 kb and polyadenylated. The direction of transcription was also determined. From these results, we propose a structure for the gene in which at least three small introns separate the amino acid coding region into at least four segments.

Animals↗
PubMed1981

Mapping functional domains in the promoter region of the herpes thymidine kinase gene.

The cloned herpes simplex virus type 1 (HSV-1) thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene can be used to transform TK- cells to a TK+ phenotype. Transformants generated in this way express TK at a basal constitutive level that is inducible to a higher level by infection with TK- herpes virus. We have studied the effect of mutations generated in vitro on both the constitutive and virus-induced expression of TK in transformants. Four Xho I linker insertions and two deletions in the 5' untranscribed region of the cloned HSV-1 TK gene were generated in vitro. A deletion that removed all but nine base pairs of the 5' untranscribed region virtually eliminated constitutive expression and completely prevented induction by herpes virus infection. Two of the insertions have particularly interesting properties. One, nine base pairs upstream from the cap site, inactivates constitutive expression without stopping induction. The other, 50 base pairs upstream from the cap site has the opposite effect (i.e., normal constitutive expression but no induction). Analysis of these results leads us to propose that the 5' untranscribed region of the HSV-1 TK gene is quite complex with several functional domains having differential roles in the constitutive and herpes-induced expression of the TK gene.

Base Sequence↗
PubMed1979

Purification and characterization of protease III from Escherichia coli.

An endoproteolytic enzyme of Escherichia coli, designated protease III, has been purified about 9,600-fold to homogeneity with a 6% yield. The purified enzyme consists of a single polypeptide chain of Mr 110,000 and is most active at pH 7.4. Protease III is very sensitive to metal-chelating agents and reducing agents. The EDTA-inactivated enzyme can be reactivated by Zn2+, Co2+ or Mn2+. Protease III is devoid of activity toward aminopeptidase, carboxypeptidase, or esterase substrates but rapidly degrades small proteins. When fragments of beta-galactosidase are used as substrates for protease III, the enzyme preferentially degrades proteins with molecular weights of less than 7,000. Protease III cleaves the oxidized insulin B chain at two sites with an initial rapid cleavage at Tyr-Leu (16-17) and a second slower cut at Phe-Tyr (25-26).

Cations, Divalent↗
PubMed1979

Isolation and characterization of mutations in the structural gene for protease III (ptr).

Escherichia coli mutants defective in protease III were isolated by enzyme assays of heavily mutagenized colones. One mutant produced thermolabile enzyme, and it is presumed to have a mutation in the structural gene of protease III. Two other mutants mapping at the same site had less than 5% of the wild-type protease III level. The genetic locus of these mutations, designated ptr, was located at approximately 60 min on the E. coli linkage map based on its high frequency (70%) of contransduction by P1 with argA. Strains with less than 5% of the wild-type protease III activity grew normally and degraded nonsense fragments of beta-galactosidase at wild-type rates.

Chromosome Mapping↗
PubMed1978

Deg phenotype of Escherichia coli lon mutants.

Deg. one of the Escherichia coli systems for degrading abnormal polypeptides (e.g., nonsense fragments), is also involved in the degradation of some classes of missense proteins. Both missense proteins of beta-galactosidase and temperature-sensitive phage products appear to be degraded by the Deg system. Mutations in the Deg system are indistinguishable from mutations classically called lon or capR; all map near proC, all are mucoid, defective in protein degradation, sensitive to radiomimetic agents, and defective in P1 lysogenization. All are able to propagate temperature-sensitive phage better than lon+ parental strains. Mutations that suppress the radiation sensitivity of these strains (sul) also suppress the P1 lysogenization defect, but do not affect mucoidy or the degradation defect.

Bacterial Proteins↗