Mechanisms 9f .the Influence of Uric Acid on the Precipitation of Ca-Oxalate Crystals out of Metastable Solution (Urine

One of the very actual problems in the urolithiasis research is, the ,question whether and in what way raised uric acid can influence the formation of _ Ca-oxalate stones

Current status of MELCOR 2.2 for fusion safety analyses

MELCOR is an integral code developed by Sandia National Laboratories (SNL) for the US Nuclear Regulatory Commission (USNRC) to perform severe accident analyses of Light Water Reactors (LWR). More recently, MELCOR capabilities are being extended also to analyze non-LWR fission technologies. Within the European MELCOR User Group (EMUG), organized in the framework of USNRC Cooperative Severe Accident Research Program (CSARP), an activity on the evaluation of the applicability of MELCOR 2.2 for fusion safety analyses has been launched and it has been coordinated by ENEA. The aim of the activity was to identify the physical models to be possibly implemented in MELCOR 2.2 necessary for fusion safety analyses, and to check if those models are already available in MELCOR 1.8.6 for fusion version, developed by Idaho National Laboratory (INL). From this activity, a list of modeling needs emerged from the safety analyses of fusion-related installations have been identified and described. Then, the importance of the various needs, intended as the priority for model implementation in the MELCOR 2.2 code, has been evaluated according to the technical expert judgement of the authors. In the present paper, the identified modeling needs are discussed. The ultimate goal would be to propose to have a single integrated MELCOR 2.2 code release capable to cover both fission and fusion applications

Current status of Melcor 2.2 for fusion safety analyses

MELCOR is an integral code developed by Sandia National Laboratories (SNL) for the US Nuclear Regulatory Commission (USNRC) to perform severe accident analyses of Light Water Reactors (LWR). More recently, MELCOR capabilities are being extended also to analyze non-LWR fission technologies. Within the European MELCOR User Group (EMUG), organized in the framework of the USNRC Cooperative Severe Accident Research Program (CSARP), an activity on the evaluation of the applicability of MELCOR 2.2 for fusion safety analyses has been launched and it has been coordinated by ENEA. The aim of the activity was to identify the physical models to be possibly implemented in MELCOR 2.2 necessary for fusion safety analyses, and to check if those models are already available in MELCOR 1.8.6 fusion version, developed by Idaho National Laboratory (INL). From this activity, a list of modeling needs that emerged from the safety analyses of fusion-related installations has been identified and described. Then, the importance of the various needs, intended as the priority for model implementation in the MELCOR 2.2 code, has been evaluated according to the technical expert judgment of the authors. In the present paper, the identified modeling needs are discussed. The ultimate goal would be to propose to have a single integrated MELCOR 2.2 code release capable to cover both fission and fusion applications

Auditory ossicles: a potential biomarker for maternal and infant health in utero

YesBackground: Carbon (δ13C) and nitrogen (δ15N) isotope ratios of collagen from teeth and bone are used to study human nutrition and health. As bones are constantly remodelling throughout life, isotopic values of bone collagen represent an average of several years. In contrast, human teeth do not remodel and their primary dentine contains only the isotopic data from the time of formation. In contrast to all other bones, human auditory ossicles also appear not to remodel. As they develop in utero and finish formation in the first 2 years of life, their collagen should also represent isotopic values of these two relatively short periods. Aim: By comparing δ13C and δ15N data from ossicles and incremental dentine, this study aims to investigate how two developmental periods of the ossicles, in utero and the first 2 years of life, reflect in collagen obtained from the ossicles. Subject and methods: Ossicle and tooth samples of 12 individuals aged 0.5 ± 0.4 years to 13 ± 1 years from the nineteenth century St. Peter’s burial ground in Blackburn were collected and processed to obtain bulk bone and incremental dentine collagen which was measured for δ13C and δ15N. Results: Averaged δ13C and δ15N of ossicles are lower when compared to every age group except after 3 years of age. Average offset between ossicles and dentine of different groups ranges from 0.4–0.9‰ for δ13C and from 0.3–0.9‰ for δ15N, with highest counterbalance at birth and after the first 5 months after birth. Conclusions: There appears to be a systematic offset between the dentine and ossicle data. It seems that the second phase of development does not influence the isotopic values of collagen significantly and the data we are obtaining from ossicles represents the in utero period.Research grant from The Society for the Study of Human Biology

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design

Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite

PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder caused by mutations in at least two different loci. Prior to performing mutation screening, if DNA samples of sufficient number of family members are available, it is worthwhile to assign the gene involved in disease progression by the genetic linkage analysis. METHODS: We collected samples from 36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage was assessed by the use of microsatellite polymorphic markers, four in the case of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing exons 23 and 31–46 and PKD2 . RESULTS: Lod scores indicated linkage to PKD1 in six families and to PKD2 in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial PKD1 mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed PKD2 in 2 patients where lod scores indicated linkage to PKD2 and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in PKD1 and one mutation and three polymorphisms in PKD2. CONCLUSION: In our study group of ADPKD patients we detected seven mutations: three frameshift, one missense, two nonsense and one putative splicing mutation. Three have been described previously and 4 are novel. Three newly described framesfift mutations in PKD1 seem to be associated with more severe clinical course of ADPKD. Previously described nonsense mutation in PKD2 seems to be associated with cysts in liver and milder clinical course

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%