Characterization of the PTB ultra-high pulse dose rate reference electron beam

: Purpose. This investigation aims to present the characterisation and optimisation of an ultra-high pulse dose rate (UHPDR) electron beam at the PTB facility in Germany. A Monte Carlo beam model has been developed for dosimetry study for future investigation in FLASH radiotherapy and will be presented.Material and methods. The 20 MeV electron beams generated by the research linear accelerator has been characterised both in-beamline with profile monitors and magnet spectrometer, and in-water with a diamond detector prototype. The Monte Carlo model has been used to investigate six different setups to enable different dose per pulse (DPP) ranges and beam sizes in water. The properties of the electron radiation field in water have also been characterised in terms of beam size, quality specifierR50and flatness. The beam stability has also been studied.Results. The difference between the Monte-Carlo simulated and measuredR50was smaller than 0.5 mm. The simulated beam sizes agreed with the measured ones within 2 mm. Two suitable setups have been identified for delivering reference UHPDR electron beams. The first one is characterised by a SSD of 70 cm, while in the second one an SSD of 90 cm is used in combination with a 2 mm aluminium scattering plates. The two set-ups are quick and simple to install and enable an expected overall DPP range from 0.13 Gy up to 6.7 Gy per pulse.Conclusion. The electron beams generated by the PTB research accelerator have shown to be stable throughout the four-months length of this investigation. The Monte Carlo models have shown to be in good agreement for beam size and depth dose and within 1% for the beam flatness. The diamond detector prototype has shown to be a promising tool to be used for relative measurements in UHPDR electron beams

Absorbed-dose-to-water measurement using alanine in ultra-high-pulse-dose-rate electron beams

: Objective. The aim of the presented study is to evaluate the dose response of the PTB's secondary standard system, which is based on alanine and electron spin resonance (ESR) spectroscopy measurement, in ultra-high-pulse-dose-rate (UHPDR) electron beams.Approach. The alanine dosimeter system was evaluated in the PTB's UHPDR electron beams (20 MeV) in a range of 0.15-6.2 Gy per pulse. The relationship between the obtained absorbed dose to water per pulse and the in-beamline charge measurement of the electron pulses acquired using an integrating current transformer (ICT) was evaluated. Monte Carlo simulations were used to determine the beam quality conversion and correction factors required to perform alanine dosimetry.Main results. The beam quality conversion factor from the reference quality60Co to 20 MeV obtained by Monte Carlo simulation, 1.010(1), was found to be within the standard uncertainty of the consensus value, 1.014(5). The dose-to-water relative standard uncertainty was determined to be 0.68% in PTB's UHPDR electron beams.Significance. In this investigation, the dose-response of the PTB's alanine dosimeter system was evaluated in a range of dose per pulse between 0.15 Gy and 6.2 Gy and no evidence of dose-response dependency of the PTB's secondary standard system based on alanine was observed. The alanine/ESR system was shown to be a precise dosimetry system for evaluating absorbed dose to water in UHPDR electron beams

Campylobacter in organic and conventional pig production in France: antibiotic resistance, genetic diversity and virulence

Campylobacter coli strains from 56 organic and 58 conventional pig colon contents were characterized to evaluate impact of these two productions on antibiotic resistance, genetic diversity and virulence of these strains. 76.8% of organic pigs and 74.0% of conventional pigs were positive in Campylobacter. A total of 262 strains were tested for their resistance to 7 antibiotics. Significant differences were observed for 4 antibiotics (tetracycline, erythromycin, nalidixic acid, ciprofloxacin) between the two productions with higher resistance for conventional pig Campylobacter. Multiresistance was more frequently observed for conventional pig strains (54.8%) than for organic pig strains (26.8%). Strains were typed by PFGE (262 strains) and MLST (120 strains). Genetic diversity was very high for both productions with both typing methods. Strains were distributed in 60 PFGE genotypes and in 51 Sequence Types. Ten PFGE clusters (34% of the strains) and nine ST (41.6% of the strains) were common between the two productions. Presence of 9 virulence genes was checked (120 strains) by PCR. All the strains carried the ceuE, iam, ciaB and flaA genes and more than 95% of the strains carried the cadF and cdtABC genes. The virb11 gene on plasmid was detected only for 13 organic pig strains. Capacity of adhesion and invasion of 61 strains were tested on Caco-2 cells. No link between virulence profile and strain origin was observed. However strains with the virb11 gene had higher invasive capacity. In conclusion, no impact of the type of production was observed on the genetic diversity and virulence of Campylobacter strains. The lower level of antibiotic resistance and multiresistance of C. coli strains for organic pigs may be related to the restricted use of antibiotics in this production and / or colonization of organic pigs with susceptible environmental strains

Contrasting responses of mean and extreme snowfall to climate change

Snowfall is an important element of the climate system, and one that is expected to change in a warming climate. Both mean snowfall and the intensity distribution of snowfall are important, with heavy snowfall events having particularly large economic and human impacts. Simulations with climate models indicate that annual mean snowfall declines with warming in most regions but increases in regions with very low surface temperatures. The response of heavy snowfall events to a changing climate, however, is unclear. Here I show that in simulations with climate models under a scenario of high emissions of greenhouse gases, by the late twenty-first century there are smaller fractional changes in the intensities of daily snowfall extremes than in mean snowfall over many Northern Hemisphere land regions. For example, for monthly climatological temperatures just below freezing and surface elevations below 1,000 metres, the 99.99th percentile of daily snowfall decreases by 8% in the multimodel median, compared to a 65% reduction in mean snowfall. Both mean and extreme snowfall must decrease for a sufficiently large warming, but the climatological temperature above which snowfall extremes decrease with warming in the simulations is as high as −9 °C, compared to −14 °C for mean snowfall. These results are supported by a physically based theory that is consistent with the observed rain–snow transition. According to the theory, snowfall extremes occur near an optimal temperature that is insensitive to climate warming, and this results in smaller fractional changes for higher percentiles of daily snowfall. The simulated changes in snowfall that I find would influence surface snow and its hazards; these changes also suggest that it may be difficult to detect a regional climate-change signal in snowfall extremes.National Science Foundation (U.S.) (Grant AGS-1148594)United States. National Aeronautics and Space Administration (ROSES Grant 09-IDS09-0049

Anopheles Gambiae PRS1 Modulates Plasmodium Development at Both Midgut and Salivary Gland Steps

Background: Invasion of the mosquito salivary glands by Plasmodium is a critical step for malaria transmission. From a SAGE analysis, we previously identified several genes whose expression in salivary glands was regulated coincident with sporozoite invasion of salivary glands. To get insights into the consequences of these salivary gland responses, here we have studied one of the genes, PRS1 (Plasmodium responsive salivary 1), whose expression was upregulated in infected glands, using immunolocalization and functional inactivation approaches. Methodology/Principal Findings: PRS1 belongs to a novel insect superfamily of genes encoding proteins with DM9 repeat motifs of uncharacterized function. We show that PRS1 is induced in response to Plasmodium, not only in the salivary glands but also in the midgut, the other epithelial barrier that Plasmodium has to cross to develop in the mosquito. Furthermore, this induction is observed using either the rodent parasite Plasmodium berghei or the human pathogen Plasmodium falciparum. In the midgut, PRS1 overexpression is associated with a relocalization of the protein at the periphery of invaded cells. We also find that sporozoite invasion of salivary gland cells occurs sequentially and induces intra-cellular modifications that include an increase in PRS1 expression and a relocalization of the corresponding protein into vesicle-like structures. Importantly, PRS1 knockdown during the onset of midgut and salivary gland invasion demonstrates that PRS1 acts as an agonist for the development of both parasite species in the two epithelia, highlighting shared vector/parasite interactions in both tissues. Conclusions/Significance: While providing insights into potential functions of DM9 proteins, our results reveal that PRS1 likely contributes to fundamental interactions between Plasmodium and mosquito epithelia, which do not depend on the specific Anopheles/P. falciparum coevolutionary history

Malaria and obesity: obese mice are resistant to cerebral malaria

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Drosophila Araucan and Caupolican Integrate Intrinsic and Signalling Inputs for the Acquisition by Muscle Progenitors of the Lateral Transverse Fate

A central issue of myogenesis is the acquisition of identity by individual muscles. In Drosophila, at the time muscle progenitors are singled out, they already express unique combinations of muscle identity genes. This muscle code results from the integration of positional and temporal signalling inputs. Here we identify, by means of loss-of-function and ectopic expression approaches, the Iroquois Complex homeobox genes araucan and caupolican as novel muscle identity genes that confer lateral transverse muscle identity. The acquisition of this fate requires that Araucan/Caupolican repress other muscle identity genes such as slouch and vestigial. In addition, we show that Caupolican-dependent slouch expression depends on the activation state of the Ras/Mitogen Activated Protein Kinase cascade. This provides a comprehensive insight into the way Iroquois genes integrate in muscle progenitors, signalling inputs that modulate gene expression and protein activity