Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Anti-inflammatory properties of desipramine and fluoxetine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic

Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study

This trial was conducted to assess the activity and tolerability of the gemcitabine, epirubicin, taxol triplet combination in patients with operable breast cancer. After core biopsy, 43 women with stage II–IIIA breast cancer were treated with gemcitabine 1000 mg m−2 over 30 min on days 1 and 4, epirubicin 90 mg m−2 as an intravenous bolus on day 1, and taxol 175 mg m−2 as a 3-h infusion on day 1, every 21 days for four cycles. The primary end point was the percentage of pathological complete responses (pCR) in the breast; secondary end points were tolerability, clinical response rates, overall and progression-free survival, tumour biomarkers before and after primary chemotherapy (PCT). All patients were included in safety and survival analyses; 41 eligible patients were evaluated for response. The overall clinical response rate was 87.8% (95% CI 77.8–97.8), with 26.8% complete responses (95% CI 13.3–40.3). A pCR in the breast was observed in six patients (14.6%; 95% CI 3.8–25.4); 15 patients (36.6%; 95% CI 21.9–51.3) had negative axillary lymph nodes. Grade 4 neutropenia was observed in 67.4% of the patients; febrile neutropenia occurred in 1.9% of cycles (granulocyte colony-stimulating factor was used in 3.2% of the cycles to shorten the duration of neutropenia). A statistically significant difference between Mib-1 at baseline (⩾20% in 71.4% of the patients) and at definitive surgery (28.6%, P<0.05) was observed. The gemcitabine, epirubicin, taxol regimen is active and well tolerated as PCT for operable breast cancer. This combination allows the administration of full doses of active agents with a low incidence of febrile neutropenia

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Optimising care for patients with cognitive impairment and dementia following hip fracture

The global shift in demographics towards aging populations is leading to a commensurate increase in age-related disease and frailty. It is essential to optimise health services to meet current needs and prepare for anticipated future demands. This paper explores issues impacting on people living with cognitive impairment and/or dementia who experience a hip fracture and are cared for in acute settings. This is important given the high mortality and morbidity associated with this population. Given the current insufficiency of clear evidence on optimum rehabilitation of this patient group, this paper explored three key themes namely: recognition of cognitive impairment, response by way of training and education of staff to optimise care for this patient group and review of the importance of outcomes measures. Whilst there is currently insufficient evidence to draw conclusions about the optimal ways of caring for patients living with dementia following hip fracture, this paper concludes that future research should improve understanding of healthcare staff education to improve the outcomes for this important group of patients

Thermodynamic Basis for the Emergence of Genomes during Prebiotic Evolution

The RNA world hypothesis views modern organisms as descendants of RNA molecules. The earliest RNA molecules must have been random sequences, from which the first genomes that coded for polymerase ribozymes emerged. The quasispecies theory by Eigen predicts the existence of an error threshold limiting genomic stability during such transitions, but does not address the spontaneity of changes. Following a recent theoretical approach, we applied the quasispecies theory combined with kinetic/thermodynamic descriptions of RNA replication to analyze the collective behavior of RNA replicators based on known experimental kinetics data. We find that, with increasing fidelity (relative rate of base-extension for Watson-Crick versus mismatched base pairs), replications without enzymes, with ribozymes, and with protein-based polymerases are above, near, and below a critical point, respectively. The prebiotic evolution therefore must have crossed this critical region. Over large regions of the phase diagram, fitness increases with increasing fidelity, biasing random drifts in sequence space toward ‘crystallization.’ This region encloses the experimental nonenzymatic fidelity value, favoring evolutions toward polymerase sequences with ever higher fidelity, despite error rates above the error catastrophe threshold. Our work shows that experimentally characterized kinetics and thermodynamics of RNA replication allow us to determine the physicochemical conditions required for the spontaneous crystallization of biological information. Our findings also suggest that among many potential oligomers capable of templated replication, RNAs may have evolved to form prebiotic genomes due to the value of their nonenzymatic fidelity

Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment

<p>Abstract</p> <p>Background</p> <p>Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours.</p> <p>Methods</p> <p>In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-κB activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts.</p> <p>Results</p> <p>We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: <it>KLK7 </it>(<it>kallikrein 7</it>), <it>SOD2 </it>(<it>superoxide dismutase 2</it>), <it>100P </it>(<it>S100 calcium binding protein P</it>), <it>PI3 </it>(<it>protease inhibitor 3, skin-derived</it>), <it>CSTA </it>(<it>cystatin A</it>), <it>RARRES1 </it>(<it>retinoic acid receptor responder 1</it>), and <it>LXN </it>(<it>latexin</it>). The differential expression of the <it>KLK7 </it>and <it>SOD2 </it>transcripts was confirmed by Northern blot. Moreover, we observed that <it>SOD2 </it>expression correlates with the differential NF-κB activation exhibited by TNF-sensitive and TNF-resistant cells.</p> <p>Conclusion</p> <p>This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.</p

Estimates of new and total productivity in central Long Island Sound from in situ measurements of nitrate and dissolved oxygen

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 36 (2013): 74-97, doi:10.1007/s12237-012-9560-5.Biogeochemical cycles in estuaries are regulated by a diverse set of physical and biological variables that operate over a variety of time scales. Using in situ optical sensors, we conducted a high-frequency time-series study of several biogeochemical parameters at a mooring in central Long Island Sound from May to August 2010. During this period, we documented well-defined diel cycles in nitrate concentration that were correlated to dissolved oxygen, wind stress, tidal mixing, and irradiance. By filtering the data to separate the nitrate time series into various signal components, we estimated the amount of variation that could be ascribed to each process. Primary production and surface wind stress explained 59% and 19%, respectively, of the variation in nitrate concentrations. Less frequent physical forcings, including large-magnitude wind events and spring tides, served to decouple the relationship between oxygen, nitrate, and sunlight on about one-quarter of study days. Daytime nitrate minima and dissolved oxygen maxima occurred nearly simultaneously on the majority (> 80%) of days during the study period; both were strongly correlated with the daily peak in irradiance. Nighttime nitrate maxima reflected a pattern in which surface-layer stocks were depleted each afternoon and recharged the following night. Changes in nitrate concentrations were used to generate daily estimates of new primary production (182 ± 37 mg C m-2 d-1) and the f-ratio (0.25), i.e., the ratio of production based on nitrate to total production. These estimates, the first of their kind in Long Island Sound, were compared to values of community respiration, primary productivity, and net ecosystem metabolism, which were derived from in situ measurements of oxygen concentration. Daily averages of the three metabolic parameters were 1660 ± 431, 2080 ± 419, and 429 ± 203 mg C m-2 d-1, respectively. While the system remained weakly autotrophic over the duration of the study period, we observed very large day-to-day differences in the f-ratio and in the various metabolic parameters.This work was supported by the Yale Institute for Biospheric Studies, the Sounds Conservancy of the Quebec-Labrador Foundation, and the Yale School of Forestry and Environmental Studies Carpenter-Sperry Fund.2014-01-0