Hauptspannungstrajektorien in der numerischen Festkörpermechanik: Ein Algorithmus zur Visualisierung der Bauteilbeanspruchung in zwei und drei Dimensionen

Für die anschauliche Darstellung der Ergebnisse mechanischer Untersuchungen von Bauteilbeanspruchungen existieren diverse Visualisierungsformen. Eine solche Visualisierungsform ist die Darstellung von Hauptspannungstrajektorien, vorwiegend der Hauptnormalspannungstrajektorien des Spannungszustandes eines Bauteils. Trajektorienbilder sind im Bereich des Bauingenieurwesens insbesondere im Massivbau nach wie vor von großem Interesse. So werden beispielsweise die in der Stahlbetonnormung fest verankerten Stabwerkmodelle in erster Linie auf der Basis von Hauptspannungstrajektorien entwickelt. Aus diesem Grund gehören Trajektorienbilder heute nicht nur zum akademischen Standardlehrstoff, sondern werden auch in wissenschaftlichen Veröffentlichungen gern zur Erläuterung von komplexen Spannungszuständen herangezogen. Unglücklicherweise finden sich in der einschlägigen Fachliteratur und in wissenschaftlichen Arbeiten nicht selten grundlegende Fehldarstellungen. Diese Arbeit stellt einen geeigneten Algorithmus zur korrekten Darstellung von Trajektorienbildern auf der Basis numerisch (beispielsweise mit der Finite-Elemente-Methode) berechneter Spannungslösungen bereit. Anhand von systematischen Untersuchungen zu verschiedenen Bauteilgeometrien und Beanspruchungs-konstellationen konnte eine Reihe von immer wieder zu findenden Fehlinterpretationen von Trajektorienbildern aufgezeigt werden. Die oft angenommene Analogie von Spannungstrajektorien zu Stromlinien von Fluidströmungen im Sinne eines „Kraftflusses“ wurde widerlegt. Das Problem bei herkömmlichen Trajektorienbildern, dass diese nicht imstande sind, Auskunft über die Größe der Spannungen zu geben, führte mitunter zu der bisweilen verbreiteten Annahme, die Verdichtung von Trajektorien in einem Trajektorienbild bedeute eine Spannungskonzentration an entsprechender Stelle. Anhand von Beispielen wird dies eindeutig widerlegt. Zur Vermeidung dieses Fehleindrucks wurde eine neue Darstellungsform eingeführt, die neben den Richtungen auch die Größen der Hauptspannungen anhand eines Farbmaßstabes ablesbar macht. Mithilfe einer variablen Schrittweitensteuerung konnte die Genauigkeit bei der Pfadverfolgung der Trajektorien gegenüber festen Schrittweiten maßgeblich verbessert werden. Geeignete Abbruchkriterien gewährleisten das zuverlässige Auffinden von äußeren sowie innenliegenden Bauteilbegrenzungen und die Detektion geschlossener Trajektorien. Einen wesentlichen Punkt stellen mögliche Singularitäten wie isotrope Punkte, isotrope Grenzen oder isotrope Gebiete dar, in denen die Hauptspannungsrichtungen mithilfe der Lösung des Eigenwertproblems nicht eindeutig ermittelbar sind. Deren Nichtbeachtung ist eine wesentliche Ursache für Fehldarstellungen in der Literatur. Die an solchen Stellen auftretenden Effekte und entstehenden Probleme bei der Ermittlung und Interpretierbarkeit von Trajektorienbildern wurden systematisch analysiert und entsprechende Lösungsvorschläge erarbeitet. Bisher blieb die Verwendung von Trajektorienbildern praktisch auf zweidimensionale Probleme beschränkt. Das Potenzial von Spannungstrajektorien zur Visualisierung dreidimensionaler Spannungszustände war bislang noch unerforscht. Daher wurde das Verfahren zur Berechnung von Spannungstrajektorien auf dreidimensionale Spannungszustände übertragen. Während sich einige Teilbereiche des entwickelten Algorithmus, wie beispielsweise die Schrittweitensteuerung, problemlos unter Hinzuziehung einer weiteren Richtungskomponente für dreidimensionale Probleme erweitern lassen, hat sich gezeigt, dass diese Erweiterung auch diverse Nichttrivialitäten enthält. Bei den aus der Berechnung erhaltenen Trajektorien handelt es sich im dreidimensionalen Fall um räumliche Kurven. Eine wesentliche Erkenntnis aus berechneten dreidimensionalen Trajektorienbildern ist, dass sich diese Raumkurven im Unterschied zum ebenen Fall in der Regel nicht schneiden und somit keine Maschen zwischen den Trajektorien wie im Zweidimensionalen aufspannen. Eine noch verbleibende Schwierigkeit bei der Anwendung dreidimensionaler Trajektorienbilder besteht in deren interpretierbarer Darstellung. In der vorliegenden Arbeit wurden hierzu einige Vorschläge erarbeitet sowie deren Anwendbarkeit getestet und bewertet. Um die Möglichkeit der eigenständigen Berechnung von Trajektorienbildern einem breiten Nutzerkreis zugänglich zu machen, können aufbauend auf den Erkenntnissen dieser Arbeit leicht bedienbare Softwarelösungen mit grafischer Benutzeroberfläche entwickelt werden. Der Algorithmus zur Trajektorienermittlung wurde mit diesem Ansinnen in allen Details beschrieben. Auf dem Gebiet der Trajektorien dreidimensionaler Spannungszustände hat sich darüber hinaus noch weiterer Forschungsbedarf herausgestellt, hierzu werden in der Arbeit an den entsprechenden Stellen einige Vorschläge zur Weiterentwicklung gemacht. Der entwickelte Algorithmus ermöglicht darüber hinaus auch direkt auch die Ermittlung von Trajektorien materiell oder geometrisch nichtlinearer sowie dynamischer und sonstiger Probleme, sofern der entsprechende Spannungszustand vorliegt. Außerdem kann der Algorithmus prinzipiell auch zur Bestimmung von Hauptschubspannungstrajektorien oder Hauptmomentenlinien angewandt werden.There are several kinds of visualisation for the illustration of the results of mechanical investigations of structural elements’ load bearing behaviour. The illustration of the stress state via principal stress trajectories, mainly principal normal stress trajectories, is one of them. In the field of civil engineering, trajectory plots are still of notable interest, particularly in solid construction. Thus, the truss models as part of the European engineering standards for steel-reinforced concrete are primarily developed using principal stress trajectories. For this reason, trajectory plots are not only part of the academic subjects taught at university, but they are also used in scientific publications for the illustration of complex stress states. Unfortunately, fundamental misrepresentations are not rare in the relevant literature and scientific works. This work provides a suitable algorithm for accurate trajectory plots based on numerically computed stress solutions (e.g. using the finite element method). By means of systematic investigations of several structural element’s geometries and loading situations, a number of prevalent misinterpretations was identified. The analogy often assumed between stress trajectories and streamlines of fluid flow in terms of “load flow” has been disproved. A property of traditional trajectory plots is not able to indicate the level of stress. Thus, in areas of narrowing trajectories stress concentrations are often assumed. By means of examples this assumption was clearly disproved. To prevent the appearance of such misimpressions, the stress levels are represented using a colour scale known from contour plots. An adaptive incrementation during path tracing allows a significant increase of accuracy compared with uniform incrementation. Suitable stop criteria ensure reliable detection of outer and inner borders as well as closing of trajectories. One important aspect is the appearance of singularities like isotropic points, isotropic borders and isotropic areas, where the principal stress directions in terms of eigenvectors are not unique. Non-observance is one of the main causes of misrepresentations of trajectory plots in literature. The effects due to the appearance of isotropic points and the arising problems for calculation and interpretation of stress trajectories were systematically analysed, and proposals for a solution were made. Up to now, the usage of trajectory plots was limited to two-dimensional problems. The potential of stress trajectories for the visualisation of three-dimensional stress states was still unexplored. Therefore, the algorithm for the calculation of stress trajectories was augmented in three dimensions. Some parts of the two-dimensional algorithm like adaptive incrementation could be directly translated simply considering the third coordinate, whereas the necessary modifications of some parts turned out to be non-trivial. The stress trajectories of three-dimensional stress states prove to be space curves. An essential finding from the calculated three-dimensional trajectory plots was, that three-dimensional trajectories – compared to two-dimensional trajectories – generally do not intersect each other. According to this, three-dimensional trajectories generally do not build meshes. The interpretable display of three-dimensional trajectories is still a difficulty. In this work, the applicability of some methods has been tested and assessed. To enable a large group of users to create stress trajectory plots individually, easily operated software solutions with a graphical user interface should be developed. For this purpose, the developed algorithm for tracing trajectories is described in every detail. In the field of three-dimensional stress trajectories need of further research came to light, which is specified in the corresponding parts of this work. In addition, the developed algorithm allows also the calculation of stress trajectories of geometrical and material non-linear as well as dynamic and other problems, if only the stress state is available. Furthermore, the algorithm can be applied for the calculation of principal shear stress trajectories and principal moment trajectories

Aspekte der Modellierung des Tragverhaltens von Textilbeton unter biaxialer Beanspruchung

Zur Bemessung und Simulation von flächigen Textilbetonstrukturen werden Berechnungsmodelle benötigt, die das Materialverhalten unter biaxialer Beanspruchung abbilden können. Für eindimensionale Strukturen existieren einige Modelle, zu deren Weiterentwicklung eine Erweiterung zur Abbildung des biaxialen Materialverhaltens vorgeschlagen wird. In diesem Beitrag werden die notwendigen Erweiterungen und deren Umsetzbarkeit bei der Modellierung diskutiert und bewertet.For design and simulation of plane textile reinforced concrete structures mechanical models representing the material behaviour under biaxial loading are necessary. For one-dimensional structures several models were presented in the past. For their further development an extension for biaxial material behaviour is usually proposed. In this paper the required extensions are discussed and their feasibility for modelling is assessed

Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans

<p>Abstract</p> <p>Background</p> <p>Coenzyme Q₁₀(CoQ₁₀) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ₁₀deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ₁₀status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3^G272S, CoQ6^M406V, CoQ7^M103T), reduction (NQO1^P187S, NQO2^L47F) and metabolism (apoE3/4) of CoQ₁₀and their association with CoQ₁₀status. For this purpose, CoQ₁₀serum levels of 54 healthy male volunteers were determined before (T₀) and after a 14 days supplementation (T₁₄) with 150 mg/d of the reduced form of CoQ₁₀.</p> <p>Findings</p> <p>At T₀, the CoQ₁₀level of heterozygous NQO1^P187Scarriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ₁₀plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3^G272Scarriers had higher CoQ₁₀plasma levels at T₁₄compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082).</p> <p>Conclusions</p> <p>In conclusion, our pilot study provides evidence that NQO1^P187Sand apoE polymorphisms influence CoQ₁₀status in humans.</p

Global Genotype-Phenotype Correlations in Pseudomonas aeruginosa

Once the genome sequence of an organism is obtained, attention turns from identifying genes to understanding their function, their organization and control of metabolic pathways and networks that determine its physiology. Recent technical advances in acquiring genome-wide data have led to substantial progress in identifying gene functions. However, we still do not know the function of a large number of genes and, even when a gene product has been assigned to a functional class, we cannot normally predict its contribution to the phenotypic behaviour of the cell or organism - the phenome. In this study, we assessed bacterial growth parameters of 4030 non-redundant PA14 transposon mutants in the pathogenic bacterium Pseudomonas aeruginosa. The genome-wide simultaneous analysis of 119 distinct growth-related phenotypes uncovered a comprehensive phenome and provided evidence that most genotypes are not phenotypically isolated but rather define specific complex phenotypic clusters of genotypes. Since phenotypic overlap was demonstrated to reflect the relatedness of genotypes on a global scale, knowledge of an organism's phenome might significantly contribute to the advancement of functional genomics

Functional Polymorphism of the Mu-Opioid Receptor Gene (OPRM1) Influences Reinforcement Learning in Humans

Previous reports on the functional effects (i.e., gain or loss of function), and phenotypic outcomes (e.g., changes in addiction vulnerability and stress response) of a commonly occurring functional single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1 A118G) have been inconsistent. Here we examine the effect of this polymorphism on implicit reward learning. We used a probabilistic signal detection task to determine whether this polymorphism impacts response bias to monetary reward in 63 healthy adult subjects: 51 AA homozygotes and 12 G allele carriers. OPRM1 AA homozygotes exhibited typical responding to the rewarded response—that is, their bias to the rewarded stimulus increased over time. However, OPRM1 G allele carriers exhibited a decline in response to the rewarded stimulus compared to the AA homozygotes. These results extend previous reports on the heritability of performance on this task by implicating a specific polymorphism. Through comparison with other studies using this task, we suggest a possible mechanism by which the OPRM1 polymorphism may confer reduced response to natural reward through a dopamine-mediated decrease during positive reinforcement learning

Treatment of Peritoneal Carcinomatosis by Targeted Delivery of the Radio-Labeled Tumor Homing Peptide 213Bi-DTPA-[F3]2 into the Nucleus of Tumor Cells

BACKGROUND: Alpha-particle emitting isotopes are effective novel tools in cancer therapy, but targeted delivery into tumors is a prerequisite of their application to avoid toxic side effects. Peritoneal carcinomatosis is a widespread dissemination of tumors throughout the peritoneal cavity. As peritoneal carcinomatosis is fatal in most cases, novel therapies are needed. F3 is a tumor homing peptide which is internalized into the nucleus of tumor cells upon binding to nucleolin on the cell surface. Therefore, F3 may be an appropriate carrier for alpha-particle emitting isotopes facilitating selective tumor therapies. PRINCIPAL FINDINGS: A dimer of the vascular tumor homing peptide F3 was chemically coupled to the alpha-emitter (213)Bi ((213)Bi-DTPA-[F3](2)). We found (213)Bi-DTPA-[F3](2) to accumulate in the nucleus of tumor cells in vitro and in intraperitoneally growing tumors in vivo. To study the anti-tumor activity of (213)Bi-DTPA-[F3](2) we treated mice bearing intraperitoneally growing xenograft tumors with (213)Bi-DTPA-[F3](2). In a tumor prevention study between the days 4-14 after inoculation of tumor cells 6x1.85 MBq (50 microCi) of (213)Bi-DTPA-[F3](2) were injected. In a tumor reduction study between the days 16-26 after inoculation of tumor cells 6x1.85 MBq of (213)Bi-DTPA-[F3](2) were injected. The survival time of the animals was increased from 51 to 93.5 days in the prevention study and from 57 days to 78 days in the tumor reduction study. No toxicity of the treatment was observed. In bio-distribution studies we found (213)Bi-DTPA-[F3](2) to accumulate in tumors but only low activities were found in control organs except for the kidneys, where (213)Bi-DTPA-[F3](2) is found due to renal excretion. CONCLUSIONS/SIGNIFICANCE: In conclusion we report that (213)Bi-DTPA-[F3](2) is a novel tool for the targeted delivery of alpha-emitters into the nucleus of tumor cells that effectively controls peritoneal carcinomatosis in preclinical models and may also be useful in oncology

Breast imaging technology: Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects - applications to breast cancer

A variety of imaging technologies is being investigated as tools for studying gene expression in living subjects. Two technologies that use radiolabeled isotopes are single photon emission computed tomography (SPECT) and positron emission tomography (PET). A relatively high sensitivity, a full quantitative tomographic capability, and the ability to extend small animal imaging assays directly into human applications characterize radionuclide approaches. Various radiolabeled probes (tracers) can be synthesized to target specific molecules present in breast cancer cells. These include antibodies or ligands to target cell surface receptors, substrates for intracellular enzymes, antisense oligodeoxynucleotide probes for targeting mRNA, probes for targeting intracellular receptors, and probes for genes transferred into the cell. We briefly discuss each of these imaging approaches and focus in detail on imaging reporter genes. In a PET reporter gene system for in vivo reporter gene imaging, the protein products of the reporter genes sequester positron emitting reporter probes. PET subsequently measures the PET reporter gene dependent sequestration of the PET reporter probe in living animals. We describe and review reporter gene approaches using the herpes simplex type 1 virus thymidine kinase and the dopamine type 2 receptor genes. Application of the reporter gene approach to animal models for breast cancer is discussed. Prospects for future applications of the transgene imaging technology in human gene therapy are also discussed. Both SPECT and PET provide unique opportunities to study animal models of breast cancer with direct application to human imaging. Continued development of new technology, probes and assays should help in the better understanding of basic breast cancer biology and in the improved management of breast cancer patients

Development of a primary care-based complex care management intervention for chronically ill patients at high risk for hospitalization: a study protocol

Background: Complex care management is seen as an approach to face the challenges of an ageing society with increasing numbers of patients with complex care needs. The Medical Research Council in the United Kingdom has proposed a framework for the development and evaluation of complex interventions that will be used to develop and evaluate a primary care-based complex care management program for chronically ill patients at high risk for future hospitalization in Germany. Methods and design: We present a multi-method procedure to develop a complex care management program to implement interventions aimed at reducing potentially avoidable hospitalizations for primary care patients with type 2 diabetes mellitus, chronic obstructive pulmonary disease, or chronic heart failure and a high likelihood of hospitalization. The procedure will start with reflection about underlying precipitating factors of hospitalizations and how they may be targeted by the planned intervention (pre-clinical phase). An intervention model will then be developed (phase I) based on theory, literature, and exploratory studies (phase II). Exploratory studies are planned that entail the recruitment of 200 patients from 10 general practices. Eligible patients will be identified using two ways of 'case finding': software based predictive modelling and physicians' proposal of patients based on clinical experience. The resulting subpopulations will be compared regarding healthcare utilization, care needs and resources using insurance claims data, a patient survey, and chart review. Qualitative studies with healthcare professionals and patients will be undertaken to identify potential barriers and enablers for optimal performance of the complex care management program. Discussion: This multi-method procedure will support the development of a primary care-based care management program enabling the implementation of interventions that will potentially reduce avoidable hospitalizations