TY - JOUR A1 - Mardoukhi, Yousof A1 - Jeon, Jae-Hyung A1 - Metzler, Ralf T1 - Geometry controlled anomalous diffusion in random fractal geometries BT - looking beyond the infinite cluster JF - Physical chemistry, chemical physics : PCCP ; a journal of European Chemical Societies N2 - We investigate the ergodic properties of a random walker performing (anomalous) diffusion on a random fractal geometry. Extensive Monte Carlo simulations of the motion of tracer particles on an ensemble of realisations of percolation clusters are performed for a wide range of percolation densities. Single trajectories of the tracer motion are analysed to quantify the time averaged mean squared displacement (MSD) and to compare this with the ensemble averaged MSD of the particle motion. Other complementary physical observables associated with ergodicity are studied, as well. It turns out that the time averaged MSD of individual realisations exhibits non-vanishing fluctuations even in the limit of very long observation times as the percolation density approaches the critical value. This apparent non-ergodic behaviour concurs with the ergodic behaviour on the ensemble averaged level. We demonstrate how the non-vanishing fluctuations in single particle trajectories are analytically expressed in terms of the fractal dimension and the cluster size distribution of the random geometry, thus being of purely geometrical origin. Moreover, we reveal that the convergence scaling law to ergodicity, which is known to be inversely proportional to the observation time T for ergodic diffusion processes, follows a power-law BT� h with h o 1 due to the fractal structure of the accessible space. These results provide useful measures for differentiating the subdiffusion on random fractals from an otherwise closely related process, namely, fractional Brownian motion. Implications of our results on the analysis of single particle tracking experiments are provided. Y1 - 2015 U6 - https://doi.org/10.1039/c5cp03548a SN - 1439-7641 IS - 17 SP - 30134 EP - 30147 PB - Wiley-VCH Verl. CY - Weinheim ER - TY - JOUR A1 - Kuschpel, Maxim S. A1 - Liu, Shuyan A1 - Schad, Daniel A1 - Heinzel, Stephan A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Differential effects of wakeful rest, music and video game playing on working memory performance in the n-back task JF - Frontiers in psychology N2 - The interruption of learning processes by breaks filled with diverse activities is common in everyday life. We investigated the effects of active computer gaming and passive relaxation (rest and music) breaks on working memory performance. Young adults were exposed to breaks involving (i) eyes-open resting, (ii) listening to music and (iii) playing the video game “Angry Birds” before performing the n-back working memory task. Based on linear mixed-effects modeling, we found that playing the “Angry Birds” video game during a short learning break led to a decline in task performance over the course of the task as compared to eyes-open resting and listening to music, although overall task performance was not impaired. This effect was associated with high levels of daily mind wandering and low self-reported ability to concentrate. These findings indicate that video games can negatively affect working memory performance over time when played in between learning tasks. We suggest further investigation of these effects because of their relevance to everyday activity. KW - break interventions KW - computer games KW - mozart effect KW - working memory KW - attention KW - cognitive resources KW - mind wandering Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.01683 SN - 1664-1078 IS - 6 PB - Frontiers Research Foundation CY - Lausanne ER - TY - THES A1 - Jung, Jörg T1 - Efficient credit based server load balancing Y1 - 2015 ER - TY - THES A1 - Allroggen, Niklas T1 - Observation of subsurface flow from the surface : applications of ground-penetrating radar BT - non-invasive time-lapse observation of subsurface flow by using ground-penetrating radar Y1 - 2015 ER - TY - THES A1 - Heyneke, Elmien T1 - The role of the calcineurin B-like interacting protein kinase, CIPK14 in regulating plant nutrient metabolism Y1 - 2015 ER - TY - THES A1 - Shivanand, Lathe Rahul T1 - DUF1068 protein family members are involved in cell wall formation in Arabidopsis thaliana Y1 - 2015 ER - TY - THES A1 - Abon, Catherine Cristobal T1 - Radar-based rainfall retrieval for flood forecasting in a meso-scale catchment BT - the Philippines Y1 - 2015 ER - TY - JOUR A1 - Sbragaglia, Valerio A1 - Lamanna, Francesco A1 - Mat, Audrey M. A1 - Rotllant, Guiomar A1 - Joly, Silvia A1 - Ketmaier, Valerio A1 - de la Iglesia, Horacio O. A1 - Aguzzi, Jacopo T1 - Identification, Characterization, and Diel Pattern of Expression of Canonical Clock Genes in Nephrops norvegicus (Crustacea: Decapoda) Eyestalk JF - PLoS one N2 - The Norway lobster, Nephrops norvegicus, is a burrowing decapod with a rhythmic burrow emergence (24 h) governed by the circadian system. It is an important resource for European fisheries and its behavior deeply affects its availability. The current knowledge of Nephrops circadian biology is phenomenological as it is currently the case for almost all crustaceans. In attempt to elucidate the putative molecular mechanisms underlying circadian gene regulation in Nephrops, we used a transcriptomics approach on cDNA extracted from the eyestalk, a structure playing a crucial role in controlling behavior of decapods. We studied 14 male lobsters under 12–12 light-darkness blue light cycle. We used the Hiseq 2000 Illumina platform to sequence two eyestalk libraries (under light and darkness conditions) obtaining about 90 millions 100-bp paired-end reads. Trinity was used for the de novo reconstruction of transcriptomes; the size at which half of all assembled bases reside in contigs (N50) was equal to 1796 (light) and 2055 (darkness). We found a list of candidate clock genes and focused our attention on canonical ones: timeless, period, clock and bmal1. The cloning of assembled fragments validated Trinity outputs. The putative Nephrops clock genes showed high levels of identity (blastx on NCBI) with known crustacean clock gene homologs such as Eurydice pulchra (period: 47%, timeless: 59%, bmal1: 79%) and Macrobrachium rosenbergii (clock: 100%). We also found a vertebrate-like cryptochrome 2. RT-qPCR showed that only timeless had a robust diel pattern of expression. Our data are in accordance with the current knowledge of the crustacean circadian clock, reinforcing the idea that the molecular clockwork of this group shows some differences with the established model in Drosophila melanogaster. Y1 - 2015 U6 - https://doi.org/10.1371/journal.pone.0141893 SN - 1932-6203 VL - 10 IS - 11 PB - Public Library of Science CY - Lawrence ER - TY - JOUR A1 - Vormoor, Klaus Josef A1 - Lawrence, D. A1 - Heistermann, Maik A1 - Bronstert, Axel T1 - Climate change impacts on the seasonality and generation processes of floods BT - projections and uncertainties for catchments with mixed snowmelt/rainfall regimes JF - Hydrology and earth system sciences : HESS N2 - Climate change is likely to impact the seasonality and generation processes of floods in the Nordic countries, which has direct implications for flood risk assessment, design flood estimation, and hydropower production management. Using a multi-model/multi-parameter approach to simulate daily discharge for a reference (1961–1990) and a future (2071–2099) period, we analysed the projected changes in flood seasonality and generation processes in six catchments with mixed snowmelt/rainfall regimes under the current climate in Norway. The multi-model/multi-parameter ensemble consists of (i) eight combinations of global and regional climate models, (ii) two methods for adjusting the climate model output to the catchment scale, and (iii) one conceptual hydrological model with 25 calibrated parameter sets. Results indicate that autumn/winter events become more frequent in all catchments considered, which leads to an intensification of the current autumn/winter flood regime for the coastal catchments, a reduction of the dominance of spring/summer flood regimes in a high-mountain catchment, and a possible systematic shift in the current flood regimes from spring/summer to autumn/winter in the two catchments located in northern and south-eastern Norway. The changes in flood regimes result from increasing event magnitudes or frequencies, or a combination of both during autumn and winter. Changes towards more dominant autumn/winter events correspond to an increasing relevance of rainfall as a flood generating process (FGP) which is most pronounced in those catchments with the largest shifts in flood seasonality. Here, rainfall replaces snowmelt as the dominant FGP primarily due to increasing temperature.We further analysed the ensemble components in contributing to overall uncertainty in the projected changes and found that the climate projections and the methods for downscaling or bias correction tend to be the largest contributors. The relative role of hydrological parameter uncertainty, however, is highest for those catchments showing the largest changes in flood seasonality, which confirms the lack of robustness in hydrological model parameterization for simulations under transient hydrometeorological conditions. Y1 - 2015 U6 - https://doi.org/10.5194/hess-19-913-2015 SN - 1027-5606 SN - 1607-7938 VL - 19 IS - 2 SP - 913 EP - 931 PB - Copernicus Publications CY - Göttingen ER - TY - THES A1 - Karo, Nihad Majeed T1 - Metamorphic evolution of the Northern Zagros Suture Zone (NZSZ) Y1 - 2015 ER - TY - THES A1 - Siegel, Daniel T1 - Binary neutron star mergers and short gamma-ray bursts BT - magnetohydrodynamics and electromagnetic emission Y1 - 2015 ER - TY - THES A1 - Timofeeva, Nadezda T1 - Effect of ions and amino-acid sequence on collagen structure BT - a molecular dynamics study Y1 - 2015 ER - TY - CHAP A1 - Lottes, Günther T1 - Language and Content BT - the political thought of algernon Sidney between Republicanism and Enlightenment T2 - Perspectives on English revolutionary republicanism Y1 - 2014 SP - 53 EP - 61 PB - Ashgate CY - Farnham ER - TY - JOUR A1 - Wiemann, Dirk A1 - Mahlberg, Gaby ED - Wiemann, Dirk ED - Mahlberg, Gaby T1 - Introduction : Perspectives on English revolutionary republicanism JF - Perspectives on English revolutionary republicanism Y1 - 2014 SP - 1 EP - 12 PB - Ashgate CY - Farnham ER - TY - BOOK A1 - Wiemann, Dirk A1 - Mahlberg, Gaby A1 - Dzelzainis, Martin A1 - Cuttica, Cesare A1 - Lottes, Günther A1 - Davis, J. C. A1 - Pankratz, Anette A1 - Sedlmayr, Gerold A1 - Vallance, Edward A1 - Vanderbeke, Dirk A1 - Borot, Luc A1 - Champion, Justin A1 - Burgess, Glenn ED - Wiemann, Dirk ED - Mahlberg, Gaby T1 - Perspectives on English revolutionary republicanism N2 - Perspectives on English Revolutionary Republicanism takes stock of developments in the scholarship of seventeenth-century English republicanism by looking at the movements and schools of thought that have shaped the field over the decades: the linguistic turn, the cultural turn and the religious turn. While scholars of seventeenth-century republicanism share their enthusiasm for their field, they have approached their subject in diverse ways. The contributors to the present volume have taken the opportunity to bring these approaches together in a number of case studies covering republican language, republican literary and political culture, and republican religion, to paint a lively picture of the state of the art in republican scholarship. The volume begins with three chapters influenced by the theory and methodology of the linguistic turn, before moving on to address cultural history approaches to English republicanism, including both literary culture and (practical) political culture. The final section of the volume looks at how religion intersected with ideas of republican thought. Taken together the essays demonstrate the vitality and diversity of what was once regarded as a narrow topic of political research. KW - Großbritannien KW - Republikanismus KW - Geschichte 1600-1700 KW - Republicanism KW - Great Britain KW - History KW - 17th century Y1 - 2014 SN - 978-1-4094-5567-7 PB - Ashgate CY - Farnham ER - TY - THES A1 - Swiadek, Magdalena Agnieszka T1 - Hybrid necrosis in local populations of Arabidopsis thaliana Y1 - 2015 ER - TY - THES A1 - El Kassar, Nadja T1 - Towards a theory of epistemically significant perception BT - how we relate to the world N2 - How does perceptual experience make us knowledgeable? This book argues that the answer lies in the nature of perceptual experience: this experience involves conceptual capacities and is a relation between perceiver and world. The author develops her position via a critical examination of conceptualist and relationist theories of perception. A discussion of recent work in vision science rounds up this contribution to the philosophy of perception. Y1 - 2015 SN - 978-3-11-044563-3 PB - De Gruyter CY - Berlin ER - TY - THES A1 - Heistermann, Maik T1 - Advancing weather radar in hydrology BT - the role of open source software Y1 - 2015 ER - TY - THES A1 - Baer-Henney, Dinah T1 - Learners' Little Helper BT - Strength and Weakness of the Substantive Bias Phonological Acquisition Y1 - 2015 ER - TY - THES A1 - Grune, Jana T1 - Effects of a novel non-steroidal mineralocorticoid receptor antagonist on cardiac hypertrophy Y1 - 2015 ER - TY - JOUR A1 - Moser, Othmar A1 - Tschakert, Gerhard A1 - Müller, Alexander A1 - Groeschl, Werner A1 - Pieber, Thomas R. A1 - Obermayer-Pietsch, Barbara A1 - Koehler, Gerd A1 - Hofmann, Peter T1 - Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin JF - PLoS one N2 - Introduction We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Material and Methods Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. Results BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Conclusion Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. KW - Insulin KW - Exercise KW - Glucose KW - Hypoglycemia KW - Carbohydrates KW - Blood KW - Blood sugar KW - Heart rate Y1 - 2015 U6 - https://doi.org/10.1371/journal.pone.0136489 SN - 1932-6203 VL - 10 IS - 8 PB - Public Library of Science CY - Lawrence ER - TY - JOUR A1 - Jahn, Karolina A1 - Buschmann, Volker A1 - Hille, Carsten T1 - Simultaneous Fluorescence and Phosphorescence Lifetime Imaging Microscopy in Living Cells JF - Scientific Reports N2 - In living cells, there are always a plethora of processes taking place at the same time. Their precise regulation is the basis of cellular functions, since small failures can lead to severe dysfunctions. For a comprehensive understanding of intracellular homeostasis, simultaneous multiparameter detection is a versatile tool for revealing the spatial and temporal interactions of intracellular parameters. Here, a recently developed time-correlated single-photon counting (TCSPC) board was evaluated for simultaneous fluorescence and phosphorescence lifetime imaging microscopy (FLIM/PLIM). Therefore, the metabolic activity in insect salivary glands was investigated by recording ns-decaying intrinsic cellular fluorescence, mainly related to oxidized flavin adenine dinucleotide (FAD) and the μs-decaying phosphorescence of the oxygen-sensitive ruthenium-complex Kr341. Due to dopamine stimulation, the metabolic activity of salivary glands increased, causing a higher pericellular oxygen consumption and a resulting increase in Kr341 phosphorescence decay time. Furthermore, FAD fluorescence decay time decreased, presumably due to protein binding, thus inducing a quenching of FAD fluorescence decay time. Through application of the metabolic drugs antimycin and FCCP, the recorded signals could be assigned to a mitochondrial origin. The dopamine-induced changes could be observed in sequential FLIM and PLIM recordings, as well as in simultaneous FLIM/PLIM recordings using an intermediate TCSPC timing resolution. KW - Confocal microscopy KW - Fluorescence imaging KW - Fluorescence spectroscopy KW - Fluorescent probes Y1 - 2015 U6 - https://doi.org/10.1038/srep14334 SN - 2045-2322 IS - 5 PB - Nature Publishing Group CY - London ER - TY - THES A1 - Krishnamoorthy, Praveen T1 - Regulatory roles of Ptdlns(4,5)P2 in trafficking of the cellulose synthase complex and identification of distinct plasma membrane localisation patterns of Arabidopsis PiP5-kinases Y1 - 2015 ER - TY - THES A1 - Heidemann-Malreddy, Birte T1 - Lost in a liminal space? BT - post-agreement north irish literature Y1 - 2015 ER - TY - THES A1 - Ogone, James Odhiambo T1 - Domesticating modernity in Africa BT - local epistemologies, foreign technologies and dynamics of mediation Y1 - 2015 ER - TY - THES A1 - Taßler, Stephanie T1 - Physical-Chemical Investigation of newly-synthesised Lysine-Based Amino-Functionalised Lipids for gene transfection in 2D and 3D model systems Y1 - 2015 ER - TY - JOUR A1 - Kröner, Dominik T1 - Laser-driven electron dynamics for circular dichroism in mass spectrometry BT - from one-photon excitations to multiphoton ionization JF - Physical chemistry, chemical physics : PCCP ; a journal of European Chemical Societies N2 - The distinction of enantiomers is a key aspect of chemical analysis. In mass spectrometry the distinction of enantiomers has been achieved by ionizing the sample with circularly polarized laser pulses and comparing the ion yields for light of opposite handedness. While resonant excitation conditions are expected to be most efficient, they are not required for the detection of a circular dichroism (CD) in the ion yield. However, the prediction of the size and sign of the circular dichroism becomes challenging if non-resonant multiphoton excitations are used to ionize the sample. Employing femtosecond laser pulses to drive electron wavepacket dynamics based on ab initio calculations, we attempt to reveal underlying mechanisms that determine the CD under non-resonant excitation conditions. Simulations were done for (R)-1,2-propylene oxide, using time-dependent configuration interaction singles with perturbative doubles (TD-CIS(D)) and the aug-cc-pVTZ basis set. Interactions between the electric field and the electric dipole and quadrupole as well as between the magnetic field and the magnetic dipole were explicitly accounted for. The ion yield was determined by treating states above the ionization potential as either stationary or non-stationary with energy-dependent lifetimes based on an approved heuristic approach. The observed population dynamics do not allow for a simple interpretation, because of highly non-linear interactions. Still, the various transition pathways are governed by resonant enantiospecific n-photon excitation, with preferably high transition dipole moments, which eventually dominate the CD in the ionized population. Y1 - 2015 U6 - https://doi.org/10.1039/C5CP02193F SN - 1463-9076 SN - 1463-9084 VL - 29 IS - 17 SP - 19643 EP - 19655 PB - The Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Lohren, Hanna A1 - Bornhorst, Julia A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja T1 - The blood–cerebrospinal fluid barrier BT - First evidence for an active transport of organic mercury compounds out of the brain JF - Metallomics : integrated biometal science N2 - Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood–brain barrier, limited data are available regarding the second brain regulating interface, the blood–cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood–CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport. Y1 - 2015 U6 - https://doi.org/10.1039/C5MT00171D SN - 1756-5901 SN - 1756-591X VL - 10 IS - 7 SP - 1420 EP - 1430 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Meyer, S. A1 - Raber, G. A1 - Ebert, Franziska A1 - Leffers, L. A1 - Müller, Sandra Marie A1 - Taleshi, M. S. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites JF - Toxicology research N2 - Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids. Y1 - 2015 U6 - https://doi.org/10.1039/c5tx00122f SN - 2045-4538 VL - 5 IS - 4 SP - 1289 EP - 1296 PB - Royal Society of Chemistry CY - Cambridge ER - TY - THES A1 - Pfestorf, Hans T1 - Land use intensity and insect root herbivores BT - from spatial pattern to plant community feedback Y1 - 2015 ER - TY - THES A1 - Zupok, Arkadiusz T1 - The psbB-operon is a major locus for plastome-genome incompatibility in Oenothera Y1 - 2015 ER - TY - THES A1 - Hainich, Rainer T1 - The Wolf-Rayet stars of the nitrogen sequence in environments of different metallicities Y1 - 2015 ER - TY - JOUR A1 - Kirchhecker, Sarah A1 - Tröger-Müller, Steffen A1 - Bake, Sebastian A1 - Antonietti, Markus A1 - Taubert, Andreas A1 - Esposito, Davido T1 - Renewable pyridinium ionic liquids from the continuous hydrothermal decarboxylation of furfural-amino acid derived pyridinium zwitterions JF - Green chemistry N2 - Fully renewable pyridinium ionic liquids were synthesised via the hydrothermal decarboxylation of pyridinium zwitterions derived from furfural and amino acids in flow. The functionality of the resulting ionic liquid (IL) can be tuned by choice of different amino acids as well as different natural carboxylic acids as the counterions. A representative member of this new class of ionic liquids was successfully used for the synthesis of ionogels and as a solvent for the Heck coupling. Y1 - 2015 U6 - https://doi.org/10.1039/c5gc00913h SN - 1463-9262 SN - 1463-9270 VL - 8 IS - 17 SP - 4151 EP - 4156 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Bartoloni, Marco A1 - Jin, Xian A1 - Marcaida, Maria José A1 - Banha, Joao A1 - Dibonaventura, Ivan A1 - Bongoni, Swathi A1 - Bartho, Kathrin A1 - Gräbner, Olivia A1 - Sefkow, Michael A1 - Darbre, Tamis A1 - Reymond, Jean-Louis T1 - Bridged bicyclic peptides as potential drug scaffolds BT - synthesis, structure, protein binding and stability JF - Chemical Science N2 - Double cyclization of short linear peptides obtained by solid phase peptide synthesis was used to prepare bridged bicyclic peptides (BBPs) corresponding to the topology of bridged bicyclic alkanes such as norbornane. Diastereomeric norbornapeptides were investigated by 1H-NMR, X-ray crystallography and CD spectroscopy and found to represent rigid globular scaffolds stabilized by intramolecular backbone hydrogen bonds with scaffold geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Proteome profiling by capture compound mass spectrometry (CCMS) led to the discovery of the norbornapeptide 27c binding selectively to calmodulin as an example of a BBP protein binder. This and other BBPs showed high stability towards proteolytic degradation in serum. Y1 - 2015 U6 - https://doi.org/10.1039/C5SC01699A SN - 2041-6520 SN - 2041-6539 VL - 10 IS - 6 SP - 5473 EP - 5490 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Schulze, Michael A1 - Utecht, Manuel Martin A1 - Moldt, Thomas A1 - Przyrembel, Daniel A1 - Gahl, Cornelius A1 - Weinelt, Martin A1 - Saalfrank, Peter A1 - Tegeder, Petra T1 - Nonlinear optical response of photochromic azobenzene-functionalized self-assembled monolayers JF - Physical chemistry, chemical physics : PCCP ; a journal of European Chemical Societies N2 - The combination of photochromic and nonlinear optical (NLO) properties of azobenzene-functionalized self-assembled monolayers (SAMs) constitutes an intriguing step towards novel photonic and optoelectronic devices. By utilizing the second-order NLO process of second harmonic generation (SHG), supported by density-functional theory and correlated wave function method calculations, we demonstrate that the photochromic interface provides the necessary prerequisites en route towards possible future technical applications: we find a high NLO contrast on the order of 16% between the switching states. These are furthermore accessible reversibly and with high efficiencies in terms of cross sections on the order of 10−18 cm2 for both photoisomerization reactions, i.e., drivable by means of low-power LED light sources. Finally, both photostationary states (PSSs) are thermally stable at ambient conditions. Y1 - 2015 U6 - https://doi.org/10.1039/c5cp03093e SN - 1463-9076 SN - 1463-9084 VL - 27 IS - 17 SP - 18079 EP - 18086 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Guha, S. A1 - Warsinke, A. A1 - Tientcheu, Ch. M. A1 - Schmalz, K. A1 - Meliani, C. A1 - Wenger, Ch. T1 - Label free sensing of creatinine using a 6 GHz CMOS near-field dielectric immunosensor JF - The analyst : the analytical journal of the Royal Society of Chemistry N2 - In this work we present a CMOS high frequency direct immunosensor operating at 6 GHz (C-band) for label free determination of creatinine. The sensor is fabricated in standard 0.13 μm SiGe:C BiCMOS process. The report also demonstrates the ability to immobilize creatinine molecules on a Si3N4 passivation layer of the standard BiCMOS/CMOS process, therefore, evading any further need of cumbersome post processing of the fabricated sensor chip. The sensor is based on capacitive detection of the amount of non-creatinine bound antibodies binding to an immobilized creatinine layer on the passivated sensor. The chip bound antibody amount in turn corresponds indirectly to the creatinine concentration used in the incubation phase. The determination of creatinine in the concentration range of 0.88–880 μM is successfully demonstrated in this work. A sensitivity of 35 MHz/10 fold increase in creatinine concentration (during incubation) at the centre frequency of 6 GHz is gained by the immunosensor. The results are compared with a standard optical measurement technique and the dynamic range and sensitivity is of the order of the established optical indication technique. The C-band immunosensor chip comprising an area of 0.3 mm2 reduces the sensing area considerably, therefore, requiring a sample volume as low as 2 μl. The small analyte sample volume and label free approach also reduce the experimental costs in addition to the low fabrication costs offered by the batch fabrication technique of CMOS/BiCMOS process. Y1 - 2015 U6 - https://doi.org/10.1039/c4an02194k SN - 0003-2654 SN - 1364-5528 VL - 9 IS - 140 SP - 3019 EP - 3027 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Niedl, Robert Raimund A1 - Beta, Carsten T1 - Hydrogel-driven paper-based microfluidics JF - LAB on a chip : miniaturisation for chemistry and biology N2 - Paper-based microfluidics provide an inexpensive, easy to use technology for point-of-care diagnostics in developing countries. Here, we combine paper-based microfluidic devices with responsive hydrogels to add an entire new class of functions to these versatile low-cost fluidic systems. The hydrogels serve as fluid reservoirs. In response to an external stimulus, e.g. an increase in temperature, the hydrogels collapse and release fluid into the structured paper substrate. In this way, chemicals that are either stored on the paper substrate