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Up in the clouds and above fuels and construction materials must be very carefully selected to ensure a smooth flight and touchdown. Out of around 38,000 single and dual-engined propeller aeroplanes, roughly a third are affected by a new trend in the fuel sector that may lead to operating troubles or even emergency landings: The admixture of bio-ethanol to conventional gasoline. Experiences with these fuels may be projected to alternative mixtures containing new components.
Biotechnologie und die mit ihr verbundenen technischen Prozesse prägen seit Jahrtausenden die Entwicklung der Menschheit. Ausgehend von empirischen Verfahren, insbesondere zur Herstellung von Lebensmitteln und täglichen Gebrauchsgütern, haben sich diese Disziplinen zu einem der innovativsten Zukunftsfelder entwickelt. Durch das immer detailliertere Verständnis zellulärer Vorgänge können mittlerweile Produktionsstämme gezielt optimiert werden. Im Zusammenspiel mit moderner Prozesstechnik können so eine Vielzahl von Bulk- und Feinchemikalien sowie Pharmazeutika effizient hergestellt werden. In diesem Artikel werden exemplarisch einige der aktuellen Trends vorgestellt.
Biotechnologische Wertstoffgewinnung entlang der Prozessketten Grüner und Pflanzenöl-Bioraffinerien
(2014)
Der nachwachsende Rohstoff Raps ist in großen Mengen verfügbar und eine Quelle für Biomoleküle mit hohem Wertschöpfungspotenzial. Entwicklungen zur biotechnologischen Wertstoffgewinnung werden dabei schwerpunktmäßig in den Bereichen Aufarbeitung und Funktionalisierung von Polyphenolen und Fetten betrieben. Bei der Verarbeitung der Pflanzenmaterialien werden dabei insbesondere Verfahren zur adsorptiven Aufreinigung und Auftrennung mittels Materialien mit modifizierten Bleicherden und anderen organischen oder anorganischen Adsorbentien untersucht. Ferner wurden für die Aufreinigung von Polyphenolen adsorptive sowie extraktive Prozesse entwickelt. Bei den Entwicklungen wird berücksichtigt, dass Bioraffinerien auf eine fortwährende Gewährleistung eines hohen Produktions- bzw. Lieferbedarfs nachwachsender Rohstoffe angewiesen sind. Somit werden Optionen dezentraler regionaler Vorbehandlungs- und Wertschöpfungsketten in der Nähe landwirtschaftlicher Betriebe einbezogen. Neben neuen Aufreinigungsverfahren werden mikrobielle und enzymatische Prozesse zur wertsteigernden Umsetzung von Glycerin, Polyphenolen und Zuckermonomeren vorgestellt sowie Limitierungen nachwachsender Rohstoffe der 2. Generation diskutiert.
For the sterilisation of aseptic food packages it is taken advantage of the microbicidal properties of hydrogen peroxide (H2O2). Especially, when applied in vapour phase, it has shown high potential of microbial inactivation. In addition, it offers a high environmental compatibility compared to other chemical sterilisation agents, as it decomposes into oxygen and water, respectively. Due to a lack in sensory detection possibilities, a continuous monitoring of the H2O2 concentration was recently not available. Instead, the sterilisation efficacy is validated using microbiological tests. However, progresses in the development of calorimetric gas sensors during the last 7 years have made it possible to monitor the H2O2 concentration during operation. This chapter deals with the fundamentals of calorimetric gas sensing with special focus on the detection of gaseous hydrogen peroxide. A sensor principle based on a calorimetric differential set-up is described. Special emphasis is given to the sensor design with respect to the operational requirements under field conditions. The state-of-the-art regarding a sensor set-up for the on-line monitoring and secondly, a miniaturised sensor for in-line monitoring are summarised. Furthermore, alternative detection methods and a novel multi-sensor system for the characterisation of aseptic sterilisation processes are described.
Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC–MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed.
Today, the assembly of laser systems requires a large share of manual operations due to its complexity regarding the optimal alignment of optics. Although the feasibility of automated alignment of laser optics has been shown in research labs, the development effort for the automation of assembly does not meet economic requirements – especially for low-volume laser production. This paper presents a model-based and sensor-integrated assembly execution approach for flexible assembly cells consisting of a macro-positioner covering a large workspace and a compact micromanipulator with camera attached to the positioner. In order to make full use of available models from computer-aided design (CAD) and optical simulation, sensor systems at different levels of accuracy are used for matching perceived information with model data. This approach is named "chain of refined perception", and it allows for automated planning of complex assembly tasks along all major phases of assembly such as collision-free path planning, part feeding, and active and passive alignment. The focus of the paper is put on the in-process image-based metrology and information extraction used for identifying and calibrating local coordinate systems as well as the exploitation of that information for a part feeding process for micro-optics. Results will be presented regarding the processes of automated calibration of the robot camera as well as the local coordinate systems of part feeding area and robot base.
High-intensity discharge lamps can be driven by radio-frequency signals in the ISM frequency band at 2.45 GHz, using a matching network to transform the impedance of the plasma to the source impedance. To achieve an optimal operating condition, a good characterization of the lamp in terms of radio frequency equivalent circuits under operating conditions is necessary, enabling the design of an efficient matching network. This paper presents the characterization technique for such lamps and presents the design of the required matching network. For the characterization, a high-intensity discharge lamp was driven by a monofrequent large signal at 2.45 GHz, whereas a frequency sweep over 300 MHz was performed across this signal to measure so-called small-signal hot S-parameters using a vector network analyzer. These parameters are then used as an equivalent load in a circuit simulator to design an appropriate matching network. Using the measured data as a black-box model in the simulation results in a quick and efficient method to simulate and design efficient matching networks in spite of the complex plasma behavior. Furthermore, photometric analysis of high-intensity discharge lamps are carried out, comparing microwave operation to conventional operation.
High-k perovskite oxide of barium strontium titanate (BST) represents a very attractive multi-functional transducer material for the development of (bio-)chemical sensors for liquids. In this work, BST films have been applied as a sensitive transducer material for a label-free detection of adsorbed charged macromolecules (positively charged polyelectrolytes) and concentration of hydrogen peroxide vapor as well as protection insulator layer for a contactless electrolyte-conductivity sensor. The experimental results of characterization of individual sensors are presented. Special emphasis is devoted towards the development of a capacitively-coupled contactless electrolyte-conductivity sensor.
In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.
Der Embedded Wireless-Report
(2014)
Ab dem 1.1.2015 ist es soweit: Deutschland erhält einen flächendeckenden und weitgehend branchenunabhängigen gesetzlichen Mindestlohn. Danach haben grundsätzlich alle abhängig beschäftigten Arbeitnehmer einen Anspruch auf eine Entlohnung von wenigstens 8,50 EUR brutto je Arbeitsstunde. Die Auswirkungen dürften enorm sein. Das Bundesministerium für Arbeit und Soziales geht jedenfalls davon aus, dass aufgrund der Einführung des gesetzlichen Mindestlohns mehrere Millionen Beschäftigte einen höheren Lohn beanspruchen können. Der nachfolgende Beitrag gibt einen Überblick über die wesentlichen Inhalte des gesetzlichen Mindestlohns und Hinweise für Anwendungsprobleme in der betrieblichen Praxis.
Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
In this work, the catalyst manganese(IV) oxide (MnO2), of calorimetric gas sensors (to monitor the sterilization agent vaporized hydrogen peroxide) has been investigated in more detail. Chemical analyses by means of X-ray-induced photoelectron spectroscopy have been performed to unravel the surface chemistry prior and after exposure to hydrogen peroxide vapor at elevated temperature, as applied in the sterilization processes of beverage cartons. The surface characterization reveals a change in oxidation states of the metal oxide catalyst after exposure to hydrogen peroxide. Additionally, a cleaning effect of the catalyst, which itself is attached to the sensor surface by means of a polymer interlayer, could be observed.
Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer
(2014)
As a semiconductor-based electrochemical sensor, the light-addressable potentiometric sensor (LAPS) can realize two dimensional visualization of (bio-)chemical reactions at the sensor surface addressed by localized illumination. Thanks to this imaging capability, various applications in biochemical and biomedical fields are expected, for which the spatial resolution is critically significant. In this study, therefore, the spatial resolution of the LAPS was investigated in detail based on the device simulation. By calculating the spatiotemporal change of the distributions of electrons and holes inside the semiconductor layer in response to a modulated illumination, the photocurrent response as well as the spatial resolution was obtained as a function of various parameters such as the thickness of the Si substrate, the doping concentration, the wavelength and the intensity of illumination.
The simulation results verified that both thinning the semiconductor substrate and increasing the doping concentration could improve the spatial resolution, which were in good agreement with known experimental results and theoretical analysis. More importantly, new findings of interests were also obtained. As for the dependence on the wavelength of illumination, it was found that the known dependence was not always the case. When the Si substrate was thick, a longer wavelength resulted in a higher spatial resolution which was known by experiments. When the Si substrate was thin, however, a longer wavelength of light resulted in a lower spatial resolution. This finding was explained as an effect of raised concentration of carriers, which reduced the thickness of the space charge region.
The device simulation was found to be helpful to understand the relationship between the spatial resolution and device parameters, to understand the physics behind it, and to optimize the device structure and measurement conditions for realizing higher performance of chemical imaging systems.
A novel photoexcitation method for the light-addressable potentiometric sensor (LAPS) realized a higher spatial resolution of chemical imaging. In this method, a modulated light probe, which generates the alternating photocurrent signal, is surrounded by a ring of constant light, which suppresses the lateral diffusion of photocarriers by enhancing recombination. A device simulation verified that a higher spatial resolution could be obtained by adjusting the gap between the modulated and constant light. It was also found that a higher intensity and a longer wavelength of constant light was more effective. However, there exists a tradeoff between the spatial resolution and the amplitude of the photocurrent, and thus, the signal-to-noise ratio. A tilted incidence of constant light was applied, which could achieve even higher resolution with a smaller loss of photocurrent.
Die Beschäftigung von Prokuristen ist gängige betriebliche Praxis. Unternehmen stehen dabei immer wieder vor der Frage, ob und welche Arbeitnehmer sie zu Prokuristen bestellen sollen. Nicht selten bleiben hierbei die arbeitsrechtlichen Konsequenzen, die mit der Bestellung eines Arbeitnehmers zum Prokuristen einhergehen können, unberücksichtigt, wie diverse Gerichtsentscheidungen zeigen. Dieser Beitrag soll einen Überblick über die arbeitsrechtlichen Folgen bei der Beschäftigung von Prokuristen geben und der betrieblichen Praxis somit gleichzeitig als Entscheidungshilfe dienen, wenn es um das Ob und Wie der möglichen Bestellung eines Arbeitnehmers zum Prokuristen geht.
DNA-hybridization detection using light-addressable potentiometric sensor modified with gold layer
(2014)
Does stiffer electoral competition reduce political shirking? For a micro-analysis of this question, I construct a new data set spanning the years 2005 to 2012 covering biographical and political information about German Members of Parliament (MPs), including their attendance rates in voting sessions. For the parliament elected in 2009, I show that indeed opposition party MPs who expect to face a close race in their district show significantly and relevantly lower absence rates in parliament beforehand. MPs of governing parties seem not to react significantly to electoral competition. These results are confirmed by an analysis of the parliament elected in 2005, by several robustness checks, and also by employing an instrumental variable strategy exploiting convenient peculiarities of the German electoral system. The study also shows how MPs elected via party lists react to different levels of electoral competition.
Üblicherweise werden biotechnologische Reaktionssysteme im mikrofluidischen Maßstab in vorstrukturierten Bauteilen oder mit auf Wellplatten basierenden Robotersystemen realisiert. In dem hier vorgestellten System werden chemische oder biologische Reaktionen mit magnetischen Mikroreaktoren (MR) durchgeführt, bei denen hydrophobe magnetische Mikropartikel einen wässrigen Kern umschließen. Solche MR bieten eine gute Kontrolle der Reaktionsbedingungen, eine verbesserte Sicherheit und Portabilität. Die neue Plattformtechnologie ermöglicht die zweidimensionale Bewegung der magnetischen MR auf einer planaren Ebene. Oberhalb oder unterhalb der Plattform werden Magnetfeldgradienten zum Manipulieren und Bewegen eines oder mehrerer magnetischer MR erzeugt. Die optimal auf die MR wirkenden magnetischen Kräfte werden experimentell ermittelt und simuliert. Die Aktivierung der Magnetfelder wird automatisiert durch elektrische Spulen mit Eisenkern bzw. Neodymmagnet gesteuert. Angewendet wurde das System beim reversiblen Öffnen von MR, um z. B. Reaktionspartner in den wässrigen Kern zu injizieren oder Proben zu entnehmen. Ferner wurde Lac-case A und b-Glucosidase auf einer Quarzglasoberfläche immobilisiert und mit einem MR zum Reagieren gebracht. Weiterhin wurden MR fusioniert und so ein wässriger Kern bestehend aus Laccase mit einem aus dem entsprechenden Substrat Syringaldazin vereint.
Einleitung vor § 1297
(2014)
Die Informationsbroschüre „Elektromobilität in einer vernetzten Welt“ richtet sich an IT-Dienstleister. In dieser Broschüre werden mögliche Potenziale im Bereich der Elektromobilität aufgezeigt. Die Mobilität der Zukunft ist eine interdisziplinäre Angelegenheit und kein reines Automotive-Thema mehr. Beispiele wie Mobilitätsmanagement, eCommerce und Individualisierung sind im Mobilitätsbereich für die IT-Branche relevant.
Use of textile structures for reinforcement of pelvic floor structures has to consider mechanical forces to the implant, which are quite different to the tension free conditions of the abdominal wall. Thus, biomechanical analysis of textile devices has to include the impact of strain on stretchability and effective porosity. Prolift® and Prolift + M®, developed for tension free conditions, were tested by measuring stretchability and effective porosity applying mechanical strain. For comparison, we used Dynamesh-PR4®, which was designed for pelvic floor repair to withstand mechanical strain. Prolift® at rest showed moderate porosity with little stretchability but complete loss of effective porosity at strain of 4.9 N/cm. Prolift + M® revealed an increased porosity at rest, but at strain showed high stretchability, with subsequent loss of effective porosity at strain of 2.5 N/cm. Dynamesh PR4® preserved its high porosity even under strain, but as consequence of limited stretchability. Though in tension free conditions Prolift® and Prolift + M® can be considered as large pore class I meshes, application of mechanical strain rapidly lead to collapse of pores. The loss of porosity at mechanical stress can be prevented by constructions with high structural stability. Assessment of porosity under strain was found helpful to define requirements for pelvic floor devices. Clinical studies have to prove whether devices with high porosity as well as high structural stability can improve the patients' outcome.
Engineering of functional interfaces / Patrick Wagner ; Theodor Doll ; Michael J. Schöning (eds.)
(2014)
The chemical imaging sensor, which is based on the principle of the light-addressable potentiometric sensor (LAPS), is a powerful tool to visualize the spatial distribution of chemical species on the sensor surface. The spatial resolution of this sensor depends on the diffusion of photocarriers excited by a modulated light. In this study, a novel hybrid fiber-optic illumination was developed to enhance the spatial resolution. It consists of a modulated light probe to generate a photocurrent signal and a ring of constant light, which suppresses the lateral diffusion of minority carriers excited by the modulated light. It is demonstrated that the spatial resolution was improved from 92 μm to 68 μm.
The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹.
A semiconductor field-effect device has been used for an enzymatically catalyzed degradation of biopolymers for the first time. This novel technique is capable to monitor the degradation process of multiple samples in situ and in real-time. As model system, the degradation of the biopolymer poly(D, L-lactic acid) has been monitored in the degradation medium containing the enzyme lipase from Rhizomucor miehei. The obtained results demonstrate the potential of capacitive field-effect sensors for degradation studies of biodegradable polymers.
This article describes the fabrication, characterization and application of an epidermal temporary-transfer tattoo-based potentiometric sensor, coupled with a miniaturized wearable wireless transceiver, for real-time monitoring of sodium in the human perspiration. Sodium excreted during perspiration is an excellent marker for electrolyte imbalance and provides valuable information regarding an individual's physical and mental wellbeing. The realization of the new skin-worn non-invasive tattoo-like sensing device has been realized by amalgamating several state-of-the-art thick film, laser printing, solid-state potentiometry, fluidics and wireless technologies. The resulting tattoo-based potentiometric sodium sensor displays a rapid near-Nernstian response with negligible carryover effects, and good resiliency against various mechanical deformations experienced by the human epidermis. On-body testing of the tattoo sensor coupled to a wireless transceiver during exercise activity demonstrated its ability to continuously monitor sweat sodium dynamics. The real-time sweat sodium concentration was transmitted wirelessly via a body-worn transceiver from the sodium tattoo sensor to a notebook while the subjects perspired on a stationary cycle. The favorable analytical performance along with the wearable nature of the wireless transceiver makes the new epidermal potentiometric sensing system attractive for continuous monitoring the sodium dynamics in human perspiration during diverse activities relevant to the healthcare, fitness, military, healthcare and skin-care domains.
Die Erdbeben in Albstadt 1978 (Magnitude 5,7), Roermond 1992 (Magnitude 5,9) oder in Waldkirch 2004 (Magnitude 5,1) haben verdeutlicht, dass die erdbebensichere Auslegung von Mauerwerksbauten auch in Deutschland von großer Bedeutung ist. Bereits im Jahr 1981 wurde die DIN 4149 (1981) “Bauten in deutschen Erdbebengebieten – Lastannahmen, Bemessung und Ausführung üblicher Hochbauten“ eingeführt, in der aber für Mauerwerksbauten nur wenige Anforderungen gestellt wurden. Diese Norm wurde durch den NABau-Arbeitsausschuss “Erdbeben; Sonderfragen“ des Deutschen Instituts für Normung e.V. (DIN) auf Grundlage des Eurocode 8 (2004) vollständig überarbeitet und durch die DIN 4149 (2005) abgelöst, die umfangreiche Regelungen für die seismische Auslegung von Mauerwerksbauten enthält. Mittlerweile liegen die DIN EN 1998-1 (2010) und der Nationale Anhang DIN EN 1998-1/NA (2011) vor, die nach Einarbeitung der Ergebnisse der durchgeführten Anwendungserprobung bauaufsichtlich eingeführt und die DIN 4149 (2005) ersetzen werden. Der folgende Beitrag gibt einen Überblick über die seismische Berechnung und Bemessung von Mauerwerksbauten nach dem europäischen Regelwerk und illustriert deren Anwendung an einem baupraktischen Beispiel.
EU-Projekt INSYSME : innovative Systeme für erdbebentaugliche Ausfachungswände aus Ziegelmauerwerk
(2014)
Am 1. Oktober 2013 ist das auf drei Jahre angelegte EU-Forschungsprojekt INSYSME – Innovative Systeme für erdbebentaugliche Ausfachungswände aus Ziegelmauerwerk in Stahlbetonrahmentragwerken – gestartet. Unter der Koordination der Universität Padua beteiligen sich 16 Partner aus sechs europäischen Ländern (Deutschland, Griechenland, Italien, Portugal, Rumänien, Türkei). Als deutsche Partner nehmen die Arbeitsgemeinschaft Mauerziegel aus Bonn, die Universität Kassel sowie das Ingenieurbüro SDA-engineering GmbH aus Herzogenrath, teil. Ziel der deutschen Partner ist die Entwicklung von innovativen Ausfachungssystemen aus monolithischem wärmedämmenden Ziegelmauerwerk, mit denen nicht nur eine erhöhte Erdbebensicherheit, sondern auch die sichere Erfüllung der steigenden Anforderungen aus Windbeanspruchungen gewährleistet werden können. Die Forschungsergebnisse sollen vom Partner SDA-engineering GmbH in die bereits seit einigen Jahren verfügbare Softwarelösung MINEA [1] integriert werden. Weitere Informationen stehen auf den Websites des Projektes [2] zur Verfügung. Im vorliegenden Beitrag werden nach einer kurzen thematischen Einführung die Ergebnisse von Tastversuchen an senkrecht zur Ebene belasteten Ausfachungswänden aus Planziegelmauerwerk vorgestellt. Im Anschluss wird das geplante Arbeitsprogramm der deutschen Partner im Projekt INSYSME beschrieben.
Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.
Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.
The Dry Low NOx (DLN) Micromix combustion principle with increased energy density is adapted for the industrial gas turbine APU GTCP 36-300 using hydrogen and hydrogen-rich syngas with a composition of 90%-Vol. hydrogen (H₂) and 10%-Vol. carbon-monoxide (CO). Experimental and numerical studies of several combustor geometries for hydrogen and syngas show the successful advance of the DLN Micromix combustion from pure hydrogen to hydrogen-rich syngas. The impact of the different fuel properties on the combustion principle and aerodynamic flame stabilization design laws, flow field, flame structure and emission characteristics is investigated by numerical analysis using a hybrid Eddy Break Up combustion model and validated against experimental results.
Planning the layout and operation of a technical system is a common task
for an engineer. Typically, the workflow is divided into consecutive stages: First,
the engineer designs the layout of the system, with the help of his experience or of
heuristic methods. Secondly, he finds a control strategy which is often optimized
by simulation. This usually results in a good operating of an unquestioned sys-
tem topology. In contrast, we apply Operations Research (OR) methods to find a
cost-optimal solution for both stages simultaneously via mixed integer program-
ming (MILP). Technical Operations Research (TOR) allows one to find a provable
global optimal solution within the model formulation. However, the modeling error
due to the abstraction of physical reality remains unknown. We address this ubiq-
uitous problem of OR methods by comparing our computational results with mea-
surements in a test rig. For a practical test case we compute a topology and control
strategy via MILP and verify that the objectives are met up to a deviation of 8.7%.
Vor dem Hintergrund zunehmender gesellschaftlicher Veränderungen bei den Lebens- und Familienformen hat es sich die Commission on European Family Law (CEFL) seit 2001 zum Ziel gesetzt, unverbindliche Regelungsvorschläge für ein europaweit einheitliches Familienrecht zu schaffen. Die Vorstellung und Diskussion dieser auf rechtsvergleichender Basis erstellten Principles erfolgt auf den regelmäßig veranstalteten Tagungen der CEFL. Die nunmehr fünfte Konferenz zum Thema „Family Law and Culture in Europe – Developments, Challenges and Opportunities“ fand erstmals in Deutschland statt. Ausgerichtet wurde die Veranstaltung, zu der ca. 200 Teilnehmerinnen und Teilnehmern aus Wissenschaft und Praxis aus insgesamt 33 Ländern angereist waren, von Nina Dethloff (Direktorin des Instituts für Deutsches, Europäisches und Internationales Familienrecht an der Universität Bonn), Katharina Boele-Woelki (Direktorin des Utrecht Centre for European Research into Family Law und Preisträgerin des Anneliese Maier-Forschungspreises der Alexander von Humboldt-Stiftung) und Werner Gephart (Direktor des Käte Hamburger Kollegs „Recht als Kultur“).
Purpose
To demonstrate that high quality T₂-weighted (T2w) turbo spin-echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only.
Methods
Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B₀ and radiofrequency shimming and localized flip angle calibration. T₁ and T₂ relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000–3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate.
Results
High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction.
Conclusion
High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array.
Feldbustechnologie
(2014)
This paper develops a new finite element method (FEM)-based upper bound algorithm for limit and shakedown analysis of hardening structures by a direct plasticity method. The hardening model is a simple two-surface model of plasticity with a fixed bounding surface. The initial yield surface can translate inside the bounding surface, and it is bounded by one of the two equivalent conditions: (1) it always stays inside the bounding surface or (2) its centre cannot move outside the back-stress surface. The algorithm gives an effective tool to analyze the problems with a very high number of degree of freedom. Our numerical results are very close to the analytical solutions and numerical solutions in literature.
The concept of an injective affine embedding of the quantum states into a set of classical states, i.e., into the set of the probability measures on some measurable space, as well as its relation to statistically complete observables is revisited, and its limitation in view of a classical reformulation of the statistical scheme of quantum mechanics is discussed. In particular, on the basis of a theorem concerning a non-denseness property of a set of coexistent effects, it is shown that an injective classical embedding of the quantum states cannot be supplemented by an at least approximate classical description of the quantum mechanical effects. As an alternative approach, the concept of quasi-probability representations of quantum mechanics is considered.
Gebaute Geschichte in Turin
(2014)
Generation Y
(2014)
1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described.
2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created.
3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment.
4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.
Geologisch-geotechnischer Planungsprozess von Tunnelbauten mit Schwerpunkt tiefliegender Tunnel
(2014)
A technology reference study for a multiple near-Earth object (NEO) rendezvous mission with solar sailcraft is currently carried out by the authors of this paper. The investigated mission builds on previous concepts, but adopts a strong micro-spacecraft philosophy based on the DLR/ESA Gossamer technology. The main scientific objective of the mission is to explore the diversity of NEOs. After direct interplanetary insertion, the solar sailcraft should—within less than 10 years—rendezvous three NEOs that are not only scientifically interesting, but also from the point of human spaceight and planetary defense. In this paper, the objectives of the study are outlined and a preliminary potential mission profile is presented.
A technology reference study for a solar polar mission is presented. The study uses novel analytical methods to quantify the mission design space including the required sail performance to achieve a given solar polar observation angle within a given timeframe and thus to derive mass allocations for the remaining spacecraft sub-systems, that is excluding the solar sail sub-system. A parametric, bottom-up, system mass budget analysis is then used to establish the required sail technology to deliver a range of science payloads, and to establish where such payloads can be delivered to within a given timeframe. It is found that a solar polar mission requires a solar sail of side-length 100–125 m to deliver a ‘sufficient value’ minimum science payload, and that a 2.5 μm sail film substrate is typically required, however the design is much less sensitive to the boom specific mass.
A technology reference study for a displaced Lagrange point space weather mission is presented. The mission builds on previous concepts, but adopts a strong micro-spacecraft philosophy to deliver a low mass platform and payload which can be accommodated on the DLR/ESA Gossamer-3 technology demonstration mission. A direct escape from Geostationary Transfer Orbit is assumed with the sail deployed after the escape burn. The use of a miniaturized, low mass platform and payload then allows the Gossamer-3 solar sail to potentially double the warning time of space weather events. The mission profile and mass budgets will be presented to achieve these ambitious goals.
Der zunehmende Bedarf an fossilen Rohstoffen bei gleichzeitig abnehmender Versorgungssicherheit führt zu einer intensiven Suche nach erneuerbaren Ressourcen. Ein vielversprechendes Ausgangsmaterial mit einer weltweiten Verfügbarkeit stellt Gras dar. In 2012 wurden in Deutschland 33 Millionen Tonnen (Heugewicht) Gras auf 4,82 Millionen Hektar Ackerland produziert, davon wurden 60,5 % siliert. Durch die Silierung kann Gras als Substrat zeitlich uneingeschränkt verfügbar sein, ohne dem Risiko des schnellen Verderbs ausgesetzt zu sein. Eine Schlüsselrolle im Rahmen des Silierprozesses nimmt die Produktion von Milchsäure ein. Milchsäure ist einbedeutendes biotechnologisches Produkt für die Lebensmittel- und die chemische Industrie. Im Rahmen dieser Arbeit wird die vollständige Umwandlung der fermentierbaren Zucker in der Silage zu Milchsäure angestrebt, um die maximale Ausbeute der organischen Säure zu erreichen. Im ersten Verfahrensschritt wird die Silage gepresst und der erhaltene Presskuchen einer Liquid-Hot-Water-Behandlung unterzogen. Durch diese einfache Vorbehandlung können hohe Glucoseausbeuten im nachfolgenden SSF-Schritt bei gleichzeitig geringem Enzymeinsatz und Chemikalienverbrauch realisiert werden. Zur Aufreinigung der Milchsäure wurden extraktive und chromatographische Methoden untersucht.
