TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase

Tuberous sclerosis complex (TSC) 1 and TSC2 are thought to be involved in protein translational regulation and cell growth, and loss of their function is a cause of TSC and lymphangioleiomyomatosis (LAM). However, TSC1 also activates Rho and regulates cell adhesion. We found that TSC2 modulates actin dynamics and cell adhesion and the TSC1-binding domain (TSC2-HBD) is essential for this function of TSC2. Expression of TSC2 or TSC2-HBD in TSC2−/− cells promoted Rac1 activation, inhibition of Rho, stress fiber disassembly, and focal adhesion remodeling. The down-regulation of TSC1 with TSC1 siRNA in TSC2−/− cells activated Rac1 and induced loss of stress fibers. Our data indicate that TSC1 inhibits Rac1 and TSC2 blocks this activity of TSC1. Because TSC1 and TSC2 regulate Rho and Rac1, whose activities are interconnected in a reciprocal fashion, loss of either TSC1 or TSC2 function may result in the deregulation of cell motility and adhesion, which are associated with the pathobiology of TSC and LAM

Properties of Fibrous Scaffolds from Poly(3-Hydroxybutyrate), Polylactide, Polyglycolide and Poly(Lactide-Glycolide) with Various Methods of Electrostatic Forming

Методом электростатического формования с использованием одного или двух подающих капилляров на один собирающий коллектор получены нетканые изделия из растворов полимеров поли-3-гидроксибутирата, полилактида и полигликолида и сополимера поли(лактид-гликолида) и исследованы их характеристики. Показано, что при использовании двух подающих капилляров происходит пространственное распределение волокон, имеющих различную химическую структуру, по слоям нетканого изделия. Выявлено влияние состава используемых растворов полимеров на гидрофильно-гидрофобные свойства нетканых изделий вне зависимости от способа электростатического формованияFibrous scaffolds from polymer solutions of poly-3-hydroxybutyrate, polylactide and polyglycolide, and copolymer of poly(lactide-glycolide) were obtained using electrostatic shaping with one or two feeding capillaries on one collecting manifold and their characteristics were studied. The spatial distribution of fibers having different chemical structure in layers of fibrous scaffolds occurred when two feeding capillaries were used. The composition of polymer solutions influenced on the hydrophilic-hydrophobic properties of fibrous scaffolds, regardless of the method of electrostatic moldin

Rheology of Polyhydroxyalkanoate Solutions

Исследована реология растворов ПГА различного химического строения в хлороформе и дихлорметане. Показано, что динамическая вязкость растворов зависит от типа растворителя и типа ПГА, при этом исследуемые растворы полимеров при увеличении температуры ведут себя как ньютоновские жидкости. Повышение концентрации полимеров в растворе способствует увеличению динамической вязкости независимо от растворителя. Растворы ПГА по убыванию величины динамической вязкости можно расположить в следующем порядке: П(3ГБ) – П(3ГБ-3ГВ) – П(3ГБ-3ГГ) – П(3ГБ-4ГБ). При этом величина динамической вязкости растворов при одинаковых концентрации и температуре у растворов на основе хлороформа в 3–3,5 раза выше, чем у растворов на основе дихлорметана. Полученные значения динамической вязкости для разных типов полигидроксиалканоатов и двух основных типов растворителей свидетельствуют о зависимости исследуемого реологического параметра как от химического состава полимера, так и от характеристик (состав, температура, концентрация) используемого растворителяThe rheology of solutions of polyhydroxyalkanoates in chloroform and dichloromethane was studied. The dynamic viscosity of solutions depended on type of solvent and PHA. The polymer solutions with increase of temperature behave as Newtonian fluids. Dynamic viscosity was increasing with the concentration of polymer in solution, regardless of the solvent. Solutions of PHAs in descending order of magnitude of dynamic viscosity can be positioned in the following order: P(3HB) – P(3HB-3HV) – P(3GB-3HH) – P(3HB-4HB). The magnitude of the dynamic viscosity of solutions based on chloroform in 3-3,5 times higher than that of solutions based on dichloromethane at identical concentration and temperature. The obtained values of dynamic viscosity have demonstrated the dependence of rheological parameter on the chemical composition of the polymer, and the characteristics of solvent (composition, temperature, and concentration

THE THERMODYNAIC PROPERTIES OF MELTS OF THE SYSTEM MgO – Al2O3 – SiO2, MgO – CaF2 – SiO2, Al2O3 – CaF2 – SiO2

Abstract. Method of forecasting thermodynamic properties of melts from the liquidus coordinates ofphase diagram in the area of equilibrium of a solid component with a solution is presented. Gibbs mixingenergies in the binary boundary MgO – Al2O3, MgO – SiO2, MgO – CaF2, Al2O3 – SiO2, Al2O3 – CaF2,SiO2 – CaF2 systems are calculated by this method.Keywords: a activity, coordinates of liquidus, the diagrams of the state, the double and triple systems, theequalization of Hauffe-Wagner, the melts, the partial molar energy of Gibbs, the thermodynamics properties

Dynamical renormalization group methods in theory of eternal inflation

Dynamics of eternal inflation on the landscape admits description in terms of the Martin-Siggia-Rose (MSR) effective field theory that is in one-to-one correspondence with vacuum dynamics equations. On those sectors of the landscape, where transport properties of the probability measure for eternal inflation are important, renormalization group fixed points of the MSR effective action determine late time behavior of the probability measure. I argue that these RG fixed points may be relevant for the solution of the gauge invariance problem for eternal inflation.Comment: 11 pages; invited mini-review for Grav.Cos

Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction

Objective: Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF. Approach and Results: Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle. Conclusions: Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease

Design, Performance, and Calibration of CMS Hadron Endcap Calorimeters

Detailed measurements have been made with the CMS hadron calorimeter endcaps (HE) in response to beams of muons, electrons, and pions. Readout of HE with custom electronics and hybrid photodiodes (HPDs) shows no change of performance compared to readout with commercial electronics and photomultipliers. When combined with lead-tungstenate crystals, an energy resolution of 8\% is achieved with 300 GeV/c pions. A laser calibration system is used to set the timing and monitor operation of the complete electronics chain. Data taken with radioactive sources in comparison with test beam pions provides an absolute initial calibration of HE to approximately 4\% to 5\%

Frataxin deficiency promotes endothelial senescence in pulmonary hypertension

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls endothelial senescence. An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S–containing polymerases, promoting replication stress, DNA damage response, and senescence. This was also observed in stem cell–derived endothelial cells from Friedreich’s ataxia (FRDA), a genetic disease of FXN deficiency, ataxia, and cardiomyopathy, often with PH. In vivo, FXN deficiency–dependent senescence drove vessel inflammation, remodeling, and PH, whereas pharmacologic removal of senescent cells in Fxn-deficient rodents ameliorated PH. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis