Inboard and outboard radial electric field wells in the H- and I-mode pedestal of Alcator C-Mod and poloidal variations of impurity temperature

We present inboard (HFS) and outboard (LFS) radial electric field (E[subscript r]) and impurity temperature (T[subscript z]) measurements in the I-mode and H-mode pedestal of Alcator C-Mod. These measurements reveal strong Er wells at the HFS and the LFS midplane in both regimes and clear pedestals in T[subscript z], which are of similar shape and height for the HFS and LFS. While the H-mode E[subscript r] well has a radially symmetric structure, the E[subscript r] well in I-mode is asymmetric, with a stronger ExB shear layer at the outer edge of the E[subscript r] well, near the separatrix. Comparison of HFS and LFS profiles indicates that impurity temperature and plasma potential are not simultaneously flux functions. Uncertainties in radial alignment after mapping HFS measurements along flux surfaces to the LFS do not, however, allow direct determination as to which quantity varies poloidally and to what extent. Radially aligning HFS and LFS measurements based on the T[subscript z] profiles would result in substantial inboard-outboard variations of plasma potential and electron density. Aligning HFS and LFS E[subscript r] wells instead also approximately aligns the impurity poloidal flow profiles, while resulting in a LFS impurity temperature exceeding the HFS values in the region of steepest gradients by up to 70%. Considerations based on a simplified form of total parallel momentum balance and estimates of parallel and perpendicular heat transport time scales seem to favor an approximate alignment of the E[subscript r] wells and a substantial poloidal asymmetry in impurity temperature.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)Swiss National Science Foundatio

Pauli Spin Blockade in a Highly Tunable Silicon Double Quantum Dot

Double quantum dots are convenient solid-state platforms to encode quantum information. Two-electron spin states can be detected and manipulated using quantum selection rules based on the Pauli exclusion principle, leading to Pauli spin blockade of electron transport for triplet states. Coherent spin states would be optimally preserved in an environment free of nuclear spins, which is achievable in silicon by isotopic purification. Here we report on a deliberately engineered, gate-defined silicon metal-oxide-semiconductor double quantum dot system. The electron occupancy of each dot and the inter-dot tunnel coupling are independently tunable by electrostatic gates. At weak inter-dot coupling we clearly observe Pauli spin blockade and measure a large intra-dot singlet-triplet splitting > 1 meV. The leakage current in spin blockade has a peculiar magnetic field dependence, unrelated to electron-nuclear effects and consistent with the effect of spin-flip cotunneling processes. The results obtained here provide excellent prospects for realising singlet-triplet qubits

Making Informed Choices about Microarray Data Analysis

This article describes the typical stages in the analysis of microarray data for non-specialist researchers in systems biology and medicine. Particular attention is paid to significant data analysis issues that are commonly encountered among practitioners, some of which need wider airing. The issues addressed include experimental design, quality assessment, normalization, and summarization of multiple-probe data. This article is based on the ISMB 2008 tutorial on microarray data analysis. An expanded version of the material in this article and the slides from the tutorial can be found at http://www.people.vcu.edu/~mreimers/OGMDA/index.html

ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions

Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I ("Risk Of Bias In Non-randomised Studies-of Interventions"), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies

Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature

<p>Abstract</p> <p>Background</p> <p>There are several methods of assessing nutritional status in cancer of which serum albumin is one of the most commonly used. In recent years, the role of malnutrition as a predictor of survival in cancer has received considerable attention. As a result, it is reasonable to investigate whether serum albumin has utility as a prognostic indicator of cancer survival in cancer. This review summarizes all available epidemiological literature on the association between pretreatment serum albumin levels and survival in different types of cancer.</p> <p>Methods</p> <p>A systematic search of the literature using the MEDLINE database (January 1995 through June 2010) to identify epidemiologic studies on the relationship between serum albumin and cancer survival. To be included in the review, a study must have: been published in English, reported on data collected in humans with any type of cancer, had serum albumin as <it>one of the </it>or <it>only </it>predicting factor, had survival as one of the outcome measures (primary or secondary) and had any of the following study designs (case-control, cohort, cross-sectional, case-series prospective, retrospective, nested case-control, ecologic, clinical trial, meta-analysis).</p> <p>Results</p> <p>Of the 29 studies reviewed on cancers of the gastrointestinal tract, all except three found higher serum albumin levels to be associated with better survival in multivariate analysis. Of the 10 studies reviewed on lung cancer, all excepting one found higher serum albumin levels to be associated with better survival. In 6 studies reviewed on female cancers and multiple cancers each, lower levels of serum albumin were associated with poor survival. Finally, in all 8 studies reviewed on patients with other cancer sites, lower levels of serum albumin were associated with poor survival.</p> <p>Conclusions</p> <p>Pretreatment serum albumin levels provide useful prognostic significance in cancer. Accordingly, serum albumin level could be used in clinical trials to better define the baseline risk in cancer patients. A critical gap for demonstrating causality, however, is the absence of clinical trials demonstrating that raising albumin levels by means of intravenous infusion or by hyperalimentation decreases the excess risk of mortality in cancer.</p

Gene Expression, Function and Ischemia Tolerance in Male and Female Rat Hearts After Sub-Toxic Levels of Angiotensin II

To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter–matched rats were treated with 400 ng kg−1 min−1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, β-MCH, Ankrd-1, PKC-α, PKC-δ TNF-α); fibrosis (Col I-α1, Col III-α1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response

SYSGENET: a meeting report from a new European network for systems genetics

The first scientific meeting of the newly established European SYSGENET network took place at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, April 7-9, 2010. About 50 researchers working in the field of systems genetics using mouse genetic reference populations (GRP) participated in the meeting and exchanged their results, phenotyping approaches, and data analysis tools for studying systems genetics. In addition, the future of GRP resources and phenotyping in Europe was discussed

Molecular Characterization of a Novel Intracellular ADP-Ribosyl Cyclase

Background. ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates. Methodology/Principal Findings. Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1) is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained. Conclusions/Significance. Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized

Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of <it>Plasmodium </it><it>falciparum </it>through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration.</p> <p>Results</p> <p>Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle.</p> <p>Conclusions</p> <p>We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c), a Zinc finger transcription factor (PFL0465c) both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c).</p