143 research outputs found

    Two-colorings with many monochromatic cliques in both colors

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    Color the edges of the n-vertex complete graph in red and blue, and suppose that red k-cliques are fewer than blue k-cliques. We show that the number of red k-cliques is always less than cknk, where ck∈(0, 1) is the unique root of the equation zk=(1-z)k+kz(1-z)k-1. On the other hand, we construct a coloring in which there are at least cknk-O(nk-1) red k-cliques and at least the same number of blue k-cliques. © 2013 Elsevier Inc

    Intersection problems in the q-ary cube

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    We propose new intersection problems in the q-ary n-dimensional hypercube. The answers to the problems include the Katona's t-intersection theorem and the Erdos-Ko-Rado theorem as special cases. We solve some of the basic cases of our problems, and for example we get an Erdos-Ko-Rado type result for t-intersecting k-uniform families of multisets with bounded repetitions. Another case is obtained by counting the number of lattice points in a polytope having an intersection property. © 2016 Elsevier Inc

    Uniform eventown problems

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    Let n≥. k. l≥. 2 be integers, and let F be a family of k-element subsets of an n-element set. Suppose that l divides the size of the intersection of any two (not necessarily distinct) members in F. We prove that the size of F is at most ([n/l][k/l]) provided n is sufficiently large for fixed k and l

    Multiply union families in Nn

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    Let An Nn be an r-wise s-union family, that is, a family of sequences with n components of non-negative integers such that for any r sequences in A the total sum of the maximum of each component in those sequences is at most s. We determine the maximum size of A and its unique extremal configuration provided (i) n is sufficiently large for fixed r and s, or (ii) n = r + 1. © 2016 Elsevier Ltd

    Discovery of a novel biomarker in the urine in women with endometriosis

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    Objective: To investigate whether proteins secreted in urine differ between women with and without endometriosis. Design: Laboratory study using human urine. Setting: University-based laboratory. Patient(s): Women with and without endometriosis undergoing laparoscopy, hysteroscopy and curettage. Intervention(s): Urine collection from women with and without endometriosis. Main Outcome Measure(s): Proteomic techniques and mass spectrometry to identify proteins secreted in the urine of women with and without endometriosis. Result(s): On average, 133 proteins were significantly different between women with and without endometriosis. Cytokeratin-19 was highly up-regulated in the urine of women with endometriosis. Conclusion(s): Cytokeratin-19 may be a valuable urinary biomarker for endometriosis. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc

    Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease

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    <p>Abstract</p> <p>Background</p> <p>In a genome-wide association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (<it>PNPLA3</it>) was strongly associated with increased liver fat content. We investigated whether this SNP is associated with the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) in the Japanese population.</p> <p>Methods</p> <p>SNP rs738409 was genotyped by the Taqman assay in 253 patients with NAFLD (189 with nonalcoholic steatohepatitis [NASH] and 64 with simple steatosis) and 578 control subjects. All patients with NAFLD underwent liver biopsy. Control subjects had no metabolic disorders. For a case-control study, the <it>χ</it><sup>2</sup>-test (additive model) was performed. Odds ratios (ORs) were adjusted for age, gender, and body mass index (BMI) by using multiple logistic regression analysis with genotypes (additive model), age, gender, and BMI as the independent variables. Multiple linear regression analysis was performed to test the independent effect of risk allele on clinical parameters while considering the effects of other variables (age, gender, and BMI), which were assumed to be independent of the effect of the SNP.</p> <p>Results</p> <p>The risk allele (G-allele) frequency of rs738409 was 0.44 in the control subjects and 0.60 in patients with NAFLD; this shows a strong association with NAFLD (additive model, <it>P </it>= 9.4 × 10<sup>-10</sup>). The OR (95% confidence interval) adjusted for age, gender, and BMI was 1.73 (1.25-2.38). Multiple linear regression analysis indicated that the G-allele of rs738409 was significantly associated with increases in aspartate transaminase (AST) (<it>P </it>= 0.00013), alanine transaminase (ALT) (<it>P </it>= 9.1 × 10<sup>-6</sup>), and ferritin levels (<it>P </it>= 0.014), and the fibrosis stage (<it>P </it>= 0.011) in the patients with NAFLD, even after adjustment for age, gender, and BMI. The steatosis grade was not associated with rs738409.</p> <p>Conclusions</p> <p>We found that in the Japanese population, individuals harboring the G-allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated with plasma levels of ALT, AST, and ferritin, and the histological fibrosis stage. Our study suggests that <it>PNPLA3 </it>may be involved in the progression of fibrosis in NAFLD.</p

    TNFα-Induced Apoptosis Enabled by CCN1/CYR61: Pathways of Reactive Oxygen Species Generation and Cytochrome c Release

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    Although TNFα is a strong inducer of apoptosis, its cytotoxicity in most normal cells in vitro requires blockade of NFκB signaling or inhibition of de novo protein synthesis, typically by the addition of cycloheximide. However, several members of CCN (CYR61/CTGF/NOV) family of extracellular matrix proteins enable TNFα-dependent apoptosis in vitro without inhibiting NFκB or de novo protein synthesis, and CCN1 (CYR61) is essential for optimal TNFα cytotoxicity in vivo. Previous studies showed that CCN1 unmasks the cytotoxicity of TNFα by binding integrins αvβ5, α6β1, and the cell surface heparan sulfate proteoglycan syndecan 4 to induce the accumulation of a high level of reactive oxygen species (ROS), leading to a biphasic activation of JNK necessary for apoptosis. Here we show for the first time that CCN1 interacts with the low density lipoprotein receptor-related protein 1 (LRP1) in a protein complex, and that binding to LRP1 is critical for CCN1-induced ROS generation and apoptotic synergism with TNFα. We also found that neutral sphingomyelinase 1 (nSMase1), which contributes to CCN1-induced ROS generation, is required for CCN1/TNFα-induced apoptosis. Furthermore, CCN1 promotes the activation of p53 and p38 MAPK, which mediate enhanced cytochrome c release to amplify the cytotoxicity of TNFα. By contrast, LRP1, nSMase1, p53, and p38 MAPK are not required when TNFα-dependent apoptosis is facilitated by the presence of cycloheximide, indicating that they function in the CCN1 signaling pathway that converges with TNFα-induced signaling events. Since CCN1/CYR61 is a physiological regulator of TNFα cytotoxicity at least in some contexts, these findings may reveal important mediators of TNFα-induced apoptosis in vivo and identify potential therapeutic targets for thwarting TNFα-dependent tissue damage

    Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome

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    Dengue has become one of the most common viral diseases transmitted by infected mosquitoes (with any of the four dengue virus serotypes: DEN-1, -2, -3, or -4). It may present as asymptomatic or illness, ranging from mild to severe disease. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. The pathogenesis of DHF/DSS, however, is not yet completely understood. The immune response, virus virulence, and host genetic background are considered to be risk factors contributing to disease severity. Human leucocyte antigens (HLA) expressed on the cell surface function as antigen presenting molecules and those polymorphism can change individuals' immune response. We investigated the HLA-A, -B (class I), and -DRB1 (class II) polymorphism in Vietnamese children with different severity (DHF/DSS) by a hospital-based case-control study. The study showed persons carrying HLA-A*2402/03/10 are about 2 times more likely to have severe dengue infection than others. On the other hand, HLA-DRB1*0901 persons are less likely to develop DSS with DEN-2 virus infection. These results clearly demonstrated that HLA controlled the susceptibility to severe forms of DV infection

    Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

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    Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis
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