1,089 research outputs found

    Magnetism and its microscopic origin in iron-based high-temperature superconductors

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    High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and Neˊ\rm \acute{e}el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic

    Visualizing peripheral nerve regeneration by whole mount staining.

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    Peripheral nerve trauma triggers a well characterised sequence of events both proximal and distal to the site of injury. Axons distal to the injury degenerate, Schwann cells convert to a repair supportive phenotype and macrophages enter the nerve to clear myelin and axonal debris. Following these events, axons must regrow through the distal part of the nerve, re-innervate and finally are re-myelinated by Schwann cells. For nerve crush injuries (axonotmesis), in which the integrity of the nerve is maintained, repair may be relatively effective whereas for nerve transection (neurotmesis) repair will likely be very poor as few axons may be able to cross between the two parts of the severed nerve, across the newly generated nerve bridge, to enter the distal stump and regenerate. Analysing axon growth and the cell-cell interactions that occur following both nerve crush and cut injuries has largely been carried out by staining sections of nerve tissue, but this has the obvious disadvantage that it is not possible to follow the paths of regenerating axons in three dimensions within the nerve trunk or nerve bridge. To try and solve this problem, we describe the development and use of a novel whole mount staining protocol that allows the analysis of axonal regeneration, Schwann cell-axon interaction and re-vascularisation of the repairing nerve following nerve cut and crush injuries

    Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis

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    To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Application of 3D Zernike descriptors to shape-based ligand similarity searching

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    Background: The identification of promising drug leads from a large database of compounds is an important step in the preliminary stages of drug design. Although shape is known to play a key role in the molecular recognition process, its application to virtual screening poses significant hurdles both in terms of the encoding scheme and speed. Results: In this study, we have examined the efficacy of the alignment independent three-dimensional Zernike descriptor (3DZD) for fast shape based similarity searching. Performance of this approach was compared with several other methods including the statistical moments based ultrafast shape recognition scheme (USR) and SIMCOMP, a graph matching algorithm that compares atom environments. Three benchmark datasets are used to thoroughly test the methods in terms of their ability for molecular classification, retrieval rate, and performance under the situation that simulates actual virtual screening tasks over a large pharmaceutical database. The 3DZD performed better than or comparable to the other methods examined, depending on the datasets and evaluation metrics used. Reasons for the success and the failure of the shape based methods for specific cases are investigated. Based on the results for the three datasets, general conclusions are drawn with regard to their efficiency and applicability

    TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities.

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    The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders. TMX2 encodes one of the five TMX proteins of the protein disulfide isomerase family, hitherto not linked to human developmental brain disease. Our mechanistic studies on protein function show that TMX2 localizes to the ER mitochondria-associated membranes (MAMs), is involved in posttranslational modification and protein folding, and undergoes physical interaction with the MAM-associated and ER folding chaperone calnexin and ER calcium pump SERCA2. These interactions are functionally relevant because TMX2-deficient fibroblasts show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity. Intriguingly, under basal conditions TMX2 occurs in both reduced and oxidized monomeric form, while it forms a stable dimer under treatment with hydrogen peroxide, recently recognized as a signaling molecule in neural morphogenesis and axonal pathfinding. Exogenous expression of the pathogenic TMX2 variants or of variants with an in vitro mutagenized TRX domain induces a constitutive TMX2 polymerization, mimicking an increased oxidative state. Altogether these data uncover TMX2 as a sensor in the MAM-regulated redox signaling pathway and identify it as a key adaptive regulator of neuronal proliferation, migration, and organization in the developing brain

    Changes in appetite, energy intake, body composition and circulating ghrelin constituents during an incremental trekking ascent to high altitude

