A Large Scale Double Beta and Dark Matter Experiment: GENIUS

The recent results from the HEIDELBERG-MOSCOW experiment have demonstrated the large potential of double beta decay to search for new physics beyond the Standard Model. To increase by a major step the present sensitivity for double beta decay and dark matter search much bigger source strengths and much lower backgrounds are needed than used in experiments under operation at present or under construction. We present here a study of a project proposed recently, which would operate one ton of 'naked' enriched GErmanium-detectors in liquid NItrogen as shielding in an Underground Setup (GENIUS). It improves the sensitivity to neutrino masses to 0.01 eV. A ten ton version would probe neutrino masses even down to 10^-3 eV. The first version would allow to test the atmospheric neutrino problem, the second at least part of the solar neutrino problem. Both versions would allow in addition significant contributions to testing several classes of GUT models. These are especially tests of R-parity breaking supersymmetry models, leptoquark masses and mechanism and right-handed W-boson masses comparable to LHC. The second issue of the experiment is the search for dark matter in the universe. The entire MSSM parameter space for prediction of neutralinos as dark matter particles could be covered already in a first step of the full experiment - with the same purity requirements but using only 100 kg of 76Ge or even of natural Ge - making the experiment competitive to LHC in the search for supersymmetry. The layout of the proposed experiment is discussed and the shielding and purity requirements are studied using GEANT Monte Carlo simulations. As a demonstration of the feasibility of the experiment first results of operating a 'naked' Ge detector in liquid nitrogen are presented.Comment: 22 pages, 12 figures, see also http://pluto.mpi-hd.mpg.de/~betalit/genius.htm

Considering the role of cognitive control in expert performance

© 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

Serum Fetuin-A Associates with Type 2 Diabetes and Insulin Resistance in Chinese Adults

Previous studies have demonstrated that fetuin-A is related to insulin resistance among subjects with normal glucose tolerance but not patients with type 2 diabetes. There are limited data available concerning fetuin-A and insulin resistance in Chinese. We aimed to study the association of fetuin-A with insulin resistance among participants with or without type 2 diabetes in a large sample size of adults aged 40 and older.A community-based cross-sectional study was performed among 5,227 Chinese adults. The average age of our study was 61.5±9.9 years. Serum fetuin-A concentrations were not significantly different between male and female (296.9 vs. 292.9 mg/l, p = 0.11). Compared with the lowest quartile, the highest quartile of serum fetuin-A revealed a significant higher proportion of type 2 diabetic patients (34.8% vs. 27.3%, p<0.0001). In the multinomial logit models, the risk of type 2 diabetes was associated with each one quartile increase of serum fetuin-A concentrations when referenced not only to normal glucose tolerance (OR 1.24, 95% CI 1.07-1.43, p = 0.004) but also to impaired glucose regulation (OR 1.25, 95% CI 1.08-1.44, p = 0.003, respectively), after adjustment for age, sex, community, current smoking, and current drinking. The logistic regression analysis showed that fetuin-A were associated with elevated HOMA-IR and fasting serum insulin both among the participants with or without type 2 diabetes in the full adjusted analysis. There was no significant association between elevated serum fetuin-A concentrations and impaired glucose regulation (all p≥0.12).Higher fetuin-A concentrations were associated with type 2 diabetes and insulin resistance in middle aged and elderly Chinese

High Resolution MEMS Accelerometers to Estimate VO2 and Compare Running Mechanics between Highly Trained Inter-Collegiate and Untrained Runners

BACKGROUND: The purposes of this study were to determine the validity and reliability of high resolution accelerometers (HRA) relative to VO(2) and speed, and compare putative differences in HRA signal between trained (T) and untrained (UT) runners during treadmill locomotion. METHODOLOGY: Runners performed 2 incremental VO(2max) trials while wearing HRA. RMS of high frequency signal from three axes (VT, ML, AP) and the Euclidean resultant (RES) were compared to VO(2) to determine validity and reliability. Additionally, axial rms relative to speed, and ratio of axial accelerations to RES were compared between T and UT to determine if differences in running mechanics could be identified between the two groups. PRINCIPAL FINDINGS: Regression of RES was strongly related to VO(2), but T was different than UT (r = 0.96 vs 0.92; p<.001) for walking and running. During walking, only the ratio of ML and AP to RES were different between groups. For running, nearly all acceleration parameters were lower for T than UT, the exception being ratio of VT to RES, which was higher in T than UT. All of these differences during running were despite higher VO(2), O(2) cost, and lower RER in T vs UT, which resulted in no significant difference in energy expenditure between groups. CONCLUSIONS/SIGNFICANCE: These results indicate that HRA can accurately and reliably estimate VO(2) during treadmill locomotion, but differences exist between T and UT that should be considered when estimating energy expenditure. Differences in running mechanics between T and UT were identified, yet the importance of these differences remains to be determined

Methane emission by Camelids

Methane emissions from ruminant livestock have been intensively studied in order to reduce contribution to the greenhouse effect. Ruminants were found to produce more enteric methane than other mammalian herbivores. As camelids share some features of their digestive anatomy and physiology with ruminants, it has been proposed that they produce similar amounts of methane per unit of body mass. This is of special relevance for countrywide greenhouse gas budgets of countries that harbor large populations of camelids like Australia. However, hardly any quantitative methane emission measurements have been performed in camelids. In order to fill this gap, we carried out respiration chamber measurements with three camelid species (Vicugna pacos, Lama glama, Camelus bactrianus; n = 16 in total), all kept on a diet consisting of food produced from alfalfa only. The camelids produced less methane expressed on the basis of body mass (0.3260.11 L kg21 d21) when compared to literature data on domestic ruminants fed on roughage diets (0.5860.16 L kg21 d21). However, there was no significant difference between the two suborders when methane emission was expressed on the basis of digestible neutral detergent fiber intake (92.7633.9 L kg21 in camelids vs. 86.2612.1 L kg21 in ruminants). This implies that the pathways of methanogenesis forming part of the microbial digestion of fiber in the foregut are similar between the groups, and that the lower methane emission of camelids can be explained by their generally lower relative food intake. Our results suggest that the methane emission of Australia’s feral camels corresponds only to 1 to 2% of the methane amount produced by the countries’ domestic ruminants and that calculations of greenhouse gas budgets of countries with large camelid populations based on equations developed for ruminants are generally overestimating the actual levels

FGF-23: More Than a Regulator of Renal Phosphate Handling?

Fibroblast growth factor 23 (FGF-23) is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through FGF receptors and the coreceptor Klotho. Besides reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, FGF-23 inhibits the renal 1α-hydroxylase and stimulates the 24-hydroxylase, and it appears to reduce parathyroid hormone (PTH) secretion in short-term studies. FGF-23 synthesis and secretion by osteocytes and osteoblasts is upregulated through 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and through an increased dietary phosphate intake. FGF-23 levels are elevated or inappropriately normal in patients with tumor-induced osteomalacia and several inherited hypophosphatemic disorders, but the most significant increases are found in patients with chronic kidney disease (CKD). During the early stages of CKD, increased FGF-23 production enhances urinary phosphate excretion and thus prevents the development of hyperphosphatemia, reduces the circulating levels of 1,25(OH)2D3, and therefore contributes to the development of secondary hyperparathyroidism. In patients with end-stage renal disease (ESRD), FGF-23 levels can be extremely high and were shown to be predictors of bone mineralization, left ventricular hypertrophy, vascular calcification, and mortality. It remains to be determined, however, whether FGF-23 represents simply a sensitive biomarker of an abnormal phosphate homeostasis or has, independent of serum phosphate levels, potentially negative “off-target” effects. Nonetheless, reducing the production and/or the biologic activity of FGF-23 may be an important therapeutic goal for this patient population. © 2010 American Society for Bone and Mineral Research

Physical exercise, fitness and dietary pattern and their relationship with circadian blood pressure pattern, augmentation index and endothelial dysfunction biological markers: EVIDENT study protocol

