The constant background bag model of the hadron

We have constructed the bag model having a central constant color field. The motion of the quark is studied in this bag and the Dirac equation is solved for it. The energy spectrum found has a branching due to the interaction of the quarks with the color background. It is pointed out that this model can be applied for taking into account, in the mass spectrum of hadrons, the coupling of the constituent quarks with the gluon condensation as the interaction with the color background.Comment: 10 pages, improved English, will be published in the Eur. Phys. Jour.

Automation and validation of micronucleus detection in the 3D EpiDerm™ human reconstructed skin assay and correlation with 2D dose responses.

Recent restrictions on the testing of cosmetic ingredients in animals have resulted in the need to test the genotoxic potential of chemicals exclusively in vitro prior to licensing. However, as current in vitro tests produce some misleading positive results, sole reliance on such tests could prevent some chemicals with safe or beneficial exposure levels from being marketed. The 3D human reconstructed skin micronucleus (RSMN) assay is a promising new in vitro approach designed to assess genotoxicity of dermally applied compounds. The assay utilises a highly differentiated in vitro model of the human epidermis. For the first time, we have applied automated micronucleus detection to this assay using MetaSystems Metafer Slide Scanning Platform (Metafer), demonstrating concordance with manual scoring. The RSMN assay's fixation protocol was found to be compatible with the Metafer, providing a considerably shorter alternative to the recommended Metafer protocol. Lowest observed genotoxic effect levels (LOGELs) were observed for mitomycin-C at 4.8 µg/ml and methyl methanesulfonate (MMS) at 1750 µg/ml when applied topically to the skin surface. In-medium dosing with MMS produced a LOGEL of 20 µg/ml, which was very similar to the topical LOGEL when considering the total mass of MMS added. Comparisons between 3D medium and 2D LOGELs resulted in a 7-fold difference in total mass of MMS applied to each system, suggesting a protective function of the 3D microarchitecture. Interestingly, hydrogen peroxide (H2O2), a positive clastogen in 2D systems, tested negative in this assay. A non-genotoxic carcinogen, methyl carbamate, produced negative results, as expected. We also demonstrated expression of the DNA repair protein N-methylpurine-DNA glycosylase in EpiDerm™. Our preliminary validation here demonstrates that the RSMN assay may be a valuable follow-up to the current in vitro test battery, and together with its automation, could contribute to minimising unnecessary in vivo tests by reducing in vitro misleading positives

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

On the spectrum of the periodic Dirac operator

The absolute continuity of the spectrum for the periodic Dirac operator $$\hat D=\sum_{j=1}^n(-i\frac {\partial}{\partial x_j}-A_j)\hat \alpha_j + \hat V^{(0)}+\hat V^{(1)}, x\in R^n, n\geq 3,$$ is proved given that either $A\in C(R^n;R^n)\cap H^q_{loc}(R^n;R^n)$, 2q > n-2, or the Fourier series of the vector potential $A:R^n\to R^n$ is absolutely convergent. Here, $\hat V^{(s)}=(\hat V^{(s)})^*$ are continuous matrix functions and \hat V^{(s)}\hat \alpha_j=(-1}^s\hat \alpha_j\hat V^{(s)} for all anticommuting Hermitian matrices $\hat \alpha_j$, $\hat \alpha_j^2=\hat I$, s=0,1.Comment: 17 page

Comparison of Coulomb Blockade Thermometers with the International Temperature Scale PLTS-2000

The operation of the primary Coulomb blockade thermometer (CBT) is based on a measurement of bias voltage dependent conductance of arrays of tunnel junctions between normal metal electrodes. Here we report on a comparison of a CBT with a high accuracy realization of the PLTS-2000 temperature scale in the range from 0.008 K to 0.65 K. An overall agreement of about 1% was found for temperatures above 0.25 K. For lower temperatures increasing differences are caused by thermalization problems which are accounted for by numerical calculations based on electron-phonon decoupling.Comment: 6 pages, 5 figure

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease

Adjoint of the Global Eulerian Lagrangian Coupled Atmospheric transport model (A-GELCA v1.0): development and validation

Abstract. We present the development of the Adjoint of the Global Eulerian–Lagrangian Coupled Atmospheric (A-GELCA) model that consists of the National Institute for Environmental Studies (NIES) model as an Eulerian three-dimensional transport model (TM), and FLEXPART (FLEXible PARTicle dispersion model) as the Lagrangian plume diffusion model (LPDM). The tangent and adjoint components of the Eulerian model were constructed directly from the original NIES TM code using an automatic differentiation tool known as TAF (Transformation of Algorithms in Fortran; http://www.FastOpt.com), with additional manual pre- and post-processing aimed at improving the performance of the computing, including MPI (Message Passing Interface). As results, the adjoint of Eulerian model is discrete. Construction of the adjoint of the Lagrangian component did not require any code modification, as LPDMs are able to track a significant number of particles back in time and thereby calculate the sensitivity of observations to the neighboring emissions areas. Eulerian and Lagrangian adjoint components were coupled at the time boundary in the global domain.The results are verified using a series of test experiments. The forward simulation shown the coupled model is effective in reproducing the seasonal cycle and short-term variability of CO2 even in the case of multiple limiting factors, such as high uncertainty of fluxes and the low resolution of the Eulerian model. The adjoint model demonstrates the high accuracy compared to direct forward sensitivity calculations and fast performance. The developed adjoint of the coupled model combines the flux conservation and stability of an Eulerian discrete adjoint formulation with the flexibility, accuracy, and high resolution of a Lagrangian backward trajectory formulation. </jats:p

Phlegmonous colitis: another source of sepsis in cirrhotic patients?

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of phlegmonous colitis (PC), a rare autopsy finding in cirrhotic patients, is poorly documented. We postulated that PC might be a source of sepsis in patients with portal hypertensive colopathy (PHC).</p> <p>Case presentation</p> <p>We report three cirrhotic patients who were admitted with abdominal sepsis and who illustrate, to various degrees, the clinico-pathological sequence of colonic alterations associated with portal hypertension. Two cirrhotic patients with PHC developed gram-negative bacteraemia and quickly responded to intravenous antibiotics. Another cirrhotic patient underwent emergency colectomy for PC, and subsequently died from multiple organ failure. Histological alterations in the operative specimen included: a) mucosal ulcerations; b) disseminated micro-abscesses in the submucosa; and c) a severe vasculopathy leading to complete obliteration of submucosal blood vessels.</p> <p>Conclusions</p> <p>These data suggest that cirrhotic patients with PHC may progress towards PC, which, in turn, may be the cause for life-threatening sepsis.</p