Coev-web: a web platform designed to simulate and evaluate coevolving positions along a phylogenetic tree.

BACKGROUND: Available methods to simulate nucleotide or amino acid data typically use Markov models to simulate each position independently. These approaches are not appropriate to assess the performance of combinatorial and probabilistic methods that look for coevolving positions in nucleotide or amino acid sequences. RESULTS: We have developed a web-based platform that gives a user-friendly access to two phylogenetic-based methods implementing the Coev model: the evaluation of coevolving scores and the simulation of coevolving positions. We have also extended the capabilities of the Coev model to allow for the generalization of the alphabet used in the Markov model, which can now analyse both nucleotide and amino acid data sets. The simulation of coevolving positions is novel and builds upon the developments of the Coev model. It allows user to simulate pairs of dependent nucleotide or amino acid positions. CONCLUSIONS: The main focus of our paper is the new simulation method we present for coevolving positions. The implementation of this method is embedded within the web platform Coev-web that is freely accessible at http://coev.vital-it.ch/, and was tested in most modern web browsers

Data scientists

What is a data scientist? How can you become one? How can you form a team of data scientists that fits your organization? In this chapter, we trace the skillset of a successful data scientist and define the necessary competencies. We give a disambiguation to other historically or contemporary definitions of the term, and show how a career as a data scientist might get started. Finally we will answer the above mentioned third question, i.e. how to build analytics teams within a data-driven organization

Effects of neutrino oscillations and neutrino magnetic moments on elastic neutrino-electron scattering

We consider elastic antineutrino-electron scattering taking into account possible effects of neutrino masses and mixing and of neutrino magnetic moments and electric dipole moments. Having in mind antineutrinos produced in a nuclear reactor we compute, in particular, the weak-electromagnetic interference terms which are linear in the magnetic (electric dipole) moments and also in the neutrino masses. We show that these terms are, however, suppressed compared to the pure weak and electromagnetic cross section. We also comment upon the possibility of using the electromagnetic cross section to investigate neutrino oscillations.Comment: 12 pages, REVTEX file, no figures, submitted to Phys.Rev.

Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development.

The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we have investigated the AHR interactome in embryonic stem cells by mass spectrometry and show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylation). The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling

Distributed Computing Grid Experiences in CMS

The CMS experiment is currently developing a computing system capable of serving, processing and archiving the large number of events that will be generated when the CMS detector starts taking data. During 2004 CMS undertook a large scale data challenge to demonstrate the ability of the CMS computing system to cope with a sustained data-taking rate equivalent to 25% of startup rate. Its goals were: to run CMS event reconstruction at CERN for a sustained period at 25 Hz input rate; to distribute the data to several regional centers; and enable data access at those centers for analysis. Grid middleware was utilized to help complete all aspects of the challenge. To continue to provide scalable access from anywhere in the world to the data, CMS is developing a layer of software that uses Grid tools to gain access to data and resources, and that aims to provide physicists with a user friendly interface for submitting their analysis jobs. This paper describes the data challenge experience with Grid infrastructure and the current development of the CMS analysis system

T Cell Activation Results in Conformational Changes in the Src Family Kinase Lck to Induce Its Activation

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Recommended Medical and Non-Medical Factors to Assess Military Preventable Deaths: Subject Matter Experts Provide Valuable Insights

INTRODUCTION: Historically, there has been variability in the methods for determining preventable death within the US Department of Defense. Differences in methodologies partially explain variable preventable death rates ranging from 3% to 51%. The lack of standard review process likely misses opportunities for improvement in combat casualty care. This project identified recommended medical and non-medical factors necessary to (1) establish a comprehensive preventable death review process and (2) identify opportunities for improvement throughout the entire continuum of care. METHODS: This qualitative study used a modified rapid assessment process that includes the following steps: (1) identification and recruitment of US government subject matter experts (SMEs); (2) multiple cycles of data collection via key informant interviews and focus groups; (3) consolidation of information collected in these interviews; and (4) iterative analysis of data collected from interviews into common themes. Common themes identified from SME feedback were grouped into the following subject areas: (1) prehospital, (2) in-hospital and (3) forensic pathology. RESULTS: Medical recommendations for military preventable death reviews included the development, training, documentation, collection, analysis and reporting of the implementation of the Tactical Combat Casualty Care Guidelines, Joint Trauma System Clinical Practice Guidelines and National Association of Medical Examiners autopsy standards. Non-medical recommendations included training, improved documentation, data collection and analysis of non-medical factors needed to understand how these factors impact optimal medical care. CONCLUSIONS: In the operational environment, medical care must be considered in the context of non-medical factors. For a comprehensive preventable death review process to be sustainable in the military health system, the process must be based on an appropriate conceptual framework implemented consistently across all military services

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions

Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanisms are largely unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signaling via the endogenous ligand FICZ reduced the inflammatory response in the imiquimod-induced model of skin inflammation and AhR-deficient mice exhibited a substantial exacerbation of the disease, compared to AhR-sufficient controls. Nonhematopoietic cells, in particular keratinocytes, were responsible for this hyperinflammatory response, which involved upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders