48 research outputs found

    Structural insights into crista junction formation by the Mic60-Mic19 complex

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    Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie–shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function

    Drug-drug interactions and QT prolongation as a commonly assessed cardiac effect - comprehensive overview of clinical trials

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    Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

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    <p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

    Thermal effects on the I-V characteristics of filamentary VCM based ReRAM-cells using a nanometer-sized heater

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    The physical principle of redox based resistive switching memory cells is based on ionic and electronic transport propertips. Both normally reveal a strong temperature dependence. A novel heating setup enables to study the influence of high temperatures on the switching mechanism of these memories. It consists of a 100 nm-wide Pt heating line and includes a Pt/Ta2O5/Ta-based ReRAM cell. It is heated up by inducing a current through the Pt line and employing the Joule heating effect. From this setup unique features are obtained by I-V measurements of the ReRAM cell. For instance, a negative differential resistance during the SET process is observed, which results from the circuitry of the heating structure. In case of the high resistive state, an increase in the current is observed at higher temperatures. In contrast, the current in the low resistive state is temperature independent. The increasing temperatures also lead to a reduction of the switching voltages of the SET and RESET events

    RBF Morphing Techniques for Simulation-based Design Optimization

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    Sieger D, Menzel S, Botsch M. RBF Morphing Techniques for Simulation-based Design Optimization. Engineering with Computers. 2014;30(2):161-174

    Implicit Boundary Control of Vector Field Based Shape Deformations

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    Abstract. We present a shape deformation approach which preserves volume, prevents self-intersections and allows for exact control of the deformation impact. Volume preservation and prevention of self-intersections are achieved by utilizing the method of Vector Field Based Shape Deformations. This method produces physically plausible deformations efficiently by integrating formally constructed divergence-free vector fields, where the region of influence is described by implicitly defined shapes. We introduce an implicit representation of deformation boundaries, which allows for an exact control of the deformation: By placing the boundaries directly on the shape surface, the user can specify precisely where the shape should be deformed and where not. The simple polygonal representation of the boundaries allows for a GPU implementation, which is able to deform high-resolution meshes in real-time.
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