Paraoxonase gene polymorphisms and haplotype analysis in a stroke population

Peer reviewedPublisher PD

Preliminary report on sand-streaming in Agadez and Tahoua Departments, Republic of Niger

There are no author-identified significant results in this report

HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents

The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process

Enhancing urban autonomy : towards a new political project for cities.

As the 21st Century world assumes an increasingly urban landscape, the question of how definitive urban spaces are to be governed intensifies. At the heart of this debate lies a question about the degree and type of autonomy that towns and cities might have in shaping their economic, environmental, social and cultural geography. This paper aims to examine this question. Starting with the premise that the degree of autonomy any particular town or city has is inherently an empirical question – one which can only be conceptualised in relational terms vis-à-vis the distributed, networked and territorialised responsibilities and powers of the city and the nation-state and other zones of connection – we examine four different contexts where debates over autonomy have intensified in recent history (Brazil, UK, India and South Africa). Drawing on recent respective histories, we identify key elements and enablers in the making of urban autonomy: a characteristic that exists in a variety of guises and forms and creates a patchwork landscape of differentially powerful fragments. We reveal how, beyond its characteristic as a political ideal, autonomy surfaces as a practice that emerges from within specific sectors of particular societies and through their relationship with national and regional politics. Four alternative forms of urban autonomy are delineated: fragmented, coerced (or enclave), distributed and networked. We contend that the spatial templates for autonomy are not predetermined but can be enhanced in multiple different sites and forms of political space within the city. This enhancement appears essential for the integration and strengthening of capacities for sustainable and just forms of development throughout the urban

Enhancing urban autonomy: towards a new political project for cities

As the 21st Century world assumes an increasingly urban landscape, the question of how definitive urban spaces are to be governed intensifies. At the heart of this debate lies a question about the degree and type of autonomy that towns and cities might have in shaping their economic, environmental, social and cultural geography. This paper aims to examine this question. Starting with the premise that the degree of autonomy any particular town or city has is inherently an empirical question – one which can only be conceptualised in relational terms vis-à-vis the distributed, networked and territorialised responsibilities and powers of the city and the nation-state and other zones of connection – we examine four different contexts where debates over autonomy have intensified in recent history (Brazil, UK, India and South Africa). Drawing on recent respective histories, we identify key elements and enablers in the making of urban autonomy: a characteristic that exists in a variety of guises and forms and creates a patchwork landscape of differentially powerful fragments. We reveal how, beyond its characteristic as a political ideal, autonomy surfaces as a practice that emerges from within specific sectors of particular societies and through their relationship with national and regional politics. Four alternative forms of urban autonomy are delineated: fragmented, coerced (or enclave), distributed and networked. We contend that the spatial templates for autonomy are not predetermined but can be enhanced in multiple different sites and forms of political space within the city. This enhancement appears essential for the integration and strengthening of capacities for sustainable and just forms of development throughout the urban

Electro-optic time profile monitors for femtosecond electron bunches at the soft x-ray free-electron laser FLASH

Precise measurements of the temporal profile of ultrashort electron bunches are of high interest for the optimization and operation of ultraviolet and x-ray free-electron lasers. The electro-optic (EO) technique has been applied for a single-shot direct visualization of the time profile of individual electron bunches at FLASH. This paper presents a thorough description of the experimental setup and the results. An absolute calibration of the EO technique has been performed utilizing simultaneous measurements with a transverse-deflecting radio-frequency structure that transforms the longitudinal bunch charge distribution into a transverse streak. EO signals as short as 60 fs (rms) have been observed using a gallium-phosphide (GaP) crystal, which is a new record in the EO detection of single electron bunches and close to the physical limit imposed by the EO material properties. The data are in quantitative agreement with a numerical simulation of the EO detection process

The effect of estrogen on intracellular Ca2+ and Na+ regulation in heart failure

Background: Under-representation of women in heart failure (HF) trials and contradictory findings of estrogen supplementation highlight the need to investigate the involvement of estrogen in the progression of heart failure. Objectives: To characterize the influence of estrogen on cardiac function during the onset of heart failure in a controlled animal model that lacks traditional comorbidities. Methods: HF was induced by aortic constriction (AC) in female guinea pigs. Selected AC animals were ovariectomized (ACOV) and a group of these received 17β-estradiol (ACOV+E) supplementation. 150 days post-AC surgery, left ventricular myocytes were isolated and their electrophysiology and Ca2+ and Na+ regulation examined. Results: ACOV animals heart weight/body weight ratios increased by 11% and in vivo fractional shortening decreased by 14% compared with the AC group, suggesting greater impairment of cardiac function in the absence of estrogen. Action potential duration increased in all three HF groups, the extent of the changes being estrogen-dependent. Myocytes from ACOV animals had reduced Ca2+ transient amplitudes, slower transient decay kinetics, decreased SR Ca2+ contents but increased Ca2+ spark frequencies and spark-mediated SR leak compared with the AC and ACOV+E groups. The Na+/K+ ATPase current densities and Na+ extrusion rates were reduced by 13% and 19%, respectively, in parallel with a 17% increase in INa,L current densities in the ACOV group compared with the AC group. Conclusions: Long-term absence of ovarian hormones exacerbates the decline in cardiac function during the progression to HF. Estrogen supplementation reverses these aggravating effects

European Non-native Species in Aquaculture Risk Analysis Scheme - a summary of assessment protocols and decision support tools for use of alien species in aquaculture

The European Non-native Species in Aquaculture Risk Analysis Scheme (ENSARS) was developed in response to European 'Council Regulation No. 708/2007 of 11 June 2007 concerning use of alien and locally absent species in aquaculture' to provide protocols for identifying and evaluating the potential risks of using non-native species in aquaculture. ENSARS is modular in structure and adapted from non-native species risk assessment schemes developed by the European and Mediterranean Plant Protection Organisation and for the UK. Seven of the eight ENSARS modules contain protocols for evaluating the risks of escape, introduction to and establishment in open waters, of any non-native aquatic organism being used (or associated with those used) in aquaculture, that is, transport pathways, rearing facilities, infectious agents, and the potential organism, ecosystem and socio-economic impacts. A concluding module is designed to summarise the risks and consider management options. During the assessments, each question requires the assessor to provide a response and confidence ranking for that response based on expert opinion. Each module can also be used individually, and each requires a specific form of expertise. Therefore, a multidisciplinary assessment team is recommended for its completion

Benchmarking of electro-optic monitors for femtosecond electron bunches

The longitudinal profiles of ultrashort relativistic electron bunches at the soft x-ray free-electron laser FLASH have been investigated using two single-shot detection schemes: an electro-optic (EO) detector measuring the Coulomb field of the bunch and a radio-frequency structure transforming the charge distribution into a transverse streak. A comparison permits an absolute calibration of the EO technique. EO signals as short as 60 fs (rms) have been observed, which is a new record in the EO detection of single electron bunches and close to the limit given by the EO material properties