Showing papers by "Ludwig Maximilian University of Munich published in 2009"
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Cardiff University1, Medical Research Council2, University of Bristol3, National Institute for Health Research4, King's College5, Trinity College, Dublin6, University of Cambridge7, University of Nottingham8, Queen's University Belfast9, University of Southampton10, University of Manchester11, John Radcliffe Hospital12, UCL Institute of Neurology13, University of Bonn14, University of Hamburg15, Charité16, University of Erlangen-Nuremberg17, University of Duisburg-Essen18, Ludwig Maximilian University of Munich19, Heidelberg University20, University College Dublin21, University of Freiburg22, Washington University in St. Louis23, Brigham Young University24, University of Antwerp25, University College London26, Wellcome Trust Sanger Institute27, King's College London28, Aristotle University of Thessaloniki29, National Institutes of Health30, Mayo Clinic31
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).
2,956 citations
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TL;DR: The aim of this work is to introduce the principles of the standard recursive partitioning methods as well as recent methodological improvements, to illustrate their usage for low and high-dimensional data exploration, but also to point out limitations of the methods and potential pitfalls in their practical application.
Abstract: Recursive partitioning methods have become popular and widely used tools for nonparametric regression and classification in many scientific fields. Especially random forests, which can deal with large numbers of predictor variables even in the presence of complex interactions, have been applied successfully in genetics, clinical medicine, and bioinformatics within the past few years. High-dimensional problems are common not only in genetics, but also in some areas of psychological research, where only a few subjects can be measured because of time or cost constraints, yet a large amount of data is generated for each subject. Random forests have been shown to achieve a high prediction accuracy in such applications and to provide descriptive variable importance measures reflecting the impact of each variable in both main effects and interactions. The aim of this work is to introduce the principles of the standard recursive partitioning methods as well as recent methodological improvements, to illustrate their usage for low and high-dimensional data exploration, but also to point out limitations of the methods and potential pitfalls in their practical application. Application of the methods is illustrated with freely available implementations in the R system for statistical computing.
2,001 citations
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Cristen J. Willer, Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Ruth J. F. Loos +163 more•Institutions (36)
TL;DR: Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
1,710 citations
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TL;DR: A meta-analysis of randomised controlled trials to compare the effects of second-generation antipsychotic drugs in patients with schizophrenia provided data for individualised treatment based on efficacy, side-effects, and cost.
1,682 citations
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deCODE genetics1, Maastricht University Medical Centre2, Utrecht University3, University of California, Los Angeles4, University of Oslo5, University of Bonn6, Ludwig Maximilian University of Munich7, Copenhagen University Hospital8, Wellcome Trust Sanger Institute9, Aarhus University Hospital10, Aarhus University11, University of Iceland12, University of Helsinki13, Bispebjerg Hospital14, Glostrup Hospital15, Heidelberg University16, Semmelweis University17, University of Verona18, Radboud University Nijmegen Medical Centre19, Russian Academy20, University of Valencia21, King's College London22, Royal Cornhill Hospital23, Duke University24, University of Santiago de Compostela25, Hospital General Universitario Gregorio Marañón26, Karolinska Institutet27, Hammersmith Hospital28, GlaxoSmithKline29, Sichuan University30
TL;DR: Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
1,625 citations
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University of Michigan1, University of Texas at Austin2, ETH Zurich3, Ludwig Maximilian University of Munich4, Carnegie Institution for Science5, University of California, Santa Cruz6, University of California, Berkeley7, University of Arizona8, Durham University9, Ohio Northern University10, Université libre de Bruxelles11
TL;DR: In this article, improved versions of the relations between supermassive black hole mass (M BH) and host-galaxy bulge velocity dispersion (σ) and luminosity (L; the M-σ and M-L relations), based on 49 M BH measurements and 19 upper limits, were derived.
Abstract: We derive improved versions of the relations between supermassive black hole mass (M BH) and host-galaxy bulge velocity dispersion (σ) and luminosity (L; the M-σ and M-L relations), based on 49 M BH measurements and 19 upper limits. Particular attention is paid to recovery of the intrinsic scatter (e0) in both relations. We find log(M BH/M) = α + βlog(σ/200 km s-1) with (α, β, e0) = (8.12 0.08, 4.24 0.41, 0.44 0.06) for all galaxies and (α, β, e0) = (8.23 0.08, 3.96 0.42, 0.31 0.06) for ellipticals. The results for ellipticals are consistent with previous studies, but the intrinsic scatter recovered for spirals is significantly larger. The scatter inferred reinforces the need for its consideration when calculating local black hole mass function based on the M-σ relation, and further implies that there may be substantial selection bias in studies of the evolution of the M-σ relation. We estimate the M-L relationship as log(M BH/M) = α + βlog(LV /1011 L V) of (α, β, e0) = (8.95 0.11, 1.11 0.18, 0.38 0.09); using only early-type galaxies. These results appear to be insensitive to a wide range of assumptions about the measurement errors and the distribution of intrinsic scatter. We show that culling the sample according to the resolution of the black hole's sphere of influence biases the relations to larger mean masses, larger slopes, and incorrect intrinsic residuals. © 2009. The American Astronomical Society.
1,528 citations
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University of Michigan1, University of Texas at Austin2, ETH Zurich3, Ludwig Maximilian University of Munich4, Carnegie Institution for Science5, University of California, Santa Cruz6, University of California, Berkeley7, University of Arizona8, Durham University9, Ohio Northern University10, Université libre de Bruxelles11
TL;DR: This article derived improved versions of the relations between supermassive black hole mass and host-galaxy bulge velocity dispersion (sigma) and luminosity (L) (the M-sigma and M-L relations), based on 49 M_BH measurements and 19 upper limits.
Abstract: We derive improved versions of the relations between supermassive black hole mass (M_BH) and host-galaxy bulge velocity dispersion (sigma) and luminosity (L) (the M-sigma and M-L relations), based on 49 M_BH measurements and 19 upper limits. Particular attention is paid to recovery of the intrinsic scatter (epsilon_0) in both relations. We find log(M_BH / M_sun) = alpha + beta * log(sigma / 200 km/s) with (alpha, beta, epsilon_0) = (8.12 +/- 0.08, 4.24 +/- 0.41, 0.44 +/- 0.06) for all galaxies and (alpha, beta, epsilon_0) = (8.23 +/- 0.08, 3.96 +/- 0.42, 0.31 +/- 0.06) for ellipticals. The results for ellipticals are consistent with previous studies, but the intrinsic scatter recovered for spirals is significantly larger. The scatter inferred reinforces the need for its consideration when calculating local black hole mass function based on the M-sigma relation, and further implies that there may be substantial selection bias in studies of the evolution of the M-sigma relation. We estimate the M-L relationship as log(M_BH / M_sun) = alpha + beta * log(L_V / 10^11 L_sun,V) of (alpha, beta, epsilon_0) = (8.95 +/- 0.11, 1.11 +/- 0.18, 0.38 +/- 0.09); using only early-type galaxies. These results appear to be insensitive to a wide range of assumptions about the measurement errors and the distribution of intrinsic scatter. We show that culling the sample according to the resolution of the black hole's sphere of influence biases the relations to larger mean masses, larger slopes, and incorrect intrinsic residuals.
1,522 citations
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TL;DR: This survey tries to clarify the different problem definitions related to subspace clustering in general; the specific difficulties encountered in this field of research; the varying assumptions, heuristics, and intuitions forming the basis of different approaches; and how several prominent solutions tackle different problems.
Abstract: As a prolific research area in data mining, subspace clustering and related problems induced a vast quantity of proposed solutions. However, many publications compare a new proposition—if at all—with one or two competitors, or even with a so-called “naive” ad hoc solution, but fail to clarify the exact problem definition. As a consequence, even if two solutions are thoroughly compared experimentally, it will often remain unclear whether both solutions tackle the same problem or, if they do, whether they agree in certain tacit assumptions and how such assumptions may influence the outcome of an algorithm. In this survey, we try to clarify: (i) the different problem definitions related to subspace clustering in general; (ii) the specific difficulties encountered in this field of research; (iii) the varying assumptions, heuristics, and intuitions forming the basis of different approaches; and (iv) how several prominent solutions tackle different problems.
1,206 citations
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Christopher Newton-Cheh1, Christopher Newton-Cheh2, Toby Johnson3, Toby Johnson4 +359 more•Institutions (64)
TL;DR: In this paper, the association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2(P = 1 × 10-23), FGF5 (P=1 × 10 -21), SH2B3(P= 3 × 10−18), MTHFR(MTHFR), c10orf107(P), ZNF652(ZNF652), PLCD3 (P,P = 5 × 10 −9),
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
1,205 citations
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Harvard University1, Broad Institute2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, McMaster University4, McGill University5, University of Leicester6, University of Lübeck7, University of Pennsylvania8, Vanderbilt University9, University of Missouri–Kansas City10, University of Münster11, University of Verona12, Queen's University Belfast13, University of Washington14, Boston University15, University of Helsinki16, National Institute for Health and Welfare17, Lund University18, University of Cambridge19, Vita-Salute San Raffaele University20, University of Ferrara21, University of Turin22, Hebrew University of Jerusalem23, University of Girona24, University of Milan25, University of Leeds26, University of Regensburg27, Ludwig Maximilian University of Munich28, University of Kiel29, Wellcome Trust Sanger Institute30, University of Paris31, MedStar Washington Hospital Center32, deCODE genetics33, University of Iceland34
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk
1,092 citations
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TL;DR: This review describes many examples of how modern molecular-biological methods can enable us to understand the various synergistic mechanisms underlying these effects of herbal drug combinations.
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TL;DR: In this paper, a theoretical model linking achievement goals and achievement emotions to academic performance was proposed, which was tested in a prospective study with undergraduates, using exam-specific assessments of both goals and emotions as predictors of exam performance in an introductory-level psychology course.
Abstract: The authors propose a theoretical model linking achievement goals and achievement emotions to academic performance. This model was tested in a prospective study with undergraduates (N = 213), using exam-specific assessments of both goals and emotions as predictors of exam performance in an introductory-level psychology course. The findings were consistent with the authors' hypotheses and supported all aspects of the proposed model. In multiple regression analysis, achievement goals (mastery, performance approach, and performance avoidance) were shown to predict discrete achievement emotions (enjoyment, boredom, anger, hope, pride, anxiety, hopelessness, and shame), achievement emotions were shown to predict performance attainment, and 7 of the 8 focal emotions were documented as mediators of the relations between achievement goals and performance attainment. All of these findings were shown to be robust when controlling for gender, social desirability, positive and negative trait affectivity, and scholastic ability. The results are discussed with regard to the underdeveloped literature on discrete achievement emotions and the need to integrate conceptual and applied work on achievement goals and achievement emotions.
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TL;DR: In this article, the authors provide evidence that the robust association between cognitive skills and economic growth reflects a causal effect of cognitive skills, and support the economic benefits of effective school policy and develop a new common metric that allows tracking student achievement across countries, over time, and along the within-country distribution.
Abstract: We provide evidence that the robust association between cognitive skills and economic growth reflects a causal effect of cognitive skills and supports the economic benefits of effective school policy. We develop a new common metric that allows tracking student achievement across countries, over time, and along the within-country distribution. Extensive sensitivity analyses of cross-country growth regressions generate remarkably stable results across specifications, time periods, and country samples. In addressing causality, we find, first, significant growth effects of cognitive skills when instrumented by institutional features of school systems. Second, home-country cognitive-skill levels strongly affect the earnings of immigrants on the U.S. labor market in a difference-in-differences model that compares home-educated to U.S.-educated immigrants from the same country of origin. Third, countries that improved their cognitive skills over time experienced relative increases in their growth paths. From a policy perspective, the shares of basic literates and high performers have independent significant effects on growth that are complementary to each other, and the high-performer effect is larger in poorer countries.
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TL;DR: A detailed Raman investigation of graphene flakes with edges oriented at different crystallographic directions is presented and a real space theory for Raman scattering is developed to analyze the general case of disordered edges.
Abstract: Graphene edges are of particular interest since their orientation determines the electronic properties. Here we present a detailed Raman investigation of graphene flakes with edges oriented at different crystallographic directions. We also develop a real space theory for Raman scattering to analyze the general case of disordered edges. The position, width, and intensity of G and D peaks are studied as a function of the incident light polarization. The D-band is strongest for polarization parallel to the edge and minimum for perpendicular. Raman mapping shows that the D peak is localized in proximity of the edge. For ideal edges, the D peak is zero for zigzag orientation and large for armchair, allowing in principle the use of Raman spectroscopy as a sensitive tool for edge orientation. However, for real samples, the D to G ratio does not always show a significant dependence on edge orientation. Thus, even though edges can appear macroscopically smooth and oriented at well-defined angles, they are not necessarily microscopically ordered.
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TL;DR: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency and effective protection against infections and improvement in physical development made a normal lifestyle possible.
Abstract: Background We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. Methods We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. Results All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxificati...
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TL;DR: In this article, a review of work on graphene monolayers adsorbed on metal surfaces is presented, with a focus on the metal/graphene interaction. But the authors do not consider the effect of the metal-graphenes interaction on the electronic structure.
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TL;DR: A link comprising the gp130/Stat3 transcription factor signaling axis is established comprising the common tumor cell-autonomous mechanism that bridges chronic inflammation to tumor promotion in colitis-associated cancer models.
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TL;DR: In this article, a cross-sectional, international, multicenter, observational study was conducted to estimate the radiation dose of CCTA in routine clinical practice as well as the association of currently available strategies with dose reduction.
Abstract: Context Cardiac computed tomography (CT) angiography (CCTA) has emerged as a useful diagnostic imaging modality in the assessment of coronary artery disease. However, the potential risks due to exposure to ionizing radiation associated with CCTA have raised concerns. Objectives To estimate the radiation dose of CCTA in routine clinical practice as well as the association of currently available strategies with dose reduction and to identify the independent factors contributing to radiation dose. Design, Setting, and Patients A cross-sectional, international, multicenter, observational study (50 study sites: 21 university hospitals and 29 community hospitals) of estimated radiation dose in 1965 patients undergoing CCTA between February and December 2007. Linear regression analysis was used to identify independent predictors associated with dose. Main Outcome Measure Dose-length product (DLP) of CCTA. Results The median DLP of 1965 CCTA examinations performed at 50 study sites was 885 mGy × cm (interquartile range, 568-1259 mGy × cm), which corresponds to an estimated radiation dose of 12 mSv (or 1.2 × the dose of an abdominal CT study or 600 chest x-rays). A high variability in DLP was observed between study sites (range of median DLPs per site, 331-2146 mGy × cm). Independent factors associated with radiation dose were patient weight (relative effect on DLP, 5%; 95% confidence interval [CI], 4%-6%), absence of stable sinus rhythm (10%; 95% CI, 2%-19%), scan length (5%; 95% CI, 4%-6%), electrocardiographically controlled tube current modulation (−25%; 95% CI, −23% to −28%; applied in 73% of patients), 100-kV tube voltage (−46%; 95% CI, −42% to −51%; applied in 5% of patients), sequential scanning (−78%; 95% CI, −77% to −79%; applied in 6% of patients), experience in cardiac CT (−1%; 95% CI, −1% to 0%), number of CCTAs per month (0%; 95% CI, 0%-1%), and type of 64-slice CT system (for highest vs lowest dose system, 97%; 95% CI, 88%-106%). Algorithms for dose reduction were not associated with deteriorated diagnostic image quality in this observational study. Conclusions Median doses of CCTA differ significantly between study sites and CT systems. Effective strategies to reduce radiation dose are available but some strategies are not frequently used. The comparable diagnostic image quality may support an increased use of dose-saving strategies in adequately selected patients.
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TL;DR: Recent insights into the structure, function, and cellular regulation of HCN channels are summarized and evidence on the role of individual HCN channel types arising from the analysis ofHCN knockout mouse models is discussed.
Abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN channel family com...
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TL;DR: It is shown that a high-salt diet in rats leads to interstitial hypertonic Na+ accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network and VEGFC is identified as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertension.
Abstract: In salt-sensitive hypertension, the accumulation of Na(+) in tissue has been presumed to be accompanied by a commensurate retention of water to maintain the isotonicity of body fluids We show here that a high-salt diet (HSD) in rats leads to interstitial hypertonic Na(+) accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network The mechanisms underlying these effects on lymphatics involve activation of tonicity-responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells infiltrating the interstitium of the skin TonEBP binds the promoter of the gene encoding vascular endothelial growth factor-C (VEGF-C, encoded by Vegfc) and causes VEGF-C secretion by macrophages MPS cell depletion or VEGF-C trapping by soluble VEGF receptor-3 blocks VEGF-C signaling, augments interstitial hypertonic volume retention, decreases endothelial nitric oxide synthase expression and elevates blood pressure in response to HSD Our data show that TonEBP-VEGF-C signaling in MPS cells is a major determinant of extracellular volume and blood pressure homeostasis and identify VEGFC as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertension
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TL;DR: The results demonstrate the molecular basis for IL-1β production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo.
Abstract: Immunocompromised individuals are at high risk from fungal infection, yet the molecular mechanisms that govern host defence against fungi are not well understood. Gross et al. now show that Candida albicans infection in mice activates the NALP3 inflammasome via a mechanism involving Sky-induced production of reactive oxygen induced by the tyrosine kinase Syk.
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Austrian Institute of Technology1, Télécom ParisTech2, University of Geneva3, Masaryk University4, Centre national de la recherche scientifique5, University of Surrey6, Toshiba7, Ludwig Maximilian University of Munich8, Austrian Academy of Sciences9, University of Vienna10, University of Waterloo11, University of Erlangen-Nuremberg12, BearingPoint13, Université de Montréal14, Max Planck Society15, Siemens16
TL;DR: The paper presents the architecture and functionality of the principal networking agent?the SECOQC node module, which enables the authentic classical communication required for key distillation, manages the generated key material, determines a communication path between any destinations in the network, and realizes end-to-end secure transport of key material between these destinations.
Abstract: In this paper, we present the quantum key distribution (QKD) network designed and implemented by the European project SEcure COmmunication based on Quantum Cryptography (SECOQC) (2004?2008), unifying the efforts of 41 research and industrial organizations. The paper summarizes the SECOQC approach to QKD networks with a focus on the trusted repeater paradigm. It discusses the architecture and functionality of the SECOQC trusted repeater prototype, which has been put into operation in Vienna in 2008 and publicly demonstrated in the framework of a SECOQC QKD conference held from October 8 to 10, 2008. The demonstration involved one-time pad encrypted telephone communication, a secure (AES encryption protected) video-conference with all deployed nodes and a number of rerouting experiments, highlighting basic mechanisms of the SECOQC network functionality.The paper gives an overview of the eight point-to-point network links in the prototype and their underlying technology: three plug and play systems by id Quantique, a one way weak pulse system from Toshiba Research in the UK, a coherent one-way system by GAP Optique with the participation of id Quantique and the AIT Austrian Institute of Technology (formerly ARC), an entangled photons system by the University of Vienna and the AIT, a continuous-variables system by Centre National de la Recherche Scientifique (CNRS) and THALES Research and Technology with the participation of Universit? Libre de Bruxelles, and a free space link by the Ludwig Maximillians University in Munich connecting two nodes situated in adjacent buildings (line of sight 80?m). The average link length is between 20 and 30?km, the longest link being 83?km.The paper presents the architecture and functionality of the principal networking agent?the SECOQC node module, which enables the authentic classical communication required for key distillation, manages the generated key material, determines a communication path between any destinations in the network, and realizes end-to-end secure transport of key material between these destinations.The paper also illustrates the operation of the network in a number of typical exploitation regimes and gives an initial estimate of the network transmission capacity, defined as the maximum amount of key that can be exchanged, or alternatively the amount of information that can be transmitted with information theoretic security, between two arbitrary nodes.
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TL;DR: This review gives a short outline of currently discussed pathways and induction methods for protein aggregation and describes currently employed set of analytical techniques and emerging technologies for aggregate detection, characterization and quantification.
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TL;DR: In this review, basic concepts of hair follicle biology are presented and important recent advances in the field are summarized.
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TL;DR: In this paper, a parameterized stellar-to-halo mass (SHM) relation was derived by populating halos and subhalos in an N-body simulation with galaxies and requiring that the observed stellar mass function be reproduced.
Abstract: We use a statistical approach to determine the relationship between the stellar masses of galaxies and the masses of the dark matter halos in which they reside. We obtain a parameterized stellar-to-halo mass (SHM) relation by populating halos and subhalos in an N-body simulation with galaxies and requiring that the observed stellar mass function be reproduced. We find good agreement with constraints from galaxy-galaxy lensing and predictions of semi-analytic models. Using this mapping, and the positions of the halos and subhalos obtained from the simulation, we find that our model predictions for the galaxy two-point correlation function (CF) as a function of stellar mass are in excellent agreement with the observed clustering properties in the SDSS at z=0. We show that the clustering data do not provide additional strong constraints on the SHM function and conclude that our model can therefore predict clustering as a function of stellar mass. We compute the conditional mass function, which yields the average number of galaxies with stellar masses in the range [m, m+dm] that reside in a halo of mass M. We study the redshift dependence of the SHM relation and show that, for low mass halos, the SHM ratio is lower at higher redshift. The derived SHM relation is used to predict the stellar mass dependent galaxy CF and bias at high redshift. Our model predicts that not only are massive galaxies more biased than low mass ones at all redshifts, but the bias increases more rapidly with increasing redshift for massive galaxies than for low mass ones. We present convenient fitting functions for the SHM relation as a function of redshift, the conditional mass function, and the bias as a function of stellar mass and redshift.
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TL;DR: In this paper, the authors compared the probability of survival in patients with blunt trauma who had whole-body CT during resuscitation with those who had not, and found that the use of CT for early assessment of primary trauma is increasing.
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TL;DR: The European Psychiatric Association (EPA) supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published a statement with the aim of improving the care of patients suffering from severe mental illness as mentioned in this paper.
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University of Chicago1, University of Washington2, Wayne State University3, Fermilab4, University of Copenhagen5, University of Queensland6, Rutgers University7, New Mexico State University8, University of Portsmouth9, University of Pennsylvania10, University of Cape Town11, Stanford University12, Ludwig Maximilian University of Munich13, Texas A&M University14, University of Tokyo15, Institute for the Physics and Mathematics of the Universe16, University of California, Berkeley17, Harvard University18, University of Notre Dame19, University of Göttingen20, Stockholm University21, Ohio State University22, Rochester Institute of Technology23, Johns Hopkins University24, Space Telescope Science Institute25, Pennsylvania State University26, University of Texas at Austin27
TL;DR: In this article, the authors present measurements of the Hubble diagram for 103 Type Ia supernovae with redshifts 0.04 < z < 0.42, discovered during the first season (Fall 2005) of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey.
Abstract: We present measurements of the Hubble diagram for 103 Type Ia supernovae (SNe) with redshifts 0.04 < z < 0.42, discovered during the first season (Fall 2005) of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. These data fill in the redshift "desert" between low- and high-redshift SN Ia surveys. Within the framework of the MLCS2K2 light-curve fitting method, we use the SDSS-II SN sample to infer the mean reddening parameter for host galaxies, RV = 2.18 ± 0.14stat ± 0.48syst, and find that the intrinsic distribution of host-galaxy extinction is well fitted by an exponential function, P(AV ) = exp(–AV /τV), with τV = 0.334 ± 0.088 mag. We combine the SDSS-II measurements with new distance estimates for published SN data from the ESSENCE survey, the Supernova Legacy Survey (SNLS), the Hubble Space Telescope (HST), and a compilation of Nearby SN Ia measurements. A new feature in our analysis is the use of detailed Monte Carlo simulations of all surveys to account for selection biases, including those from spectroscopic targeting. Combining the SN Hubble diagram with measurements of baryon acoustic oscillations from the SDSS Luminous Red Galaxy sample and with cosmic microwave background temperature anisotropy measurements from the Wilkinson Microwave Anisotropy Probe, we estimate the cosmological parameters w and ΩM, assuming a spatially flat cosmological model (FwCDM) with constant dark energy equation of state parameter, w. We also consider constraints upon ΩM and ΩΛ for a cosmological constant model (ΛCDM) with w = –1 and non-zero spatial curvature. For the FwCDM model and the combined sample of 288 SNe Ia, we find w = –0.76 ± 0.07(stat) ± 0.11(syst), ΩM = 0.307 ± 0.019(stat) ± 0.023(syst) using MLCS2K2 and w = –0.96 ± 0.06(stat) ± 0.12(syst), ΩM = 0.265 ± 0.016(stat) ± 0.025(syst) using the SALT-II fitter. We trace the discrepancy between these results to a difference in the rest-frame UV model combined with a different luminosity correction from color variations; these differences mostly affect the distance estimates for the SNLS and HST SNe. We present detailed discussions of systematic errors for both light-curve methods and find that they both show data-model discrepancies in rest-frame U band. For the SALT-II approach, we also see strong evidence for redshift-dependence of the color-luminosity parameter (β). Restricting the analysis to the 136 SNe Ia in the Nearby+SDSS-II samples, we find much better agreement between the two analysis methods but with larger uncertainties: w = –0.92 ± 0.13(stat)+0.10 –0.33(syst) for MLCS2K2 and w = –0.92 ± 0.11(stat)+0.07 –0.15 (syst) for SALT-II.
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Wellcome Trust Centre for Human Genetics1, Medical Research Council2, Broad Institute3, Harvard University4, King's College London5, Wellcome Trust Sanger Institute6, deCODE genetics7, Boston University8, University of Michigan9, Erasmus University Rotterdam10, National Institutes of Health11, VU University Amsterdam12, University of Oulu13, Lund University14, University of Virginia15, University Hospital of Lausanne16, University of Lausanne17, University of Southern California18, Imperial College London19, Ninewells Hospital20, University of California, Los Angeles21, University of Düsseldorf22, Novartis23, Swiss Institute of Bioinformatics24, European Bioinformatics Institute25, University of Eastern Finland26, GlaxoSmithKline27, University of North Carolina at Chapel Hill28, Oulu University Hospital29, University Medical Center Groningen30, University of Helsinki31, Ludwig Maximilian University of Munich32, University of Cambridge33, Leiden University Medical Center34, VU University Medical Center35, Brigham and Women's Hospital36, Massachusetts Institute of Technology37, University of Iceland38, University of Oxford39
TL;DR: Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten genome-wide association scans, and previous associations of fasting glucose with variants at the G6PC2 and GCK loci are confirmed.
Abstract: To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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TL;DR: It is shown that the nuclear architecture of rod photoreceptor cells differs fundamentally in nocturnal and diurnal mammals and suggests that the conventional architecture prevails in eukaryotic nuclei because it results in more flexible chromosome arrangements, facilitating positional regulation of nuclear functions.