312 research outputs found

    Architecture Design Space Exploration for Streaming Applications Through Timing Analysis

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    In this paper we compare the maximum achievable throughput of different memory organisations of the processing elements that constitute a multiprocessor system on chip. This is done by modelling the mapping of a task with input and output channels on a processing element as a homogeneous synchronous dataflow graph, and use maximum cycle mean analysis to derive the throughput. In a HiperLAN2 case study we show how these techniques can be used to derive the required clock frequency and communication latencies in order to meet the application's throughput requirement on a multiprocessor system on chip that has one of the investigated memory organisations

    Genetic Variation in FADS Genes and Plasma Cholesterol Levels in 2-Year-Old Infants

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    Single nucleotide polymorphisms (SNPs) in genes involved in fatty acid metabolism (FADS1 FADS2 gene cluster) are associated with plasma lipid levels. We aimed to investigate whether these associations are already present early in life and compare the relative contribution of FADS SNPs vs traditional (non-genetic) factors as determinants of plasma lipid levels. Information on infants' plasma total cholesterol levels, genotypes of five FADS SNPs (rs174545, rs174546, rs174556, rs174561, and rs3834458), anthropometric data, maternal characteristics, and breastfeeding history was available for 521 2-year-old children from the KOALA Birth Cohort Study. For 295 of these 521 children, plasma HDLc and non-HDLc levels were also known. Multivariable linear regression analysis was used to study the associations of genetic and non-genetic determinants with cholesterol levels. All FADS SNPs were significantly associated with total cholesterol levels. Heterozygous and homozygous for the minor allele children had about 4% and 8% lower total cholesterol levels than major allele homozygotes. In addition, homozygous for the minor allele children had about 7% lower HDLc levels. This difference reached significance for the SNPs rs174546 and rs3834458. The associations went in the same direction for non-HDLc, but statistical significance was not reached. The percentage of total variance of total cholesterol levels explained by FADS SNPs was relatively low (lower than 3%) but of the same order as that explained by gender and the non-genetic determinants together. FADS SNPs are associated with plasma total cholesterol and HDLc levels in preschool children. This brings a new piece of evidence to explain how blood lipid levels may track from childhood to adulthood. Moreover, the finding that these SNPs explain a similar amount of variance in total cholesterol levels as the non-genetic determinants studied reveals the potential importance of investigating the effects of genetic variations in early life

    Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

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    Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an anti-fibrotic compound available for the treatment of idiopathic pulmonary fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were cultured in the absence and presence of pirfenidone. Cell proliferation was measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell motility was monitored by live cell imaging. Cytotoxicity and cell viability were analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) assays. Gene expression of fibrosis markers was determined by quantitative reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) signaling was analyzed by Western blotting and type I collagen protein expression additionally by immunofluorescence microscopy. Pirfenidone dose-dependently inhibited p-hIF proliferation and motility, without inducing cell death. Pirfenidone suppressed mRNA levels of genes that contribute to extracellular matrix production, as well as basal and TGF-beta 1-induced collagen I protein production, which was associated with inhibition of the rapamycin-sensitive mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of intestinal fibroblasts and suppresses collagen I production through the TGF-beta 1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis

    Unsuitability of the Oxidation-Reduction Potential Measurement for the Quantification of Fecal Redox Status in Inflammatory Bowel Disease

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    Oxidative stress is a key pathophysiological process associated with the development and progression of inflammatory bowel disease (IBD). Biomarkers for oxidative stress, however, are scarce, as are diagnostic tools that can interrogate an individual’s gut redox status. This proof- of-concept study aimed to evaluate the potential utility of an oxidation-reduction potential (ORP) measurement probe, to quantify redox status in the feces of both patients with IBD and healthy controls. Previous studies using this ORP measurement probe demonstrated promising data when comparing ORP from severely malnourished individuals with that of healthy controls. To date, ORP analyses have not been performed in the context of IBD. We hypothesized that measuring the ORP of fecal water in patients with IBD might have diagnostic value. The current study, however, did not show significant differences in ORP measurement values between patients with IBD (median [IQR] 46.5 [33.0–61.2] mV) and healthy controls (25 [8.0–52.0] mV; p = 0.221). Additionally, ORP measurements were highly unstable and rapidly fluctuated throughout time, with ORP values varying from +24 to +303 mV. Due to potential biological processes and limitations of the measuring equipment, this study was unable to reliably measure ORP. As a result, our findings indicate that ORP quantification may not be a suitable method for assessing fecal redox status and, therefore, does not currently support further exploration as a diagnostic or monitoring tool

    Effects of an intervention aimed at reducing the intake of sugar-sweetened beverages in primary school children: A controlled trial

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    Abstract Background Since sugar-sweetened beverages (SSB) may contribute to the development of overweight in children, effective interventions to reduce their consumption are needed. Here we evaluated the effect of a combined school- and community-based intervention aimed at reducing children’s SSB consumption by promoting the intake of water. Favourable intervention effects on children’s SSB consumption were hypothesized. Methods In 2011-2012, a controlled trial was conducted among four primary schools, comprising 1288 children aged 6-12 years who lived in multi-ethnic, socially deprived neighbourhoods in Rotterdam, the Netherlands. Intervention schools adopted the ‘water campaign’, an intervention developed using social marketing. Control schools continued with their regular health promotion programme. Primary outcome was children’s SSB consumption, measured using parent and child questionnaires and through observations at school, both at baseline and after one year of intervention. Results Significant positive intervention effects were found for average SSB consumption (B -0.19 litres, 95% CI -0.28;-0.10; parent report), average SSB servings (B -0.54 servings, 95% CI -0.82;-0.26; parent report) and bringing SSB to school (OR 0.51, 95% CI 0.36;0.72; observation report). Conclusions This study supports the effectiveness of the water campaign intervention in reducing children’s SSB consumption. Further studies are needed to replicate our findings. Trial registration Current Controlled Trials: NTR3400 webcit

    Electroencephalography in normotensive and hypertensive pregnancies and subsequent quality of life

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    Objectives: To compare electroencephalography (EEG) findings during pregnancy and postpartum in women with normotensive pregnancies and pregnancies complicated by hypertensive disorders. Also the health related quality of life postpartum was related to these EEG findings. Materials and Methods: An observational case-control study in a university hospital in the Netherlands. Twenty-nine normotensive and 58 hypertensive pregnant women were included. EEG's were recorded on several occasions during pregnancy and 6-8 weeks postpartum. Postpartum, the women filled out health related quality of life questionnaires. Main outcome measures were qualitative and quantitative assessments on EEG, multidimensional fatigue inventory, Short Form (36) Health Survey and EuroQol visual analogue scale. Results: In women with severe preeclampsia significantly lower alpha peak frequency, more delta and theta activity bilaterally and a higher EEG Sum Score were seen. Postpartum, these women showed impaired mental health, mental fatigue and social functioning, which could not be related to the EEG findings. Conclusions: Severe preeclamptic patients show more EEG abnormalities and have impaired mental wellbeing postpartum, but these findings are not correlated

    Внебрачный секс и его психопрофилактика

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    Описана предложенная автором поэтапная система психопрофилактики супружеской дезадаптации, ведущей к внебрачному сексу.The original staged system of psychoprevention of spouse deadaptation causing extramarital sex is described

    HIF1α-Dependent Induction of TFRC by a Combination of Intestinal Inflammation and Systemic Iron Deficiency in Inflammatory Bowel Disease

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    Background and Aims: Iron deficiency (ID) is a frequent extra-intestinal manifestation in patients with Inflammatory Bowel Disease (IBD), who often do not respond to iron supplementation. Iron is a cofactor for hydroxylases that suppress the hypoxia-inducible factor-1α (HIF1α), a transcription factor regulating iron homeostasis. We hypothesized that iron deficiency affects mucosal HIF1α activity in IBD. Methods: IBD patients (n = 101) were subdivided based on iron status (ferritin levels or transferrin saturation) and systemic inflammation (C-reactive protein levels). 154 corresponding ileal and colonic biopsies were analyzed for differential expression of 20 HIF1α pathway-associated genes and related to iron and inflammation status. In vitro expression of selected HIF1α pathway genes were analyzed in wild-type and HIF1A-null Caco-2 cells. Results: Gene expression of the mucosal HIF1α pathway was most affected by intestinal location and inflammatory status. Especially, ileal mucosal TFRC expression, encoding the transferrin receptor TFR1, was increased in inflamed tissue (p < 0.001), and further enhanced in ID. Accordingly, TFRC expression in inflamed tissue associated negatively with serum iron levels, which was not observed in the non-inflamed mucosa. The HIF1α pathway agonist DMOG increased TFRC expression in Caco-2 cells, which was blunted in HIF1A-null cells. Conclusion: We demonstrate that inflammation and anatomical location primarily determine HIF1α pathway activation and downstream TFRC expression in the intestinal mucosa. IBD patients with ID may benefit from treatment with HIF1α-agonists by 1) increasing TFRC-mediated iron absorption in non-inflamed tissue and 2) decreasing mucosal inflammation, thereby improving their responsiveness to oral iron supplementation
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