88 search hits
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A generalized job-shop problem with more than one resource demand per task
(2011)
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Joachim Schauer
Cornelius Schwarz
- We study a generalized job-shop problem called the Laser Sharing Problem with fixed tours (LSP-T) where the tasks may need more than one resource simultaneously. This fact will be used to model possible collisions between industrial robots. For three robots we will show that the special case where only one resource is used by more than one robot is already NP-hard. This also implies that one machine scheduling with chained min delay precedence constraints is NP-hard for at least three chains. On the positive side, we present a polynomial algorithm for the two robot case and a pseudo-polynomial algorithm together with an FPTAS for an arbitrary but constant number of robots. This gives a sharp boundary of the complexity status for a constant number of robots.
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A strictly feasible sequential convex programming method
(2011)
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Sonja Lehmann
- In free material optimization (FMO), one tries to find the best mechanical structure by minimizing the weight or by maximizing the stiffness with respect to given load cases. Design variables are the material properties represented by elasticity tensors or elementary material matrices, respectively, based on a given finite element discretization. Material properties are as general as possible, i.e., anisotropic, leading to positive definite elasticity tensors, which may be arbitrarily small in case of vanishing material. To guarantee a positive definite global stiffness matrix for computing design constraints, it is required that all iterates of an optimization algorithm retain positive definite tensors. Otherwise, some constraints, e.g., the compliance, cannot be evaluated and the algorithm fails. FMO problems are generalizations of topology optimization problems. The goal of topology optimization is to find the stiffest structure subject to given loads and a limited amount of material. In contrast to FMO the material is explicitly given and cannot vary. Based on a finite element discretization, in each element it is decided whether to use material or not. The regions with vanishing material are interpreted as void. The resulting optimization problem can be solved by numerous efficient nonlinear optimization methods, for example sequential convex programming methods. Sequential convex programming (SCP) formulates separable and strictly convex nonlinear subproblems iteratively by approximating the objective and the constraints. Lower and upper asymptotes are introduced to truncate the feasible region. Due to the special structure, the resulting subproblems can be solved efficiently by appropriate methods, e.g., interior point methods. To ensure global convergence, a line search procedure is introduced. Moreover, an active set strategy is applied to reduce computation time. The iterates of SCP are not guaranteed to be inside the corresponding feasible region described by the constraints. As a consequence it is not able to solve free material optimization problems as the compliance function is only well-defined on the feasible region of some of the constraints. We propose a modification of a SCP method that ensures feasibility with respect to a given set of inequality constraints. The resulting procedure is called feasible sequential convex programming method (SCPF). SCPF expands the resulting subproblems by additional nonlinear constraints, that are passed to the subproblem directly to ensure their feasibility in each iteration step. They are referred as feasibility constraints. In addition, other constraints may be violated within the optimization process. As globalization technique a line search procedure is used to ensure convergence. The resulting subproblems can be solved efficiently taking the sparse structure into account. Moreover, semidefinite constraints have to be replaced by nonlinear ones, such that SCPF is applicable. SCPF successfully solved FMO problems with up to 120.000 variables and 60.000 constraints. Within a theoretical analysis global convergence of SCPF is shown for convex feasibility constraints.
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Active and Passive Transport at Interfaces
(2011)
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Saeedeh Aliaskarisohi
- In this thesis we studied different forms of transport at interfaces. Four different interfacial transport mechanisms have been investigated. In each of them one physical aspect of active and passive transport is discussed. The four systems are arranged and discussed in four separate chapters. In chapter 3 and 4 we study the effect of static or hydrodynamic interactions on the cross over from individual diffusion towards collective diffusion. In chapter 3 the diffusion of circular domains on a giant unilamellar vesicle is measured. By tracking the motion of hydrodynamic interacting domains on a curved membrane we determined whether it is possible to extract rheological properties of the bilayer membrane. A similar two dimensional system interacting via static dipole interactions is studied in chapter 4. A mixture of paramagnetic and nonmagnetic colloidal particles immersed into a diluted ferrofluid is self assembled into colloidal flowers. In this experiment the effect of static interactions on the modes of diffusion of the petals of the colloidal flower is investigated in a one dimensional system. The results are compared with the single file diffusion of a hard core interacting one dimensional system. In chapter 5, the effect of actively directing particles with fluctuating active forces in a symmetry broken environment is studied. We address the question how to competing symmetry breaking effects decide on the direction of motion. The system consists of paramagnetic colloidal particles placed into an aqueous solution above the liquid-solid interface of a magnetic garnet film. An external modulated field supplies the fluctuations and the symmetry is broken by tilting the external field with respect to the magnetic film and/or by a magnetic symmetry broken pattern of the magnetic film. The direction of motion of the paramagnetic colloids is measured and we give a theoretical explanation of why which symmetry breaking wins. The fluidization of a two dimensional solid to a two dimensional liquid via the yielding of the monolayer is studied in chapter 6. The monolayer is locally yielded with thermo capillary interactions by focusing a laser onto it. We investigate the yielding as a function of the chemical nature of the monolayer and determine the thermodynamic requirements necessary for thermo capillary yielding.
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Agent Assignment for Process Management: Resource Management Support for Skill Intensive Applications of Workflow Technology Technical and Methodological Issues
(2011)
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Muhammad Ramzan Talib
- Managing an organization’s resource talent particularly in assigning the right person to the right job at the right time is among the top challenges of today’s competitive business environments especially in skill intensive applications of workflow technology since skills of their employees directly affect the business paybacks. Despite that many companies already deal with managing their processes and their human resources, organizations are still feeling the problem of poor resource management. The dilemma is that Workflow Management Systems (WfMSs) support the execution of business process but do only offer static assignment strategies for resources such that an overall poor process performance results. Furthermore, Human Resource Management (HRM) performance evaluation methods lack agility and analytical capabilities that results in poor resource development. To solve this dilemma of poor resource management, this thesis contributes some technical and methodological supports considering some use case scenarios from a textile industry. It offers Agent Performance Evaluation (APE) Framework and Competency-driven Dynamic Resource Management (CDRM) Methodology to overcome the problem of static assignments and also to support proper resource development. Our APE framework not only evaluates and gives feedbacks of employees’ competency profiles but also performs an analysis of employees’ competencies for making best use of their talents thus supporting proper resource development. While, our CDRM methodology allocates dynamically only successful employees to their business processes through consistent support of APE framework and thus supports process optimization. This thesis also contributes a construct in the form of Goal concept and a methodology for continuous resource development in the form of Workflow Lifecycle Support for Continuous Resource Improvement. Defining goals within the process layer, enables organizations to define success criteria of their employees in parallel with all other criteria that influence the performance of an employee within the process. In fact, our APE Framework uses this criteria for evaluating the employees’ competency profiles that are latter used by CDRM methodology to allocate only successful employees to their business processes. The Workflow Lifecycle Support for Continuous Resource Improvement aims to define a precise and comprehensive methodology to elaborate a set of basic tasks that are needed to be performed during different phases of the standard workflow lifecycle to achieve continuous resource improvement.
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Amphiphilic Diblock Copolymers: Study of Interpolyelectrolyte Complexation in Organic Media and Nanoencapsulation of Melatonin
(2011)
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Evis Karina Penott-Chang
- Two oppositely charged homopolyelectrolytes poly(2-(methacryloyloxy)ethyl¬dimethyl-ethyl¬ammonium bromide) (PDMAEMAQ) and poly(acrylic acid) (PAA), and amphiphilic diblock copolymers based on polystyrene and the ionizable block poly(acrylic acid) were synthesized via Atom Transfer Radical Polymerization (ATRP). All polymers were characterized using 1H NMR and gel permeation chromatography to confirm their structure, molecular weight distribution and to follow the conversion. Poly(2-(dimethylamino)ethyl methacrylate), PDMAEMA, was quaternized with ethyl bromide to produce PDMAEMAQ with a quaternization degree of 98%. Furthermore, poly(acrylic acid) segments were obtained after hydrolysis of the poly(t-butyl acrylate) block. After characterization of all polymers, interpolyelectrolyte complexation in chloroform was carried out. A novel method was developed to transfer the insoluble polyelectrolytes into the organic solvent and subsequently form polymer/polymer interpolyelectrolyte (IPECs) in organic media. Therein, the polyelectrolyte were first reacted with oppositely charged low molecular weight surfactants (sodium dodecyl sulfate, SDS, and cetyltrimethylammonium