Gene regulatory mechanisms underpinning prostate cancer susceptibility

Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms. We identify 57 expression quantitative trait loci at 35 risk loci, which we validate through analysis of allele-specific expression. We further validate predicted regulatory SNPs and target genes in prostate cancer cell line models. Finally, our integrated analysis can be accessed through an interactive visualization tool. This analysis elucidates how genome sequence variation affects disease predisposition via gene regulatory mechanisms and identifies relevant genes for downstream biomarker and drug development.

Magnetic collimation of petawatt driven fast electron beam for prospective fast ignition studies

Collimated transport of fast electron beam through solid density matter is one of the key issues behind the success of the fast ignition scheme by means of which the required amount of ignition energy can be delivered to the hot spot region of the compressed fuel. Here we report on a hot electron beam collimation scheme in solids by tactfully using the strong magnetic fields generated by an electrical resistivity gradient according to Faraday's law. This was accomplished by appropriately fabricating the targets in such a way that the electron beam is directed to flow in a metal which is embedded in a much lower resistivity and atomic number metal. Experimental results showed guided transport of hot electron beam over hundreds of microns length inside solid density plasma, which were obtained from two experiments examining the scheme for petawatt laser driven hot electron beam while employing various target configurations.

Changes in the Pollen Seasons of the Early Flowering Trees Alnus spp. and Corylus spp. in Worcester United Kingdom 1996-2005

Previous work on Betula spp. (birch) in the UK and at five sites in Europe has shown that pollen seasons for this taxon have tended to become earlier by about 5–10 days per decade in most regions investigated over the last 30 years. This pattern has been linked to the trend to warmer winters and springs in recent years. However, little work has been done to investigate the changes in the pollen seasons for the early flowering trees. Several of these, such as Alnus spp. and Corylus spp., have allergens, which cross-react with those of Betula spp., and so have a priming effect on allergic people. This paper investigates pollen seasons for Alnus spp. and Corylus spp. for the years 1996–2005 at Worcester, in the West Midlands, United Kingdom. Pollen data for daily average counts were collected using a Burkard volumetric trap sited on the exposed roof of a three-storey building. The climate is western maritime. Meteorological data for daily temperatures (maximum and minimum) and rainfall were obtained from the local monitoring sites. The local area up to approximately 10 km surrounding the site is mostly level terrain with some undulating hills and valleys. The local vegetation is mixed farmland and deciduous woodland. The pollen seasons for the two taxa investigated are typically late December or early January to late March. Various ways of defining the start and end of the pollen seasons were considered for these taxa, but the most useful was the 1% method whereby the season is deemed to have started when 1% of the total catch is achieved and to have ended when 99% is reached. The cumulative catches (in grains/m3) for Alnus spp. varied from 698 (2001) to 3,467 (2004). For Corylus spp., they varied from 65 (2001) to 4,933 (2004). The start dates for Alnus spp. showed 39 days difference in the 10 years (earliest 2000 day 21, latest 1996 day 60). The end dates differed by 26 days and the length of season differed by 15 days. The last 4 years in the set had notably higher cumulative counts than the first 2, but there was no trend towards earlier starts. For Corylus spp. start days also differed by 39 days (earliest 1999 day 5, latest 1996 day 44). The end date differed by 35 days and length of season by 26 days. Cumulative counts and lengths of season showed a distinct pattern of alternative high (long) and low (short) years. There is some evidence of a synchronous pattern for Alnus spp.. These patterns show some significant correlations with temperature and rainfall through the autumn, winter and early spring, and some relationships with growth degree 4s and chill units, but the series is too short to discern trends. The analysis has provided insight to the variation in the seasons for these early flowering trees and will form a basis for future work on building predictive models for these taxa.

Factors that Determine the Severity of Betula spp. Pollen Seasons in Poland (Poznań and Krakow) and the United Kingdom (Worcester and London)

The aim of this paper is to analyse variations in the severity of Betula pollen seasons, particularly in relation to meteorological parameters at four sites, Poznań and Krakow in Poland and Worcester and London in the United Kingdom. Results show that there is a significant relationship between Betula pollen season severity and weather conditions in the year before pollination as well as conditions in the same year that pollen is released from the plant. Furthermore, it is likely that the magnitude of birch pollen seasons in Poznań, Worcester and London is linked in some way to different phases of the North Atlantic Oscillation (NAO). Significant positive relationships exist between birch pollen counts at Poznań and temperatures, rainfall and averages of the NAO in the year before pollination. An opposite relationship is evident at the two sites studied in the British Isles. There were significant positive correlations between the severity of birch pollen seasons recorded at Worcester and London and temperatures and averages of the NAO during the year of pollination, and negative correlations with similar variables from the previous year. In addition, Betula pollen seasons in Krakow do not appear to be influenced by the NAO, which is probably the result of Krakow having a more continental climate.

Pollen Season and Climate: Is the Timing of Birch Pollen Release in the UK Approaching its Limit?

In light of heightened interest in the response of pollen phenology to temperature, we investigated recent changes to the onset of Betula (birch) pollen seasons in central and southern England, including a test of predicted advancement of the Betula pollen season for London. We calculated onset of birch pollen seasons using daily airborne pollen data obtained at London, Plymouth and Worcester, determined trends in the start of the pollen season and compared timing of the birch pollen season with observed temperature patterns for the period 1995–2010. We found no overall change in the onset of birch pollen in the study period although there was evidence that the response to temperature was nonlinear and that a lower asymptotic start of the pollen season may exist. The start of the birch pollen season was strongly correlated with March mean temperature. These results reinforce previous findings showing that the timing of the birch pollen season in the UK is particularly sensitive to spring temperatures. The climate relationship shown here persists over both longer decadal-scale trends and shorter, seasonal trends as well as during periods of ‘sign-switching’ when cooler spring temperatures result in later start dates. These attributes, combined with the wide geographical coverage of airborne pollen monitoring sites, some with records extending back several decades, provide a powerful tool for the detection of climate change impacts, although local site factors and the requirement for winter chilling may be confounding factors.

Comparison of Poaceae Pollen Counts Recorded at Sites in Portugal, Spain and the UK

The main aim of this study was to analyse the temporal and spatial variations in grass (Poaceae) pollen counts (2005–2011) recorded in Évora (Portugal), Badajoz (Spain) and Worcester (UK). Weekly average data were examined using nonparametric statistics to compare differences between places. On average, Évora recorded the earliest start dates of the Poaceae pollen seasons and Worcester the latest. The intensity of the Poaceae pollen season varied between sites, with Worcester usually recording the least and Évora the most grass pollen in a season. Mean durations of grass pollen seasons were 77 days in Évora, 78 days in Badajoz and 59 days in Worcester. Overall, longer Poaceae pollen seasons coincided with earlier pollen season start dates. Weekly pollen data, from March to September, from the three pollen-monitoring stations studied were compared. The best fit and most statistically significant correlations were obtained by moving Worcester data backward by 4 weeks (Évora, r = 0.810, p < 0.001) and 5 weeks (Badajoz,r = 0.849, p < 0.001). Weekly data from Worcester therefore followed a similar pattern to that of Badajoz and Évora but at a distance of more than 1,500 km and 4–5 weeks later. The sum of pollen recorded in a season was compared with monthly rainfall between January and May. The strongest positive relationship between season intensity and rainfall was between the annual sum of Poaceae pollen recorded in the season at Badajoz and Évora and total rainfall during January and February. Winter rainfall noticeably affects the intensity of Poaceae pollen seasons in Mediterranean areas, but this was not as important in Worcester.

Pollen From Alder (Alnus sp.), Birch (Betula sp.) and Oak (Quercus sp.) in the UK Originate From Small Woodlands

We have analysed the pollen seasons in Worcester for the period 2005–12 for alder (Alnus), birch (Betula) and oak (Quercus) by using back trajectory calculations and produced the first detailed source maps for these three pollen types. The study shows considerable variations in the source–receptor relationship of three of the most important tree pollen types in England with respect to allergy. Long Distance Transport is observed for Quercus and Betula but not for Alnus. The new source maps show a number of high emitting areas for Betula and Quercus, mainly near London, in the Midlands and in Wales. The production of source maps is sensitive to the used type of land cover data and how well they incorporate small woodlands. Two satellite products, Corine Land Cover and Globcover, are compared with the detailed national land cover product Land Cover Map 2007. The broad scale satellite products show either up to 50% less woody coverage or a direct misplacement of woodlands. The Lagrangian back trajectory model, the pollen count observations and the source maps altogether suggest that small woodlands (below 25 ha) play a major role in the overall pollen load in urban areas in England.

Comparisons of Fungal Spore Distributions Using Air Sampling at Worcester, England (2006-2010)

This study determined annual and monthly fluctuations in concentration of 20 fungal genera. The selection of taxa was made based upon their high frequency in the air as well as their well-known allergenic properties. Air samples were collected using a spore trap of Hirst design at an urban site where the trap continuously worked throughout a 5-year survey. Weather data were acquired from a meteorological station co-located with the air sampler. Influence of several meteorological parameters was then examined to reveal species–environment interactions and the potential location of fungal spore sources within the urban area. The maximum monthly sum of mean daily spore concentration varied between genera, and the earliest peaks were recorded for Pleospora sp. in April and Ustilago sp. in June. However, the majority of investigated spore types occurred in the greatest concentrations between August and September. Out of the 20 studied taxa, the most dominant genus was Cladosporium sp., which exceeded an allergenic threshold of 3000 s m-3 40 times during very rainy years and twice as much during dry years. A Spearman’s rank test showed that statistically significant (p B 0.05) relationships between spore concentration and weather parameters were mainly rs B 0.50. Potential sources of spores at Worcester were likely to be localised outside the city area.

Presidential power and congressional acquiescence in the "war" on terrorism: a new constitutional equilibrium?

US presidents have expanded executive power in times of war and emergency,sometimes aggressively so. This article builds on the application of punctuated equilibria theory by Burnham (1999 and Ackerman (1999). Underpinning this theory is the notion that rapid changes in - or external shocks to - domestic and international society impose new and insistent demands on the state. In so doing, they produce important and decisive moments of institutional mobilization and creativity, disrupt a pre-existing, relatively stable, equilibrium between the Congress and the president, and precipitate decisions or nondecisions by the electorate and political leaders that define the contours for action when the next crisis or external shock occurs. The article suggests that the combination of President George W. Bush's presidentialist doctrine, 9/11 and the 'war' on terror has consolidated a new, constitutional equilibrium. While some members of Congress contest the new order, the Congress collectively has acquiesced in its own marginalization. The article surveys a wide range of executive power assertions and legislative retreats. It argues that power assertions generally draw on precedent: on, for example, a tradition of wartime presidential extraconstitutional leadership extending to presidents, such as John Adams and Abraham Lincoln,as well as to Cold War and post-Cold War presidentialism.

U.W. Percussion and Steel Drum Ensembles, June 2, 2005

Concert Program for U.W. Percussion and Steel Drum Ensembles

Tsunami Hazard Assessment of the Strait of Juan de Fuca

This study presents and discusses the tsunami hazard posed by an updated CSZ earthquake scenerio to the coastal communities of Port Angeles and Port Townsend, based on the results of a high resolution GeoClaw simulation with 2/3 arc second resolution (about 20.56 meters) surrounding these towns. In addition, we will also present the results of a coarse regional simulation of the Strait of Juan de Fuca. This coarse study encompasses 28 regions that span the Strait’s coast, including the communities of Anacortes, Bellingham, Friday Harbor, and Victoria, BC in addition to extended areas around Port Angeles and Port Townsend. The finest grid for these 28 regions where we collected results had 2 arc sec resolution (around 62 meters). Finally, we will discuss some inherent uncertainties in the specification of the earthquake scenario, the limitations of the GeoClaw model, and the associated uncertainites in the results.

Symposium: Editing Political Diaries

The witness seminar was held in December 1991 at the Institute of Historical Research in London. It examined some of the key issues surrounding the editing of political diaries, including what to edit, the motivation of the diarist and the value of diaries to historians. Peter Catterall of the ICBH was in the chair. The three principal speakers were Ruth Winstone, editor of Tony Benn's diaries, David Brooks, editor of the diary of Sir Edward Hamilton, and John Barnes, co‐editor with David Nicholson, of the diary of Leo Amery. Other contributors included Jad Adams (biographer of Tony Benn), Kathleen Burk (co‐author of a study of the 1976 IMF crisis), Philip Williamson (editor of the diary of William Bridgeman), M.R.D. Foot (an editor of the Gladstone diaries), and Stuart Ball (editor of the diary of Sir Cuthbert Headlam).

Projecto suspensão formula student

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Curso E-learning de sistemas multicorpo (multibody systems) para engenheiros mecânicos

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.