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NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.
The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation.
A multi-spot light-addressable potentiometric sensor (LAPS), which belongs to the family of semiconductor field-effect devices, was applied for label-free detection of double-stranded deoxyribonucleic acid (dsDNA) molecules by their intrinsic molecular charge. To reduce the distance between the DNA charge and sensor surface and thus, to enhance the electrostatic coupling between the dsDNA molecules and the LAPS, the negatively charged dsDNA molecules were electrostatically adsorbed onto the gate surface of the LAPS covered with a positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)). The surface potential changes in each spot of the LAPS, induced by the layer-by-layer adsorption of a PAH/dsDNA bilayer, were recorded by means of photocurrent-voltage and constant-photocurrent measurements. In addition, the surface morphology of the gate surface before and after consecutive electrostatic adsorption of PAH and dsDNA layers was studied by atomic force microscopy measurements. Moreover, fluorescence microscopy was used to verify the successful adsorption of dsDNA molecules onto the PAH-modified LAPS surface. A high sensor signal of 25 mV was registered after adsorption of 10 nM dsDNA molecules. The lower detection limit is down to 0.1 nM dsDNA. The obtained results demonstrate that the PAH-modified LAPS device provides a convenient and rapid platform for the direct label-free electrical detection of in-solution hybridized dsDNA molecules.
This article discusses the contrast between the information transportation companies provide to travellers and that of their brand messaging. Companies’ brand messaging often portrays the service they provide as pleasant, stress free and perfect. Customers and users of the service, on the other hand, often describe their experience of the service as a negative one. This article suggests that the brand value would be greater if transportation companies paid more attention to the users’ experience when designing their information systems, particularly in worst case scenarios.
IoT von der Stange
(2016)
Das IoT ist ohne eingebettete Systeme undenkbar. Erst kleine und kleinste Mikrocontroller mit intelligenten Kommunikationsschnittstellen und Anbindung ans Internet ermöglichen sinnvolles und flächendeckendes Einsammeln von Daten. Doch wie kompliziert ist der Einstieg in die Embedded-Welt? Dieser Artikel gibt Einblick, wie die »Arduino-Plattform« die Einstiegshürden für eingebettete Systeme dramatisch reduzieren kann.
Low-end-Embedded-Plattformen stellen eine hohe Anforderung an die Entscheidungsfähigkeit des Entwicklers: Zum nächstgrößeren Prozessor greifen und ein Betriebssystem benutzen oder doch besser auf das Betriebssystem verzichten? Die Frage lässt sich einfach beantworten: Einen Nanokernel verwenden und das Embedded-System mit einem minimalen Footprint realisieren. Adam Dunkels Protothreads sind eine ausgesprochen effiziente Art, Mikrocontroller gut strukturiert zu programmieren und gleichzeitig auf Overhead zu verzichten. So können auch mit kleinen 8-bit-Prozessoren anspruchsvolle Aufgaben in einem Thread-Modell bearbeitet werden. Man muss also nicht immer das Rad neu erfinden oder gleich auf Linux-basierte Systeme zurückgreifen.
While plate fixation of proximal ulna fractures might lead to superior clinical results compared to tension band wiring, regular plates represent an established risk factor for wound complications. The olecranon double plates (Medartis, Basel, CH) might decrease complications related to the osteosynthesis because of their low profile and better anatomical fit. This study aimed to evaluate the biomechanical performance and clinical results of the olecranon double plates.
Manufacturing process simulation enables the evaluation and improvement of autoclave mold concepts early in the design phase. To achieve a high part quality at low cycle times, the thermal behavior of the autoclave mold can be investigated by means of simulations. Most challenging for such a simulation is the generation of necessary boundary conditions. Heat-up and temperature distribution in an autoclave mold are governed by flow phenomena, tooling material and shape, position within the autoclave, and the chosen autoclave cycle. This paper identifies and summarizes the most important factors influencing mold heat-up and how they can be introduced into a thermal simulation. Thermal measurements are used to quantify the impact of the various parameters. Finally, the gained knowledge is applied to develop a semi-empirical approach for boundary condition estimation that enables a simple and fast thermal simulation of the autoclave curing process with reasonably high accuracy for tooling optimization.
