A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Bayesian joint modeling of longitudinal and spatial survival AIDS data

"Joint analysis of longitudinal and survival data has received increasing attention in the recent years, especially for analyzing cancer and AIDS data. As both repeated measurements (longitudinal) and time-to-event (survival) outcomes are observed in an individual, a joint modeling is more appropriate because it takes into account the dependence between the two types of responses, which are often analyzed separately. We propose a Bayesian hierarchical model for jointly modeling longitudinal and survival data considering functional time and spatial frailty effects, respectively. That is, the proposed model deals with nonlinear longitudinal effects and spatial survival effects accounting for the unobserved heterogeneity among individuals living in the same region. This joint approach is applied to a cohort study of patients with HIV/AIDS in Brazil during the years 2002–2006. Our Bayesian joint model presents considerable improvements in the estimation of survival times of the Brazilian HIV/AIDS patients when compared with those ones obtained through a separate survival model and shows that the spatial risk of death is the same across the different Brazilian states."info:eu-repo/semantics/acceptedVersio

Genetic Architecture of a Reinforced, Postmating, Reproductive Isolation Barrier between Neurospora Species Indicates Evolution via Natural Selection

A role for natural selection in reinforcing premating barriers is recognized, but selection for reinforcement of postmating barriers remains controversial. Organisms lacking evolvable premating barriers can theoretically reinforce postmating isolation, but only under restrictive conditions: parental investment in hybrid progeny must inhibit subsequent reproduction, and selected postmating barriers must restore parents' capacity to reproduce successfully. We show that reinforced postmating isolation markedly increases maternal fitness in the fungus Neurospora crassa, and we detect the evolutionary genetic signature of natural selection by quantitative trait locus (QTL) analysis of the reinforced barrier. Hybrid progeny of N. crassa and N. intermedia are highly inviable. Fertilization by local N. intermedia results in early abortion of hybrid fruitbodies, and we show that abortion is adaptive because only aborted maternal colonies remain fully receptive to future reproduction. In the first QTL analysis of postmating reinforcement in microbial eukaryotes, we identify 11 loci for abortive hybrid fruitbody development, including three major QTLs that together explain 30% of trait variance. One of the major QTLs and six QTLs of lesser effect are found on the mating-type determining chromosome of Neurospora. Several reinforcement QTLs are flanked by genetic markers showing either segregation distortion or non-random associations with alleles at other loci in a cross between N. crassa of different clades, suggesting that the loci also are associated with local effects on same-species reproduction. Statistical analysis of the allelic effects distribution for abortive hybrid fruitbody development indicates its evolution occurred under positive selection. Our results strongly support a role for natural selection in the evolution of reinforced postmating isolation in N. crassa

Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience

<p>Abstract</p> <p>Background</p> <p>To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.</p> <p>Methods</p> <p>Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation.</p> <p>Results</p> <p>Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse.</p> <p>Conclusion</p> <p>When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.</p

Volume 05

Introduction from Dean Dr. Charles Ross The Tallis House as an Extension of Emily Tallis in McEwan\u27s Atonement by Ian Karamarkovich Graphic Design by Jessica Cox Graphic Design by Kyle Fowlkes Graphic Design by Allison Pawlowski Incorporating Original Research in The Classroom: A Case Study Analyzing the Influence of the Chesapeake Bay on Local Temperatures by Kaitlin Major, Carrie Dunham and Dr. Kelsey Scheitlin Graphic Design by Kathryn Grayson Graphic Design by Ashley Johnson Facing the Music: Environmental Impact Assessment of Building A Concert Hall on North Campus by Jennifer Nehrt, Kelsey Stolzenbach And Dr. Kelsey Scheitlin Art by Kristin McQuarrie Art by Sara Nelson Art by Melisa Michelle Prosocial Behavior as a Result of Prosocial Music by Jessica Sudlow Graphic Design by Perry Bason Graphic Design by Danielle Dmuchawski Graphic Design by Mariah Asbell Graphic Design by Matthew Sakach Identifying Pathogenic Salmonella Serotypes Isolated from Prince Edward County, VA Waterways via Mutiplex PCR Analysis by Timothy Smith, Jr. Art by Annaliese Troxell Art by T. Dane Summerell Development of Salicylidene Anilines for Application in the High School Laboratory by Sarah Ganrude Graphic Design by Malina Rutherford Graphic Design by Hannah Hopper, and Matthew Sakach Because That\u27s What Daddies Do: Effects of Fathering Patterns on Son\u27s Self and Gender Identities by John Berry, Jr. Graphic Design by James Early Graphic Design by Colleen Festa The Influence of Tropical Cyclones on Chesapeake Bay Dead Zones by Chelsea D. Taylor and Dr. Kelsey Scheitlin Graphic Design by Michelle Maddox Graphic Design by Kaitlyn Smith Graphic Design by Sarah Schu Graphic Design by Perry Bason, Cabell Edmunds, Katherine Grayson, Matthew Sakach, and Kayla Torna

