Системный анализ процесса затвердевания литых заготовок разной массы и назначения

Выявлены особенности пространственно-временной эволюции температурных полей в процессе затвердевания разных заготовок (слитков и отливок) для повышения их качества.Виявлено особливості просторово-часової еволюції температурних полів в процесі тверднення різних заготовок (зливків та виливків) для підвищення їх якості.It is revealed the peculiarities of distance-time evolution of the temperature fields in solidification process different billets (ingots and casts) for raise them quality

Absorbing and transferring risk: assessing the impact of a statewide high-risk-pregnancy telemedical program on VLBW maternal transports

BACKGROUND: Prior research has shown that resources have an impact on birth outcomes. In this paper we ask how combinations of telemedical and hospital-level resources impact transports of mothers expecting very low birth weight (VLBW) babies in Arkansas. METHODS: Using de-identified birth certificate data from the Arkansas Department of Health, data were gathered on transports of women carrying VLBW babies for two six-month periods: a period just before the start of ANGELS (12/02-05/03), a telemedical outreach program for high-risk pregnancies, and a period after the program had been running for six months (12/03-05/04). For each maternal transport, the following information was recorded: maternal race-ethnicity, maternal age, and the birth weight of the infant. Logistic regression was used to assess the relationship between the predictors (telemedicine, hospital level, maternal characteristics) and the probability of a transport. RESULTS: Having a telemedical site available increases the probability of a mother carrying a VLBW baby being transported to a level III facility either before or during birth. Having at least a level II nursery also increases the chance of a maternal transport. Where both level II nurseries and telemedical access are available, the odds of VLBW maternal transports are only modestly increased in comparison to the case where neither is present. At the individual level, Hispanic mothers were less likely to be transported than other mothers, and teenaged mothers were more likely to be transported than those 18 and over. A mother's being Black or being over 35 did not have an impact on the odds of being transported to a level III facility. CONCLUSION: Combinations of resources have an impact on physician decisions regarding VLBW transports and are interpretable in terms of the capacity to diagnose and absorb risk. We suggest a collegial review of transport patterns and birth outcomes from areas with different levels of resources as a vehicle for moving the entire system of care forward over time. With such an evidence-based review in place, the collegial relations among level III specialists and obstetricians from around the state can, over time, develop workable protocols for when and how level III facilities should be involved

Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine

The variation in antibody response to vaccination likely involves small contributions of numerous genetic variants, such as single-nucleotide polymorphisms (SNPs), which interact in gene networks and pathways. To accumulate the bits of genetic information relevant to the phenotype that are distributed throughout the interaction network, we develop a network eigenvector centrality algorithm (SNPrank) that is sensitive to the weak main effects, gene–gene interactions and small higher-order interactions through hub effects. Analogous to Google PageRank, we interpret the algorithm as the simulation of a random SNP surfer (RSS) that accumulates bits of information in the network through a dynamic probabilistic Markov chain. The transition matrix for the RSS is based on a data-driven genetic association interaction network (GAIN), the nodes of which are SNPs weighted by the main-effect strength and edges weighted by the gene–gene interaction strength. We apply SNPrank to a GAIN analysis of a candidate-gene association study on human immune response to smallpox vaccine. SNPrank implicates a SNP in the retinoid X receptor α (RXRA) gene through a network interaction effect on antibody response. This vitamin A- and D-signaling mediator has been previously implicated in human immune responses, although it would be neglected in a standard analysis because its significance is unremarkable outside the context of its network centrality. This work suggests SNPrank to be a powerful method for identifying network effects in genetic association data and reveals a potential vitamin regulation network association with antibody response

Transcriptomics and adaptive genomics of the asymptomatic bacteriuria Escherichia coli strain 83972

Escherichia coli strains are the major cause of urinary tract infections in humans. Such strains can be divided into virulent, UPEC strains causing symptomatic infections, and asymptomatic, commensal-like strains causing asymptomatic bacteriuria, ABU. The best-characterized ABU strain is strain 83972. Global gene expression profiling of strain 83972 has been carried out under seven different sets of environmental conditions ranging from laboratory minimal medium to human bladders. The data reveal highly specific gene expression responses to different conditions. A number of potential fitness factors for the human urinary tract could be identified. Also, presence/absence data of the gene expression was used as an adaptive genomics tool to model the gene pool of 83972 using primarily UPEC strain CFT073 as a scaffold. In our analysis, 96% of the transcripts filtered present in strain 83972 can be found in CFT073, and genes on six of the seven pathogenicity islands were expressed in 83972. Despite the very different patient symptom profiles, the two strains seem to be very similar. Genes expressed in CFT073 but not in 83972 were identified and can be considered as virulence factor candidates. Strain 83972 is a deconstructed pathogen rather than a commensal strain that has acquired fitness properties

Evaluation of a group based cognitive behavioural therapy programme for menstrual pain management in young women with intellectual disabilities: protocol for a mixed methods controlled clinical trial

BACKGROUND: Menstrual pain which is severe enough to impact on daily activities is very common amongst menstruating females. Research suggests that menstrual pain which impacts on daily functioning may be even more prevalent amongst those with intellectual disabilities. Despite this, little research attention has focused on pain management programmes for those with intellectual disabilities. The aims of this pilot study were to develop and evaluate a theory-based cognitive behavioural therapy (CBT) programme for menstrual pain management in young women with intellectual disabilities. METHODS/DESIGN: The study utilised a mixed methods controlled clinical trial to evaluate elements from a CBT programme called Feeling Better (McGuire & McManus, 2010). The Feeling Better programme is a modular, manualised intervention designed for people with an intellectual disability and their carers. The programme was delivered to 36 young women aged 12 – 30 years who have a Mild - Moderate Intellectual Disability, split between two conditions. The treatment group received the Feeling Better intervention and the control group received treatment as usual. To evaluate the effectiveness of the programme, measures were taken of key pain variables including impact, knowledge, self-efficacy and coping. Process evaluation was conducted to examine which elements of the programme were most successful in promoting change. DISCUSSION: Participants in the intervention group were expected to report the use of a greater number of coping strategies and have greater knowledge of pain management strategies following participation in the intervention and at three month follow-up, when compared to control group participants. A significant advantage of the study was the use of mixed methods and inclusion of process evaluation to determine which elements of a cognitive behavioural therapy programme work best for individuals with intellectual disabilities. TRIAL REGISTRATION: Current Controlled Trials ISRCTN7556775

Systematic identification of conserved motif modules in the human genome

<p>Abstract</p> <p>Background</p> <p>The identification of motif modules, groups of multiple motifs frequently occurring in DNA sequences, is one of the most important tasks necessary for annotating the human genome. Current approaches to identifying motif modules are often restricted to searches within promoter regions or rely on multiple genome alignments. However, the promoter regions only account for a limited number of locations where transcription factor binding sites can occur, and multiple genome alignments often cannot align binding sites with their true counterparts because of the short and degenerative nature of these transcription factor binding sites.</p> <p>Results</p> <p>To identify motif modules systematically, we developed a computational method for the entire non-coding regions around human genes that does not rely upon the use of multiple genome alignments. First, we selected orthologous DNA blocks approximately 1-kilobase in length based on discontiguous sequence similarity. Next, we scanned the conserved segments in these blocks using known motifs in the TRANSFAC database. Finally, a frequent pattern mining technique was applied to identify motif modules within these blocks. In total, with a false discovery rate cutoff of 0.05, we predicted 3,161,839 motif modules, 90.8% of which are supported by various forms of functional evidence. Compared with experimental data from 14 ChIP-seq experiments, on average, our methods predicted 69.6% of the ChIP-seq peaks with TFBSs of multiple TFs. Our findings also show that many motif modules have distance preference and order preference among the motifs, which further supports the functionality of these predictions.</p> <p>Conclusions</p> <p>Our work provides a large-scale prediction of motif modules in mammals, which will facilitate the understanding of gene regulation in a systematic way.</p

Nicotine exposure and transgenerational impact: a prospective study on small regulatory microRNAs

