A Shift Symmetry in the Higgs Sector: Experimental Hints and Stringy Realizations

We interpret reported hints of a Standard Model Higgs boson at ~ 125 GeV in terms of high-scale supersymmetry breaking with a shift symmetry in the Higgs sector. More specifically, the Higgs mass range suggested by recent LHC data extrapolates, within the (non-supersymmetric) Standard Model, to a vanishing quartic Higgs coupling at a UV scale between 10^6 and 10^18 GeV. Such a small value of lambda can be understood in terms of models with high-scale SUSY breaking if the Kahler potential possesses a shift symmetry, i.e., if it depends on H_u and H_d only in the combination (H_u+\bar{H}_d). This symmetry is known to arise rather naturally in certain heterotic compactifications. We suggest that such a structure of the Higgs Kahler potential is common in a wider class of string constructions, including intersecting D7- and D6-brane models and their extensions to F-theory or M-theory. The latest LHC data may thus be interpreted as hinting to a particular class of compactifications which possess this shift symmetry.Comment: v2: References added. v3: References added, published versio

Analysing public service outsourcing: the value of a regulatory perspective

This article draws on findings from two longitudinal case studies of voluntary organisations engaged in delivering social care services via purchaser – provider relations with local authorities. The study focuses on changes to contractual relations, employment conditions in provider organisations and service quality. The article argues the influence of the market on these changes can only be adequately comprehended by rooting the analysis in an understanding of the way in which surrounding regulatory frameworks shape its structure and operation. In doing so, it reveals how in an era of shifting market conditions characterised by greater competition and dramatic local authority cuts, a ‘soft’ regulatory framework offers little support to partnership relations between voluntary organisations and local authorities. Instead, the regulatory environment undermines financial security among voluntary organisations, degrades employment conditions in them and raises concerns regarding their service quality

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Policy mixes for incumbency: the destructive recreation of renewable energy, shale gas 'fracking,' and nuclear power in the United Kingdom

The notion of a ‘policy mix’ can describe interactions across a wide range of innovation policies, including ‘motors for creation’ as well as for ‘destruction’. This paper focuses on the United Kingdom’s (UK) ‘new policy direction’ that has weakened support for renewables and energy efficiency schemes while strengthening promotion of nuclear power and hydraulic fracturing for natural gas (‘fracking’). The paper argues that a ‘policy apparatus for incumbency’ is emerging which strengthens key regimebased technologies while arguably damaging emerging niche innovations. Basing the discussion around the three technology-based cases of renewable energy and efficiency, fracking, and nuclear power, this paper refers to this process as “destructive recreation”. Our study raises questions over the extent to which policymaking in the energy field is not so much driven by stated aims around sustainability transitions, as by other policy drivers. It investigates different ‘strategies of incumbency’ including ‘securitization’, ‘masking’, ‘reinvention’, and ‘capture.’ It suggests that analytical frameworks should extend beyond the particular sectors in focus, with notions of what counts as a relevant ‘policy maker’ correspondingly also expanded, in order to explore a wider range of nodes and critical junctures as entry points for understanding how relations of incumbency are forged and reproduced

Generation and Characterization of a genetic zebrafish model of SMA carrying the human SMN2 gene

<p>Abstract</p> <p>Background</p> <p>Animal models of human diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of spinal muscular atrophy (SMA) in the vertebrate zebrafish to complement existing zebrafish, mouse, and invertebrate models and show its utility for testing compounds that alter <it>SMN2 </it>splicing.</p> <p>Results</p> <p>The human motoneuron disease SMA is caused by low levels, as opposed to a complete absence, of the survival motor neuron protein (SMN). To generate a true model of SMA in zebrafish, we have generated a transgenic zebrafish expressing the human <it>SMN2 </it>gene (<it>hSMN2</it>), which produces only a low amount of full-length SMN, and crossed this onto the <it>smn</it>^-/-background. We show that human <it>SMN2 </it>is spliced in zebrafish as it is in humans and makes low levels of SMN protein. Moreover, we show that an antisense oligonucleotide that enhances correct <it>hSMN2 </it>splicing increases full-length <it>hSMN </it>RNA in this model. When we placed this transgene on the <it>smn </it>mutant background it rescued the neuromuscular presynaptic SV2 defect that occurs in <it>smn </it>mutants and increased their survival.</p> <p>Conclusions</p> <p>We have generated a transgenic fish carrying the human <it>hSMN2 </it>gene. This gene is spliced in fish as it is in humans and mice suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length SMN generated from this transgene. Having this transgene on the <it>smn </it>mutant fish rescued the presynaptic defect and increased survival. This model of zebrafish SMA has all of the components of human SMA and can thus be used to understand motoneuron dysfunction in SMA, can be used as an vivo test for drugs or antisense approaches that increase full-length SMN, and can be developed for drug screening.</p

The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase

Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Contralateral hip fractures and other osteoporosis-related fractures in hip fracture patients: Incidence and risk factors. An observational cohort study of 1,229 patients

Purpose: To report risk factors, 1-year and overall risk for a contralateral hip and other osteoporosis-related fractures in a hip fracture population. Methods: An observational study on 1,229 consecutive patients of 50 years and older, who sustained a hip fracture between January 2005 and June 2009. Fractures were scored retrospectively for 2005-2008 and prospectively for 2008-2009. Rates of a contralateral hip and other osteoporosis- related fractures were compared between patients with and without a history of a fracture. Previous fractures, gender, age and ASA classification were analysed as possible risk factors. Results: The absolute risk for a contralateral hip fracture was 13.8 %, for one or more osteoporosis-related fracture( s) 28.6 %. First-, second- and third-year risk for a second hip fracture was 2, 1 and 0 %. Median (IQR) interval between both hip fractures was 18.5 (26.6) months. One-year incidence of other fractures was 6 %. Only age was a risk factor for a contralateral hip fracture, hazard ratio (HR) 1.02 (1.006-1.042, p = 0.008). Patients with a history of a fracture (33.1 %) did not have a higher incidence of fractures during follow-up (16.7 %) than patients without fractures in their history (14 %). HR for a contralateral hip fracture for the fracture versus the non-fracture group was 1.29 (0.75-2.23, p = 0.360). Conclusion: The absolute risk of a contralateral hip fracture after a hip fracture is 13.8 %, the 1-year risk was 2 %, with a short interval between the 2 hip fractures. Age was a risk factor for sustaining a contralateral hip fracture; a fracture in history was not

Mice lacking endoglin in macrophages show an impaired immune response

24 p.-9 fig.-1 tab. Ojeda Fernández, Luisa et al.Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-OslerWeber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Engfl/flLysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Engfl/flLysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients.This work was funded by: Ministerio de Economía y Competitividad of Spain (SAF2011-23475 to LMB; SAF2013-43421-R and SAF2010- 19222 to CB.Peer reviewe

Abnormal septal convexity into the left ventricle occurs in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point. RESULTS: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls. CONCLUSIONS: Septal convexity is an additional previously undescribed feature of subclinical HCM