Oscillatory subglacial drainage in the absence of surface melt

The presence of strong diurnal cycling in basal water pressure records obtained during the melt season is well established for many glaciers. The behaviour of the drainage system outside the melt season is less well understood. Here we present borehole observations from a surge-type valley glacier in the St Elias Mountains, Yukon Territory, Canada. Our data indicate the onset of strongly correlated multi-day oscillations in water pressure in multiple boreholes straddling a main drainage axis, starting several weeks after the disappearance of a dominant diurnal mode in August 2011 and persisting until at least January 2012, when multiple data loggers suffered power failure. Jökulhlaups provide a template for understanding spontaneous water pressure oscillations not driven by external supply variability. Using a subglacial drainage model, we show that water pressure oscillations can also be driven on a much smaller scale by the interaction between conduit growth and distributed water storage in smaller water pockets, basal crevasses and moulins, and that oscillations can be triggered when water supply drops below a critical value. We suggest this in combination with a steady background supply of water from ground water or englacial drainage as a possible explanation for the observed wintertime pressure oscillations

Impacto de la jornada ?nica escolar en la instituci?n educativa la reforma de Rovira Tolima

60 p. Recurso Electr?nicoLa jornada ?nica nace como una estrategia del plan nacional de desarrollo 2014-2018 que tiene como objetivo garantizar un mejor futuro para el pa?s. En Colombia son muy pocas las investigaciones que han estudiado los resultados de esta pol?tica educativa. A trav?s de la presente investigaci?n se realiz? un estudio en el que se determinaron dos variables (social y acad?mica) para evaluar el impacto de la jornada ?nica en los niveles de b?sica y media de la sede central de la Instituci?n Educativa La Reforma de Rovira Tolima, luego de un a?o de su implementaci?n. Para esto se analizaron y contrastaron los beneficios y dificultades que ha generado la implementaci?n de la Jornada ?nica en este plantel educativo, as? como la inversi?n que el estado ha suministrado en la ejecuci?n de la misma y la visi?n que tiene la comunidad educativa sobre la extensi?n del horario escolar en esta instituci?n. Palabras claves: Jornada ?nica, Impacto, Estrategia, Horario escolarSingle-shift school system is born like a 2014-2018 National Development Plan strategy that aims to guarantee a better future for the nation. In Colombia, very few researches have studied the results of this educational policy. Through the present investigation a study was carried out in which two variables (academic and social) were determined to evaluate the Single School Day impact in grades 6th to 11th from La Reforma School headquarters in Rovira Tolima after a year of its implementation. For this, benefits and difficulties generated by the single-shift school implementation in this educational establishment were analyzed and contrasted, as well as the investment that state has provided in its execution and vision that community has about the school schedule extension. Keywords: Single School Day, Impact, Strategy, School schedul

Geographical information retrieval with ontologies of place

Geographical context is required of many information retrieval tasks in which the target of the search may be documents, images or records which are referenced to geographical space only by means of place names. Often there may be an imprecise match between the query name and the names associated with candidate sources of information. There is a need therefore for geographical information retrieval facilities that can rank the relevance of candidate information with respect to geographical closeness of place as well as semantic closeness with respect to the information of interest. Here we present an ontology of place that combines limited coordinate data with semantic and qualitative spatial relationships between places. This parsimonious model of geographical place supports maintenance of knowledge of place names that relate to extensive regions of the Earth at multiple levels of granularity. The ontology has been implemented with a semantic modelling system linking non-spatial conceptual hierarchies with the place ontology. An hierarchical spatial distance measure is combined with Euclidean distance between place centroids to create a hybrid spatial distance measure. This is integrated with thematic distance, based on classification semantics, to create an integrated semantic closeness measure that can be used for a relevance ranking of retrieved objects

Expression, purification and osteogenic bioactivity of recombinant human BMP-4, -9, -10, -11 and -14

Bone morphogenetic proteins (BMPs) are cytokines from the TGF-b superfamily, with important roles during embryonic development and in the induction of bone and cartilage tissue differentiation in the adult body. In this contribution, we report the expression of recombinant human BMP-4, BMP-9, BMP-10, BMP-11 (or growth differentiation factor- 11, GDF-11) and BMP-14 (GDF-5), using Escherichia coli pET-25b vector. BMPs were overexpressed, purified by affinity his-tag chromatography and shown to induce the expression of early markers of bone differentiation (e.g. smad-1, smad-5, runx2/cbfa1, dlx5, osterix, osteopontin, bone sialoprotein and alkaline phosphatase) in C2C12 cells and in human adipose stem cells. The described approach is a promising method for producing large amounts of different recombinant BMPs that show potential for novel biomedical applications.The author wishes to acknowledge the Sanger Institute for kindly offering the bacterial clones for cloning of human BMP-9 to -14. This work was supported by Fundacao para a Ciencia e Tecnologia (PhD grant SFRH/BD/17049/2004, project ElastM POCI/CTM/57177/2004 funded by FEDER and the Fundacao para a Ciencia e Tecnologia; and European STREP Project HIPPOCRATES (NMP3-CT-2003-505758). This work was carried out under the scope of the European NoE EXPERTISSUES (NMP3-CT-2004-500283)

Field-based tests for the assessment of physical fitness in children and adolescents practicing sport: A systematic review within the ESA program

High levels of physical fitness (PF) can positively affect both health and cognitive function, thus monitoring its levels in youth can help increase health and quality of life in adult populations later on. This systematic review aims to identify PF field-based tests used in young European populations practicing sport to find tools that are adequate for the considered target involving a new battery within the Enriched Sport Activities (ESA) project. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. In the 83 identified articles, the main tests used were: vertical/horizontal jumps (for muscular strength/power); push-ups, running at maximum effort, sit-ups (for muscular strength/endurance); multistage non-intermittent and intermittent tests (for aerobic endurance); sit and reach (for flexibility); sprinting and agility T-tests (for speed and agility, respectively); 10 x 5 m shuttle run (SR) (for both speed and agility). Few studies assessed coordination, reaction time, power, and balance. Although the selected tests are widely used and validated, they do not determine all PF aspects and do not reflect sport-specific features. A final decision was made for the inclusion of the following tests: standing broad jump, seated medicine ball throw, 20 m SR test, 30 m sprint, Illinois test, and a new test, i.e., the crunning test, to assess different skill-related components at once. The use of this combination of tests allows for the assessment of all PF components and can help planning eective training programs and cultivate sporting talent

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Dynamic culture of osteogenic cells in biomimetically coated poly(caprolactone) nanofibre mesh constructs

In our previous work, biomimetic calcium phosphate-coated poly(caprolactone) nanofibre meshes (BCP-NMs) were demonstrated to be more effective for supporting cell attachment and proliferation under static conditions, when compared with poly(caprolactone) nanofibre meshes (PCL-NMs). In many applications, in vitro cultivation of constructs using bioreactors that support efficient nutrition of cells has appeared as an important step toward the development of functional grafts. This work aimed at studying the effects of dynamic culture conditions and biomimetic coating on bone cells grown on the nanofibre meshes. BCP-NM and PCL-NM were seeded with osteoblast-like cells (MG63--human osteosarcoma-derived cell line). The cell-seeded constructs were cultured within a rotating bioreactor that simulated microgravity, at a fixed rotating speed, for different time periods, and then characterized. Cell morphology, viability, and phenotype were assessed. PCL-NM constructs presented a higher number of dead cells than BCP-NM constructs. Under dynamic conditions, the production of proteins associated with the extracellular matrix of bone was higher on BCP-NM constructs than in the PCL-NM ones, which indicates that coated samples may provide cells with a better environment for tissue growth. It is suggested that improved mass transfer in the bioreactor in combination with the appropriate substrate were decisive factors for this highly positive outcome for generating bone.This work was developed under the scope of the EU Project Network of Excellence "Expertissues'' (NMP3-CT-2004-500283) and supported by Alea jacta est Marie Curie Actions (MEST-CT-2004-008104). M. Alves da Silva would like to acknowledge the Portuguese Foundation for Science and Technology for her grant (SFRH-BD-28708-2006). Jose V. Araujo is grateful to S. Rathbone, H. Sura, I. Wimpenny, I. Dublon, G. Jones, and E. D. Pinho for useful technical discussions

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors