975 research outputs found

    Phonon drag thermopower and weak localization

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    Previous experimental work on a two-dimensional (2D) electron gas in a Si-on-sapphire device led to the conclusion that both conductivity and phonon drag thermopower SgS^g are affected to the same relative extent by weak localization. The present paper presents further experimental and theoretical results on these transport coefficients for two very low mobility 2D electron gases in ή−\delta-doped GaAs/Gax_xAl1−x_{1-x}As quantum wells. The experiments were carried out in the temperature range 3-7K where phonon drag dominates the thermopower and, contrary to the previous work, the changes observed in the thermopower due to weak localization were found to be an order of magnitude less than those in the conductivity. A theoretical framework for phonon drag thermopower in 2D and 3D semiconductors is presented which accounts for this insensitivity of SgS^g to weak localization. It also provides transparent physical explanations of many previous experimental and theoretical results.Comment: 19 page Revtex file, 3 Postscript figur

    Ranking ligand affinity for the DNA minor groove by experiment and simulation

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    The structural and thermodynamic basis for the strength and selectivity of the interactions of minor-groove binders (MGBs) with DNA is not fully understood. In 2003 we reported the first example of a thiazole containing MGB that bound in a phase shifted pattern that spanned 6 base-pairs rather than the usual 4 (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and molecular dynamics, we have established that the flanking bases around the central 4 being read by the ligand have subtle effects on recognition. We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences

    The F# Computation Expression Zoo

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    Program logic can often be structured using abstract computation types such as monoids, monad transformers or applicative functors. Functional programmers use those abstractions directly while main-stream languages often integrate concrete instances as language features – e.g. generators in Python or asynchronous computations in C# 5.0. The question is, is there a sweet spot between convenient, hardwired language features, and an inconvenient but flexible libraries? F# computation expressions answer this question in the affirmative. Unlike the “do” notation in Haskell, computation expressions are not tied to a single kind of abstraction. They support a wide range of abstractions, depending on what operations are available. F# also provides greater syntactic flexibility leading to a more intuitive syntax, without resorting to full macro-based meta-programming. We present computation expressions in a principled way, developing a type system that captures the semantics of the calculus. We demonstrate how computation expressions structure well-known abstractions including monoidal list comprehensions, monadic parsers, applicative formlets and asynchronous sequences based on monad transformers

    Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

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    BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

    Compilation of extended recursion in call-by-value functional languages

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    This paper formalizes and proves correct a compilation scheme for mutually-recursive definitions in call-by-value functional languages. This scheme supports a wider range of recursive definitions than previous methods. We formalize our technique as a translation scheme to a lambda-calculus featuring in-place update of memory blocks, and prove the translation to be correct.Comment: 62 pages, uses pi

    A multi-model approach to stakeholder engagement in complex environmental problems

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    We describe the different types of models we used as part of an effort to inform policy-making aiming at the management of the Ningaloo coast in the Gascoyne region, Western Australia. This provides an overview of how these models interact, the different roles they cover, how they fit into a full decision making process and what we learnt about the stakeholders involved in our project via their use. When modelling is explicitly used to address socio-ecological issues, the key determinant of success is whether the models, their results and recommendations are taken up by stakeholders; such uptake in turn depends on addressing stakeholders’ concerns, on engaging them in the project, on ensuring they feel ownership of the decision process at large, and that they understand and trust the modelling effort. This observation has guided our approach and has resulted in treating ‘building a model’ as the catalyst, rather than the final aim, of the process. In other words, extensive interactions in order to introduce, showcase, discuss and tune the model used for final decision making have represented both a requirement and an opportunity to ensure (i) model relevance, (ii) its acceptance, (iii) that all information available in the stakeholder team was accounted for and (iv) that stakeholders holding different levels of understanding of modelling, what it does and what it can provide to decision-making could develop an informed opinion on its use. To fulfil these roles we developed five broad classes of models: conceptual models, toy-models, singlesystem models, shuttle-models and a full-system model. In conceptual models the main drivers of a system are highlighted for subsequent representation as components of the full-system model. This usually results in a diagram summarising our understanding of how the system works. In toy-models a problem is simplified in such a way that only a handful of components are included. The purpose of these models is mostly educational: we want to understand how each component affects the problem and in order to achieve this, we temporarily renounce a satisfactory understanding of the overall problem. In single-system models we include a fairly detailed representation of a single component of the system (in our case recreational fishing and tourism); these models can be used to introduce stakeholders to modelling, provide temporary results from the study of a single activity, which will feed into the development of the final full-system model, or address sector-specific issues. In shuttle-models, we include the minimum number of processes we believe are crucial for a basic understanding of the overall problem. We know these models are still too simple for full system description, but they provide a sufficient understanding to enable us to contemplate, build and use the more complex models needed for full problem description. The term ‘shuttle’ refers to taking us from a minimum to a full description of the problem, a journey which is necessary both to developers in model definition and parameterisation and to stakeholders in the interpretation of the final full-system model results. Finally, the full-system model includes all information collected through the project and addresses all scenarios of stakeholders concern, and whose definition has been greatly eased by use of the ‘simpler’ models. As an example, a conceptual model may identify fishing and tourism as the main drivers of a region; a toymodel may describe how catches affect fish stocks; a single-system model may include the effect of gear, regulations and other processes affecting recreational fishing; a shuttle-model may include a simplified representation of the interaction between fishing, tourism, and infrastructure development on the overall health of the local ecosystem; this will gradually ‘take’ us to comprehend the ‘full’ model which may include tourism pressure, fish market values, climate effect, larger food-webs, etc

    Comparison of Efficacy of Long-term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease

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    Background: The efficacy and benefits of telmisartan in cats with chronic kidney disease (CKD) have not previously been reported. Hypothesis: Long-term treatment of cats with CKD using telmisartan decreases urine protein-to-creatinine ratio (UP/C) similar to benazepril. Animals: Two-hundred and twenty-four client-owned adult cats with CKD. Methods: Prospective, multicenter, controlled, randomized, parallel group, blinded clinical trial with noninferiority design. Cats were allocated in a 1 : 1 ratio to either telmisartan (1 mg/kg; n = 112) or benazepril (0.5-1.0 mg/kg; n = 112) PO q24 h. The primary endpoint was prospectively defined as the change in proteinuria (benazepril:telmisartan) based on a log transformed weighted average of UP/C change from baseline (AUC 0?t/t) as a percentage compared using a confidence interval (CI) approach. Changes of UP/C from baseline were assessed on all study days and corrected for multiple comparisons. Results: Telmisartan proved noninferior to benazepril in controlling proteinuria (CI, À0.035 to 0.268). At Day 180, UP/C compared to baseline in the telmisartan group was significantly lower (À0.05 AE 0.31; P = .016), whereas in the benazepril group the change (À0.02 AE 0.48) was not statistically significant (P = .136). Similar results were obtained at all assessment points with significant decrease in UP/C occurring with telmisartan but not benazepril. Conclusion and Clinical Importance: Both telmisartan and benazepril were well tolerated and safe. Telmisartan proved to be noninferior to benazepril and significantly decreased proteinuria relative to baseline at all assessment points whereas benazepril did not
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