New pixelized Micromegas detector with low discharge rate for the COMPASS experiment

New Micromegas (Micro-mesh gaseous detectors) are being developed in view of the future physics projects planned by the COMPASS collaboration at CERN. Several major upgrades compared to present detectors are being studied: detectors standing five times higher luminosity with hadron beams, detection of beam particles (flux up to a few hundred of kHz/mm^{2}, 10 times larger than for the present Micromegas detectors) with pixelized read-out in the central part, light and integrated electronics, and improved robustness. Two solutions of reduction of discharge impact have been studied, with Micromegas detectors using resistive layers and using an additional GEM foil. Performance of such detectors has also been measured. A large size prototypes with nominal active area and pixelized read-out has been produced and installed at COMPASS in 2010. In 2011 prototypes featuring an additional GEM foil, as well as an resistive prototype, are installed at COMPASS and preliminary results from those detectors presented very good performance. We present here the project and report on its status, in particular the performance of large size prototypes with an additional GEM foil.Comment: 11 pages, 5 figures, proceedings to the Micro-Pattern Gaseous Detectors conference (MPGD2011), 29-31 August 2011, Kobe, Japa

Uremic Toxins Inhibit Transport by Breast Cancer Resistance Protein and Multidrug Resistance Protein 4 at Clinically Relevant Concentrations

During chronic kidney disease (CKD), there is a progressive accumulation of toxic solutes due to inadequate renal clearance. Here, the interaction between uremic toxins and two important efflux pumps, viz. multidrug resistance protein 4 (MRP4) and breast cancer resistance protein (BCRP) was investigated. Membrane vesicles isolated from MRP4- or BCRP-overexpressing human embryonic kidney cells were used to study the impact of uremic toxins on substrate specific uptake. Furthermore, the concentrations of various uremic toxins were determined in plasma of CKD patients using high performance liquid chromatography and liquid chromatography/tandem mass spectrometry. Our results show that hippuric acid, indoxyl sulfate and kynurenic acid inhibit MRP4-mediated [3H]-methotrexate ([3H]-MTX) uptake (calculated Ki values: 2.5 mM, 1 mM, 25 µM, respectively) and BCRP-mediated [3H]-estrone sulfate ([3H]-E1S) uptake (Ki values: 4 mM, 500 µM and 50 µM, respectively), whereas indole-3-acetic acid and phenylacetic acid reduce [3H]-MTX uptake by MRP4 only (Ki value: 2 mM and IC50 value: 7 mM, respectively). In contrast, p-cresol, p-toluenesulfonic acid, putrescine, oxalate and quinolinic acid did not alter transport mediated by MRP4 or BCRP. In addition, our results show that hippuric acid, indole-3-acetic acid, indoxyl sulfate, kynurenic acid and phenylacetic acid accumulate in plasma of end-stage CKD patients with mean concentrations of 160 µM, 4 µM, 129 µM, 1 µM and 18 µM, respectively. Moreover, calculated Ki values are below the maximal plasma concentrations of the tested toxins. In conclusion, this study shows that several uremic toxins inhibit active transport by MRP4 and BCRP at clinically relevant concentrations

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/

It’s not the size, it’s the relationship: from ‘small states’ to asymmetry

Debate about the definition of “small state” has produced more fragmentation than consensus, even as the literature has demonstrated its subjects’ roles in joining international organizations propagating norms, executing creative diplomacy, influencing allies, avoiding and joining conflicts, and building peace. However, work on small states has struggled to identify commonalities in these states’ international relations, to cumulate knowledge, or to impact broader IR theory. This paper advocates a changed conceptual and definitional framework. Analysis of “small states” should pivot to examine the dynamics of the asymmetrical relationships in which these states are engaged. Instead of seeking an overall metric for size as the relevant variable—falling victim in a different way Dahl’s “lump-of-power fallacy,” we can recognize the multifaceted, variegated nature of power, whether in war or peacetime

ANTARES: the first undersea neutrino telescope

The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given

A Novel Repertoire of Blood Transcriptome Modules Based on Co-expression Patterns across sixteen Disease and Physiological States

Blood transcriptomics measures the abundance of circulating leukocyte RNA on a genome-wide scale. Dimension reduction is an important analytic step which condenses the number of variables and permits to enhance the robustness of data analyses and functional interpretation. An approach consisting in the construction of modular repertoires based on differential co-expression observed across multiple biological states of a given system has been described before. In this report, a new blood transcriptome modular repertoire is presented based on an expended range of disease and physiological states (16 in total, encompassing 985 unique transcriptome profiles). The input datasets have been deposited in NCBI public repository, GEO. The composition of the set of 382 modules constituting the repertoire is shared, along with extensive functional annotations and a custom fingerprint visualization scheme. Finally, the similarities and differences between the blood transcriptome profiles of this wide range of biological states are presented and discussed