938 research outputs found

    The Achilles tendon myth and true facts

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    Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRĪ².

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    Mechanisms underlying the development of idiopathic dilated cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor-Ī² (ESRRĪ²), a member of the nuclear receptor family of transcription factors, as highly expressed in murine hearts and other highly oxidative striated muscle beds. Mice bearing cardiac-specific deletion of ESRRĪ² (MHC-ERRB KO) develop DCM and sudden death at ~10 mo of age. Isolated adult cardiomyocytes from the MHC-ERRB KO mice showed an increase in calcium sensitivity and impaired cardiomyocyte contractility, which preceded echocardiographic cardiac remodeling and dysfunction by several months. Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRĪ² protein is absent from the nucleus of cardiomyocytes from patients with DCM but not other forms of cardiomyopathy (ischemic, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy). Taken together these observations suggest that ESRRĪ² is a critical component in the onset of DCM by affecting contractility and calcium balance.NEW & NOTEWORTHY Estrogen-related receptor-Ī² (ESRRĪ²) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRĪ² is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRĪ² in the pathogenesis of DCM in humans

    Ductile Metallic Glasses in Supercooled Martensitic Alloys

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    We report ductile bulk metallic glasses based on martensitic alloys. The slowly cooled specimens contain a mixture of parent 'austenite' and martensite phase. The slightly faster cooled bulk metallic glasses with 2-5 nm sized 'austenite'-like crystalline cluster reveal high strength and large ductility (16%). Shear bands propagate in a slither mode in this spatially inhomogeneous glassy structure and undergo considerable 'thickening' from 5-25 nm. A 'stress induced displacive transformation' is proposed to be responsible for both plasticity and work-hardening-like behavior of these 'M-Glasses'

    Towards the Formalization of Fractional Calculus in Higher-Order Logic

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    Fractional calculus is a generalization of classical theories of integration and differentiation to arbitrary order (i.e., real or complex numbers). In the last two decades, this new mathematical modeling approach has been widely used to analyze a wide class of physical systems in various fields of science and engineering. In this paper, we describe an ongoing project which aims at formalizing the basic theories of fractional calculus in the HOL Light theorem prover. Mainly, we present the motivation and application of such formalization efforts, a roadmap to achieve our goals, current status of the project and future milestones.Comment: 9 page

    Evidence for a fractional quantum Hall state with anisotropic longitudinal transport

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    At high magnetic fields, where the Fermi level lies in the N=0 lowest Landau level (LL), a clean two-dimensional electron system (2DES) exhibits numerous incompressible liquid phases which display the fractional quantized Hall effect (FQHE) (Das Sarma and Pinczuk, 1997). These liquid phases do not break rotational symmetry, exhibiting resistivities which are isotropic in the plane. In contrast, at lower fields, when the Fermi level lies in the Nā‰„2N\ge2 third and several higher LLs, the 2DES displays a distinctly different class of collective states. In particular, near half filling of these high LLs the 2DES exhibits a strongly anisotropic longitudinal resistance at low temperatures (Lilly et al., 1999; Du et al., 1999). These "stripe" phases, which do not exhibit the quantized Hall effect, resemble nematic liquid crystals, possessing broken rotational symmetry and orientational order (Koulakov et al., 1996; Fogler et al., 1996; Moessner and Chalker, 1996; Fradkin and Kivelson, 1999; Fradkin et al, 2010). Here we report a surprising new observation: An electronic configuration in the N=1 second LL whose resistivity tensor simultaneously displays a robust fractionally quantized Hall plateau and a strongly anisotropic longitudinal resistance resembling that of the stripe phases.Comment: Nature Physics, (2011

    Child and parental sleep in young children with epilepsy: A population-based case-control study

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    Objective: To determine the prevalence of parent-reported sleep problems in young children with epilepsy and their parents, and to compare findings with those in a non-epilepsy-related neurodisability (neurodevelopmental/neurological difficulties) group. Method: Parents of young children (1-7Ā years) with epilepsy (nĀ =Ā 48 [91% ascertainment]) completed the Child Sleep Habits Questionnaire (CSHQ). Parents (mothers and fathers) also completed the Pittsburgh Sleep Quality Index (PSQI) and the Iowa Fatigue Scale (IFS) in relation to their own functioning. The responses of parents of children with epilepsy were compared with parents of developmental-, age-, and gender-matched children with nonepilepsy-related neurodisability (nĀ =Ā 48). Results: There was not a significant difference in the proportion of children with epilepsy and the children with neurodisability scoring in the at-risk range on the CSHQ (81% vs. 71% respectively) (pĀ =Ā 0.232). 62% of mothers and 44% of fathers of children with epilepsy had 'poor quality sleep' on the PSQI; there was not a significant difference between mothers of children with epilepsy and those of children with neurodisability (pĀ =Ā 0.526) or IFS (pĀ =Ā 0.245) total scores. However, mothers of children with epilepsy had significantly more difficulties on the productivity subscale of the IFS (pĀ =Ā 0.004). There were no significant differences between fathers' scores on either measure. In the epilepsy group, child behavioral problems (pĀ =Ā 0.001) were independently associated with child sleep difficulties and maternal mental health problems were associated with parental sleep difficulties (pĀ =Ā 0.04) and fatigue (pĀ =Ā 0.018). Significance: Young children with epilepsy and their parents have a high rate of sleep difficulties. There is a need to develop effective interventions for this population, taking into consideration of the role of child behavioral problems and parental mental health difficulties

    MicroRNAs in pulmonary arterial remodeling

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    Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH
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