An integrative analysis of cancer gene expression studies using Bayesian latent factor modeling

We present an applied study in cancer genomics for integrating data and inferences from laboratory experiments on cancer cell lines with observational data obtained from human breast cancer studies. The biological focus is on improving understanding of transcriptional responses of tumors to changes in the pH level of the cellular microenvironment. The statistical focus is on connecting experimentally defined biomarkers of such responses to clinical outcome in observational studies of breast cancer patients. Our analysis exemplifies a general strategy for accomplishing this kind of integration across contexts. The statistical methodologies employed here draw heavily on Bayesian sparse factor models for identifying, modularizing and correlating with clinical outcome these signatures of aggregate changes in gene expression. By projecting patterns of biological response linked to specific experimental interventions into observational studies where such responses may be evidenced via variation in gene expression across samples, we are able to define biomarkers of clinically relevant physiological states and outcomes that are rooted in the biology of the original experiment. Through this approach we identify microenvironment-related prognostic factors capable of predicting long term survival in two independent breast cancer datasets. These results suggest possible directions for future laboratory studies, as well as indicate the potential for therapeutic advances though targeted disruption of specific pathway components.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS261 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Restoring Constitutional Balance: Accommodating the Evolution of War

When drafting the Constitution, the Framers implemented a structural system of checks and balances to guard against the executive tyranny they had experienced under British rule. During the Vietnam War many in Congress perceived the executive branch as over-reaching, and in response they passed the War Powers Resolution of 1973, which was an attempt to place a procedural check on executive power. This Note examines changes in the technology and actors involved in modern warfare against the scope of the Resolution. The 2011 conflict in Libya is presented as a specific example to demonstrate that modern warfare has evolved outside the scope of the Resolution. Based on the assumption that war powers should be balanced between the executive and legislative branches, this Note argues for new war powers legislation that is more broad and flexible in scope to accommodate the evolution of war

The septin cytoskeleton facilitates membrane retraction during motility and blebbing.

Increasing evidence supports a critical role for the septin cytoskeleton at the plasma membrane during physiological processes including motility, formation of dendritic spines or cilia, and phagocytosis. We sought to determine how septins regulate the plasma membrane, focusing on this cytoskeletal element's role during effective amoeboid motility. Surprisingly, septins play a reactive rather than proactive role, as demonstrated during the response to increasing hydrostatic pressure and subsequent regulatory volume decrease. In these settings, septins were required for rapid cortical contraction, and SEPT6-GFP was recruited into filaments and circular patches during global cortical contraction and also specifically during actin filament depletion. Recruitment of septins was also evident during excessive blebbing initiated by blocking membrane trafficking with a dynamin inhibitor, providing further evidence that septins are recruited to facilitate retraction of membranes during dynamic shape change. This function of septins in assembling on an unstable cortex and retracting aberrantly protruding membranes explains the excessive blebbing and protrusion observed in septin-deficient T cells

Digitale Maßnahmen zur Flexibilisierung des Lernens an der Wirtschaftsuniversität Wien

An der Wirtschaftsuniversität Wien (WU) werden bereits verschiedene digitale Maßnahmen gesetzt, um die Flexibilisierung von Lernen zu unterstützen. In diesem Werkstattbericht wird gezeigt, inwiefern diese Maßnahmen die Bedürfnisse der Studierenden hinsichtlich flexiblen Lernens aufgreifen. Die Daten aus den WU-Studierendenbefragungen zur Studienmitte wurden quantitativ und qualitativ ausgewertet, um die Bedürfnisse der Studierenden darzustellen und mit den individuellen Lebenskontexten der Studierenden zu analysieren. Die Ergebnisse dieser Untersuchung werden mit den Maßnahmen an der WU in Bezug gesetzt und zeigen ein aktuelles Bild zur Förderung flexiblen Lernens an der WU

Asymptotically Safe Standard Model via Vector-Like Fermions

We construct asymptotically safe extensions of the Standard Model by adding gauged vector-like fermions. Using large number-of-flavour techniques we argue that all gauge couplings, including the hypercharge and, under certain conditions, the Higgs coupling can achieve an interacting ultraviolet fixed point.Comment: 5 pages, 3 figures, typos fixe

China and Europe: Reconnecting Across a New Silk Road

Since 2013, economic and trade relations between China and Europe have grown significantly. In this article, the authors look beyond conventional economic indicators, like trade, and political issues, like human rights, instead focusing on transport infrastructure, real estate and tourism to show that a new page is unfolding in the history of China-Europe relations

Estimating correlation between multivariate longitudinal data in the presence of heterogeneity

Abstract Background Estimating correlation coefficients among outcomes is one of the most important analytical tasks in epidemiological and clinical research. Availability of multivariate longitudinal data presents a unique opportunity to assess joint evolution of outcomes over time. Bivariate linear mixed model (BLMM) provides a versatile tool with regard to assessing correlation. However, BLMMs often assume that all individuals are drawn from a single homogenous population where the individual trajectories are distributed smoothly around population average. Methods Using longitudinal mean deviation (MD) and visual acuity (VA) from the Ocular Hypertension Treatment Study (OHTS), we demonstrated strategies to better understand the correlation between multivariate longitudinal data in the presence of potential heterogeneity. Conditional correlation (i.e., marginal correlation given random effects) was calculated to describe how the association between longitudinal outcomes evolved over time within specific subpopulation. The impact of heterogeneity on correlation was also assessed by simulated data. Results There was a significant positive correlation in both random intercepts (ρ = 0.278, 95% CI: 0.121–0.420) and random slopes (ρ = 0.579, 95% CI: 0.349–0.810) between longitudinal MD and VA, and the strength of correlation constantly increased over time. However, conditional correlation and simulation studies revealed that the correlation was induced primarily by participants with rapid deteriorating MD who only accounted for a small fraction of total samples. Conclusion Conditional correlation given random effects provides a robust estimate to describe the correlation between multivariate longitudinal data in the presence of unobserved heterogeneity (NCT00000125)