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Mathematische Modellbildung zur Befahrbarkeitssimulation einer mobilen Tiefsee-Arbeitsmaschine
(1988)
Die Forderung nach dem systematischen Gewinnen von Tiefsee-Erzen, wie beispielsweise Manganknollen, mit selbstfahrenden Arbeitsmaschinen führt auf das schwierige Problem der Befahrbarkeit (Traffikabilität) des Tiefseebodens. Im vorliegenden Beitrag wird ein mathematisches Modell zur Befahrbarkeitssimulation einer ferngesteuerten Sammelmaschine vorgestellt. Am Beispiel eines, als Konstruktionsentwurf spezifizierten, aktiven Manganknollenkollektors im großtechnischen Maßstab werden die Modellannahmen und Voraussetzungen für den zugrundeliegenden Tiefseeboden, das Fahrwerk und die betrachteten Betriebszustände und Lastsituationen beschrieben. Mit Hilfe eines koordinatentransformierten Kräftesystems werden die Wechselbeziehungen zwischen Tiefseeboden und einem Vierraupen-Fahrwerk in einem Algorithmus zusammengefaßt. Als Anwendungsbeispiele werden mittels EDV-Programmierung interessierende Betriebszustände und Lastsituationen simuliert. Abschließend werden weitere Modellvarianten aufgezeigt.
Yams of the most widely differing nature are produced in textile mills. The production stages necessary for this are carried out with the aid of textile machines. Between these individual textile machines - from cards to spinning machines - sliver cans serve as a rule as transport containers, in which the sensitive sliver material is temporarily stored, and presented to the next production stage.
Der vorliegende Beitrag befaßt sich mit Automatisierungsmöglichkeiten in Textilbetrieben für konventionelle als auch für nichtkonventionelle Spinnverfahren. Aus der Vielzahl derzeit existenter Produktionsschritte werden die standardisierbaren Automatisierungskombinationen zwischen den eingesetzten Textilmaschinen von Karden bis zu Spinnautomaten herausgearbeitet. Hierfür werden die heute in der Praxis befindlichen Transportmittel aufgezeigt und, vom Materialfluß ausgehend, die Zuordnungsmöglichkeiten der Maschinen in den Produktionsschritten und deren Automatisierungsbausteine definiert. Durch eine ganzheitliche Betrachtungsweise werden je nach Automatisierungsziel die verschiedenen Lösungsansätze diskutiert und als Bausteine gegenübergestellt. Hierdurch werden neue mechatronische Automatisierungslösungen vorgestellt, die eine Integration von Produktionsschritten oder die Automatisierung zwischen den einzelnen Produktionsschritten ermöglicht.
Bond graph modelling was devised by Professor Paynter at the Massachusetts Institute of Technology in 1959 and subsequently developed into a methodology for modelling multidisciplinary systems at a time when nobody was speaking of object-oriented modelling. On the other hand, so-called object-oriented modelling has become increasingly popular during the last few years. By relating the characteristics of both approaches, it is shown that bond graph modelling, although much older, may be viewed as a special form of object-oriented modelling. For that purpose the new object-oriented modelling language Modelica is used as a working language which aims at supporting multiple formalisms. Although it turns out that bond graph models can be described rather easily, it is obvious that Modelica started from generalized networks and was not designed to support bond graphs. The description of bond graph models in Modelica is illustrated by means of a hydraulic drive. Since VHDL-AMS as an important language standardized and supported by IEEE has been extended to support also modelling of non-electrical systems, it is briefly investigated as to whether it can be used for description of bond graphs. It turns out that currently it does not seem to be suitable.
Multidisciplinary systems are described most suitably by bond graphs. In order to determine unnormalized frequency domain sensitivities in symbolic form, this paper proposes to construct in a systematic manner a bond graph from another bond graph, which is called the associated incremental bond graph in this paper. Contrary to other approaches reported in the literature the variables at the bonds of the incremental bond graph are not sensitivities but variations (incremental changes) in the power variables from their nominal values due to parameter changes. Thus their product is power. For linear elements their corresponding model in the incremental bond graph also has a linear characteristic. By deriving the system equations in symbolic state space form from the incremental bond graph in the same way as they are derived from the initial bond graph, the sensitivity matrix of the system can be set up in symbolic form. Its entries are transfer functions depending on the nominal parameter values and on the nominal states and the inputs of the original model. The sensitivities can be determined automatically by the bond graph preprocessor CAMP-G and the widely used program MATLAB together with the Symbolic Toolbox for symbolic mathematical calculation. No particular program is needed for the approach proposed. The initial bond graph model may be non-linear and may contain controlled sources and multiport elements. In that case the sensitivity model is linear time variant and must be solved in the time domain. The rationale and the generality of the proposed approach are presented. For illustration purposes a mechatronic example system, a load positioned by a constant-excitation d.c. motor, is presented and sensitivities are determined in symbolic form by means of CAMP-G/MATLAB.
Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance. This study was designed to evaluate p27 expression and p27 genotyping with respect to early breast cancer prognosis. 279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry. From 108 patients, the CDKN1B genotype was examined by PCR and subsequent direct sequencing. 55.2% of the tumors were considered p27 positive. p27 expression did not correlate with any of the established parameters except for nodal involvement but significantly correlated to prolonged disease-free survival. In 35% of the tumors analyzed, the CDKN1B gene showed a polymorphism at codon 109 (V109G). The V109G polymorphism correlated with greater nodal involvement. In the node-negative subgroup, V109G correlated significantly with a shortened disease-free survival. In conclusion, the determination of the CDKN1B genotype might be a powerful tool for the prognosis of patients with early breast cancer.
One of the issues that has been debated in the context of fairly open learning partnerships such as tandem learning has been whether and, if so, how much pedagogical support should be provided. Another issue is how do language learners who have grown accustomed to maximising their learning through comprehensible input and output make the transition to a reciprocal learning partnership where they are supposed to switch between the roles of learner and expert or resource. The three principles behind tandem learning are bilingualism; reciprocity; and learner autonomy. At Trinity College Dublin we have conducted extensive research into tandem learning in object-oriented Multiple User Domains (MOOs) since 1998. Of the three tandem principles, we found that balanced bilingualism, where both languages are used equally in the exchange, is difficult to achieve, particularly though not surprisingly in partnerships where L2 proficiency differs substantially. We think that technology, at least in MOOs, can contribute towards a solution to the problem. The bilingual tandem analyser (BTA) analyses MOO input while users are communicating and gives feedback to learners (and possibly teachers) on bilingualism in the exchange. Here, we discuss what attitudes towards bilingualism learners bring towards the tandem exchange and how they react to the BTA as a tool to monitor and regulate bilingualism: will learners perceive balanced bilingualism as a necessary principle of the partnership; what efforts do they make to keep the balance between the languages; how do they see the BTA: as an instrument of control, directed by the teacher; or do they perceive it as a useful tool to support their tandem exchanges?
Im Herbst 2005 hat Giso Deussen seine Tätigkeit als Professor für Medienpolitik und Medienethik an der Fachhochschule Bonn-Rhein-Sieg in Sankt Augustin beendet. Am 5. August war er 65 Jahre alt geworden. Fast 20 Jahre seines Berufslebens hat er in enger Verbindung mit "Communicatio Socialis" (ComSoc) verbracht, konkret: Er hat unserer Zeitschrift einen Teil seiner Arbeitskraft geschenkt. Von 1976 bis 1988 war er Mitglied des Redaktion genannten Fähnleins von nicht einmal sieben Aufrechten, die unter der organisatorischen Leitung von Josef Hosse und Franz-Josef Eilers die redaktionellen Lasten trug.
Background: Type 2 diabetes mellitus is associated with increased cardiovascular risk. One laboratory marker for cardiovascular risk assessment is high-sensitivity C-reactive protein (hsCRP).
Methods: This cross-sectional study attempted to analyze the association of hsCRP levels with insulin resistance, β-cell dysfunction and macrovascular disease in 4270 non-insulin-treated patients with type 2 diabetes [2146 male, 2124 female; mean age ±SD, 63.9±11.1years; body mass index (BMI) 30.1±5.5kg/m2; disease duration 5.4±5.6years; hemoglobin A1c (HbA1c) 6.8±1.3%]. It consisted of a single morning visit with collection of a fasting blood sample. Observational parameters included several clinical scores and laboratory biomarkers.
Results: Stratification into cardiovascular risk groups according to hsCRP levels revealed that 934 patients had low risk (hsCRP <1mg/L), 1369 patients had intermediate risk (hsCRP 1–3mg/L), 1352 patients had high risk (hsCRP >3–10mg/L), and 610 patients had unspecific hsCRP elevation (>10mg/L). Increased hsCRP levels were associated with other indicators of diabetes-related cardiovascular risk (homeostatic model assessment, intact proinsulin, insulin, BMI, β-cell dysfunction, all p<0.001), but showed no correlation with disease duration or glucose control. The majority of the patients were treated with diet (34.1%; hsCRP levels 2.85±2.39mg/L) or metformin monotherapy (21.1%; 2.95±2.50mg/L hsCRP). The highest hsCRP levels were observed in patients treated with sulfonylurea (17.0%; 3.00±2.43mg/L).
Conclusions: Our results indicate that hsCRP may be used as a cardiovascular risk marker in patients with type 2 diabetes mellitus and should be evaluated in further prospective studies.
Purpose – To describe the development of a novel polyether(meth)acrylate-based resin material class for stereolithography with alterable material characteristics.
Design/methodology/approach – A complete overview of details to composition parameters, the optimization and bandwidth of mechanical and processing parameters is given. Initial biological characterization experiments and future application felds are depicted. Process parameters are studied in a commercial 3D systems Viper stereolithography system, and a new method to determine these parameters is described herein.
Findings – Initial biological characterizations show the non-toxic behavior in a biological environment, caused mainly by the (meth)acrylate-based core components. These photolithographic resins combine an adjustable low Young’s modulus with the advantages of a non-toxic (meth)acrylate-based process material. In contrast to the mostly rigid process materials used today in the rapid prototyping industry, these polymeric formulations are able to fulfll the extended need for a soft engineering material. A short overview of sample applications is given.
Practical implications – These polymeric formulations are able to meet the growing demand for a resin class for rapid manufacturing that covers a bandwidth from softer to stiffer materials.
