508 research outputs found

    Mass-Matching in Higgsless

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    Modern extra-dimensional Higgsless scenarios rely on a mass-matching between fermionic and bosonic KK resonances to evade constraints from precision electroweak measurements. After analyzing all of the Tevatron and LEP bounds on these so-called Cured Higgsless scenarios, we study their LHC signatures and explore how to identify the mass-matching mechanism, the key to their viability. We find singly and pair produced fermionic resonances show up as clean signals with 2 or 4 leptons and 2 hard jets, while neutral and charged bosonic resonances are visible in the dilepton and leptonic WZ channels, respectively. A measurement of the resonance masses from these channels shows the matching necessary to achieve S0S\simeq 0. Moreover, a large single production of KK-fermion resonances is a clear indication of compositeness of SM quarks. Discovery reach is below 10 fb1^{-1} of luminosity for resonances in the 700 GeV range.Comment: 28 pages, 18 figure

    A portable RNA sequence whose recognition by a synthetic antibody facilitates structural determination

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    RNA crystallization and phasing represent major bottlenecks in RNA structure determination. Seeking to exploit antibody fragments as RNA crystallization chaperones, we have used an arginine-enriched synthetic Fab library displayed on phage to obtain Fabs against the class I ligase ribozyme. We solved the structure of a Fab–ligase complex at 3.1-Å resolution using molecular replacement with Fab coordinates, confirming the ribozyme architecture and revealing the chaperone's role in RNA recognition and crystal contacts. The epitope resides in the GAAACAC sequence that caps the P5 helix, and this sequence retains high-affinity Fab binding within the context of other structured RNAs. This portable epitope provides a new RNA crystallization chaperone system that easily can be screened in parallel to the U1A RNA-binding protein, with the advantages of a smaller loop and Fabs′ high molecular weight, large surface area and phasing power.National Institutes of Health (U.S.) (GM61835

    The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

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    Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)

    Speaker- versus listener-oriented disfluency: A re-examination of arguments and assumptions from autism spectrum disorder

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    We re-evaluate conclusions about disfluency production in high-functioning forms of autism spectrum disorder (HFA). Previous studies examined individuals with HFA to address a theoretical question regarding speaker- and listener-oriented disfluencies. Individuals with HFA tend to be self-centric and have poor pragmatic language skills, and should be less likely to produce listener-oriented disfluency. However, previous studies did not account for individual differences variables that affect disfluency. We show that both matched and unmatched controls produce fewer repairs than individuals with HFA. For silent pauses, there was no difference between matched controls and HFA, but both groups produced more than unmatched controls. These results identify limitations in prior research and shed light on the relationship between autism spectrum disorders and disfluent speech

    Early-life predictors of resilience and related outcomes up to 66 years later in the 6-day sample of the 1947 Scottish mental survey.

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    PURPOSE: Psychological resilience, the ability to manage and quickly recover from stress and trauma, is associated with a range of health and wellbeing outcomes. Resilience is known to relate to personality, self-esteem and positive affect, and may also depend upon childhood experience and stress. In this study, we investigated the role of early-life contributors to resilience and related factors in later life. METHODS: We used data from the 6-day sample of the Scottish mental survey 1947, an initially representative sample of Scottish children born in 1936. They were assessed on a range of factors between the ages of 11 and 27 years, and resilience and other outcomes at 77 years. RESULTS: Higher adolescent dependability unexpectedly predicted lower resilience in older-age, as did childhood illnesses, while a count of specific stressors experienced throughout early life significantly predicted higher later-life resilience. We also observed significant cross-sectional correlations between resilience and measures of physical health, mental health, wellbeing and loneliness. Some of the associations between early-life predictors and later-life outcomes were significantly mediated by resilience. CONCLUSIONS: Our results support the hypothesis that stress throughout early life may help to build resilience in later-life, and demonstrate the importance of resilience as a mediator of other influences on health and wellbeing in older age. We suggest that the mechanisms determining how early-life stress leads to higher resilience are worthy of further investigation, and that psychological resilience should be a focus of research and a target for therapeutic interventions aiming to improve older-age health and wellbeing

    Recent development of allele frequencies and exclusion probabilities of microsatellites used for parentage control in the German Holstein Friesian cattle population

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    BACKGROUND: Methods for parentage control in cattle have changed since their initial implementation in the late 1950’s from blood group typing to more current single nucleotide polymorphism determination. In the early 1990’s, 12 microsatellites were selected by the International Society for Animal Genetics based on their informativeness and robustness in a variety of different cattle breeds. Since then this panel is used as standard in cattle herd book breeding and its application is accompanied by recurrent international comparison tests ensuring permanent validity for the most common commercial dairy and beef cattle breeds for example Holstein Friesian, Simmental, Angus, and Hereford. Although, nearly every parentage can be resolved using these microsatellites, cases with very close relatives became an emerging resolution problem during recent years. This is mainly due to an increase of monomorphism and a trend to the fixation of alleles, although no direct selection against their variability was applied. Thus other effects must be presumed resulting in a loss of polymorphism information content, heterozygosity, and exclusion probabilities. RESULTS: To determine changes of allele frequencies and exclusion probabilities, we analyzed the development of these parameters for the 12 microsatellites from 2004 to 2014. One hundred sixty eight thousand recorded Holstein Friesian cattle genotypes were evaluated. During this period certain alleles of nine microsatellites increased significantly (t-values >5). When calculating the exclusion probabilities for 11 microsatellites, reduction was determined for the three situations, i.e. one parent is wrongly identified (p = 0.01), both parents are wrongly identified (p = 0.005), and the genotype of one parent is missing (p = 0.048). With the addition of BM1818 to the marker set in 2009, this development was corrected leading to significant increases in exclusion probabilities. Although, the exclusion probabilities for the three family situations using the 12 microsatellites are >99 %, the clarification of 142 relationships in 40,000 situations where one parent is missing will still be impossible. Twenty-five sires were identified that are responsible for the most significant microsatellite allele increases in the population. The corresponding alleles are mainly associated with milk protein and fat yield, body weight at birth and weaning, as well as somatic cell score, milk fat percentage, and longissimus muscle area. CONCLUSIONS: Our data show that most of the microsatellites used for parentage control in cattle show directional changes in allele frequencies consistent with the history of artificial selection in the German Holstein population

    The Effects of Hydrogen Peroxide on the Circadian Rhythms of Microcystis aeruginosa

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    Background: The cyanobacterium Microcystis aeruginosa is one of the principal bloom-forming cyanobacteria present in a wide range of freshwater ecosystems. M. aeruginosa produces cyanotoxins, which can harm human and animal health. Many metabolic pathways in M. aeruginosa, including photosynthesis and microcystin synthesis, are controlled by its circadian rhythms. However, whether xenobiotics affect the cyanobacterial circadian system and change its growth, physiology and biochemistry is unknown. We used real-time PCR to study the effect of hydrogen peroxide (H2O2) on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD) cycle. Results: The results revealed that H 2O 2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA) and significantly decreases the transcript levels of kaiB, kaiC and sasA. H2O2 treatment also decreased the transcription of circadian genes, such as photosynthesis-related genes (psaB, psbD1 and rbcL) and microcystin-related genes (mcyA, mcyD and mcyH), and changed their circadian expression patterns. Moreover, the physiological functions of M. aeruginosa, including its growth and microcystin synthesis, were greatly influenced by H 2O 2 treatment during LD. These results indicate that changes in the cyanobacterial circadian system can affect its physiological and metabolic pathways. Conclusion: Our findings show that a xenobiotic can change the circadian expression patterns of its clock genes t

    Mutational Analysis of the Cyanobacterial Nitrogen Regulator PipX

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    PipX provides a functional link between the cyanobacterial global transcriptional regulator NtcA and the signal transduction protein PII, a protein found in all three domains of life as integrators of signals of the nitrogen and carbon balance. PipX, which is toxic in the absence of PII, can form alternative complexes with NtcA and PII and these interactions are respectively stimulated and inhibited by 2-oxoglutarate, providing a mechanism by which PII can modulate expression at the NtcA regulon. Structural information on PipX-NtcA complexes suggests that PipX coactivates NtcA controlled genes by stabilizing the active conformation of NtcA bound to 2-oxoglutarate and by possibly helping recruit RNA polymerase. To get insights into PipX functions, we perform here a mutational analysis of pipX informed by the structures of PipX-PII and PipX-NtcA complexes and evaluate the impact of point mutations on toxicity and gene expression. Two amino acid substitutions (Y32A and E4A) were of particular interest, since they increased PipX toxicity and activated NtcA dependent genes in vivo at lower 2-oxoglutarate levels than wild type PipX. While both mutations impaired complex formation with PII, only Y32A had a negative impact on PipX-NtcA interactions
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