bromide, CTAB) to form polyelectrolyte-surfactant complexes (PESCs). In organic solvents, analogously to the formation of IPECs in aqueous media, interpolyelectrolyte complexation takes place upon the direct mixing of organic solutions of two complementary PESCs. This process is accompanied by an entropically favorable release of the surfactant counterions (in the form of ion pairs or their aggregates in low polarity organic solvents), which were previously associated with the ionic groups of the polyelectrolytes in solution. These reactions are fast and lead to frozen and non-equilibrium macromolecular co-assemblies. The size and the morphologies of the IPECs in chloroform were extensively investigated using transmission electronic microscopy (TEM), scanning force microscopy (SFM), dynamic/static light scattering techniques, 1HMR and turbidimetric titrations, for two different systems: (i) homopolyelectrolyte/homopolyelectrolyte and (ii) homopolycation/negatively charged amphiphilic diblock copolymer. For the first system, the possible particle structures consist either of particles with a core formed by IPECs stabilized by fragments of the excess polymeric component or of vesicles (polymersomes). In system (ii), particles of micellar type with a core assembled from electrostatically coupled segments of the polymeric components can be found, surrounded by a corona built up either from a mixture of polystyrene blocks and excess segments of PDMAEMAQ+DS- chains or from a mixture of polystyrene blocks and excess parts of PA-CTA+ blocks, depending on which polymeric component was present in surplus during the interpolyelectrolyte complexation. Finally, nanocapsules loaded with melatonin were fabricated using a simple nanoprecipitation route employing a mixture of a diblock copolymer based on poly(methyl methacrylate) and PDMAEMA (PMMA-b-PDMAEMA) in combination with poly(ε-caprolactone), PCL. The diblock copolymers were synthesized via ATRP using PMMA-macroinitiators for the DMAEMA polymerization. Shape and size of the nanocarriers were visualized by TEM, cryogenic TEM and scanning electron microscopy (SEM). Standard TEM for nanocapsules showed an oily core surrounded by a thin layer composed of PCL/PMMA-b-PDMAEMA. Cryo-TEM also indicated the presence of spherical nanoobjects with a diffuse polymer corona. Encapsulation efficiencies were determined assaying the nanoparticles by HPLC and values of ca. 30-35% are shown by the nanocapsules. DLS measurements further confirmed well-defined unimodal particle size distributions for all formulations. It was also possible to successfully incorporate platinum nanoparticles into the nanocarrier, as evidenced by TEM, which opens up possibilities for promising applications like monitoring the circulation of the drug carrier within the body.
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Analysis of the "nurse-tree effect" of exotic shelter trees on the growth of the indigenous Podocarpus falcatus in an Ethiopian montane forest
(2011)
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Simone Strobl
- Ethiopian forests disappear with a rate of 1.1% per year due to the high demand of firewood and timber. To protect the remaining parts of the forests, exotic tree plantations were established 60 years ago. But there are considerable concerns regarding exotic plantations: they have the reputation to cause damage to the ecosystems due to high demand of water and nutrients. Considering the environmental deterioration caused by monotonous plantations of exotic tree species, the chance for indigenous woody plants to rejuvenate naturally in those plantations appears to be very small. But there are observations of indigenous tree species regenerating under the shelter of exotic tree plantations. This enhanced growth of indigenous saplings under the canopy of exotics has been termed “nurse-tree effect”. In the Munessa-Shashamene Forest, a tropical montane forest in Ethiopia consisting of plantations of exotic tree species and remnants of natural forest, regeneration and an enhanced growth of native Podocarpus falcatus saplings under the shelter of exotic tree plantations (Pinus and Eucalyptus) was observed. The focus of this work was to examine the different growth patterns of the saplings in the sites, the effects of the on the photosynthetic performance, and to compare the water relations of the Podocarpus saplings and those of the shelter-trees. The results of the study are summarized as follows: 1. Observations over two years showed that the relative growth rates of the saplings were more than three times higher in the Pinus plantation compared to the natural forest and the Eucalyptus plantation. Relative growth rates during the dry and the rainy season were more or less identical. 2. Investigation of the sub-canopy microclimate proved PAR and VPD as major components with impact on the photosynthetic performance of the saplings. 71% of the variations in photosynthetic carbon uptake could be explained by PAR and 4% by VPD. The Pinus plantation was slightly warmer and drier compared to the other two sites. Also highest PAR values of all sites were recorded in the Pinus plantation. In the Eucalyptus plantation, PAR values were the lowest of the three sites, caused by the two-tired canopy of coppiced and uncoppiced Eucalyptus trees. 3. For an assessment of the photosynthetic efficiency of the light climate, the efficacy of the shares of the irradiation from diffuse light and light flecks were determined from light curves. The time spans and distribution of these shares of the daily accumulated radiation were recorded from the daily courses. In the Pinus plantation, the efficiency of the radiation was relatively low (70%), because of the high intensity of the sunflecks, especially during the dry season. On cloudy days the efficiency was nearly 100% and resulted in an optimum photosynthetic performance of the saplings in the Pinus plantation. In the Eucalyptus plantation, the two-tired canopy resulted in a higher proportion of diffuse radiation and less daily accumulated PAR from sunflecks (46%). Also the efficiency of the actual radiation was the lowest of all sites on cloudy (72%) and sunny (53%) days. Daily accumulated PAR under the canopy of the natural forest was in between the other forest types. Such mid-position was also true for the share of the sunflecks and the CO2 uptake. Efficacy of the radiation was 80% on sunny and 86% on cloudy days. 4. Water relations can substantially affect the photosynthetic performance of plants. Especially in the afternoons of the dry season a decrease of photosynthetic CO2 uptake by the Podocarpus saplings became apparent. Whole-tree water consumption was determined by measuring sap flow with the Granier system. In principle sap flow (and transpiration) followed VPD. Comparison of the daily courses of transpiration and stomatal conductance and sap flow showed an earlier decrease of transpiration by the leaves of the saplings than by the shelter-trees, suggesting slight water shortage especially during the dry season. This interpretation is corroborated by the higher 13C values in the leaf tissue of the saplings from the Pinus plantation. Nevertheless severe drought stress did not occur during the two years of investigation. 5. The literature on the „nurse-tree effect“ mentions in particular Eucalyptus as shelter-tree, a finding which is not in agreement with the data of this study: Neither photosynthesis nor growth was enhanced compared with the control saplings in the natural forest. The discrepancy between this work and the literature can be solved when the management of the Eucalyptus plantation is considered. As long as the Podocarpus saplings grow under the two-tired canopy of the coppiced trees, growth is as slow as in the natural forest. However, after coppicing the light climate for the saplings ameliorates considerably and growth rates increase. Thus, a shelter-tree effect could also be observed under Eucalyptus, but its dynamics is stepwise rather than continuous.
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Applying regional climate change projections for spatio-temporal risk analyses of vector-borne diseases
(2011)
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Dominik Fischer