Originality/value – This paper gives an overview about the novel developed material class for stereolithography and should be therefore of high interest to people with interest in novel rapid manufacturing materials and technology.
This paper introduces our robotic system named UGAV (Unmanned Ground-Air Vehicle) consisting of two semi-autonomous robot platforms, an Unmanned Ground Vehicle (UGV) and an Unmanned Aerial Vehicles (UAV). The paper focuses on three topics of the inspection with the combined UGV and UAV: (A) teleoperated control by means of cell or smart phones with a new concept of automatic configuration of the smart phone based on a RKI-XML description of the vehicles control capabilities, (B) the camera and vision system with the focus to real time feature extraction e.g. for the tracking of the UAV and (C) the architecture and hardware of the UAV.
The automated annotation of data from high throughput sequencing and genomics experiments is a significant challenge for bioinformatics. Most current approaches rely on sequential pipelines of gene finding and gene function prediction methods that annotate a gene with information from different reference data sources. Each function prediction method contributes evidence supporting a functional assignment. Such approaches generally ignore the links between the information in the reference datasets. These links, however, are valuable for assessing the plausibility of a function assignment and can be used to evaluate the confidence in a prediction. We are working towards a novel annotation system that uses the network of information supporting the function assignment to enrich the annotation process for use by expert curators and predicting the function of previously unannotated genes. In this paper we describe our success in the first stages of this development. We present the data integration steps that are needed to create the core database of integrated reference databases (UniProt, PFAM, PDB, GO and the pathway database Ara-Cyc) which has been established in the ONDEX data integration system. We also present a comparison between different methods for integration of GO terms as part of the function assignment pipeline and discuss the consequences of this analysis for improving the accuracy of gene function annotation. The methods and algorithms presented in this publication are an integral part of the ONDEX system which is freely available from http://ondex.sf.net/.
We have designed an inexpensive intelligent pedestrian counting system. The pedestrian counting system consists of several counters that can be connected together in a distributed fashion and communicate over the wireless channel. The motion pattern is recorded using a set of passive infrared (PIR) sensors. Each counter has one wireless sensor node that processes the PIR sensor data and transmits it to a base station. Then echo state network, a special kind of recurrent neural network, is used to predict the pedestrian count from the input pattern. The evaluation of the performance of such networks in a novel kind of application is one focus of this work. The counter gave a performance of 80.4% which is better than the commercially available low-priced pedestrian counters. The article reports the experiments we did for analyzing the counterperformance and lists the strengths and limitations of the current implementation. It will also report the preliminary test results obtained by substituting the PIR sensors with low-cost active IR distance sensors which can improve the counter performance further.
In this paper, residual sinks are used in bond graph model-based quantitative fault detection for the coupling of a model of a faultless process engineering system to a bond graph model of the faulty system. By this way, integral causality can be used as the preferred computational causality in both models. There is no need for numerical differentiation. Furthermore, unknown variables do not need to be eliminated from power continuity equations in order to obtain analytical redundancy relations (ARRs) in symbolic form. Residuals indicating faults are computed numerically as components of a descriptor vector of a differential algebraic equation system derived from the coupled bond graphs. The presented bond graph approach especially aims at models with non-linearities that make it cumbersome or even impossible to derive ARRs from model equations by elimination of unknown variables. For illustration, the approach is applied to a non-controlled as well as to a controlled hydraulic two-tank system. Finally, it is shown that not only the numerical computation of residuals but also the simultaneous numerical computation of their sensitivities with respect to a parameter can be supported by bond graph modelling.
Background: Bile acids, end products of the pathway for cholesterol elimination, are required for dietary lipid and fatsoluble vitamin absorption and maintain the balance between cholesterol synthesis in the liver and cholesterol excretion. They are composed of a steroid structure and are primarily made in the liver by the oxidation of cholesterol. Cholesterol is also highly abundant in the human ovarian follicle, where it is used in the formation of the sex steroids.
Methodology/Principal Findings: Here we describe for the first time evidence that all aspects of the bile acid synthesis pathway are present in the human ovarian follicle, including the enzymes in both the classical and alternative pathways, the nuclear receptors known to regulate the pathway, and the end product bile acids. Furthermore, we provide functional evidence that bile acids are produced by the human follicular granulosa cells in response to cholesterol presence in the culture media.
Conclusions/Significance: These findings establish a novel pathway present in the human ovarian follicle that has the capacity to compete directly with sex steroid synthesis.
Quereinsteiger und Neulinge der Vermittlung von Informationskompetenz werden grundlegend auf der Basis der vielfältigen praktischen Erfahrungen des Multiplikatorennetzwerks der AG Informationskompetenz NRW über strategische Konzepte, unterschiedliche Schulungsangebote für verschiedene Zielgruppen, Methodik und Didaktik von Schulungsveranstaltungen, Organisation und Infrastruktur sowie Evaluation und Qualitätsmanagement informiert.
Background: Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues.
Methodology/Principal Findings: Here, we present evidence that raft-associated endocytic proteins (flotillins) are preassembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions.
Conclusions: Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization.
Balanites aegyptiaca (Balanitaceae) is a widely grown desert plant with multiuse potential. In the present paper, a crude extract from B. aegyptiaca seeds equivalent to a ratio of 1 : 2000 seeds to the extract was screened for antiplasmodial activity. The determined IC(50) value for the chloroquine-susceptible Plasmodium falciparum NF54 strain was 68.26 μg/μL ± 3.5. Analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(H)-1,2,4-triazin-5-one oxime, an inhibitor of the parasitic M18 Aspartyl Aminopeptidase as one of the compounds which is responsible for the in vitro antiplasmodial activity. The crude plant extract had a K(i) of 2.35 μg/μL and showed a dose-dependent response. After depletion of the compound, a significantly lower inhibition was determined with a K(i) of 4.8 μg/μL. Moreover, two phenolic compounds, that is, 2,6-di-tert-butyl-phenol and 2,4-di-tert-butyl-phenol, with determined IC(50) values of 50.29 μM ± 3 and 47.82 μM ± 2.5, respectively, were detected. These compounds may contribute to the in vitro antimalarial activity due to their antioxidative properties. In an in vivo experiment, treatment of BALB/c mice with the aqueous Balanite extract did not lead to eradication of the parasites, although a reduced parasitemia at day 12 p.i. was observed.
In this paper, the performance evaluation of Frequency Modulated Chaotic On-Off Keying (FM-COOK) in AWGN, Rayleigh and Rician fading channels is given. The simulation results show that an improvement in BER can be gained by incorporating the FM modulation with COOK for SNR values less than 10dB in AWGN case and less than 6dB for Rayleigh and Rician fading channels.
In a research project funded by the German Research Foundation, meteorologists, data publication experts, and computer scientists optimised the publication process of meteorological data and developed software that supports metadata review. The project group placed particular emphasis on scientific and technical quality assurance of primary data and metadata. At the end, the software automatically registers a Digital Object Identifier at DataCite. The software has been successfully integrated into the infrastructure of the World Data Center for Climate, but a key was to make the results applicable to data publication processes in other sciences as well.
We present our approach to extend a Virtual Reality software framework towards the use for Augmented Reality applications. Although VR and AR applications have very similar requirements in terms of abstract components (like 6DOF input, stereoscopic output, simulation engines), the requirements in terms of hardware and software vary considerably. In this article we would like to share the experience gained from adapting our VR software framework for AR applications. We will address design issues for this task. The result is a VR/AR basic software that allows us to implement interactive applications without fixing their type (VR or AR) beforehand. Switching from VR to AR is a matter of changing the configuration file of the application. We also give an example of the use of the extended framework: Augmenting the magnetic field of bar magnets in physics classes. We describe the setup of the system and the real-time calculation of the magnetic field, using a GPU.
Anfang Januar 2007 trat in Nordrhein-Westfalen (NRW) das Hochschulfreiheitsgesetz (HFG) in Kraft. Mit dem HFG hat sich die Landesregierung in NRW weit aus der Detailsteuerung der Hochschulen zurückgezogen und tritt lediglich noch für existenzielle Schadensereignisse ein. So sind die Hochschulen – Universitäten und Fachhochschulen – in NRW keine staatlichen Einrichtungen mehr, sondern Körperschaften des öffentlichen Rechts in staatlicher Trägerschaft. Hiermit folgt das neue Hochschulgesetz dem hochschulpolitischen Paradigmenwechsel von einem staatlich geplanten, weitgehend einheitlich gestalteten System zu einem durch Profilbildung und Wettbewerb geprägten Hochschulsystem. In diesem Artikel werden die damit verbundenen Problemstellungen und Lösungsoptionen aufgezeigt und als Empfehlung die Einführung eines Chancen- und Risikomanagements beschrieben.
For the case when the abstraction of instantaneous state transitions is adopted, this paper proposes to start fault detection and isolation in an engineering system from a single time-invariant causality bond graph representation of a hybrid model. To that end, the paper picks up on a long-known proposal to model switching devices by a transformer modulated by a Boolean variable and a resistor in fixed conductance causality accounting for its ON resistance. Bond graph representations of hybrid system models developed in this way have been used so far mainly for the purpose of simulation. The paper shows that they can well constitute an approach to the bond-graph-based quantitative fault detection and isolation of hybrid models. Advantages are that the standard sequential causality assignment procedure can be a used without modification. A single set of analytical redundancy relations valid for all physically feasible system modes can be (automatically) derived from the bond graph. Stiff model equations due to small values of the ON resistance in the switch model may be avoided by symbolic reformulation of equations and letting the ON resistance of some switches tend to zero, turning them into ideal switches.
First, for two examples considered in the literature, it is shown that the approach proposed in this paper can produce the same analytical redundancy relations as were obtained from a hybrid bond graph with controlled junctions and the use of a sequential causality assignment procedure especially for fault detection and isolation purpose. Moreover, the usefulness of the proposed approach is illustrated in two case studies by its application to standard switching circuits extensively used in power electronic systems and by simulation of some fault scenarios. The approach, however, is not confined to the fault detection and isolation of such systems. Analytically validated simulation results obtained by means of the program Scilab give confidence in the approach.
A bond graph representation of switching devices known for a long time has been a modulated transformer with a modulus b(t)∈{0,1}∀t≥0 in conjunction with a resistor R:Ron accounting for the ON-resistance of a switch considered non-ideal. Besides other representations, this simple model has been used in bond graphs for simulation of the dynamic behaviour of hybrid systems. A previous article of the author has proposed to use the transformer–resistor pair in bond graphs for fault diagnosis in hybrid systems. Advantages are a unique bond graph for all system modes, the application of the unmodified standard Sequential Causality Assignment Procedure, fixed computational causalities and the derivation of analytical redundancy relations incorporating ‘Boolean’ transformer moduli so that they hold for all system modes. Switches temporarily connect and disconnect model parts. As a result, some independent storage elements may temporarily become dependent, so that the number of state variables is not time-invariant. This article addresses this problem in the context of modelling and simulation of fault scenarios in hybrid systems. In order to keep time-invariant preferred integral causality at storage ports, residual sinks previously introduced by the author are used. When two storage elements become dependent at a switching time instance ts, a residual sink is activated. It enforces that the outputs of two dependent storage elements become immediately equal by imposing the conjugate3 power variable of appropriate value on their inputs. The approach is illustrated by the bond graph modelling and simulation of some fault scenarios in a standard three-phase switched power inverter supplying power into an RL-load in a delta configuration. A well-developed approach to model-based fault detection and isolation is to evaluate the residual of analytical redundancy relations. In this article, analytical redundancy relation residuals have been computed numerically by coupling a bond graph of the faulty system to one of the non-faulty systems by means of residual sinks. The presented approach is not confined to power electronic systems but can be used for hybrid systems in other domains as well. In further work, the RL-load may be replaced by a bond graph model of an alternating current motor in order to study the effect of switch failures in the power inverter on to the dynamic behaviour of the motor.
Human mesenchymal stem cells (hMSCs) are considered a promising cell source for regenerative medicine, because they have the potential to differentiate into a variety of lineages among which the mesoderm-derived lineages such adipo- or osteogenesis are investigated best. Human MSCs can be harvested in reasonable to large amounts from several parts of the patient’s body and due to this possible autologous origin, allorecognition can be avoided. In addition, even in allogenic origin-derived donor cells, hMSCs generate a local immunosuppressive microenvironment, causing only a weak immune reaction. There is an increasing need for bone replacement in patients from all ages, due to a variety of reasons such as a new recreational behavior in young adults or age-related diseases. Adipogenic differentiation is another interesting lineage, because fat tissue is considered to be a major factor triggering atherosclerosis that ultimately leads to cardiovascular diseases, the main cause of death in industrialized countries. However, understanding the differentiation process in detail is obligatory to achieve a tight control of the process for future clinical applications to avoid undesired side effects. In this review, the current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.
The biological effects of bilirubin, still poorly understood, are concentration-dependent ranging from cell protection to toxicity. Here we present data that at high nontoxic physiological concentrations, bilirubin inhibits growth of proliferating human coronary artery smooth muscle cells by three events. It impairs the activation of Raf/ERK/MAPK pathway and the cellular Raf and cyclin D1 content that results in retinoblastoma protein hypophosphorylation on amino acids S608 and S780. These events impede the release of YY1 to the nuclei and its availability to regulate the expression of genes and to support cellular proliferation. Moreover, altered calcium influx and calpain II protease activation leads to proteolytical degradation of transcription factor YY1. We conclude that in the serum-stimulated human vascular smooth muscle primary cell cultures, bilirubin favors growth arrest, and we propose that this activity is regulated by its interaction with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis. We propose that these activities together culminate in diminished 5 S and 45 S ribosomal RNA synthesis and cell growth arrest. The observations provide important mechanistic insight into the molecular mechanisms underlying the transition of human vascular smooth muscle cells from proliferative to contractile phenotype and the role of bilirubin in this transition.
This article concerns with the accessibility of Business process modelling tools (BPMo tools) and business process modelling languages (BPMo languages). Therefore the reader will be introduced to business process management and the authors' motivation behind this inquiry. Afterwards, the paper will reflect problems when applying inaccessible BPMo tools. To illustrate these problems the authors distinguish between two different categories of issues and provide practical examples. Finally the article will present three approaches to improve the accessibility of BPMo tools and BPMo languages.
After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.
