A5064022214- Gene Regulatory Network Analysis
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- COVID-19 epidemiological studies
- Pancreatic and Hepatic Oncology Research
- Microbial Metabolic Engineering and Bioproduction
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- SARS-CoV-2 and COVID-19 Research
- Machine Learning in Materials Science
- Influenza Virus Research Studies
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Data-Driven Disease Surveillance
- Fungal and yeast genetics research
- Click Chemistry and Applications
- DNA and Nucleic Acid Chemistry
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Mast cells and histamine
- Evolutionary Algorithms and Applications
- Protein Structure and Dynamics
- Advanced Multi-Objective Optimization Algorithms
Northern Arizona University
2015-2024
Los Alamos National Laboratory
1989-2021
Sandia National Laboratories California
2021
Oak Ridge National Laboratory
2021
University of California, Davis
2021
University of Michigan
1994-2020
Hanover College
2020
Library of Michigan
2020
Ann Arbor Center for Independent Living
2020
Translational Genomics Research Institute
2006-2017
Increased extracellular matrix (ECM) deposition is a characteristic observed in many solid tumors. levels of one ECM component-namely, hyaluronan (HA)-leads to reduced elasticity tumor tissue and increased interstitial fluid pressure. Multiple initial reports showed that the addition hyaluronidase (HYAL) chemotherapeutic regimens could greatly improve efficacy. Unfortunately, bovine HYAL used those studies was limited therapeutically by immunologic responses treatment. Newly developed...
Abstract Pancreatic cancer is characterized by a desmoplastic reaction that creates dense fibroinflammatory microenvironment, promoting hypoxia and limiting drug delivery due to decreased blood perfusion. Here, we describe novel tumor–stroma interaction may help explain the prevalence of desmoplasia in this cancer. Specifically, found activation hypoxia-inducible factor-1α (HIF-1α) tumor strongly activates secretion sonic hedgehog (SHH) ligand cells, which turn causes stromal fibroblasts...
Halogen bonding has recently come to play as a target for lead optimization in rational drug design. However, most docking program don't account halogen their scoring functions and are not able utilize this new approach. In study improved function (XBSF) is presented along with its implementation the AutoDock Vina molecular software. This termed VinaXB, where XB stands parameters that were added.XBSF derived based on X···A distance C-X···A angle of interacting atoms. The term was further...
Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 seasons, 26 forecasting teams provided national jurisdiction-specific probabilistic predictions of weekly confirmed hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using Weighted Interval Score (WIS), relative WIS, coverage. Six out 23 models outperform baseline model across forecast locations in 12 18 2022-23. Averaging all...
The epidermal growth factor receptor (EGFR) kinase is generally considered to be activated by either ligand-induced dimerisation or a conformational change within pre-formed dimers. We report the relationship between higher-order EGFR oligomerization and phosphorylation on surface of intact cells. have combined lifetime-detected Forster resonance energy transfer, as probe state image correlation spectroscopy, extract relative association versus unactivated EGFR, determine ratio average...
Pancreatic adenocarcinoma (PAC) is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads been difficult and majority currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC patients understand range aberrations that are occurring each tumor. Because understanding tumorigenesis limited, evaluation separate cases may reveal...
In systems biology modeling, important steps include model parameterization, uncertainty quantification, and evaluation of agreement with experimental observations. To help modelers perform these steps, we developed the software PyBioNetFit, which in addition supports checking models against known system properties solving design problems. PyBioNetFit introduces Biological Property Specification Language (BPSL) for formal declaration properties. BPSL allows qualitative data to be used alone...
Interactions of molecules, such as signaling proteins, with multiple binding sites and/or post-translational covalent modification can be modeled using reaction rules. Rules comprehensively, but implicitly, define the individual chemical species and reactions that molecular interactions potentially generate. Although rules automatically processed to a biochemical network, network implied by set is often too large generate completely or simulate conventional procedures. To address this...
Abstract Background The system-level dynamics of many molecular interactions, particularly protein-protein can be conveniently represented using reaction rules, which specified model-specification languages, such as the BioNetGen language (BNGL). A set rules implicitly defines a (bio)chemical network. network implied by is often very large, and result, generation tends to computationally expensive. Moreover, cost commonly used methods for simulating function size. Together these factors have...
We describe a general approach for the quantitative analysis of interaction among fluorescent peptide ligands (L), receptors (R), and G proteins (G) using fluorescence flow cytometry. The scheme depends upon use commercially available microbeads as standards to calibrate concentration peptides in solution receptor number on cells suspension. have characterized family fluoresceinated formyl analyzed both steady-state dynamic aspects ligand peptide-receptor interactions digitonin-permeabilized...
The N-methyl-3'-O-anthranoyl (MANT) guanine nucleotide analogs are useful environmentally sensitive fluorescent probes for studying G protein mechanisms. Both MANT-GTP gamma S (mGTP S) and (mGTP) displayed a magnesium-dependent increase in fluorescence upon binding to bovine brain G(o). A much greater MANT-guanine was observed with excitation at 280 nm compared 350 nm, due energy transfer from tryptophan G(o)-bound mGTP displays blue-shift its emission spectrum indicating nonpolar...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAggregation of IgE-receptor complexes on rat basophilic leukemia cells does not change the intrinsic affinity but can alter kinetics ligand-IgE interactionRichard G. Posner, Benjamin Lee, Daniel H. Conrad, David Holowka, Barbara Baird, and Byron GoldsteinCite this: Biochemistry 1992, 31, 23, 5350–5356Publication Date (Print):July 16, 1992Publication History Published online1 May 2002Published inissue 16 July...
Macroautophagy (autophagy) is a cellular recycling program essential for homeostasis and survival during cytotoxic stress. This process, which has an emerging role in disease etiology treatment, executed four stages through the coordinated action of more than 30 proteins. An effective strategy studying complicated processes, such as autophagy, involves construction analysis mathematical or computational models. When developed refined from experimental knowledge, these models can be used to...
Rule-based modeling provides a means to represent cell signaling systems in way that captures site-specific details of molecular interactions. For rule-based models be more widely understood and (re)used, conventions for model visualization annotation are needed. We have developed the concepts an extended contact map guide illustrating annotating models. An represents scope by providing illustration each molecule, component, direct physical interaction, post-translational modification,...
Abstract Summary: Rule-based models are analyzed with specialized simulators, such as those provided by the BioNetGen and NFsim open-source software packages. Here, we present BioNetFit, a general-purpose fitting tool that is compatible NFsim. BioNetFit designed to take advantage of distributed computing resources. This feature facilitates (i.e. optimization parameter values for consistency data) when simulations computationally expensive. Availability implementation: can be used on...
Although many persons in the United States have acquired immunity to COVID-19, either through vaccination or infection with SARS-CoV-2, COVID-19 will pose an ongoing threat non-immune so long as disease transmission continues. We can estimate when sustained end a population by calculating population-specific basic reproduction number ℛ0, expected of secondary cases generated infected person absence any interventions. The value ℛ0 relates herd threshold (HIT), which is given 1−1/ℛ0. When...
Abstract Background Mathematical/computational models are needed to understand cell signaling networks, which complex. Signaling proteins contain multiple functional components and sites of post-translational modification. The multiplicity modification ensures that interactions among have the potential generate myriad protein complexes states. As a result, number chemical species can be populated in network, hence equations an ordinary differential equation model required capture dynamics...