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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.
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.
Peyre, Marie-Josephe
(2017)
Peyre, Antoine-Francois
(2017)
Patte, Pierre
(2017)
Ranson, Pierre
(2017)
Names of individuals
(2017)
Small Claims Regulation
(2017)
Gearboxes are mechanical transmission systems that provide speed and torque conversions from a rotating power source. Being a central element of the drive train, they are relevant for the efficiency and durability of motor vehicles. In this work, we present a new approach for gearbox design: Modeling the design problem as a mixed-integer nonlinear program (MINLP) allows us to create gearbox designs from scratch for arbitrary requirements and—given enough time—to compute provably globally optimal designs for a given objective. We show how different degrees of freedom influence the runtime and present an exemplary solution.
Mathematik PLuS als E-Book. Kann ein E-Book zur Ingenieursmathematik alle Lerntypen ansprechen?
(2017)
Einleitung vor § 1297
(2017)
Vorbemerkung vor § 1297
(2017)
Vorbemerkung vor § 1353
(2017)
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.
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.
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.
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.
Engineers and therefore engineering education are challenged by the increasing complexity of questions to be answered globally. The education of future engineers therefore has to answer with curriculums that build up relevant skills. This chapter will give an example how to bring engineering and social responsibility successful together to build engineers of tomorrow. Through the integration of gender and diversity perspectives, engineering research and teaching is expanded with new perspectives and contents providing an important potential for innovation. Aiming on the enhancement of engineering education with distinctive competencies beyond technical expertise, the teaching approach introduced in the chapter represents key factors to ensure that coming generations of engineers will be able to meet the requirements and challenges a changing globalized world holds for them. The chapter will describe how this approach successfully has been implemented in the curriculum in engineering of a leading technical university in Germany.
Künstlerische Einlassungen auf den öffentlichen Raum folgten lange Zeit dem Prinzip des subkulturellen Widerstands. Nur in dem strategischen, invasiven Akt der Intervention sah man noch die Möglichkeit einer weitgreifenden Kritik am kulturellen System. Begriffe wie Cultural Hacking, Guerilla Marketing, Adbusting, Konsumguerilla oder parasitäre Strategien prägten eine rebellische Auffassung der künstlerischen Einmischung. Gleichzeitig konnten diese Haltungen aufgrund ihres rebellischen Chics mühelos von dem, was sie kritisierten, aufgenommen und vereinnahmt werden. Künstlerisches Handeln verharrt jedoch nicht in der Pose des Widerständigen, sondern arbeitet kontinuierlich an der Problematisierung und Gestaltung der öffentlichen Wahrnehmung. Viele Interventionen der Gegenwartskunst weisen unterschiedliche Grade der Ästhetisierung, der Partizipation und der Kooperation in der Auseinandersetzung mit dem öffentlichen Raum auf. Das wache Agieren im urbanen Kontext, die Irritation von Erwartungshaltungen, Fake und Desillusionierungsarbeit verstehen sich als künstlerische Arbeit an der Sensibilisierung der Wahrnehmung.
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.
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.
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).
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.
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.
Around 60% of the paper worldwide is made from recovered paper. Especially adhesive contaminants, so called stickies, reduce paper quality. To remove stickies but at the same time keep as many valuable fibers as possible, multi-stage screening systems with several interconnected pressure screens are used. When planning such systems, suitable screens have to be selected and their interconnection as well as operational parameters have to be defined considering multiple conflicting objectives. In this contribution, we present a Mixed-Integer Nonlinear Program to optimize system layout, component selection and operation to find a suitable trade-off between output quality and yield.
Highly competitive markets paired with tremendous production volumes demand particularly cost efficient products. The usage of common parts and modules across product families can potentially reduce production costs. Yet, increasing commonality typically results in overdesign of individual products. Multi domain virtual prototyping enables designers to evaluate costs and technical feasibility of different single product designs at reasonable computational effort in early design phases. However, savings by platform commonality are hard to quantify and require detailed knowledge of e.g. the production process and the supply chain. Therefore, we present and evaluate a multi-objective metamodel-based optimization algorithm which enables designers to explore the trade-off between high commonality and cost optimal design of single products.
The energy-efficiency of technical systems can be improved by a systematic design approach. Technical Operations Research (TOR) employs methods known from Operations Research to find a global optimal layout and operation strategy of technical systems. We show the practical usage of this approach by the systematic design of a decentralized water supply system for skyscrapers. All possible network options and operation strategies are modeled by a Mixed-Integer Nonlinear Program. We present the optimal system found by our approach and highlight the energy savings compared to a conventional system design.
Im Rahmen der digitalen Transformation werden innovative Technologiekonzepte, wie z. B. das Internet der Dinge und Cloud Computing als Treiber für weitreichende Veränderungen von Organisationen und Geschäftsmodellen angesehen. In diesem Kontext ist Robotic Process Automation (RPA) ein neuartiger Ansatz zur Prozessautomatisierung, bei dem manuelle Tätigkeiten durch sogenannte Softwareroboter erlernt und automatisiert ausgeführt werden. Dabei emulieren Softwareroboter die Eingaben auf der bestehenden Präsentationsschicht, so dass keine Änderungen an vorhandenen Anwendungssystemen notwendig sind. Die innovative Idee ist die Transformation der bestehenden Prozessausführung von manuell zu digital, was RPA von traditionellen Ansätzen des Business Process Managements (BPM) unterscheidet, bei denen z. B. prozessgetriebene
Anpassungen auf Ebene der Geschäftslogik notwendig sind. Am Markt werden bereits unterschiedliche RPA-Lösungen als Softwareprodukte angeboten. Gerade bei operativen Prozessen mit sich wiederholenden Verarbeitungsschritten in unterschiedlichen Anwendungssystemen sind gute Ergebnisse durch RPA dokumentiert, wie z. B. die Automatisierung von 35 % der Backoffice-Prozesse bei Telefonica. Durch den vergleichsweise niedrigen Implementierungsaufwand verbunden mit einem hohen Automatisierungspotenzial ist in der Praxis (z. B. Banken, Telekommunikation, Energieversorgung) ein hohes Interesse an RPA vorhanden. Der Beitrag diskutiert RPA als innovativen Ansatz zur
Prozessdigitalisierung und gibt konkrete Handlungsempfehlungen für die Praxis. Dazu wird zwischen modellgetriebenen und selbstlernenden Ansätzen unterschieden. Anhand von generellen Architekturen von RPA-Systemen werden Anwendungsszenarien sowie deren Automatisierungspotenziale, aber auch Einschränkungen, diskutiert. Es folgt ein strukturierter Marktüberblick ausgewählter RPA-Produkte. Anhand von drei konkreten Anwendungsbeispielen wird die Nutzung von RPA in der Praxis verdeutlicht.
Nutzen und Rahmenbedingungen 5 informationsgetriebener Geschäftsmodelle des Internets der Dinge
(2018)
Im Kontext der zunehmenden Digitalisierung wird das Internet der Dinge (englisch: Internet of Things, IoT) als ein technologischer Treiber angesehen, durch den komplett neue Geschäftsmodelle im Zusammenspiel unterschiedlicher Akteure entstehen können. Identifizierte Schlüsselakteure sind unter anderem traditionelle Industrieunternehmen, Kommunen und Telekommunikationsunternehmen. Letztere sorgen mit der Bereitstellung von Konnektivität dafür, dass kleine Geräte mit winzigen Batterien nahezu überall und direkt an das Internet angebunden werden können. Es sind schon viele IoT-Anwendungsfälle auf dem Markt, die eine Vereinfachung für Endkunden darstellen, wie beispielsweise Philips Hue Tap. Neben Geschäftsmodellen basierend auf Konnektivität besteht ein großes Potenzial für informationsgetriebene Geschäftsmodelle, die bestehende Geschäftsmodelle unterstützen sowie weiterentwickeln können. Ein Beispiel dafür ist der IoT-Anwendungsfall Park and Joy der Deutschen Telekom AG, bei dem Parkplätze mithilfe von Sensoren vernetzt und Autofahrer in Echtzeit über verfügbare Parkplätze informiert werden. Informationsgetriebene Geschäftsmodelle können auf Daten aufsetzen, die in IoT-Anwendungsfällen erzeugt werden. Zum Beispiel kann ein Telekommunikationsunternehmen Mehrwert schöpfen, indem es aus Daten entscheidungsrelevantere Informationen – sogenannte Insights – ableitet, die zur Steigerung der Entscheidungsagilität genutzt werden. Außerdem können Insights monetarisiert werden. Die Monetarisierung von Insights kann nur nachhaltig stattfinden, wenn sorgfältig gehandelt wird und Rahmenbedingungen berücksichtigt werden. In diesem Kapitel wird das Konzept informationsgetriebener Geschäftsmodelle erläutert und anhand des konkreten Anwendungsfalls Park and Joy verdeutlicht. Darüber hinaus werden Nutzen, Risiken und Rahmenbedingungen diskutiert.
Prozessorientierte Messung der Customer Experience am Beispiel der Telekommunikationsindustrie
(2018)
Hohe Wettbewerbsintensität und gestiegene Kundenanforderungen erfordern bei Telekommunikationsunternehmen eine aktive Gestaltung der Customer Experience (CX). Ein wichtiger Aspekt dabei ist die CX-Messung. Traditionelle Zufriedenheitsmessungen sind oft nicht ausreichend, um die Kundenerfahrung in komplexen Prozessen vollständig zu erfassen. Daher wird in diesem Kapitel eine prozessübergreifende Referenzlösung zur CX-Messung am Beispiel der Telekommunikationsindustrie vorgeschlagen. Ausgangspunkt ist ein industriespezifisches Prozessmodell, das sich an dem Referenzmodell eTOM orientiert. Dieses wird um Messpunkte erweitert, die Schwachstellen in Bezug auf die CX identifizieren. Für die erkannten Schwachstellen werden über eine Referenzmatrix mögliche Auslöser abgeleitet und anhand von typischen Geschäftsfallmengen bewertet. Somit ist eine direkte Zuordnung und Erfolgsmessung konkreter Maßnahmen zur Behebung der Schwachstellen möglich. Die so entwickelte Referenzlösung wurde im Projekt K1 bei der Deutschen Telekom erfolgreich umgesetzt. Details zur Umsetzung werden als Fallstudien dargestellt.
Because of customer churn, strong competition, and operational inefficiencies, the telecommunications operator ME Telco (fictitious name due to confidentiality) launched a strategic transformation program that included a Business Process Management (BPM) project. Major problems were silo-oriented process management and missing cross-functional transparency. Process improvements were not consistently planned and aligned with corporate targets. Measurable inefficiencies were observed on an operational level, e.g., high lead times and reassignment rates of the incident management process.
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.
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.
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.