Early developmental stages are highly sensitive to stress and it has been reported that pre-conditioning with tobacco smoking during adolescence predisposes those youngsters to become smokers as adults. However, the molecular mechanisms of nicotine-induced transgenerational consequences are unknown. In this study, we genome-widely investigated the impact of nicotine exposure on small regulatory microRNAs (miRNAs) and its implication on health disorders at a transgenerational aspect. Our results demonstrate that nicotine exposure, even at the low dose, affected the global expression profiles of miRNAs not only in the treated worms (F0 parent generation) but also in two subsequent generations (F1 and F2, children and grandchildren). Some miRNAs were commonly affected by nicotine across two or more generations while others were specific to one. The general miRNA patterns followed a “two-hit� model as a function of nicotine exposure and abstinence. Target prediction and pathway enrichment analyses showed daf-4, daf-1, fos-1, cmk-1, and unc-30 to be potential effectors of nicotine addiction. These genes are involved in physiological states and phenotypes that paralleled previously published nicotine induced behavior. Our study offered new insights and further awareness on the transgenerational effects of nicotine exposed during the vulnerable post-embryonic stages, and identified new biomarkers for nicotine addiction.ECU Open Access Publishing Support Fun

A General Framework for Formal Tests of Interaction after Exhaustive Search Methods with Applications to MDR and MDR-PDT

The initial presentation of multifactor dimensionality reduction (MDR) featured cross-validation to mitigate over-fitting, computationally efficient searches of the epistatic model space, and variable construction with constructive induction to alleviate the curse of dimensionality. However, the method was unable to differentiate association signals arising from true interactions from those due to independent main effects at individual loci. This issue leads to problems in inference and interpretability for the results from MDR and the family-based compliment the MDR-pedigree disequilibrium test (PDT). A suggestion from previous work was to fit regression models post hoc to specifically evaluate the null hypothesis of no interaction for MDR or MDR-PDT models. We demonstrate with simulation that fitting a regression model on the same data as that analyzed by MDR or MDR-PDT is not a valid test of interaction. This is likely to be true for any other procedure that searches for models, and then performs an uncorrected test for interaction. We also show with simulation that when strong main effects are present and the null hypothesis of no interaction is true, that MDR and MDR-PDT reject at far greater than the nominal rate. We also provide a valid regression-based permutation test procedure that specifically tests the null hypothesis of no interaction, and does not reject the null when only main effects are present. The regression-based permutation test implemented here conducts a valid test of interaction after a search for multilocus models, and can be applied to any method that conducts a search to find a multilocus model representing an interaction

Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria

The severity of urinary tract infection (UTI) reflects the quality and magnitude of the host response. While strong local and systemic innate immune activation occurs in patients with acute pyelonephritis, the response to asymptomatic bacteriuria (ABU) is low. The immune response repertoire in ABU has not been characterized, due to the inherent problem to distinguish bacterial differences from host-determined variation. In this study, we investigated the host response to ABU and genetic variants affecting innate immune signaling and UTI susceptibility. Patients were subjected to therapeutic urinary tract inoculation with E. coli 83972 to ensure that they were exposed to the same E. coli strain. The innate immune response repertoire was characterized in urine samples, collected from each patient before and after inoculation with bacteria or PBS, if during the placebo arm of the study. Long-term E. coli 83972 ABU was established in 23 participants, who were followed for up to twelve months and the innate immune response was quantified in 233 urine samples. Neutrophil numbers increased in all but two patients and in an extended urine cytokine/chemokine analysis (31 proteins), the chemoattractants IL-8 and GRO-α, RANTES, Eotaxin-1 and MCP-1, the T cell chemoattractant and antibacterial peptide IP-10, inflammatory regulators IL-1-α and sIL-1RA and the T lymphocyte/dendritic cell product sIL-2Rα were detected and variably increased, compared to sterile samples. IL-6, which is associated with symptomatic UTI, remained low and numerous specific immune mediators were not detected. The patients were also genotyped for UTI-associated IRF3 and TLR4 promoter polymorphisms. Patients with ABU associated TLR4 polymorphisms had low neutrophil numbers, IL-6, IP-10, MCP-1 and sIL-2Rα concentrations. Patients with the ABU-associated IRF3 genotype had lower neutrophils, IL-6 and MCP-1 responses than the remaining group. The results suggest that the host-specific, low immune response to ABU mainly includes innate immune mediators and that host genetics directly influence the magnitude of this response