Kaon semileptonic decays near the physical point

Extent: 7p.The CKM matrix element jVusj can be extracted from the experimental measurement of semileptonic K -φ decays. The determination depends on theory input for the corresponding vector form factor in QCD. We present a preliminary update on our efforts to compute it in Nf = 2+1 lattice QCD using domain wall fermions for several lattice spacings and with a lightest pion mass of about 170MeV. By using partially twisted boundary conditions we avoid systematic errors associated with an interpolation of the form factor in momentum-transfer, while simulated pion masses near the physical point reduce the systematic error due to the chiral extrapolation.K. Sivalingam, P.A. Boyle, J.M. Flynn, A. Jüttner, C.T. Sachrajda, J.M. Zanotti, RBC and UKQCD Collaborationshttp://pos.sissa.it/cgi-bin/reader/conf.cgi?confid=16

Can electron distribution functions be derived through the Sunyaev-Zel'dovich effect?

Measurements of the Sunyaev-Zel'dovich (hereafter SZ) effect distortion of the cosmic microwave background provide methods to derive the gas pressure and temperature of galaxy clusters. Here we study the ability of SZ effect observations to derive the electron distribution function (DF) in massive galaxy clusters. Our calculations of the SZ effect include relativistic corrections considered within the framework of the Wright formalism and use a decomposition technique of electron DFs into Fourier series. Using multi-frequency measurements of the SZ effect, we find the solution of a linear system of equations that is used to derive the Fourier coefficients; we further analyze different frequency samples to decrease uncertainties in Fourier coefficient estimations. We propose a method to derive DFs of electrons using SZ multi-frequency observations of massive galaxy clusters. We found that the best frequency sample to derive an electron DF includes high frequencies $\nu$=375, 600, 700, 857 GHz. We show that it is possible to distinguish a Juttner DF from a Maxwell-Bolzman DF as well as from a Juttner DF with the second electron population by means of SZ observations for the best frequency sample if the precision of SZ intensity measurements is less than 0.1%. We demonstrate by means of 3D hydrodynamic numerical simulations of a hot merging galaxy cluster that the morphologies of SZ intensity maps are different for frequencies $\nu$=375, 600, 700, 857 GHz. We stress that measurements of SZ intensities at these frequencies are a promising tool for studying electron distribution functions in galaxy clusters.Comment: 11 pages, 12 figures, published in Astronomy and Astrophysic

A pilot randomised controlled trial using prophylactic dressings to minimise sacral pressure injuries in high risk hospitalised patients

This pilot randomised controlled trial examined the effect of prophylactic dressings to minimise sacral pressure injuries in high-risk hospitalised patients and assessed feasibility criteria to inform a larger study. Eighty patients were recruited at admission points (the Emergency Department and Surgical Care Unit) or directly from participating wards in the general medical surgical setting following assessment of high risk for sacral pressure injury. Participants were randomised into either the routine care or routine care and silicone foam border dressing group. Outcome assessment comprised digital photographs of each participant’s sacrum every 72 hours for evaluation by a blind-to-intervention assessor. Sixty-seven participants had at least one sacral photograph taken and assessed by a blind-to-intervention assessor. Three participants were assessed as having a Stage I pressure injury. While the use of photography was effective, feasibility criteria identified challenges related to bias, blinding, weight assessment, preparation of nursing staff and sample size estimation

The role of the VEGF-C/VEGFR-3 axis in cancer progression

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor

The Cyanobacterial Hepatotoxin Microcystin Binds to Proteins and Increases the Fitness of Microcystis under Oxidative Stress Conditions

Microcystins are cyanobacterial toxins that represent a serious threat to drinking water and recreational lakes worldwide. Here, we show that microcystin fulfils an important function within cells of its natural producer Microcystis. The microcystin deficient mutant ΔmcyB showed significant changes in the accumulation of proteins, including several enzymes of the Calvin cycle, phycobiliproteins and two NADPH-dependent reductases. We have discovered that microcystin binds to a number of these proteins in vivo and that the binding is strongly enhanced under high light and oxidative stress conditions. The nature of this binding was studied using extracts of a microcystin-deficient mutant in vitro. The data obtained provided clear evidence for a covalent interaction of the toxin with cysteine residues of proteins. A detailed investigation of one of the binding partners, the large subunit of RubisCO showed a lower susceptibility to proteases in the presence of microcystin in the wild type. Finally, the mutant defective in microcystin production exhibited a clearly increased sensitivity under high light conditions and after hydrogen peroxide treatment. Taken together, our data suggest a protein-modulating role for microcystin within the producing cell, which represents a new addition to the catalogue of functions that have been discussed for microbial secondary metabolites

A Mixed Tau-Electroproduction Sum Rule for V_us

The interpretation of results of recent tau decay determinations of |V_us|, which yield values ~3 sigma low compared to 3-family unitarity expectations, is complicated by the slow convergence of the relevant integrated D=2 OPE series. We introduce a class of sum rules involving both electroproduction and tau decay data designed to deal with this problem by strongly suppressing D=2 OPE contributions at the correlator level. Experimental complications are briefly discussed and an example of the improved control over theoretical errors presented. The uncertainty on the resulting determination, |V_{us}| =0.2202(39), is entirely dominated by experimental errors, and should be subject to significant near-term improvement.Comment: 12 pages, 2 figures; minor changes to reflect published version, in particular, details on theoretical uncertainties in conventional, purely tau-decay sum rule for V_us being larger than quoted previously in the literatur

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Using laser-captured microdissection and a real-time RT–PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55–3.67)), high DPD (HR: 2.04 (1.37–3.02)), low EGFR (HR: 0.34 (0.20–0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001–1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC

Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment