Synthesis and Stoichiometry of MgB2

The system MgxB2 has been investigated to investigate possible nonstoichiometry in MgB2. When synthesized at 850oC, MgB2 is a line compound with a possible Mg vacancy content of about 1%. Small changes in lattice constants as a function of starting composition result from grain interaction stresses, whose character is different in the Mg-rich, near-stoichiometric, and Mg-deficient regimes. A small linear decrease of the superconducting transition temperature, Tc, in the Mg-rich regime results from accidental impurity doping.Comment: Accepted for publication in Physica C. 24 pages, 7 figure

A Dissipative-Particle-Dynamics Model for Simulating Dynamics of Charged Colloid

A mesoscopic colloid model is developed in which a spherical colloid is represented by many interacting sites on its surface. The hydrodynamic interactions with thermal fluctuations are taken accounts in full using Dissipative Particle Dynamics, and the electrostatic interactions are simulated using Particle-Particle-Particle Mesh method. This new model is applied to investigate the electrophoretic mobility of a charged colloid under an external electric field, and the influence of salt concentration and colloid charge are systematically studied. The simulation results show good agreement with predictions from the electrokinetic theory.Comment: 17 pages, 8 figures, submitted to the proceedings of High Performance Computing in Science & Engineering '1

Stimulation of cholesterol biosynthesis in mitochondrial complex I-deficiency lowers reductive stress and improves motor function and survival in mice

Contains fulltext : 229007.pdf (publisher's version ) (Open Access)The majority of cellular energy is produced by the mitochondrial oxidative phosphorylation (OXPHOS) system. Failure of the first OXPHOS enzyme complex, NADH:ubiquinone oxidoreductase or complex I (CI), is associated with multiple signs and symptoms presenting at variable ages of onset. There is no approved drug treatment yet to slow or reverse the progression of CI-deficient disorders. Here, we present a comprehensive human metabolic network model of genetically characterized CI-deficient patient-derived fibroblasts. Model calculations predicted that increased cholesterol production, export, and utilization can counterbalance the surplus of reducing equivalents in patient-derived fibroblasts, as these pathways consume considerable amounts of NAD(P)H. We show that fibrates attenuated increased NAD(P)H levels and improved CI-deficient fibroblast growth by stimulating the production of cholesterol via enhancement of its cellular efflux. In CI-deficient (Ndufs4(-/-)) mice, fibrate treatment resulted in prolonged survival and improved motor function, which was accompanied by an increased cholesterol efflux from peritoneal macrophages. Our results shine a new light on the use of compensatory biological pathways in mitochondrial dysfunction which may lead to novel therapeutic interventions for mitochondrial diseases for which currently no cure exists

A Self-Policing Policy Language

Abstract. Formal policies allow the non-ambiguous definition of sit-uations in which usage of certain entities are allowed, and enable the automatic evaluation whether a situation is compliant. This is useful for example in applications using data provided via standardized interfaces. The low technical barriers of integrating such data sources is in contrast to the manual evaluation of natural language policies as they currently exist. Usage situations can themselves be regulated by policies, which can be restricted by the policy of a used entity. Consider for example the Google Maps API, which requires that applications using the API must be available without a fee, i.e. the application’s policy must not require a payment. In this paper we present a policy language that can express such constraints on other policies, i.e. a self-policing policy language. We validate our approach by realizing a use case scenario, using a policy engine developed for our language.

Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition

Contains fulltext : 154004.pdf (publisher's version ) (Closed access)Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of mitochondrial complex III (CIII) activity, up to 84% inhibition. The lactones were in general three times more potent inducers of cytotoxicity than their corresponding acid forms. The Qo binding site of CIII was identified as off-target of the statin lactones. These findings could be confirmed in muscle tissue of patients suffering from statin-induced myopathies, in which CIII enzyme activity was reduced by 18%. Respiratory inhibition in C2C12 myoblasts could be attenuated by convergent electron flow into CIII, restoring respiration up to 89% of control. In conclusion, CIII inhibition was identified as a potential off-target mechanism associated with statin-induced myopathies