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- no (255)
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.
Hotelling’s T² tests in paired and independent survey samples are compared using the traditional asymptotic efficiency concepts of Hodges–Lehmann, Bahadur and Pitman, as well as through criteria based on the volumes of corresponding confidence regions. Conditions characterizing the superiority of a procedure are given in terms of population canonical correlation type coefficients. Statistical tests for checking these conditions are developed. Test statistics based on the eigenvalues of a symmetrized sample cross-covariance matrix are suggested, as well as test statistics based on sample canonical correlation type coefficients.
Implikationen der Digitalisierung für den Finanzbereich der Unternehmung und das Rollenbild des CFO
(2017)
The link between diversity and innovation is broadly discussed in the context of research and innovation processes. Many institutions and enterprises, specifically in commerce, have already tried to establish sustainable diversity management concepts, in order to increase the diversity of their workforce in addition to establishing a corporate culture of openness. Alongside the creation of a working place where different experiences and skills are valued equally, the entrepreneurial intention is to transfer diversity into economically relevant advantages. Taking into account the potential of diversity in research and innovation processes, the project “Diversity- and Innovation Management” was incorporated within a large interdisciplinary research Cluster. The project’s purpose was to study the context between diversity and innovation in research associations and to later develop a customised management concept into an interdisciplinary research Cluster on integrative production technology with full integration. The challenge of such research associations lays in an organisational structure which is often described as being decentralised. Researchers coming from different academic disciplines, while having diverse habits, conduct research on large scientific issues and challenges. In addition, these researchers are socialised in different institutions and university chairs. Theses differences in leadership styles, business cultures and organisational strategies, follow into their research team work. Taking a closer look into the management of human resources suggests that decentral organised recruitment processes, as well as allocation of human resources, lead to a lacking overview in regard to missing competencies, perspectives and backgrounds in research networks. These circumstances are comparable to big corporate groups. While developing a management concept for research associations, these characteristics must be considered. To ensure this, the project follows a human-centred approach, which considers top-down, as well as bottom-up perspectives. This paper presents the applied mixed-method approach in the scientific issue described above. In the frame of the Cluster of Excellence “Integrative Production Technology for High-Wage Countries” research results based on quantitative, as well as qualitative studies, were presented as an application example. This paper provides a new perspective on the innovation and diversity context. Against the background of complex research organisations, the development approach of a management concept is particularly interesting.
Acknowledging that a diverse workforce could be a potential source of innovation, the current research deals with the fine details of why diversity management is central to achieving innovation in heterogeneous research groups and how this could be effectively realized in an organization. The types of heterogeneities addressed mainly include gender, qualification, academic discipline and intercultural perspectives. The type of organization being dealt with in this work is a complex association of research institutes at a technical university in Germany (RWTH Aachen University), namely a 'Cluster of Excellence', whereby several institutes of the university work collaboratively in different sub-projects. The 'Cluster of Excellence' is a part of the 'Excellence Initiative' of the German federal and state governments German Research Foundation (DFG) and German Council of Science and Humanities, with the ultimate aim of promoting cutting-edge research. To support interdisciplinary collaboration and thus the performance of the cluster, the development of a diversity and innovation management concept is presently in the conceptual phase and will be described in the frame of this paper. The 3-S-Diversity Model, composed of the three elements: skills, structure and strategy, serves as a basis for the development of the concept. The proposed concept consists of six phases; the first two phases lay the ground work by developing an understanding of the status quo on the forms of diversity in the Cluster of Excellence, the type of organizational structure of the member institutes and the varieties of specialist work cultures of the same. The third and the fourth phases build up on this foundation by means of qualitative and quantitative studies. While the third phase deals with the sensitization of the management level to the close connection between diversity and innovation; the need to manage them thereafter and find tailor-made methods of doing so, the fourth phase shall mainly focus on the mindset of the employees in this regard. The fifth phase shall consolidate the learnings and the ideas developed in the course of the first four phases into an implementable strategy. The ultimate phase shall be the implementation of this concept in the Cluster. The first three phases have been accomplished successfully and the preliminary results are already available.
