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Catalytic amounts of a weak base are sufficient to induce the decomposition of anthracene endoperoxides to anthraquinone. The mechanism has been elucidated by isolation of intermediates in combination with DFT calculations. The whole process is suitable for the convenient generation of hydrogen peroxide under very mild conditions.
Understanding interactions of bacterial surface polysaccharides with receptor protein scaffolds is important for the development of antibiotic therapies. The corresponding protein recognition domains frequently form low-affinity complexes with polysaccharides that are difficult to address with experimental techniques due to the conformational flexibility of the polysaccharide. In this work, we studied the tailspike protein (TSP) of the bacteriophage Sf6. Sf6TSP binds and hydrolyzes the high-rhamnose, serotype Y O-antigen polysaccharide of the Gram-negative bacterium Shigella flexneri (S. flexneri) as a first step of bacteriophage infection. Spectroscopic analyses and enzymatic cleavage assays confirmed that Sf6TSP binds long stretches of this polysaccharide. Crystal structure analysis and saturation transfer difference (STD) NMR spectroscopy using an enhanced method to interpret the data permitted the detailed description of affinity contributions and flexibility in an Sf6TSP-octasaccharide complex. Dodecasaccharide fragments corresponding to three repeating units of the O-antigen in complex with Sf6TSP were studied computationally by molecular dynamics simulations. They showed that distortion away from the low-energy solution conformation found in the octasaccharide complex is necessary for ligand binding. This is in agreement with a weak-affinity functional polysaccharide protein contact that facilitates correct placement and thus hydrolysis of the polysaccharide close to the catalytic residues. Our simulations stress that the flexibility of glycan epitopes together with a small number of specific protein contacts provide the driving force for Sf6TSP-polysaccharide complex formation in an overall weak-affinity interaction system.
Background
Non-typhoid Salmonella Typhimurium (S. Typhimurium) accounts for a high number of registered salmonellosis cases, and O-serotyping is one important tool for monitoring epidemiology and spread of the disease. Moreover, variations in glucosylated O-antigens are related to immunogenicity and spread in the host. However, classical autoagglutination tests combined with the analysis of specific genetic markers cannot always reliably register phase variable glucose modifications expressed on Salmonella O-antigens and additional tools to monitor O-antigen glucosylation phenotypes of S. Typhimurium would be desirable.
Results
We developed a test for the phase variable O-antigen glucosylation state of S. Typhimurium using the tailspike proteins (TSP) of Salmonella phages 9NA and P22. We used this ELISA like tailspike adsorption (ELITA) assay to analyze a library of 44 Salmonella strains. ELITA was successful in discriminating strains that carried glucose 1-6 linked to the galactose of O-polysaccharide backbone (serotype O1) from non-glucosylated strains. This was shown by O-antigen compositional analyses of the respective strains with mass spectrometry and capillary electrophoresis. The ELITA test worked rapidly in a microtiter plate format and was highly O-antigen specific. Moreover, TSP as probes could also detect glucosylated strains in flow cytometry and distinguish multiphasic cultures differing in their glucosylation state.
Conclusions
Tailspike proteins contain large binding sites with precisely defined specificities and are therefore promising tools to be included in serotyping procedures as rapid serotyping agents in addition to antibodies. In this study, 9NA and P22TSP as probes could specifically distinguish glucosylation phenotypes of Salmonella on microtiter plate assays and in flow cytometry. This opens the possibility for flow sorting of cell populations for subsequent genetic analyses or for monitoring phase variations during large scale O-antigen preparations necessary for vaccine production.
Background: Non-typhoid Salmonella Typhimurium (S. Typhimurium) accounts for a high number of registered salmonellosis cases, and O-serotyping is one important tool for monitoring epidemiology and spread of the disease. Moreover, variations in glucosylated O-antigens are related to immunogenicity and spread in the host. However, classical autoagglutination tests combined with the analysis of specific genetic markers cannot always reliably register phase variable glucose modifications expressed on Salmonella O-antigens and additional tools to monitor O-antigen glucosylation phenotypes of S. Typhimurium would be desirable. Results: We developed a test for the phase variable O-antigen glucosylation state of S. Typhimurium using the tailspike proteins (TSP) of Salmonella phages 9NA and P22. We used this ELISA like tailspike adsorption (ELITA) assay to analyze a library of 44 Salmonella strains. ELITA was successful in discriminating strains that carried glucose 1-6 linked to the galactose of O-polysaccharide backbone (serotype O1) from non-glucosylated strains. This was shown by O-antigen compositional analyses of the respective strains with mass spectrometry and capillary electrophoresis. The ELITA test worked rapidly in a microtiter plate format and was highly O-antigen specific. Moreover, TSP as probes could also detect glucosylated strains in flow cytometry and distinguish multiphasic cultures differing in their glucosylation state. Conclusions: Tailspike proteins contain large binding sites with precisely defined specificities and are therefore promising tools to be included in serotyping procedures as rapid serotyping agents in addition to antibodies. In this study, 9NA and P22TSP as probes could specifically distinguish glucosylation phenotypes of Salmonella on microtiter plate assays and in flow cytometry. This opens the possibility for flow sorting of cell populations for subsequent genetic analyses or for monitoring phase variations during large scale O-antigen preparations necessary for vaccine production.
Environmental stress is detrimental to cell viability and requires an adequate reprogramming of cellular activities to maximize cell survival. We present a global analysis of the response of Escherichia coli to acute heat and osmotic stress. We combine deep sequencing of total mRNA and ribosome-protected fragments to provide a genome-wide map of the stress response at transcriptional and translational levels. For each type of stress, we observe a unique subset of genes that shape the stress-specific response. Upon temperature upshift, mRNAs with reduced folding stability up-and downstream of the start codon, and thus with more accessible initiation regions, are translationally favoured. Conversely, osmotic upshift causes a global reduction of highly translated transcripts with high copy numbers, allowing reallocation of translation resources to not degraded and newly synthesized mRNAs.
B fields in OB stars (BOB): Detection of a magnetic field in the He-strong star CPD-57 degrees 3509
(2016)
Methods. Spectropolarimetric observations with FORS2 and HARPSpol are analysed using two independent approaches to quantify the magnetic field strength. A high-S/N FLAMES/GIRAFFE spectrum is analysed using a hybrid non-LTE model atmosphere technique. Comparison with stellar evolution models constrains the fundamental parameters of the star. Results. We obtain a firm detection of a surface averaged longitudinal magnetic field with a maximum amplitude of about 1 kG. Assuming a dipolar configuration of the magnetic field, this implies a dipolar field strength larger than 3.3 kG. Moreover, the large amplitude and fast variation (within about 1 day) of the longitudinal magnetic field implies that CPD-57 degrees 3509 is spinning very fast despite its apparently slow projected rotational velocity. The star should be able to support a centrifugal magnetosphere, yet the spectrum shows no sign of magnetically confined material; in particular, emission in H alpha is not observed. Apparently, the wind is either not strong enough for enough material to accumulate in the magnetosphere to become observable or, alternatively, some leakage process leads to loss of material from the magnetosphere. The quantitative spectroscopic analysis of the star yields an effective temperature and a logarithmic surface gravity of 23 750 +/- 250 K and 4.05 +/- 0.10, respectively, and a surface helium fraction of 0.28 +/- 0.02 by number. The surface abundances of C, N, O, Ne, S, and Ar are compatible with the cosmic abundance standard, whereas Mg, Al, Si, and Fe are depleted by about a factor of 2. This abundance pattern can be understood as the consequence of a fractionated stellar wind. CPD-57 degrees 3509 is one of the most evolved He-strong stars known with an independent age constraint due to its cluster membership.
We introduce azobenzene-functionalized polyelectrolyte multilayers as efficient, inexpensive optoacoustic transducers for hyper-sound strain waves in the GHz range. By picosecond transient reflectivity measurements we study the creation of nanoscale strain waves, their reflection from interfaces, damping by scattering from nanoparticles and propagation in soft and hard adjacent materials like polymer layers, quartz and mica. The amplitude of the generated strain epsilon similar to 5 x 10(-4) is calibrated by ultrafast X-ray diffraction.
We present the Neural-network-based Upper hybrid Resonance Determination (NURD) algorithm for automatic inference of the electron number density from plasma wave measurements made on board NASA's Van Allen Probes mission. A feedforward neural network is developed to determine the upper hybrid resonance frequency, fuhr, from electric field measurements, which is then used to calculate the electron number density. In previous missions, the plasma resonance bands were manually identified, and there have been few attempts to do robust, routine automated detections. We describe the design and implementation of the algorithm and perform an initial analysis of the resulting electron number density distribution obtained by applying NURD to 2.5 years of data collected with the Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) instrumentation suite of the Van Allen Probes mission. Densities obtained by NURD are compared to those obtained by another recently developed automated technique and also to an existing empirical plasmasphere and trough density model.
Apart from their central role during 3D structure determination of proteins the backbone chemical shift assignment is the basis for a number of applications, like chemical shift perturbation mapping and studies on the dynamics of proteins. This assignment is not a trivial task even if a 3D protein structure is known and needs almost as much effort as the assignment for structure prediction if performed manually. We present here a new algorithm based solely on 4D [H-1, N-15]-HSQC-NOESY-[H-1, N-15]-HSQC spectra which is able to assign a large percentage of chemical shifts (73-82 %) unambiguously, demonstrated with proteins up to a size of 250 residues. For the remaining residues, a small number of possible assignments is filtered out. This is done by comparing distances in the 3D structure to restraints obtained from the peak volumes in the 4D spectrum. Using dead-end elimination, assignments are removed in which at least one of the restraints is violated. Including additional information from chemical shift predictions, a complete unambiguous assignment was obtained for Ubiquitin and 95 % of the residues were correctly assigned in the 251 residue-long N-terminal domain of enzyme I. The program including source code is available at https://github.com/thomasexner/4Dassign.
Analysis of time-lapse ground-penetrating radar (GPR) data can provide information regarding subsurface hydrological processes, such as preferential flow. However, the analysis of time-lapse data is often limited by data quality; for example, for noisy input data, the interpretation of difference images is often difficult. Motivated by modern image-processing tools, we have developed two robust GPR attributes, which allow us to distinguish amplitude (contrast similarity) and time-shift (structural similarity) variations related to differences between individual time-lapse GPR data sets. We tested and evaluated our attributes using synthetic data of different complexity. Afterward, we applied them to a field data example, in which subsurface flow was induced by an artificial rainfall event. For all examples, we identified our structural similarity attribute to be a robust measure for highlighting time-lapse changes also in data with low signal-to-noise ratios. We determined that our new attribute-based workflow is a promising tool to analyze time-lapse GPR data, especially for imaging subsurface hydrological processes.
The link between cognitive scripts for consensual sexual interactions and attitudes towards sexual coercion was studied in 524 Polish high school students. We proposed that risky sexual scripts, containing risk elements linked to sexual aggression, would be associated with attitudes condoning sexual coercion. Pornography use and religiosity were included as predictors of participants’ risky sexual scripts and attitudes towards sexual coercion. Risky sexual scripts were linked to attitudes condoning sexual coercion. Pornography use was indirectly linked to attitudes condoning sexual coercion via risky sexual scripts. Religiosity showed a positive direct link with attitudes towards sexual coercion, but a negative indirect link through risky sexual scripts. The results are discussed regarding the significance of risky sexual scripts, pornography use, and religiosity in understanding attitudes towards sexual coercion as well as their implications for preventing sexually aggressive behaviour.
Attitudes Toward Doping
(2016)
This article examines whether a training program in ethical decision making can change young athletes’ doping attitudes. Fifty-two young elite athletes were randomly assigned to either an ethical decision-making training group or a standard-knowledge-based educational program group. Another 17 young elite athletes were recruited for no-treatment control purposes. The ethical decision-making training comprised six 30-min online sessions in which the participants had to work through 18 ethical dilemmas related to doping. The standard-knowledge-based educational program was also conducted in six online sessions of comparable length to that of the ethical training. A short version of the Performance Enhancement Attitude Scale was administered to measure the effects of the trainings on doping attitude. Prior to as well as after the intervention, the mean doping attitude scores of the young athletes were low to very low, indicating vehement rejections of doping. The results of our experiment showed that the ethical training led to an attenuation of these rejections. No intervention effect was found in the standard education group. The observed slight increase in the doping attitude score could be an indication that the ethical decision-making training was successful in breaking up the athletes’ stereotypical style of reasoning about doping.
A promising replacement for the radioactive sources commonly encountered in ion mobility spectrometers is a miniaturized, energy-efficient photoionization source that produce the reactant ions via soft X-radiation (2.8 keV). In order to successfully apply the photoionization source, it is imperative to know the spectrum of reactant ions and the subsequent ionization reactions leading to the detection of analytes. To that end, an ionization chamber based on the photoionization source that reproduces the ionization processes in the ion mobility spectrometer and facilitates efficient transfer of the product ions into a mass spectrometer was developed. Photoionization of pure gasses and gas mixtures containing air, N-2, CO2 and N2O and the dopant CH2Cl2 is discussed. The main product ions of photoionization are identified and compared with the spectrum of reactant ions formed by radioactive and corona discharge sources on the basis of literature data. The results suggest that photoionization by soft X-radiation in the negative mode is more selective than the other sources. In air, adduct ions of O-2 - with H2O and CO2 were exclusively detected. Traces of CO2 impact the formation of adduct ions of O-2 - and Cl -(upon addition of dopant) and are capable of suppressing them almost completely at high CO2 concentrations. Additionally, the ionization products of four alkyl nitrates (ethylene glycol dinitrate, nitroglycerin, erythritol tetranitrate and pentaerythritol tetranitrate) formed by atmospheric pressure chemical ionization induced by X-ray photoionization in different gasses (air, N-2 and N2O) and dopants (CH2Cl2, C2H5Br and CH3I) are investigated. The experimental studies are complemented by density functional theory calculations of the most important adduct ions of the alkyl nitrates (M) used for their spectrometric identification. In addition to the adduct ions [M + NO3](-) and [M + Cl](-), adduct ions such as [M + N2O2](-), [M + Br](-) and [M+ I](-) were detected, and their gas-phase structures and energetics are investigated by density functional theory calculations. Copyright (C) 2016 John Wiley & Sons, Ltd.
Although many behavioral studies have investigated the effect of processing fluency on subsequent recognition memory, little research has examined the neural mechanism of this phenomenon. The present study aimed to explore the electrophysiological correlates of the effects of processing fluency on subsequent recognition memory by using an event-related potential (ERP) approach. The masked repetition priming paradigm was used to manipulate processing fluency in the study phase, and the R/K paradigm was utilized to investigate which recognition memory process (familiarity or recollection) was affected by processing fluency in the test phase. Converging behavioral and ERP results indicated that increased processing fluency impaired subsequent recollection. Results from the analysis of ERP priming effects in the study phase indicated that increased perceptual processing fluency of object features, reflected by the N/P 190 priming effect, can hinder encoding activities, reflected by the LPC priming effect, which leads to worse subsequent recollection based recognition memory. These results support the idea that processing fluency can influence subsequent recognition memory and provide a potential neural mechanism underlying this effect. However, further studies are needed to examine whether processing fluency can affect subsequent familiarity.
We study operators on singular manifolds, here of conical or edge type, and develop a new general approach of representing asymptotics of solutions to elliptic equations close to the singularities. We introduce asymptotic parametrices, using tools from cone and edge pseudo-differential algebras. Our structures are motivated by models of many-particle physics with singular Coulomb potentials that contribute higher order singularities in Euclidean space, determined by the number of particles.
Balance, strength and power relationships may contain important information at various maturational stages to determine training priorities. Purpose: The objective was to examine maturity-specific relationships of static/dynamic balance with strength and power measures in young male athletes. Method: Soccer players (N = 130) aged 10-16 were assessed with the Stork and Y balance (YBT) tests. Strength/power measures included back extensor muscle strength, standing long jump (SLJ), countermovement jump (CMJ), and 3-hop jump tests. Associations between balance with strength/power variables were calculated according to peak-height-velocity (PHV). Results: There were significant medium-large sized correlations between all balance measures with back extensor strength (r =.486.791) and large associations with power (r =.511.827). These correlation coefficients were significantly different between pre-PHV and circa PHV as well as pre-PHV and post-PHV with larger associations in the more mature groups. Irrespective of maturity-status, SLJ was the best strength/ power predictor with the highest proportion of variance (12-47%) for balance (i.e., Stork eyes opened) and the YBT was the best balance predictor with the highest proportion of variance (43-78%) for all strength/ power variables. Conclusion: The associations between balance and muscle strength/power measures in youth athletes that increase with maturity may imply transfer effects from balance to strength/power training and vice versa in youth athletes.
Background: Despite extensive research in the past decades, the influence of genetics on cognitive functions in schizophrenia remains unclear. Dystrobrevin-binding protein 1 (DTNBP1) is one of the most promising candidate genes in schizophrenia. An association of DTNBP1 with cognitive dysfunction, particularly memory impairment, has been reported in a number of studies. However, the results remain inconsistent. The aim of this study was to measure the association between DTNBP1 polymorphisms and cognitive domains in a well-characterized sample. Methods: Ninety-one clinically stable schizophrenia outpatients underwent a battery of cognitive tests. Six single nucleotide polymorphisms (SNPs) of DTNBP1 were genotyped in all participants. Statistical and multivariate analyses were performed. Results: Factor analysis revealed 4 factors corresponding to distinct cognitive domains, namely sustained attention, set-shifting, executive functioning, and memory. We found a significant association of the rs909706 polymorphism with attention (p = 0.030) and a nonsignificant trend for set-shifting (p = 0.060). The other SNPs and haplotypes were not associated with cognitive function. Discussion: Replication of this finding in a larger sample is needed in order to confirm the importance of this particular polymorphism in the genetics of schizophrenia, particularly the distinct cognitive domains. In conclusion, the present study supports the involvement of DTNBP1 in the regulation of cognitive processes and demonstrates association in particular with sustained attention and set-shifting in schizophrenia patients. (C) 2016 S. Karger AG, Basel
Snowfall comprises a significant percentage of the annual water budget in High Mountain Asia (HMA), but snow water equivalent (SWE) is poorly constrained due to lack of in-situ measurements and complex terrain that limits the efficacy of modeling and observations. Over the past few decades, SWE has been estimated with passive microwave (PM) sensors with generally good results in wide, flat, terrain, and lower reliability in densely forested, complex, or high-elevation areas. In this study, we use raw swath data from five satellite - sensors the Special Sensor Microwave/Imager (SSMI) and Special Sensor Microwave Imager/Sounder (SSMIS) (1987-2015, F08, F11, F13, F17), Advanced Microwave Scanning Radiometer - Earth Observing System (AMSR-E, 2002-2011), AMSR2 (2012-2015), and the Global Precipitation Measurement (GPM, 2014-2015) - in order to understand the spatial and temporal structure of native sensor, topographic, and land cover biases in SWE estimates in HMA. We develop a thorough understanding of the uncertainties in our SWE estimates by examining the impacts of topographic parameters (aspect, relief, hillslope angle, and elevation), land cover, native sensor biases, and climate parameters (precipitation, temperature, and wind speed). HMA, with its high seasonality, large topographic gradients and low relief at high elevations provides an excellent context to examine a wide range of climatic, land-cover, and topographic settings to better constrain SWE uncertainties and potential sensor bias. Using a multi-parameter regression, we compare long-term SWE variability to forest fraction, maximal multiyear snow depth, topographic parameters, and long-term average wind speed across both individual sensor time series and a merged multi-sensor dataset. In regions where forest cover is extensive, it is the strongest control on SWE variability. In those regions where forest density is low (<5%), maximal snow depth dominates the uncertainty signal. In our regression across HMA, we find that forest fraction is the strongest control on SWE variability (75.8%), followed by maximal multi-year snow depth (7.82%), 90th percentile 10-m wind speed of a 10-year December-January-February (DJF) time series (5.64%), 25th percentile DJF 10-m wind speed (5.44%), and hillslope angle (5.24%). Elevation, relief, and terrain aspect show very low influence on SWE variability (<1%). We find that the GPM sensor provides the most robust regression results, and can be reliably used to estimate SWE in our study region. While forest cover and elevation have been integrated into many SWE algorithms, wind speed and long-term maximal snow depth have not. Our results show that wind redistribution of snow can have impacts on SWE, especially over large, flat, areas. Using our regression results, we have developed an understanding of sensor specific SWE uncertainties and their spatial patterns. The uncertainty maps developed in this study provide a first-order approximation of SWE-estimate reliability for much of HMA, and imply that high-fidelity SWE estimates can be produced for many high-elevation areas. (C) 2016 Elsevier Inc. All rights reserved.
This paper assesses the seasonality of the urban heat island (UHI) effect in the Greater London area (United Kingdom). Combining satellite-based observations and urban boundary layer climate modeling with the UrbClim model, the authors are able to address the seasonality of UHI intensity, on the basis of both land surface temperature (LST) and 2-m air temperature, for four individual times of the day (0130, 1030, 1330, and 2230 local time) and the daily means derived from them. An objective of this paper is to investigate whether the UHI intensities that are based on both quantities exhibit a similar hysteresis-like trajectory that is observed for LST when plotting the UHI intensity against the background temperature. The results show that the UrbClim model can satisfactorily reproduce both the observed urban rural LSTs and 2-m air temperatures as well as their differences and the hysteresis in the surface UHI. The hysteresis-like seasonality is largely absent in both the observed and modeled 2-m air temperatures, however. A sensitivity simulation of the UHI intensity to incoming solar radiation suggests that the hysteresis of the LST can mainly be attributed to the seasonal variation in incoming solar radiation.
People with mental disorders, especially personality disorders, often face low acceptance at work. This is particularly problematic when returning to work after sick leave, because it impedes reintegration into the former workplace. This study explores colleagues’ reactions towards a problematic worker dependent on the returning person’s reintegration strategy: The returning person undertaking changes in their behaviour is compared with the person requesting adjustments of the workplace. In an experimental study, 188 employed persons read one of four vignettes that described a return-to-work-situation of a problematic co-worker. Across all vignettes, the co-worker was depicted as having previously caused problems in the work team. In the first vignette, the co-worker did not change anything (control condition) when she returned to work; in the second, she asked for workplace adjustments; in the third vignette she initiated efforts to change her own behaviour; and the fourth vignette combined both workplace adjustments and behavioural change. Study participants were asked for their reactions towards the problematic co-worker. Vignettes that included a behavioural change evoked more positive reactions towards the co-worker than vignettes without any behavioural change. Asking for workplace adjustments alone did not yield more positive reactions compared to not initiating any change. When preparing employees with interactional problems for their return to work, it is not effective to only instruct them on their statutory entitlement for workplace adjustments. Instead, it is advisable to encourage them to proactively strive for behaviour changes.
Zur Wiedergutmachung nationalsozialistischen Unrechts garantiert Art. 116 Abs. 2 GG Abkömmlingen von in diskriminierender Weise ausgebürgerten Deutschen die deutsche Staatsangehörigkeit. Dadurch soll der Zustand wiederhergestellt werden, der ohne die Ausbürgerung bestehen würde. Daher wird insoweit regelmäßig auf das geltende Staatsangehörigkeitsrecht abgestellt. § 4 Abs. 4 StAG hat im Jahr 2000 eine Beschränkung der Weitergabe der deutschen Staatsangehörigkeit für im Ausland geborene Kinder deutscher Staatsangehöriger eingeführt, die selbst bereits im Ausland geboren wurden. Dadurch wird möglicherweise der Anwendungsbereich des Art. 116 Abs. 2 GG dauerhaft signifikant eingeschränkt; unter Umständen wird die Norm gar obsolet. Vor diesem Hintergrund wird das Spannungsverhältnis zwischen der uneingeschränkten Anwendung des § 4 Abs. 4 StAG mit dem verfassungsrechtlich verbürgerten Recht auf Wiedereinbürgerung von Kindern zu Unrecht ausgebürgerter Deutscher erörtert.
Arf-like Protein 3 (ARL3) Regulates Protein Trafficking and Ciliogenesis in Mouse Photoreceptors
(2016)
Arf-like protein 3 (ARL3) is a ubiquitous small GTPase expressed in ciliated cells of plants and animals. Germline deletion of Arl3 in mice causes multiorgan ciliopathy reminiscent of Bardet-Biedl or Joubert syndromes. As photoreceptors are elegantly compartmentalized and have cilia, we probed the function of ARL3 (ADP-ribosylation factor (Arf)-like 3 protein) by generating rod photoreceptor-specific (prefix (rod)) and retina-specific (prefix (ret)) Arl3 deletions. In predegenerate (rod)Arl3(-/-) mice, lipidated phototransduction proteins showed trafficking deficiencies, consistent with the role of ARL3 as a cargo displacement factor for lipid-binding proteins. By contrast, (ret)Arl3(-/-) rods and cones expressing Cre recombinase during embryonic development formed neither connecting cilia nor outer segments and degenerated rapidly. Absence of cilia infers participation of ARL3 in ciliogenesis and axoneme formation. Ciliogenesis was rescued, and degeneration was reversed in part by subretinal injection of adeno-associated virus particles expressing ARL3-EGFP. The conditional knock-out phenotypes permitted identification of two ARL3 functions, both in the GTP-bound form as follows: one as a regulator of intraflagellar transport participating in photoreceptor ciliogenesis and the other as a cargo displacement factor transporting lipidated protein to the outer segment. Surprisingly, a farnesylated inositol polyphosphate phosphatase only trafficked from the endoplasmic reticulum to the Golgi, thereby excluding it from a role in photoreceptor cilia physiology.
Arabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling
(2016)
Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the FORGETTER1 (FGT1) locus, with fgt1 mutants displaying reduced maintenance of heat-induced gene expression. FGT1 encodes the Arabidopsis thaliana orthologue of Strawberry notch (Sno), and the protein globally associates with the promoter regions of actively expressed genes in a heat-dependent fashion. FGT1 interacts with chromatin remodelers of the SWI/ SNF and ISWI families, which also display reduced heat stress memory. Genomic targets of the BRM remodeler overlap significantly with FGT1 targets. Accordingly, nucleosome dynamics at loci with altered maintenance of heat-induced expression are affected in fgt1. Together, our results suggest that by modulating nucleosome occupancy, FGT1 mediates stress-induced chromatin memory.
This report describes the aggregation behavior of an ABC-type ampholytic block copolypeptide, poly(ethylene oxide)-block-poly(L-lysine)-block-poly(L-glutamate), in aqueous media in dependence of pH. Polypeptide secondary structures and self-assemblies are investigated by circular dichroism (CD), Fourier transform infrared (FT-IR) and NMR spectroscopy, zeta potential measurements, analytical ultracentrifugation (AUC), dynamic/static light scattering (DLS/SLS), and cryogenic transmission electron microscopy (cryoTEM). The polymer chains tend to form vesicles when the hydrophobic polypeptide helix is located at the chain end (acidic pH) and are existing as single chains when it is located in the center and flanked by the two hydrophilic segments (basic pH). Precipitation occurs in the intermediate pH range due to polyion complexation of the charged polypeptide segments.
Variational methods are employed in situations where exact Bayesian inference becomes intractable due to the difficulty in performing certain integrals. Typically, variational methods postulate a tractable posterior and formulate a lower bound on the desired integral to be approximated, e.g. marginal likelihood. The lower bound is then optimised with respect to its free parameters, the so-called variational parameters. However, this is not always possible as for certain integrals it is very challenging (or tedious) to come up with a suitable lower bound. Here, we propose a simple scheme that overcomes some of the awkward cases where the usual variational treatment becomes difficult. The scheme relies on a rewriting of the lower bound on the model log-likelihood. We demonstrate the proposed scheme on a number of synthetic and real examples, as well as on a real geophysical model for which the standard variational approaches are inapplicable.
This article contributes to the debate on the use of performance information in the context of public sector performance management. Based on case studies, the authors analyze the appropriateness of the performance information provided in the newly established performance budgets of municipalities in Germany and Italy. They also examine the interest of politicians and senior managers in using such information for decision-making and monitoring within the municipal budget cycle. They find that the use of performance information is generally quite modest, and that the interest of different local actors varies to a great extent. Politicians are generally less interested in such information than top managers, particularly chief financial officers. The results are discussed by applying a theoretical framework based on institutional and legitimacy theories, and are compared with the literature on performance information use.
Background: Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)). Methods: Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (beta 2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-beta 2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human beta 2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human beta 2GPI or after CL-micelle absorption. Results: Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM a beta 2GPI and aCL. Anti-CL and anti-beta 2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and beta 2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL) + samples than in patients with APS. HumoAb against domain 1 recognized beta 2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-beta 2GPI humoAbs. Conclusions: The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.
Pleurotus ostreatus has been widely used as food because of its nutritional and medicinal properties. These have been attributed to the presence of macronutrients, minerals, vitamins, and amino acids, among other secondary metabolites. There are, however, few reports on the antimicrobial activities of different classes of purified compounds from P. ostreatus. This led to the current study, the objective of which was to chemically characterize the antibiotic activities of P. ()streams against selected human pathogenic bacteria and endophytic fungi. Chemical structures were determined using spectroscopic methods and by comparison with values of related structures reported in the literature. Pure compounds from P. ostreatus were tested in vitro against pathogenic bacteria (Staphylococcus aureus and Escherichia coli) and endophytic fungi (Pencillium digitatum and Fusarium prolferatum). A new compound, (E)-5,7-dimethoxy-6-(3-methylbuta-1,3-dienyl)-2H-chromen-2-one (5-methoxy-(E)-suberodiene) (compound 2), along with ergosterol (compound I.) and 5,7-dimethoxy-6-(3-methylbut-2-enyl)-2H-chromen-2-one (toddaculin; compound 3), were isolated from the fruiting bodies of P. ostreatus. The growth of S. aureus,E proliferatum, and P. digitatum colonies was inhibited in media containing compound 2, with minimum inhibitory concentrations closely comparable to those of conventional antibiotics.
Anti-Stokes resonant x-ray Raman scattering for atom specific and excited state selective dynamics
(2016)
Ultrafast electronic and structural dynamics of matter govern rate and selectivity of chemical reactions, as well as phase transitions and efficient switching in functional materials. Since x-rays determine electronic and structural properties with elemental, chemical, orbital and magnetic selectivity, short pulse x-ray sources have become central enablers of ultrafast science. Despite of these strengths, ultrafast x-rays have been poor at picking up excited state moieties from the unexcited ones. With time-resolved anti-Stokes resonant x-ray Raman scattering (AS-RXRS) performed at the LCLS, and ab initio theory we establish background free excited state selectivity in addition to the elemental, chemical, orbital and magnetic selectivity of x-rays. This unparalleled selectivity extracts low concentration excited state species along the pathway of photo induced ligand exchange of Fe(CO)(5) in ethanol. Conceptually a full theoretical treatment of all accessible insights to excited state dynamics with AS-RXRS with transform-limited x-ray pulses is given-which will be covered experimentally by upcoming transform-limited x-ray sources.
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.
Polyadenylation is a critical 3-end processing step during maturation of pre-mRNAs, and the length of the poly(A) tail affects mRNA stability, nuclear export and translation efficiency. The Arabidopsis thaliana genome encodes three canonical nuclear poly(A) polymerase (PAPS) isoforms fulfilling specialized functions, as reflected by their different mutant phenotypes. While PAPS1 affects several processes, such as the immune response, organ growth and male gametophyte development, the roles of PAPS2 and PAPS4 are largely unknown. Here we demonstrate that PAPS2 and PAPS4 promote flowering in a partially redundant manner. The enzymes act antagonistically to PAPS1, which delays the transition to flowering. The opposite flowering-time phenotypes in paps1 and paps2 paps4 mutants are at least partly due to decreased or increased FLC activity, respectively. In contrast to paps2 paps4 mutants, plants with increased PAPS4 activity flower earlier than the wild-type, concomitant with reduced FLC expression. Double mutant analyses suggest that PAPS2 and PAPS4 act independently of the autonomous pathway components FCA, FY and CstF64. The direct polyadenylation targets of the three PAPS isoforms that mediate their effects on flowering time do not include FLC sense mRNA and remain to be identified. Thus, our results uncover a role for canonical PAPS isoforms in flowering-time control, raising the possibility that modulating the balance of the isoform activities could be used to fine tune the transition to flowering. Significance Statement The length of the poly(A) tail affects mRNA stability, nuclear export and translation efficiency. Arabidopsis has three isoforms of nuclear poly(A) polymerase (PAPS): PAPS1 plays a major role in organ growth and plant defence. Here we show that PAPS2 and PAPS4 redundantly promote flowering and act antagonistically to PAPS1, which delays flowering. We suggest that modulating the activity of these isoforms fine-tunes the transition to flowering.
Acyclicity constraints are prevalent in knowledge representation and applications where acyclic data structures such as DAGs and trees play a role. Recently, such constraints have been considered in the satisfiability modulo theories (SMT) framework, and in this paper we carry out an analogous extension to the answer set programming (ASP) paradigm. The resulting formalism, ASP modulo acyclicity, offers a rich set of primitives to express constraints related to recursive structures. In the technical results of the paper, we relate the new generalization with standard ASP by showing (i) how acyclicity extensions translate into normal rules, (ii) how weight constraint programs can be instrumented by acyclicity extensions to capture stability in analogy to unfounded set checking, and (iii) how the gap between supported and stable models is effectively closed in the presence of such an extension. Moreover, we present an efficient implementation of acyclicity constraints by incorporating a respective propagator into the state-of-the-art ASP solver CLASP. The implementation provides a unique combination of traditional unfounded set checking with acyclicity propagation. In the experimental part, we evaluate the interplay of these orthogonal checks by equipping logic programs with supplementary acyclicity constraints. The performance results show that native support for acyclicity constraints is a worthwhile addition, furnishing a complementary modeling construct in ASP itself as well as effective means for translation-based ASP solving.
A topic of intense current investigation pursues the question of how the highly crowded environment of biological cells affects the dynamic properties of passively diffusing particles. Motivated by recent experiments we report results of extensive simulations of the motion of a finite sized tracer particle in a heterogeneously crowded environment made up of quenched distributions of monodisperse crowders of varying sizes in finite circular two-dimensional domains. For given spatial distributions of monodisperse crowders we demonstrate how anomalous diffusion with strongly non-Gaussian features arises in this model system. We investigate both biologically relevant situations of particles released either at the surface of an inner domain or at the outer boundary, exhibiting distinctly different features of the observed anomalous diffusion for heterogeneous distributions of crowders. Specifically we reveal an asymmetric spreading of tracers even at moderate crowding. In addition to the mean squared displacement (MSD) and local diffusion exponent we investigate the magnitude and the amplitude scatter of the time averaged MSD of individual tracer trajectories, the non-Gaussianity parameter, and the van Hove correlation function. We also quantify how the average tracer diffusivity varies with the position in the domain with a heterogeneous radial distribution of crowders and examine the behaviour of the survival probability and the dynamics of the tracer survival probability. Inter alia, the systems we investigate are related to the passive transport of lipid molecules and proteins in two-dimensional crowded membranes or the motion in colloidal solutions or emulsions in effectively two-dimensional geometries, as well as inside supercrowded, surface adhered cells.
We consider the diffusion-advection problem in two simple cellular flow models ( often invoked as examples of subdiffusive tracer motion) and concentrate on the intermediate time range, in which the tracer motion indeed may show subdiffusion. We perform extensive numerical simulations of the systems under different initial conditions and show that the pure intermediate-time subdiffusion regime is only evident when the particles start at the border between different cells, i.e., at the separatrix, and is less pronounced or absent for other initial conditions. The motion moreover shows quite peculiar aging properties, which are also mirrored in the behavior of the time-averaged mean squared displacement for single trajectories. This kind of behavior is due to the complex motion of tracers trapped inside the cell and is absent in classical models based on continuous-time random walks with no dynamics in the trapped state.
We investigate the ensemble and time averaged mean squared displacements for particle diffusion in a simple model for disordered media by assuming that the local diffusivity is both fluctuating in time and has a deterministic average growth or decay in time. In this study we compare computer simulations of the stochastic Langevin equation for this random diffusion process with analytical results. We explore the regimes of normal Brownian motion as well as anomalous diffusion in the sub- and superdiffusive regimes. We also consider effects of the inertial term on the particle motion. The investigation of the resulting diffusion is performed for unconfined and confined motion.
We investigate the ensemble and time averaged mean squared displacements for particle diffusion in a simple model for disordered media by assuming that the local diffusivity is both fluctuating in time and has a deterministic average growth or decay in time. In this study we compare computer simulations of the stochastic Langevin equation for this random diffusion process with analytical results. We explore the regimes of normal Brownian motion as well as anomalous diffusion in the sub- and superdiffusive regimes. We also consider effects of the inertial term on the particle motion. The investigation of the resulting diffusion is performed for unconfined and confined motion.
Self-assembling biomolecules provide attractive templates for the preparation of metallic nanostructures. However, the intuitive transfer of the "outer shape" of the assembled macromolecules to the final metallic particle depends on the intermolecular forces among the biomolecules which compete with interactions between template molecules and the metal during metallization. The shape of the bio-template may thus be more dynamic than generally assumed. Here, we have studied the metallization of phospholipid nanodiscs which are discoidal particles of similar to 10 nm diameter containing a lipid bilayer similar to 5 nm thick. Using negatively charged lipids, electrostatic adsorption of amine-coated Au nanoparticles was achieved and followed by electroless gold deposition. Whereas Au nanoparticle adsorption preserves the shape of the bio-template, metallization proceeds via invasion of Au into the hydrophobic core of the nanodisc. Thereby, the lipidic phase induces a lateral growth that increases the diameter but not the original thickness of the template. Infrared spectroscopy reveals lipid expansion and suggests the existence of internal gaps in the metallized nanodiscs, which is confirmed by surface-enhanced Raman scattering from the encapsulated lipids. Interference of metallic growth with non-covalent interactions can thus become itself a shape-determining factor in the metallization of particularly soft and structurally anisotropic biomaterials.
With increasing numbers of flights worldwide and a continuing rise in airport traffic, air-traffic management is faced with a number of challenges. These include monitoring, reporting, planning, and problem analysis of past and current air traffic, e.g., to identify hotspots, minimize delays, or to optimize sector assignments to air-traffic controllers. To cope with these challenges, cyber worlds can be used for interactive visual analysis and analytical reasoning based on aircraft trajectory data. However, with growing data size and complexity, visualization requires high computational efficiency to process that data within real-time constraints. This paper presents a technique for real-time animated visualization of massive trajectory data. It enables (1) interactive spatio-temporal filtering, (2) generic mapping of trajectory attributes to geometric representations and appearance, and (3) real-time rendering within 3D virtual environments such as virtual 3D airport or 3D city models. Different visualization metaphors can be efficiently built upon this technique such as temporal focus+context, density maps, or overview+detail methods. As a general-purpose visualization technique, it can be applied to general 3D and 3+1D trajectory data, e.g., traffic movement data, geo-referenced networks, or spatio-temporal data, and it supports related visual analytics and data mining tasks within cyber worlds.
Species diversity is changing globally and locally, but the complexity of ecological communities hampers a general understanding of the consequences of animal species loss on ecosystem functioning. High animal diversity increases complementarity of herbivores but also increases feeding rates within the consumer guild. Depending on the balance of these counteracting mechanisms, species-rich animal communities may put plants under top-down control or may release them from grazing pressure. Using a dynamic food-web model with body-mass constraints, we simulate ecosystem functions of 20,000 communities of varying animal diversity. We show that diverse animal communities accumulate more biomass and are more exploitative on plants, despite their higher rates of intra-guild predation. However, they do not reduce plant biomass because the communities are composed of larger, and thus energetically more efficient, plant and animal species. This plasticity of community body-size structure reconciles the debate on the consequences of animal species loss for primary productivity.
Was sollten Mitarbeiter in einem empirisch ausgerichteten Forschungsprojekt können, und welche Kernkompetenzen sollte die Ausbildung an den Universitäten daher vermitteln? Die Antworten auf diese Fragen hängen – wie sollte es anders sein – von der inhaltlichen Fragestellung und methodischen Ausrichtung des jeweiligen Forschungsprojektes ab. Natürlich sollten Projektmitarbeiter über Vorkenntnisse zum Forschungsthema verfügen. Natürlich sollten Kenntnisse des projektspezifischen (statistischen) Methodenarsenals vorliegen.
Ancient DNA studies have revolutionized the study of extinct species and populations, providing insights on phylogeny, phylogeography, admixture and demographic history. However, inferences on behaviour and sociality have been far less frequent. Here, we investigate the complete mitochondrial genomes of extinct Late Pleistocene cave bears and middle Holocene brown bears that each inhabited multiple geographically proximate caves in northern Spain. In cave bears, we find that, although most caves were occupied simultaneously, each cave almost exclusively contains a unique lineage of closely related haplotypes. This remarkable pattern suggests extreme fidelity to their birth site in cave bears, best described as homing behaviour, and that cave bears formed stable maternal social groups at least for hibernation. In contrast, brown bears do not show any strong association of mitochondrial lineage and cave, suggesting that these two closely related species differed in aspects of their behaviour and sociality. This difference is likely to have contributed to cave bear extinction, which occurred at a time in which competition for caves between bears and humans was likely intense and the ability to rapidly colonize new hibernation sites would have been crucial for the survival of a species so dependent on caves for hibernation as cave bears. Our study demonstrates the potential of ancient DNA to uncover patterns of behaviour and sociality in ancient species and populations, even those that went extinct many tens of thousands of years ago.
Dromedaries have been fundamental to the development of human societies in arid landscapes and for long-distance trade across hostile hot terrains for 3,000 y. Today they continue to be an important livestock resource in marginal agro-ecological zones. However, the history of dromedary domestication and the influence of ancient trading networks on their genetic structure have remained elusive. We combined ancient DNA sequences of wild and early-domesticated dromedary samples from arid regions with nuclear microsatellite and mitochondrial genotype information from 1,083 extant animals collected across the species’ range. We observe little phylogeographic signal in the modern population, indicative of extensive gene flow and virtually affecting all regions except East Africa, where dromedary populations have remained relatively isolated. In agreement with archaeological findings, we identify wild dromedaries from the southeast Arabian Peninsula among the founders of the domestic dromedary gene pool. Approximate Bayesian computations further support the “restocking from the wild” hypothesis, with an initial domestication followed by introgression from individuals from wild, now-extinct populations. Compared with other livestock, which show a long history of gene flow with their wild ancestors, we find a high initial diversity relative to the native distribution of the wild ancestor on the Arabian Peninsula and to the brief coexistence of early-domesticated and wild individuals. This study also demonstrates the potential to retrieve ancient DNA sequences from osseous remains excavated in hot and dry desert environments.
Context. The massive Wolf-Rayet type star WR102c is located near the Quintuplet Cluster, one of the three massive star clusters in the Galactic centre region. Previous studies indicated that WR102c may have a dusty circumstellar nebula and is among the main ionising sources of the Sickle Nebula associated with the Quintuplet Cluster. Aims. The goals of our study are to derive the stellar parameters of WR102c from the analysis of its spectrum and to investigate its stellar and nebular environment. Methods. We obtained observations with the ESO VLT integral field spectrograph SINFONI in the K-band, extracted the stellar spectra, and analysed them by means of stellar atmosphere models. Results. Our new analysis supersedes the results previously reported for WR102c. We significantly decrease its bolometric luminosity and hydrogen content. We detect four early OB type stars close to WR102c. These stars have radial velocities similar to that of WR102c. We suggest that together with WR102c these stars belong to a distinct star cluster with a total mass of similar to 1000 M-circle dot. We identify a new WR nebula around WR102c in the SINFONI map of the di ff use Br gamma emission and in the HST Pa ff images. The Br gamma line at di ff erent locations is not significantly broadened and similar to the width of nebular emission elsewhere in the H i i region around WR102c. Conclusions. The massive star WR102c located in the Galactic centre region resides in a star cluster containing additional early-type stars. The stellar parameters of WR102c are typical for hydrogen-free WN6 stars. We identify a nebula surrounding WR102c that has a morphology similar to other nebulae around hydrogen-free WR stars, and propose that the formation of this nebula is linked to interaction of the fast stellar wind with the matter ejected at a previous evolutionary stage of WR102c.
The slicing facility FemtoSpeX at BESSY II offers unique opportunities to study photo-induced dynamics on femtosecond time scales by means of X-ray magnetic circular dichroism, resonant and non-resonant X-ray diffraction, and X-ray absorption spectroscopy experiments in the soft X-ray regime. Besides femtosecond X-ray pulses, slicing sources inherently also produce a so-called `halo' background with a different time structure, polarization and pointing. Here a detailed experimental characterization of the halo radiation is presented, and a method is demonstrated for its correct and unambiguous removal from femtosecond time-resolved data using a special laser triggering scheme as well as analytical models. Examples are given for time-resolved measurements with corresponding halo correction, and errors of the relevant physical quantities caused by either neglecting or by applying a simplified model to describe this background are estimated.
The analytical evaluation of diurnal temperature variation in riverbed sediments provides detailed information on exchange fluxes between rivers and groundwater. The underlying assumption of the stationary, one-dimensional vertical flow field is frequently violated in natural systems where subsurface water flow often has a significant horizontal component. In this paper, we present a new methodology for identifying the geometry of the subsurface flow field using vertical temperature profiles. The statistical analyses are based on model optimisation and selection and are used to evaluate the shape of vertical amplitude ratio profiles. The method was applied to multiple profiles measured around in-stream geomorphological structures in a losing reach of a gravel bed river. The predominant subsurface flow field was systematically categorised in purely vertical and horizontal (hyporheic, parafluvial) components. The results highlight that river groundwater exchange flux at the head, crest and tail of geomorphological structures significantly deviated from the one-dimensional vertical flow, due to a significant horizontal component. The geometry of the subsurface water flow depended on the position around the geomorphological structures and on the river level. The methodology presented in this paper features great potential for characterising the spatial patterns and temporal dynamics of complex subsurface flow geometries by using measured temperature time series in vertical profiles. (C) 2016 Elsevier B.V. All rights reserved.
The folding of single-stranded telomeric DNA into guanine (G) quadruplexes is a conformational change that plays a major role in sensing and drug targeting. The telomeric DNA can be placed on DNA origami nanostructures to make the folding process extremely selective for K+ ions even in the presence of high Na+ concentrations. Here, we demonstrate that the K+-selective G-quadruplex formation is reversible when using a cryptand to remove K+ from the G-quadruplex. We present a full characterization of the reversible switching between single-stranded telomeric DNA and G-quadruplex structures using Forster resonance energy transfer (FRET) between the dyes fluorescein (FAM) and cyanine3 (Cy3). When attached to the DNA origami platform, the G-quadruplex switch can be incorporated into more complex photonic networks, which is demonstrated for a three-color and a four-color FRET cascade from FAM over Cy3 and Cy5 to IRDye700 with G-quadruplex-Cy3 acting as a switchable transmitter.
The folding of single-stranded telomeric DNA into guanine (G) quadruplexes is a conformational change that plays a major role in sensing and drug targeting. The telomeric DNA can be placed on DNA origami nanostructures to make the folding process extremely selective for K+ ions even in the presence of high Na+ concentrations. Here, we demonstrate that the K+-selective G-quadruplex formation is reversible when using a cryptand to remove K+ from the G-quadruplex. We present a full characterization of the reversible switching between single-stranded telomeric DNA and G-quadruplex structures using Förster resonance energy transfer (FRET) between the dyes fluorescein (FAM) and cyanine3 (Cy3). When attached to the DNA origami platform, the G-quadruplex switch can be incorporated into more complex photonic networks, which is demonstrated for a three-color and a four-color FRET cascade from FAM over Cy3 and Cy5 to IRDye700 with G-quadruplex-Cy3 acting as a switchable transmitter.
An innovative approach to improve SRTM DEM using multispectral imagery and artificial neural network
(2016)
Although the Shuttle Radar Topography Mission [SRTM) data are a publicly accessible Digital Elevation Model [DEM) provided at no cost, its accuracy especially at forested area is known to be limited with root mean square error (RMSE) of approx. 14 m in Singapore's forested area. Such inaccuracy is attributed to the 5.6 cm wavelength used by SRTM that does not penetrate vegetation well. This paper considers forested areas of central catchment of Singapore as a proof of concept of an approach to improve the SRTM data set. The approach makes full use of (1) the introduction of multispectral imagery (Landsat 8), of 30 m resolution, into SRTM data; (2) the Artificial Neural Network (ANN) to flex its known strengths in pattern recognition and; (3) a reference DEM of high accuracy (1 m) derived through the integration of stereo imaging of worldview-1 and extensive ground survey points. The study shows a series of significant improvements of the SRTM when assessed with the reference DEM of 2 different areas, with RMSE reduction of ∼68% (from 13.9 m to 4.4 m) and ∼52% (from 14.2 m to 6.7 m). In addition, the assessment of the resulting DEM also includes comparisons with simple denoising methodology (Low Pass Filter) and commercially available product called NEXTMap® World 30™.
Previous research on open innovation (OI) has primarily focused on the organisational level of R&D intensive industries. With this paper, we contribute to research on the individual level of analysis by analysing specific perspectives in the context of creative industries. Our study is based on 36 interviews with Haute cuisine chefs in France, Germany, Great Britain, Italy, Spain, Sweden, and Switzerland listed in the 2012 Michelin Guide. Building on the OI capability concept, our results demonstrate that chefs use absorptive and desorptive capacity (AC, DC) as means to generate and market culinary innovations, respectively. Moreover, we found that chefs almost exclusively rely on their own inventive and innovative capabilities in the early stages of the culinary innovation process. In subsequent phases, however, chefs increasingly integrate other sources such as employees, suppliers, and guests. Our study contributes to the literature in two ways. First, we research the individual level within the OI process, and second, we provide insight into OI practices in the creative industries.
The resonance frequency of the transmission response in layered half-space model is important in the study of site effect because it is the frequency where the shake-ability of the ground is enhanced significantly. In practice, it is often determined by the H/V ratio technique in which the peak frequency of recorded H/V spectral ratio is interpreted as the resonance frequency. Despite of its importance, there has not been any formula of the resonance frequency of the layered half-space structure. In this paper, a simple approximate formula of the fundamental resonance frequency is presented after an exact formula in explicit form of the response function of vertically SH incident wave is obtained. The formula is in similar form with the one used in H/V ratio technique but it reflects several major effects of the model to the resonance frequency such as the arrangement of layers, the impedance contrast between layers and the half-space. Therefore, it could be considered as an improved formula used in H/V ratio technique. The formula also reflects the consistency between two approaches of the H/V ratio technique based on SH body waves or Rayleigh surface waves on the peak frequency under high impedance contrast condition. This formula is in explicit form and, therefore, may be used in the direct and inverse problem efficiently. A numerical illustration of the improved formula for an actual layered half-space model already investigated by H/V ratio technique is presented to demonstrate its new features and its improvement to the currently used formula.
Aims. Doubly ionized silicon (Si III) is a powerful tracer of diffuse ionized gas inside and outside of galaxies. It can be observed in the local Universe in ultraviolet (UV) absorption against bright extragalactic background sources. We here present an extensive study of intervening Si III-selected absorbers and study the properties of the warm circumgalactic medium (CGM) around low-redshift (z <= 0.1) galaxies. Methods. We analyzed the UV absorption spectra of 303 extragalactic background sources, as obtained with the Cosmic Origins Spectrograph (COS) on-board the Hubble Space Telescope (HST). We developed a geometrical model for the absorption-cross section of the CGM around the local galaxy population and compared the observed Si III absorption statistics with predictions provided by the model. We also compared redshifts and positions of the absorbers with those of similar to 64 000 galaxies using archival galaxy-survey data to investigate the relation between intervening Si III absorbers and the CGM. Results. Along a total redshift path of Delta z approximate to 24, we identify 69 intervening Si III systems that all show associated absorption from other low and high ions (e.g., H I, Si II, Si IV, C II, C IV). We derive a bias-corrected number density of dN/dz(Si III) = 2.5 +/- 0.4 for absorbers with column densities log N(Si III) > 12.2, which is similar to 3 times the number density of strong Mg II systems at z = 0. This number density matches the expected cross section of a Si III absorbing CGM around the local galaxy population with a mean covering fraction of < f(c)> = 0.69. For the majority (similar to 60 percent) of the absorbers, we identify possible host galaxies within 300 km s(-1) of the absorbers and derive impact parameters rho < 200 kpc, demonstrating that the spatial distributions of Si III absorbers and galaxies are highly correlated. Conclusions. Our study indicates that the majority of Si III-selected absorbers in our sample trace the CGM of nearby galaxies within their virial radii at a typical covering fraction of similar to 70 percent. We estimate that diffuse gas in the CGM around galaxies, as traced by Si III, contains substantially more (more than twice as much) baryonic mass than their neutral interstellar medium.
During the summer of 2013, a 4-month spectroscopic campaign took place to observe the variabilities in three Wolf-Rayet stars. The spectroscopic data have been analysed for WR 134 (WN6b), to better understand its behaviour and long-term periodicity, which we interpret as arising from corotating interaction regions (CIRs) in the wind. By analysing the variability of the He ii lambda 5411 emission line, the previously identified period was refined to P = 2.255 +/- 0.008 (s.d.) d. The coherency time of the variability, which we associate with the lifetime of the CIRs in the wind, was deduced to be 40 +/- 6 d, or similar to 18 cycles, by cross-correlating the variability patterns as a function of time. When comparing the phased observational grey-scale difference images with theoretical grey-scales previously calculated from models including CIRs in an optically thin stellar wind, we find that two CIRs were likely present. A separation in longitude of Delta I center dot a parts per thousand integral 90A degrees was determined between the two CIRs and we suggest that the different maximum velocities that they reach indicate that they emerge from different latitudes. We have also been able to detect observational signatures of the CIRs in other spectral lines (C iv lambda lambda 5802,5812 and He i lambda 5876). Furthermore, a DAC was found to be present simultaneously with the CIR signatures detected in the He i lambda 5876 emission line which is consistent with the proposed geometry of the large-scale structures in the wind. Small-scale structures also show a presence in the wind, simultaneously with the larger scale structures, showing that they do in fact co-exist.
An Exploration of Rhythmic Grouping of Speech Sequences by French- and German-Learning Infants
(2016)
Rhythm in music and speech can be characterized by a constellation of several acoustic cues. Individually, these cues have different effects on rhythmic perception: sequences of sounds alternating in duration are perceived as short-long pairs (weak-strong/iambic pattern), whereas sequences of sounds alternating in intensity or pitch are perceived as loud-soft, or high-low pairs (strong-weak/trochaic pattern). This perceptual bias—called the Iambic-Trochaic Law (ITL)–has been claimed to be an universal property of the auditory system applying in both the music and the language domains. Recent studies have shown that language experience can modulate the effects of the ITL on rhythmic perception of both speech and non-speech sequences in adults, and of non-speech sequences in 7.5-month-old infants. The goal of the present study was to explore whether language experience also modulates infants’ grouping of speech. To do so, we presented sequences of syllables to monolingual French- and German-learning 7.5-month-olds. Using the Headturn Preference Procedure (HPP), we examined whether they were able to perceive a rhythmic structure in sequences of syllables that alternated in duration, pitch, or intensity. Our findings show that both French- and German-learning infants perceived a rhythmic structure when it was cued by duration or pitch but not intensity. Our findings also show differences in how these infants use duration and pitch cues to group syllable sequences, suggesting that pitch cues were the easier ones to use. Moreover, performance did not differ across languages, failing to reveal early language effects on rhythmic perception. These results contribute to our understanding of the origin of rhythmic perception and perceptual mechanisms shared across music and speech, which may bootstrap language acquisition.
Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5 end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.
An ellipsometric approach towards the description of inhomogeneous polymer-based Langmuir layers
(2016)
The applicability of nulling-based ellipsometric mapping as a complementary method next to Brewster angle microscopy (BAM) and imaging ellipsometry (IE) is presented for the characterization of ultrathin films at the air-water interface. First, the methodology is demonstrated for a vertically nonmoving Langmuir layer of star-shaped, 4-arm poly(omega-pentadecalactone) (PPDL-D4). Using nulling-based ellipsometric mapping, PPDL-D4-based inhomogeneously structured morphologies with a vertical dimension in the lower nm range could be mapped. In addition to the identification of these structures, the differentiation between a monolayer and bare water was possible. Second, the potential and limitations of this method were verified by applying it to more versatile Langmuir layers of telechelic poly[(rac-lactide)-co-glycolide]-diol (PLGA). All ellipsometric maps were converted into thickness maps by introduction of the refractive index that was derived from independent ellipsometric experiments, and the result was additionally evaluated in terms of the root mean square roughness, R-q. Thereby, a three-dimensional view into the layers was enabled and morphological inhomogeneity could be quantified.
Surveys for more than 9,500 households were conducted in the growing seasons 2002/2003 or 2003/2004 in eleven African countries: Burkina Faso, Cameroon, Ghana, Niger and Senegal in western Africa; Egypt in northern Africa; Ethiopia and Kenya in eastern Africa; South Africa, Zambia and Zimbabwe in southern Africa. Households were chosen randomly in districts that are representative for key agro-climatic zones and farming systems. The data set specifies farming systems characteristics that can help inform about the importance of each system for a country’s agricultural production and its ability to cope with short- and long-term climate changes or extreme weather events. Further it informs about the location of smallholders and vulnerable systems and permits benchmarking agricultural systems characteristics.
The amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominently for APLP1, and (ii) by reducing the concentrations of neurotrophic soluble APP/APLP ectodomains.
The general electromagnetic fluctuation theory is a powerful tool to analyze the magnetic fluctuation spectrum of a plasma. Recent works utilizing this theory for a magnetized non-relativistic isotropic Maxwellian electron-proton plasma have demonstrated that the equilibrium ratio of vertical bar delta B vertical bar/B-0 can be as high as 10(-12). This value results from the balance between spontaneous emission of fluctuations and their damping, and it is considerably smaller than the observed value vertical bar delta B vertical bar/B-0 in the solar wind at 1 au, where 10(-3) less than or similar to vertical bar delta B vertical bar/B-0 less than or similar to 10(-1). In the present manuscript, we consider an anisotropic bi-Maxwellian distribution function to investigate the effect of plasma instabilities on the magnetic field fluctuations. We demonstrate that these instabilities strongly amplify the magnetic field fluctuations and provide a sufficient mechanism to explain the observed value of vertical bar delta B vertical bar/B-0 in the solar wind at 1 au.
In this work, three ligands produced from amino acids were synthesized and used to produce five bis- and PEPPSI-type palladium-NHC complexes using a novel synthesis route from sustainable starting materials. Three of these complexes were used as precatalysts in the aqueous-phase Suzuki-Miyaura coupling of various substrates displaying high activity. TEM and mercury poisoning experiments provide evidence for Pd-nanoparticle formation stabilized in water.
Amides as thermo-sensitive tracers for investigating the thermal state of geothermal reservoirs
(2016)
The application of thermo-sensitive tracers is a promising technique for evaluating the thermal state of geothermal reservoirs. To extend the compound spectrum for hydrolyzable compounds to reservoir temperatures between 100 and 200 degrees C carboxamides were studied. The kinetic parameters of 17 self-synthesized amides were determined in hydrothermal batch and autoclave experiments. The influence of the molecular structure and the role of pH/pOH on hydrolysis kinetics were studied. Additionally, the thermal stabilities of the hydrolysis products were evaluated. The results demonstrate the high potential of tracers based on amide hydrolysis for use in medium enthalpy reservoirs. (C) 2016 Elsevier Ltd. All rights reserved.
Air pollution is the number one environmental cause of premature deaths in Europe. Despite extensive regulations, air pollution remains a challenge, especially in urban areas. For studying summertime air quality in the Berlin–Brandenburg region of Germany, the Weather Research and Forecasting Model with Chemistry (WRF-Chem) is set up and evaluated against meteorological and air quality observations from monitoring stations as well as from a field campaign conducted in 2014. The objective is to assess which resolution and level of detail in the input data is needed for simulating urban background air pollutant concentrations and their spatial distribution in the Berlin–Brandenburg area. The model setup includes three nested domains with horizontal resolutions of 15, 3 and 1 km and anthropogenic emissions from the TNO-MACC III inventory. We use RADM2 chemistry and the MADE/SORGAM aerosol scheme. Three sensitivity simulations are conducted updating input parameters to the single-layer urban canopy model based on structural data for Berlin, specifying land use classes on a sub-grid scale (mosaic option) and downscaling the original emissions to a resolution of ca. 1 km × 1 km for Berlin based on proxy data including traffic density and population density. The results show that the model simulates meteorology well, though urban 2 m temperature and urban wind speeds are biased high and nighttime mixing layer height is biased low in the base run with the settings described above. We show that the simulation of urban meteorology can be improved when specifying the input parameters to the urban model, and to a lesser extent when using the mosaic option. On average, ozone is simulated reasonably well, but maximum daily 8 h mean concentrations are underestimated, which is consistent with the results from previous modelling studies using the RADM2 chemical mechanism. Particulate matter is underestimated, which is partly due to an underestimation of secondary organic aerosols. NOx (NO + NO2) concentrations are simulated reasonably well on average, but nighttime concentrations are overestimated due to the model's underestimation of the mixing layer height, and urban daytime concentrations are underestimated. The daytime underestimation is improved when using downscaled, and thus locally higher emissions, suggesting that part of this bias is due to deficiencies in the emission input data and their resolution. The results further demonstrate that a horizontal resolution of 3 km improves the results and spatial representativeness of the model compared to a horizontal resolution of 15 km. With the input data (land use classes, emissions) at the level of detail of the base run of this study, we find that a horizontal resolution of 1 km does not improve the results compared to a resolution of 3 km. However, our results suggest that a 1 km horizontal model resolution could enable a detailed simulation of local pollution patterns in the Berlin–Brandenburg region if the urban land use classes, together with the respective input parameters to the urban canopy model, are specified with a higher level of detail and if urban emissions of higher spatial resolution are used.
Ainmianus Marcellinus
(2016)
We analyze a general class of difference operators H-epsilon = T-epsilon + V-epsilon on l(2)(((epsilon)Z)(d)), where V-epsilon is a multi-well potential and epsilon is a small parameter. We construct approximate eigenfunctions in neighbourhoods of the different wells and give weighted l(2)-estimates for the difference of these and the exact eigenfunctions of the associated Dirichlet-operators.
A 2-fold thermoresponsive diblock copolymer PSPP430-b-PNIPAM(200) consisting of a zwitterionic polysulfobetaine (PSPP) block and a nonionic poly(N-isopropylacrylamide) (PNIPAM) block is prepared by successive RAFT polymerizations. In aqueous solution, the corresponding homopolymers PSPP and PNIPAM feature both upper and lower critical solution temperature (UCST and LCST) behavior, respectively. The diblock copolymer exhibits thermally induced "schizophrenic" aggregation behavior in aqueous solutions. Moreover, the ion sensitivity of the, cloud point of the zwitterionic PSPP block to both the ionic strength and the nature of the salt offers the possibility to create switchable systems which respond sensitively to changes of the temperature and of the electrolyte type and concentration. The diblock copolymer solutions in D2O are investigated by means of turbidimetry and small-angle neutron scattering (SANS) with respect to the phase behavior and the self-assembled structures in dependence on temperature and electrolyte content. Marked, differences of the aggregation below the UCST-type and above the LCST-type transition are observed. The addition of a small amount of NaBr (0.004 M) does not affect the overall behavior, and only the UCST-type transition and aggregate structures are slightly altered, reflecting the well-known ion sensitivity of the zwitterionic PSPP block.
We study the properties of ageing Scher-Montroll transport in terms of a biased subdiffusive continuous time random walk in which the waiting times between consecutive jumps of the charge carriers are distributed according to the power law probability with . As we show, the dynamical properties of the Scher-Montroll transport depend on the ageing time span between the initial preparation of the system and the start of the observation. The Scher-Montroll transport theory was originally shown to describe the photocurrent in amorphous solids in the presence of an external electric field, but it has since been used in many other fields of physical sciences, in particular also in the geophysical context for the description of the transport of tracer particles in subsurface aquifers. In the absence of ageing () the photocurrent of the classical Scher-Montroll model or the breakthrough curves in the groundwater context exhibit a crossover between two power law regimes in time with the scaling exponents and . In the presence of ageing a new power law regime and an initial plateau regime of the current emerge. We derive the different power law regimes and crossover times of the ageing Scher-Montroll transport and show excellent agreement with simulations of the process. Experimental data of ageing Scher-Montroll transport in polymeric semiconductors are shown to agree well with the predictions of our theory.
A growing number of local energy conflicts around wind power and power-grid extensions are slowing down the deployment of the German Energiewende. In this paper, a local conflict on wind energy in the state of Baden-Württemberg is analysed in detail. In the little community of Engelsbrand, local opposition against a planned wind park was able to turn around a set of favourable a priori conditions, such as a supporting state government planning process, a local supporter group, a transparent planning process, including a majority vote pro wind energy, and a round table discussion. Distancing itself from the NIMBY-explanation (‘Not In My Back Yard’), the paper applies insights from discourse network analysis and micro-sociology in order to study the local conflict dynamics. Special attention is given to the resource mobilisation strategies of the opponents, including social networks, mass and social media use. The paper ends by drawing some general conclusions for the German Energiewende.
A synchronization experiment on two mutual interacting organ pipes is compared with a theoretical model which takes into account the coupling mechanisms by the underlying first principles of fluid mechanics and aeroacoustics. The focus is on the Arnold-tongue, a mathematical object in the parameter space of detuning and coupling strength which quantitatively captures the interaction of the synchronized sound sources. From the experiment, a nonlinearly shaped Arnold-tongue is obtained, describing the coupling of the synchronized pipe-pipe system. This is in contrast to the linear shaped Arnold-tongue found in a preliminary experiment of the coupled system pipe-loudspeaker. To understand the experimental result, a coarse-grained model of two nonlinear coupled self-sustained oscillators is developed. The model, integrated numerically, is in very good agreement with the synchronization experiment for separation distances of the pipes in the far field and in the intermediate field. The methods introduced open the door for a deeper understanding of the fundamental processes of sound generation and the coupling mechanisms on mutual interacting acoustic oscillators. (C) 2016 Acoustical Society of America.
Uremia is a phenomenon caused by retention of uremic toxins in the plasma due to functional impairment of kidneys in the elimination of urinary waste products. Uremia is presently treated by dialysis techniques like hemofiltration, dialysis or hemodiafiltration. However, these techniques in use are more favorable towards removing hydrophilic than hydrophobic uremic toxins. Hydrophobic uremic toxins, such as hydroxy hipuric acid (OH-HPA), phenylacetic acid (PAA), indoxyl sulfate (IDS) and p-cresylsulfate (pCRS), contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease. Therefore, objective of the present study is to test adsorption capacity of highly porous microparticles prepared from poly(ether imide) (PEI) as an alternative technique for the removal of uremic toxins. Two types of nanoporous, spherically shaped microparticles were prepared from PEI by a spraying/coagulation process. PEI particles were packed into a preparative HPLC column to which a mixture of the four types of uremic toxins was injected and eluted with ethanol. Eluted toxins were quantified by analytical HPLC. PEI particles were able to adsorb all four toxins, with the highest affinity for PAA and pCR. IDS and OH-HPA showed a partially non-reversible binding. In summary, PEI particles are interesting candidates to be explored for future application in CKD.
Hydrophobins are highly surface active proteins which self-assemble at hydrophilic-hydrophobic interfaces into amphipathic membranes. We investigate hydrophobin self-assembly at oil/water interfaces to deepen the understanding of protein behavior in order to improve our biomimetic synthesis. Therefore, we carried out pendant drop measurements of hydrophobin stabilized oil/water systems determining the time-dependent IFT and the dilatational rheology with additional adaptation to the Serrien protein model. We show that the class I hydrophobin H*Protein B adsorbs at an oil/water interface where it forms a densely-packed interfacial protein layer, which dissipates energy during droplet oscillation. Furthermore, the interfacial protein layer exhibits shear thinning behavior. (C) 2016 Elsevier Inc. All rights reserved.
Research based on the Eccles model of parent socialization demonstrated that parents are an important source of value and ability information for their children. Little is known, however, about the bidirectional effects between students’ perceptions of their parents’ beliefs and behaviors and the students’ own domain-specific values. This study analyzed how students’ perceptions of parents’ beliefs and behaviors and students’ mathematics values and mathematics-related career plans affect each other bidirectionally, and analyzed the role of students’ gender as a moderator of these relations. Data from 475 students in 11th and 12th grade (girls: 50.3%; 31 classrooms; 12 schools), who participated in 2 waves of the study, were analyzed. Results of longitudinal structural equation models demonstrated that students’ perceptions of their parents’ mathematics value beliefs at Time 1 affected the students’ own mathematics utility value at Time 2. Bidirectional effects were not shown in the full sample but were identified for boys. The paths within the tested model varied for boys and girls. For example, boys’, not girls’, mathematics intrinsic value predicted their reported conversations with their fathers about future occupational plans. Boys’, not girls’, perceived parents’ mathematics value predicted the mathematics utility value. Findings are discussed in relation to their implications for parents and teachers, as well as in relation to gendered motivational processes.
On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet—indicating the spreading and activation of the platelets—was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials.
Our study addresses the following research questions: Are there differences between handwriting movements on paper and on a tablet computer? Can experienced writers, such as most adults, adapt their graphomotor execution during writing to a rather unfamiliar surface for instance a tablet computer? We examined the handwriting performance of adults in three tasks with different complexity: (a) graphomotor abilities, (b) visuomotor abilities and (c) handwriting. Each participant performed each task twice, once on paper and once on a tablet computer with a pen. We tested 25 participants by measuring their writing duration, in air time, number of pen lifts, writing velocity and number of inversions in velocity. The data were analyzed using linear mixed-effects modeling with repeated measures. Our results reveal differences between writing on paper and on a tablet computer which were partly task-dependent. Our findings also show that participants were able to adapt their graphomotor execution to the smoother surface of the tablet computer during the tasks. (C) 2016 Elsevier B.V. All rights reserved.
Adaptation to physical activity and mental stress in the context of pain. Psychobiological aspects
(2016)
The genesis of chronic pain is predominantly explained by a multidimensional pain model approach that is based on the dysfunctional influence of biological, psychological and social variables as key risk factors inducing aberrant long-term changes. Biological facets comprise adaptation processes on the neuronal, musculoskeletal and (psycho) biological level that can be influenced by physical training or psychosocial factors, such as stress. These factors can play a causative role in developing dysfunctional adaptation mechanisms, which in turn prepare the biological ground to facilitate negative long-term changes in the peripheral and central nervous systems. Hence, these processes can be assumed to be fundamentally involved in the transition from acute to chronic and persistent pain. The aim of this review article is to discuss hypotheses for the genesis of chronic pain and possible treatment strategies. Selected research results about maladaptive processes in chronic pain due to psychological stress and physical activity are presented in order to inspire discussions about the ideal dose-response relationship of physical activity and the combination of different therapeutic concepts.
At the end of the 18th century, the Jewish enlighteners invented the Genre of Jewish German Children’s Bibles in their aim to reform the Jewish education system in German speaking areas. This paper initially provides a short introduction to some of the main features of the genre. Subsequently, the story of Eve’s creation as it appears in two of its earliest representatives, Peter Beer’s Sefer toledot yisra’el (1796) and Immanuel Moritz Neumann’s Sefer torat ha-elohim (1816), is analyzed and compared, exploring the literary and interpretative strategies of the two authors in their respective contemporary contexts. Finally, the paper illustrates some of the contributions of Jewish Children’s Bibles to our understanding of the Haskala and the early stages of Jewish modernization.
Molecular signalling in living cells occurs at low copy numbers and is thereby inherently limited by the noise imposed by thermal diffusion. The precision at which biochemical receptors can count signalling molecules is intimately related to the noise correlation time. In addition to passive thermal diffusion, messenger RNA and vesicle-engulfed signalling molecules can transiently bind to molecular motors and are actively transported across biological cells. Active transport is most beneficial when trafficking occurs over large distances, for instance up to the order of 1 metre in neurons. Here we explain how intermittent active transport allows for faster equilibration upon a change in concentration triggered by biochemical stimuli. Moreover, we show how intermittent active excursions induce qualitative changes in the noise in effectively one-dimensional systems such as dendrites. Thereby they allow for significantly improved signalling precision in the sense of a smaller relative deviation in the concentration read-out by the receptor. On the basis of linear response theory we derive the exact mean field precision limit for counting actively transported molecules. We explain how intermittent active excursions disrupt the recurrence in the molecular motion, thereby facilitating improved signalling accuracy. Our results provide a deeper understanding of how recurrence affects molecular signalling precision in biological cells and novel medical-diagnostic devices.
We applied the geomorphic indices (hypsometry and stream length gradient) to evaluate the differential uplift of the central and southern Longmenshan, a mountain range characterized by rapid erosion, strong tectonic uplift, and devastating seismic hazards. The results of the geomorphic analysis indicate that the Beichuan-Yingxiu fault and the Shuangshi-Dachuan fault act as major tectonic boundaries separating areas experiencing rapid uplift from slow uplift. The results of the geomorphic analysis also suggest that the Beichuan-Yingxiu fault is the most active fault with the largest relative uplift rates compared to the rest of the faults in the Longmenshan fault system. We compared reflected relative uplift rates based on the hypsometry and stream length gradient indices with geological/geodetic absolute rates. Along-strike and across-strike variations in the hypsometry and stream length gradient correlate with the spatial patterns derived from the apatite fission track exhumation rates, the leveling-derived uplift rate, and coseismic vertical displacements during the 2008 Wenchuan earthquake. These data defined multiple fault relationships in a complex thrust zone and provided geomorphic evidence to evaluate the potential seismic hazards of the southern Longmenshan range.
Previous research indicates that infants’ prediction of the goals of observed actions is influenced by own experience with the type of agent performing the action (i.e., human hand vs. non-human agent) as well as by action-relevant features of goal objects (e.g., object size). The present study investigated the combined effects of these factors on 12-month-olds’ action prediction. Infants’ (N = 49) goal-directed gaze shifts were recorded as they observed 14 trials in which either a human hand or a mechanical claw reached for a small goal area (low-saliency goal) or a large goal area (high-saliency goal). Only infants who had observed the human hand reaching for a high-saliency goal fixated the goal object ahead of time, and they rapidly learned to predict the action goal across trials. By contrast, infants in all other conditions did not track the observed action in a predictive manner, and their gaze shifts to the action goal did not change systematically across trials. Thus, high-saliency goals seem to boost infants’ predictive gaze shifts during the observation of human manual actions, but not of actions performed by a mechanical device. This supports the assumption that infants’ action predictions are based on interactive effects of action-relevant object features (e.g., size) and own action experience.
Ecological niches of organisms vary across geographical space, but niche shift patterns between regions and the underlying mechanisms remain largely unexplored. We studied shifts in the pH niche of 42 temperate forest plant species across a latitudinal gradient from northern France to boreo-nemoral Sweden. We asked 1) whether species restrict their niches with increasing latitude as they reach their northern range margin (environmental constraints); 2) whether species expand their niches with increasing latitude as regional plant species richness decreases (competitive release); and 3) whether species shift their niche position toward more acidic sites with increasing latitude as the relative proportion of acidic soils increases (local adaptation). Based on 1458 vegetation plots and corresponding soil pH values, we modelled species response curves using Huisman-Olff-Fresco models. Four niche measures (width, position, left and right border) were compared among regions by randomization tests. We found that with increasing latitude, neutrophilic species tended to retreat from acidic sites, indicating that these species retreat to more favorable sites when approaching their range margin. Alternatively, these species might benefit from enhanced nitrogen deposition on formerly nutrient-poor, acidic sites in southern regions or lag behind in post-glacial recolonization of potential habitats in northern regions. Most acidophilic species extended their niche toward more base-rich sites with increasing latitude, indicating competitive release from neutrophilic species. Alternatively, acidophilic species might benefit from optimal climatic conditions in the north where some have their core distribution area. Shifts in the niche position suggested that local adaptation is of minor importance. We conclude that shifts in the pH niche of temperate forest plants are the rule, but the directions of the niche shifts and possible explanations vary. Our study demonstrates that differentiating between acidophilic and neutrophilic species is crucial to identify general patterns and underlying mechanisms.
The performance of different GW methods is assessed for a set of 24 organic acceptors. Errors are evaluated with respect to coupled cluster singles, doubles, and perturbative triples [CCSD(T)] reference data for the vertical ionization potentials (IPs) and electron affinities (EAs), extrapolated to the complete basis set limit. Additional comparisons are made to experimental data, where available. We consider fully self-consistent GW (scGW), partial self-consistency in the Green’s function (scGW0), non-self-consistent G0W0 based on several mean-field starting points, and a “beyond GW” second-order screened exchange (SOSEX) correction to G0W0. We also describe the implementation of the self-consistent Coulomb hole with screened exchange method (COHSEX), which serves as one of the mean-field starting points. The best performers overall are G0W0+SOSEX and G0W0 based on an IP-tuned long-range corrected hybrid functional with the former being more accurate for EAs and the latter for IPs. Both provide a balanced treatment of localized vs delocalized states and valence spectra in good agreement with photoemission spectroscopy (PES) experiments.
The performance of non-empirically tuned long-range corrected hybrid functionals for the prediction of vertical ionization potentials (IPs) and electron affinities (EAs) is assessed for a set of 24 organic acceptor molecules. Basis set extrapolated coupled cluster singles, doubles, and perturbative triples [CCSD(T)] calculations serve as a reference for this study. Compared to standard exchange-correlation functionals, tuned long-range corrected hybrid functionals produce highly reliable results for vertical IPs and EAs, yielding mean absolute errors on par with computationally more demanding GW calculations. In particular, it is demonstrated that long-range corrected hybrid functionals serve as ideal starting points for non-self-consistent GW calculations.
Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5% below (L) and above (M) the first lactate turn point (LTP1), and 5% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (-3.44, 5.15) mmol.L-1, -0.45 (-3.95, 3.05) mmol.L-1, -0.31 (-8.83, 8.20) mmol.L-1 and at 1.17 (-2.06, 4.40) mmol.L-1, 0.11 (-5.79, 6.01) mmol.L-1, 1.48 (-2.60, 5.57) mmol.L-1 in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.
Accessing morphosyntax in L1 and L2 word recognition A priming study of inflected German adjectives
(2016)
In fusional languages, inflectional affixes may encode multiple morphosyntactic features such as case, number, and gender. To determine how these features are accessed during both native (L1) and non-native (L2) word recognition, the present study compares the results from a masked visual priming experiment testing inflected adjectives of German to those of a previous overt (cross-modal) priming experiment on the same phenomenon. While for the L1 group both experiments produced converging results, a group of highly-proficient Russian L2 learners of German showed native-like modulations of repetition priming effects under overt, but not under masked priming conditions. These results indicate that not only affixes but also their morphosyntactic features are accessible during initial form-based lexical access, albeit only for L1 and not for L2 processing. We argue that this contrast is in line with other findings suggesting that non-native language processing is less influenced by structural information than the L1.
Conflict is a ubiquitous feature of interpersonal relationships, yet many of these relationships preserve their value following conflict. Our ability to refrain from punishment despite the occurrence of conflict is a characteristic of human beings. Using a combination of behavioral and neuroimaging techniques, we show that prosocial decision-making is modulated by relationship closeness. In an iterated social exchange, participants were more likely to cooperate with their partner compared to an unknown person by accepting unfair exchanges. Importantly, this effect was not influenced by how resources were actually being shared with one’s partner. The medial prefrontal cortex (MPFC) was activated when the partner, rather than the unknown person, behaved unfairly and, in the same context, the MPFC demonstrated greater functional connectivity with the dorsal anterior cingulate cortex (DACC). MPFC–DACC connectivity was inversely associated with participants’ tendency to “forgive” their partner for unfairness as well as performance outside the scanner on a behavioral measure of forgiveness. We conclude that relationship closeness modulates a neural network comprising the MPFC/DACC during economic exchanges.
Galactic cosmic rays reach energies of at least a few petaelectronvolts (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators (‘PeVatrons’), but all proposed models of Galactic cosmic-ray accelerators encounter difficulties at exactly these energies. Dozens of Galactic accelerators capable of accelerating particles to energies of tens of teraelectronvolts (of the order of 1013 electronvolts) were inferred from recent γ-ray observations3. However, none of the currently known accelerators—not even the handful of shell-type supernova remnants commonly believed to supply most Galactic cosmic rays—has shown the characteristic tracers of petaelectronvolt particles, namely, power-law spectra of γ-rays extending without a cut-off or a spectral break to tens of teraelectronvolts4. Here we report deep γ-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy. We propose that the supermassive black hole Sagittarius A* is linked to this PeVatron. Sagittarius A* went through active phases in the past, as demonstrated by X-ray outbursts5and an outflow from the Galactic Centre6. Although its current rate of particle acceleration is not sufficient to provide a substantial contribution to Galactic cosmic rays, Sagittarius A* could have plausibly been more active over the last 106–107 years, and therefore should be considered as a viable alternative to supernova remnants as a source of petaelectronvolt Galactic cosmic rays.
Let (M, g) be a closed Riemannian manifold of dimension n >= 3 and let f is an element of C-infinity (M), such that the operator P-f := Delta g + f is positive. If g is flat near some point p and f vanishes around p, we can define the mass of P1 as the constant term in the expansion of the Green function of P-f at p. In this paper, we establish many results on the mass of such operators. In particular, if f := n-2/n(n-1)s(g), i.e. if P-f is the Yamabe operator, we show the following result: assume that there exists a closed simply connected non-spin manifold M such that the mass is non-negative for every metric g as above on M, then the mass is non-negative for every such metric on every closed manifold of the same dimension as M. (C) 2016 Elsevier Inc. All rights reserved.
Water research is introduced from the combined perspectives of natural and social science and cases of citizen and stakeholder coproduction of knowledge. Using the overarching notion of transdisciplinarity, we examine how interdisciplinary and participatory water research has taken place and could be developed further. It becomes apparent that water knowledge is produced widely within society, across certified disciplinary experts and noncertified expert stakeholders and citizens. However, understanding and management interventions may remain partial, or even conflicting, as much research across and between traditional disciplines has failed to integrate disciplinary paradigms due to philosophical, methodological, and communication barriers. We argue for more agonistic relationships that challenge both certified and noncertified knowledge productively. These should include examination of how water research itself embeds and is embedded in social context and performs political work. While case studies of the cultural and political economy of water knowledge exist, we need more empirical evidence on how exactly culture, politics, and economics have shaped this knowledge and how and at what junctures this could have turned out differently. We may thus channel the coproductionist critique productively to bring perspectives, alternative knowledges, and implications into water politics where they were not previously considered; in an attempt to counter potential lock-in to particular water policies and technologies that may be inequitable, unsustainable, or unacceptable. While engaging explicitly with politics, transdisciplinary water research should remain attentive to closing down moments in the research process, such as framings, path-dependencies, vested interests, researchers’ positionalities, power, and scale.
Reward-dependent instrumental behavior must continuously be re-adjusted according to environmental conditions. Failure to adapt to changes in reward contingencies may incur psychiatric disorders like anxiety and depression. When an expected reward is omitted, behavior undergoes extinction. While extinction involves active re-learning, it is also accompanied by emotional behaviors indicative of frustration, anxiety, and despair (extinction-induced depression). Here, we report evidence for a sphingolipid mechanism in the extinction of behavior. Rapid extinction, indicating efficient re-learning, coincided with a decrease in the activity of the enzyme acid sphingomyelinase (ASM), which catalyzes turnover of sphingomyelin to ceramide, in the dorsal hippocampus of rats. The stronger the decline in ASM activity, the more rapid was the extinction. Sphingolipid-focused lipidomic analysis showed that this results in a decline of local ceramide species in the dorsal hippocampus. Ceramides shape the fluidity of lipid rafts in synaptic membranes and by that way can control neural plasticity. We also found that aging modifies activity of enzymes and ceramide levels in selective brain regions. Aging also changed how the chronic treatment with corticosterone (stress) or intranasal dopamine modified regional enzyme activity and ceramide levels, coinciding with rate of extinction. These data provide first evidence for a functional ASM-ceramide pathway in the brain involved in the extinction of learned behavior. This finding extends the known cellular mechanisms underlying behavioral plasticity to a new class of membrane-located molecules, the sphingolipids, and their regulatory enzymes, and may offer new treatment targets for extinction- and learning-related psychopathological conditions.
A single predator charging a herd of prey: effects of self volume and predator-prey decision-making
(2016)
We study the degree of success of a single predator hunting a herd of prey on a two-dimensional square lattice landscape. We explicitly consider the self volume of the prey restraining their dynamics on the lattice. The movement of both predator and prey is chosen to include an intelligent, decision making step based on their respective sighting ranges, the radius in which they can detect the other species (prey cannot recognise each other besides the self volume interaction): after spotting each other the motion of prey and predator turns from a nearest neighbour random walk into directed escape or chase, respectively. We consider a large range of prey densities and sighting ranges and compute the mean first passage time for a predator to catch a prey as well as characterise the effective dynamics of the hunted prey. We find that the prey's sighting range dominates their life expectancy and the predator profits more from a bad eyesight of the prey than from his own good eye sight. We characterise the dynamics in terms of the mean distance between the predator and the nearest prey. It turns out that effectively the dynamics of this distance coordinate can be captured in terms of a simple Ornstein–Uhlenbeck picture. Reducing the many-body problem to a simple two-body problem by imagining predator and nearest prey to be connected by an effective Hookean bond, all features of the model such as prey density and sighting ranges merge into the effective binding constant.
In recent decades, the Greenland Ice Sheet has been losing mass and has thereby contributed to global sea-level rise. The rate of ice loss is highly relevant for coastal protection worldwide. The ice loss is likely to increase under future warming. Beyond a critical temperature threshold, a meltdown of the Greenland Ice Sheet is induced by the self-enforcing feedback between its lowering surface elevation and its increasing surface mass loss: the more ice that is lost, the lower the ice surface and the warmer the surface air temperature, which fosters further melting and ice loss. The computation of this rate so far relies on complex numerical models which are the appropriate tools for capturing the complexity of the problem. By contrast we aim here at gaining a conceptual understanding by deriving a purposefully simple equation for the self-enforcing feedback which is then used to estimate the melt time for different levels of warming using three observable characteristics of the ice sheet itself and its surroundings. The analysis is purely conceptual in nature. It is missing important processes like ice dynamics for it to be useful for applications to sea-level rise on centennial timescales, but if the volume loss is dominated by the feedback, the resulting logarithmic equation unifies existing numerical simulations and shows that the melt time depends strongly on the level of warming with a critical slow-down near the threshold: the median time to lose 10% of the present-day ice volume varies between about 3500 years for a temperature level of 0.5 degrees C above the threshold and 500 years for 5 degrees C. Unless future observations show a significantly higher melting sensitivity than currently observed, a complete meltdown is unlikely within the next 2000 years without significant ice-dynamical contributions.
We present a new, seismologically consistent expression for the total area and volume of populations of earthquake-triggered landslides. This model builds on a set of scaling relationships between key parameters, such as landslide spatial density, seismic ground acceleration, fault length, earthquake source depth, and seismic moment. To assess the model we have assembled and normalized a catalog of landslide inventories for 40 shallow, continental earthquakes. Low landscape steepness causes systematic overprediction of the total area and volume of landslides. When this effect is accounted for, the model predicts the total landslide volume of 63% of 40 cases to within a factor 2 of the volume estimated from observations (R-2 = 0.76). The prediction of total landslide area is also sensitive to the landscape steepness, but less so than the total volume, and it appears to be sensitive to controls on the landslide size-frequency distribution, and possibly the shaking duration. Some outliers are likely associated with exceptionally strong rock mass in the epicentral area, while others may be related to seismic source complexities ignored by the model. However, the close match between prediction and estimate for about two thirds of cases in our database suggests that rock mass strength is similar in many cases and that our simple seismic model is often adequate, despite the variety of lithologies and tectonic settings covered. This makes our expression suitable for integration into landscape evolution models and application to the anticipation or rapid assessment of secondary hazards associated with earthquakes.
A SEARCH FOR VERY HIGH ENERGY GAMMA RAYS FROM THE MISSING LINK BINARY PULSAR J1023+0038 WITH VERITAS
(2016)
The binary millisecond radio pulsar PSR J1023+0038 exhibits many characteristics similar to the gamma-ray binary system PSR B1259-63/LS 2883, making it an ideal candidate for the study of high-energy nonthermal emission. It has been the subject of multiwavelength campaigns following the disappearance of the pulsed radio emission in 2013 June, which revealed the appearance of an accretion disk around the neutron star. We present the results of very high energy (VHE) gamma-ray observations carried out by the Very Energetic Radiation Imaging Telescope Array System before and after this change of state. Searches for steady and pulsed emission of both data sets yield no significant gamma-ray signal above 100 GeV, and upper limits are given for both a steady and pulsed gamma-ray flux. These upper limits are used to constrain the magnetic field strength in the shock region of the PSR J1023+0038 system. Assuming that VHE gamma rays are produced via an inverse Compton mechanism in the shock region, we constrain the shock magnetic field to be greater than similar to 2 G before the disappearance of the radio pulsar and greater than similar to 10 G afterward.
The F-type star KIC. 8462852 has recently been identified as an exceptional target for search for extraterrestrial intelligence (SETI) observations. We describe an analysis methodology for optical SETI, which we have used to analyze nine hours of serendipitous archival observations of KIC. 8462852 made with the VERITAS gamma-ray observatory between 2009 and 2015. No evidence of pulsed optical beacons, above a pulse intensity at the Earth of approximately 1 photon m(-2), is found. We also discuss the potential use of imaging atmospheric Cherenkov telescope arrays in searching for extremely short duration optical transients in general.
The social inhibition of return (sIOR) effect refers to the finding that response initiation times are longer if a movement is executed to a location where another person has responded to just before. Previous studies have examined the influence of the goal of the action on sIOR. In these studies, however, the movement endpoint and to-be-attained goal (e.g., touching/pressing a response key) were at the same spatial location. In the present two experiments, we disentangled movement endpoint and goal's identity and locations by means of introducing action effects that followed directly from a movement. Similar methods were previously shown powerful enough to clearly show the importance of action goals for other phenomena—a finding consistent with effect-based theories of action control, such as the ideomotor theory. The results of the present study revealed that sIOR was shaped by the movement endpoint location, not the goal's identity or location. That is, in both experiments, an sIOR effect was observed, but the magnitude of the sIOR effect was not modulated by repetitions/switches of goals or their locations. Thus, results indicate that goals play a negligible role in the emergence of the sIOR and, consequently, highlight the importance of action observation for the emergence of the sIOR effect.
We discuss the chiral anomaly for a Weyl field in a curved background and show that a novel index theorem for the Lorentzian Dirac operator can be applied to describe the gravitational chiral anomaly. A formula for the total charge generated by the gravitational and gauge field background is derived directly in Lorentzian signature and in a mathematically rigorous manner. It contains a term identical to the integrand in the Atiyah-Singer index theorem and another term involving the.-invariant of the Cauchy hypersurfaces.
Let A be a nonlinear differential operator on an open set X subset of R-n and S a closed subset of X. Given a class F of functions in X, the set S is said to be removable for F relative to A if any weak solution of A(u) = 0 in XS of class F satisfies this equation weakly in all of X. For the most extensively studied classes F, we show conditions on S which guarantee that S is removable for F relative to A.
This essay aims at discussing the new literature on Franco-German relations during the period 1918-1930. It highlights how many works now question the idea that the Treaty of Versailles and the European order that ensued inevitably wore within themselves the seeds of a new war. On the contrary, by examining in particular the detente efforts of the Twenties, the most recent historiography often emphasizes how the inevitability of the authoritarian turn of Twenties and Thirties, which led to the Second World War, has often been exaggerated by historians and that different paths could have been undertaken.
Extra-tropical circulation systems impede poleward moisture advection by the Indian Summer Monsoon. In this context, the Himalayan range is believed to insulate the south Asian circulation from extra-tropical influences and to delineate the northern extent of the Indian Summer Monsoon in central Asia. Paleoclimatic evidence, however, suggests increased moisture availability in the Early Holocene north of the Himalayan range which is attributed to an intensification of the Indian Summer Monsoon. Nevertheless, mechanisms leading to a surpassing of the Himalayan range and the northern maximum extent of summer monsoonal influence remain unknown. Here we show that the Kunlun barrier on the northern Tibetan Plateau [similar to 36 degrees N] delimits Indian Summer Monsoon precipitation during the Holocene. The presence of the barrier relocates the insulation effect 1,000 km further north, allowing a continental low intensity branch of the Indian Summer Monsoon which is persistent throughout the Holocene. Precipitation intensities at its northern extent seem to be driven by differentiated solar heating of the Northern Hemisphere indicating dependency on energy-gradients rather than absolute radiation intensities. The identified spatial constraints of monsoonal precipitation will facilitate the prediction of future monsoonal precipitation patterns in Central Asia under varying climatic conditions.