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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 BTh 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.
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.
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.
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.
Language and Content
(2014)
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.
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.
Learners' Little Helper
(2015)
Effects of a novel non-steroidal mineralocorticoid receptor antagonist on cardiac hypertrophy
(2015)
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.
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.
Lost in a liminal space?
(2015)
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.
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.
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.
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.
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.
Nonlinear optical response of photochromic azobenzene-functionalized self-assembled monolayers
(2015)
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.
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.
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.
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.
Poly(Ionic Liquid)s
(2015)
Function by structure
(2015)
Forcing Earth’s sea level
(2015)