Control mechanisms like Industrial Controls Systems (ICS) and its subgroup SCADA (Supervisory Control and Data Acquisition) are a prerequisite to automate industrial processes. While protection of ICS on process management level is relatively straightforward – well known office IT security mechanisms can be used – protection on field bus level is harder to achieve as there are real-time and production requirements like 24x7 to consider. One option to improve security on field bus level is to introduce controls that help to detect and to react on attacks. This paper introduces an initial set of intrusion detection mechanisms for the field bus protocol EtherCAT. To this end existing Ethernet attack vectors including packet injection and man-in-the-middle attacks are tested in an EtherCAT environment, where they could interrupt the EtherCAT network and may even cause physical damage. Based on the signatures of such attacks, a preprocessor and new rule options are defined for the open source intrusion detection system Snort demonstrating the general feasibility of intrusion detection on field bus level.
Investigation Of The Seismic Behaviour Of Infill Masonry Using Numerical Modelling Approaches
(2017)
Masonry is a widely spread construction type which is used all over the world for different types of structures. Due to its simple and cheap construction, it is used as non-structural as well as structural element. In frame structures, such as
reinforced concrete frames, masonry may be used as infill. While the bare frame itself is able to carry the loads when it comes to seismic events, the infilled frame is not able to warp freely due to the constrained movement. This restraint results in a complex interaction between the infill and the surrounding frame, which may lead to severe damage to the infill as well as the surrounding frame. The interaction is studied in different projects and effective approaches for the description of the behavior are still lacking. Experimental programs are usually quite expensive, while numerical models, once validated, do offer an efficient approach for the investigation of the interaction when horizontally loaded. In order to study the numerous parameters influencing the seismic load bearing behavior, numerical models may be used. Therefore, this contribution presents a numerical approach for the simulation of infill masonry in reinforced concrete frames. Both parts, the surrounding frame as well as the infill are represented by micro modelling approaches to correctly take into account the different types of failure. The adopted numerical model describes the inelastic behavior of the system, as indicated by the obtained results of the overall structural response as well as the formation of damage in the infilled wall. Comparison of the numerical and experimental results highlights the valuable contribution of numerical simulations in the study and design of infilled frames. As damage of the infill masonry may occur in-plane due to the interaction as well as out-of-plane due to the low vertical load, both directions of loading are investigated.
Die Verbindung der Welten dressierter Elektronen und grenzenloser Kreativität bietet ein großes Potential; zum Beispiel bei modernen Skulpturen, deren Form sich durch Motoren verändern kann. An der FH Aachen wurde ein solches Projekt verwirklicht: Eine Matrix aus Holzkugeln kann Piktogramme anzeigen, aber auch mathematische Funktionen visualisieren. In diesem Artikel beschreiben wir die clevere Ansteuerung der Motoren.
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.
In this study, polyelectrolyte-modified field-effect-based electrolyte-insulator-semiconductor (EIS) devices have been used for the label-free electrical detection of double-stranded deoxyribonucleic acid (dsDNA)molecules. The sensor-chip functionalization with a positively charged polyelectrolyte layer provides the possibility of direct adsorptive binding of negatively charged target DNA oligonucleotides onto theSiO2-chip surface.EIS sensors can be utilized as a tool to detect surface-charge changes; the electrostatic adsorption of oligonucleotides onto the polyelectrolyte layer leads to a measureable surface-potential change. Signals of 39mV have been recorded after the incubation with the oligonucleotide solution. Besides the electrochemical experiments, the successful adsorption of dsDNA onto the polyelectrolyte layer has been verified via fluorescence microscopy. The presented results demonstrate that the signal recording of EISchips, which are modified with a polyelectrolyte layer, canbe used as a favorable approach for a fast, cheap and simple detection method for dsDNA.
Field-effect EIS (electrolyte-insulator-semiconductor) sensors modified with a positively charged weak polyelectrolyte layer have been applied for the electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge. The EIS sensors are able to detect the existence of target DNA amplicons in PCR (polymerase chain reaction) samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process. Due to their miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge, those sensors can serve as possible platform for the development of label-free DNA chips. Possible application fields as well as challenges and limitations will be discussed.
To study chemical and biological processes, spatially resolved determination of the concentrations of one or more analyte species is of distinct interest. With a light-addressable potentiometric sensor (LAPS), chemical images can be created, which visualize the concentration distribution above the sensor plate. One important challenge is to achieve a good lateral resolution in order to detect events that take place in a small and limited region. LAPS utilizes a focused light spot to address the measurement region. By moving this light spot along the semiconductor sensor plate, the concentration distribution can be observed. In this study, we show that utilizing a pulse as light excitation instead of a traditionally used continuously modulated light excitation, the lateral resolution can be improved by a factor of 6 or more.
Light-addressable potentiometric sensors for quantitative spatial imaging of chemical species
(2017)
A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.
Mathematik PLuS als E-Book. Kann ein E-Book zur Ingenieursmathematik alle Lerntypen ansprechen?
(2017)
A laser-enhanced solar sail is a solar sail that is not solely propelled by solar radiation but additionally by a laser beam that illuminates the sail. This way, the propulsive acceleration of the sail results from the combined action of the solar and the laser radiation pressure onto the sail. The potential source of the laser beam is a laser satellite that coverts solar power (in the inner solar system) or nuclear power (in the outer solar system) into laser power. Such a laser satellite (or many of them) can orbit anywhere in the solar system and its optimal orbit (or their optimal orbits) for a given mission is a subject for future research. This contribution provides the model for an ideal laser-enhanced solar sail and investigates how a laser can enhance the thrusting capability of such a sail. The term ”ideal” means that the solar sail is assumed to be perfectly reflecting and that the laser beam is assumed to have a constant areal power density over the whole sail area. Since a laser beam has a limited divergence, it can provide radiation pressure at much larger solar distances and increase the radiation pressure force into the desired direction. Therefore, laser-enhanced solar sails may make missions feasible, that would otherwise have prohibitively long flight times, e.g. rendezvous missions in the outer solar system. This contribution will also analyze exemplary mission scenarios and present optimial trajectories without laying too much emphasis on the design and operations of the laser satellites. If the mission studies conclude that laser-enhanced solar sails would have advantages with respect to ”traditional” solar sails, a detailed study of the laser satellites and the whole system architecture would be the second next step
Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task
(2017)
Multi-dimensional fragility analysis of a RC building with components using response surface method
(2017)
Conventional fragility curves describe the vulnerability of the main structure under external hazards. However, in complex structures such as nuclear power plants, the safety or the risk depends also on the components associated with a system. The classical fault tree analysis gives an overall view of the failure and contains several subsystems to the main event, however, the interactions in the subsystems are not well represented. In order to represent the interaction of the components, a method suggested by Cimellaro et al. (2006) using multidimensional performance limit state functions to obtain the system fragility curves is adopted. This approach gives the possibility of deriving the cumulative fragility taking into account the interaction of the response of different components. In this paper, this approach is used to evaluate seismic risk of a representative electrical building infrastructure, including the component, of a nuclear power plant. A simplified model of the structure, with nonlinear material behavior is employed for the analysis in Abaqus©. The input variables considered are the material parameters, boundary conditions and the seismic input. The variability of the seismic input is obtained from selected ground motion time histories of spectrum compatible synthetic ccelerograms. Unlike the usual Monte Carlo methods used for the probabilistic analysis of the structure, a computationally effective response surface method is used. This method reduces the computational effort of the calculations by reducing the required
number of samples.
In times of planned obsolescence the demand for sustainability keeps growing. Ideally, a technical system is highly reliable, without failures and down times due to fast wear of single components. At the same time, maintenance should preferably be limited to pre-defined time intervals. Dispersion of load between multiple components can increase a system’s reliability and thus its availability inbetween maintenance points. However, this also results in higher investment costs and additional efforts due to higher complexity. Given a specific load profile and resulting wear of components, it is often unclear which system structure is the optimal one. Technical Operations Research (TOR) finds an optimal structure balancing availability and effort. We present our approach by designing a hydrostatic transmission system.