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Scheer, Nico ; Henderson, Colin James ; Kapelyukh, Yury ; Rode, Anja ; Mclaren, Aileen W. ; MacLeod, Alastair Kenneth ; Lin, De ; Wright, Jayne ; Stanley, Lesley ; Wolf, C. Roland
Scheer, Nico ; Kapelyukh, Yury ; McEwan, Jillian ; Beuger, Vincent ; Stanley, Lesley A. ; Rode, Anja ; Wolf, C. Roland
The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.
Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.
Scheer, Nico ; Kapelyukh, Yury ; Rode, Anja ; Oswald, Stefan ; Busch, Diana ; Mclaughlin, Lesley A. ; Lin, De ; Henderson, Colin J. ; Wolf, C. Roland
Scheer, Nico ; Mclaughlin, Lesley A. ; Rode, Anja ; MacLeod, Alastair Kenneth ; Henderson, Colin J. ; Wolf, Roland C.
In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.
Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.
Scheer, Nico ; Ross, Jillian ; Rode, Anja ; Zevnik, Branko ; Niehaves, Sandra ; Faust, Nicole ; Wolf, C. Roland
Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.
1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described.
2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created.
3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment.
4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.
We present a new Min-Max theorem for an optimization problem closely connected to matchings and vertex covers in balanced hypergraphs. The result generalizes Kőnig’s Theorem (Berge and Las Vergnas in Ann N Y Acad Sci 175:32–40, 1970; Fulkerson et al. in Math Progr Study 1:120–132, 1974) and Hall’s Theorem (Conforti et al. in Combinatorica 16:325–329, 1996) for balanced hypergraphs.
Biodiversity and the coexistence of species have puzzled and fascinated biologists since decades and is a hotspot in todays’ natural sciences. Preserving this biodiversity is a great challenge as habitats and environments underlying tremendous changes like climate change and the loss of natural habitats, which are mainly due to anthropogenic influences. The coexistence of numerous species even in homogeneous environments is a stunning feature of natural communities and has been summarized under the term ‘paradox of plankton’. Up to now, there are several mechanisms discussed, which may contribute to local and global diversity of organisms. Several interspecific trade offs have been identified maintaining the coexistence of species like their abilities regarding competition and predator avoidance, their capability to disperse in space and time, and their ability to exploit variable resources. Further, micro-evolutionary dynamics supporting the coexistence of species have been added to our knowledge, and deriving from theoretical deterministic models, non-linear dynamics which describe the temporal fluctuation of abundances of organisms. Whereas competition and predation seem to be clue structural elements within interacting organisms, the intrinsic dynamic behavior – by means of temporal changes in abundance - plays an important role regarding coexistence within a community. The present work sheds light on different factors affecting the coexistence of species using experimental microbial model systems consisting of a bacterivorous ciliate as the predator and two bacteria strains as prey organism. Additionally, another experimental setup consisting of two up to five bacteria species competing for one limiting resource was investigated. Highly controllable chemostat systems were established to exclude extrinsic disturbances. According to theoretical analyses I was able to show - experimentally and theoretically - that phenotypic plasticity of one species within a microbial one-predator-two-prey food web enlarges the range of possible coexistence of all species under different dynamic conditions, compared to a food web without phenotypic plasticity. This was accompanied by non-linear (chaotic) population dynamics within all experimental systems showing phenotypic plasticity. The experiments on the interplay of competition, predation and invasion showed that all aspects have an influence on species coexistence. Under undisturbed controlled conditions all aspects were analyzed in detail and in combination. Populations showed oscillations which were shown by quasi-chaotic attractors in phase space diagrams. Competition experiments with two up to five bacteria species competing for one limiting resource showed that all organisms were able to coexist which was mediated by species oscillations entering a regime of chaos. Besides that fact it was found, that the productivity (biomass) as well as the total cell numbers – under the same nutrition supply – increased by an increasing number of species in the experimental systems. Up to now, the occurrence of non-linear dynamics in well controlled experimental studies has been recognized several times and this phenomenon seemed to be more common in natural systems than generally assumed.