- Bei vorliegender Dissertation handelt es sich um eine Abhandlung zu vektor-assoziierten Krankheiten in Zeiten des Klimawandels. Bei vektor-assoziierten Krankheiten wird ein Pathogen durch einen Vektor (Überträger), auf ein Wirtstier übertragen. Als solche Vektoren agieren meist Arthropoden. Klimatische Veränderungen beeinflussen vektor-assoziierte Krankheiten insbesondere dadurch, dass Arthropoden ihre Körpertemperatur nicht selbst regeln können und zudem bestimmte Temperaturansprüche zur Pathogenentwicklung im Vektor erfüllt sein müssen. Das Klimaänderungssignal des 21. Jahrhunderts wird von Klimamodellen in verschiedenen räumlichen und zeitlichen Auflösungen wiedergegeben. Die Projektionen beruhen auf Emissionsszenarien klimawirksamer Treibhausgase. In der Arbeit werden die Einsatzmöglichkeiten von regionalen Klimamodellen zur Gefährdungsabschätzung anhand verschiedener Fallbeispiele aufgezeigt. Deren Nutzen und Einsatzmöglichkeiten werden einführend aufgeführt. Für die Risikoanalysen werden regionalen Klimamodelle REMO und COSMO-CLM angewandt, die durch dynamisches „Downscaling“ globaler Modelle generiert wurden. Beide sind in ihrem neuesten Prozesslauf in das globale Modell ECHAM5 eingebettet. Der direkte Übertrag bekannter Temperaturansprüche von Vektor und/oder Pathogen auf künftig zu erwartende Bedingungen stellt den ersten methodologischen Schwerpunkt dieser Arbeit dar. Eine Amplifikation des Dengue-Virus im Überträger der Stechmücke Aedes aegypti könnte demnach zunächst in Südeuropa, im weiteren Verlauf des 21. Jhd. aber auch in weiteren europäischen Regionen möglich sein. Weiterhin verdeutlichen die Ergebnisse, dass sich auch das Zeitfenster einer potentiellen Übertragung des Dengue-Virus verlängern kann. Durch das Überlagern der bekannten Temperaturansprüchen von Sandmücken (Gattung Phlebotomus) und der von ihnen übertragbaren Erreger - Leishmania infantum Komplex - können potentielle Regionen Deutschlands identifiziert werden, in denen einer autochthone Übertragung der Leishmaniose möglich ist. Es ist zu erwarten, dass ein solches Risiko zunächst in südwestlichen und westlichen Regionen Deutschlands, im späteren Verlaufe des des 21. Jhd. jedoch auch für eher nördlich und östlich gelegene Regionen bestehen wird. Der zweite innerhalb dieser Arbeit gewählte methodologische Ansatz zeigt die Einsatzmöglichkeiten regionaler Klimaprojektion für die bioklimatische Nischenmodellierung von Krankheitsüberträgern auf. Die anhand statistischer Verfahren ermittelte bioklimatische Nische der jeweiligen Art wird hierbei auf zukünftig zu erwartende klimatische Bedingungen übertragen. Anhand dieser Analyse kann aufgezeigt werden, dass sich die klimatische Eignung für die invasive Stechmücke Aedes albopictus (Überträger mehrere human-pathogener Viren) ausgehend von westlichen Regionen Europas über Mitteleuropa und schließlich Osteuropas erhöhen wird. Der Transfer der ermittelten spezifischen klimatischen Nische ausgewählter Sandmücken-Arten (u.a. Überträger der zum Leishmania-Komplex zählenenden Pathogenen) auf künftige Bedingungen lässt vermuten, dass deren klimatische Eignung in Mitteleuropa - abgesehen von alpinen Regionen - zunehmen wird. Künftige potenzielle Ausbreitungswege der Sandmücken in einer sich verändernden Umwelt, werden via “least-cost analysis“ ermittelt. Die Ergebnisse deuten darauf hin, dass aufgrund der eingeschränkten natürlichen Ausbreitungsfähigkeit, einige der künftig potenziell geeigneten Lebensräume nicht erreicht werden. In den verschiedenen Fallstudien kann gezeigt werden, dass die zu erwartenden klimatischen Veränderungen im 21. Jhd. eine mögliche Ausbreitung der in dieser Arbeit adressierten Vektoren und vektor-assoziierter Krankheiten in Europa begünstigen werden. Als einheitliche Tendenz kann speziell für Mitteleuropa festgehalten werden, dass sich die Gefährdung, Ende des 21.Jhd. erhöhen wird. Dies begründet sich höchstwahrscheinlich durch die projizierte raschere Erwärmung in der zweiten Jahrhunderthälfte. Abschließend bleibt jedoch festzuhalten, dass es neben klimatischen Veränderungen weitere Faktoren für die Ausbreitung bzw. Neuetablierung von Vektoren und den damit verbundenen übertragbaren Infektionskrankheiten ausschlaggebend sind. Der Einfluss einzelner Faktoren auf die Etablierung bzw. Ausbreitung vektor-assoziierte Krankheiten variiert auf raum-zeitlichen Skalen. Für die ermittelten klimatisch-abgeleiteten Risikogebiete sollten in Folgestudien auf kleineren Skalen wirksam werdenden Faktoren integriert werden. Diese Ergebnisse können wiederum die Entwicklung von Surveillance- und Monitoringprogramme unterstützen, um somit Maßnahmen gegen die Ausbreitung von vektor-assoziierten Krankheiten initiieren zu können.
