1,721,538 research outputs found
Vitamin D and Intimal Hyperplasia in Coronary Artery
No full textAtherosclerosis is the leading cause of disability and death worldwide. The whole spectrum of atherosclerosis develops through series of highly specific cellular and molecular events that lead to the formation and progression of atherosclerotic plaque and finally its complications. Coronary artery disease (CAD), most common among cardiovascular diseases, is characterized by insufficient oxygen supply to the heart muscle which primarily occurs due to coronary artery atherosclerosis. During last three decades, percutaneous coronary intervention has become the major strategy to treat coronary artery disease but, restenosis (re-narrowing of the vessel after an interventional procedure) is the major limitation of this approach. Although, the rate of restenosis is significantly reduced by stent implantation, especially drug eluting stents, there is a concern that drug eluting stents might increase the rate of in-stent thrombosis, a potentially fatal complication. Neointimal hyperplasia, a cell proliferation and differentiation process, is the predominant mechanism in the development of in-stent restenosis. |Vitamin D is a secosteroid which functions through vitamin D receptor (VDR), a transcription factor, and directly or indirectly controls more than 200 heterogeneous genes including genes that regulate cellular differentiation, proliferation, and angiogenesis. Vitamin D receptors are distributed in a variety of tissues including, vascular smooth muscle cells (VSMCs), cardiomyocytes, endothelium, and cells of immune system. The growth suppressant and immunomodulatory effects of calcitriol are of great interest because of their potential use in the management of disorders, including post-interventional restenosis, atherosclerosis and post-transplant vasculopathy in which the underlying pathological mechanisms are uncontrolled cell growth and remodeling in the vascular wall. |The central hypothesis is that calcitriol inhibits proliferation, migration and phenotypic modulation of porcine coronary artery smooth muscle cells (PCASMCs) through VDR and that vitamin D supplementation reduces the incidence of restenosis by decreasing neointimal hyperplasia after coronary artery intervention in coronary artery disease. |In this study, the effect of calcitriol stimulation on the expression of VDR and vitamin D metabolizing enzymes including CYP24A1 and CYP27B1 was examined in cultured PCASMCs. Further, the effect of calcitriol stimulation on cell proliferation, migration, phenotypic modulation and apoptosis was investigated in cultured PCASMCs. Next, expression of TNF-α and VDR in the neointimal lesions in postintervention hypercholesterolemic swine coronary arteries were examined. Finally, the effect of vitamin D deficiency and vitamin D supplementation on the development of post-intervention restenosis was investigated in a well-controlled atherosclerotic swine model of coronary restenosis. |PCASMCs express VDR and vitamin D metabolizing enzymes. Treatment of PCASMCs with calcitriol significantly increased the mRNA and protein expression of VDR and CYP24A1 in a dose-dependent manner while expression of CYP27B1 was significantly decreased as compared to control. Calcitriol treatment significantly decreased serum-induced proliferation of PCASMCs and has no effect on the apoptosis in these cells. Calcitriol also decreased PDGF-BB-induced proliferation, migration and phenotypic modulation in PCASMCs. In vivo morphometric analysis of tissues revealed that coronary intervention in hypercholesterolemic Yucatan miniature swine induced significant restenosis. Histological evaluation of post-intervention swine coronary arteries showed expression of smooth muscle α-actin and significantly increased expression of TNF-α in neointimal lesions. Interestingly, there was significantly decreased expression of VDR in PCASMCs of neointimal region compared to normal media. Vitamin D deficiency increased the magnitude of restenosis and PCNA-positive cells in neointimal tissue of post-intervention coronary arteries, which is suppressed by supplementation of vitamin D post-intervention. Vitamin D supplementation significantly downregulated the levels of TNF-α and IFN-γ, upregulated the levels of IL-10, and had no effect on serum IL-6 levels. |These data suggest that calcitriol inhibits proliferation in PCASMCs through VDR and there is significant downregulation of VDR in proliferating PCASMCs of neointimal lesions. Thus, downregulation of VDR in VSMCs of post-interventional arteries due to high concentration of TNF-α could be a potentially contributing factor for uncontrolled growth of VSMCs in injured arteries leading to neointimal hyperplasia and restenosis. Expression of VDR is increased by VDR ligands and growth inhibitory and immunomodulatory actions of VDR may likely be enhanced in the presence of vitamin D ligands. Therefore, anti-proliferative effect of VDR ligands can prevent/decrease VSMC proliferation after mechanical injury to the artery and attenuate restenosis. This could be an inexpensive and safe therapeutic approach for reduction in cardiovascular disease burden.ProQuest Traditional Publishing Option203 pages, 3 unnumbered page
Software watermarking resilient to debugging attacks
No full textIn 2006, Gaurav Gupta and Josef Pieprzyk presented an attack on the branch-based software watermarking scheme proposed by Ginger Myles and Hongxia Jin in 2005. The software watermarking model is based on replacing jump instructions or unconditional branch statements (UBS) by calls to a fingerprint branch function (FBF) that computes the correct target address of the UBS as a function of the generated fingerprint and integrity check. If the program is tampered with, the fingerprint and/or integrity checks change and the target address is not computed correctly. Gupta and Pieprzyk's attack uses debugger capabilities such as register and address lookup and breakpoints to minimize the requirement to manually inspect the software. Using these resources, the FBF and calls to the same is identified, correct displacement values are generated and calls to FBF are replaced by the original UBS transferring control of the attack to the correct target instruction. In this paper, we propose a watermarking model that provides security against such debugging attacks. Two primary measures taken are shifting the stack pointer modification operation from the FBF to the individual UBSs, and coding the stack pointer modification in the same language as that of the rest of the code rather than assembly language to avoid conspicuous contents. The manual component complexity increases from O(1) in the previous scheme to O(n) in our proposed scheme
Reversible and semi-blind relational database watermarking
No full textDatabase watermarking has received significant research attention in the current decade. Although, almost all watermarking models have been either irreversible (the original relation cannot be restored from the watermarked relation) and/or non-blind (requiring original relation to detect the watermark in watermarked relation). This model has several disadvantages over reversible and blind watermarking (requiring only watermarked relation and secret key from which the watermark is detected and original relation is restored) including inability to identify rightful owner in case of successful secondary watermarking, inability to revert the relation to original data set (required in high precision industries) and requirement to store unmarked relation at a secure secondary storage. To overcome these problems, we propose a watermarking scheme that is reversible as well as blind. We utilize difference expansion on integers to achieve reversibility. The major advantages provided by our scheme are reversibility to high quality original data set, rightful owner identification, resistance against secondary watermarking attacks, and no need to store original database at a secure secondary storage
Socio-technological phishing prevention\ud
No full textPhishing is deceptive collection of personal information leading to embezzlement, identity theft, and so on. Preventive and combative measures have been taken by banking institutions, software vendors, and network authorities to fight phishing. At the forefront of this resilience are consortiums such as APWG (Anti-Phishing Working Group) and PhishTank, the latter being a collaborative platform where everyone can submit potentially phishing web-pages and classify web-pages as either phish or genuine. PhishTank also has an API that the browsers use to notify users when she tries to load a phishing page. There are some organizations and individuals who are very active and highly accurate in classifying web-pages on PhishTank. In this paper, we propose a defense model that uses these experts to fight phishing
Increased Expression of Importin α3 (KPNA4) and Decreased VDR in the Lung of OVA-Sensitized and Challenged Mice
No full textRationale: The nuclear import of p65 and p50 subunits of activated NF-кB is dependent on importin α3 (KPNA4) and importin α4 (KPNA3). We previously reported that pro-inflammatory cytokines increase the expression of importin α3 and decrease the expression of VDR in Human bronchial smooth muscle cells (HBSMCs). Our results also demonstrate that co- stimulation with calcitriol attenuated the increased expression of importin α3 thereby leading to decrease in the activated NF-κB in the nucleus through a mechanism mediated by VDR. In this study, we evaluated the mRNA and protein expression of VDR and importin α3 in the lungs of OVA-sensitized and challenged mice as compared to control mice.
Methods: BALB/c mice were sensitized and challenged with OVA and AHR to methacholine was established. Protein and mRNA expressions of VDR, and importin α3 in whole lung tissue were analyzed using immunofluorescence and qPCR, respectively. Results: There was significantly higher mRNA and protein expression of importin α3 and decreased expression of VDR in the lung tissue of OVA-sensitized and challenged mice as compared to PBS mice.
Conclusions: The decrease in the expression of VDR in OVA sensitized mice suggest the role of vitamin D in allergic asthma. An increase in importin α3 is likely due to a decrease in VDR expression in lungs of OVA-sensitized mice. We, therefore, conclude that Vitamin D supplementation in asthmatic mice can decrease the AHR and the expression of importin α3 and thus inflammation. Thus, Vitamin D might be helpful in alleviating allergic airway inflammation and airway hyperresponsiveness in allergic asthma
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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