REFERQUAL: A pilot study of a new service quality assessment instrument in the GP Exercise Referral scheme setting

Background The development of an instrument accurately assessing service quality in the GP Exercise Referral Scheme (ERS) industry could potentially inform scheme organisers of the factors that affect adherence rates leading to the implementation of strategic interventions aimed at reducing client drop-out. Methods A modified version of the SERVQUAL instrument was designed for use in the ERS setting and subsequently piloted amongst 27 ERS clients. Results Test re-test correlations were calculated via Pearson's 'r' or Spearman's 'rho', depending on whether the variables were Normally Distributed, to show a significant (mean r = 0.957, SD = 0.02, p < 0.05; mean rho = 0.934, SD = 0.03, p < 0.05) relationship between all items within the questionnaire. In addition, satisfactory internal consistency was demonstrated via Cronbach's 'α'. Furthermore, clients responded favourably towards the usability, wording and applicability of the instrument's items. Conclusion REFERQUAL is considered to represent promise as a suitable tool for future evaluation of service quality within the ERS community. Future research should further assess the validity and reliability of this instrument through the use of a confirmatory factor analysis to scrutinise the proposed dimensional structure

TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells

TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)

Genetic Investigation of Bisphosphonate-Related Osteonecrosis of Jaw (BRONJ) via Whole Exome Sequencing and Bioinformatics

Complications associated with the use of bisphosphonate (BP) have risen over the years due to an increase in the prescription of BP. BP-related osteonecrosis of jaw (BRONJ), one of the complications linked to the consumption of BP, greatly affects patients with minor dental trauma, incurring a long healing period. While BRONJ afflicts only a minority of patients prescribed with BP, BRONJ is a multigenic disease affected both by environmental and genetic factors having a distinctive phenotype. This study aims to discover genetic biomarkers associated with BRONJ via whole exome sequencing (WES) followed by statistical analysis. Sixteen individuals who had been prescribed with bisphosphonate medication and diagnosed as BRONJ were chosen and each individual&apos;s saliva sample was collected for WES. 126 randomized subsamples from the GSK project representing 109 male and 17 female Koreans were used as a control data set. Fisher&apos;s exact test was carried out to assess the significance of genetic variants in BRONJ patients. Gene set enrichment analysis (GSEA) (DAVID Bioinformatics Resource 6.7) was used to perform a cluster analysis of variants found from Fisher&apos;s exact test. The results from this study suggest that BRONJ-inducing factors are genetically associated and BRONJ occurs due to the malfunctioning of post-translational modification in osteoclast leading to the impairment of cell morphology and adhesion.open1142sciescopu

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Hrk1 Plays Both Hog1-Dependent and -Independent Roles in Controlling Stress Response and Antifungal Drug Resistance in Cryptococcus neoformans

The HOG (High Osmolarity Glycerol response) pathway plays a central role in controlling stress response, ergosterol biosynthesis, virulence factor production, and differentiation of Cryptococcus neoformans, which causes fatal fungal meningoencephalitis. Recent transcriptome analysis of the HOG pathway discovered a Hog1-regulated gene (CNAG_00130.2), encoding a putative protein kinase orthologous to Rck1/2 in Saccharomyces cerevisiae and Srk1 in Schizosaccharomyces pombe. Its function is not known in C. neoformans. The present study functionally characterized the role of Hrk1 in C. neoformans. Northern blot analysis confirmed that HRK1 expression depends on the Hog1 MAPK. Similar to the hog1Δ mutant, the hrk1Δ mutant exhibited almost complete resistance to fludioxonil, which triggers glycerol biosynthesis via the HOG pathway. Supporting this, the hrk1Δ mutant showed reduced intracellular glycerol accumulation and swollen cell morphology in response to fludioxonil, further suggesting that Hrk1 works downstream of the HOG pathway. However, Hrk1 also appeared to have Hog1-independent functions. Mutation of HRK1 not only further increased osmosensitivity of the hog1Δ mutant, but also suppressed increased azole-resistance of the hog1Δ mutant in an Erg11-independent manner. Furthermore, unlike the hog1Δ mutant, Hrk1 was not involved in capsule biosynthesis. Hrk1 was slightly involved in melanin production but dispensable for virulence of C. neoformans. These findings suggest that Hrk1 plays both Hog1-dependent and –independent roles in stress and antifungal drug susceptibility and virulence factor production in C. neoformans. Particularly, the finding that inhibition of Hrk1 substantially increases azole drug susceptibility provides a novel strategy for combination antifungal therapy

