EMMA 2--a MAGE-compliant system for the collaborative analysis and integration of microarray data

Background: Understanding transcriptional regulation by genome-wide microarray studies can contribute to unravel complex relationships between genes. Attempts to standardize the annotation of microarray data include the Minimum Information About a Microarray Experiment (MIAME) recommendations, the MAGE-ML format for data interchange, and the use of controlled vocabularies or ontologies. The existing software systems for microarray data analysis implement the mentioned standards only partially and are often hard to use and extend. Integration of genomic annotation data and other sources of external knowledge using open standards is therefore a key requirement for future integrated analysis systems. Results: The EMMA 2 software has been designed to resolve shortcomings with respect to full MAGE-ML and ontology support and makes use of modern data integration techniques. We present a software system that features comprehensive data analysis functions for spotted arrays, and for the most common synthesized oligo arrays such as Agilent, Affymetrix and NimbleGen. The system is based on the full MAGE object model. Analysis functionality is based on R and Bioconductor packages and can make use of a compute cluster for distributed services. Conclusion: Our model-driven approach for automatically implementing a full MAGE object model provides high flexibility and compatibility. Data integration via SOAP-based web-services is advantageous in a distributed client-server environment as the collaborative analysis of microarray data is gaining more and more relevance in international research consortia. The adequacy of the EMMA 2 software design and implementation has been proven by its application in many distributed functional genomics projects. Its scalability makes the current architecture suited for extensions towards future transcriptomics methods based on high-throughput sequencing approaches which have much higher computational requirements than microarrays.

Glucose-dependent insulinotropic polypeptide (GIP) dose-dependently reduces osteoclast differentiation and resorption

International audience

Homogenization of the p-Laplacian with nonlinear boundary condition on critical size particles: Identifying the strange term for the some non smooth and multivalued operators

We extend previous papers in the literature concerning the homogenization of Robin type boundary conditions for quasilinear equations, in the case of microscopic obstacles of critical size: here we consider nonlinear boundary conditions involving some maximal monotone graphs which may correspond to discontinuous or non-Lipschitz functions arising in some catalysis problems.

The impacts of US agricultural and trade policy on trade liberalization and integration via a US- Central America free trade agreement

Resumen Este estudio analiza importantes acciones legislativas del 2002 que afectarán sustancialmente las negociaciones comerciales con Estados Unidos; examina, asimismo, la protección de importaciones de ese país con respecto a productos agrícolas que serán críticos en las negociaciones con los países centroamericanos. Las acciones legislativas mencionadas fueron la aprobación del Proyecto de ley Agrícola del 2002 y la aprobación de la Autorización de Promoción Legal, que provee tratamiento del ‘trámite rápido’ de los acuerdos comerciales…

Erythropoietin reduces pathogenic humoral immunity by inhibiting T Follicular Helper cell differentiation and function

A large fraction of organ transplant recipients develop anti-donor antibodies (DSA), with accelerated graft loss and increased mortality. We tested the hypothesis that erythropoietin (EPO) reduces DSA formation by inhibiting T follicular helper (TFH) cells. We measured DSA levels, splenic TFH, TFR cells, germinal center (GC), and class switched B cells, in murine models of allogeneic sensitization, allogeneic transplantation and in parent-to-F1 models of graft versus host disease (GVHD). We quantified the same cell subsets and specific antibodies, upon EPO or vehicle treatment, in wild type mice and animals lacking EPO receptor selectively on T or B cells, immunized with T-independent or T-dependent stimuli. In vitro, we tested the EPO effect on TFH induction. We isolated TFH and TFR cells to perform in vitro assay and clarify their role. EPO reduced DSA levels, GC, class switched B cells, and increased the TFR/TFH ratio in the heart transplanted mice and in two GVHD models. EPO did also reduce TFH and GC B cells in SRBC-immunized mice, while had no effect in TNP-AECM-FICOLL-immunized animals, indicating that EPO inhibits GC B cells by targeting TFH cells. EPO effects were absent in T cells EPOR conditional KO mice, confirming that EPO affects TFH in vivo through EPOR. In vitro, EPO affected TFH induction through an EPO-EPOR-STAT5-dependent pathway. Suppression assay demonstrated that the reduction of IgG antibodies was dependent on TFH cells, sustaining the central role of the subset in this EPO-mediated mechanism. In conclusion, EPO prevents DSA formation in mice through a direct suppression of TFH. Development of DSA is associated with high risk of graft rejection, giving our data a strong rationale for studies testing the hypothesis that EPO administration prevents their formation in organ transplant recipients. Our findings provide a foundation for testing EPO as a treatment of antibody mediated disease processes.

Development of machine learning methods for multi-modal biomarkers detection and integration

In medicine, innovation depends on a better knowledge of the human body mechanism, which represents a complex system of multi-scale constituents. Unraveling the complexity underneath diseases proves to be challenging. A deep understanding of the inner workings comes with dealing with many heterogeneous information. Exploring the molecular status and the organization of genes, proteins, metabolites provides insights on what is driving a disease, from aggressiveness to curability. Molecular constituents, however, are only the building blocks of the human body and cannot currently tell the whole story of diseases. This is why nowadays attention is growing towards the contemporary exploitation of multi-scale information. Holistic methods are then drawing interest to address the problem of integrating heterogeneous data. The heterogeneity may derive from the diversity across data types and from the diversity within diseases. Here, four studies conducted data integration using customly designed workflows that implement novel methods and views to tackle the heterogeneous characterization of diseases. The first study devoted to determine shared gene regulatory signatures for onco-hematology and it showed partial co-regulation across blood-related diseases. The second study focused on Acute Myeloid Leukemia and refined the unsupervised integration of genomic alterations, which turned out to better resemble clinical practice. In the third study, network integration for artherosclerosis demonstrated, as a proof of concept, the impact of network intelligibility when it comes to model heterogeneous data, which showed to accelerate the identification of new potential pharmaceutical targets. Lastly, the fourth study introduced a new method to integrate multiple data types in a unique latent heterogeneous-representation that facilitated the selection of important data types to predict the tumour stage of invasive ductal carcinoma. The results of these four studies laid the groundwork to ease the detection of new biomarkers ultimately beneficial to medical practice and to the ever-growing field of Personalized Medicine.

