3,021 research outputs found

    A Multivariate Approach for Checking Resiliency in Access Control

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    In recent years, several combinatorial problems were introduced in the area of access control. Typically, such problems deal with an authorization policy, seen as a relation UR⊆U×RUR \subseteq U \times R, where (u,r)∈UR(u, r) \in UR means that user uu is authorized to access resource rr. Li, Tripunitara and Wang (2009) introduced the Resiliency Checking Problem (RCP), in which we are given an authorization policy, a subset of resources P⊆RP \subseteq R, as well as integers s≥0s \ge 0, d≥1d \ge 1 and t≥1t \geq 1. It asks whether upon removal of any set of at most ss users, there still exist dd pairwise disjoint sets of at most tt users such that each set has collectively access to all resources in PP. This problem possesses several parameters which appear to take small values in practice. We thus analyze the parameterized complexity of RCP with respect to these parameters, by considering all possible combinations of ∣P∣,s,d,t|P|, s, d, t. In all but one case, we are able to settle whether the problem is in FPT, XP, W[2]-hard, para-NP-hard or para-coNP-hard. We also consider the restricted case where s=0s=0 for which we determine the complexity for all possible combinations of the parameters

    Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

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    Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

    Association of PCSK1 rs6234 with Obesity and Related Traits in a Chinese Han Population

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    Background: Common variants in PCSK1 have been reported to be associated with obesity in populations of European origin. We aimed to replicate this association in Chinese. Methodology/Principal Findings: Two PCSK1 variants rs6234 and rs6235 (in strong LD with each other, r 2 = 0.98) were genotyped in a population-based cohort of 3,210 Chinese Hans. The rs6234 was used for further association analyses with obesity and related traits. We found no significant association of rs6234 with obesity, overweight, BMI, waist circumference, or body fat percentage (P.0.05) in all participants. However, the rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight (OR 1.21[1.03–1.43], P = 0.0193) and a trend toward association with obesity (OR 1.25[0.98–1.61], P = 0.08) in men, but not in women (P0.29).Consistently,thers6234G−alleleshowedsignificantassociationwithincreasedBMI(P=0.0043),waistcircumference(P=0.008)andbodyfatpercentage(P=0.0131)onlyinmen,notinwomen(P0.29). Consistently, the rs6234 G-allele showed significant association with increased BMI (P = 0.0043), waist circumference (P = 0.008) and body fat percentage (P = 0.0131) only in men, not in women (P0.24). Interestingly, the rs6234 G-allele was significantly associated with increased HOMA-B (P = 0.0059) and decreased HOMA-S (P = 0.0349) in all participants. Conclusion/Significance: In this study, we found modest evidence for association of the PCSK1 rs6234 with BMI and overweight in men only but not in women, which suggested that PCSK1 rs6234 might not be an important contributor t

    Transcription factor 7-like 2 (TCF7L2) variant is associated with familial breast cancer risk: a case-control study

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    BACKGROUND: The transcription factor 7-like 2 (TCF7L2) is a critical component of the Wnt/β-catenin pathway. Aberrant TCF7L2 expression modifies Wnt signaling and mediates oncogenic effects through the upregulation of c-MYC and cyclin D. Genetic alterations in TCF7L2 may therefore affect cancer risk. Recently, TCF7L2 variants, including the microsatellite marker DG10S478 and the nearly perfectly linked SNP rs12233372, were identified to associate with type 2 diabetes. METHODS: We investigated the effect of the TCF7L2 rs12255372 variant on familial breast cancer (BC) risk by means of TaqMan allelic discrimination, analyzing BRCA1/2 mutation-negative index patients of 592 German BC families and 735 control individuals. RESULTS: The T allele of rs12255372 showed an association with borderline significance (OR = 1.19, 95% C.I. = 1.01-1.42, P = 0.04), and the Cochran-Armitage test for trend revealed an allele dose-dependent association of rs12255372 with BC risk (P(trend )= 0.04). CONCLUSION: Our results suggest a possible influence of TCF7L2 rs12255372 on the risk of familial BC

    Two Simple W' Models for the Early LHC

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    W' gauge bosons are good candidates for early LHC discovery. We define two reference models, one containing a W'_R and one containing a W'_L, which may serve as ``simplified models'' for presenting experimental results of W' searches at the LHC. We present the Tevatron bounds on each model and compute the constraints from precision electroweak observables. We find that indirect low-energy constraints on the W'_L are quite strong. However, for a W'_R coupling to right-handed fermions there exists a sizeable region in parameter space beyond the bounds from the Tevatron and low-energy precision measurements where even 50 inverse picobarns of integrated LHC luminosity are sufficient to discover the W'_R. The most promising final states are two leptons and two jets, or one lepton recoiling against a ``neutrino jet''. A neutrino jet is a collimated object consisting of a hard lepton and two jets arising from the decay of a highly boosted massive neutrino.Comment: 20 pages, 8 figures. v2: references adde