Background: Healthy lifestyles may help to delay arterial aging. The purpose of this study is to analyze the relationship of physical activity and dietary pattern to the circadian pattern of blood pressure, central and peripheral blood pressure, pulse wave velocity, carotid intima-media thickness and biological markers of endothelial dysfunction in active and sedentary individuals without arteriosclerotic disease. Methods/Design Design: A cross-sectional multicenter study with six research groups. Subjects: From subjects of the PEPAF project cohort, in which 1,163 who were sedentary became active, 1,942 were sedentary and 2,346 were active. By stratified random sampling, 1,500 subjects will be included, 250 in each group. Primary measurements: We will evaluate height, weight, abdominal circumference, clinical and ambulatory blood pressure with the Radial Pulse Wave Acquisition Device (BPro), central blood pressure and augmentation index with Pulse Wave Application Software (A-Pulse) and SphymgoCor System Px (Pulse Wave Analysis), pulse wave velocity (PWV) with SphymgoCor System Px (Pulse Wave Velocity), nutritional pattern with a food intake frequency questionnaire, physical activity with the 7-day PAR questionnaire and accelerometer (Actigraph GT3X), physical fitness with the cycle ergometer (PWC-170), carotid intima-media thickness by ultrasound (Micromax), and endothelial dysfunction biological markers (endoglin and osteoprotegerin). Discussion: Determining that sustained physical activity and the change from sedentary to active as well as a healthy diet improve circadian pattern, arterial elasticity and carotid intima-media thickness may help to propose lifestyle intervention programs. These interventions could improve the cardiovascular risk profile in some parameters not routinely assessed with traditional risk scales. From the results of this study, interventional approaches could be obtained to delay vascular aging that combine physical exercise and diet

Double trouble at high density::Cross-level test of ressource-related adaptive plasticity and crowding-related fitness.

Population size is often regulated by negative feedback between population density and individual fitness. At high population densities, animals run into double trouble: they might concurrently suffer from overexploitation of resources and also from negative interference among individuals regardless of resource availability, referred to as crowding. Animals are able to adapt to resource shortages by exhibiting a repertoire of life history and physiological plasticities. In addition to resource-related plasticity, crowding might lead to reduced fitness, with consequences for individual life history. We explored how different mechanisms behind resource-related plasticity and crowding-related fitness act independently or together, using the water flea Daphnia magna as a case study. For testing hypotheses related to mechanisms of plasticity and crowding stress across different biological levels, we used an individual-based population model that is based on dynamic energy budget theory. Each of the hypotheses, represented by a sub-model, is based on specific assumptions on how the uptake and allocation of energy are altered under conditions of resource shortage or crowding. For cross-level testing of different hypotheses, we explored how well the sub-models fit individual level data and also how well they predict population dynamics under different conditions of resource availability. Only operating resource-related and crowding-related hypotheses together enabled accurate model predictions of D. magna population dynamics and size structure. Whereas this study showed that various mechanisms might play a role in the negative feedback between population density and individual life history, it also indicated that different density levels might instigate the onset of the different mechanisms. This study provides an example of how the integration of dynamic energy budget theory and individual-based modelling can facilitate the exploration of mechanisms behind the regulation of population size. Such understanding is important for assessment, management and the conservation of populations and thereby biodiversity in ecosystems

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a Kiapp value of 3.8±0.8 µM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 µM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 Å2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750–1,500 Å2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a Ki value of 760±170 nM using synthesis-based computer-aided molecular design (SBCAMD). This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight into structural modification of known small-molecule BoNTAe inhibitors. It also demonstrates that SBCAMD is capable of improving potency of an inhibitor lead by nearly one order of magnitude, even for BoNTAe as one of the most challenging protein targets. The results are insightful for developing effective small-molecule inhibitors of protein targets with large active sites

Observational Constraints on the Common Envelope Phase

The common envelope phase was first proposed more than forty years ago to explain the origins of evolved, close binaries like cataclysmic variables. It is now believed that the phase plays a critical role in the formation of a wide variety of other phenomena ranging from type Ia supernovae through to binary black holes, while common envelope mergers are likely responsible for a range of enigmatic transients and supernova imposters. Yet, despite its clear importance, the common envelope phase is still rather poorly understood. Here, we outline some of the basic principles involved, the remaining questions as well as some of the recent observational hints from common envelope phenomena - namely planetary nebulae and luminous red novae - which may lead to answering these open questions.Comment: 29 pages, 8 figures. To appear in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds. Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556