One-loop Corrections to the S Parameter in the Four-site Model

We compute the leading chiral-logarithmic corrections to the S parameter in the four-site Higgsless model. In addition to the usual electroweak gauge bosons of the Standard Model, this model contains two sets of heavy charged and neutral gauge bosons. In the continuum limit, the latter gauge bosons can be identified with the first excited Kaluza-Klein states of the W^\pm and Z bosons of a warped extra-dimensional model with an SU(2)_L \times SU(2)_R \times U(1)_X bulk gauge symmetry. We consider delocalized fermions and show that the delocalization parameter must be considerably tuned from its tree-level ideal value in order to reconcile experimental constraints with the one-loop results. Hence, the delocalization of fermions does not solve the problem of large contributions to the S parameter in this class of theories and significant contributions to S can potentially occur at one-loop.Comment: 28 pages, 7 figure

Hiding the Higgs Boson with Multiple Scalars

We consider models with multiple Higgs scalar gauge singlets and the resulting restrictions on the parameters from precision electroweak measurements. In these models, the scalar singlets mix with the SU(2) Higgs doublet, potentially leading to reduced couplings of the scalars to fermions and gauge bosons relative to the Standard Model Higgs boson couplings. Such models can make the Higgs sector difficult to explore at the LHC. We emphasize the new physics resulting from the addition of at least two scalar Higgs singlets.Comment: 13 page

Discovering the Higgs Bosons of Minimal Supersymmetry with Muons and a Bottom Quark

We investigate the prospects for the discovery at the CERN Large Hadron Collider of a neutral Higgs boson produced with one bottom quark followed by Higgs decay into a muon pair. We work within the framework of the minimal supersymmetric model. The dominant physics background from the production of $b \mu^+\mu^-$, $j\mu^+\mu^-$, j=g,u,d,s,c, and $b {\bar b} W^+W^-$ is calculated with realistic acceptance cuts. Promising results are found for the CP-odd pseudoscalar ($A^0$) and the heavier CP-even scalar ($H^0$) Higgs bosons with masses up to 600 GeV. This discovery channel with one energetic bottom quark greatly improves the discovery potential of the LHC beyond the inclusive channel $pp\to \phi^0\to \mu^+\mu^- +X$.Comment: Version to appear in Phys. Rev. Let

SUSY QCD Corrections to Higgs Pair Production from Bottom Quark Fusion

We present a complete next-to-leading order (NLO) calculation for the total cross section for inclusive Higgs pair production via bottom-quark fusion at the CERN Large Hadron Collider (LHC) in the minimal supersymmetric standard model (MSSM) and the minimal supergravity model (mSUGRA). We emphasize the contributions of squark and gluino loops (SQCD) and the decoupling properties of our results for heavy squark and gluino masses. The enhanced couplings of the b quark to the Higgs bosons in supersymmetric models with large tanb yield large NLO SQCD corrections in some regions of parameter space.Comment: 24 pages, 10 figure

An emerging role for stress granules in neurodegenerative disease and hearing loss

Stress granules (SGs) are membrane-less cytosolic assemblies that form in response to stress (e.g., heat, oxidative stress, hypoxia, viral infection and UV). Composed of mRNA, RNA binding proteins and signalling proteins, SGs minimise stress-related damage and promote cell survival. Recent research has shown that the stress granule response is vital to the cochlea's response to stress. However, emerging evidence suggests stress granule dysfunction plays a key role in the pathophysiology of multiple neurodegenerative diseases, several of which present with hearing loss as a symptom. Hearing loss has been identified as the largest potentially modifiable risk factor for dementia. The underlying reason for the link between hearing loss and dementia remains to be established. However, several possible mechanisms have been proposed including a common pathological mechanism. Here we will review the role of SGs in the pathophysiology of neurodegenerative diseases and explore possible links and emerging evidence that they may play an important role in maintenance of hearing and may be a common mechanism underlying age-related hearing loss and dementia

Drug-induced stress granule formation protects sensory hair cells in mouse cochlear explants during ototoxicity

Stress granules regulate RNA translation during cellular stress, a mechanism that is generally presumed to be protective, since stress granule dysregulation caused by mutation or ageing is associated with neurodegenerative disease. Here, we investigate whether pharmacological manipulation of the stress granule pathway in the auditory organ, the cochlea, affects the survival of sensory hair cells during aminoglycoside ototoxicity, a common cause of acquired hearing loss. We show that hydroxamate (-)-9, a silvestrol analogue that inhibits eIF4A, induces stress granule formation in both an auditory cell line and ex-vivo cochlear cultures and that it prevents ototoxin-induced hair-cell death. In contrast, preventing stress granule formation using the small molecule inhibitor ISRIB increases hair-cell death. Furthermore, we provide the first evidence of stress granule formation in mammalian hair cells in-vivo triggered by aminoglycoside treatment. Our results demonstrate that pharmacological induction of stress granules enhances cell survival in native-tissue, in a clinically-relevant context. This establishes stress granules as a viable therapeutic target not only for hearing loss but also other neurodegenerative diseases.EI:595 - Action on Hearing Loss; 091092/Z/09/Z - Wellcome Trust (Wellcome); MR/N004329/1 - RCUK | Medical Research Council (MRC)Published versio

The ototoxic drug cisplatin localises to stress granules altering their dynamics and composition

Cisplatin is an effective platinum-based chemotherapeutic with several side effects, including ototoxicity. Cochlear cells have low rates of proliferation yet are highly susceptible to cisplatin. We hypothesized that cisplatin ototoxicity may be caused by cisplatin-protein interactions rather than cisplatin-DNA interactions. Two known cisplatin-binding proteins are involved in the stress granule (SG) response. SGs are a pro-survival mechanism involving formation of transient ribonucleoprotein complexes during stress. We examined the effects of cisplatin on SG dynamics and composition in cell lines derived from the cochlea and retinal pigment epithelium. Cisplatin-induced SGs are significantly diminished in size and quantity compared to arsenite-induced SGs and are persistent after 24 hours recovery. Additionally, cisplatin pre-treated cells were unable to form a typical SG response to subsequent arsenite stress. Cisplatin-induced SGs had significant reductions in the sequestration of eIF4G and proteins RACK1 and DDX3X. Live cell imaging of cisplatin-TR revealed localisation to SGs and retention for at least 24 hours. We show cisplatin-induced SGs have impaired assembly, altered composition and are persistent, providing evidence of an alternate mechanism for cisplatin-induced ototoxicity via an impaired SG response

Discrimination, labour markets and the Labour Market Prospects of Older Workers: What Can a Legal Case Teach us?

As governments become increasingly concerned about the fiscal implications of the ageing population, labour market policies have sought to encourage mature workers to remain in the labour force. The ‘human capital’ discourses motivating these policies rest on the assumption that older workers armed with motivation and vocational skills will be able to return to fulfilling work. This paper uses the post-redundancy recruitment experiences of former Ansett Airlines flight attendants to develop a critique of these expectations. It suggests that policies to increase older workers’ labour market participation will not succeed while persistent socially constructed age- and gender- typing shape labour demand. The conclusion argues for policies sensitive to the institutional structures that shape employer preferences, the competitive rationality of discriminatory practices, and the irresolvable tension between workers’ human rights and employers’ property rights

Safe and just operating spaces for regional social-ecological systems

Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockström et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development