    Acyl Homoserine Lactones from Culture Supernatants of Pseudomonas aeruginosa Accelerate Host Immunomodulation

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    The virulence of Pseudomonas aeruginosa is multifactorial and under the control of quorum sensing signals, such as acyl homoserine lactones (AHLs). The importance of these molecules in the establishment of infection has been previously reported. These molecules either improve the virulence potential of P. aeruginosa or modulate the host immune response. To establish the immune modulating potential of quorum sensing signal molecules, previous studies have only used synthetic AHLs. However, there can be differences in the biological properties of synthetic and natural AHLs. The use of naturally extracted AHLs from the culture supernatant of P. aeruginosa is likely to simulate natural conditions more than the use of synthetic AHLs. Therefore, in the present study, the immune modulating potential of synthetic and naturally extracted AHLs was compared using a thymidine uptake assay, immunophenotyping and sandwich ELISA in order to assess mouse T-cell proliferation and production of Th1 and Th2 cytokines. Natural AHLs were able to suppress T-cell proliferation, even at low concentrations, compared to synthetic AHLs. The majority of cells undergoing proliferation were CD4+, as revealed by immunophenotyping. The inhibition of T-cells was stronger with natural AHLs compared to synthetic AHLs. Moreover, the natural AHLs were also able to shift immune responses away from host protective Th1 responses to pathogen protective Th2 responses

    Use of photosensitising diuretics and risk of skin cancer: a population-based case–control study

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    Diuretics have photosensitising properties. However, little is known about how these diuretics affect the risk of skin cancers. In North Jutland County, Denmark, we investigated whether the use of photosensitising diuretics was associated with an increased risk for developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). From the cancer registry, we identified primary cases of BCC, SCC and MM during the period of 1989–2003. We selected four population controls for each case from the Danish Civil Registration System, matched on age and gender. Prescriptions for photosensitising diuretics before cancer diagnosis were ascertained in the county's Prescription Database. We used conditional logistic regression to compute incidence rate ratio (IRR), controlling for the chronic medical conditions and for the previous use of oral glucocorticoids. We found an increased risk of SCC (IRR of 1.79 (95% confidence interval (CI): 1.45–2.21)) and MM (IRR of 1.43 (95% CI: 1.09–1.88)) among users of combined amiloride and hydrochlorothiazide therapy. An increased risk of MM (IRR of 3.30 (95% CI: 1.34–8.10)) was found among users of indapamide. We found little associations with risk of BCC. Our findings provide evidence that the use of some photosensitising diuretics is associated with an increased risk for SCC and MM

    Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study

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    Background Anemia, which has many etiologies, is a moderate/severe public health problem in young children and women of reproductive age in many developing countries. The aim of this study was to investigate prevalence of iron deficiency, anemia, and iron deficiency anemia using multiple biomarkers and to evaluate their association with food insecurity and food consumption patterns in non-pregnant women from a rural area of southern Ethiopia. Methods A cross-sectional study was conducted in 202 rural women of reproductive age in southern Ethiopia. Anthropometrics and socio-demographic data were collected. A venipuncture blood sample was analyzed for hemoglobin (Hb) and for biomarkers of iron status. Biomarkers were skewed and were log transformed before analysis. Mean, median, Pearson\u27s correlations and ordinary least-squares regressions were calculated. Results Median (IQR) Hb was 138 (127, 151) g/L. Based on an altitude-adjusted (1708 m) cutoff of 125 g/L for Hb, 21.3% were anemic. Plasma ferritin was \u3c15 μg/L in 18.6% of the women. Only one woman had α-1-acid glycoprotein (AGP) \u3e1.0 g/L; four women (2%) had \u3e 5 mg/L of C-reactive protein (CRP). Of the 43 women who were anemic, 23.3% (10 women) had depleted iron stores based on plasma ferritin. Three of these had elevated soluble transferring receptors (sTfR). Hemoglobin (Hb) concentration was negatively correlated with sTfR (r = -0.24, p = 0.001), and positively correlated with ferritin (r = 0.17, p = 0.018), plasma iron (r = 0.15, p = 0.046), transferrin saturation (TfS) (r = 0.15, p = 0.04) and body iron (r = 0.14, p = 0.05). Overall prevalence of iron deficiency anemia was only 5%. Conclusion Iron deficiency anemia was not prevalent in the study population, despite the fact that anemia would be classified as a moderate public health problem
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