Physical Sciences and Mathematics Commons^™

Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll

Mathematics Faculty Articles

The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using …

Investigating The Role Of The Host Multidrug Resistance Associated Protein Transporter Family In Burkholderia Cepacia Complex Pathogenicity Using A Caenorhabditis Elegans Infection Model, Pietro Tedesco, Marco Visone, Ermenegilda Parrilli, Maria Luisa Tutino, Elena Perrin, Isabel Maida, Renato Fani, Francesco Ballestriero, Radleigh Santos, Clemencia Pinilla, Elia Di Schiavi, George Tegos, Donatella De Pascale

Mathematics Faculty Articles

This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were …

Modeling Of Humoral Immune Response To Repeated Influenza A Virus Infections, Abbiana Arenas, Safiyah Muhammad, Ly Nguyen, Samita Andreansky, Evan Haskell

Mathematics Faculty Proceedings, Presentations, Speeches, Lectures

Seasonal infections by Influenza A virus (IAV) causes hundreds of thousands of deaths worldwide each year, with most individuals being infected multiple times throughout their lifetimes. The relative impact of the components of the host immune system in controlling the severity and duration of repeated challenges from an IAV infection remains unclear. In particular, the differential contribution of the humoral immune response in primary and secondary challenges from IAV are relatively little explored. We develop a parsimonious mathematical model of the humoral immune response to IAV infection with biologically meaningful and identifiable parameters. We show the relative sensitivity of the …

Modeling The Geographic Spread Of Rabies In China, Jing Chen, Lan Zou, Shigui Ruan

Mathematics Faculty Articles

Abstract

In order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans, in which each province is regarded as a patch. In each patch the submodel consists of susceptible, exposed, infectious, and vaccinated subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The existence of the disease-free equilibrium is discussed, the basic reproduction number is calculated, and the effect of moving rates of dogs between …

Antigen Discovery For The Identification Of Vaccine Candidates And Biomarkers Using A T Cell Driven Approach In Combination With Positional Scanning Peptide Libraries, Valeria A. Judkowski, Radleigh Santos, Gonzalo R. Acevedo, Marc Giulianotti, Jon R. Appel, Silvia A. Longhi, Karina A. Gomez, Clemencia Pinilla

Mathematics Faculty Articles

The prevention and treatment of infectious diseases is highly dependent on the availability of reliable diagnostic tests and protective or therapeutic vaccines. There also exists an urgent need to develop reliable biomarkers to monitor treatment success and to predict disease progression from asymptomatic to symptomatic disease in several disease scenarios. The elucidation of the disease-relevant antigens that elicit the protective immune responses is critical and required for the development of biomarkers, diagnostics, and vaccines. However; one of the main obstacles to the study of antigen specificity in human T cells is their low frequency in PBMC samples. To overcome this …