Simbol-X Hard X-ray Focusing Mirrors: Results Obtained During the Phase A Study

Simbol-X will push grazing incidence imaging up to 80 keV, providing a strong improvement both in sensitivity and angular resolution compared to all instruments that have operated so far above 10 keV. The superb hard X-ray imaging capability will be guaranteed by a mirror module of 100 electroformed Nickel shells with a multilayer reflecting coating. Here we will describe the technogical development and solutions adopted for the fabrication of the mirror module, that must guarantee an Half Energy Width (HEW) better than 20 arcsec from 0.5 up to 30 keV and a goal of 40 arcsec at 60 keV. During the phase A, terminated at the end of 2008, we have developed three engineering models with two, two and three shells, respectively. The most critical aspects in the development of the Simbol-X mirrors are i) the production of the 100 mandrels with very good surface quality within the timeline of the mission; ii) the replication of shells that must be very thin (a factor of 2 thinner than those of XMM-Newton) and still have very good image quality up to 80 keV; iii) the development of an integration process that allows us to integrate these very thin mirrors maintaining their intrinsic good image quality. The Phase A study has shown that we can fabricate the mandrels with the needed quality and that we have developed a valid integration process. The shells that we have produced so far have a quite good image quality, e.g. HEW <~30 arcsec at 30 keV, and effective area. However, we still need to make some improvements to reach the requirements. We will briefly present these results and discuss the possible improvements that we will investigate during phase B.Comment: 6 pages, 3 figures, invited talk at the conference "2nd International Simbol-X Symposium", Paris, 2-5 december, 200

An evidence-based decision assistance model for predicting training outcome in juvenile guide dogs

Working dog organisations, such as Guide Dogs, need to regularly assess the behaviour of the dogs they train. In this study we developed a questionnaire-style behaviour assessment completed by training supervisors of juvenile guide dogs aged 5, 8 and 12 months old (n = 1,401), and evaluated aspects of its reliability and validity. Specifically, internal reliability, temporal consistency, construct validity, predictive criterion validity (comparing against later training outcome) and concurrent criterion validity (comparing against a standardised behaviour test) were evaluated. Thirty-nine questions were sourced either from previously published literature or created to meet requirements identified via Guide Dogs staff surveys and staff feedback. Internal reliability analyses revealed seven reliable and interpretable trait scales named according to the questions within them as: Adaptability; Body Sensitivity; Distractibility; Excitability; General Anxiety; Trainability and Stair Anxiety. Intra-individual temporal consistency of the scale scores between 5±8, 8±12 and 5±12 months was high. All scales excepting Body Sensitivity showed some degree of concurrent criterion validity. Predictive criterion validity was supported for all seven scales, since associations were found with training outcome, at at-least one age. Thresholds of z-scores on the scales were identified that were able to distinguish later training outcome by identifying 8.4% of all dogs withdrawn for behaviour and 8.5% of all qualified dogs, with 84% and 85% specificity. The questionnaire assessment was reliable and could detect traits that are consistent within individuals over time, despite juvenile dogs undergoing development during the study period. By applying thresholds to scores produced from the questionnaire this assessment could prove to be a highly valuable decision-making tool for Guide Dogs. This is the first questionnaire-style assessment of juvenile dogs that has shown value in predicting the training outcome of individual working dogs

Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study

Introduction Some molecular subtypes of breast cancer have preferential sites of distant relapse. The protein expression pattern of the primary tumor may influence the first distant metastasis site. Methods We identified from the files of the Finnish Cancer Registry patients diagnosed with breast cancer in five geographical regions Finland in 1991-1992, reviewed the hospital case records, and collected primary tumor tissue. Out of the 2,032 cases identified, 234 developed distant metastases after a median follow-up time of 2.7 years and had the first metastatic site documented (a total of 321 sites). Primary tumor microarray (TMA) cores were analyzed for 17 proteins using immunohistochemistry and for erbB2 using chromogenic in situ hybridization, and their associations with the first metastasis site were examined. The cancers were classified into luminal A, luminal B, HER2+ enriched, basal-like or non-expressor subtypes. Results A total of 3,886 TMA cores were analyzed. Luminal A cancers had a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases. Primary tumors that gave first rise to bone metastases expressed frequently estrogen receptor (ER) and SNAI1 (SNAIL) and rarely COX2 and HER2, tumors with first metastases in the liver expressed infrequently SNAI1, those with lung metastases expressed frequently the epidermal growth factor receptor (EGFR), cytokeratin-5 (CK5) and HER2, and infrequently progesterone receptor (PgR), tumors with early skin metastases expressed infrequently E-cadherin, and breast tumors with first metastases in the brain expressed nestin, prominin-1 and CK5 and infrequently ER and PgR. Conclusions Breast tumor biological subtypes have a tendency to give rise to first distant metastases at certain body sites. Several primary tumor proteins were associated with homing of breast cancer cells.BioMed Central Open acces

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection

Seascape Genetics of a Globally Distributed, Highly Mobile Marine Mammal: The Short-Beaked Common Dolphin (Genus Delphinus)

Identifying which factors shape the distribution of intraspecific genetic diversity is central in evolutionary and conservation biology. In the marine realm, the absence of obvious barriers to dispersal can make this task more difficult. Nevertheless, recent studies have provided valuable insights into which factors may be shaping genetic structure in the world's oceans. These studies were, however, generally conducted on marine organisms with larval dispersal. Here, using a seascape genetics approach, we show that marine productivity and sea surface temperature are correlated with genetic structure in a highly mobile, widely distributed marine mammal species, the short-beaked common dolphin. Isolation by distance also appears to influence population divergence over larger geographical scales (i.e. across different ocean basins). We suggest that the relationship between environmental variables and population structure may be caused by prey behaviour, which is believed to determine common dolphins' movement patterns and preferred associations with certain oceanographic conditions. Our study highlights the role of oceanography in shaping genetic structure of a highly mobile and widely distributed top marine predator. Thus, seascape genetic studies can potentially track the biological effects of ongoing climate-change at oceanographic interfaces and also inform marine reserve design in relation to the distribution and genetic connectivity of charismatic and ecologically important megafauna

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Evidence for Top Quark Production in Nucleus-Nucleus Collisions

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Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe