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Live-cell labelling techniques to visualize proteins with minimal disturbance are important; however, the currently available methods are limited in their labelling efficiency, specificity and cell permeability. We describe high-throughput protein labelling facilitated by minimalistic probes delivered to mammalian cells by microfluidic cell squeezing. High-affinity and target-specific tracing of proteins in various subcellular compartments is demonstrated, culminating in photoinduced labelling within live cells. Both the fine-tuned delivery of subnanomolar concentrations and the minimal size of the probe allow for live-cell super-resolution imaging with very low background and nanometre precision. This method is fast in probe delivery (∼1,000,000 cells per second), versatile across cell types and can be readily transferred to a multitude of proteins. Moreover, the technique succeeds in combination with well-established methods to gain multiplexed labelling and has demonstrated potential to precisely trace target proteins, in live mammalian cells, by super-resolution microscopy.
This work describes development of a comprehensive methodology for analyzing vibro-acoustic and wear mechanisms in transmission systems. The thesis addresses certain gaps present in the fields of structure dynamics and abrasion mechanism and opens new areas for further research.
The paper attempts to understand new and relatively unexplored challenges like influences of wear on the dynamics of drive train. It also focuses on developing new techniques for analyzing the vibration and acoustic behavior of the drive unit structures and surrounding fluids respectively.
The developed methodology meets the requirements of both the complete system and component level modeling by using specially identified combination of different simulation techniques. Based on the created template model, a three-stage spur plus helical gearbox is constructed and simulated as an application example. In addition to the internal mechanical excitation mechanisms, the transmission model also includes the rotational and translational dynamics of the gears, shafts and bearings. It is followed by illustration of wear among the rotating components.
Different kinds of static and dynamic analyses are performed and coupled at various levels depending on the mechanical complexities involved. Furthermore, the structure dynamic vibration of the housing and the associated sound particle radiations are mapped into the surrounding fluid. Additionally, the approach for selection of the potential parameters for optimization is depicted. Final part focuses on the measurements of different system states used for validation of the model. In the end, results obtained from both simulations and experiments are analyzed and assessed for there respective performances.
The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.
Asset transaction prices sampled at high frequency are much staler than one might expect in the sense that they frequently lack new updates showing zero returns. In this paper, we propose a theoretical framework for formalizing this phenomenon. It hinges on the existence of a latent continuous-time stochastic process pt valued in the open interval (0; 1), which represents at any point in time the probability of the occurrence of a zero return. Using a standard infill asymptotic design, we develop an inferential theory for nonparametrically testing, the null hypothesis that pt is constant over one day. Under the alternative, which encompasses a semimartingale model for pt, we develop non-parametric inferential theory for the probability of staleness that includes the estimation of various integrated functionals of pt and its quadratic variation. Using a large dataset of stocks, we provide empirical evidence that the null of the constant probability of staleness is fairly rejected. We then show that the variability of pt is mainly driven by transaction volume and is almost unaffected by bid-ask spread and realized volatility.
Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.
This thesis explores a variety of methods of text quantification applicable in the field of educational text technology. Besides the cohort of existing linguistic, lexical, syntactic, and semantic text quantification methods, additional methods based on Bidirectional Encoder Representations from Transformers (BERT) are introduced and analysed. The model, developed in this thesis, is tested on a multilingual data composed of task descriptions used in Test of Understanding in College Economics (TUCE). Quantitative features extracted from raw textual data are analysed using an array of evaluation methods with the goal of finding the best predictors of the target variable - the rate of correct student responses in TUCE.
Event-by-event multiplicity fluctuations in nucleus-nucleus collisions from low SPS up to RHIC energies have been studied within the HSD transport approach. Fluctuations of baryonic number and electric charge also have been explored for Pb+Pb collisions at SPS energies in comparison to the experimental data from NA49. We find a dominant role of the fluctuations in the nucleon participant number for the final hadron multiplicity fluctuations and a strong influence of the experimental acceptance on the final results. Critical Point and Onset of Deconfinement - 4th International Workshop July 9 - 13, 2007 Darmstadt, Germany
The multiplicity fluctuations in A+A collisions at SPS and RHIC energies are studied within the HSD transport approach. We find a dominant role of the fluctuations in the nucleon participant number for the final fluctuations. In order to extract physical fluctuations one should decrease the fluctuations in the participants number. This can be done considering very central collisions. The system size dependence of the multiplicity fluctuations in central A+A collisions at the SPS energy range – obtained in the HSD and UrQMD transport models – is presented. The results can be used as a ‘background’ for experimental measurements of fluctuations as a signal of the critical point. Event-by-event fluctuations of the K/p , K/p and p/p ratios in A+A collisions are also studied. Event-by-event fluctuations of the kaon to pion number ratio in nucleus-nucleus collisions are studied for SPS and RHIC energies. We find that the HSD model can qualitatively reproduce the measured excitation function for the K/p ratio fluctuations in central Au+Au (or Pb+Pb) collisions from low SPS up to top RHIC energies. The forward-backward correlation coefficient measured by the STAR Collaboration in Au+Au collisions at RHIC is also studied. We discuss the effects of initial collision geometry and centrality bin definition on correlations in nucleus-nucleus collisions. We argue that a study of the dependence of correlations on the centrality bin definition as well as the bin size may distinguish between these ‘trivial’ correlations and correlations arising from ‘new physics’. 5th International Workshop on Critical Point and Onset of Deconfinement - CPOD 2009, June 08 - 12 2009 Brookhaven National Laboratory, Long Island, New York, USA
Background: Subarachnoid hemorrhage (SAH) is mainly caused by ruptured cerebral aneurysms but in up to 15% of patients with SAH no bleeding source could be identified. Our objective was to analyze patient characteristics, clinical outcome and prognostic factors in patients suffering from non-aneurysmal SAH.
Methods: From 1999 to 2009, data of 125 patients with non-aneurysmal SAH were prospectively entered into a database. All patients underwent repetitive cerebral angiography. Outcome was assessed according to the modified Rankin Scale (mRS) (mRS 0-2 favorable vs. 3-6 unfavorable). Also, patients were divided in two groups according to the distribution of blood in the CT scan (perimesencephalic and non-perimesencephalic SAH).
Results: 106 of the 125 patients were in good WFNS grade (I-III) at admission (85%). Overall, favorable outcome was achieved in 104 of 125 patients (83%). Favorable outcome was associated with younger age (P < 0.001), good admission status (P < 0.0001), and absence of hydrocephalus (P = 0.001).73 of the 125 patients suffered from perimesencephalic SAH, most patients (90%) were in good grade at admission, and 64 achieved favorable outcome.52 of the 125 patients suffered from non-perimesencephalic SAH and 40 were in good grade at admission. Also 40 patients achieved favorable outcome.
Conclusions: Patients suffering from non-aneurysmal SAH have better prognosis compared to aneurysm related SAH and poor admission status was the only independent predictor of unfavorable outcome in the multivariate analysis. Patients with a non-perimesencephalic SAH have an increased risk of a worse neurological outcome. These patients should be monitored attentively.
This thesis contributes to the field of machine learning with a specific focus on the methods for learning relations between the inputs. Learning relationships between images is the most common primitive in vision. There are many vision tasks in which relationships across images play an important role. Some of them are motion estimation, activity recognition, stereo vision, multi-view geometry and visual odometry. Many of such tasks mainly depend on motion and disparity cues, which are inferred based on the relations across multiple image pairs. The approaches presented in this thesis mainly deal with, but are not limited to, learning of the representations for motion and depth. This thesis by articles consists of five articles which present relational feature learning models along with their applications in computer vision. In the first article, we present an approach for encoding motion in videos. To this end, we show that the detection of spatial transformations can be viewed as detection of coincidence or synchrony between the given sequence of frames and a sequence of features which are related by the transformation we wish to detect. Learning to detect synchrony is possible by introducing "multiplicative interactions'' into the hidden units of single layered sparse coding models.
We show that the learned motion representations employed for the task of activity recognition achieve competitive performance on multiple benchmarks. Stereo vision is an important challenge in computer vision and useful for many applications in that field. In the second article, we extend the energy based learning models, which were previously used for motion encoding, to the context of depth perception. Given the common architecture of the models for encoding motion and depth, we show that it is possible to define a single model for learning a unified representation for both the cues. Our experimental results show that learning a combined representation for depth and motion makes it possible to achieve state-of-the-art performance at the task of 3-D activity analysis, and to perform better than the existing hand-engineered 3-D motion features. Autoencoder is a popular unsupervised learning method for learning efficient encoding for a given set of data samples. Typically, regularized autoencoders which are used to learn over-complete and sparse representations for the input data, were shown to fail on intrinsically high dimensional data like videos. In the third article, we investigate the reason for such a behavior. It can be observed that the regularized autoencoders typically learn negative hidden unit biases. We show that the learning of negative biases is the result of hidden units being responsible for both the sparsity and the representation of the input data. It is shown that, as a result, the behavior of the model resembles clustering methods which would require exponentially large number of features to model intrinsically high dimensional data. Based on this understanding, we propose a new activation function which decouples the roles of hidden layer and uses linear encoding. This allows to learn representations on data with very high intrinsic dimensionality. We also show that gating connections in the bi-linear models and the single layer models from articles one and two of this thesis can be thought of as a way to attain a linear encoding scheme which allows them to learn good representations on videos. Visual odometry is the task of inferring egomotion of a moving object from visual information such as images and videos. It can primarily be used for the task of localization and has many applications in the fields of robotics and navigation. The work in article four was motivated by the idea of using deep learning techniques, which are successful methods for many vision tasks, for visual odometry. The visual odometry task mainly requires inference of motion and depth information from visual input which can then be mapped to velocity and change in direction. We use relational feature models presented in the articles one and two for inferring a combined motion and depth representation from stereo video sequences. The combined representation is then mapped to discrete velocity and change in direction labels using convolutional neural networks. Our approach is an end-to-end deep learning-based architecture which uses a single type of computational model and learning rule. Preliminary results show that the architecture is capable of learning the mapping from input video to egomotion. Activity recognition is a challenging computer vision task with many real world applications. It is well know that it is a hard task to use computer vision research for real-time applications. In the fifth article of this thesis, we present a real-time activity recognition system based on deep learning based methods. Our approach uses energy based relational feature learning models for the computation of local motion features directly from videos. A bag-of-words over the local motion features is used for the analysis of activity in a given video sequence. We implement this system on a distributed computational platform and demonstrate its performance on the iCub robot. Using GPUs we demonstrate real time performance which makes the deployment of activity recognition systems in real world scenarios possible.
The prevention of tau protein aggregations is a therapeutic goal for the treatment of Alzheimer's disease (AD), and hydromethylthionine (HMT) (also known as leucomethylthioninium-mesylate [LMTM]), is a potent inhibitor of tau aggregation in vitro and in vivo. In two Phase 3 clinical trials in AD, HMT had greater pharmacological activity on clinical endpoints in patients not receiving approved symptomatic treatments for AD (acetylcholinesterase (AChE) inhibitors and/or memantine) despite different mechanisms of action. To investigate this drug interaction in an animal model, we used tau-transgenic L1 and wild-type NMRI mice treated with rivastigmine or memantine prior to adding HMT, and measured changes in hippocampal acetylcholine (ACh) by microdialysis. HMT given alone doubled hippocampal ACh levels in both mouse lines and increased stimulated ACh release induced by exploration of the open field or by infusion of scopolamine. Rivastigmine increased ACh release in both mouse lines, whereas memantine was more active in tau-transgenic L1 mice. Importantly, our study revealed a negative interaction between HMT and symptomatic AD drugs: the HMT effect was completely eliminated in mice that had been pre-treated with either rivastigmine or memantine. Rivastigmine was found to inhibit AChE, whereas HMT and memantine had no effects on AChE or on choline acetyltransferase (ChAT). The interactions observed in this study demonstrate that HMT enhances cholinergic activity in mouse brain by a mechanism of action unrelated to AChE inhibition. Our findings establish that the drug interaction that was first observed clinically has a neuropharmacological basis and is not restricted to animals with tau aggregation pathology. Given the importance of the cholinergic system for memory function, the potential for commonly used AD drugs to interfere with the treatment effects of disease-modifying drugs needs to be taken into account in the design of clinical trials.
Schätzungen der WHO zufolge waren 2015 weltweit rund 71 Millionen Menschen von einer chronischen Hepatitis C-Infektion betroffen. Die chronische Hepatitis C ist mit einem erhöhten Risiko für die Entstehung einer Leberzirrhose und eines hepatozellulären Karzinoms assoziiert. Die NS3/4A-Protease als zentraler Bestandteil der Replikationsmaschinerie des Virus spaltet das HCV-Polyprotein und ist in die Inaktivierung antiviraler Proteine involviert. Durch ihren maßgeblichen Einfluss auf die virale Fitness stellt sie einen entscheidenden Faktor für die chronische Persistenz des Virus im Wirtsorganismus dar. Die Protease ist auch eine wichtige Zielstruktur für spezifische antivirale Medikamente in der Behandlung der chronischen Hepatitis C. Der natürlich vorkommende Polymorphismus Q80K in der NS3/4A-Protease ist bei bis zu 47 % der Patienten schon vor Therapiebeginn feststellbar, insbesondere beim Genotyp 1a. Q80K führt zum Therapieversagen bei makrozyklischen Proteaseinhibitoren, insbesondere Simeprevir. Phylogenetische Analysen konnten zeigen, dass 96 % aller HCV-Gensequenzen mit Q80K von einem gemeinsamen, genetischen Vorfahren abstammen und sich die Mutation seit Mitte des 20. Jahrhunderts scheinbar stabil ausgehend vom nordamerikanischen Kontinent etabliert hat. Daneben wurden mit A91S/T und S174N sogenannte second site-Austausche identifiziert, die assoziiert mit Q80K vorkommen. Ziel dieser Arbeit war es herauszufinden, welchen Einfluss diese second site-Austausche auf die Enzymaktivität und Proteinfaltung der Protease haben und ob sie mögliche Veränderungen durch den Q80K-Polymorphismus kompensieren. Nach Expression und Aufreinigung der NS3/4A-Protease wurden die Effekte von Q80K, A91S/T und S174N auf die Enzymaktivität und Thermostabilität mittels fluoreszenzbasierter Verfahren untersucht und im Zusammenhang mit einer in silico-3D-Strukturanalyse der Protease interpretiert. Es zeigte sich, dass A91S/T und S174N jeweils zu einer Angleichung der Thermostabilität des Proteins an den Wildtyp führen und somit Defizite in der Faltung der Protease durch Q80K kompensiert werden. Aufgrund der experimentellen Daten und der Topografie dieser Austausche innerhalb der NS3-Protease-Helikase-Struktur ist von indirekten Effekten der second site-Austausche auf die replikative Fitness der Virusvarianten auszugehen. Die hier charakterisierten Austausche in der NS3/4A-Protease tragen durch eine Stabilisierung der Proteinfaltung kritisch zur Stabilität des Q80K-Polymorphismus im Proteasegen des HCV Genotyp 1a bei.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Motivated by the on-going discussion on the nature of magnetism in the quantum Ising chain CoNb2O6, we present a first-principles-based analysis of its exchange interactions by applying an \textit{ab initio} approach with additional modelling that accounts for various drawbacks of a purely density functional theory ansatz. With this method we are able to extract and understand the origin of the magnetic couplings under inclusion of all symmetry-allowed terms, and to resolve the conflicting model descriptions in CoNb2O6. We find that the twisted Kitaev chain and the transverse-field ferromagnetic Ising chain views are mutually compatible, although additional off-diagonal exchanges are necessary to provide a complete picture. We show that the dominant exchange interaction is a ligand-centered exchange process - involving the eg electrons -, which is rendered anisotropic by the low-symmetry crystal fields environments in CoNb2O6, giving rise to the dominant Ising exchange, while the smaller bond-dependent anisotropies are found to originate from d−d kinetic exchange processes involving the t2g electrons. We demonstrate the validity of our approach by comparing the predictions of the obtained low-energy model to measured THz and inelastic neutron scattering spectra.
The marine hydrocarbonoclastic bacterium Alcanivorax borkumensis is well known for its ability to successfully degrade various mixtures of n-alkanes occurring in marine oil spills. For effective growth on these compounds, the bacteria possess the unique capability not only to incorporate but also to modify fatty intermediates derived from the alkane degradation pathway. High efficiency of both these processes provides better competitiveness for a single bacteria species among hydrocarbon degraders. To examine the efficiency of A. borkumensis to cope with different sources of fatty acid intermediates, we studied the growth rates and membrane fatty acid patterns of this bacterium cultivated on diesel, biodiesel and rapeseed oil as carbon and energy source. Obtained results revealed significant differences in both parameters depending on growth substrate. Highest growth rates were observed with biodiesel, while growth rates on rapeseed oil and diesel were lower than on the standard reference compound (hexadecane). The most remarkable observation is that cells grown on rapeseed oil, biodiesel, and diesel showed significant amounts of the two polyunsaturated fatty acids linoleic acid and linolenic acid in their membrane. By direct incorporation of these external fatty acids, the bacteria save energy allowing them to degrade those pollutants in a more efficient way. Such fast adaptation may increase resilience of A. borkumensis and allow them to strive and maintain populations in more complex hydrocarbon degrading microbial communities.
In der vorliegenden Arbeit wurde der tageszeitkorrelierte Serotonin-Gehalt des SCO, sowie die Expression der 5-HT1A- und 5-HT2A-Rezeptoren und die Synthese- bzw. Sekretionsleistung des SCO bei Goldhamstern untersucht. Serotonin entfaltet im SCO des Goldhamsters eine inhibitorische Wirkung und hemmt die Sezernierungsrate von Glykoproteinen, die den RF formen. Dies bestätigt die Tatsache, dass mit steigender Rezeptorausprägung die Immunreaktivität für AFRU abnimmt. Ob Serotonin beim Hamster auch auf die Synthese von Glykoproteinen wirkt, muss nachfolgend geklärt werden, da in unserem Versuchsaufbau lediglich die Glykoprotein-Sezernierung untersucht wurde. Aussagen bezüglich der Auswirkung von Serotonin auf die Synthese und Sezernierung von löslichen Komponenten des SCO konnten bei dem von uns verwendeten Versuchsaufbau nicht gemacht werden. Deren mögliche Funktionen bleiben noch fraglich und eröffnen neue Optionen. Geklärt ist nun auch die quantitative Relation von 5-HT1A- und 5-HT2A-Rezeptoren im SCO. Es sind deutlich mehr 5-HT1A-Rezeptoren exprimiert. Dies lässt darauf schließen, dass Serotonin im SCO einen entscheidenden Einfluss auf die Glykoprotein-Synthese oder -Sekretion hat. Die tageszeitkorrelierte Rezeptorausprägung muss diskutiert werden. Sie ist tageszeitkorreliert relativ konstant, fraglich bleibt jedoch, wieso die Rezeptorausprägung im zweiten Abschnitt der Tiefschlafphase der Tiere abnimmt, obwohl hier der serotonerge Input weiterhin hoch sein müsste, um in der Aktivitätsphase wieder abzunehmen. Wahrscheinlich ist die Erklärung hierfür in den Expressionsmechanismen der G-Protein-gekoppelten Rezeptoren selbst zu finden. Welche Proteine die geschwindigkeitsbestimmenden Faktoren der 5-HT1A- und 5-HT2A-Rezeptorexpression sind, bleibt zu klären und auch ob sich der Verdacht bestätigt, dass die 5-HT1A-Rezeptorausprägung deutlich schneller voran geht als die der 5-HT2A-Rezeptoren und damit mehr 5-HT1A--Rezeptoren zur Prezeption von Serotonin zur Verfügung stehen. Mit dieser tageszeitkorrelierten Ausprägung schützt sich das SCO unter Umständen vor einer völligen Entleerung der Glykoprotein-Speicher unter erheblichem Serotonin-Einfluss während der Schlafphase. Dieser Aspekt und dessen mögliche Folgen müssen weiter untersucht werden. Weiterhin bleibt fraglich, wie die relative Konstanz in der Glykoprotein-Ausschüttung am Tag und in der Nacht etabliert werden kann, da die Serotonin-Ausschüttung der Raphe-Kerne am SCO nachweislich einer periodischen Rhythmik unterworfen ist. Neben dem Nucleus raphe dorsalis und dem Nucleus raphe medianus ist der Einfluss weiterer Aktivitätszentren auf das SCO denkbar. Auch eine Co-Stimulation der ependymalen und hypendymalen SCO-Zellen mit anderen Transmitterklassen ist möglich und teilweise auch bewiesen. Beide genannten Aspekte könnten Teil eines Feedback-Mechanismus sein, der das SCO vor vollständiger Entspeicherung schützt.
Background: Athletic competition has been a source of interest to the scientific community for many years, as a surrogate of the limits of human ambulatory ability. One of the remarkable things about athletic competition is the observation that some athletes suddenly reduce their pace in the mid-portion of the race and drop back from their competitors. Alternatively, other athletes will perform great accelerations in mid-race (surges) or during the closing stages of the race (the endspurt). This observation fits well with recent evidence that muscular power output is regulated in an anticipatory way, designed to prevent unreasonably large homeostatic disturbances.
Principal Findings: Here we demonstrate that a simple index, the product of the momentary Rating of Perceived Exertion (RPE) and the fraction of race distance remaining, the Hazard Score, defines the likelihood that athletes will change their velocity during simulated competitions; and may effectively represent the language used to allow anticipatory regulation of muscle power output.
Conclusions: These data support the concept that the muscular power output during high intensity exercise performance is actively regulated in an anticipatory manner that accounts for both the momentary sensations the athlete is experiencing as well as the relative amount of a competition to be completed.
During the second part of the TROCCINOX campaign that took place in Brazil in early 2005, chemical species were measured on-board of the high altitude research aircraft Geophysica (ozone, water vapor, NO, NOy, CH4 and CO) in the altitude range up to 20 km (or up to 450 K potential temperature), i.e. spanning the TTL region roughly extending between 350 and 420 K.
Analysis of transport across TTL is performed using a new version of the Chemical Lagrangian Model of the Stratosphere (CLaMS). In this new version, the stratospheric model has been extended to the earth surface. Above the tropopause, the isentropic and cross-isentropic advection in CLaMS is driven by ECMWF winds and heating/cooling rates derived from a radiation calculation. Below the tropopause the model smoothly transforms from the isentropic to hybrid-pressure coordinate and, in this way, takes into account the effect of large-scale convective transport as implemented in the ECMWF vertical wind. As with other CLaMS simulations, the irreversible transport, i.e. mixing, is controlled by the local horizontal strain and vertical shear rates.
Stratospheric and tropospheric signatures in the TTL can be seen both in the observation and in the model. The composition of air above ≈350 K is mainly controlled by mixing on a time scale of weeks or even months. Based on CLaMS transport studies where mixing can be completely switched off, we deduce that vertical mixing, mainly driven by the vertical shear in the outflow regions of the large-scale convection and in the vicinity of the subtropical jets, is necessary to understand the upward transport of the tropospheric air from the main convective outflow around 350 K up to the tropical tropopause around 380 K. This mechanism is most effective if the outflow of the mesoscale convective systems interacts with the subtropical jets.
Recently the LIGO and VIRGO Collaborations reported the observation of gravitational-wave signal corresponding to the inspiral and merger of two black holes, resulting into formation of the final black hole. It was shown that the observations are consistent with the Einstein theory of gravity with high accuracy, limited mainly by the statistical error. Angular momentum and mass of the final black hole were determined with rather large allowance of tens of percents. Here we shall show that this indeterminacy in the range of the black-hole parameters allows for some non-negligible deformations of the Kerr spacetime leading to the same frequencies of the black-hole ringing. This means that at the current precision of the experiment there remains some possibility for alternative theories of gravity.
In the strong coupling and heavy quark mass regime, lattice QCD dimensionally reduces to effective theories of Polyakov loops depending on the parameters of the original Wilson action β,κ and Nτ. We apply coarse graining techniques to such theories in 1d and 2d, corresponding to lattice QCD at finite temperature and non-zero chemical potential in 1+1d and 2+1d, respectively. In 1d the method is applied to the effective theories up to O(κ4). Using the transfer matrix, the recursion relations are solved analytically. The thermodynamic limit is taken for some observables. Afterwards, continuum extrapolation is performed numerically and results are discussed. In 2d the coarse graining method is applied in the pure gauge and static quark limit. Running couplings are obtained and the fixed points of the transformations are discussed. Finally, the critical coupling of the deconfinement transition is determined in both limits. Agreement to about 12% with Monte Carlo results of 2+1d Yang-Mills theory from the literature is observed.
For the exploration of the phase diagram of QCD, effective Polyakov loop theories derived from lattice QCD provide a valuable tool in the heavy quark mass regime. In practice, the evaluation of these theories is complicated by the appearance of long-range and multipoint interaction terms. On the other hand, it is well known that for theories with such kind of interactions mean field approximations can be expected to yield reliable results. Here, we apply this framework to the critical endpoint of the deconfinement transition and results are compared to the literature. This treatment can also be used to investigate the phase diagram at non-zero baryon and isospin chemical potential.
Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder
(2021)
Background: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses of female CD.
Methods: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9–18 years), compared to 864 sex- and age-matched typically developing controls.
Results: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the ‘gender paradox’ hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the ‘delayed-onset pathway’ hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology.
Conclusions: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex-specific clinical profiles of CD will be critical in informing intervention and prevention programmes.
Verbreitungsbilder von Artefakten regten die archäologische Forschung seit dem späten 19. Jahrhundert dazu an, "Kulturkreise" zu definieren und auf dieser Basis Siedlungsräume ethnischer Gruppen, deren (Fremd)bezeichnung in lateinischen und griechischen Schriftquellen überliefert ist, zu lokalisieren. Diese Herangehensweise provoziert seit nunmehr fast zwei Jahrzehnten eine heftige Diskussion über die Interpretierbarkeit materieller Quellen im Hinblick auf die Benennung, Definition und Lokalisierung antiker Ethnien und Identitäten. ...
