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IAIMS
May 2003 Symposium Posters
---Genomics, Proteomics, Pharmacogenomics and
Bioinformatics---
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Title
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Schools/Companies
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Description
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Comparison of Clustering Methods applied to Microarray Data, and Data
Depth Based Clustering and Cluster Validation
Jonathan
Z. Pan, Rebecka Jornsten and
Ronald P. Hart
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Rutgers University
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Comparison of some traditional methods such as principal components
and principal components shaving for finding gene clusters, as well
as a novel data depth based method.
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Quantitative morphologic studies in neuroradiology
using shape signatures and dynamic databases
Gabriela Niculescu,
David J. Foran2
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Rutgers1 University, University
of Medicine & Dentistry of New Jersey2
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Developed a dynamic imaging database for
performing comparative morphologic studies in diagnostic radiology
to facilitate clinical assessment. 3D
object recognition methods based on Fourier descriptors provided
greater discriminatory power among disorders than did the traditional
volumetric measurements
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Computer-Aided Molecular Modeling of Androgen Receptor and Its Ligands
Ni
Ai1, Seong-Jae Yu2,
Robert K. Delisle3 and William J. Welsh1.
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1University
of Medicine and Dentistry New Jersey, RWJMS
2FMC
Corporation,
3Accelrys
Inc
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A strong correlation was found between
the computed binding energies for this series of compound and the
corresponding
published values of the observed relative binding affinity for rat
AR. Comparison of ligand binding energies revealed a
general trend of enhanced binding affinity for this AR variant over
the wild-type AR, consistent with published experimental findings
that this AR variant exhibits reduced ligand specificity and is inappropriately
activated by progestin, estrogen, and even the anti-androgen hydroxyflutamide.
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Molecular Modeling and Design of Subtype
Selective Compounds that Target the Opioid Receptors
Youyi Peng1, Seong Jae Yu2,
Qiang Zhang1 and
William J. Welsh1
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1University
of Medicine and Dentistry of New Jersey- RWJMS
2FMC Corporation
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Employing approaches in computer-aided
molecular modeling and design, conducted a study aimed at the discovery
of novel d-opioid selective small-molecule compounds useful for therapeutic
applications. Three-dimensional quantitative structure-activity relationship
(3D-QSAR) models were constructed. These models will be used to guide
the rational design of new analogs exhibiting high affinity and selectivity
for d-opioid receptor.
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Synthesis of Novel Opioid Receptor Active
Agents
Qiang Zhang, Youyi Peng and William
J. Welsh
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Department of Pharmacology,UMDNJ-RWJMS
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The chemical synthesis of novel small-molecule
compounds that were computer designed to bind the delta (d), kappa
(k) and mu (m) opioid receptors using
a facile reaction pathway that produces product in high yield.
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Analysis of Global Changes in Gene Expression Due
to Mst1 Overexpression in the Murine Heart.
Daniela
Zablocki, Lin Yan, Hui Ge,BS, Junichi Sadoshima
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Department of Cell Biology and Molecular
Medicine-Cardiovascular Research Institute
University of Medicine and Dentistry of New Jersey-NJMS
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The aim of the project was to investigate
the mechanisms of overexpression of Mst1 induces this phenotype analysis
of global changes in gene
and protein. The gene expression was carried out using cDNA microarrays
and proteomics. The analysis indicated that a variety ofmetabolic
genes, both mitochondrial and cytoplasmic, are down-regulated in
the left ventricles of Mst1 transgenic mice when compared to non-transgenic
mice.
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Genesis of the Catalytic of Cleft DNA Polymerases: Bioinformatics Approach
Using 3d Structure Database.
K.
Singh and M.Modak
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Department
of Biochemistry and Molecular Biology,
University of Medicine and Dentistry of
New Jersey –NJMS
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Using Bioinformatics approach reported that
a number of diverse proteins that interact with the nucleic acids,
nucleotides and divalent cations with
or without catalytic function utilize the same structural motif as
seen in DNA polymerases. A search of protein databank is performed
using the palm sub domain of E.coli DNA
polymerase I as a template. A total of 181 proteins containing 3D
homology with the palm sub domain were identified.
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Analysis of the Fingers Subdomain in Various
Families of DNA Polymerases: A Bioinformatic Approach
Deborah Josko , K.Singh, & M.
Modak
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Department of Health Informatic-SHRP
Department of Clinical Laboratory Sciences,
Department of Biochemistry and Molecular Biology-UMDNJ
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This research presents a structural bioinformatics
analysis of the fingers subdomain of the six families together
with viral DNA polymerases. The crystal structures of the members
of various DNA polymerase families show that they all share motifs
that resemble the fingers, palm and thumb of a half-opened right
hand. The palm region, which contains the active site, has been conserved
throughout evolution. The fingers and thumb subdomains however
vary considerably across families.
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Design, Implementation and Monitoring of Internet-based Prospective
Data Collection in an Epidemiologic Study of Asthma and the Environment.
Alan
C. Diamond1,2, Clifford P. Weisel, Ph.D.3, Neil
Lee1, Stanley H. Weiss, M.D.1 (PI).
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1Department
of Preventive Medicine and Community Health, University of Medicine
and Dentistry of New Jersey –NJMS
2 Rochester Institute of Technology
3 EOHSI
UMDNJ-RWJMS
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This is a research report on the development of the www.njasthma.org
website. The overall purpose of the study is to investigate the causes
of asthma exacerbation in the community among school children in
Warren County, NJ. Created an interactive (web based) database, which
allows student to submit the data from the Asthma patient.
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Alteration of Protein Turn-over Detected by Proteomic Analysis During
the Transition from Stable Hypertrophy to Failure.
Lin Yan,
Hong Li, Song-Jung Kim, Li Chen, Oian Wang, Hui Ge, Azhar Mahmood,
Dorothy E. Vatner, Christophe Depre, Kiran Madura, Stephen F. Vatner
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University of Medicine and Dentistry of
New Jersey –NJMS
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The goal of this study was to use proteomic approaches to reveal alterations
in protein expression between LVH and LVH/HF in this novel large
mammalian model, and to elucidate molecular mechanisms in the transition
from severe compensated LVH to the development of decompensate LVH/HF.
Developed a novel canine model of severe left ventricular hypertrophy
(LVH) and HF, where HF is induced in the setting of stable, severe,
chronic (2 yrs) LVH. The combined LVH and HF model mimics HF developed
in patients.
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Computer-Aided Design of Polymers for Biomedical Applications
Hongxia Zhao1, Sascha Abramson2,
Vladyslav Kholodovych3,
Doyle Knight1, Joachim Kohn2 and William
J. Welsh3
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1Department
of Mechanical and Aerospace Engineering, 2Department
of Chemistry and Chemical Biology Rutgers University,3Department
of Pharmacology, University of Medicine and Dentistry-RWJMS
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Presented an Artificial Neural Network
(ANN) model that correlates the chemical properties of 62 polyarylates
with
the proliferation of Fetal Rat Lung Fibroblasts (FRLF) and Normal
Fetal Foreskin (NFF) cells grown in tissue culture in these polymers.
Thirty-one polymers were chosen at random (the training set)
to train the ANN for each cell type and the remaining subset (the validation
set) was evaluated against the ANN.
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Unsupervised Imaging, Registration and Archiving Of Tissue Microarrays
Wenjin Chen, Dr. Michael Reiss, Dr.
David J. Foran
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Pathology, Cancer Institute of New Jersey , University
of Medicine and Dentistry
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Developed a web-based prototype which features automated imaging, registration
and intelligent archiving of tissue Microarrays (TMA) in multi-user,
network environments.
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Effect of Muscle Unloading on Energy Metabolism
Pathways in the Liver of Hindlimb Suspended Rats.
T.P.
Stein, PhD1, M.D. Schluter1, A.T. Galante2,
P. Soteropoulos2, L. Baer3, R.E. Grindeland3,
T.J. Wang3 and C.E. Wade, PhD3
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1SOM & 2Center
for Applied Genomics, University of Medicine and Dentistry of New
Jersey – NJMS
3NASA Ames Research Center,
CA
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Muscle atrophy is associated with a shift
in fuel metabolism away from the use of lipid fuels towards an increased
reliance on glycolyis. We hypothesized that if amino acids requirements
by atrophied muscle some of the excess amino acids will be degraded
via gluconeogenesis thereby increasing
glucose supply to muscle. To test this hypothesis
the combination
of the rodent hind limb suspension model and microarray expression
analysis are used . Conclusion: Decreased metabolic activity by unloaded
muscle is associated with an increase in gluconeogenesis in
the liver with excess amino acids being the most likely precursors. Amino
acids could be in excess because amino acid needs by atrophied muscle
are reduced.
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Fetal Gene Expression and Pregnancy Outcome.
T.
Peter Stein1, Margaret D. Schluter1, Patricia
A. Soteropoulos2, Anthony T. Galante2, Peter
P. Tolias2, Theresa O. Scholl3
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1SOM & 2Center
for Applied Genomics, University of Medicine and Dentistry of New
Jersey – NJMS
3 Obstetrics
and Gynecology, UMDNJ-SOM
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The objectives of this study were to use
mRNA expression analysis of fetal lymphocyte metabolism to determine
whether there was a correlation
between aberrant fetal gene expression and pregnancy outcome. The
Affymetrix GeneChip Expression analysis software (version 5.0) was
used to identify probes present
and the GenMAPP program to identify their biochemical role.
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An Image Funnel for Generating Selective Cell Archives.
Wei He1, M.S., Lauri A.
Goodell2, M.D. David J. Foran1,2, Ph.D
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1 Center for Biomedical Imaging & Informatics, 2 Department
of Pathology & Laboratory Medicine University of Medicine & Dentistry
of New Jersey-RWJMS
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Developed software which automatically drives and coordinates the functions
of a robotic microscope and image acquisition device while simultaneously
performing color filtering, histogram minimization, and convolution.
Pattern recognition algorithms first identify candidate cells during
a low-resolution pilot scan of the specimen. The system subsequently
performs a high-resolution scan of each candidate target while generating
the spectral and spatial signature for each. Cells which meet specific
search criteria are automatically serialized and streamed to one
or more mirror sites
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Method for the Discovery Of Novel Na+, K+-Atpase
Inhibitors for the Therapeutic Treatment of Cardiovascular Diseases
and Conditions
Susan
M. Keenan1, Vladyslav Kholodovych1, Robert K. Delisle2,
William J. Ball3,and William J. Welsh1
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1Department
of Pharmacology University of Medicine and Dentistry-RWJMS 2Pharmacopia,
3 Department
of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati
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Research group has modeled the extracellular
and transmembrane domains of the human 1a-subunit of the of the Na,
K-ATPase from
the high-resolution crystal structure of SERCA1a (skeletal muscle
sarcoplasmic recticulum/endoplasmic recticulum Ca2+-ATPase)
and in doing so has developed a pharmacophore,
which, for the first time, will allow for the de novo design
of drug candidates based on receptor structure.
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Characteristics of the Plasmodium Falciparum PK5
ATP-Binding Site: Implications for the Design of Novel Antimalarial
Agents
Susan
M. Keenan and William J. Welsh
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Department of Pharmacology, University
of Medicine and Dentistry of New Jersey ,
Robert Wood Johnson Medical School
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Presented a three-dimensional structural model of PfPK5
constructed using computer-based homology modeling techniques. This
model was used to compare the ATP binding-site of PfPK5 with
that of the mammalian kinase CDK2. Furthermore, kinase-ligand
interactions of PfPK5 with known inhibitors were investigated
and compared to available crystal structures of CDK2 with inhibitors
bound. The focus of the study is to identify similarities and differences
between the ATP binding sites of the two kinases that
can be exploited for future rational drug design.
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A Cell Model-Based Analysis of Microarray Data.
Sungchul Ji, (a), Pamela Ohman-Strickland (b),
and Jong-kook (c)
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a) Department of Pharmacology and Toxicology,
Rutgers University, (b) Division of Biostatistics, UMDNJ-SPH, (c)
Division of Information
Science, Korea Nazarene University, Chun Ahn, Korea.
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Research group proposed that mRNA levels
and gene expression rates cannot be so simply correlated, manly because
the mRNA levels in
the cell are determined not only by the rates of mRNA synthesis (V_syn)
(i.e., gene expression) but also by the rates of mRNA hydroslysis
(V_hyd). An equation that relates changes in the cellular levels
of mRNA,
measured over the time period, dt, i.e., dRcel l/dt, and
changes in the rates of mRNA synthesis, dVsyn, and hydrolysis,
dVhyd,
that are induced by control mechanisms of the cell other than mRNA
levels: (1) dRcell/dt = dVsyn - dVhyd, where
d indicates the difference between final and initial states.
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A Multiple-Imputation Method for Analyzing Microarray
Data
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(a) Department of Statistics, Dongguk University, Korea,
(b) Computational Chemodynamics Laboratory,
UMDNJ-RWJMS.
(c) Division of Information Science, Nazaren
University
(d) Department of Pharmacology and Toxicology
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Due to fabrication defects in microarrays
and/or experimental errors in gene activity assays, a significant
fraction
(~10%) of gene activity measurements is routinely deleted before
microarray data are subjected to statistical analyses. The data set
before deleting any obviously defective measurements is here referred
to as the "original data set (ODS)" and the one after removing
faulty measurements as the “deleted data set (DDS)". It
is generally assumed that deleting whole rows of measurements from
ODS
due to some defective elements in them has no significant effect
on the results of cluster analysis.
Defined "the core clusters (CC)" as
the clusters resulting from the intersection of sets of individual
clusters generated by
multiple imputations. CC so defined have the stability and reliability
that appear essential for representing the clustering properties
of microarray data.
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Use
of DNA Arrays to Isolate Genes Involved in Morphine Tolerance and
Dependence
M.
A. Ansonoff, T. Wen J. E. Pintar
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Dept. of Neuroscience and Cell Biology,
UMDNJ-Robert Wood Johnson Medical School
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Studies of morphine action in opioid receptor
knockout mice have demonstrated that all actions of morphine in regards
to analgesia require a functional MOR-1 gene. However, the development
of morphine tolerance requires the presence of the DOR-1 gene. Likewise,
the KOR-1 gene has been implicated in the development of morphine
dependence. By performing DNA arrays on wild type, MOR-1, DOR-1,
and KOR-1 knockout mice, we have been able to isolate the subset
of regulated genes responsible for morphine tolerance and dependence
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