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Two-pore domain K+ channel TASK-1 in human pulmonary artery smooth muscle cells and its regulation by the vasoconstrictor endothelin-1

Two-pore domain K+ channel TASK-1 in human pulmonary artery smooth muscle cells and its regulation by the vasoconstrictor endothelin-1

The essential property of the TASK-1 channels is their extreme sensitivity to variations in extracellular pH (pHo) in a narrow physiological range. Figure 8A shows the pHo dependence of I KN of primary hPASMC across the full voltage range over which I KN is apparent. Modification of I KN by pHo was reflected in the resting membrane potential. A pH of 8.3 significantly hyperpolarized the cells, whereas acidification caused membrane depolarization in primary hPASMC (-10±1 mV versus 13±2 mV; n=5). Overall, we have found a functional expression of kinetically and pharmacologically identical background K + current carried by TASK-1 in primary hPASMC. In order to provide a certain evidence for the involvement of TASK-1 in I KN , we tested the effects of 10 mmol/L tetraethylammonium (TEA, a blocker of K Ca ), 3 mmol/L 4-aminopyridine (4-AP, a blocker of K V ), 5 μmol/L ruthenium red (a blocker of TASK-3), and different concentrations of ZnCl 2 . We found that TEA and 4-AP failed to inhibit I KN (Figure 8B). In contrast, ruthenium red caused a reduction of I KN (Figure 8C). However, the ruthenium red–sensitive current was linear and the reversal potential varied between 0 and -20 mV. The calculated Nernst equilibrium potential was -84 mV for K + . It is well known that the ruthenium red is active at various sites (eg, ryanodine receptors (Hohenegger et al., 2002) and TRPV channels (Guler et al., 2002), therefore, this effect in primary hPASMC was not be surprising. The divalent zinc cation was also reported to inhibit TASK-1 at higher concentrations. However, in our study, the Zn-sensitive ion current had a reversal potential close to 0 mV (Figure 8D), indicating the presence of a nonspecific leak current.
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Expression and role of TASK-1 channels in pulmonary vessels and airways

Expression and role of TASK-1 channels in pulmonary vessels and airways

Oxygen dependent modulation of TASK-1 has been described differently in different organs and model systems. In transfected HEK293 cells, TASK-1 channel function of sensing O 2 was moderately inhibited [121] . In human brain, TASK-1 was potentially inhibited by hypoxia [186] . In contrast, no response to changes in O 2 tension was observed in TASK-1 expressing Xenopus oocytes [62] and the TASK-like current in adrenomedullary chromaffin cells was also O 2 insensitive [187] . Hypoxia causes rise in pulmonary vascular resistance, constriction of pulmonary vessels, pulmonary artery cell proliferation and ultimately can lead to PH [4, 20, 188-191] . PAP in response to hypoxia was measured in the laboratory of Prof. Norbert Weissmann, Excellence Cluster Cardio- Pulmonary System, Justus-Liebig-University, Giessen, in isolated, buffer perfused and ventilated lungs from TASK-1 WT and corresponding KO mice. There was no difference of rise in PAP under hypoxia between TASK-1 WT and KO mice, although there was a slight reduction in HPV at certain time points in larger pre-acinar arteries in PCLS prepared from KO mice. Most recently, Paddenberg et al. [185] demonstrated that HPV was prevented only in intra-acinar arteries in mitochondrial complex II heterozygous mice, and rise in hypoxic PAP remained unaffected in these mice. These findings can be assigned to the presence of a different muscularisation along the length of pulmonary arteries, and difference in sensitivity of cells to hormones, neurotransmitters, and hypoxia. The difference in response to hypoxia along the length of pulmonary arteries from heart to the capillaries can also be attributed to the presence of different proteins which sense changes in oxygen tension, their low and high expression, their translation from mRNA, and certain genes which regulate contraction of vessels. In a previous study [192] , TRPC6 gene KO mice showed impaired PAP under acute hypoxic conditions. With respect to PH, different species can adapt to chronic hypoxic conditions and vascular remodeling is not induced. Pika, yak, snow pig, and llama [3, 193-195] represent such cases. Moreover, intensity and magnitude of hypoxia- induced changes vary according to the species, sex and the developmental stages of animal [196-199] .
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Die kardiale Phänotypisierung von TASK-1- und Pannexin-1-defizienten Mäusen