Einem ganz anderen Sujet widmet sich der abschließende archäobiologische Beitrag "Searching for Rome’s boundaries: An archaeobiological perspective" von Sabine Deschler-Erb, die anhand des Tierknochenspektrums verschiedener Fundplätze im Dreieck zwischen Avenches, Bregenz und Chur der Frage des Einflusses naturräumlicher Faktoren im Tierknochenbestand und den daraus resultierenden Speisegewohnheiten nachgeht. ...
Data supporting the role of the non-glycosylated isoform of MIC26 in determining cristae morphology
(2015)
Membrane architecture is crucially important for mitochondrial function and integrity. The MICOS complex is located at crista junctions and determines cristae membrane morphology and the formation of crista junctions. Here we provide data of the bona fide MICOS subunit MIC26 for determining cristae morphology. MiRNA-mediated downregulation of MIC26 results in higher protein levels of MIC27 and in lower levels of Mic10. Using a miRNA-resistant form to MIC26 we show that this effect is specific to MIC26. Our data further demonstrate that depletion of MIC26 primarily affects the level of the 22 kDa mitochondrial isoform of MIC26 but not the amount of the secreted 55 kDa isoform of MIC26. Depletion of MIC27, however, increases secretion of the latter isoform. Overexpression of a myc-tagged version of MIC26 resulted in altered cristae morphology with swollen and partly vesicular cristae-structures.
Resonance assignments are challenging for membrane proteins due to the size of the lipid/detergent-protein complex and the presence of line-broadening from conformational exchange. As a consequence, many correlations are missing in the triple-resonance NMR experiments typically used for assignments. Herein, we present an approach in which correlations from these solution-state NMR experiments are supplemented by data from 13C unlabeling, single-amino acid type labeling, 4D NOESY data and proximity of moieties to lipids or water in combination with a structure of the protein. These additional data are used to edit the expected peaklists for the automated assignment protocol FLYA, a module of the program package CYANA. We demonstrate application of the protocol to the 262-residue proton pump from archaeal bacteriorhodopsin (bR) in lipid nanodiscs. The lipid-protein assembly is characterized by an overall correlation time of 44 ns. The protocol yielded assignments for 62% of all backbone (H, N, Cα, Cβ, C′) resonances of bR, corresponding to 74% of all observed backbone spin systems, and 60% of the Ala, Met, Ile (δ1), Leu and Val methyl groups, thus enabling to assign a large fraction of the protein without mutagenesis data. Most missing resonances stem from the extracellular half, likely due intermediate exchange line-broadening. Further analysis revealed that missing information of the amino acid type of the preceding residue is the largest problem, and that 4D NOESY experiments are particularly helpful to compensate for that information loss.
Cataract surgery is one of the oldest and the most frequent outpatient clinic operations in medicine performed worldwide. The clouded human crystalline lens is replaced by an artificial intraocular lens implanted into the capsular bag. During the last six decades, cataract surgery has undergone rapid development from a traumatic, manual surgical procedure with implantation of a simple lens to a minimally invasive intervention increasingly assisted by high technology and a broad variety of implants customized for each patient’s individual requirements. This review discusses the major advances in this field and focuses on the main challenge remaining – the treatment of presbyopia. The demand for correction of presbyopia is increasing, reflecting the global growth of the ageing population. Pearls and pitfalls of currently applied methods to correct presbyopia and different approaches under investigation, both in lens implant technology and in surgical technology, are discussed.
In welcher Welt leben wir? : Soziologiekongress zum Thema "Transnationale Vergesellschaftungen"
(2010)
Frankfurt wird vom 11. bis 15. Oktober zum fünften Mal Austragungsort des Kongresses der Deutschen Gesellschaft für Soziologie (DGS) sein. Zu diesem mittlerweile 35. DGS-Kongress – der erste fand vor 100 Jahren ebenfalls in Frankfurt statt – werden rund 3000 Wissenschaftlerinnen und Wissenschaftler aus aller Welt erwartet. ...
Die vorliegende Arbeit untersucht die Zulässigkeit von sog. anti-suit injunctions im Anwendungsbereich der EuGVVO. Dabei wird anhand der Antworten des Europäischen Gerichtshofs auf Vorlageersuchen zu den Rechtssachen Turner v. Grovit und West Tankers v. Allianz/Generali herausgearbeitet, dass der Grundsatz des gegenseitigen Vertrauens der Mitgliedstaaten in die Funktions- und Leistungsfähigkeit der Rechtssysteme und Rechtspflegeorgane zu einer Inkompatibilität von anti-suit injunctions mit der EuGVVO führt. In einem weiteren Schritt folgt ein kursorischer Überblick über die aktuellen Entwicklungen im deutschen Prozessrecht rund um die sog. anti-anti-suit injunction. Abschließend wird die Frage nach der Aktualität des Rechtsmittels näher beleuchtet und unter besonderer Berücksichtigung des Brexits bestätigt.
Die Etablierung eines HIV-1 Tiermodells ist ein großes Ziel auf dem Weg zur Entwicklung antiretroviraler Medikamente und Impfstoffe gegen HIV-1. Speziesspezifische Restriktionsfaktoren und fehlende Kofaktoren verhindern jedoch die Replikation von HIV-1 in Tieren. Restriktionsfaktoren sind Bestandteil der intrinsischen Immunität und entwickelten sich im Laufe der Evolution als Abwehrmechanismus gegen diverse Pathogene. Dazu gehören die Proteine der APOBEC3-Familie, TRIM5􀀁 und Tetherin, welche die Virusreplikation von HIV-1 an verschiedenen Punkten seines Lebenszyklus inhibieren. Koevolutionär entwickelten Retroviren Antagonisten, um die restriktive Funktion ihrer Wirtsproteine zu umgehen. Um ein replikationskompetentes, simiantropes HIV zu generieren, wurden im Rahmen dieser Arbeit die Sequenzen vifHIV-1 und vpuHIV-1 gegen vifagm.tan aus SIVagm.tan und vpugsn/den aus den Immundefizienzviren SIVgsn und SIVden substituiert, um die Restriktion gegen A3G und Tetherin in Zellen der Afrikanischen Grünen Meerkatze zu umgehen. Die TRIM5 vermittelte Restriktion wurde über eine Mutation in der Cyclophilin A Bindedomäne des Kapsids verhindert. Die Analyse der Vifagm.tan Funktion bestätigte den geänderten Tropismus des chimären HIV-1 bezüglich der APOBEC3G vermittelten Restriktion. Denn nach Austausch des vifHIV-1 Gens war das Virus nicht mehr in der Lage, die Aktivität des humanen APOBEC3G zu unterbinden und initiierte stattdessen die Degradation des Analogons aus der Afrikanischen Grünen Meerkatze. Weiterhin konnte die erfolgreiche Klonierung des vpugsn/den Gens in HIV-1 die Aktivität der SHIV-Konstrukte gegen Tetherin der Afrikanischen Grünen Meerkatze und der Rhesusaffen ändern, wohingegen humanes Tetherin nicht mehr abgebaut werden konnte. Trotz der erfolgreichen Aktivität der konstruierten SHIVs gegen die zellulären Restriktionsfaktoren der Afrikanischen Grünen Meerkatze, replizierten die generierten chimären Viren in einer AGM Zelllinie, nicht aber in periphären mononuklearen Blutzellen der Afrikanischen Grünen Meerkatze. Ein Indiz, das für weitere strukturelle Anpassungen der Viren gegenüber ihren Wirten spricht, die zur Bildung der Spezies-Barriere beitragen und Zoonosen erschweren. Im zweiten Teil der Dissertation wurden die Aktivitäten der Proteine der APOBEC3-Familie und VifHIV-1 auf ihre Regulation durch Phosphorylierung untersucht. Proteinphosphorylierungen gehören zu den wichtigsten posttranslationalen Proteinmodifikationen, um diverse Funktionen wie die Enzymaktivität, Proteininteraktionen und die zelluläre Lokalisation zu steuern. Dabei konnte die durch Yang et al. postulierte Phosphorylierung von VifHIV-1 nicht bestätigt werden. Analysen der mutmaßlichen VifHIV-1 Phosphomutanten enthüllten, dass die Funktion von VifHIV-1, die Infektiosität von HIV-1 zu gewährleisten, durch Substitution der mutmaßlichen Phosphoaminosäuren nicht beeinträchtigt wird und ebenso sämtliche Phosphomutanten die Degradation von A3G initiierten, wenn auch in unterschiedlichem Maße. Weiterhin wurde im Rahmen dieser Arbeit gezeigt, dass A3C entweder in einem phosphorylierten Protein-Komplex vorliegt oder ein phosphoryliertes Protein bindet. Zudem konnte ermittelt werden, dass APOBEC3A als einziges Protein der APOBEC3-Familie nach TPA- und cAMP-Stimulation phosphoryliert wird. In vitro Kinase Studien konnten zeigen, dass die Phosphorylierung unter anderem durch ERK2 erfolgt. Es konnte jedoch kein Zusammenhang zwischen der Phosphorylierung von A3A und dessen zellulärer Lokalisation, Aktivität gegen HIV-1 als auch gegen die Retrotranspositionselemente IAP und LINE-1 hergestellt werden. Dies lässt den Schluss zu, dass die Phosphorylierung die untersuchten Aktivitäten von APOBEC3A nicht beeinflusst oder APOBEC3A eine bisher unbekannte durch Phosphorylierung regulierte Funktion besitzt.
The TATA Box Binding Protein (TBP) is a 20 kD protein that is essential and universally conserved in eucarya and archaea. Especially among archaea, organisms can be found that live below 0°C as well as organisms that grow above 100°C. The archaeal TBPs show a high sequence identity and a similar structure consisting of α-helices and β-sheets that are arranged in a saddle-shape 2-symmetric fold. In previous studies, we have characterized the thermal stability of thermophilic and mesophilic archaeal TBPs by infrared spectroscopy and showed the correlation between the transition temperature (Tm) and the optimal growth temperature (OGT) of the respective donor organism. In this study, a “new” mutant TBP has been constructed, produced, purified and analyzed for a deeper understanding of the molecular mechanisms of thermoadaptation. The β-sheet part of the mutant consists of the TBP from Methanothermobacter thermoautotrophicus (OGT 65°C, MtTBP65) whose α-helices have been exchanged by those of Methanosarcina mazei (OGT 37°C, MmTBP37). The Hybrid-TBP irreversibly aggregates after thermal unfolding just like MmTBP37 and MtTBP65, but the Tm lies between that of MmTBP37 and MtTBP65 indicating that the interaction between the α-helical and β-sheet part of the TBP is crucial for the thermal stability. The temperature stability is probably encoded in the variable α-helices that interact with the highly conserved and DNA binding β-sheets.
Die kathetergestützte Thrombektomie ist, spätestens seitdem 2015 verschiedene Studien ihre Überlegenheit zur alleinigen medikamentösen Behandlung gezeigt haben, die bevorzugte Therapie bei Patienten mit akutem ischämi-schem Schlaganfall und embolischen Verschluss einer großen intrakraniellen Arterie. Obwohl die mechanische Thrombektomie mittlerweile zur Standardthe-rapie zählt, ist der Zusammenhang zwischen Lokalisation des Infarktareals und klinischem Behandlungsergebnis nach Thrombektomie bisher nicht gut untersucht. Die dieser Studie zugrunde liegende Hypothese war, dass Infarktdemar-kationen in der zentralen Corona radiata, Capsula interna und/oder den Ba-salganglien aufgrund einer potenziellen Schädigung der Fasern des Tractus corticospinalis mit einem schlechten Behandlungsergebnis (mRS 3 bis 6) nach mechanischer Thrombektomie assoziiert sind. Ziel dieser Studie war es somit, den Behandlungserfolg nach Thrombektomie bei Patienten mit entsprechender Infarktlokalisation zu untersuchen.
Hierfür wurden die Daten von 70 erwachsenen Patienten analysiert, die im Zeitraum von April 2016 bis Januar 2020 im Institut für Neuroradiologie des Universitätsklinikums Frankfurt aufgrund eines ischämischen Infarktes mit entsprechender Infarktdemarkation eine mechanische Thrombektomie erhalten haben. Alle erhobenen Daten stammen aus der elektronischen Krankenakte, dem Radiologie-Informations-System oder einem prospektiven Register zur internen Qualitätssicherung. Es erfolgte außerdem eine Unterteilung der Studi-enkohorte anhand des zusätzlichen kortikalen Infarktausmaßes bzw. der kortikalen Infarktlokalisation, um den Einfluss kortikaler Infarkte auf das Behandlungsergebnis beurteilen zu können. Die wichtigsten Endpunkte der Studie waren das klinische Behandlungsergebnis gemessen anhand der mRS nach 90 Tagen sowie die Ergebnisse der Subgruppenanalyse.
51,4 % der Studienpopulation erzielten nach 90 Tagen ein gutes klinische Be-handlungsergebnis (mRS 0 bis 2), 32,9 % der Patienten erreichten sogar ein exzellentes Ergebnis (mRS 0 bis 1). Insgesamt verstarben innerhalb von 90 Tagen nach dem Schlaganfallereignis 15,7 % aller Patienten und 32,9 % konn-ten nur ein schlechtes Behandlungsergebnis (mRS 3 bis 5) erzielen. Die Ergebnisse zeigen, dass die in der routinemäßig angefertigten Bildgebung nachgewiesenen Infarktdemarkationen im Verlauf der langen Bahnen nicht zwingend ein schlechtes Behandlungsergebnis bedingen. Bei Patienten mit ausge-dehnter Beteiligung des Kortex und Infarkten in definierten eloquenten Arealen waren die klinischen Behandlungsergebnisse allerdings schlechter als in der Vergleichsgruppe mit isolierten Läsionen der langen Bahnen.