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    Purpose Circulating acylated ghrelin concentrations are associated with altitude-induced anorexia in laboratory environments, but have never been measured at terrestrial altitude. This study examined time course changes in appetite, energy intake, body composition, and ghrelin constituents during a high-altitude trek. Methods Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m−2] completed a 14-day trek in the Himalayas. Energy intake, appetite perceptions, body composition, and circulating acylated, des-acylated, and total ghrelin concentrations were assessed at baseline (113 m, 12 days prior to departure) and at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10; 5140 m, day 12). Results Relative to baseline, energy intake was lower at 3619 m (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056). Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline. Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P = 0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des-acylated ghrelin concentrations did not significantly change during the trek (P = 0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P = 0.045). Skinfold thickness was lower at all points during the trek compared with baseline (P ≤ 0.001) and calf girth decreased incrementally during the trek (P = 0.010). Conclusions Changes in plasma acylated and total ghrelin concentrations may contribute to the suppression of appetite and energy intake at altitude, but differences in the time course of these responses suggest that additional factors are also involved. Interventions are required to maintain appetite and energy balance during trekking at terrestrial altitudes

    Predicting complete loss to follow-up after a health-education program: number of absences and face-to-face contact with a researcher

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    <p>Abstract</p> <p>Background</p> <p>Research on health-education programs requires longitudinal data. Loss to follow-up can lead to imprecision and bias, and <it>complete </it>loss to follow-up is particularly damaging. If that loss is predictable, then efforts to prevent it can be focused on those program participants who are at the highest risk. We identified predictors of complete loss to follow-up in a longitudinal cohort study.</p> <p>Methods</p> <p>Data were collected over 1 year in a study of adults with chronic illnesses who were in a program to learn self-management skills. Following baseline measurements, the program had one group-discussion session each week for six weeks. Follow-up questionnaires were sent 3, 6, and 12 months after the baseline measurement. A person was classified as completely lost to follow-up if none of those three follow-up questionnaires had been returned by two months after the last one was sent.</p> <p>We tested two hypotheses: that complete loss to follow-up was directly associated with the number of absences from the program sessions, and that it was less common among people who had had face-to-face contact with one of the researchers. We also tested predictors of data loss identified previously and examined associations with specific diagnoses.</p> <p>Using the unpaired t-test, the U test, Fisher's exact test, and logistic regression, we identified good predictors of complete loss to follow-up.</p> <p>Results</p> <p>The prevalence of complete loss to follow-up was 12.2% (50/409). Complete loss to follow-up was directly related to the number of absences (odds ratio; 95% confidence interval: 1.78; 1.49-2.12), and it was inversely related to age (0.97; 0.95-0.99). Complete loss to follow-up was less common among people who had met one of the researchers (0.51; 0.28-0.95) and among those with connective tissue disease (0.29; 0.09-0.98). For the multivariate logistic model the area under the ROC curve was 0.77.</p> <p>Conclusions</p> <p>Complete loss to follow-up after this health-education program can be predicted to some extent from data that are easy to collect (age, number of absences, and diagnosis). Also, face-to-face contact with a researcher deserves further study as a way of increasing participation in follow-up, and health-education programs should include it.</p

    Automatic Detection of Cyberbullying in Social Media Text

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    While social media offer great communication opportunities, they also increase the vulnerability of young people to threatening situations online. Recent studies report that cyberbullying constitutes a growing problem among youngsters. Successful prevention depends on the adequate detection of potentially harmful messages and the information overload on the Web requires intelligent systems to identify potential risks automatically. The focus of this paper is on automatic cyberbullying detection in social media text by modelling posts written by bullies, victims, and bystanders of online bullying. We describe the collection and fine-grained annotation of a training corpus for English and Dutch and perform a series of binary classification experiments to determine the feasibility of automatic cyberbullying detection. We make use of linear support vector machines exploiting a rich feature set and investigate which information sources contribute the most for this particular task. Experiments on a holdout test set reveal promising results for the detection of cyberbullying-related posts. After optimisation of the hyperparameters, the classifier yields an F1-score of 64% and 61% for English and Dutch respectively, and considerably outperforms baseline systems based on keywords and word unigrams.Comment: 21 pages, 9 tables, under revie
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