Schieren, Mark ; Kleinschmidt, Joris ; Schmutz, Axel ; Loop, Torsten ; Gatzweiler, Karl-Heinz ; Staat, Manfred ; Wappler, Frank ; Defosse, Jerome
Schiffels, Johannes ; Pinkenburg, Olaf ; Schelden, Maximilian ; Aboulnaga, El-Hussiny A. A. ; Baumann, Marcus ; Selmer, Thorsten
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.
In this work, we report on our attempt to design and implement an early introduction to basic robotics principles for children at kindergarten age. One of the main challenges of this effort is to explain complex robotics contents in a way that pre-school children could follow the basic principles and ideas using examples from their world of experience. What sets apart our effort from other work is that part of the lecturing is actually done by a robot itself and that a quiz at the end of the lesson is done using robots as well. The humanoid robot Pepper from Softbank, which is a great platform for human–robot interaction experiments, was used to present a lecture on robotics by reading out the contents to the children making use of its speech synthesis capability. A quiz in a Runaround-game-show style after the lecture activated the children to recap the contents they acquired about how mobile robots work in principle. In this quiz, two LEGO Mindstorm EV3 robots were used to implement a strongly interactive scenario. Besides the thrill of being exposed to a mobile robot that would also react to the children, they were very excited and at the same time very concentrated. We got very positive feedback from the children as well as from their educators. To the best of our knowledge, this is one of only few attempts to use a robot like Pepper not as a tele-teaching tool, but as the teacher itself in order to engage pre-school children with complex robotics contents.
Reasoning with Qualitative Positional Information for Domestic Domains in the Situation Calculus
(2011)
In this paper we present CAESAR, an intelligent domestic service robot. In domestic settings for service robots complex tasks have to be accomplished. Those tasks benefit from deliberation, from robust action execution and from flexible methods for human–robot interaction that account for qualitative notions used in natural language as well as human fallibility. Our robot CAESAR deploys AI techniques on several levels of its system architecture. On the low-level side, system modules for localization or navigation make, for instance, use of path-planning methods, heuristic search, and Bayesian filters. For face recognition and human–machine interaction, random trees and well-known methods from natural language processing are deployed. For deliberation, we use the robot programming and plan language READYLOG, which was developed for the high-level control of agents and robots; it allows combining programming the behaviour using planning to find a course of action. READYLOG is a variant of the robot programming language Golog. We extended READYLOG to be able to cope with qualitative notions of space frequently used by humans, such as “near” and “far”. This facilitates human–robot interaction by bridging the gap between human natural language and the numerical values needed by the robot. Further, we use READYLOG to increase the flexible interpretation of human commands with decision-theoretic planning. We give an overview of the different methods deployed in CAESAR and show the applicability of a system equipped with these AI techniques in domestic service robotics
Schindler, Kaspar A. ; Bialonski, Stephan ; Horstmann, Marie-Therese ; Elger, Christian E. ; Lehnertz, Klaus
The impact of wake model effects is investigated for two highly
non-planar lifting systems. Dependent on the geometrical
arrangement of the configuration, the wake model shape is found
to considerably affect the estimation. Particularly at higher angles
of attack, an accurate estimation based on the common linear wake
model approaches is involved.
Euler-based induced drag estimation for highly non-planar lifting systems during conceptional design
(2013)
Schlamann, Marc ; Voigt, Melanie A. ; Maderwald, Stefan ; Bitz, Andreas ; Kraff, Oliver ; Ladd, Susanne C. ; Ladd, Mark E. ; Forsting, Michael ; Wilhelm, Hans
Purpose
To assess potential cognitive deficits under the influence of static magnetic fields at various field strengths some studies already exist. These studies were not focused on attention as the most vulnerable cognitive function. Additionally, mostly no magnetic resonance imaging (MRI) sequences were performed.
Materials and Methods
In all, 25 right-handed men were enrolled in this study. All subjects underwent one MRI examination of 63 minutes at 1.5 T and one at 7 T within an interval of 10 to 30 days. The order of the examinations was randomized. Subjects were referred to six standardized neuropsychological tests strictly focused on attention immediately before and after each MRI examination. Differences in neuropsychological variables between the timepoints before and after each MRI examination were assessed and P-values were calculated
Results
Only six subtests revealed significant differences between pre- and post-MRI. In these tests the subjects achieved better results in post-MRI testing than in pre-MRI testing (P = 0.013–0.032). The other tests revealed no significant results.
Conclusion
The improvement in post-MRI testing is only explicable as a result of learning effects. MRI examinations, even in ultrahigh-field scanners, do not seem to have any persisting influence on the attention networks of human cognition immediately after exposure.
Short term effects of magnetic resonance imaging on excitability of the motor cortex at 1.5T and 7T
(2010)
Schlamann, Marc ; Yoon, Min-Suk ; Maderwald, Stefan ; Pietrzyk, Thomas ; Bitz, Andreas ; Gerwig, Marcus ; Forsting, Michael ; Ladd, Susanne C. ; Ladd, Mark E. ; Kastrup, Oliver
Rationale and Objectives
The increasing spread of high-field and ultra-high-field magnetic resonance imaging (MRI) scanners has encouraged new discussion of the safety aspects of MRI. Few studies have been published on possible cognitive effects of MRI examinations. The aim of this study was to examine whether changes are measurable after MRI examinations at 1.5 and 7 T by means of transcranial magnetic stimulation (TMS).
Materials and Methods
TMS was performed in 12 healthy, right-handed male volunteers. First the individual motor threshold was specified, and then the cortical silent period (SP) was measured. Subsequently, the volunteers were exposed to the 1.5-T MRI scanner for 63 minutes using standard sequences. The MRI examination was immediately followed by another TMS session. Fifteen minutes later, TMS was repeated. Four weeks later, the complete setting was repeated using a 7-T scanner. Control conditions included lying in the 1.5-T scanner for 63 minutes without scanning and lying in a separate room for 63 minutes. TMS was performed in the same way in each case. For statistical analysis, Wilcoxon's rank test was performed.
Results
Immediately after MRI exposure, the SP was highly significantly prolonged in all 12 subjects at 1.5 and 7 T. The motor threshold was significantly increased. Fifteen minutes after the examination, the measured value tended toward normal again. Control conditions revealed no significant differences.
Conclusion
MRI examinations lead to a transient and highly significant alteration in cortical excitability. This effect does not seem to depend on the strength of the static magnetic field.
The potential of SMART climbing robot combined with a weatherproof cabin for rotor blade maintenance
(2016)
Risk factors for cardiovascular calcifications in non-diabetic Caucasian haemodialysis patients
(2009)
Schlieper, G. ; Brandenburg, V. ; Djuric, Z. ; Damjanovic, T. ; Markovic, N. ; Schurgers, L. ; Krüger, T. ; Westenfeld, R. ; Ackermann, D. ; Haselhuhn, Angelika ; Dimkovic, S. ; Ketteler, M. ; Floege, J. ; Dimkovic, N.
Detection and identification of free radicals in hydrocarbon pyrolysis by an iodine trapping method
(1992)
The SG1-mediated solution polymerization of methyl methacrylate (MMA) and oligo(ethylene glycol) methacrylate (OEGMA, Mₙ = 300 g mol⁻¹) in the presence of a small amount of functional/reactive styrenic comonomer is investigated. Moieties such as pentafluorophenyl ester, triphenylphosphine, azide, pentafluorophenyl, halide, and pyridine are considered. A comonomer fraction as low as 5 mol% typically results in a controlled/living behavior, at least up to 50% conversion. Chain extensions with styrene for both systems were successfully performed. Variation of physical properties such as refractive index (for MMA) and phase transition temperature (for OEGMA) were evaluated by comparing to 100% pure homopolymers. The introduction of an activated ester styrene derivative in the polymerization of OEGMA allows for the synthesis of reactive and hydrophilic polymer brushes with defined thickness. Finally, using the example of pentafluorostyrene as controlling comonomer, it is demonstrated that functional PMMA-b-PS are able to maintain a phase separation ability, as evidenced by the formation of nanostructured thin films.
