171 research outputs found
Complementarity of Dark Matter Searches at Resonance
We consider models of dark matter where the couplings between the standard
model and the dark sector fall at resonance due to kinematics and direct
detection experiments become insensitive. To be specific, we consider a simple
model of 100 GeV - TeV scale dark matter coupled to the standard model via a
vector boson. We explore whether it will be possible to exclude such regions of
the parameter space using future observations of dijet rates at the LHC and CTA
and AMS observations of the Galactic Centre.Comment: 7 pages, 9 figure
De-novo design of complementary (antisense) peptide mini-receptor inhibitor of interleukin 18 (IL-18).
Complementary (antisense) peptide mini-receptor inhibitors are complementary peptides designed to be receptor-surrogates that act by binding to selected surface features of biologically important proteins thereby inhibiting protein-cognate receptor interactions and subsequent biological effects. Previously, we described a complementary peptide mini-receptor inhibitor of interleukin-1beta (IL-1beta) that was designed to bind to an external surface loop (beta-bulge) of IL-1beta (Boraschi loop) clearly identified in the X-ray crystal structure of this cytokine. Here, we report the de-novo design and rational development of a complementary peptide mini-receptor inhibitor of cytokine interleukin-18 (IL-18), a protein for which there is no known X-ray crystal structure. Using sequence homology comparisons with IL-1beta, putative IL-18 surface loops are identified and used as a starting point for design, including a loop region 1 thought to be equivalent with the Boraschi loop of IL-1beta. Only loop region 1 complementary peptides are found to be promising leads as mini-receptor inhibitors of IL-18 but these are prevented from being properly successful owing to solubility problems. The application of "M-I pair mutagenesis" and inclusion of a C-terminal arginine residue are then sufficient to solve this problem and convert one lead peptide into a functional complementary peptide mini-receptor inhibitor of IL-18. This suggests that the biophysical and biological properties of complementary peptides can be improved in a rational and logical manner where appropriate, further strengthening the potential importance of complementary peptides as inhibitors of protein-protein interactions, even when X-ray crystal structural information is not readily available
The felt hat industry of Bristol and South Gloucestershire, 1530-1909
This thesis reconstructs the felt hat industry of Bristol and South Gloucestershire from its arrival in the region about 1530 until its local demise in 1909. It is a reinstatement and interpretation of a local industrial powerhouse largely neglected by Bristol's historians. The extent and influence of the trade through its ownership, employment and markets, and the lives of its workers, is discussed. No previous work has investigated the subject. There were studies of the early London hatters (Unwin, 1900-1904), those in the north west (Housley, 1929 MA; Giles, 1959; Turner 1986 MSc), and a national perspective, emphasizing one dominant firm (Smith, 1980 PhD).1 Early manufacture around the city soon led to a dispute over civic monopoly. Until the eighteenth century, the feltmakers of South Gloucestershire serviced the Bristol wholesalers and became the admired princes of the 'rough' trade.' At the acme, about 1,000 men were employed to make hats that satisfied the city's merchants in their domestic arrangements and in their overseas trade, principally in the colonies and in the slave business. About 1800, London interests displaced those of Bristol; the low-wage, high-skilled village workforce became a dependency of the capital. Through all this time, the men had a determined commitment to unchanging craft skills and a firm control of craft entry. The industry died as a backwater after enervating fights against legislation, innovation, capital and mechanisation. Few British institutions, let alone industries, can offer an historical view covering nearly 400 years of English development. The regional felt hat trade brushed against, and was sometimes in conflict with, much of the national regulation and taxation of markets and employment, and gives a particular and often surprisingly refreshing perspective. The reality on the ground, away from broader theory, is often unexpected.'EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Towards a World Environment Organisation?
Summary This article explores the possible need for a new international body to address environmental problems along the lines of a World Environment Organisation (WEO). A case is made that existing institutions and policy mechanisms for combating environmental problems have fallen short in several crucial respects. Perhaps most notable among the failings of contemporary approaches is a failure of internalisation. A WEO is argued to facilitate the internationalisation of environmental costs, as well as redress many of the other problems identified with existing international cooperative responses. The article is a summary of a larger project on the perspectives of different LDCs towards the possible creation of such an institution
Predictors of mortality and disability in stroke-associated pneumonia
Whilst stroke-associated pneumonia (SAP) is common and associated with poor outcomes, less is known about the determinants of these adverse clinical outcomes in SAP. To identify the factors that influence mortality and morbidity in SAP. Data for patients with SAP (n = 854) were extracted from a regional Hospital Stroke Register in Norfolk, UK (2003-2015). SAP was defined as pneumonia occurring within 7 days of admission by the treating clinicians. Mutlivariable regression models were constructed to assess factors influencing survival and the level of disability at discharge using modified Rankin Scale [mRS]. Mean (SD) age was 83.0 (8.7) years and ischaemic stroke occurred in 727 (85.0%). Mortality was 19.0% at 30 days and 44.0% at 6 months. Stroke severity assessment using National Institutes of Health Stroke Scale was not recorded in the data set although Oxfordshire Community Stroke Project was Classification. In the multivariable analyses, 30-day mortality was independently associated with age (OR 1.04, 95% CI 1.01-1.07, p = 0.01), haemorrhagic stroke (2.27, 1.07-4.78, p = 0.03) and pre-stroke disability (mRS 4-5 v 0-1: 6.45, 3.12-13.35, p < 0.001). 6-month mortality was independently associated with age (< 0.001), pre-stroke disability (p < 0.001) and certain comorbidities, including the following: dementia (6.53, 4.73-9.03, p < 0.001), lung cancer (2.07, 1.14-3.77, p = 0.017) and previous transient ischemic attack (1.94, 1.12-3.36, p = 0.019). Disability defined by mRS at discharge was independently associated with age (1.10, 1.05-1.16, p < 0.001) and plasma C-reactive protein (1.02, 1.01-1.03, p = 0.012). We have identified non-modifiable determinants of poor prognosis in patients with SAP. Further studies are required to identify modifiable factors which may guide areas for intervention to improve the prognosis in SAP in these patients
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