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- inclusive education (8)
- inference (8)
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- isomerization (8)
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- noise (8)
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- pain (8)
- parliamentary government (8)
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- plant diversity (8)
- plasmonics (8)
- polarization (8)
- policy (8)
- polyelectrolyte (8)
- production control (8)
- professional development (8)
- pronouns (8)
- proteomics (8)
- psychotherapy training (8)
- quality (8)
- quantification (8)
- quasars: general (8)
- race (8)
- reanalysis (8)
- recombination (8)
- reproducibility (8)
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- restoration (8)
- right-wing extremism (8)
- risk perception (8)
- rotation (8)
- sediment transport (8)
- sedimentary ancient DNA (8)
- seed dispersal (8)
- snow (8)
- spatial frequencies (8)
- stars: activity (8)
- stars: emission-line, Be (8)
- sustainable development (8)
- taste (8)
- teaching quality (8)
- thermokarst (8)
- time series (8)
- time-series (8)
- tracking (8)
- transition (8)
- treeline (8)
- trends (8)
- trust (8)
- ultrafast (8)
- urbanization (8)
- ventral striatum (8)
- verification (8)
- vitamin A (8)
- von Humboldts Hand (8)
- wh-questions (8)
- work (8)
- yellow flags (8)
- youth sports (8)
- Öffentliche Verwaltung (8)
- Anisotropy (7)
- Anisotropy effect (7)
- Anpassung (7)
- Antike (7)
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- Balance (7)
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- Complex networks (7)
- Crustal structure (7)
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- Design (7)
- Digitale Plattformen (7)
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- Disturbance (7)
- E-Government (7)
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- East African Rift System (7)
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- Emotionen (7)
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- Fortbildung (7)
- Fredholm property (7)
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- Geschäftsprozessmanagement (7)
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- Hertzsprung-Russell and C-M diagrams (7)
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- Indian Summer Monsoon (7)
- Inspiration (7)
- Interaction (7)
- Interest (7)
- Interoception (7)
- Johann Wolfgang von Goethe (7)
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- Kartographie (7)
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- LCSM (7)
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- Lehrer (7)
- LiDAR (7)
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- Neotektonik (7)
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- RIXS (7)
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- Reading motivation (7)
- Recht (7)
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- Stickstoff (7)
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- Survey (7)
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- Synthesis (7)
- Teacher training (7)
- Tien Shan (7)
- Time series (7)
- Time series analysis (7)
- Transfer (7)
- Transkriptionsfaktoren (7)
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- Vegetation (7)
- Vulnerabilität (7)
- Walking (7)
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- Water quality (7)
- Weltbegriff (7)
- X-rays: ISM (7)
- academic achievement (7)
- acquisition (7)
- age of acquisition (7)
- aggregation (7)
- air pollution (7)
- algorithms (7)
- alignment (7)
- allostatic load (7)
- amino acids (7)
- amygdala (7)
- anthropometry (7)
- apoptosis (7)
- arctic (7)
- articulation (7)
- attitudes (7)
- augmented reality (7)
- autonomy (7)
- bias (7)
- binaries: eclipsing (7)
- biogenic amines (7)
- birth weight (7)
- business processes (7)
- bystander (7)
- calibration (7)
- catalogs (7)
- charge generation (7)
- children and adolescents (7)
- circadian clock (7)
- circulation (7)
- circumstellar matter (7)
- cities (7)
- climate-change mitigation (7)
- cluster expansion (7)
- coastal erosion (7)
- cognitive development (7)
- coherence (7)
- colonialism (7)
- community ecology (7)
- competence (7)
- complexes (7)
- computer games (7)
- conversation analysis (7)
- corruption (7)
- cyber aggression (7)
- data (7)
- databases (7)
- defense (7)
- density (7)
- depressive symptoms (7)
- developmental dyscalculia (7)
- dietary patterns (7)
- digitale Medien (7)
- discrepancy principle (7)
- distribution (7)
- duplicate detection (7)
- dust (7)
- ecological modelling (7)
- ecosystem functioning (7)
- effectiveness (7)
- ensemble Kalman filter (7)
- enzyme (7)
- enzyme catalysis (7)
- ethics (7)
- ethnicity (7)
- eutrophication (7)
- exercise therapy (7)
- extinction (7)
- extraction (7)
- extreme rainfall (7)
- fiction (7)
- films (7)
- first passage time (7)
- fiscal policy (7)
- flood (7)
- floodplain (7)
- flow (7)
- fluorescence correlation spectroscopy (7)
- food webs (7)
- function (7)
- functional magnetic resonance imaging (7)
- galaxies (7)
- galaxies: abundances (7)
- gene flow (7)
- giving-up density (7)
- global (7)
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- gravity (7)
- habitat (7)
- heart (7)
- heart rate variability (7)
- heat stress (7)
- heterogeneous catalysis (7)
- holocene (7)
- home range (7)
- human impact (7)
- hydrolysis (7)
- ideology (7)
- imaging spectroscopy (7)
- income (7)
- infrared: stars (7)
- institutions (7)
- insula (7)
- interoceptive awareness (7)
- isotopes (7)
- jumping (7)
- kardiologische Rehabilitation (7)
- kinematics (7)
- knowledge (7)
- land-use change (7)
- language contact (7)
- last glacial maximum (7)
- lipid metabolism (7)
- low-energy electrons (7)
- magnetism (7)
- meaning (7)
- mechanisms (7)
- media violence (7)
- memory retrieval (7)
- mental disorders (7)
- metaanalysis (7)
- metaphor (7)
- microbial ecology (7)
- minerals (7)
- mobility (7)
- music (7)
- myocardial infarction (7)
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- neu gelesen (7)
- neutron diffraction (7)
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- nitrogen deposition (7)
- nuclear envelope (7)
- nuclear lamina (7)
- nucleus (7)
- number (7)
- numerical simulations (7)
- openHPI (7)
- organic matter (7)
- organic photovoltaics (7)
- orthography (7)
- oscillations (7)
- pH (7)
- palaeoecology (7)
- paleoecology (7)
- pandemic (7)
- parafoveal processing (7)
- parameter estimation (7)
- pathogens (7)
- perceptual span (7)
- perturbation (7)
- phase transition (7)
- phase transitions (7)
- phonological awareness (7)
- photoelectron spectroscopy (7)
- planetary nebulae: general (7)
- planets and satellites: rings (7)
- plyometric training (7)
- pollution (7)
- polyelectrolytes (7)
- porous materials (7)
- predator-prey dynamics (7)
- pregnancy (7)
- presidential government (7)
- preview benefit (7)
- production (7)
- programming (7)
- pronoun resolution (7)
- propensity score matching (7)
- prosodic boundary cues (7)
- proteasome (7)
- protection (7)
- public sector (7)
- pulsars: general (7)
- quality assurance (7)
- racism (7)
- radiocarbon (7)
- reduction (7)
- repair (7)
- retinol (7)
- rheology (7)
- roughness (7)
- scale development (7)
- scattering (7)
- screening (7)
- secular trend (7)
- seismic hazard (7)
- self-concept (7)
- sensors (7)
- serotonin (7)
- shape-memory effect (7)
- sharing economy (7)
- silicon (7)
- size (7)
- soccer (7)
- social rejection (7)
- social support (7)
- socioeconomic status (7)
- software (7)
- software engineering (7)
- soil erosion (7)
- solar wind (7)
- sorption (7)
- spelling (7)
- stabile Isotope (7)
- standardization (7)
- stars: late-type (7)
- sunspots (7)
- support vector machine (7)
- surfactants (7)
- surveillance (7)
- tVNS (7)
- techniques: image processing (7)
- terrorism (7)
- thermoresponsiv (7)
- thermoresponsive polymers (7)
- tomato (7)
- tomography (7)
- trunk (7)
- ultrafast dynamics (7)
- ultrasound (7)
- uplift (7)
- vesicles (7)
- water management (7)
- weight loss (7)
- wh-in-situ (7)
- working memory capacity (7)
- world literature (7)
- Ästhetik (7)
- 3D (6)
- 3D visualization (6)
- AFM (6)
- Adhäsion (6)
- Ageing (6)
- Agency (6)
- Alaska (6)
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- Alps (6)
- Antibiotikaresistenz (6)
- Antikörper (6)
- Antwortmengenprogrammierung (6)
- Arsenolipids (6)
- Artificial Intelligence (6)
- Autoritarismus (6)
- Bakterien (6)
- Bayesian data analysis (6)
- Berühren (6)
- Bewegung (6)
- Bewegungsökologie (6)
- Bioelectrocatalysis (6)
- Biogenic amine (6)
- Blockcopolymer (6)
- Briefe (6)
- C-reactive protein (6)
- CO2 (6)
- Cardiovascular diseases (6)
- Centrosom (6)
- Chytridiomycota (6)
- Click chemistry (6)
- Clusteranalyse (6)
- Complexity (6)
- Computational modelling (6)
- Computerspiele (6)
- Copper (6)
- Cystic fibrosis (6)
- Data assimilation (6)
- Deep learning (6)
- Dielektrophorese (6)
- Diskriminierung (6)
- Diskurs (6)
- Dynamic NMR (6)
- Dynamik (6)
- EEG/ERP (6)
- Earthquake dynamics (6)
- Earthquake hazards (6)
- Electrical conductivity (6)
- Ellenberg indicator values (6)
- Emotions (6)
- Energy (6)
- Entzündung (6)
- Erinnerung (6)
- Ethik (6)
- European hare (6)
- Fachdidaktik Latein (6)
- Fachwissen (6)
- Flood risk (6)
- Fluorescence spectroscopy (6)
- Forschendes Lernen (6)
- Föderalismus (6)
- Gammastrahlungsastronomie (6)
- Gene-environment interaction (6)
- Genomics (6)
- Geomorphology (6)
- Geschmack (6)
- H II regions (6)
- HIREC (6)
- Hebrew (6)
- Humboldtian Science (6)
- Hypertension (6)
- ISM: kinematics and dynamics (6)
- Indien (6)
- Induced seismicity (6)
- Informatik (6)
- Instructional quality (6)
- Insulin (6)
- Insurance (6)
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- Kalter Krieg (6)
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- Landnutzung (6)
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- Late Quaternary (6)
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- Ludwig Leichhardt (6)
- Lysiphlebus fabarum (6)
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- Mannheimer Risikokinderstudie (6)
- Maschinen- und Anlagenbau (6)
- Menderes Massif (6)
- Mental arithmetic (6)
- Mental disorders (6)
- Mental health (6)
- Meta-analysis (6)
- Methane (6)
- Microarray (6)
- Microcystis aeruginosa (6)
- Mikrofluidik (6)
- Mitochondrien (6)
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- Mongolia (6)
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- NAFLD (6)
- NASH (6)
- NCA (6)
- Nanostruktur (6)
- Navier-Stokes equations (6)
- Neural networks (6)
- Neuroenhancement (6)
- Neurotoxicity (6)
- Norway (6)
- Onlinekurs (6)
- Ontologie (6)
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- gene regulation (5)
- geovisualization (5)
- giftedness (5)
- glacier (5)
- globular clusters: general (5)
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- 1800 (3)
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- transmission (3)
- transthyretin (3)
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Institute
- Institut für Biochemie und Biologie (5440)
- Institut für Physik und Astronomie (5322)
- Institut für Geowissenschaften (3641)
- Institut für Chemie (3406)
- Wirtschaftswissenschaften (2487)
- Department Psychologie (2223)
- Historisches Institut (2079)
- Sozialwissenschaften (1838)
- Institut für Mathematik (1821)
- Institut für Romanistik (1762)
Risk-based insurance is a commonly proposed and discussed flood risk adaptation mechanism in policy debates across the world such as in the United Kingdom and the United States of America. However, both risk-based premiums and growing risk pose increasing difficulties for insurance to remain affordable. An empirical concept of affordability is required as the affordability of adaption strategies is an important concern for policymakers, yet such a concept is not often examined. Therefore, a robust metric with a commonly acceptable affordability threshold is required. A robust metric allows for a previously normative concept to be quantified in monetary terms, and in this way, the metric is rendered more suitable for integration into public policy debates. This paper investigates the degree to which risk-based flood insurance premiums are unaffordable in Europe. In addition, this paper compares the outcomes generated by three different definitions of unaffordability in order to investigate the most robust definition. In doing so, the residual income definition was found to be the least sensitive to changes in the threshold. While this paper focuses on Europe, the selected definition can be employed elsewhere in the world and across adaption measures in order to develop a common metric for indicating the potential unaffordability problem.
Increasing demand for analytical processing capabilities can be managed by replication approaches. However, to evenly balance the replicas' workload shares while at the same time minimizing the data replication factor is a highly challenging allocation problem. As optimal solutions are only applicable for small problem instances, effective heuristics are indispensable. In this paper, we test and compare state-of-the-art allocation algorithms for partial replication. By visualizing and exploring their (heuristic) solutions for different benchmark workloads, we are able to derive structural insights and to detect an algorithm's strengths as well as its potential for improvement. Further, our application enables end-to-end evaluations of different allocations to verify their theoretical performance.
The possibilities and limits of structure refinement of Langmuir-Blodgett films by means of symmetrical reflection of X- rays are described using the example of a stearic acid multilayer. Three different techniques for the determiantion of the electron density profile from reflectivity data are compared; a Fourier method, a Patterson method, and model calculations. The important role of the a priori information for finding the besft structure model is outlined.
A comparative whole-genome approach identifies bacterial traits for marine microbial interactions
(2022)
Luca Zoccarato, Daniel Sher et al. leverage publicly available bacterial genomes from marine and other environments to examine traits underlying microbial interactions.
Their results provide a valuable resource to investigate clusters of functional and linked traits to better understand marine bacteria community assembly and dynamics.
Microbial interactions shape the structure and function of microbial communities with profound consequences for biogeochemical cycles and ecosystem health. Yet, most interaction mechanisms are studied only in model systems and their prevalence is unknown. To systematically explore the functional and interaction potential of sequenced marine bacteria, we developed a trait-based approach, and applied it to 473 complete genomes (248 genera), representing a substantial fraction of marine microbial communities.
We identified genome functional clusters (GFCs) which group bacterial taxa with common ecology and life history. Most GFCs revealed unique combinations of interaction traits, including the production of siderophores (10% of genomes), phytohormones (3-8%) and different B vitamins (57-70%). Specific GFCs, comprising Alpha- and Gammaproteobacteria, displayed more interaction traits than expected by chance, and are thus predicted to preferentially interact synergistically and/or antagonistically with bacteria and phytoplankton. Linked trait clusters (LTCs) identify traits that may have evolved to act together (e.g., secretion systems, nitrogen metabolism regulation and B vitamin transporters), providing testable hypotheses for complex mechanisms of microbial interactions.
Our approach translates multidimensional genomic information into an atlas of marine bacteria and their putative functions, relevant for understanding the fundamental rules that govern community assembly and dynamics.
A successful assignment for the fundamental bands observed in the experimental IR spectra of mn-12S(2)O(2) and fn-12S(2)O(2) dithiacrown ethers was achieved by the aid of the density functional theory (DFT) based quantum mechanical calculations carried out at the 133LYP/6-31G(d) and B3LYP/6-31 + G(d) level of theory. Two different scaling approaches, '(i) scaled quantum mechanics force field (SQM FF) methodology', and (ii) the 'scaling frequencies with dual empirical scale factors', were used in order to fit the calculated harmonic frequencies to the experimental ones. Potential energy distribution (PED) calculations were carried out to define the internal coordinate contributions to each normal mode and to define the corresponding normal modes of the molecules. The effects of the conformational differences onto the IR active normal modes of the two isomeric molecules and their corresponding experimental frequencies were discussed in the light of the calculated spectral data.
Flooding is assessed as the most important natural hazard in Europe, causing thousands of deaths, affecting millions of people and accounting for large economic losses in the past decade. Little is known about the damage processes associated with extreme rainfall in cities, due to a lack of accurate, comparable and consistent damage data. The objective of this study is to investigate the impacts of extreme rainfall on residential buildings and how affected households coped with these impacts in terms of precautionary and emergency actions. Analyses are based on a unique dataset of damage characteristics and a wide range of potential damage explaining variables at the household level, collected through computer-aided telephone interviews (CATI) and an online survey. Exploratory data analyses based on a total of 859 completed questionnaires in the cities of Munster (Germany) and Amsterdam (the Netherlands) revealed that the uptake of emergency measures is related to characteristics of the hazardous event. In case of high water levels, more efforts are made to reduce damage, while emergency response that aims to prevent damage is less likely to be effective. The difference in magnitude of the events in Munster and Amsterdam, in terms of rainfall intensity and water depth, is probably also the most important cause for the differences between the cities in terms of the suffered financial losses. Factors that significantly contributed to damage in at least one of the case studies are water contamination, the presence of a basement in the building and people's awareness of the upcoming event. Moreover, this study confirms conclusions by previous studies that people's experience with damaging events positively correlates with precautionary behaviour. For improving future damage data acquisition, we recommend the inclusion of cell phones in a CATI survey to avoid biased sampling towards certain age groups.
In this paper two groups supporting different views on the mechanism of light induced polymer deformation argue about the respective underlying theoretical conceptions, in order to bring this interesting debate to the attention of the scientific community. The group of Prof. Nicolae Hurduc supports the model claiming that the cyclic isomerization of azobenzenes may cause an athermal transition of the glassy azobenzene containing polymer into a fluid state, the so-called photo-fluidization concept. This concept is quite convenient for an intuitive understanding of the deformation process as an anisotropic flow of the polymer material. The group of Prof. Svetlana Santer supports the re-orientational model where the mass-transport of the polymer material accomplished during polymer deformation is stated to be generated by the light-induced re-orientation of the azobenzene side chains and as a consequence of the polymer backbone that in turn results in local mechanical stress, which is enough to irreversibly deform an azobenzene containing material even in the glassy state. For the debate we chose three polymers differing in the glass transition temperature, 32 °C, 87 °C and 95 °C, representing extreme cases of flexible and rigid materials. Polymer film deformation occurring during irradiation with different interference patterns is recorded using a homemade set-up combining an optical part for the generation of interference patterns and an atomic force microscope for acquiring the kinetics of film deformation. We also demonstrated the unique behaviour of azobenzene containing polymeric films to switch the topography in situ and reversibly by changing the irradiation conditions. We discuss the results of reversible deformation of three polymers induced by irradiation with intensity (IIP) and polarization (PIP) interference patterns, and the light of homogeneous intensity in terms of two approaches: the re-orientational and the photo-fluidization concepts. Both agree in that the formation of opto-mechanically induced stresses is a necessary prerequisite for the process of deformation. Using this argument, the deformation process can be characterized either as a flow or mass transport.
In this paper two groups supporting different views on the mechanism of light induced polymer deformation argue about the respective underlying theoretical conceptions, in order to bring this interesting debate to the attention of the scientific community. The group of Prof. Nicolae Hurduc supports the model claiming that the cyclic isomerization of azobenzenes may cause an athermal transition of the glassy azobenzene containing polymer into a fluid state, the so-called photo-fluidization concept. This concept is quite convenient for an intuitive understanding of the deformation process as an anisotropic flow of the polymer material. The group of Prof. Svetlana Santer supports the re-orientational model where the mass-transport of the polymer material accomplished during polymer deformation is stated to be generated by the light-induced re-orientation of the azobenzene side chains and as a consequence of the polymer backbone that in turn results in local mechanical stress, which is enough to irreversibly deform an azobenzene containing material even in the glassy state. For the debate we chose three polymers differing in the glass transition temperature, 32 degrees C, 87 degrees C and 95 degrees C, representing extreme cases of flexible and rigid materials. Polymer film deformation occurring during irradiation with different interference patterns is recorded using a homemade set-up combining an optical part for the generation of interference patterns and an atomic force microscope for acquiring the kinetics of film deformation. We also demonstrated the unique behaviour of azobenzene containing polymeric films to switch the topography in situ and reversibly by changing the irradiation conditions. We discuss the results of reversible deformation of three polymers induced by irradiation with intensity (IIP) and polarization (PIP) interference patterns, and the light of homogeneous intensity in terms of two approaches: the re-orientational and the photo-fluidization concepts. Both agree in that the formation of opto-mechanically induced stresses is a necessary prerequisite for the process of deformation. Using this argument, the deformation process can be characterized either as a flow or mass transport.
The importance of cultural ecosystem services in agricultural landscapes is increasingly recognized as agricultural scale enlargement and abandonment affect aesthetic and recreational values of agricultural landscapes. Landscape preference studies addressing these type of values often yield context-specific outcomes, limiting the applicability of their outcomes in landscape policy. Our approach measures the relative importance of landscape features across agricultural landscapes. This approach was applied in the agricultural landscapes of Winterswijk, The Netherlands (n=191) and the Markische Schweiz, Germany (n=113) among visitors in the agricultural landscape. We set up a parallel designed choice experiment, using regionally specific, photorealistic visualizations of four comparable landscape attributes. In the Dutch landscape visitors highly value hedgerows and tree lines, whereas groups of trees and crop diversity are highly valued in the German landscape. Furthermore, we find that differences in relative preference for landscape attributes are, to some extent, explained by socio-cultural background variables such as education level and affinity with agriculture of the visitors. This approach contributes to a better understanding of the cross-regional variation of aesthetic and recreational values and how these values relate to characteristics of the agricultural landscape, which could support the integration of cultural services in landscape policy. (C) 2015 Elsevier B.V. All rights reserved.
In this paper, we analyse the effectiveness of flood management measures based on the concept known as "retaining water in the landscape". The investigated measures include afforestation, micro-ponds and small-reservoirs. A comparative and model-based methodological approach has been developed and applied for three meso-scale catchments located in different European hydro-climatological regions: Poyo (184 km(2)) in the Spanish Mediterranean, Upper Iller (954 km(2)) in the German Alps and Kamp (621 km(2)) in Northeast-Austria representing the Continental hydro-climate. This comparative analysis has found general similarities in spite of the particular differences among studied areas. In general terms, the flood reduction through the concept of "retaining water in the landscape" depends on the following factors: the storage capacity increase in the catchment resulting from such measures, the characteristics of the rainfall event, the antecedent soil moisture condition and the spatial distribution of such flood management measures in the catchment. In general, our study has shown that, this concept is effective for small and medium events, but almost negligible for the largest and less frequent floods: this holds true for all different hydro-climatic regions, and with different land-use, soils and morphological settings.
Genomic prediction has revolutionized crop breeding despite remaining issues of transferability of models to unseen environmental conditions and environments. Usage of endophenotypes rather than genomic markers leads to the possibility of building phenomic prediction models that can account, in part, for this challenge. Here, we compare and contrast genomic prediction and phenomic prediction models for 3 growth-related traits, namely, leaf count, tree height, and trunk diameter, from 2 coffee 3-way hybrid populations exposed to a series of treatment-inducing environmental conditions. The models are based on 7 different statistical methods built with genomic markers and ChlF data used as predictors. This comparative analysis demonstrates that the best-performing phenomic prediction models show higher predictability than the best genomic prediction models for the considered traits and environments in the vast majority of comparisons within 3-way hybrid populations. In addition, we show that phenomic prediction models are transferrable between conditions but to a lower extent between populations and we conclude that chlorophyll a fluorescence data can serve as alternative predictors in statistical models of coffee hybrid performance. Future directions will explore their combination with other endophenotypes to further improve the prediction of growth-related traits for crops.
Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.
Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.
Objective Pre-eclampsia is a serious complication of pregnancy with high morbidity and mortality and an incidence of 3-5% in all pregnancies. Early prediction is still insufficient in clinical practice. Although most pre- eclamptic patients have pathological uterine perfusion in the second trimester, perfusion disturbance has a positive predictive accuracy (PPA) only of approximately 30%. Methods Non-invasive continuous blood pressure recordings were taken simultaneously via a finger cuff for 30 min. Time series of systolic as well as diastolic beat-to-beat pressure values were extracted to analyse heart rate and blood pressure variability and baroreflex sensitivity in 102 second- trimester pregnancies, to assess predictability for pre-eclampsia (n = 16). All women underwent Doppler investigations of the uterine arteries. Results We identified a combination of three variability and baroreflex parameters to best predict pre-eclampsia several weeks before clinical manifestation. The discriminant function of these three parameters classified patients with later pre-eclampsia with a sensitivity of 87.5%, a specificity of 83.7%, and a PPA of 50.0%. Combined with Doppler investigations of uterine arteries, PPA increased to 71.4%. Conclusions This technique of incorporating one-stop clinical assessment of uterine perfusion and variability parameters in the second trimester produces the most effective prediction of pre-eclampsia to date
X-ray photoelectron spectroscopy (XPS) is a powerful tool for probing the local chemical environment of atoms near surfaces. When applied to soft matter, such as polymers, XPS spectra are frequently shifted and broadened due to thermal atom motion and by interchain interactions. We present a combined quantum mechanical QM/molecular dynamics (MD) simulation of X-ray photoelectron spectra of polyvinyl alcohol (PVA) using oligomer models in order to account for and quantify these effects on the XPS (C1s) signal. In our study, molecular dynamics at finite temperature were performed with a classical forcefield and by ab initio MD (AIMD) using the Car-Parrinello method. Snapshots along, the trajectories represent possible conformers and/or neighbouring environments, with different C1s ionization potentials for individual C atoms leading to broadened XPS peaks. The latter are determined by Delta-Kohn Sham calculations. We also examine the experimental practice of gauging XPS (C1s) signals of alkylic C-atoms in C-containing polymers to the C1s signal of polyethylene.
We find that (i) the experimental XPS (C1s) spectra of PVA (position and width) can be roughly represented by single-strand models, (ii) interchain interactions lead to red-shifts of the XPS peaks by about 0.6 eV, and (iii) AIMD simulations match the findings from classical MD semi-quantitatively. Further, (iv) the gauging procedure of XPS (C1s) signals to the values of PE, introduces errors of about 0.5 eV. (C) 2014 Elsevier B.V. All rights reserved.
Diatom diversity in lakes of northwest Yakutia (Siberia) was investigated by microscopic and genetic analysis of surface and cored lake sediments, to evaluate the use of sedimentary DNA for paleolimnological diatom studies and to identify obscure genetic diversity that cannot be detected by microscopic methods. Two short (76 and 73 bp) and one longer (577 bp) fragments of the ribulose 1,5-bisphosphate carboxylase/oxygenase (rbcL) gene, encoding the large subunit of the rbcL, were used as genetic markers. Diverse morphological assemblages of diatoms, dominated by small benthic fragilarioid taxa, were retrieved from the sediments of each lake. These minute fragilarioid taxa were examined by scanning electron microscopy, revealing diverse morphotypes in Staurosira and Staurosirella from the different lakes. Genetic analyses indicated a dominance of haplotypes that were assigned to fragilarioid taxa and less genetic diversity in other diatom taxa. The long rbcL_577 amplicon identified considerable diversification among haplotypes clustering within the Staurosira/Staurosirella genera, revealing 19 different haplotypes whose spatial distribution appears to be primarily related to the latitude of the lakes, which corresponds to a vegetation and climate gradient. Our rbcL markers are valuable tools for tracking differences between diatom lineages that are not visible in their morphologies. These markers revealed putatively high genetic diversity within the Staurosira/Staurosirella species complex, at a finer scale than is possible to resolve by microscopic determination. The rbcL markers may provide additional reliable information on the diversity of barely distinguishable minute benthic fragilarioids. Environmental sequencing may thus allow the tracking of spatial and temporal diversification in Siberian lakes, especially in the context of diatom responses to recent environmental changes, which remains a matter of controversy.
We present new radio/millimeter measurements of the hot magnetic star HR5907 obtained with the VLA and ALMA interferometers. We find that HR5907 is the most radio luminous early type star in the cm-mm band among those presently known. Its multi-wavelength radio light curves are strongly variable with an amplitude that increases with radio frequency. The radio emission can be explained by the populations of the non-thermal electrons accelerated in the current sheets on the outer border of the magnetosphere of this fast-rotating magnetic star. We classify HR5907 as another member of the growing class of strongly magnetic fast-rotating hot stars where the gyro-synchrotron emission mechanism efficiently operates in their magnetospheres. The new radio observations of HR5907 are combined with archival X-ray data to study the physical condition of its magnetosphere. The X-ray spectra of HR5907 show tentative evidence for the presence of non-thermal spectral component. We suggest that non-thermal X-rays originate a stellar X-ray aurora due to streams of non-thermal electrons impacting on the stellar surface. Taking advantage of the relation between the spectral indices of the X-ray power-law spectrum and the non-thermal electron energy distributions, we perform 3-D modelling of the radio emission for HR5907. The wavelength-dependent radio light curves probe magnetospheric layers at different heights above the stellar surface. A detailed comparison between simulated and observed radio light curves leads us to conclude that the stellar magnetic field of HR 5907 is likely non-dipolar, providing further indirect evidence of the complex magnetic field topology of HR5907.
Next-generation sequencing methods provide comprehensive data for the analysis of structural and functional analysis of the genome. The draft genomes with low contig number and high N50 value can give insight into the structure of the genome as well as provide information on the annotation of the genome. In this study, we designed a pipeline that can be used to assemble prokaryotic draft genomes with low number of contigs and high N50 value. We aimed to use combination of two de novo assembly tools (SPAdes and IDBA-Hybrid) and evaluate the impact of this approach on the quality metrics of the assemblies. The followed pipeline was tested with the raw sequence data with short reads (< 300) for a total of 10 species from four different genera. To obtain the final draft genomes, we firstly assembled the sequences using SPAdes to find closely related organism using the extracted 16 s rRNA from it. IDBA-Hybrid assembler was used to obtain the second assembly data using the closely related organism genome. SPAdes assembler tool was implemented using the second assembly, produced by IDBA-hybrid as a hint. The results were evaluated using QUAST and BUSCO. The pipeline was successful for the reduction of the contig numbers and increasing the N50 statistical values in the draft genome assemblies while preserving the coverage of the draft genomes.
The aim of this doctoral thesis was to establish a technique for the analysis of biomolecules with infrared matrix-assisted laser dispersion (IR-MALDI) ion mobility (IM) spectrometry. The main components of the work were the characterization of the IR-MALDI process, the development and characterization of different ion mobility spectrometers, the use of IR-MALDI-IM spectrometry as a robust, standalone spectrometer and the development of a collision cross-section estimation approach for peptides based on molecular dynamics and thermodynamic reweighting.
First, the IR-MALDI source was studied with atmospheric pressure ion mobility spectrometry and shadowgraphy. It consisted of a metal capillary, at the tip of which a self-renewing droplet of analyte solution was met by an IR laser beam. A relationship between peak shape, ion desolvation, diffusion and extraction pulse delay time (pulse delay) was established. First order desolvation kinetics were observed and related to peak broadening by diffusion, both influenced by the pulse delay. The transport mechanisms in IR-MALDI were then studied by relating different laser impact positions on the droplet surface to the corresponding ion mobility spectra. Two different transport mechanisms were determined: phase explosion due to the laser pulse and electrical transport due to delayed ion extraction. The velocity of the ions stemming from the phase explosion was then measured by ion mobility and shadowgraphy at different time scales and distances from the source capillary, showing an initially very high but rapidly decaying velocity. Finally, the anatomy of the dispersion plume was observed in detail with shadowgraphy and general conclusions over the process were drawn.
Understanding the IR-MALDI process enabled the optimization of the different IM spectrometers at atmospheric and reduced pressure (AP and RP, respectively). At reduced pressure, both an AP and an RP IR-MALDI source were used. The influence of the pulsed ion extraction parameters (pulse delay, width and amplitude) on peak shape, resolution and area was systematically studied in both AP and RP IM spectrometers and discussed in the context of the IR-MALDI process. Under RP conditions, the influence of the closing field and of the pressure was also examined for both AP and RP sources. For the AP ionization RP IM spectrometer, the influence of the inlet field (IF) in the source region was also examined. All of these studies led to the determination of the optimal analytical parameters as well as to a better understanding of the initial ion cloud anatomy.
The analytical performance of the spectrometer was then studied. Limits of detection (LOD) and linear ranges were determined under static and pulsed ion injection conditions and interpreted in the context of the IR-MALDI mechanism. Applications in the separation of simple mixtures were also illustrated, demonstrating good isomer separation capabilities and the advantages of singly charged peaks. The possibility to couple high performance liquid chromatography (HPLC) to IR-MALDI-IM spectrometry was also demonstrated. Finally, the reduced pressure spectrometer was used to study the effect of high reduced field strength on the mobility of polyatomic ions in polyatomic gases.
The last focus point was on the study of peptide ions. A dataset obtained with electrospray IM spectrometry was characterized and used for the calibration of a collision cross-section (CCS) determination method based on molecular dynamics (MD) simulations at high temperature. Instead of producing candidate structures which are evaluated one by one, this semi-automated method uses the simulation as a whole to determine a single average collision cross-section value by reweighting the CCS of a few representative structures. The method was compared to the intrinsic size parameter (ISP) method and to experimental results. Additional MD data obtained from the simulations was also used to further analyze the peptides and understand the experimental results, an advantage with regard to the ISP method. Finally, the CCS of peptide ions analyzed by IR-MALDI were also evaluated with both ISP and MD methods and the results compared to experiment, resulting in a first validation of the MD method. Thus, this thesis brings together the soft ionization technique that is IR-MALDI, which produces mostly singly charged peaks, with ion mobility spectrometry, which can distinguish between isomers, and a collision cross-section determination method which also provides structural information on the analyte at hand.
To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the out-cross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes.
The present study approaches the Spanish postposed constructions creo Ø and creo yo ‘[p], [I] think’ from a cognitive-constructionist perspective. It is argued that both constructions are to be distinguished from one another because creo Ø has a subjective function, while in creo yo, it is the intersubjective dimension that is particularly prominent. The present investigation takes both a qualitative and a quantitative perspective. With regard to the latter, the problem of quantitative representativity is addressed. The discussion posed the question of how empirical research can feed back into theory, more precisely, into the framework of Cognitive Construction Grammar. The data to be analyzed here are retrieved from the corpora Corpus de Referencia del Español Actual and Corpus del Español.
The origin of Galactic cosmic rays is a century-long puzzle. Indirect evidence points to their acceleration by supernova shockwaves, but we know little of their escape from the shock and their evolution through the turbulent medium surrounding massive stars. Gamma rays can probe their spreading through the ambient gas and radiation fields. The Fermi Large Area Telescope (LAT) has observed the star-forming region of Cygnus X. The 1- to 100-gigaelectronvolt images reveal a 50-parsec-wide cocoon of freshly accelerated cosmic rays that flood the cavities carved by the stellar winds and ionization fronts from young stellar clusters. It provides an example to study the youth of cosmic rays in a superbubble environment before they merge into the older Galactic population.
A close call
(2018)
The present study investigated how lexical selection is influenced by the number of semantically related representations (semantic neighbourhood density) and their similarity (semantic distance) to the target in a speeded picture-naming task. Semantic neighbourhood density and similarity as continuous variables were used to assess lexical selection for which competitive and noncompetitive mechanisms have been proposed. Previous studies found mixed effects of semantic neighbourhood variables, leaving this issue unresolved. Here, we demonstrate interference of semantic neighbourhood similarity with less accurate naming responses and a higher likelihood of producing semantic errors and omissions over accurate responses for words with semantically more similar (closer) neighbours. No main effect of semantic neighbourhood density and no interaction between semantic neighbourhood density and similarity was found. We assessed further whether semantic neighbourhood density can affect naming performance if semantic neighbours exceed a certain degree of semantic similarity. Semantic similarity between the target and each neighbour was used to split semantic neighbourhood density into two different density variables: The number of semantically close neighbours versus distant neighbours. The results showed a significant effect of close, but not of distant, semantic neighbourhood density: Naming pictures of targets with more close semantic neighbours led to longer naming latencies, less accurate responses, and a higher likelihood for the production of semantic errors and omissions over accurate responses. The results show that word inherent semantic attributes such as semantic neighbourhood similarity and the number of coactivated close semantic neighbours modulate lexical selection supporting theories of competitive lexical processing.
In recent years, there has been a large amount of disparate work concerning the representation and reasoning with qualitative preferential information by means of approaches to nonmonotonic reasoning. Given the variety of underlying systems, assumptions, motivations, and intuitions, it is difficult to compare or relate one approach with another. Here, we present an overview and classification for approaches to dealing with preference. A set of criteria for classifying approaches is given, followed by a set of desiderata that an approach might be expected to satisfy. A comprehensive set of approaches is subsequently given and classified with respect to these sets of underlying principles
A circulatory loop
(2023)
In the digitalization debate, gender biases in digital technologies play a significant role because of their potential for social exclusion and inequality. It is therefore remarkable that organizations as drivers of digitalization and as places for social integration have been widely overlooked so far. Simultaneously, gender biases and digitalization have structurally immanent connections to organizations. Therefore, a look at the reciprocal relationship between organizations, digitalization, and gender is needed. The article provides answers to the question of whether and how organizations (re)produce, reinforce, or diminish gender‐specific inequalities during their digital transformations. On the one hand, gender inequalities emerge when organizations use post‐bureaucratic concepts through digitalization. On the other hand, gender inequalities are reproduced when organizations either program or implement digital technologies and fail to establish control structures that prevent gender biases. This article shows that digitalization can act as a catalyst for inequality‐producing mechanisms, but also has the potential to mitigate inequalities. We argue that organizations must be considered when discussing the potential of exclusion through digitalization.
Current assessment of visual neglect involves paper-and-pencil tests or computer-based tasks. Both have been criticised because of their lack of ecological validity as target stimuli can only be presented in a restricted visual range. This study examined the user-friendliness and diagnostic strength of a new "Circle-Monitor" (CM), which enlarges the range of the peripersonal space, in comparison to a standard paper-and-pencil test (Neglect-Test, NET).
Methods: Ten stroke patients with neglect and ten age-matched healthy controls were examined by the NET and the CM test comprising of four subtests (Star Cancellation, Line Bisection, Dice Task, and Puzzle Test).
Results: The acceptance of the CM in elderly controls and neglect patients was high. Participants rated the examination by CM as clear, safe and more enjoyable than NET. Healthy controls performed at ceiling on all subtests, without any systematic differences between the visual fields. Both NET and CM revealed significant differences between controls and patients in Line Bisection, Star Cancellation and visuo-constructive tasks (NET: Figure Copying, CM: Puzzle Test). Discriminant analyses revealed cross-validated assignment of patients and controls to groups was more precise when based on the CM (hit rate 90%) as compared to the NET (hit rate 70%).
Conclusion: The CM proved to be a sensitive novel tool to diagnose visual neglect symptoms quickly and accurately with superior diagnostic validity compared to a standard neglect test while being well accepted by patients. Due to its upgradable functions the system may also be a valuable tool not only to test for non-visual neglect symptoms, but also to provide treatment and assess its outcome.
Incorporation of noncanonical amino acids (ncAAs) with bioorthogonal reactive groups by amber suppression allows the generation of synthetic proteins with desired novel properties. Such modified molecules are in high demand for basic research and therapeutic applications such as cancer treatment and in vivo imaging. The positioning of the ncAA-responsive codon within the protein's coding sequence is critical in order to maintain protein function, achieve high yields of ncAA-containing protein, and allow effective conjugation. Cell-free ncAA incorporation is of particular interest due to the open nature of cell-free systems and their concurrent ease of manipulation. In this study, we report a straightforward workflow to inquire ncAA positions in regard to incorporation efficiency and protein functionality in a Chinese hamster ovary (CHO) cell-free system. As a model, the well-established orthogonal translation components Escherichia coli tyrosyl-tRNA synthetase (TyrRS) and tRNATyr(CUA) were used to site-specifically incorporate the ncAA p-azido-l-phenylalanine (AzF) in response to UAG codons. A total of seven ncAA sites within an anti-epidermal growth factor receptor (EGFR) single-chain variable fragment (scFv) N-terminally fused to the red fluorescent protein mRFP1 and C-terminally fused to the green fluorescent protein sfGFP were investigated for ncAA incorporation efficiency and impact on antigen binding. The characterized cell-free dual fluorescence reporter system allows screening for ncAA incorporation sites with high incorporation efficiency that maintain protein activity. It is parallelizable, scalable, and easy to operate. We propose that the established CHO-based cell-free dual fluorescence reporter system can be of particular interest for the development of antibody-drug conjugates (ADCs).
This study investigates the characteristics of narrative-speech production and the use of verbs in Turkish agrammatic speakers (n = 10) compared to non-brain-damaged controls (n = 10). To elicit narrative-speech samples, personal interviews and storytelling tasks were conducted. Turkish has a large and regular verb inflection paradigm where verbs are inflected for evidentiality (i.e. direct versus indirect evidence available to the speaker). Particularly, we explored the general characteristics of the speech samples (e.g. utterance length) and the uses of lexical, finite and non-finite verbs and direct and indirect evidentials. The results show that speech rate is slow, verbs per utterance are lower than normal and the verb diversity is reduced in the agrammatic speakers. Verb inflection is relatively intact; however, a trade-off pattern between inflection for direct evidentials and verb diversity is found. The implications of the data are discussed in connection with narrative-speech production studies on other languages.
Let v be a valuation of terms of type tau, assigning to each term t of type tau a value v(t) greater than or equal to 0. Let k greater than or equal to 1 be a natural number. An identity s approximate to t of type tau is called k- normal if either s = t or both s and t have value greater than or equal to k, and otherwise is called non-k-normal. A variety V of type tau is said to be k-normal if all its identities are k-normal, and non-k-normal otherwise. In the latter case, there is a unique smallest k-normal variety N-k(A) (V) to contain V , called the k-normalization of V. Inthe case k = 1, for the usual depth valuation of terms, these notions coincide with the well-known concepts of normal identity, normal variety, and normalization of a variety. I. Chajda has characterized the normalization of a variety by means of choice algebras. In this paper we generalize his results to a characterization of the k-normalization of a variety, using k-choice algebras. We also introduce the concept of a k-inflation algebra, and for the case that v is the usual depth valuation of terms, we prove that a variety V is k-normal iff it is closed under the formation of k- inflations, and that the k-normalization of V consists precisely of all homomorphic images of k-inflations of algebras in V
To asymptotic complete scattering systems {M(+) + V, M(+)} on H(+) := L(2)(R(+), K, d lambda), where M(+) is the multiplication operator on H(+) and V is a trace class operator with analyticity conditions, a decay semigroup is associated such that the spectrum of the generator of this semigroup coincides with the set of all resonances (poles of the analytic continuation of the scattering matrix into the lower half plane across the positive half line), i.e. the decay semigroup yields a "time-dependent" characterization of the resonances. As a counterpart a "spectral characterization" is mentioned which is due to the "eigenvalue-like" properties of resonances.
Channel transmission losses in drylands take place normally in extensive alluvial channels or streambeds underlain by fractured rocks. They can play an important role in streamflow rates, groundwater recharge, freshwater supply and channel-associated ecosystems. We aim to develop a process-oriented, semi-distributed channel transmission losses model, using process formulations which are suitable for data-scarce dryland environments and applicable to both hydraulically disconnected losing streams and hydraulically connected losing(/gaining) streams. This approach should be able to cover a large variation in climate and hydro-geologic controls, which are typically found in dryland regions of the Earth. Our model was first evaluated for a losing/gaining, hydraulically connected 30 km reach of the Middle Jaguaribe River (MJR), Ceara, Brazil, which drains a catchment area of 20 000 km(2). Secondly, we applied it to a small losing, hydraulically disconnected 1.5 km channel reach in the Walnut Gulch Experimental Watershed (WGEW), Arizona, USA. The model was able to predict reliably the streamflow volume and peak for both case studies without using any parameter calibration procedure. We have shown that the evaluation of the hypotheses on the dominant hydrological processes was fundamental for reducing structural model uncertainties and improving the streamflow prediction. For instance, in the case of the large river reach (MJR), it was shown that both lateral stream-aquifer water fluxes and groundwater flow in the underlying alluvium parallel to the river course are necessary to predict streamflow volume and channel transmission losses, the former process being more relevant than the latter. Regarding model uncertainty, it was shown that the approaches, which were applied for the unsaturated zone processes (highly nonlinear with elaborate numerical solutions), are much more sensitive to parameter variability than those approaches which were used for the saturated zone (mathematically simple water budgeting in aquifer columns, including backwater effects). In case of the MJR-application, we have seen that structural uncertainties due to the limited knowledge of the subsurface saturated system interactions (i.e. groundwater coupling with channel water; possible groundwater flow parallel to the river) were more relevant than those related to the subsurface parameter variability. In case of the WEGW application we have seen that the non-linearity involved in the unsaturated flow processes in disconnected dryland river systems (controlled by the unsaturated zone) generally contain far more model uncertainties than do connected systems controlled by the saturated flow. Therefore, the degree of aridity of a dryland river may be an indicator of potential model uncertainty and subsequent attainable predictability of the system.
We present the results from Chandra X-ray observations, and near- and mid-infrared analysis, using VISTA/VVV and Spitzer/GLIMPSE catalogs, of the high-mass star-forming region IRAS 16562-3959, which contains a candidate for a high-mass protostar. We detected 249 X-ray sources within the ACIS-I field of view. The majority of the X-ray sources have low count rates (<0.638 cts/ks) and hard X-ray spectra. The search for YSOs in the region using VISTA/VVV and Spitzer/GLIMPSE catalogs resulted in a total of 636 YSOs, with 74 Class I and 562 Class II YSOs. The search for near- and mid-infrared counterparts of the X-ray sources led to a total of 165 VISTA/VVV counterparts, and a total of 151 Spitzer/GLIMPSE counterparts. The infrared analysis of the X-ray counterparts allowed us to identify an extra 91 Class III YSOs associated with the region. We conclude that a total of 727 YSOs are associated with the region, with 74 Class I, 562 Class II, and 91 Class III YSOs. We also found that the region is composed of 16 subclusters. In the vicinity of the high-mass protostar, the stellar distribution has a core-halo structure. The subcluster containing the high-mass protostar is the densest and the youngest in the region, and the high-mass protostar is located at its center. The YSOs in this cluster appear to be substantially older than the high-mass protostar.
A Cell-free Expression Pipeline for the Generation and Functional Characterization of Nanobodies
(2022)
Cell-free systems are well-established platforms for the rapid synthesis, screening, engineering and modification of all kinds of recombinant proteins ranging from membrane proteins to soluble proteins, enzymes and even toxins. Also within the antibody field the cell-free technology has gained considerable attention with respect to the clinical research pipeline including antibody discovery and production. Besides the classical full-length monoclonal antibodies (mAbs), so-called "nanobodies" (Nbs) have come into focus. A Nb is the smallest naturally-derived functional antibody fragment known and represents the variable domain (VHH, similar to 15 kDa) of a camelid heavy-chain-only antibody (HCAb). Based on their nanoscale and their special structure, Nbs display striking advantages concerning their production, but also their characteristics as binders, such as high stability, diversity, improved tissue penetration and reaching of cavity-like epitopes. The classical way to produce Nbs depends on the use of living cells as production host. Though cell-based production is well-established, it is still time-consuming, laborious and hardly amenable for high-throughput applications. Here, we present for the first time to our knowledge the synthesis of functional Nbs in a standardized mammalian cell-free system based on Chinese hamster ovary (CHO) cell lysates. Cell-free reactions were shown to be time-efficient and easy-to-handle allowing for the "on demand" synthesis of Nbs. Taken together, we complement available methods and demonstrate a promising new system for Nb selection and validation.
Oxidative stress causes dramatic changes in the expression levels of many genes. The formation of a functional protein through successful mRNA translation is central to a coordinated cellular response. To what extent the response towards reactive oxygen species (ROS) is regulated at the translational level is poorly understood. Here we analysed leaf- and tissue-specific translatomes using a set of transgenic Arabidopsis thaliana lines expressing a FLAG-tagged ribosomal protein to immunopurify polysome-bound mRNAs before and after oxidative stress. We determined transcript levels of 171 ROS-responsive genes upon paraquat treatment, which causes formation of superoxide radicals, at the whole-organ level. Furthermore, the translation of mRNAs was determined for five cell types: mesophyll, bundle sheath, phloem companion, epidermal and guard cells. Mesophyll and bundle sheath cells showed the strongest response to paraquat treatment. Interestingly, several ROS-responsive transcription factors displayed cell type-specific translation patterns, while others were translated in all cell types. In part, cell type-specific translation could be explained by the length of the 5-untranslated region (5-UTR) and the presence of upstream open reading frames (uORFs). Our analysis reveals insights into the translational regulation of ROS-responsive genes, which is important to understanding cell-specific responses and functions during oxidative stress.
The study illustrates the response of different Arabidopsis thaliana leaf cells and tissues to oxidative stress at the translational level, an aspect of reactive oxygen species (ROS) biology that has been little studied in the past. Our data reveal insights into how translational regulation of ROS-responsive genes is fine-tuned at the cellular level, a phenomenon contributing to the integrated physiological response of leaves to stresses involving changes in ROS levels.
Hydrocarbons can be found in many different habitats and represent an important carbon source for microbes. As fossil fuels, they are also an important economical resource and through natural seepage or accidental release they can be major pollutants. DNA-specific stains and molecular probes bind to hydrocarbons, causing massive background fluorescence, thereby hampering cell enumeration. The cell extraction procedure of Kallmeyer et al. (2008) separates the cells from the sediment matrix. In principle, this technique can also be used to separate cells from oily sediments, but it was not originally optimized for this application. Here we present a modified extraction method in which the hydrocarbons are removed prior to cell extraction. Due to the reduced background fluorescence the microscopic image becomes clearer, making cell identification, and enumeration much easier. Consequently, the resulting cell counts from oily samples treated according to our new protocol are significantly higher than those treated according to Kallmeyer et al. (2008). We tested different amounts of a variety of solvents for their ability to remove hydrocarbons and found that n-hexane and in samples containing more mature oils methanol, delivered the best results. However, as solvents also tend to lyse cells, it was important to find the optimum solvent to sample ratio, at which hydrocarbon extraction is maximized and cell lysis minimized. A volumetric ratio of 1:2-1:5 between a formalin-fixed sediment slurry and solvent delivered highest cell counts. Extraction efficiency was around 30-50% and was checked on both oily samples spiked with known amounts of E. coli cells and oil-free samples amended with fresh and biodegraded oil. The method provided reproducible results on samples containing very different kinds of oils with regard to their degree of biodegradation. For strongly biodegraded oil MeOH turned out to be the most appropriate solvent, whereas for less biodegraded samples n-hexane delivered best results.
We study the Cauchy problem for a nonlinear elliptic equation with data on a piece S of the boundary surface partial derivative X. By the Cauchy problem is meant any boundary value problem for an unknown function u in a domain X with the property that the data on S, if combined with the differential equations in X, allows one to determine all derivatives of u on S by means of functional equations. In the case of real analytic data of the Cauchy problem, the existence of a local solution near S is guaranteed by the Cauchy-Kovalevskaya theorem. We discuss a variational setting of the Cauchy problem which always possesses a generalized solution.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
A case of primary progressive ahasia : a 14year follow-up study with neuropathological findings
(1998)
With the advent of increasingly powerful computational architectures, scientists use these possibilities to create simulations of ever-increasing size and complexity. Large-scale simulations of environmental systems require huge amounts of resources. Managing these in an operational way becomes increasingly complex and difficult to handle for individual scientists. State-of-the-art simulation infrastructures usually provide the necessary re-sources in a centralised setup, which often results in an all-or-nothing choice for the user. Here, we outline an alternative approach to handling this complexity, while rendering the use of high-performance hardware and large datasets still possible. It retains a number of desirable properties: (i) a decentralised structure, (ii) easy sharing of resources to promote collaboration and (iii) secure access to everything, including natural delegation of authority across levels and system boundaries. We show that the object capability paradigm will cover these issues, and present the first steps towards developing a simulation infrastructure based on these principles.
We analyze the problem of response suggestion in a closed domain along a real-world scenario of a digital library. We present a text-processing pipeline to generate question-answer pairs from chat transcripts. On this limited amount of training data, we compare retrieval-based, conditioned-generation, and dedicated representation learning approaches for response suggestion. Our results show that retrieval-based methods that strive to find similar, known contexts are preferable over parametric approaches from the conditioned-generation family, when the training data is limited. We, however, identify a specific representation learning approach that is competitive to the retrieval-based approaches despite the training data limitation.
One of the fundamental challenges in anti-doping is identifying athletes who use, or are at risk of using, prohibited performance enhancing substances. The growing trend to employ a forensic approach to doping control aims to integrate information from social sciences (e.g., psychology of doping) into organised intelligence to protect clean sport. Beyond the foreseeable consequences of a positive identification as a doping user, this task is further complicated by the discrepancy between what constitutes a doping offence in the World Anti-Doping Code and operationalized in doping research. Whilst psychology plays an important role in developing our understanding of doping behaviour in order to inform intervention and prevention, its contribution to the array of doping diagnostic tools is still in its infancy. In both research and forensic settings, we must acknowledge that (1) socially desirable responding confounds self-reported psychometric test results and (2) that the cognitive complexity surrounding test performance means that the response-time based measures and the lie detector tests for revealing concealed life-events (e.g., doping use) are prone to produce false or non-interpretable outcomes in field settings. Differences in social-cognitive characteristics of doping behaviour that are tested at group level (doping users vs. non-users) cannot be extrapolated to individuals; nor these psychometric measures used for individual diagnostics. In this paper, we present a position statement calling for policy guidance on appropriate use of psychometric assessments in the pursuit of clean sport. We argue that, to date, both self-reported and response-time based psychometric tests for doping have been designed, tested and validated to explore how athletes feel and think about doping in order to develop a better understanding of doping behaviour, not to establish evidence for doping. A false 'positive' psychological profile for doping affects not only the individual 'clean' athlete but also their entourage, their organisation and sport itself. The proposed policy guidance aims to protect the global athletic community against social, ethical and legal consequences from potential misuse of psychological tests, including erroneous or incompetent applications as forensic diagnostic tools in both practice and research. (C) 2015 Elsevier B.V. All rights reserved.
Stochastically triggered photospheric light variations reaching similar to 40 mmag peak-to-valley amplitudes have been detected in the O8 Iaf supergiant V973 Scorpii as the outcome of 2 months of high-precision time-resolved photometric observations with the BRIght Target Explorer (BRITE) nanosatellites. The amplitude spectrum of the time series photometry exhibits a pronounced broad bump in the low-frequency regime (less than or similar to 0.9 d(-1)) where several prominent frequencies are detected. A time-frequency analysis of the observations reveals typical mode lifetimes of the order of 5-10 d. The overall features of the observed brightness amplitude spectrum of V973 Sco match well with those extrapolated from two-dimensional hydrodynamical simulations of convectively driven internal gravity waves randomly excited from deep in the convective cores of massive stars. An alternative or additional possible source of excitation from a sub-surface convection zone needs to be explored in future theoretical investigations.
Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
On 6 June 1982, Israel invaded Lebanon to fight the Palestinian Liberation Organization (PLO). Between August 1982 and February 1984, the US, France, Britain and Italy deployed a Multinational Force (MNF) to Beirut. Its task was to act as an interposition force to bolster the government and to bring peace to the people. The mission is often forgotten or merely remembered in context with the bombing of US Marines’ barracks. However, an analysis of the Italian contingent shows that the MNF was not doomed to fail and could accomplish its task when operational and diplomatic efforts were coordinated. The Italian commander in Beirut, General Franco Angioni, followed a successful approach that sustained neutrality, respectful behaviour and minimal force, which resulted in a qualified success of the Italian efforts.
On 6 June 1982, Israel invaded Lebanon to fight the Palestinian
Liberation Organization (PLO). Between August 1982 and February
1984, the US, France, Britain and Italy deployed a Multinational
Force (MNF) to Beirut. Its task was to act as an interposition force to
bolster the government and to bring peace to the people. The
mission is often forgotten or merely remembered in context with
the bombing of US Marines’ barracks. However, an analysis of the
Italian contingent shows that the MNF was not doomed to fail and
could accomplish its task when operational and diplomatic efforts
were coordinated. The Italian commander in Beirut, General Franco
Angioni, followed a successful approach that sustained neutrality,
respectful behaviour and minimal force, which resulted in a
qualified success of the Italian efforts.
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.
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.
A Biosensor for aromatic aldehydes comprising the mediator dependent PaoABC-Aldehyde oxidoreductase
(2013)
A novel aldehyde oxidoreductase (PaoABC) from Escherichia coli was utilized for the development of an oxygen insensitive biosensor for benzaldehyde. The enzyme was immobilized in polyvinyl alcohol and currents were measured for aldehyde oxidation with different one and two electron mediators with the highest sensitivity for benzaldehyde in the presence of hexacyanoferrate(III). The benzaldehyde biosensor was optimized with respect to mediator concentration, enzyme loading and pH using potassium hexacyanoferrate(III). The linear measuring range is between 0.5200 mu M benzaldehyde. In correspondence with the substrate selectivity of the enzyme in solution the biosensor revealed a preference for aromatic aldehydes and less effective conversion of aliphatic aldehydes. The biosensor is oxygen independent, which is a particularly attractive feature for application. The biosensor can be applied to detect contaminations with benzaldehyde in solvents such as benzyl alcohol, where traces of benzaldehyde in benzyl alcohol down to 0.0042?% can be detected.
"Left" and "right" coordinates control our spatial behavior and even influence abstract thoughts. For number concepts, horizontal spatial-numerical associations (SNAs) have been widely documented: we associate few with left and many with right. Importantly, increments are universally coded on the right side even in preverbal humans and nonhuman animals, thus questioning the fundamental role of directional cultural habits, such as reading or finger counting. Here, we propose a biological, nonnumerical mechanism for the origin of SNAs on the basis of asymmetric tuning of animal brains for different spatial frequencies (SFs). The resulting selective visual processing predicts both universal SNAs and their context-dependence. We support our proposal by analyzing the stimuli used to document SNAs in newborns for their SF content. As predicted, the SFs contained in visual patterns with few versus many elements preferentially engage right versus left brain hemispheres, respectively, thus predicting left-versus rightward behavioral biases. Our "brain's asymmetric frequency tuning" hypothesis explains the perceptual origin of horizontal SNAs for nonsymbolic visual numerosities and might be extensible to the auditory domain.
We report the influence of different nutritional modes-autotrophy, mixotrophy, and heterotrophy-on the fatty acid and sterol composition of the freshwater flagellate Ochromonas sp. and discuss the ecological significance of our results with respect to the resource competition theory (rct). Polyunsaturated fatty acids (PUFAs) are the most efficient biochemical variable distinguishing between nutritional modes of Ochromonas sp. Decreasing concentrations of PUFAs were observed in the order autotrophs, mixotrophs, heterotrophs. In mixotrophs and heterotrophs, concentrations of saturated fatty acids were higher than those of monounsaturated fatty acids and PUFAs as a result of bacterivory. Stigmasterol was the main sterol in Ochromonas sp., regardless of nutritional mode. Mixotrophs showed higher growth rates than heterotrophs, which could not be explained by rct. Heterotrophs, in turn, exhibited higher growth rates than autotrophs, which were cultured under the same light conditions as mixotrophs. Mixotrophs can synthesize PUFAs, which are important for many physiological functions such as membrane permeability and growth. Thus, mixotrophy facilitated efficient growth as well as the ability to synthesize complex and essential biomolecules. These strong synergetic effects are due to the combination of biochemical benefits of heterotrophic and autotrophic metabolic pathways and cannot be predicted by rct.
Aldol reactions play an important role in organic synthesis, as they belong to the class of highly beneficial C-C-linking reactions. Aldol-type reactions can be efficiently and stereoselectively catalyzed by the enzyme 2-deoxy-D-ribose-5-phosphate aldolase (DERA) to gain key intermediates for pharmaceuticals such as atorvastatin. The immobilization of DERA would open the opportunity for a continuous operation mode which gives access to an efficient, large-scale production of respective organic intermediates. In this contribution, we synthesize and utilize DERA/polymer conjugates for the generation and fixation of a DERA bearing thin film on a polymeric membrane support. The conjugation strongly increases the tolerance of the enzyme toward the industrial relevant substrate acetaldehyde while UV-cross-linkable groups along the conjugated polymer chains provide the opportunity for covalent binding to the support. First, we provide a thorough characterization of the conjugates followed by immobilization tests on representative, nonporous cycloolefinic copolymer supports. Finally, immobilization on the target supports constituted of polyacrylonitrile (PAN) membranes is performed, and the resulting enzymatically active membranes are implemented in a simple membrane module setup for the first assessment of biocatalytic performance in the continuous operation mode using the combination hexanal/acetaldehyde as the substrate.
Binding or catalysis? Both can be distinguished with a molecularly imprinted polymer (MIP) by the different patterns of heat generation. The catalytically active sites, like in the corresponding enzyme, generate a steady-state temperature increase. Thus, enzyme-like catalysis and antibody-analogue binding are analyzed simultaneously in a bifunctional MIP for the first time (see scheme).
Ecological communities are complex adaptive systems that exhibit remarkable feedbacks between their biomass and trait dynamics. Trait-based aggregate models cope with this complexity by focusing on the temporal development of the community’s aggregate properties such as its total biomass, mean trait and trait variance. They are based on particular assumptions about the shape of the underlying trait distribution, which is commonly assumed to be normal. However, ecologically important traits are usually restricted to a finite range, and empirical trait distributions are often skewed or multimodal. As a result, normal distribution-based aggregate models may fail to adequately represent the biomass and trait dynamics of natural communities. We resolve this mismatch by developing a new moment closure approach assuming the trait values to be beta-distributed. We show that the beta distribution captures important shape properties of both observed and simulated trait distributions, which cannot be captured by a Gaussian. We further demonstrate that a beta distribution-based moment closure can strongly enhance the reliability of trait-based aggregate models. We compare the biomass, mean trait and variance dynamics of a full trait distribution (FD) model to the ones of beta (BA) and normal (NA) distribution-based aggregate models, under different selection regimes. This way, we demonstrate under which general conditions (stabilizing, fluctuating or disruptive selection) different aggregate models are reliable tools. All three models predicted very similar biomass and trait dynamics under stabilizing selection yielding unimodal trait distributions with small standing trait variation. We also obtained an almost perfect match between the results of the FD and BA models under fluctuating selection, promoting skewed trait distributions and ongoing oscillations in the biomass and trait dynamics. In contrast, the NA model showed unrealistic trait dynamics and exhibited different alternative stable states, and thus a high sensitivity to initial conditions under fluctuating selection. Under disruptive selection, both aggregate models failed to reproduce the results of the FD model with the mean trait values remaining within their ecologically feasible ranges in the BA model but not in the NA model. Overall, a beta distribution-based moment closure strongly improved the realism of trait-based aggregate models.
Background: With increasing age neuromuscular deficits (e.g., sarcopenia) may result in impaired physical performance and an increased risk for falls. Prominent intrinsic fall-risk factors are age-related decreases in balance and strength / power performance as well as cognitive decline. Additional studies are needed to develop specifically tailored exercise programs for older adults that can easily be implemented into clinical practice. Thus, the objective of the present trial is to assess the effects of a fall prevention program that was developed by an interdisciplinary expert panel on measures of balance, strength / power, body composition, cognition, psychosocial well-being, and falls self-efficacy in healthy older adults. Additionally, the time-related effects of detraining are tested.
Methods/Design: Healthy old people (n = 54) between the age of 65 to 80 years will participate in this trial. The testing protocol comprises tests for the assessment of static / dynamic steady-state balance (i.e., Sharpened Romberg Test, instrumented gait analysis), proactive balance (i.e., Functional Reach Test; Timed Up and Go Test), reactive balance (i.e., perturbation test during bipedal stance; Push and Release Test), strength (i.e., hand grip strength test; Chair Stand Test), and power (i.e., Stair Climb Power Test; countermovement jump). Further, body composition will be analysed using a bioelectrical impedance analysis system. In addition, questionnaires for the assessment of psychosocial (i.e., World Health Organisation Quality of Life Assessment-Bref), cognitive (i.e., Mini Mental State Examination), and fall risk determinants (i.e., Fall Efficacy Scale -International) will be included in the study protocol. Participants will be randomized into two intervention groups or the control / waiting group. After baseline measures, participants in the intervention groups will conduct a 12-week balance and strength / power exercise intervention 3 times per week, with each training session lasting 30 min. (actual training time). One intervention group will complete an extensive supervised training program, while the other intervention group will complete a short version (` 3 times 3') that is home-based and controlled by weekly phone calls. Post-tests will be conducted right after the intervention period. Additionally, detraining effects will be measured 12 weeks after program cessation. The control group / waiting group will not participate in any specific intervention during the experimental period, but will receive the extensive supervised program after the experimental period.
Discussion: It is expected that particularly the supervised combination of balance and strength / power training will improve performance in variables of balance, strength / power, body composition, cognitive function, psychosocial well-being, and falls self-efficacy of older adults. In addition, information regarding fall risk assessment, dose-response-relations, detraining effects, and supervision of training will be provided. Further, training-induced health-relevant changes, such as improved performance in activities of daily living, cognitive function, and quality of life, as well as a reduced risk for falls may help to lower costs in the health care system. Finally, practitioners, therapists, and instructors will be provided with a scientifically evaluated feasible, safe, and easy-to-administer exercise program for fall prevention.
Background: With increasing age neuromuscular deficits (e.g., sarcopenia) may result in impaired physical performance and an increased risk for falls. Prominent intrinsic fall-risk factors are age-related decreases in balance and strength / power performance as well as cognitive decline. Additional studies are needed to develop specifically tailored exercise programs for older adults that can easily be implemented into clinical practice. Thus, the objective of the present trial is to assess the effects of a fall prevention program that was developed by an interdisciplinary expert panel on measures of balance, strength / power, body composition, cognition, psychosocial well-being, and falls self-efficacy in healthy older adults. Additionally, the time-related effects of detraining are tested.
Methods/Design: Healthy old people (n = 54) between the age of 65 to 80 years will participate in this trial. The testing protocol comprises tests for the assessment of static / dynamic steady-state balance (i.e., Sharpened Romberg Test, instrumented gait analysis), proactive balance (i.e., Functional Reach Test; Timed Up and Go Test), reactive balance (i.e., perturbation test during bipedal stance; Push and Release Test), strength (i.e., hand grip strength test; Chair Stand Test), and power (i.e., Stair Climb Power Test; countermovement jump). Further, body composition will be analysed using a bioelectrical impedance analysis system. In addition, questionnaires for the assessment of psychosocial (i.e., World Health Organisation Quality of Life Assessment-Bref), cognitive (i.e., Mini Mental State Examination), and fall risk determinants (i.e., Fall Efficacy Scale -International) will be included in the study protocol. Participants will be randomized into two intervention groups or the control / waiting group. After baseline measures, participants in the intervention groups will conduct a 12-week balance and strength / power exercise intervention 3 times per week, with each training session lasting 30 min. (actual training time). One intervention group will complete an extensive supervised training program, while the other intervention group will complete a short version (` 3 times 3') that is home-based and controlled by weekly phone calls. Post-tests will be conducted right after the intervention period. Additionally, detraining effects will be measured 12 weeks after program cessation. The control group / waiting group will not participate in any specific intervention during the experimental period, but will receive the extensive supervised program after the experimental period.
Discussion: It is expected that particularly the supervised combination of balance and strength / power training will improve performance in variables of balance, strength / power, body composition, cognitive function, psychosocial well-being, and falls self-efficacy of older adults. In addition, information regarding fall risk assessment, dose-response-relations, detraining effects, and supervision of training will be provided. Further, training-induced health-relevant changes, such as improved performance in activities of daily living, cognitive function, and quality of life, as well as a reduced risk for falls may help to lower costs in the health care system. Finally, practitioners, therapists, and instructors will be provided with a scientifically evaluated feasible, safe, and easy-to-administer exercise program for fall prevention.
Data stream processing systems (DSPSs) are a key enabler to integrate continuously generated data, such as sensor measurements, into enterprise applications. DSPSs allow to steadily analyze information from data streams, e.g., to monitor manufacturing processes and enable fast reactions to anomalous behavior. Moreover, DSPSs continuously filter, sample, and aggregate incoming streams of data, which reduces the data size, and thus data storage costs.
The growing volumes of generated data have increased the demand for high-performance DSPSs, leading to a higher interest in these systems and to the development of new DSPSs. While having more DSPSs is favorable for users as it allows choosing the system that satisfies their requirements the most, it also introduces the challenge of identifying the most suitable DSPS regarding current needs as well as future demands. Having a solution to this challenge is important because replacements of DSPSs require the costly re-writing of applications if no abstraction layer is used for application development. However, quantifying performance differences between DSPSs is a difficult task. Existing benchmarks fail to integrate all core functionalities of DSPSs and lack tool support, which hinders objective result comparisons. Moreover, no current benchmark covers the combination of streaming data with existing structured business data, which is particularly relevant for companies.
This thesis proposes a performance benchmark for enterprise stream processing called ESPBench. With enterprise stream processing, we refer to the combination of streaming and structured business data. Our benchmark design represents real-world scenarios and allows for an objective result comparison as well as scaling of data. The defined benchmark query set covers all core functionalities of DSPSs. The benchmark toolkit automates the entire benchmark process and provides important features, such as query result validation and a configurable data ingestion rate.
To validate ESPBench and to ease the use of the benchmark, we propose an example implementation of the ESPBench queries leveraging the Apache Beam software development kit (SDK). The Apache Beam SDK is an abstraction layer designed for developing stream processing applications that is applied in academia as well as enterprise contexts. It allows to run the defined applications on any of the supported DSPSs. The performance impact of Apache Beam is studied in this dissertation as well. The results show that there is a significant influence that differs among DSPSs and stream processing applications. For validating ESPBench, we use the example implementation of the ESPBench queries developed using the Apache Beam SDK. We benchmark the implemented queries executed on three modern DSPSs: Apache Flink, Apache Spark Streaming, and Hazelcast Jet. The results of the study prove the functioning of ESPBench and its toolkit. ESPBench is capable of quantifying performance characteristics of DSPSs and of unveiling differences among systems.
The benchmark proposed in this thesis covers all requirements to be applied in enterprise stream processing settings, and thus represents an improvement over the current state-of-the-art.
1. New patterns and trends in land use are becoming increasingly evident in Europe's heavily modified landscape and else whereas sustainable agriculture and nature restoration are developed as viable long-term alternatives to intensively farmed arable land. The success of these changes depends on how soil biodiversity and processes respond to changes in management. To improve our understanding of the community structure and ecosystem functioning of the soil biota, we analyzed abiotic variables across 200 sites, and biological variables across 170 sites in The Netherlands, one of the most intensively farmed countries. The data were derived from the Dutch Soil Quality Network (DSQN), a long-term monitoring framework designed to obtain ecological insight into soil types (STs) and ecosystem types (ETs).
2. At the outset we describe STs and biota, and we estimate the contribution of various groups to the provision of ecosystem services. We focused on interactive effects of soil properties on community patterns and ecosystem functioning using food web models. Ecologists analyze soil food webs by means of mechanistic and statistical modelling, linking network structure to energy flow and elemental dynamics commonly based on allometric scaling.
3. We also explored how predatory and metabolic processes are constrained by body size, diet and metabolic type, and how these constraints govern the interactions within and between trophic groups. In particular, we focused on how elemental fluxes determine the strengths of ecological interactions, and the resulting ecosystem services, in terms of sustenance of soil fertility.
4. We discuss data mining, food web visualizations, and an appropriate categorical way to capture subtle interrelationships within the DSQN dataset. Sampled metazoans were used to provide an overview of below-ground processes and influences of land use. Unlike most studies to date we used data from the entire size spectrum, across 15 orders of magnitude, using body size as a continuous trait crucial for understanding ecological services.
5. Multimodality in the frequency distributions of body size represents a performance filter that acts as a buffer to environmental change. Large differences in the body-size distributions across ETs and STs were evident. Most observed trends support the hypothesis that the direct influence of ecological stoichiometry on the soil biota as an independent predictor (e.g. in the form of nutrient to carbon ratios), and consequently on the allometric scaling, is more dominant than either ET or ST. This provides opportunities to develop a mechanistic and physiologically oriented model for the distribution of species' body sizes, where responses of invertebrates can be predicted.
6. Our results highlight the different roles that organisms play in a number of key ecosystem services. Such a trait-based research has unique strengths in its rigorous formulation of fundamental scaling rules, as well as in its verifiability by empirical data. Nonetheless, it still has weaknesses that remain to be addressed, like the consequences of intraspecific size variation, the high degree of omnivory, and a possibly inaccurate assignment to trophic groups.
7. Studying the extent to which nutrient levels influence multitrophic interactions and how different land-use regimes affect soil biodiversity is clearly a fruitful area for future research to develop predictive models for soil ecosystem services under different management regimes. No similar efforts have been attempted previously for soil food webs, and our dataset has the potential to test and further verify its usefulness at an unprecedented space scale.
The estimation of a log-concave density on R is a canonical problem in the area of shape-constrained nonparametric inference. We present a Bayesian nonparametric approach to this problem based on an exponentiated Dirichlet process mixture prior and show that the posterior distribution converges to the log-concave truth at the (near-) minimax rate in Hellinger distance. Our proof proceeds by establishing a general contraction result based on the log-concave maximum likelihood estimator that prevents the need for further metric entropy calculations. We further present computationally more feasible approximations and both an empirical and hierarchical Bayes approach. All priors are illustrated numerically via simulations.
In eye-movement control during reading, advanced process-oriented models have been developed to reproduce behavioral data. So far, model complexity and large numbers of model parameters prevented rigorous statistical inference and modeling of interindividual differences. Here we propose a Bayesian approach to both problems for one representative computational model of sentence reading (SWIFT; Engbert et al., Psychological Review, 112, 2005, pp. 777-813). We used experimental data from 36 subjects who read the text in a normal and one of four manipulated text layouts (e.g., mirrored and scrambled letters). The SWIFT model was fitted to subjects and experimental conditions individually to investigate between- subject variability. Based on posterior distributions of model parameters, fixation probabilities and durations are reliably recovered from simulated data and reproduced for withheld empirical data, at both the experimental condition and subject levels. A subsequent statistical analysis of model parameters across reading conditions generates model-driven explanations for observable effects between conditions.
A balance to death
(2018)
Leaf senescence plays a crucial role in nutrient recovery in late-stage plant development and requires vast transcriptional reprogramming by transcription factors such as ORESARA1 (ORE1). A proteolytic mechanism is now found to control ORE1 degradation, and thus senescence, during nitrogen starvation.
We recorded large data sets of swimming trajectories of the soil bacterium Pseudomonas putida. Like other prokaryotic swimmers, P. putida exhibits a motion pattern dominated by persistent runs that are interrupted by turning events. An in-depth analysis of their swimming trajectories revealed that the majority of the turning events is characterized by an angle of phi(1) = 180 degrees (reversals). To a lesser extent, turning angles of phi(2 Sigma Sigma Sigma Sigma) = 00 are also found. Remarkably, we observed that, upon a reversal, the swimming speed changes by a factor of two on average a prominent feature of the motion pattern that, to our knowledge, has not been reported before. A theoretical model, based on the experimental values for the average run time and the rotational diffusion, recovers the mean-square displacement of P. putida if the two distinct swimming speeds are taken into account. Compared to a swimmer that moves with a constant intermediate speed, the mean-square displacement is strongly enhanced. We furthermore observed a negative dip in the directional autocorrelation at intermediate times, a feature that is only recovered in an extended model, where the nonexponential shape of the run-time distribution is taken into account.
The emerging threat of antibiotic-resistant bacteria has become a global challenge in the last decades, leading to a rising demand for alternative treatments for bacterial infections. One approach is to target the bacterial cell envelope, making understanding its biophysical properties crucial. Specifically, bacteriophages use the bacterial envelope as an entry point to initiate infection, and they are considered important building blocks of new antibiotic strategies against drug-resistant bacteria.. Depending on the structure of the cell wall, bacteria are classified as Gram-negative and Gram-positive. Gram-negative bacteria are equipped with a complex cell envelope composed of two lipid membranes enclosing a rigid peptidoglycan layer. The synthesis machinery of the Gram-negative cell envelope is the target of antimicrobial agents, including new physical sanitizing procedures addressing the outer membrane (OM). It is therefore very important to study the biophysical properties of the Gram-negative bacterial cell envelope. The high complexity of the Gram-negative OM sets the demand for a model system in which the contribution of individual components can be evaluated separately. In this respect, giant unilamellar vesicles (GUVs) are promising membrane systems to study membrane properties while controlling parameters such as membrane composition and surrounding medium conditions.
The aim of this work was to develop methods and approaches for the preparation and characterization of a GUV-based membrane model that mimics the OM of the Gram-negative cell envelope. A major component of the OM is the lipopolysaccharide (LPS) on the outside of the OM heterobilayer. The vesicle model was designed to contain LPS in the outer leaflet and lipids in the inner leaflet. Furthermore, the interaction of the prepared LPS-GUVs with bacteriophages was tested. LPS containing GUVs were prepared by adapting the inverted emulsion technique to meet the challenging properties of LPS, namely their high self-aggregation rate in aqueous solutions. Notably, an additional emulsification step together with the adaption of solution conditions was employed to asymmetrically incorporate LPS containing long polysaccharide chains into the artificial membranes. GUV membrane asymmetry was verified with a fluorescence quenching assay. Since the necessary precautions for handling the quenching agent sodium dithionite are often underestimated and poorly described, important parameters were tested and identified to obtain a stable and reproducible assay. In the context of varied LPS incorporation, a microscopy-based technique was introduced to determine the LPS content on individual GUVs and to directly compare vesicle properties and LPS coverage. Diffusion coefficient measurements in the obtained GUVs showed that increasing LPS concentrations in the membranes resulted in decreased diffusivity.
Employing LPS-GUVs we could demonstrate that a Salmonella bacteriophage bound with high specificity to its LPS receptor when presented at the GUV surface, and that the number of bound bacteriophages scaled with the amount of presented LPS receptor. In addition to binding, the bacteriophages were able to eject their DNA into the vesicle lumen. LPS-GUVs thus provide a starting platform for bottom-up approaches for the generation of more complex membranes, in which the effects of individual components on the membrane properties and the interaction with antimicrobial agents such as bacteriophages could be explored.
Controlled conversion of leaf starch to sucrose at night is essential for the normal growth of Arabidopsis. The conversion involves the cytosolic metabolism of maltose to hexose phosphates via an unusual, multidomain protein with 4-glucanotransferase activity, DPE2, believed to transfer glucosyl moieties to a complex heteroglycan prior to their conversion to hexose phosphate via a cytosolic phosphorylase. The significance of this complex pathway is unclear; conversion of maltose to hexose phosphate in bacteria proceeds via a more typical 4-glucanotransferase that does not require a heteroglycan acceptor. It has recently been suggested that DPE2 generates a heterogeneous series of terminal glucan chains on the heteroglycan that acts as a glucosyl buffer to ensure a constant rate of sucrose synthesis in the leaf at night. Alternatively, DPE2 and/or the heteroglycan may have specific properties important for their function in the plant. To distinguish between these ideas, we compared the properties of DPE2 with those of the Escherichia coli glucanotransferase MalQ. We found that MalQ cannot use the plant heteroglycan as an acceptor for glucosyl transfer. However, experimental and modeling approaches suggested that it can potentially generate a glucosyl buffer between maltose and hexose phosphate because, unlike DPE2, it can generate polydisperse malto-oligosaccharides from maltose. Consistent with this suggestion, MalQ is capable of restoring an essentially wild-type phenotype when expressed in mutant Arabidopsis plants lacking DPE2. In light of these findings, we discuss the possible evolutionary origins of the complex DPE2-heteroglycan pathway.
A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component
(2022)
Beyond its role in cellular homeostasis, autophagy plays anti- and promicrobial roles in host-microbe interactions, both in animals and plants.
One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy.
Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination.
Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown.
Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection.
Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery.
Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense-related autophagy in plant-bacteria interactions.
The potential increase in frequency and magnitude of extreme floods is currently discussed in terms of global warming and the intensification of the hydrological cycle. The profound knowledge of past natural variability of floods is of utmost importance in order to assess flood risk for the future. Since instrumental flood series cover only the last ~150 years, other approaches to reconstruct historical and pre-historical flood events are needed. Annually laminated (varved) lake sediments are meaningful natural geoarchives because they provide continuous records of environmental changes > 10000 years down to a seasonal resolution. Since lake basins additionally act as natural sediment traps, the riverine sediment supply, which is preserved as detrital event layers in the lake sediments, can be used as a proxy for extreme discharge events. Within my thesis I examined a ~ 8.50 m long sedimentary record from the pre-Alpine Lake Mondsee (Northeast European Alps), which covered the last 7000 years. This sediment record consists of calcite varves and intercalated detrital layers, which range in thickness from 0.05 to 32 mm. Detrital layer deposition was analysed by a combined method of microfacies analysis via thin sections, Scanning Electron Microscopy (SEM), μX-ray fluorescence (μXRF) scanning and magnetic susceptibility. This approach allows characterizing individual detrital event layers and assigning a corresponding input mechanism and catchment. Based on varve counting and controlled by 14C age dates, the main goals of this thesis are (i) to identify seasonal runoff processes, which lead to significant sediment supply from the catchment into the lake basin and (ii) to investigate flood frequency under changing climate boundary conditions. This thesis follows a line of different time slices, presenting an integrative approach linking instrumental and historical flood data from Lake Mondsee in order to evaluate the flood record inferred from Lake Mondsee sediments. The investigation of eleven short cores covering the last 100 years reveals the abundance of 12 detrital layers. Therein, two types of detrital layers are distinguished by grain size, geochemical composition and distribution pattern within the lake basin. Detrital layers, which are enriched in siliciclastic and dolomitic material, reveal sediment supply from the Flysch sediments and Northern Calcareous Alps into the lake basin. These layers are thicker in the northern lake basin (0.1-3.9 mm) and thinner in the southern lake basin (0.05-1.6 mm). Detrital layers, which are enriched in dolomitic components forming graded detrital layers (turbidites), indicate the provenance from the Northern Calcareous Alps. These layers are generally thicker (0.65-32 mm) and are solely recorded within the southern lake basin. In comparison with instrumental data, thicker graded layers result from local debris flow events in summer, whereas thin layers are deposited during regional flood events in spring/summer. Extreme summer floods as reported from flood layer deposition are principally caused by cyclonic activity from the Mediterranean Sea, e.g. July 1954, July 1997 and August 2002. During the last two millennia, Lake Mondsee sediments reveal two significant flood intervals with decadal-scale flood episodes, during the Dark Ages Cold Period (DACP) and the transition from the Medieval Climate Anomaly (MCA) into the Little Ice Age (LIA) suggesting a linkage of transition to climate cooling and summer flood recurrences in the Northeastern Alps. In contrast, intermediate or decreased flood episodes appeared during the MWP and the LIA. This indicates a non-straightforward relationship between temperature and flood recurrence, suggesting higher cyclonic activity during climate transition in the Northeast Alps. The 7000-year flood chronology reveals 47 debris flows and 269 floods, with increased flood activity shifting around 3500 and 1500 varve yr BP (varve yr BP = varve years before present, before present = AD 1950). This significant increase in flood activity shows a coincidence with millennial-scale climate cooling that is reported from main Alpine glacier advances and lower tree lines in the European Alps since about 3300 cal. yr BP (calibrated years before present). Despite relatively low flood occurrence prior to 1500 varve yr BP, floods at Lake Mondsee could have also influenced human life in early Neolithic lake dwellings (5750-4750 cal. yr BP). While the first lake dwellings were constructed on wetlands, the later lake dwellings were built on piles in the water suggesting an early flood risk adaptation of humans and/or a general change of the Late Neolithic Culture of lake-dwellers because of socio-economic reasons. However, a direct relationship between the final abandonment of the lake dwellings and higher flood frequencies is not evidenced.
A 3-D crustal shear wave velocity model and Moho map below the Semail Ophiolite, eastern Arabia
(2022)
The Semail Ophiolite in eastern Arabia is the largest and best-exposed slice of oceanic lithosphere on land. Detailed knowledge of the tectonic evolution of the shallow crust, in particular during and after ophiolite obduction in Late Cretaceous times is contrasted by few constraints on physical and compositional properties of the middle and lower continental crust below the obducted units. The role of inherited, pre-obduction crustal architecture remains therefore unaccounted for in our understanding of crustal evolution and the present-day geology. Based on seismological data acquired during a 27-month campaign in northern Oman, Ambient Seismic Noise Tomography and Receiver Function analysis provide for the first time a 3-D radially anisotropic shear wave velocity (V-S) model and a consistent Moho map below the iconic Semail Ophiolite. The model highlights deep crustal boundaries that segment the eastern Arabian basement in two distinct units. The previously undescribed Western Jabal Akhdar Zone separates Arabian crust with typical continental properties and a thickness of similar to 40-45 km in the northwest from a compositionally different terrane in the southeast that is interpreted as a terrane accreted during the Pan-African orogeny in Neoproterozoic times. East of the Ibra Zone, another deep crustal boundary, crustal thickness decreases to 30-35 km and very high lower crustal V-S suggest large-scale mafic intrusions into, and possible underplating of the Arabian continental crust that occurred most likely during Permian breakup of Pangea. Mafic reworking is sharply bounded by the (upper crustal) Semail Gap Fault Zone, northwest of which no such high velocities are found in the crust. Topography of the Oman Mountains is supported by a mild crustal root and Moho depth below the highest topography, the Jabal Akhdar Dome, is similar to 42 km. Radial anisotropy is robustly resolved in the upper crust and aids in discriminating dipping allochthonous units from autochthonous sedimentary rocks that are indistinguishable by isotropic V-S alone. Lateral thickness variations of the ophiolite highlight the Haylayn Ophiolite Massif on the northern flank of Jabal Akhdar Dome and the Hawasina Window as the deepest reaching unit. Ophiolite thickness is similar to 10 km in the southern and northern massifs, and <= 5 km elsewhere.
Timing and magnitude of surface uplift are key to understanding the impact of crustal deformation and topographic growth on atmospheric circulation, environmental conditions, and surface processes. Uplift of the East African Plateau is linked to mantle processes, but paleoaltimetry data are too scarce to constrain plateau evolution and subsequent vertical motions associated with rifting. Here, we assess the paleotopographic implications of a beaked whale fossil (Ziphiidae) from the Turkana region of Kenya found 740 km inland from the present-day coastline of the Indian Ocean at an elevation of 620 m. The specimen is similar to 17 My old and represents the oldest derived beaked whale known, consistent with molecular estimates of the emergence of modern straptoothed whales (Mesoplodon). The whale traveled from the Indian Ocean inland along an eastward-directed drainage system controlled by the Cretaceous Anza Graben and was stranded slightly above sea level. Surface uplift from near sea level coincides with paleoclimatic change from a humid environment to highly variable and much drier conditions, which altered biotic communities and drove evolution in east Africa, including that of primates.
Formation or destruction of hyperbolic chaotic attractor under parameter variation is considered with an example represented by Smale-Williams solenoid in stroboscopic Poincare map of two alternately excited non-autonomous van der Pol oscillators. The transition occupies a narrow but finite parameter interval and progresses in such way that periodic orbits constituting a "skeleton" of the attractor undergo saddle-node bifurcation events involving partner orbits from the attractor and from a non-attracting invariant set, which forms together with its stable manifold a basin boundary of the attractor.
Background: Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable.
Methodology/Principal Findings: To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics'' analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4(+)T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset.
Conclusions/Significance: Our study shows that the intra- individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective.