Do nonfinancial firms hold risky financial assets? Evidence from Germany

Recent empirical evidence suggests that US industrial firms invest heavily in noncash, risky financial assets. Using hand-collected data on financial portfolios of German firms, we show that risky asset holdings are not an anomaly unique to the US. We find that industrial firms in Germany invest 11.6% of their financial assets in noncash and risky assets. Value-weighted, this percentage increases to 25.4 %. While the equally-weighted average is substantial, it is clearly lower (5 percentage points or 30% in relative terms) than that in the US. After accounting for cross-country compositional differences (especially the dominance of large firms in the US technologysector), this difference in risky financial asset holdings decreases but remains at 3 percentage points. The remaining difference is driven by institutional differences that affect the relationship between firm characteristics and risky financial asset holdings in the two countries. In contrast to the US, German firms largely follow the precautionary savings motive and do not seem to misappropriate their funds when shifting them towards riskier asset allocations. Our results have implications for how asset management by nonfinancial firms should be regulated

Development and validation of a neurotoxicological test battery for neurotoxicity risk assessment

The present study was conducted as part of the research project "Tox-Box: securing drops of life - an enhanced health-related approach for risk assessment of drinking water in Germany”, funded by the Federal Ministry of Education and Research (02WRS1282G). The main fields of research within this project were endocrine disruption, genotoxicity, germ cell toxicity and neurotoxicity. The central task was to provide a compilation of methods to gain information about emerging pollutants to rank these in the health-related indicator value (HRIV) supported by the Federal Environmental Agency. The thesis, embedded in the field of neurotoxicity, aims at developing and validating a test battery for neurotoxicity, based on zebrafish embryo within scope of the 3R principle. The test systems comprised: (1) an extended embryo toxicity test (FET) to assess the general toxicity of substances and sediment extracts as well as to discriminate between neurotoxic and general physiological effects, (2) the acetylcholinesterase activity, (3) the lateral line system, (4) the olfactory epithelium and (5) the retina of zebrafish embryos. The methods were evaluated by screening test with various substances, namely amidotrizoic acid, caffeine, cypermethrin, 2,4-dichlorophenol, 2,4-dinitrotoluene, dichlorvos, 4-nonylphenol, paraoxon-methyl, perfluorooctanoic acid and perfluorooctane sulfonic acid. The extended embryo toxicity test proved useful to detect physiopathological effects and led to the determination of the EC10 value, which was used in subsequent neurotoxicity test to exclude side effects by physiological influences. The acetylcholinesterase test detects both, inhibition (dichlorvos / paraoxon) and activation (cypermethrin) and can be used as an in vivo and in vitro assay, as well as for pure substances and sediment extracts. A few substances were positive in one method exclusively, either in vivo or in vitro. Three out of nine substances triggered the test system at all, but, far below the EC10, constituting a high sensitivity and high specificity. The neuromast assay proved to be more sensitive than most comparable studies. Observing anterior and posterior neuromasts separately, led to a reduction of false-negative results. Additionally, 80 % of the substances showed effects at the EC10, which documents a high sensitivity, but limited specificity. Furthermore, being affected by endocrine disruptors (nonylphenol, perfluorooctansulfonic acid) as well, this methods also covers effects outside neurotoxicity. Specific olfactory antibodies (Golf , ANO2-, GAP43-Antibody) have been detected in the olfactory system. Anti-Golf was detected in the cilia of ciliary receptor neurons, leading to the use of Golf as a marker in the olfactory epithelium. The combination of wholemount staining and cryosectioning led to a sufficient structure resolution. Since only the positive control zinc sulfate and none of the standard substances had effects in the olfactory epithelium, the use in a test battery is not yet given. For the presentation of histopathological effects in the retina, a classic hematoxylin / eosin staining of paraffin sections has proved useful. However, effects in layer arrangement could be detected for any of the substances tested at the EC10. Therefore, the retina is quite insensitive for neurotoxicity testing in the range of EC10. In summary, the combination of embryo toxicity testing, the acetylcholinesterase assay (in vivo and in vitro) and the neuromast assay, seems suitable for a neurotoxicity test battery

Changes of Maximum Leg Strength Indices During Adulthood a Cross-Sectional Study With Non-athletic Men Aged 19–91

Age-related loss of muscle mass and function, also called sarcopenia, was recently added to the ICD-10 as an independent condition. However, declines in muscle mass and function are inevitable during the adulthood aging process. Concerning muscle strength as a crucial aspect of muscle function, maximum knee extension strength might be the most important physical parameter for independent living in the community. In this study, we aimed to determine the age-related decline in maximum isokinetic knee extension (MIES) and flexion strength (MIFS) in adult men. The primary study hypothesis was that there is a slight gradual decrease of MIES up to ≈age 60 years with a significant acceleration of decline after this “changepoint.” We used a closed kinetic chain system (leg-press), which is seen as providing functionally more relevant results on maximum strength, to determine changes in maximum isokinetic hip/leg extensor (MIES) and flexor strength (MIFS) during adulthood in men. Apart from average annual changes, we aimed to identify whether the decline in maximum lower extremity strength is linear. MIES and MIFS data determined by an isokinetic leg-press of 362 non-athletic, healthy, and community-dwelling men 19–91 years old were included in the analysis. A changepoint analysis was conducted based on a multiple regression analysis adjusted for selected co-variables that might confound the proper relationship between age and maximum strength. In summary, maximum isokinetic leg-strength decline during adulthood averaged around 0.8–1.0% p.a.; however, the reduction was far from linear. MIES demonstrated a non-significant reduction of 5.2 N/p.a. (≈0.15% p.a.) up to the estimated breakpoint of 52.0 years and an accelerated loss of 44.0 N/p.a. (≈1.3% p.a.; p < 0.001). In parallel, the decline in MIFS (10.0 N/p.a.; ≈0.5% p.a.) prior to the breakpoint at age 59.0 years was significantly more pronounced. Nevertheless, we observed a further marked accelerated loss of MIFS (25.0 N/p.a.; ≈1.3% p.a.) in men ≥60 years. Apart from the “normative value” and closed kinetic chain aspect of this study, the practical application of our results suggests that sarcopenia prophylaxis in men should be started in the 5th decade in order to address the accelerated muscle decline of advanced age

Physical signatures of discontinuities of the time-dependent exchange-correlation potential

The exact exchange-correlation (XC) potential in time-dependent density-functional theory (TDDFT) is known to develop steps and discontinuities upon change of the particle number in spatially confined regions or isolated subsystems. We demonstrate that the self-interaction corrected adiabatic local-density approximation for the XC potential has this property, using the example of electron loss of a model quantum well system. We then study the influence of the XC potential discontinuity in a real-time simulation of a dissociation process of an asymmetric double quantum well system, and show that it dramatically affects the population of the resulting isolated single quantum wells. This indicates the importance of a proper account of the discontinuities in TDDFT descriptions of ionization, dissociation or charge transfer processes.Comment: 17 pages, 6 figure

Effect of Exercise Training on Bone Mineral Density in Post-menopausal Women : A Systematic Review and Meta-Analysis of Intervention Studies

Osteoporosis is a major health problem in post-menopausal women (PMW). Exercise training is considered a cost-effective strategy to prevent osteoporosis in middle aged-older people. The purpose of this study is to summarize the effect of exercise on BMD among PMW. A comprehensive search of electronic databases was conducted through PubMed, Scopus, Web of Science, Cochrane, Science Direct, Eric, ProQuest, and Primo. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) femoral neck (FN) and/or total hip were considered as outcome measures. After subgroup categorization, statistical methods were used to combine data and compare subgroups. Seventy-five studies were included. The pooled number of participants was 5,300 (intervention group:n= 2,901, control group:n= 2,399). The pooled estimate of random effect analysis was SMD = 0.37, 95%-CI: 0.25-0.50, SMD = 0.33, 95%-CI: 0.23-0.43, and SMD = 0.40, 95%-CI: 0.28-0.51 for LS, FN, and total Hip-BMD, respectively. In the present meta-analysis, there was a significant (p<0.001), but rather low effect (SMD = 0.33-0.40) of exercise on BMD at LS and proximal femur. A large variation among the single study findings was observed, with highly effective studies but also studies that trigger significant negative results. These findings can be largely attributed to differences among the exercise protocols of the studies. Findings suggest that the true effect of exercise on BMD is diluted by a considerable amount of studies with inadequate exercise protocols.Peer reviewe

Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in isolated mouse ventricular myocytes

