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We consider recent reports on small-world topologies of interaction networks derived from the dynamics of spatially extended systems that are investigated in diverse scientific fields such as neurosciences, geophysics, or meteorology. With numerical simulations that mimic typical experimental situations, we have identified an important constraint when characterizing such networks: indications of a small-world topology can be expected solely due to the spatial sampling of the system along with the commonly used time series analysis based approaches to network characterization.
The concept of an injective affine embedding of the quantum states into a set of classical states, i.e., into the set of the probability measures on some measurable space, as well as its relation to statistically complete observables is revisited, and its limitation in view of a classical reformulation of the statistical scheme of quantum mechanics is discussed. In particular, on the basis of a theorem concerning a non-denseness property of a set of coexistent effects, it is shown that an injective classical embedding of the quantum states cannot be supplemented by an at least approximate classical description of the quantum mechanical effects. As an alternative approach, the concept of quasi-probability representations of quantum mechanics is considered.
Researching the field of business intelligence and analytics (BI & A) has a long tradition within information systems research. Thereby, in each decade the rapid development of technologies opened new room for investigation. Since the early 1950s, the collection and analysis of structured data were the focus of interest, followed by unstructured data since the early 1990s. The third wave of BI & A comprises unstructured and sensor data of mobile devices. The article at hand aims at drawing a comprehensive overview of the status quo in relevant BI & A research of the current decade, focusing on the third wave of BI & A. By this means, the paper’s contribution is fourfold. First, a systematically developed taxonomy for BI & A 3.0 research, containing seven dimensions and 40 characteristics, is presented. Second, the results of a structured literature review containing 75 full research papers are analyzed by applying the developed taxonomy. The analysis provides an overview on the status quo of BI & A 3.0. Third, the results foster discussions on the predicted and observed developments in BI & A research of the past decade. Fourth, research gaps of the third wave of BI & A research are disclosed and concluded in a research agenda.
The paper presents the derivation of a new equivalent skin friction coefficient for estimating the parasitic drag of short-to-medium range fixed-wing unmanned aircraft. The new coefficient is derived from an aerodynamic analysis of ten different unmanned aircraft used for surveillance, reconnaissance, and search and rescue missions. The aircraft is simulated using a validated unsteady Reynolds-averaged Navier Stokes approach. The UAV’s parasitic drag is significantly influenced by the presence of miscellaneous components like fixed landing gears or electro-optical sensor turrets. These components are responsible for almost half of an unmanned aircraft’s total parasitic drag. The new equivalent skin friction coefficient accounts for these effects and is significantly higher compared to other aircraft categories. It is used to initially size an unmanned aircraft for a typical reconnaissance mission. The improved parasitic drag estimation yields a much heavier unmanned aircraft when compared to the sizing results using available drag data of manned aircraft.
Biotechnological downstream processing is usually an elaborate procedure, requiring a multitude of unit operations to isolate the target component. Besides the disadvantageous space-time yield, the risks of cross-contaminations and product loss grow fast with the complexity of the isolation procedure. A significant reduction of unit operations can be achieved by application of magnetic particles, especially if these are functionalized with affinity ligands. As magnetic susceptible materials are highly uncommon in biotechnological processes, target binding and selective separation of such particles from fermentation or reactions broths can be done in a single step. Since the magnetizable particles can be produced from iron salts and low priced polymers, a single-use implementation of these systems is highly conceivable. In this article, the principles of magnetizable particles, their synthesis and functionalization are explained. Furthermore, applications in the area of reaction engineering, microfluidics and downstream processing are discussed focusing on established single-use technologies and development potential.
Fundamentals and ignition of a microplasma at 2.45 GHZ / Holtrup, Stephan ; Heuermann, Holger
(2009)
Different analytical approaches exist to describe the structural substance or wear reserve of sewer systems. The aim is to convert engineering assessments of often complex defect patterns into computational algorithms and determine a substance class for a sewer section or manhole. This analytically determined information is essential for strategic rehabilitation planning processes up to network level, as it corresponds to the most appropriate rehabilitation type and can thus provide decision-making support. Current calculation methods differ clearly from each other in parts, so that substance classes determined by the different approaches are only partially comparable with each other. The objective of the German R&D cooperation project ‘SubKanS’ is to develop a methodology for classifying the specific defect patterns resulting from the interaction of all the individual defects, and their severities and locations. The methodology takes into account the structural substance of sewer sections and manholes, based on real data and theoretical considerations analogous to the condition classification of individual defects. The result is a catalogue of defect patterns and characteristics, as well as associated structural substance classifications of sewer systems (substance classes). The methodology for sewer system substance classification is developed so that the classification of individual defects can be transferred into a substance class of the sewer section or manhole, eventually taking into account further information (e.g. pipe material, nominal diameter, etc.). The result is a validated methodology for automated sewer system substance classification.
Future evolution of risk management for structures : Advancement for the future IEC 62305-2 Ed3
(2011)
Virtual Reality (VR) offers novel possibilities for remote training regardless of the availability of the actual equipment, the presence of specialists, and the training locations. Research shows that training environments that adapt to users' preferences and performance can promote more effective learning. However, the observed results can hardly be traced back to specific adaptive measures but the whole new training approach. This study analyzes the effects of a combined point and leveling VR-based gamification system on assembly training targeting specific training outcomes and users' motivations. The Gamified-VR-Group with 26 subjects received the gamified training, and the Non-Gamified-VR-Group with 27 subjects received the alternative without gamified elements. Both groups conducted their VR training at least three times before assembling the actual structure. The study found that a level system that gradually increases the difficulty and error probability in VR can significantly lower real-world error rates, self-corrections, and support usages. According to our study, a high error occurrence at the highest training level reduced the Gamified-VR-Group's feeling of competence compared to the Non-Gamified-VR-Group, but at the same time also led to lower error probabilities in real-life. It is concluded that a level system with a variable task difficulty should be combined with carefully balanced positive and negative feedback messages. This way, better learning results, and an improved self-evaluation can be achieved while not causing significant impacts on the participants' feeling of competence.
Gas sensor investigation based on a catalytically activated thin-film thermopile for H2O2 detection
(2010)
The international partnership of space agencies has agreed to proceed forward to the Moon sustainably. Activities on the Lunar surface (0.16 g) will allow crewmembers to advance the exploration skills needed when expanding human presence to Mars (0.38 g). Whilst data from actual hypogravity activities are limited to the Apollo missions, simulation studies have indicated that ground reaction forces, mechanical work, muscle activation, and joint angles decrease with declining gravity level. However, these alterations in locomotion biomechanics do not necessarily scale to the gravity level, the reduction in gastrocnemius medialis activation even appears to level off around 0.2 g, while muscle activation pattern remains similar. Thus, it is difficult to predict whether gastrocnemius medialis contractile behavior during running on Moon will basically be the same as on Mars. Therefore, this study investigated lower limb joint kinematics and gastrocnemius medialis behavior during running at 1 g, simulated Martian gravity, and simulated Lunar gravity on the vertical treadmill facility. The results indicate that hypogravity-induced alterations in joint kinematics and contractile behavior still persist between simulated running on the Moon and Mars. This contrasts with the concept of a ceiling effect and should be carefully considered when evaluating exercise prescriptions and the transferability of locomotion practiced in Lunar gravity to Martian gravity.
Rehabilitative body weight supported gait training aims at restoring walking function as a key element in activities of daily living. Studies demonstrated reductions in muscle and joint forces, while kinematic gait patterns appear to be preserved with up to 30% weight support. However, the influence of body weight support on muscle architecture, with respect to fascicle and series elastic element behavior is unknown, despite this having potential clinical implications for gait retraining. Eight males (31.9 ± 4.7 years) walked at 75% of the speed at which they typically transition to running, with 0% and 30% body weight support on a lower-body positive pressure treadmill. Gastrocnemius medialis fascicle lengths and pennation angles were measured via ultrasonography. Additionally, joint kinematics were analyzed to determine gastrocnemius medialis muscle–tendon unit lengths, consisting of the muscle's contractile and series elastic elements. Series elastic element length was assessed using a muscle–tendon unit model. Depending on whether data were normally distributed, a paired t-test or Wilcoxon signed rank test was performed to determine if body weight supported walking had any effects on joint kinematics and fascicle–series elastic element behavior. Walking with 30% body weight support had no statistically significant effect on joint kinematics and peak series elastic element length. Furthermore, at the time when peak series elastic element length was achieved, and on average across the entire stance phase, muscle–tendon unit length, fascicle length, pennation angle, and fascicle velocity were unchanged with respect to body weight support. In accordance with unchanged gait kinematics, preservation of fascicle–series elastic element behavior was observed during walking with 30% body weight support, which suggests transferability of gait patterns to subsequent unsupported walking.
With a steady increase of regulatory requirements for business processes, automation support of compliance management is a field garnering increasing attention in Information Systems research. Several approaches have been developed to support compliance checking of process models. One major challenge for such approaches is their ability to handle different modeling techniques and compliance rules in order to enable widespread adoption and application. Applying a structured literature search strategy, we reflect and discuss compliance-checking approaches in order to provide an insight into their generalizability and evaluation. The results imply that current approaches mainly focus on special modeling techniques and/or a restricted set of types of compliance rules. Most approaches abstain from real-world evaluation which raises the question of their practical applicability. Referring to the search results, we propose a roadmap for further research in model-based business process compliance checking.
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.
Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line
(2012)
The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.
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.
Table of Contents Introduction 1. Generative Manufacturing Processes 2. Classification of Generative Manufacturing Processes 3. Application of Generative Processes on the Fabrication of Ceramic Parts 3.1 Extrusion 3.2 3D-Printing 3.3 Sintering – Laser Sintering 3.4 Layer-Laminate Processes 3.5 Stereolithography (sometimes written: Stereo Lithography) 4. Layer Milling 5. Conclusion - Vision
Disruption experiments targeted at the Bacillus licheniformis degSU operon and GFP-reporter analysis provided evidence for promoter activity immediately upstream of degU. pMutin mediated concomitant introduction of the degU32 allele – known to cause hypersecretion in Bacillus subtilis – resulted in a marked increase in protease activity. Application of 5-fluorouracil based counterselection through establishment of a phosphoribosyltransferase deficient Δupp strain eventually facilitated the marker-free introduction of degU32 leading to further protease enhancement achieving levels as for hypersecreting wild strains in which degU was overexpressed. Surprisingly, deletion of rapG – known to interfere with DegU DNA-binding in B. subtilis – did not enhance protease production neither in the wild type nor in the degU32 strain. The combination of degU32 and Δupp counterselection in the type strain is not only equally effective as in hypersecreting wild strains with respect to protease production but furthermore facilitates genetic strain improvement aiming at biological containment and effectiveness of biotechnological processes.
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.