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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.
Organisation
(2014)
The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress.
The impact of wake model effects is investigated for two highly
non-planar lifting systems. Dependent on the geometrical
arrangement of the configuration, the wake model shape is found
to considerably affect the estimation. Particularly at higher angles
of attack, an accurate estimation based on the common linear wake
model approaches is involved.
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.
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.
Multimodal bioimage sensor
(2014)
To visualize the biochemical distribution two-dimensionally, we invented a solid-state-type ion image sensor that indicates the chemical activity of solutions and cells. The device, which consists of a CCD array covered with a functionalized membrane to detect charge accumulation, is highly sensitive to changes in the concentration and two-dimensional distribution of ions and biomaterials.
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.
The 2nd edition of the lightning risk management
standard (IEC 62305-2) considers structures, which may
endanger environment. In these cases, the loss is not limited to
the structure itself, which is valid for usual structures. In the past
(Edition 1) this danger was simply taken into account by a special
hazard factor, multiplying the existing risk for the structure with
a number. Now, in the edition 2, we add to the risk for the
structure itself a “second risk” due to the losses outside the
structure. The losses outside can be treated independently from
what occurs inside. This is a major advantage to analyze the risk
for sensitive structures, like chemical plants, nuclear plants, or
structures containing explosives, etc. In this paper, the existing
procedure given by the European version EN 62305-2 Ed.2 is
further developed and applied to a few structures.
Die Informationsbroschüre „3D-Druck – Prozessmanagement für individualisierte Massenprodukte“ richtet sich an 3D-Druckdienstleister, die additive Fertigungsverfahren (Additive Manufacturing) nutzen, sowie an IT-Dienstleister, die eine Plattform für den Datenaustausch und die Individualisierung anbieten.
Mit der additiven 3D-Drucktechnologie erfolgt die Fertigung von Produkten durch einen schichtweisen Aufbau. In dieser Broschüre werden mögliche Potenziale im Bereich der Herstellung mittels additiver Fertigungsverfahren aufgezeigt.
Die Informationsbroschüre „Anforderungen an die Gestaltung multimodaler Mobilitätsanwendungen“ richtet sich an IT-Dienstleister. In dieser Broschüre werden mögliche Potenziale im Bereich des allgemeinen Mobilitätsmanagements aufgezeigt. Automobilhersteller vernetzten sich zunehmend mit Technologie-Unternehmen. Es geht nicht nur um die besondere Entwicklung von spezieller Elektronik- und Softwarelösungen für Navigations- und Entertainmentsysteme oder auch Fahrassistenz-Systemen in modernen PKW, sondern um einen übergreifenden Design- und Interaktionsansatz für miteinander vernetzte Geräte.
This study describes a label-free impedimetric sensor based on short ssDNA recognition elements for the detection of hybridization events. We concentrate on the elucidation of the influence of target length and recognition sequence position on the sensorial performance. The impedimetric measurements are performed in the presence of the redox system ferri-/ferrocyanide and show an increase in charge transfer resistance upon hybridization of ssDNA to the sensor surface. Investigations on the impedimetric signal stability demonstrate a clear influence of the buffers used during the sensor preparation and the choice of the passivating mercaptoalcanol compound. A stable sensor system has been developed, enabling a reproducible detection of 25mer target DNA in the low nanomolar range. After hybridization, a sensor regeneration can be reached with deionized water by adjustment of effective convection conditions, ensuring a sensor reusability. By investigations of longer targets with overhangs exposed to the solution, we can demonstrate applicability of the impedimetric detection for longer ssDNA. However, a decreasing charge transfer resistance change (ΔRct) is found by extending the overhang. As a strategy to increase the impedance change for longer target strands, the position of the recognition sequence can be designed in a way that a small overhang is exposed to the electrode surface. This is found to result in an increase in the relative Rct change. These results suggest that DNA and consequently negative charge near the electrode possess a larger impact on the impedimetric signal than DNA further away.
In this work the transient simulations of four hybrid solar tower power plant concepts with open-volumetric receiver technology for a location in Barstow-Daggett, USA, are presented. The open-volumetric receiver uses ambient air as heat transfer fluid and the hybridization is realized with a gas turbine. The Rankine cycle is heated by solar-heated air and/or by the gas turbine's flue gases. The plant can be operated in solar-only, hybrid parallel or combined cycle-only mode as well as in any intermediate load levels where the solar portion can vary between 0 to 100%.
The simulated plant is based on the configuration of a solar-hybrid power tower project, which is in planning for a site in Northern Algeria. The meteorological data for Barstow-Daggett was taken from the software meteonorm. The solar power tower simulation tool has been developed in the simulation environment MATLAB/Simulink and is validated.
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.
An array of electrically isolated nanoplate field-effect silicon-on-insulator (SOI) capacitors as a new transducer structure for multiparameter (bio-)chemical sensing is presented. The proposed approach allows addressable biasing and electrical readout of multiple nanoplate field-effect capacitive (bio-)chemical sensors on the same SOI chip, as well as differential-mode measurements. The realized sensor chip has been applied for pH and penicillin concentration measurements, electrical monitoring of polyelectrolyte multilayer formation, and the label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization and denaturation events.
Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers.
Die Marktübersicht „Unterschiedliche Entwicklungsansätze von Multiplattform-Anwendungen“ richtet sich an IT-Dienstleister, Entwickler und IT-Abteilungen von Unternehmen, die Multiplattform Anwendungen entwickeln. In dieser Marktübersicht werden verschiedene Entwicklungsansätze beschrieben und ihre jeweiligen Vor- und Nachteile aufgezeigt.
This paper describes two courses on
simulation methods for graduate students:
“Simulation Methods” and “Simulation and
Optimization in Virtual Engineering” The
courses were planned to teach young engineers
how to work with simulation software as well as
to understand the necessary mathematical background.
As simulation software COMSOL is
used. The main philosophy was to combine
theory and praxis in a way that motivates the
students. In addition “soft skills” should be
improved. This was achieved by project work as
final examination. As underlying didactical principle
the ideas of Bloom’s revised taxonomy
were followed. The paper basically focusses on
educational aspects, e.g. how to structure the
course, plan the exercises, organize the project
work and include practical COMSOL examples.
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.
High gradient magnetic separation (HGMS) has been established since the early 1970s. A more recent application of these systems is the use in bioprocesses. To integrate the HGMS in a fermentation process, it is necessary to optimize the separation matrix with regard to the magnetic separation characteristics and permeability of the non-magnetizable components of the fermentation broth. As part of the work presented here, a combined fluidic and magnetic force finite element model simulation was created using the software COMSOL Multiphysics and compared with separation experiments. Finally, as optimal lattice orientation of the separation matrix, a transversal rhombohedral arrangement was defined. The high suitability of the new filter matrix has been verified by separation experiments.
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.
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.