907 resultados para Key non-malleability
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If conducted poorly and without support from all employee levels, performance management programs at institutions may devolve into annual evaluations that represent a staff burden rather than an ongoing career development opportunity. This brief analyzes the key components of successful performance evaluation systems for non-academic staff, incorporating insights from employers outside of the higher education sector as well. It examines the importance of midyear check-in meetings; employee goal-setting; simplified rating scales on evaluation forms; and core staff competencies that reflect institutional priorities. It also describes how institutions communicate modifications to the evaluation system and offers recommendations for the implementation of process change.
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In trade agreements, governments can design remedies to ensure compliance (property rule) or to compensate victims (liability rule). This paper describes an economic framework to explain the pattern of remedies over non-tariff restrictions—particularly domestic subsidies and nonviolation complaints subject to liability rules. The key determinants of the contract form for any individual measure are the expected joint surplus from an agreement and the expected loss to the constrained government. The loss is higher for domestic subsidies and nonviolations because these are the policies most likely to correct domestic distortions. Governments choose property rules when expected gains from compliance are sufficiently high and expected losses to the constrained country are sufficiently low. Liability rules are preferable when dispute costs are relatively high, because inefficiencies in the compensation process reduce the number of socially inefficient disputes filed.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Usually referral letters are the only means of communication between general practitioners and specialists in the health area. However, they are inadequate if important basic data are omitted. The aim of this study was to compare the content of standard and non-standard letters. A total of 1956 files from the Oral Medicine Service were consecutively evaluated (March 1996 to September 2000). Key items were considered for analysis and the results were stored in a database using the Epinfo 6.04 program. The X-2 test (a=0.05) was applied to the results. of the 1956 files examined, 34% (662) had a referral letter, 31% of them being standard letters and 69% non-standard letters. Most standard letters (87%) were from professionals of public health institutions. Most percent discrepancies between standard and non-standard letters were observed for patient address (14.90 vs 1.32%), patient age (54.81 vs 9.47%), chief complaint (32.21 vs 8.37%), fundamental lesion (29.33 vs 13.66%), and symptoms (27.81 vs 15.42%,,). Statistically significant differences were observed for patient age, professional referring the patient, chief complaint, and site of the lesion. The quality and quantity of the information differed significantly between the two types of letters. The standard letters were more complete and contained information commonly absent in the non-standard letters. We suggest the use of standard letters for improving the quality of communication among professionals.
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1. Fine needle aspirates from ten patients with high-grade malignant non-Hodgkin's lymphomas were analyzed by cytomorphology and immunocytochemistry.2. The following morphologic diagnoses were made: lymphoblastic lymphoma (3 cases), Burkitt's lymphoma (3 cases), mixed small and large cell lymphomas with predominance of large cells (2 cases), and centroblastic lymphoma (2 cases). Immunocytochemistry showed a B-cell phenotype in five cases and a T-cell phenotype in four. One case of lymphoblastic lymphoma was negative for the T and B cell markers used.3. The results of histological and immunohistochemical analyses performed on surgical biopsies from 8 patients confirmed the morphological diagnosis in all cases. Two cases of Burkitt's lymphoma were submitted only to cytological and immunological diagnosis.4. The high diagnostic accuracy of combined cytomorphology and immunocytochemical assessment of fine needle aspirate samples validates the use of the technique in the diagnostic work-up of high-grade non Hodgkin's lymphomas.
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Includes bibliography
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Aims: Metformin is an insulin sensitizing agent with beneficial effects in diabetic patients on glycemic levels and in the cardiovascular system. We examined whether the metabolic changes and the vascular dysfunction in monosodium glutamate-induced obese non-diabetic (MSG) rats might be improved by metformin. Main methods: 16 week-old MSG rats were treated with metformin for 15 days and compared with age-matched untreated MSG and non-obese non-diabetic rats (control). Blood pressure, insulin sensitivity, vascular reactivity and prostanoid release in the perfused mesenteric arteriolar bed as well as nitric oxide production and reactive oxygen species generation in isolated mesenteric arteries were analyzed. Key findings: 18-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia, insulin resistance and hyperinsulinemia. Metformin treatment improved these alterations. The norepinephrine-induced response, increased in the mesenteric arteriolar bed from MSG rats, was corrected by metformin. Indomethacin corrected the enhanced contractile response in MSG rats but did not affect metformin effects. The sensitivity to acetylcholine, reduced in MSG rats, was also corrected by metformin. Indomethacin corrected the reduced sensitivity to acetylcholine in MSG rats but did not affect metformin effects. The sensitivity to sodium nitroprusside was increased in preparations from metformin-treated rats. Metformin treatment restored both the reduced PGI2/TXA2 ratio and the increased reactive oxygen species generation in preparations from MSG rats. Significance: Metformin improved the vascular function in MSG rats through reduction in reactive oxygen species generation, modulation of membrane hyperpolarization. correction of the unbalanced prostanoids release and increase in the sensitivity of the smooth muscle to nitric oxide. (c) 2011 Elsevier Inc. All rights reserved.
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Coding region alterations of ZIC2 are the second most common type of mutation in holoprosencephaly (HPE). Here we use several complementary bioinformatic approaches to identify ultraconserved cis-regulatory sequences potentially driving the expression of human ZIC2. We demonstrate that an 804 bp element in the 3' untranslated region (3'UTR) is highly conserved across the evolutionary history of vertebrates from fish to humans. Furthermore, we show that while genetic variation of this element is unexpectedly common among holoprosencephaly subjects (6/528 or >1%), it is not present in control individuals. Two of six proband-unique variants are de novo, supporting their pathogenic involvement in HPE outcomes. These findings support a general recommendation that the identification and analysis of key ultraconserved elements should be incorporated into the genetic risk assessment of holoprosencephaly cases.
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Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple beta-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the beta(1) isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the beta(1) selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the beta(1) gene (KO of beta(1) adrenergic receptor (beta 1KO)) developed hypothermia during cold exposure and exhibited decreased iBAT thermal response to NE or DB infusion. Thirdly, when placed on a high-fat diet (HFD; 40% fat) for 5 weeks, beta 1KO mice were more susceptible to obesity than WT controls and failed to develop diet-induced thermogenesis as assessed by BAT Ucp1 mRNA levels and oxygen consumption. Furthermore, beta 1KO mice exhibited fasting hyperglycemia and more intense glucose intolerance, hypercholesterolemia, and hypertriglyceridemia when placed on the HFD, developing marked non-alcoholic steatohepatitis. In conclusion, the beta(1) signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis. Journal of Endocrinology (2012) 214, 359-365
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The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.
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Background: Several studies in Drosophila have shown excessive movement of retrogenes from the X chromosome to autosomes, and that these genes are frequently expressed in the testis. This phenomenon has led to several hypotheses invoking natural selection as the process driving male-biased genes to the autosomes. Metta and Schlotterer (BMC Evol Biol 2010, 10:114) analyzed a set of retrogenes where the parental gene has been subsequently lost. They assumed that this class of retrogenes replaced the ancestral functions of the parental gene, and reported that these retrogenes, although mostly originating from movement out of the X chromosome, showed female-biased or unbiased expression. These observations led the authors to suggest that selective forces (such as meiotic sex chromosome inactivation and sexual antagonism) were not responsible for the observed pattern of retrogene movement out of the X chromosome. Results: We reanalyzed the dataset published by Metta and Schlotterer and found several issues that led us to a different conclusion. In particular, Metta and Schlotterer used a dataset combined with expression data in which significant sex-biased expression is not detectable. First, the authors used a segmental dataset where the genes selected for analysis were less testis-biased in expression than those that were excluded from the study. Second, sex-biased expression was defined by comparing male and female whole-body data and not the expression of these genes in gonadal tissues. This approach significantly reduces the probability of detecting sex-biased expressed genes, which explains why the vast majority of the genes analyzed (parental and retrogenes) were equally expressed in both males and females. Third, the female-biased expression observed by Metta and Schltterer is mostly found for parental genes located on the X chromosome, which is known to be enriched with genes with female-biased expression. Fourth, using additional gonad expression data, we found that autosomal genes analyzed by Metta and Schlotterer are less up regulated in ovaries and have higher chance to be expressed in meiotic cells of spermatogenesis when compared to X-linked genes. Conclusions: The criteria used to select retrogenes and the sex-biased expression data based on whole adult flies generated a segmental dataset of female-biased and unbiased expressed genes that was unable to detect the higher propensity of autosomal retrogenes to be expressed in males. Thus, there is no support for the authors' view that the movement of new retrogenes, which originated from X-linked parental genes, was not driven by selection. Therefore, selection-based genetic models remain the most parsimonious explanations for the observed chromosomal distribution of retrogenes.
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[EN] This article examines a variety of options for expressing speaker and writer stance in a subcorpus of MarENG, a maritime English learning tool sponsored by the EU (35,041 words). Non-verbal markers related to key areas of modal expression are presented; (1)epistemic adverbs and adverbial expressions, (2) epistemic adjectives, (3) deontic adjectives, (4) evidential adverbs, (5) evidential adjectives, (6) evidential interpersonal markers, and (7) single adverbials conveying the speaker’s attitudes, feelings or value judgments. The overall aim is to present an overview of how these non-verbal markers operate in this LSP genre.
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Hydrothermal fluids are a fundamental resource for understanding and monitoring volcanic and non-volcanic systems. This thesis is focused on the study of hydrothermal system through numerical modeling with the geothermal simulator TOUGH2. Several simulations are presented, and geophysical and geochemical observables, arising from fluids circulation, are analyzed in detail throughout the thesis. In a volcanic setting, fluids feeding fumaroles and hot spring may play a key role in the hazard evaluation. The evolution of the fluids circulation is caused by a strong interaction between magmatic and hydrothermal systems. A simultaneous analysis of different geophysical and geochemical observables is a sound approach for interpreting monitored data and to infer a consistent conceptual model. Analyzed observables are ground displacement, gravity changes, electrical conductivity, amount, composition and temperature of the emitted gases at surface, and extent of degassing area. Results highlight the different temporal response of the considered observables, as well as the different radial pattern of variation. However, magnitude, temporal response and radial pattern of these signals depend not only on the evolution of fluid circulation, but a main role is played by the considered rock properties. Numerical simulations highlight differences that arise from the assumption of different permeabilities, for both homogeneous and heterogeneous systems. Rock properties affect hydrothermal fluid circulation, controlling both the range of variation and the temporal evolution of the observable signals. Low temperature fumaroles and low discharge rate may be affected by atmospheric conditions. Detailed parametric simulations were performed, aimed to understand the effects of system properties, such as permeability and gas reservoir overpressure, on diffuse degassing when air temperature and barometric pressure changes are applied to the ground surface. Hydrothermal circulation, however, is not only a characteristic of volcanic system. Hot fluids may be involved in several mankind problems, such as studies on geothermal engineering, nuclear waste propagation in porous medium, and Geological Carbon Sequestration (GCS). The current concept for large-scale GCS is the direct injection of supercritical carbon dioxide into deep geological formations which typically contain brine. Upward displacement of such brine from deep reservoirs driven by pressure increases resulting from carbon dioxide injection may occur through abandoned wells, permeable faults or permeable channels. Brine intrusion into aquifers may degrade groundwater resources. Numerical results show that pressure rise drives dense water up to the conduits, and does not necessarily result in continuous flow. Rather, overpressure leads to new hydrostatic equilibrium if fluids are initially density stratified. If warm and salty fluid does not cool passing through the conduit, an oscillatory solution is then possible. Parameter studies delineate steady-state (static) and oscillatory solutions.
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Das Hepatitis C Virus (HCV) ist ein umhülltes RNA Virus aus der Familie der Flaviviridae. Sein Genom kodiert für ein ca. 3000 Aminosäuren langes Polyprotein, welches co- und posttranslational in seine funktionellen Einheiten gespalten wird. Eines dieser viralen Proteine ist NS5A. Es handelt sich hierbei um ein stark phosphoryliertes Protein, das eine amphipatische α-Helix im Amino-Terminus trägt, welche für die Membran-Assoziation von NS5A verantwortlich ist. Welche Rolle die Phosphorylierung für die Funktion des Proteins spielt, bzw. welche Funktion NS5A überhaupt ausübt, ist zur Zeit noch unklar. Beobachtungen lassen Vermutungen über eine Funktion von NS5A bei der Resistenz infizierter Zellen gegenüber Interferon-alpha zu. Weiterhin wird vermutet, das NS5A als Komponente des membranständigen HCV Replikasekomplexes an der RNA Replikation beteiligt ist. Das Ziel dieser Doktorarbeit war es, die Funktion von NS5A für die RNA Replikation zu untersuchen. Zu diesem Zweck wurde eine Serie von Phosphorylierungsstellen-Mutanten generiert, die auf Ihre Replikationsfähigkeit und den Phosphorylierungsstatus hin untersucht wurden. Wir fanden, dass bestimmte Serin-Substitutionen im Zentrum von NS5A zu einer gesteigerten RNA Replikation führten, bei gleichzeitig reduzierter NS5A Hyperphosphorylierung. Weiterhin studierten wir den Einfluß von Mutationen in der Amino-terminalen amphipatischen α-Helix von NS5A auf die RNA-Replikation, sowie Phosphorylierung und subzelluläre Lokalisation des Proteins. Wir fanden, dass geringfügige strukturelle Veränderungen der amphipatischen Helix zu einer veränderten subzellulären Lokalisation von NS5A führten, was mit einer reduzierten oder komplett inhibierten RNA Replikation einherging. Zudem interferierten die strukturellen Veränderungen mit der Hyperphosphorylierung des Proteins, was den Schluß nahe legt, dass die amphipatische Helix eine wichtige strukturelle Komponente des Proteins darstellt, die für die korrekte Faltung und Phosphorylierung des Proteins essentiell ist. Als weitere Aspekte wurden die Trans-Komplementationsfähigkeit der verschiedenen viralen Komponenten des HCV Replikasekomplexes untersucht, sowie zelluläre Interaktionspartner von NS5A identifiziert. Zusammenfassend zeigen die Ergebnisse dieser Doktorarbeit, dass NS5A eine wichtige Rolle bei der RNA-Replikation spielt. Diese Funktion wird wahrscheinlich über den Phosphorylierungszustand des Proteins reguliert.