Die kardiale Phänotypisierung von TASK-1- und Pannexin-1-defizienten Mäusen

Besonders deutlich wird die Verlängerung der QT- und auch der QTc-Intervalle von wachen und narkotisierten Pannexin-1 und TASK-1 WT- und KO-Mäusen unter niedrigen Herzfrequenzen: Je geringer die Herzfrequenz, desto länger die QT- beziehungsweise QTc- Zeit. Beide Mausstämme haben demnach einen klinischen Phänotyp, der dem eines LQTS3 beim Menschen ähnelt (Schwartz 1997; Schwartz et al., 2001; Petric et al., 2016). Beim LQTS3 besteht während Ruhephasen ein erhöhtes Risiko für Torsades-de-Pointes- Arrhythmien und einen plötzlichen Herztod (Petric et al., 2016). Dies könnte erklären, weshalb bei körperlicher Belastung und unter Isoprenalinstimulation bei Pannexin-1- defizienten Mäusen keinerlei Herzrhythmusstörungen auftreten. Ein verborgenes LQTS1 hingegen, das heute mit Gentests diagnostiziert wird und früher durch Belastungsuntersuchungen und Katecholamingabe demaskiert wurde (Ackerman et al., 2002; Shimizu und Antzelevitch, 2000), würde anders als LQTS2 und LQTS3 (Ackerman et al., 2002; Shimizu und Antzelevitch, 2000) zu einem paradoxen Anstieg des QT-Intervalls bei hohen Herzfrequenzen führen (Ackerman et al., 2002). Bei Pannexin-1 -/- - und TASK-
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Die kardiale Phänotypisierung der TASK-1-defizienten Maus

Die kardiale Phänotypisierung der TASK-1-defizienten Maus

Die bisher beschriebenen Arbeitsschritte ermöglichen die qualitative Analyse eines Proteins. Durch die spezifische Antigen-Antikörperreaktion und den Nachweis der Proteingröße anhand des Vergleiches mit dem geeichten Marker ist es möglich, ein bestimmtes Protein zu identifizieren. Um Aussagen hinsichtlich der Proteinkonzentration im Ursprungsgewebe oder im Vergleich zu anderen Proteinen zu treffen, müssen weitere Analysen erfolgen. Da es sich in der vorliegenden Arbeit um die Fragestellung handelte, ob ein bestimmtes Kanalprotein überhaupt vorhanden (TASK-1 bei TASK-1 (-/-) Mäusen im Vergleich zu Wildtypen) oder ein Eiweiß stärker exprimiert ist (TWIK-2; TREK-1 bei TASK 1 (-/-) Mäusen im Vergleich zu TASK-1 (+/+) Mäusen), also ob eine komparative oder semi-quantiative Aussage zu treffen ist, kann eine relative Quantifizierung durch einen sogenannten „Housekeeper“ erfolgen. Als „Housekeeper“ werden in diesem Fall Proteine bezeichnet, die unabhängig vom Zelltyp, Zellstadium und äußeren Einflüssen in allen Zellen vergleichbar stabil exprimiert werden und darum als interner Standard oder endogene Kontrolle fungieren können. Beispiele sind ß- Actin (ACTB), β-Glukuronidase (GUS), Hypoxanthin-Phosphoribosyl-Transferase (HPRT), PTATA box binding Protein (TBT) und die hier verwendete Glycerinaldehyd-3-phosphat- dehydrogenase (GAPDH). Indem in allen Proben die gleiche Menge an GAPDH nachzuweisen ist (erkennbar an der Intensität der Röntgenfilm-Schwärzung), ermöglicht eine Abstufung der Schwärzung bei der ersten Nachweisreaktion vergleichende Aussagen zu Konzentrationsunterschieden der einzelnen Proteine (zum Beispiel TASK vs. TREK). Je stärker die Schwärzung, desto höher die Proteinkonzentration in der jeweiligen Probe.
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Die Rolle von SCAMP Proteinen beim intrazellulären Transport des Kaliumkanals TASK-1

Die Rolle von SCAMP Proteinen beim intrazellulären Transport des Kaliumkanals TASK-1

123 Adapterprotein fungiert. Wie sich in den Strommessungen zeigte, fiel die Reduzierung der Stromstärke von TASK-1 am geringsten aus, wenn SCAMP5 zusammen mit dem SCAMP1--NPF und SCAMP2--NPF koexprimiert wurde (Abb. 4.2.1.12). Dies bestätigt die Vermutung, dass SCAMP5 SCAMP1 oder 2 benötigt, um die TASK-1-Strom zu verringern. Dieses Ergebnis ist ein weiterer Hinweis darauf, dass SCAMP5 als Adapterprotein zwischen TASK-1 und SCAMP1 bzw. SCAMP2 fungiert. Um diese Theorie weiter zu verfolgen, müsste in Oozyten ein Knockdown von endogenem SCAMP5 durchgeführt werden. Dann sollte bei einer Koinjektion von TASK-1 mit SCAMP1 der Strom des Kanals nicht mehr reduziert werden. Da die NPF Mutanten den Effekt von SCAMP5 auf TASK-1 nicht vollständig blockieren, scheint SCAMP5 noch in gewissem Ausmaß mit den endogenen Wildtypen von SCAMP1 und SCAMP2 interagieren zu können. Des Weiteren könnte auch eine Interaktion von SCAMP5 mit endogenem SCAMP3 verantwortlich für die Verringerung des TASK-1 Stromes sein. Denn auch SCAMP3 besitzt wie in Punkt 1.5 dieser Arbeit beschrieben NPF-repeats im N-Terminus und käme als weiterer Interaktionspartner in Frage.
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Common Cognitive Control Processes Underlying Performance in Task-Switching and Dual-Task Contexts

Common Cognitive Control Processes Underlying Performance in Task-Switching and Dual-Task Contexts

Similarities and Differences Between Task-Switching and Dual- Tasking The reason for the traditionally independent investigation of task- switching and dual-tasking may be that task-switching and dual-task paradigms usually differ decidedly with respect to how the tasks are performed. In task-switching paradigms, costs of strictly serial switching from one task to another are measured by asking subjects to perform two successive tasks, thereby following an instructed (alternating-runs paradigm; e.g., Rogers & Monsell, 1995 ) or a random task sequence with a cue indicating the upcoming task to be performed (cueing paradigm; e.g., Meiran, 1996 ). In contrast, in dual-task para- digms, such as the psychological refractory period (PRP) paradigm (see, e.g., Pashler, 1994 , for a review), subjects react with independent responses to two stimuli—Stimulus 1 (S1) and Stimulus 2 (S2)—which are presented with a varying stimulus onset asynchrony (SOA), and costs of performing two different tasks—Task 1 and Task 2 (T2)—in temporal overlap are assessed.
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Dynamic task management in MPSoC platformson

Dynamic task management in MPSoC platformson

In the mainstream commercial devices, RISC architectures are also the most popu- lar choice for the implementation of the task manager. For example, the master of the OMAP processors is based on the ARM architectures. While on the OMAP 1 platform, only one ARM926EJ-S processor controls one C55x DSP, in the latest OMAP systems, a MPCore technology based master (ARM Cortex-A15 with four parallel cores) is used to control a bunch of slave components including two ARM Cortex-M4 microcon- trollers, a mini-C64x DSP, a PowerVR GPU and several other hardware accelerators for image, video and audio processing. Similar to the OMAP processors, the Qual- comm Snapdragon processors apply a single ARM11 processor as the master in its first generation, and later on a quad-core Krait processor (ARM instruction-set based) in the latest generation. The Samsung Exynos application processor family [159] also follows the same strategy. In its early generation, only one ARM processor is used to control the system. In the later generations multi-core processors based on the MPCore technology or even eight cores (a quad-core A15 and a quad-core A7), con- figured as the ARM big.LITTLE architecture [72], are used. In the big.LITTLE archi- tecture, the quad-core A15 is larger and has higher performance, while the quad-core A7 is smaller but more power-efficient. Depending on the system load, the task man- agement can be internally switched between both quad-cores. Another commercial example is made by the Cell Broadband Engine, which was jointly developed by IBM, Sony and Toshiba. In this system, one PowerPC is used as the master of the sys- tem, which runs the operating system and coordinates eight specialized coprocessors known as Synergistic Processing Elements (SPEs).
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Symbolic Task Compression in Structured Task Learning

Symbolic Task Compression in Structured Task Learning

Abstract—Learning everyday tasks from human demonstra- tions requires unsupervised segmentation of seamless demon- strations, which may result in highly fragmented and widely spread symbolic representations. Since the time needed to plan the task depends on the amount of possible behaviors, it is preferable to keep the number of behaviors as low as possible. In this work, we present an approach to simplify the symbolic representation of a learned task which leads to a reduction of the number of possible behaviors. The simplification is achieved by merging sequential behaviors, i.e. behaviors which are logically sequential and act on the same object. Assuming that the task at hand is encoded in a rooted tree, the approach traverses the tree searching for sequential nodes (behaviors) to merge. Using simple rules to assign pre- and post-conditions to each node, our approach significantly reduces the number of nodes, while keeping unaltered the task flexibility and avoiding perceptual aliasing. Experiments on automatically generated and learned tasks show a significant reduction of the planning time.
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Dynamic task management in MPSoC platformson

Dynamic task management in MPSoC platformson

parison to the work presented in [218] and [209], this one exhibits more centralized characteristics. Very often, task management in large systems is also organized using clusters [5, 29, 61, 104]. The clusters do not necessarily have a fixed size. Instead, they can be resized and organized virtually at runtime. Within each local cluster, one PE is chosen as the manager. As the clusters are built at runtime, the managers can, but not necessarily have to be bound to certain fixed PEs. In addition to local managers, global managers might also exist in the systems. In [5], global managers are applied, which have global information of all clusters. Therefore, when a task mapping request arrives at a global manager, it is able to choose the most suitable cluster to execute the task (probably with task migration), or even resizes the clusters, if the task can not be mapped to any of the existing clusters. Similarly, a global manager is applied in the system of [29], in which the position of each local manager is fixed and the clusters are initially equally sized. During runtime, the cluster sizes can vary. In case that more computational power is needed, a local manager can borrow processing resources from other clusters over the global manager. In contrast to the two systems above, the system presented in [104] does not have a global manager. Each local cluster manager negotiates processing resources with its neighboring managers and identifies its local domain for an application. During the time of building the local domain, the role of the task manager can be transferred from one PE to another within the cluster. Generally, due to the virtual clusters and variable local resource managers, these cluster-based approaches are more suitable for homogeneous systems.
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Flexibility of individual multitasking strategies in task-switching with preview: are preferences for serial versus overlapping task processing dependent on between-task conflict?

Flexibility of individual multitasking strategies in task-switching with preview: are preferences for serial versus overlapping task processing dependent on between-task conflict?

Brüning, J., & Manzey, D. (2017). Flexibility of individual multitasking strategies in task-switching with preview: are preferences for serial versus overlapping task processing dependent on between-task conflict? Psychological Research, 82(1), 92–108. https://doi.org/10.1007/s00426-017-0924-0 This is a post-peer-review, pre-copyedit version of an article published in Psychological Research. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00426-017-0924-0.

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Overview of GermEval Task 2, 2019 shared task on the identification of offensive language

Overview of GermEval Task 2, 2019 shared task on the identification of offensive language

average system that took part in this year’s edition of the shared task is notably stronger than last year. In terms of the best overall scores that have been achieved in subtasks 1 and 2 in this year’s edition of the shared task, there is hardly any improvement. We re-trained last year’s winning system on this year’s training data and compared the classifica- tion on this year’s test data (cf. Tables 7 and 8) with the best performing system in this year’s com- petition (cf. Tables 10 and 11). Surprisingly, we obtained only marginally worse results with last year’s system (subtask 1: 76.46 vs. 76.95; subtask 2: 53.61 vs. 53.95). Given that this year’s training set was larger, this could mean one of two things. First, the additional data might not have helped even though test and training data were otherwise similar because the system was not able to make use of relevant features. Alternatively, the increase in data this year might have been offset by the new data being more difficult so that overall the system reached only the same level of performance as last year. These questions can best be addressed by running the same system on various combinations of this and last year’s data, which unfortunately is outside the scope of this overview paper.
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Task Shifting in der inter-professionellen Zusammenarbeit