or inside the hydrogel pads can be dissolved, premixed, and brought to reaction to fulfill specific analytic tasks. We demonstrate that multi-step sequences of chemical reactions can be implemented in a paper-based system and operated without the need for external precision pumps. We exemplify this technology by integrating an antibody-based E. coli test on a small and easy to use paper device. Y1 - 2015 U6 - https://doi.org/10.1039/c5lc00276a SN - 1473-0197 SN - 1473-0189 VL - 11 IS - 15 SP - 2452 EP - 2459 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Nöchel, Ulrich A1 - Reddy, Chaganti Srinivasa A1 - Wang, Ke A1 - Cui, Jing A1 - Zizak, Ivo A1 - Behl, Marc A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Nanostructural changes in crystallizable controlling units determine the temperature-memory of polymers JF - Journal of Materials Chemistry A, Materials for energy and sustainability N2 - Temperature-memory polymers remember the temperature, where they were deformed recently, enabled by broad thermal transitions. In this study, we explored a series of crosslinked poly[ethylene-co-(vinyl acetate)] networks (cPEVAs) comprising crystallizable polyethylene (PE) controlling units exhibiting a pronounced temperature-memory effect (TME) between 16 and 99 °C related to a broad melting transition (∼100 °C). The nanostructural changes in such cPEVAs during programming and activation of the TME were analyzed via in situ X-ray scattering and specific annealing experiments. Different contributions to the mechanism of memorizing high or low deformation temperatures (Tdeform) were observed in cPEVA, which can be associated to the average PE crystal sizes. At high deformation temperatures (>50 °C), newly formed PE crystals, which are established during cooling when fixing the temporary shape, dominated the TME mechanism. In contrast, at low Tdeform (<50 °C), corresponding to a cold drawing scenario, the deformation led preferably to a disruption of existing large crystals into smaller ones, which then fix the temporary shape upon cooling. The observed mechanism of memorizing a deformation temperature might enable the prediction of the TME behavior and the knowledge based design of other TMPs with crystallizable controlling units. Y1 - 2015 U6 - https://doi.org/10.1039/c4ta06586g SN - 2050-7488 SN - 2050-7496 VL - 16 IS - 3 SP - 8284 EP - 8293 PB - Royal Society of Chemistry CY - Cambridge ER - TY - THES A1 - Primus, Philipp-Alexander T1 - High resolution spectroscopy as a tool to unravel structure-reactivity relationships in Eu3+ doped ceria/ceria-zirconia based catalyst nanomaterials Y1 - 2015 ER - TY - THES A1 - Adamla, Frauke T1 - Polyglutamine- and aging-dependent aberrancies in transcription and translation Y1 - 2015 ER - TY - THES A1 - Tetzner, Julia T1 - Stability and change in academic, social, and emotional development from early adolescence to young adulthood BT - the interplay with negative life events and protective factors Y1 - 2014 ER - TY - THES A1 - Alseekh, Saleh T1 - Identification and mode of inheritance of quantitative trait loci (QTL) for metabolite abundance in tomato Y1 - 2015 ER - TY - THES A1 - Al-Saedy, Ammar Jaffar Muhesin T1 - Normally solvable lagrangian boundary value problems Y1 - 2015 ER - TY - THES A1 - Yuan, Jiayin T1 - Poly(Ionic Liquid)s BT - innovative polyelectrolytes for materials applications Y1 - 2015 ER - TY - THES A1 - Tian, Fang T1 - Vegetation and environmental changes on millennial, centennial and decadal time-scales in central Mongolia and their driving forces Y1 - 2014 ER - TY - THES A1 - Sauter, Tilman T1 - Function by structure BT - microstructural approaches to tailor surface, mechanical and shape-memory properties of porous polymer structures Y1 - 2015 ER - TY - THES A1 - Mengel, Matthias T1 - Forcing Earth’s sea level BT - instabilities and linear responses Y1 - 2015 ER - TY - THES A1 - Müller, Jörg T1 - Response of bryophyte diversity to land-use and management in forest and grassland habitats Y1 - 2014 ER - TY - THES A1 - Brem, Patrick T1 - Compact objects in dense astrophysical environments BT - numerical simulations and implications for gravitational wave astronomy Y1 - 2014 ER - TY - THES A1 - Soja, Aleksandra Maria T1 - Transcriptomic and metabolomic analysis of Arabidopsis thaliana during abiotic stress Y1 - 2014 ER - TY - THES A1 - Sklodowski, Kamil T1 - Regulation of plant potassium channels Y1 - 2015 ER - TY - THES A1 - Zhao, Liming T1 - Characterization genes involved in leaf development and senescence of arabidopsis Y1 - 2015 ER - TY - THES A1 - Eggers, Ute T1 - Environmental impacts on white stork (Ciconia ciconia) breeding success BT - a long-term study with a focus on effects of weather conditions at the breeding grounds Y1 - 2014 ER - TY - THES A1 - Schönebeck, Maria T1 - Behavioural, visual, and electrophysiological correlates of infant reasoning about others' intentional actions BT - an integrative analysis of infant attention, encoding, and reproduction measures Y1 - 2014 ER - TY - THES A1 - Lang, Iris Scarlett T1 - Fetal programming of growth and metabolism by maternal dietary composition BT - effects of high and low dietary protein:carbohydrate ratios in pregnant primiparous sows Y1 - 2014 ER - TY - JOUR A1 - Mondal, Suvendu Sekhar A1 - Behrens, Karsten A1 - Matthes, Philipp R. A1 - Schönfeld, Fabian A1 - Nitsch, Jörn A1 - Steffen, Andreas A1 - Primus, Philipp-Alexander A1 - Kumke, Michael Uwe A1 - Müller-Buschbaum, Klaus A1 - Holdt, Hans-Jürgen T1 - White light emission of IFP-1 by in situ co-doping of the MOF pore system with Eu3+ and Tb3+ JF - Journal of materials chemistry : C, Materials for optical and electronic devices N2 - Co-doping of the MOF 3∞[Zn(2-methylimidazolate-4-amide-5-imidate)] (IFP-1 = Imidazolate Framework Potsdam-1) with luminescent Eu3+ and Tb3+ ions presents an approach to utilize the porosity of the MOF for the intercalation of luminescence centers and for tuning of the chromaticity to the emission of white light of the quality of a three color emitter. Organic based fluorescence processes of the MOF backbone as well as metal based luminescence of the dopants are combined to one homogenous single source emitter while retaining the MOF's porosity. The lanthanide ions Eu3+ and Tb3+ were doped in situ into IFP-1 upon formation of the MOF by intercalation into the micropores of the growing framework without a structure directing effect. Furthermore, the color point is temperature sensitive, so that a cold white light with a higher blue content is observed at 77 K and a warmer white light at room temperature (RT) due to the reduction of the organic emission at higher temperatures. The study further illustrates the dependence of the amount of luminescent ions on porosity and sorption properties of the MOF and proves the intercalation of luminescence centers into the pore system by low-temperature site selective photoluminescence spectroscopy, SEM and EDX. It also covers an investigation of the border of homogenous uptake within the MOF pores and the formation of secondary phases of lanthanide formates on the surface of the MOF. Crossing the border from a homogenous co-doping to a two-phase composite system can be beneficially used to adjust the character and warmth of the white light. This study also describes two-color emitters of the formula Ln@IFP-1a–d (Ln: Eu, Tb) by doping with just one lanthanide Eu3+ or Tb3+. Y1 - 2015 U6 - https://doi.org/10.1039/C4TC02919D SN - 2050-7534 SN - 2050-7526 VL - 18 IS - 3 SP - 4623 EP - 4631 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Megow, Jörg A1 - Röhr, Merle I. S. A1 - Schmidt am Busch, Marcel A1 - Renger, Thomas A1 - Mitrić, Roland A1 - Kirstein, Stefan A1 - Rabe, Jürgen P. A1 - May, Volkhard T1 - Site-dependence of van der Waals interaction explains exciton spectra of double-walled tubular J-aggregates JF - Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies N2 - The simulation of the optical properties of supramolecular aggregates requires the development of methods, which are able to treat a large number of coupled chromophores interacting with the environment. Since it is currently not possible to treat large systems by quantum chemistry, the Frenkel exciton model is a valuable alternative. In this work we show how the Frenkel exciton model can be extended in order to explain the excitonic spectra of a specific double-walled tubular dye aggregate explicitly taking into account dispersive energy shifts of ground and excited states due to van der Waals interaction with all surrounding molecules. The experimentally observed splitting is well explained by the site-dependent energy shift of molecules placed at the inner or outer side of the double-walled tube, respectively. Therefore we can conclude that inclusion of the site-dependent dispersive effect in the theoretical description of optical properties of nanoscaled dye aggregates is mandatory. Y1 - 2015 U6 - https://doi.org/10.1039/c4cp05945j SN - 1463-9084 SN - 1463-9076 VL - 17 IS - 10 SP - 6741 EP - 6747 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Crone, Barbara A1 - Aschner, Michael A. A1 - Schwerdtle, Tanja A1 - Karst, Uwe A1 - Bornhorst, Julia T1 - Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS JF - Metallomics N2 - cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable. Y1 - 2015 U6 - https://doi.org/10.1039/c5mt00096c SN - 1756-591X SN - 1756-5901 VL - 2015 IS - 7 SP - 1189 EP - 1195 PB - Royal Society of Chemistry CY - Cambridge ER - TY - THES A1 - Beinrucker, Andre T1 - Variable selection in high dimensional data analysis with applications Y1 - 2015 ER - TY - JOUR A1 - Pietra, Stefano A1 - Lang, Patricia A1 - Grebe, Markus T1 - SABRE is required for stabilization of root hair patterning in Arabidopsis thaliana JF - Physiologia Plantarum N2 - Patterned differentiation of distinct cell types is essential for the development of multicellular organisms. The root epidermis of Arabidopsis thaliana is composed of alternating files of root hair and non-hair cells and represents a model system for studying the control of cell-fate acquisition. Epidermal cell fate is regulated by a network of genes that translate positional information from the underlying cortical cell layer into a specific pattern of differentiated cells. While much is known about the genes of this network, new players continue to be discovered. Here we show that the SABRE (SAB) gene, known to mediate microtubule organization, anisotropic cell growth and planar polarity, has an effect on root epidermal hair cell patterning. Loss of SAB function results in ectopic root hair formation and destabilizes the expression of cell fate and differentiation markers in the root epidermis, including expression of the WEREWOLF (WER) and GLABRA2 (GL2) genes. Double mutant analysis reveal that wer and caprice (cpc) mutants, defective in core components of the epidermal patterning pathway, genetically interact with sab. This suggests that SAB may act on epidermal patterning upstream of WER and CPC. Hence, we provide evidence for a role of SAB in root epidermal patterning by affecting cell-fate stabilization. Our work opens the door for future studies addressing SAB-dependent functions of the cytoskeleton during root epidermal patterning. Y1 - 2015 UR - http://onlinelibrary.wiley.com/doi/10.1111/ppl.12257/epdf U6 - https://doi.org/DOI: 10.1111/ppl.12257 VL - 153 IS - 3 SP - 440 EP - 453 ER - TY - JOUR A1 - Kiefer, Christian S. A1 - Claes, Andrea R. A1 - Nzayisenga, Jean-Claude A1 - Pietra, Stefano A1 - Stanislas, Thomas A1 - Ikeda, Yoshihisa A1 - Grebe, Markus T1 - Arabidopsis AIP1-2 restricted by WER-mediated patterning modulates planar polarity JF - Development N2 - The coordination of cell polarity within the plane of the tissue layer (planar polarity) is crucial for the development of diverse multicellular organisms. Small Rac/Rho-family GTPases and the actin cytoskeleton contribute to planar polarity formation at sites of polarity establishment in animals and plants. Yet, upstream pathways coordinating planar polarity differ strikingly between kingdoms. In the root of Arabidopsis thaliana, a concentration gradient of the phytohormone auxin coordinates polar recruitment of Rho-of-plant (ROP) to sites of polar epidermal hair initiation. However, little is known about cytoskeletal components and interactions that contribute to this planar polarity or about their relation to the patterning machinery. Here, we show that ACTIN7 (ACT7) represents a main actin isoform required for planar polarity of root hair positioning, interacting with the negative modulator ACTIN-INTERACTING PROTEIN1-2 (AIP1-2). ACT7, AIP1-2 and their genetic interaction are required for coordinated planar polarity of ROP downstream of ethylene signalling. Strikingly, AIP1-2 displays hair cell file-enriched expression, restricted by WEREWOLF (WER)-dependent patterning and modified by ethylene and auxin action. Hence, our findings reveal AIP1-2, expressed under control of the WER-dependent patterning machinery and the ethylene signalling pathway, as a modulator of actin-mediated planar polarity. KW - AIP1 KW - Actin KW - Arabidopsis KW - Patterning KW - Planar polarity Y1 - 2015 UR - http://dev.biologists.org/content/142/1/151.long U6 - https://doi.org/doi: 10.1242/dev.111013 IS - 142 SP - 151 EP - 161 ER - TY - JOUR A1 - Metzler, Ralf A1 - Bauer, Maximilian A1 - Rasmussen, Emil S. A1 - Lomholt, Michael A. T1 - Real sequence effects on the search dynamics of transcription factors on DNA JF - Scientific Reports N2 - Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs. KW - gene regulatory networks KW - biological physics Y1 - 2015 U6 - https://doi.org/10.1038/srep10072 SN - 2045-2322 VL - 5 IS - 10072 PB - Nature Publishing Group CY - London ER - TY - THES A1 - Gaßmöller, René T1 - The interaction of subducted slabs and plume generation zones in geodynamic models Y1 - 2014 ER - TY - JOUR A1 - Haendler, Yair A1 - Kliegl, Reinhold A1 - Adani, Flavia T1 - Discourse accessibility constraints in children´s processing of object relative clauses JF - Frontiers in psychology N2 - Children’s poor performance on object relative clauses has been explained in terms of intervention locality. This approach predicts that object relatives with a full DP head and an embedded pronominal subject are easier than object relatives in which both the head noun and the embedded subject are full DPs. This prediction is shared by other accounts formulated to explain processing mechanisms. We conducted a visual-world study designed to test the off-line comprehension and on-line processing of object relatives in German-speaking 5-year-olds. Children were tested on three types of object relatives, all having a full DP head noun and differing with respect to the type of nominal phrase that appeared in the embedded subject position: another full DP, a 1st- or a 3rd-person pronoun. Grammatical skills and memory capacity were also assessed in order to see whether and how they affect children’s performance. Most accurately processed were object relatives with 1st-person pronoun, independently of children’s language and memory skills. Performance on object relatives with two full DPs was overall more accurate than on object relatives with 3rd-person pronoun. In the former condition, children with stronger grammatical skills accurately processed the structure and their memory abilities determined how fast they were; in the latter condition, children only processed accurately the structure if they were strong both in their grammatical skills and in their memory capacity. The results are discussed in the light of accounts that predict different pronoun effects like the ones we find, which depend on the referential properties of the pronouns. We then discuss which role language and memory abilities might have in processing object relatives with various embedded nominal phrases. KW - child language KW - relative clauses KW - discourse KW - pronouns KW - intervention locality KW - visual-world paradigm Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.00860 SN - 1664-1078 VL - 6 IS - 860 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Häussler, Jana A1 - Bader, Markus T1 - An interference account of the missing-VP effect JF - Frontiers in psychology N2 - Sentences with doubly center-embedded relative clauses in which a verb phrase (VP) is missing are sometimes perceived as grammatical, thus giving rise to an illusion of grammaticality. In this paper, we provide a new account of why missing-VP sentences, which are both complex and ungrammatical, lead to an illusion of grammaticality, the so-called missing-VP effect. We propose that the missing-VP effect in particular, and processing difficulties with multiply center-embedded clauses more generally, are best understood as resulting from interference during cue-based retrieval. When processing a sentence with double center-embedding, a retrieval error due to interference can cause the verb of an embedded clause to be erroneously attached into a higher clause. This can lead to an illusion of grammaticality in the case of missing-VP sentences and to processing complexity in the case of complete sentences with double center-embedding. Evidence for an interference account of the missing-VP effect comes from experiments that have investigated the missing-VP effect in German using a speeded grammaticality judgments procedure. We review this evidence and then present two new experiments that show that the missing-VP effect can be found in German also with less restricting procedures. One experiment was a questionnaire study which required grammaticality judgments from participants without imposing any time constraints. The second experiment used a self-paced reading procedure and did not require any judgments. Both experiments confirm the prior findings of missing-VP effects in German and also show that the missing-VP effect is subject to a primacy effect as known from the memory literature. Based on this evidence, we argue that an account of missing-VP effects in terms of interference during cue-based retrieval is superior to accounts in terms of limited memory resources or in terms of experience with embedded structures. KW - sentence parsing KW - center embedding KW - grammatical illusion KW - missing-VP effect KW - cue-based retrieval KW - interference KW - German Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.00766 SN - 1664-1078 VL - 6 IS - 766 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Felser, Claudia A1 - Patterson, Clare A1 - Cunnings, Ian T1 - Structural constraints on pronoun binding and coreference: Evidence from eye movements during reading JF - Frontiers in psychology N2 - A number of recent studies have investigated how syntactic and non-syntactic constraints combine to cue memory retrieval during anaphora resolution. In this paper we investigate how syntactic constraints and gender congruence interact to guide memory retrieval during the resolution of subject pronouns. Subject pronouns are always technically ambiguous, and the application of syntactic constraints on their interpretation depends on properties of the antecedent that is to be retrieved. While pronouns can freely corefer with non-quantified referential antecedents, linking a pronoun to a quantified antecedent is only possible in certain syntactic configurations via variable binding. We report the results from a judgment task and three online reading comprehension experiments investigating pronoun resolution with quantified and non-quantified antecedents. Results from both the judgment task and participants' eye movements during reading indicate that comprehenders freely allow pronouns to corefer with non-quantified antecedents, but that retrieval of quantified antecedents is restricted to specific syntactic environments. We interpret our findings as indicating that syntactic constraints constitute highly weighted cues to memory retrieval during anaphora resolution. KW - pronoun resolution KW - memory retrieval KW - quantification KW - eye movements KW - reading KW - English Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.00840 SN - 1664-1078 VL - 6 IS - 840 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Metzler, Ralf A1 - Cherstvy, Andrey G. A1 - Chechkin, Aleksei V. A1 - Bodrova, Anna S. T1 - Ultraslow scaled Brownian motion JF - New journal of physics : the open-access journal for physics N2 - We define and study in detail utraslow scaled Brownian motion (USBM) characterized by a time dependent diffusion coefficient of the form . For unconfined motion the mean squared displacement (MSD) of USBM exhibits an ultraslow, logarithmic growth as function of time, in contrast to the conventional scaled Brownian motion. In a harmonic potential the MSD of USBM does not saturate but asymptotically decays inverse-proportionally to time, reflecting the highly non-stationary character of the process. We show that the process is weakly non-ergodic in the sense that the time averaged MSD does not converge to the regular MSD even at long times, and for unconfined motion combines a linear lag time dependence with a logarithmic term. The weakly non-ergodic behaviour is quantified in terms of the ergodicity breaking parameter. The USBM process is also shown to be ageing: observables of the system depend on the time gap between initiation of the test particle and start of the measurement of its motion. Our analytical results are shown to agree excellently with extensive computer simulations. KW - anomalous diffusion KW - stochastic processes KW - ageing Y1 - 2015 U6 - https://doi.org/10.1088/1367-2630/17/6/063038 SN - 1367-2630 VL - 17 IS - 063038 PB - Dt. Physikalische Ges., IOP CY - Bad Honnef, London ER - TY - THES A1 - Müller, Eva Nora T1 - The ecohydrological transfers, interactions and degradation arising from high-intensity storm events Y1 - 2015 ER - TY - THES A1 - Pinchasik, Bat-El Shani T1 - Manipulaton of Microbubbles Inspired by Bubble Use in Nature KW - fff Y1 - 2015 ER - TY - THES A1 - Zhou, Xu T1 - Atmospheric interactions with land surface in the arctic based on regional climate model solutions Y1 - 2014 ER - TY - THES A1 - Hoffmann Robbiani, Sandra T1 - But 7 is yellower than Q, isn't it? BT - The appearance and representation of typographic synaesthesia Y1 - 2015 SN - 978-3-946069-01-0 PB - Hoffmann CY - Darmstadt ER - TY - THES A1 - Prill, Sebastian T1 - Real-Time in vitro toxicity monotoring in a microfluidic bioreactor for drug and chemical safety assessment Y1 - 2015 ER - TY - THES A1 - Kamprath, Martin T1 - A microfoundations perspectives on fresight and business models BT - Competence development and business model design in times of digital industry transformation Y1 - 2014 ER - TY - THES A1 - Kocyan, Alexander T1 - Evolution within the speciose plant group of asparagales BT - insights from molecular and morphological data Y1 - 2014 ER - TY - THES A1 - Gericke, Lutz T1 - Tele-Board - Supporting and analyzing creative collaboration in synchronous and asynchronous scenario Y1 - 2014 ER - TY - JOUR A1 - Lamprecht, Anna-Lena A1 - Margaria, Tiziana ED - Lamprecht, Anna-Lena ED - Margaria, Tiziana T1 - Scientific workflows and XMDD JF - Process design for natural scientists Y1 - 2015 SN - 978-3-662-45006-2 SP - 1 EP - 13 PB - Springer CY - Berlin ER - TY - JOUR A1 - Blaese, Leif T1 - Data mining for unidentified protein squences JF - Process design for natural scientists: an agile model-driven approach N2 - Through the use of next generation sequencing (NGS) technology, a lot of newly sequenced organisms are now available. Annotating those genes is one of the most challenging tasks in sequence biology. Here, we present an automated workflow to find homologue proteins, annotate sequences according to function and create a three-dimensional model. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 73 EP - 87 PB - Springer CY - Berlin ER - TY - JOUR A1 - Schütt, Christine T1 - Identification of differentially expressed genes JF - Process design for natural scientists: an agile model-driven approach N2 - With the jABC it is possible to realize workflows for numerous questions in different fields. The goal of this project was to create a workflow for the identification of differentially expressed genes. This is of special interest in biology, for it gives the opportunity to get a better insight in cellular changes due to exogenous stress, diseases and so on. With the knowledge that can be derived from the differentially expressed genes in diseased tissues, it becomes possible to find new targets for treatment. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 127 EP - 139 PB - Springer CY - Berlin ER - TY - JOUR A1 - Kuntzsch, Christian T1 - Visualization of data transfer paths JF - Process design for natural scientists: an agile model-driven approach N2 - A workflow for visualizing server connections using the Google Maps API was built in the jABC. It makes use of three basic services: An XML-based IP address geolocation web service, a command line tool and the Static Maps API. The result of the workflow is an URL leading to an image file of a map, showing server connections between a client and a target host. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 140 EP - 148 PB - Springer CY - Berlin ER - TY - JOUR A1 - Teske, Daniel T1 - Geocoder accuracy ranking JF - Process design for natural scientists: an agile model-driven approach N2 - Finding an address on a map is sometimes tricky: the chosen map application may be unfamiliar with the enclosed region. There are several geocoders on the market, they have different databases and algorithms to compute the query. Consequently, the geocoding results differ in their quality. Fortunately the geocoders provide a rich set of metadata. The workflow described in this paper compares this metadata with the aim to find out which geocoder is offering the best-fitting coordinate for a given address. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 161 EP - 174 PB - Springer CY - Berlin ER - TY - JOUR A1 - Schulze, Gunnar T1 - Workflow for rapid metagenome analysis JF - Process design for natural scientists: an agile model-driven approach N2 - Analyses of metagenomes in life sciences present new opportunities as well as challenges to the scientific community and call for advanced computational methods and workflows. The large amount of data collected from samples via next-generation sequencing (NGS) technologies render manual approaches to sequence comparison and annotation unsuitable. Rather, fast and efficient computational pipelines are needed to provide comprehensive statistics and summaries and enable the researcher to choose appropriate tools for more specific analyses. The workflow presented here builds upon previous pipelines designed for automated clustering and annotation of raw sequence reads obtained from next-generation sequencing technologies such as 454 and Illumina. Employing specialized algorithms, the sequence reads are processed at three different levels. First, raw reads are clustered at high similarity cutoff to yield clusters which can be exported as multifasta files for further analyses. Independently, open reading frames (ORFs) are predicted from raw reads and clustered at two strictness levels to yield sets of non-redundant sequences and ORF families. Furthermore, single ORFs are annotated by performing searches against the Pfam database Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 88 EP - 100 PB - Springer CY - Berlin ER - TY - THES A1 - Stutz, Franziska T1 - Reading motivation, reading amount, and reading comprehension in the early elementary years Y1 - 2014 ER - TY - THES A1 - Pagel, Jörn T1 - Statistical process-based models for the understanding and prediction of range dynamics Y1 - 2014 ER - TY - BOOK ED - Lambrecht, Anna-Lena ED - Margaria, Tizian T1 - Process design for natural scientists BT - an agile model-driven approach T3 - Communications in computer and information science ; 500 N2 - This book presents an agile and model-driven approach to manage scientific workflows. The approach is based on the Extreme Model Driven Design (XMDD) paradigm and aims at simplifying and automating the complex data analysis processes carried out by scientists in their day-to-day work. Besides documenting the impact the workflow modeling might have on the work of natural scientists, this book serves three major purposes: 1. It acts as a primer for practitioners who are interested to learn how to think in terms of services and workflows when facing domain-specific scientific processes. 2. It provides interesting material for readers already familiar with this kind of tools, because it introduces systematically both the technologies used in each case study and the basic concepts behind them. 3. As the addressed thematic field becomes increasingly relevant for lectures in both computer science and experimental sciences, it also provides helpful material for teachers that plan similar courses. Y1 - 2014 SN - 978-3-662-45005-5 PB - Springer CY - Wiesbaden ER - TY - JOUR A1 - Sens, Henriette T1 - Web-Based map generalization tools put to the test: a jABC workflow JF - Process Design for Natural Scientists: an agile model-driven approach N2 - Geometric generalization is a fundamental concept in the digital mapping process. An increasing amount of spatial data is provided on the web as well as a range of tools to process it. This jABC workflow is used for the automatic testing of web-based generalization services like mapshaper.org by executing its functionality, overlaying both datasets before and after the transformation and displaying them visually in a .tif file. Mostly Web Services and command line tools are used to build an environment where ESRI shapefiles can be uploaded, processed through a chosen generalization service and finally visualized in Irfanview. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 175 EP - 185 PB - Springer CY - Berlin ER - TY - JOUR A1 - Noack, Franziska T1 - CREADED: Colored-Relief application for digital elevation data JF - Process design for natural scientists: an agile model-driven approach N2 - In the geoinformatics field, remote sensing data is often used for analyzing the characteristics of the current investigation area. This includes DEMs, which are simple raster grids containing grey scales representing the respective elevation values. The project CREADED that is presented in this paper aims at making these monochrome raster images more significant and more intuitively interpretable. For this purpose, an executable interactive model for creating a colored and relief-shaded Digital Elevation Model (DEM) has been designed using the jABC framework. The process is based on standard jABC-SIBs and SIBs that provide specific GIS functions, which are available as Web services, command line tools and scripts. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 186 EP - 199 PB - Springer CY - Berlin ER - TY - JOUR A1 - Respondek, Tobias T1 - A workflow for computing potential areas for wind turbines JF - Process design for natural scientists: an agile model-driven approach N2 - This paper describes the implementation of a workflow model for service-oriented computing of potential areas for wind turbines in jABC. By implementing a re-executable model the manual effort of a multi-criteria site analysis can be reduced. The aim is to determine the shift of typical geoprocessing tools of geographic information systems (GIS) from the desktop to the web. The analysis is based on a vector data set and mainly uses web services of the “Center for Spatial Information Science and Systems” (CSISS). This paper discusses effort, benefits and problems associated with the use of the web services. Y1 - 2014 SN - 978-3-662-45005-5 IS - 500 SP - 200 EP - 215 PB - Springer CY - Berlin ER - TY - JOUR A1 - Scheele, Lasse T1 - Location analysis for placing artificial reefs JF - Process design for natural scientists: an agile model-driven approach N2 - Location analyses are among the most common tasks while working with spatial data and geographic information systems. Automating the most frequently used procedures is therefore an important aspect of improving their usability. In this context, this project aims to design and implement a workflow, providing some basic tools for a location analysis. For the implementation with jABC, the workflow was applied to the problem of finding a suitable location for placing an artificial reef. For this analysis three parameters (bathymetry, slope and grain size of the ground material) were taken into account, processed, and visualized with the The Generic Mapping Tools (GMT), which were integrated into the workflow as jETI-SIBs. The implemented workflow thereby showed that the approach to combine jABC with GMT resulted in an user-centric yet user-friendly tool with high-quality cartographic outputs. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 216 EP - 228 PB - Springer CY - Berlin ER - TY - JOUR A1 - Kind, Josephine T1 - Creation of topographic maps JF - Process design for natural scientists: an agile model-driven approach N2 - Location analyses are among the most common tasks while working with spatial data and geographic information systems. Automating the most frequently used procedures is therefore an important aspect of improving their usability. In this context, this project aims to design and implement a workflow, providing some basic tools for a location analysis. For the implementation with jABC, the workflow was applied to the problem of finding a suitable location for placing an artificial reef. For this analysis three parameters (bathymetry, slope and grain size of the ground material) were taken into account, processed, and visualized with the The Generic Mapping Tools (GMT), which were integrated into the workflow as jETI-SIBs. The implemented workflow thereby showed that the approach to combine jABC with GMT resulted in an user-centric yet user-friendly tool with high-quality cartographic outputs. Y1 - 2014 SN - 978-3-662-45005-5 IS - 500 SP - 229 EP - 238 PB - Springer CY - Berlin ER - TY - JOUR A1 - Holler, Robin T1 - GraffDok - a graffiti documentation application JF - Process design for natural scientists: an agile model-driven approach N2 - GraffDok is an application helping to maintain an overview over sprayed images somewhere in a city. At the time of writing it aims at vandalism rather than at beautiful photographic graffiti in an underpass. Looking at hundreds of tags and scribbles on monuments, house walls, etc. it would be interesting to not only record them in writing but even make them accessible electronically, including images. GraffDok’s workflow is simple and only requires an EXIF-GPS-tagged photograph of a graffito. It automatically determines its location by using reverse geocoding with the given GPS-coordinates and the Gisgraphy WebService. While asking the user for some more meta data, GraffDok analyses the image in parallel with this and tries to detect fore- and background – before extracting the drawing lines and make them stand alone. The command line based tool ImageMagick is used here as well as for accessing EXIF data. Any meta data is written to csv-files, which will stay easily accessible and can be integrated in TeX-files as well. The latter ones are converted to PDF at the end of the workflow, containing a table about all graffiti and a summary for each – including the generated characteristic graffiti pattern image. Y1 - 2014 SN - 978-3-662-45005-5 SN - 1865-0929 IS - 500 SP - 239 EP - 251 PB - Springer CY - Berlin ER - TY - BOOK A1 - Thompson, Sandra A. A1 - Fox, Barbara A. A1 - Couper-Kuhlen, Elizabeth T1 - Grammar in everyday talk BT - building responsive actions T3 - Studies in interactional sociolinguistics ; 31 N2 - This book surveys how English speakers use grammar to formulate responses in ordinary conversation. The authors show that speakers build their responses in a variety of ways: the responses can be longer or shorter, repetitive or not, and can be uttered with different intonational 'melodies'"-- "Drawing on everyday telephone and video interactions, this book surveys how English speakers use grammar to formulate responses in ordinary conversation. The authors show that speakers build their responses in a variety of ways: the responses can be longer or shorter, repetitive or not, and can be uttered with different intonational 'melodies'. Focusing on four sequence types: responses to questions ('What time are we leaving?' - 'Seven'), responses to informings ('The May Company are sure having a big sale' - 'Are they?'), responses to assessments ('Track walking is so boring. Even with headphones' - 'It is'), and responses to requests ('Please don't tell Adeline' - 'Oh no I won't say anything'), they argue that an interactional approach holds the key to explaining why some types of utterances in English conversation seem to have something 'missing' and others seem overly wordy. Y1 - 2015 SN - 978-1-107-03102-9 PB - Cambridge Univ. Press CY - Cambridge ER - TY - JOUR A1 - Jäger, Lena Ann A1 - Engelmann, Felix A1 - Vasishth, Shravan T1 - Retrieval interference in reflexive processing BT - Experimental evidence from Mandarin, and computational modeling JF - Frontiers in psychology N2 - We conducted two eye-tracking experiments investigating the processing of the Mandarin reflexive ziji in order to tease apart structurally constrained accounts from standard cue-based accounts of memory retrieval. In both experiments, we tested whether structurally inaccessible distractors that fulfill the animacy requirement of ziji influence processing times at the reflexive. In Experiment 1, we manipulated animacy of the antecedent and a structurally inaccessible distractor intervening between the antecedent and the reflexive. In conditions where the accessible antecedent mismatched the animacy cue, we found inhibitory interference whereas in antecedent-match conditions, no effect of the distractor was observed. In Experiment 2, we tested only antecedent-match configurations and manipulated locality of the reflexive-antecedent binding (Mandarin allows non-local binding). Participants were asked to hold three distractors (animate vs. inanimate nouns) in memory while reading the target sentence. We found slower reading times when animate distractors were held in memory (inhibitory interference). Moreover, we replicated the locality effect reported in previous studies. These results are incompatible with structure-based accounts. However, the cue-based ACT-R model of Lewis and Vasishth (2005) cannot explain the observed pattern either. We therefore extend the original ACT-R model and show how this model not only explains the data presented in this article, but is also able to account for previously unexplained patterns in the literature on reflexive processing. KW - Chinese reflexives KW - ACT-R KW - eye-tracking KW - interference KW - cue-based retrieval KW - computational modeling KW - ziji KW - content-addressable memory Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.00617 SN - 1664-1078 VL - 6 IS - 617 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Jäger, Lena Ann A1 - Benz, Lena A1 - Roeser, Jens A1 - Dillon, Brian W. A1 - Vasishth, Shravan T1 - Teasing apart retrieval and encoding interference in the processing of anaphors JF - Frontiers in psychology N2 - Two classes of account have been proposed to explain the memory processes subserving the processing of reflexive-antecedent dependencies. Structure-based accounts assume that the retrieval of the antecedent is guided by syntactic tree-configurational information without considering other kinds of information such as gender marking in the case of English reflexives. By contrast, unconstrained cue-based retrieval assumes that all available information is used for retrieving the antecedent. Similarity-based interference effects from structurally illicit distractors which match a non-structural retrieval cue have been interpreted as evidence favoring the unconstrained cue-based retrieval account since cue-based retrieval interference from structurally illicit distractors is incompatible with the structure-based account. However, it has been argued that the observed effects do not necessarily reflect interference occurring at the moment of retrieval but might equally well be accounted for by interference occurring already at the stage of encoding or maintaining the antecedent in memory, in which case they cannot be taken as evidence against the structure-based account. We present three experiments (self-paced reading and eye-tracking) on German reflexives and Swedish reflexive and pronominal possessives in which we pit the predictions of encoding interference and cue-based retrieval interference against each other. We could not find any indication that encoding interference affects the processing ease of the reflexive-antecedent dependency formation. Thus, there is no evidence that encoding interference might be the explanation for the interference effects observed in previous work. We therefore conclude that invoking encoding interference may not be a plausible way to reconcile interference effects with a structure-based account of reflexive processing. KW - anaphors KW - reflexives KW - possessives KW - eye-tracking KW - German KW - Swedish KW - working-memory KW - interference Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.00506 SN - 1664-1078 VL - 6 IS - 506 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Goychuk, Igor A1 - Goychuk, Andriy T1 - Stochastic Wilson BT - Cowan models of neuronal network dynamics with memory and delay JF - New journal of physics N2 - We consider a simple Markovian class of the stochastic Wilson–Cowan type models of neuronal network dynamics, which incorporates stochastic delay caused by the existence of a refractory period of neurons. From the point of view of the dynamics of the individual elements, we are dealing with a network of non-Markovian stochastic two-state oscillators with memory, which are coupled globally in a mean-field fashion. This interrelation of a higher-dimensional Markovian and lower-dimensional non-Markovian dynamics is discussed in its relevance to the general problem of the network dynamics of complex elements possessing memory. The simplest model of this class is provided by a three-state Markovian neuron with one refractory state, which causes firing delay with an exponentially decaying memory within the two-state reduced model. This basic model is used to study critical avalanche dynamics (the noise sustained criticality) in a balanced feedforward network consisting of the excitatory and inhibitory neurons. Such avalanches emerge due to the network size dependent noise (mesoscopic noise). Numerical simulations reveal an intermediate power law in the distribution of avalanche sizes with the critical exponent around −1.16. We show that this power law is robust upon a variation of the refractory time over several orders of magnitude. However, the avalanche time distribution is biexponential. It does not reflect any genuine power law dependence. KW - neuronal networks KW - stochastic models KW - memory and delay KW - critical avalanche dynamics Y1 - 2015 U6 - https://doi.org/10.1088/1367-2630/17/4/045029 SN - 1367-2630 VL - 17 IS - 4 PB - Deutsche Physikalische Gesellschaft, Institute of Physics CY - Bad Honnef, London ER - TY - JOUR A1 - Wiebking, Christine A1 - Northoff, Georg T1 - Neural activity during interoceptive awareness and its associations with alexithymia BT - An fMRI study in major depressive disorder and non-psychiatric controls JF - Frontiers in psychology N2 - Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD. KW - major depressive disorder KW - alexithymia KW - interoceptive awareness KW - insula KW - sACC KW - fMRI KW - neuroimaging Y1 - 2015 U6 - https://doi.org/10.3389/fpsyg.2015.00589 SN - 1664-1078 VL - 6 IS - 589 PB - Frontiers Research Foundation ER - TY - THES A1 - Sprenger, Heike T1 - Characterization of drought tolerance in potato cultivars for identification of molecular markers Y1 - 2014 ER - TY - THES A1 - Ippen, Christian Justus T1 - Indium phosphide and zinc selenide quantum dots for light-emitting devices BT - relationships between surface structure and device performance Y1 - 2014 ER - TY - THES A1 - Geckin, Vasfiye T1 - The interpretation of logical connections by monolingual and bilingual children Y1 - 2015 ER - TY - THES A1 - Omidbakhshfard, Mohammad Amin T1 - Functional analysis of the role of GRF9 in leaf development and establishment of Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) in Arabidopsis thaliana Y1 - 2014 ER - TY - THES A1 - Omranian, Nooshin T1 - Inferring gene regulatory networks and cellular phases from time-resolved transcriptomics data Y1 - 2014 ER -