2,470 research outputs found

    Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes

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    In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca2+ handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca2+ transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca2+ transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca2+ concentration ([Ca 2+]o), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca2+ level and peak intracellular Ca 2+ concentration ([Ca2+]i), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca2+]i transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca2+]i transient was not normalized by increasing [Ca2+]o to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca2+ release. Blockade of sarcoplasmic reticulum (SR) Ca2+-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca2+]o, which was slowed in IL-2-treated myocytes when [Ca2+]o was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca 2+]o. The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na+-Ca2+ exchange activity, but not to any change in L-type Ca2+ channels. © 2003 Elsevier Ltd. All rights reserved.postprin

    Dynamic Role-Based Access Control for Decentralized Applications

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    Access control management is an integral part of maintaining the security of an application. Although there has been significant work in the field of cloud access control mechanisms, however, with the advent of Distributed Ledger Technology (DLT), on-chain access control management frameworks hardly exist. Existing access control management mechanisms are tightly coupled with the business logic, resulting in governance issues, non-coherent with existing Identity Management Solutions, low security, and compromised usability. We propose a novel framework to implement dynamic role-based access control for decentralized applications (dApps). The framework allows for managing access control on a dApp, which is completely decoupled from the business application and integrates seamlessly with any dApps. The smart contract architecture allows for the independent management of business logic and execution of access control policies. It also facilitates secure, low cost, and a high degree of flexibility of access control management. The proposed framework promotes decentralized governance of access control policies and efficient smart contract upgrades. We also provide quantitative and qualitative metrics for the efficacy and efficiency of the framework. Any Turing complete smart contract programming language is an excellent fit to implement the framework. We expect this framework to benefit enterprise and non-enterprise dApps and provide greater access control flexibility and effective integration with traditional and state of the art identity management solutions.Comment: 6 pages, 3 figures, 1 tabl

    Algorithms for outerplanar graph roots and graph roots of pathwidth at most 2

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    Deciding whether a given graph has a square root is a classical problem that has been studied extensively both from graph theoretic and from algorithmic perspectives. The problem is NP-complete in general, and consequently substantial effort has been dedicated to deciding whether a given graph has a square root that belongs to a particular graph class. There are both polynomial-time solvable and NP-complete cases, depending on the graph class. We contribute with new results in this direction. Given an arbitrary input graph G, we give polynomial-time algorithms to decide whether G has an outerplanar square root, and whether G has a square root that is of pathwidth at most 2

    Healthcare costs associated with progressive diabetic retinopathy among National Health Insurance enrollees in Taiwan, 2000-2004

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    <p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy is one of the most common microvascular complications of diabetes and one of the major causes of adult visual impairment in national surveys in Taiwan. This study aimed to identify the healthcare costs of Taiwan's National Health Insurance program on behalf of diabetic patients with stable or progressive retinopathy.</p> <p>Methods</p> <p>A retrospective cohort study was conducted with 4,988 medication-using diabetic retinopathy subjects ≥ 40 years of age under National Health Insurance Program coverage between 2000 and 2004. Study cohort subjects were recorded as having diabetic retinopathy according to ICD-9-CM codes. States of diabetic retinopathy were strategically divided into stable and progressive categories according to subjects' conditions at follow-up in 2004. Expenditures were calculated and compared for the years 2000 and 2004.</p> <p>Results</p> <p>During the 4-year follow-up (2000 through 2004), 4,116 subjects (82.5%) of 4,988 diabetic subjects were in the stable category, and 872 (17.5%) were in the progressive category. Average costs of those in the normal category increased by US 48fromUS48 from US 1921 in 2000 to US 1969in2004(p=0.594),whereascostsforthoseprogressingfromnormaltononproliferativediabeticretinopathy(NPDR)orproliferativediabeticretinopathy(PDR)increasedbyUS1969 in 2004 (p = 0.594), whereas costs for those progressing from normal to non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) increased by US 1760, from US 1566in2000toUS1566 in 2000 to US 3326 in 2004 (p < 0.001). The PDR category had the highest average costs at US 3632in2000.TheNPDRtoPDRcategoryexperiencedthegreatestincreaseincostsatUS3632 in 2000. The NPDR-to-PDR category experienced the greatest increase in costs at US 3482, from US 2723in2000toUS2723 in 2000 to US 6204 in 2004 (p = 0.042), and the greatest percentage of increase at 2.3% (2.2% when adjusted by comparing to normal category).</p> <p>Conclusions</p> <p>This large-scale longitudinal study provides evidence that increased healthcare costs are associated with progressive diabetic retinopathy among diabetic NHI enrollees in Taiwan.</p

    Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

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    Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 μM CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFNγ through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPARγ receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2α, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2α induced by LPS/IFNγ. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the ‘oligoprotective' effects of CBD during inflammation

    A structural comparison of human serum transferrin and human lactoferrin

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    The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences

    Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

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    Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization
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