Analysis of a Single Species Model with Dissymmetric Bidirectional Impulsive Diffusion and Dispersal Delay

In most models of population dynamics, diffusion between two patches is assumed to be either continuous or discrete, but in the real natural ecosystem, impulsive diffusion provides a more suitable manner to model the actual dispersal (or migration) behavior for many ecological species. In addition, the species not only requires some time to disperse or migrate among the patches but also has some possibility of loss during dispersal. In view of these facts, a single species model with dissymmetric bidirectional impulsive diffusion and dispersal delay is formulated. Criteria on the permanence and extinction of species are established. Furthermore, the realistic conditions for the existence, uniqueness, and the global stability of the positive periodic solution are obtained. Finally, numerical simulations and discussion are presented to illustrate our theoretical results

A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer

Background: The epithelial-to-mesenchymal transition is an important mechanism in cancer metastasis. Although transcription factors including SNAIL, SLUG, and TWIST1 regulate the epithelial-to-mesenchymal transition, other unknown transcription factors could also be involved. Identification of the full complement of transcription factors is essential for a more complete understanding of gene regulation in this process. Chromatin immunoprecipitation-sequencing (ChIP-Seq) technologies have been used to detect genome-wide binding of transcription factors; here, we developed a systematic approach to integrate existing ChIP-Seq and transcriptome data. We scanned multiple transcription factors to investigate their functional impact on the epithelial-to-mesenchymal transition in the human A549 lung adenocarcinoma cell line. Results: Among the transcription factors tested, impact scores identified the forkhead box protein A1 (FOXA1) as the most significant transcription factor in the epithelial-to-mesenchymal transition. FOXA1 physically associates with the promoters of its predicted target genes. Several critical epithelial-to-mesenchymal transition effectors involved in cellular adhesion and cellular communication were identified in the regulatory network of FOXA1, including FOXA2, FGA, FGB, FGG, and FGL1. The implication of FOXA1 in the epithelial-to-mesenchymal transition via its regulatory network indicates that FOXA1 may play an important role in the initiation of lung cancer metastasis. Conclusions: We identified FOXA1 as a potentially important transcription factor and negative regulator in the initial stages of lung cancer metastasis. FOXA1 may modulate the epithelial-to-mesenchymal transition via its transcriptional regulatory network. Further, this study demonstrates how ChIP-Seq and expression data could be integrated to delineate the impact of transcription factors on a specific biological process

Towards pathway-centric cancer therapies via pharmacogenomic profiling analysis of ERK signalling pathway

Background: Genomic heterogeneity in human cancers complicates gene-centric personalized medicine. Malignant tumors often share a core group of pathways that are perturbed by diverse genetic mutations. Therefore, one possible solution to overcome the heterogeneity challenge is a shift from gene-centric to pathway-centric therapies. Pathway-centric perspectives, which underscore the need to understand key pathways and their critical properties, could address the complexity of cancer heterogeneity better than gene-centric approaches to aid cancer drug discovery and therapy. Methods: We used large-scale pharmacogenomic profiling data provided by the Cancer Genome Project of the Wellcome Trust Sanger Institute and the Cancer Cell Line Encyclopedia. In a systematic in silico investigation of ERK signalling pathway components and topological structures determines their influences on pathway activity and targeted therapies. Mann–Whitney U test was used to identify gene alterations associated with drug sensitivity with p values and Benjamini–Hochberg correction for multiple hypotheses testing. Results: The analysis demonstrated that genetic alterations were crucial to activation of effector pathway and subsequent tumorigenesis, however drug sensitivity suffered from both drug effector and non-effector pathways, which were determined by not only underlying genomic alterations, but also interplay and topological relationship of components in pathway, suggesting that the combinatorial targets of key nodes in perturbed pathways may yield better treatment outcome. Furthermore, we proposed a model to provide a more comprehensive insight and understanding of pathway-centric cancer therapies. Conclusions: Our study provides a holistic view of factors influencing drug sensitivity and sheds light on pathway-centric cancer therapies. Electronic supplementary material The online version of this article (doi:10.1186/s40169-015-0066-1) contains supplementary material, which is available to authorized users

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

An Integrative Pharmacogenomic Approach Identifies Two-drug Combination Therapies for Personalized Cancer Medicine

An individual tumor harbors multiple molecular alterations that promote cell proliferation and prevent apoptosis and differentiation. Drugs that target specific molecular alterations have been introduced into personalized cancer medicine, but their effects can be modulated by the activities of other genes or molecules. Previous studies aiming to identify multiple molecular alterations for combination therapies are limited by available data. Given the recent large scale of available pharmacogenomic data, it is possible to systematically identify multiple biomarkers that contribute jointly to drug sensitivity, and to identify combination therapies for personalized cancer medicine. In this study, we used pharmacogenomic profiling data provided from two independent cohorts in a systematic in silico investigation of perturbed genes cooperatively associated with drug sensitivity. Our study predicted many pairs of molecular biomarkers that may benefit from the use of combination therapies. One of our predicted biomarker pairs, a mutation in the BRAF gene and upregulated expression of the PIM1 gene, was experimentally validated to benefit from a therapy combining BRAF inhibitor and PIM1 inhibitor in lung cancer. This study demonstrates how pharmacogenomic data can be used to systematically identify potentially cooperative genes and provide novel insights to combination therapies in personalized cancer medicine

Search for narrow resonances using the dijet mass spectrum in pp collisions at s√=8 TeV

Results are presented of a search for the production of new particles decaying to pairs of partons (quarks, antiquarks, or gluons), in the dijet mass spectrum in proton-proton collisions at s√=8  TeV. The data sample corresponds to an integrated luminosity of 4.0  fb−1, collected with the CMS detector at the LHC in 2012. No significant evidence for narrow resonance production is observed. Upper limits are set at the 95% confidence level on the production cross section of hypothetical new particles decaying to quark-quark, quark-gluon, or gluon-gluon final states. These limits are then translated into lower limits on the masses of new resonances in specific scenarios of physics beyond the standard model. The limits reach up to 4.8 TeV, depending on the model, and extend previous exclusions from similar searches performed at lower collision energies. For the first time mass limits are set for the Randall–Sundrum graviton model in the dijet channel