Task Shifting in der inter-professionellen Zusammenarbeit

Die Delegation von Aufgabenbereichen von medizinischem Personal an andere Gesundheitsfachpersonen(GF) ist aus einer direkten betriebswirtschaftlichen Kostenbetrachtung als eher kostenneutral zu bewerten, da die erweiter- ten Rollenfunktionen der Gesundheitsfachpersonen mit entsprechenden höheren Gehaltseinstufungen verbunden sind, wodurch sich keine Personalkosten als Betrieb einsparen lassen. Indirekt sollten sich positive Effekte auf die Kosteneffizienz ergeben, aufgrund der zu erwartenden positiven Effekte des Task Shiftings auf die Versorgungs- qualität. Andererseits verursachen höhere Koordinationsaufwände und eine gelingende IPZ zusätzliche Koordina- tionskosten, die zu höheren betriebswirtschaftlichen Kosten führen. Aus einer systemischen Perspektive kann dem- nach nur aufgrund der Qualitätseffekte (geringere Verweildauern, weniger Komplikationen) von positiven Effekten auf die Kosteneffizienz der Gesundheitsversorgung ausgegangen werden. Die höheren Koordinationskosten nach der Implementierung von Task Shifting werden bislang unzureichend im Tarifsystem abgegolten. Im Falle neuer Tarifpositionen oder der Erweiterung bestehender Tarifpositionen wären sogar Kostensteigerungen im System durch TS denkbar.
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Model-centric task debugging at scale

Model-centric task debugging at scale

runtime does not support a control request which is critical for the tool’s operation, the tool returns with an error code from the initialisation func- tion. The public interface of TCA is very slim; the only visible symbol is the initialisation function tca_initialize, which has three parameters. A pointer to the lookup, the runtime_version and the tca_version. All other symbols, i.e. control request functions, are publicised during TCA initialisation through the lookup mechanism described below. The second argument, runtime_version, is a version string that unambiguously identi- fies a runtime system’s implementation. The third argument, tca_version, indicates the version of the tasking control API, supported by the runtime. The version of TCA described by this document is known as version 1. The first argument, lookup, is a pointer to the lookup function. This lookup function is provided by the runtime system. The tool repeatedly calls lookup for every entry_point, i.e. control request function. If the named entry point is available, the lookup function returns a pointer to it. Otherwise, the NULL pointer is returned. In general, the runtime system should start the initialisation procedure as soon as possible during its on startup procedure and before any user code is executed. If the tool initialisation is unsuccessful, i.e. if the tool does not return with TCA_SUCCESS, the runtime system does not need to maintain any information or state to support tools.
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Task Force SELECT. Final Report

Task Force SELECT. Final Report

The 12 innovation agencies forming the Task Force Select have a multitude of functions in the innovation systems they are part of. They fulfil these functions in different ways and with a variety of programmes, which again are run by utilising different processes (Biegelbauer/Palfinger 2016). The ensuing variety is directly linked to the environment the agencies have to work in, e.g. the specific governance structures, the level of GDP per capita, the structure of the national economy and the national research and innovation system as well as the system of law of the organisation’s country. Also the historical development and the organisational culture of the agency itself have a strong influence on how agencies work.
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Steuerbetrug: Task Force: irreführender Begriff

Steuerbetrug: Task Force: irreführender Begriff

Steuerbetrug Task Force: irreführender Begriff Angeblich richtet Finanzminister Scholz eine Task Force „gegen Steuerbetrug“ ein. Diese Task Force soll 48 Per- sonen umfassen, von denen 43 beim Bundeszentralamt für Steuern (BZSt) und fünf im Bundesfi nanzministerium (BMF) angesiedelt sein sollen. Die veranschlagten Kosten von 21 Mio. Euro seien bereits im Bundeshaushalt 2020 eingeplant. Außerdem soll der Apparat auf über 100 Per- sonen ausgebaut werden.

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Examining context-based task characteristics: the effects of task characteristics on students' motivation and metacognitive experiences

Examining context-based task characteristics: the effects of task characteristics on students' motivation and metacognitive experiences

(thermodynamics) problem situation to be solved. Though the task topic (thermodynamics) was kept the same for all versions, each version of the task was perceptually different to one another as a result of the level of contextualization and transparency (high or low). The highly contextualized versions described a real-life situation, which is the discovery of a glacier mummy named “Ötzi” (Frozen Fritz). The tasks contained the explanation concerning the mummy, artifacts, temperatures, and other images. The low contextualized versions presented the same convection problem, but using a traditional textbook approach, were abstract and detailed information of temperatures, symbols, and numbers are provided, and only one picture is included. The highly transparent versions include in the problem’s description physics concepts, terms, and measurements of heat, whereas in the low transparent versions, less scientific and more common concepts are being used. The main difference between all tasks is how physics concepts are explicitly varied throughout each of the tasks.
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The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy

TLE is understood as a network disease impacting the dis- tributed language system beyond the seizure focus. Over the recent years, functional magnetic resonance imaging (fMRI) has been established as a means to study cognitive functions in patients with epilepsy. The possibility to analyse functional connectivity (FC) has significantly increased our understanding of epilepsy as a network disease, providing insights about seizure generation and propagation, by studying the neuronal basis of epileptic networks and networks that sub-serve cognitive tasks. Several FC-studies have demonstrated that within the epileptic network functional connectivity was altered, which was also suggested for networks of cognitive function. In both, left and right TLE, FC was reduced within the expressive language network, which was linked to an impaired performance in language assessment ( Waites et al., 2006 ). More recently, during an fMRI naming task stronger connec- tivity between left posterior inferior temporal and bilateral tempo- ral and frontal lobe regions was associated with improved naming performance ( Trimmel et al., 2018 ).
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Interruptible Task Execution with Resumption in Golog

Interruptible Task Execution with Resumption in Golog

Belief-Desire-Intention (BDI) systems like PRS [10] or AgentS- peak(L) [17] allow to execute multiple plans in an interleaved or par- allel manner. In this context the challenges that arise with parallel execution of multiple plans have been discussed. In [1] summaries of concurrent hierarchical plans are used to identify associated precon- ditions and effects that can be used to reduce backtracking. Their for- malism however only considers propositional, STRIPS-style actions and is less expressive than G OLOG , in particular regarding loops and recursive procedures. Harland et al. [8] propose to perform clean- up steps when suspending and resuming plans. The corresponding clean-up methods have to be defined for every plan. In comparison, our promises are action-specific; the intermediate steps necessary to suspend and resume a certain task are then implicit.
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Der Effekt von dual-task Aufgaben bei älteren, sturzgefährdeten Personen : stürzen ältere Personen ab 65 Jahre weniger nach einem dual-task Training?

Der Effekt von dual-task Aufgaben bei älteren, sturzgefährdeten Personen : stürzen ältere Personen ab 65 Jahre weniger nach einem dual-task Training?

In der Studie von Silsupadol et al. (2009a) zeigte sich ein interessantes Ergebnis. Im Selbstvertrauen, gemessen anhand der ABC-Skala, konnten sich einzig die Teilneh- mer der single-task Gruppe statistisch signifikant verbessern. Dieses Ergebnis ist für die Autorin insofern von Interesse, weil es zeigt, dass Teilnehmer der dual-task Trai- ningsgruppen sich häufig überfordert fühlen und eventuell zu wenig Erfolgserlebnisse verzeichnen können, sodass sie sich unsicherer fühlen als die Teilnehmer der single- task Gruppe. In diesem Fall werden sich diese Personen mit Sicherheit weniger Her- ausforderungen stellen, was somit eine potentielle Gefahr für Immobilität aufzeigt. Dies zeigt, wie enorm wichtig es ist, die Teilnehmer eines Präventionsprogramms nicht zu überfordern und ihnen auch die Möglichkeit zu geben, erfolgreich zu sein, was zum Beispiel durch positives, externes Feedback seitens der Therapeuten zu erreichen ist.
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LIMSI@WMT'15 : Translation Task

LIMSI@WMT'15 : Translation Task

(+0.72 BLEU) for Ru-En task. Using normal- ized Russian as the source language allows us to achieve a slight gain of +0.4 over the baseline for both systems. Moreover, the addition of SOUL models yields a further improvement of 1.1 BLEU score (see Table 7). The English-into-normalized- Russian task has been performed for the sake of comparison, to assess the gain we could expect if we were able to always predict the right case for the normalized Russian output. The comparison of BLEU scores between translating directly into Russian and producing an intermediate normal- ized Russian shows differences of 3.15 BLEU for N CODE and 3.44 BLEU for M OSES . These scores
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