Data Bridge: solving diverse Data Access in Scientific Applications

The nature of data for scientific computation is very diverse in the age of big data. First, it may be available at a number of locations, e.g. the scientist’s machine, some institutional filesystem, a remote service, or some sort of database. Second, the size of the data may vary from a few kilobytes to many terabytes. In order to be available for computation, data has to be transferred to the location where the computation takes place. This requires a diverse set of middleware tools that are compatible both with the data and the compute resources. However, using this tools requires additional knowledge and makes running the experiments an inconvenient task. In this paper we present the Data Bridge, a high-level service that can be used easily in scientific computations to perform data transfer to and from a diverse set of storage services. The Data Bridge not only unifies access to different types of storage services, but it can also be used at different levels (e.g., single jobs, parameter sweeps, scientific workflows) in scientific computations

Intranasal Delivery of a Methyllanthionine-Stabilized Galanin Receptor-2-Selective Agonist Reduces Acute Food Intake

The regulatory (neuro)peptide galanin is widely distributed in the central and peripheral nervous systems, where it mediates its effects via three G protein-coupled receptors (GAL(1-3)R). Galanin has a vast diversity of biological functions, including modulation of feeding behavior. However, the clinical application of natural galanin is not practicable due to its rapid in vivo breakdown by peptidases and lack of receptor subtype specificity. Much effort has been put into the development of receptor-selective agonists and antagonists, and while receptor selectivity has been attained to some degree, most ligands show overlapping affinity. Therefore, we aimed to develop a novel ligand with specificity to a single galanin receptor subtype and increased stability. To achieve this, a lanthionine amino acid was enzymatically introduced into a galanin-related peptide. The residue’s subsequent cyclization created a conformational constraint which increased the peptide’s receptor specificity and proteolytic resistance. Further exchange of certain other amino acids resulted in a novel methyllanthionine-stabilized galanin receptor agonist, a G1pE-T3N-S6A-G12A-methyllanthionine[13–16]-galanin-(1–17) variant, termed M89b. M89b has exclusive specificity for GAL(2)R and a prolonged half-life in serum. Intranasal application of M89b to unfasted rats significantly reduced acute 24 h food intake inducing a drop in body weight. Combined administration of M89b and M871, a selective GAL(2)R antagonist, abolished the anorexigenic effect of M89b, indicating that the effect of M89b on food intake is indeed mediated by GAL(2)R. This is the first demonstration of in vivo activity of an intranasally administered lanthipeptide. Consequently, M89b is a promising candidate for clinical application as a galanin-related peptide-based therapeutic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01155-x

Age and nutritional state influence the effects of cholecystokinin on energy balance

AbstractCholecystokinin (CCK) is anorexic, irrespective whether it is applied intraperitoneally (IP) or intracerebroventricularly (ICV) in male Wistar rats. The metabolic effects depend on the route of administration: by the IP route it elicits hypothermia (presumably by type-1 receptors, CCK1R-s), while ICV administration is followed by fever-like hypermetabolism and hyperthermia via activation of CCK2R-s, which latter response seems to be most important in the postprandial (compensatory) hypermetabolism. The efficacy of the IP injected CCK varies with age: it causes strong anorexia in young adult 4 and 6-months old and again in old rats (aged 18–24months), but the middle-aged (12-month old) ones seem to be resistant to this effect. Such pattern of effects may contribute to the explanation of age-related obesity observed in middle-aged animals as well as to the aging anorexia and loss of body weight in old ones. Diet-induced obesity accelerates the appearance of CCK-resistance as well as the return of high sensitivity to CCK in further aging, while chronic calorie-restriction prevents the development of resistance, as if the speed of the age-related regulatory changes was altered by the nutritional state. The effects of ICV applied CCK also change with age: the characteristic anorexic and hypermetabolic/hyperthermic effects can be observed in young adult rats, but the effects gradually and monotonically decline with age and disappear by the old age of 24months. These disparate age-related patterns of CCK efficacy upon peripheral or central administration routes may indicate that although both peripheral and central CCKR-s exert anorexic effects, they may have dissimilar roles in the regulation of overall energy balance

CODEX-CT-1 experiment: Quenching of fuel bundle after long term oxidation in hydrogen rich steam KFKI-2008-01/G

The cleaning tank incident at the unit 2 of Paks NPP in 2003 resulted in severe fuel damage of 30 assemblies. The fuel rods heated up due to insufficient cooling and the zirconium components suffered heavy oxidation. Opening of the tank and quenching of the assemblies by cold water led to fragmentation of brittle zirconium components. Due to the poor instrumentation there were many open questions concerning the course of the incident and the behaviour of fuel assemblies. In order to improve the understanding of the phenomena that took place during the Paks-2 incident integral tests have been carried out in the CODEX (Core Degradation Experiment) facility. The tests simulated the whole scenario of the incident using electrically heated fuel rods. The final state of the fuel rods showed many similarities with the conditions observed after the incident at the NPP and for this reason it is very probable that the thermal conditions and chemical reactions were also similar in the tests and in the incident. The post-test examination of CODEX-CT-1 bundle indicated that the high degree of embrittlement was a common result of oxidation and hydrogen uptake by the Zr components

CODEX-B4C Experiment: Cored Degradation Test With Boron Carbide Control Rod KFKI-2003-01/G (2003)

The CODEX-B4C bundle test has been successfully performed on 25th May 2001 in the framework of the COLOSS project of the EU 5th FWP. The high temperature degradation of a VVER-1000 type bundle with B4C control rod was investigated with electrically heated fuel rods. The experiment was carried out according to a scenario selected in favour of methane formation. Degradation of control rod and fuel bundle took place at temperatures ~2000 oC, cooling down of the bundle was performed in steam atmosphere. The gas composition measurement indicated no methane production during the experiment. High release of aerosols was detected in the high temperature oxidation phase. The on-line measured data are collected into a database and are available for code validation and development

CODEX-CT-2 experiment: Long term treatment in high temperature hydrogen and water quenching of a fuel bundle KFKI-2008-02/G

The simulation of the Paks-2 incident was carried out in the frame of an experimental programme in the CODEX facility with electrically heated fuel rod bundles. The main boundary conditions for the CODEX-CT-2 were similar to the previous CODEX-CT-1 test. The most significant difference between the two tests was the operation of the air let down valve that was open in the first test and closed in the second one. In the second test the hydrogen produced in the Zr-steam reaction could not escape from the test section and it prevented the access of steam to the Zr surfaces and caused much less oxidation than was observed in the first tests. The final quench by water led to temperature excursion in the bundle and in the shroud. The final state of the bundle was very brittle, the fuel rods and the shroud were cracked and fragmented

Pleasure in decision-making situations

BACKGROUND: This study explores the role of pleasure in decision making. RESULTS: In Experiment 1, 12 subjects were presented with a questionnaire containing 46 items taken from the literature. Twenty-three items described a situation where a decision should be made and ended with a suggested solution. The other items served as filler items. The subjects were requested not to make a decision but to rate the pleasure or displeasure they experienced when reading the situation described in the item. The subjects' ratings were then compared to the decisions on the same situations made by the other subjects of the studies published by other workers. The ratings of pleasure/displeasure given by our subjects correlated significantly with the choices published by other authors. This result satisfies a necessary condition for pleasure to be the key of the decision making process in theoretical situations. In Experiment 2, a new group of 12 subjects rated their experience of pleasure/displeasure when reading various versions of 50 situations taken from daily life where an ethical decision had to be made (Questionnaire I) including 200 items. This was followed by a multiple-choice test with the 50 situations (Questionnaire II) using the same 200 items and offering the various behaviors. Subjects tended to choose ethical and unethical responses corresponding to their highest pleasure rating within each problem. In all cases the subjects' behavior was higher than chance level, and thus, followed the trend to maximize pleasure. In Experiment 3, 12 subjects reading 50 mathematical short problems followed by correct and incorrect versions of the answer to the problem (Questionnaire III), including 200 items. This was followed by a multiple-choice mathematical test with the 50 problems (Questionnaire IV) using the same 200 items and offering the correct and incorrect answers. In questionnaire IV, subjects tended to choose correct as well as incorrect responses corresponding to their highest hedonic rating within each problem. In all cases the subjects' behavior was higher than chance level, and thus, followed the trend to maximize pleasure. CONCLUSIONS: The results of the three experiments support the hypothesis according to which decisions are made in the hedonic dimension of conscious experience

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies

BACKGROUND: Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. OBJECTIVES: We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). METHODS: A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. STATISTICAL METHODS: Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (chi2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. RESULTS: The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. CONCLUSIONS: This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet

In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis

BACKGROUND: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. OBJECTIVES: We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. DATA SOURCES: 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. STATISTICAL METHODS: We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. RESULTS: Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone. CONCLUSIONS: Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss