143 research outputs found

    Singlet Portal to the Hidden Sector

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    Ultraviolet physics typically induces a kinetic mixing between gauge singlets which is marginal and hence non-decoupling in the infrared. In singlet extensions of the minimal supersymmetric standard model, e.g. the next-to-minimal supersymmetric standard model, this furnishes a well motivated and distinctive portal connecting the visible sector to any hidden sector which contains a singlet chiral superfield. In the presence of singlet kinetic mixing, the hidden sector automatically acquires a light mass scale in the range 0.1 - 100 GeV induced by electroweak symmetry breaking. In theories with R-parity conservation, superparticles produced at the LHC invariably cascade decay into hidden sector particles. Since the hidden sector singlet couples to the visible sector via the Higgs sector, these cascades necessarily produce a Higgs boson in an order 0.01 - 1 fraction of events. Furthermore, supersymmetric cascades typically produce highly boosted, low-mass hidden sector singlets decaying visibly, albeit with displacement, into the heaviest standard model particles which are kinematically accessible. We study experimental constraints on this broad class of theories, as well as the role of singlet kinetic mixing in direct detection of hidden sector dark matter. We also present related theories in which a hidden sector singlet interacts with the visible sector through kinetic mixing with right-handed neutrinos.Comment: 12 pages, 5 figure

    Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

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    Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

    Low-Energy Signals from Kinetic Mixing with a Warped Abelian Hidden Sector

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    We investigate the detailed phenomenology of a light Abelian hidden sector in the Randall-Sundrum framework. Relative to other works with light hidden sectors, the main new feature is a tower of hidden Kaluza-Klein vectors that kinetically mix with the Standard Model photon and Z. We investigate the decay properties of the hidden sector fields in some detail, and develop an approach for calculating processes initiated on the ultraviolet brane of a warped space with large injection momentum relative to the infrared scale. Using these results, we determine the detailed bounds on the light warped hidden sector from precision electroweak measurements and low-energy experiments. We find viable regions of parameter space that lead to significant production rates for several of the hidden Kaluza-Klein vectors in meson factories and fixed-target experiments. This offers the possibility of exploring the structure of an extra spacetime dimension with lower-energy probes.Comment: (1+32) Pages, 13 Figures. v2: JHEP version (minor modifications, results unchanged

    Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

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    The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

    How residents and interns utilise and perceive the personal digital assistant and UpToDate

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    <p>Abstract</p> <p>Background</p> <p>In this era of evidence-based medicine, doctors are increasingly using information technology to acquire medical knowledge. This study evaluates how residents and interns utilise and perceive the personal digital assistant (PDA) and the online resource UpToDate.</p> <p>Methods</p> <p>This is a questionnaire survey of all residents and interns in a tertiary teaching hospital.</p> <p>Results</p> <p>Out of 168 doctors, 134 (79.8%) responded to the questionnaire. Only 54 doctors (40.3%) owned a PDA. Although these owners perceived that the PDA was most useful for providing drug information, followed by medical references, scheduling and medical calculators, the majority of them did not actually have medical software applications downloaded on their PDAs. The greatest concerns highlighted for the PDA were the fear of loss and breakage, and the preference for working with desktop computers and paper. Meanwhile, only 76 doctors (56.7%) used UpToDate, even though the hospital had an institutional subscription for it. Although 93.4% of these users would recommend UpToDate to a colleague, only 57.9% stated that the use of UpToDate had led to a change in their management of patients.</p> <p>Conclusion</p> <p>Although UpToDate and various PDA software applications were deemed useful by some of the residents and interns in our study, both digital tools were under-utilised. More should be done to facilitate the use of medical software applications on PDAs, to promote awareness of tools for evidence-based medicine such as UpToDate, and to facilitate the application of evidence-based medicine in daily clinical practice.</p

    Patient and caregiver perspectives on blood pressure in children with chronic kidney disease

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    Background: More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care. / Methods: Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology—Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8–21 years) and caregivers (of children ages 0–21 years) pertaining to blood pressure. / Results: Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects). / Conclusions: For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD

    Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion

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    Membrane fusion is the core process in membrane trafficking and is essential for cellular transport of proteins and other biomacromolecules. During protein-mediated membrane fusion, membrane proteins are often excluded from the membrane-membrane contact, indicating that local structural transformations in lipid domains play a major role. However, the rearrangements of lipid domains during fusion have not been thoroughly examined. Here using a newly developed Fluorescence Surface Forces Apparatus (FL-SFA), migration of liquid-disordered clusters and depletion of liquid-ordered domains at the membrane-membrane contact are imaged in real time during hemifusion of model lipid membranes, together with simultaneous force-distance and lipid membrane thickness measurements. The load and contact time-dependent hemifusion results show that the domain rearrangements decrease the energy barrier to fusion, illustrating the significance of dynamic domain transformations in membrane fusion processes. Importantly, the FL-SFA can unambiguously correlate interaction forces and in situ imaging in many dynamic interfacial systems.open0

    Secluded Dark Matter Coupled to a Hidden CFT

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    Models of secluded dark matter offer a variant on the standard WIMP picture and can modify our expectations for hidden sector phenomenology and detection. In this work we extend a minimal model of secluded dark matter, comprised of a U(1)'-charged dark matter candidate, to include a confining hidden-sector CFT. This provides a technically natural explanation for the hierarchically small mediator-scale, with hidden-sector confinement generating m_{gamma'}>0. Furthermore, the thermal history of the universe can differ markedly from the WIMP picture due to (i) new annihilation channels, (ii) a (potentially) large number of hidden-sector degrees of freedom, and (iii) a hidden-sector phase transition at temperatures T << M_{dm} after freeze out. The mediator allows both the dark matter and the Standard Model to communicate with the CFT, thus modifying the low-energy phenomenology and cosmic-ray signals from the secluded sector.Comment: ~50p, 8 figs; v2 JHEP versio
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