Novel Indirect Calorimetry Technology to Analyze Metabolism in Individual Neonatal Rodent Pups

BACKGROUND: The ability to characterize the development of metabolic function in neonatal rodents has been limited due to technological constraints. Low respiratory volumes and flows at rest pose unique problems, making it difficult to reliably measure O(2) consumption, CO(2) production, respiratory quotient (RQ), and energy expenditure (EE). Our aim was to develop and validate a commercial-grade indirect calorimetry system capable of characterizing the metabolic phenotype of individual neonatal rodents. METHODOLOGY/PRINCIPAL FINDINGS: To address this research need, we developed a novel, highly sensitive open-circuit indirect calorimetry system capable of analyzing respiratory gas exchange in a single neonatal rodent pup. Additionally, we derived an equation from known metabolic relationships to estimate inlet flow rates, improving the efficiency of data collection. To validate the neonatal rodent indirect calorimetry system and evaluate the applicability of the derived equation for predicting appropriate flow rates, we conducted a series of experiments evaluating the impact of sex, litter size, time of day (during the light phase), and ambient temperature on neonatal rat metabolic parameters. Data revealed that the only metabolic parameter influenced by litter size is a neonatal rat's RQ, with rat pups reared in a small litter (5 pups) having lower RQ's than rat pups reared in either medium (8 pups) or large (11 pups) litters. Furthermore, data showed that ambient temperature affected all metabolic parameters measured, with colder temperatures being associated with higher CO(2) production, higher O(2) consumption, and higher energy expenditure. CONCLUSION/SIGNIFICANCE: The results of this study demonstrate that the modified Panlab Oxylet system reliably assesses early postnatal metabolism in individual neonatal rodents. This system will be of paramount importance to further our understanding of processes associated with the developmental origins of adult metabolic disease

Dysphoric milk ejection reflex: A case report

Dysphoric Milk Ejection Reflex (D-MER) is an abrupt emotional "drop" that occurs in some women just before milk release and continues for not more than a few minutes. The brief negative feelings range in severity from wistfulness to self-loathing, and appear to have a physiological cause. The authors suggest that an abrupt drop in dopamine may occur when milk release is triggered, resulting in a real or relative brief dopamine deficit for affected women. Clinicians can support women with D-MER in several ways; often, simply knowing that it is a recognized phenomenon makes the condition tolerable. Further study is needed

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Structure in 6D and 4D N=1 supergravity theories from F-theory

We explore some aspects of 4D supergravity theories and F-theory vacua that are parallel to structures in the space of 6D theories. The spectrum and topological terms in 4D supergravity theories correspond to topological data of F-theory geometry, just as in six dimensions. In particular, topological axion-curvature squared couplings appear in 4D theories; these couplings are characterized by vectors in the dual to the lattice of axion shift symmetries associated with string charges. These terms are analogous to the Green-Schwarz terms of 6D supergravity theories, though in 4D the terms are not generally linked with anomalies. We outline the correspondence between F-theory topology and data of the corresponding 4D supergravity theories. The correspondence of geometry with structure in the low-energy action illuminates topological aspects of heterotic-F-theory duality in 4D as well as in 6D. The existence of an F-theory realization also places geometrical constraints on the 4D supergravity theory in the large-volume limit.Comment: 63 page