990 resultados para Accessible Subring


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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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The cell is continuously subjected to various forms of external and intrinsic proteindamaging stresses, including hyperthermia, pathophysiological states, as well as cell differentiation and proliferation. Proteindamaging stresses result in denaturation and improper folding of proteins, leading to the formation of toxic aggregates that are detrimental for various pathological conditions, including Alzheimer’s and Huntington’s diseases. In order to maintain protein homeostasis, cells have developed different cytoprotective mechanisms, one of which is the evolutionary well-conserved heat shock response. The heat shock response results in the expression of heat shock proteins (Hsps), which act as molecular chaperones that bind to misfolded proteins, facilitate their refolding and prevent the formation of protein aggregates. Stress-induced expression of Hsps is mediated by a family of transcription factors, the heat shock factors, HSFs. Of the four HSFs found in vertebrates, HSF1-4, HSF1 is the major stress-responsive factor that is required for the induction of the heat shock response. HSF2 cannot alone induce Hsps, but modulates the heat shock response by forming heterotrimers with HSF1. HSFs are not only involved in the heat shock response, but they have also been found to have a function in development, neurodegenerative disorders, cancer, and longevity. Therefore, insight into how HSFs are regulated is important for the understanding of both normal physiological and disease processes. The activity of HSF1 is mainly regulated by intricate post-translational modifications, whereas the activity of HSF2 is concentrationdependent. However, there is only limited understanding of how the abundance of HSF2 is regulated. This study describes two different means of how HSF2 levels are regulated. In the first study it was shown that microRNA miR-18, a member of the miR-17~92 cluster, directly regulates Hsf2 mRNA stability and thus protein levels. HSF2 has earlier been shown to play a profound role in the regulation of male germ cell maturation during the spermatogenesis. The effect on miR-18 on HSF2 was examined in vivo by transfecting intact seminiferous tubules, and it was found that inhibition of miR-18 resulted in increased HSF2 levels and modified expression of the HSF2 targets Ssty2 and Speer4a. HSF2 has earlier been reported to modulate the heat shock response by forming heterotrimers with HSF1. In the second study, it was shown that HSF2 is cleared off the Hsp70 promoter and degraded by the ubiquitinproteasome pathway upon acute stress. By silencing components of the anaphase promoting complex/cyclosome (APC/C), including the co-activators Cdc20 and Cdh1, it was shown that APC/C mediates the heatinduced ubiquitylation of HSF2. Furthermore, down-regulation of Cdc20 was shown to alter the expression of heat shock-responsive genes. Next, we studied if APC/C-Cdc20, which controls cell cycle progression, also regulates HSF2 during the cell cycle. We found that both HSF2 mRNA and protein levels decreased during mitosis in several but not all human cell lines, indicating that HSF2 has a function in mitotic cells. Interestingly, although transcription is globally repressed during mitosis, mainly due to the displacement of RNA polymerase II and transcription factors, including HSF1, from the mitotic chromatin, HSF2 is capable of binding DNA during mitosis. Thus, during mitosis the heat shock response is impaired, leaving mitotic cells vulnerable to proteotoxic stress. However, in HSF2-deficient mitotic cells the Hsp70 promoter is accessible to both HSF1 and RNA polymerase II, allowing for stress-inducible Hsp expression to occur. As a consequence HSF2-deficient mitotic cells have a survival advantage upon acute heat stress. The results, presented in this thesis contribute to the understanding of the regulatory mechanisms of HSF2 and its function in the heat shock response in both interphase and mitotic cells.

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Above-ground litter production is one of the most accessible ways to estimate ecosystem productivity, nutrient fluxes and carbon transfers. Phenological patterns and climatic conditions are still not fully explained well for tropical and subtropical forests under less pronounced dry season and non-seasonal climates, as well as the interaction of these patterns with successional dynamics. Monthly litterfall was estimated for two years in a 9 to 10 year old secondary alluvial Atlantic Rain forest. Total litterfall was higher in the site with more developed vegetation (6.4 ± 1.2 ton ha-1 year-1; 95% confidence interval) as compared to the site with less developed vegetation (3.0 ± 1.0 ton ha-1 year-1). The monthly production of 11 litter fractions (eight fractions comprising the leaf litter of the seven main species of the community and other species; reproductive parts, twigs £ 2 cm diameter, and miscellaneous material) were correlated with meteorological variables making possible to identify three patterns of deposition. The main pattern, dominated by leaf-exchanging species, consisted of a cycle with the highest litterfall at the beginning of the rainy season, preceding by basically three months the peaks of the annual cycles of rainfall and temperatures. Other two patterns, dominated by brevi-deciduous species, peaked at the end of the rainy season and at the end of the non-rainy season. Tropical and subtropical dry forests that present the highest leaf fall gradually earlier than rain forests (as the studied sites) are possibly related to the start of senescence process. It seems that such process is triggered earlier by a more severe hydric stress, besides other factors linked to a minor physiological activity of plants that result in abscission.

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The binding of chlorpromazine (CPZ) and hemin to bovine serum albumin was studied by the fluorescence quenching technique. CPZ is a widely used anti-psychotic drug that interacts with blood components, influences bioavailability, and affects function of several biomolecules. Hemin is an important ferric residue of hemoglobin that binds within the hydrophobic region of albumin with high specificity. Quenching of the intrinsic fluorescence of bovine serum albumin (BSA) was observed by selectively exciting tryptophan residues at 290 nm. Emission spectra were recorded in the range from 300 to 450 nm for each quencher addition. Stern-Volmer graphs were plotted, and the quenching constant estimated for BSA solution titrated with hemin at 25ºC was 1.44 (± 0.05) x 10(5) M-1. Results showed that bovine albumin tryptophans are not equally accessible to CPZ, in agreement with the idea that polar or charged quenchers have more affinity for amino acid residues on the outer wall of the protein. Hemin added to albumin solution at a molar ratio of 1:1 quenched about 25% of their fluorescence. The quenching effect of CPZ on albumin-hemin solution was stronger than on pure BSA. This increase can be the result of combined conformational changes in the structure of albumin caused firstly by hemin and then by CPZ. Our results suggest that the primary binding site for hemin on bovine albumin may be located asymmetrically between the two tryptophans along the sequence formed by subdomains IB and IIA, closer to tryptophan residue 212.

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Large-scale genome projects have generated a rapidly increasing number of DNA sequences. Therefore, development of computational methods to rapidly analyze these sequences is essential for progress in genomic research. Here we present an automatic annotation system for preliminary analysis of DNA sequences. The gene annotation tool (GATO) is a Bioinformatics pipeline designed to facilitate routine functional annotation and easy access to annotated genes. It was designed in view of the frequent need of genomic researchers to access data pertaining to a common set of genes. In the GATO system, annotation is generated by querying some of the Web-accessible resources and the information is stored in a local database, which keeps a record of all previous annotation results. GATO may be accessed from everywhere through the internet or may be run locally if a large number of sequences are going to be annotated. It is implemented in PHP and Perl and may be run on any suitable Web server. Usually, installation and application of annotation systems require experience and are time consuming, but GATO is simple and practical, allowing anyone with basic skills in informatics to access it without any special training. GATO can be downloaded at [http://mariwork.iq.usp.br/gato/]. Minimum computer free space required is 2 MB.

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The main objective of the study is to evaluate the impact of Lean Innovation management philosophy on the creativity potential of the large multinational enterprise. A theory of Lean Innovation indicates that the modern company in any industry can successfully combine both waste-decreasing approach and innovative potential promotion through creativity cultivation or, at least, preservation. The theoretical part of the work covers the main factors, pros and cons of Lean thinking and Innovation management separately, along with generalized new product development overview. While the modern international market becomes more accessible for entrepreneural initiatives, small enterprises and start-ups, large international corporations are more subject to adopt the Lean Innovation approach in both operational and product development sectors due to extended resources and capabilities. Moreover, a multinational enterprise is a highly probable pioneer in Lean innovation implementation. The empirical part of the thesis refers to a case of large European enterprise, operating in many markets around the globe, that currently undergoes innovation management adjustments and implementations in product development while already have related themselves with operational process optimization process through Lean thinking. A goal of the work is to understand what kind of difficulties and consequences a large international firm faces when dealing with Lean Innovation to improve own performance, if they can be sealed for generalized approach.