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Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.
In the past decade, many IS researchers focused on researching the phenomenon of Big Data. At the same time, the relevance of data protection gets more attention than ever before. In particular, since the enactment of the European General Data Protection Regulation in May 2018 Information Systems research should provide answers for protecting personal data. The article at hand presents a structuring framework for Big Data research outcome and the consideration of data protection. IS Researchers might use the framework in order to structure Big Data literature and to identify research gaps that should be addressed in the future.
In competition with other modes of transport, rail freight transport is looking for solutions to become more attractive. Short-term success can be achieved through the data-driven optimization of operations and maintenance as well as the application of novel strategies such as prescriptive maintenance. After introducing the concept of prescriptive maintenance, this paper aims to prove that vehicle-focused applications of this approach indeed have the potential to increase attractiveness. However, even greater advantages can be activated if data from the horizontal network of the vehicle is available. Drawing on the state of the art in research and technology in the field of cyber-physical systems (CPS) as well as digital twins and shadows, our work serves to design a system of systems for the horizontal interconnection of a rail vehicle and to conceptualize a draft for a digital twin of a locomotive.
Kombination quantitativer und qualitativer Methoden zur Untersuchung der Studieneingangsphase
(2019)
Die Batterie ist eine der absolut zentralen Komponenten des Elektrofahrzeugs. Die serielle Entwicklung und Produktion dieser Batterien und die Verbesserung der Leistungen wird entscheidend für den Erfolg der Elektromobilität sein. Die Batterie ist jedoch nicht das einzige elektrofahrzeugspezifische System, das neu entwickelt, umkonzipiert oder verbessert werden muss. So sind ebenso die Entwicklung der neuen Fahrzeugstruktur sowie des elektrifizierten Antriebsstranges Teil dieses Kapitels. Weiterhin wird ein Blick auf das bedeutende Thema des Thermomanagements geworfen.
Forschendes Lernen ist dazu geeignet, epistemische Neugier – definiert als Freude an neuen Erkenntnissen - anzuregen und zu befriedigen. Neben der Selbstwirksamkeit zeigt sich die Neugier als relevant für den Studienerfolg. Allerdings ist bisher nicht geklärt, in welcher Beziehung diese beiden Konstrukte zueinanderstehen.
Small Claims Regulation
(2017)
Names of individuals
(2017)
Einleitung vor § 1297
(2014)
Vorbemerkung vor § 1297
(2014)
Vorbemerkung vor § 1353
(2014)
Einleitung vor § 1297 BGB
(2011)
This chapter introduces performance and acceptance testing and describes state-of-the-art tools, methods, and instruments to assess the plant performance or realize plant acceptance testing. The status of the development of standards for performance assessment is given.
Enzyme und Biosensorik
(2018)
Enzymbasierte Biosensoren finden seit mehr als fünf Jahrzehnten einen prosperierenden Wachstumsmarkt und werden zunehmend auch in biotechnologischen Prozessen eingesetzt. In diesem Kapitel werden, ausgehend vom Sensorbegriff und typischen Kenngrößen für Biosensoren (Abschn. 18.1), elektrochemische Enzym-Biosensoren vorgestellt und deren typischen Einsatzgebiete diskutiert (Abschn. 18.2). Ein Blick über den „Tellerrand“ hinaus zeigt alternative Transduktorprinzipien (Abschn. 18.3) und führt abschließend in aktuelle Forschungstrends ein (Abschn. 18.4).
Vorbemerkung vor § 1353
(2017)
Einleitung vor § 1297
(2017)
Vorbemerkung vor § 1297
(2017)
Grenzenlose Liebe
(2008)
Kombination qualitativer und quantitativer Methoden zur Untersuchung der Studieneinstiegsphase
(2019)
Mit Hilfe der Kombination von qualitativen und quantitativen Verfahren zielen Mixed-Methods Ansätze darauf ab, einen vertieften Einblick in komplexe Gegenstände zu gewinnen. In der Hochschulbildungsforschung finden sie zunehmend Anklang, da sie besonders geeignet erscheinen, das vielschichtige Wirkungsgefüge zu erfassen, das das Lehren und Lernen an Hochschulen auszeichnet. Der Beitrag geht den Potenzialen von Mixed-Methods Ansätzen am Beispiel einer Studie zur Studieneingangsphase nach, die den Wirkungszusammenhang zwischen der Nutzung von Angeboten für den Studieneinstieg und der Entwicklung von Studierfähigkeit untersucht. Der Beitrag veranschaulicht die Integration von Methoden und Ergebnissen, um Chancen und Grenzen von Mixed-Methods Studien für die Hochschulbildungsforschung zu diskutieren.
Die Studiengangentwicklung ist ein komplexer Prozess, in dem strukturelle Vorgaben beachtet, viele unterschiedliche Akteure/-innen einbezogen und nicht zuletzt angemessene didaktische Lösungen zum Erreichen der angestrebten Lernergebnisse gefunden werden müssen. Der vorliegende Text nimmt besonders den letzten Punkt in den Blick: Er zeigt, wie Studiengangentwicklung zu einem Thema der (Hochschul-)Didaktik geworden ist und wie sich der didaktische Ansatz von struktur- und prozessorientierten Ansätzen unterscheidet, aber auch, wie er mit diesen zusammenhängt. An einem Beispiel aus dem Wirtschaftsingenieurwesen wird veranschaulicht, was didaktische Studiengangentwicklung in der Praxis ausmacht und wie eine konkrete Implementierung verlaufen kann. Auf dieser Grundlage wird abschließend ein erweitertes Modell der didaktischen Studiengangentwicklung vorgeschlagen.
The light-addressable potentiometric sensor (LAPS) and scanning photo-induced impedance microscopy (SPIM) are two closely related methods to visualise the distributions of chemical species and impedance, respectively, at the interface between the sensing surface and the sample solution. They both have the same field-effect structure based on a semiconductor, which allows spatially resolved and label-free measurement of chemical species and impedance in the form of a photocurrent signal generated by a scanning light beam. In this article, the principles and various operation modes of LAPS and SPIM, functionalisation of the sensing surface for measuring various species, LAPS-based chemical imaging and high-resolution sensors based on silicon-on-sapphire substrates are described and discussed, focusing on their technical details and prospective applications.
Epilepsy
(2010)
The network approach towards the analysis of the dynamics of complex systems has been successfully applied in a multitude of studies in the neurosciences and has yielded fascinating insights. With this approach, a complex system is considered to be composed of different constituents which interact with each other. Interaction structures can be compactly represented in interaction networks. In this contribution, we present a brief overview about how interaction networks are derived from multivariate time series, about basic network characteristics, and about challenges associated with this analysis approach.
The development prospects of the world markets for petroleum and other liquid fuels are diverse and partly contradictory. However, comprehensive changes for the energy supply of the future are essential. Notwithstanding the fact that there are still very large deposits of energy resources from a geological point of view, the finite nature of conventional oil reserves is indisputable. To reduce our dependence on oil, the EU, the USA, and other major economic zones rely on energy diversification. For this purpose, alternative materials and technologies are being sought, and is most obvious in the transport sector. The objective is to progressively replace fossil fuels with renewable and more sustainable fuels. In this respect, biofuels have a pre-eminent position in terms of their capability of blending with fossil fuels and being usable in existing cars without substantial modification. Ethanol can be considered as the primary renewable liquid fuel. In this chapter enzymes, micro-organisms, and processes for ethanol production based on renewable resources are described.
In comparison to crude oil, biorefinery raw materials are challenging in concerns of transport and storage. The plant raw materials are more voluminous, so that shredding and compacting usually are necessary before transport. These mechanical processes can have a negative influence on the subsequent biotechnological processing and shelf life of the raw materials. Various approaches and their effects on renewable raw materials are shown. In addition, aspects of decentralized pretreatment steps are discussed. Another important aspect of pretreatment is the varying composition of the raw materials depending on the growth conditions. This problem can be solved with advanced on-site spectrometric analysis of the material.
The terms bioeconomy and biorefineries are used for a variety of processes and developments. This short introduction is intended to provide a delimitation and clarification of the terminology as well as a classification of current biorefinery concepts. The basic process diagrams of the most important biorefinery types are shown.
Nanotubular tobacco mosaic virus (TMV) particles and RNA-free lower-order coat protein (CP) aggregates have been employed as enzyme carriers in different diagnostic layouts and compared for their influence on biosensor performance. In the following, we describe a label-free electrochemical biosensor for improved glucose detection by use of TMV adapters and the enzyme glucose oxidase (GOD). A specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CP aggregates was achieved via bioaffinity binding. Glucose sensors with adsorptively immobilized [SA]-GOD, and with [SA]-GOD cross-linked with glutardialdehyde, respectively, were tested in parallel on the same sensor chip. Comparison of these sensors revealed that TMV adapters enhanced the amperometric glucose detection remarkably, conveying highest sensitivity, an extended linear detection range and fastest response times. These results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for applications in biosensorics and biochips. Here, we describe the fabrication and use of amperometric sensor chips combining an array of circular Pt electrodes, their loading with GOD-modified TMV nanotubes (and other GOD immobilization methods), and the subsequent investigations of the sensor performance.
