442 research outputs found

    Simple de Sitter Solutions

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    We present a framework for de Sitter model building in type IIA string theory, illustrated with specific examples. We find metastable dS minima of the potential for moduli obtained from a compactification on a product of two Nil three-manifolds (which have negative scalar curvature) combined with orientifolds, branes, fractional Chern-Simons forms, and fluxes. As a discrete quantum number is taken large, the curvature, field strengths, inverse volume, and four dimensional string coupling become parametrically small, and the de Sitter Hubble scale can be tuned parametrically smaller than the scales of the moduli, KK, and winding mode masses. A subtle point in the construction is that although the curvature remains consistently weak, the circle fibers of the nilmanifolds become very small in this limit (though this is avoided in illustrative solutions at modest values of the parameters). In the simplest version of the construction, the heaviest moduli masses are parametrically of the same order as the lightest KK and winding masses. However, we provide a method for separating these marginally overlapping scales, and more generally the underlying supersymmetry of the model protects against large corrections to the low-energy moduli potential.Comment: 37 pages, harvmac big, 4 figures. v3: small correction

    Improvements in 25 Years of Implantable Cardioverter Defibrillator Therapy

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    In 1980, Dr. Michel Mirowski and his team inserted the first implantable cardioverter defibrillator (ICD) in a patient. Initially, ICD therapy was not widely accepted, and many physicians actually considered this therapy unethical. Large secondary and primary prevention trials, demonstrating a beneficial effect of ICD therapy in selected patients not only on arrhythmic death but also on all-cause mortality, stimulated a rapid growth in the number of implants and increased patient’s and physician’s acceptance. Improvements in size and weight, arrhythmia discrimination capabilities, battery technology, shock waveform and output, monitoring capabilities and defibrillator electrode technology eventually resulted in the current large number of yearly implants. Today, almost 40 years after the conception of the ICD and 25 years after the first human implant, ICD therapy is the treatment of choice for patients at risk for life-threatening arrhythmias either as secondary or primary prevention. Furthermore, with the more recent addition of resynchronisation therapy to standard ICD therapy, it became possible to treat selected patients with advanced symptoms of heart failure and to lower the risk of sudden death

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

    13C-assisted metabolic flux analysis to investigate heterotrophic and mixotrophic metabolism in Cupriavidus necator H16

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    Introduction. Cupriavidus necator H16 is a gram-negative bacterium, capable of lithoautotrophic growth by utilizing hydrogen as an energy source and fixing carbon dioxide (CO2) through Calvin-Benson-Bassham (CBB) cycle. The potential to utilize synthesis gas (Syngas) and the prospects of rerouting carbon from polyhydroxybutyrate synthesis to value-added compounds makes C. necator an excellent chassis for industrial application. Objectives. In the context of lack of sufficient quantitative information of the metabolic pathways and to advance in rational metabolic engineering for optimized product synthesis in C. necator H16, we carried out a metabolic flux analysis based on steady-state 13C-labelling. Methods. In this study, steady-state carbon labelling experiments, using either D-[1-13C]fructose or [1,2-13C]glycerol, were undertaken to investigate the carbon flux through the central carbon metabolism in C. necator H16 under heterotrophic and mixotrophic growth conditions, respectively. Results. We found that the CBB cycle is active even under heterotrophic condition, and growth is indeed mixotrophic. While Entner-Doudoroff (ED) pathway is shown to be the major route for sugar degradation, tricarboxylic acid (TCA) cycle is highly active in mixotrophic condition. Enhanced flux is observed in reductive pentose phosphate pathway (redPPP) under the mixotrophic condition to supplement the precursor requirement for CBB cycle. The flux distribution was compared to the mRNA abundance of genes encoding enzymes involved in key enzymatic reactions of the central carbon metabolism. Conclusion. This study leads the way to establishing 13C-based quantitative fluxomics for rational pathway engineering in C. necator H16

    Effective Rheology of Bubbles Moving in a Capillary Tube

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    We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur
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