The light-addressable potentiometric sensor (LAPS) has the unique feature to address different regions of a sensor surface without the need of complex structures. Measurements at different locations on the sensor surface can be performed in a common analyte solution, which distinctly simplifies the fluidic set-up. However, the measurement in a single analyte chamber prevents the application of different drugs or different concentrations of a drug to each measurement spot at the same time as in the case of multi-reservoir-based set-ups. In this work, the authors designed a LAPS-based set-up for cell culture screening that utilises magnetic beads loaded with the endotoxin (lipopolysaccharides, LPS), to generate a spatially distributed gradient of analyte concentration. Different external magnetic fields can be adjusted to move the magnetic beads loaded with a specific drug within the measurement cell. By recording the metabolic activities of a cell layer cultured on top of the LAPS surface, this work shows the possibility to apply different concentrations of a sample along the LAPS measurement spots within a common analyte solution.
Verfügbarkeit und Nachhaltigkeit sind wichtige Anforderungen bei der Planung langlebiger technischer Systeme. Meist werden bei Lebensdaueroptimierungen lediglich einzelne Komponenten vordefinierter Systeme untersucht. Ob eine optimale Lebensdauer eine gänzlich andere Systemvariante bedingt, wird nur selten hinterfragt. Technical Operations Research (TOR) erlaubt es, aus Obermengen technischer Systeme automatisiert die lebensdaueroptimale Systemstruktur auszuwählen. Der Artikel zeigt dies am Beispiel eines hydrostatischen Getriebes.
Self-aeration is traditionally explained by the water turbulent boundary layer outer edge intersection with the free surface. This paper presents a discussion on the commonly accepted hypothesis behind the computation of the critical point of self-aeration in spillway flows and a new formulation is proposed based on the existence of a developing air flow over the free surface. Upstream of the inception point of self-aeration, some surface roughening has been often reported in previous studies which consequently implies some entrapped air transport and air–water flows coupling. Such air flow is proven in this study by presenting measured air velocities and computing the air boundary layer thickness for a 1V:2H smooth chute flow. Additionally, the growth rate of free surface waves has been analysed by means of Ultrasonic Sensors measurements, obtaining also the entrapped air concentration. High-speed camera imaging has been used for qualitative study of the flow perturbations.
Sensitivity of turbulent Schmidt number and turbulence model to simulations of jets in crossflow
(2016)
Environmental discharges have been traditionally designed by means of cost-intensive and time-consuming experimental studies. Some extensively validated models based on an integral approach have been often employed for water quality problems, as recommended by USEPA (i.e.: CORMIX). In this study, FLOW-3D is employed for a full 3D RANS modelling of two turbulent jet-to-crossflow cases, including free surface jet impingement. Results are compared to both physical modelling and CORMIX to better assess model performance. Turbulence measurements have been collected for a better understanding of turbulent diffusion's parameter sensitivity. Although both studied models are generally able to reproduce jet trajectory, jet separation downstream of the impingement has been reproduced only by RANS modelling. Additionally, concentrations are better reproduced by FLOW-3D when the proper turbulent Schmidt number is used. This study provides a recommendation on the selection of the turbulence model and the turbulent Schmidt number for future outfall structures design studies.
At the present time, one of the most serious environmental problems of Central Asia and South Kazakhstan is the ongoing large-scale deterioration of principal urban tree populations. Several major centers of massive spread of invasive plant pests have been found in urban dendroflora of this region. The degree of damage of seven most wide-spread aboriginal tree species was found to range from 21.4±1.1 to 85.4±1.8%. In particular, the integrity of the native communities of sycamore (Platanus spp.), willow (Salix spp.), poplar (Populus spp.) and elm (Ulmus spp.) is highly endangered. Our taxonomic analysis of the most dangerous tree pests of the region has revealed them as neobiontic xylophilous insects such as Cossus cossus L. (Order: Lepidoptera L.) Monochamus urussovi Fisch., Monochamus sutor L., Acanthocinus aedelis L. and Ñetonia aureate L. (Order: Coleoptera L.). We relate the origin of this threatening trend with the import of industrial wood in the mid 90s of the last century that was associated with high degree of the constructional work in the region. Because of the absence of efficient natural predators of the pest species, the application of microbiological methods of the pest control and limitation is suggested.
Genussrechte als Instrument der Unternehmensfinanzierung von kommunalen Wohnungs- baugesellschaften
(2016)
Die kommunalen Wohnungsbaugesellschaften und ihr Geschäftszweck bzw. Versorgungsauftrag erfahren aus gesamtgesellschaftlichen Gründen aktuell einen erheblichen Bedeutungszuwachs. Der kommunale Wohnungsbau soll und muss intensiviert werden, da z.B. zunehmend Wohnungsbindungen auslaufen. Bezahlbare Neubauten fehlen speziell Familien, Senioren, Studenten und Flüchtlingen. Um das Investitionsvolumen zu bewältigen, bedarf es nicht nur der Förderkredite, sondern auch der Zuführung „frischen Kapitals“. Der Beitrag stellt dar, dass Genussrechte ein interessantes und oft unbekanntes Finanzierungsinstrument für kommunale Wohnungsbaugesellschaften mit passgenauen Ausgestaltungsmöglichkeiten sind. Mit Hilfe von Genussrechten können die notwendigen Neubau-Investitionen solide mit Quasi-Eigenkapital unterlegt werden und den sozialen Wohnungsbau wiederbeleben. Genussrechte als Hybridkapital lassen sich mangels gesetzlicher Eingrenzung exakt und individuell ebenso an die Bedürfnisse der kommunalen Wohnungsbaugesellschaft anpassen wie an die der Gesellschafter und des jeweiligen Neubauvorhabens.
We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward.
20 Years of RoboCup
(2016)
When exploring glacier ice it is often necessary to take samples or implement sensors at a certain depth underneath the glacier surface. One way of doing this is by using heated melting probes. In their common form these devices experience a straight one-dimensional downwards motion and can be modeled by standard close-contact melting theory. A recently developed melting probe however, the IceMole, achieves maneuverability by simultaneously applying a surface temperature gradient to induce a change in melting direction and controlling the effective contact-force by means of an ice screw to stabilize its change in attitude. A modeling framework for forced curvilinear melting does not exist so far and will be the content of this paper. At first, we will extend the existing theory for quasi-stationary close-contact melting to curved trajectories. We do this by introducing a rotational mode. This additional unknown in the system implies yet the need for another model closure. Within this new framework we will focus on the effect of a variable contact-force as well as different surface temperature profiles. In order to solve for melting velocity and curvature of the melting path we present both an inverse solution strategy for the analytical model, and a more general finite element framework implemented into the open source software package ELMER. Model results are discussed and compared to experimental data conducted in laboratory tests.
Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold.
This paper describes the development of a capacitively coupled high-pressure lamp with input power between 20 and 43 W at 2.45 GHz, using a coaxial line network. Compared with other electrodeless lamp systems, no cavity has to be used and a reduction in the input power is achieved. Therefore, this lamp is an alternative to the halogen incandescent lamp for domestic lighting. To serve the demands of domestic lighting, the filling of the lamp is optimized over all other resulting requirements, such as high efficacy at low induced powers and fast startups. A workflow to develop RF-driven plasma applications is presented, which makes use of the hot S-parameter technique. Descriptions of the fitting process inside a circuit and FEM simulator are given. Results of the combined ignition and operation network from simulations and measurements are compared. An initial prototype is built and measurements of the lamp's lighting properties are presented along with an investigation of the efficacy optimizations using large signal amplitude modulation. With this lamp, an efficacy of 135 lmW -1 is achieved.
Compared to peripheral pain, trigeminal pain elicits higher levels of fear, which is assumed to enhance the interruptive effects of pain on concomitant cognitive processes. In this fMRI study we examined the behavioral and neural effects of trigeminal (forehead) and peripheral (hand) pain on visual processing and memory encoding. Cerebral activity was measured in 23 healthy subjects performing a visual categorization task that was immediately followed by a surprise recognition task. During the categorization task subjects received concomitant noxious electrical stimulation on the forehead or hand. Our data show that fear ratings were significantly higher for trigeminal pain. Categorization and recognition performance did not differ between pictures that were presented with trigeminal and peripheral pain. However, object categorization in the presence of trigeminal pain was associated with stronger activity in task-relevant visual areas (lateral occipital complex, LOC), memory encoding areas (hippocampus and parahippocampus) and areas implicated in emotional processing (amygdala) compared to peripheral pain. Further, individual differences in neural activation between the trigeminal and the peripheral condition were positively related to differences in fear ratings between both conditions. Functional connectivity between amygdala and LOC was increased during trigeminal compared to peripheral painful stimulation. Fear-driven compensatory resource activation seems to be enhanced for trigeminal stimuli, presumably due to their exceptional biological relevance.
In this paper we present an extension of the action language Golog that allows for using fuzzy notions in non-deterministic argument choices and the reward function in decision-theoretic planning. Often, in decision-theoretic planning, it is cumbersome to specify the set of values to pick from in the non-deterministic-choice-of-argument statement. Also, even for domain experts, it is not always easy to specify a reward function. Instead of providing a finite domain for values in the non-deterministic-choice-of-argument statement in Golog, we now allow for stating the argument domain by simply providing a formula over linguistic terms and fuzzy uents. In Golog’s forward-search DT planning algorithm, these formulas are evaluated in order to find the agent’s optimal policy. We illustrate this in the Diner Domain where the agent needs to calculate the optimal serving order.
We present a new Min-Max theorem for an optimization problem closely connected to matchings and vertex covers in balanced hypergraphs. The result generalizes Kőnig’s Theorem (Berge and Las Vergnas in Ann N Y Acad Sci 175:32–40, 1970; Fulkerson et al. in Math Progr Study 1:120–132, 1974) and Hall’s Theorem (Conforti et al. in Combinatorica 16:325–329, 1996) for balanced hypergraphs.
Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.
The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase.
Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium
(2016)
Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹.
Eine seismische Anregung verursacht in einem Flüssigkeitstank einen kombinierten Spannungszustand, was zu einem Stabilitätsversagen der häufig sehr dünnwandigen Konstruktionen führen kann. Für die Durchführung von Stabilitätsnachweisen stehen verschiedene Verfahren zur Verfügung. Üblicherweise werden aus Gründen der Einfachheit spannungsbasierte Verfahren angewendet. Diese sind für Einheitslastfälle experimentell abgesichert, wobei eine Übertragung auf kombinierte Spannungszustände wie im Erdbebenfall nur begrenzt möglich ist. Alternativ kann ein globales, numerisches Konzept, das LBA/MNA-Verfahren, angewendet werden. Das Verfahren kombiniert eine materiell nichtlineare Berechnung (MNA) mit einer linearen Beulanalyse (LBA) und erfasst die Interaktion verschiedener gleichzeitig auftretender Beanspruchungen implizit im Nachweis. Dieser Beitrag demonstriert die Anwendung der Verfahren am Beispiel verschiedener Tankgeometrien mit Höhe/Radius-Verhältnissen zwischen 1 ≤ H/R ≤ 2 und Radius/Tankwand-Verhältnissen zwischen 500 ≤ R/t ≤ 1000 und diskutiert zusätzlich die Defizite der spannungsbasierten Nachweisverfahren.
The aim of this work was to perform a detailed investigation of the use of Selective Laser Melting (SLM) technology to process eutectic silver-copper alloy Ag 28 wt. % Cu (also called AgCu28). The processing occurred with a Realizer SLM 50 desktop machine. The powder analysis (SEM-topography, EDX, particle distribution) was reported as well as the absorption rates for the near-infrared (NIR) spectrum. Microscope imaging showed the surface topography of the manufactured parts. Furthermore, microsections were conducted for the analysis of porosity. The Design of Experiments approach used the response surface method in order to model the statistical relationship between laser power, spot distance and pulse time.
Mit steigenden Dämmstandards und höheren Komfortanforderungen der Nutzer gerät die Problematik der sommerlichen Überhitzung zunehmend in den Fokus. Um die Überhitzung möglichst gering zu halten, sind Maßnahmen und Lösungen zu entwickeln, die den potenziellen Kühlbedarf eines Gebäudes vermeiden sowie reduzieren. Im Rahmen des europäischen Forschungsprojektes BATIMASS wurden Techniken untersucht, die die sommerliche Raumtemperatur ohne zusätzliche Kühlung (passiv) oder aber mit energieeffizienter wasserbasierter Flächenkühlung (aktiv) reduzieren und die besonders für Gebäude in Stahl(leicht)bauweise geeignet sind. Dafür wurde die Methodik der thermisch äquivalenten Decke weiterentwickelt, um das thermische Verhalten von Profilblechdecken in Gebäuden für beide Lösungsansätze analysieren zu können. Darüber hinaus wurde der Einsatz von Phasenwechselmaterial (PCM) zur Steigerung der Speicherfähigkeit von leichten Decken mit besonders geringer thermischer Masse in Simulationen sowie im Labor untersucht und bewertet.
Purpose
Two semi-empirical models were recently published, both making use of existing literature data, but each taking into account different physical phenomena that trigger hemolysis. In the first model, hemoglobin (Hb) release is described as a permeation procedure across the membrane, assuming a shear stress-dependent process (sublethal model). The second model only accounts for hemoglobin release that is caused by cell membrane breakdown, which occurs when red blood cells (RBC) undergo mechanically induced shearing for a period longer than the threshold time (nonuniform threshold model). In this paper, we introduce a model that considers the hemolysis generated by both these possible phenomena.
Methods
Since hemolysis can possibly be caused by permeation of hemoglobin through the RBC functional membrane as well as by release of hemoglobin from RBC membrane breakdown, our proposed model combines both these models. An experimental setup consisting of a Couette device was utilized for validation of our proposed model.
Results
A comparison is presented between the damage index (DI) predicted by the proposed model vs. the sublethal model vs. the nonthreshold model and experimental datasets. This comparison covers a wide range of shear stress for both human and porcine blood. An appropriate agreement between the measured DI and the DI predicted by the present model was obtained.
Conclusions
The semiempirical hemolysis model introduced in this paper aims for significantly enhanced conformity with experimental data. Two phenomenological outcomes become possible with the proposed approach: an estimation of the average time after which cell membrane breakdown occurs under the applied conditions, and a prediction of the ratio between the phenomena involved in hemolysis.
Regardless of size or destination, synthetic biology starts with com-parably small information units, which need to be combined and properly arranged in order to achieve a certain goal. This may be the de novo synthesis of individual genes from oligonucleotides, a shuffling of protein domains in order to create novel biocatalysts, the assembly of multiple enzyme encoding genes in metabolic pathway design, or strain development at the production stage. The CoLibry concept has been designed in order to close the gap between recombinant production of individual genes and genome editing.
Schienenverkehrssysteme stehen in zunehmendem Wettbewerb, sowohl untereinander als auch mit anderen Verkehrsträgern. Als wichtiger Aspekt zur Steigerung der Kosteneffizienz wird die Digitalisierung des Betriebs und der Fahrzeuge betrachtet. Über eine Prognose der Ausfallwahrscheinlichkeit bzw. Restlebensdauer von Subsystemen können mittels Digitalisierung die Instandhaltungskosten gesenkt werden. Die geringen Fehlerraten im System Bahn machen die Nutzung besonderer Simulationstechniken notwendig. In diesem Beitrag wird gezeigt, wie sich die Subsystemverfügbarkeit aus den beobachteten Fehlerraten der Teilfunktionen vorhersagen lässt.
The scientific interest for near-Earth asteroids as well as the interest in potentially hazardous asteroids from the perspective of planetary defense led the space community to focus on near-Earth asteroid mission studies. A multiple near-Earth asteroid rendezvous mission with close-up observations of several objects can help to improve the characterization of these asteroids. This work explores the design of a solar-sail spacecraft for such a mission, focusing on the search of possible sequences of encounters and the trajectory optimization. This is done in two sequential steps: a sequence search by means of a simplified trajectory model and a set of heuristic rules based on astrodynamics, and a subsequent optimization phase. A shape-based approach for solar sailing has been developed and is used for the first phase. The effectiveness of the proposed approach is demonstrated through a fully optimized multiple near-Earth asteroid rendezvous mission. The results show that it is possible to visit five near-Earth asteroids within 10 years with near-term solar-sail technology.
[⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3.
Purpose
To calculate local specific absorption rate (SAR) correctly, both the amplitude and phase of the signal in each transmit channel have to be known. In this work, we propose a method to derive a conservative upper bound for the local SAR, with a reasonable safety margin without knowledge of the transmit phases of the channels.
Methods
The proposed method uses virtual observation points (VOPs). Correction factors are calculated for each set of VOPs that prevent underestimation of local SAR when the VOPs are applied with the correct amplitudes but fixed phases.
Results
The proposed method proved to be superior to the worst-case calculation based on the maximum eigenvalue of the VOPs. The mean overestimation for six coil setups could be reduced, whereas no underestimation of the maximum local SAR occurred. In the best investigated case, the overestimation could be reduced from a factor of 3.3 to a factor of 1.7.
Conclusion
The upper bound for the local SAR calculated with the proposed method allows a fast estimation of the local SAR based on power measurements in the transmit channels and facilitates SAR monitoring in systems that do not have the capability to monitor transmit phases
Die bereits mit Koalitionsvertrag vom 16.12.2013 in Aussicht genommene Neuregulierung der Leiharbeit steht nunmehr kurz bevor. Nach diversen Korrekturen des ursprünglichen Referentenentwurfes des Bundesministeriums für Arbeit und Soziales liegt seit dem 20.7.2016 der endgültige Entwurf des Gesetzes zur Änderung des Arbeitnehmerüberlassungsgesetzes und anderer Gesetze vor (AÜG-E). Die Änderungen sollen zum 1.1.2017 in Kraft treten. Von größeren Änderungen des Gesetzesentwurfs wird allgemein nicht mehr ausgegangen. Für die betriebliche Praxis sollte dies Anlass sein, sich bereits jetzt mit den sich abzeichnenden wichtigsten Neuerungen vertraut zu machen und diese entsprechend umzusetzen, um nachteilige Konsequenzen zu vermeiden.
Elektromobilität ist das Thema der Zukunft. Schon jetzt hat es sich die Bundesregierung zur Aufgabe gemacht, hierzulande bis 2030 den Absatz von Elektroautos kontinuierlich auf sechs Mio. Fahrzeuge zu steigern. Und auch die Nachfrage nach Elektrofahrrädern steigt zunehmend. Vor allem der derzeit durch den Gesetzgeber gewährte Umweltbonus sowie weitere steuerliche Anreize machen den Einsatz von Elektroautos und -fahrrädern als Dienstfahrzeuge auch für Arbeitgeber zunehmend attraktiv. Will der Arbeitgeber seinen Arbeitnehmern Elektrofahrzeuge überlassen, stellt sich die Frage nach der Gestaltung der entsprechenden Überlassungsverträge. Der nachfolgende Beitrag gibt hierzu einen Überblick und beinhaltet Formulierungshilfen für die Vertragsgestaltung.
Der Gesetzgeber hat kürzlich eine Änderung des Rechts der AGB beschlossen. Diese hat für Arbeitgeber zur Folge, dass sie ihre Muster-Arbeitsverträge anpassen müssen, wenn sie andernfalls drohende wirtschaftliche Nachteile vermeiden wollen. Mit Wirkung zum 1.10.2016 hat der Gesetzgeber § 309 Nr. 13 BGB neu gefasst. Nach der bisherigen Fassung waren vorformulierte Vertragsbedingungen unwirksam, die Anzeigen oder Erklärungen gegenüber dem Vertragspartner an „eine strengere Form als die Schriftform“ banden. Seit dem 1.10.2016 sind vorformulierte Vertragsbedingungen unwirksam, die derartige Anzeigen oder Erklärungen an „eine strengere Form als die Textform“ binden. Diese gesetzliche Neuregelung wirkt sich maßgeblich auf die Gestaltung von Arbeitsverträgen aus. Dies betrifft insbesondere die in Arbeitsverträgen gebräuchlichen Ausschlussfristen.
Nach jahrelangem Ringen haben sich die zuständigen Institutionen der EU auf ein einheitliches Datenschutzgesetz, die Datenschutz-Grundverordnung (DS-GV), geeinigt. Diese ist am 25.5.2016 in Kraft getreten und wird nach einer zweijährigen Übergangszeit am 25.5.2018 für alle EU-Mitgliedstaaten unmittelbar verbindlich. Verstöße hiergegen können erhebliche Sanktionen nach sich ziehen. Es drohen Bußgelder von bis zu 20 Mio. € oder bis zu 4 % des gruppenweiten Jahresumsatzes – je nachdem, welcher Betrag höher ist. Die betriebliche Praxis tut also gut daran, sich rechtzeitig mit den neuen Anforderungen zu befassen und diese umzusetzen. Dieser Beitrag gibt einen ersten Überblick über die sich aus der DS-GV ergebenden Konsequenzen für die betriebliche Praxis im Allgemeinen sowie im Hinblick auf die Datenverarbeitung im Beschäftigungskontext im Besonderen.
Kaum ein anderer Begriff hält so viele Varianten und Facetten bereit wie die Arbeitszeit. Für die betriebliche Praxis stellt sich dabei regelmäßig die Frage, was überhaupt zur Arbeitszeit gehört, entsprechend als solche zu vergüten ist und welche Optionen bei der Gestaltung der Arbeitsverträge bestehen. Der folgende Praxisleitfaden gibt einen Überblick über die aktuelle Rechtslage und enthält zugleich Hinweise für die Vertragsgestaltung. Die hierzu insbesondere in den letzten Jahren ergangenen zahlreichen aktuellen Gerichtsentscheidungen werden besonders berücksichtigt.
Das Bundeskabinett hat sich am 14.9.2016 mit der sog. Flexi-Rente befasst und eine sog. Formulierungshilfe verabschiedet, der ein aus den Regierungsfraktionen des Bundestages einzubringender entsprechender Gesetzesentwurf zur „Flexibilisierung des Übergangs vom Erwerbsleben in den Ruhestand und zur Stärkung von Prävention und Rehabilitation im Erwerbsleben (Flexirentengesetz)“ folgen soll. Eine entsprechende Vorabfassung des Gesetzesentwurfs liegt bereits vor (BT-Drucks. 18/9787). Mit der Flexi-Rente sollen im Wesentlichen zwei Ziele erreicht werden: Das flexible Arbeiten bis zum Erreichen der Regelaltersgrenze soll gefördert und das Weiterarbeiten über die Regelaltersgrenze hinaus attraktiver gemacht werden. Hierfür ist eine Reihe von gesetzlichen Änderungen geplant, insbesondere im SGB VI und SGB III. Teile des Gesetzes sollen schon zum 1.1.2017 in Kraft treten. Grund genug, sich bereits jetzt einen ersten Überblick über die geplanten Neuerungen zu verschaffen.
Replacement tissues, designed to fill in articular cartilage defects, should exhibit the same properties as the native material. The aim of this study is to foster the understanding of, firstly, the mechanical behavior of the material itself and, secondly, the influence of cultivation parameters on cell seeded implants as well as on cell migration into acellular implants. In this study, acellular cartilage replacement material is theoretically, numerically and experimentally investigated regarding its viscoelastic properties, where a phenomenological model for practical applications is developed. Furthermore, remodeling and cell migration are investigated.
We investigate the suitability of selected measures of complexity based on recurrence quantification analysis and recurrence networks for an identification of pre-seizure states in multi-day, multi-channel, invasive electroencephalographic recordings from five epilepsy patients. We employ several statistical techniques to avoid spurious findings due to various influencing factors and due to multiple comparisons and observe precursory structures in three patients. Our findings indicate a high congruence among measures in identifying seizure precursors and emphasize the current notion of seizure generation in large-scale epileptic networks. A final judgment of the suitability for field studies, however, requires evaluation on a larger database.