Sampling of dry surfaces for microorganisms is a main component of microbiological safety and is of critical importance in many fields including epidemiology, astrobiology as well as numerous branches of medical and food manufacturing. Aspects of biofilm formation, analysis and removal in aqueous solutions have been thoroughly discussed in literature. In contrast, microbial communities on air-exposed (dry) surfaces have received significantly less attention. Diverse surface sampling methods have been developed in order to address various surfaces and microbial groups, but they notoriously show poor repeatability, low recovery rates and suffer from lack of mutual consistency. Quantitative sampling for viable microorganisms represents a particular challenge, especially on porous and irregular surfaces. Therefore, it is essential to examine in depth the factors involved in microorganisms’ recovery efficiency and accuracy depending on the sampling technique used. Microbial colonization, retention and community composition on different dry surfaces are very complex and rely on numerous physicochemical and biological factors. This study is devoted to analyze and review the (a) physical phenomena and intermolecular forces relevant for microbiological surface sampling; (b) challenges and problems faced by existing sampling methods for viable microorganisms and (c) current directions of engineering and research aimed at improvement of quality and efficiency of microbiological surface sampling.
For pelvic floor disorders that cannot be treated with non-surgical procedures, minimally invasive surgery has become a more frequent and safer repair procedure. More than 20 million prosthetic meshes are implanted each year worldwide. The simple selection of a single synthetic mesh construction for any level and type of pelvic floor dysfunctions without adopting the design to specific requirements increase the risks for mesh related complications. Adverse events are closely related to chronic foreign body reaction, with enhanced formation of scar tissue around the surgical meshes, manifested as pain, mesh erosion in adjacent structures (with organ tissue cut), mesh shrinkage, mesh rejection and eventually recurrence. Such events, especially scar formation depend on effective porosity of the mesh, which decreases discontinuously at a critical stretch when pore areas decrease making the surgical reconstruction ineffective that further augments the re-operation costs. The extent of fibrotic reaction is increased with higher amount of foreign body material, larger surface, small pore size or with inadequate textile elasticity. Standardized studies of different meshes are essential to evaluate influencing factors for the failure and success of the reconstruction. Measurements of elasticity and tensile strength have to consider the mesh anisotropy as result of the textile structure. An appropriate mesh then should show some integration with limited scar reaction and preserved pores that are filled with local fat tissue. This chapter reviews various tissue reactions to different monofilament mesh implants that are used for incontinence and hernia repairs and study their mechanical behavior. This helps to predict the functional and biological outcomes after tissue reinforcement with meshes and permits further optimization of the meshes for the specific indications to improve the success of the surgical treatment.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.
Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries.
Mechanical forces/tensile stresses are critical determinants of cellular growth, differentiation and migration patterns in health and disease. The innovative “CellDrum technology” was designed for measuring mechanical tensile stress of cultured cell monolayers/thin tissue constructs routinely. These are cultivated on very thin silicone membranes in the so-called CellDrum. The cell layers adhere firmly to the membrane and thus transmit the cell forces generated. A CellDrum consists of a cylinder which is sealed from below with a 4 μm thick, biocompatible, functionalized silicone membrane. The weight of cell culture medium bulbs the membrane out downwards. Membrane indentation is measured. When cells contract due to drug action, membrane, cells and medium are lifted upwards. The induced indentation changes allow for lateral drug induced mechanical tension quantification of the micro-tissues. With hiPS-induced (human) Cardiomyocytes (CM) the CellDrum opens new perspectives of individualized cardiac drug testing. Here, monolayers of self-beating hiPS-CMs were grown in CellDrums. Rhythmic contractions of the hiPS-cells induce membrane up-and-down deflections. The recorded cycles allow for single beat amplitude, single beat duration, integration of the single beat amplitude over the beat time and frequency analysis. Dose effects of agonists and antagonists acting on Ca2+ channels were sensitively and highly reproducibly observed. Data were consistent with published reference data as far as they were available. The combination of the CellDrum technology with hiPS-Cardiomyocytes offers a fast, facile and precise system for pharmacological and toxicological studies. It allows new preclinical basic as well as applied research in pharmacolgy and toxicology.
Lepautre
(2015)
Ranson, Pierre
(2017)
Patte, Pierre
(2017)
Peyre, Antoine-Francois
(2017)
Peyre, Marie-Josephe
(2017)
Digitalisierung bezeichnet die Nutzung großer Datenmengen, die zu einer umfassenden Vernetzung aller Bereiche der Wirtschaft und Gesellschaft führen wird (BMWi, 2015 und ähnlich Köhler/Wollschläger, 2014: 79). Sie umfasst die Erhebung von analogen Informationen („Big Data“ in einem engen Sinne; z.B. O´Leary, 2013), ihre Speicherung in einem digitaltechnischen System (lokale Speicherung oder „Cloud Computing“ durch die Weiterentwickelung des Internets; z.B. Hashem et al., 2015: 101), die Analyse und Interpretation sowie den Transfer in andere Systeme („Internet der Dinge“ bzw. „Internet of Things“; z.B. Ashton, 2009).
The methodological discourse of mixed-methods research offers general procedures to combine quantitative and qualitative methods for investigating complex fields of research such as higher education. However, integrating different methods still poses considerable challenges. To move beyond general recommendations for mixed-methods research, this chapter proposes to discuss methodological issues with respect to a particular research domain. Taking current studies on the transition to higher education as an example, the authors first provide an overview of the potentials and limitations of quantitative and qualitative methods in the research domain. Second, they show the need for a conceptual framework grounded in the theory of the research object to guide the integration of different methods and findings. Finally, an example study that investigates transition with regard to the interplay of the individual student and the institutional context serves to illustrate the guiding role of theory. The framework integrates different theoretical perspectives on transition, informs the selection of the research methods, and defines the nexus of the two strands that constitute the mixed-methods design. As the interplay of individual and context is of concern for teaching and learning in general, the example presented may be fruitful for the wider field of higher education research.
Pelvic floor dysfunction (PFD) is characterized by the failure of the levator ani (LA) muscle to maintain the pelvic hiatus, resulting in the descent of the pelvic organs below the pubococcygeal line. This chapter adopts the modified Humphrey material model to consider the effect of the muscle fiber on passive stretching of the LA muscle. The deformation of the LA muscle subjected to intra-abdominal pressure during Valsalva maneuver is compared with the magnetic resonance imaging (MRI) examination of a nulliparous female. Numerical result shows that the fiber-based Humphrey model simulates the muscle behavior better than isotropic constitutive models. Greater posterior movement of the LA muscle widens the levator hiatus due to lack of support from the anococcygeal ligament and the perineal structure as a consequence of birth-related injury and aging. Old and multiparous females with uncontrolled urogenital and rectal hiatus tend to develop PFDs such as prolapse and incontinence.
Die Fallstudie FAYMONVILLE beschäftigt sich damit, wie es dem Familienunternehmen Faymonville aus Ostbelgien gelungen ist, sich zu einem der führenden Hersteller in seiner Branche zu entwickeln. Die gezielte Identifizierung neuer Märkte, die Fokussierung auf die relevanten Kundenbedürfnisse und eine konsistente Produktpolitik mit einem abgestimmten Fertigungskonzept legen die Grundsteine für den Erfolg. Das vorliegende Fallbeispiel zeigt anschaulich, wie es gelingen kann, den prinzipiellen Widerspruch zwischen wirtschaftlicher und kundenindividueller Fertigung erfolgreich aufzulösen.
In the future, we expect manufacturing companies to follow a new paradigm that mandates more automation and autonomy in production processes. Such smart factories will offer a variety of production technologies as services that can be combined ad hoc to produce a large number of different product types and variants cost-effectively even in small lot sizes. This is enabled by cyber-physical systems that feature flexible automated planning methods for production scheduling, execution control, and in-factory logistics.
During development, testbeds are required to determine the applicability of integrated systems in such scenarios. Furthermore, benchmarks are needed to quantify and compare system performance in these industry-inspired scenarios at a comprehensible and manageable size which is, at the same time, complex enough to yield meaningful results.
In this chapter, based on our experience in the RoboCup Logistics League (RCLL) as a specific example, we derive a generic blueprint for how a holistic benchmark can be developed, which combines a specific scenario with a set of key performance indicators as metrics to evaluate the overall integrated system and its components.
Cyber-physical systems are ever more common in manufacturing industries. Increasing their autonomy has been declared an explicit goal, for example, as part of the Industry 4.0 vision. To achieve this system intelligence, principled and software-driven methods are required to analyze sensing data, make goal-directed decisions, and eventually execute and monitor chosen tasks. In this chapter, we present a number of knowledge-based approaches to these problems and case studies with in-depth evaluation results of several different implementations for groups of autonomous mobile robots performing in-house logistics in a smart factory. We focus on knowledge-based systems because besides providing expressive languages and capable reasoning techniques, they also allow for explaining how a particular sequence of actions came about, for example, in the case of a failure.
In this paper we propose a stochastic programming method to analyse limit and shakedown of structures under uncertainty condition of strength. Based on the duality theory, the shakedown load multiplier formulated by the kinematic theorem is proved actually to be the dual form of the shakedown load multiplier formulated by static theorem. In this investigation a dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) with three-node linear triangular elements is used for structural analysis.
The coupling of charged molecules, nanoparticles, and more generally, inorganic/organic nanohybrids with semiconductor field-effect devices based on an electrolyte–insulator–semiconductor (EIS) system represents a very promising strategy for the active tuning of electrochemical properties of these devices and, thus, opening new opportunities for label-free biosensing by the intrinsic charge of molecules. The simplest field-effect sensor is a capacitive EIS sensor, which represents a (bio-)chemically sensitive capacitor. In this chapter, selected examples of recent developments in the field of label-free biosensing using nanomaterial-modified capacitive EIS sensors are summarized. In the first part, we present applications of EIS sensors modified with negatively charged gold nanoparticles for the label-free electrostatic detection of positively charged small proteins and macromolecules, for monitoring the layer-by-layer formation of oppositely charged polyelectrolyte (PE) multilayers as well as for the development of an enzyme-based biomolecular logic gate. In the second part, examples of a label-free detection by means of EIS sensors modified with a positively charged weak PE layer are demonstrated. These include electrical detection of on-chip and in-solution hybridized DNA (deoxyribonucleic acid) as well as an EIS sensor with pH-responsive weak PE/enzyme multilayers for enhanced field-effect biosensing.
Bio-feedstocks
(2011)
Mathematik PLuS als E-Book. Kann ein E-Book zur Ingenieursmathematik alle Lerntypen ansprechen?
(2017)
Neben dem durch Unfälle und Krankheiten entstehenden menschlichen Leids und der daraus resultierenden moralischen Verpflichtung, sich und seine Mitmenschen vor Schaden zu bewahren, ist der Arbeits- und Gesundheitsschutz auch ein Gebot wirtschaftlichen Handelns, da Arbeitsunfälle und Berufskrankheiten Ausfallzeiten und Kosten verursachen. So gehören Arbeits- und Gesundheitsschutz zu den wichtigen Aufgaben eines Unternehmens.
Kalkulation
(2016)
Das Kapitel behandelt die Kosten- und Preisermittlung, die Kostenvorgabe und Kostenkontrolle.
Der Angebotspreis wird aufgeschlüsselt in die Einzelkosten der Teilleistungen, die Baustellengemeinkosten, die Allgemeinen Geschäftskosten und einen Zuschlag für Wagnis und Gewinn. Auf der Basis der Angebotskalkulation werden die Vorgaben für die Kostenkontrolle entwickelt.
Betriebsorganisation
(2016)
Das Kapitel behandelt, ausgehend von Begriffen und Aufgaben der Betriebsorganisation, die Aufbau- und Ablauforganisation der Bauunternehmung sowie die Gestaltung einer Projekt-organisation. Es folgt eine Darstellung der Managementsysteme für Qualität, Umwelt und Arbeitsschutz, die sich zunehmend als sog. integrierte Managementsysteme (IMS) auch in Bauunternehmen etablieren. Grundlagen des Personalmanagements und des betrieblichen Rechnungswesens, die für eine(n) Baubetriebler(in) relevant sein können, ergänzen das Kap. Betriebsorganisation. Den Abschluss bilden Hinweise zum Berichtswesen der Baustelle.
Schalung und Gerüste
(2016)
Systemschalungen und Systemgerüste haben den Baustellenbetrieb in vielen Bereichen sehr vereinfacht. Dennoch sind Kenntnisse in diesen Feldern für eine erfolgreiche und effektive Bauleitung unverzichtbar. In diesem Kapitel werden Hinweise und Empfehlungen für die Bemessung und Einsatz von Schalungen, Trag- und Arbeitsgerüsten für den Baustellenbetrieb gegeben.
Boden, Baugrube, Verbau
(2016)
Die Lösung den Baugrund betreffender Fragestellungen beginnen i. d. R. mit der Durchführung von Baugrunderkundungen, um alle notwendigen Parameter zu erhalten, die für die Planung und Durchführung von Bauvorhaben notwendig sind. Im Folgenden werden die wichtigsten Erkundungen in Abhängigkeit der erforderlichen Güteklasse der Proben beschrieben und vorgestellt.
Baumaschinen
(2016)