Impacto das comunidades de consumidores no valor das marcas

International Congress Marketing Trends Annual Conference in Paris, 17 – 19 January 2013

What's the difference under the gown? : new professors' development as university teachers

This study explores how new university teachers develop a teaching identity. Despite the significance ofteaching, which usually comprises 40% of a Canadian academic's workload, few new professors have any formal preparation for that aspect of their role. Discipline-specific education for postsecondary professors is a well-defined path; graduates applying for faculty positions will have the terminal degree to attest to their knowledge and skill conducting research in the discipline. While teaching is usually given the same workload balance as research, it is not clear how professors create themselves as teaching professionals. Drawing on Kelly's (1955) personal construct theory and Kegan's (1982, 1994) model ofdevelopmental constructivism through differentiation and integration, this study used a phenomenographic framework~(Marton, 1986, 1994; Trigwell & Prosser, 1996) to investigate the question of how new faculty members construe their identity as university teachers. Further, my own role development as researcher was used as an additional lens through which to view the study results. The study focused particularly on the challenges and supports to teaching role development and outlines recommendations the participants made for supporting other newcomers. In addition, the variations and similarities in the results suggest a developmental model to conceptions ofteaching roles, one in which teaching, research, and service roles are viewed as more integrated over time. Developing a teacher identity was seen as a progression on a hierarchical model similar to Maslow's (1968) hierarchy of needs.

Los comportamientos del liderazgo y su relación con el desarrollo de los modelos de gestión

El propósito de este trabajo de investigación teórica, es lograr basados en el estudio de variables del entorno empresarial, como lo son los modelos de negocio, comportamiento, cultura y complejidad organizacional, estructurar un artículo que invite a la reflexión sobre la incidencia del comportamiento de los líderes para con los modelos de gestión. Con base en la información recolectada, se observan patrones funcionales en el comportamiento de las organizaciones, derivados de los modelos de comportamiento de quienes las dirigen. Las implicaciones podrían ser calificadas de favorables o desfavorables, si se les asocia como condición relevante en la perdurabilidad de las mismas en el tiempo.

Diseño de un proceso estratégico para la empresa New Care – Creciendo Saludable

En este trabajo de grado se elabora una breve presentación de propuestas, modelos y teorías de organizaciones saludables desde diferentes perspectivas, con el fin de lograr un análisis y aplicación de un modelo en una pequeña empresa del sector cosmetico para lograr la propuesta y formulacion estrategica de un modelo aplicable. En este ejercicio se logra un diagnóstico, evaluación y direccionamiento estrategico de la compañía para la elaboración de una propuesta que le permita a la compañía crecer saludablemente.

An analysis of the management of a public sector project: a systems-based case study

The management of a public sector project is analysed using a model developed from systems theory. Linear responsibility analysis is used to identify the primary and key decision structure of the project and to generate quantitative data regarding differentiation and integration of the operating system, the managing system and the client/project team. The environmental context of the project is identified. Conclusions are drawn regarding the project organization structure's ability to cope with the prevailing environmental conditions. It is found that the complexity of the managing system imposed on the project was unable to achieve this and created serious deficiencies in the outcome of the project.

La construcción de sentido (‘sensemaking’) de un entorno estratégico turbulento por parte de los altos directivos: un estudio en una multinacional automotriz

Este artículo presenta los resultados de una investigación realizada al interior de dos contextos. Por un lado, el teórico, en el marco de uno de los discursos más relevantes en los campos de la estrategia organizacional, de la managerial and organizational cognition (MOC) y, en general, de los estudios organizacionales (organization studies): la construcción de sentido (sensemaking). Por el otro, el empírico, en una de las grandes compañías multinacionales del sector automotriz con presencia global. Esta corporación enfrenta una permanente tensión entre lo que dicta la casa matriz, en relación con el cumplimiento de metas y estándares específicos, considerando el mundo entero, y los retos que, teniendo en cuenta lo regional y lo local, experimentan los altos directivos encargados de hacer prosperar la empresa en estos lugares. La aproximación implementada fue cualitativa. Esto en atención a la naturaleza de la problemática abordada y la tradición del campo. Los resultados permiten ampliar el actual nivel de comprensión acerca de los procesos de sensemaking de los altos directivos al enfrentar un entorno estratégico turbulento.

Certain Properties of Fractional Calculus Operators Associated with Generalized Mittag-Leffler Function

Mathematics Subject Classification: 26A33, 33E12, 33C20.

Generalized Fractional Calculus, Special Functions and Integral Transforms: What is the Relation?

Виржиния С. Кирякова - В този обзор илюстрираме накратко наши приноси към обобщенията на дробното смятане (анализ) като теория на операторите за интегриране и диференциране от произволен (дробен) ред, на класическите специални функции и на интегралните трансформации от лапласов тип. Показано е, че тези три области на анализа са тясно свързани и взаимно индуцират своето възникване и по-нататъшно развитие. За конкретните твърдения, доказателства и примери, вж. Литературата.