300 research outputs found

    Застосування сервісно-орієнтованих архітектур у процесах інтеграції інформаційних ресурсів

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    Розглянуто окремі аспекти застосування сервісно-орієнтованої архітектури для рішення завдань горизонтальної інтеграції автономних інформаційних ресурсів.Рассмотрены отдельные аспекты использования сервисно-ориентированной архитектуры для решения задач горизонтальной интеграции автономных информационных ресурсов.Some issues of service-oriented architecture application for solving the task of autonomous information resources horizontal integration are considered

    Effects of experience and opponents on pacing behavior and 2-km cycling performance of novice youths

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    Purpose: To study the pacing behavior and performance of novice youth exercisers in a controlled laboratory setting. Method: Ten healthy participants (seven male, three female, 15.8 ± 1.0 years) completed four, 2-km trials on a Velotron cycling ergometer. Visit 1 was a familiarization trial. Visits 2 to 4 involved the following conditions, in randomized order: no opponent (NO), a virtual opponent (starting slow and finishing fast) (OP-SLOWFAST), and a virtual opponent (starting fast and finishing slow) (OP-FASTSLOW). Repeated measurement ANOVAs (p < .05) were used to examine differences in both pacing behavior and also performance related to power output, finishing- and split times, and RPE between the four successive visits and the three conditions. Expected performance outcome was measured using a questionnaire. Results: Power output increased (F3,27 = 5.651, p = .004, η2p = .386) and finishing time decreased (F3,27 = 9.972, p .05). Conclusion: Performance was improved by an increase in experience after one visit, parallel with the ability to anticipate future workload

    Auditory experience modulates frontoparietal theta activity serving fluid intelligence

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    Children who are hard of hearing are at risk for developmental language and academic delays compared with children with normal hearing. Some work suggests that high-order cognitive function, including fluid intelligence, may relate to language and academic outcomes in children with hearing loss, but findings in these studies have been mixed and to date, there have been no studies of the wholebrain neural dynamics serving fluid intelligence in the context of hearing loss. To this end, this study sought to identify the impact of hearing loss and subsequent hearing aid use on the neural dynamics serving abstract reasoning in children who are hard of hearing relative to children with normal hearing using magnetoencephalography. We found significant elevations in occipital and parietal theta activity during early stimulus evaluation in children who are hard of hearing relative to normal-hearing peers. In addition, we found that greater hearing aid use was significantly related to reduced activity throughout the fronto-parietal network. Notably, there were no differences in alpha dynamics between groups during later-stage processing nor did alpha activity correlate with hearing aid use. These cross-sectional data suggest that differences in auditory experience lead to widespread alterations in the neural dynamics serving initial stimulus processing in fluid intelligence in children

    Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY

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    Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (Tyr(B26)) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated the use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomistic simulations of 3-[iodo-Tyr(B26)]insulin to predict its structural features, and (ii) tested these predictions by X-ray crystallography. Using an electrostatic model of the modified aromatic ring based on quantum chemistry, the calculations suggested that the analog, as a dimer and hexamer, exhibits subtle differences in aromatic-aromatic interactions at the dimer interface. Aromatic rings (Tyr(B16), Phe(B24), Phe(B25), 3-I-Tyr(B26), and their symmetry-related mates) at this interface adjust to enable packing of the hydrophobic iodine atoms within the core of each monomer. Strikingly, these features were observed in the crystal structure of a 3-[iodo-Tyr(B26)]insulin analog (determined as an R6 zinc hexamer). Given that residues B24-B30 detach from the core on receptor binding, the environment of 3-I-Tyr(B26) in a receptor complex must differ from that in the free hormone. Based on the recent structure of a "micro-receptor" complex, we predict that 3-I-Tyr(B26) engages the receptor via directional halogen bonding and halogen-directed hydrogen bonding as follows: favorable electrostatic interactions exploiting, respectively, the halogen's electron-deficient σ-hole and electronegative equatorial band. Inspired by quantum chemistry and molecular dynamics, such "halogen engineering" promises to extend principles of medicinal chemistry to proteins

    Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

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    markdownabstract__Background:__ The introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases. __Methods:__ This is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past. __Discussion:__ OPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy. Trial registration:NTR4499. Registered on 7 April 2014

    The structure of emotion regulation strategies in adolescence: Differential links to internalizing and externalizing problems

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    Emotion regulation is a multi-modal construct, that includes both adaptive and maladaptive cognitive-behavioral processes. However, many classifications of regulation strategies do not take this multi-modality into account. In this study, two classification systems were integrated. Participants were 336 adolescents (56% boys, Mage = 15.41, SD = 1.45). Anger regulation strategies were measured with a questionnaire that assessed general strategies, and a vignette measure that assessed contextual strategies. Confirmatory factor analyses supported a 4-factor classification that consisted of cognitive maladaptive, behavioral maladaptive, cognitive adaptive, and behavioral adaptive strategies. The four categories of regulation strategies were differentially associated with age, and gender and psychological problem differences were found. Adolescents wit
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