Our knowledge on tree responses to drought is mainly based on short-term manipulation experiments which do not capture any possible long-term adjustments in this response. Therefore, historical water channels in inner-Alpine dry valleys were used as century-long irrigation experiments to investigate adjustments in tree growth to contrasting water supply. This involved quantifying the tree-ring growth of irrigated and non-irrigated (control) Scots pine (Pinus sylvestris L.) in Valais (Switzerland), as well as European larch (Larix decidua Mill.) and black pine (Pinus nigra Arnold) in Vinschgau (Italy). Furthermore, the adjustments in radial growth of Scots pine and European larch to an abrupt stop in irrigation were analyzed.
Irrigation promoted the radial growth of all tree species investigated compared to the control: (1) directly through increased soil water availability, and (2) indirectly through increased soil nutrients and humus contents in the irrigated plots. Irrigation led to a full elimination of growth responses to climate for European larch and black pine, but not for Scots pine, which might become more sensitive to drought with increasing tree size in Valais. For the control trees, the response of the latewood increment to water availability in July/August has decreased in recent decades for all species, but increased in May for Scots pine only. The sudden irrigation stop caused a drop in radial growth to a lower level for Scots pine or similar level for larch compared to the control for up to ten years. However, both tree species were then able to adjust to the new conditions and subsequently grew with similar (Scots pine) or even higher growth rates (larch) than the control.
To estimate the impact of climate change on future forest development, the duration of manipulation experiments should be on longer time scales in order to capture adjustment processes and feedback mechanisms of forest ecosystems.
Heat production in the windings of the stators of electric machines under stationary condition
(2014)
In electric machines due to high currents and resistive losses (joule heating) heat is produced. To avoid damages by overheating the design of effective cooling systems is required. Therefore the knowledge of heat sources and heat transfer processes is necessary. The purpose of this paper is to illustrate a good and effective calculation method for the temperature analysis based on homogenization techniques. These methods have been applied for the stator windings in a slot of an electric machine consisting of copper wires and resin. The key quantity here is an effective thermal conductivity, which characterizes the heterogeneous wire resin-arrangement inside the stator slot. To illustrate the applicability of the method, the analysis of a simplified, homogenized model is compared with the detailed analysis of temperature behavior inside a slot of an electric machine according to the heat generation. We considered here only the stationary situation. The achieved numerical results are accurate and show that the applied homogenization technique works in practice. Finally the results of simulations for the two cases, the original model of the slot and the homogenized model chosen for the slot (unit cell), are compared to experimental results.
Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 Å as well as in complex with CoA at a resolution of 1.59 Å. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called “hot dog fold” which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all “hot dog fold” proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041–2053. © 2014 Wiley Periodicals, Inc.
In this study, a high-speed chemical imaging system was developed for visualization of the interior of a microfluidic channel. A microfluidic channel was constructed on the sensor surface of the light-addressable potentiometric sensor (LAPS), on which the ion concentrations could be measured in parallel at up to 64 points illuminated by optical fibers. The temporal change of pH distribution inside the microfluidic channel was recorded at a maximum rate of 100 frames per second (fps). The high frame rate allowed visualization of moving interfaces and plugs in the channel even at a flow velocity of 111 mm/s, which suggests the feasibility of plug-based microfluidic devices for flow-injection analysis (FIA).
This paper describes the modeling of a high-temperature storage system for an existing solar tower power plant with open volumetric receiver technology, which uses air as heat transfer medium (HTF). The storage system model has been developed in the simulation environment Matlab/Simulink®. The storage type under investigation is a packed bed thermal energy storage system which has the characteristics of a regenerator. Thermal energy can be stored and discharged as required via the HTF air. The air mass flow distribution is controlled by valves, and the mass flow by two blowers. The thermal storage operation strategy has a direct and significant impact on the energetic and economic efficiency of the solar tower power plants.