The Transmembrane Domains of the EBV-Encoded Latent Membrane Protein 1 (LMP1) Variant CAO Regulate Enhanced Signalling Activity

AbstractSequence variants of the Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) have been reported in association with EBV-linked malignancies but little is known about their effects on signalling pathways and phenotype. We have examined the ability of the nasopharyngeal carcinoma (NPC)-derived variant, CAO-LMP1 to activate the transcription factors NF-κB and AP-1 in epithelial cells. In this study, transient expression of CAO-LMP1 was found to activate higher levels of NF-κB and AP-1 than the prototype B95.8-LMP1 in human embryonic kidney (HEK) 293 cells and SV40-transformed keratinocytes (SVK). In addition, pulse–chase analysis revealed that CAO-LMP1 has a longer half-life than B95.8-LMP1. Chimera studies localised these phenomena to the transmembrane domains of CAO-LMP1, suggesting that this enhanced signalling capacity may be a consequence of its prolonged half-life. The ability of CAO-LMP1 to activate higher levels of NF-κB and AP-1 may contribute to its potent transforming properties

Cosmokinetics: A joint analysis of Standard Candles, Rulers and Cosmic Clocks

We study the accelerated expansion of the universe by using the kinematic approach. In this context, we parameterize the deceleration parameter, q(z), in a model independent way. Assuming three simple parameterizations we reconstruct q(z). We do the joint analysis with combination of latest cosmological data consisting of standard candles (Supernovae Union2 sample), standard ruler (CMB/BAO), cosmic clocks (age of passively evolving galaxies) and Hubble (H(z)) data. Our results support the accelerated expansion of the universe.Comment: PDFLatex, 15 pages, 12 pdf figures, revised version to appear in JCA

An experimental study of the flow-induced noise created by a wall-mounted finite length airfoil

AIAA 2014-3290This paper presents the results of an experimental investigation of the sound produced by flow interaction with a wall-mounted finite length airfoil at low-to-moderate Reynolds number. Acoustic measurements have been taken in an anechoic wind tunnel at a range of Reynolds numbers, angles of attack and for a variety of airfoil aspect ratios (airfoil length to chord ratio) with a single microphone and two perpendicular planar microphone arrays. For comparison, measurements have also been taken with a semi-infinite or two- dimensional airfoil and a half-span airfoil with tip flow but no boundary layer impingement. The experimental data is used to examine changes in wall-mounted finite airfoil noise production as a function of Reynolds number, angle of attack and airfoil aspect ratio. Additionally, the data gives insight into the airfoil noise generation mechanisms and the influence of flow at the airfoil tip and wall junction on noise productionDanielle J. Moreau , Zebb Prime and Con J. Doola

Modeling of complex oxide materials from the first principles: systematic applications to vanadates RVO3 with distorted perovskite structure

"Realistic modeling" is a new direction of electronic structure calculations, where the main emphasis is made on the construction of some effective low-energy model entirely within a first-principle framework. Ideally, it is a model in form, but with all the parameters derived rigorously, on the basis of first-principles electronic structure calculations. The method is especially suit for transition-metal oxides and other strongly correlated systems, whose electronic and magnetic properties are predetermined by the behavior of some limited number of states located near the Fermi level. After reviewing general ideas of realistic modeling, we will illustrate abilities of this approach on the wide series of vanadates RVO3 (R= La, Ce, Pr, Nd, Sm, Gd, Tb, Yb, and Y) with distorted perovskite structure. Particular attention will be paid to computational tools, which can be used for microscopic analysis of different spin and orbital states in the partially filled t2g-band. We will explicitly show how the lifting of the orbital degeneracy by the monoclinic distortion stabilizes C-type antiferromagnetic (AFM) state, which can be further transformed to the G-type AFM state by changing the crystal distortion from monoclinic to orthorhombic one. Two microscopic mechanisms of such a stabilization, associated with the one-electron crystal field and electron correlation interactions, are discussed. The flexibility of the orbital degrees of freedom is analyzed in terms of the magnetic-state dependence of interatomic magnetic interactions.Comment: 23 pages, 13 figure

Population Modeling Highlights Drug Disposition Differences Between Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate in the Blood and Semen

Understanding antiretroviral disposition in the male genital tract, a distinct viral compartment, can provide insight for the eradication of HIV. Population pharmacokinetic modeling was conducted to investigate the disposition of tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and emtricitabine and their metabolites in blood and semen. Blood plasma and seminal plasma (SP) concentrations of tenofovir and emtricitabine were measured, as were tenofovir-diphosphate and emtricitabine-triphosphate concentrations in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells. Sequential compartmental modeling described drug disposition in blood and semen. Our modeling suggests slower elimination of apparent tenofovir-diphosphate PBMC and faster elimination of tenofovir SP after administration of TAF compared with TDF, likely reflecting flip-flop kinetics. Additionally, TAF metabolism to tenofovir appeared slower in semen compared with blood; however, SP elimination of TAF-derived tenofovir appeared faster than its blood plasma elimination. These findings provide valuable insight for further mechanistic study of cellular entry and drug metabolism in the male genital tract

Deviation From \Lambda CDM With Cosmic Strings Networks

In this work, we consider a network of cosmic strings to explain possible deviation from \Lambda CDM behaviour. We use different observational data to constrain the model and show that a small but non zero contribution from the string network is allowed by the observational data which can result in a reasonable departure from \Lambda CDM evolution. But by calculating the Bayesian Evidence, we show that the present data still strongly favour the concordance \Lambda CDM model irrespective of the choice of the prior.Comment: 15 Pages, Latex Style, 4 eps figures, Revised Version, Accepted for publication in European Physical Journal

When work keeps us apart: a thematic analysis of the experience of business travellers

Whilst business travel is deemed important for organizational success and economic outcomes, little is known about the actual process of business travelling from the perspective of individuals who undertake such travel on a regular basis. Thus the current qualitative study examined how business travellers (three women and eight men) attempt to find a balance between work and family, by focusing on how time together and time apart are experienced. The results can be interpreted and framed within work/family border theory in that business travellers’ borders are less defined and less permeable, thus requiring them to border-cross more frequently. This necessitates a process of negotiation with key border-keepers (their spouse/partner). Business travellers also undertake compensatory behaviours to make up for their time away from family. In order to find a work/family balance they go through a process of adapting, negotiating and tailoring their lives around their work commitments to alleviate work-life conflict

Differential Extracellular, but Similar Intracellular, Disposition of two Tenofovir Formulations in the Male Genital Tract

Background: The male genital tract (MGT) is a viral sanctuary and likely HIV reservoir; understanding MGT pharmacokinet-ics (PK) of antiretrovirals (ARVs) used for curative strategies is critical to eradication and cure. Tenofovir alafenamide (TAF) is a tenofovir (TFV) formulation designed to maximize efficacy/minimize toxicity with unknown MGT PK. Methods: HIV-positive and HIV-negative men receiving TFV-based regimens provided six paired blood plasma (BP) and semen samples. Extracellular (TFV, TAF, emtricitabine [FTC]) drug concentrations in BP and seminal plasma (SP), and intracellular metabolite (IM) and endogenous nucleotide (EN) concentrations were measured in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs). Exposure ratios for SP:BP, SMC:PBMC and IM:EN were calculated from PK parameters generated by noncompartmental analysis. HIV viral load was measured in BP and SP. Results: Sixteen HIV-positive (n=8, TDF/FTC; n=8, TAF/FTC) and eight HIV-negative (TDF/FTC) men provided samples. Median TFV SP:BP ratios differed between TDF and TAF (1.5 versus 7.4), due to lower TFV BP concentrations with TAF coupled with TFV SP concentrations similar to TDF. FTC SP:BP ratios were approximately 3. SMC concentrations of IMs and ENs were a fraction of PBMC concentrations (1–22%), though IM:EN ratios exceed a suggested protective threshold. Conclusions: TAF SP PK was unexpected. IM SMC concentrations were low relative to PBMC, as were EN concentrations, suggesting differences in cell phenotype and lineage in the MGT; these differences in phenotype and pharmacology may have an impact on selecting and dosing ARVs used in cure strategies

Indicadores de qualidade do solo em sistemas de cultivo orgânico e convencional no semi-árido Cearense.

A qualidade do solo pode mudar com o passar do tempo, em decorrência de eventos naturais ou ações antrópicas. A adoção de práticas de cultivo orgânico reduz o revolvimento do solo, favorecendo a recuperação de suas propriedades físicas e químicas. Este trabalho teve como objetivo comparar propriedades físicas,químicas e biológicas de solos cultivados com algodão em bases orgânicas e no sistema convencional, assim como identificar as que possam ser utilizadas como indicadores de qualidade do solo. Selecionaram-se seis áreas submetidas ao cultivo orgânico e três ao cultivo convencional para coleta de amostras de solo deformadas e indeformadas, nas camadas de 0–10, 10–20 e 20–30 cm. Técnicas de estatística univariada e multivariada foram utilizadas para análise dos dados. Os resultados mostraram que os indicadores físicos e químicos testados individualmente não foram sensíveis para diferenciar as áreas sob sistema de cultivo orgânico daquelas sob cultivo convencional. No entanto, a aplicação de técnicas de análise multivariada – no caso, componentes principais e a discriminante de Anderson – permitiu a distinção entre algumas áreas cultivadas sob cultivo orgânico comparativamente às convencionais, até mesmo as que estavam em transição.Dos indicadores biológicos, a fauna edáfica mostrou-se mais precisa na avaliação da qualidade do solo, distinguindo de forma satisfatória as áreas sob sistema de cultivo orgânico das que estavam sob sistema convencional