Efficient production of inhibitor-free foamy virus glycoprotein-containing retroviral vectors by proteoglycan-deficient packaging cells

Foamy viruses (FVs) or heterologous retroviruses pseudotyped with FV glycoprotein enable transduction of a great variety of target tissues of disparate species. Specific cellular entry receptors responsible for this exceptionally broad tropism await their identification. Though, ubiquitously expressed heparan sulfate proteoglycan (HS-PG) is known to serve as an attachment factor of FV envelope (Env)-containing virus particles, greatly enhancing target cell permissiveness. Production of high-titer, FV Env-containing retroviral vectors is strongly dependent on the use of cationic polymer-based transfection reagents like polyethyleneimine (PEI). We identified packaging cell-surface HS-PG expression to be responsible for this requirement. Efficient release of FV Env-containing virus particles necessitates neutralization of HS-PG binding sites by PEI. Remarkably, remnants of PEI in FV Env-containing vector supernatants, which are not easily removable, negatively impact target cell transduction, in particular those of myeloid and lymphoid origin. To overcome this limitation for production of FV Env-containing retrovirus supernatants, we generated 293T-based packaging cell lines devoid of HS-PG by genome engineering. This enabled, for the first, time production of inhibitor-free, high-titer FV Env-containing virus supernatants by non-cationic polymer-mediated transfection. Depending on the type of virus, produced titers were 2- to 10-fold higher compared with those obtained by PEI transfection

Structural and biosynthetic features of the Mo5 human myeloid differentiation antigen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65573/1/j.1399-0039.1993.tb02007.x.pd

The search for rare non-hadronic B-meson decays with final-state Neutrinos using the BaBar detector

This thesis presents the searches for two rare B meson decays: the radiative leptonic decay B+ -> l+ nu gamma (l = e, mu) and the flavor-changing neutral current B -> K(*) nu nubar. These searches use the full dataset collected by the BaBar experiment, which corresponds to almost 500 million BB pairs. After fully reconstructing the hadronic decay of one of the B mesons in Upsilon(4S) -> BB decays, evidence of B+ -> l+ nu gamma or B -> K(*) nu nubar is looked for in the rest of the event. No significant evidence of either signal decay is observed. Model-independent branching-fraction upper limits are set at BR(B ->e nu gamma)<17 x10^{-6}, BR(B ->mu nu gamma)<24 x10^{-6}, and BR(B ->l nu gamma)<15.6 x10^{-6}, all at the 90% confidence level. These are currently the most stringent published upper limits for B+ -> l+ nu gamma. In addition, branching-fraction upper limits are set at BR(B -> K+ nu nubar)<3.7 x10^{-5}, BR(B -> K0 nu nubar)<8.0 x10^{-5}, BR(B -> K*+ nu nubar)<11.5 x10^{-5}, and BR(B -> K*0 nu nubar)<9.2 x10^{-5}, all at the 90% confidence level. For additional sensitivity to New Physics contributions, partial B -> K(*) nu nubar branching-fraction upper limits are also determined over the full kinematic range.Cette thèse présente l'étude de deux désintégrations rares de mésons B: la désintégration radiative leptonique B+ -> l+ nu gamma (l = e, mu) et le courant neutre qui change la saveur B -> K(*) nu nubar. Ces études utilisent l'ensemble des données recueuillies par l'expérience BaBar, ce qui correspond à près de 500 millions paires BB. Après la reconstruction totale de la désintégration hadronique de l'un des mésons B dans la désintégration Upsilon(4S) -> BB, la manifestation de B+ -> l+ nu gamma ou B -> K(*) nu nubar est recherché dans le reste de l'événement. Aucune preuve significative de la désintégration du signal n'a été observée. Les limites supérieures du rapport d'embranchement indépendantes du modèle sont évaluées à BR(B -> e nu gamma)<17 x10^{-6}, BR(B -> mu nu gamma)<24 x10^{-6}, et BR(B -> l nu gamma)<15,6 x10^{-6}, à un niveau de confiance de 90%. Ce sont actuellement les limites supérieures les plus strictes publiés pour B+ -> l+ nu gamma. De plus, les limites supérieure du rapport d'embranchement sont évaluées à BR(B -> K+ nu nubar)<3,7 x10^{-5}, BR(B -> K0 nu nubar)<8,0 x10^{-5}, BR(B -> K*+ nu nubar)<11,5 x10^{-5}, et BR(B -> K*0 nu nubar)<9,2 x10^{-5}, à un niveau de confiance de 90%. Pour demeurer réceptives aux contributions de la nouvelle physique, les limites supérieures du rapport d'embranchement partiel de B -> K(*) nu nubar sont déterminés dans le spectre cinématique complet

Epidemiology of Emydoidea Herpesvirus 1 in free-ranging Blanding’s turtles (Emydoidea Blandingii) from Illinois

While herpesvirus infections have been associated with high morbidity and mortality in populations of captive Emydid chelonians worldwide, novel herpesviruses (Terrapene herpesvirus 1, Emydid herpesvirus 1 and 2, and Glyptemys herpesvirus 1 and 2) have also recently been identified in apparently healthy free-ranging Emydid populations. The clinical significance of this finding in the absence of an outbreak is currently unknown. The authors hypothesize that herpesvirus prevalence may be used as a sentinel of population health due to the virus’ propensity to recrudesce in times of stress or concurrent disease. Blanding’s turtles (Emydoidea blandingii), an endangered species in Illinois, have experienced range-wide declines because of habitat loss, degradation, and fragmentation. While ongoing studies are crucial to a thorough understanding of the natural history and demographics in disjointed Illinois populations, infectious disease threats have been largely unevaluated. In 2015, 20 free-ranging Blanding’s turtles in DuPage County, Illinois were screened for a herpesvirus using consensus PCR. A novel herpesvirus, Emydoidea herpesvirus 1 (EBHV1), was identified. Subsequently, the investigators developed a highly sensitive and specific TaqMan® quantitative PCR assay to target the DNA-dependent DNA polymerase gene of EBHV1. Validation results indicate that this assay is specific for EBHV1, has a linear range of detection from 108-101 viral copies per reaction, and can categorically detect as few as 1 viral copy per reaction. In an epidemiological investigation, combined oral-cloacal swabs were collected from radiotelemetered and trapped Blanding’s turtles in DuPage (n=60 turtles) and Lake (n=81 turtles) County from May-September 2016. Repeated samples of 50 adult females had a significantly higher prevalence of EBHV1 in May (23.8%, n=10) than June (2.9%, n=1), July (0%, n=0), August (0%, n=0), or September (7.7%, n=3) (odds ratio [OR]: 12.97; 95% CI: 3.83-43.92). This corresponds to the onset of nesting and may be associated with increased physiologic demands; however, all positive turtles were negative in subsequent months. Furthermore, there were no clinical signs associated with any turtle at the time they were detected with EBHV1. This investigation is the critical first step to characterizing the implications of EBHV1 on Blanding’s turtle population health and identifying management changes that may improve sustainability

Use of Contract Grading to Improve Grades Among College Freshmen in Introductory Psychology

The use of behavioral techniques in college teaching has declined during the past three decades. The purpose of this study was to compare a behaviorally based grading approach with a traditional point-based system. A total of 40 college freshmen were randomly assigned to a Traditionally Graded or Contract Graded Introductory Psychology course. Contract graded students were one third as likely to fail or withdraw, 3 times more likely to earn an A grade, and were more likely to perceive a high degree of control over their grade. These findings support use of a contract grading system in the contemporary college classroom