Epidermal growth factor induces HCCR expression via PI3K/Akt/mTOR signaling in PANC-1 pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Human cervical cancer oncoprotein 1 (HCCR-1), reported as a negative regulator of p53, is over-expressed in a variety of human cancers. However, it is yet unknown whether HCCR-1 plays any role in pancreatic cancer development. The aim of this study was to investigate the effect of epidermal growth factor on the expression of HCCR in pancreatic cancer cells, and to explore if PI3K/Akt/mTOR signaling pathway mediated this expression.</p> <p>Methods</p> <p>A polyclonal antibody against HCCR protein was raised by immunizing Balb/c mice with the purified recombinant protein pMBPc-HCCR. Tissue samples were constructed on a tissue chip, and the expression of HCCR was investigated by immunohistochemistry assay and Western blotting. Pancreatic cell line, PANC-1 cells were stably transfected with plasmids containing sense-HCCR-1 fragment and HCCR siRNA fragment. MTT and transwell assay were used to investigate the proliferation and invasion of stable tansfectants. The specific inhibitor of PI3K and mTOR was used to see if PI3K/mTOR signal transduction was involved in the induction of HCCR gene expression. A Luciferase assay was used to see if Akt can enhance the HCCR promoter activity.</p> <p>Results</p> <p>HCCR was up-regulated in pancreatic tumor tissues (mean Allred score 4.51 ± 1.549 <it>vs</it>. 2.87 ± 2.193, P < 0.01), especially with high expression in poorly differentiated pancreatic cancer. The growth of cells decreased in HCCR-1 siRNA transfected cells compared with vector transfectants. The number of invasion cells was significantly lower in HCCR-1 siRNA transfected cells (24.4 ± 9.9) than that in vector transfectants (49.1 ± 15.4). Treatment of PANC-1 cells with epidermal growth factor increased HCCR protein level in a dose- and time-dependent manner. However, application of LY294002 and rapamycin caused a dramatic reduction of epidermal growth factor-induced HCCR expression. Over-expression of exogenous constitutively active Akt increased the HCCR promoter activity; in contrast, dominant negative Akt decreased the promoter activity.</p> <p>Conclusions</p> <p>EGF-induced HCCR-1 over-expression is mediated by PI3K/AKT/mTOR signaling which plays a pivotal role in pancreatic tumor progression, suggesting that HCCR-1 could be a potential target for cancer therapeutics.</p

Study of the decays B->D_s1(2536)+ anti-D(*)

We report a study of the decays B -> D_s1(2536)+ anti-D(*), where anti-D(*) is anti-D0, D- or D*-, using a sample of 657 x 10^6 B anti-B pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. The branching fractions of the decays B+ -> D_s1(2536)+ anti-D0, B0 -> D_s1(2536)+ D- and B0 -> D_s1(2536)+ D*- multiplied by that of D_s1(2536)+ -> (D*0K+ + D*+K0) are found to be (3.97+-0.85+-0.56) x 10^-4, (2.75+-0.62+-0.36) x 10^-4 and (5.01+-1.21+-0.70) x 10^-4, respectively.Comment: 6 pages, 2 figues, submitted to PRD (RC

Evidence for B- -> tau- nu_bar with a Semileptonic Tagging Method

We present a measurement of the decay B- -> tau- nu_bar using a data sample containing 657 million BB_bar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. A sample of BB_bar pairs are tagged by reconstructing one B meson decaying semileptonically. We detect the B- -> tau- nu_bar candidate in the recoil. We obtain a signal with a significance of 3.6 standard deviations including systematic uncertainties, and measure the branching fraction to be Br(B- -> tau- nu_bar) = [1.54+0.38-0.37(stat)+0.29-0.31(syst)]*10^-4. This result confirms the evidence for B- -> tau- nu_bar obtained in a previous Belle measurement that used a hadronic B tagging method.Comment: 7 pages, 3 figures, corrected references, to appear in PRD-R

Selective formation of tungsten nanowires

We report on a process for fabricating self-aligned tungsten (W) nanowires with polycrystalline silicon core. Tungsten nanowires as thin as 10 nm were formed by utilizing polysilicon sidewall transfer technology followed by selective deposition of tungsten by chemical vapor deposition (CVD) using WF6 as the precursor. With selective CVD, the process is self-limiting whereby the tungsten formation is confined to the polysilicon regions; hence, the nanowires are formed without the need for lithography or for additional processing. The fabricated tungsten nanowires were observed to be perfectly aligned, showing 100% selectivity to polysilicon and can be made to be electrically isolated from one another. The electrical conductivity of the nanowires was characterized to determine the effect of its physical dimensions. The conductivity for the tungsten nanowires were found to be 40% higher when compared to doped polysilicon nanowires of similar dimensions