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This paper addresses semantic/pragmatic variability of tag questions in German and makes three main contributions. First, we document the prevalence and variety of question tags in German across three different types of conversational corpora. Second, by annotating question tags according to their syntactic and semantic context, discourse function, and pragmatic effect, we demonstrate the existing overlap and differences between the individual tag variants. Finally, we distinguish several groups of question tags by identifying the factors that influence the speakers’ choices of tags in the conversational context, such as clause type, function, speaker/hearer knowledge, as well as conversation type and medium. These factors provide the limits of variability by constraining certain question tags in German against occurring in specific contexts or with individual functions.
Similar Yet Different
(2020)
The importance of intrinsically disordered late embryogenesis abundant (LEA) proteins in the tolerance to abiotic stresses involving cellular dehydration is undisputed. While structural transitions of LEA proteins in response to changes in water availability are commonly observed and several molecular functions have been suggested, a systematic, comprehensive and comparative study of possible underlying sequence-structure-function relationships is still lacking. We performed molecular dynamics (MD) simulations as well as spectroscopic and light scattering experiments to characterize six members of two distinct, lowly homologous clades of LEA_4 family proteins from Arabidopsis thaliana. We compared structural and functional characteristics to elucidate to what degree structure and function are encoded in LEA protein sequences and complemented these findings with physicochemical properties identified in a systematic bioinformatics study of the entire Arabidopsis thaliana LEA_4 family. Our results demonstrate that although the six experimentally characterized LEA_4 proteins have similar structural and functional characteristics, differences concerning their folding propensity and membrane stabilization capacity during a freeze/thaw cycle are obvious. These differences cannot be easily attributed to sequence conservation, simple physicochemical characteristics or the abundance of sequence motifs. Moreover, the folding propensity does not appear to be correlated with membrane stabilization capacity. Therefore, the refinement of LEA_4 structural and functional properties is likely encoded in specific patterns of their physicochemical characteristics.
Radical reactions have found many applications in carbohydrate chemistry, especially in the construction of carbon–carbon bonds. The formation of carbon–heteroatom bonds has been less intensively studied. This mini-review will summarize the efforts to add heteroatom radicals to unsaturated carbohydrates like endo-glycals. Starting from early examples, developed more than 50 years ago, the importance of such reactions for carbohydrate chemistry and recent applications will be discussed. After a short introduction, the mini-review is divided in sub-chapters according to the heteroatoms halogen, nitrogen, phosphorus, and sulfur. The mechanisms of radical generation by chemical or photochemical processes and the subsequent reactions of the radicals at the 1-position will be discussed. This mini-review cannot cover all aspects of heteroatom-centered radicals in carbohydrate chemistry, but should provide an overview of the various strategies and future perspectives
Plants located adjacent to agricultural fields are important for maintaining biodiversity in semi-natural landscapes. To avoid undesired impacts on these plants due to herbicide application on the arable fields, regulatory risk assessments are conducted prior to registration to ensure proposed uses of plant protection products do not present an unacceptable risk. The current risk assessment approach for these non-target terrestrial plants (NTTPs) examines impacts at the individual-level as a surrogate approach for protecting the plant community due to the inherent difficulties of directly assessing population or community level impacts. However, modelling approaches are suitable higher tier tools to upscale individual-level effects to community level. IBC-grass is a sophisticated plant community model, which has already been applied in several studies. However, as it is a console application software, it was not deemed sufficiently user-friendly for risk managers and assessors to be conveniently operated without prior expertise in ecological models. Here, we present a user-friendly and open source graphical user interface (GUI) for the application of IBC-grass in regulatory herbicide risk assessment. It facilitates the use of the plant community model for predicting long-term impacts of herbicide applications on NTTP communities. The GUI offers two options to integrate herbicide impacts: (1) dose responses based on current standard experiments (acc. to testing guidelines) and (2) based on specific effect intensities. Both options represent suitable higher tier options for future risk assessments of NTTPs as well as for research on the ecological relevance of effects.
Many institutions struggle to tap into the potential of their large archives of radar reflectivity: these data are often affected by miscalibration, yet the bias is typically unknown and temporally volatile. Still, relative calibration techniques can be used to correct the measurements a posteriori. For that purpose, the usage of spaceborne reflectivity observations from the Tropical Rainfall Measuring Mission (TRMM) and Global Precipitation Measurement (GPM) platforms has become increasingly popular: the calibration bias of a ground radar (GR) is estimated from its average reflectivity difference to the spaceborne radar (SR). Recently, Crisologo et al. (2018) introduced a formal procedure to enhance the reliability of such estimates: each match between SR and GR observations is assigned a quality index, and the calibration bias is inferred as a quality-weighted average of the differences between SR and GR. The relevance of quality was exemplified for the Subic S-band radar in the Philippines, which is greatly affected by partial beam blockage.
The present study extends the concept of quality-weighted averaging by accounting for path-integrated attenuation (PIA) in addition to beam blockage. This extension becomes vital for radars that operate at the C or X band. Correspondingly, the study setup includes a C-band radar that substantially overlaps with the S-band radar. Based on the extended quality-weighting approach, we retrieve, for each of the two ground radars, a time series of calibration bias estimates from suitable SR overpasses. As a result of applying these estimates to correct the ground radar observations, the consistency between the ground radars in the region of overlap increased substantially. Furthermore, we investigated if the bias estimates can be interpolated in time, so that ground radar observations can be corrected even in the absence of prompt SR overpasses. We found that a moving average approach was most suitable for that purpose, although limited by the absence of explicit records of radar maintenance operations.
German orthography systematically marks all nouns (even other nominalized word classes) by capitalizing their first letter. It is often claimed that readers benefit from the uppercase-letter syntactic and semantic information, which makes the processing of sentences easier (e.g., Bock et al., 1985, 1989). In order to test this hypothesis, we asked 54 German readers to read single sentences systematically manipulated by a target word (N). In the experimental condition (EXP), we used semantic priming (in the following example: sick → cold) in order to build up a strong expectation of a noun, which was actually an attribute for the following noun (N+1) (translated to English e.g., “The sick writer had a cold (N) nose (N+1) …”). The sentences in the control condition were built analogously, but word N was purposefully altered (keeping word length and frequency constant) to make its interpretation as a noun extremely unlikely (e.g., “The sick writer had a blue (N) nose (N+1) …”). In both conditions, the sentences were presented either following German standard orthography (Cap) or in lowercase spelling (NoCap). The capitalized nouns in the EXP/Cap condition should then prevent garden-path parsing, as capital letters can be recognized parafoveally. However, in the EXP/NoCap condition, we expected a garden-path effect on word N+1 affecting first-pass fixations and the number of regressions, as the reader realizes that word N is instead an adjective. As the control condition does not include a garden-path, we expected to find (small) effects of the violation of the orthographic rule in the CON/NoCap condition, but no garden-path effect. As a global result, it can be stated that reading sentences in which nouns are not marked by a majuscule slows a native German reader down significantly, but from an absolute point of view, the effect is small. Compared with other manipulations (e.g., transpositions or substitutions), a lowercase letter still represents the correct allograph in the correct position without affecting phonology. Furthermore, most German readers do have experience with other alphabetic writing systems that lack consistent noun capitalization, and in (private) digital communication lowercase nouns are quite common. Although our garden-path sentences did not show the desired effect, we found an indication of grammatical pre-processing enabled by the majuscule in the regularly spelled sentences: In the case of high noun frequency, we post hoc located parafovea-on-fovea effects, i.e., longer fixation durations, on the attributive adjective (word N). These benefits of capitalization could only be detected under specific circumstances. In other cases, we conclude that longer reading durations are mainly the result of disturbance in readers' habituation when the expected capitalization is missing.
Commentary
(2020)
Recent studies have suggested that musical rhythm perception ability can affect the phonological system. The most prevalent causal account for developmental dyslexia is the phonological deficit hypothesis. As rhythm is a subpart of phonology, we hypothesized that reading deficits in dyslexia are associated with rhythm processing in speech and in music. In a rhythmic grouping task, adults with diagnosed dyslexia and age-matched controls listened to speech streams with syllables alternating in intensity, duration, or neither, and indicated whether they perceived a strong-weak or weak-strong rhythm pattern. Additionally, their reading and musical rhythm abilities were measured. Results showed that adults with dyslexia had lower musical rhythm abilities than adults without dyslexia. Moreover, lower musical rhythm ability was associated with lower reading ability in dyslexia. However, speech grouping by adults with dyslexia was not impaired when musical rhythm perception ability was controlled: like adults without dyslexia, they showed consistent preferences. However, rhythmic grouping was predicted by musical rhythm perception ability, irrespective of dyslexia. The results suggest associations among musical rhythm perception ability, speech rhythm perception, and reading ability. This highlights the importance of considering individual variability to better understand dyslexia and raises the possibility that musical rhythm perception ability is a key to phonological and reading acquisition.
Background
Multi-component cardiac rehabilitation (CR) is performed to achieve an improved prognosis, superior health-related quality of life (HRQL) and occupational resumption through the management of cardiovascular risk factors, as well as improvement of physical performance and patients’ subjective health. Out of a multitude of variables gathered at CR admission and discharge, we aimed to identify predictors of returning to work (RTW) and HRQL 6 months after CR.
Design
Prospective observational multi-centre study, enrolment in CR between 05/2017 and 05/2018.
Method
Besides general data (e.g. age, sex, diagnoses), parameters of risk factor management (e.g. smoking, hypertension), physical performance (e.g. maximum exercise capacity, endurance training load, 6-min walking distance) and patient-reported outcome measures (e.g. depression, anxiety, HRQL, subjective well-being, somatic and mental health, pain, lifestyle change motivation, general self-efficacy, pension desire and self-assessment of the occupational prognosis using several questionnaires) were documented at CR admission and discharge. These variables (at both measurement times and as changes during CR) were analysed using multiple linear regression models regarding their predictive value for RTW status and HRQL (SF-12) six months after CR.
Results
Out of 1262 patients (54±7 years, 77% men), 864 patients (69%) returned to work. Predictors of failed RTW were primarily the desire to receive pension (OR = 0.33, 95% CI: 0.22–0.50) and negative self-assessed occupational prognosis (OR = 0.34, 95% CI: 0.24–0.48) at CR discharge, acute coronary syndrome (OR = 0.64, 95% CI: 0.47–0.88) and comorbid heart failure (OR = 0.51, 95% CI: 0.30–0.87). High educational level, stress at work and physical and mental HRQL were associated with successful RTW. HRQL was determined predominantly by patient-reported outcome measures (e.g. pension desire, self-assessed health prognosis, anxiety, physical/mental HRQL/health, stress, well-being and self-efficacy) rather than by clinical parameters or physical performance.
Conclusion
Patient-reported outcome measures predominantly influenced return to work and HRQL in patients with heart disease. Therefore, the multi-component CR approach focussing on psychosocial support is crucial for subjective health prognosis and occupational resumption.
Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se
Purpose: Psychosocial variables are known risk factors for the development and chronification of low back pain (LBP). Psychosocial stress is one of these risk factors. Therefore, this study aims to identify the most important types of stress predicting LBP. Self-efficacy was included as a potential protective factor related to both, stress and pain.
Participants and Methods: This prospective observational study assessed n = 1071 subjects with low back pain over 2 years. Psychosocial stress was evaluated in a broad manner using instruments assessing perceived stress, stress experiences in work and social contexts, vital exhaustion and life-event stress. Further, self-efficacy and pain (characteristic pain intensity and disability) were assessed. Using least absolute shrinkage selection operator regression, important predictors of characteristic pain intensity and pain-related disability at 1-year and 2-years follow-up were analyzed.
Results: The final sample for the statistic procedure consisted of 588 subjects (age: 39.2 (± 13.4) years; baseline pain intensity: 27.8 (± 18.4); disability: 14.3 (± 17.9)). In the 1-year follow-up, the stress types “tendency to worry”, “social isolation”, “work discontent” as well as vital exhaustion and negative life events were identified as risk factors for both pain intensity and pain-related disability. Within the 2-years follow-up, Lasso models identified the stress types “tendency to worry”, “social isolation”, “social conflicts”, and “perceived long-term stress” as potential risk factors for both pain intensity and disability. Furthermore, “self-efficacy” (“internality”, “self-concept”) and “social externality” play a role in reducing pain-related disability.
Conclusion: Stress experiences in social and work-related contexts were identified as important risk factors for LBP 1 or 2 years in the future, even in subjects with low initial pain levels. Self-efficacy turned out to be a protective factor for pain development, especially in the long-term follow-up. Results suggest a differentiation of stress types in addressing psychosocial factors in research, prevention and therapy approaches.
As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences.
During the last decade, intracellular actin waves have attracted much attention due to their essential role in various cellular functions, ranging from motility to cytokinesis. Experimental methods have advanced significantly and can capture the dynamics of actin waves over a large range of spatio-temporal scales. However, the corresponding coarse-grained theory mostly avoids the full complexity of this multi-scale phenomenon. In this perspective, we focus on a minimal continuum model of activator–inhibitor type and highlight the qualitative role of mass conservation, which is typically overlooked. Specifically, our interest is to connect between the mathematical mechanisms of pattern formation in the presence of a large-scale mode, due to mass conservation, and distinct behaviors of actin waves.
The Ornstein–Uhlenbeck process is a stationary and ergodic Gaussian process, that is fully determined by its covariance function and mean. We show here that the generic definitions of the ensemble- and time-averaged mean squared displacements fail to capture these properties consistently, leading to a spurious ergodicity breaking. We propose to remedy this failure by redefining the mean squared displacements such that they reflect unambiguously the statistical properties of any stochastic process. In particular we study the effect of the initial condition in the Ornstein–Uhlenbeck process and its fractional extension. For the fractional Ornstein–Uhlenbeck process representing typical experimental situations in crowded environments such as living biological cells, we show that the stationarity of the process delicately depends on the initial condition.
The decision to exercise is not only bound to rational considerations but also automatic affective processes. The affective–reflective theory of physical inactivity and exercise (ART) proposes a theoretical framework for explaining how the automatic affective process (type‑1 process) will influence exercise behavior, i.e., through the automatic activation of exercise-related associations and a subsequent affective valuation of exercise. This study aimed to empirically test this assumption of the ART with data from 69 study participants. A single-measurement study, including within-subject experimental variation, was conducted. Automatic associations with exercise were first measured with a single-target implicit association test. The somato-affective core of the participants’ automatic valuation of exercise-related pictures was then assessed via heart rate variability (HRV) analysis, and the affective valence of the valuation was tested with a facial expression (FE; smile and frown) task. Exercise behavior was assessed via self-report. Multiple regression (path) analysis revealed that automatic associations predicted HRV reactivity (β = −0.24, p = .044); the signs of the correlation between automatic associations and the smile FE score was in the expected direction but remained nonsignificant (β = −0.21, p = .078). HRV reactivity predicted self-reported exercise behavior (β = −0.28, p = .013) (the same pattern of results was achieved for the frown FE score). The HRV-related results illustrate the potential role of automatic negative affective reactions to the thought of exercise as a restraining force in exercise motivation. For better empirical distinction between the two ART type‑1 process components, automatic associations and the affective valuation should perhaps be measured separately in the future. The results support the notion that automatic and affective processes should be regarded as essential aspects of the motivation to exercise.
Sedimentary ancient DNA has been proposed as a key methodology for reconstructing biodiversity over time. Yet, despite the concentration of Earth’s biodiversity in the tropics, this method has rarely been applied in this region. Moreover, the taphonomy of sedimentary DNA, especially in tropical environments, is poorly understood. This study elucidates challenges and opportunities of sedimentary ancient DNA approaches for reconstructing tropical biodiversity. We present shotgun-sequenced metagenomic profiles and DNA degradation patterns from multiple sediment cores from Mubwindi Swamp, located in Bwindi Impenetrable Forest (Uganda), one of the most diverse forests in Africa. We describe the taxonomic composition of the sediments covering the past 2200 years and compare the sedimentary DNA data with a comprehensive set of environmental and sedimentological parameters to unravel the conditions of DNA degradation. Consistent with the preservation of authentic ancient DNA in tropical swamp sediments, DNA concentration and mean fragment length declined exponentially with age and depth, while terminal deamination increased with age. DNA preservation patterns cannot be explained by any environmental parameter alone, but age seems to be the primary driver of DNA degradation in the swamp. Besides degradation, the presence of living microbial communities in the sediment also affects DNA quantity. Critically, 92.3% of our metagenomic data of a total 81.8 million unique, merged reads cannot be taxonomically identified due to the absence of genomic references in public databases. Of the remaining 7.7%, most of the data (93.0%) derive from Bacteria and Archaea, whereas only 0–5.8% are from Metazoa and 0–6.9% from Viridiplantae, in part due to unbalanced taxa representation in the reference data. The plant DNA record at ordinal level agrees well with local pollen data but resolves less diversity. Our animal DNA record reveals the presence of 41 native taxa (16 orders) including Afrotheria, Carnivora, and Ruminantia at Bwindi during the past 2200 years. Overall, we observe no decline in taxonomic richness with increasing age suggesting that several-thousand-year-old information on past biodiversity can be retrieved from tropical sediments. However, comprehensive genomic surveys of tropical biota need prioritization for sedimentary DNA to be a viable methodology for future tropical biodiversity studies.
Despite the increasing number of species invasions, the factors driving invasiveness are still under debate. This is particularly the case for “invisible” invasions by aquatic microbial species. Since in many cases only a few individuals or propagules enter a new habitat, their genetic variation is low and might limit their invasion success, known as the genetic bottleneck. Thus, a key question is, how genetic identity and diversity of invading species influences their invasion success and, subsequently, affect the resident community. We conducted invader-addition experiments using genetically different strains of the globally invasive, aquatic cyanobacterium Raphidiopsis raciborskii (formerly: Cylindrospermopsis raciborskii) to determine the role of invader identity and genetic diversity (strain richness) at four levels of herbivory. We tested the invasion success of solitary single strain invasions against the invader genetic diversity, which was experimentally increased up to ten strains (multi-strain populations). By using amplicon sequencing we determined the strain-specific invasion success in the multi-strain treatments and compared those with the success of these strains in the single-strain treatments. Furthermore, we tested for the invasion success under different herbivore pressures. We showed that high grazing pressure by a generalist herbivore prevented invasion, whereas a specialist herbivore enabled coexistence of consumer and invader. We found a weak effect of diversity on invasion success only under highly competitive conditions. When invasions were successful, the magnitude of this success was strain-specific and consistent among invasions performed with single-strain or multi-strain populations. A strain-specific effect was also observed on the resident phytoplankton community composition, highlighting the strong role of invader genetic identity. Our results point to a strong effect of the genetic identity on the invasion success under low predation pressure. The genetic diversity of the invader population, however, had little effect on invasion success in our study, in contrast to most previous findings. Instead, it is the interaction between the consumer abundance and type together with the strain identity of the invader that defined invasion success. This study underlines the importance of strain choice in invasion research and in ecological studies in general.
Die Universität Potsdam verwaltet seit 2015 einen DFG-geförderten Publikationsfonds. In den Publikationsjahren 2015 und 2017 wurden Outputanalysen durchgeführt. Open Access ist seit 2018 ein zentraler Bestandteil des Mittelverteilungsmodells. Der Artikel thematisiert die zentralen Erkenntnisse der letzten fünf Jahre und illustriert die entstandene Infrastruktur. Außerdem werden aktuelle Herausforderungen und mögliche Lösungsansätze der Transformation auf dem Weg hin zu 100 Prozent Open Access thematisiert.
This study presents the evaluation of a computer-based learning program for children with developmental dyscalculia and focuses on factors affecting individual responsiveness. The adaptive training program Calcularis 2.0 has been developed according to current neuro-cognitive theory of numerical cognition. It aims to automatize number representations, supports the formation and access to the mental number line and trains arithmetic operations as well as arithmetic fact knowledge in expanding number ranges. Sixty-seven children with developmental dyscalculia from second to fifth grade (mean age 8.96 years) were randomly assigned to one of two groups (Calcularis group, waiting control group). Training duration comprised a minimum of 42 training sessions à 20 min within a maximum period of 13 weeks. Compared to the waiting control group, children of the Calcularis group demonstrated a higher benefit in arithmetic operations and number line estimation. These improvements were shown to be stable after a 3-months post training interval. In addition, this study examines which predictors accounted for training improvements. Results indicate that this self-directed training was especially beneficial for children with low math anxiety scores and without an additional reading and/or spelling disorder. In conclusion, Calcularis 2.0 supports children with developmental dyscalculia to improve their arithmetical abilities and their mental number line representation. However, it is relevant to further adapt the setting to the individual circumstances.
Although a relatively large number of studies on acquired language impairments have tested the case of derivational morphology, none of these have specifically investigated whether there are differences in how prefixed and suffixed derived words are impaired. Based on linguistic and psycholinguistic considerations on prefixed and suffixed derived words, differences in how these two types of derivations are processed, and consequently impaired, are predicted. In the present study, we investigated the errors produced in reading aloud simple, prefixed, and suffixed words by three German individuals with agrammatic aphasia (NN, LG, SA). We found that, while NN and LG produced similar numbers of errors with prefixed and suffixed words, SA showed a selective impairment for prefixed words. Furthermore, NN and SA produced more errors specifically involving the affix with prefixed words than with suffixed words. We discuss our findings in terms of relative position of stem and affix in prefixed and suffixed words, as well as in terms of specific properties of prefixes and suffixes.
Objective: To determine immediate performance measures for short-term, multicomponent cardiac rehabilitation (CR) in clinical routine in patients of working age, taking into
account cardiovascular risk factors, physical performance, social medicine, and subjective health parameters and to explore the underlying dimensionality.
Design: Prospective observational multicenter register study in 12 rehabilitation centers throughout Germany.
Setting: Comprehensive 3-week CR.
Background
Aim of the study was to find predictors of allocating patients after transcatheter aortic valve implantation (TAVI) to geriatric (GR) or cardiac rehabilitation (CR) and describe this new patient group based on a differentiated characterization.
Methods
From 10/2013 to 07/2015, 344 patients with an elective TAVI were consecutively enrolled in this prospective multicentric cohort study. Before intervention, sociodemographic parameters, echocardiographic data, comorbidities, 6-min walk distance (6MWD), quality of life and frailty (score indexing activities of daily living [ADL], cognition, nutrition and mobility) were documented. Out of these, predictors for assignment to CR or GR after TAVI were identified using a multivariable regression model.
Results
After TAVI, 249 patients (80.7 ± 5.1 years, 59.0% female) underwent CR (n = 198) or GR (n = 51). GR patients were older, less physically active and more often had a level of care, peripheral artery disease as well as a lower left ventricular ejection fraction. The groups also varied in 6MWD. Furthermore, individual components of frailty revealed prognostic impact: higher values in instrumental ADL reduced the probability for referral to GR (OR:0.49, p < 0.001), while an impaired mobility was positively associated with referral to GR (OR:3.97, p = 0.046). Clinical parameters like stroke (OR:0.19 of GR, p = 0.038) and the EuroSCORE (OR:1.04 of GR, p = 0.026) were also predictive.
Conclusion
Advanced age patients after TAVI referred to CR or GR differ in several parameters and seem to be different patient groups with specific needs, e.g. regarding activities of daily living and mobility. Thus, our data prove the eligibility of both CR and GR settings.
Climate change heavily impacts smallholder farming worldwide. Cross-scale vulnerability assessment has a high potential to identify nested measures for reducing vulnerability of smallholder farmers. Despite their high practical value, there are currently only limited examples of cross-scale assessments. The presented study aims at assessing the vulnerability of smallholder farmers in the Northeast of Brazil across three scales: regional, farm and field scale. In doing so, it builds on existing vulnerability indices and compares results between indices at the same scale and across scales. In total, six independent indices are tested, two at each scale. The calculated indices include social, economic and ecological indicators, based on municipal statistics, meteorological data, farm interviews and soil analyses. Subsequently, indices and overlapping indicators are normalized for intra- and cross-scale comparison. The results show considerable differences between indices across and within scales. They indicate different activities to reduce vulnerability of smallholder farmers. Major shortcomings arise from the conceptual differences between the indices. We therefore recommend the development of hierarchical indices, which are adapted to local conditions and contain more overlapping indicators for a better understanding of the nested vulnerabilities of smallholder farmers.
Social comparison processes and the social position within a school class already play a major role in performance evaluation as early as in elementary school. The influence of contrast and assimilation effects on self-evaluation of performance as well as task interest has been widely researched in observational studies under the labels big-fish-little-pond and basking-in-reflected-glory effect. This study examined the influence of similar contrast and assimilation effects in an experimental paradigm. Fifth and sixth grade students (n = 230) completed a computer-based learning task during which they received social comparative feedback based on 2 × 2 experimentally manipulated feedback conditions: social position (high vs. low) and peer performance (high vs. low). Results show a more positive development of task interest and self-evaluation of performance in both the high social position and the high peer performance condition. When applied to the school setting, results of this study suggest that students who already perform well in comparison to their peer group are also the ones who profit most from social comparative feedback, given that they are the ones who usually receive the corresponding positive performance feedback.
Spiked gold nanotriangles
(2020)
We show the formation of metallic spikes on the surface of gold nanotriangles (AuNTs) by using the same reduction process which has been used for the synthesis of gold nanostars. We confirm that silver nitrate operates as a shape-directing agent in combination with ascorbic acid as the reducing agent and investigate the mechanism by dissecting the contribution of each component, i.e., anionic surfactant dioctyl sodium sulfosuccinate (AOT), ascorbic acid (AA), and AgNO3. Molecular dynamics (MD) simulations show that AA attaches to the AOT bilayer of nanotriangles, and covers the surface of gold clusters, which is of special relevance for the spike formation process at the AuNT surface. The surface modification goes hand in hand with a change of the optical properties. The increased thickness of the triangles and a sizeable fraction of silver atoms covering the spikes lead to a blue-shift of the intense near infrared absorption of the AuNTs. The sponge-like spiky surface increases both the surface enhanced Raman scattering (SERS) cross section of the particles and the photo-catalytic activity in comparison with the unmodified triangles, which is exemplified by the plasmon-driven dimerization of 4-nitrothiophenol (4-NTP) to 4,4'-dimercaptoazobenzene (DMAB).
Magnetite containing aerogels were synthesized by freeze-drying olive oil/silicone oil-based Janus emulsion gels containing gelatin and sodium carboxymethylcellulose (NaCMC). The magnetite nanoparticles dispersed in olive oil are processed into the gel and remain in the macroporous aerogel after removing the oil components. The coexistence of macropores from the Janus droplets and mesopores from freeze-drying of the hydrogels in combination with the magnetic properties offer a special hierarchical pore structure, which is of relevance for smart supercapacitors, biosensors, and spilled oil sorption and separation. The morphology of the final structure was investigated in dependence on initial compositions. More hydrophobic aerogels with magnetic responsiveness were synthesized by bisacrylamide-crosslinking of the hydrogel. The crosslinked aerogels can be successfully used in magnetically responsive clean up experiments of the cationic dye methylene blue.
In this paper, we present the convergence rate analysis of the modified Landweber method under logarithmic source condition for nonlinear ill-posed problems. The regularization parameter is chosen according to the discrepancy principle. The reconstructions of the shape of an unknown domain for an inverse potential problem by using the modified Landweber method are exhibited.
Differentially-charged liposomes interact with alphaherpesviruses and interfere with virus entry
(2020)
Exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane is induced by infection with several members of the Alphaherpesvirinae subfamily. There is evidence that PS is used by the equine herpesvirus type 1 (EHV-1) during entry, but the exact role of PS and other phospholipids in the entry process remains unknown. Here, we investigated the interaction of differently charged phospholipids with virus particles and determined their influence on infection. Our data show that liposomes containing negatively charged PS or positively charged DOTAP (N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium) inhibited EHV-1 infection, while neutral phosphatidylcholine (PC) had no effect. Inhibition of infection with PS was transient, decreased with time, and was dose dependent. Our findings indicate that both cationic and anionic phospholipids can interact with the virus and reduce infectivity, while, presumably, acting through different mechanisms. Charged phospholipids were found to have antiviral effects and may be used to inhibit EHV-1 infection.
RainNet v1.0
(2020)
In this study, we present RainNet, a deep convolutional neural network for radar-based precipitation nowcasting. Its design was inspired by the U-Net and SegNet families of deep learning models, which were originally designed for binary segmentation tasks. RainNet was trained to predict continuous precipitation intensities at a lead time of 5min, using several years of quality-controlled weather radar composites provided by the German Weather Service (DWD). That data set covers Germany with a spatial domain of 900km × 900km and has a resolution of 1km in space and 5min in time. Independent verification experiments were carried out on 11 summer precipitation events from 2016 to 2017. In order to achieve a lead time of 1h, a recursive approach was implemented by using RainNet predictions at 5min lead times as model inputs for longer lead times. In the verification experiments, trivial Eulerian persistence and a conventional model based on optical flow served as benchmarks. The latter is available in the rainymotion library and had previously been shown to outperform DWD's operational nowcasting model for the same set of verification events.
RainNet significantly outperforms the benchmark models at all lead times up to 60min for the routine verification metrics mean absolute error (MAE) and the critical success index (CSI) at intensity thresholds of 0.125, 1, and 5mm h⁻¹. However, rainymotion turned out to be superior in predicting the exceedance of higher intensity thresholds (here 10 and 15mm h⁻¹). The limited ability of RainNet to predict heavy rainfall intensities is an undesirable property which we attribute to a high level of spatial smoothing introduced by the model. At a lead time of 5min, an analysis of power spectral density confirmed a significant loss of spectral power at length scales of 16km and below. Obviously, RainNet had learned an optimal level of smoothing to produce a nowcast at 5min lead time. In that sense, the loss of spectral power at small scales is informative, too, as it reflects the limits of predictability as a function of spatial scale. Beyond the lead time of 5min, however, the increasing level of smoothing is a mere artifact – an analogue to numerical diffusion – that is not a property of RainNet itself but of its recursive application. In the context of early warning, the smoothing is particularly unfavorable since pronounced features of intense precipitation tend to get lost over longer lead times. Hence, we propose several options to address this issue in prospective research, including an adjustment of the loss function for model training, model training for longer lead times, and the prediction of threshold exceedance in terms of a binary segmentation task. Furthermore, we suggest additional input data that could help to better identify situations with imminent precipitation dynamics. The model code, pretrained weights, and training data are provided in open repositories as an input for such future studies.
Electrochemical methods offer the simple characterization of the synthesis of molecularly imprinted polymers (MIPs) and the readouts of target binding. The binding of electroinactive analytes can be detected indirectly by their modulating effect on the diffusional permeability of a redox marker through thin MIP films. However, this process generates an overall signal, which may include nonspecific interactions with the nonimprinted surface and adsorption at the electrode surface in addition to (specific) binding to the cavities. Redox-active low-molecular-weight targets and metalloproteins enable a more specific direct quantification of their binding to MIPs by measuring the faradaic current. The in situ characterization of enzymes, MIP-based mimics of redox enzymes or enzyme-labeled targets, is based on the indication of an electroactive product. This approach allows the determination of both the activity of the bio(mimetic) catalyst and of the substrate concentration.
The other-race effect (ORE) can be described as difficulties in discriminating between faces of ethnicities other than one’s own, and can already be observed at approximately 9 months of age. Recent studies also showed that infants visually explore same-and other-race faces differently. However, it is still unclear whether infants’ looking behavior for same- and other-race faces is related to their face discrimination abilities. To investigate this question we conducted a habituation–dishabituation experiment to examine Caucasian 9-month-old infants’ gaze behavior, and their discrimination of same- and other-race faces, using eye-tracking measurements. We found that infants looked longer at the eyes of same-race faces over the course of habituation, as compared to other-race faces. After habituation, infants demonstrated a clear other-race effect by successfully discriminating between same-race faces, but not other-race faces. Importantly, the infants’ ability to discriminate between same-race faces significantly correlated with their fixation time towards the eyes of same-race faces during habituation. Thus, our findings suggest that for infants old enough to begin exhibiting the ORE, gaze behavior during habituation is related to their ability to differentiate among same-race faces, compared to other-race faces.
Botulinum neurotoxins (BoNTs) are potent neurotoxins produced by bacteria, which inhibit neurotransmitter release, specifically in their physiological target known as motor neurons (MNs). For the potency assessment of BoNTs produced for treatment in traditional and aesthetic medicine, the mouse lethality assay is still used by the majority of manufacturers, which is ethically questionable in terms of the 3Rs principle. In this study, MNs were differentiated from human induced pluripotent stem cells based on three published protocols. The resulting cell populations were analyzed for their MN yield and their suitability for the potency assessment of BoNTs. MNs produce specific gangliosides and synaptic proteins, which are bound by BoNTs in order to be taken up by receptor-mediated endocytosis, which is followed by cleavage of specific soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) proteins required for neurotransmitter release. The presence of receptors and substrates for all BoNT serotypes was demonstrated in MNs generated in vitro. In particular, the MN differentiation protocol based on Du et al. yielded high numbers of MNs in a short amount of time with high expression of BoNT receptors and targets. The resulting cells are more sensitive to BoNT/A1 than the commonly used neuroblastoma cell line SiMa. MNs are, therefore, an ideal tool for being combined with already established detection methods.
All you can feed
(2020)
The laboratory mouse is the most common used mammalian research model in biomedical research. Usually these animals are maintained in germ-free, gnotobiotic, or specific-pathogen-free facilities. In these facilities, skilled staff takes care of the animals and scientists usually don’t pay much attention about the formulation and quality of diets the animals receive during normal breeding and keeping. However, mice have specific nutritional requirements that must be met to guarantee their potential to grow, reproduce and to respond to pathogens or diverse environmental stress situations evoked by handling and experimental interventions. Nowadays, mouse diets for research purposes are commercially manufactured in an industrial process, in which the safety of food products is addressed through the analysis and control of all biological and chemical materials used for the different diet formulations. Similar to human food, mouse diets must be prepared under good sanitary conditions and truthfully labeled to provide information of all ingredients. This is mandatory to guarantee reproducibility of animal studies. In this review, we summarize some information on mice research diets and general aspects of mouse nutrition including nutrient requirements of mice, leading manufacturers of diets, origin of nutrient compounds, and processing of feedstuffs for mice including dietary coloring, autoclaving and irradiation. Furthermore, we provide some critical views on the potential pitfalls that might result from faulty comparisons of grain-based diets with purified diets in the research data production resulting from confounding nutritional factors.
Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action
(2020)
Overconsumption of high-fat and cholesterol-containing diets is detrimental for metabolism and mitochondrial function, causes inflammatory responses and impairs insulin action in peripheral tissues. Dietary fatty acids can enter the brain to mediate the nutritional status, but also to influence neuronal homeostasis. Yet, it is unclear whether cholesterol-containing high-fat diets (HFDs) with different combinations of fatty acids exert metabolic stress and impact mitochondrial function in the brain. To investigate whether cholesterol in combination with different fatty acids impacts neuronal metabolism and mitochondrial function, C57BL/6J mice received different cholesterol-containing diets with either high concentrations of long-chain saturated fatty acids or soybean oil-derived poly-unsaturated fatty acids. In addition, CLU183 neurons were stimulated with combinations of palmitate, linoleic acid and cholesterol to assess their effects on metabolic stress, mitochondrial function and insulin action. The dietary interventions resulted in a molecular signature of metabolic stress in the hypothalamus with decreased expression of occludin and subunits of mitochondrial electron chain complexes, elevated protein carbonylation, as well as c-Jun N-terminal kinase (JNK) activation. Palmitate caused mitochondrial dysfunction, oxidative stress, insulin and insulin-like growth factor-1 (IGF-1) resistance, while cholesterol and linoleic acid did not cause functional alterations. Finally, we defined insulin receptor as a novel negative regulator of metabolically stress-induced JNK activation.
Vor achtzig Jahren
(2020)
Die Locarno-Verträge haben in der völkerrechtlichen Literatur der 1920er und 1930er Jahre viel Aufmerksamkeit erfahren. Auch die zeitgenössische Publizistik beschäftigte sich ausführlich mit diesem Thema, wobei das Verhältnis von Verständigung mit den Nachbarn und Revision der Grenzregelungen im Mittelpunkt der Debatte stand.
Später gehörte Locarno zur Geschichte der Zwischenkriegszeit und wurde im Rahmen der Völkerbundsgeschichte, der Völkerrechts- und Diplomatiegeschichte und der Geschichte der Weimarer Republik behandelt. Für die politikwissenschaftliche Literatur spielte Locarno fast ausschließlich auf dem Gebiet der Sicherheits- und Abrüstungspolitik eine Rolle; eine (system)theoretische Erörterung steht bislang aus.
In diesem Beitrag sollen nach einem kurzen Überblick über das Vertragswerk zunächst die geschichtliche Ausgangslage knapp umrissen und Vorgeschichte und Ergebnis der Konferenz von Locarno skizziert werden. Anschließend werden Inhalte und Lösungsansätze des Vertragswerkes beleuchtet, bevor zum Schluß eine kurze Einordnung in das System des Völkerbundes erfolgt.
Am Beispiel der Erd- und Umweltwissenschaften (einschließlich der landschafts- und standortbezogenen Teilgebiete der Agrarwissenschaften) zeigt dieser Beitrag, dass auch in scheinbar „unverdächtigen“ Disziplinen personenbezogene Forschungsdaten vorkommen. Eine Auswertung der Literatur zeigt, dass allgemeine Handreichungen zum Datenschutz in der Forschung kaum Unterstützung bei der Arbeit mit den für diese Disziplinen besonders relevanten Fällen bieten. Für die in den Erd- und Umweltwissenschaften besonders relevanten raumbezogenen Daten kommt hinzu, dass selbst unter Fachjuristinnen Uneinigkeit über die datenschutzrechtliche Bewertung herrscht. Die Ergebnisse einer empirischen Vorstudie zeigen eine ganze Reihe verschiedener Arten personenbezogener Forschungsdaten auf, die in der Forschungspraxis der Erd- und Umweltwissenschaften eine Rolle spielen. Sie legen außerdem nahe, dass der Umgang mit personenbezogenen Daten in der Forschungspraxis der Erd- und Umweltwissenschaften auf Grund der mangelnden Vertrautheit mit dem Datenschutz nicht immer den rechtlichen Anforderungen entspricht. Auch Unterstützung durch Fachgesellschaften und Infrastruktureinrichtungen – etwa in Form disziplinspezifischer Handreichungen, qualifizierter Beratung oder institutionalisierten Möglichkeiten, Daten sicher zu archivieren und gegebenenfalls zugangsbeschränkt zu publizieren – bestehen kaum. Aus dieser Situation ergeben sich Herausforderungen an die Weiterentwicklung der disziplinären Datenkultur und Dateninfrastruktur, beispielsweise im Rahmen des Prozesses zum Aufbau einer Nationalen Forschungsdateninfrastruktur (NFDI). Zu den Möglichkeiten für Infrastruktureinrichtungen, diese Weiterentwicklung zu unterstützen, zeigt dieser Beitrag Handlungsoptionen auf.
We consider the emerging dynamics of a separable continuous time random walk (CTRW) in the case when the random walker is biased by a velocity field in a uniformly growing domain. Concrete examples for such domains include growing biological cells or lipid vesicles, biofilms and tissues, but also macroscopic systems such as expanding aquifers during rainy periods, or the expanding Universe. The CTRW in this study can be subdiffusive, normal diffusive or superdiffusive, including the particular case of a Lévy flight. We first consider the case when the velocity field is absent. In the subdiffusive case, we reveal an interesting time dependence of the kurtosis of the particle probability density function. In particular, for a suitable parameter choice, we find that the propagator, which is fat tailed at short times, may cross over to a Gaussian-like propagator. We subsequently incorporate the effect of the velocity field and derive a bi-fractional diffusion-advection equation encoding the time evolution of the particle distribution. We apply this equation to study the mixing kinetics of two diffusing pulses, whose peaks move towards each other under the action of velocity fields acting in opposite directions. This deterministic motion of the peaks, together with the diffusive spreading of each pulse, tends to increase particle mixing, thereby counteracting the peak separation induced by the domain growth. As a result of this competition, different regimes of mixing arise. In the case of Lévy flights, apart from the non-mixing regime, one has two different mixing regimes in the long-time limit, depending on the exact parameter choice: in one of these regimes, mixing is mainly driven by diffusive spreading, while in the other mixing is controlled by the velocity fields acting on each pulse. Possible implications for encounter–controlled reactions in real systems are discussed.
Sediment Transit Time and Floodplain Storage Dynamics in Alluvial Rivers Revealed by Meteoric 10Be
(2020)
Quantifying the time scales of sediment transport and storage through river systems is fundamental for understanding weathering processes, biogeochemical cycling, and improving watershed management, but measuring sediment transit time is challenging. Here we provide the first systematic test of measuring cosmogenic meteoric Beryllium-10 (10Bem) in the sediment load of a large alluvial river to quantify sediment transit times. We take advantage of a natural experiment in the Rio Bermejo, a lowland alluvial river traversing the east Andean foreland basin in northern Argentina. This river has no tributaries along its trunk channel for nearly 1,300 km downstream from the mountain front. We sampled suspended sediment depth profiles along the channel and measured the concentrations of 10Bem in the chemically extracted grain coatings. We calculated depth-integrated 10Bem concentrations using sediment flux data and found that 10Bem concentrations increase 230% from upstream to downstream, indicating a mean total sediment transit time of 8.4 ± 2.2 kyr. Bulk sediment budget-based estimates of channel belt and fan storage times suggest that the 10Bem tracer records mixing of old and young sediment reservoirs. On a reach scale, 10Bem transit times are shorter where the channel is braided and superelevated above the floodplain, and longer where the channel is incised and meandering, suggesting that transit time is controlled by channel morphodynamics. This is the first systematic application of 10Bem as a sediment transit time tracer and highlights the method's potential for inferring sediment routing and storage dynamics in large river systems.
Nanoporous carbon materials (NCMs) provide the "function" of high specific surface area and thus have large interface area for interactions with surrounding species, which is of particular importance in applications related to adsorption processes. The strength and mechanism of adsorption depend on the pore architecture of the NCMs. In addition, chemical functionalization can be used to induce changes of electron density and/or electron density distribution in the pore walls, thus further modifying the interactions between carbons and guest species. Typical approaches for functionalization of nanoporous materials with regular atomic construction like porous silica, metal-organic frameworks, or zeolites, cannot be applied to NCMs due to their less defined local atomic construction and abundant defects. Therefore, synthetic strategies that offer a higher degree of control over the process of functionalization are needed. Synthetic approaches for covalent functionalization of NCMs, that is, for the incorporation of heteroatoms into the carbon backbone, are critically reviewed with a special focus on strategies following the concept "from molecules to materials." Approaches for coordinative functionalization with metallic species, and the functionalization by nanocomposite formation between pristine carbon materials and heteroatom-containing carbons, are introduced as well. Particular focus is given to the influences of these functionalizations in adsorption-related applications.
In this paper the use of two different scaffolds in a seminar on the topic of heterocycles is discussed. The students first used both scaffolds (stepped supporting tools and a task navigator) on two tasks and could then choose for one other task the scaffold that suited them more. The scaffolds were evaluated in a mixedmethods study by the use of questionnaires and the conducting of a focus group interview. Both scaffolds were assessed as being helpful. However, students who thought they didn’t need different sorts of tips, as provided by the task navigator, chose the stepped supporting tools. All students reflected on their use of the scaffolds; their choices for one of both are therefore well-founded. As the reasons for choosing the scaffold are very individual, in future seminars both types of scaffolds will be provided.
We study the experimentally measured ciprofloxacin antibiotic diffusion through a gel-like artificial sputum medium (ASM) mimicking physiological conditions typical for a cystic fibrosis layer, in which regions occupied by Pseudomonas aeruginosa bacteria are present. To quantify the antibiotic diffusion dynamics we employ a phenomenological model using a subdiffusion-absorption equation with a fractional time derivative. This effective equation describes molecular diffusion in a medium structured akin Thompson’s plumpudding model; here the ‘pudding’ background represents the ASM and the ‘plums’ represent the bacterial biofilm. The pudding is a subdiffusion barrier for antibiotic molecules that can affect bacteria found in plums. For the experimental study we use an interferometric method to determine the time evolution of the amount of antibiotic that has diffused through the biofilm. The theoretical model shows that this function is qualitatively different depending on whether or not absorption of the antibiotic in the biofilm occurs. We show that the process can be divided into three successive stages: (1) only antibiotic subdiffusion with constant biofilm parameters, (2) subdiffusion and absorption of antibiotic molecules with variable biofilm transport parameters, (3) subdiffusion and absorption in the medium but the biofilm parameters are constant again. Stage 2 is interpreted as the appearance of an intensive defence build–up of bacteria against the action of the antibiotic, and in the stage 3 it is likely that the bacteria have been inactivated. Times at which stages change are determined from the experimentally obtained temporal evolution of the amount of antibiotic that has diffused through the ASM with bacteria. Our analysis shows good agreement between experimental and theoretical results and is consistent with the biologically expected biofilm response. We show that an experimental method to study the temporal evolution of the amount of a substance that has diffused through a biofilm is useful in studying the processes occurring in a biofilm. We also show that the complicated biological process of antibiotic diffusion in a biofilm can be described by a fractional subdiffusion-absorption equation with subdiffusion and absorption parameters that change over time.
Engineering biotechnological microorganisms to use methanol as a feedstock for bioproduction is a major goal for the synthetic metabolism community. Here, we aim to redesign the natural serine cycle for implementation in E. coli. We propose the homoserine cycle, relying on two promiscuous formaldehyde aldolase reactions, as a superior pathway design. The homoserine cycle is expected to outperform the serine cycle and its variants with respect to biomass yield, thermodynamic favorability, and integration with host endogenous metabolism. Even as compared to the RuMP cycle, the most efficient naturally occurring methanol assimilation route, the homoserine cycle is expected to support higher yields of a wide array of products. We test the in vivo feasibility of the homoserine cycle by constructing several E. coli gene deletion strains whose growth is coupled to the activity of different pathway segments. Using this approach, we demonstrate that all required promiscuous enzymes are active enough to enable growth of the auxotrophic strains. Our findings thus identify a novel metabolic solution that opens the way to an optimized methylotrophic platform.
Formaldehyde is a highly reactive compound that participates in multiple spontaneous reactions, but these are mostly deleterious and damage cellular components. In contrast, the spontaneous condensation of formaldehyde with tetrahydrofolate (THF) has been proposed to contribute to the assimilation of this intermediate during growth on C1 carbon sources such as methanol. However, the in vivo rate of this condensation reaction is unknown and its possible contribution to growth remains elusive. Here, we used microbial platforms to assess the rate of this condensation in the cellular environment. We constructed Escherichia coli strains lacking the enzymes that naturally produce 5,10-methylene-THF. These strains were able to grow on minimal medium only when equipped with a sarcosine (N-methyl-glycine) oxidation pathway that sustained a high cellular concentration of formaldehyde, which spontaneously reacts with THF to produce 5,10-methylene-THF. We used flux balance analysis to derive the rate of the spontaneous condensation from the observed growth rate. According to this, we calculated that a microorganism obtaining its entire biomass via the spontaneous condensation of formaldehyde with THF would have a doubling time of more than three weeks. Hence, this spontaneous reaction is unlikely to serve as an effective route for formaldehyde assimilation.
Starch and Glycogen Analyses
(2020)
For complex carbohydrates, such as glycogen and starch, various analytical methods and techniques exist allowing the detailed characterization of these storage carbohydrates. In this article, we give a brief overview of the most frequently used methods, techniques, and results. Furthermore, we give insights in the isolation, purification, and fragmentation of both starch and glycogen. An overview of the different structural levels of the glucans is given and the corresponding analytical techniques are discussed. Moreover, future perspectives of the analytical needs and the challenges of the currently developing scientific questions are included
Economic impact of clinical decision support interventions based on electronic health records
(2020)
Background
Unnecessary healthcare utilization, non-adherence to current clinical guidelines, or insufficient personalized care are perpetual challenges and remain potential major cost-drivers for healthcare systems around the world. Implementing decision support systems into clinical care is promised to improve quality of care and thereby yield substantial effects on reducing healthcare expenditure. In this article, we evaluate the economic impact of clinical decision support (CDS) interventions based on electronic health records (EHR).
Methods
We searched for studies published after 2014 using MEDLINE, CENTRAL, WEB OF SCIENCE, EBSCO, and TUFTS CEA registry databases that encompass an economic evaluation or consider cost outcome measures of EHR based CDS interventions. Thereupon, we identified best practice application areas and categorized the investigated interventions according to an existing taxonomy of front-end CDS tools.
Results and discussion
Twenty-seven studies are investigated in this review. Of those, twenty-two studies indicate a reduction of healthcare expenditure after implementing an EHR based CDS system, especially towards prevalent application areas, such as unnecessary laboratory testing, duplicate order entry, efficient transfusion practice, or reduction of antibiotic prescriptions. On the contrary, order facilitators and undiscovered malfunctions revealed to be threats and could lead to new cost drivers in healthcare. While high upfront and maintenance costs of CDS systems are a worldwide implementation barrier, most studies do not consider implementation cost. Finally, four included economic evaluation studies report mixed monetary outcome results and thus highlight the importance of further high-quality economic evaluations for these CDS systems.
Conclusion
Current research studies lack consideration of comparative cost-outcome metrics as well as detailed cost components in their analyses. Nonetheless, the positive economic impact of EHR based CDS interventions is highly promising, especially with regard to reducing waste in healthcare.
Abiotic stresses cause oxidative damage in plants. Here, we demonstrate that foliar application of an extract from the seaweed Ascophyllum nodosum, SuperFifty (SF), largely prevents paraquat (PQ)-induced oxidative stress in Arabidopsis thaliana. While PQ-stressed plants develop necrotic lesions, plants pre-treated with SF (i.e., primed plants) were unaffected by PQ. Transcriptome analysis revealed induction of reactive oxygen species (ROS) marker genes, genes involved in ROS-induced programmed cell death, and autophagy-related genes after PQ treatment. These changes did not occur in PQ-stressed plants primed with SF. In contrast, upregulation of several carbohydrate metabolism genes, growth, and hormone signaling as well as antioxidant-related genes were specific to SF-primed plants. Metabolomic analyses revealed accumulation of the stress-protective metabolite maltose and the tricarboxylic acid cycle intermediates fumarate and malate in SF-primed plants. Lipidome analysis indicated that those lipids associated with oxidative stress-induced cell death and chloroplast degradation, such as triacylglycerols (TAGs), declined upon SF priming. Our study demonstrated that SF confers tolerance to PQ-induced oxidative stress in A. thaliana, an effect achieved by modulating a range of processes at the transcriptomic, metabolic, and lipid levels.
Identifying the entirety of gene regulatory interactions in a biological system offers the possibility to determine the key molecular factors that affect important traits on the level of cells, tissues, and whole organisms. Despite the development of experimental approaches and technologies for identification of direct binding of transcription factors (TFs) to promoter regions of downstream target genes, computational approaches that utilize large compendia of transcriptomics data are still the predominant methods used to predict direct downstream targets of TFs, and thus reconstruct genome-wide gene-regulatory networks (GRNs). These approaches can broadly be categorized into unsupervised and supervised, based on whether data about known, experimentally verified gene-regulatory interactions are used in the process of reconstructing the underlying GRN. Here, we first describe the generic steps of supervised approaches for GRN reconstruction, since they have been recently shown to result in improved accuracy of the resulting networks? We also illustrate how they can be used with data from model organisms to obtain more accurate prediction of gene regulatory interactions.
In a changing world, phytoplankton communities face a large variety of challenges including altered light regimes. These alterations are caused by more pronounced stratification due to rising temperatures, enhanced eutrophication, and browning of lakes. Community responses toward these effects can emerge as alterations in physiology, biomass, biochemical composition, or diversity. In this study, we addressed the combined effects of changes in light and nutrient conditions on community responses. In particular, we investigated how light intensity and variability under two nutrient conditions influence (1) fast responses such as adjustments in photosynthesis, (2) intermediate responses such as pigment adaptation and (3) slow responses such as changes in community biomass and species composition. Therefore, we exposed communities consisting of five phytoplankton species belonging to different taxonomic groups to two constant and two variable light intensity treatments combined with two levels of phosphorus supply. The tested phytoplankton communities exhibited increased fast reactions of photosynthetic processes to light variability and light intensity. The adjustment of their light harvesting mechanisms via community pigment composition was not affected by light intensity, variability, or nutrient supply. However, pigment specific effects of light intensity, light variability, and nutrient supply on the proportion of the respective pigments were detected. Biomass was positively affected by higher light intensity and nutrient concentrations while the direction of the effect of variability was modulated by light intensity. Light variability had a negative impact on biomass at low, but a positive impact at high light intensity. The effects on community composition were species specific. Generally, the proportion of green algae was higher under high light intensity, whereas the cyanobacterium performed better under low light conditions. In addition to that, the diatom and the cryptophyte performed better with high nutrient supply while the green algae as well as the cyanobacterium performed better at low nutrient conditions. This shows that light intensity, light variability, and nutrient supply interactively affect communities. Furthermore, the responses are highly species and pigment specific, thus to clarify the effects of climate change a deeper understanding of the effects of light variability and species interactions within communities is important.
Bayesian Data Assimilation to Support Informed Decision Making in Individualized Chemotherapy
(2020)
An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most probable model parameters (maximum a posteriori (MAP) estimate). This MAP-based approach, however, does neither necessarily predict the most probable outcome nor does it quantify the risks of treatment inefficacy or toxicity. Bayesian data assimilation (DA) methods overcome these limitations by providing a comprehensive uncertainty quantification. We compare DA methods with MAP-based approaches and show how probabilistic statements about key markers related to chemotherapy-induced neutropenia can be leveraged for more informative decision support in individualized chemotherapy. Sequential Bayesian DA proved to be most computationally efficient for handling interoccasion variability and integrating TDM data. For new digital monitoring devices enabling more frequent data collection, these features will be of critical importance to improve patient care decisions in various therapeutic areas.
We investigate whether political ideology has an observable effect on decarbonization ambition, renewable power aims, and preferences for power system balancing technologies in four European countries. Based on the Energy Logics framework, we identify ideologically different transition strategies (state-centered, market-centered, grassroots-centered) contained in government policies and opposition party programs valid in 2019. We compare these policies and programs with citizen poll data. We find that ideology has a small effect: governments and political parties across the spectrum have similar, and relatively ambitious, decarbonization and renewables targets. This mirrors citizens' strong support for ambitious action regardless of their ideological self-description. However, whereas political positions on phasing out fossil fuel power are clear across the policy space, positions on phasing in new flexibility options to balance intermittent renewables are vague or non-existent. As parties and citizens agree on strong climate and renewable power aims, the policy ambition is likely to remain high, even if governments change.