Effect of phospholipids and bile acids on cholesterol nucleation time and vesicular/micellar cholesterol in gallbladder bile of patients with cholesterol stones

Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. We, therefore, investigated whether increases of bile acid or phospholipid concentrations in bile by in vitro supplementation affect the cholesterol nucleation time. Bile samples were obtained at surgery from patients with cholesterol gallstones. Prior to the nucleation assay the bile samples were divided into 0.5-ml aliquots and supplemented with 1.25, 2.5, 5.0, and 10.0 mumol/ml of different phosphatidylcholines (PC-dimyristoyl, PC- dipalmitoyl, PC-distearoyl, and extracted biliary PCs) or with 5.0, 10.0, and 20.0 mumol/ml of bile acids (glycine or taurine conjugates of cholic acid, deoxycholic acid, or chenodeoxycholic acid). The increase of phosphatidylcholine or bile acid concentration decreased the mean cholesterol saturation index to a similar extent (PC: 0.1-0.3; BA: 0.1- 0.2). Supplementations of bile with increasing amounts of synthetic or biliary PCs caused a marked prolongation of the nucleation time in bile from 1.5 +/- 0.2 up to > or = 21 days or 2.5 +/- 0.7 up to > or = 21 days. Concurrently, biliary cholesterol was shifted from vesicles to mixed micelles and the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. In contrast, the addition of bile acids to gallbladder bile did not affect the cholesterol nucleation time (2.2 +/- 0.3 days), the percentage of vesicular cholesterol, or the cholesterol/phospholipid ratio of vesicles and micelles

Low energy constants from the chirally improved Dirac operator D_CI

The leading order low energy parameters like the pion decay constant or the quark condensate are well-known from "classical" low energy theorems and experiments. It is a challenge, however, to find these parameters based exclusively on an ab-initio QCD calculation. We discuss results of a quenched lattice calculation of low energy constants using the chirally improved Dirac operator. Several lattice sizes at different lattice spacings are studied, using pseudoscalar and axial vector correlators. We find consistent results for f_\pi = 96(2) MeV, f_K = 105(2) MeV, \Sigma = -(286(4) MeV)^3, the average light quark mass m = 4.1(2.4) MeV and m_s = 101(8) MeV.Comment: Poster presented at Lattice2005 (Chiral fermions), Dublin, July 25-30, 2005; 6 pages, 4 figures, uses PoS.cls; to appear in Proceedings of Scienc

The impact of a dedicated training program for oral examiners at a medical school in Germany: a survey among participants from operative and non-operative disciplines

BACKGROUND: Oral examinations have been a crucial format in ancient and modern assessment to evaluate and guarantee quality of medical education and thereby to secure patient safety. To achieve a high level of quality in the oral part of the final examination of medical students, a training program for oral examiners at the Medical Faculty of Ulm (Germany) has been established since 2007. However, little is known about the attitude of the examiners in regard to the impact of this training program and of oral examinations as instruments to ensure patient safety. METHODS: All 367 academic clinicians from operative and non-operative disciplines, attending the one-day examiner training program at the University of Ulm between 2007 and 2012 have been asked to answer an online survey (EvaSys 5.0). Focus of the survey was to find out in which respect the examiners profited from the trainings, if the training effects were discipline-dependent, and to which degree the oral examinations could contribute to patient safety. Statistical analysis was performed using the t-test for independent samples. Results were considered statistically significant when p < 0.05. RESULTS: A total of 63 participants answered the survey, but in 4 cases the questionnaire was not fully completed (with single items missing). More than half of the study participants (n = 34/59; 58%) have experienced (at least sometimes or rarely) candidates that they deemed incompetent and perhaps even dangerous to the patients’ health who nevertheless passed the oral exam successfully. The majority of participants were convinced that oral examinations using concrete clinical cases could significantly contribute to patient safety, if grading is based on clear criteria and if examinations as well as grading are performed more critically. The impact of the training program was rated significantly stronger by surgeons than by non-surgeons in several categories. These categories included “strengths and weaknesses of oral examinations”, “reliability”, “validity”, “competence in grading”, “critical grading”, and “departmental improvements” concerning oral examinations. CONCLUSIONS: In respect to patient safety, it seems crucial to prevent incompetent candidates from passing the oral examination. The present study indicates the importance to continue and to develop our examiner trainings, with main emphasis on concrete clinical problems and a criteria-based critical grading system for oral examinations. Since the impact of the training was particularly high for colleagues from the operative disciplines, the training program should be offered especially in surgical departments

Majorana modes and p-wave superfluids for fermionic atoms in optical lattices.

The quest for realization of non-Abelian phases of matter, driven by their possible use in fault-tolerant topological quantum computing, has been spearheaded by recent developments in p-wave superconductors. The chiral p(x)+ip(y)-wave superconductor in two-dimensions exhibiting Majorana modes provides the simplest phase supporting non-Abelian quasiparticles and can be seen as the blueprint of fractional topological order. Alternatively, Kitaev's Majorana wire has emerged as an ideal toy model to understand Majorana modes. Here we present a way to make the transition from Kitaev's Majorana wires to two-dimensional p-wave superconductors in a system with cold atomic gases in an optical lattice. The main idea is based on an approach to generate p-wave interactions by coupling orbital degrees of freedom with strong s-wave interactions. We demonstrate how this design can induce Majorana modes at edge dislocations in the optical lattice, and we provide an experimentally feasible protocol for the observation of the non-Abelian statistics.We acknowledge support by the Center for Integrated Quantum Science and Technology (IQST) and the Deutsche Forschungsgemeinschaft (DFG) within SFB TRR 21, the Leverhulme Trust (ECF-2011-565), the Newton Trust of the University of Cambridge, the Royal Society (UF120157), SFB FoQus (FWF Project No. F4006-N16), the ERC Synergy Grant UQUAM, SIQS, and Swiss National Science Foundation. GM, SH, CK, and HB thank the Institut d’Etudes Scientifiques Cargèse and CECAM for their hospitality.This is the accepted manuscript of an article published in Nature Communications [A Bühler, N Lang, CV Kraus, G Möller, SD Huber, HP Büchler Nature Communications 5:4504 doi: 10.1038/ncomms5504 (2014)]

Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma

According to the American skin cancer foundation, there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung, and colon each year, and malignant melanoma represents its deadliest form. About 50% of all cases are characterized by a particular mutation BRAFV600E in the BRAF (Rapid Acceleration of Fibrosarcoma gene B) gene. Recently developed highly specific drugs are able to fight BRAFV600E mutated tumors but require diagnostic tools for fast and reliable mutation detection to warrant treatment efficiency. We completed a preliminary clinical trial applying cantilever array sensors to demonstrate identification of a BRAFV600E single-point mutation using total RNA obtained from biopsies of metastatic melanoma of diverse sources (surgical material either frozen or fixated with formalin and embedded in paraffin). The method is faster than the standard Sanger or pyrosequencing methods and comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis is below 1 day and does not require PCR amplification, sequencing, and labels

Nanosensors for cancer detection.

Cancer is a major burden in today's society and one of the leading causes of death in industrialised countries. Various avenues for the detection of cancer exist, most of which rely on standard methods, such as histology, ELISA, and PCR. Here we put the focus on nanomechanical biosensors derived from atomic force microscopy cantilevers. The versatility of this novel technology has been demonstrated in different applications and in some ways surpasses current technologies, such as microarray, quartz crystal microbalance and surface plasmon resonance. The technology enables label free biomarker detection without the necessity of target amplification in a total cellular background, such as BRAF mutation analysis in malignant melanoma. A unique application of the cantilever array format is the analysis of conformational dynamics of membrane proteins associated to surface stress changes. Another development is characterisation of exhaled breath which allows assessment of a patient's condition in a non-invasive manner

LEED analysis of a dense lead monolayer on copper (100)

A LEED intensity analysis is reported for the c(5√2 × √2)R45° structure, which is formed by a dense lead monolayer on the (100) surface of copper. Evidence was found that the adsorbate atoms do not arrange pseudo-hexagonally (i.e. without sixfold intra-layer coordination) as expected for a dense two-dimensional package. It was confirmed that the lead atoms still tend to occupy the hollow sites of the (100) surface and arrange in the narrow domains of a strained c(2 × 2) structure. These domains are regularly intersected by dislocation lines, so that adjacent domains are in antiphase position. Within this arrangement the adsorbate atoms are mutually equidistant with closer spacings than in bulk lead. The growth of the monolayer and the epitaxial growth of lead on copper (100) in Stranski-Krastanov mode are correlated to this structure

Development of Robust and Standardized Cantilever Sensors Based on Biotin/Neutravidin Coupling for Antibody Detection

A cantilever-based protein biosensor has been developed providing a customizable multilayer platform for the detection of antibodies. It consists of a biotin-terminated PEG layer pre-functionalized on the gold-coated cantilever surface, onto which NeutrAvidin is adsorbed through biotin/NeutrAvidin specific binding. NeutrAvidin is used as a bridge layer between the biotin-coated surface and the biotinylated biomolecules, such as biotinylated bovine serum albumin (biotinylated BSA), forming a multilayer sensor for direct antibody capture. The cantilever biosensor has been successfully applied to the detection of mouse anti-BSA (m-IgG) and sheep anti-BSA(s-IgG) antibodies. As expected, the average differential surface stress signals of about 5.7 +/- 0.8 x 10(-3) N/m are very similar for BSA/m-IgG and BSA/s-IgG binding, i.e., they are independent of the origin of the antibody. A statistic evaluation of 112 response curves confirms that the multilayer protein cantilever biosensor shows high reproducibility. As a control test, a biotinylated maltose binding protein was used for detecting specificity of IgG, the result shows a signal of bBSA layer in response to antibody is 5.8 x 10(-3) N/m compared to bMBP. The pre-functionalized biotin/PEG cantilever surface is found to show a long shelf-life of at least 40 days and retains its responsivity of above 70% of the signal when stored in PBS buffer at 4 degrees C. The protein cantilever biosensor represents a rapid, label-free, sensitive and reliable detection technique for a real-time protein assay