34 research outputs found

    Collapsing three-manifolds under a lower curvature bound

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    The purpose of this paper is to completely characterize the topology of three-dimensional Riemannian manifolds with a uniform lower bound of sectional curvature which converges to a metric space of lower dimension

    Causes of Abnormal Ca2+ Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca2+ and Action Potential Imaging at Cellular Level

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    BACKGROUND: Abnormal Ca(2+) transients are often observed in heart muscles under a variety of pathophysiological conditions including ventricular tachycardia. To clarify whether these abnormal Ca(2+) transients can be attributed to abnormal action potential generation or abnormal Ca(2+) handling/excitation-contraction (EC) coupling, we developed a procedure to determine Ca(2+) and action potential signals at the cellular level in isolated heart tissues. METHODOLOGY/PRINCIPAL FINDINGS: After loading ventricular papillary muscle with rhod-2 and di-4-ANEPPS, mono-wavelength fluorescence images from rhod-2 and ratiometric images of two wavelengths of emission from di-4-ANEPPS were sequentially obtained. To mimic the ventricular tachycardia, the ventricular muscles were field-stimulated in non-flowing Krebs solution which elicited abnormal Ca(2+) transients. For the failed and alternating Ca(2+) transient generation, there were two types of causes, i.e., failed or abnormal action potential generation and abnormal EC coupling. In cells showing delayed initiation of Ca(2+) transients with field stimulation, action potential onset was delayed and the rate of rise was slower than in healthy cells. Similar delayed onset was also observed in the presence of heptanol, an inhibitor of gap junction channels but having a non-specific channel blocking effect. A Na(+) channel blocker, on the other hand, reduced the rate of rise of the action potentials but did not result in desynchronization of the action potentials. The delayed onset of action potentials can be explained primarily by impaired gap junctions and partly by Na(+) channel inactivation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that there are multiple patterns for the causes of abnormal Ca(2+) signals and that our methods are useful for investigating the physiology and pathophysiology of heart muscle

    Multistep Ion Channel Remodeling and Lethal Arrhythmia Precede Heart Failure in a Mouse Model of Inherited Dilated Cardiomyopathy

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    Background: Patients with inherited dilated cardiomyopathy (DCM) frequently die with severe heart failure (HF) or die suddenly with arrhythmias, although these symptoms are not always observed at birth. It remains unclear how and when HF and arrhythmogenic changes develop in these DCM mutation carriers. In order to address this issue, properties of the myocardium and underlying gene expressions were studied using a knock-in mouse model of human inherited DCM caused by a deletion mutation DK210 in cardiac troponinT. Methodology/Principal Findings: By 1 month, DCM mice had already enlarged hearts, but showed no symptoms of HF and a much lower mortality than at 2 months or later. At around 2 months, some would die suddenly with no clear symptoms of HF, whereas at 3 months, many of the survivors showed evident symptoms of HF. In isolated left ventricular myocardium (LV) from 2 month-mice, spontaneous activity frequently occurred and action potential duration (APD) was prolonged. Transient outward (Ito) and ultrarapid delayed rectifier K + (IKur) currents were significantly reduced in DCM myocytes. Correspondingly, down-regulation of Kv4.2, Kv1.5 and KChIP2 was evident in mRNA and protein levels. In LVs at 3-months, more frequent spontaneous activity, greater prolongation of APD and further down-regulation in above K + channels were observed. At 1 month, in contrast, infrequent spontaneous activity and down-regulation of Kv4.2, but not Kv1.5 or KChIP2, were observed

    Clustering Stream Data by Regression Analysis

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    In data clustering, many approaches have been proposed such as K-means method and hierarchical method. One of the problems is that the results depend heavily on initial values and criterion to combine clusters. In this investigation, we propose a new method to cluster stream data while avoiding this deficiency. Here we assume there exists aspects of local regression in data. Then we develop our theory to combine clusters using values by regression analysis as criterion and to adapt to stream data. We examine experiments and show how well the theory works

    Two-dimensional metric spaces with curvature bounded above I

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    We determine the local geometric structure of two-dimensional metric spaces with curvature bounded above as the union of finitely many properly embedded/branched immersed Lipschitz disks. As a result, we obtain a graph structure of the topological singular point set of such a singular surface.Comment: 73 pages, 12figures, Mainly Section 3 is modified, and Section 7 is adde

    Hierarchical Summarizing and Evaluating for Web Pages

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    Abstract. In this investigation we propose a novel summarization method of Web pages using hierarchical expression. We discuss close relationship between summarization and hierarchical clustering to obtain the results, and we examine how to evaluate hierarchical summarization based on both correlation and structural aspects. We describe some experimental results using NTCIR Web documents to examine our method.
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