HPC in Computational Micromechanics of Composite Materials

Proceedings of: Second International Workshop on Sustainable Ultrascale Computing Systems (NESUS 2015). Krakow (Poland), September 10-11, 2015.This work was supported by the European Regional Development Fund in the IT4Innovations Centre of Excellence project (CZ.1.05/1.1.00/02.0070) and the COST NESUS project with an additional CZ MEYS LD15105 support

SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival

Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum ΔV capability of 600 ms−1. Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule

Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages

Objective An increased rate of fractures has been reported in patients with Turner syndrome (TS). We aimed to assess bone geometry and volumetric bone mineral density (vBMD) at the radius in girls with TS and to evaluate the relationships between bone parameters and fracture history. Methods and design Sixty-seven girls with TS aged 6âÂÂ19 years treated currently or in the past with growth hormone (GH) and/or oestrogens were examined using peripheral quantitative computed tomography. Results were compared to reference data. Results Cortical area and cortical thickness were low in all age groups (all P < 0.001). Height-adjusted total bone area at the diaphysis was increased in prepubertal and postpubertal girls (mean Z-score 1.0, P < 0.05 for both) and normal in the pubertal group (mean Z-score 0.1). Cortical vBMD was decreased (mean age-specific Z-scores )2.0, )1ÃÂ6 and )1.0 for prepubertal, pubertal and postpubertal groups, respectively, P < 0.01 for all groups). Height- , age- and cortical thickness-adjusted cortical vBMD was positively correlated to the duration of GH therapy (P = 0.012) and to oestrogen administration (P = 0.047). Girls with a history of fractures had lower total vBMD at the metaphysis compared to nonfractured TS girls (mean Z-scores )1.7 vs )0.9, P = 0.04). Conclusions There is a cortical bone deficit in girls with TS characterized by low cortical area, thin cortex and probably decreased cortical vBMD. Early commencement of GH therapy, as well as oestrogen replacement, is associated with higher cortical vBMD. Further studies should investigate the potential causality of this relation

Chemistry of Molten Salt Reactor Fuel Salt Candidates

Molten salt reactor (MSR) concepts are based on using a molten salt mixture as a primary nuclear reactor coolant, while the fuel can be either directly dissolved in the coolant or can be solid. MSRs can be operated with (epi)thermal or fast neutron spectra, as simple convertors or breeder reactors utilising, e.g., the 232Th-233U cycle, but also as accelerator-driven sub-critical reactors or transuranium elements (TRU) burners. The main advantages of the MSRs using a liquid molten salt fuel resides in the enhanced safety features such as a large negative temperature coefficient of reactivity due to a high thermal expansion, low atmospheric pressure in the core during the operation and no need of transport and fabrication of new fuel elements in the case of closed fuel cycle option. In addition, the liquid fuel brings possibility of continuous fission-product removal via physical and pyrochemical processes which brings flexibility in the fuel cycle. In the last years, development of MSR technology is on the increase in many countries and since 2002, the MSR concept is included to the Generation IV initiative. Since 2001, the European Commission (EC) carries on coordinated R&D activities on the MSR concept within the EC/EURATOM framework programmes. Several projects have been funded exploring the feasibility and safety of the Molten Salt Fast Reactor (MSFR) concept studied in Europe. MSFR is based on a non-moderated epi-thermal neutron spectrum with its fuel dissolved in a fluoride molten salt carrier and utilising a closed thorium fuel cycle. Basic thermodynamic and electrochemical data of pure actinide fluorides and their mixtures are required for the design and safety assessment of any presently studied molten salt reactor concept based on molten fluoride salt fuel. The present work is summarising the recent research in this field carried out at Joint Research Centre (JRC) of the European Commission. It is particularly focused on the synthesis and characterisation of pure actinide fluorides UF4, ThF4 and PuF3 needed for the experimental assessment of the thermodynamic properties of the MSR fuel salt candidates. In addition, the recent achievements of these studies are presented, e.g., re-determination of the UF4 melting point and measurement of the novel thermodynamic data of PuF3-LiF system.JRC.G.I.3-Nuclear Fuel Safet

On the fluorination of plutonium dioxide by ammonium hydrogen fluoride

A method for synthesis of PuF3 from PuO2 by fluorination using NH4HF2 was investigated. The text comprises the literature study on the published methods for PuF3 syntheses, principles of the applied NH4HF2 fluorination, the developed experimental apparatus, the procedure of the synthesis and analysis of the product. The results showed possibility to use the proposed method for PuF3 preparation in a sufficient purity and with a good reaction yield.JRC.E.5-Nuclear chemistr

Nephrotic syndrome sera induce different transcriptomes in podocytes based on the steroid response

As the molecular mechanism of nephrotic syndrome remains largely undiscovered, patients continue to be exposed to the pros and cons of uniform glucocorticoid treatment. We explored whether the exposure of in vitro-cultivated podocytes to sera from children with steroid-sensitive or steroid-resistant nephrotic syndrome induces differences in gene expression profiles, which could help to elucidate the pathogenesis of the steroid response. Human immortalized podocytes were cultivated with patient sera for 3 days. After cell lysis, RNA extraction, 3'-mRNA libraries were prepared and sequenced. There were 34 significantly upregulated and 14 downregulated genes (fold difference &lt;0.5 and &gt;2.0, respectively, and false discovery rate-corrected p &lt; 0.05) and 22 significantly upregulated and 6 downregulated pathways (false discovery rate-corrected p &lt; 0.01) in the steroid-sensitive (n = 9) versus steroid-resistant group (n = 4). The observed pathways included upregulated redox reactions, DNA repair, mitosis, protein translation and downregulated cholesterol biosynthesis. Sera from children with nephrotic syndrome induce disease subtype-specific transcriptome changes in human podocytes in vitro. However, further exploration of a larger cohort is needed to verify whether clinically distinct types of nephrotic syndrome or disease activity may be differentiated by specific transcriptomic profiles and whether this information may help to elucidate the pathogenesis of the steroid response.</p

A 6-Year Follow-Up of Fracture Incidence and Volumetric Bone Mineral Density Development in Girls With Turner Syndrome

Context: Patients with Turner syndrome (TS) are at risk for osteoporotic fractures. Objective: The aims of this study were to assess the incidence of clinically important fractures in girls with TS and prospectively describe the development of volumetric bone mineral density (BMD). Design: Peripheral quantitative computerized tomography (pQCT) of the radius every other year over the 6 years of observation. Setting: Government-funded university referral center. Participants: Thirty-two girls with TS, aged 6 to 16 years, were included in the analyses. Fracture incidence was compared with the data in the general population. Bone density and strength were compared with data from 185 healthy girls. Outcomes: The main clinical outcome was the fracture occurrence. The secondary outcomes were the changes in Z-scores of the bone parameters. Results: Three girls with TS sustained four fractures during 6 years of observation. The fracture rate in TS was not substantially higher than the downward-biased fracture-rate estimate from age-matched, healthy controls (P = 0.48). Whereas the trabecular BMD Z-score decreased with age (beta estimate -0.21 +/- 0.04, P < 0.001), total bone cross-sectional area correspondingly increased (+ 0.16 +/- 0.04, P < 0.001), which led to normal bone strength. A positive history of incident fractures was not significantly associated with any of the pQCT-derived bone parameters. Conclusions: Current pediatric TS patients that are treated with growth hormone and estrogens are not at risk for osteoporotic fractures. Low BMD in TS may be counterweighted by enlarged bone radius, which leads to normal bone strength at the appendicular skeleton

Mitochondrial Respiration of Platelets: Comparison of Isolation Methods

Multiple non-aggregatory functions of human platelets (PLT) are widely acknowledged, yet their functional examination is limited mainly due to a lack of standardized isolation and analytic methods. Platelet apheresis (PA) is an established clinical method for PLT isolation aiming at the treatment of bleeding diathesis in severe thrombocytopenia. On the other hand, density gradient centrifugation (DC) is an isolation method applied in research for the analysis of the mitochondrial metabolic profile of oxidative phosphorylation (OXPHOS) in PLT obtained from small samples of human blood. We studied PLT obtained from 29 healthy donors by high-resolution respirometry for comparison of PA and DC isolates. ROUTINE respiration and electron transfer capacity of living PLT isolated by PA were significantly higher than in the DC group, whereas plasma membrane permeabilization resulted in a 57% decrease of succinate oxidation in PA compared to DC. These differences were eliminated after washing the PA platelets with phosphate buffer containing 10 mmol&middot;L&minus;1 ethylene glycol-bis (2-aminoethyl ether)-N,N,N&prime;,N&prime;-tetra-acetic acid, suggesting that several components, particularly Ca2+ and fuel substrates, were carried over into the respiratory assay from the serum in PA. A simple washing step was sufficient to enable functional mitochondrial analysis in subsamples obtained from PA. The combination of the standard clinical PA isolation procedure with PLT quality control and routine mitochondrial OXPHOS diagnostics meets an acute clinical demand in biomedical research of patients suffering from thrombocytopenia and metabolic diseases