Molecular modeling is an important subdomain in the field of computational modeling, regarding both scientific and industrial applications. This is because computer simulations on a molecular level are a virtuous instrument to study the impact of microscopic on macroscopic phenomena. Accurate molecular models are indispensable for such simulations in order to predict physical target observables, like density, pressure, diffusion coefficients or energetic properties, quantitatively over a wide range of temperatures. Thereby, molecular interactions are described mathematically by force fields. The mathematical description includes parameters for both intramolecular and intermolecular interactions. While intramolecular force field parameters can be determined by quantum mechanics, the parameterization of the intermolecular part is often tedious. Recently, an empirical procedure, based on the minimization of a loss function between simulated and experimental physical properties, was published by the authors. Thereby, efficient gradient-based numerical optimization algorithms were used. However, empirical force field optimization is inhibited by the two following central issues appearing in molecular simulations: firstly, they are extremely time-consuming, even on modern and high-performance computer clusters, and secondly, simulation data is affected by statistical noise. The latter provokes the fact that an accurate computation of gradients or Hessians is nearly impossible close to a local or global minimum, mainly because the loss function is flat. Therefore, the question arises of whether to apply a derivative-free method approximating the loss function by an appropriate model function. In this paper, a new Sparse Grid-based Optimization Workflow (SpaGrOW) is presented, which accomplishes this task robustly and, at the same time, keeps the number of time-consuming simulations relatively small. This is achieved by an efficient sampling procedure for the approximation based on sparse grids, which is described in full detail: in order to counteract the fact that sparse grids are fully occupied on their boundaries, a mathematical transformation is applied to generate homogeneous Dirichlet boundary conditions. As the main drawback of sparse grids methods is the assumption that the function to be modeled exhibits certain smoothness properties, it has to be approximated by smooth functions first. Radial basis functions turned out to be very suitable to solve this task. The smoothing procedure and the subsequent interpolation on sparse grids are performed within sufficiently large compact trust regions of the parameter space. It is shown and explained how the combination of the three ingredients leads to a new efficient derivative-free algorithm, which has the additional advantage that it is capable of reducing the overall number of simulations by a factor of about two in comparison to gradient-based optimization methods. At the same time, the robustness with respect to statistical noise is maintained. This assertion is proven by both theoretical considerations and practical evaluations for molecular simulations on chemical example substances.
Qualitätsverbesserung und Zeitersparnis bei der Stipendienvergabe durch automatisierten Workflow
(2013)
Für die Vergabe der Deutschlandstipendien hatte die Hochschule anfangs ein Verfahren festgelegt, das viel manuelle Arbeitsschritte umfasst: Die Studierenden hatten ihre Bewerbungsunterlagen schriftlich einzureichen. Dazu gehörten neben einem Motivationsschreiben, einem Ausdruck des aktuellen Notenspiegels alle weiteren Referenzen zur Einschätzung der Bewerbung gemäß den gesetzlichen Auswahlkriterien. Als Grundlage zur Bewertung der „sozialen Kriterien“ sollten die Bewerberinnen und Bewerber ein Gutachten eines Professors oder einer Professorin der Hochschule einholen.
Tamoxifen therapy of invasive breast cancer has been associated with increased levels of endothelin-1 (ET-1) so that an endothelin-1 receptor (ETR) blockade has been suggested as a new therapeutic approach. This study analyzed the relationship between Tamoxifen and ET-1 signalling in invasive breast cancer. Using paraffinized tissue from 50 randomly chosen cases of invasive and in-situ ductal carcinoma from our archive, the expression of ETRs was analyzed by immune histology. ETRs were regularly detectable in normal breast tissue, but rarely in adjacent tumor areas (3/50 cases). By immunoprecipitation, a complex was found consisting of ET-1, estrogen receptors and Tamoxifen. Consequently, transcription of several target genes of ET-1 and estrogen receptors was detectable (interleukin-6, wnt-11 and a vimentin spliceform). In particular, the combination of Tamoxifen, ET-1, and estrogen receptors induced further increasing levels of these target genes. Some of these genes have been found upregulated in metastatically spreading breast cancer cells. We conclude: i) ETRs do not play a role in invasive or in-situ ductal breast cancer; ii) estrogen receptors and Tamoxifen build a complex with ET-1; and iii) upregulated transcription of target genes by ET-1–estrogen receptor–Tamoxifen complex may negatively influence breast cancer prognosis. These results indicate a role for ET-1 in Tamoxifen treated breast cancer patients leading to a potentially worsening prognosis.
Increased endothelin-1 decreases PKC alpha (PKCα), resulting in high miRNA 15a levels in kidney tumors. Breast cancer cells treated with ET-1, β-estrogen, Tamoxifen, Tamoxifen + β-estrogen and Tamoxifen + ET-1 were analysed regarding miRNA 15a expression. Significantly increased miRNA 15a levels were found after ET-1, becoming further increased in Tamoxifen + ET-1 treated cells. Our group already showed that miRNA 15a induces MAPK p38 splicing resulting in a truncated product called Mxi-2, whose function has yet to be defined in tumors. We described for the first time in ET-1 induced tumor cells that Mxi-2 builds a complex with Ago2, a miRNA binding protein, which is important for the localization of miRNAs to the 3′UTR of target genes. Furthermore, we show that Mxi-2/Ago2 is important for the interaction with the miRNA 1285 which binds to the 3′end of the tumor suppressor gene p53, being responsible for the downregulation of p53. Tissue arrays from breast cancer patients were performed, analysing Mxi-2, p53 and PKCα. Since the Mxi-2 levels increase in Tamoxifen + ET-1 treated cells, we claim that increasing ET-1 levels in Tamoxifen treated breast cancer patients are responsible for decreasing p53 levels. In summary, ET-1 decreases nuclear PKCα levels, while increasing the amount of miRNA 15a. This causes high levels of Mxi-2, necessary for complex formation with Ago2. The newly identified Mxi-2/Ago2 complex interacting with miRNA 1285 leads to increased 3′UTR p53 interaction, resulting in decreased p53 levels and subsequent tumor progression. This newly identified mechanism is a possible explanation for the development of ET-1 induced tumors.
The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation.
Generating and visualizing large areas of vegetation that look natural makes terrain surfaces much more realistic. However, this is a challenging field in computer graphics, because ecological systems are complex and visually appealing plant models are geometrically detailed. This work presents Silva (System for the Instantiation of Large Vegetated Areas), a system to generate and visualize large vegetated areas based on the ecological surrounding. Silva generates vegetation on Wang-tiles with associated reusable distributions enabling multi-level instantiation. This paper presents a method to generate Poisson Disc Distributions (PDDs) with variable radii on Wang-tile sets (without a global optimization) that is able to generate seamless tilings. Because Silva has a freely configurable generation pipeline and can consider plant neighborhoods it is able to incorporate arbitrary abiotic and biotic components during generation. Based on multi-levelinstancing and nested kd-trees, the distributions on the Wang-tiles allow their acceleration structures to be reused during visualization. This enables Silva to visualize large vegetated areas of several hundred square kilometers with low render times and a small memory footprint.
Introduction: Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis.
Methods: For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13–/–) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacrificed every second day for histological examination of the ankle joints. Ankle sections were evaluated histologically for infiltration of inflammatory cells, pannus tissue formation and bone/cartilage destruction. Semi-quantitative PCR was used to determine MMP-13 expression levels in ankle joints of untreated and K/BxN serum-injected mice.
Results: This study shows that MMP-13 is a regulator of inflammation. We observed increased expression of MMP-13 in ankle joints of WT mice during K/BxN serum-induced arthritis and both K/BxN serum-treated WT and MMP-13–/– mice developed progressive arthritis with a similar onset. However, MMP-13–/– mice showed significantly reduced disease over the whole arthritic period. Ankle joints of WT mice showed severe joint destruction with extensive inflammation and erosion of cartilage and bone. In contrast, MMP-13–/– mice displayed significantly decreased severity of arthritis (50% to 60%) as analyzed by clinical and histological scoring methods.
Conclusions: MMP-13 deficiency acts to suppress the local inflammatory responses. Therefore, MMP-13 has a role in the pathogenesis of arthritis, suggesting MMP-13 is a potential therapeutic target.
Mathematische Vorkurse werden zur Vorbereitung auf das Studium allen Studienanfängerinnen und Studienanfängern der Ingenieurmathematik dringend empfohlen, aber leider fällt es immer schwerer, die Lücke zwischen den Erwartungen an die Vorkenntnisse der Studierenden und dem tatsächlichen Rüstwerkzeug der Studienanfänger/innen zu schließen. In diesem Artikel wird die Projektidee vorgestellt, im Rahmen einer Zusammenarbeit mit dem internationalen ROLE-Projekt einen mathematischen Vorkurs durch zusätzliche Elemente aus dem Bereich der Open Educational Resources sinnvoll zu ergänzen, um eine Binnendifferenzierung zu ermöglichen und den Studierenden zu erleichtern, sich in den Lehrstoff individuell einzuarbeiten.
In this paper we present the steps towards a well-designed concept of a 5VR6 system for school experiments in scientific domains like physics, biology and chemistry. The steps include the analysis of system requirements in general, the analysis of school experiments and the analysis of input and output devices demands. Based on the results of these steps we show a taxonomy of school experiments and provide a comparison between several currently available devices which can be used for building such a system. We also compare the advantages and shortcomings of 5VR6 and 5AR6 systems in general to show why, in our opinion, 5VR6 systems are better suited for school-use.
Das AD 2000-Regelwerk ist der dominierende Standard für den Druckbehälterbau in Deutschland. Die bereits in anderen europäischen Ländern verbreitete DIN EN 13445 findet kaum Berücksichtigung. Dies allerdings zu Unrecht, denn ein aktueller Vergleich, der im Rahmen einer Bachelorarbeit durchgeführte wurde, zeigt: Die EN 13445 ist zu einer echten Alternative gereift. Gerade das Hauptargument gegen eine Umstellung, die steigenden Kosten, ist längst überholt.
The contribution of the most common reciprocal translocation in childhood B-cell precursor leukemia t(12;21)(p13;q22) to leukemia development is still under debate. Direct as well as secondary indirect effects of the TEL-AML1 fusion protein are commonly recorded by using cell lines and patient samples, often bearing the TEL-AML1 fusion protein for decades. To identify direct targets of the fusion protein a short-term induction of TEL-AML1 is needed. We here describe in detail the experimental procedure, quality controls and contents of the ChIP, mRNA expression and SILAC datasets associated with the study published by Linka and colleagues in the Blood Cancer Journal [1] utilizing a short term induction of TEL-AML1 in an inducible precursor B-cell line model.
We investigated graphene structures grafted with fullerenes. The size of the graphene sheets ranges from 6400 to 640,000 atoms. The fullerenes (C60 and C240) are placed on top of the graphene sheets, using different impact velocities we could distinguish three types of impact. Furthermore, we investigated the changes of the vibrational properties. The modified graphene planes show additional features in the vibronic density of states.
We are happy to present you the special issue on Best Practice in Robot Software Development of the Journal on Software Engineering for Robotics! The spark for this special issue came during the eighth workshop on Software Development and Integration in Robotics (SDIR) at the 2013 IEEE International Conference on Robotics and Automation. The workshop focused on Robot Software Architectures, and the fruitful discussions made it clear that the design, development, and deployment of robot software is always an interplay between competing aspects. These are often couched in antagonistic pairs, such as dependability versus performance, and prominently include quality attributes as well as functional, nonfunctional, and application requirements.
