1,320 research outputs found

    Electron Identification, Electronics Upgrades, And Electroweak Supersymmetry At Atlas

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    This thesis presents two searches for direct production of “electroweakinos”, the supersymmetric partner particles (“superpartners”) of the Standard Model photon, W, Z, and Higgs bosons. These searches were performed using 36 fb⁻¹ of √s = 13 TeV data collected by the ATLAS detector during Run 2 of the Large Hadron Collider (LHC). The first search focuses on a final state with three prompt leptons (electrons or muons) from on-shell W and Z bosons produced in decays of the electroweakinos. The second search focuses on compressed scenarios where the electroweakinos decay via off-shell W and Z bosons to pairs of leptons with small transverse momenta (pT). This second search allowed for the first exclusions of directly produced compressed Higgsinos at the LHC. In describing these searches, particular emphasis is placed on the estimation of backgrounds which mimic prompt leptons. This thesis also details the ATLAS electron identification algorithm, which distinguishes prompt electrons from backgrounds using a likelihood-based method. Significant improvements have been made to this algorithm during Run 2 including reoptimization of the selection criteria for new detector conditions, extension of the algorithm to a wider range of electron pT, and adaptation of the algorithm for the real-time selection of events. The corresponding measurements of the efficiencies for electron identification and other electron selection criteria are also described. Finally, readout electronics designed for upgrades to the ATLAS tracking system for use during the high-luminosity phase of the LHC are discussed. During this high-luminosity phase, an expected 3000 fb⁻¹ of data will be delivered to ATLAS. It is therefore essential to ensure that ATLAS will be able to efficiently operate and collect data despite the significant radiation damage it will receive. The expected performance of one readout chip (“AMAC”) is demonstrated via functionality and irradiation tests of several prototypes, and good performance is observed

    I Want To Learn From You: Relational Strategies To Engage Boys In School

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    The Role of Family and Friends in Return Migration and Its Labor Market Outcomes

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    Drawing on survey data on individuals’ motives for migration in Sweden (N = 2172), we examine the importance of family and friends for return versus onward migration, including their importance for different age groups and in different communities on the rural–urban spectrum. The results point to a significant relationship between the importance of family and return versus onward migration, with family importance decreasing with age among returning migrants. At the same time, the importance of friends for returning increases with age. The findings did not suggest a significant relationship between urbanicity and returning versus migration elsewhere. Based on a subset of respondents who were employed prior to migrating (n = 1056), we further examined labor market outcomes for onward versus returning migrants. The results broadly indicate that return migrations are linked to lower likelihoods of labor market deterioration and improvement, suggesting greater labor market stability for return vis-à-vis onward migrations. However, the importance of family for returning (versus moving elsewhere) is associated with higher likelihoods of labor market deterioration and improvement compared with staying the same, indicating greater volatility in labor market outcomes when the importance of family is considered

    A clickable analogue of ketamine retains NMDA receptor activity, psychoactivity, and accumulates in neurons

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    Ketamine is a psychotomimetic and antidepressant drug. Although antagonism of cell-surface NMDA receptors (NMDARs) may trigger ketamine’s psychoactive effects, ketamine or its major metabolite norketamine could act intracellularly to produce some behavioral effects. To explore the viability of this latter hypothesis, we examined intracellular accumulation of novel visualizable analogues of ketamine/norketamine. We introduced an alkyne “click” handle into norketamine (alkyne-norketamine, A-NK) at the key nitrogen atom. Ketamine, norketamine, and A-NK, but not A-NK-amide, showed acute and persisting psychoactive effects in mice. This psychoactivity profile paralleled activity of the compounds as NMDAR channel blockers; A-NK-amide was inactive at NMDARs, and norketamine and A-NK were active but ~4-fold less potent than ketamine. We incubated rat hippocampal cells with 10 μM A-NK or A-NK-amide then performed Cu(2+) catalyzed cycloaddition of azide-Alexa Fluor 488, which covalently attaches the fluorophore to the alkyne moiety in the compounds. Fluorescent imaging revealed intracellular localization of A-NK but weak A-NK-amide labeling. Accumulation was not dependent on membrane potential, NMDAR expression, or NMDAR activity. Overall, the approach revealed a correlation among NMDAR activity, intracellular accumulation/retention, and behavioral effects. Thus, we advance first generation chemical biology tools to aid in the identification of ketamine targets

    Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT

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    <p>Abstract</p> <p>Background</p> <p>It has previously been shown that specific microdeletions and microduplications, many of which also associated with cognitive impairment (CI), can present with autism spectrum disorders (ASDs). Multiplex ligation-dependent probe amplification (MLPA) represents an efficient method to screen for such recurrent microdeletions and microduplications.</p> <p>Methods</p> <p>In the current study, a total of 279 unrelated subjects ascertained for ASDs were screened for genomic disorders associated with CI using MLPA. Fluorescence in situ hybridization (FISH), quantitative polymerase chain reaction (Q-PCR) and/or direct DNA sequencing were used to validate potential microdeletions and microduplications. Methylation-sensitive MLPA was used to characterize individuals with duplications in the Prader-Willi/Angelman (PWA) region.</p> <p>Results</p> <p>MLPA showed two subjects with typical ASD-associated interstitial duplications of the 15q11-q13 PWA region of maternal origin. Two additional subjects showed smaller, <it>de novo </it>duplications of the PWA region that had not been previously characterized. Genes in these two novel duplications include <it>GABRB3 </it>and <it>ATP10A </it>in one case, and <it>MKRN3</it>, <it>MAGEL2 </it>and <it>NDN </it>in the other. In addition, two subjects showed duplications of the 22q11/DiGeorge syndrome region. One individual was found to carry a 12 kb deletion in one copy of the <it>ASPA </it>gene on 17p13, which when mutated in both alleles leads to Canavan disease. Two subjects showed partial duplication of the <it>TM4SF2 </it>gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. A partial duplication in the <it>ASMT </it>gene, located in the pseudoautosomal region 1 (PAR1) of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6–7% of the cases but in only 2% of controls (P = 0.003).</p> <p>Conclusion</p> <p>MLPA proves to be an efficient method to screen for chromosomal abnormalities. We identified duplications in 15q11-q13 and in 22q11, including new <it>de novo </it>small duplications, as likely contributing to ASD in the current sample by increasing liability and/or exacerbating symptoms. Our data indicate that duplications in <it>TM4SF2</it> are not associated with the phenotype given their presence in controls. The results in PAR1/PAR2 are the first large-scale studies of gene dosage in these regions, and the findings at the <it>ASMT </it>locus indicate that further studies of the duplication of the <it>ASMT </it>gene are needed in order to gain insight into its potential involvement in ASD. Our studies also identify some limitations of MLPA, where single base changes in probe binding sequences alter results. In summary, our studies indicate that MLPA, with a focus on accepted medical genetic conditions, may be an inexpensive method for detection of microdeletions and microduplications in ASD patients for purposes of genetic counselling if MLPA-identified deletions are validated by additional methods.</p

    Quasi-three-level Model Applied to Measured Spectra of Nonlinear Absorption and Refraction in Organic Molecules

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    Materials with a large nonlinear refractive index (2) and relatively small linear and nonlinear absorption losses, namely, two-photon absorption (2PA, of coefficient 2), have long been sought after for applications such as all-optical switching (AOS). Here we experimentally determine the linear and 2PA properties of several organic molecules, which we approximate as centrosymmetric, and use a simplified essential-state model (quasi-three-level model) to predict the dispersion of 2. We then compare these predictions with experimental measurements of 2 and find good agreement. Here “quasi”-three-level means using a single one-photon allowed intermediate state and multiple (here two) two-photon allowed states. This also allows predictions of the figure-of-merit (FOM), defined as the ratio of nonlinear refractive phase shift to the 2PA fractional loss, that determines the viability for such molecules to be used in device applications. The model predicts that the optimized wavelength range for a large FOM lies near the short wavelength linear absorption edge for cyanine-like dyes where the magnitude of 2 is quite large. However, 2PA bands lying close to the linear absorption edge in certain classes of molecules can greatly reduce this FOM. We identify two molecules having a large FOM for AOS. We note that the FOM is often defined as the ratio of real to imaginary parts of the third-order susceptibility ((3)) with multiple processes leading to both components. As explained later in this paper, such definitions require care to only include the 2PA contribution to the imaginary part of (3) in regions of transparency.Abstract © 2016 Optical Society of Americ

    Hand to Mouth: A Systematic Review and Meta-Analysis of the Association between Rheumatoid Arthritis and Periodontitis

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    Background: Rheumatoid arthritis (RA) and periodontitis are both chronic inflammatory diseases, which demonstrate similarities in terms of mechanism, histopathology, and demography. An association between these conditions has been demonstrated previously but has been called into question more recently. Methods: The published databases, such as MEDLINE, EMBASE, and PsycINFO, were searched using search terms related to RA and periodontitis. Articles were selected if they included data on the number of people with RA diagnosed with periodontitis (or periodontal disease parameters) compared to a control comparison group. Review articles, case reports, animal model studies, non-English language, and articles with unavailable abstracts were excluded. Data were extracted, critically appraised using the Downs and Black tool, and a random-effect Mantel–Haenszel meta-analysis was performed. Results: Twenty-one papers met the eligibility criteria and provided data for the meta-analysis; 17 studies (including a total of 153,492 participants) comparing RA to healthy controls and 4 (including a total of 1378 participants) comparing RA to osteoarthritis (OA). There was a significantly increased risk of periodontitis in people with RA compared to healthy controls (relative risk: 1.13; 95% CI: 1.04, 1.23; p = 0.006; N = 153,277) with a significantly raised mean probing depth, risk of bleeding on probing (BOP), and absolute value of clinical attachment loss in those with RA. When comparing RA and OA, there was no significant difference in the prevalence of periodontitis; however, the risk of BOP was greater in OA than RA. Conclusion: A significant association between RA and periodontitis is supported by the results of our systematic review and meta-analysis of studies comparing RA to healthy controls. In our meta-analysis, however, this is not replicated when comparing RA to OA controls
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