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Modern health care systems are characterized by pronounced prevention and cost-optimized treatments. This dissertation offers novel empirical evidence on how useful such measures can be. The first chapter analyzes how radiation, a main pollutant in health care, can negatively affect cognitive health. The second chapter focuses on the effect of Low Emission Zones on public heath, as air quality is the major external source of health problems. Both chapters point out potentials for preventive measures. Finally, chapter three studies how changes in treatment prices affect the reallocation of hospital resources. In the following, I briefly summarize each chapter and discuss implications for health care systems as well as other policy areas. Based on the National Educational Panel Study that is linked to data on radiation, chapter one shows that radiation can have negative long-term effects on cognitive skills, even at subclinical doses. Exploiting arguably exogenous variation in soil contamination in Germany due to the Chernobyl disaster in 1986, the findings show that people exposed to higher radiation perform significantly worse in cognitive tests 25 years later. Identification is ensured by abnormal rainfall within a critical period of ten days. The results show that the effect is stronger among older cohorts than younger cohorts, which is consistent with radiation accelerating cognitive decline as people get older. On average, a one-standarddeviation increase in the initial level of CS137 (around 30 chest x-rays) is associated with a decrease in the cognitive skills by 4.1 percent of a standard deviation (around 0.05 school years). Chapter one shows that sub-clinical levels of radiation can have negative consequences even after early childhood. This is of particular importance because most of the literature focuses on exposure very early in life, often during pregnancy. However, population exposed after birth is over 100 times larger. These results point to substantial external human capital costs of radiation which can be reduced by choices of medical procedures. There is a large potential for reductions because about one-third of all CT scans are assumed to be not medically justified (Brenner and Hall, 2007). If people receive unnecessary CT scans because of economic incentives, this chapter points to additional external costs of health care policies. Furthermore, the results can inform the cost-benefit trade-off for medically indicated procedures. Chapter two provides evidence about the effectiveness of Low Emission Zones. Low Emission Zones are typically justified by improvements in population health. However, there is little evidence about the potential health benefits from policy interventions aiming at improving air quality in inner-cities. The chapter ask how the coverage of Low Emission Zones air pollution and hospitalization, by exploiting variation in the roll out of Low Emission Zones in Germany. It combines information on the geographic coverage of Low Emission Zones with rich panel data on the universe of German hospitals over the period from 2006 to 2016 with precise information on hospital locations and the annual frequency of detailed diagnoses. In order to establish that our estimates of Low Emission Zones’ health impacts can indeed be attributed to improvements in local air quality, we use data from Germany’s official air pollution monitoring system and assign monitor locations to Low Emission Zones and test whether measures of air pollution are affected by the coverage of a Low Emission Zone. Results in chapter two confirm former results showing that the introduction of Low Emission Zones improved air quality significantly by reducing NO2 and PM10 concentrations. Furthermore, the chapter shows that hospitals which catchment areas are covered by a Low Emission Zone, diagnose significantly less air pollution related diseases, in particular by reducing the incidents of chronic diseases of the circulatory and the respiratory system. The effect is stronger before 2012, which is consistent with a general improvement in the vehicle fleet’s emission standards. Depending on the disease, a one-standard-deviation increase in the coverage of a hospitals catchment area covered by a Low Emission Zone reduces the yearly number of diagnoses up to 5 percent. These findings have strong implications for policy makers. In 2015, overall costs for health care in Germany were around 340 billion euros, of which 46 billion euros for diseases of the circulatory system, making it the most expensive type of disease caused by 2.9 million cases (Statistisches Bundesamt, 2017b). Hence, reductions in the incidence of diseases of the circulatory system may directly reduce society’s health care costs. Whereas chapter one and two study the demand-side in health care markets and thus preventive potential, chapter three analyzes the supply-side. By exploiting the same hospital panel data set as in chapter two, chapter three studies the effect of treatment price shocks on the reallocation of hospital resources in Germany. Starting in 2005, the implementation of the German-DRG-System led to general idiosyncratic treatment price shocks for individual hospitals. Thus far there is little evidence of the impact of general price shocks on the reallocation of hospital resources. Additionally, I add to the exiting literature by showing that price shocks can have persistent effects on hospital resources even when these shocks vanish. However, simple OLS regressions would underestimate the true effect, due to endogenous treatment price shocks. I implement a novel instrument variable strategy that exploits the exogenous variation in the number of days of snow in hospital catchment areas. A peculiarity of the reform allowed variation in days of snow to have a persistent impact on treatment prices. I find that treatment price increases lead to increases in input factors such as nursing staff, physicians and the range of treatments offered but to decreases in the treatment volume. This indicates supplier-induced demand. Furthermore, the probability of hospital mergers and privatization decreases. Structural differences in pre-treatment characteristics between hospitals enhance these effects. For instance, private and larger hospitals are more affected. IV estimates reveal that OLS results are biased towards zero in almost all dimensions because structural hospital differences are correlated with the reallocation of hospital resources. These results are important for several reasons. The G-DRG-Reform led to a persistent polarization of hospital resources, as some hospitals were exposed to treatment price increases, while others experienced reductions. If hospitals increase the treatment volume as a response to price reductions by offering unnecessary therapies, it has a negative impact on population wellbeing and public spending. However, results show a decrease in the range of treatments if prices decrease. Hospitals might specialize more, thus attracting more patients. From a policy perspective it is important to evaluate if such changes in the range of treatments jeopardize an adequate nationwide provision of treatments. Furthermore, the results show a decrease in the number of nurses and physicians if prices decrease. This could partly explain the nursing crisis in German hospitals. However, since hospitals specialize more they might be able to realize efficiency gains which justify reductions in input factors without loses in quality. Further research is necessary to provide evidence for the impact of the G-DRG-Reform on health care quality. Another important aspect are changes in the organizational structure. Many public hospitals have been privatized or merged. The findings show that this is at least partly driven by the G-DRG-Reform. This can again lead to a lack in services offered in some regions if merged hospitals specialize more or if hospitals are taken over by ecclesiastical organizations which do not provide all treatments due to moral conviction. Overall, this dissertation reveals large potential for preventive health care measures and helps to explain reallocation processes in the hospital sector if treatment prices change. Furthermore, its findings have potentially relevant implications for other areas of public policy. Chapter one identifies an effect of low dose radiation on cognitive health. As mankind is searching for new energy sources, nuclear power is becoming popular again. However, results of chapter one point to substantial costs of nuclear energy which have not been accounted yet. Chapter two finds strong evidence that air quality improvements by Low Emission Zones translate into health improvements, even at relatively low levels of air pollution. These findings may, for instance, be of relevance to design further policies targeted at air pollution such as diesel bans. As pointed out in chapter three, the implementation of DRG-Systems may have unintended side-effects on the reallocation of hospital resources. This may also apply to other providers in the health care sector such as resident doctors.
We present measurements of the large-scale (≈40 comoving Mpc) effective optical depth of He ii Lyα absorption, ${\tau }_{\mathrm{eff}}$, at 2.54 < z < 3.86 toward 16 He ii-transparent quasars observed with the Cosmic Origins Spectrograph on the Hubble Space Telescope, to characterize the ionization state of helium in the intergalactic medium (IGM). We provide the first statistical sample of ${\tau }_{\mathrm{eff}}$ measurements in six signal-to-noise ratio gsim3 He ii sightlines at z > 3.5, and study the redshift evolution and sightline-to-sightline variance of ${\tau }_{\mathrm{eff}}$ in 24 He ii sightlines. We confirm an increase of the median ${\tau }_{\mathrm{eff}}$ from sime2 at z = 2.7 to ${\tau }_{\mathrm{eff}}\gtrsim 5$ at z > 3, and a scatter in ${\tau }_{\mathrm{eff}}$ that increases with redshift. The z > 3.5 He ii absorption is predominantly saturated, but isolated narrow (Δv < 650 km s−1) transmission spikes indicate patches of reionized helium. We compare our measurements to predictions for a range of UV background models applied to outputs of a large-volume (146 comoving Mpc)3 hydrodynamical simulation by forward-modeling our sample's quality and size. At z > 2.74, the variance in ${\tau }_{\mathrm{eff}}$ significantly exceeds expectations for a spatially uniform UV background, but is consistent with a fluctuating radiation field sourced by variations in the quasar number density and the mean free path in the post-reionization IGM. We develop a method to infer the approximate median He ii photoionization rate ${{\rm{\Gamma }}}_{\mathrm{He}{\rm{II}}}$ of a fluctuating UV background from the median ${\tau }_{\mathrm{eff}}$, finding a factor sime5 decrease in ${{\rm{\Gamma }}}_{\mathrm{He}{\rm{II}}}$ between z sime 2.6 and z sime 3.1. At z sime 3.1, ${{\rm{\Gamma }}}_{\mathrm{He}{\rm{II}}}=\left[{9.1}_{-1.2}^{+1.1}\,(\mathrm{stat}.){\,}_{-3.4}^{+2.4}\,(\mathrm{sys}.)\right]\times {10}^{-16}$ s−1 corresponds to a median He ii fraction of sime2.5%, indicating that our data probe the tail end of He ii reionization.
Electron acceleration at Saturn due to whistler mode chorus waves has previously been assumed to be ineffective; new data closer to the planet show it can be very rapid (factor of 104 flux increase at 1 MeV in 10 days compared to factor of 2). A full survey of chorus waves at Saturn is combined with an improved plasma density model to show that where the plasma frequency falls below the gyrofrequency additional strong resonances are observed favoring electron acceleration. This results in strong chorus acceleration between approximately 2.5 R-S and 5.5 R-S outside which adiabatic transport may dominate. Strong pitch angle dependence results in butterfly pitch angle distributions that flatten over a few days at 100s keV, tens of days at MeV energies which may explain observations of butterfly distributions of MeV electrons near L = 3. Including cross terms in the simulations increases the tendency toward butterfly distributions. Plain Language Summary Radiation belts are hazardous regions found around several of the planets in our Solar System. They consist of very hot, electrically charged particles trapped in the magnetic field of the planet. At Saturn the most important way to heat these particles has for many years been thought to involve the particles drifting closer toward the planet. This paper adds to the emerging idea at Saturn that a different way to heat the particles is also possible where the heating is done by waves, in a similar way to what we find at the Earth. We use recent information from the Cassini spacecraft on the number and location of particles and also of the waves strength and location combined with computer simulations to show that a particular wave called chorus is excellent at heating the particles where the surrounding number of cold particles is low.
Perovskite solar cells combine high carrier mobilities with long carrier lifetimes and high radiative efficiencies. Despite this, full devices suffer from significant nonradiative recombination losses, limiting their VOC to values well below the Shockley–Queisser limit. Here, recent advances in understanding nonradiative recombination in perovskite solar cells from picoseconds to steady state are presented, with an emphasis on the interfaces between the perovskite absorber and the charge transport layers. Quantification of the quasi‐Fermi level splitting in perovskite films with and without attached transport layers allows to identify the origin of nonradiative recombination, and to explain the VOC of operational devices. These measurements prove that in state‐of‐the‐art solar cells, nonradiative recombination at the interfaces between the perovskite and the transport layers is more important than processes in the bulk or at grain boundaries. Optical pump‐probe techniques give complementary access to the interfacial recombination pathways and provide quantitative information on transfer rates and recombination velocities. Promising optimization strategies are also highlighted, in particular in view of the role of energy level alignment and the importance of surface passivation. Recent record perovskite solar cells with low nonradiative losses are presented where interfacial recombination is effectively overcome—paving the way to the thermodynamic efficiency limit.
Perovskite solar cells combine high carrier mobilities with long carrier lifetimes and high radiative efficiencies. Despite this, full devices suffer from significant nonradiative recombination losses, limiting their V-OC to values well below the Shockley-Queisser limit. Here, recent advances in understanding nonradiative recombination in perovskite solar cells from picoseconds to steady state are presented, with an emphasis on the interfaces between the perovskite absorber and the charge transport layers. Quantification of the quasi-Fermi level splitting in perovskite films with and without attached transport layers allows to identify the origin of nonradiative recombination, and to explain the V-OC of operational devices. These measurements prove that in state-of-the-art solar cells, nonradiative recombination at the interfaces between the perovskite and the transport layers is more important than processes in the bulk or at grain boundaries. Optical pump-probe techniques give complementary access to the interfacial recombination pathways and provide quantitative information on transfer rates and recombination velocities. Promising optimization strategies are also highlighted, in particular in view of the role of energy level alignment and the importance of surface passivation. Recent record perovskite solar cells with low nonradiative losses are presented where interfacial recombination is effectively overcome-paving the way to the thermodynamic efficiency limit.
The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction
(2019)
The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subangstrom length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
We studied the photoinduced ultrafast relaxation dynamics of the nucleobase thymine using gas-phase time-resolved photoelectron spectroscopy. By employing extreme ultraviolet pulses from high harmonic generation for photoionization, we substantially extend our spectral observation window with respect to previous studies. This enables us to follow relaxation of the excited state population all the way to low-lying electronic states including the ground state. In thymine, we observe relaxation from the optically bright (1)pi pi* state of thymine to a dark (1)n pi* state within 80 +/- 30 fs. The (1)n pi* state relaxes further within 3.5 +/- 0.3 ps to a low-lying electronic state. By comparison with quantum chemical simulations, we can unambiguously assign its spectroscopic signature to the (3)pi pi* state. Hence, our study draws a comprehensive picture of the relaxation mechanism of thymine including ultrafast intersystem crossing to the triplet manifold.
The conversion of light energy into other molecular energetic degrees of freedom is often dominated by ultrafast, non-adiabatic processes. Femtosecond spectroscopy with optical pulses has helped in shaping our understanding of crucial processes in molecular energy-conversion. The advent of new, ultrashort and bright X-ray free electron laser sources opens the possibility to use X-ray-typical element and site sensitivity for ultrafast molecular research. We present two types of spectroscopy, ultrafast Auger and ultrafast X-ray absorption spectroscopy, and discuss their sensitivity to molecular processes. While Auger spectroscopy is able to monitor bond distance changes in the vicinity of an X-ray created core hole, near-edge absorption spectroscopy can deliver high-fidelity information on non-adiabatic transitions involving lone-pair orbitals. We demonstrate these features on the example of the UV-excited nucleobase thymine, investigated at the oxygen K-edge. We find a C-O bond elongation in the Auger data in addition to pi pi*/n pi* non-adiabatic transition in X-ray near-edge absorption. We compare the results from both methods and draw a conclusive scenario of non-adiabatic molecular relaxation after UV excitation.
Partial melting is a first order process for the chemical differentiation of the crust (Vielzeuf et al., 1990). Redistribution of chemical elements during melt generation crucially influences the composition of the lower and upper crust and provides a mechanism to concentrate and transport chemical elements that may also be of economic interest. Understanding of the diverse processes and their controlling factors is therefore not only of scientific interest but also of high economic importance to cover the demand for rare metals.
The redistribution of major and trace elements during partial melting represents a central step for the understanding how granite-bound mineralization develops (Hedenquist and Lowenstern, 1994). The partial melt generation and mobilization of ore elements (e.g. Sn, W, Nb, Ta) into the melt depends on the composition of the sedimentary source and melting conditions. Distinct source rocks have different compositions reflecting their deposition and alteration histories. This specific chemical “memory” results in different mineral assemblages and melting reactions for different protolith compositions during prograde metamorphism (Brown and Fyfe, 1970; Thompson, 1982; Vielzeuf and Holloway, 1988). These factors do not only exert an important influence on the distribution of chemical elements during melt generation, they also influence the volume of melt that is produced, extraction of the melt from its source, and its ascent through the crust (Le Breton and Thompson, 1988). On a larger scale, protolith distribution and chemical alteration (weathering), prograde metamorphism with partial melting, melt extraction, and granite emplacement are ultimately depending on a (plate-)tectonic control (Romer and Kroner, 2016). Comprehension of the individual stages and their interaction is crucial in understanding how granite-related mineralization forms, thereby allowing estimation of the mineralization potential of certain areas. Partial melting also influences the isotope systematics of melt and restite. Radiogenic and stable isotopes of magmatic rocks are commonly used to trace back the source of intrusions or to quantify mixing of magmas from different sources with distinct isotopic signatures (DePaolo and Wasserburg, 1979; Lesher, 1990; Chappell, 1996). These applications are based on the fundamental requirement that the isotopic signature in the melt reflects that of the bulk source from which it is derived. Different minerals in a protolith may have isotopic compositions of radiogenic isotopes that deviate from their whole rock signature (Ayres and Harris, 1997; Knesel and Davidson, 2002). In particular, old minerals with a distinct parent-to-daughter (P/D) ratio are expected to have a specific radiogenic isotope signature. As the partial melting reaction only involves selective phases in a protolith, the isotopic signature of the melt reflects that of the minerals involved in the melting reaction and, therefore, should be different from the bulk source signature. Similar considerations hold true for stable isotopes.
Research question: The purpose of this study was to evaluate the test-retest reliability of lower extremity kinematics during squat, hip abduction and lunge exercises captured by the Kinect and to evaluate the agreement to a reference 3D camera-based motion system. Methods: Twenty-one healthy individuals performed five repetitions of each lower limb exercise on two different days. Movements were simultaneously assessed by the Kinect and the reference 3D motion system. Joint angles and positions of the lower limb were calculated for sagittal and frontal plane. For the inter-session reliability and the agreement between the two systems standard error of measurement (SEM), bias with limits of agreement (LoA) and Pearson Correlation Coefficient (r) were calculated. Results: Parameters indicated varying reliability for the assessed joint angles and positions and decreasing reliability with increasing task complexity. Across all exercises, measurement deviations were shown especially for small movement amplitudes. Variability was acceptable for joint angles and positions during the squat, partially acceptable during the hip abduction and predominately inacceptable during the lunge. The agreement between systems was characterized by systematic errors. Overestimations by the Kinect were apparent for hip flexion during the squat and hip abduction/adduction during the hip abduction exercise as well as for the knee positions during the lunge. Knee and hip flexion during hip abduction and lunge were underestimated by the Kinect. Significance: The Kinect system can reliably assess lower limb joint angles and positions during simple exercises. The validity of the system is however restricted. An application in the field of early orthopedic rehabilitation without further development of post-processing techniques seems so far limited.
Identification and Characterization of Three Epithiospecifier Protein Isoforms in Brassica oleracea
(2019)
Glucosinolates present in Brassicaceae play a major role in herbivory defense. Upon tissue disruption, glucosinolates come into contact with myrosinase, which initiates their breakdown to biologically active compounds. Among these, the formation of epithionitriles is triggered by the presence of epithiospecifier protein (ESP) and a terminal double bond in the glucosinolate side chain. One ESP gene is characterized in the model plant Arabidopsis thaliana (AtESP; At1g54040.2). However, Brassica species underwent genome triplication since their divergence from the Arabidopsis lineage. This indicates the presence of multiple ESP isoforms in Brassica crops that are currently poorly characterized. We identified three B. oleracea ESPs, specifically BoESP1 (LOC106296341), BoESP2 (LOC106306810), and BoESP3 (LOC106325105) based on in silico genome analysis. Transcript and protein abundance were assessed in shoots and roots of four B. oleracea vegetables, namely broccoli, kohlrabi, white, and red cabbage, because these genotypes showed a differential pattern for the formation of glucosinolate hydrolysis products as well for their ESP activity. BoESP1 and BoESP2 were expressed mainly in shoots, while BoESP3 was abundant in roots. Biochemical characterization of heterologous expressed BoESP isoforms revealed different substrate specificities towards seven glucosinolates: all isoforms showed epithiospecifier activity on alkenyl glucosinolates, but not on non-alkenyl glucosinolates. The pH-value differently affected BoESP activity: while BoESP1 and BoESP2 activities were optimal at pH 6-7, BoESP3 activity remained relatively stable from pH 4 to 7. In order test their potential for the in vivo modification of glucosinolate breakdown, the three isoforms were expressed in A. thaliana Hi-0, which lacks AtESP expression, and analyzed for the effect on their respective hydrolysis products. The BoESPs altered the hydrolysis of allyl glucosinolate in the A. thaliana transformants to release 1-cyano-2,3-epithiopropane and reduced formation of the corresponding 3-butenenitrile and allyl isothiocyanate. Plants expressing BoESP2 showed the highest percentage of released epithionitriles. Given these results, we propose a model for isoform-specific roles of B. oleracea ESPs in glucosinolate breakdown.
Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes
(2019)
Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk.
Aims/hypothesis This study aimed to evaluate associations of height as well as components of height (sitting height and leg length) with risk of type 2 diabetes and to explore to what extent associations are explainable by liver fat and cardiometabolic risk markers. Methods A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 26,437 participants who provided blood samples was designed. We randomly selected a subcohort of 2500 individuals (2029 diabetes-free at baseline and with anamnestic, anthropometrical and metabolic data for analysis). Of the 820 incident diabetes cases identified in the full cohort during 7 years of follow-up, 698 remained for analyses after similar exclusions. Results After adjustment for age, potential lifestyle confounders, education and waist circumference, greater height was related to lower diabetes risk (HR per 10 cm, men 0.59 [95% CI 0.47, 0.75] and women 0.67 [0.51, 0.88], respectively). Leg length was related to lower risk among men and women, but only among men if adjusted for total height. Adjustment for liver fat and triacylglycerols, adiponectin and C-reactive protein substantially attenuated associations between height and diabetes risk, particularly among women. Conclusions/interpretation We observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile.
Chronic stress and emotion: Differential effects on attentional processing and recognition memory
(2019)
Previous research indicates that acute stress around the time of learning facilitates attention and memory for emotionally salient information. Despite accumulating evidence for these acute stress effects, less is known about the role of chronic stress. In the present study, we therefore tested emotional and neutral scene processing and later recognition memory in female participants using hair cortisol concentrations as a biological marker for chronic stress. Event-related potentials recorded during picture viewing indicated enhanced late positive potentials (LPPs) for emotional, relative to neutral contents. These brain potentials varied as a function of long-term hair cortisol levels: hair-cortisol levels were positively related to overall LPP amplitudes. Results from recognition memory testing one week after encoding revealed better memory for emotional relative to neutral scenes. Hair-cortisol levels, however, were related to poorer memory accuracy. Taken together, our results indicate that chronic stress enhanced attentional processing during encoding of new stimuli and impaired later recognition memory. Results are discussed with regard to putatively opposite effects of chronic stress on certain brain regions (e.g., amygdala and hippocampus).
Stress and bone health
(2019)
Southeast Asia is one of the most dynamic regions in the world. It is experiencing rapid socioeconomic change that may influence the level of sexual aggression, but data on the scale of sexual aggression in the region remain sparse. The aim of the present article was to systematically review the findings of studies available in English on the prevalence of self-reported sexual aggression and victimization among women and men above the age of 12 years in the 11 countries of Southeast Asia (Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam). Based on four scientific databases, the search engine Google, Opengrey database, and reference checking, 49 studies were found on sexual victimization. Of those, 32 included only women. Self-reported perpetration was assessed by only three studies and included all-male samples. Prevalence rates varied widely across studies but showed that sexual victimization was widespread among different social groups, irrespective of sex and sexual orientation. Methodological heterogeneity, lack of representativeness of samples, imbalance of information available by country, missing information within studies, and cultural differences hampered the comparability between and within countries. There is a need for operationalizations that specifically address sexual aggression occurring after the age of consent, based on detailed behavioral descriptions of unwanted sexual experiences and allied to a qualitative approach with cultural sensitivity. Data on sexual aggression in conflict settings and in human trafficking are also limited. Recommendations for future research are presented in the discussion.
Design flood estimation is an essential part of flood risk assessment. Commonly applied are flood frequency analyses and design storm approaches, while the derived flood frequency using continuous simulation has been getting more attention recently. In this study, a continuous hydrological modelling approach on an hourly time scale, driven by a multi-site weather generator in combination with a -nearest neighbour resampling procedure, based on the method of fragments, is applied. The derived 100-year flood estimates in 16 catchments in Vorarlberg (Austria) are compared to (a) the flood frequency analysis based on observed discharges, and (b) a design storm approach. Besides the peak flows, the corresponding runoff volumes are analysed. The spatial dependence structure of the synthetically generated flood peaks is validated against observations. It can be demonstrated that the continuous modelling approach can achieve plausible results and shows a large variability in runoff volume across the flood events.
Background: Epidemiological studies suggest that an increased red meat intake is associated with a higher risk of type 2 diabetes, whereas an increased fiber intake is associated with a lower risk. Objectives: We conducted an intervention study to investigate the effects of these nutritional factors on glucose and lipid metabolism, body-fat distribution, and liver fat content in subjects at increased risk of type 2 diabetes. Methods: This prospective, randomized, and controlled dietary intervention study was performed over 6 mo. All groups decreased their daily caloric intake by 400 kcal. The "control" group (N = 40) only had this requirement. The "no red meat" group (N = 48) in addition aimed to avoid the intake of red meat, and the "fiber" group (N = 44) increased intake of fibers to 40 g/d. Anthropometric parameters and frequently sampled oral glucose tolerance tests were performed before and after intervention. Body-fat mass and distribution, liver fat, and liver iron content were assessed by MRI and single voxel proton magnetic resonance spectroscopy. Results: Participants in all groups lost weight (mean 3.3 +/- 0.5 kg, P < 0.0001). Glucose tolerance and insulin sensitivity improved (P < 0.001), and body and visceral fat mass decreased in all groups (P < 0.001). These changes did not differ between groups. Liver fat content decreased significantly (P < 0.001) with no differences between the groups. The decrease in liver fat correlated with the decrease in ferritin during intervention (r(2) = 0.08, P = 0.0021). This association was confirmed in an independent lifestyle intervention study (Tuebingen Lifestyle Intervention Program, N = 229, P = 0.0084). Conclusions: Our data indicate that caloric restriction leads to a marked improvement in glucose metabolism and body-fat composition, including liver-fat content. The marked reduction in liver fat might be mediated via changes in ferritin levels. In the context of caloric restriction, there seems to be no additional beneficial impact of reduced red meat intake and increased fiber intake on the improvement in cardiometabolic risk parameters. This trial was registered at clinicaltrials.gov as NCT03231839.
We investigate the ultrafast magnetization dynamics of FePt in the L1(0) phase after an optical heating pulse, as used in heat-assisted magnetic recording. We compare continuous and nano-granular thin films and emphasize the impact of the finite size on the remagnetization dynamics. The remagnetization speeds up significantly with increasing external magnetic field only for the continuous film, where domain-wall motion governs the dynamics. The ultrafast remagnetization dynamics in the continuous film are only dominated by heat transport in the regime of high magnetic fields, whereas the timescale required for cooling is prevalent in the granular film for all magnetic field strengths. These findings highlight the necessary conditions for studying the intrinsic heat transport properties in magnetic materials.
Ultrafast magnetisation dynamics have been investigated intensely for two decades. The recovery process after demagnetisation, however, was rarely studied experimentally and discussed in detail. The focus of this work lies on the investigation of the magnetisation on long timescales after laser excitation. It combines two ultrafast time resolved methods to study the relaxation of the magnetic and lattice system after excitation with a high fluence ultrashort laser pulse. The magnetic system is investigated by time resolved measurements of the magneto-optical Kerr effect. The experimental setup has been implemented in the scope of this work. The lattice dynamics were obtained with ultrafast X-ray diffraction. The combination of both techniques leads to a better understanding of the mechanisms involved in magnetisation recovery from a non-equilibrium condition. Three different groups of samples are investigated in this work: Thin Nickel layers capped with nonmagnetic materials, a continuous sample of the ordered L10 phase of Iron Platinum and a sample consisting of Iron Platinum nanoparticles embedded in a carbon matrix. The study of the remagnetisation reveals a general trend for all of the samples: The remagnetisation process can be described by two time dependences. A first exponential recovery that slows down with an increasing amount of energy absorbed in the system until an approximately linear time dependence is observed. This is followed by a second exponential recovery. In case of low fluence excitation, the first recovery is faster than the second. With increasing fluence the first recovery is slowed down and can be described as a linear function. If the pump-induced temperature increase in the sample is sufficiently high, a phase transition to a paramagnetic state is observed. In the remagnetisation process, the transition into the ferromagnetic state is characterised by a distinct transition between the linear and exponential recovery. From the combination of the transient lattice temperature Tp(t) obtained from ultrafast X-ray measurements and magnetisation M(t) gained from magneto-optical measurements we construct the transient magnetisation versus temperature relations M(Tp). If the lattice temperature remains below the Curie temperature the remagnetisation curve M(Tp) is linear and stays below the M(T) curve in equilibrium in the continuous transition metal layers. When the sample is heated above phase transition, the remagnetisation converges towards the static temperature dependence. For the granular Iron Platinum sample the M(Tp) curves for different fluences coincide, i.e. the remagnetisation follows a similar path irrespective of the initial laser-induced temperature jump.
We have investigated the structural dynamics in photoexcited 1,2-diiodotetrafluoroethane molecules (C2F4I2) in the gas phase experimentally using ultrafast electron diffraction and theoretically using FOMO-CASCI excited-state dynamics simulations. The molecules are excited by an ultraviolet femtosecond laser pulse to a state characterized by a transition from the iodine 5p perpendicular to orbital to a mixed 5p parallel to sigma hole and CF2 center dot antibonding orbital, which results in the cleavage of one of the carbon-iodine bonds. We have observed, with sub-Angstrom resolution, the motion of the nuclear wave packet of the dissociating iodine atom followed by coherent vibrations in the electronic ground state of the C2F4I radical. The radical reaches a stable classical (nonbridged) structure in less than 200 fs.
Sphingolipids are a class of lipids that share a sphingoid base backbone. They exert various effects in eukaryotes, ranging from structural roles in plasma membranes to cellular signaling. De novo sphingolipid synthesis takes place in the endoplasmic reticulum (ER), where the condensation of the activated C₁₆ fatty acid palmitoyl-CoA and the amino acid L-serine is catalyzed by serine palmitoyltransferase (SPT). The product, 3-ketosphinganine, is then converted into more complex sphingolipids by additional ER-bound enzymes, resulting in the formation of ceramides. Since sphingolipid homeostasis is crucial to numerous cellular functions, improved assessment of sphingolipid metabolism will be key to better understanding several human diseases. To date, no assay exists capable of monitoring de novo synthesis sphingolipid in its entirety. Here, we have established a cell-free assay utilizing rat liver microsomes containing all the enzymes necessary for bottom-up synthesis of ceramides. Following lipid extraction, we were able to track the different intermediates of the sphingolipid metabolism pathway, namely 3-ketosphinganine, sphinganine, dihydroceramide, and ceramide. This was achieved by chromatographic separation of sphingolipid metabolites followed by detection of their accurate mass and characteristic fragmentations through high-resolution mass spectrometry and tandem-mass spectrometry. We were able to distinguish, unequivocally, between de novo synthesized sphingolipids and intrinsic species, inevitably present in the microsome preparations, through the addition of stable isotope-labeled palmitate-d₃ and L-serine-d₃. To the best of our knowledge, this is the first demonstration of a method monitoring the entirety of ER-associated sphingolipid biosynthesis. Proof-of-concept data was provided by modulating the levels of supplied cofactors (e.g., NADPH) or the addition of specific enzyme inhibitors (e.g., fumonisin B₁). The presented microsomal assay may serve as a useful tool for monitoring alterations in sphingolipid de novo synthesis in cells or tissues. Additionally, our methodology may be used for metabolism studies of atypical substrates – naturally occurring or chemically tailored – as well as novel inhibitors of enzymes involved in sphingolipid de novo synthesis.
Sphingolipids are a class of lipids that share a sphingoid base backbone. They exert various effects in eukaryotes, ranging from structural roles in plasma membranes to cellular signaling. De novo sphingolipid synthesis takes place in the endoplasmic reticulum (ER), where the condensation of the activated C₁₆ fatty acid palmitoyl-CoA and the amino acid L-serine is catalyzed by serine palmitoyltransferase (SPT). The product, 3-ketosphinganine, is then converted into more complex sphingolipids by additional ER-bound enzymes, resulting in the formation of ceramides. Since sphingolipid homeostasis is crucial to numerous cellular functions, improved assessment of sphingolipid metabolism will be key to better understanding several human diseases. To date, no assay exists capable of monitoring de novo synthesis sphingolipid in its entirety. Here, we have established a cell-free assay utilizing rat liver microsomes containing all the enzymes necessary for bottom-up synthesis of ceramides. Following lipid extraction, we were able to track the different intermediates of the sphingolipid metabolism pathway, namely 3-ketosphinganine, sphinganine, dihydroceramide, and ceramide. This was achieved by chromatographic separation of sphingolipid metabolites followed by detection of their accurate mass and characteristic fragmentations through high-resolution mass spectrometry and tandem-mass spectrometry. We were able to distinguish, unequivocally, between de novo synthesized sphingolipids and intrinsic species, inevitably present in the microsome preparations, through the addition of stable isotope-labeled palmitate-d₃ and L-serine-d₃. To the best of our knowledge, this is the first demonstration of a method monitoring the entirety of ER-associated sphingolipid biosynthesis. Proof-of-concept data was provided by modulating the levels of supplied cofactors (e.g., NADPH) or the addition of specific enzyme inhibitors (e.g., fumonisin B₁). The presented microsomal assay may serve as a useful tool for monitoring alterations in sphingolipid de novo synthesis in cells or tissues. Additionally, our methodology may be used for metabolism studies of atypical substrates – naturally occurring or chemically tailored – as well as novel inhibitors of enzymes involved in sphingolipid de novo synthesis.
We previously showed that purified 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate, a secondary plant metabolite in Brassica species, is mutagenic in various in vitro systems and forms DNA and protein adducts in mouse models. In the present study, we administered 1-MIM glucosinolate in a natural matrix to mice, by feeding a diet containing pak choi powder and extract. Groups of animals were killed after 1, 2, 4 and 8 days of pak choi diet, directly or, in the case of the 8-day treatment, after 0, 8 and 16 days of recovery with pak choi-free diet. DNA adducts [N-2-(1-MIM)-dG, N-6-(1-MIM)-dA] in six tissues, as well as protein adducts [tau N-(1-MIM)-His] in serum albumin (SA) and hemoglobin (Hb) were determined using UPLC-MS/MS with isotopically labeled internal standards. None of the samples from the 12 control animals under standard diet contained any 1-MIM adducts. All groups receiving pak choi diet showed DNA adducts in all six tissues (exception: lung of mice treated for a single day) as well as SA and Hb adducts. During the feeding period, all adduct levels continuously increased until day 8 (in the jejunum until day 4). During the 14-day recovery period, N-2-(1-MIM)-dG in liver, kidney, lung, jejunum, cecum and colon decreased to 52, 41, 59, 11, 7 and 2%, respectively, of the peak level. The time course of N-6-(1-MIM)-dA was similar. Immunohistochemical analyses indicated that cell turnover is a major mechanism of DNA adduct elimination in the intestine. In the same recovery period, protein adducts decreased more rapidly in SA than in Hb, to 0.7 and 37%, respectively, of the peak level, consistent with the differential turnover of these proteins. In conclusion, the pak choi diet lead to the formation of high levels of adducts in mice. Cell and protein turnover was a major mechanism of adduct elimination, at least in gut and blood.
Alluvial and transport-limited bedrock rivers constitute the majority of fluvial systems on Earth. Their long profiles hold clues to their present state and past evolution. We currently possess first-principles-based governing equations for flow, sediment transport, and channel morphodynamics in these systems, which we lack for detachment-limited bedrock rivers. Here we formally couple these equations for transport-limited gravel-bed river long-profile evolution. The result is a new predictive relationship whose functional form and parameters are grounded in theory and defined through experimental data. From this, we produce a power-law analytical solution and a finite-difference numerical solution to long-profile evolution. Steady-state channel concavity and steepness are diagnostic of external drivers: concavity decreases with increasing uplift rate, and steepness increases with an increasing sediment-to-water supply ratio. Constraining free parameters explains common observations of river form: to match observed channel concavities, gravel-sized sediments must weather and fine - typically rapidly - and valleys typically should widen gradually. To match the empirical square-root width-discharge scaling in equilibrium-width gravel-bed rivers, downstream fining must occur. The ability to assign a cause to such observations is the direct result of a deductive approach to developing equations for landscape evolution.
Alluvial and transport-limited bedrock rivers constitute the majority of fluvial systems on Earth. Their long profiles hold clues to their present state and past evolution. We currently possess first-principles-based governing equations for flow, sediment transport, and channel morphodynamics in these systems, which we lack for detachment-limited bedrock rivers. Here we formally couple these equations for transport-limited gravel-bed river long-profile evolution. The result is a new predictive relationship whose functional form and parameters are grounded in theory and defined through experimental data. From this, we produce a power-law analytical solution and a finite-difference numerical solution to long-profile evolution. Steady-state channel concavity and steepness are diagnostic of external drivers: concavity decreases with increasing uplift rate, and steepness increases with an increasing sediment-to-water supply ratio. Constraining free parameters explains common observations of river form: to match observed channel concavities, gravel-sized sediments must weather and fine – typically rapidly – and valleys typically should widen gradually. To match the empirical square-root width–discharge scaling in equilibrium-width gravel-bed rivers, downstream fining must occur. The ability to assign a cause to such observations is the direct result of a deductive approach to developing equations for landscape evolution.
Recent research indicates that non- invasive stimulation of the afferent auricular vagal nerve (tVNS) may modulate various cognitive and affec-tive functions, likely via activation of the locus coeruleus- norepinephrine (LC- NE) system. In a series of ERP studies we found that the attention- related P300 component is enhanced during continuous vagal stimula-tion, compared to sham, which is also related to increased salivary alpha amylase levels (a putative indirect marker for central NE activation). In another study, we investigated the effect of continuous tVNS on the late positive potential (LPP), an electrophysiological index for motivated atten-tion toward emotionally evocative cues, and the effects of tVNS on later recognition memory (1- week delay). Here, vagal stimulation prompted earlier LPP differences (300- 500 ms) between unpleasant and neutral scenes. During retrieval, vagal stimulation significantly improved memory performance for unpleasant, but not neutral pictures, compared to sham stimulation, which was also related to enhanced salivary alpha amylase levels. In line, unpleasant images encoded under tVNS compared to sham stimulation also produced enhanced ERP old/new differences (500- 800 ms) during retrieval indicating better recollection. Taken together, our studies suggest that tVNS facilitates attention, learning and episodic memory, likely via afferent projections to the arousal- modulated LC- NE system. We will, however, also show data that point to critical stimulation parameters (likely duration and frequency) that need to be considered when applying tVNS
In daily life, we automatically form impressions of other individuals on basis of subtle facial features that convey trustworthiness. Because these face-based judgements influence current and future social interactions, we investigated how perceived trustworthiness of faces affects long-term memory using event-related potentials (ERPs). In the current study, participants incidentally viewed 60 neutral faces differing in trustworthiness, and one week later, performed a surprise recognition memory task, in which the same old faces were presented intermixed with novel ones. We found that after one week untrustworthy faces were better recognized than trustworthy faces and that untrustworthy faces prompted early (350–550 ms) enhanced frontal ERP old/new differences (larger positivity for correctly remembered old faces, compared to novel ones) during recognition. Our findings point toward an enhanced long-lasting, likely familiarity-based, memory for untrustworthy faces. Even when trust judgments about a person do not necessarily need to be accurate, a fast access to memories predicting potential harm may be important to guide social behaviour in daily life.
In daily life, we automatically form impressions of other individuals on basis of subtle facial features that convey trustworthiness. Because these face-based judgements influence current and future social interactions, we investigated how perceived trustworthiness of faces affects long-term memory using event-related potentials (ERPs). In the current study, participants incidentally viewed 60 neutral faces differing in trustworthiness, and one week later, performed a surprise recognition memory task, in which the same old faces were presented intermixed with novel ones. We found that after one week untrustworthy faces were better recognized than trustworthy faces and that untrustworthy faces prompted early (350–550 ms) enhanced frontal ERP old/new differences (larger positivity for correctly remembered old faces, compared to novel ones) during recognition. Our findings point toward an enhanced long-lasting, likely familiarity-based, memory for untrustworthy faces. Even when trust judgments about a person do not necessarily need to be accurate, a fast access to memories predicting potential harm may be important to guide social behaviour in daily life.
Late Quaternary landscapes of unglaciated Beringia were largely shaped by ice-wedge polygon tundra. Ice Complex (IC) strata preserve such ancient polygon formations. Here we report on the Yukagir IC from Bol'shoy Lyakhovsky Island in northeastern Siberia and suggest that new radioisotope disequilibria (230Th/U) dates of the Yukagir IC peat confirm its formation during the Marine Oxygen Isotope Stage (MIS) 7a–c interglacial period. The preservation of the ice-rich Yukagir IC proves its resilience to last interglacial and late glacial–Holocene warming. This study compares the Yukagir IC to IC strata of MIS 5, MIS 3, and MIS 2 ages exposed on Bol'shoy Lyakhovsky Island. Besides high intrasedimental ice content and syngenetic ice wedges intersecting silts, sandy silts, the Yukagir IC is characterized by high organic matter (OM) accumulation and low OM decomposition of a distinctive Drepanocladus moss-peat. The Yukagir IC pollen data reveal grass-shrub-moss tundra indicating rather wet summer conditions similar to modern ones. The stable isotope composition of Yukagir IC wedge ice is similar to those of the MIS 5 and MIS 3 ICs pointing to similar atmospheric moisture generation and transport patterns in winter. IC data from glacial and interglacial periods provide insights into permafrost and climate dynamics since about 200 ka.
Previous research has identified students' personality traits, especially conscientiousness, as highly relevant predictors of academic success. Less is known about the role of Big Five personality traits in students when it comes to teachers' decisions about students' educational trajectories and whether personality traits differentially affect these decisions by teachers in different grade levels. This study examines to what extent students' Big Five personality traits affect teacher decisions on grade retention, looking at two cohorts of 12,146 ninth-grade and 6002 seventh-grade students from the German National Educational Panel Study. In both grade levels, multilevel logistic mediation models show that students' conscientiousness indirectly predicts grade retention through the assignment of grades by teachers. In the ninth-grade sample, students' conscientiousness was additionally a direct predictor of retention, distinct from teacher-assigned grades. We discuss potential underlying mechanisms and explore whether teachers base their decisions on different indicators when retaining seventh-grade students or ninth-grade students.
Convergence between the Indian and Asian plates has reshaped large parts of Asia, changing regional climate and biodiversity, yet geodynamic models fundamentally diverge on how convergence was accommodated since the India-Asia collision. Here we report palaeomagnetic data from the Burma Terrane, which is at the eastern edge of the collision zone and is famous for its Cretaceous amber biota, to better determine the evolution of the India-Asia collision. The Burma Terrane was part of a Trans-Tethyan island arc and stood at a near-equatorial southern latitude at similar to 95 Ma, suggesting island endemism for the Burmese amber biota. The Burma Terrane underwent significant clockwise rotation between similar to 80 and 50 Ma, causing its subduction margin to become hyper-oblique. Subsequently, it was translated northward on the Indian Plate by an exceptional distance of at least 2,000 km along a dextral strike-slip fault system in the east. Our reconstructions are only compatible with geodynamic models involving an initial collision of India with a near-equatorial Trans-Tethyan subduction system at similar to 60 Ma, followed by a later collision with the Asian margin.
Enzyme immobilization using nanomaterials offers new approaches to enhanced bioelectrochemical performance and is essential for the preparation of bioelectrodes with high reproducibility and low cost. In this report, we describe the development of new three-dimensional (3D) bioelectrodes by immobilizing a "bioink" of glucose oxidase (GOD) in a matrix of reduced graphene oxides (RGOs), polyethylenimine (PEI), and ferrocene carboxylic acid (FcCOOH) on carbon paper (CP). CP with 3D interwoven carbon fibers serves as a solid porous and electronically conducting skeleton, providing large surface areas and space for loading the bioink and diffusion of substrate molecules, respectively. RGO enhances contact between the GOD-matrix and CP, maintaining high conductivity. The composition of the bioink has been systematically optimized. The GOD bioelectrodes show linearly increasing electrocatalytic oxidation current toward glucose concentration up to 48 mM. A hybrid enzymatic biofuel cell equipped with the GOD bioelectrode as a bioanode and a platinum cathode furthermore registers a maximum power density of 5.1 mu W cm(-2) and an open circuit voltage of 0.40 V at 25 degrees C. The new method reported of preparing a bioelectrode by drop-casting the bioink onto the substrate electrode is facile and versatile, with the potential of application also for other enzymatic bioelectrodes.
Aquifer thermal energy storage (ATES) as a complement to fluctuating renewable energy systems is a reliable technology to guarantee continuous energy supply for heating and air conditioning. We investigated a high-temperature (HT) mono-well system (c. 100 degrees C), where the well screens are separated vertically within the aquifer, as an alternative to conventional doublet ATES systems for an underground storage in northern Oman. We analysed the impact of thermal inference between injection and extraction well screens on the heat recovery factor (HRF) in order to define the optimal screento-screen distance for best possible systems efficiency. Two controlling interference parameters were considered: the vertical screen-to-screen distance and aquifer heterogeneities. The sensitivity study shows that with decreasing screen-to-screen distances, thermal interference increases storage performance. A turning point is reached if the screen distance is too close, causing either water breakthrough or negative thermal interference between the screens. Our simulations show that a combined heat plume with spherical geometry results in the highest heat recovery factors due to the lowest surface area to volume ratios. Thick aquifers for mono-well HT-ATES are thus not mandatory Our study shows that a HT-ATES mono-well system is a feasible storage design with high heat recovery factors for continuous cooling or heating purposes.
Making performance Pay Work
(2019)
Performance pay has been one of the main trends in public sector reform over the last decade and aims to increase employees’ motivation. However, positive results are sparse. In a majority of cases, pay scheme designers neglect that intrinsic motivation may be distorted by the introduction of extrinsic rewards (crowding out). Nevertheless, under certain conditions, performance pay schemes may also enhance intrinsic motivation (crowding-in). The perception of rewards has proven to be an especially crucial factor for the outcome of performance pay. Based on psychological contract theory, this paper analyzes the relationships between intrinsic motivation, public service motivation (PSM), personality characteristics, and the design of the performance- appraisal scheme. The empirical analysis relies on a structural equation modeling (SEM) approach. Model findings reveal that a fair, participatory, and transparent design reduces the controlling perception while fostering the intrinsic motivation of employees. In addition, participants who score high on neuroticism perceive performance pay schemes to be more controlling and have lower values of intrinsic motivation.
Given the rising popularity of social networking sites (SNSs), the influence of these platforms on the subjective well-being (SWB) of their users is an emerging topic in information systems research. Building on the norm of reciprocity and the social functional approach to positive emotions, we posit that targeted reciprocity-evoking forms of SNS activities are best suited to promote users’ positive emotions. The favourable potential of these activities is likely to be particularly pronounced among adolescents who pay special attention to social acceptance, which can be channelled with the help of reciprocal communication. Therefore, we conducted a quantitative 7-day diary study of 162 adolescent Facebook users attending German schools, looking at the impact of their daily SNS activities on their SWB. Based on a linear mixed model analysis, our results confirm a positive link between targeted reciprocity-evoking activities – such as chatting, giving and receiving feedback – and adolescents’ positive emotions. Our findings provide a reassuring perspective on the implications of the sociotechnical design of SNS communication channels. Specifically, by encouraging targeted activities, providers, users, and other stakeholders can ensure the beneficial impact of this technology on users’ SWB.
Social networking sites (SNSs) are central to social interaction and information sharing in the digital age. However, consuming social information on SNSs invites social upward comparisons with highly socially desirable profile representations, which easily elicits envy in users and leads to unfavorable behaviors on SNSs. This in turn can erode the subjective well-being of users and the sustainability of the SNS platform. Therefore, this paper seeks to develop a better theoretical understanding of how users respond to envy on SNSs. We review literature on envy in offline interactions to derive three behavioral strategies to reduce envy, which we then transfer to the SNS context (self-enhancement, gossiping, and discontinuous intention). Further, we propose a research model and examine how culture, specifically individualism-collectivism, affects the relationship between envy on an SNS and the three strategies. We empirically test the variance-based structural equation model through survey data collected of Facebook users from Germany and Hong Kong. Our findings provide first insights into the link between envy on SNSs, related behavioral strategies and the moderating role of individualism for self-enhancement.
Proteasomes are key proteases in regulating protein homeostasis. Their holo-enzymes are composed of 40 different subunits which are arranged in a proteolytic core (CP) flanked by one to two regulatory particles (RP). Proteasomal proteolysis is essential for the degradation of proteins which control time-sensitive processes like cell cycle progression and stress response. In dividing yeast and human cells, proteasomes are primarily nuclear suggesting that proteasomal proteolysis is mainly required in the nucleus during cell proliferation. In yeast, which have a closed mitosis, proteasomes are imported into the nucleus as immature precursors via the classical import pathway. During quiescence, the reversible absence of proliferation induced by nutrient depletion or growth factor deprivation, proteasomes move from the nucleus into the cytoplasm. In the cytoplasm of quiescent yeast, proteasomes are dissociated into CP and RP and stored in membrane-less cytoplasmic foci, named proteasome storage granules (PSGs). With the resumption of growth, PSGs clear and mature proteasomes are transported into the nucleus by Blm10, a conserved 240 kDa protein and proteasome-intrinsic import receptor. How proteasomes are exported from the nucleus into the cytoplasm is unknown.
This paper introduces a novel measure to assess similarity between event hydrographs. It is based on cross recurrence plots (CRP) and recurrence quantification analysis (RQA), which have recently gained attention in a range of disciplines when dealing with complex systems. The method attempts to quantify the event runoff dynamics and is based on the time delay embedded phase space representation of discharge hydrographs. A phase space trajectory is reconstructed from the event hydrograph, and pairs of hydrographs are compared to each other based on the distance of their phase space trajectories. Time delay embedding allows considering the multidimensional relationships between different points in time within the event. Hence, the temporal succession of discharge values is taken into account, such as the impact of the initial conditions on the runoff event. We provide an introduction to cross recurrence plots and discuss their parameterization. An application example based on flood time series demonstrates how the method can be used to measure the similarity or dissimilarity of events, and how it can be used to detect events with rare runoff dynamics. It is argued that this methods provides a more comprehensive approach to quantify hydrograph similarity compared to conventional hydrological signatures.
We present follow-up observations of the K2-133 multiplanet system. Previously, we announced that K2-133 contained three super-Earths orbiting an M1.5V host star – with tentative evidence of a fourth outer-planet orbiting at the edge of the temperate zone. Here, we report on the validation of the presence of the fourth planet, determining a radius of 1.73+0.14−0.13 R⊕. The four planets span the radius gap of the exoplanet population, meaning further follow-up would be worthwhile to obtain masses and test theories of the origin of the gap. In particular, the trend of increasing planetary radius with decreasing incident flux in the K2-133 system supports the claim that the gap is caused by photo-evaporation of exoplanet atmospheres. Finally, we note that K2-133 e orbits on the edge of the star's temperate zone, and that our radius measurement allows for the possibility that this is a rocky world. Additional mass measurements are required to confirm or refute this scenario.
JavaScript is the most popular programming language for web applications. Static analysis of JavaScript applications is highly challenging due to its dynamic language constructs and event-driven asynchronous executions, which also give rise to many security-related bugs. Several static analysis tools to detect such bugs exist, however, research has not yet reported much on the precision and scalability trade-off of these analyzers. As a further obstacle, JavaScript programs structured in Node. js modules need to be collected for analysis, but existing bundlers are either specific to their respective analysis tools or not particularly suitable for static analysis.
Ocean-land thermal feedback mechanisms in the Indian Summer Monsoon (ISM) domain are an important but not well understood component of regional climate dynamics. Here we present a O-18 record analyzed in the mixed-layer dwelling planktonic foraminifer Globigerinoides ruber (sensu stricto) from the northernmost Bay of Bengal (BoB). The O-18 time series provides a spatially integrated measure of monsoonal precipitation and Himalayan meltwater runoff into the northern BoB and reveals two brief episodes of anomalously low O-18 values between 16.30.4 and 160.5 and 12.60.4 and 12.30.4 thousand years before present. The timing of these events is centered at Heinrich event 1 and the Younger Dryas, well-known phases of weak northern hemisphere monsoon systems. Numerical climate model experiments, simulating Heinrich event-like conditions, suggest a surface warming over the monsoon-dominated Himalaya and foreland in response to ISM weakening. Corroborating the simulation results, our analysis of published moraine exposure ages in the monsoon-dominated Himalaya indicates enhanced glacier retreats that, considering age model uncertainties, coincide and overlap with the episodes of anomalously low O-18 values in the northernmost BoB. Our climate proxy and simulation results provide insights into past regional climate dynamics, suggesting reduced cloud cover, increased solar radiation, and air warming of the Himalaya and foreland areas and, as a result, glacier mass losses in response to weakened ISM. Plain Language Summary Indian Summer Monsoon rainfall and Himalayan glacier/snow melts constitute the main water source for the densely populated Indian subcontinent. Better understanding of how future climate changes will affect the monsoon rainfall and Himalayan glaciers requires a long climate record. In this study, we create a 13,000-year-long climate record that allows us to better understand the response of Indian Summer Monsoon rainfall and Himalayan glaciers to past climate changes. The focus of our study is the time window between 9,000 and 22,000 years ago, an episode where the global climate experienced large and rapid changes. Our sediment record from the northern Bay of Bengal and climate change simulation indicate that during episodes of weak monsoon, the melting of the Himalayan glaciers increases substantially significantly. This is because the weakening of the monsoon results in less cloud cover and, as a result, the surface receives more sunlight and causes glacier melting.
Isolated extreme habitats are ideally suited to investigate pivotal ecological processes such as niche use, local adaptation and dispersal. Extremophilic animals living in isolated habitats face the problem that dispersal is limited through the absence of suitable dispersal corridors, which in turn facilitates local adaptation. We used five rotifer isolates from extremely acidic mining lakes with a pH of below 3 as model organisms to test whether these isolates are acidotolerant or acidophilic, whether they survive and reproduce at their niche edges (here pH 2 and circum-neutral pH) and whether local adaptation has evolved. To evaluate potential dispersal limitation, we tested whether animals and their parthenogenetic eggs survive and remain reproductive or viable at unfavourable pH-conditions. All five isolates were acidophilic with a pH-optimum in the range of 4-6, which is well above the pH (< 3) of their lakes of origin. At unfavourable high pH, in four out of the five isolates parthenogenetic females produced a high number of non-viable eggs. Females and eggs produced at favourable pH (4) remained vital at an otherwise unfavourable pH of 7, indicating that for dispersal no acidic dispersal corridors are necessary. Common garden experiments revealed no clear evidence for local adaptation in any of the five isolates. Despite their acidophilic nature, all five isolates can potentially disperse via circum-neutral water bodies as long as their residence time is short, suggesting a broader dispersal niche than their realized niche. Local adaptation might have been hampered by the low population sizes of the rotifers in their isolated habitat and the short time span the mining lakes have existed.
Trait-based approaches to investigate (short- and long-term) phytoplankton dynamics and community assembly have become increasingly popular in freshwater and marine science. Although the nature of the pelagic habitat and the main phytoplankton taxa and ecology are relatively similar in both marine and freshwater systems, the lines of research have evolved, at least in part, separately. We compare and contrast the approaches adopted in marine and freshwater ecosystems with respect to phytoplankton functional traits. We note differences in study goals relating to functional trait use that assess community assembly and those that relate to ecosystem processes and biogeochemical cycling that affect the type of characteristics assigned as traits to phytoplankton taxa. Specific phytoplankton traits relevant for ecological function are examined in relation to
herbivory, amplitude of environmental change and spatial and temporal scales of study. Major differences are identified, including the shorter time scale for regular environmental change in freshwater ecosystems compared to that in the open oceans as well as the
type of sampling done by researchers based on site-accessibility. Overall, we encourage researchers to better motivate why they apply trait-based analyses to their studies and to make use of process-driven approaches, which are more common in marine studies. We further propose fully comparative trait studies conducted along the habitat gradient spanning freshwater to brackish to marine systems, or along geographic gradients. Such studies will benefit from the combined strength of both fields.
Trait-based approaches to investigate (short- and long-term) phytoplankton dynamics and community assembly have become increasingly popular in freshwater and marine science. Although the nature of the pelagic habitat and the main phytoplankton taxa and ecology are relatively similar in both marine and freshwater systems, the lines of research have evolved, at least in part, separately. We compare and contrast the approaches adopted in marine and freshwater ecosystems with respect to phytoplankton functional traits. We note differences in study goals relating to functional trait use that assess community assembly and those that relate to ecosystem processes and biogeochemical cycling that affect the type of characteristics assigned as traits to phytoplankton taxa. Specific phytoplankton traits relevant for ecological function are examined in relation to
herbivory, amplitude of environmental change and spatial and temporal scales of study. Major differences are identified, including the shorter time scale for regular environmental change in freshwater ecosystems compared to that in the open oceans as well as the
type of sampling done by researchers based on site-accessibility. Overall, we encourage researchers to better motivate why they apply trait-based analyses to their studies and to make use of process-driven approaches, which are more common in marine studies. We further propose fully comparative trait studies conducted along the habitat gradient spanning freshwater to brackish to marine systems, or along geographic gradients. Such studies will benefit from the combined strength of both fields.
Aims Plant-plant interactions, being positive or negative, are recognized to be key factors in structuring plant communities. However, it is thought that root competition may be less important than shoot competition due to greater size symmetry belowground. Because direct experimental tests on the importance of root competition are scarce, we aim at elucidating whether root competition may have direct or indirect effects on community structure. Indirect effects may occur by altering the overall size asymmetry of competition through root-shoot competitive interactions. Methods We used a phytometer approach to examine the effects of root, shoot and total competition intensity and importance on evenness of experimental plant communities. Thereby two different phytometer species, Festuca brevipila and Dianthus carthusianorum, were grown in small communities of six grassland species over three levels of light and water availability, interacting with neighbouring shoots, roots, both or not at all. Important Findings We found variation in community evenness to be best explained if root and shoot (but not total) competition were considered. However, the effects were species specific: in Dianthus communities increasing root competition increased plant community evenness, while in Festuca communities shoot competition was the driving force of this evenness response. Competition intensities were influenced by environmental conditions in Dianthus, but not in Festuca phytometer plants. While we found no evidence for root-shoot interactions for neither phytometer species root competition in Dianthus communities led to increased allocation to shoots, thereby increasing the potential ability to perform in size-asymmetric competition for light. Our experiment demonstrates the potential role of root competition in structuring plant communities.
Deformation associated with plate convergence at subduction zones is accommodated by a complex system involving fault slip and viscoelastic flow. These processes have proven difficult to disentangle. The 2010 M-w 8.8 Maule earthquake occurred close to the Chilean coast within a dense network of continuously recording Global Positioning System stations, which provide a comprehensive history of surface strain. We use these data to assemble a detailed picture of a structurally controlled megathrust fault frictional patchwork and the three-dimensional rheological and time-dependent viscosity structure of the lower crust and upper mantle, all of which control the relative importance of afterslip and viscoelastic relaxation during postseismic deformation. These results enhance our understanding of subduction dynamics including the interplay of localized and distributed deformation during the subduction zone earthquake cycle.
Photoisomerization in some azobenzene-containing polymers (azopolymers) results in reversible solid-to-liquid transitions because trans- and cis-azopolymers have different glass transition temperatures. This property enables photoinduced healing and processing of azopolymers with high spatiotemporal resolution. However, a general lack of knowledge about the influence of the polymer structure on photoinduced reversible solid-to-liquid transitions hinders the design of such novel polymers. Herein, the synthesis and photoresponsive behavior of new azopolymers with different lengths of spacers between the polymer backbone and the azobenzene group on the side chain are reported. Azopolymers with no and 20 methylene spacers did not show photoinduced solid-to-liquid transitions. Azopolymers with 6 or 12 methylene spacers showed photoinduced solid-to-liquid transitions. This study demonstrates that spacers are essential for azopolymers with photoinduced reversible solid-to-liquid transitions, and thus, gives an insight into how to design azopolymers for photoinduced healing and processing.
Unfinished work tasks have been identified as a significant job-related stressor in recent occupational stress research. Extending this research, we examine how and when not finishing one’s tasks by the end of the work week affects work-related rumination at the weekend. Drawing on control theory, we examined competence need satisfaction as a mediating mechanism that links unfinished tasks at the end of the work week to work-related rumination at the weekend. Furthermore, we scrutinized whether proactive work behavior within the work week may neutralize the detrimental effects of unfinished tasks on competence need satisfaction and rumination. Using diary methodology, we collected weekly observations from 58 employees at the beginning and at the end of the work week over a period of 12 consecutive weeks, yielding 377 matched observations. Multilevel modeling analyses provided evidence for the assumed indirect effect at the intraindividual level. Higher levels of unfinished tasks were associated with lower levels of competence need satisfaction during the weekend. Competence need satisfaction, in turn, was negatively related to work-related rumination. Proactive work behavior attenuated the detrimental effects of unfinished tasks on competence need satisfaction and rumination at the weekend. These results imply that proactive work behavior facilitates switching off mentally during the weekend as it may restore competence need satisfaction in the face of unfinished tasks.
A large literature exists examining the functions of legislatures and the behaviour of MPs in established democracies. But little efforts have been made to observe how MPs behave in new democratic assemblies. This article seeks to address this shortcoming through an exploration of the use of parliamentary questions in two new democracies: Kenya and Zambia. Analysing an innovative dataset we offer one of the few attempts to directly measure legislative behaviour in new democracies. We examine how the factors found in the literature on parliamentary questions in liberal democracies react to this shift of context and to what degree legislatures in these countries fulfil their core functions. Results show that opposition MPs are not necessarily among the most active but that electoral incentives such as the margin by which MPs have won their seats or the number of voters they represent explain the use and content of parliamentary questions.
Germany and the United Kingdom have domestic shale gas reserves which they may exploit in the future to complement their national energy strategies. However gas production releases volatile organic compounds (VOC) and nitrogen oxides (NOx), which through photochemical reaction form ground-level ozone, an air pollutant that can trigger adverse health effects e.g. on the respiratory system. This study explores the range of impacts of a potential shale gas industry in these two countries on local and regional ambient ozone. To this end, comprehensive emission scenarios are used as the basis for input to an online-coupled regional chemistry transport model (WRF-Chem). Here we simulate shale gas scenarios over summer (June, July, August) 2011, exploring the effects of varying VOC emissions, gas speciation, and concentration of NOx emissions over space and time, on ozone formation. An evaluation of the model setup is performed, which exhibited the model’s ability to predict surface meteorological and chemical variables well compared with observations, and consistent with other studies. When different shale gas scenarios were employed, the results show a peak increase in maximum daily 8-hour average ozone from 3.7 to 28.3 μg m–3. In addition, we find that shale gas emissions can force ozone exceedances at a considerable percentage of regulatory measurement stations locally (up to 21% in Germany and 35% in the United Kingdom) and in distant countries through long-range transport, and increase the cumulative health-related metric SOMO35 (maximum percent increase of ~28%) throughout the region. Findings indicate that VOC emissions are important for ozone enhancement, and to a lesser extent NOx, meaning that VOC regulation for a future European shale gas industry will be of especial importance to mitigate unfavorable health outcomes. Overall our findings demonstrate that shale gas production in Europe can worsen ozone air quality on both the local and regional scales.
The present dissertation investigates profit-maximizing behavior in different phases of the negotiation process. Over the last decades, research dealt in detail with behavior of negotiation actors with the aim of identifying performance enhancing factors. The majority of those studies focused on behavior within the main negotiation phase. This work, however, considers phases which are, so far, underrepresented in research but show an impact on the negotiation process and outcome. Those phases are the pre-negotiation, the first offer, and the main negotiation phase which is further divided by breaks into several rounds. Within these phases, traits of behavior are analyzed that can be used strategically in order to impact the negotiation outcome. The dissertation contains three papers, each one dealing with a specific strategy within one phase. The first paper investigates communication behavior in the pre-negotiation phase. Content analysis of a negotiation experiment shows that the employment of positive communication elements such as the generation of enthusiasm for an upcoming project results in an increase of agreements on entering a negotiation and also leads to a higher willingness to make concessions. The second paper explores the impact of a semantic first anchor, which does not contain a specific number but only gives a numerical direction, on the opponent’s concession behavior and the final outcome. By means of two scenario-based questionnaires and a negotiation experiment it is demonstrated that semantic offers reveal an anchoring effect and lead to better negotiation outcomes. The third paper deals with the introduction of breaks and their effect on the following negotiation process. Therefore, content and outcome of another negotiation experiment are investigated. The analysis shows that breaks evoke a dominant impression but can negatively impact the atmosphere and thereby also the outcome. Finally, the gathered insights are brought together and discussed. The dissertation closes with implications for practice, limitations of the work, and ideas for future research.
The development of new and better optimization and approximation methods for Job Shop Scheduling Problems (JSP) uses simulations to compare their performance. The test data required for this has an uncertain influence on the simulation results, because the feasable search space can be changed drastically by small variations of the initial problem model. Methods could benefit from this to varying degrees. This speaks in favor of defining standardized and reusable test data for JSP problem classes, which in turn requires a systematic describability of the test data in order to be able to compile problem adequate data sets. This article looks at the test data used for comparing methods by literature review. It also shows how and why the differences in test data have to be taken into account. From this, corresponding challenges are derived which the management of test data must face in the context of JSP research.
Keywords
The development of new and better optimization and approximation methods for Job Shop Scheduling Problems (JSP) uses simulations to compare their performance. The test data required for this has an uncertain influence on the simulation results, because the feasable search space can be changed drastically by small variations of the initial problem model. Methods could benefit from this to varying degrees. This speaks in favor of defining standardized and reusable test data for JSP problem classes, which in turn requires a systematic describability of the test data in order to be able to compile problem adequate data sets. This article looks at the test data used for comparing methods by literature review. It also shows how and why the differences in test data have to be taken into account. From this, corresponding challenges are derived which the management of test data must face in the context of JSP research.
In nature as well as in the context of infection and medical applications, bacteria often have to move in highly complex environments such as soil or tissues. Previous studies have shown that bacteria strongly interact with their surroundings and are often guided by confinements. Here, we investigate theoretically how the dispersal of swimming bacteria can be augmented by microfluidic environments and validate our theoretical predictions experimentally. We consider a system of bacteria performing the prototypical run-and-tumble motion inside a labyrinth with square lattice geometry. Narrow channels between the square obstacles limit the possibility of bacteria to reorient during tumbling events to an area where channels cross. Thus, by varying the geometry of the lattice it might be possible to control the dispersal of cells. We present a theoretical model quantifying diffusive spreading of a run-and-tumble random walker in a square lattice. Numerical simulations validate our theoretical predictions for the dependence of the diffusion coefficient on the lattice geometry. We show that bacteria moving in square labyrinths exhibit enhanced dispersal as compared to unconfined cells. Importantly, confinement significantly extends the duration of the phase with strongly non-Gaussian diffusion, when the geometry of channels is imprinted in the density profiles of spreading cells. Finally, in good agreement with our theoretical findings, we observe the predicted behaviors in experiments with E. coli bacteria swimming in a square lattice labyrinth created in amicrofluidic device. Altogether, our comprehensive understanding of bacterial dispersal in a simple two-dimensional labyrinth makes the first step toward the analysis of more complex geometries relevant for real world applications.
In nature as well as in the context of infection and medical applications, bacteria often have to move in highly complex environments such as soil or tissues. Previous studies have shown that bacteria strongly interact with their surroundings and are often guided by confinements. Here, we investigate theoretically how the dispersal of swimming bacteria can be augmented by microfluidic environments and validate our theoretical predictions experimentally. We consider a system of bacteria performing the prototypical run-and-tumble motion inside a labyrinth with square lattice geometry. Narrow channels between the square obstacles limit the possibility of bacteria to reorient during tumbling events to an area where channels cross. Thus, by varying the geometry of the lattice it might be possible to control the dispersal of cells. We present a theoretical model quantifying diffusive spreading of a run-and-tumble random walker in a square lattice. Numerical simulations validate our theoretical predictions for the dependence of the diffusion coefficient on the lattice geometry. We show that bacteria moving in square labyrinths exhibit enhanced dispersal as compared to unconfined cells. Importantly, confinement significantly extends the duration of the phase with strongly non-Gaussian diffusion, when the geometry of channels is imprinted in the density profiles of spreading cells. Finally, in good agreement with our theoretical findings, we observe the predicted behaviors in experiments with E. coli bacteria swimming in a square lattice labyrinth created in amicrofluidic device. Altogether, our comprehensive understanding of bacterial dispersal in a simple two-dimensional labyrinth makes the first step toward the analysis of more complex geometries relevant for real world applications.
Research on weight-loss interventions in emerging adulthood is warranted. Therefore, a cognitive-behavioral group treatment (CBT), including development-specific topics for adolescents and young adults with obesity (YOUTH), was developed. In a controlled study, we compared the efficacy of this age-specific CBT group intervention to an age-unspecific CBT group delivered across ages in an inpatient setting. The primary outcome was body mass index standard deviation score (BMI-SDS) over the course of one year; secondary outcomes were health-related and disease-specific quality of life (QoL). 266 participants aged 16 to 21 years (65% females) were randomized. Intention-to-treat (ITT) and per-protocol analyses (PPA) were performed. For both group interventions, we observed significant and clinically relevant improvements in BMI-SDS and QoL over the course of time with small to large effect sizes. Contrary to our hypothesis, the age-specific intervention was not superior to the age-unspecific CBT-approach.
Research on weight-loss interventions in emerging adulthood is warranted. Therefore, a cognitive-behavioral group treatment (CBT), including development-specific topics for adolescents and young adults with obesity (YOUTH), was developed. In a controlled study, we compared the efficacy of this age-specific CBT group intervention to an age-unspecific CBT group delivered across ages in an inpatient setting. The primary outcome was body mass index standard deviation score (BMI-SDS) over the course of one year; secondary outcomes were health-related and disease-specific quality of life (QoL). 266 participants aged 16 to 21 years (65% females) were randomized. Intention-to-treat (ITT) and per-protocol analyses (PPA) were performed. For both group interventions, we observed significant and clinically relevant improvements in BMI-SDS and QoL over the course of time with small to large effect sizes. Contrary to our hypothesis, the age-specific intervention was not superior to the age-unspecific CBT-approach.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Hormonal regulation of neuronal mitochondrial unfolded protein response and its impact on metabolism
(2019)
The hypothalamus is the main brain area of central regulation of whole body metabolism through impacting food intake and energy expenditure. For the complex regulation, high amounts of energy are needed and mainly provided by mitochondria. Hence, mitochondrial function is crucial for cell homeostasis and modulates central insulin sensitivity. Thus, mitochondrial dysfunction is associated with insulin resistance in the brain and therefore is involved in the pathogenesis of type-2 diabetes (T2D). Mitochondrial health and protein homeostasis is propagated by mitochondrial stress responses like e.g. mitochondrial unfolded protein response (UPRmt). Therefore, studies regarding the regulation of mitochondrial homeostasis are crucial for understanding its effects on the central nervous system (CNS) for the progression of metabolic and nutrition-dependent disorders.
One main aim of this thesis was to investigate the metabolic regulation of mitochondrial stress responsiveness in the hypothalamus. The observed results showed that functional ERK-dependent insulin signaling is needed for regulation of mitochondrial stress response (MSR) genes and positively impacted the metabolism by controlling mitochondrial proteostasis without affecting mitochondrial biogenesis.
To further explore the role of MSR genes for brain cell homeostasis and its consequences for the metabolism, one of the key players - the mitochondrial chaperone heat shock protein 10 (Hsp10) – was studied in detail. Hsp10 expression was decreased in insulin-resistant, hyperglycemic db/db mice brains along with increased protein oxidation. Leptin, another key hormone in regulating metabolism, was able to induce Hsp10 in neurons. Appropriately, lentiviral-mediated knock down (KD) of Hsp10 introduced into hypothalamic CLU-183 cells induced mitochondrial dysfunction, altered mitochondrial dynamics and increased contact sites between mitochondria and endoplasmic reticulum (ER). In addition, Hsp10 KD caused cellular insulin resistance along with increasing oxidative stress specifically in mitochondrial fraction.
Interestingly, acute Hsp10 KD in the arcuate nucleus of the hypothalamus in C57BL/6N male mice did not change body weight or food intake, but it increased plasma leptin concentrations suggesting an effect on global leptin signaling. It increased hepatic markers of gluconeogenesis and hepatic insulin resistance along with features of low-grade inflammation.
Long-term studies of hypothalamic Hsp10 KD mice revealed unaltered systemic insulin sensitivity. The demonstrated increase in markers of hepatic gluconeogenesis of acute Hsp10 KD was still exhibited after 13 weeks, but insulin resistance in the liver was no longer observed.
In conclusion, hypothalamic insulin action regulates MSR and ensures proper mitochondrial function which positively affects metabolism. In addition, hypothalamic Hsp10 acts as a modulator of both insulin and leptin signaling and is identified as pivotal for the regulation of central mitochondrial function as well as insulin sensitivity in the brain and it impacts liver function. It may present a regulator of brain-liver crosstalk influencing hepatic gluconeogenesis and insulin sensitivity through a novel regulatory signaling mechanism.
Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration
(2019)
Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.
Following the Middle Permian (Capitanian) mass extinction there was a global ‘reef eclipse’, and this event had an important role in the Paleozoic-Mesozoic transition of reef ecosystems. Furthermore, the recovery pattern of reef ecosystems in the Wuchiapingian of South China, before the radiation of Changhsingian reefs, is poorly understood. Here, we present a detailed sedimentological account of the Tieqiao section, South China, which records the only known Wuchiapingian reef setting from South China. Six reef growing phases were identified within six transgressive-regressive cycles. The cycles represent changes of deposition in a shallow basin to a subtidal outer platform setting, and the reefal build-ups are recorded in the shallowest part of the cycles above wave base in the euphotic zone. Our results show that the initial reef recovery started from the shallowing up part of the 1st cycle, within the Clarkina leveni conodont zone, which is two conodont zones earlier than previously recognized. In addition, even though metazoans, such as sponges, do become important in the development of the reef bodies, they are not a major component until later in the Wuchiapingian in the 5th and 6th transgressive-regressive cycles. This suggests a delayed recovery of metazoan reef ecosystems following the Middle Permian extinction. Furthermore, even though sponges do become abundant within the reefs, it is the presence and growth of the encrusters Archaeolithoporella and Tubiphytes and abundance of microbial micrites that play an important role in stabilizing the reef structures that form topographic highs.
Non-swelling hydrophobic poly(n-butyl acrylate) network (cPnBA) is a candidate material for synthetic vascular grafts owing to its low toxicity and tailorable mechanical properties. Mesenchymal stem cells (MSCs) are an attractive cell type for accelerating endothelialization because of their superior anti-thrombosis and immune modulatory function. Further, they can differentiate into smooth muscle cells or endothelial-like cells and secret pro-angiogenic factors such as vascular endothelial growth factor (VEGF). MSCs are sensitive to the substrate mechanical properties, with the alteration of their major cellular behavior and functions as a response to substrate elasticity. Here, we cultured human adipose-derived mesenchymal stem cells (hADSCs) on cPnBAs with different mechanical properties (cPnBA250, Young’s modulus (E) = 250 kPa; cPnBA1100, E = 1100 kPa) matching the elasticity of native arteries, and investigated their cellular response to the materials including cell attachment, proliferation, viability, apoptosis, senescence and secretion. The cPnBA allowed high cell attachment and showed negligible cytotoxicity. F-actin assembly of hADSCs decreased on cPnBA films compared to classical tissue culture plate. The difference of cPnBA elasticity did not show dramatic effects on cell attachment, morphology, cytoskeleton assembly, apoptosis and senescence. Cells on cPnBA250, with lower proliferation rate, had significantly higher VEGF secretion activity. These results demonstrated that tuning polymer elasticity to regulate human stem cells might be a potential strategy for constructing stem cell-based artificial blood vessels.
Bank filtration (BF) is an established indirect water-treatment technology. The quality of water gained via BF depends on the subsurface capture zone, the mixing ratio (river water versus ambient groundwater), spatial and temporal distribution of subsurface travel times, and subsurface temperature patterns. Surface-water infiltration into the adjacent aquifer is determined by the local hydraulic gradient and riverbed permeability, which could be altered by natural clogging, scouring and artificial decolmation processes. The seasonal behaviour of a BF system in Germany, and its development during and about 6 months after decolmation (canal reconstruction), was observed with a long-term monitoring programme. To quantify the spatial and temporal variation in the BF system, a transient flow and heat transport model was implemented and two model scenarios, 'with' and 'without' canal reconstruction, were generated. Overall, the simulated water heads and temperatures matched those observed. Increased hydraulic connection between the canal and aquifer caused by the canal reconstruction led to an increase of similar to 23% in the already high share of BF water abstracted by the nearby waterworks. Subsurface travel-time distribution substantially shifted towards shorter travel times. Flow paths with travel times <200 days increased by similar to 10% and those with <300 days by 15%. Generally, the periodic temperature signal, and the summer and winter temperature extrema, increased and penetrated deeper into the aquifer. The joint hydrological and thermal effects caused by the canal reconstruction might increase the potential of biodegradable compounds to further penetrate into the aquifer, also by potentially affecting the redox zonation in the aquifer.
Two new hole selective materials (HSMs) based on dangling methylsulfanyl groups connected to the C-9 position of the fluorene core are synthesized and applied in perovskite solar cells. Being structurally similar to a half of Spiro-OMeTAD molecule, these HSMs (referred as FS and DFS) share similar redox potentials but are endowed with slightly higher hole mobility, due to the planarity and large extension of their structure. Competitive power conversion efficiency (up to 18.6%) is achieved by using the new HSMs in suitable perovskite solar cells. Time-resolved photoluminescence decay measurements and electrochemical impedance spectroscopy show more efficient charge extraction at the HSM/perovskite interface with respect to Spiro-OMeTAD, which is reflected in higher photocurrents exhibited by DFS/FS-integrated perovskite solar cells. Density functional theory simulations reveal that the interactions of methylammonium with methylsulfanyl groups in DFS/FS strengthen their electrostatic attraction with the perovskite surface, providing an additional path for hole extraction compared to the sole presence of methoxy groups in Spiro-OMeTAD. Importantly, the low-cost synthesis of FS makes it significantly attractive for the future commercialization of perovskite solar cells.
Chorus waves play an important role in the dynamic evolution of energetic electrons in the Earth's radiation belts and ring current. Using more than 5 years of Van Allen Probe data, we developed a new analytical model for upper‐band chorus (UBC; 0.5fce < f < fce) and lower‐band chorus (LBC; 0.05fce < f < 0.5fce) waves, where fce is the equatorial electron gyrofrequency. By applying polynomial fits to chorus wave root mean square amplitudes, we developed regression models for LBC and UBC as a function of geomagnetic activity (Kp), L, magnetic latitude (λ), and magnetic local time (MLT). Dependence on Kp is separated from the dependence on λ, L, and MLT as Kp‐scaling law to simplify the calculation of diffusion coefficients and inclusion into particle tracing codes. Frequency models for UBC and LBC are also developed, which depends on MLT and magnetic latitude. This empirical model is valid in all MLTs, magnetic latitude up to 20°, Kp ≤ 6, L‐shell range from 3.5 to 6 for LBC and from 4 to 6 for UBC. The dependence of root mean square amplitudes on L are different for different bands, which implies different energy sources for different wave bands. This analytical chorus wave model is convenient for inclusion in quasi‐linear diffusion calculations of electron scattering rates and particle simulations in the inner magnetosphere, especially for the newly developed four‐dimensional codes, which require significantly improved wave parameterizations.
Modeling and observations have shown that energy diffusion by chorus waves is an important source of acceleration of electrons to relativistic energies. By performing long-term simulations using the three-dimensional Versatile Electron Radiation Belt code, in this study, we test how the latitudinal dependence of chorus waves can affect the dynamics of the radiation belt electrons. Results show that the variability of chorus waves at high latitudes is critical for modeling of megaelectron volt (MeV) electrons. We show that, depending on the latitudinal distribution of chorus waves under different geomagnetic conditions, they cannot only produce a net acceleration but also a net loss of MeV electrons. Decrease in high-latitude chorus waves can tip the balance between acceleration and loss toward acceleration, or alternatively, the increase in high-latitude waves can result in a net loss of MeV electrons. Variations in high-latitude chorus may account for some of the variability of MeV electrons.
Sociocultural valuation (SCV) of ecosystem services (ES) discloses the principles, importance or preferences expressed by people towards nature. Although ES research has increasingly addressed sociocultural values in past years, little effort has been made to systematically review the components of sociocultural valuation applications for different decision contexts (i.e. awareness raising, accounting, priority setting, litigation and instrument design). In this analysis, we investigate the characteristics of 48 different sociocultural valuation applications—characterised by unique combinations of decision context, methods, data collection formats and participants—across ten European case studies. Our findings show that raising awareness for the sociocultural value of ES by capturing people’s perspective and establishing the status quo, was found the most frequent decision context in case studies, followed by priority setting and instrument development. Accounting and litigation issues were not addressed in any of the applications. We reveal that applications for particular decision contexts are methodologically similar, and that decision contexts determine the choice of methods, data collection formats and participants involved. Therefore, we conclude that understanding the decision context is a critical first step to designing and carrying out fit-for-purpose sociocultural valuation of ES in operational ecosystem management.
Interannual variations in ecosystem primary productivity are dominated by water availability. Until recently, characterizing the photosynthetic response of different ecosystems to soil moisture anomalies was hampered by observational limitations. Here, we use a number of satellite-based proxies for productivity, including spectral indices, sun-induced chlorophyll fluorescence, and data-driven estimates of gross primary production, to reevaluate the relationship between terrestrial photosynthesis and water. In contrast to nonwoody vegetation, we find a resilience of forested ecosystems to reduced soil moisture. Sun-induced chlorophyll fluorescence and data-driven gross primary production indicate an increase in photosynthesis as a result of the accompanying higher amounts of light and temperature despite lowered light-use-efficiency. Conversely, remote sensing indicators of greenness reach their detection limit and largely remain stable. Our study thus highlights the differential responses of ecosystems along a tree cover gradient and illustrates the importance of differentiating photosynthesis indicators from those of greenness for the monitoring and understanding of ecosystems. Plain Language Summary The capacity of vegetation to thrive and to sequester carbon depends on how much water they can have access to. In this work, we evaluate how different types of satellite observations can describe the response of vegetation to changes in soil moisture over the entire planet. The first source of observation measures only the greenness of the land surface, the second measures light that is emitted by pigments in plants which are photosynthetically active (chlorophyll fluorescence), and the third are simulations of gross carbon uptake derived from machine learning techniques. For periods of water shortage all three indicate a reduction of growth in ecosystems with few trees. However, in cold boreal forests, when soil moisture is particularly low, we still detect an increase in photosynthesis due to higher light and temperature conditions, but this is not reflected in the greenness indicator. This work illustrates how lack of water is not necessarily harmful for catching carbon through photosynthesis, but to monitor this effect, we need remote sensing indicators that measure more than just how green the plants are, and fluorescence is likely a good candidate.
The application of electrical resistivity tomography to peatlands supports conventional coring by providing data on the current condition of peatlands, including data on stratigraphy, peat properties and thickness of organic deposits. Data on the current condition of drained peatlands are particularly required to improve estimates of carbon storage as well as losses and emissions from agriculturally used peatlands. However, most of the studies focusing on electrical resistivity tomography surveys have been conducted on natural peatlands with higher groundwater levels. Peatlands drained for agriculture have not often been studied using geophysical techniques. Drained sites are characterized by low groundwater levels and high groundwater fluctuations during the year, which lead to varying levels of water saturation. To validate better electrical resistivity tomography surveys of drained peatlands, the aim of this laboratory study is to investigate the influence of varying water saturation levels on electrical conductivity (reciprocal of resistivity) for a variety of peat and gyttja types, as well as for different degrees of peat decomposition. Results show that different levels of water saturation strongly influence bulk electrical conductivity. Distinct differences in this relationship exist between peat and gyttja substrates and between different degrees of peat decomposition. Peat shows an exponential relationship for all degrees of decomposition, whereas gyttja, in particular organic-rich gyttja, is characterized by a rather unimodal relationship. The slopes for the relationship between electrical conductivity and water content are steeper at high degrees of decomposition than for peat of low degrees of decomposition. These results have direct implications for field electrical resistivity tomography surveys. In drained peatlands that are strongly susceptible to drying, electrical resistivity tomography surveys have a high potential to monitor the actual field water content. In addition, at comparable water saturations, high or low degrees of decomposition can be inferred from electrical conductivity.
A thermodynamic study of the adsorption of Human Serum Albumin (HSA) onto spherical polyelectrolyte brushes (SPBs) by isothermal titration calorimetry (ITC) is presented. The SPBs are composed of a solid polystyrene core bearing long chains of poly(acrylic acid). ITC measurements done at different temperatures and ionic strengths lead to a full set of thermodynamicbinding constants together with the enthalpies and entropies of binding. The adsorption of HSA onto SPBs is described with a two-step model. The free energy of binding Delta Gb depends only weakly on temperature because of a marked compensation of enthalpy by entropy. Studies of the adsorbed HSA by Fourier transform infrared spectroscopy (FT-IR) demonstrate no significant disturbance in the secondary structure of the protein. The quantitative analysis demonstrates that counterion release is the major driving force for adsorption in a process where proteins become multivalent counterions of the polyelectrolyte chains upon adsorption. A comparison with the analysis of other sets of data related to the binding of HSA to polyelectrolytes demonstrates that the cancellation of enthalpy and entropy is a general phenomenon that always accompanies the binding of proteins to polyelectrolytes dominated by counterion release.
Thermal treatment of hexaazatriphenylene-hexacarbonitrile (HAT-CN) in the temperature range from 500 degrees C to 700 degrees C leads to precise control over the degree of condensation, and thus atomic construction and porosity of the resulting C2N-type materials. Depending on the condensation temperature of HAT-CN, nitrogen contents of more than 30 at% can be reached. In general, these carbons show adsorption properties which are comparable to those known for zeolites but their pore size can be adjusted over a wider range. At condensation temperatures of 525 degrees C and below, the uptake of nitrogen gas remains negligible due to size exclusion, but the internal pores are large and polarizing enough that CO2 can still adsorb on part of the internal surface. This leads to surprisingly high CO2 adsorption capacities and isosteric heat of adsorption of up to 52 kJ mol(-1). Theoretical calculations show that this high binding enthalpy arises from collective stabilization effects from the nitrogen atoms in the C2N layers surrounding the carbon atom in the CO2 molecule and from the electron acceptor properties of the carbon atoms from C2N which are in close proximity to the oxygen atoms in CO2. A true CO2 molecular sieving effect is achieved for the first time in such a metal-free organic material with zeolite-like properties, showing an IAST CO2/N-2 selectivity of up to 121 at 298 K and a N-2/CO2 ratio of 90/10 without notable changes in the CO2 adsorption properities over 80 cycles.
The growing energy demand of the modern economies leads to the increased consumption of fossil fuels in form of coal, oil, and natural gases, as the mains sources. The combustion of these carbon-based fossil fuels is inevitably producing greenhouse gases, especially CO2. Approaches to tackle the CO2 problem are to capture it from the combustion sources or directly from air, as well as to avoid CO2 production in energy consuming sources (e.g., in the refrigeration sector). In the former, relatively low CO2 concentrations and competitive adsorption of other gases is often leading to low CO2 capacities and selectivities. In both approaches, the interaction of gas molecules with porous materials plays a key role. Porous carbon materials possess unique properties including electric conductivity, tunable porosity, as well as thermal and chemical stability. Nevertheless, pristine carbon materials offer weak polarity and thus low CO2 affinity. This can be overcome by nitrogen doping, which enhances the affinity of carbon materials towards acidic or polar guest molecules (e.g., CO2, H2O, or NH3). In contrast to heteroatom-free materials, such carbon materials are in most cases “noble”, that is, they oxidize other matter rather than being oxidized due to the very positive working potential of their electrons. The challenging task here is to achieve homogenous distribution of significant nitrogen content with similar bonding motives throughout the carbon framework and a uniform pore size/distribution to maximize host-guest interactions. The aim of this thesis is the development of novel synthesis pathways towards nitrogen-doped nanoporous noble carbon materials with precise design on a molecular level and understanding of their structure-related performance in energy and environmental applications, namely gas adsorption and electrochemical energy storage.
A template-free synthesis approach towards nitrogen-doped noble microporous carbon materials with high pyrazinic nitrogen content and C2N-type stoichiometry was established via thermal condensation of a hexaazatriphenylene derivative. The materials exhibited high uptake of guest molecules, such as H2O and CO2 at low concentrations, as well as moderate CO2/N2 selectivities. In the following step, the CO2/N2 selectivity was enhanced towards molecular sieving of CO2 via kinetic size exclusion of N2. The precise control over the condensation degree, and thus, atomic construction and porosity of the resulting materials led to remarkable CO2/N2 selectivities, CO2 capacities, and heat of CO2 adsorption. The ultrahydrophilic nature of the pore walls and the narrow microporosity of these carbon materials served as ideal basis for the investigation of interface effects with more polar guest molecules than CO2, namely H2O and NH3.
H2O vapor physisorption measurements, as well as NH3-temperature programmed desorption and thermal response measurements showed exceptionally high affinity towards H2O vapor and NH3 gas. Another series of nitrogen-doped carbon materials was synthesized by direct condensation of a pyrazine-fused conjugated microporous polymer and their structure-related performance in electrochemical energy storage, namely as anode materials for sodium-ion battery, was investigated.
All in all, the findings in this thesis exemplify the value of molecularly designed nitrogen-doped carbon materials with remarkable heteroatom content implemented as well-defined structure motives. The simultaneous adjustment of the porosity renders these materials suitable candidates for fundamental studies about the interactions between nitrogen-doped carbon materials and different guest species.
In recent years, named entity linking (NEL) tools were primarily developed in terms of a general approach, whereas today numerous tools are focusing on specific domains such as e.g. the mapping of persons and organizations only, or the annotation of locations or events in microposts. However, the available benchmark datasets necessary for the evaluation of NEL tools do not reflect this focalizing trend. We have analyzed the evaluation process applied in the NEL benchmarking framework GERBIL [in: Proceedings of the 24th International Conference on World Wide Web (WWW’15), International World Wide Web Conferences Steering Committee, Republic and Canton of Geneva, Switzerland, 2015, pp. 1133–1143, Semantic Web 9(5) (2018), 605–625] and all its benchmark datasets. Based on these insights we have extended the GERBIL framework to enable a more fine grained evaluation and in depth analysis of the available benchmark datasets with respect to different emphases. This paper presents the implementation of an adaptive filter for arbitrary entities and customized benchmark creation as well as the automated determination of typical NEL benchmark dataset properties, such as the extent of content-related ambiguity and diversity. These properties are integrated on different levels, which also enables to tailor customized new datasets out of the existing ones by remixing documents based on desired emphases. Besides a new system library to enrich provided NIF [in: International Semantic Web Conference (ISWC’13), Lecture Notes in Computer Science, Vol. 8219, Springer, Berlin, Heidelberg, 2013, pp. 98–113] datasets with statistical information, best practices for dataset remixing are presented, and an in depth analysis of the performance of entity linking systems on special focus datasets is presented.
Editorial
(2019)
Background Problem behaviour theory postulates that different forms of norm violations cluster and can be explained by similar antecedents. One such cluster may include cyberbullying and cyberhate perpetration. A potential explanatory mechanism includes toxic online disinhibition, characterised by anonymity, an inability to empathise and to recognise and interpret social cues. The current study to develop a better understanding of the relationship between cyberhate and cyberbullying to inform effective intervention and prevention efforts. Aims To test the link between cyberbullying and cyberhate and whether this relationship was moderated by toxic online disinhibition. Methods Self-report questionnaires on cyberbullying, cyberhate, and toxic online disinhibition were completed by 1,480 adolescents between 12 and 17 years old (M = 14.21 years; SD = 1.68). Results Increases in cyberbullying perpetration and toxic online disinhibition were positively related to cyberhate perpetration. Furthermore, cyberbullies reported more cyberhate perpetration when they reported higher levels of toxic online disinhibition and less frequent cyberhate perpetration when they reported lower levels of toxic online disinhibition. Conclusion The current study provides evidence of a possible link between cyberbullying and cyberhate perpetration, moderated by toxic online disinhibition. This suggests that, to be effective, prevention and intervention programmes should (i) consider the co-occurrence of varying forms of cyberaggression and (ii) consider potential effects of the online environment on aggressive online behaviour among young people.
Online hate is a topic that has received considerable interest lately, as online hate represents a risk to self-determination and peaceful coexistence in societies around the globe. However, not much is known about the explanations for adolescents posting or forwarding hateful online material or how adolescents cope with this newly emerging online risk. Thus, we sought to better understand the relationship between a bystander to and perpetrator of online hate, and the moderating effects of problem-focused coping strategies (e.g., assertive, technical coping) within this relationship. Self-report questionnaires on witnessing and committing online hate and assertive and technical coping were completed by 6829 adolescents between 12 and 18 years of age from eight countries. The results showed that increases in witnessing online hate were positively related to being a perpetrator of online hate. Assertive and technical coping strategies were negatively related with perpetrating online hate. Bystanders of online hate reported fewer instances of perpetrating online hate when they reported higher levels of assertive and technical coping strategies, and more frequent instances of perpetrating online hate when they reported lower levels of assertive and technical coping strategies. In conclusion, our findings suggest that, if effective, prevention and intervention programs that target online hate should consider educating young people about problem-focused coping strategies, self-assertiveness, and media skills. Implications for future research are discussed.
Online hate is a topic that has received considerable interest lately, as online hate represents a risk to self-determination and peaceful coexistence in societies around the globe. However, not much is known about the explanations for adolescents posting or forwarding hateful online material or how adolescents cope with this newly emerging online risk. Thus, we sought to better understand the relationship between a bystander to and perpetrator of online hate, and the moderating effects of problem-focused coping strategies (e.g., assertive, technical coping) within this relationship. Self-report questionnaires on witnessing and committing online hate and assertive and technical coping were completed by 6829 adolescents between 12 and 18 years of age from eight countries. The results showed that increases in witnessing online hate were positively related to being a perpetrator of online hate. Assertive and technical coping strategies were negatively related with perpetrating online hate. Bystanders of online hate reported fewer instances of perpetrating online hate when they reported higher levels of assertive and technical coping strategies, and more frequent instances of perpetrating online hate when they reported lower levels of assertive and technical coping strategies. In conclusion, our findings suggest that, if effective, prevention and intervention programs that target online hate should consider educating young people about problem-focused coping strategies, self-assertiveness, and media skills. Implications for future research are discussed.
Online hatred based on attributes, such as origin, race, gender, religion, or sexual orientation, has become a rising public concern across the world. Past research on aggressive behavior suggests strong associations between victimization and perpetration and that toxic online disinhibition and sex might influence this relationship. However, no study investigated both the relationship between online hate victimization and perpetration and the potential moderation effects of toxic online disinhibition on this relationship. To this end, the present study was conducted. The sample consists of 1,480 7th to 10th graders from Germany. Results revealed positive associations between online hate victimization and perpetration. Furthermore, the results support the idea that toxic online disinhibition and sex, by way of moderator effects, affect the relationship between online hate victimization and perpetration. Victims of online hate reported more online hate perpetration when they reported higher levels of online disinhibition and less frequent online hate perpetration when they reported lower levels of toxic online disinhibition. Additionally, the relationship between online hate victimization and perpetration was significantly greater among boys than among girls. Taken together, our results extend previous findings to online hate involvement among adolescents and substantiate the importance to conduct more research on online hate. In addition, our findings highlight the need for prevention and intervention programs that help adolescents deal with the emerging issue of online hate.
Hepcidin-25 (Hep-25) plays a crucial role in the control of iron homeostasis. Since the dysfunction of the hepcidin pathway leads to multiple diseases as a result of iron imbalance, hepcidin represents a potential target for the diagnosis and treatment of disorders of iron metabolism. Despite intense research in the last decade targeted at developing a selective immunoassay for iron disorder diagnosis and treatment and better understanding the ferroportin-hepcidin interaction, questions remain. The key to resolving these underlying questions is acquiring exact knowledge of the 3D structure of native Hep-25. Since it was determined that the N-terminus, which is responsible for the bioactivity of Hep-25, contains a small Cu(II)-binding site known as the ATCUN motif, it was assumed that the Hep-25-Cu(II) complex is the native, bioactive form of the hepcidin. This structure has thus far not been elucidated in detail. Owing to the lack of structural information on metal-bound Hep-25, little is known about its possible biological role in iron metabolism. Therefore, this work is focused on structurally characterizing the metal-bound Hep-25 by NMR spectroscopy and molecular dynamics simulations. For the present work, a protocol was developed to prepare and purify properly folded Hep-25 in high quantities. In order to overcome the low solubility of Hep-25 at neutral pH, we introduced the C-terminal DEDEDE solubility tag. The metal binding was investigated through a series of NMR spectroscopic experiments to identify the most affected amino acids that mediate metal coordination. Based on the obtained NMR data, a structural calculation was performed in order to generate a model structure of the Hep-25-Ni(II) complex. The DEDEDE tag was excluded from the structural calculation due to a lack of NMR restraints. The dynamic nature and fast exchange of some of the amide protons with solvent reduced the overall number of NMR restraints needed for a high-quality structure. The NMR data revealed that the 20 Cterminal Hep-25 amino acids experienced no significant conformational changes, compared to published results, as a result of a pH change from pH 3 to pH 7 and metal binding. A 3D model of the Hep-25-Ni(II) complex was constructed from NMR data recorded for the hexapeptideNi(II) complex and Hep-25-DEDEDE-Ni(II) complex in combination with the fixed conformation of 19 C-terminal amino acids. The NMR data of the Hep-25-DEDEDE-Ni(II) complex indicates that the ATCUN motif moves independently from the rest of the structure. The 3D model structure of the metal-bound Hep-25 allows for future works to elucidate hepcidin’s interaction with its receptor ferroportin and should serve as a starting point for the development of antibodies with improved selectivity.
Hot subdwarf B (sdB) stars are evolved core helium burning stars that have lost most of their hydrogen envelope due to binary interaction on the red giant branch. As sdB stars in wide binary systems can only be created by stable Roche lobe overflow, they are a great test sample to constrain the theoretical models for stable mass loss on the red giant branch. We present here the findings of a long term monitoring program of wide sdB+MS binaries. We found two main features in the orbital parameters. The majority of the systems have eccentric orbits with systems on longer orbital period having a higher eccentricity. As these systems have undergone mass loss near the tip of the RGB, tidal circularisation theory predicts them to be circularized. Our observations suggest that efficient eccentricity pumping mechanisms are active during the mass loss phase. Secondly we find a strong correlation between the mass ratio and the orbital period. Using binary evolution models, this relation is used to derive both an upper and lower limit on the initial mass ratio at which RLOF will be stable. These limits depend on the core mass of the sdB progenitor.
The propagation of a seismic rupture on a fault introduces spatial variations in the seismic wave field surrounding the fault. This directivity effect results in larger shaking amplitudes in the rupture propagation direction. Its seismic radiation pattern also causes amplitude variations between the strike-normal and strike-parallel components of horizontal ground motion. We investigated the landslide response to these effects during the 2016 Kumamoto earthquake (M-w 7.1) in central Kyushu (Japan). Although the distribution of some 1500 earthquake-triggered landslides as a function of rupture distance is consistent with the observed Arias intensity, the landslides were more concentrated to the northeast of the southwest-northeast striking rupture. We examined several landslide susceptibility factors: hillslope inclination, the median amplification factor (MAF) of ground shaking, lithology, land cover, and topographic wetness. None of these factors sufficiently explains the landslide distribution or orientation (aspect), although the landslide head scarps have an elevated hillslope inclination and MAF. We propose a new physics-based ground-motion model (GMM) that accounts for the seismic rupture effects, and we demonstrate that the low-frequency seismic radiation pattern is consistent with the overall landslide distribution. Its spatial pattern is influenced by the rupture directivity effect, whereas landslide aspect is influenced by amplitude variations between the fault-normal and fault-parallel motion at frequencies < 2 Hz. This azimuth dependence implies that comparable landslide concentrations can occur at different distances from the rupture. This quantitative link between the prevalent landslide aspect and the low-frequency seismic radiation pattern can improve coseismic landslide hazard assessment.
This is the eleventh of a series of miscellaneous contributions, by various authors, where hitherto unpublished data relevant to both the Med-Checklist and the Euro+Med (or Sisyphus) projects are presented. This instalment deals with the families Anacardiaceae, Asparagaceae (incl. Hyacinthaceae), Bignoniaceae, Cactaceae, Compositae, Cruciferae, Cyperaceae, Ericaceae, Gramineae, Labiatae, Leguminosae, Orobanchaceae, Polygonaceae, Rosaceae, Solanaceae and Staphyleaceae. It includes new country and area records and taxonomic and distributional considerations for taxa in Bidens, Campsis, Centaurea, Cyperus, Drymocallis, Engem, Hoffmannseggia, Hypopitys, Lavandula, Lithraea, Melilotus, Nicotiana, Olimarabidopsis, Opuntia, Orobanche, Phelipanche, Phragmites, Rumex, Salvia, Schinus, Staphylea, and a new combination in Drimia.
In light of the debate on the consequences of competitive contracting out of traditionally public services, this research compares two mechanisms used to allocate funds in development cooperation—direct awarding and competitive contracting out—aiming to identify their potential advantages and disadvantages.
The agency theory is applied within the framework of rational-choice institutionalism to study the institutional arrangements that surround two different money allocation mechanisms, identify the incentives they create for the behavior of individual actors in the field, and examine how these then transfer into measurable differences in managerial quality of development aid projects. In this work, project management quality is seen as an important determinant of the overall project success.
For data-gathering purposes, the German development agency, the Gesellschaft für Internationale Zusammenarbeit (GIZ), is used due to its unique way of work. Whereas the majority of projects receive funds via direct-award mechanism, there is a commercial department, GIZ International Services (GIZ IS) that has to compete for project funds.
The data concerning project management practices on the GIZ and GIZ IS projects was gathered via a web-based, self-administered survey of project team leaders. Principal component analysis was applied to reduce the dimensionality of the independent variable to total of five components of project management. Furthermore, multiple regression analysis identified the differences between the separate components on these two project types. Enriched by qualitative data gathered via interviews, this thesis offers insights into everyday managerial practices in development cooperation and identifies the advantages and disadvantages of the two allocation mechanisms.
The thesis first reiterates the responsibility of donors and implementers for overall aid effectiveness. It shows that the mechanism of competitive contracting out leads to better oversight and control of implementers, fosters deeper cooperation between the implementers and beneficiaries, and has a potential to strengthen ownership of recipient countries. On the other hand, it shows that the evaluation quality does not tremendously benefit from the competitive allocation mechanism and that the quality of the component knowledge management and learning is better when direct-award mechanisms are used. This raises questions about the lacking possibilities of actors in the field to learn about past mistakes and incorporate the finings into the future interventions, which is one of the fundamental issues of aid effectiveness. Finally, the findings show immense deficiencies in regard to oversight and control of individual projects in German development cooperation.
In older persons, the origin of malnutrition is often multifactorial with a multitude of factors involved. Presently, a common understanding about potential causes and their mode of action is lacking, and a consensus on the theoretical framework on the etiology of malnutrition does not exist. Within the European Knowledge Hub "Malnutrition in the Elderly (MaNuEL)," a model of "Determinants of Malnutrition in Aged Persons" (DoMAP) was developed in a multistage consensus process with live meetings and written feedback (modified Delphi process) by a multiprofessional group of 33 experts in geriatric nutrition. DoMAP consists of three triangle-shaped levels with malnutrition in the center, surrounded by the three principal conditions through which malnutrition develops in the innermost level: low intake, high requirements, and impaired nutrient bioavailability. The middle level consists of factors directly causing one of these conditions, and the outermost level contains factors indirectly causing one of the three conditions through the direct factors. The DoMAP model may contribute to a common understanding about the multitude of factors involved in the etiology of malnutrition, and about potential causative mechanisms. It may serve as basis for future research and may also be helpful in clinical routine to identify persons at increased risk of malnutrition.
Malnutrition is widespread in older people and represents a major geriatric syndrome with multifactorial etiology and severe consequences for health outcomes and quality of life. The aim of the present paper is to describe current approaches and evidence regarding malnutrition treatment and to highlight relevant knowledge gaps that need to be addressed. Recently published guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) provide a summary of the available evidence and highlight the wide range of different measures that can be taken—from the identification and elimination of potential causes to enteral and parenteral nutrition—depending on the patient’s abilities and needs. However, more than half of the recommendations therein are based on expert consensus because of a lack of evidence, and only three are concern patient-centred outcomes. Future research should further clarify the etiology of malnutrition and identify the most relevant causes in order to prevent malnutrition. Based on limited and partly conflicting evidence and the limitations of existing studies, it remains unclear which interventions are most effective in which patient groups, and if specific situations, diseases or etiologies of malnutrition require specific approaches. Patient-relevant outcomes such as functionality and quality of life need more attention, and research methodology should be harmonised to allow for the comparability of studies.
We investigate anomalous diffusion processes governed by the fractional Langevin equation and confined to a finite or semi-infinite interval by reflecting potential barriers. As the random and damping forces in the fractional Langevin equation fulfill the appropriate fluctuation-dissipation relation, the probability density on a finite interval converges for long times towards the expected uniform distribution prescribed by thermal equilibrium. In contrast, on a semi-infinite interval with a reflecting wall at the origin, the probability density shows pronounced deviations from the Gaussian behavior observed for normal diffusion. If the correlations of the random force are persistent (positive), particles accumulate at the reflecting wall while antipersistent (negative) correlations lead to a depletion of particles near the wall. We compare and contrast these results with the strong accumulation and depletion effects recently observed for nonthermal fractional Brownian motion with reflecting walls, and we discuss broader implications.
DNA is effectively damaged by radiation, which can on the one hand lead to cancer and is on the other hand directly exploited in the treatment of tumor tissue. DNA strand breaks are already induced by photons having an energy below the ionization energy of DNA. At high photon energies, most of the DNA strand breaks are induced by low-energy secondary electrons. In the present study we quantified photon and electron induced DNA strand breaks in four different 12mer oligonucleotides. They are irradiated directly with 8.44 eV vacuum ultraviolet (VUV) photons and 8.8 eV low energy electrons (LEE). By using Si instead of VUV transparent CaF2 as a substrate the VUV exposure leads to an additional release of LEEs, which have a maximum energy of 3.6 eV and can significantly enhance strand break cross sections. Atomic force microscopy is used to visualize strand breaks on DNA origami platforms and to determine absolute values for the strand break cross sections. Upon irradiation with 8.44 eV photons all the investigated sequences show very similar strand break cross sections in the range of 1.7-2.3x10(-16) cm(2). The strand break cross sections for LEE irradiation at 8.8 eV are one to two orders of magnitude larger than the ones for VUV photons, and a slight sequence dependence is observed. The sequence dependence is even more pronounced for LEEs with energies <3.6 eV. The present results help to assess DNA damage by photons and electrons close to the ionization threshold.
Radiation therapy is a basic part of cancer treatment. To increase the DNA damage in carcinogenic cells and preserve healthy tissue at the same time, radiosensitizing molecules such as halogenated nucleobase analogs can be incorporated into the DNA during the cell reproduction cycle. In the present study 8.44 eV photon irradiation induced single strand breaks (SSB) in DNA sequences modified with the radiosensitizer 5-bromouracil (U-5Br) and 8-bromoadenine ((8Br)A) are investigated. U-5Br was incorporated in the 13mer oligonucleotide flanked by different nucleobases. It was demonstrated that the highest SSB cross sections were reached, when cytosine and thymine were adjacent to U-5Br, whereas guanine as a neighboring nucleobase decreases the activity of U-5Br indicating that competing reaction mechanisms are active. This was further investigated with respect to the distance of guanine to U-5Br separated by an increasing number of adenine nucleotides. It was observed that the SSB cross sections were decreasing with an increasing number of adenine spacers between guanine and U-5Br until the SSB cross sections almost reached the level of a non-modified DNA sequence, which demonstrates the high sequence dependence of the sensitizing effect of U-5Br. (8Br)A was incorporated in a 13mer oligonucleotide as well and the strand breaks were quantified upon 8.44 eV photon irradiation in direct comparison to a non-modified DNA sequence of the same composition. No clear enhancement of the SSB yield of the modified in comparison to the non-modified DNA sequence could be observed. Additionally, secondary electrons with a maximum energy of 3.6 eV were generated when using Si as a substrate giving rise to further DNA damage. A clear enhancement in the SSB yield can be ascertained, but to the same degree for both the non-modified DNA sequence and the DNA sequence modified with (8Br)A.
All-in-One "Schizophrenic" self-assembly of orthogonally tuned thermoresponsive diblock copolymers
(2019)
Smart, fully orthogonal switching was realized in a highly biocompatible diblock copolymer system with variable trigger-induced aqueous self-assembly. The polymers are composed of nonionic and zwitterionic blocks featuring lower and upper critical solution temperatures (LCSTs and UCSTs). In the system investigated, diblock copolymers from poly(N-isopropyl methacrylamide) (PNIPMAM) and a poly(sulfobetaine methacrylamide), systematic variation of the molar mass of the latter block allowed for shifting the UCST of the latter above the LCST of the PNIPMAM block in a salt-free condition. Thus, successive thermal switching results in "schizophrenic" micellization, in which the roles of the hydrophobic core block and the hydrophilic shell block are interchanged depending on the temperature. Furthermore, by virtue of the strong electrolyte-sensitivity of the zwitterionic polysulfobetaine block, we succeeded to shift its UCST below the LCST of the PNIPMAM block by adding small amounts of an electrolyte, thus inverting the pathway of switching. This superimposed orthogonal switching by electrolyte addition enabled us to control the switching scenarios between the two types of micelles (i) via an insoluble state, if the LCST-type cloud point is below the UCST-type cloud point, which is the case at low salt concentrations or (ii) via a molecularly dissolved state, if the LCST-type cloud point is above the UCST-type cloud point, which is the case at high salt concentrations. Systematic variation of the block lengths allowed for verifying the anticipated behavior and identifying the molecular architecture needed. The versatile and tunable self-assembly offers manifold opportunities, for example, for smart emulsifiers or for sophisticated carrier systems.
Electrospray ionization-ion mobility spectrometry was employed for the determination of collision cross sections (CCS) of 25 synthetically produced peptides in the mass range between 540-3310 Da. The experimental measurement of the CCS is complemented by their calculation applying two different methods. One prediction method is the intrinsic size parameter (ISP) method developed by the Clemmer group. The second new method is based on the evaluation of molecular dynamics (MD) simulation trajectories as a whole, resulting in a single, averaged collision cross-section value for a given peptide in the gas phase. A high temperature MD simulation is run in order to scan through the whole conformational space. The lower temperature conformational distribution is obtained through thermodynamic reweighting. In the first part, various correlations, e.g. CCS vs. mass and inverse mobility vs. m/z correlations, are presented. Differences in CCS between peptides are also discussed in terms of their respective mass and m/z differences, as well as their respective structures. In the second part, measured and calculated CCS are compared. The agreement between the prediction results and the experimental values is in the same range for both calculation methods. While the calculation effort of the ISP method is much lower, the MD method comprises several tools providing deeper insights into the conformations of peptides. Advantages and limitations of both methods are discussed. Based on the separation of two pairs of linear and cyclic peptides of virtually the same mass, the influence of the structure on the cross sections is discussed. The shift in cross section differences and peak shape after transition from the linear to the cyclic peptide can be well understood by applying different MD tools, e.g. the root-mean-square deviation (RMSD) and the root mean square fluctuation (RMSF). (C) 2018 Elsevier B.V. All rights reserved.
Peer cultural socialisation
(2019)
This study investigated how peers can contribute to cultural minority students’ cultural identity, life satisfaction, and school values (school importance, utility, and intrinsic values) by talking about cultural values, beliefs, and behaviours associated with heritage and mainstream culture (peer cultural socialisation). We further distinguished between heritage and mainstream identity as two separate dimensions of cultural identity. Analyses were based on self-reports of 662 students of the first, second, and third migrant generation in Germany (Mean age = 14.75 years, 51% female). Path analyses revealed that talking about heritage culture with friends was positively related to heritage identity. Talking about mainstream culture with friends was negatively associated with heritage identity, but positively with mainstream identity as well as school values. Both dimensions of cultural identity related to higher life satisfaction and more positive school values. As expected, heritage and mainstream identity mediated the link between peer cultural socialisation and adjustment outcomes. Findings highlight the potential of peers as socialisation agents to help promote cultural belonging as well as positive adjustment of cultural minority youth in the school context.