Purpose – The aim of the study is to investigate the implementation of corporate sustainability (CS) in the German real estate sector.
Design/methodology/approach – The authors begin by outlining the framework set by the European Union and the German Federal Government for companies wanting to be classified as sustainable. After this, the relevance of sustainability for German real estate companies is discussed. Their empirical section contains an international comparison. Finally, they present an analysis checking the implementation of CS for the main 135 German real estate companies.
Findings – The present analysis shows that German real estate companies compare well with their international counterparts, in 2012 representing 15 per cent of all real estate firms reporting on the basis of the Global Reporting Initiative. However, of the 135 companies in Germany surveyed, only a small proportion classify themselves as CS and CSR (corporate social responsibility) enterprises. This number could be rapidly increased by better documentation of companies’ commitment to sustainability.
Practical implications – The study’s importance lies in the overview it provides of CS activities in the German real estate industry. In addition, it provides hints on how companies can improve their documentation to classify as CSR enterprises. Although the analysis concentrates on Germany, the results are also relevant for companies in other European countries.
Might the gravity levels found on other planets and on the moon be sufficient to provide an adequate perception of upright for astronauts? Can the amount of gravity required be predicted from the physiological threshold for linear acceleration? The perception of upright is determined not only by gravity but also visual information when available and assumptions about the orientation of the body. Here, we used a human centrifuge to simulate gravity levels from zero to earth gravity along the long-axis of the body and measured observers' perception of upright using the Oriented Character Recognition Test (OCHART) with and without visual cues arranged to indicate a direction of gravity that differed from the body's long axis. This procedure allowed us to assess the relative contribution of the added gravity in determining the perceptual upright. Control experiments off the centrifuge allowed us to measure the relative contributions of normal gravity, vision, and body orientation for each participant. We found that the influence of 1 g in determining the perceptual upright did not depend on whether the acceleration was created by lying on the centrifuge or by normal gravity. The 50% threshold for centrifuge-simulated gravity's ability to influence the perceptual upright was at around 0.15 g, close to the level of moon gravity but much higher than the threshold for detecting linear acceleration along the long axis of the body. This observation may partially explain the instability of moonwalkers but is good news for future missions to Mars.
Automated parameterization of intermolecular pair potentials using global optimization techniques
(2014)
In this work, different global optimization techniques are assessed for the automated development of molecular force fields, as used in molecular dynamics and Monte Carlo simulations. The quest of finding suitable force field parameters is treated as a mathematical minimization problem. Intricate problem characteristics such as extremely costly and even abortive simulations, noisy simulation results, and especially multiple local minima naturally lead to the use of sophisticated global optimization algorithms. Five diverse algorithms (pure random search, recursive random search, CMA-ES, differential evolution, and taboo search) are compared to our own tailor-made solution named CoSMoS. CoSMoS is an automated workflow. It models the parameters’ influence on the simulation observables to detect a globally optimal set of parameters. It is shown how and why this approach is superior to other algorithms. Applied to suitable test functions and simulations for phosgene, CoSMoS effectively reduces the number of required simulations and real time for the optimization task.
Nitrile-type inhibitors are known to interact with cysteine proteases in a covalent-reversible manner. The chemotype of 3-cyano-3-aza-β-amino acid derivatives was designed in which the N-cyano group is centrally arranged in the molecule to allow for interactions with the nonprimed and primed binding regions of the target enzymes. These compounds were evaluated as inhibitors of the human cysteine cathepsins K, S, B, and L. They exhibited slow-binding behavior and were found to be exceptionally potent, in particular toward cathepsin K, with second-order rate constants up to 52 900 × 103 M–1 s–1.
Das sogenannte „Deutschlandstipendium“ ist 2010 ins Leben gerufen worden. Gemäß den gesetzlichen Vorgaben sollen die Stipendien nach Begabung und Leistung vergeben werden. Darüber hinaus sollen auch gesellschaftliches Engagement oder besondere soziale, familiäre oder persönliche Umstände berücksichtigt werden. Bei der Finanzierung sind die Hochschulen zunächst auf das Einwerben privater Fördermittel angewiesen, die von Bund und Land um denselben Betrag aufgestockt werden. Die privaten Mittelgeber können für die von ihnen anteilig finanzierten Stipendien festlegen, aus welchen Studiengängen ihre Stipendiaten ausgewählt werden sollen. Die Hochschulen haben jedoch darauf zu achten, dass ein Drittel aller zu vergebenden Stipendien ohne eine entsprechende Zweckbindung vergeben werden. Einen direkten Einfluss auf die Auswahl einzelner Kandidaten dürfen die Förderer nicht haben. Vor diesem Hintergrund sind die Hochschulen angehalten, Anreize für private Förderer zu schaffen und parallel Bewerbungs- und Auswahlverfahren zu konzipieren, die die genannten gesetzlichen Vorgaben einhalten. Dadurch entsteht bei den Hochschulen ein erheblicher Verwaltungsaufwand. Zu dessen Reduzierung wird in diesem Artikel ein transparenter, nachvollziehbarer, zeit- und kostensparender Prozess durch einen programmierten Workflow beschrieben.