Solitonic supersymmetry restoration

Q-balls are a possible feature of any model with a conserved, global U(1) symmetry and no massless, charged scalars. It is shown that for a broad class of models of metastable supersymmetry breaking they are extremely influential on the vacuum lifetime and make seemingly viable vacua catastrophically short lived. A net charge asymmetry is not required as there is often a significant range of parameter space where statistical fluctuations alone are sufficient. This effect is examined for two supersymmetry breaking scenarios. It is found that models of minimal gauge mediation (which necessarily have a messenger number U(1)) undergo a rapid, supersymmetry restoring phase transition unless the messenger mass is greater than 10^8 GeV. Similarly the ISS model, in the context of direct mediation, quickly decays unless the perturbative superpotential coupling is greater than the Standard Model gauge couplings.Comment: 17 pages, 3 figures, minor comments added, accepted for publication in JHE

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

Pharmacists in general practice: a qualitative interview case study of stakeholders’ experiences in a West London GP Federation

Background Increased patient demand for healthcare services coupled with a shortage of general practitioners necessitates changes in professional roles and service delivery. In 2016, NHS England began a three year pilot study of pharmacists in general practice, however, this is not an entirely new initiative. There is limited, current, evidence-based, UK research to inform the pilot so studies of pre-existing services must suffice until findings from a formal national evaluation are available. Methods The aim of this exploratory, descriptive interview study was to explore the experiences of stakeholders in eight general practices in the Ealing GP Federation, West London, where pharmacy services have been provided for several years. Forty-seven participants, including pharmacy team members (pre-registration and clinical pharmacists, independent prescribers and pharmacy technicians), general practitioners, patients, practice managers, practice nurses and receptionists took part in semi-structured, audio-recorded qualitative interviews which were transcribed verbatim, coded and analysed thematically to extract the issues raised by participants and the practicalities of providing pharmacy services in general practice. Results Findings are reported under the themes of Complementarity (incorporating roles, skills, education and workloads); Integration (incorporating relationships, trust and communication) and Practicalities (incorporating location and space, access, and costs). Participants reported the need for time to develop and understand the various roles, develop communication processes and build inter-professional trust. Once these were established, however, experiences were positive and included decreased workloads, increased patient safety, improved job satisfaction, improved patient relationships, and enhanced cost savings. Areas for improvement included patients’ awareness of services; pharmacists’ training; and regular, onsite access for practice staff to the pharmacy team. Conclusions Recommendations are made for the development of clear role definitions, identification of training needs, dedication of time for team building, production of educational materials for practice staff members and patients, and provision of on-site, full-time pharmacy services. Future work should focus on evaluation of various models of employing pharmacy teams in general practice; integration of pharmacists and pharmacy technicians into multidisciplinary general practice teams; relationships between local community pharmacy and general practice personnel and patients’ service and information needs. A formal national evaluation of the pilot scheme is overdue

Higgs Portal to Visible Supersymmetry Breaking

We propose a supersymmetric extension of the standard model whose Higgs sector induces a spontaneous supersymmetry breaking by itself. Unlike the minimal extension, the current Higgs mass bound can be evaded even at the tree-level without the help of the soft breaking terms due to the usual hidden sector, as is reminiscent of the next to minimal case. We also have a possibly light pseudo-goldstino in our visible sector in addition to extra Higgs particles, both of which stem from supersymmetry breaking dynamics. In such a setup of visible supersymmetry breaking, we may see a part of supersymmetry breaking dynamics rather directly in future experiments.Comment: 23 pages, 6 figures, references adde

Regulation of ErbB2 Receptor Status by the Proteasomal DUB POH1

Understanding the factors, which control ErbB2 and EGF receptor (EGFR) status in cells is likely to inform future therapeutic approaches directed at these potent oncogenes. ErbB2 is resistant to stimulus-induced degradation and high levels of over-expression can inhibit EGF receptor down-regulation. We now show that for HeLa cells expressing similar numbers of EGFR and ErbB2, EGFR down-regulation is efficient and insensitive to reduction of ErbB2 levels. Deubiquitinating enzymes (DUBs) may extend protein half-lives by rescuing ubiquitinated substrates from proteasomal degradation or from ubiquitin-dependent lysosomal sorting. Using a siRNA library directed at the full complement of human DUBs, we identified POH1 (also known as Rpn11 or PSMD14), a component of the proteasome lid, as a critical DUB controlling the apparent ErbB2 levels. Moreover, the effects on ErbB2 levels can be reproduced by administration of proteasomal inhibitors such as epoxomicin used at maximally tolerated doses. However, the extent of this apparent loss and specificity for ErbB2 versus EGFR could not be accounted for by changes in transcription or degradation rate. Further investigation revealed that cell surface ErbB2 levels are only mildly affected by POH1 knock-down and that the apparent loss can at least partially be explained by the accumulation of higher molecular weight ubiquitinated forms of ErbB2 that are detectable with an extracellular but not intracellular domain directed antibody. We propose that POH1 may deubiquitinate ErbB2 and that this activity is not necessarily coupled to proteasomal degradation

Prostaglandin E2 Reverses Aberrant Production of an Inflammatory Chemokine by Microglia from Sandhoff Disease Model Mice through the cAMP-PKA Pathway

Background: Sandhoff disease (SD) is a neurodegenerative lysosomal b-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including terminal GlcNAc-oligosaccharides and GM2 ganglioside. Microglia-mediated neuroinflammation contributes to the pathogenesis and progression of SD. Our previous study demonstrated that MIP-1a, a putative pathogenic factor for SD, is up-regulated in microglial cells derived from SD model mice (SD-Mg) through activation of Akt and JNK. Methodology/Principal Findings: In this study, we first demonstrated that prostaglandin E2 (PGE2), which is one of the lipid mediators derived from arachidonic acid and is known to suppress activation of microglia, reduced the aberrant MIP-1a production by SD-Mg to the same level as by WT-Mg. PGE2 also attenuated the activation of Akt and JNK. The inhibition of MIP-1a production and the activation of Akt and JNK occurred through the EP2 and 4/cAMP/PKA signaling pathway in the murine microglia derived from SD model mice. Conclusions/Significance: We propose that PGE2 plays a role as a negative regulator of MIP-1a production in th

Malaria and Helminth Co-infections in School and Preschool Children: A Cross-sectional Study in Magu district, north-Western Tanzania.

Malaria, schistosomiasis and soil transmitted helminth infections (STH) are important parasitic infections in Sub-Saharan Africa where a significant proportion of people are exposed to co-infections of more than one parasite. In Tanzania, these infections are a major public health problem particularly in school and pre-school children. The current study investigated malaria and helminth co-infections and anaemia in school and pre-school children in Magu district, Tanzania. School and pre-school children were enrolled in a cross-sectional study. Stool samples were examined for Schistosoma mansoni and STH infections using Kato Katz technique. Urine samples were examined for Schistosoma haematobium using the urine filtration method. Blood samples were examined for malaria parasites and haemoglobin concentrations using the Giemsa stain and Haemoque methods, respectively. Out of 1,546 children examined, 1,079 (69.8%) were infected with one or more parasites. Malaria-helminth co-infections were observed in 276 children (60% of all children with P. falciparum infection). Malaria parasites were significantly more prevalent in hookworm infected children than in hookworm free children (p = 0.046). However, this association was non-significant on multivariate logistic regression analysis (OR = 1.320, p = 0.064). Malaria parasite density decreased with increasing infection intensity of S. mansoni and with increasing number of co-infecting helminth species. Anaemia prevalence was 34.4% and was significantly associated with malaria infection, S. haematobium infection and with multiple parasite infections. Whereas S. mansoni infection was a significant predictor of malaria parasite density, P. falciparum and S. haematobium infections were significant predictors of anaemia. These findings suggest that multiple parasite infections are common in school and pre-school children in Magu district. Concurrent P. falciparum, S. mansoni and S. haematobium infections increase the risk of lower Hb levels and anaemia, which in turn calls for integrated disease control interventions. The associations between malaria and helminth infections detected in this study need further investigation

Vitamin D and breast cancer: interpreting current evidence

Preclinical investigations and selected clinical observational studies support an association between higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk. However, the recently updated report from the Institute of Medicine concluded that, for cancer and vitamin D, the evidence was 'inconsistent and insufficient to inform nutritional requirements'. Against this background, reports examining vitamin D intake, 25-hydroxyvitamin D levels and breast cancer incidence and outcome were reviewed. Current evidence supports the pursuit of several research questions but not routine 25-hydroxyvitamin D monitoring and vitamin D supplementation to reduce breast cancer incidence or improve breast cancer outcome