935 resultados para investigation of head-first binding of substrate with the phe557 mutant soybean lipoxygenase-1
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Significant changes in accounting disclosure are observed in periods of economic change such as those relating to emerging capital markets and programs of privatization. Measurement of the level of accounting disclosure should ideally be designed to capture the complexity of change in order to give insight and explanation to match the causes and consequences of change. This paper shows the added interpretive value in subdividing the disclosure checklist to reflect the requirements of national accounting regulations, the location of disclosure items in the annual report, and limitations on the availability of regulations in official translation to the local language. Defining targeted disclosure categories leads to significance testing of specific aspects of changes in accounting disclosure in the Egyptian capital market in the 1990s. Strong correlation of disclosure with the presence of majority government ownership of the company and the relative activity of share trading supports the applicability of political costs and capital need theories, respectively. The relation between International Accounting Standards (IASs) disclosure and the type of audit firm points to additional theoretical explanations, including relative familiarity with the legislation and compliance features identifiable with the emerging capital market. The approach described in this paper has the potential for enhancing understanding of the complexity of accounting change in other emerging capital markets and developing economies.
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Background and Purpose Although it is established that the receptor activity modifying proteins (RAMPs) can interact with a number of GPCRs, little is known about the consequences of these interactions. Here the interaction of RAMPs with the glucagon-like peptide 1 receptor (GLP-1 receptor), the human vasoactive intestinal polypeptide/pituitary AC-Activating peptide 2 receptor (VPAC) and the type 1 corticotrophin releasing factor receptor (CRF) has been examined. Experimental Approach GPCRs were co-transfected with RAMPs in HEK 293S and CHO-K1 cells. Cell surface expression of RAMPs and GPCRs was examined by elisa. Where there was evidence for interactions, agonist-stimulated cAMP production, Ca mobilization and GTPγS binding to G, G, G and G were examined. The ability of CRF to stimulate adrenal corticotrophic hormone release in Ramp2 mice was assessed. Key Results The GLP-1 receptor failed to enhance the cell surface expression of any RAMP. VPAC enhanced the cell surface expression of all three RAMPs. CRF enhanced the cell surface expression of RAMP2; the cell surface expression of CRF was also increased. There was no effect on agonist-stimulated cAMP production. However, there was enhanced G-protein coupling in a receptor and agonist-dependent manner. The CRF: RAMP2 complex resulted in enhanced elevation of intracellular calcium to CRF and urocortin 1 but not sauvagine. In Ramp2 mice, there was a loss of responsiveness to CRF. Conclusions and Implications The VPAC and CRF receptors interact with RAMPs. This modulates G-protein coupling in an agonist-specific manner. For CRF, coupling to RAMP2 may be of physiological significance. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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Significant changes in accounting disclosure are observed in periods of economic change such as those relating to emerging capital markets and programs of privatization. Measurement of the level of accounting disclosure should ideally be designed to capture the complexity of change in order to give insight and explanation to match the causes and consequences of change. This paper shows the added interpretive value in subdividing the disclosure checklist to reflect the requirements of national accounting regulations, the location of disclosure items in the annual report, and limitations on the availability of regulations in official translation to the local language. Defining targeted disclosure categories leads to significance testing of specific aspects of changes in accounting disclosure in the Egyptian capital market in the 1990s. Strong correlation of disclosure with the presence of majority government ownership of the company and the relative activity of share trading supports the applicability of political costs and capital need theories, respectively. The relation between International Accounting Standards (IASs) disclosure and the type of audit firm points to additional theoretical explanations, including relative familiarity with the legislation and compliance features identifiable with the emerging capital market. The approach described in this paper has the potential for enhancing understanding of the complexity of accounting change in other emerging capital markets and developing economies.
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Online enquiry communities such as Question Answering (Q&A) websites allow people to seek answers to all kind of questions. With the growing popularity of such platforms, it is important for community managers to constantly monitor the performance of their communities. Although different metrics have been proposed for tracking the evolution of such communities, maturity, the process in which communities become more topic proficient over time, has been largely ignored despite its potential to help in identifying robust communities. In this paper, we interpret community maturity as the proportion of complex questions in a community at a given time. We use the Server Fault (SF) community, a Question Answering (Q&A) community of system administrators, as our case study and perform analysis on question complexity, the level of expertise required to answer a question. We show that question complexity depends on both the length of involvement and the level of contributions of the users who post questions within their community. We extract features relating to askers, answerers, questions and answers, and analyse which features are strongly correlated with question complexity. Although our findings highlight the difficulty of automatically identifying question complexity, we found that complexity is more influenced by both the topical focus and the length of community involvement of askers. Following the identification of question complexity, we define a measure of maturity and analyse the evolution of different topical communities. Our results show that different topical communities show different maturity patterns. Some communities show a high maturity at the beginning while others exhibit slow maturity rate. Copyright 2013 ACM.
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Background and aims: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in subjects with type 2 diabetes mellitus. We evaluated 2-hour glucose, glucagon and insulin changes following a standardized mixed-meal tolerance test before and after 24 weeks of treatment with the once-daily prandial GLP-1 receptor agonist lixisenatide (approved for a therapeutic dose of 20 μg once daily) in six randomized, placebo-controlled studies within the lixisenatide Phase III GetGoal programme. In the studies, the mixed-meal test was conducted before and after: (1) lixisenatide treatment in patients insufficiently controlled despite diet and exercise (GetGoal-Mono), (2) lixisenatide treatment in combination with oral antidiabetic drugs (OADs) (GetGoal-M and GetGoal-S), or (3) lixisenatide treatment in combination with basal insulin ± OAD (GetGoal-Duo 1, GetGoal-L and GetGoal-L-Asia).Materials and methods: A meta-analysis was performed (lixisenatide n=1124 vs placebo n=707) combining ANCOVA least squares (LS) mean values using an inverse variance weighted analysis. Results: Lixisenatide significantly reduced 2-hour postprandial glucose from baseline (LS mean difference vs placebo: -4.9 mmol/L, p<0.0001, Figure) and glucose excursions (LS mean difference vs placebo: -4.5 mmol/L, p<0.0001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs placebo: -19.0 ng/L, p<0.0001) and insulin (LS mean difference vs placebo: -64.8 pmol/L, p<0.0001), although the glucagon/insulin ratio was increased (LS mean difference vs placebo: 0.15, p=0.02) compared with placebo. Conclusion: The results show that lixisenatide potently reduces the glucose excursion after meal ingestion in subjects with type 2 diabetes, in association with marked reductions in glucagon and insulin levels. It is suggested that diminished glucagon secretion and slower gastric emptying contribute to reduced hepatic glucose production and delayed glucose absorption, enabling postprandial glycaemia to be controlled with less demand on beta-cell insulin secretion. Clinical Trial Registration Number: NCT00688701; NCT00712673; NCT00713830; NCT00975286; NCT00715624; NCT00866658 Supported by: Sanofi
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A cikk központi kérdése a vállalati versenyképesség. Két meghatározó menedzsmentmegközelítés – a vevői érték és az erőforrás-, képességalapú stratégiai menedzsment – fogalmi rendszerére, illetve koncepcióira alapozva a szerzők kialakítottak és a "Versenyben a világgal 2004–2006 – gazdasági versenyképességünk vállalati nézőpontból" című kutatás adatbázisát használva teszteltek egy a vállalati versenyképesség belső struktúrájára rávilágító elméleti modellt. A modell empirikus tesztelésének eredménye szerint a kialakított koncepció a vállalati versenyképesség elemzésének hasznos eszköze, mely alkalmas arra, hogy a vizsgált vállalatok esetében igazolja, vagy éppen megcáfolja a meghatározott, ún. összehangolt kompetenciák meglétét. ________The main issue of this article is the competitiveness of firms. Based on conceptual system and concepts of two determinant management approaches – the customer value and the resource and capability based strategic management – the authors have developed and tested a theoretical model of the inside structure of the competitiveness of firms using the database of Competing with the World 2004-2006 – the competitiveness of the Hungarian economy from enterprise point of view. According to the result of the empiric test of the model the developed concept has been a profitable tool of the analysis of the enterprise competitiveness and it has been suited for confirming or confuting determinated so called aligned competencies being in the case of examined firms.
