964 resultados para Triple hélice


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Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets. We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -‘good’ outcome no relapse > 3 years; ‘poor’ outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in ‘good’ outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression. We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.

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A key issue in pulse detonation engine development is better understanding of the detonation structure and its propagation mechanism. Thus, in the present work the turbulent structure of an irregular detonation is studied through very high resolution numerical simulations of 600 points per half reaction length. The aim is to explore the nature of the transverse waves during the collision and reflection processes of the triple point with the channel walls. Consequently the formation and consumption mechanism of unreacted gas pockets is studied. Results show that the triple point and the transverse wave collide simultaneously with the wall. The strong transverse wave switches from a primary triple point before collision to a new one after reflection. Due to simultaneous interaction of the triple point and the transverse wave with the wall in the second half of the detonation cell, a larger high-pressurised region appears on the wall. During the reflection the reaction zone detaches from the shock front and produces a pocket of unburned gas. Three mechanisms found to be of significance in the re-initiation mechanism of detonation at the end of the detonation cell; i: energy resealed via consumption of unburned pockets by turbulent mixing ii: compression waves arise due to collision of the triple point on the wall which helps the shock to jump abruptly to an overdriven detonation iii: drastic growth of the Richtmyer–Meshkov instability causing a part of the front to accelerate with respect to the neighbouring portions.

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The present study investigated the management of social, environmental and economic sustainability practices employed by 72 oil companies in Rio Grande do Norte state in Brazil associated to Joint Business Network for Enhancing the Competitive Ability of Suppliers of Goods and Services to the Gas and Oil Industry in Rio Grande do Norte (REDEPETRO-RN). Thus, our investigation aimed to determine the extent to which sustainability practices of companies associated to REDEPETRO-RN are developed through their own efforts or influenced by the Triple Helix interorganizational arrangement (governamental organizations, education and research institutions, and industries). The research instrument used was a questionnaire in order to map and characterize the sustainability practices. The research subjects were business owners and managers. The data collected supported the descriptive, correspondence and correlation analyzes. Were identified a greater emphasis of the companies surveyed in developing sustainability practices and greater economic influence of business organizations in the construction of sustainability status. It was concluded with confirmation of thesis of the REDEPETRO-RN arrangement exhibits the characteristics and functioning of a common Interorganizational Cooperative Arrangement, not those of a triple helix interorganizational arrangement, given that the influences exerted for the development of social, environmental and economical sustainability on the part of teaching and research institutions, and government and business organizations do not interact with one another sufficiently to create a virtuous circle of cooperation among the associated companies. By contrast, the Interorganizational Cooperative Arrangement plays an important role in strengthening the competitiveness of companies affiliated to REDEPETRO-RN, by combining different competencies in an attempt at supporting the adoption of sustainability practices, a role reinforced by the scope of PETROBRAS, which, due to its economic importance, has considerable weight in the managerial decisions of associated companies

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Triple negative breast cancers (TNBC) are often described as biologically aggressive tumors, with poorer survival compared to other breast cancer subtypes. The fact that TNBC lacks an obvious target like estrogen receptor and HER2 represents a major challenge in the management of these patients. Genomic analyses have revealed that TNBC comprises a diverse group of cancers, which have distinct molecular profiles and different prognosis. These studies also highlighted molecular aberrations that could serve as potential treatment targets. On the other hand, a high percentage of TNBCs express some important surface receptors that have been already exploited in the development of promising targeted therapies, which are currently tested in clinical trials. In this review, we will provide an overview on the molecular diversity of TNBC with special emphasis on the evolving role of some potential biomarkers that may be utilized in the near future.

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Acompanha: Dupla-hélice: a construção de um conhecimento

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Despite a commitment by the European Union to protect its migratory bat populations, conservation efforts are hindered by a poor understanding of bat migratory strategies and connectivity between breeding and wintering grounds. Traditional methods like mark-recapture are ineffective to study broad-scale bat migratory patterns. Stable hydrogen isotopes (delta D) have been proven useful in establishing spatial migratory connectivity of animal populations. Before applying this tool, the method was calibrated using bat samples of known origin. Here we established the potential of delta D as a robust geographical tracer of breeding origins of European bats by measuring delta D in hair of five sedentary bat species from 45 locations throughout Europe. The delta D of bat hair strongly correlated with well-established spatial isotopic patterns in mean annual precipitation in Europe, and therefore was highly correlated with latitude. We calculated a linear mixed-effects model, with species as random effect, linking delta D of bat hair to precipitation delta D of the areas of hair growth. This model can be used to predict breeding origins of European migrating bats. We used delta C-13 and delta N-15 to discriminate among potential origins of bats, and found that these isotopes can be used as variables to further refine origin predictions. A triple-isotope approach could thereby pinpoint populations or subpopulations that have distinct origins. Our results further corroborated stable isotope analysis as a powerful method to delineate animal migrations in Europe.

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Integration of multiple herbicide-resistant genes (trait stacking) into crop plants would allow over the top application of herbicides that are otherwise fatal to crops. The US has just approved Bollgard II® XtendFlex™ cotton which has dicamba, glyphosate and glufosinate resistance traits stacked. The pace of glyphosate resistance evolution is expected to be slowed by this technology. In addition, over the top application of two more herbicides may help to manage hard to kill weeds in cotton such as flax leaf fleabane and milk thistle. However, there are some issues that need to be considered prior to the adoption of this technology. Wherever herbicide tolerant technology is adopted, volunteer crops can emerge as a weed problem, as can herbicide resistant weeds. For cotton, seed movement is the most likely way for resistant traits to move around. Management of multiple stack volunteers may add additional complexity to volunteer management in cotton fields and along roadsides. This paper attempts to evaluate the pros and cons of trait stacking technology by analysing the available literature in other crop growing regions across the world. The efficacy of dicamba and glufosinate on common weeds of the Australian cotton system, herbicide resistance evolution, synergy and antagonisms due to herbicide mixtures, drift hazards and the evolution of herbicide resistance to glyphosate, glufosinate and dicamba were analysed based on the available literature.

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The present study investigated the management of social, environmental and economic sustainability practices employed by 72 oil companies in Rio Grande do Norte state in Brazil associated to Joint Business Network for Enhancing the Competitive Ability of Suppliers of Goods and Services to the Gas and Oil Industry in Rio Grande do Norte (REDEPETRO-RN). Thus, our investigation aimed to determine the extent to which sustainability practices of companies associated to REDEPETRO-RN are developed through their own efforts or influenced by the Triple Helix interorganizational arrangement (governamental organizations, education and research institutions, and industries). The research instrument used was a questionnaire in order to map and characterize the sustainability practices. The research subjects were business owners and managers. The data collected supported the descriptive, correspondence and correlation analyzes. Were identified a greater emphasis of the companies surveyed in developing sustainability practices and greater economic influence of business organizations in the construction of sustainability status. It was concluded with confirmation of thesis of the REDEPETRO-RN arrangement exhibits the characteristics and functioning of a common Interorganizational Cooperative Arrangement, not those of a triple helix interorganizational arrangement, given that the influences exerted for the development of social, environmental and economical sustainability on the part of teaching and research institutions, and government and business organizations do not interact with one another sufficiently to create a virtuous circle of cooperation among the associated companies. By contrast, the Interorganizational Cooperative Arrangement plays an important role in strengthening the competitiveness of companies affiliated to REDEPETRO-RN, by combining different competencies in an attempt at supporting the adoption of sustainability practices, a role reinforced by the scope of PETROBRAS, which, due to its economic importance, has considerable weight in the managerial decisions of associated companies

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Dissertação (mestrado)—Universidade de Brasília, Faculdade UnB Gama, Programa de Pós-graduação em Integridade de Materiais da Engenharia, 2015.

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In this paper, we show that if X is a smooth variety of general type of dimension m≥3 for which the canonical map induces a triple cover onto Y, where Y is a projective bundle over P1 or onto a projective space or onto a quadric hypersurface, embedded by a complete linear series (except Q3 embedded in P4), then the general deformation of the canonical morphism of X is again canonical and induces a triple cover. The extremal case when Y is embedded as a variety of minimal degree is of interest, due to its appearance in numerous situations. For instance, by looking at threefolds Y of minimal degree we find components of the moduli of threefolds X of general type with KX3=3pg−9,KX3≠6, whose general members correspond to canonical triple covers. Our results are especially interesting as well because they have no lower dimensional analogues.