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Activated carbons are known as excellent adsorbents. Their applications include the adsorptive removal of color, odor, taste, undesirable organic and inorganic pollutants from drinking and waste water; air purification in inhabited spaces; purification of many chemicals, pharmaceutical products and many others. This chapter elucidates the role of normal microflora in the maintenance of human health and presents materials on possible clinical displays of microecological infringements and ways of their correction. It presents new developments concerning new probiotics with immobilized Lactobacillus and Bacillus. The chapter considers the mechanisms of the intestine disbacteriosis correction by sorbed probiotics. It demonstrates the advantages and creation prospects of immobilized probiotics developed on the basis of carbonized rice husk. There are great prospects for the development of medical biotechnology due to use of carbon sorbents with a nanostructured surface. Microbial communities form a biocenosis of the biotope and together with the host organism create permanent or temporary ecosystems.
This study describes the development of a new combined polysaccharide-matrix-based technology for the immobilization of Lactobacillus rhamnosus GG (LGG) bacteria in biofilm form. The new composition allows for delivering the bacteria to the digestive tract in a manner that improves their robustness compared with planktonic cells and released biofilm cells. Granules consisting of a polysaccharide matrix with probiotic biofilms (PMPB) with high cell density (>9 log CFU/g) were obtained by immobilization in the optimized nutrient medium. Successful probiotic loading was confirmed by fluorescence microscopy and scanning electron microscopy. The developed prebiotic polysaccharide matrix significantly enhanced LGG viability under acidic (pH 2.0) and bile salt (0.3%) stress conditions. Enzymatic extract of feces, mimicking colon fluid in terms of cellulase activity, was used to evaluate the intestinal release of probiotics. PMPB granules showed the ability to gradually release a large number of viable LGG cells in the model colon fluid. In vivo, the oral administration of PMPB granules in rats resulted in the successful release of probiotics in the colon environment. The biofilm-forming incubation method of immobilization on a complex polysaccharide matrix tested in this study has shown high efficacy and promising potential for the development of innovative biotechnologies.
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.
Solar-electric propulsion (SEP) is superior with
respect to payload capacity, flight time and
flexible launch window to the conventional
interplanetary transfer method using chemical
propulsion combined with gravity assists. This fact
results from the large exhaust velocities of electric
low–thrust propulsion and is favourable also for
missions to the giant planets, Kuiper-belt objects
and even for a heliopause probe (IHP) as shown in
three studies by the authors funded by DLR. They
dealt with a lander for Europa and a sample return
mission from a mainbelt asteroid [1], with the
TANDEM mission [2]; the third recent one
investigates electric propulsion for the transfer to
the edge of the solar system.
All studies are based on triple-junction solar arrays,
on rf-ion thrusters of the qualified RIT-22 type and
they use the intelligent trajectory optimization
program InTrance [3].
Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line
(2012)
The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.
The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.
Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.
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.
Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.
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.
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.
Das Fußballtrikot – Arbeitsbekleidung, Identifikationsmerkmal, Distinktionsmerkmal? Was ist das Fußballtrikot, was sind seine identitätsstiftenden Merkmale und welche Gestaltungsparameter prägen sein heutiges Aussehen? In dieser Publikation wird die Geschichte des Trikots ebenso wie die äußeren Einflüsse auf sein heutiges Erscheinungsbild dokumentiert und analysiert. Die Publikation definiert die verschiedenen Gestaltungsparameter, erläutert diese und ordnet sie ein. Ebenso wird ein Einblick in den kreativen Gestaltungsprozess von Fußballtrikots gewährt. Das Ziel dieser Publikation besteht darin, das Erscheinungsbild von Trikots zu verstehen und eine kritische Reflexion darüber zu ermöglichen, wie das Fußballtrikot individuell definiert wird.
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.
Im Rahmen des Exzellenzclusters „Integrative Produktionstechnik für Hochlohnländer“ der RWTHAachen University werden derzeit alternative Verfahren zur Herstellung von Metall/Kunststoff- Verbindungen untersucht. Eines davon ist das thermische Direktfügen, das eine stoffschlüssige Verbindung zwischen Kunststoff und Metall ermöglicht und ohne die Verwendung von Klebstoffen, Haftvermittlern oder mechanischen Verbindungshilfen auskommt.
1. Die Wirksamkeitsvoraussetzungen der Verdachtskündigung gegenüber einem Arbeitnehmer - Jana Scheilen | Seite 4-66
2. Besteuerungsinkongruenzen im Internationalen Steuerrecht - die Umsetzung der ATAD II in Form des § 4k EStG in Bezug auf hybride Gesellschaften und Betriebsstätten
- Max Peiffer | Seite 67-126
3. Der Zuzug einer Gesellschaft aus einem Drittstaat nach Deutschland - Herausforderungen durch die modifizierte Sitztheorie und Lösungsmöglichkeiten
- Anna-Luisa Görlich | Seite 127-189
4. Escalation of Commitment und seine Einflussfaktoren in der unternehmerischen Entscheidungsfindung: Ein Szenario-Experiment
- Theresa Hacke | Seite 190-245
Mathematik im ingenieurwissenschaftlichen Bachelorstudium : Lösung der Übungs- und Klausuraufgaben
(2010)
Eine Applikation für die soziale Interaktion zwischen Teams und Arbeitnehmern eines Unternehmens, welche Remote und/oder Hybrid arbeiten.
Wissen teilen, Weiterbilden, Wohlfühlen
In den letzten zwei Jahren kam es auf Grund der Corona-Pandemie, trotz der vielen Kommunikationsmöglichkeiten, im Privat-, sowie Arbeitsleben zu erheblichen sozialen Einschränkungen.
Genau hier setzt die Applikation „Companion“ an, um dem Arbeitnehmer das In-Office-Gefühl auch Remote übersetzen zu können. Der Arbeitnehmer kann mit seinen Kollegen sozialisieren, diese besser kennenlernen und wird zusätzlich durch Events und Workshops professionell weitergebildet.
Bei der Beschreibung der Studiengänge und Module durch die Hochschulen kommt der Ergebnisorientierung eine hohe Bedeutung zu. Der Beitrag beschreibt in diesem Zusammenhang zunächst die Vorgaben des europäischen Qualifikationsrahmens und der sich daraus ergebenden Fokussierung auf die Formulierung von Lernergebnissen. Der Schwerpunkt aber liegt auf praxisrelevanten Vorschlägen zu einem methodischen Vorgehen auf allen Ebenen von der Studiengangsbeschreibung über die Verteilung der Kompetenzarten über mehrere Module bis zur Wortwahl. Abschließend wird die an die Wahl der Lehr- und Lernformen geknüpfte Notwendigkeit der Veränderung der Prüfungsformen betont. Diese sollten inhaltlich und methodisch an die in den Studiengängen und Modulen beschriebenen Lernergebnisse und die Art der zu vermittelnden Kompetenzen angepasst werden. Vorabdruck des Aufsatzes. Erschienen in: Handbuch Qualität in Studium und Lehre : Evaluation nutzen, Akkreditierung sichern, Profil schärfen ( Hrsg. Winfried Benz ... . Berlin: Raabe Kapitel E 3.3 S. 1-30. ISBN 978-3-8183-0207-8 ; 3-8183-0207-3 1. Auflage des Aufsatzes unter dem Titel: Lernergebnisse - Begriffe, Zusammenhänge, Umsetzung und Erfolgsermittlung : Lernergebnisse und Kompetenzvermittlung als elementare Orientierungen des Bologna-Prozesses http://opus.bibliothek.fh-aachen.de/opus/volltexte/2007/232/
Zur Bedeutung der Workload
(2005)
zuerst erschienen In: Handbuch Qualität in Studium und Lehre : Evaluation nutzen, Akkreditierung sichern, Profil schärfen / Hrsg.: Winfried Benz .... Berlin: Raabe ISBN 978-3-8183-0207-8 ; 3-8183-0207-3 , Kapitel E.3.3 S. 1-30 Sonderdruck unter dem Titel: Schermutzki, Lernergebnisse - Begriffe, Zusammenhänge, Umsetzung und Erfolgsermittlung. Fachhochschule Aachen, 2007. 39 S.: graph. Darst. Der Beitrag beschreibt die Bedeutung und Notwendigkeit der Verwendung von Lernergebnissen als gemeinsame Sprache zwischen den verschiedenen Hochschulen und zwischen Hochschule und beruflicher Bildung, um zu einem feststellenden Validitätsurteil und zu funktionstüchtigen Anerkennungsmechanismen zu kommen. Hierbei kommt der ergebnisorientierten Beschreibung der Studiengänge und Module durch die Hochschulen große Bedeutung zu. Der Beitrag beschreibt die diesbezüglichen Grundlagen und schlägt Methoden vor, die bei der praktischen Beschreibung, der Wahl der Lehr- und Lernformen und Prüfungsformen von Studiengängen und Modulen angewendet werden können.
Bei der Einführung von Bachelor- und Masterstudiengängen sind die entsprechenden gesetzlichen Anforderungen zu beachten sowie die Anforderungen von Akkreditierungsrat und Akkreditierungsagentur. Bachelor- und Masterstudiengänge müssen modularisiert sein und in ein Leistungspunktesystem integriert. Die Leistungspunkte müssen auf der tatsächlichen Arbeitsbelastung der Studierenden basieren. Bei der Konzeption von Bachelor- und Masterstudiengängen soll zunächst eine Bedarfsermittlung erfolgen. Besteht ein Bedarf, soll ein Abschlussprofil basierend auf den Kompetenzen (besondere Beachtung verdienen die Schlüsselqualifikationen), über die der Absolvent verfügen soll, erstellt werden. Aus diesem wird ein Curriculum mit Modulen abgeleitet. Die Module werden mit Leistungspunkten versehen und auf einem Modulbogen zwecks Transparenz beschrieben. Dabei ist der Paradigmenwechsel vom Lehrenden zum Lernenden zu beachten – Lernergebnisse statt Lernziele. Die Lernergebnisse werden mittels Kompetenzen ausgedrückt. Der Studiengang wird des weiteren im Diploma Supplement, welches der Studierende bei Abschluss zusätzlich zum Zeugnis erhält, dokumentiert. ECTS ist aber auch mit weiteren Auflagen verbunden. Noch herrührend von ECTS als reinem Transfersystem müssen beim Austausch von Studierenden die Formulare ECTS Application, Learning Agreement und Transcript of Records vom Fachbereich in Abstimmung mit der jeweiligen Partnerhochschule ausgefüllt werden, (siehe Anlagen 4 und 5). Zur Information aller Studierenden sollen die folgenden Dokumente bereitstehen: Ein Ratgeber für Gaststudierende, eine Beschreibung der Hochschule und der Fachbereiche (nach bestimmten Kriterien) sowie Beschreibungen aller Module (siehe Anlage). Die Fachhochschule hat diese Informationen schon zum größten Teil auf ihrer Website dargestellt. Wichtig ist die Pflege der Daten, die von den einzelnen Fachbereichen bzw. den Lehrenden übernommen werden muss, da nur sie die Richtigkeit und Aktualität der Daten gewährleisten können.
AP 1 : Verknüpfung der organisatorischen Bildung von Modulen mit der Umstellung auf ein Leistungspunktesystem ; Abschlussbericht. Einleitung, Auswahl eines Leistungspunktesystems, Bedingungen bei der Einführung von ECTS, Verknüpfung der Kriterien Learning Outcomes und Workload, Konzeption eines Studiengangs, Erfassung der Arbeitsbelastung Studierender, Ergebnisse der Umfrage zu allgemeinen Kompetenzen, Diploma Supplement, Öffentlichkeitsarbeit
Biodiversity and the coexistence of species have puzzled and fascinated biologists since decades and is a hotspot in todays’ natural sciences. Preserving this biodiversity is a great challenge as habitats and environments underlying tremendous changes like climate change and the loss of natural habitats, which are mainly due to anthropogenic influences. The coexistence of numerous species even in homogeneous environments is a stunning feature of natural communities and has been summarized under the term ‘paradox of plankton’. Up to now, there are several mechanisms discussed, which may contribute to local and global diversity of organisms. Several interspecific trade offs have been identified maintaining the coexistence of species like their abilities regarding competition and predator avoidance, their capability to disperse in space and time, and their ability to exploit variable resources. Further, micro-evolutionary dynamics supporting the coexistence of species have been added to our knowledge, and deriving from theoretical deterministic models, non-linear dynamics which describe the temporal fluctuation of abundances of organisms. Whereas competition and predation seem to be clue structural elements within interacting organisms, the intrinsic dynamic behavior – by means of temporal changes in abundance - plays an important role regarding coexistence within a community. The present work sheds light on different factors affecting the coexistence of species using experimental microbial model systems consisting of a bacterivorous ciliate as the predator and two bacteria strains as prey organism. Additionally, another experimental setup consisting of two up to five bacteria species competing for one limiting resource was investigated. Highly controllable chemostat systems were established to exclude extrinsic disturbances. According to theoretical analyses I was able to show - experimentally and theoretically - that phenotypic plasticity of one species within a microbial one-predator-two-prey food web enlarges the range of possible coexistence of all species under different dynamic conditions, compared to a food web without phenotypic plasticity. This was accompanied by non-linear (chaotic) population dynamics within all experimental systems showing phenotypic plasticity. The experiments on the interplay of competition, predation and invasion showed that all aspects have an influence on species coexistence. Under undisturbed controlled conditions all aspects were analyzed in detail and in combination. Populations showed oscillations which were shown by quasi-chaotic attractors in phase space diagrams. Competition experiments with two up to five bacteria species competing for one limiting resource showed that all organisms were able to coexist which was mediated by species oscillations entering a regime of chaos. Besides that fact it was found, that the productivity (biomass) as well as the total cell numbers – under the same nutrition supply – increased by an increasing number of species in the experimental systems. Up to now, the occurrence of non-linear dynamics in well controlled experimental studies has been recognized several times and this phenomenon seemed to be more common in natural systems than generally assumed.
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.