BackgroundThe Bruton tyrosine kinase (BTK) inhibitor Ibrutinib is associated with a higher incidence of cardiotoxic side effects including heart failure (HF).ObjectivesIbrutinib is capable of inhibiting PI3K/Akt signaling in neonatal rat ventricular cardiomyocytes when stimulated with insulin-like growth factor 1 (IGF-1). We therefore hypothesized that Ibrutinib might disrupt IGF-1-mediated activation of intracellular Ca handling in adult mouse cardiomyocytes by inhibiting PI3K/Akt signaling.MethodsIsolated ventricular myocytes (C57BL6/J) were exposed to IGF-1 at 10 nmol/L in the presence or absence of Ibrutinib (1 µmol/L) or Acalabrutinib (10 µmol/L; cell culture for 24 ± 2 h). Intracellular Ca handling was measured by epifluorescence (Fura-2 AM) and confocal microscopy (Fluo-4 AM). Ruptured-patch whole-cell voltage-clamp was used to measure ICa. Levels of key cardiac Ca handling proteins were investigated by immunoblots.ResultsIGF-1 significantly increased Ca transient amplitudes by ∼83% as compared to vehicle treated control cells. This was associated with unaffected diastolic Ca, enhanced SR Ca loading and increased ICa. Co-treatment with Ibrutinib attenuated both the IGF-1-mediated increase in SR Ca content and in ICa. IGF-1 treated cardiomyocytes had significantly increased levels of pS473Akt/Akt and SERCA2a expression as compared to cells concomitantly treated with IGF-1 and Ibrutinib. SR Ca release (as assessed by Ca spark frequency) was unaffected by either treatment. In order to test for potential off-target effects, second generation BTK inhibitor Acalabrutinib with greater BTK selectivity and lower cardiovascular toxicity was tested for IGF1-mediated activation of intracellular Ca handling. Acalabrutinib induced similar effects on Ca handling in IGF-1 treated cultured myocytes as Ibrutinib in regard to decreased Ca transient amplitude and slowed Ca transient decay, hence implying a functional class effect of BTK inhibitors in cardiac myocytes.ConclusionsInhibition of BTK by Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in adult ventricular mouse myocytes in the face of disrupted Akt signaling and absent SERCA2a upregulation

Benchmarking CMIP5 models with a subset of ESA CCI Phase 2 data using the ESMValTool

The Coupled Model Intercomparison Project (CMIP) is now moving into its sixth phase and aims at a more routine evaluation of the models as soon as the model output is published to the Earth System Grid Federation (ESGF). To meet this goal the Earth System Model Evaluation Tool (ESMValTool), a community diagnostics and performance metrics tool for the systematic evaluation of Earth system models (ESMs) in CMIP, has been developed and a first version (1.0) released as open source software in 2015. Here, an enhanced version of the ESMValTool is presented that exploits a subset of Essential Climate Variables (ECVs) from the European Space Agency's Climate Change Initiative (ESA CCI) Phase 2 and this version is used to demonstrate the value of the data for model evaluation. This subset includes consistent, long-term time series of ECVs obtained from harmonized, reprocessed products from different satellite instruments for sea surface temperature, sea ice, cloud, soil moisture, land cover, aerosol, ozone, and greenhouse gases. The ESA CCI data allow 'extending the calculation of performance metrics as summary statistics for some variables and add an important alternative data set in other cases where observations are already available. The provision of uncertainty estimates on a per grid basis for the ESA CCI data sets is used in a new extended version of the Taylor diagram and provides important additional information for a more objective evaluation of the models. In our analysis we place a specific focus on the comparability of model and satellite data both in time and space. The ESA CCI data are well suited for an evaluation of results from global climate models across ESM compartments as well as an analysis of long-term trends, variability and change in the context of a changing climate. The enhanced version of the ESMValTool is released as open source software and ready to support routine model evaluation in CMIP6 and at individual modeling centers. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Diversity and specialization responses to climate and land use differ between deadwood fungi and bacteria

Climate and land use are major determinants of biodiversity, and declines in species richness in cold and human exploited landscapes can be caused by lower rates of biotic interactions. Deadwood fungi and bacteria interact strongly with their hosts due to long-lasting evolutionary trajectories. However, how rates of biotic interactions (specialization) change with temperature and land-use intensity are unknown for both microbial groups. We hypothesize a decrease in species richness and specialization of communities with decreasing temperature and increasing land use intensity while controlling for precipitation. We used a full-factorial nested design to disentangle land use at habitat and landscape scale and temperature spanning an area of 300 × 300 km in Germany. We exposed four deadwood objects representing the main tree species in Central Europe (beech, oak, spruce, pine) in 175 study plots. Overall, we found that fungal and bacterial richness, community composition and specialization were weakly related to temperature and land use. Fungal richness was slightly higher in near-natural than in urban landscapes. Bacterial richness was positively associated with mean annual temperature, negatively associated with local temperature and highest in grassland habitats. Bacterial richness was positively related to the covariate mean annual precipitation. We found strong effects of host-tree identity on species richness and community composition. A generally high level of fungal host-tree specialization might explain the weak response to temperature and land use. Effects of host-tree identity and specialization were more pronounced in fungi. We suggest that host tree changes caused by land use and climate change will be more important for fungal communities, while changes in climate will affect bacterial communities more directly. Contrasting responses of the two taxonomic groups suggest a reorganization of deadwood microbial communities, which might have further consequences on diversity and decomposition in the Anthropocene

Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex

Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. Using X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core, together with cross-linking coupled to mass spectrometry, we were able to use IMP to position and orient all eIF3 components on the 40S•eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. For more information about how to reproduce this modeling, see https://salilab.org/40S-eIF1-eIF3 or the README file