Um künftig ein besseres Verständnis darüber zu erlangen, welche Patienten mit bestimmter Infarktlokalisation von einer mechanischen Thrombektomie langfristig profitieren können, sind weitere prospektive Studien mit exakt definierten Vergleichsgruppen und höherwertiger MRT-basierter Bildgebung erforderlich.
Die Arbeit widmet sich Jim Jarmuschs Film DEAD MAN (1995) unter besonderer Berücksichtigung der akustischen Ebene. Dabei geht es einerseits um eine Interpretation und historische Einordnung des Werkes sowie andererseits um die exemplifizierte Darstellung der besonderen Bedeutung der auditiven Gestaltungsebene innerhalb des vermeintlich primär visuellen Mediums Film.
All lifeforms have to sense changes in their environment and adapt to possibly detrimental conditions. On a cellular level, the highly elaborate proteostasis network (PN) consisting of housekeeping and stress-induced proteins, confers this tolerance against stress and maintains cellular protein homoestasis. This is essential for survival, as an accumulation of stress-induced protein aggregation will eventually affect the functionality of crucial cellular components and ultimately lead to cell death. The guardians of this balance are the molecular chaperones and their activity-regulating co-haperones. They are engaged in all aspects of protein biogenesis, maintenance and degradation, especially during stress.
The heat shock proteins (HSPs) are the major chaperones in mammals and encompass constitutive and stress-induced isoforms. Among them, the HSP70 and the HSP90 family are the most abundant HSPs and their activity is involved in a great variety of homoestasis and stress-induced tasks.
As part of the protein triage the E3 ligase CHIP (C-terminal HSC70-interacting protein) is an essential activity regulating co-chaperone of HSP70 and HSP90 which provides a link between chaperone mediated protein-folding and various degradation pathways. Due to its decisive function, CHIP is involved in a wide array of cellular processes, especially in clearing misfolded HSP70 client proteins that are prone to aggregate. As a consequence, CHIP was reported to confer protection against many aggregation-induced pathologies of the neuronal system. Additionally, CHIP has been identified as a critical factor in various types of cancer and is implied to affect the development and the longevity of mammals.
Despite the significant progress in the understanding of CHIP’s structure and function, many aspects surrounding its chaperone dependency and its substrate recognition remain unclear. Moreover, due to the variety of substrates in diverse cellular pathways, there are yet many connections to elucidate between CHIP and components of the cellular proteostasis network.
The work of this thesis was focused on the role of CHIP in acute stress response and the corresponding status of chaperone association. Moreover, it was investigated if CHIP, as the connecting ligase of folding and degradation systems, might also provide a link between the PN and the reorganisation of the cellular architecture upon stress exposure.
This has become of increasing interest as recent reports highlight the importance of spatial sequestration in protein quality control.
To this end, subcellular distribution of CHIP was analysed by live-cell microscopy during heat stress. It became obvious that during the heat-induced challenge of the chaperone system, CHIP migrated to new cellular sites. Further experiments suggested that the observed migration to the plasma membrane is a chaperone-independent process and in vitro reconstitution of membrane association confirmed the competitive nature of membranes and chaperones for CHIP binding. A detailed in vivo and in vitro analysis of the newly observed membrane association of CHIP revealed a distinct lipid specificity and a novel direct association with lipids. Binding experiments with recombinantly purified deletion mutants of CHIP identified the TPR domain and a positive patch in the coiled-coil domain as main determinants for the lipid association. Through biochemical and biophysical approaches, the structural integrity and functionality of CHIP upon membrane binding was confirmed and further characterised.
Moreover, mass spectrometry analysis provided a high confidence identification of chaperone-free interactors of CHIP at the plasma membrane and other membranous compartments.
In accordance with the lipid specificity, the Golgi apparatus was one of these sites. Only chaperone-free CHIP had a significant effect on the morphology of the organelle, again confirming the competitive role of chaperones and lipids. With respect to the physiological consequences of the changed localisation of CHIP, preliminary results indicated increased cell death when the ligase localises to cellular membranes. The results lead to the conclusion that CHIP acts as an initiator of early stress adaptation and as a sensor for the severity and strength of the stress reaction.
Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic protein misfolding are less clear. Here we show that the mammalian ubiquitin ligase C-terminal Hsp70-interacting protein (CHIP), if freed from chaperones during acute stress, can dock on cellular membranes thus performing a proteostasis sensor function. We reconstituted this process in vitro and found that mainly phosphatidic acid and phosphatidylinositol-4-phosphate enhance association of chaperone-free CHIP with liposomes. HSP70 and membranes compete for mutually exclusive binding to the tetratricopeptide repeat domain of CHIP. At new cellular locations, access to compartment-specific substrates would enable CHIP to participate in the reorganization of the respective organelles, as exemplified by the fragmentation of the Golgi apparatus (effector function).
Objective: Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD.
Design: A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol.
Results: A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34–5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73–3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure.
Conclusion: Our study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects.
In Germany, a grave labor shortage in the nursing and elderly care sectors has prompted the response of recruiting skilled nursing staff from abroad in recent years. This article analyzes these recruitment practices as forms of “migration management”: German migration policy has changed according to this paradigm to attempt utilitarian control over migration processes and mediate between labor market concerns on the one hand and isolationist, politico-cultural seclusion on the other. Based on original research through interviews and document analysis, we identify four relevant levels of analysis in researching migration management in the context of the recruitment of skilled nurses: (1) Definition of problem areas: How is migration programmatically legitimized as a solution to social problems? (2) Categorization of migration: How are migration processes classified? (3) Change in statehood: How are sites and actors of migration control being privatized and diversified? (4) Technologies: By means of which procedures, legal foundations and political instruments does migration management take place in the everyday? We believe that taking these four foci as points of departure would be beneficial for further inquiries in critical migration research.
Leben braucht Licht und den täglichen Wechsel von Licht und Dunkel. Das gilt auch für den Menschen. Licht dient unserer Orientierung – nicht nur im Raum, sondern auch in der Zeit. Der Tag-Nacht-Wechsel ist der wichtigste Umweltreiz für die Taktung unserer Inneren Uhr. Zu wenig Licht am Tag und zu viel Licht in der Nacht kann sie aus dem Takt bringen und zu Schlafstörungen und Depressionen führen.
Die Erkenntnis, dass das Gehirn Hormone produziert, gehört heute zum Allgemeingut des biomedizinischen Wissens. Ausgangspunkt der modernen Neuroendokrinologie ist das weit gespannte biologische Konzept der Neurosekretion, das Ernst und Berta Scharrer in den 1930er Jahren aus einer Reihe von fundamentalen Einzelentdeckungen entwickelten. Das Fundament dieses Konzeptes legte das Paar am Neurologischen Institut (Edinger Institut) in Frankfurt am Main.
In their study on "The modern anthropology of Southeast Asia", Victor King and William Wilder raise the question in how far the region can be taken as a field of anthropological enquiry. After their initial discussion of cultural and social trends as well as anthropological studies, they conclude that the common issue of the region is its diversity. They come to the rather pragmatic solution that "South-East Asia constitutes a convenient unit of study, ... but ... we should not think of it in terms of a bounded, unified and homogenous socio-cultural area" (King/Wilder 2003: 24). We doubt that there are homogenous socio-cultural areas anywhere else. These are usually constructed through the invention of traditions and ideological simulations. The interesting case with regards to Southeast Asia is, why no such homogeneity has been constructed, not even by anthropologists or sociologists. ...
Gegenstand der Untersuchung ist eine umfassende Analyse der zeitgenössischen Medienprominenz, hier deutschsprachige Singer-Songwriter, eingebettet in die Kontexte ‘psychische Störungen‘ (erhoben mit dem SKID-II/M.I.N.I.), ‘Kreativität‘ (TSD-Z) und ‘Perfektionismus hinsichtlich des Aussehens‘ (AAS), mit der Zielsetzung dieses heterogene Phänomen mittels einer ganzheitlichen Perspektive zu erfassen. An der Studie nahmen insgesamt 31 prominente und 31 nicht promiente deutschsprachige Singer-Songwriter teil, wobei 15 der prominenten Singer-Songwriter in Besitz von mindestens einem ‘ECHO‘, 14 in Besitz von mindestens einer ‘Goldenen Schallplatte‘ und 2 mit mehr als 200 Nennungen in der Gruner + Jahr Pressedatenbank verzeichnet sind. Zunächst geht die Arbeit der Fragestellung nach, ob sich die prominenten Singer-Songwriter in den Störungsbildern ‘affektive Störung‘, ‘narzisstische Persönlichkeitsstörung‘, ‘Borderline-Persönlichkeitsstörung‘, ‘Alkoholmissbrauch/-abhängigkeit und ‘Substanzmissbrauch/-abhängigkeit‘ von den nicht prominenten Singer-Songwritern unterscheiden. Die Ergebnisse zeigen auf, dass prominente Singer-Songwriter signifikant häufiger unter einer narzisstischen Persönlichkeitsstörung, Alkoholabhängigkeit und Substanzmissbrauchs leiden als nicht prominente Singer-Songwriter. Außerdem wird ersichtlich, dass die prominenten Singer-Songwriter vermehrt Kokain und die nicht prominenten Singer-Songwriter vermehrt Marihuana konsumieren. Die Werte der prominenten und nicht prominenten Singer-Songwriter in Bezug auf die narzisstische Persönlichkeitsstörung sowie Alkoholmissbrauch/-abhängigkeit übersteigen bei weitem die Prävalenzzahlen der deutschen Allgemeinbevölkerung. Als nächstes wurde geprüft, ob prominente Singer-Songwriter kreativer sind als nicht prominente Singer-Songwriter. Diese Annahme konnte, ebenso wie die darauffolgende Annahme, nämlich dass die Kreativität den Zusammenhang zwischen einer psychischen Störung und der Prominenz erklärt, nicht bestätigt werden. Die Kreativität stellt des Weiteren auch kein Moderatoreffekt dar und wirkt somit nicht, gemeinsam mit einer narzisstischen Persönlichkeitsstörung, verstärkend auf die Prominenz. Wiederum ergab sich hypothesenkonform, dass prominente Singer-Songwriter perfektionistischer hinsichtlich ihres Aussehens eingestellt sind als nicht prominente Singer-Songwriter. Zuletzt zeigen die Ergebnisse, dass die Prominenz den Zusammenhang zwischen einer narzisstischen Persönlichkeitsstörung und der perfektionistischen Einstellung hinsichtlich des Aussehens nicht erklärt, jedoch verstärkt die Prominenz den Einfluss einer Depression auf die soziale Isolation.
Previous reports of improved oral reading performance for dyslexic children but not for regular readers when between-letter spacing was enlarged led to the proposal of a dyslexia-specific deficit in visual crowding. However, it is in this context also critical to understand how letter spacing affects visual word recognition and reading in unimpaired readers. Adopting an individual differences approach, the present study, accordingly, examined whether wider letter spacing improves reading performance also for non-impaired adults during silent reading and whether there is an association between letter spacing and crowding sensitivity. We report eye movement data of 24 German students who silently read texts presented either with normal or wider letter spacing. Foveal and parafoveal crowding sensitivity were estimated using two independent tests. Wider spacing reduced first fixation durations, gaze durations, and total fixation time for all participants, with slower readers showing stronger effects. However, wider letter spacing also reduced skipping probabilities and elicited more fixations, especially for faster readers. In terms of words read per minute, wider letter spacing did not provide a benefit, and faster readers in particular were slowed down. Neither foveal nor parafoveal crowding sensitivity correlated with the observed letter-spacing effects. In conclusion, wide letter spacing reduces single word processing time in typically developed readers during silent reading, but affects reading rates negatively since more words must be fixated. We tentatively propose that wider letter spacing reinforces serial letter processing in slower readers, but disrupts parallel processing of letter chunks in faster readers. These effects of letter spacing do not seem to be mediated by individual differences in crowding sensitivity.
The reading acceleration phenomenon refers to the effect that experimentally induced time constraints can generate instantaneous improvements of reading rate, accuracy and comprehension among typical and reading impaired readers of different age groups. An overview of studies applying the fading manipulation (i.e., letters are erased in reading direction), which induces the time constraints causing the acceleration phenomenon, is provided in the first part of this review. The second part summarises the outcomes of studies using a training approach called the reading acceleration program (RAP) that integrated core principles of the acceleration phenomenon to generate persistent reading performance improvements. Our review shows ample evidence for the validity of the acceleration phenomenon, since it has been replicated across various languages and populations. However, although there are several explanatory approaches for underlying mechanisms, none of them is well substantiated by empirical evidence so far. Similarly, although generally positive effects of RAP training were reported for several languages and groups of readers, the exact mechanisms causing improved reading rates and comprehension are not well understood. Our critical discussion points out several limitations of RAP that call for further research. However, we also highlight several benefits regarding RAP's potential as an intervention approach for enhancements in reading performance. Video abstract link: https://youtu.be/wO6aEXavk8w