561 research outputs found
T lymphocyte Recruitment to the Lung in Asthma
No full textT cells play an important part in the pathogenesis of asthma. In this study greater numbers of T cells were seen in the bronchial epithelium of severe asthmatics compared to normal subjects. There were greater percentages of both IL-4+ and IFN-γ+ T cells in the bronchoalveolar lavage of asthmatics compared to normal subjects. Chemokines and their receptors are thought to act as signals that guide particular subsets of T cells to the lung in asthma. Using flow cytometry I had explored whether the chemokine receptors CCR8 and CRTh2 played any role in recruiting T cells and in particular IL-4+ T cells to the lung in asthma. Both receptors selectively identified IL-4+ and IL-13+ T cells in the blood and bronchoalveolar lavage from asthmatics and normal subjects. Cells expressing CCR8 but not CRTh2 were found at a higher percentage in the blood of severe asthmatics compared to normal controls. The percentage of CCR8+ T in the bronchoalveolar lavage of asthmatics was higher compared to normal subjects and furthermore, there was a greater percentage of CCR8+ T cells in the bronchoalveolar lavage compared to blood within the same asthmatic subject. This difference in the percentage of CCR8+ T cells between blood and BAL was not seen in normal subjects. This suggests that there may be a role for CCR8 in the recruitment of T cells to the lung in asthma. In support of this, higher concentrations of the ligand CCL1, were seen in the bronchoalveolar lavage of asthmatics compared to that from normal subjects. Little experimental evidence was found that supported the contention that CRTh2 played a significant role in T cell recruitment to the lung. As a marker of IL-4+ T cells in asthmatics, CCR8 compared favourably with CRTh2 as they identified a greater percentage of IL-4+ T cells in bronchoalveolar lavage than CRTh2. CCR8 also compared favourably with CCR4 as a marker for IL-4+ T cells due to higher specificity. The iNKT subset of T cells has been claimed to be an important group of T cells in asthma and was reported to be present at high percentages in the lung of moderate to severe asthmatics. In this study we had shown that in asthmatics these cells are present in very low percentages, similar to that in normal subjects and that they probably do not play a significant role in severe asthma
A 1.2 Gb/s Data Transmission Unit in CMOS 0.18 μm technology for the ALICE Inner Tracking System front-end ASIC
No full textupgrade of the ALICE Inner Tracking System is based on a Monolithic Active Pixel Sensor and ASIC designed in a CMOS 0.18 mu m process. In order to provide the required output bandwidth (1.2 Gb/s for the inner layers and 400 Mb/s for the outer ones) on a single high speed serial link, a custom Data Transmission Unit (DTU) has been developed in the same process. The DTU includes a clock multiplier PLL, a double data rate serializer and a pseudo-LVDS driver with pre-emphasis and is designed to be SEU tolerant
T lymphocyte recruitment to the lung in asthma
No full textT cells play an important part in the pathogenesis of asthma. In this study greater numbers of T cells were seen in the bronchial epithelium of severe asthmatics compared to normal subjects. There were greater percentages of both IL-4+ and IFN-γ+ T cells in the bronchoalveolar lavage of asthmatics compared to normal subjects. Chemokines and their receptors are thought to act as signals that guide particular subsets of T cells to the lung in asthma. Using flow cytometry I had explored whether the chemokine receptors CCR8 and CRTh2 played any role in recruiting T cells and in particular IL-4+ T cells to the lung in asthma. Both receptors selectively identified IL-4+ and IL-13+ T cells in the blood and bronchoalveolar lavage from asthmatics and normal subjects. Cells expressing CCR8 but not CRTh2 were found at a higher percentage in the blood of severe asthmatics compared to normal controls. The percentage of CCR8+ T in the bronchoalveolar lavage of asthmatics was higher compared to normal subjects and furthermore, there was a greater percentage of CCR8+ T cells in the bronchoalveolar lavage compared to blood within the same asthmatic subject. This difference in the percentage of CCR8+ T cells between blood and BAL was not seen in normal subjects. This suggests that there may be a role for CCR8 in the recruitment of T cells to the lung in asthma. In support of this, higher concentrations of the ligand CCL1, were seen in the bronchoalveolar lavage of asthmatics compared to that from normal subjects. Little experimental evidence was found that supported the contention that CRTh2 played a significant role in T cell recruitment to the lung. As a marker of IL-4+ T cells in asthmatics, CCR8 compared favourably with CRTh2 as they identified a greater percentage of IL-4+ T cells in bronchoalveolar lavage than CRTh2. CCR8 also compared favourably with CCR4 as a marker for IL-4+ T cells due to higher specificity. The iNKT subset of T cells has been claimed to be an important group of T cells in asthma and was reported to be present at high percentages in the lung of moderate to severe asthmatics. In this study we had shown that in asthmatics these cells are present in very low percentages, similar to that in normal subjects and that they probably do not play a significant role in severe asthma.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Fast identification of biological pathways associated with a quantitative trait using group lasso with overlaps.
No full textWhere causal SNPs (single nucleotide polymorphisms) tend to accumulate within biological pathways, the incorporation of prior pathways information into a statistical model is expected to increase the power to detect true associations in a genetic association study. Most existing pathways-based methods rely on marginal SNP statistics and do not fully exploit the dependence patterns among SNPs within pathways.We use a sparse regression model, with SNPs grouped into pathways, to identify causal pathways associated with a quantitative trait. Notable features of our "pathways group lasso with adaptive weights" (P-GLAW) algorithm include the incorporation of all pathways in a single regression model, an adaptive pathway weighting procedure that accounts for factors biasing pathway selection, and the use of a bootstrap sampling procedure for the ranking of important pathways. P-GLAW takes account of the presence of overlapping pathways and uses a novel combination of techniques to optimise model estimation, making it fast to run, even on whole genome datasets.In a comparison study with an alternative pathways method based on univariate SNP statistics, our method demonstrates high sensitivity and specificity for the detection of important pathways, showing the greatest relative gains in performance where marginal SNP effect sizes are small
Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease
No full textInflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 × 10-8 and 6.95 × 10-8, respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 × 10-8; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively. © 2008 Nature Publishing Group
Structural damage and its effects on load carrying capacity of storage rack columns
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Low power, high resolution MAPS for particle tracking and imaging
No full textWe describe here the first monolithic pixel detector prototype embedding the OrthoPix architecture, specifically designed to deal with imaging applications where the relevant number of pixel hit per frame (occupancy) is small (on the order or less than 1%), like in High Energy Physics, Medical Imaging and other applications. Current state of the art employs complex circuitry into the pixel cell to discriminate relevant signals, leading to an extremely effective, non-destructive compression at the price of large power consumption and pixel area limitations. The OrthoPix architecture instead implements a passive projective compression scheme, leading to low power, small pixel cell and large area devices
CD11c APC populations isolated from BAL, lung and spleen were infected with AdOVA and co-cultured either for 48 hours with CFSE-labelled OT-I CD8 T cells or for 72 hours with CFSE-labelled OT-II CD4 T cells
No full textThe rate of transgenic T cell proliferation was analyzed by FACS. A, OT-I CD8 T cell proliferation. B, OT-II CD4 T cell proliferation. Representative histograms of T cell proliferation are shown. The average T cell proliferation rates are shown in bar graphs after subtracting from appropriate controls. Results are presented as the mean ± SD of triplicate samples. *p < 0.05.<p><b>Copyright information:</b></p><p>Taken from "CD11c+ antigen presenting cells from the alveolar space, lung parenchyma and spleen differ in their phenotype and capabilities to activate naïve and antigen-primed T cells"</p><p>http://www.biomedcentral.com/1471-2172/9/48</p><p>BMC Immunology 2008;9():48-48.</p><p>Published online 13 Aug 2008</p><p>PMCID:PMC2527294.</p><p></p
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