Wind-induced operational variability is one of the major challenges for structural health monitoring of slender engineering structures like aircraft wings or wind turbine blades. Damage sensitive features often show an even bigger sensitivity to operational variability. In this study a composite cantilever was subjected to multiple mass configurations, velocities and angles of attack in a controlled wind tunnel environment. A small-scale impact damage was introduced to the specimen and the structural response measurements were repeated. The proposed damage detection methodology is based on automated operational modal analysis. A novel baseline preparation procedure is described that reduces the amount of user interaction to the provision of a single consistency threshold. The procedure starts with an indeterminate number of operational modal analysis identifications from a large number of datasets and returns a complete baseline matrix of natural frequencies and damping ratios that is suitable for subsequent anomaly detection. Mahalanobis distance-based anomaly detection is then applied to successfully detect the damage under varying severities of operational variability and with various degrees of knowledge about the present operational conditions. The damage detection capabilities of the proposed methodology were found to be excellent under varying velocities and angles of attack. Damage detection was less successful under joint mass and wind variability but could be significantly improved through the provision of the currently encountered operational conditions.
Operational Modal Analysis (OMA) is a promising candidate for flutter testing and Structural Health Monitoring (SHM) of aircraft wings that are passively excited by wind loads. However, no studies have been published where OMA is tested in transonic flows, which is the dominant condition for large civil aircraft and is characterized by complex and unique aerodynamic phenomena. We use data from the HIRENASD large-scale wind tunnel experiment to automatically extract modal parameters from an ambiently excited wing operated in the transonic regime using two OMA methods: Stochastic Subspace Identification (SSI) and Frequency Domain Decomposition (FDD). The system response is evaluated based on accelerometer measurements. The excitation is investigated from surface pressure measurements. The forcing function is shown to be non-white, non-stationary and contaminated by narrow-banded transonic disturbances. All these properties violate fundamental OMA assumptions about the forcing function. Despite this, all physical modes in the investigated frequency range were successfully identified, and in addition transonic pressure waves were identified as physical modes as well. The SSI method showed superior identification capabilities for the investigated case. The investigation shows that complex transonic flows can interfere with OMA. This can make existing approaches for modal tracking unsuitable for their application to aircraft wings operated in the transonic flight regime. Approaches to separate the true physical modes from the transonic disturbances are discussed.
A refined substructure technique in the frequency domain is developed, which permits consideration of the interaction effects among adjacent containers through the supporting deformable soil medium. The tank-liquid systems are represented by means of mechanical models, whereas discrete springs and dashpots stand for the soil beneath the foundations. The proposed model is employed to assess the responses of adjacent circular, cylindrical tanks for harmonic and seismic excitations over wide range of tank proportions and soil conditions. The influence of the number, spatial arrangement of the containers and their distance on the overall system's behavior is addressed. The results indicate that the cross-interaction effects can substantially alter the impulsive components of response of each individual element in a tank farm. The degree of this impact is primarily controlled by the tank proportions and the proximity of the predominant natural frequencies of the shell-liquid-soil systems and the input seismic motion. The group effects should be not a priori disregarded, unless the tanks are founded on shallow soil deposit overlying very stiff material or bedrock.
In this study, we show that synthetic sapphire (Al₂O₃), an established implant material, can also serve as a platform material for biosensors comparable to nanocrystalline diamond. Sapphire chips, beads, and powder were first modified with (3-aminopropyl) triethoxysilane (APTES), followed by succinic anhydride (SA), and finally single-stranded probe DNA was EDC coupled to the functionalized layer. The presence of the APTES-SA layer on sapphire powders was confirmed by thermogravimetric analyis and Fourier-transform infrared spectroscopy. Using planar sapphire chips as substrates and X-ray photoelectron spectroscopy (XPS) as surface-sensitive tool, the sequence of individual layers was analyzed with respect to their chemical state, enabling the quantification of areal densities of the involved molecular units. Fluorescence microscopy was used to demonstrate the hybridization of fluorescently tagged target DNA to the probe DNA, including denaturation- and re-hybridization experiments. Due to its high thermal conductivity, synthetic sapphire is especially suitable as a chip material for the heat-transfer method, which was employed to distinguish complementary- and non-complementary DNA duplexes containing single-nucleotide polymorphisms. These results indicate that it is possible to detect mutations electronically with a chemically resilient and electrically insulating chip material.