2,263 research outputs found

    Optimization of 2-d lattice cellular automata for pseudorandom number generation

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    This paper proposes a generalized approach to 2-d CA PRNGs – the 2-d lattice CA PRNG – by introducing vertical connections to arrays of 1-d CA. The structure of a 2-d lattice CA PRNG lies in between that of 1-d CA and 2-d CA grid PRNGs. With the generalized approach, 2-d lattice CA PRNG offers more 2-d CA PRNG variations. It is found that they can do better than the conventional 2-d CA grid PRNGs. In this paper, the structure and properties of 2-d lattice CA are explored by varying the number and location of vertical connections, and by searching for different 2-d array settings that can give good randomness based on Diehard test. To get the most out of 2-d lattice CA PRNGs, genetic algorithm is employed in searching for good neighborhood characteristics. By adopting an evolutionary approach, the randomness quality of 2-d lattice CA PRNGs is optimized. In this paper, a new metric, #rn is introduced as a way of finding a 2-d lattice CA PRNG with the least number of cells required to pass Diehard test. Following the introduction of the new metric #rn, a cropping technique is presented to further boost the CA PRNG performance. The cost and efficiency of 2-d lattice CA PRNG is compared with past works on CA PRNGs

    A modified routine analysis of arsenic content in drinking-water in Bangladesh by hydride generation-atomic absorption spectrophotometry.

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    The high prevalence of elevated levels of arsenic in drinking-water in many countries, including Bangladesh, has necessitated the development of reliable and rapid methods for the determination of a wide range of arsenic concentrations in water. A simple hydride generation-atomic absorption spectrometry (HG-AAS) method for the determination of arsenic in the range of microg/L to mg/L concentrations in water is reported here. The method showed linearity over concentrations ranging from 1 to 30 microg/L, but requires dilution of samples with higher concentrations. The detection limit ranged from 0.3 to 0.5 microg/L. Evaluation of the method, using internal quality-control (QC) samples (pooled water samples) and spiked internal QC samples throughout the study, and Standard Reference Material in certain lots, showed good accuracy and precision. Analysis of duplicate water samples at another laboratory also showed good agreement. In total, 13,286 tubewell water samples from Matlab, a rural area in Bangladesh, were analyzed. Thirty-seven percent of the water samples had concentrations below 50 microg/L, 29% below the WHO guideline value of 10 microg/L, and 17% below 1 microg/L. The HG-AAS was found to be a precise, sensitive, and reasonably fast and simple method for analysis of arsenic concentrations in water samples

    Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes.

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    BACKGROUND: Genealogy and molecular genetic studies of a Swedish river valley population resulted in a large pedigree, showing that the hereditary hemochromatosis (HH) HFE/p.C282Y mutation is inherited with other recessive disorders such as Wilson´s disease (WND), a rare recessive disorder of copper overload. The population also contain individuals with the Swedish long QT syndrome (LQTS1) founder mutation (KCNQ1/p.Y111C) which in homozygotes causes the Jervell & Lange Nielsen syndrome (JLNS) and hearing loss (HL).Aims of the study were to test whether the Swedish long QT founder mutation originated in an ancestral HFE family and if carriers had an increased risk for hemochromatosis (HH), a treatable disorder. We also aimed to identify the pathogenic mutation causing the hearing loss disorder segregating in the pedigree. METHODS: LQTS patients were asked about their ancestry and possible origin in a HH family. They were also offered a predictive testing for the HFE genotype. Church books were screened for families with hearing loss. One HH family had two members with hearing loss, who underwent molecular genetic analysis of the LQTS founder mutation, connexin 26 and thereafter exome sequencing. Another family with hearing loss in repeat generations was also analyzed for connexin 26 and underwent exome sequencing. RESULTS: Of nine LQTS patients studied, four carried a HFE mutation (two p.C282Y, two p.H63D), none was homozygous. Three LQTS patients confirmed origin in a female founder ( b 1694, identical to AJ b 1694, a HFE pedigree member from the Fax river. Her descent of 44 HH families, included also 29 families with hearing loss (HL) suggesting JLNS. Eleven LQTS probands confirmed origin in a second founder couple (b 1614/1605) in which the woman b 1605 was identical to a HFE pedigree member from the Fjällsjö river. In her descent there were not only 64 HH, six WND families, one JLNS, but also 48 hearing loss families. Most hearing loss was non syndromic and caused by founder effects of the late 16th century. One was of Swedish origin carrying the WHRN, c.1977delC, (p.S660Afs*30) mutation, the other was a TMC1(NM_138691),c.1814T>C,(p.L605P) mutation, possibly of Finnish origin. CONCLUSIONS: Deep human HFE genealogies show HFE to be associated with other genetic disorders like Wilson´s disease, LQTS, JLNS, and autosomal recessive hearing loss. Two new homozygous HL mutations in WHRN/p.S660Afs*30 and TMC1/p.L605P were identified,none of them previously reported from Scandinavia. The rarity of JLNS was possibly caused by miscarriage or intrauterine death. Most hearing loss (81.7%) was seen after 1844 when first cousin marriages were permitted. However, only 10 (10.3%) came from 1st cousin unions and only 2 (2.0 %) was born out of wedlock

    Heightened immune response to autocitrullinated porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis

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    Background: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. Objectives: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. Methods: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). Results: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. Conclusions: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy

    In situ chelation of phosphorus using microencapsulated aluminum and iron sulfate to bind intestinal phosphorus in rainbow trout (Oncorhynchus mykiss)

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    Excess phosphorus (P) in freshwater ecosystems increases primary production which, left uncontrolled, may lead to eutrophication, accelerating the ageing process of receiving water bodies. To limit phosphorus release resulting from freshwater aquaculture, we propose to incorporate microencapsulated P-chelating agents into fish diets. In a first trial, alum (Al2SO4) and ferrous sulfate (FeSO4) were encapsulated by spray-chilling in a hydrogenated lipid matrix. Two practical diets incorporating one of these two chelating elements (6 g/kg) were fed to fish for five weeks (w), and P release from resulting feces was compared. In a second trial, a similar approach was used to evaluate the impact of increasing supplementation of encapsulated alum (3, 6, 15 g/kg of diet). Feces from the fish fed with the diets incorporating alum and ferrous sulfate released 62 % and 54 % respectively less P than feces from fish fed with control diets. The second experiment revealed a negative correlation between the level of encapsulated Al2SO4 included in the diet and phosphorus released by the feces (y = 0.18x2 ˗ 4.78x + 62.7; R2 = 0.93). Feces from feed incorporating Al2SO4 at 0, 3, 6 and 15 g/kg released 62 %, 52 %, 39 %, and 32 % of the total fecal P after 14 days respectively. Fish fed encapsulated Al2SO4 have similar growth performance and mineral status. Incorporation of encapsulated P-chelating agents into fish feed offers an opportunity to manage P release from fish feces. Long-term feeding studies are required for validation of dietary Al2SO4 and FeSO4 impacts on potential toxicity and growth/environmental performance following chronic feeding of encapulated P chelating agents

    Understanding the Association of Biomedical, Psychosocial and Behavioral Risks with Adverse Pregnancy Outcomes

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    Objectives: This study investigates the relationship between diabetes, hypertension, preeclampsia, and Body Mass Index (BMI) -- the most common and interrelated medical conditions occurring during pregnancy; sociodemographic and behavioral risk factors; and adverse pregnancy outcomes in high-risk urban African American women in Washington, DC. Methods: Data are from a randomized controlled trial conducted in 6 prenatal clinics. Women in their 1st or 2nd trimester were screened for behavioral risks (smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) and demographic eligibility. 1,044 were eligible, interviewed and followed through their pregnancies. Classification and Regression Trees (CART) methodology was used to: 1) explore the relationship between medical and behavioral risks (reported at enrollment), sociodemographic factors and pregnancy outcomes, 2) identify the relative importance of various predictors of adverse pregnancy outcomes, and 3) characterize women at the highest risk of poor pregnancy outcomes. Results: Overall, the strongest predictors of poor outcomes were prepregnancy BMI, preconceptional diabetes, employment status, intimate partner violence, and depression. In CART analysis, preeclampsia was the first splitter for low birthweight; preconceptional diabetes was the first splitter for preterm birth (PTB) and neonatal intensive care admission; BMI was the first splitter for very PTB, large for gestational age, Cesarean section and perinatal death; and employment was the first splitter for miscarriage. Conclusions: Preconceptional factors play a very important role in pregnancy outcomes. For many of these women, the risks that they bring into the pregnancy were more likely to impact their pregnancy outcome than events during pregnancy

    TIRR regulates 53BP1 by masking its histone methyl-lysine binding function

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    53BP1 is a multi-functional double-strand break (DSB) repair protein that is essential for class switch recombination in B lymphocytes and for sensitizing BRCA1-deficient tumors to PARP inhibitors. Central to all 53BP1 activities is its recruitment to DSBs via the interaction of the tandem Tudor domain with dimethylated lysine 20 of histone H4 (H4K20me2). Here we identify an uncharacterized protein, TIRR (Tudor Interacting Repair Regulator) that directly binds the tandem Tudor domain and masks its H4K20me2 binding motif. Upon DNA damage, ATM phosphorylates 53BP1 and recruits RIF1 to dissociate the 53BP1–TIRR complex. However, overexpression of TIRR impedes 53BP1 function by blocking its localization to DSBs. Depletion of TIRR destabilizes 53BP1 in the nuclear soluble fraction and also alters the DSB-induced protein complex centering 53BP1. These findings identify TIRR as a new factor that influences DSB repair utilizing a unique mechanism of masking the histone methyl-lysine binding function of 53BP1

    A Modified Routine Analysis of Arsenic Content in Drinking-water in Bangladesh by Hydride Generation-Atomic Absorption Spectrophotometry

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    The high prevalence of elevated levels of arsenic in drinking-water in many countries, including Bangladesh, has necessitated the development of reliable and rapid methods for the determination of a wide range of arsenic concentrations in water. A simple hydride generation-atomic absorption spectrometry (HG-AAS) method for the determination of arsenic in the range of \u3bcg/L to mg/L concentrations in water is reported here. The method showed linearity over concentrations ranging from 1 to 30 \u3bcg/L, but requires dilution of samples with higher concentrations. The detection limit ranged from 0.3 to 0.5 \u3bcg/L. Evaluation of the method, using internal quality-control (QC) samples (pooled water samples) and spiked internal QC samples throughout the study, and Standard Reference Material in certain lots, showed good accuracy and precision. Analysis of duplicate water samples at another laboratory also showed good agreement. In total, 13,286 tubewell water samples from Matlab, a rural area in Bangladesh, were analyzed. Thirty-seven percent of the water samples had concentrations below 50 \u3bcg/L, 29% below the WHO guideline value of 10 \u3bcg/L, and 17% below 1 \u3bcg/L. The HG-AAS was found to be a precise, sensitive, and reasonably fast and simple method for analysis of arsenic concentrations in water samples
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