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Leaf senescence represents a key developmental process through which resources trapped in the photosynthetic organ are degraded in an organized manner and transported away to sustain the growth of other organs including newly forming leaves, roots, seeds, and fruits. The optimal timing of the initiation and progression of senescence are thus prerequisites for controlled plant growth, biomass accumulation, and evolutionary success through seed dispersal. Recent research has uncovered a multitude of regulatory factors including transcription factors, micro-RNAs, protein kinases, and others that constitute the molecular networks that regulate senescence in plants. The timing of senescence is affected by environmental conditions and abiotic or biotic stresses typically trigger a faster senescence. Various phytohormones, including for example ethylene, abscisic acid, and salicylic acid, promote senescence, whereas cytokinins delay it. Recently, several reports have indicated an involvement of auxin in the control of senescence, however, its mode of action and point of interference with senescence control mechanisms remain vaguely defined at present and contrasting observations regarding the effect of auxin on senescence have so far hindered the establishment of a coherent model. Here, we summarize recent studies on auxin-related genes that affect senescence in plants and highlight how these findings might be integrated into current molecular-regulatory models of senescence.
Aims. Recent magnetic field surveys in O- and B-type stars revealed that about 10% of the core-hydrogen-burning massive stars host large-scale magnetic fields. The physical origin of these fields is highly debated. To identify and model the physical processes responsible for the generation of magnetic fields in massive stars, it is important to establish whether magnetic massive stars are found in very young star-forming regions or whether they are formed in close interacting binary systems.
Methods. In the framework of our ESO Large Program, we carried out low-resolution spectropolarimetric observations with FORS 2 in 2013 April of the three most massive central stars in the Trifid nebula, HD 164492A, HD 164492C, and HD 164492D. These observations indicated a strong longitudinal magnetic field of about 500-600 G in the poorly studied component HD 164492C. To confirm this detection, we used HARPS in spectropolarimetric mode on two consecutive nights in 2013 June.
Results. Our HARPS observations confirmed the longitudinal magnetic field in HD 164492C. Furthermore, the HARPS observations revealed that HD 164492C cannot be considered as a single star as it possesses one or two companions. The spectral appearance indicates that the primary is most likely of spectral type B1-B1.5 V. Since in both observing nights most spectral lines appear blended, it is currently unclear which components are magnetic. Long-term monitoring using high-resolution spectropolarimetry is necessary to separate the contribution of each component to the magnetic signal. Given the location of the system HD 164492C in one of the youngest star formation regions, this system can be considered as a Rosetta Stone for our understanding of the origin of magnetic fields in massive stars.
Attachment of phages to host cells, followed by phage DNA ejection, represents the first stage of viral infection of bacteria. Salmonella phage P22 has been extensively studied, serving as an experimental model for bacterial infection by phages. P22 engages bacteria by binding to the sugar moiety of lipopolysaccharides using the viral tailspike protein for attachment. While the structures of the N-terminal particle-binding domain and the major receptor-binding domain of the tailspike have been analyzed individually, the three-dimensional organization of the intact protein, including the highly conserved linker region between the two domains, remained unknown. A single amino-acid exchange in the linker sequence made it possible to crystallize the full-length protein. Two crystal structures of the linker region are presented: one attached to the N-terminal domain and the other present within the complete tailspike protein. Both retain their biological function, but the mutated full-length tailspike displays a retarded folding pathway. Fitting of the full-length tailspike into a published cryo-electron microscopy map of the P22 virion requires an elastic distortion of the crystal structure. The conservation of the linker suggests a role in signal transmission from the distal tip of the molecule to the phage head, eventually leading to DNA ejection.
The inverse problem of determining the flow at the Earth's core-mantle boundary according to an outer core magnetic field and secular variation model has been investigated through a Bayesian formalism. To circumvent the issue arising from the truncated nature of the available fields, we combined two modeling methods. In the first step, we applied a filter on the magnetic field to isolate its large scales by reducing the energy contained in its small scales, we then derived the dynamical equation, referred as filtered frozen flux equation, describing the spatiotemporal evolution of the filtered part of the field. In the second step, we proposed a statistical parametrization of the filtered magnetic field in order to account for both its remaining unresolved scales and its large-scale uncertainties. These two modeling techniques were then included in the Bayesian formulation of the inverse problem. To explore the complex posterior distribution of the velocity field resulting from this development, we numerically implemented an algorithm based on Markov chain Monte Carlo methods. After evaluating our approach on synthetic data and comparing it to previously introduced methods, we applied it to a magnetic field model derived from satellite data for the single epoch 2005.0. We could confirm the existence of specific features already observed in previous studies. In particular, we retrieved the planetary scale eccentric gyre characteristic of flow evaluated under the compressible quasi-geostrophy assumption although this hypothesis was not considered in our study. In addition, through the sampling of the velocity field posterior distribution, we could evaluate the reliability, at any spatial location and at any scale, of the flow we calculated. The flow uncertainties we determined are nevertheless conditioned by the choice of the prior constraints we applied to the velocity field.
Modern natural hazards research requires dealing with several uncertainties that arise from limited process knowledge, measurement errors, censored and incomplete observations, and the intrinsic randomness of the governing processes. Nevertheless, deterministic analyses are still widely used in quantitative hazard assessments despite the pitfall of misestimating the hazard and any ensuing risks.
In this paper we show that Bayesian networks offer a flexible framework for capturing and expressing a broad range of uncertainties encountered in natural hazard assessments. Although Bayesian networks are well studied in theory, their application to real-world data is far from straightforward, and requires specific tailoring and adaptation of existing algorithms. We offer suggestions as how to tackle frequently arising problems in this context and mainly concentrate on the handling of continuous variables, incomplete data sets, and the interaction of both. By way of three case studies from earthquake, flood, and landslide research, we demonstrate the method of data-driven Bayesian network learning, and showcase the flexibility, applicability, and benefits of this approach.
Our results offer fresh and partly counterintuitive insights into well-studied multivariate problems of earthquake-induced ground motion prediction, accurate flood damage quantification, and spatially explicit landslide prediction at the regional scale. In particular, we highlight how Bayesian networks help to express information flow and independence assumptions between candidate predictors. Such knowledge is pivotal in providing scientists and decision makers with well-informed strategies for selecting adequate predictor variables for quantitative natural hazard assessments.
BEEHAVE offers a valuable tool for researchers to design and focus field experiments, for regulators to explore the relative importance of stressors to devise management and policy advice and for beekeepers to understand and predict varroa dynamics and effects of management interventions. We expect that scientists and stakeholders will find a variety of applications for BEEHAVE, stimulating further model development and the possible inclusion of other stressors of potential importance to honeybee colony dynamics.
Central to ecology and ecosystem management, succession theory aims to mechanistically explain and predict the assembly and development of ecological communities. Yet processes at lower hierarchical levels, e. g. at the species and functional group level, are rarely mechanistically linked to the under-investigated system-level processes which drive changes in ecosystem properties and functioning and are comparable across ecosystems. As a model system for secondary succession, seasonal plankton succession during the growing season is readily observable and largely driven autogenically. We used a long-term dataset from large, deep Lake Constance comprising biomasses, auto-and heterotrophic production, food quality, functional diversity, and mass-balanced food webs of the energy and nutrient flows between functional guilds of plankton and partly fish. Extracting population-and system-level indices from this dataset, we tested current hypotheses about the directionality of successional progress which are rooted in ecosystem theory, the metabolic theory of ecology, quantitative food web theory, thermodynamics, and information theory. Our results indicate that successional progress in Lake Constance is quantifiable, passing through predictable stages. Mean body mass, functional diversity, predator-prey weight ratios, trophic positions, system residence times of carbon and nutrients, and the complexity of the energy flow patterns increased during succession. In contrast, both the mass-specific metabolic activity and the system export decreased, while the succession rate exhibited a bimodal pattern. The weighted connectance introduced here represents a suitable index for assessing the evenness and interconnectedness of energy flows during succession. Diverging from earlier predictions, ascendency and eco-exergy did not increase during succession. Linking aspects of functional diversity to metabolic theory and food web complexity, we reconcile previously disjoint bodies of ecological theory to form a complete picture of successional progress within a pelagic food web. This comprehensive synthesis may be used as a benchmark for quantifying successional progress in other ecosystems.
The increased emphasis on labour market activation in many European countries has led to new forms of governance in recent decades. Primarily through qualitative data and document analysis, this article compares the restructuring of labour market service delivery in the UK and Germany. The comparison suggests the emergence of complex governance arrangements that seek to balance public regulation and accountability with the creation of room for market competition. As a result, we can observe in both countries a greater use of markets, but also of rules. While in both countries the relationships between different providers of labour market services can best be described as a mixture of cooperation and competition, differences exist in terms of instruments and the comprehensiveness of coordination initiatives. The findings suggest that the distinctions between governance models may be more important in theory than in practice, although the combinations of theoretical forms vary in different circumstances.
The article analyses a certain type of bicameralism not merely as a form of legislative organisation, but as a form of government-as a hybrid between parliamentarism and presidentialism. A new typology of pure and hybrid forms of government is proposed, which classifies bicameralism in Australia and Japan as chamber-independent government. This type is systematically compared with other forms of government, including hybrids like semi-presidentialism, elected prime-ministerial government in Israel (from 1996 to 2002) and assembly-independent government in Switzerland. The article highlights how chamber-independent government has the potential to combine different visions of democracy without leading to presidentialisation of political parties.
Molybdenum and tungsten enzymes require specific chaperones for folding and cofactor insertion. PaoD is the chaperone of the periplasmic aldehyde oxidoreductase PaoABC. It is the last gene in the paoABCD operon in Escherichia coli and its presence is crucial for obtaining mature enzyme. PaoD is an unstable, 35 kDa, protein. Our biochemical studies showed that it is a dimer in solution with a tendency to form large aggregates, especially after freezing/thawing cycles. In order to improve stability, PaoD was thawed in the presence of two ionic liquids [C(4)mim]Cl and [C(2)OHmim]PF6 and no protein precipitation was observed. This allowed protein concentration and crystallization using polyethylene glycol or ammonium sulfate as precipitating agents. Saturation transfer difference - nuclear magnetic resonance (STD-NMR) experiments have also been performed in order to investigate the effect of the ionic liquids in the stabilization process, showing a clear interaction between the acidic ring protons of the cation and, most likely, negatively charged residues at the protein surface. DLS assays also show a reduction of the overall size of the protein aggregates in presence of ionic liquids. Furthermore, cofactor binding studies on PaoD showed that the protein is able to discriminate between molybdenum and tungsten bound to the molybdenum cofactor, since only a Mo-MPT form of the cofactor remained bound to PaoD.
The ratio of unsupported protactinium-231 to thorium-230 in marine sediments, (Pa/Th)(xs), is potentially sensitive to several processes of oceanographic and climatological interest: deep ocean circulation, marine biological productivity (as it relates to total particle flux) and particle composition (specifically, biogenic opal and authigenic Mn). In order to attribute variations in (Pa/Th)(xs) observed in sediment records to changes in specific processes through time, a better understanding of the chemical cycling of these elements in the modern ocean is necessary. To this end, a survey was undertaken of (Pa/Th)(xs) in surface sediments from the subarctic Pacific (SO202-INOPEX expedition) in combination with a Pacific-wide compilation of published data. Throughout the Pacific, (Pa/Th)(xs) is robustly correlated with the opal content of sediments. In the North and equatorial Pacific, simultaneous positive correlations with productivity indicators suggest that boundary scavenging and opal scavenging combine to enhance the removal of Pa in the eastern equatorial Pacific and subarctic Pacific. Deep ocean water mass ageing (>3.5 km) associated with the Pacific overturning appears to play a secondary role in determining the basin scale distribution of (Pa/Th)(xs). A basin-wide extrapolation of Pa removal is performed which suggests that the Pacific Pa budget is nearly in balance. We hypothesize that through time (Pa/Th)(xs) distributions in the Pacific could define the evolving boundaries of contrasting biogeographic provinces in the North Pacific, while the influence of hydrothermal scavenging of Pa potentially confounds this approach in the South Pacific.
Biological materials have ever been used by humans because of their remarkable properties. This is surprising since the materials are formed under physiological conditions and with commonplace constituents. Nature thus not only provides us with inspiration for designing new materials but also teaches us how to use soft molecules to tune interparticle and external forces to structure and assemble simple building blocks into functional entities. Magnetotactic bacteria and their chain of magnetosomes represent a striking example of such an accomplishment where a very simple living organism controls the properties of inorganics via organics at the nanometer-scale to form a single magnetic dipole that orients the cell in the Earth magnetic field lines. My group has developed a biological and a bio-inspired research based on these bacteria. My research, at the interface between chemistry, materials science, physics, and biology focuses on how biological systems synthesize, organize and use minerals. We apply the design principles to sustainably form hierarchical materials with controlled properties that can be used e.g. as magnetically directed nanodevices towards applications in sensing, actuating, and transport. In this thesis, I thus first present how magnetotactic bacteria intracellularly form magnetosomes and assemble them in chains. I developed an assay, where cells can be switched from magnetic to non-magnetic states. This enabled to study the dynamics of magnetosome and magnetosome chain formation. We found that the magnetosomes nucleate within minutes whereas chains assembles within hours. Magnetosome formation necessitates iron uptake as ferrous or ferric ions. The transport of the ions within the cell leads to the formation of a ferritin-like intermediate, which subsequently is transported and transformed within the magnetosome organelle in a ferrihydrite-like precursor. Finally, magnetite crystals nucleate and grow toward their mature dimension. In addition, I show that the magnetosome assembly displays hierarchically ordered nano- and microstructures over several levels, enabling the coordinated alignment and motility of entire populations of cells. The magnetosomes are indeed composed of structurally pure magnetite. The organelles are partly composed of proteins, which role is crucial for the properties of the magnetosomes. As an example, we showed how the protein MmsF is involved in the control of magnetosome size and morphology. We have further shown by 2D X-ray diffraction that the magnetosome particles are aligned along the same direction in the magnetosome chain. We then show how magnetic properties of the nascent magnetosome influence the alignment of the particles, and how the proteins MamJ and MamK coordinate this assembly. We propose a theoretical approach, which suggests that biological forces are more important than physical ones for the chain formation. All these studies thus show how magnetosome formation and organization are under strict biological control, which is associated with unprecedented material properties. Finally, we show that the magnetosome chain enables the cells to find their preferred oxygen conditions if the magnetic field is present. The synthetic part of this work shows how the understanding of the design principles of magnetosome formation enabled me to perform biomimetic synthesis of magnetite particles within the highly desired size range of 25 to 100 nm. Nucleation and growth of such particles are based on aggregation of iron colloids termed primary particles as imaged by cryo-high resolution TEM. I show how additives influence magnetite formation and properties. In particular, MamP, a so-called magnetochrome proteins involved in the magnetosome formation in vivo, enables the in vitro formation of magnetite nanoparticles exclusively from ferrous iron by controlling the redox state of the process. Negatively charged additives, such as MamJ, retard magnetite nucleation in vitro, probably by interacting with the iron ions. Other additives such as e.g. polyarginine can be used to control the colloidal stability of stable-single domain sized nanoparticles. Finally, I show how we can “glue” magnetic nanoparticles to form propellers that can be actuated and swim with the help of external magnetic fields. We propose a simple theory to explain the observed movement. We can use the theoretical framework to design experimental conditions to sort out the propellers depending on their size and effectively confirm this prediction experimentally. Thereby, we could image propellers with size down to 290 nm in their longer dimension, much smaller than what perform so far.
Recent advances in high-throughput omics techniques render it possible to decode the function of genes by using the "guilt-by-association" principle on biologically meaningful clusters of gene expression data. However, the existing frameworks for biological evaluation of gene clusters are hindered by two bottleneck issues: (1) the choice for the number of clusters, and (2) the external measures which do not take in consideration the structure of the analyzed data and the ontology of the existing biological knowledge. Here, we address the identified bottlenecks by developing a novel framework that allows not only for biological evaluation of gene expression clusters based on existing structured knowledge, but also for prediction of putative gene functions. The proposed framework facilitates propagation of statistical significance at each of the following steps: (1) estimating the number of clusters, (2) evaluating the clusters in terms of novel external structural measures, (3) selecting an optimal clustering algorithm, and (4) predicting gene functions. The framework also includes a method for evaluation of gene clusters based on the structure of the employed ontology. Moreover, our method for obtaining a probabilistic range for the number of clusters is demonstrated valid on synthetic data and available gene expression profiles from Saccharomyces cerevisiae. Finally, we propose a network-based approach for gene function prediction which relies on the clustering of optimal score and the employed ontology. Our approach effectively predicts gene function on the Saccharomyces cerevisiae data set and is also employed to obtain putative gene functions for an Arabidopsis thaliana data set.
Biomass allometries and coarse root biomass distribution of mountain birch in southern Iceland
(2014)
Root systems are an important pool of biomass and carbon in forest ecosystems. However, most allometric studies on forest trees focus only on the aboveground components. When estimated, root biomass has most often been calculated by using a fixed conversion factor from aboveground biomass. In order to study the size-related development of the root system of native mountain birch (Betula pubescens Ehrh. ssp. czerepanovii), we collected the coarse root system of 25 different aged birch trees (stem diameter at 50 cm length between 0.2 and 14.1 cm) and characterized them by penetration depth (< 1 m) and root thickness. Based on this dataset, allometric functions for coarse roots (> 5 mm and > 2 mm), root stock, total belowground biomass and aboveground biomass components were calculated by a nonlinear and a linear fitting approach. The study showed that coarse root biomass of mountain birch was almost exclusively (> 95 weight-%) located in the top 30 cm, even in a natural old-growth woodland. By using a cross-validation approach, we found that the nonlinear fitting procedure performed better than the linear approach with respect to predictive power. In addition, our results underscore that general assumptions of fixed conversion factors lead to an underestimation of the belowground biomass. Thus, our results provide allometric functions for a more accurate root biomass estimation to be utilized in inventory reports and ecological studies.
Patterns of past vegetation changes over time and space can help facilitate better understanding of the interactions among climate, ecosystem, and human impact. Biome changes in China over the last 22,000 yr (calibrated radiocarbon date, a BP) were numerically reconstructed by using a standard approach of pollen-plant functional type-biome assignment (biomization). The biomization procedure involves pollen data from 2434 surface sites and 228 fossil sites with a high quality of pollen count and C-14 dating, 51 natural and three anthropogenic plant functional types (PFTs), as well as 19 natural and one anthropogenic biome. Surface pollen-based reconstruction of modern natural biome patterns is in good agreement (74.4%) with actual vegetation distribution in China. However, modem large-scale anthropogenic biome reconstruction has not been successful based on the current setup of three anthropogenic PFTs (plantation, secondary, and disturbed PFT) because of the limitation of non-species level pollen identification and the difficulty in the clear assignment of disturbed PFTs. The non-anthropogenic biome distributions of 44 time slices at 500-year intervals show large-scale discrepant and changed vegetation patterns from the last glacial maximum (LGM) to the Holocene throughout China. From 22 ka BP to 19 ka BP, temperate grassland, xerophytic shrubland, and desert dominated northern China, whereas cold or cool forests flourished in central China. Warm-temperate evergreen forests were restricted to far southern China, and tropical forests were absent During 18.5 ka BP to 12 ka BP, cold, cool, and dry biomes extended to some parts of northern, westem, and eastern China. Warm-temperate evergreen and mixed forests gradually expanded to occupy the whole of southern China. A slight northward shift of forest biomes occurred from 15 ka BP to 12 lea BP. During 11.5 ka BP to 9 ka BP, temperate grassland and shrubland gradually stretched to northern and western China. Cold and cool forests widely expanded into northern and central China, as well as in the northern margin of South China along with temperate deciduous forest. Since the early mid-Holocene (approximately 8.5 ka BP to 5.5 ka BP), all forest biomes shifted northward at the expense of herbaceous and shrubby biomes. Simultaneously, cold and cool forest biomes occupied the marginal areas of the Tibetan Plateau and the high mountains in western China. During the middle to late Holocene, from 5 ka to the present, temperate grassland and xerophytic shrubland expanded to the south and east, whereas temperate deciduous forests slightly shifted southward. After 3 lea BP, forest biomes were absent in western China and on the Tibetan plateau surface. Dramatic biome shifts from the LGM to the Holocene were observed in the forest-grassland ecotone and transitional zones between temperate and subtropical climates, between subtropical and tropical regions, and in the mountainous margins of the eastern Tibetan Plateau. Evidence showed more human disturbances during the late Holocene. More pollen records and historical documents are therefore further needed to understand fully the human disturbance-induced large-scale forest changes. In addition, more classifications of anthropogenic biome or land cover, more distinct assignment of pollen taxa to anthropogenic PFTs, and more effective numerical and/or mechanistic techniques in building large-scale human disturbances are required. (C) 2014 Elsevier B.V. All rights reserved.
The relative contribution of personal and social information to explain individual and collective behavior in different species and contexts is an open question in animal ecology. In particular, there is a major lack of studies combining theoretical and empirical approaches to test the relative relevance of different hypothesized individual behaviors to predict empirical collective patterns. We used an individual-based model to confront three hypotheses about the information transfer between social scavengers (Griffon Vultures, Gyps fulvus) when searching for carrion: (1) Vultures only use personal information during foraging ("nonsocial" hypothesis); (2) they create long chains of vultures by following both other vultures that are flying towards carcasses and vultures that are following other vultures that are flying towards carcasses ("chains of vultures" hypothesis); and (3) vultures are only attracted by other vultures that are sinking vertically to a carcass ("local enhancement" hypothesis). The chains of vultures hypothesis has been used in existing models, but never been confronted with field data. Testing is important, though, because these hypotheses could have different management implications. The model was parameterized to mimic the behavior and the densities of both Griffon Vultures and carcasses in a 10 000-km(2) study area in northeastern Spain. We compared the number of vultures attending simulated carcasses with those attending 25 continuously monitored experimental carcasses in the field. Social hypotheses outperformed the nonsocial hypothesis. The chains of vultures hypothesis overestimated the number of vultures feeding on carcasses; the local enhancement hypothesis fitted closely to the empirical data. Supported by our results, we discuss mechanistic and adaptive considerations that reveal that local enhancement may be the key social mechanism behind collective foraging in this and likely other avian scavengers and/or social birds. It also highlights the current need for more studies confronting alternative models of key behaviors with empirical patterns in order to understand how collective behavior emerges in animal societies.
H-1 NMR relaxation is used to study the self-assembly of a double thermoresponsive diblock copolymer in dilute aqueous solution. Above the first transition temperature, at which aggregation into micellar structures is observed, the trimethylsilyl (TMS)-labeled end group attached to the shell-forming block shows a biphasic T-2 relaxation. The slow contribution reflects the TMS groups located at the periphery of the hydrophilic shell, in agreement with a star-like micelle. The fast T-2 contribution corresponds to the TMS groups, which fold back toward the hydrophobic core, reflecting a flower-like micelle. These results confirm the formation of block copolymer micelles of an intermediate nature (i.e., of partial flower-like and star-like character), in which a part of the TMS end groups folds back to the core due to hydrophobic interactions.
During heart development, the onset of heartbeat and blood flow coincides with a ballooning of the cardiac chambers. Here, we have used the zebrafish as a vertebrate model to characterize chamber ballooning morphogenesis of the endocardium, a specialized population of endothelial cells that line the interior of the heart. By combining functional manipulations, fate mapping studies, and high-resolution imaging, we show that endocardial growth occurs without an influx of external cells. Instead, endocardial cell proliferation is regulated, both by blood flow and by Bmp signaling, in a manner independent of vascular endothelial growth factor (VEGF) signaling. Similar to myocardial cells, endocardial cells obtain distinct chamber-specific and inner- versus outer-curvature-specific surface area sizes. We find that the hemodynamic-sensitive transcription factor Klf2a is involved in regulating endocardial cell morphology. These findings establish the endocardium as the flow-sensitive tissue in the heart with a key role in adapting chamber growth in response to the mechanical stimulus of blood flow.
We sought to investigate the effects of wearing a mobile respiratory gas analysis system during a treadmill test on blood lactate (bLa) concentrations and commonly applied bLa thresholds. A total of 16 recreational athletes (31 +/- 3 years, V0205: 58 6 ml min(-1)-kg(-1)) performed one multistage treadmill test with and one without gas exchange measurements (GEM and noGEM). The whole bLa curve, the lactate threshold (LT), the individual anaerobic thresholds according to Stegmann(IAT(sr)) and Dickhuth (IAT(Di)), and a fixed bLa concentration of 4 mmob.l(-1) (OBLA) were evaluated. The bLa curve was shifted slightly leftward in GEM compared to noGEM (P<0.05), whereas the heart rate response was not different between conditions (P= 0.89). There was no difference between GEM and noGEM for LT (2.61 +/- 0.34 vs. 2.64 +/- 0.39 m(-1) s(-1) P=0.49) and IAT(st) (3.47 +/- 0.42 vs. 3.55 +/- 0.47m-s(-1), P=0.12). However, IATD(Di) (3.57 +/- 0.39 vs. 3.66 +/- 0.44m-s(-1), P<0.01) and OBLA (3.85 +/- 0.46 vs. 3.96 +/- 0.47m-s-1, P<0.01) occurred at slower running velocities in GEM. The bLa response to treadmill tests is mildly affected by wearing a mobile gas analysis system. This also applies to bLa thresholds located at higher exercise intensities. While the magnitude of the effects is of little importance for recreational athletes, it might be relevant for elite athletes and scientific studies.
Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.
Method: This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes.
Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril. Ten-week-old male diabetic db/db mice were treated for 3 months with either vehicle (n = 10), 3 mg linagliptin/kg per day (n = 8), or 20 mg enalapril/kg per day (n = 10). Heterozygous db/m mice treated with vehicle served as healthy controls (n = 8). Results: Neither linagliptin nor enalapril had significant effects on the parameters of glucose metabolism or blood pressure in diabetic db/db mice. However, linagliptin treatment reduced albuminuria and attenuated kidney injury. In addition, expression of podocyte marker podocalyxin was normalized. We also analysed DPP-4 expression by immunofluorescence in human kidney biopsies and detected upregulation of DPP-4 in the glomeruli of patients with diabetic nephropathy, suggesting that our findings might be of relevance for human kidney disease as well.
Conclusion: Treatment with DPP-4 inhibitor linagliptin delays the progression of diabetic nephropathy damage in a glucose-independent and blood-pressure-independent manner. The observed effects may be because of the attenuation of podocyte injury and inhibition of myofibroblast transformation.
Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro
(2014)
The prevention of an inflammation in the brain is one of the most important goals the body has to achieve. As pericytes are located on the abluminal side of the capillaries in the brain, their role in fighting against invading pathogens has been investigated in some points, mostly in their ability to behave like macrophages. Here we studied the potential of pericytes to react as immune cells under inflammatory conditions, especially regarding the expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), major histocompatibility complex II (MHC II) molecules, CD68, as well as the generation of reactive oxygen and nitrogen species (RONS), and their ability in phagocytosis. Quantitative real time PCR and western blot analysis showed that pericytes are able to increase the expression of typical inflammatory marker proteins after the stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), interferon-gamma (IFN-gamma), or lipopolysaccharides (LPS). Depending on the different specific pro-inflammatory factors pericytes changed the expression of alpha smooth muscle actin (alpha SMA), the most predominant pericyte marker. We conclude that the role of the pericytes within the immune system is regulated and fine-tuned by different cytokines strongly depending on the time when the cytokines are released and their concentration. The present results will help to understand the pericyte mediated defense mechanisms in the brain.
Neuroscientific studies have shown that brain activity correlated with a decision to move can be observed before a person reports being consciously aware of having made that decision (e.g., Libet, Gleason, Wright, & Pearl, 1983; Soon, Brass, Heinze, & Haynes, 2008). Given that a later event (i.e., conscious awareness) cannot cause an earlier one (i.e., decision-related brain activity), such results have been interpreted as evidence that decisions are made unconsciously (e.g., Libet, 1985). We argue that this interpretation depends upon an all-or-none view of consciousness, and we offer an alternative interpretation of the early decision-related brain activity based on models in which conscious awareness of the decision to move develops gradually up to the level of a reporting criterion. Under this interpretation, the early brain activity reflects sub-criterion levels of awareness rather than complete absence of awareness and thus does not suggest that decisions are made unconsciously.
We present and study a family of finite amplitude breathers on a genuinely anharmonic Klein-Gordon lattice embedded in a nonlinear site potential. The direct numerical simulations are supported by a quasilinear Schrodinger equation (QLS) derived by averaging out the fast oscillations assuming small, albeit finite, amplitude vibrations. The genuinely anharmonic interlattice forces induce breathers which are strongly localized with tails evanescing at a doubly exponential rate and are either close to a continuum, with discrete effects being suppressed, or close to an anticontinuum state, with discrete effects being enhanced. Whereas the D-QLS breathers appear to be always stable, in general there is a stability threshold which improves with spareness of the lattice.
We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction epsilon(hb)(AT) for an AT base pair and the ring factor. turn out to be the most sensitive parameters. In addition, the stacking interaction epsilon(st)(TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization. (c) 2014 AIP Publishing LLC.
We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction epsilon(hb)(AT) for an AT base pair and the ring factor. turn out to be the most sensitive parameters. In addition, the stacking interaction epsilon(st)(TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization.
While the maturity of process mining algorithms increases and more process mining tools enter the market, process mining projects still face the problem of different levels of abstraction when comparing events with modeled business activities. Current approaches for event log abstraction try to abstract from the events in an automated way that does not capture the required domain knowledge to fit business activities. This can lead to misinterpretation of discovered process models. We developed an approach that aims to abstract an event log to the same abstraction level that is needed by the business. We use domain knowledge extracted from existing process documentation to semi-automatically match events and activities. Our abstraction approach is able to deal with n:m relations between events and activities and also supports concurrency. We evaluated our approach in two case studies with a German IT outsourcing company. (C) 2014 Elsevier Ltd. All rights reserved.
The correctness of model transformations is a crucial element for model-driven engineering of high-quality software. A prerequisite to verify model transformations at the level of the model transformation specification is that an unambiguous formal semantics exists and that the implementation of the model transformation language adheres to this semantics. However, for existing relational model transformation approaches, it is usually not really clear under which constraints particular implementations really conform to the formal semantics. In this paper, we will bridge this gap for the formal semantics of triple graph grammars (TGG) and an existing efficient implementation. While the formal semantics assumes backtracking and ignores non-determinism, practical implementations do not support backtracking, require rule sets that ensure determinism, and include further optimizations. Therefore, we capture how the considered TGG implementation realizes the transformation by means of operational rules, define required criteria, and show conformance to the formal semantics if these criteria are fulfilled. We further outline how static and runtime checks can be employed to guarantee these criteria.
Methods: We approached a group of 61 male competitive bodybuilders and collected urine samples for biochemical testing. The pictorial doping Brief Implicit Association Test (BIAT) was used for attitude measurement. This test quantifies the difference in response latencies (in milliseconds) to stimuli representing related concepts (i.e. doping-dislike/like-[health food]).
The emission characteristics of a novel, specially designed broad area diode laser (BAL) with on-chip transversal Bragg resonance (TBR) grating in lateral direction were investigated in an off-axis external cavity setup. The internal TBR grating defines a low loss transversal mode at a specific angle of incidence and a certain wavelength. By providing feedback at this specific angle with an external mirror, it is possible to select this low loss transverse mode and stabilize the BAL. Near diffraction limited emission with an almost single lobed far field pattern could be realized, in contrast to the double lobed far field pattern of similar setups using standard BALs or phase-locked diode laser arrays. Furthermore, we could achieve a narrow bandwidth emission with a simplified setup without external frequency selective elements. (C) 2014 Optical Society of America
In the field of disk-based parallel database management systems exists a great variety of solutions based on a shared-storage or a shared-nothing architecture. In contrast, main memory-based parallel database management systems are dominated solely by the shared-nothing approach as it preserves the in-memory performance advantage by processing data locally on each server. We argue that this unilateral development is going to cease due to the combination of the following three trends: a) Nowadays network technology features remote direct memory access (RDMA) and narrows the performance gap between accessing main memory inside a server and of a remote server to and even below a single order of magnitude. b) Modern storage systems scale gracefully, are elastic, and provide high-availability. c) A modern storage system such as Stanford's RAMCloud even keeps all data resident in main memory. Exploiting these characteristics in the context of a main-memory parallel database management system is desirable. The advent of RDMA-enabled network technology makes the creation of a parallel main memory DBMS based on a shared-storage approach feasible.
This thesis describes building a columnar database on shared main memory-based storage. The thesis discusses the resulting architecture (Part I), the implications on query processing (Part II), and presents an evaluation of the resulting solution in terms of performance, high-availability, and elasticity (Part III).
In our architecture, we use Stanford's RAMCloud as shared-storage, and the self-designed and developed in-memory AnalyticsDB as relational query processor on top. AnalyticsDB encapsulates data access and operator execution via an interface which allows seamless switching between local and remote main memory, while RAMCloud provides not only storage capacity, but also processing power. Combining both aspects allows pushing-down the execution of database operators into the storage system. We describe how the columnar data processed by AnalyticsDB is mapped to RAMCloud's key-value data model and how the performance advantages of columnar data storage can be preserved.
The combination of fast network technology and the possibility to execute database operators in the storage system opens the discussion for site selection. We construct a system model that allows the estimation of operator execution costs in terms of network transfer, data processed in memory, and wall time. This can be used for database operators that work on one relation at a time - such as a scan or materialize operation - to discuss the site selection problem (data pull vs. operator push). Since a database query translates to the execution of several database operators, it is possible that the optimal site selection varies per operator. For the execution of a database operator that works on two (or more) relations at a time, such as a join, the system model is enriched by additional factors such as the chosen algorithm (e.g. Grace- vs. Distributed Block Nested Loop Join vs. Cyclo-Join), the data partitioning of the respective relations, and their overlapping as well as the allowed resource allocation.
We present an evaluation on a cluster with 60 nodes where all nodes are connected via RDMA-enabled network equipment. We show that query processing performance is about 2.4x slower if everything is done via the data pull operator execution strategy (i.e. RAMCloud is being used only for data access) and about 27% slower if operator execution is also supported inside RAMCloud (in comparison to operating only on main memory inside a server without any network communication at all). The fast-crash recovery feature of RAMCloud can be leveraged to provide high-availability, e.g. a server crash during query execution only delays the query response for about one second. Our solution is elastic in a way that it can adapt to changing workloads a) within seconds, b) without interruption of the ongoing query processing, and c) without manual intervention.
This work introduces concepts and corresponding tool support to enable a complementary approach in dealing with recovery. Programmers need to recover a development state, or a part thereof, when previously made changes reveal undesired implications. However, when the need arises suddenly and unexpectedly, recovery often involves expensive and tedious work. To avoid tedious work, literature recommends keeping away from unexpected recovery demands by following a structured and disciplined approach, which consists of the application of various best practices including working only on one thing at a time, performing small steps, as well as making proper use of versioning and testing tools. However, the attempt to avoid unexpected recovery is both time-consuming and error-prone. On the one hand, it requires disproportionate effort to minimize the risk of unexpected situations. On the other hand, applying recommended practices selectively, which saves time, can hardly avoid recovery. In addition, the constant need for foresight and self-control has unfavorable implications. It is exhaustive and impedes creative problem solving. This work proposes to make recovery fast and easy and introduces corresponding support called CoExist. Such dedicated support turns situations of unanticipated recovery from tedious experiences into pleasant ones. It makes recovery fast and easy to accomplish, even if explicit commits are unavailable or tests have been ignored for some time. When mistakes and unexpected insights are no longer associated with tedious corrective actions, programmers are encouraged to change source code as a means to reason about it, as opposed to making changes only after structuring and evaluating them mentally. This work further reports on an implementation of the proposed tool support in the Squeak/Smalltalk development environment. The development of the tools has been accompanied by regular performance and usability tests. In addition, this work investigates whether the proposed tools affect programmers’ performance. In a controlled lab study, 22 participants improved the design of two different applications. Using a repeated measurement setup, the study examined the effect of providing CoExist on programming performance. The result of analyzing 88 hours of programming suggests that built-in recovery support as provided with CoExist positively has a positive effect on programming performance in explorative programming tasks.
Entrepreneurship is known to be a main driver of economic growth. Hence, governments have an interest in supporting and promoting entrepreneurial activities. Start-up subsidies, which have been analyzed extensively, only aim at mitigating the lack of financial capital. However, some entrepreneurs also lack in human, social, and managerial capital. One way to address these shortcomings is by subsidizing coaching programs for entrepreneurs. However, theoretical and empirical evidence about business coaching and programs subsidizing coaching is scarce. This dissertation gives an extensive overview of coaching and is the first empirical study for Germany analyzing the effects of coaching programs on its participants. In the theoretical part of the dissertation the process of a business start-up is described and it is discussed how and in which stage of the company’s evolvement coaching can influence entrepreneurial success. The concept of coaching is compared to other non-monetary types of support as training, mentoring, consulting, and counseling. Furthermore, national and international support programs are described. Most programs have either no or small positive effects. However, there is little quantitative evidence in the international literature. In the empirical part of the dissertation the effectiveness of coaching is shown by evaluating two German coaching programs, which support entrepreneurs via publicly subsidized coaching sessions. One of the programs aims at entrepreneurs who have been employed before becoming self-employed, whereas the other program is targeted at former unemployed entrepreneurs. The analysis is based on the evaluation of a quantitative and a qualitative dataset. The qualitative data are gathered by intensive one-on-one interviews with coaches and entrepreneurs. These data give a detailed insight about the coaching topics, duration, process, effectiveness, and the thoughts of coaches and entrepreneurs. The quantitative data include information about 2,936 German-based entrepreneurs. Using propensity score matching, the success of participants of the two coaching programs is compared with adequate groups of non-participants. In contrast to many other studies also personality traits are observed and controlled for in the matching process. The results show that only the program for former unemployed entrepreneurs has small positive effects. Participants have a larger survival probability in self-employment and a larger probability to hire employees than matched non-participants. In contrast, the program for former employed individuals has negative effects. Compared to individuals who did not participate in the coaching program, participants have a lower probability to stay in self-employment, lower earned net income, lower number of employees and lower life satisfaction. There are several reasons for these differing results of the two programs. First, former unemployed individuals have more basic coaching needs than former employed individuals. Coaches can satisfy these basic coaching needs, whereas former employed individuals have more complex business problems, which are not very easy to be solved by a coaching intervention. Second, the analysis reveals that former employed individuals are very successful in general. It is easier to increase the success of former unemployed individuals as they have a lower base level of success than former employed individuals. An effect heterogeneity analysis shows that coaching effectiveness differs by region. Coaching for previously unemployed entrepreneurs is especially useful in regions with bad labor market conditions. In summary, in line with previous literature, it is found that coaching has little effects on the success of entrepreneurs. The previous employment status, the characteristics of the entrepreneur and the regional labor market conditions play a crucial role in the effectiveness of coaching. In conclusion, coaching needs to be well tailored to the individual and applied thoroughly. Therefore, governments should design and provide coaching programs only after due consideration.
Recently, C K-edge Near Edge X-ray Absorption Fine Structure (NEXAFS) spectra of graphite (HOPG) surfaces have been measured for the pristine material, and for HOPG treated with either bromine or krypton plasmas (Lippitz et al., Surf. Sci., 2013, 611, L1). Changes of the NEXAFS spectra characteristic for physical (krypton) and/or chemical/physical modifications of the surface (bromine) upon plasma treatment were observed. Their molecular origin, however, remained elusive. In this work we study by density functional theory, the effects of selected point and line defects as well as chemical modifications on NEXAFS carbon K-edge spectra of single graphene layers. For Br-treated surfaces, also Br 3d X-ray Photoelectron Spectra (XPS) are simulated by a cluster approach, to identify possible chemical modifications. We observe that some of the defects related to plasma treatment lead to characteristic changes of NEXAFS spectra, similar to those in experiment. Theory provides possible microscopic origins for these changes.
Recently, C K-edge Near Edge X-ray Absorption Fine Structure (NEXAFS) spectra of graphite (HOPG) surfaces have been measured for the pristine material, and for HOPG treated with either bromine or krypton plasmas (Lippitz et al., Surf. Sci., 2013, 611, L1). Changes of the NEXAFS spectra characteristic for physical (krypton) and/or chemical/physical modifications of the surface (bromine) upon plasma treatment were observed. Their molecular origin, however, remained elusive. In this work we study by density functional theory, the effects of selected point and line defects as well as chemical modifications on NEXAFS carbon K-edge spectra of single graphene layers. For Br-treated surfaces, also Br 3d X-ray Photoelectron Spectra (XPS) are simulated by a cluster approach, to identify possible chemical modifications. We observe that some of the defects related to plasma treatment lead to characteristic changes of NEXAFS spectra, similar to those in experiment. Theory provides possible microscopic origins for these changes.
Recently, C K-edge Near Edge X-ray Absorption Fine Structure (NEXAFS) spectra of graphite (HOPG) surfaces have been measured for the pristine material, and for HOPG treated with either bromine or krypton plasmas (Lippitz et al., Surf. Sci., 2013, 611, L1). Changes of the NEXAFS spectra characteristic for physical (krypton) and/or chemical/physical modifications of the surface (bromine) upon plasma treatment were observed. Their molecular origin, however, remained elusive. In this work we study by density functional theory, the effects of selected point and line defects as well as chemical modifications on NEXAFS carbon K-edge spectra of single graphene layers. For Br-treated surfaces, also Br 3d X-ray Photoelectron Spectra (XPS) are simulated by a cluster approach, to identify possible chemical modifications. We observe that some of the defects related to plasma treatment lead to characteristic changes of NEXAFS spectra, similar to those in experiment. Theory provides possible microscopic origins for these changes.
The ubiquitous InsP(3)/Ca2+ signalling pathway is modulated by diverse mechanisms, i.e. feedback of Ca2+ and interactions with other signalling pathways. In the salivary glands of the blowfly Calliphora vicina, the hormone serotonin (5-HT) causes a parallel rise in intracellular [Ca2+] and [cAMP] via two types of 5-HT receptors. We have shown recently that cAMP/protein kinase A (PKA) sensitizes InsP(3)-induced Ca2+ release. We have now identified the protein phosphatase that counteracts the effect of PKA on 5-HT-induced InsP(3)/Ca2+ signalling. We demonstrate that (1) tautomycin and okadaic acid, inhibitors of protein phosphatases PP1 and PP2A, have no effect on 5-HT-induced Ca2+ signals; (2) cyclosporin A and FK506, inhibitors of Ca2+/calmodulin-activated protein phosphatase calcineurin, cause an increase in the frequency of 5-HT-induced Ca2+ oscillations; (3) the sensitizing effect of cyclosporin A on 5-HT-induced Ca2+ responses does not involve Ca2+ entry into the cells; (4) cyclosporin A increases InsP(3)-dependent Ca2+ release; (5) inhibition of PKA abolishes the effect of cyclosporin A on the 5-HT-induced Ca2+ responses, indicating that PKA and calcineurin act antagonistically on the InsP(3)/Ca2+ signalling pathway. These findings suggest that calcineurin provides a negative feedback on InsP(3)/Ca2+ signalling in blowfly salivary glands, counteracting the effect of PKA and desensitizing the signalling cascade at higher 5-HT concentrations. (C) 2014 Elsevier Ltd. All rights reserved.
The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P(3). Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P(3)-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts.
Changes in performance parameters over four consecutive maximal incremental cycling tests were investigated to determine how many tests can be performed within one single day without negatively affecting performance. Sixteen male and female subjects (eight trained (T): 25 +/- 3 yr, BMI 22.6 +/- 2.5 kg center dot m(-2), maximal power output (P-max) 4.6 +/- 0.5 W center dot kg(-1); eight untrained (UT): 27 +/- 3 yr, BMI 22.3 +/- 1.2 kg center dot m(-2), P-max 2.9 +/- 0.3 W center dot kg(-1)) performed four successive maximal incremental cycling tests separated by 1.5 h of passive rest. Individual energy requirements were covered by standardised meals between trials. Maximal oxygen uptake (VO2max) remained unchanged over the four tests in both groups (P = 0.20 and P = 0.33, respectively). P-max did not change in the T group (P = 0.32), but decreased from the third test in the UT group (P < 0.01). Heart rate responses to submaximal exercise were elevated from the third test in the T group and from the second test in the UT group (P < 0.05). The increase in blood lactate shifted rightward over the four tests in both groups (P < 0.001 and P < 0.01, respectively). Exercise-induced net increases in epinephrine and norepinephrine were not different between the tests in either group (P 0.15). If VO2max is the main parameter of interest, trained and untrained individuals can perform at least four maximal incremental cycling tests per day. However, because other parameters changed after the first and second test, respectively, no more than one test per day should be performed if parameters other than VO2max are the prime focus.
Can PPPs make it anywhere? how limited statehood and other area factors influence PPP effectiveness
(2014)
Can short-term incentives induce long-lasting cooperation? Results from a public-goods experiment
(2014)
This paper investigates whether providing strong cooperation incentives only at the outset of a group interaction spills over to later periods to ensure cooperation in the long run. We study a repeated linear public-good game with punishment opportunities and a parameter change after the first ten (of twenty) rounds. Our data shows that cooperation among subjects who had experienced a higher marginal return on public-good contributions or low punishment costs in rounds 1-10 rapidly deteriorated in rounds 11-20 once these incentives were removed, eventually trending below the level of cooperation in the control group. This suggests the possibility of temporary incentives backfiring in the long run. This paper ties in with the literature highlighting the potentially adverse effects of the use of incentives. (C) 2014 Elsevier Inc. All rights reserved.
In adults, the level of ability to perceive one's own body signals plays an important role for many concepts of emotional experience as demonstrated for emotion processing or emotion regulation. Representative data on perception of body signals and its emotional correlates in children is lacking. Therefore, the present study investigated the cardiac sensitivity of 1,350 children between 6 and 11 years of age in a heartbeat perception task. Our main findings demonstrated the distribution of cardiac sensitivity in children as well as associations with interpersonal emotional intelligence and adaptability. Furthermore, independent of body mass index, boys showed a significantly higher cardiac sensitivity than girls. We conclude that cardiac sensitivity in children appears to show weaker but similar characteristics and relations to emotional parameters as found in adults, so that a dynamic developmental process can be assumed.
It is proposed that xanthophylls, and carotenoids in general, may assist in energy transfer from the chlorophyll Soret band to the Q band. Ground-state (1A(g)) and excited-state (1B(u)) optimizations of violaxanthin (Vx) and zeaxanthin (Zx) are performed in an environment mimicking the light-harvesting complex II (LHCII), including the closest chlorophyll b molecule (Chl). Time-dependent density functional theory (TD-DFT, CAM-B3LYP functional) is used in combination with a semi-empirical description to obtain the excited-state geometries, supported by additional DFT/multireference configuration interaction calculations, with and without point charges representing LHCII. In the ground state, Vx and Zx show similar properties. At the 1B(u) minimum, the energy of the Zx 1Bu state is below the Chl Q band, in contrast to Vx. Both Vx and Zx may act as acceptors of Soret-state energy; transfer to the Q band seems to be favored for Vx. These findings suggest that carotenoids may generally mediate Soret-to-Q energy flow in LHCII.
Catalytic bio-chemo and bio-bio tandem oxidation reactions for amide and carboxylic acid synthesis
(2014)
A catalytic toolbox for three different water-based one-pot cascades to convert aryl alcohols to amides and acids and cyclic amines to lactams, involving combination of oxidative enzymes (monoamine oxidase, xanthine dehydrogenase, galactose oxidase and laccase) and chemical oxidants (TBHP or Cul(cat)/H2O2) at mild temperatures, is presented. Mutually compatible conditions were found to afford products in good to excellent yields.
Catalytic bio–chemo and bio–bio tandem oxidation reactions for amide and carboxylic acid synthesis
(2014)
A catalytic toolbox for three different water-based one-pot cascades to convert aryl alcohols to amides and acids and cyclic amines to lactams, involving combination of oxidative enzymes (monoamine oxidase, xanthine dehydrogenase, galactose oxidase and laccase) and chemical oxidants (TBHP or CuI(cat)/H2O2) at mild temperatures, is presented. Mutually compatible conditions were found to afford products in good to excellent yields.
The onset of a solar eruption is formulated here as either a magnetic catastrophe or as an instability. Both start with the same equation of force balance governing the underlying equilibria. Using a toroidal flux rope in an external bipolar or quadrupolar field as a model for the current-carrying flux, we demonstrate the occurrence of a fold catastrophe by loss of equilibrium for several representative evolutionary sequences in the stable domain of parameter space. We verify that this catastrophe and the torus instability occur at the same point; they are thus equivalent descriptions for the onset condition of solar eruptions.
Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24-30 years) and 25 older (aged 60-75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.
Cell-penetrating peptide-mediated delivery of phosphorodiamidate morpholino oligomers (PMOs) has shown great promise for exon-skipping therapy of Duchenne Muscular Dystrophy (DMD). Pip6a-PMO, a recently developed conjugate, is particularly efficient in a murine DMD model, although mechanisms responsible for its increased biological activity have not been studied. Here, we evaluate the cellular trafficking and the biological activity of Pip6a-PMO in skeletal muscle cells and primary cardiomyocytes. Our results indicate that Pip6a-PMO is taken up in the skeletal muscle cells by an energy-and caveolae-mediated endocytosis. Interestingly, its cellular distribution is different in undifferentiated and differentiated skeletal muscle cells (vesicular versus nuclear). Likewise, Pip6a-PMO mainly accumulates in cytoplasmic vesicles in primary cardiomyocytes, in which clathrin-mediated endocytosis seems to be the predominant uptake pathway. These differences in cellular trafficking correspond well with the exon-skipping data, with higher activity in myotubes than in myoblasts or cardiomyocytes. These differences in cellular trafficking thus provide a possible mechanistic explanation for the variations in exon-skipping activity and restoration of dystrophin protein in heart muscle compared with skeletal muscle tissues in DMD models. Overall, Pip6a-PMO appears as the most efficient conjugate to date (low nanomolar EC50), even if limitations remain from endosomal escape.
New low-temperature thermochronological data from 80 samples in eastern Kyrgyzstan are combined with previously published data from 61 samples to constrain exhumation in a number of mountain ranges in the Central Kyrgyz Tien Shan. All sampled ranges are found to have a broadly consistent Cenozoic exhumation history, characterized by initially low cooling rates (<1 degrees C/Myr) followed by a series of increases in exhumation that occurred diachronously across the region in the late Cenozoic that are interpreted to record the onset of deformation in different mountain ranges. Combined with geological estimates for the onset of proximal deformation, our data suggest that the Central Kyrgyz Tien Shan started deforming in the late Oligocene-early Miocene, leading to the development of several, widely spaced mountain ranges separated by large intermontane basins. Subsequently, more ranges have been constructed in response to significant shortening increases across the Central Kyrgyz Tien Shan, notably in the late Miocene. The order of range construction is interpreted to reflect variations in the susceptibility of inherited structures to reactivation. Reactivated structures are also shown to have significance along strike variations in fault vergence and displacement, which have influenced the development and growth of individual mountain ranges. Moreover, the timing of deformation allows the former extent of many intermontane basins that have since been partitioned to be inferred; this can be linked to the highly time-transgressive onset of late Cenozoic coarse clastic sedimentation.
Cenozoic magnetostratigraphy and magnetic properties of the southern Issyk-Kul basin, Kyrgyzstan
(2014)
We present paleomagnetic data from the northern flank of the Tianshan range, southeast of Lake Issyk-Kul (Kyrgyzstan). 613 cores were collected in two parallel sections with a total thickness of 960 m (Chon Kyzylsuu, CK) and 990 m Jeti Oguz, JO), as well as 48 cores at six sites in a nearby anticline. Rock magnetic analyses identify both magnetite and hematite in the fluvial-lacustrine sediments. The concentration of both minerals, the magnetite:hematite ratio, and the average magnetite grain size increase upward in both sections. Anisotropy of anhysteretic remanent magnetization defines a tectonic fabric with sub-horizontal maximum axes that parallel the strike direction together with intermediate and minimum axes that streak out about a great circle orthogonal to the maximum axes suggestive of a tectonic fabric emplaced during folding. Stepwise thermal demagnetization isolates interpretable magnetization components in 284 samples that define 26 polarity chrons in CK and 19 in JO. A positive fold test, dual polarities and systematic changes in rock-magnetic parameters with depth suggest that the high temperature magnetization component was acquired coevally with deposition. An age model based on a visual magnetostratigraphic correlation of both sections with the geomagnetic polarity time scale defines absolute ages from 26.0 to 13.3 Ma, with a fairly constant sedimentation rate of 9-10 cm/ka. A correlation based on a numerical algorithm arrives at a slightly different conclusion, with deposition ages from 25.2 to 11.0 Ma and sedimentation rates from 5 to 8 cm/ka. In comparison with sedimentation rates found at other magnetostratigraphic sections in the Tianshan realm, we infer that the sedimentary record in this part of the Issyk-Kul Basin precedes the more rapid phase of uplift of the Kyrgyz Tianshan. The onset of deposition and concomitant erosion of the adjacent Terskey Range is in good agreement with independent assessments of the exhumation history of this mountain range, with erosion increasing at 25-20 Ma and accelerating after 11-13 Ma. (C) 2014 Elsevier B.V. All rights reserved.
Herein, we report the chain-growth tin-free room temperature polymerization method to synthesize n-type perylene diimide-dithiophene-based conjugated polymers (PPDIT2s) suitable for solar cell and transistor applications. The palladium/electron-rich tri-tert-butylphosphine catalyst is effective to enable the chain-growth polymerization of anion-radical monomer Br-TPDIT-Br/Zn to PPDIT2 with a molecular weight up to Mw ≈ 50 kg mol−1 and moderate polydispersity. This is the second example of the polymerization of unusual anion-radical aromatic complexes formed in a reaction of active Zn and electron-deficient diimide-based aryl halides. As such, the discovered polymerization method is not a specific reactivity feature of the naphthalene-diimide derivatives but is rather a general polymerization tool. This is an important finding, given the significantly higher maximum external quantum efficiency that can be reached with PDI-based copolymers (32–45%) in all-polymer solar cells compared to NDI-based materials (15–30%). Our studies revealed that PPDIT2 synthesized by the new method and the previously published polymer prepared by step-growth Stille polycondensation show similar electron mobility and all-polymer solar cell performance. At the same time, the polymerization reported herein has several technological advantages as it proceeds relatively fast at room temperature and does not involve toxic tin-based compounds. Because several chain-growth polymerization reactions are well-suited for the preparation of well-defined multi-functional polymer architectures, the next target is to explore the utility of the discovered polymerization in the synthesis of end-functionalized polymers and block copolymers. Such materials would be helpful to improve the nanoscale morphology of polymer blends in all-polymer solar cells.
Herein, we report the chain-growth tin-free room temperature polymerization method to synthesize n-type perylene diimide-dithiophene-based conjugated polymers (PPDIT2s) suitable for solar cell and transistor applications. The palladium/electron-rich tri-tert-butylphosphine catalyst is effective to enable the chain-growth polymerization of anion-radical monomer Br-TPDIT-Br/Zn to PPDIT2 with a molecular weight up to M-w approximate to 50 kg mol(-1) and moderate polydispersity. This is the second example of the polymerization of unusual anion-radical aromatic complexes formed in a reaction of active Zn and electron-deficient diimide-based aryl halides. As such, the discovered polymerization method is not a specific reactivity feature of the naphthalene-diimide derivatives but is rather a general polymerization tool. This is an important finding, given the significantly higher maximum external quantum efficiency that can be reached with PDI-based copolymers (32-45%) in all-polymer solar cells compared to NDI-based materials (15-30%). Our studies revealed that PPDIT2 synthesized by the new method and the previously published polymer prepared by step-growth Stille polycondensation show similar electron mobility and all-polymer solar cell performance. At the same time, the polymerization reported herein has several technological advantages as it proceeds relatively fast at room temperature and does not involve toxic tin-based compounds. Because several chain-growth polymerization reactions are well-suited for the preparation of well-defined multi-functional polymer architectures, the next target is to explore the utility of the discovered polymerization in the synthesis of end-functionalized polymers and block copolymers. Such materials would be helpful to improve the nanoscale morphology of polymer blends in all-polymer solar cells.
Recently, interest in collecting and mining large sets of educational data on student background and performance to conduct research on learning and instruction has developed as an area generally referred to as learning analytics. Higher education leaders are recognising the value of learning analytics for improving not only learning and teaching but also the entire educational arena. However, theoretical concepts and empirical evidence need to be generated within the fast evolving field of learning analytics. In this paper, we introduce a holistic learning analytics framework. Based on this framework, student, learning, and curriculum profiles have been developed which include relevant static and dynamic parameters for facilitating the learning analytics framework. Based on the theoretical model, an empirical study was conducted to empirically validate the parameters included in the student profile. The paper concludes with practical implications and issues for future research.
For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here, we study the influence of whole blood-and PRP-storage times on changes in platelet morphology and function.
Whole blood PFA100 closure times increased after stimulation with collagen/ADP and collagen/epinephrine. Twenty four hours after blood collection, both parameters were prolonged pathologically above the upper limit of the reference range. Numbers of circulating platelets, measured in PRP, decreased after four hours, but no longer after twenty four hours. Mean platelet volumes (MPV) and platelet large cell ratios (P-LCR, 12 fL - 40 fL) decreased over time. Immediately after blood collection, no debris or platelet aggregates could be visualized microscopically. After four hours, first debris and very small aggregates occurred. After 24 hours, platelet aggregates and also debris progressively increased. In accordance to this, the CASY system revealed an increase of platelet aggregates (up to 90 mu m diameter)with increasing storage time.
The percentage of CD62P positive platelets and PF4 increased significantly with storage time in resting PRP. When soluble ADP was added to stored PRP samples, the number of activatable platelets decreased significantly over storage time. The present study reveals the importance of a consequent standardization in the preparation of WB and PRP. Platelet morphology and function, particularly platelet reactivity to adherent or soluble agonists in their surrounding milieu, changed rapidly outside the vascular system. This knowledge is of crucial interest, particularly in the field of biomaterial development for cardiovascular applications, and may help to define common standards in the in vitro hemocompatibility testing of biomaterials.
We produced low temperature (15 degrees C) processed green tea (LTPGT) with higher aroma contents than normal green tea (Sencha). Normal temperature processed green tea (NTPGT), involved storing at 25 degrees C, and Sencha had no storing process. Sensory evaluation showed LTPGT had higher levels of floral and sweet odorants than NTPGT and Sencha. Aroma extract dilution analysis and gas chromatography-mass spectrometry-olfactometry indicated LTPGT had 12 aroma compounds with high factor dilution values (FD). Amongst LTPGT's 12 compounds, indole, jasmine lactone, cis-jasmone, coumarin, and methyl epijasmonate contributed to floral, fruity and sweet characters. In particular, indole increased initially, peaking at 16 h, then gradually decreased; Feeding experiments suggested [N-15]indole and [N-15]oxygenated indoles (OX-indoles) were produced from [N-15]anthranilic acid. We proposed the increase in indole was due to transformation of anthranilic acid during the 16 h storage and the subsequent decline in indole level was due to its conversion to OX-indoles.
The non-random chromosomal translocations t(10;11)(p13;q23) and t(10;11)(p13;q14-21) result in leukemogenic fusion proteins comprising the coiled coil domain of the transcription factor AF10 and the proteins MLL or CALM, respectively, and subsequently cause certain types of acute leukemia. The AF10 coiled-coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma. Using sequential synthetic peptides, we mapped the potential AF10/GAS41 interaction site, which was subsequently be used as scaffold for a library targeting the AF10 coiled-coil domain. Using phage display, we selected a peptide that binds the AF10 coiled-coil domain with higher affinity than the respective coiled-coil region of wild-type GAS41, as demonstrated by phage ELISA, CD, and PCAs. Furthermore, we were able to successfully deploy the inhibitory peptide in a mammalian cell line to lower the expression of Hoxa genes that have been described to be overexpressed in these leukemias. This work dissects molecular determinants mediating AF10-directed interactions in leukemic fusions comprising the N-terminal parts of the proteins MLL or CALM and the C-terminal coiled-coil domain of AF10. Furthermore, it outlines the first steps in recognizing and blocking the leukemia-associated AF10 interaction in histiocytic lymphoma cells and therefore, may have significant implications in future diagnostics and therapeutics. Copyright (c) 2014 European Peptide Society and John Wiley & Sons, Ltd.
Background: Localization and identification of interaction partners of two splice variants of the human 3-mercaptopyruvate sulfurtransferase TUM1. Results: We show that TUM1 interacts with proteins involved in Moco and FeS cluster biosynthesis. Conclusion: Human TUM1 is a dual localized protein in the cytosol and mitochondria with distinct roles in sulfur transfer and interaction partners. Significance: The study contributes to the sulfur transfer pathway for the biosynthesis of sulfur-containing biofactors.
The human tRNA thiouridine modification protein (TUM1), also designated as 3-mercaptopyruvate sulfurtransferase (MPST), has been implicated in a wide range of physiological processes in the cell. The roles range from an involvement in thiolation of cytosolic tRNAs to the generation of H2S as signaling molecule both in mitochondria and the cytosol. TUM1 is a member of the sulfurtransferase family and catalyzes the conversion of 3-mercaptopyruvate to pyruvate and protein-bound persulfide. Here, we purified and characterized two novel TUM1 splice variants, designated as TUM1-Iso1 and TUM1-Iso2. The purified proteins showed similar kinetic behavior and comparable pH and temperature dependence. Cellular localization studies, however, showed a different localization pattern between the isoforms. TUM1-Iso1 is exclusively localized in the cytosol, whereas TUM1-Iso2 showed a dual localization both in the cytosol and mitochondria. Interaction studies were performed with the isoforms both in vitro using the purified proteins and in vivo by fluorescence analysis in human cells, using the split-EGFP system. The studies showed that TUM1 interacts with the l-cysteine desulfurase NFS1 and the rhodanese-like protein MOCS3, suggesting a dual function of TUM1 both in sulfur transfer for the biosynthesis of the molybdenum cofactor, and for the thiolation of tRNA. Our studies point to distinct roles of each TUM1 isoform in the sulfur transfer processes in the cell, with different compartmentalization of the two splice variants of TUM1.
The contractile vacuole (CV) is an osmoregulatory organelle found exclusively in algae and protists. In addition to expelling excessive water out of the cell, it also expels ions and other metabolites and thereby contributes to the cell's metabolic homeostasis. The interest in the CV reaches beyond its immediate cellular roles. The CV's function is tightly related to basic cellular processes such as membrane dynamics and vesicle budding and fusion; several physiological processes in animals, such as synaptic neurotransmission and blood filtration in the kidney, are related to the CV's function; and several pathogens, such as the causative agents of sleeping sickness, possess CVs, which may serve as pharmacological targets. The green alga Chlamydomonas reinhardtii has two CVs. They are the smallest known CVs in nature, and they remain relatively untouched in the CV-related literature. Many genes that have been shown to be related to the CV in other organisms have close homologues in C. reinhardtii. We attempted to silence some of these genes and observe the effect on the CV. One of our genes, VMP1, caused striking, severe phenotypes when silenced. Cells exhibited defective cytokinesis and aberrant morphologies. The CV, incidentally, remained unscathed. In addition, mutant cells showed some evidence of disrupted autophagy. Several important regulators of the cell cycle as well as autophagy were found to be underexpressed in the mutant. Lipidomic analysis revealed many meaningful changes between wild-type and mutant cells, reinforcing the compromised-autophagy observation. VMP1 is a singular protein, with homologues in numerous eukaryotic organisms (aside from fungi), but usually with no relatives in each particular genome. Since its first characterization in 2002 it has been associated with several cellular processes and functions, namely autophagy, programmed cell-death, secretion, cell adhesion, and organelle biogenesis. It has been implicated in several human diseases: pancreatitis, diabetes, and several types of cancer. Our results reiterate some of the observations in VMP1's six reported homologues, but, importantly, show for the first time an involvement of this protein in cell division. The mechanisms underlying this involvement in Chlamydomonas, as well as other key aspects, such as VMP1's subcellular localization and interaction partners, still await elucidation.
Para-maleimidophenyl (p-MP) modified gold surfaces have been prepared by one-step electrochemical deposition and used in surface plasmon resonance (SPR) studies. Therefore, a FITC mimotope peptide (MP1, 12 aa), a human mucin 1 epitope peptide (MUC, 9 aa) and a protein with their specific antibodies were used as model systems. The peptides were modified with an N-terminal cysteine for covalent and directed coupling to the maleimido functionalized surface by means of Michael addition. The coupling yield of the peptide, the binding characteristics of antibody and the unspecific adsorption of the analytes were investigated. The results expand the spectrum of biosensors usable with p-MP by widely used SPR and support its potential to be versatile for several electrochemical and optical biosensors. This allows the combination of an electrochemical and optical read-out for a broad variety of biomolecular interactions on the same chip. Copyright (c) 2014 John Wiley & Sons, Ltd.
We have isolated a cDNA coding for a putative invertebrate-type dopamine receptor (Peadop2) from P. americana brain by using a PCR-based strategy. The mRNA is present in samples from brain and salivary glands. We analyzed the distribution of the PeaDOP2 receptor protein with specific affinity-purified polyclonal antibodies. On Western blots, PeaDOP2 was detected in protein samples from brain, subesophageal ganglion, thoracic ganglia, and salivary glands. In immunocytochemical experiments, we detected PeaDOP2 in neurons with their somata being located at the anterior edge of the medulla bilaterally innervating the optic lobes and projecting to the ventro-lateral protocerebrum. In order to determine the functional and pharmacological properties of the cloned receptor, we generated a cell line constitutively expressing PeaDOP2. Activation of PeaDOP2-expressing cells with dopamine induced an increase in intracellular cAMP. In contrast, a C-terminally truncated splice variant of this receptor did not exhibit any functional property by itself. The molecular and pharmacological characterization of the first dopamine receptor from P. americana provides the basis for forthcoming studies focusing on the significance of the dopaminergic system in cockroach behavior and physiology.
Characterization of drought tolerance in potato cultivars for identification of molecular markers
(2014)
A series of multiblock copolymers (PDLCL) synthesized from oligo(omega-pentadecalactone) diol (OPDL) and oligo(epsilon-caprolactone) diol (OCL), which are linked by 2,2(4), 4-trimethyl-hexamethylene diisocyanate (TMDI), is investigated by the Langmuir monolayer technique at the air-water interface. Brewster angle microscopy (BAM) and spectroscopic ellipsometry are employed to characterize the polymer film morphologies in situ. PDLCL containing >= 40 wt% OCL segments form homogeneous Langmuir monofilms after spreading. The film elasticity modulus decreases with increasing amounts of OPDL segments in the copolymer. In contrast, the OCL-free polyesterurethane OPDL-TMDI cannot be spread to monomolecular films on the water surface properly, and movable slabs are observed by BAM even at low surface pressures. The results of the in situ morphological characterization clearly show that essential information concerning the reliability of Langmuir monolayer degradation (LMD) experiments cannot be obtained from the evaluation of the pi-A isotherms only. Consequently, in situ morphological characterization turns out to be indispensable for characterization of Langmuir layers before LMD experiments.
The adaptation of cell growth and proliferation to environmental changes is essential for the surviving of biological systems. The evolutionary conserved Ser/Thr protein kinase “Target of Rapamycin” (TOR) has emerged as a major signaling node that integrates the sensing of numerous growth signals to the coordinated regulation of cellular metabolism and growth. Although the TOR signaling pathway has been widely studied in heterotrophic organisms, the research on TOR in photosynthetic eukaryotes has been hampered by the reported land plant resistance to rapamycin. Thus, the finding that Chlamydomonas reinhardtii is sensitive to rapamycin, establish this unicellular green alga as a useful model system to investigate TOR signaling in photosynthetic eukaryotes.
The observation that rapamycin does not fully arrest Chlamydomonas growth, which is different from observations made in other organisms, prompted us to investigate the regulatory function of TOR in Chlamydomonas in context of the cell cycle. Therefore, a growth system that allowed synchronously growth under widely unperturbed cultivation in a fermenter system was set up and the synchronized cells were characterized in detail. In a highly resolved kinetic study, the synchronized cells were analyzed for their changes in cytological parameters as cell number and size distribution and their starch content. Furthermore, we applied mass spectrometric analysis for profiling of primary and lipid metabolism. This system was then used to analyze the response dynamics of the Chlamydomonas metabolome and lipidome to TOR-inhibition by rapamycin
The results show that TOR inhibition reduces cell growth, delays cell division and daughter cell release and results in a 50% reduced cell number at the end of the cell cycle. Consistent with the growth phenotype we observed strong changes in carbon and nitrogen partitioning in the direction of rapid conversion into carbon and nitrogen storage through an accumulation of starch, triacylglycerol and arginine. Interestingly, it seems that the conversion of carbon into triacylglycerol occurred faster than into starch after TOR inhibition, which may indicate a more dominant role of TOR in the regulation of TAG biosynthesis than in the regulation of starch.
This study clearly shows, for the first time, a complex picture of metabolic and lipidomic dynamically changes during the cell cycle of Chlamydomonas reinhardtii and furthermore reveals a complex regulation and adjustment of metabolite pools and lipid composition in response to TOR inhibition.
Binding of heme to the amyloid peptides A beta 40/42 is thought to be an initial step in the development of symptoms in the early stages of Alzheimer's disease by enhancing the intrinsic peroxidatic activity of heme. We found considerably higher acceleration of the reaction for the physiologically relevant neurotransmitters dopamine and serotonin than reported earlier for the artificial substrate 3,3',5,5'-tetramethylbenzidine (TMB). Thus, the binding of hemin to A beta peptides might play an even more crucial role in the early stages of Alzheimer's disease than deduced from these earlier results. To mimic complex formation, a new surface architecture has been developed: The interaction between the truncated amyloid peptide A beta 1-16 and hemin immobilized on an aminohexanethiol spacer on a gold electrode has been analyzed by cyclic voltammetry. The resulting complex has a redox pair with a 25 mV more cathodic formal potential than hemin alone.
BACKGROUND/OBJECTIVES: Preterm infants have low vitamin A stores at birth, and parenteral administration of high-dose vitamin A reduces pulmonary morbidity. The aim was to characterize vitamin A transport and status.
SUBJECTS/METHODS: Prospective study of 69 preterm infants (median birth weight 995 g, gestational age 28 weeks), in which 51 received 5000 IU vitamin A three times per week intramuscular (i.m.) for 4 weeks and 18 infants without i.m. vitamin A served as controls. Serum retinol, retinyl palmitate, total retinol-binding protein 4 (RBP4), retinol-unbound RBP4 (apo-RBP4) and transthyretin concentrations were determined at days 3 (D3) and 28 (D28) of life.
RESULTS: D3 retinol concentrations were low for the entire group (382 (285/531) nmol/l; median/interquartile range) and unrelated to gestational age. D28 retinol was unchanged in controls (382 (280/471) nmol/l), but increased in the vitamin A group (596 (480/825) nmol/l; P < 0.001). A similar pattern was observed for RBP4. The calculated retinol-to-RBP4 ratio rose in vitamin A infants (D3: 0.81 (0.57/0.94), D28: 0.98 (0.77/1.26); P < 0.01) but not in controls. In the vitamin A group, the retinol-to-RBP4 ratio was 41 in 15% of all infants on D3 and in 45% of infants on D28, but was <= 1 in all, but one, controls on D28.
CONCLUSIONS: In preterm infants receiving a 4-week course of high-dose i. m. vitamin A, serum retinol concentrations increased by 55%, with molar concentrations of retinol exceeding those of RBP4 in 45% of the infants suggesting transport mechanisms other than RBP4.
Charge transport anisotropy in highly oriented thin films of the acceptor polymer P(NDI2OD-T2)
(2014)
The nanomorphology of the high mobility polymer poly{[N,N'-bis(2-octyldodecyl)-1,4,5,8-naphthalenedicarboximide-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} P(NDI2OD-T2) in thin films is explored as a function of different annealing conditions and correlated to optical and electrical properties. While nanofibrils with face-on orientation in form I are obtained directly after spin-coating and annealing below the melt transition temperature, clear evidence of lamellar structures is found after melt-annealing followed by slow cooling to room temperature. Interestingly these structural changes are accompanied by distinct changes in the absorption patterns. Electron diffraction measurements further show clear transitions towards predominant edge-on oriented chains in form II upon melt-annealing. Large-scale alignment with dichroic ratios up to 10 and improved order is achieved by high temperature rubbing and subsequent post-rubbing annealing. These highly oriented morphologies allow anisotropic in-plane charge transport to be probed with top-gate transistors parallel and perpendicular to the polymer chain direction. Mobilities up to 0.1 cm(2) V-1 s(-1) are observed parallel to the polymer chain, which is up to 10 times higher than those perpendicular to the polymer chain.
We demonstrate the emergence of a complex state in a homogeneous ensemble of globally coupled identical oscillators, reminiscent of chimera states in nonlocally coupled oscillator lattices. In this regime some part of the ensemble forms a regularly evolving cluster, while all other units irregularly oscillate and remain asynchronous. We argue that the chimera emerges because of effective bistability, which dynamically appears in the originally monostable system due to internal delayed feedback in individual units. Additionally, we present two examples of chimeras in bistable systems with frequency-dependent phase shift in the global coupling.
We analyse a 162 ks high energy transmission grating Chandra observation of the O7.5 III(n)((f)) star xi Per, together with contemporaneous H alpha observations. The X-ray spectrum of this star is similar to other single O stars, and not pathological in any way. Its UV wind lines are known to display cyclical time variability, with a period of 2.086 d, which is thought to be associated with corotating interaction regions (CIRs). We examine the Chandra and H alpha data for variability on this time-scale. We find that the X-rays vary by similar to 15 per cent over the course of the observations and that this variability is out of phase with variable absorption on the blue wing of the H alpha profiles (assumed to be a surrogate for the UV absorption associated with CIRs). While not conclusive, both sets of data are consistent with models where the CIRs are either a source of X-rays or modulate them.
claspfolio 2
(2014)
Building on the award-winning, portfolio-based ASP solver claspfolio, we present claspfolio 2, a modular and open solver architecture that integrates several different portfolio-based algorithm selection approaches and techniques. The claspfolio 2 solver framework supports various feature generators, solver selection approaches, solver portfolios, as well as solver-schedule-based pre-solving techniques. The default configuration of claspfolio 2 relies on a light-weight version of the ASP solver clasp to generate static and dynamic instance features. The flexible open design of claspfolio 2 is a distinguishing factor even beyond ASP. As such, it provides a unique framework for comparing and combining existing portfolio-based algorithm selection approaches and techniques in a single, unified framework. Taking advantage of this, we conducted an extensive experimental study to assess the impact of different feature sets, selection approaches and base solver portfolios. In addition to gaining substantial insights into the utility of the various approaches and techniques, we identified a default configuration of claspfolio 2 that achieves substantial performance gains not only over clasp's default configuration and the earlier version of claspfolio, but also over manually tuned configurations of clasp.
claspfolio 2
(2014)
Building on the award-winning, portfolio-based ASP solver claspfolio, we present claspfolio 2, a modular and open solver architecture that integrates several different portfolio-based algorithm selection approaches and techniques. The claspfolio 2 solver framework supports various feature generators, solver selection approaches, solver portfolios, as well as solver-schedule-based pre-solving techniques. The default configuration of claspfolio 2 relies on a light-weight version of the ASP solver clasp to generate static and dynamic instance features. The flexible open design of claspfolio 2 is a distinguishing factor even beyond ASP. As such, it provides a unique framework for comparing and combining existing portfolio-based algorithm selection approaches and techniques in a single, unified framework. Taking advantage of this, we conducted an extensive experimental study to assess the impact of different feature sets, selection approaches and base solver portfolios. In addition to gaining substantial insights into the utility of the various approaches and techniques, we identified a default configuration of claspfolio 2 that achieves substantial performance gains not only over clasp's default configuration and the earlier version of claspfolio, but also over manually tuned configurations of clasp.
A class of adsorbents currently receiving growing attention is the clay-polymer nanocomposite (CPN) adsorbents. CPNs effectively treat water by adsorption and flocculation of both inorganic and organic micropollutants from aqueous solutions. Some of these CPNs - when modified with biocides - also have the ability to efficiently remove microorganisms such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans from water. CPNs are far more easily recovered from aqueous media than neat clay. They also exhibit far better treatment times than either polymer or clay adsorbents. They have higher adsorption capacity and better life cycles compared with clay alone. CPNs therefore show an excellent potential as highly efficient water and waste treatment agents.
This article reviews the various CPNs that have been prepared recently and used as adsorbents in the removal of micropollutants (inorganic, organic and biological) from aqueous solutions. A special focus is placed on CPNs that are not only interesting from an academic point of view but also effectively reduce the concentration of micropollutants in water to safe limits and also on new developments bordering on CPN use as water treatment agent that have not yet realized their full potential. (C) 2014 Elsevier B.V. All rights reserved.
Our study aims at gaining insights into the processes determining the current treeline dynamics in Finnish Lapland. Using forest surveys conducted in 1978 and 2003 we modelled the occurrence and abundance of three dominant tree species in Finnish Lapland, i.e. Pinus sylvestris, Picea abies and Betula pubescens, with boosted regression trees. We assessed the importance of climatic, biotic and topographic variables in predicting tree occurrence and abundance based on their relative importance and response curves. We compared temporal and spatial transferability by using an extended transferability index.
Site fertility, the abundance of co-occurring species and growing degree days were generally the most important predictors for both occurrence and abundance across all species and datasets. Climatic predictors were more important for modelling occurrences than for modelling abundances. Occurrence models were able to reproduce the observed treeline pattern within one time period or region. Abundance models underestimated basal area but captured the general pattern of low and high values. Model performance as well as transferability differed considerably between species and datasets. Pinus sylvestris was modelled more successfully than P. abies and B. pubescens. Generally, spatial transferability was greater than temporal transferability. Comparing the environmental space between datasets revealed that transferring models means extrapolating to novel environments, providing a plausible explanation for limited transferability.
Our study illustrates how climate change can shift the environmental space and lead to limited model transferability. We identified non-climatic factors to be important in predicting the distribution of dominant tree species, contesting the widespread assumption of climatically induced range expansion.
Climate impacts on human livelihoods: where uncertainty matters in projections of water availability
(2014)
Climate change will have adverse impacts on many different sectors of society, with manifold consequences for human livelihoods and well-being. However, a systematic method to quantify human well-being and livelihoods across sectors is so far unavailable, making it difficult to determine the extent of such impacts. Climate impact analyses are often limited to individual sectors (e.g. food or water) and employ sector-specific target measures, while systematic linkages to general livelihood conditions remain unexplored. Further, recent multi-model assessments have shown that uncertainties in projections of climate impacts deriving from climate and impact models, as well as greenhouse gas scenarios, are substantial, posing an additional challenge in linking climate impacts with livelihood conditions. This article first presents a methodology to consistently measure what is referred to here as AHEAD (Adequate Human livelihood conditions for wEll-being And Development). Based on a trans-disciplinary sample of concepts addressing human well-being and livelihoods, the approach measures the adequacy of conditions of 16 elements. We implement the method at global scale, using results from the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) to show how changes in water availability affect the fulfilment of AHEAD at national resolution. In addition, AHEAD allows for the uncertainty of climate and impact model projections to be identified and differentiated. We show how the approach can help to put the substantial inter-model spread into the context of country-specific livelihood conditions by differentiating where the uncertainty about water scarcity is relevant with regard to livelihood conditions - and where it is not. The results indicate that livelihood conditions are compromised by water scarcity in 34 countries. However, more often, AHEAD fulfilment is limited through other elements. The analysis shows that the water-specific uncertainty ranges of the model output are outside relevant thresholds for AHEAD for 65 out of 111 countries, and therefore do not contribute to the overall uncertainty about climate change impacts on livelihoods. In 46 of the countries in the analysis, water-specific uncertainty is relevant to AHEAD. The AHEAD method presented here, together with first results, forms an important step towards making scientific results more applicable for policy decisions.
In general, a moderate drying trend is observed in mid-latitude arid Central Asia since the Mid-Holocene, attributed to the progressively weakening influence of the mid-latitude Westerlies on regional climate. However, as the spatio-temporal pattern of this development and the underlying climatic mechanisms are yet not fully understood, new high-resolution paleoclimate records from this region are needed. Within this study, a sediment core from Lake Son Kol (Central Kyrgyzstan) was investigated using sedimentological, (bio) geochemical, isotopic, and palynological analyses, aiming at reconstructing regional climate development during the last 6000 years. Biogeochemical data, mainly reflecting summer moisture conditions, indicate predominantly wet conditions until 4950 cal. yr BP, succeeded by a pronounced dry interval between 4950 and 3900 cal. yr BP. In the following, a return to wet conditions and a subsequent moderate drying trend until present times are observed. This is consistent with other regional paleoclimate records and likely reflects the gradual Late Holocene diminishment of the amount of summer moisture provided by the mid-latitude Westerlies. However, climate impact of the Westerlies was apparently not only restricted to the summer season but also significant during winter as indicated by recurrent episodes of enhanced allochthonous input through snowmelt, occurring before 6000 cal. yr BP and at 5100-4350, 3450-2850, and 1900-1500 cal. yr BP. The distinct similar to 1500year periodicity of these episodes of increased winter precipitation in Central Kyrgyzstan resembles similar cyclicities observed in paleoclimate records around the North Atlantic, likely indicating a hemispheric-scale climatic teleconnection and an impact of North Atlantic Oscillation (NAO) variability in Central Asia.
Cloud security mechanisms
(2014)
Cloud computing has brought great benefits in cost and flexibility for provisioning services. The greatest challenge of cloud computing remains however the question of security. The current standard tools in access control mechanisms and cryptography can only partly solve the security challenges of cloud infrastructures. In the recent years of research in security and cryptography, novel mechanisms, protocols and algorithms have emerged that offer new ways to create secure services atop cloud infrastructures. This report provides introductions to a selection of security mechanisms that were part of the "Cloud Security Mechanisms" seminar in summer term 2013 at HPI.
We propose a novel cluster-based reduced-order modelling (CROM) strategy for unsteady flows. CROM combines the cluster analysis pioneered in Gunzburger's group (Burkardt, Gunzburger & Lee, Comput. Meth. Appl. Mech. Engng, vol. 196, 2006a, pp. 337-355) and transition matrix models introduced in fluid dynamics in Eckhardt's group (Schneider, Eckhardt & Vollmer, Phys. Rev. E, vol. 75, 2007, art. 066313). CROM constitutes a potential alternative to POD models and generalises the Ulam-Galerkin method classically used in dynamical systems to determine a finite-rank approximation of the Perron-Frobenius operator. The proposed strategy processes a time-resolved sequence of flow snapshots in two steps. First, the snapshot data are clustered into a small number of representative states, called centroids, in the state space. These centroids partition the state space in complementary non-overlapping regions (centroidal Voronoi cells). Departing from the standard algorithm, the probabilities of the clusters are determined, and the states are sorted by analysis of the transition matrix. Second, the transitions between the states are dynamically modelled using a Markov process. Physical mechanisms are then distilled by a refined analysis of the Markov process, e. g. using finite-time Lyapunov exponent (FTLE) and entropic methods. This CROM framework is applied to the Lorenz attractor (as illustrative example), to velocity fields of the spatially evolving incompressible mixing layer and the three-dimensional turbulent wake of a bluff body. For these examples, CROM is shown to identify non-trivial quasi-attractors and transition processes in an unsupervised manner. CROM has numerous potential applications for the systematic identification of physical mechanisms of complex dynamics, for comparison of flow evolution models, for the identification of precursors to desirable and undesirable events, and for flow control applications exploiting nonlinear actuation dynamics.
The extremophilic green microalga Chlamydomonas acidophila grows in very acidic waters (pH 2.3-3.4), where CO2 is the sole inorganic carbon source. Previous work has revealed that the species can accumulate inorganic carbon (Ci) and exhibits high affinity CO2 utilization under low-CO2 (air-equilibrium) conditions, similar to organisms with an active CO2 concentrating mechanism (CCM), whereas both processes are down-regulated under high CO2 (4.5 % CO2) conditions. Responses of this species to phosphorus (Pi)-limited conditions suggested a contrasting regulation of the CCM characteristics. Therefore, we measured external carbonic anhydrase (CA(ext)) activities and protein expression (CAH1), the internal pH, Ci accumulation, and CO2-utilization in cells adapted to high or low CO2 under Pi-replete and Pi-limited conditions. Results reveal that C. acidophila expressed CA(ext) activity and expressed a protein cross-reacting with CAH1 (the CA(ext) from Chlamydomonas reinhardtii). Although the function of this CA remains unclear, CA(ext) activity and high affinity CO2 utilization were the highest under low CO2 conditions. C. acidophila accumulated Ci and expressed the CAH1 protein under all conditions tested, and C. reinhardtii also contained substantial amounts of CAH1 protein under Pi-limitation. In conclusion, Ci utilization is optimized in C. acidophila under ecologically relevant conditions, which may enable optimal survival in its extreme Ci- and Pi-limited habitat. The exact physiological and biochemical acclimation remains to be further studied.
Coastal flood damage and adaptation costs under 21st century sea-level rise are assessed on a global scale taking into account a wide range of uncertainties in continental topography data, population data, protection strategies, socioeconomic development and sea-level rise. Uncertainty in global mean and regional sea level was derived from four different climate models from the Coupled Model Intercomparison Project Phase 5, each combined with three land-ice scenarios based on the published range of contributions from ice sheets and glaciers. Without adaptation, 0.2-4.6% of global population is expected to be flooded annually in 2100 under 25-123 cm of global mean sea-level rise, with expected annual losses of 0.3-9.3% of global gross domestic product. Damages of this magnitude are very unlikely to be tolerated by society and adaptation will be widespread. The global costs of protecting the coast with dikes are significant with annual investment and maintenance costs of US$ 12-71 billion in 2100, but much smaller than the global cost of avoided damages even without accounting for indirect costs of damage to regional production supply. Flood damages by the end of this century are much more sensitive to the applied protection strategy than to variations in climate and socioeconomic scenarios as well as in physical data sources (topography and climate model). Our results emphasize the central role of long-term coastal adaptation strategies. These should also take into account that protecting large parts of the developed coast increases the risk of catastrophic consequences in the case of defense failure.
Many coasts feature sequences of Quaternary and Neogene shorelines that are shaped by a combination of sea-level oscillations and tectonics. We compiled a global synthesis of sea-level changes for the following highstands: MIS 1, MIS 3, MIS 5e and MIS 11. Also, we date the apparent onset of sequences of paleoshorelines either from published data or tentatively extrapolating an age for the uppermost, purported oldest shoreline in each sequence. Including the most documented MIS 5e benchmark, we identify 926 sequences out of which 185 also feature Holocene shorelines. Six areas are identified where elevations of the MIS 3 shorelines are known, and 31 feature elevation data for MIS 11 shorelines. Genetic relationships to regional geodynamics are further explored based on the elevations of the MIS 5e benchmark. Mean apparent uplift rates range from 0.01 0.01 mm/yr (hotspots) to 1.47 0.08 mm/yr (continental collision). Passive margins appear as ubiquitously uplifting, while tectonic segmentation is more important on active margins. From the literature and our extrapolations, we infer ages for the onset of formation for -180 coastal sequences. Sea level fingerprinting on coastal sequences started at least during mid Miocene and locally as early as Eocene. Whether due to the changes in the bulk volume of seawater or to the temporal variations in the shape of ocean basins, estimates of eustasy fail to explain the magnitude of the apparent sea level drop. Thus, vertical ground motion is invoked, and we interpret the longlasting development of those paleoshore sequences as the imprint of glacial cycles on globally uplifted margins in response to continental compression. The geomorphological expression of the sequences matches the amplitude and frequency of glacial cyclicity. From middle Pleistocene to present-day, moderately fast (100,000 yrs) oscillating sea levels favor the development of well identified strandlines that are distinct from one another. Pliocene and Lower Pleistocene strandlines associated with faster cyclicity (40,000 yrs) are more compact and easily merge into rasas, whereas older Cenozoic low-frequency eustatic changes generally led to widespread flat-lying coastal plains.
Cycling chaos is a heteroclinic connection between several chaotic attractors, at which switchings between the chaotic sets occur at growing time intervals. Here we characterize the coherence properties of these switchings, considering nearly periodic regimes that appear close to the cycling chaos due to imperfections or to instability. Using numerical simulations of coupled Lorenz, Roessler, and logistic map models, we show that the coherence is high in the case of imperfection (so that asymptotically the cycling chaos is very regular), while it is low close to instability of the cycling chaos. (C) 2014 Elsevier B. V. All rights reserved.
Based on extensive Brownian dynamics simulations we study the thermal motion of a tracer bead in a cross-linked, flexible gel in the limit when the tracer particle size is comparable to or even larger than the equilibrium mesh size of the gel. The analysis of long individual trajectories of the tracer demonstrates the existence of pronounced transient anomalous diffusion. From the time averaged mean squared displacement and the time averaged van Hove correlation functions we elucidate the many-body origin of the non-Brownian tracer bead dynamics. Our results shed new light onto the ongoing debate over the physical origin of steric tracer interactions with structured environments.
In this study, we suggest a novel approach for the retrieval of regional moment tensors for earthquakes with small to moderate magnitudes. The first modification is the combined inversion of broadband and short-period waveform data. The broadband waveforms are inverted in a frequency range suitable for surface waves, whereas for the short-period data a frequency range suitable for body waves is applied. The second modification is the use of first-motion body-wave polarities to select the most probable solution out of all solutions from inversion. To combine three different criteria for selecting the most probable solution (i.e., residual from inversion, double-couple content of solution, number of nonmatching first-motion body-wave polarities), the L2 norm is applied to the normalized parameters. We chose five earthquakes within the Alborz mountains, Iran, as a case study (3.1 <= M-w <= 4.1). In this area, several factors exacerbate the difficulty of performing inversion for moment tensors, for example, a heterogeneous station network and large azimuthal gaps. We have demonstrated that our approach supplies reliable moment tensors when inversion from broadband data alone fails. In one case, we successfully retrieved a stable solution from short-period waveform data alone. Thus, our approach enables successful determination of seismic moment tensors wherever a sparse network of broadband stations has thus far prevented it.
Quantitative geochemical modeling is today applied in a variety of geological environments from the petrogenesis of igneous rocks to radioactive waste disposal. In addition, the development of thermodynamic databases and computer programs to calculate equilibrium phase diagrams has greatly advanced our ability to model geodynamic processes. Combined with experimental data on elemental partitioning and isotopic fractionation, thermodynamic forward modeling unfolds enormous capacities that are far from exhausted.
In metamorphic petrology the combination of thermodynamic and trace element forward modeling can be used to study and to quantify processes at spatial scales from mu m to km. The thermodynamic forward models utilize Gibbs energy minimization to quantify mineralogical changes along a reaction path of a chemically open fluid/rock system. These results are combined with mass balanced trace element calculations to determine the trace element distribution between rock and melt/fluid during the metamorphic evolution. Thus, effects of mineral reactions, fluid-rock interaction and element transport in metamorphic rocks on the trace element and isotopic composition of minerals, rocks and percolating fluids or melts can be predicted.
Here we illustrate the capacities of combined thermodynamic-geochemical modeling based on two examples relevant to mass transfer during metamorphism. The first example focuses on fluid-rock interaction in and around a blueschist-facies shear zone in felsic gneisses, where fluid-induced mineral reactions and their effects on boron (B) concentrations and isotopic compositions in white mica are modeled. In the second example, fluid release from a subducted slab, the associated transport of B as well as variations in B concentrations and isotopic compositions in liberated fluids and residual rocks are modeled. We compare the modeled results of both examples to geochemical data of natural minerals and rocks and demonstrate that the combination of thermodynamic and geochemical models enables quantification of metamorphic processes and insights into element cycling that would have been unattainable if only one model approach was chosen. (C) 2014 Elsevier B.V. All rights reserved.
We describe an iterative method to combine seismicity forecasts. With this method, we produce the next generation of a starting forecast by incorporating predictive skill from one or more input forecasts. For a single iteration, we use the differential probability gain of an input forecast relative to the starting forecast. At each point in space and time, the rate in the next-generation forecast is the product of the starting rate and the local differential probability gain. The main advantage of this method is that it can produce high forecast rates using all types of numerical forecast models, even those that are not rate-based. Naturally, a limitation of this method is that the input forecast must have some information not already contained in the starting forecast. We illustrate this method using the Every Earthquake a Precursor According to Scale (EEPAS) and Early Aftershocks Statistics (EAST) models, which are currently being evaluated at the US testing center of the Collaboratory for the Study of Earthquake Predictability. During a testing period from July 2009 to December 2011 (with 19 target earthquakes), the combined model we produce has better predictive performance - in terms of Molchan diagrams and likelihood - than the starting model (EEPAS) and the input model (EAST). Many of the target earthquakes occur in regions where the combined model has high forecast rates. Most importantly, the rates in these regions are substantially higher than if we had simply averaged the models.