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T Grossman

Publications and source records attributed to T Grossman.

7 recordsLinked to original sources
PubMed1996

Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disorder recently shown to be caused by mutations in the heparan sulfate proteoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have used Southern blot analysis and polymerase chain reaction amplification of intra-exonic sequences to identify four new GPC3 mutations and further characterize three previously reported SGBS mutations. De novo GPC3 mutations were identified in 2 families. In general, the mutations were unique deletions ranging from less than 0.1 kb to more than 300 kb in length with no evidence of a mutational hot spot discerned. The lack of correlation between the phenotype of 18 affected males from these 7 families and the location and size of the GPC3 gene mutations suggest that SGBS is caused by a nonfunctional GPC3 protein.

Abnormalities, Multiple↗
PubMed1995

Neural net representations of empirical protein potentials.

Recently, there has been considerable interest in deriving and applying knowledge-based, empirical potential functions for proteins. These empirical potentials have been derived from the statistics of interacting, spatially neighboring residues, as may be obtained from databases of known protein crystal structures. In this paper we employ neural networks to redefine empirical potential functions from the point of view of discrimination functions. This approach generalizes previous work, in which simple frequency counting statistics are used on a database of known protein structures. This generalization allows us to avoid restriction to strictly pairwise interactions. Instead of frequency counting to fix adjustable parameters, one now optimizes an objective function involving a neural network parameterized probability distribution. We show how our method reduces to previous work in special situations, but also allows extensions to include orders of interaction beyond pairwise interaction. Given the close packing of proteins, steric interactions etc., the inclusion of higher order interactions is critical for developing an accurate potential. A key feature in the approach we advocate is the development of a representation to describe the spatial location of interacting residues that exist in a sphere of small fixed radius around each residue. This is a "shape representation" problem that has a natural solution for the interaction neighborhoods of protein residues. We demonstrate in a series of numerical experiments that the neural network approach improves discrimination over that obtained by previous methodologies limited to pair-wise interactions.

Amino Acid Sequence↗
PubMed1993

A neural network classifier in experimental particle physics.

A classification problem in high energy physics has been solved on simulated data using a simple multilayer perceptron comprising binary units which was trained with the CHIR algorithm. The unstable training of such a network on a nonseparable set has been overcome by selecting those weight vectors with good performance while providing a flexible choice of the two types of classification errors. Specific features of the problem have been exploited in order to simplify and optimize the solution which has been compared to the popular backpropagation algorithm and found to perform on a similar level. Additional aspects of this work are the use of the CHIR algorithm on continuous input and incorporating the classic idea of a phi-machine in a multilayer perceptron.

Algorithms↗
PubMed1992

Characterization of F-pilin as an inner membrane component of Escherichia coli K12.

Antipeptide antibodies were used to detect, purify, and characterize nonfilament F-pilin in the cell envelope of an F'tra+ strain of Escherichia coli. Affinity-purified goat antibodies raised against a peptide corresponding to the amino-terminal 14 amino acids of F-pilin detected F-pilin in immuno-overlay ("Western") blots of electrophoretically separated inner and outer membrane proteins. As expected, the molecule was absent from inner membrane preparations of F- or F'traA[Am] strains. Immunoreactive material was purified from inner membrane fractions and shown to be F-pilin by amino acid analysis. The anti-peptide antibodies also detected membrane forms of F-pilin produced by cells containing plasmid pTG801 (Grossman, T. & Silverman, P. (1989) J. Bacteriol. 171, 650-656). Most cell envelope pilin was in the inner membrane fraction, but a significant quantity fractionated with the outer membrane as well. The hydropathy profile of F-pilin suggested that the molecule is an integral membrane protein with two membrane-spanning domains. In confirmation, F-pilin and pTG801 pilins in inner membrane preparations were solubilized by a single extraction with the nonionic detergents Nonidet P-40 (2%) or Triton X-100 (2%), but not by 2 M KCl or 0.1 M NaOH. Moreover, analysis of traA'-'phoA constructs indicated that both the amino and carboxyl termini of F-pilin face the periplasm. The periplasmic location of the amino terminus was confirmed by immunoelectron microscopy of spheroplasts from F' and pTG801 strains, using a monoclonal antibody that recognizes an amino-terminal epitope. These data suggest a specific structure for membrane F-pilin. We discuss that structure in relation to the probable structure of filament F-pilin.

Amino Acid Sequence↗
PubMed1992

Imaging rounds. Synovial chondromatosis.

The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenograms are found on the first two pages. The following pages present the final clinical and roentgenographic differential diagnosis.

Chondromatosis, Synovial↗
PubMed1989

Esophageal atresia complicating the Goldenhar anomalad.

A 2200 g male infant was found to have esophageal atresia and esophageal fistula in addition to truncus arteriosus and oculo-auriculo-vertebral dysplasia. The presence of facial asymmetry in an infant with esophageal atresia should prompt a search for additional anomalies before surgery is contemplated.

Esophageal Atresia↗