Schmidt, Daniela ; Langen, Karl-J. ; Herzog, Hans ; Wirths, Jochen ; Holschbach, Markus ; Kiwit, Jürgen C. W. ; Ziemons, Karl ; Coenen, Heinz-H. ; Müller-Gärtner, Hans-W.
Compared to peripheral pain, trigeminal pain elicits higher levels of fear, which is assumed to enhance the interruptive effects of pain on concomitant cognitive processes. In this fMRI study we examined the behavioral and neural effects of trigeminal (forehead) and peripheral (hand) pain on visual processing and memory encoding. Cerebral activity was measured in 23 healthy subjects performing a visual categorization task that was immediately followed by a surprise recognition task. During the categorization task subjects received concomitant noxious electrical stimulation on the forehead or hand. Our data show that fear ratings were significantly higher for trigeminal pain. Categorization and recognition performance did not differ between pictures that were presented with trigeminal and peripheral pain. However, object categorization in the presence of trigeminal pain was associated with stronger activity in task-relevant visual areas (lateral occipital complex, LOC), memory encoding areas (hippocampus and parahippocampus) and areas implicated in emotional processing (amygdala) compared to peripheral pain. Further, individual differences in neural activation between the trigeminal and the peripheral condition were positively related to differences in fear ratings between both conditions. Functional connectivity between amygdala and LOC was increased during trigeminal compared to peripheral painful stimulation. Fear-driven compensatory resource activation seems to be enhanced for trigeminal stimuli, presumably due to their exceptional biological relevance.
Schmidt, Katharina ; Forkmann, Katarina ; Schultz, Heidrun ; Gratz, Marcel ; Bitz, Andreas ; Wiech, Katja ; Bingel, Ulrike
This paper presents the laser-based powder bed fusion (L-PBF) using various glass powders (borosilicate and quartz glass). Compared to metals, these require adapted process strategies. First, the glass powders were characterized with regard to their material properties and their processability in the powder bed. This was followed by investigations of the melting behavior of the glass powders with different laser wavelengths (10.6 µm, 1070 nm). In particular, the experimental setup of a CO2 laser was adapted for the processing of glass powder. An experimental setup with integrated coaxial temperature measurement/control and an inductively heatable build platform was created. This allowed the L-PBF process to be carried out at the transformation temperature of the glasses. Furthermore, the component’s material quality was analyzed on three-dimensional test specimen with regard to porosity, roughness, density and geometrical accuracy in order to evaluate the developed L-PBF parameters and to open up possible applications.
Often, research results from collaboration projects are not transferred into productive environments even though approaches are proven to work in demonstration prototypes. These demonstration prototypes are usually too fragile and error-prone to be transferred
easily into productive environments. A lot of additional work is required.
Inspired by the idea of an incremental delivery process, we introduce an architecture pattern, which combines the approach of Metrics Driven Research Collaboration with microservices for the ease of integration. It enables keeping track of project goals over the course of the collaboration while every party may focus on their expert skills: researchers may focus on complex algorithms,
practitioners may focus on their business goals.
Through the simplified integration (intermediate) research results can be introduced into a productive environment which enables
getting an early user feedback and allows for the early evaluation of different approaches. The practitioners’ business model benefits throughout the full project duration.
