MEN1 Gene mutation and reduced expression are associated with poor prognosis in pulmonary carcinoids

Context: MEN1 gene alterations have been implicated in lung carcinoids, but their effect on gene expression and disease outcome is unknown. Objective: Our objective was to analyze MEN1 gene and expression anomalies in lung neuroendocrine neoplasms and their correlations with clinicopathologic data and disease outcome. Design: We examined 74 lung neuroendocrine neoplasms including 58 carcinoids and 16 high-grade neuroendocrine carcinomas (HGNECs) for MEN1 mutations (n = 70) and allelic losses (n = 69), promoter hypermethylation (n = 65), and mRNA (n = 74) expression. Results were correlated with disease outcome. Results: MEN1 mutations were found in 7 of 55 (13%) carcinoids and in 1 HGNEC, mostly associated with loss of the second allele. MEN1 decreased expression levels correlated with the presence of mutations (P = .0060) and was also lower in HGNECs than carcinoids (P = .0024). MEN1 methylation was not associated with mRNA expression levels. Patients with carcinoids harboring MEN1 mutation and loss had shorter overall survival (P = .039 and P = .035, respectively) and low MEN1 mRNA levels correlated with distant metastasis (P = .00010) and shorter survival (P = .0071). In multivariate analysis, stage and MEN1 allelic loss were independent predictors of prognosis. Conclusion: Thirteen percent of pulmonary carcinoids harbor MEN1 mutation associated with reduced mRNA expression and poor prognosis. Also in mutation-negative tumors, low MEN1 gene expression correlates with an adverse disease outcome. Hypermethylation was excluded as the underlying mechanism

VHMPID: a new detector for the ALICE experiment at LHC

This article presents the basic idea of VHMPID, an upgrade detector for the ALICE experiment at LHC, CERN. The main goal of this detector is to extend the particle identification capabilities of ALICE to give more insight into the evolution of the hot and dense matter created in Pb-Pb collisions. Starting from the physics motivations and working principles the challenges and current status of development is detailed.Comment: 4 pages, 6 figures. To be published in EPJ Web of Conference

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Assessing the efficiency of mother-to-child HIV prevention in low- and middle-income countries using data envelopment analysis

AIDS is one of the most significant health care problems worldwide. Due to the difficulty and costs involved in treating HIV, preventing infection is of paramount importance in controlling the AIDS epidemic. The main purpose of this paper is to explore the potential of using Data Envelopment Analysis (DEA) to establish international comparisons on the efficiency of implementation of HIV prevention programmes. To do this we use data from 52 low- and middle-income countries regarding the prevention of mother-to-child transmission of HIV. Our results indicate that there is a remarkable variation in the efficiency of prevention services across nations, suggesting that a better use of resources could lead to more and improved services, and ultimately, prevent the infection of thousands of children. These results also demonstrate the potential strategic role of DEA for the efficient and effective planning of scarce resources to fight the epidemic

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Regulators of genetic risk of breast cancer identified by integrative network analysis.

Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.This work was funded by Cancer Research UK and the Breast Cancer Research Foundation. MAAC is funded by the National Research Council (CNPq) of Brazil. TEH held a fellowship from the US DOD Breast Cancer Research Program (W81XWH-11-1-0592) and is currently supported by an RAH Career Development Fellowship (Australia). TEH and WDT are funded by the NHMRC of Australia (NHMRC) (ID: 1008349 WDT; 1084416 WDT, TEH) and Cancer Australia/National Breast Cancer Foundation (ID 627229; WDT, TEH). BAJP is a Gibb Fellow of Cancer Research UK. We would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Charge-Free Mixing Entropy Battery Enabled by Low-Cost Electrode Materials.

Salinity gradients are a vast and untapped energy resource. For every cubic meter of freshwater that mixes with seawater, approximately 0.65 kW h of theoretically recoverable energy is lost. For coastal wastewater treatment plants that discharge to the ocean, this energy, if recovered, could power the plant. The mixing entropy battery (MEB) uses battery electrodes to convert salinity gradient energy into electricity in a four-step process: (1) freshwater exchange; (2) charging in freshwater; (3) seawater exchange; and (4) discharging in seawater. Previously, we demonstrated a proof of concept, but with electrode materials that required an energy investment during the charging step. Here, we introduce a charge-free MEB with low-cost electrodes: Prussian Blue (PB) and polypyrrole (PPy). Importantly, this MEB requires no energy investment, and the electrode materials are stable with repeated cycling. The MEB equipped with PB and PPy achieved high voltage ratios (actual voltages obtained divided by the theoretical voltages) of 89.5% in wastewater effluent and 97.6% in seawater, with over 93% capacity retention after 50 cycles of operation and 97-99% over 150 cycles with a polyvinyl alcohol/sulfosuccinic acid (PVA/SSA) coating on the PB electrode

Plasticity of the Muscle Stem Cell Microenvironment

Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes

Search for Anomalous Production of Events with a Photon, Jet, b-quark Jet, and Missing Transverse Energy

Submitted to Phys. Rev. DWe present a signature-based search for anomalous production of events containing a photon, two jets, of which at least one is identified as originating from a b quark, and missing transverse energy. The search uses data corresponding to 2.0/fb of integrated luminosity from p-pbar collisions at a center-of-mass energy of sqrt(s)=1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. From 6,697,466 events with a photon candidate with transverse energy ET> 25 GeV, we find 617 events with missing transverse energy > 25 GeV and two or more jets with ET> 15 GeV, at least one identified as originating from a b quark, versus an expectation of 607+- 113 events. Increasing the requirement on missing transverse energy to 50 GeV, we find 28 events versus an expectation of 30+-11 events. We find no indications of non-standard-model phenomena.We present a signature-based search for the anomalous production of events containing a photon, two jets, of which at least one is identified as originating from a b quark, and missing transverse energy (E̸T). The search uses data corresponding to 2.0  fb-1 of integrated luminosity from pp̅ collisions at a center-of-mass energy of √s=1.96  TeV, collected with the CDF II detector at the Fermilab Tevatron. From 6.697 47×106 events with a photon candidate with transverse energy ET>25  GeV, we find 617 events with E̸T>25  GeV and two or more jets with ET>15  GeV, at least one identified as originating from a b quark, versus an expectation of 607±113 events. Increasing the requirement on E̸T to 50 GeV, we find 28 events versus an expectation of 30±11 events. We find no indications of non-standard-model phenomena.Peer reviewe