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In the last decades, several hundred exoplanets could be detected thanks to space-based observatories, namely CNES’ COROT and NASA’s Kepler. To expand this quest ESA plans to launch CHEOPS as the f irst small class mission in the cosmic visions program (S1) and PLATO as the 3rd medium class mission, so called M3 . PLATO’s primary objective is the detection of Earth like Exoplanets orbiting solar type stars in the habitable zone and characterisation of their bulk properties. This is possible by precise lightcurve measurement via 34 cameras. That said it becomes obvious that accurate pointing is key to achieve the required signal to noise ratio for positive transit detection. The paper will start with a comprehensive overview of PLATO’s mission objectives and mission architecture. Hereafter, special focus will be devoted to PLATO’s pointing requirements. Understanding the very nature of PLATO’s pointing requirements is essential to derive a design baseline to achieve the required performance. The PLATO frequency domain is of particular interest, ranging from 40 mHz to 3 Hz. Due to the very different time-scales involved, the spectral pointing requirement is decomposed into a high frequency part dominated by the attitude control system and the low frequency part dominated by the thermo-elastic properties of the spacecraft’s configuration. Both pose stringent constraints on the overall design as well as technology properties to comply with the derived requirements and thus assure a successful mission.
Enzymatic hydrolysis of lignocellulosic material plays an important role in the classical biorefinery approach. Apart from the pretreatment of the raw material, hydrolysis is the basis for the conversion of the cellulose and hemicellulose fraction into fermentable sugars. After hydrolysis, usually a solid-liquid separation takes place, in order to separate the residual plant material from the sugar-rich fraction, which can be subsequently used in a fermentation step. In order to factor out the separation step, the usage of in alginate immobilized crude cellulose fiber beads (CFBs) were evaluated. Pretreated cellulose fibers are incorporated in an alginate matrix together with the relevant enzymes. In doing so, sugars diffuse trough the alginate matrix, allowing a simplified delivery into the surrounding fluid. This again reduces product inhibition of the glucose on the enzyme catalysts. By means of standardized bead production the hydrolysis in lab scale was possible. First results show that liberation of glucose and xylose is possible, allowing a maximum total sugar yield of 75 %.
In order to efficiently convert lignocellulose, it is often necessary to conduct a pretreatment. The biomass considered in this study typically comprises of agricultural and horticultural residues, as well as beechwood. A very environmentally friendly method, namely, fungal pretreatment using white-rot fungi, leads to an enhanced enzymatic hydrolysis. In contrast to other processes presented, the energy input is extremely low. However, the fungal growth on the lignocellulosic substrates takes several weeks at least in order to be effective. Thus, the reduction of chemicals and energy for thermal processing is a target of our current research. Liquid hot water (LHW) and solvent-based pretreatment (OrganoSolv) require more complex equipment, as they depend on high temperatures (160 – 180 °C) and enhanced pressure (up to 20 bar). However, they prove to be promising processes in regard to the fractioning of lignocellulose. For optimal lignin recovery the parameters differ from those established in cellulose extraction. A novel screening system scaled down to a reaction volume of 100 mL has been developed and successfully tested for this purpose.
Electromicrobial engineering is an emerging, highly interdisciplinary research area linking bioprocesses with electrochemistry. In this work, microbial electrosynthesis (MES) of biobutanol is carried out during acetone-butanol-ethanol (ABE) fermentations with Clostridium acetobutylicum. A constant electric potential of −600mV (vs. Ag/AgCl) with simultaneous addition of the soluble redox mediator neutral red is used in order to study the electron transfer between the working electrode and the bacterial cells. The results show an earlier initiation of solvent production for all fermentations with applied potential compared to the conventional ABE fermentation. The f inal butanol concentration can be more than doubled by the application of a negative potential combined with addition of neutral red. Moreover a higher biofilm formation on the working electrode compared to control cultivations has been observed. In contrast to previous studies, our results also indicate that direct electron transfer (DET) might be possible with C. acetobutylicum. The presented results make microbial butanol production economically attractive and therefore support the development of sustainable production processes in the chemical industry aspired by the “Centre for resource-efficient chemistry and raw material change” as well as the the project “NanoKat” working on nanostructured catalysts in Kaiserslautern.
This paper describes the procedure on the evaluation of the masonry chapter for the next generation of Eurocode 8, the European Standard for earthquake-resistant design. In CEN, TC 250/SC8, working group WG 1 has been established to support the subcommittee on the topic of masonry on both design of new structures (EN1998-1) and assessment of existing structures (EN1998-3). The aim is to elaborate suggestions for amendments which fit the current state of the art in masonry and earthquake-resistant design. Focus will be on modelling, simplified methods, linear-analysis (q-values, overstrength-values), nonlinear procedures, out-of-plane design as well as on clearer definition of limit states. Beside these, topics related to general material properties, reinforced masonry, confined masonry, mixed structures and non-structural infills will be covered too. This paper presents the preliminary work and results up to the submission date.
Development of a subject-oriented reference process model for the telecommunications industry
(2016)
Generally the usage of reference models can be structured top-down or bottom-up. The practical need of agile change and flexible organizational implementation requires a consistent mapping to an operational level. In this context, well-established reference process models are typically structured top-down. The subject-oriented Business Process Management (sBPM) offers a modeling concept that is structured bottom-up and concentrates on the process actors on an
operational level. This paper applies sBPM to the enhanced Telecom Operations Map (eTOM), a well-accepted reference process model in the telecommunications industry. The resulting design artifact is a concrete example for a combination of a bottom-up and top-down developed reference model. The results are evaluated and confirmed in practical context through the involvement of the industry body TMForum.
Engineers are of particular importance for the societies of tomorrow. The big social challenges society has to cope with in future, can only be mastered, if engineers link the development and innovation process closely with the requirements of people. As a result, in the frame of the innovation process engineers have to design and develop products for diverse users. Therefore, the consideration of diversity in this process is a core competence engineers should have. Implementing the consideration of diverse requirements into product design is also linked to the development of sustainable products and thus leads to social responsible research and development, the core concept formulated by the EU.
For this reason, future engineers should be educated to look at the technical perspectives of a problem embedded in the related questions within societies they are developing their artefacts for. As a result, the aim of teaching engineering should be to prepare engineers for these requirements and to draw attention to the diverse needs in a globalized world.
To match the competence profiles of future engineers to the global challenges and the resulting social responsibility, RWTH Aachen University, one of the leading technical universities in Germany, has established the bridging professorship “Gender and Diversity in Engineering” (GDI) which educates engineers with an interdisciplinary approach to expand engineering limits. The interdisciplinary teaching concept of the research group pursues an approach which imparts an application oriented Gender and Diversity expertise to future engineers. In the frame of an established teaching concept, which is a result of experiences and expertise of the research group, students gain theoretical knowledge about Gender and Diversity and learn how to transfer their knowledge into their later field of action.
In the frame of the conference the institutional approach will be presented as well as the teaching concept which will be introduced by concrete course examples.
Future engineers are increasingly confronted with the so-called Megatrends which are the big social challenges society has to cope with. These Megatrends, such as “Silver Society”, “Globalization”, “Mobility” and “Female Shift” require an application-oriented perspective on Diversity especially in the engineering field. Therefore, it is necessary to enable future engineers not only to look at the technical perspectives of a problem, but also to be able to see the related questions within societies they are developing their artefacts for. The aim of teaching engineering should be to prepare engineers for these requirements and to draw attention to the diverse needs in a globalized world.
Bringing together technical knowledge and social competences which go beyond a mere training of the so-called “soft skills”, is a new approach followed at RWTH Aachen University, one of the leading technical universities in Germany. RWTH Aachen University has established the bridging professorship “Gender and Diversity in Engineering” (GDI) which educates engineers with an interdisciplinary approach to expand engineering limits. In the frame of a sustainable teaching concept the research group under the leadership of Prof. Carmen Leicht-Scholten has developed an approach which imparts a supplication-specific Gender and Diversity expertise to engineers. In workshops students gain theoretical knowledge about Gender and Diversity and learn how to transfer their knowledge in their special field of study and later work. To substantiate this, the course participants have to solve case studies from real life. The cases which are developed in collaboration with non-profit organizations and enterprises from economy rise the students to challenges which are inspired by professional life. Evaluation shows the success of this approach as well as an increasing demand for such teaching formats.
Following the recent successful landings and occasional re-awakenings of PHILAE, the lander carried aboard ROSETTA to comet 67P/Churyumov-Gerasimenko, and the launch of the Mobile Asteroid Surface Scout, MASCOT, aboard the HAYABUSA2 space probe to asteroid (162173) Ryugu we present an overview of the characteristics and peculiarities of small spacecraft missions to small solar system bodies (SSSB). Their main purpose is planetary science which is transitioning from a ‘pure’ science of observation of the distant to one also supporting in-situ applications relevant for life on Earth. Here we focus on missions at the interface of SSSB science and planetary defence applications. We provide a brief overview of small spacecraft SSSB missions and on this background present recent missions, projects and related studies at the German Aerospace Center, DLR, that contribute to the worldwide planetary defence community. These range from Earth orbit technology demonstrators to active science missions in interplanetary space. We provide a summary of experience from recently flown missions with DLR participation as well as a number of studies. These include PHILAE, the lander of ESA’s ROSETTA comet rendezvous mission now on the surface of comet 67P/Churyumov-Gerasimenko, and the Mobile Asteroid Surface Scout, MASCOT, now in cruise to the ~1 km diameter C-type near-Earth asteroid (162173) Ryugu aboard the Japanese sample-return probe HAYABUSA2. We introduce the differences between the conventional methods employed in the design, integration and testing of large spacecraft and the new approaches developed by small spacecraft projects. We expect that the practical experience that can be gained from projects on extremely compressed timelines or with high-intensity operation phases on a newly explored small solar system body can contribute significantly to the study, preparation and realization of future planetary defence related missions. One is AIDA (Asteroid Impact & Deflection Assessment), a joint effort of ESA, JHU/APL, NASA, OCA and DLR, combining JHU/APL’s DART (Double Asteroid Redirection Test) and ESA’s AIM (Asteroid Impact Monitor) spacecraft in a mission towards near-Earth binary asteroid system (65803) Didymos. DLR is currently applying MASCOT heritage and lessons learned to the design of MASCOT2, a lander for the AIM mission to support a bistatic low frequency radar experiment with PHILAE/ROSETTA CONSERT heritage to explore the inner structure of Didymoon which is the designated impact target for DART.
This paper describes the results and methods used during the 8th Global Trajectory Optimization Competition (GTOC) of the DLR team. Trajectory optimization is crucial for most of the space missions and usually can be formulated as a global optimization problem. A lot of research has been done to different type of mission problems. The most demanding ones are low thrust transfers with e.g. gravity assist sequences. In that case the optimal control problem is combined with an integer problem. In most of the GTOCs we apply a filtering of the problem based on domain knowledge.
There are different types of games that try to make use of the motivation of a gaming situation in learning contexts. This paper introduces the new terminology ‘Competence Developing Game’ (CDG) as an umbrella term for all games with this intention. Based on this new terminology, an assessment framework has been developed and validated in scope of an empirical study. Now, all different types of CDGs can be evaluated according to a defined and uniform set of assessment criteria and, thus, are comparable according to their characteristics and effectiveness.
The scientific interest for near-Earth asteroids as well as the interest in potentially hazardous asteroids from the perspective of planetary defense led the space community to focus on near-Earth asteroid mission studies. A multiple near-Earth asteroid rendezvous mission with close-up observations of several objects can help to improve the characterization of these asteroids. This work explores the design of a solar-sail spacecraft for such a mission, focusing on the search of possible sequences of encounters and the trajectory optimization. This is done in two sequential steps: a sequence search by means of a simplified trajectory model and a set of heuristic rules based on astrodynamics, and a subsequent optimization phase. A shape-based approach for solar sailing has been developed and is used for the first phase. The effectiveness of the proposed approach is demonstrated through a fully optimized multiple near-Earth asteroid rendezvous mission. The results show that it is possible to visit five near-Earth asteroids within 10 years with near-term solar-sail technology.
Pure analytical or experimental methods can only find a control strategy for technical systems with a fixed setup. In former contributions we presented an approach that simultaneously finds the optimal topology and the optimal open-loop control of a system via Mixed Integer Linear Programming (MILP). In order to extend this approach by a closed-loop control we present a Mixed Integer Program for a time discretized tank level control. This model is the basis for an extension by combinatorial decisions and thus for the variation of the network topology. Furthermore, one is able to appraise feasible solutions using the global optimality gap.
Nach Stand von Wissenschaft und Technik werden Komponenten hinsichtlich ihrer Eigenschaften, wie Lebensdauer oder Energieeffizienz, optimiert. Allerdings können selbst hervorragende Komponenten zu ineffizienten oder instabilen Systemen führen, wenn ihr Zusammenspiel nur unzureichend berücksichtigt wird. Eine Systembetrachtung schafft ein größeres Optimierungspotential - dem erhöhten Potential steht jedoch auch ein erhöhter Komplexitätsgrad gegenüber. Die vorliegende Arbeit ist im Rahmen des Sonderforschungsbereichs 805 entstanden, dessen Ziel die Beherrschung von Unsicherheit in Systemen des Maschinenbaus ist. Die Arbeit zeigt anhand eines realen Systems aus dem Bereich der Hydraulik, wie Unsicherheit in der Entwicklungsphase beherrscht werden kann. Hierbei ist neu, dass die durch den späteren Betrieb zu erwartende Systemdegradation eines jeden möglichen Systemvorschlags antizipiert werden kann. Dadurch können Betriebs- und Wartungskosten vorausgesagt und minimiert werden und durch eine optimale Betriebs- und Wartungsstrategie die Verfügbarkeit des Systems garantiert werden. Wesentliche Fragen bei der optimalen Auslegung des betrachteten hydrostatischen Getriebes sind dessen physikalische Modellierung, die Darstellung des Optimierungsproblems als gemischt-ganzzahliges lineares Programm, und dessen algorithmische Behandlung zur Lösungsfindung. Hierzu werden Heuristiken zum schnelleren Auffinden sinnvoller Systemtopologien vorgestellt und mittels mathematischer Dekomposition eine Bewertung des dynamischen Verschleiß- und Wartungsverlaufs möglicher Systemvorschläge vorgenommen. Die Arbeit stellt die Optimierung technischer Systeme an der Schnittstelle von Mathematik, Informatik und Ingenieurwesen sowohl gründlich als auch anschaulich und nachvollziehbar dar.
Finding a good system topology with more than a handful of components is a
highly non-trivial task. The system needs to be able to fulfil all expected load cases, but at the
same time the components should interact in an energy-efficient way. An example for a system
design problem is the layout of the drinking water supply of a residential building. It may be
reasonable to choose a design of spatially distributed pumps which are connected by pipes in at
least two dimensions. This leads to a large variety of possible system topologies. To solve such
problems in a reasonable time frame, the nonlinear technical characteristics must be modelled
as simple as possible, while still achieving a sufficiently good representation of reality. The
aim of this paper is to compare the speed and reliability of a selection of leading mathematical
programming solvers on a set of varying model formulations. This gives us empirical evidence
on what combinations of model formulations and solver packages are the means of choice with the current state of the art.
The behaviour of infilled reinforced concrete frames under horizontal load has been widely investigated, both experimentally and numerically. Since experimental tests represent large investments, numerical simulations offer an efficient approach for a more comprehensive analysis. When RC frames with masonry infill walls are subjected to horizontal loading, their behaviour is highly non-linear after a certain limit, which makes their analysis quite difficult. The non-linear behaviour results from the complex inelastic material properties of the concrete, infill wall and conditions at the wall-frame interface. In order to investigate this non-linear behaviour in detail, a finite element model using a micro modelling approach is developed, which is able to predict the complex non-linear behaviour resulting from the different materials and their interaction. Concrete and bricks are represented by a non-linear material model, while each reinforcement bar is represented as an individual part installed in the concrete part and behaving elasto-plastically. Each brick is modelled individually and connected taking into account the non-linearity of a brick mortar interface. The same approach is followed using two finite element software packages and the results are compared with the experimental results. The numerical models show a good agreement with the experiments in predicting the overall behaviour, but also very good matching for strength capacity and drift. The results emphasize the quality and the valuable contribution of the numerical models for use in parametric studies, which are needed for the derivation of design recommendations for infilled frame structures.
Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers.
Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold.
We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward.
Manufacturing process simulation enables the evaluation and improvement of autoclave mold concepts early in the design phase. To achieve a high part quality at low cycle times, the thermal behavior of the autoclave mold can be investigated by means of simulations. Most challenging for such a simulation is the generation of necessary boundary conditions. Heat-up and temperature distribution in an autoclave mold are governed by flow phenomena, tooling material and shape, position within the autoclave, and the chosen autoclave cycle. This paper identifies and summarizes the most important factors influencing mold heat-up and how they can be introduced into a thermal simulation. Thermal measurements are used to quantify the impact of the various parameters. Finally, the gained knowledge is applied to develop a semi-empirical approach for boundary condition estimation that enables a simple and fast thermal simulation of the autoclave curing process with reasonably high accuracy for tooling optimization.
L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen – lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 % higher than in the wild-growing species.
At the present time, one of the most serious environmental problems of Central Asia and South Kazakhstan is the ongoing large-scale deterioration of principal urban tree populations. Several major centers of massive spread of invasive plant pests have been found in urban dendroflora of this region. The degree of damage of seven most wide-spread aboriginal tree species was found to range from 21.4±1.1 to 85.4±1.8%. In particular, the integrity of the native communities of sycamore (Platanus spp.), willow (Salix spp.), poplar (Populus spp.) and elm (Ulmus spp.) is highly endangered. Our taxonomic analysis of the most dangerous tree pests of the region has revealed them as neobiontic xylophilous insects such as Cossus cossus L. (Order: Lepidoptera L.) Monochamus urussovi Fisch., Monochamus sutor L., Acanthocinus aedelis L. and Ñetonia aureate L. (Order: Coleoptera L.). We relate the origin of this threatening trend with the import of industrial wood in the mid 90s of the last century that was associated with high degree of the constructional work in the region. Because of the absence of efficient natural predators of the pest species, the application of microbiological methods of the pest control and limitation is suggested.
We study the novel possibilities computer aided design and production open up for the design of building systems. Such systems today can, via individualized mass production, consist of a larger number and more complex parts than previously and therefore be assembled into more complex wholes. This opens up the possibility of designing specialized systems specifically for single buildings. The common order of starting with a building system and designing a building using this system can be reversed to designing a building first and then developing a system specifically for that building. We present and discuss research that incorporates students design projects into research work and fosters links between research and teaching.
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.
Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp−/−) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.
NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.
Divided government is often thought of as causing legislative deadlock. I investigate the link between divided government and economic reforms using a novel data set on welfare reforms in US states between 1978 and 2010. Panel data regressions show that, under divided government, a US state is around 25% more likely to adopt a welfare reform than under unified government. Several robustness checks confirm this counter-intuitive finding. Case study evidence suggests an explanation based on policy competition between governor, senate, and house.
Given the strong increase in regulatory requirements for business processes the management of business process compliance becomes a more and more regarded field in IS research. Several methods have been developed to support compliance checking of conceptual models. However, their focus on distinct modeling languages and mostly linear (i.e., predecessor-successor related) compliance rules may hinder widespread adoption and application in practice. Furthermore, hardly any of them has been evaluated in a real-world setting. We address this issue by applying a generic pattern matching approach for conceptual models to business process compliance checking in the financial sector. It consists of a model query language, a search algorithm and a corresponding modelling tool prototype. It is (1) applicable for all graph-based conceptual modeling languages and (2) for different kinds of compliance rules. Furthermore, based on an applicability check, we (3) evaluate the approach in a financial industry project setting against its relevance for decision support of audit and compliance management tasks.
The stimulation and dominance of potentially harmful phytoplankton taxa at a given locale and time are determined by local environmental conditions as well as by transport to or from neighboring regions. The present study investigated the occurrence of common harmful algal bloom (HAB) taxa within the Southern California Bight, using cross-correlation functions to determine potential dependencies between HAB taxa and environmental factors, and potential links to algal transport via local hydrography and currents. A simulation study, in which Lagrangian particles were released, was used to assess travel times due to advection by prevailing ocean currents in the bight. Our results indicate that transport of some taxa may be an important mechanism for the expansion of their distributions into other regions, which was supported by mean travel times derived from our simulation study and other literature on ocean currents in the Southern California Bight. In other cases, however, phytoplankton dynamics were rather linked to local environmental conditions, including coastal upwelling events. Overall, our study shows that complex current patterns in the Southern California Bight may contribute significantly to the formation and expansion of HABs in addition to local environmental factors determining the spatiotemporal dynamics of phytoplankton blooms.
We investigate the suitability of selected measures of complexity based on recurrence quantification analysis and recurrence networks for an identification of pre-seizure states in multi-day, multi-channel, invasive electroencephalographic recordings from five epilepsy patients. We employ several statistical techniques to avoid spurious findings due to various influencing factors and due to multiple comparisons and observe precursory structures in three patients. Our findings indicate a high congruence among measures in identifying seizure precursors and emphasize the current notion of seizure generation in large-scale epileptic networks. A final judgment of the suitability for field studies, however, requires evaluation on a larger database.
The Monte Carlo code FLUKA is used to simulate the production of a number of positron emitting radionuclides, ¹⁸F, ¹³N, ⁹⁴Tc, ⁴⁴Sc, ⁶⁸Ga, ⁸⁶Y, ⁸⁹Zr, ⁵²Mn, ⁶¹Cu and ⁵⁵Co, on a small medical cyclotron with a proton beam energy of 13 MeV. Experimental data collected at the TR13 cyclotron at TRIUMF agree within a factor of 0.6 ± 0.4 with the directly simulated data, except for the production of ⁵⁵Co, where the simulation underestimates the experiment by a factor of 3.4 ± 0.4. The experimental data also agree within a factor of 0.8 ± 0.6 with the convolution of simulated proton fluence and cross sections from literature. Overall, this confirms the applicability of FLUKA to simulate radionuclide production at 13 MeV proton beam energy.
[⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3.
The potential of SMART climbing robot combined with a weatherproof cabin for rotor blade maintenance
(2016)
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.