690 research outputs found
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Geographic information systems in spatial epidemiology and public health
Ultrafast Carrier Recombination and Generation Rates for Plasmon Emission and Absorption in Graphene
Electron-hole generation and recombination rates for plasmon emission and
absorption in Graphene are presented. The recombination times of carriers due
to plasmon emission have been found to be in the tens of femtoseconds to
hundreds of picoseconds range. The recombination times depend sensitively on
the carrier energy, carrier density, temperature, and the plasmon dispersion.
Carriers near the Dirac point are found to have much longer lifetimes compared
to carriers at higher energies. Plasmons in a Graphene layer on a polar
substrate hybridize with the surface optical phonons and this hybridization
modifies the plasmon dispersion. We also present generation and recombination
rates of carriers due to plasmon emission and absorption in Graphene layers on
polar substrates.Comment: 7 Pages, 11 Figures, To appear in Phys. Rev. B (2011
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Crime victimization and the implications for individual health and wellbeing: A Sheffield case study.
Public health and criminology have developed largely independently of one another at the research and policy levels so that the links between crime victimization and health status are not well understood. Although it is not difficult to support the idea of crime as a threat to the health of individuals and the wider community, the difficulty lies in quantifying the impact of crime on public health, while controlling other variables, including gender and ethnicity. We report the results of a study, the goals of which were to: develop an understanding conceptually of the relationships between different types of crime (violent and non-violent) and health; explore the impact of victimization on quality of life and physical and psychological wellbeing; investigate the role of social and demographic factors in shaping any relationships. The study is based on 840 responses from a postal survey administered to 4,100 households in Sheffield, England, located primarily in deprived areas where overall crime rates were high. Non-violent crimes were more frequently reported than violent crimes and in general, inner city neighbourhoods were associated with higher violent crime rates. Out of 392 victims of crime, 27% of individuals detailed physical injuries resulting directly from a crime event and 31% had taken some medical steps to treat a crime-related injury. 86% experienced at least one psychological or behavioural change, including stress, sleeping difficulties, loss of confidence, and depression. Logistic regression models estimated victimization risk based on various social and demographic variables. Violent crimes were consistently linked with higher odds of seeking medical treatment and a higher likelihood of experiencing psychological ill health effects or behavioural changes. In comparison, victims of non-violent or property crimes were not significantly associated with mental health or behavioural/lifestyle effects.This project was financed by research funds from the Gates Cambridge Trust and the Department of Geography (Philip Lake II Fund), University of Cambridge
FUS-NLS/Transportin 1 complex structure provides insights into the nuclear targeting mechanism of FUS and the implications in ALS
The C-terminal nuclear localization sequence of FUsed in Sarcoma (FUS-NLS) is critical for its nuclear import mediated by transportin (Trn1). Familial amyotrophic lateral sclerosis (ALS) related mutations are clustered in FUS-NLS. We report here the structural, biochemical and cell biological characterization of the FUS-NLS and its clinical implications. The crystal structure of the FUS-NLS/Trn1 complex shows extensive contacts between the two proteins and a unique α-helical structure in the FUS-NLS. The binding affinity between Trn1 and FUS-NLS (wide-type and 12 ALS-associated mutants) was determined. As compared to the wide-type FUS-NLS (K(D) = 1.7 nM), each ALS-associated mutation caused a decreased affinity and the range of this reduction varied widely from 1.4-fold over 700-fold. The affinity of the mutants correlated with the extent of impaired nuclear localization, and more importantly, with the duration of disease progression in ALS patients. This study provides a comprehensive understanding of the nuclear targeting mechanism of FUS and illustrates the significance of FUS-NLS in ALS
Fragment-based discovery of a regulatory site in thioredoxin glutathione reductase acting as "doorstop" for NADPH entry
Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases are difficult to inhibit in a selective manner with off target inhibition reducing usefulness of identified compounds. Thioredoxin glutathione reductase (TGR), a high molecular weight thioredoxin reductase-like enzyme, has emerged as a promising drug target for the treatment of schistosomiasis, a parasitosis afflicting more than 200 million people. Taking advantage of small molecules selected from a high-throughput screen and using X-ray crystallography, functional assays, and docking studies, we identify a critical secondary site of the enzyme. Compounds binding at this site interfere with well-known and conserved conformational changes associated with NADPH reduction, acting as a doorstop for cofactor entry. They selectivity inhibit TGR from Schistosoma mansoni and are active against parasites in culture. Since many members of the FAD/NAD-linked reductase family have similar catalytic mechanisms the unique mechanism of inhibition identified in this study for TGR broadly opens new routes to selectively inhibit homologous enzymes of central importance in numerous diseases
Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression
Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF–β-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of Bora requires the Plk1 kinase activity and is mediated by SCF–β-TrCP. Plk1 phosphorylates a conserved DSGxxT degron in Bora and promotes its interaction with β-TrCP. Mutations in this degron stabilize Bora. Expression of a nondegradable Bora variant prolongs the metaphase and delays anaphase onset, indicating a physiological requirement of Bora degradation. Interestingly, the activity of Bora is also required for normal mitotic progression, as knockdown of Bora activates the spindle checkpoint and delays sister chromatid segregation. Mechanistically, Bora regulates spindle stability and microtubule polymerization and promotes tension across sister kinetochores during mitosis. We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression
GIS and spatial data analysis: Converging perspectives
We take as our starting point the state of geographic information systems (GIS) and spatial data analysis 50 years ago when regional science emerged as a new field of enquiry. In the late 1950s and 1960s advances in computing technology were making possible forms of automated cartography that in due course would lead to th
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