An application of the multivariate extended Poisson distribution in 2 times 2 contingency tables Final report

Application of multivariate extended Poisson distribution

Responses to intensity-shifted auditory feedback during running speech

PURPOSE: Responses to intensity perturbation during running speech were measured to understand whether prosodic features are controlled in an independent or integrated manner. METHOD: Nineteen English-speaking healthy adults (age range = 21-41 years) produced 480 sentences in which emphatic stress was placed on either the 1st or 2nd word. One participant group received an upward intensity perturbation during stressed word production, and the other group received a downward intensity perturbation. Compensations for perturbation were evaluated by comparing differences in participants' stressed and unstressed peak fundamental frequency (F0), peak intensity, and word duration during perturbed versus baseline trials. RESULTS: Significant increases in stressed-unstressed peak intensities were observed during the ramp and perturbation phases of the experiment in the downward group only. Compensations for F0 and duration did not reach significance for either group. CONCLUSIONS: Consistent with previous work, speakers appear sensitive to auditory perturbations that affect a desired linguistic goal. In contrast to previous work on F0 perturbation that supported an integrated-channel model of prosodic control, the current work only found evidence for intensity-specific compensation. This discrepancy may suggest different F0 and intensity control mechanisms, threshold-dependent prosodic modulation, or a combined control scheme.R01 DC002852 - NIDCD NIH HHS; R03 DC011159 - NIDCD NIH HH

Predicting the effectiveness of hepatitis C virus neutralizing antibodies by bioinformatic analysis of conserved epitope residues using public sequence data

Hepatitis C virus (HCV) is a global health issue. Although direct-acting antivirals are available to target HCV, there is currently no vaccine. The diversity of the virus is a major obstacle to HCV vaccine development. One approach toward a vaccine is to utilize a strategy to elicit broadly neutralizing antibodies (bNAbs) that target highly-conserved epitopes. The conserved epitopes of bNAbs have been mapped almost exclusively to the E2 glycoprotein. In this study, we have used HCV-GLUE, a bioinformatics resource for HCV sequence data, to investigate the major epitopes targeted by well-characterized bNAbs. Here, we analyze the level of conservation of each epitope by genotype and subtype and consider the most promising bNAbs identified to date for further study as potential vaccine leads. For the most conserved epitopes, we also identify the most prevalent sequence variants in the circulating HCV population. We examine the distribution of E2 sequence data from across the globe and highlight regions with no coverage. Genotype 1 is the most prevalent genotype worldwide, but in many regions, it is not the dominant genotype. We find that the sequence conservation data is very encouraging; several bNAbs have a high level of conservation across all genotypes suggesting that it may be unnecessary to tailor vaccines according to the geographical distribution of genotypes

Triplet scalars and dark matter at the LHC

We investigate the predictions of a simple extension of the standard model where the Higgs sector is composed of one SU(2)L doublet and one real triplet. We discuss the general features of the model, including its vacuum structure, theoretical and phenomenological constraints, and expectations for Higgs collider studies. The model predicts the existence of a pair of light charged scalars and, for vanishing triplet vacuum expectation value, contains a cold dark matter candidate. When the latter possibility occurs, the charged scalars are long-lived, leading to a prediction of distinctive single charged track with missing transverse energy or double charged track events at the large hadron collider. The model predicts a significant excess of two-photon events compared to SM expectations due to the presence of a light charged scalar

Reduced hadronic uncertainty in the determination of VudV_{ud}

We analyze the universal radiative correction $\Delta_R^V$ to neutron and superallowed nuclear $\beta$ decay by expressing the hadronic $\gamma W$-box contribution in terms of a dispersion relation, which we identify as an integral over the first Nachtmann moment of the $\gamma W$ interference structure function $F_3^{(0)}$. By connecting the needed input to existing data on neutrino and antineutrino scattering, we obtain an updated value of $\Delta_R^V = 0.02467(22)$, wherein the hadronic uncertainty is reduced. Assuming other Standard Model theoretical calculations and experimental measurements remain unchanged, we obtain an updated value of $|V_{ud}| = 0.97366(15)$, raising tension with the first row CKM unitarity constraint. We comment on ways current and future experiments can provide input to our dispersive analysis.Comment: 5 pages, 5 figures, references updated; version submitted to PR

Trace gas transport in the subsurface of Mars

The ExoMars Trace Gas Orbiter (TGO) will have the capability of detecting and characterizing a broad suite of trace gases in the atmosphere of Mars. Interpreting the results of this mission will require an understanding of how these trace gases are transported from their sources, which may be deep underground, to the atmosphere. Here we present results of modeling designed to measure the timescales of release from putative subsurface methane sources. These transport timescales are far longer than mixing times in the atmosphere and could be up to 10 million years

Elevated interferon-stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus

Hepatitis C virus (HCV) can be classified into seven distinct genotypes that are associated with differing pathologies and respond differently to antiviral therapy. In the UK, genotype 1 and 3 are present in approximately equal proportions. Chronic infection with HCV genotype 3 is associated with increased liver steatosis and reduced peripheral total cholesterol levels, which potentially influences peripheral immune responses. To understand these differences, we investigated host gene transcription in peripheral blood mononuclear cells by microarray and quantitative PCR in patients with genotype 1 (n = 22) or genotype 3 infection (n = 22) and matched healthy controls (n = 15). Enrichment of genes involved in immune response and inflammatory pathways were present in patients infected with HCV genotype 1; however, no differences in genes involved in lipid or cholesterol metabolism were detected. This genotype-specific induction of genes is unrelated to IL28B genotype or previous treatment failure. Our data support the hypothesis that genotype 1 infection drives a skewed Type I interferon response and provides a foundation for future investigations into the host–pathogen interactions that underlie the genotype-specific clinical outcomes of chronic HCV infection

A study of an operative outcome of a basitrochanteric fractures of the hip treated by dynamic hip screw and enders nail with percutaneous canulated cancellous screw

Background: Basicervical or cervicotrochanteric fracture of the femur is considered stable variety of fracture pattern. Most common incidence is seen in elderly patient and in young patient with probably high energy trauma. Appropriate Osteosynthesis confers excellent outcome when reduction is optimally achieved.Methods: 86 basitrochanteric fractures had been treated with enders nail or dynamic hip screw (DHS) at our institute by a single surgeon. Implant selection was done purely based on plain radiograph, associated co-morbidities and fracture geometry. Patients had been followed up at 1 month, 3 month and 6 month.Results: In our study there were 86 patients out of which 63 patients (73.25%) were treated with enders nail and 23 patients (26.74%) were treated with DHS. Mean age of patients was 57 years. We noted minimum follow up of 8 months while maximum follow up of 4.5 years where as mean follow up duration is 18 months. We almost noted excellent to fair results in both groups.Conclusions: Most of the implants in basitrochanteric fractures worked on control collapse principle. Both DHS and enders nail with percutaneous cc screw follow this principle and when used with a proper technique, optimal reduction usually fetch the favourable outcomes with minimalistic approach

Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.

cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro, whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity