H NMR Studies of Eukaryotic Cytochrome c

H NMR resonance assignments in the spectra of horse, tuna, Neurmpora crassa and Candida krusei cyto-chromes c are described. Assignments have been made using NMR double-resonance techniques in conjunction with electron-exchange experiments, spectral comparison of related proteins, and consideration of the X-ray structure of tuna cytochrome c. Resonances arising from 11 residues of horse cytochrome c have been assigned

Ideas and agency in immigration policy: a discursive institutionalist approach

Political science literature tends to depict the role of ideas in policy in two distinct ways: ideas are seen as strategic tools mobilised by agents to achieve pre-given preferences; or as structures imposing constraints on what is considered legitimate or feasible. Discursive institutionalism seeks to combine these insights, suggesting that while actors are indeed constrained by deeply entrenched ideas, they nonetheless enjoy some autonomy in selecting and combining ideas. This article seeks to further develop this approach in two ways. First, we identify three discursive strategies through which policy actors can selectively mobilise ideas: they may foreground one level over others; exploit ambivalence in public philosophies; or link programme ideas over time by invoking ‘policy legacies’. Second, we elucidate the mechanisms through which such strategic selections can in turn modify existing public philosophies and programme ideas, thereby influencing policy change. We examine these claims by comparing discourse on immigration policy liberalisation in Germany and the UK between 2000-2008. We find evidence of all three discursive strategies. Moreover, we show how in the German case these discursive representations led to longer-term adjustments in underlying programme ideas and public philosophies on immigration

RAS gene polymorphisms, classical risk factors and the advent of coronary artery disease in the Portuguese population

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms within the renin-angiotensin system cluster of genes have been associated with the advent of coronary artery disease (CAD) or related pathologies. We investigated the distribution of 5 of these polymorphisms in order to find any association with CAD development and distinguish if any of the biochemical and behavioural factors interact with genetic polymorphisms in the advent of the disease.</p> <p>Methods</p> <p><it>ACE </it>I/D (rs4340), <it>ACE </it>A11860G (rs4343), <it>AT1R </it>A1166C (rs5186), <it>AGT </it>T174M (rs4762) and <it>AGT </it>M235T (rs699) gene polymorphisms were PCR-RFLP analysed in 298 CAD patients and 510 controls from Portugal. Several biochemical and behavioural markers were obtained.</p> <p>Results</p> <p><it>ACE </it>I/D DD and <it>ACE</it>11860 GG genotypes are risk factors for CAD in this population. The simultaneous presence of <it>ACE </it>I/D I and <it>ACE</it>11860 A alleles corresponds to a significant trend towards a decrease in CAD incidence. We found several synergistic effects between the studied polymorphisms and classical risk factors such as hypertension, obesity, diabetes and dyslipidaemia: the presence of the DD genotype of <it>ACE </it>I/D (and also <it>ACE</it>11860 GG) increases the odds of developing CAD when associated to each one of these classical risk factors, particularly when considering the male and early onset CAD subgroup analysis; <it>AGT</it>235 TT also increases the CAD risk in the presence of hypertension and dyslipidaemia, and <it>AT1R</it>1166 interacts positively with hypertension, smoking and obesity.</p> <p>Conclusion</p> <p><it>ACE </it>polymorphisms were shown to play a major role in individual susceptibility to develop CAD. There is also a clear interaction between RAS predisposing genes and some biochemical/environmental risk factors in CAD onset, demonstrating a significant enhancement of classical markers particularly by <it>ACE </it>I/D and <it>ACE</it>11860.</p

In situ multiple sulfur isotope analysis by SIMS of pyrite, chalcopyrite, pyrrhotite, and pentlandite to refine magmatic ore genetic models

With growing interest in the application of in situ multiple sulfur isotope analysis to a variety of mineral systems, we report here the development of a suite of sulfur isotope standards for distribution relevant to magmatic, magmatic-hydrothermal, and hydrothermal ore systems. These materials include Sierra pyrite (FeS2), Nifty-b chalcopyrite (CuFeS2), Alexo pyrrhotite (Fe(1 −x)S), and VMSO pentlandite ((Fe,Ni)9S8) that have been chemically characterized by electron microprobe analysis, isotopically characterized for δ33S, δ34S, and δ36S by fluorination gas-source mass spectrometry, and tested for homogeneity at the micro-scale by secondary ion mass spectrometry. Beam-sample interaction as a function of crystallographic orientation is determined to have no effect on δ34S and Δ33S isotopic measurements of pentlandite. These new findings provided the basis for a case study on the genesis of the Long-Victor nickel-sulfide deposit located in the world class Kambalda nickel camp in the southern Kalgoorlie Terrane of Western Australia. Results demonstrate that precise multiple sulfur isotope analyses from magmatic pentlandite, pyrrhotite and chalcopyrite can better constrain genetic models related to ore-forming processes. Data indicate that pentlandite, pyrrhotite and chalcopyrite are in isotopic equilibrium and display similar Δ33S values + 0.2‰.This isotopic equilibrium unequivocally fingerprints the isotopic signature of the magmatic assemblage. The three sulfide phases show slightly variable δ34S values (δ34Schalcopyrite = 2.9 ± 0.3‰, δ34Spentlandite = 3.1 ± 0.2‰, and δ34Spyrrhotite = 3.9 ± 0.5‰), which are indicative of natural fractionation. Careful in situ multiple sulfur isotope analysis of multiple sulfide phases is able to capture the subtle isotopic variability of the magmatic sulfide assemblage, which may help resolve the nature of the ore-forming process. Hence, this SIMS-based approach discriminates the magmatic sulfur isotope signature from that recorded in metamorphic- and alteration-related sulfides, which may not be resolved during bulk rock fluorination analysis. The results indicate that, unlike the giant dunite-hosted komatiite systems that thermo-mechanically assimilated volcanogenic massive sulfides proximal to vents and display negative Δ33S values, the Kambalda ores formed in relatively distal environments assimilating abyssal sulfidic shales

A randomized controlled trial to prevent glycemic relapse in longitudinal diabetes care: Study protocol (NCT00362193)

BACKGROUND: Diabetes is a common disease with self-management a key aspect of care. Large prospective trials have shown that maintaining glycated hemoglobin less than 7% greatly reduces complications but translating this level of control into everyday clinical practice can be difficult. Intensive improvement programs are successful in attaining control in patients with type 2 diabetes, however, many patients experience glycemic relapse once returned to routine care. This early relapse is, in part, due to decreased adherence in self-management behaviors. OBJECTIVE: This paper describes the design of the Glycemic Relapse Prevention study. The purpose of this study is to determine the optimal frequency of maintenance intervention needed to prevent glycemic relapse. The primary endpoint is glycemic relapse, which is defined as glycated hemoglobin greater than 8% and an increase of 1% from baseline. METHODS: The intervention consists of telephonic contact by a nurse practitioner with a referral to a dietitian if indicated. This intervention was designed to provide early identification of self-care problems, understanding the rationale behind the self-care lapse and problem solve to find a negotiated solution. A total of 164 patients were randomized to routine care (least intensive), routine care with phone contact every three months (moderate intensity) or routine care with phone contact every month (most intensive). CONCLUSION: The baseline patient characteristics are similar across the treatment arms. Intervention fidelity analysis showed excellent reproducibility. This study will provide insight into the important but poorly understood area of glycemic relapse prevention

Using observational data to emulate a randomized trial of dynamic treatment switching strategies

BACKGROUND: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).METHODS: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.RESULTS: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.CONCLUSIONS: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses

Effectiveness of performance appraisal:an integrated framework

Based on a robust analysis of the existing literature on performance appraisal (PA), this paper makes a case for an integrated framework of effectiveness of performance appraisal (EPA). To achieve this, it draws on the expanded view of measurement criteria of EPA, i.e. purposefulness, fairness and accuracy, and identifies their relationships with ratee reactions. The analysis reveals that the expanded view of purposefulness includes more theoretical anchors for the purposes of PA and relates to various aspects of human resource functions, e.g. feedback and goal orientation. The expansion in the PA fairness criterion suggests certain newly established nomological networks, which were ignored in the past, e.g. the relationship between distributive fairness and organization-referenced outcomes. Further, refinements in PA accuracy reveal a more comprehensive categorization of rating biases. Coherence among measurement criteria has resulted in a ratee reactions-based integrated framework, which should be useful for both researchers and practitioners