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A recently developed technique for determining past sea surface temperatures (SST), based on an analysis of the unsaturation ratio of long chain C37 methyl alkenones produced by Prymnesiophyceae phytoplankton (U37 k' ), has been applied to an upper Quaternary sediment core from the equatorial Atlantic. U37 k' temperature estimates were compared to those obtained from delta18O of the planktonic foraminifer Globigerinoides sacculifer and of planktonic foraminiferal assemblages for the last glacial cycle. The alkenone method showed 1.8°C cooling at the last glacial maximum, about 1/2 to 1/3 of the decrease shown by the isotopic method (6.3°C) and foraminiferal modern analogue technique estimates for the warm season (3.8°C). Warm season foraminiferal assemblage estimates based on transfer functions are out of phase with the other estimates, showing a 1.4°C drop at the last glacial maximum with an additional 0.9°C drop in the deglaciation. Increased alkenone abundances, total organic carbon percentage and foraminiferal accumulation rates in the last glaciation indicate an increase in productivity of as much as 4 times over present day. These changes are thought to be due to increased upwelling caused by enhanced winds during the glaciation. If U37 k' estimates are correct, as much as 50-70% (up to 4.5°C) of estimated delta18O and modern analogue temperature changes in the last glaciation may have been due to changes in thermocline depth, whereas transfer functions seem more strongly influenced by seasonality changes. This indicates these estimates may be influenced as strongly by other factors as they are by SST, which in the equatorial Atlantic was only reduced slightly in the last glaciation.
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Purpose: To qualitatively explore the communication between healthcare professionals and oncology patients based on the perception of patients undergoing chemotherapy.Method: Qualitative and exploratory design. Participants were 14 adult patients undergoing chemotherapy at different stages of the disease. A socio-demographic and clinical data form was utilized along with semi-structured interviews. The interviews were audio-recorded, transcribed and content analysis was performed. Two independent judges evaluated the interview content in regards to emerging categories and obtained a Kappa index of 0.834.Results: Three categories emerged from the data: 1) Technical communication without emotional support, in which the information provided is composed of strictly technical information regarding the diagnosis, treatment and/or prognosis; 2) Technical communication, in which the information provided is oriented towards the technical aspects of the patient’s physical condition, while also providing psychological support for the patients’ subjective needs; and 3) Insufficient technical communication, win which there are gaps in the information provided causing confusion and suffering to the patient.Conclusions: Communication with emotional support contributes to greater satisfaction of chemotherapy patients. Practical implications: the results provide elements for the training of healthcare professionals regarding the importance of the emotional support that can be offered to cancer patients during their treatment.
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The Bay of Algeciras (BA) is a marine environment subject to high levels of anthropogenic pressure. Here we analyze observations collected at the Bay and the results of an ocean circulation model to investigate its circulation and variability. Special attention is paid to the identification of the mechanisms enhancing the exchange of water with the adjacent Strait of Gibraltar and therefore contributing to maintain satisfactory levels of water quality.
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In pursuit of aligning with the European Union's ambitious target of achieving a carbon-neutral economy by 2050, researchers, vehicle manufacturers, and original equipment manufacturers have been at the forefront of exploring cutting-edge technologies for internal combustion engines. The introduction of these technologies has significantly increased the effort required to calibrate the models implemented in the engine control units. Consequently the development of tools that reduce costs and the time required during the experimental phases, has become imperative. Additionally, to comply with ever-stricter limits on 〖"CO" 〗_"2" emissions, it is crucial to develop advanced control systems that enhance traditional engine management systems in order to reduce fuel consumption. Furthermore, the introduction of new homologation cycles, such as the real driving emissions cycle, compels manufacturers to bridge the gap between engine operation in laboratory tests and real-world conditions. Within this context, this thesis showcases the performance and cost benefits achievable through the implementation of an auto-adaptive closed-loop control system, leveraging in-cylinder pressure sensors in a heavy-duty diesel engine designed for mining applications. Additionally, the thesis explores the promising prospect of real-time self-adaptive machine learning models, particularly neural networks, to develop an automatic system, using in-cylinder pressure sensors for the precise calibration of the target combustion phase and optimal spark advance in a spark-ignition engines. To facilitate the application of these combustion process feedback-based algorithms in production applications, the thesis discusses the results obtained from the development of a cost-effective sensor for indirect cylinder pressure measurement. Finally, to ensure the quality control of the proposed affordable sensor, the thesis provides a comprehensive account of the design and validation process for a piezoelectric washer test system.
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The cellular prion protein (PrPC) is a neuronal anchored glycoprotein that has been associated with distinct functions in the CNS, such as cellular adhesion and differentiation, synaptic plasticity and cognition. Here we investigated the putative involvement of the PrPC in the innate fear-induced behavioural reactions in wild-type (WT), PrPC knockout (Prnp(0/0)) and the PrPC overexpressing Tg-20 mice evoked in a prey versus predator paradigm. The behavioural performance of these mouse strains in olfactory discrimination tasks was also investigated. When confronted with coral snakes, mice from both Prnp(0/0) and Tg-20 strains presented a significant decrease in frequency and duration of defensive attention and risk assessment, compared to WT mice. Tg-20 mice presented decreased frequency of escape responses, increased exploratory behaviour, and enhancement of interaction with the snake, suggesting a robust fearlessness caused by PrPC overexpression. Interestingly, there was also a discrete decrease in the attentional defensive response (decreased frequency of defensive alertness) in Prnp(0/0) mice in the presence of coral snakes. Moreover, Tg-20 mice presented an increased exploration of novel environment and odors. The present findings indicate that the PrPC overexpression causes hyperactivity, fearlessness, and increased preference for visual, tactile and olfactory stimuli-associated novelty, and that the PrPC deficiency might lead to attention deficits. These results suggest that PrPC exerts an important role in the modulation of innate fear and novelty-induced exploration. (C) 2008 Published by Elsevier B.V.
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Introducción: El Deslizamiento Epifisiario Capital Femoral es la enfermedad de la cadera más común en adolescentes entre los 9 y 16 años. Es de causa idiopática, más frecuente en hombres, se clasifica en 4 estadios según criterios clínicos y radiológicos. Se buscó evaluar la evolución de los deslizamientos moderados y severos tratados con una de las dos técnicas propuestas. Metodología Se realizó un estudio descriptivo con pacientes que fueron llevados a fijación in situ o luxación controlada entre 2008 y 2011. Resultados: Se incluyeron 26 pacientes, los cuales el 65.4% se les realizó luxación quirúrgica controlada y el 34.6% fijación in situ. El 70,6% de pacientes tenían DECF inestable y 70,5% tenían desplazamiento severo. La evaluación de la escala WOMAC para dolor, rigidez y capacidad funcional encontró mejores beneficios para el grupo de fijación in situ, estadísticamente significativos (p<0,05), no solo en términos de dolor, rigidez y capacidad funcional sino menor frecuencia de complicaciones. Las complicaciones más frecuentes en el grupo de luxación quirúrgica controlada fueron un caso de infección, 7 casos (41,2%) de necrosis avascular de cabeza femoral, 5 casos (29,4%) de condrolisis y 2 casos (11,8%) de pseudoartrosis; En el grupo de fijación in situ, solo 1 (11,1%) presentó Infección del Sitio Operatorio y 1 (11,1%) Condrolisis. Resultados significativos solo para necrosis avascular. Discusión: Los pacientes con deslizamientos moderados y severos manejados con fijación in situ tuvieron una mejor resultado con menor proporción de complicaciones.
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Anomalous heavy snow during winter or spring has long been regarded as a possible precursor of deficient Indian monsoon rainfall during the subsequent summer. However previous work in this field is inconclusive, in terms of the mechanism that communicates snow anomalies to the monsoon summer, and even the region from which snow has the most impact. In this study we explore these issues in coupled and atmosphere-only versions of the Hadley Centre model. A 1050-year control integration of the HadCM3 coupled model, which well represents the seasonal cycle of snow cover over the Eurasian continent, is analysed and shows evidence for weakened monsoons being preceded by strong snow forcing (in the absence of ENSO) over either the Himalaya/Tibetan Plateau or north/west Eurasia regions. However, empirical orthogonal function (EOF) analysis of springtime interannual variability in snow depth shows the leading mode to have opposite signs between these two regions, suggesting that competing mechanisms may be possible. To determine the dominant region, ensemble integrations are carried out using HadAM3, the atmospheric component of HadCM3, and a variety of anomalous snow forcing initial conditions obtained from the control integration of the coupled model. Forcings are applied during spring in separate experiments over the Himalaya/Tibetan Plateau and north/west Eurasia regions, in conjunction with climatological SSTs in order to avoid the direct effects of ENSO. With the aid of idealized forcing conditions in sensitivity tests, we demonstrate that forcing from the Himalaya region is dominant in this model via a Blanford-type mechanism involving reduced surface sensible heat and longwave fluxes, reduced heating of the troposphere over the Tibetan Plateau and consequently a reduced meridional tropospheric temperature gradient which weakens the monsoon during early summer. Snow albedo is shown to be key to the mechanism, explaining around 50% of the perturbation in sensible heating over the Tibetan Plateau, and accounting for the majority of cooling through the troposphere.
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OBJECTIVE To investigate the relation between serum concentration of 25-hydroxyvitamin D [25(OH)D] and insulin action and secretion. RESEARCH DESIGN AND METHODS In a cross-sectional study of 446 Pan-European subjects with the metabolic syndrome, insulin action and secretion were assessed by homeostasis model assessment (HOMA) indexes and intravenous glucose tolerance test to calculate acute insulin response, insulin sensitivity, and disposition index. Serum 25(OH)D was measured by high-performance liquid chromatography/mass spectrometry. RESULTS The 25(OH)D3 concentration was 57.1 ± 26.0 nmol/l (mean ± SD), and only 20% of the subjects had 25(OH)D3 levels ≥75 nmol/l. In multiple linear analyses, 25(OH)D3 concentrations were not associated with parameters of insulin action or secretion after adjustment for BMI and other covariates. CONCLUSIONS In a large sample of subjects with the metabolic syndrome, serum concentrations of 25(OH)D3 did not predict insulin action or secretion. Clear evidence that D vitamin status directly influences insulin secretion or action is still lacking.
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Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is caused by mutation of the autoimmune regulator (AIRE) gene, is a highly variable disease characterized by multiple endocrine failure, chronic mucocutaneous candidiasis, and various ectodermal defects. AIRE is a transcriptional regulator classically expressed in medullary thymic epithelial cells, monocytes, macrophages, and dendritic cells. Previous studies have suggested that AIRE can shuttle between the nucleus and cytoplasm of cells, although its cytoplasmic functions are poorly characterized. Through mass spectrometry analysis of proteins co-immunoprecipitating with cytoplasmic AIRE, we identified a novel association of AIRE with the intermediate filament protein cytokeratin 17 (K17) in the THP-1 monocyte cell line. We confirmed AIRE expression in HaCaT epidermal keratinocytes, as well as its interaction with K17. Confocal microscopy of human fetal and adult scalp hair follicles demonstrated a cytoplasmic pattern of AIRE staining that moderately colocalized with K17. The cytoplasmic association of AIRE with the intermediate filament network in human epidermal and follicular keratinocytes may provide a new path to understanding the ectodermal abnormalities associated with the APECED syndrome. (Am J Pathol 2011, 178:983-988; DOI: 10.1016/j.ajpath.2010.12.007)