987 resultados para Covalent cross-link
Resumo:
VSC converters are becoming more prevalent for HVDC applications. Two circuits are commercially available at present, a traditional six-switch, PWM inverter, implemented using series connected IGBTs - ABBs HVDC Light®, and the other a modular multi-level converter (MMC) - Siemens HVDC-PLUS. This paper presents an alternative MMC topology, which utilises a novel current injection technique, and exhibits several desirable characteristics.
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The major contribution of the study is the identification of a positive link between perceived effective managerial coaching (PEMC) and team task performance and also, the examination of PEMC adopting a multilevel research design and incorporating dual-source data. Specifically, drawing on social psychology, the thesis aims at developing and testing a comprehensive conceptual framework of the antecedents and consequences of PEMC for knowledge workers. The model takes into consideration intrapersonal, interpersonal and team-level characteristics, which relate to PEMC and, subsequently associate with important work outcomes. In this regard, the thesis identifies PEMC as a practice of dual nature in that it may be experienced not only as a one-on-one workplace developmental interaction, but also as a managerial practice that is experienced by each member of a team for co-ordination purposes. Adopting a cross-sectional survey research design, the hypotheses are tested in three organisations in Greece and the UK. In particular, hierarchical linear modelling of 191 employees nested in 60 teams yields that employees’ learning goal orientation (LGO) and high-quality exchanges between an employee and a manager (LMX) are positively related to effective MC, while a manager’s LGO moderates the relationship between employees’ LGO and PEMC. In turn, PEMC, as a one-on-one practice, is related to cognitive outcomes, such as information sharing, while as a shared team practice is related also to behavioural outcomes, including individual and team performance. Overall, the study contributes to a growing body of coaching and management literature that acknowledges PEMC as a core managerial practice.
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How good is your pharmacy practice? And what does “good” look like? Take a look back at the education and training you have received in your career to date. Has it stood you in good stead? Certainly there is a need to establish a model of professional education and development that produces good pharmacists — you should be able to demonstrate your competence regardless of your sector of work. It may help if we move away from the view that excellence in pharmacy practice is primarily defined by where you practise and the kind of job that you do. The Modernising Pharmacy Careers programme’s aspirations to integrate the undergraduate degree with the preregistration training year are bold and to be applauded — provided the outcome delivers changes that are more than superficial. The new model needs to deliver greater integration of education with practice, while retaining an adequate science base. Theory should be put into the context of practice-based, cross-sector learning needs and opportunities. For example, is the classroom really the best environment in which to learn dispensing? Pharmacokinetic theory could be put into context through creatively designed work placements. And it might make more sense to learn patient counselling in a community pharmacy, and so on. Is it resources we lack to make this happen? Or do we lack the collective will to be imaginative, to be radical and to conceive new approaches to professional education? Implicit in this new approach to education is the expectation that pharmacists should teach and mentor and, conversely, that those who teach should also engage in relevant practice. University education must produce graduates whose knowledge and competence are useful to employers. Moreover, graduates must be adequately prepared to enter any area of the profession endowed with professional self-confidence (something, arguably, that needs further development within the pharmacy psyche). Of course, becoming qualified is just the beginning. Post-qualification, pharmacists need structured career paths that foster this professional confidence, support learning and ensure recognition. To this end, the Royal Pharmaceutical Society-led professional curriculum group is working to define knowledge, skills and experience for all areas of advanced practice. More than ever, the profession needs to adopt a culture of learning, teaching and practice research that is unified. The question is: how do we move away from merely collecting qualifications (trophies) to developing meaningful careers? Pharmacists in all areas and at all levels of the profession need to consider their own willingness to make this shift. The RPS and MPC are leading the way, but are we following?
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In this dissertation, I present an integrated model of organizational performance. Most prior research has relied extensively on testing individual linkages, often with cross-sectional data. In this dissertation, longitudinal unit-level data from 559 restaurants, collected over a one-year period, were used to test the proposed model. The model was hypothesized to begin with employee satisfaction as a key antecedent that would ultimately lead to improved financial performance. Several variables including turnover, efficiency, and guest satisfaction are proposed as mediators of the satisfaction-performance relationship. The current findings replicate and extend past research using individual-level data. The overall model adequately explained the data, but was significantly improved with an additional link from employee satisfaction to efficiency, which was not originally hypothesized. Management turnover was a strong predictor of hourly level team turnover, and both were significant predictors of efficiency. Full findings for each hypothesis are presented and practical organizational implications are given. Limitations and recommendations for future research are provided. ^
Resumo:
The enzyme S-adenosyl-L-homocysteine (AdoHcy) hydrolase effects hydrolytic cleavage of AdoHcy to adenosine (Ado) and L-homocysteine (Hcy). The cellular levels of AdoHcy and Hcy are critical because AdoHcy is a potent feedback inhibitor of crucial transmethylation enzymes. Also, elevated plasma levels of Hcy in humans have been shown to be a risk factor in coronary artery disease. ^ On the basis of the previous finding that AdoHcy hydrolase is able to add the enzyme-sequestered water molecule across the 5',6'-double bond of (halo or dihalohomovinyl)-adenosines causing covalent binding inhibition, we designed and synthesized AdoHcy analogues with the 5',6'-olefin motif incorporated in place of the carbon-5' and sulfur atoms. From the available synthetic methods we chose two independent approaches: the first approach was based on the construction of a new C5'-C6' double bond via metathesis reactions, and the second approach was based on the formation of a new C6'-C7' single bond via Pd-catalyzed cross-couplings. Cross-metathesis of the suitably protected 5'-deoxy-5'-methyleneadenosine with racemic 2-amino-5-hexenoate in the presence of Hoveyda-Grubb's catalyst followed by standard deprotection afforded the desired analogue as 5' E isomer of the inseparable mixture of 9'R/S diastereomers. Metathesis of chiral homoallylglycine [(2S)-amino-5-hexenoate] produced AdoHcy analogue with established stereochemistry E at C5'atom and S at C9' atom. The 5'-bromovinyl analogue was synthesized using the bromination-dehydrobromination strategy with pyridinium tribromide and DBU. ^ Since literature reports on the Pd-catalyzed monoalkylation of dihaloalkenes (Csp2-Csp3 coupling) were scarce, we were prompted to undertake model studies on Pd-catalyzed coupling between vinyl dihalides and alkyl organometallics. The 1-fluoro-1-haloalkenes were found to undergo Negishi couplings with alkylzinc bromides to give multisubstituted fluoroalkenes. The alkylation was trans-selective affording pure Z-fluoroalkenes. The highest yields were obtained with PdCl 2(dppb) catalyst, but the best stereochemical outcome was obtained with less reactive Pd(PPh3)4. Couplings of 1,1-dichloro-and 1,1-dibromoalkenes with organozinc reagents resulted in the formation of monocoupled 1-halovinyl product. ^
Resumo:
The enzyme S-adenosyl-L-homocysteine (AdoHey) hydrolase effects hydrolytic cleavage of AdoHcy to adenosine (Ado) and L-homocysteine (Hcy). The cellular levels of AdoHcy and Hcy are critical because AdoHcy is a potent feedback inhibitor of crucial transmethylation enzymes. Also, elevated plasma levels of Hcy in humans have been shown to be a risk factor in coronary artery disease. On the basis of the previous finding that AdoHcy hydrolase is able to add the enzyme-sequestered water molecule across the 5',6'-double bond of (halo or dihalohomovinyl)-adenosines causing covalent binding inhibition, we designed and synthesized AdoHcy analogues with the 5',6'-olefin motif incorporated in place of the carbon-5' and sulfur atoms. From the available synthetic methods we chose two independent approaches: the first approach was based on the construction of a new C5'- C6' double bond via metathesis reactions, and the second approach was based on the formation of a new C6'-C7' single bond via Pd-catalyzed cross-couplings. Cross-metathesis of the suitably protected 5'-deoxy-5'-methyleneadenosine with racemic 2-amino-5-hexenoate in the presence of Hoveyda-Grubb's catalyst followed by standard deprotection afforded the desired analogue as 5'E isomer of the inseparable mixture of 9'RIS diastereomers. Metathesis of chiral homoallylglycine [(2S)-amino-5-hexenoate] produced AdoHcy analogue with established stereochemistry E at C5'atom and S at C9' atom. The 5'-bromovinyl analogue was synthesized using the brominationdehydrobromination strategy with pyridinium tribromide and DBU. Since literature reports on the Pd-catalyzed monoalkylation of dihaloalkenes (Csp2-Csp3 coupling) were scarce, we were prompted to undertake model studies on Pdcatalyzed coupling between vinyl dihalides and alkyl organometallics. The 1-fluoro-1- haloalkenes were found to undergo Negishi couplings with alkylzinc bromides to give multisubstituted fluoroalkenes. The alkylation was trans-selective affording pure Zfluoroalkenes. The highest yields were obtained with PdCl 2(dppb) catalyst, but the best stereochemical outcome was obtained with less reactive Pd(PPh3)4 . Couplings of 1,1- dichloro-and 1,1-dibromoalkenes with organozinc reagents resulted in the formation of monocoupled 1-halovinyl product.
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RNA viruses are an important cause of global morbidity and mortality. The rapid evolutionary rates of RNA virus pathogens, caused by high replication rates and error-prone polymerases, can make the pathogens difficult to control. RNA viruses can undergo immune escape within their hosts and develop resistance to the treatment and vaccines we design to fight them. Understanding the spread and evolution of RNA pathogens is essential for reducing human suffering. In this dissertation, I make use of the rapid evolutionary rate of viral pathogens to answer several questions about how RNA viruses spread and evolve. To address each of the questions, I link mathematical techniques for modeling viral population dynamics with phylogenetic and coalescent techniques for analyzing and modeling viral genetic sequences and evolution. The first project uses multi-scale mechanistic modeling to show that decreases in viral substitution rates over the course of an acute infection, combined with the timing of infectious hosts transmitting new infections to susceptible individuals, can account for discrepancies in viral substitution rates in different host populations. The second project combines coalescent models with within-host mathematical models to identify driving evolutionary forces in chronic hepatitis C virus infection. The third project compares the effects of intrinsic and extrinsic viral transmission rate variation on viral phylogenies.
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Background: Alcohol plays a complex role in society. A recent study showed that over half of Irish adults drink hazardously. Adolescents report increased levels of alcohol consumption. Previous research has inferred the influence of the parent on their adolescent. Thus, the aim of the current study was to investigate the association between adolescent alcohol consumption and their parent’s consumption pattern and attitude toward alcohol use in Southern Ireland. Methods: A cross-sectional survey was undertaken in November 2014. This involved distributing a survey to adolescents (n = 982) in their final two years of second level education and at least one of their parents from a local electorate area in Southern Ireland. This survey included: alcohol use, self- reported height and weight, smoking status, mental health and well-being along with attitudinal questions. Chi-square tests and multivariate logistic regression were utilised. Results: A 37 % response rate was achieved. Over one-third (34.2 %) of adolescents and 47 % of parents surveyed reported hazardous drinking. Over 90 % of parents disagreed with allowing their adolescent to get drunk and rejected the idea that getting drunk is part of having fun as an adolescent. The majority (79.5 %) of parents surveyed believed that their alcohol consumption pattern set a good example for their adolescent. Multivariate logistic regression highlights the association between adolescent hazardous alcohol consumption and hazardous drinking by the father. Furthermore either parent permitting their adolescent to drink alcohol on special occasions was associated with hazardous alcohol consumption in the adolescent. Conclusion: The findings of this research notes a liberal attitude to alcohol and increased levels of consumption by the parent are linked to hazardous adolescent drinking behaviour. Future action plans aimed at combatting adolescent hazardous alcohol consumption should also be aimed at tackling parents’ attitudes towards and consumption of alcohol.
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River runoff is an essential climate variable as it is directly linked to the terrestrial water balance and controls a wide range of climatological and ecological processes. Despite its scientific and societal importance, there are to date no pan-European observation-based runoff estimates available. Here we employ a recently developed methodology to estimate monthly runoff rates on regular spatial grid in Europe. For this we first assemble an unprecedented collection of river flow observations, combining information from three distinct data bases. Observed monthly runoff rates are first tested for homogeneity and then related to gridded atmospheric variables (E-OBS version 12) using machine learning. The resulting statistical model is then used to estimate monthly runoff rates (December 1950 - December 2015) on a 0.5° x 0.5° grid. The performance of the newly derived runoff estimates is assessed in terms of cross validation. The paper closes with example applications, illustrating the potential of the new runoff estimates for climatological assessments and drought monitoring.
Resumo:
River runoff is an essential climate variable as it is directly linked to the terrestrial water balance and controls a wide range of climatological and ecological processes. Despite its scientific and societal importance, there are to date no pan-European observation-based runoff estimates available. Here we employ a recently developed methodology to estimate monthly runoff rates on regular spatial grid in Europe. For this we first collect an unprecedented collection of river flow observations, combining information from three distinct data bases. Observed monthly runoff rates are first tested for homogeneity and then related to gridded atmospheric variables (E-OBS version 11) using machine learning. The resulting statistical model is then used to estimate monthly runoff rates (December 1950-December 2014) on a 0.5° × 0.5° grid. The performance of the newly derived runoff estimates is assessed in terms of cross validation. The paper closes with example applications, illustrating the potential of the new runoff estimates for climatological assessments and drought monitoring.
Resumo:
Topographic variation, the spatial variation in elevation and terrain features, underpins a myriad of patterns and processes in geography and ecology and is key to understanding the variation of life on the planet. The characterization of this variation is scale-dependent, i.e. it varies with the distance over which features are assessed and with the spatial grain (grid cell resolution) of analysis. A fully standardized and global multivariate product of different terrain features has the potential to support many large-scale basic research and analytical applications, however to date, such technique is unavailable. Here we used the digital elevation model products of global 250 m GMTED and near-global 90 m SRTM to derive a suite of topographic variables: elevation, slope, aspect, eastness, northness, roughness, terrain roughness index, topographic position index, vector ruggedness measure, profile and tangential curvature, and 10 geomorphological landform classes. We aggregated each variable to 1, 5, 10, 50 and 100 km spatial grains using several aggregation approaches (median, average, minimum, maximum, standard deviation, percent cover, count, majority, Shannon Index, entropy, uniformity). While a global cross-correlation underlines the high similarity of many variables, a more detailed view in four mountain regions reveals local differences, as well as scale variations in the aggregated variables at different spatial grains. All newly-developed variables are available for download at http://www.earthenv.org and can serve as a basis for standardized hydrological, environmental and biodiversity modeling at a global extent.
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Examining factors that affect vitamin D status in the fast-growing elderly population of Miami-Dade, Florida, is needed. Vitamin D deficiency in older adults has been linked to correlates of disability, including falls and fractures, and cardiovascular disease. The purpose of this study was to determine the proportion of vitamin D insufficient individuals and their relationship with vitamin D insufficiency in older adults (n=97) living in Miami-Dade. We evaluated the association between vitamin D status and 1) dual task physical performance to understand the link between vitamin D and cognition in the context of mobility; and 2) cardiometabolic risk, measured by galvanic skin response, pulse oximetry, and blood pressure to create a composite score based on autonomic nervous system and endothelial function. Participants completed baseline assessments that included serum levels of vitamin D, anthropometrics, body composition, dual task physical performance and cardiometabolic risk. Surveys to evaluate vitamin D intake, sun exposure, physical activity, and depressive symptoms were completed. Spearman’s correlations, independent t-tests, paired t-tests, repeated measures ANOVAs, and multiple logistic and linear regressions were used to examine the relationship of vitamin D insufficiency (25(OH)D /ml) and sufficiency (25(OH)D ≥30 ng/ml) with determinants of vitamin D status, dual task physical performance variables and cardiometabolic risk scores. Although the proportion of vitamin D insufficient individuals was lower when compared to the prevalance of the general United States elderly population, it was still common in healthy community-dwelling older adults living in Miami-Dade County, especially among Hispanics. Factors that affected skin synthesis (ethnicity, and sun exposure), and bioavailability/metabolism (obesity) were significant predictors of vitamin D status. Vitamin D insufficiency was not significantly correlated with worse dual task physical performance; however, cognitive performance was worse in the vitamin D insufficient group. Our results suggest a relationship of vitamin D insufficiency with executive dysfunction, and support an association with cardiometabolic risk using an innovative electro-sensor complex, possibly by modulating autonomic nervous system activity and vascular function, thus affecting cardiac performance.
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Background: High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults. Methods: Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA. Results: Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p < 0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p > 0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals. Conclusions: Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. Trial registration: This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.