The integration of product data from heterogeneous sources and manufacturers into a single catalog is often still a laborious, manual task. Especially small- and medium-sized enterprises face the challenge of timely integrating the data their business relies on to have an up-to-date product catalog, due to format specifications, low quality of data and the requirement of expert knowledge. Additionally, modern approaches to simplify catalog integration demand experience in machine learning, word vectorization, or semantic similarity that such enterprises do not have. Furthermore, most approaches struggle with low-quality data. We propose Attribute Label Ranking (ALR), an easy to understand and simple to adapt learning approach. ALR leverages a model trained on real-world integration data to identify the best possible schema mapping of previously unknown, proprietary, tabular format into a standardized catalog schema. Our approach predicts multiple labels for every attribute of an inpu t column. The whole column is taken into consideration to rank among these labels. We evaluate ALR regarding the correctness of predictions and compare the results on real-world data to state-of-the-art approaches. Additionally, we report findings during experiments and limitations of our approach.
The integration of frequently changing, volatile product data from different manufacturers into a single catalog is a significant challenge for small and medium-sized e-commerce companies. They rely on timely integrating product data to present them aggregated in an online shop without knowing format specifications, concept understanding of manufacturers, and data quality. Furthermore, format, concepts, and data quality may change at any time. Consequently, integrating product catalogs into a single standardized catalog is often a laborious manual task. Current strategies to streamline or automate catalog integration use techniques based on machine learning, word vectorization, or semantic similarity. However, most approaches struggle with low-quality or real-world data. We propose Attribute Label Ranking (ALR) as a recommendation engine to simplify the integration process of previously unknown, proprietary tabular format into a standardized catalog for practitioners. We evaluate ALR by focusing on the impact of different neural network architectures, language features, and semantic similarity. Additionally, we consider metrics for industrial application and present the impact of ALR in production and its limitations.
Seismic design of buried pipeline systems for energy and water supply is not only important for plant and operational safety but also for the maintenance of the supply infrastructure after an earthquake. The present paper shows special issues of the seismic wave impacts on buried pipelines, describes calculation methods, proposes approaches and gives calculation examples. This paper regards the effects of transient displacement differences and resulting tensions within the pipeline due to the wave propagation of the earthquake. However, the presented model can also be used to calculate fault rupture induced displacements. Based on a three-dimensional Finite Element Model parameter studies are performed to show the influence of several parameters such as incoming wave angle, wave velocity, backfill height and synthetic displacement time histories. The interaction between the pipeline and the surrounding soil is modeled with non-linear soil springs and the propagating wave is simulated affecting the pipeline punctually, independently in time and space. Special attention is given to long-distance heat pipeline systems. Here, in regular distances expansion bends are arranged to ensure movements of the pipeline due to high temperature. Such expansion bends are usually designed with small bending radii, which during the earthquake lead to high bending stresses in the cross-section of the pipeline. Finally, an interpretation of the results and recommendations are given for the most critical parameters.
Pulmonary arterial cannulation is a common and effective method for percutaneous mechanical circulatory support for concurrent right heart and respiratory failure [1]. However, limited data exists to what effect the positioning of the cannula has on the oxygen perfusion throughout the pulmonary artery (PA). This study aims to evaluate, using computational fluid dynamics (CFD), the effect of different cannula positions in the PA with respect to the oxygenation of the different branching vessels in order for an optimal cannula position to be determined. The four chosen different positions (see Fig. 1) of the cannulas are, in the lower part of the main pulmonary artery (MPA), in the MPA at the junction between the right pulmonary artery (RPA) and the left pulmonary artery (LPA), in the RPA at the first branch of the RPA and in the LPA at the first branch of the LPA.
Due to the high number of customer contacts, fault clearances, installations, and product provisioning per year, the automation level of operational processes has a significant impact on financial results, quality, and customer experience. Therefore, the telecommunications operator Deutsche Telekom (DT) has defined a digital strategy with the objectives of zero complexity and zero complaint, one touch, agility in service, and disruptive thinking. In this context, Robotic Process Automation (RPA) was identified as an enabling technology to formulate and realize DT’s digital strategy through automation of rule-based, routine, and predictable tasks in combination with structured and stable data.