Oxygen-related traps in pentacene thin films: Energetic position and implications for transistor performance

We studied the influence of oxygen on the electronic trap states in a pentacene thin film. This was done by carrying out gated four-terminal measurements on thin-film transistors as a function of temperature and without ever exposing the samples to ambient air. Photooxidation of pentacene is shown to lead to a peak of trap states centered at 0.28 eV from the mobility edge, with trap densities of the order of 10(18) cm(-3). These trap states need to be occupied at first and cause a reduction in the number of free carriers, i.e. a consistent shift of the density of free holes as a function of gate voltage. Moreover, the exposure to oxygen reduces the mobility of the charge carriers above the mobility edge. We correlate the change of these transport parameters with the change of the essential device parameters, i.e. subthreshold performance and effective field-effect mobility. This study supports the assumption of a mobility edge for charge transport, and contributes to a detailed understanding of an important degradation mechanism of organic field-effect transistors. Deep traps in an organic field-effect transistor reduce the effective field-effect mobility by reducing the number of free carriers and their mobility above the mobility edge.Comment: 13 pages, 14 figures, to be published in Phys. Rev.

Donor variability in HIV binding to peripheral blood mononuclear cells

<p>Abstract</p> <p>Background</p> <p>HIV infection of cells varies greatly between individuals, with multiple steps in the replication cycle potentially contributing to the variability. Although entry and post-entry variability of HIV infection levels in cells has been demonstrated, variability in HIV binding has not been examined. In this study, we examined variability of HIV binding to peripheral blood mononuclear cells (PBMC) from different donors.</p> <p>Results</p> <p>HIV binding to PBMC varied up to 3.9-fold between individuals and was independent of CD4. Replication of HIV in donor PBMC required CD4 and paralleled virus binding trends of donor PBMC. To assess the stability of virus binding phenotypes over time, HIV was bound to donors with low- and high-binding phenotypes. The binding phenotypes were maintained when tested weekly over a 4-week period for 3 of 4 donors, while one high-binding donor decreased to lower binding on the 4th week. The low- and high-binding phenotypes were also preserved across different HIV strains. Experiments performed to determine if there was an association between HIV binding levels and specific cell subset levels within PBMC showed no correlation, suggesting that HIV binds to multiple cell subsets.</p> <p>Conclusion</p> <p>These results show that differences exist in HIV binding to donor PBMC. Our data also show that HIV binding to donor PBMC is CD4-independent and can change over time, suggesting that virus binding variability is due to differences in the expression of changeable cell-surface host factors. Taken together, this study highlights the impact of cell-surface factors in HIV binding to, and infection of, PBMC which likely represents an important step in HIV infection <it>in vivo</it>.</p

Bacterial vaginosis and human immunodeficiency virus infection

Epidemiologic studies indicate that bacterial vaginosis (BV), a common alteration of lower genital tract flora in women, is associated with increased susceptibility to HIV infection. Other recent studies show that HIV is detected more frequently and at higher levels in the lower genital tract of HIV-seropositive women with BV. In vitro studies show that genital tract secretions from women with BV or flora associated with BV induce HIV expression in infected cells. The increased HIV expression appears to be due at least in part to activation through Toll-like receptors (TLR), specifically TLR2. Further research is needed to elucidate how BV contributes to HIV acquisition and transmission

The Impact of Altered T Cell Receptor—Peptide-Major Histocompatibility Complex Interactions on Antigen Recognition and T Cell Function

Adoptive cell transfer (ACT) using T cell receptor (TCR) gene-modified T cells is an exciting and rapidly evolving field. Numerous basic science and clinical studies have demonstrated various levels of feasibility, safety, and efficacy using TCR-engineered T cells to treat cancer and viral infections. Genomic instability of targeted diseases, however, requires effective and safe TCRs to cross-recognize mutated antigens while minimizing on- or off-target toxicities. Thus, improvements to T cell-based therapeutics mandate a broader understanding of the principles governing antigen recognition. This dissertation addresses critical biologic questions evaluating which parameters are most important in facilitating antigen recognition, and how alterations in TCR-peptide major histocompatibility complex (pMHC) interactions affect T cell function. Our model to study antigen recognition utilizes traditional and novel approaches characterizing the capability of T cells gene-modified to express an HLA-A2-restricted, cross-reactive TCR to recognize naturally occurring mutant hepatitis C virus NS3:1406-1415 epitopes. Contrary to what is generally accepted in the field, we found that TCR-pMHC affinity is not necessarily the most important factor dictating antigen recognition. Other cellular parameters, including ligand density, TCR density, and co-receptor signaling greatly influenced the recognition of altered pMHC ligands. Additionally, we found that the field’s interpretation of antigen recognition may be misguided when evaluation of T cell function is limited to a single cytokine. Functional phenotypes by seven-parameter flow cytometry revealed that T cell functional profiles are more complex than were previously believed, and evaluation of a single functional phenotype did not accurately reflect the functional behavior of a T cell culture. Combining functional studies with structural analysis of the TCR-pMHC interface helps bring clarity to these unexpected results. Together, our data suggest that the field is oversimplifying T cell function and establish a new working model highlighting a previously unappreciated and complex relationship between kinetic, cellular, and structural parameters governing antigen recognition. This enhanced understanding will not only help steer rational, structure-guided design of TCRs to generate better functioning T cells for ACT, but will also impact the way in which we design, evaluate, and implement novel immunotherapies

Radicalism and the National Crisis

Full title: Radicalism and the national crisis : a sermon preached in the South Presbyterian Church of Brooklyn, by the pastor, Samuel T. Spear, October 19th, 1862https://digitalcommons.cedarville.edu/pamphlet_collection/1088/thumbnail.jp

Our Country and Its Cause

Full title: Our country and its cause. A discourse preached October 2d, 1864 in the South Presbyterian church, of Brooklynhttps://digitalcommons.cedarville.edu/pamphlet_collection/1013/thumbnail.jp

Differential inhibition of human cytomegalovirus (HCMV) by toll-like receptor ligands mediated by interferon-beta in human foreskin fibroblasts and cervical tissue

Human cytomegalovirus (HCMV) can be acquired sexually and is shed from the genital tract. Cross-sectional studies in women show that changes in genital tract microbial flora affect HCMV infection and/or shedding. Since genital microbial flora may affect HCMV infection or replication by stimulating cells through Toll-like receptors (TLR), we assessed the effects of defined TLR-ligands on HCMV replication in foreskin fibroblasts and ectocervical tissue. Poly I:C (a TLR3-ligand) and lipopolysaccharide (LPS, a TLR4-ligand) inhibited HCMV and induced secretion of IL-8 and Interferon-beta (IFNβ) in both foreskin fibroblasts and ectocervical tissue. The anti-HCMV effect was reversed by antibody to IFNβ. CpG (TLR9 ligand) and lipoteichoic acid (LTA, TLR2 ligand) also inhibited HCMV infection in ectocervical tissue and this anti-HCMV effect was also reversed by anti-IFNβ antibody. In contrast, LTA and CpG did not inhibit HCMV infection in foreskin fibroblasts. This study shows that TLR ligands induce an HCMV-antiviral effect that is mediated by IFNβ suggesting that changes in genital tract flora may affect HCMV infection or shedding by stimulating TLR. This study also contrasts the utility of two models that can be used for assessing the interaction of microbial flora with HCMV in the genital tract. Clear differences in the response to different TLR ligands suggests the explant model more closely reflects in vivo responses to genital infections

Adolescent, but Not Adult, Binge Ethanol Exposure Leads to Persistent Global Reductions of Choline Acetyltransferase Expressing Neurons in Brain

During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) treatment led to persistent, global reductions of choline acetyltransferase (ChAT) expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70) produced a reduction in ChAT+ IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+ IR in the basal forebrain following adolescent (P28-P48) and adult (P70-P90) binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity

Zhx2 (Zinc Fingers and Homeoboxes 2) Regulates Major Urinary Protein Gene Expression in the Mouse Liver

The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. Zhx2 is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ Zhx2 allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with in vitro assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes