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The CH2Cl2/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodiumfalciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1.4-4.6M without significant cytotoxicity against Vero and HEp2 cell lines (IC50>100M). The new compound (1) showed weak antiplasmodial activity, IC50 12.5-24.2M, but also showed selective anticancer activity against HEp2 cell line (CC50 16.9M). [GRAPHICS] .
Sensitivity to salience
(2018)
Sentence comprehension is optimised by indicating entities as salient through linguistic (i.e., information-structural) or visual means. We compare how salience of a depicted referent due to a linguistic (i.e., topic status) or visual cue (i.e., a virtual person's gaze shift) modulates sentence comprehension in German. We investigated processing of sentences with varying word order and pronoun resolution by means of self-paced reading and an antecedent choice task, respectively. Our results show that linguistic as well as visual salience cues immediately speeded up reading times of sentences mentioning the salient referent first. In contrast, for pronoun resolution, linguistic and visual cues modulated antecedent choice preferences less congruently. In sum, our findings speak in favour of a significant impact of linguistic and visual salience cues on sentence comprehension, substantiating that salient information delivered via language as well as the visual environment is integrated in the current mental representation of the discourse.
Although the detection of metastases radically changes prognosis of and treatment decisions for a cancer patient, clinically undetectable micrometastases hamper a consistent classification into localized or metastatic disease. This chapter discusses mathematical modeling efforts that could help to estimate the metastatic risk in such a situation. We focus on two approaches: (1) a stochastic framework describing metastatic emission events at random times, formalized via Poisson processes, and (2) a deterministic framework describing the micrometastatic state through a size-structured density function in a partial differential equation model. Three aspects are addressed in this chapter. First, a motivation for the Poisson process framework is presented and modeling hypotheses and mechanisms are introduced. Second, we extend the Poisson model to account for secondary metastatic emission. Third, we highlight an inherent crosslink between the stochastic and deterministic frameworks and discuss its implications. For increased accessibility the chapter is split into an informal presentation of the results using a minimum of mathematical formalism and a rigorous mathematical treatment for more theoretically interested readers.
Sub-municipal units (SMUs) in Germany differ in German Länder. In Berlin, Hamburg and München Metropole Districts fulfill a number of quasi-municipal self-government rights and functions. They have their own budget and strong councils, as well as mayors. In all other Länder, most sub-municipal councils were subordinated under the municipal council and directly elected mayor heading the administration. SMUs were introduced as a kind of compensation with different territorial reforms in the 1970s. Although directly elected, sub-municipal councilors are weak, and their advisory role competes with other newly established advisory boards. Here the focus remains on traffic and town planning. Some sub-municipal councils fulfill smaller administrative functions and become more relevant and important in recent decentralization strategies of neighborhood development.
Scenarios have become a key tool for supporting sustainability research on regional and global change. In this study we evaluate four regional scenario assessments: first, to explore a number of research challenges related to sustainability science and, second, to contribute to sustainability research in the specific case studies. The four case studies used commonly applied scenario approaches that are (i) a story and simulation approach with stakeholder participation in the Oum Zessar watershed, Tunisia, (ii) a participatory scenario exploration in the Rwenzori region, Uganda, (iii) a model-based prepolicy study in the Inner Niger Delta, Mali, and (iv) a model coupling-based scenario analysis in upper Thukela basin, South Africa. The scenario assessments are evaluated against a set of known challenges in sustainability science, with each challenge represented by two indicators, complemented by a survey carried out on the perception of the scenario assessments within the case study regions. The results show that all types of scenario assessments address many sustainability challenges, but that the more complex ones based on story and simulation and model coupling are the most comprehensive. The study highlights the need to investigate abrupt system changes as well as governmental and political factors as important sources of uncertainty. For an in-depth analysis of these issues, the use of qualitative approaches and an active engagement of local stakeholders are suggested. Studying ecological thresholds for the regional scale is recommended to support research on regional sustainability. The evaluation of the scenario processes and outcomes by local researchers indicates the most transparent scenario assessments as the most useful. Focused, straightforward, yet iterative scenario assessments can be very relevant by contributing information to selected sustainability problems.
This paper investigates the transferability of calibrated HBV model parameters under stable and contrasting conditions in terms of flood seasonality and flood generating processes (FGP) in five Norwegian catchments with mixed snowmelt/rainfall regimes. We apply a series of generalized (differential) split-sample tests using a 6-year moving window over (i) the entire runoff observation periods, and (ii) two subsets of runoff observations distinguished by the seasonal occurrence of annual maximum floods during either spring or autumn. The results indicate a general model performance loss due to the transfer of calibrated parameters to independent validation periods of -5 to -17%, on average. However, there is no indication that contrasting flood seasonality exacerbates performance losses, which contradicts the assumption that optimized parameter sets for snowmelt-dominated floods (during spring) perform particularly poorly on validation periods with rainfall-dominated floods (during autumn) and vice versa.
The newly collected Potsdam Grievance Statistics File (PGSF) holds data on the number and topics of grievances (Eingaben) that were addressed to local authorities of the German Democratic Republic (GDR) in the years 1970 to 1989. The PGSF allows quantitative analyses on topics such as participation, quality of life, and value change in the German Democratic Republic. This paper introduces the concepts of the data set and discusses the validity of its contents.
Hot localised charge carriers on the Si(111)-7x7 surface are modelled by small charged clusters. Such resonances induce non-local desorption, i.e. more than 10 nm away from the injection site, of chlorobenzene in scanning tunnelling microscope experiments. We used such a cluster model to characterise resonance localisation and vibrational activation for positive and negative resonances recently. In this work, we investigate to which extent the model depends on details of the used cluster or quantum chemistry methods and try to identify the smallest possible cluster suitable for a description of the neutral surface and the ion resonances. Furthermore, a detailed analysis for different chemisorption orientations is performed. While some properties, as estimates of the resonance energy or absolute values for atomic changes, show such a dependency, the main findings are very robust with respect to changes in the model and/or the chemisorption geometry. [GRAPHICS] .
Leaf senescence is an essential developmental process that involves diverse metabolic changes associated with degradation of macromolecules allowing nutrient recycling and remobilization. In contrast to the significant progress in transcriptomic analysis of leaf senescence, metabolomics analyses have been relatively limited. A broad overview of metabolic changes during leaf senescence including the interactions between various metabolic pathways is required to gain a better understanding of the leaf senescence allowing to link transcriptomics with metabolomics and physiology. In this chapter, we describe how to obtain comprehensive metabolite profiles and how to dissect metabolic shifts during leaf senescence in the model plant Arabidopsis thaliana. Unlike nucleic acid analysis for transcriptomics, a comprehensive metabolite profile can only be achieved by combining a suite of analytic tools. Here, information is provided for measurements of the contents of chlorophyll, soluble proteins, and starch by spectrophotometric methods, ions by ion chromatography, thiols and amino acids by HPLC, primary metabolites by GC/TOF-MS, and secondary metabolites and lipophilic metabolites by LC/ESI-MS. These metabolite profiles provide a rich catalogue of metabolic changes during leaf senescence, which is a helpful database and blueprint to be correlated to future studies such as transcriptome and proteome analyses, forward and reverse genetic studies, or stress-induced senescence studies.
The ensemble Kalman filter has become a popular data assimilation technique in the geosciences. However, little is known theoretically about its long term stability and accuracy. In this paper, we investigate the behavior of an ensemble Kalman-Bucy filter applied to continuous-time filtering problems. We derive mean field limiting equations as the ensemble size goes to infinity as well as uniform-in-time accuracy and stability results for finite ensemble sizes. The later results require that the process is fully observed and that the measurement noise is small. We also demonstrate that our ensemble Kalman-Bucy filter is consistent with the classic Kalman-Bucy filter for linear systems and Gaussian processes. We finally verify our theoretical findings for the Lorenz-63 system.
Design thinking is acknowledged as a thriving innovation practice plus something more, something in the line of a deep understanding of innovation processes. At the same time, quite how and why design thinking works-in scientific terms-appeared an open question at first. Over recent years, empirical research has achieved great progress in illuminating the principles that make design thinking successful. Lately, the community began to explore an additional approach. Rather than setting up novel studies, investigations into the history of design thinking hold the promise of adding systematically to our comprehension of basic principles. This chapter makes a start in revisiting design thinking history with the aim of explicating scientific understandings that inform design thinking practices today. It offers a summary of creative thinking theories that were brought to Stanford Engineering in the 1950s by John E. Arnold.
We applied coarse spectral analysis to more than 2 decades of daily near-surface water temperature (WT) measurements from Muggelsee, a shallow polymictic lake in Germany, to systematically characterize patterns in WT variability from daily to yearly temporal scales. Comparison of WT with local air temperature indicates that the WT variability patterns are likely attributable to both meteorological forcing and internal lake dynamics. We identified seasonal patterns of WT variability and showed that WT variability increases with increasing Schmidt stability, decreasing Lake number and decreasing ice cover duration, and is higher near the shore than in open water. We introduced the slope of WT spectra as an indicator for the degree of lake mixing to help explain the identified temporal and spatial scales of WT variability. The explanatory power of this indicator in other lakes with different mixing regimes remains to be established.
The endothelialization of synthetic surfaces applied as cardiovascular implant materials is an important issue to ensure the anti-thrombotic quality of a biomaterial. However, the rapid and constant development of a functionallycon-fluent endothelial cell monolayer is challenging. In order to investigate the compatibility of potential implant materials with endothelial cells several in vitro studies are performed. Here, glass and tissue culture plates (TCP) are often used as reference materials for in vitro pre-testing. However, a direct comparison of both substrates is lacking. Therefore, a comparison of study results is difficult, since results are often related to various reference materials. In this study, the endothelialization of glass and TCP was investigated in terms of adherence, morphology, integrity, viability and function using human umbilical vein endothelial cells (HUVEC). On both substrates an almost functionally confluent HUVEC monolayer was developed after nine days of cell seeding with clearly visible cell rims, decreased stress fiber formation and a pronounced marginal filament band. The viability of HUVEC was comparable for both substrates nine days after cell seeding with only a few dead cells. According to that, the cell membrane integrity as well as the metabolic activity showed no differences between TCP and glass. However, a significant difference was observed for the secretion of IL-6 and IL-8. The concentration of both cytokines, which are associated with migratory activity, was increased in the supernatant of HUVEC seeded on TCP. This result matches well with the slightly increased number of adherent HUVEC on TCP. In conclusion, these findings indicate that both reference materials are almost comparable and can be used equivalently as control materials in in vitro endothelialization studies.
BACKGROUND: Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts. RESULTS: Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p<0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743 +/- 434 cells. mm(-2), was about 6.5 times higher than on cPnBA73 with 115 +/- 73 cells. mm(-2). On cPnBA04 about 20% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBAnetworks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA. CONCLUSION: The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment.
Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNF alpha, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment.
We study the Ollivier-Ricci curvature of graphs as a function of the chosen idleness. We show that this idleness function is concave and piecewise linear with at most three linear parts, and at most two linear parts in the case of a regular graph. We then apply our result to show that the idleness function of the Cartesian product of two regular graphs is completely determined by the idleness functions of the factors.
Para inicios del siglo XXI se instalan nuevos medios de crítica literaria a través de soportes digitales. Estas publicaciones tensionan un campo letrado chileno que enfrenta cuestionamientos. Gestionadas mayoritariamente por creadores precedentes de la generación del 90, producen reaproximaciones a la cultura letrada. El objetivo es desafiar dinámicas de interacción lectora heredadas vinculadas a las luces patria, desarrollistas, de tipo linear y ciegas a la heterogeneidad cultural vivida en la época. El proceso comprende, de tal modo, una reeducación crítica centrada en ensayar poéticas de productividad analítico-literarias heteróclitas. Se trata de una interacción lectora diversa, sujeta a retóricas íntimas de apreciación estética, que ponen en cuestión las nociones tradicionales mayoritariamente instructiva de la cultura chilena.
Based on new Chandra X-ray telescope data, we present empirical evidence of plasma Compton cooling during a flare in the non-pulsating massive X-ray binary 4U1700-37. This behaviour might be explained by quasi-spherical accretion on to a slowly rotating magnetized neutron star (NS). In quiescence, the NS in 4U1700-37 is surrounded by a hot radiatively cooling shell. Its presence is supported by the detection of mHz quasi-periodic oscillations likely produced by its convection cells. The high plasma temperature and the relatively low X-ray luminosity observed during the quiescence, point to a small emitting area similar to 1 km, compatible with a hotspot on an NS surface. The sudden transition from a radiative to a significantly more efficient Compton cooling regime triggers an episode of enhanced accretion resulting in a flare. During the flare, the plasma temperature drops quickly. The predicted luminosity for such transitions, similar to 3 x 10(35) erg s(-1), is very close to the luminosity of 4U1700-37 during quiescence. The transition may be caused by the accretion of a clump in the stellar wind of the donor star. Thus, a magnetized NS nature of the compact object is strongly favoured.
Is there an ideal time window for language acquisition after which nativelike representation and processing are unattainable? Although this question has been heavily debated, no consensus has been reached. Here, we present evidence for a sensitive period in language development and show that it is specific to grammar. We conducted a masked priming task with a group of Turkish-German bilinguals and examined age of acquisition (AoA) effects on the processing of complex words. We compared a subtle but meaningful linguistic contrast, that between grammatical inflection and lexical-based derivation. The results showed a highly selective AoA effect on inflectional (but not derivational) priming. In addition, the effect displayed a discontinuity indicative of a sensitive period: Priming from inflected forms was nativelike when acquisition started before the age of 5 but declined with increasing AoA. We conclude that the acquisition of morphological rules expressing morphosyntactic properties is constrained by maturational factors.