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Relationships between climate, species composition, and species richness are of particular importance for understanding how boreal ecosystems will respond to ongoing climate change. This study aims to reconstruct changes in terrestrial vegetation composition and taxa richness during the glacial Late Pleistocene and the interglacial Holocene in the sparsely studied southeastern Yakutia (Siberia) by using pollen and sedimentary ancient DNA (sedaDNA) records. Pollen and sedaDNA metabarcoding data using the trnL g and h markers were obtained from a sediment core from Lake Bolshoe Toko. Both proxies were used to reconstruct the vegetation composition, while metabarcoding data were also used to investigate changes in plant taxa richness. The combination of pollen and sedaDNA approaches allows a robust estimation of regional and local past terrestrial vegetation composition around Bolshoe Toko during the last similar to 35,000 years. Both proxies suggest that during the Late Pleistocene, southeastern Siberia was covered by open steppe-tundra dominated by graminoids and forbs with patches of shrubs, confirming that steppe-tundra extended far south in Siberia. Both proxies show disturbance at the transition between the Late Pleistocene and the Holocene suggesting a period with scarce vegetation, changes in the hydrochemical conditions in the lake, and in sedimentation rates. Both proxies document drastic changes in vegetation composition in the early Holocene with an increased number of trees and shrubs and the appearance of new tree taxa in the lake's vicinity. The sedaDNA method suggests that the Late Pleistocene steppe-tundra vegetation supported a higher number of terrestrial plant taxa than the forested Holocene. This could be explained, for example, by the "keystone herbivore" hypothesis, which suggests that Late Pleistocene megaherbivores were able to maintain a high plant diversity. This is discussed in the light of the data with the broadly accepted species-area hypothesis as steppe-tundra covered such an extensive area during the Late Pleistocene.
We traced diatom composition and diversity through time using diatom-derived sedimentary ancient DNA (sedaDNA) from eastern continental slope sediments off Kamchatka (North Pacific) by applying a short, diatom-specific marker on 63 samples in a DNA metabarcoding approach. The sequences were assigned to diatoms that are common in the area and characteristic of cold water. SedaDNA allowed us to observe shifts of potential lineages from species of the genus Chaetoceros that can be related to different climatic phases, suggesting that pre-adapted ecotypes might have played a role in the long-term success of species in areas of changing environmental conditions. These sedaDNA results complement our understanding of the long-term history of diatom assemblages and their general relationship to environmental conditions of the past. Sea-ice diatoms (Pauliella taeniata [Grunow] Round & Basson, Attheya septentrionalis [ostrup] R. M. Crawford and Nitzschia frigida [Grunow]) detected during the late glacial and Younger Dryas are in agreement with previous sea-ice reconstructions. A positive correlation between pennate diatom richness and the sea-ice proxy IP25 suggests that sea ice fosters pennate diatom richness, whereas a negative correlation with June insolation and temperature points to unfavorable conditions during the Holocene. A sharp increase in proportions of freshwater diatoms at similar to 11.1 cal kyr BP implies the influence of terrestrial runoff and coincides with the loss of 42% of diatom sequence variants. We assume that reduced salinity at this time stabilized vertical stratification which limited the replenishment of nutrients in the euphotic zone.
A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope Al-27, both in animals and man. These limitations are absent in studies with Al-26 as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans-especially in toxicological relevant tissues like bone and brain-is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of Al-26 tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated Al-26 dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous Al-26 data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans.
This study examined the effects of an 8-week plyometric training (PT) program on components of physical fitness in young female handball players. Twenty-one female adolescent handball players were assigned to an experimental group (EG, n = 12; age = 15.9 +/- 0.2 years) or an active control group (CG, n = 9, age = 15.9 +/- 0.3 years). While EG performed plyometric exercises in replacement of some handball-specific drills, CG maintained the regular training schedule. Baseline and follow-up tests were performed for the assessment of linear speed (i.e., 5-, 10-, and 20-m time), change-of-direction (CoD) speed (i.e., T-test time), muscle power (i.e., countermovement jump [CMJ] height and reactive strength index [RSI]), and repeated sprint ability (RSA) (RSA total time [RSA(total)], RSA best time [RSA(best)], and RSA fatigue index [RSA(FI)]). Data were analyzed using magnitude-based inferences. Within-group analyses for the EG revealed moderate-to-large improvements for the 5-m (effect size [ES] = 0.81 [0.1-1.5]), 10-m sprint time (ES = 0.84 [0.1-1.5]), RSI (ES = 0.75 [0.1-1.4]), RSA(FI) (ES = 0.65 [0.0-1.3]), and T-test time (ES = 1.46 [0.7-2.2]). Trivial-to-small ES was observed for RSA(best) (ES = 0.18 [-0.5 to 0.9]), RSA(total) (ES = 0.45 [-0.2 to 1.1]), 20-m sprint time (ES = 0.56 [-0.1 to 1.2]), and CMJ height (ES = 0.57 [-0.1 to 1.3]). For the CG, within-group analyses showed a moderate performance decline for T-test time (ES = -0.71 [-1.5 to 0.1]), small decreases for 5-m sprint time (ES = -0.46 [-1.2 to 0.3]), and a trivial decline for 10-m (ES = -0.10 [-0.9 to 0.7]) and 20-m sprint times (ES = -0.16 [-0.9 to 0.6]), RSA(total) (ES = 0.0 [-0.8 to 0.8]), and RSA(best) (ES = -0.20 [-0.9 to 0.6]). The control group achieved trivial-to-small improvements for CMJ height (ES = 0.10 [-0.68 to 0.87]) and RSI (ES = 0.30 [-0.5 to 1.1]). In conclusion, a short-term in-season PT program, in replacement of handball-specific drills, is effective in improving measures of physical fitness (i.e., linear/CoD speed, jumping, and RSA) in young female handball players.
Background
The metabolic syndrome (MetS) is a risk cluster for a number of secondary diseases. The implementation of prevention programs requires early detection of individuals at risk. However, access to health care providers is limited in structurally weak regions. Brandenburg, a rural federal state in Germany, has an especially high MetS prevalence and disease burden. This study aims to validate and test the feasibility of a setup for mobile diagnostics of MetS and its secondary diseases, to evaluate the MetS prevalence and its association with moderating factors in Brandenburg and to identify new ways of early prevention, while establishing a “Mobile Brandenburg Cohort” to reveal new causes and risk factors for MetS.
Methods
In a pilot study, setups for mobile diagnostics of MetS and secondary diseases will be developed and validated. A van will be equipped as an examination room using point-of-care blood analyzers and by mobilizing standard methods. In study part A, these mobile diagnostic units will be placed at different locations in Brandenburg to locally recruit 5000 participants aged 40-70 years. They will be examined for MetS and advice on nutrition and physical activity will be provided. Questionnaires will be used to evaluate sociodemographics, stress perception, and physical activity. In study part B, participants with MetS, but without known secondary diseases, will receive a detailed mobile medical examination, including MetS diagnostics, medical history, clinical examinations, and instrumental diagnostics for internal, cardiovascular, musculoskeletal, and cognitive disorders. Participants will receive advice on nutrition and an exercise program will be demonstrated on site. People unable to participate in these mobile examinations will be interviewed by telephone. If necessary, participants will be referred to general practitioners for further diagnosis.
Discussion
The mobile diagnostics approach enables early detection of individuals at risk, and their targeted referral to local health care providers. Evaluation of the MetS prevalence, its relation to risk-increasing factors, and the “Mobile Brandenburg Cohort” create a unique database for further longitudinal studies on the implementation of home-based prevention programs to reduce mortality, especially in rural regions.
Trial registration
German Clinical Trials Register, DRKS00022764; registered 07 October 2020—retrospectively registered.
Exercise is known for its beneficial effects on preventing cardiometabolic diseases (CMDs) in the general population. People living with the human immunodeficiency virus (PLWH) are prone to sedentarism, thus raising their already elevated risk of developing CMDs in comparison to individuals without HIV. The aim of this cross-sectional study was to determine if exercise is associated with reduced risk of self-reported CMDs in a German HIV-positive sample (n = 446). Participants completed a self-report survey to assess exercise levels, date of HIV diagnosis, CD4 cell count, antiretroviral therapy, and CMDs. Participants were classified into exercising or sedentary conditions. Generalized linear models with Poisson regression were conducted to assess the prevalence ratio (PR) of PLWH reporting a CMD. Exercising PLWH were less likely to report a heart arrhythmia for every increase in exercise duration (PR: 0.20: 95% CI: 0.10–0.62, p < 0.01) and diabetes mellitus for every increase in exercise session per week (PR: 0.40: 95% CI: 0.10–1, p < 0.01). Exercise frequency and duration are associated with a decreased risk of reporting arrhythmia and diabetes mellitus in PLWH. Further studies are needed to elucidate the mechanisms underlying exercise as a protective factor for CMDs in PLWH.
Wildfires, as a key disturbance in forest ecosystems, are shaping the world's boreal landscapes. Changes in fire regimes are closely linked to a wide array of environmental factors, such as vegetation composition, climate change, and human activity. Arctic and boreal regions and, in particular, Siberian boreal forests are experiencing rising air and ground temperatures with the subsequent degradation of permafrost soils leading to shifts in tree cover and species composition. Compared to the boreal zones of North America or Europe, little is known about how such environmental changes might influence long-term fire regimes in Russia. The larch-dominated eastern Siberian deciduous boreal forests differ markedly from the composition of other boreal forests, yet data about past fire regimes remain sparse. Here, we present a high-resolution macroscopic charcoal record from lacustrine sediments of Lake Khamra (southwest Yakutia, Siberia) spanning the last ca. 2200 years, including information about charcoal particle sizes and morphotypes. Our results reveal a phase of increased charcoal accumulation between 600 and 900 CE, indicative of relatively high amounts of burnt biomass and high fire frequencies. This is followed by an almost 900-year-long period of low charcoal accumulation without significant peaks likely corresponding to cooler climate conditions. After 1750 CE fire frequencies and the relative amount of biomass burnt start to increase again, coinciding with a warming climate and increased anthropogenic land development after Russian colonization. In the 20th century, total charcoal accumulation decreases again to very low levels despite higher fire frequency, potentially reflecting a change in fire management strategies and/or a shift of the fire regime towards more frequent but smaller fires. A similar pattern for different charcoal morphotypes and comparison to a pollen and non-pollen palynomorph (NPP) record from the same sediment core indicate that broad-scale changes in vegetation composition were probably not a major driver of recorded fire regime changes. Instead, the fire regime of the last two millennia at Lake Khamra seems to be controlled mainly by a combination of short-term climate variability and anthropogenic fire ignition and suppression.
This study examines the institutionalization of information technologies for policy formulation by investigating the case of eNAP. The digital tool was introduced in the spring of 2018 with the aim of supporting and improving sustainability impact assessments (SIAs) within the German Federal Government. Applying a neo-institutional perspective, this study shows how a tool like eNAP is embedded into prevailing regulative, normative, and cultural–cognitive structures. Findings from 10 semi-structured interviews indicate that the application of eNAP varies according to intra-ministerial coordination practices and portfolio-specific information-processing schemata. Overall, the tool serves to translate the abstract regulation to conduct an SIA, as well as to translate the vague norm of “sustainability” into a concrete assessment requirement, thereby helping increase policy officials’ awareness of sustainability goals. However, consistent with previous studies, great importance is not attached to SIAs in policy formulation, and prevailing norms and routines make the implementation of eNAP to increase the use of evidence or in-depth considerations of policy alternatives and their consequences unlikely.
While previous research underscores the role of leaders in stimulating employee voice behaviour, comparatively little is known about what affects leaders' support for such constructive but potentially threatening employee behaviours. We introduce leader member exchange quality (LMX) as a central predictor of leaders' support for employees' ideas for constructive change. Apart from a general benefit of high LMX for leaders' idea support, we propose that high LMX is particularly critical to leaders' idea support if the idea voiced by an employee constitutes a power threat to the leader. We investigate leaders' attribution of prosocial and egoistic employee intentions as mediators of these effects. Hypotheses were tested in a quasi-experimental vignette study (N = 160), in which leaders evaluated a simulated employee idea, and a field study (N = 133), in which leaders evaluated an idea that had been voiced to them at work. Results show an indirect effect of LMX on leaders' idea support via attributed prosocial intentions but not via attributed egoistic intentions, and a buffering effect of high LMX on the negative effect of power threat on leaders' idea support. Results differed across studies with regard to the main effect of LMX on idea support.
In recent years, many efforts have been made to apply image processing techniques for plant leaf identification. However, categorizing leaf images at the cultivar/variety level, because of the very low inter-class variability, is still a challenging task. In this research, we propose an automatic discriminative method based on convolutional neural networks (CNNs) for classifying 12 different cultivars of common beans that belong to three various species. We show that employing advanced loss functions, such as Additive Angular Margin Loss and Large Margin Cosine Loss, instead of the standard softmax loss function for the classification can yield better discrimination between classes and thereby mitigate the problem of low inter-class variability. The method was evaluated by classifying species (level I), cultivars from the same species (level II), and cultivars from different species (level III), based on images from the leaf foreside and backside. The results indicate that the performance of the classification algorithm on the leaf backside image dataset is superior. The maximum mean classification accuracies of 95.86, 91.37 and 86.87% were obtained at the levels I, II and III, respectively. The proposed method outperforms the previous relevant works and provides a reliable approach for plant cultivars identification.
Electronic databases of landslides seldom include the triggering mechanisms, rendering these inventories unusable for landslide hazard modeling. We present a method for classifying the triggering mechanisms of landslides in existing inventories, thus, allowing these inventories to aid in landslide hazard modeling corresponding to the correct event chain. Our method uses various geometric characteristics of landslides as the feature space for the machine-learning classifier random forest, resulting in accurate and robust classifications of landslide triggers. We applied the method to six landslide inventories spread over the Japanese archipelago in several different tests and training configurations to demonstrate the effectiveness of our approach. We achieved mean accuracy ranging from 67% to 92%. We also provide an illustrative example of a real-world usage scenario for our method using an additional inventory with unknown ground truth. Furthermore, our feature importance analysis indicates that landslides having identical trigger mechanisms exhibit similar geometric properties.
While patients are known to respond differently to drug therapies, current clinical practice often still follows a standardized dosage regimen for all patients. For drugs with a narrow range of both effective and safe concentrations, this approach may lead to a high incidence of adverse events or subtherapeutic dosing in the presence of high patient variability. Model-informedprecision dosing (MIPD) is a quantitative approach towards dose individualization based on mathematical modeling of dose-response relationships integrating therapeutic drug/biomarker monitoring (TDM) data. MIPD may considerably improve the efficacy and safety of many drug therapies. Current MIPD approaches, however, rely either on pre-calculated dosing tables or on simple point predictions of the therapy outcome. These
approaches lack a quantification of uncertainties and the ability to account for effects that are delayed. In addition, the underlying models are not improved while applied to patient data. Therefore, current approaches are not well suited for informed clinical decision-making based on a differentiated understanding of the individually predicted therapy outcome.
The objective of this thesis is to develop mathematical approaches for MIPD, which (i) provide efficient fully Bayesian forecasting of the individual therapy outcome including associated uncertainties, (ii) integrate Markov decision processes via reinforcement learning (RL) for a comprehensive decision framework for dose individualization, (iii) allow for continuous learning across patients and hospitals. Cytotoxic anticancer chemotherapy with its major dose-limiting toxicity, neutropenia, serves as a therapeutically relevant application example.
For more comprehensive therapy forecasting, we apply Bayesian data assimilation (DA) approaches, integrating patient-specific TDM data into mathematical models of chemotherapy-induced neutropenia that build on prior population analyses. The value of uncertainty quantification is demonstrated as it allows reliable computation of the patient-specific probabilities of relevant clinical quantities, e.g., the neutropenia grade. In view of novel home monitoring devices that increase the amount of TDM data available, the data processing of
sequential DA methods proves to be more efficient and facilitates handling of the variability between dosing events.
By transferring concepts from DA and RL we develop novel approaches for MIPD. While DA-guided dosing integrates individualized uncertainties into dose selection, RL-guided dosing provides a framework to consider delayed effects of dose selections. The combined
DA-RL approach takes into account both aspects simultaneously and thus represents a holistic approach towards MIPD. Additionally, we show that RL can be used to gain insights into important patient characteristics for dose selection. The novel dosing strategies substantially reduce the occurrence of both subtherapeutic and life-threatening neutropenia grades in a simulation study based on a recent clinical study (CEPAC-TDM trial) compared to currently used MIPD approaches.
If MIPD is to be implemented in routine clinical practice, a certain model bias with respect to the underlying model is inevitable, as the models are typically based on data from comparably small clinical trials that reflect only to a limited extent the diversity in real-world patient populations. We propose a sequential hierarchical Bayesian inference framework that enables continuous cross-patient learning to learn the underlying model parameters of the target patient population. It is important to note that the approach only requires summary information of the individual patient data to update the model. This separation of the individual inference from population inference enables implementation across different centers of care.
The proposed approaches substantially improve current MIPD approaches, taking into account new trends in health care and aspects of practical applicability. They enable progress towards more informed clinical decision-making, ultimately increasing patient benefits beyond the current practice.
Long- and short-term monitoring of a dam in response to seasonal changes and ground motion loading
(2021)
An experimental multi-parameter structural monitoring system has been installed on the Kurpsai dam, western Kyrgyz Republic. This system consists of equipment for seismic and strain measurements for making longer- (days, weeks, months) and shorter- (minutes, hours) term observations, dealing with, for example seasonal (longer) effects or the response of the dam to ground motion from noise or seismic events. Fibre-optic strain sensors allow the seasonal and daily opening and closing of the spaces between the dam's segments to be tracked. For the seismic data, both amplitude (in terms of using differences in amplitudes in the Fourier spectra for mapping the modes of vibration of the dam) and their time-frequency distribution for a set of small to moderate seismic events are investigated and the corresponding phase variabilities (in terms of lagged coherency) are evaluated. Even for moderate levels of seismic-induced ground motion, some influence on the structural response can be detected, which then sees the dam quickly return to its original state. A seasonal component was identified in the strain measurements, while levels of noise arising from the operation of the dam's generators and associated water flow have been provisionally identified.
Lost in Germania
(2021)
Tacitus’ Germania is notable for its absences: lacking a preface and programmatic statements, and being the only ethnographic monograph to have survived from Greco-Roman antiquity, readers have often leapt to fill in its perceived blanks. This chapter aims at redressing the effects of overdetermined readings by interpreting the text’s absences as significant in their own right.
The olfactomotor system is especially investigated by examining the sniffing in reaction to olfactory stimuli. The motor output of respiratory-independent muscles was seldomly considered regarding possible influences of smells. The Adaptive Force (AF) characterizes the capability of the neuromuscular system to adapt to external forces in a holding manner and was suggested to be more vulnerable to possible interfering stimuli due to the underlying complex control processes. The aim of this pilot study was to measure the effects of olfactory inputs on the AF of the hip and elbow flexors, respectively. The AF of 10 subjects was examined manually by experienced testers while smelling at sniffing sticks with neutral, pleasant or disgusting odours. The reaction force and the limb position were recorded by a handheld device. The results show, inter alia, a significantly lower maximal isometric AF and a significantly higher AF at the onset of oscillations by perceiving disgusting odours compared to pleasant or neutral odours (p < 0.001). The adaptive holding capacity seems to reflect the functionality of the neuromuscular control, which can be impaired by disgusting olfactory inputs. An undisturbed functioning neuromuscular system appears to be characterized by a proper length tension control and by an earlier onset of mutual oscillations during an external force increase. This highlights the strong connection of olfaction and motor control also regarding respiratory-independent muscles.
The regulation of oxygen and blood supply during isometric muscle actions is still unclear. Recently, two behavioral types of oxygen saturation (SvO(2)) and relative hemoglobin amount (rHb) in venous microvessels were described during a fatiguing holding isometric muscle action (HIMA) (type I: nearly parallel behavior of SvO(2) and rHb; type II: partly inverse behavior). The study aimed to ascertain an explanation of these two regulative behaviors. Twelve subjects performed one fatiguing HIMA trial with each arm by weight holding at 60% of the maximal voluntary isometric contraction (MVIC) in a 90 & DEG; elbow flexion. Six subjects additionally executed one fatiguing PIMA trial by pulling on an immovable resistance with 60% of the MVIC with each side and same position. Both regulative types mentioned were found during HIMA (I: n = 7, II: n = 17) and PIMA (I: n = 3, II: n = 9). During the fatiguing measurements, rHb decreased initially and started to increase in type II at an average SvO(2)-level of 58.75 & PLUSMN; 2.14%. In type I, SvO(2) never reached that specific value during loading. This might indicate the existence of a threshold around 59% which seems to trigger the increase in rHb and could explain the two behavioral types. An approach is discussed to meet the apparent incompatibility of an increased capillary blood filling (rHb) despite high intramuscular pressures which were found by other research groups during isometric muscle actions.
The link between emotions and motor control has been discussed for years. The measurement of the Adaptive Force (AF) provides the possibility to get insights into the adaptive control of the neuromuscular system in reaction to external forces. It was hypothesized that the holding isometric AF is especially vulnerable to disturbing inputs. Here, the behavior of the AF under the influence of positive (tasty) vs. negative (disgusting) food imaginations was investigated. The AF was examined in n = 12 cases using an objectified manual muscle test of the hip flexors, elbow flexors or pectoralis major muscle, performed by one of two experienced testers while the participants imagined their most tasty or most disgusting food. The reaction force and the limb position were measured by a handheld device. While the slope of force rises and the maximal AF did not differ significantly between tasty and disgusting imaginations (p > 0.05), the maximal isometric AF was significantly lower and the AF at the onset of oscillations was significantly higher under disgusting vs. tasty imaginations (both p = 0.001). A proper length tension control of muscles seems to be a crucial functional parameter of the neuromuscular system which can be impaired instantaneously by emotionally related negative imaginations. This might be a potential approach to evaluate somatic reactions to emotions.