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Auswirkungen eines Ultralangstreckenlaufs auf ausgewählte physiologische und psychologische Parameter als mögliche Marker von Überbelastungen
(2011)
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Thomas Bossmann
- Problemstellung Überbelastungen stellen ein weit reichendes Problem im Leistungs- und ambitionierten Freizeitsport dar. Allgemein gültige Diagnoseparameter fehlen ebenso wie hinreichend verlässliche Parameter, die frühzeitige Warnhinweise bei zu hohen Belastungsfaktoren geben könnten und in der Trainingssteuerung einsetzbar sind. Für Ultralangstreckenläufer, die häufig mehrtägige Wettkämpfe absolvieren, sind besonders solche Parameter interessant, die sich im Feld und in nicht invasiver Form ermitteln lassen. Methode 6 TN ermittelten während einer Trainingsphase mit normalem Belastungsumfang, während eines 17-tägigen Ultramarathons (Deutschlandlauf) sowie während einer anschließenden Regenerationsphase täglich die morgendliche Ruheherzfrequenz, Parameter der Herzfrequenzvariabilität (HRV) sowie die psychische Befindlichkeit. Für jeden Parameter wurden zunächst Normbereiche festgelegt. Mittels Laktat-Stufentests wurde die maximale Leistungsfähigkeit der Teilnehmer zu drei unterschiedlichen Zeitpunkten ermittelt. Gleichzeitig wurden Diagnoseparameter einer Überbelastung vordefiniert und die Annahme formuliert, dass mindestens dreitägige Auslenkungen einzelner Parameter aus den während der ersten Messphase ermittelten Normwertbereichen dem Auftreten der Diagnoseparameter oder dem Abbruch des Laufs vorausgehen würden (kritische Ereignisse) Ergebnisse Vier der sechs untersuchten Sportler mussten den Lauf frühzeitig abbrechen, bei drei Sportlern wurden diagnoserelevante Veränderungen bezüglich einer Überbelastung dokumentiert. Bei den Abbrechern traten bereits während der Wettkampfphase kritisch erhöhte Ruheherzfrequenzwerte, eine kritisch erniedrigte Herzfrequenzvariabilität sowie eine kritisch verschlechterte Befindlichkeit auf. Die untersuchten Parameter reagierten individuell unterschiedlich, zeigten jedoch bereits frühzeitig Auslenkungen an, die dem Abbruch des Laufs bzw. Diagnoseparametern einer Überbelastung voraus gingen. Alle Teilnehmer zeigten während der Regenerationsphase Veränderungen, die auf eine erhöhte sympathische Aktivität schließen lassen.
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Biochemische Charakterisierung und Wirkoptimierung potentieller Chemotherapeutika auf Basis der natürlichen Chinone Doxorubicin und Thymochinon
(2011)
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Katharina Effenberger-Neidnicht
- Eine Reihe von natürlichen Chinonen weist eine Vielzahl an pharmakologisch sehr interessanten Eigenschaften auf, antitumorale Aktivitäten eingeschlossen. Das etablierte Chemotherapeutikum Doxorubicin beispielsweise – ein Sekundärmetabolit von Streptomyces peucetius var. caesius – findet seine klinische Anwendung bei der Behandlung verschiedenster Krebserkrankungen wie etwa Leukämien, Lymphomen, Karzinomen und Sarkomen. Dennoch ist die Verwendung von Doxorubicin als Chemotherapeutikum durch seine Kardiotoxizität und die Ausbildung von Resistenzen limitiert. Um diese Nebenwirkungen möglichst gering zu halten, ist die kumulative Dosis auf 550 mg / m² festgesetzt. Durch geeignete Derivatisierung von Doxorubicin mit verschiedenen gesättigten und ungesättigten bzw. Terpen-terminierten Fettsäuren sollten unerwünschte Nebenwirkungen – wie etwa die Anfälligkeit gegenüber Mehrfachresistenzen – minimiert werden, ohne jedoch einen Verlust der Wirksamkeit zu riskieren. Das Ziel dieser Arbeit war es, mithilfe biochemischer Arbeitsmethoden diejenigen Wirkstoff-Kandidaten zu finden und zu charakterisieren, die diese Kriterien erfüllen. Es konnten Doxorubicinderivate identifiziert werden, die in der Lage waren, limitierende Mehrfachresistenzen zu überwinden: Besonders erwähnenswert ist das Heptadecansäure-Doxorubicinhydrochlorid-Hydrazon, das anders als die übrigen Fettsäurederivate eine deutliche Wachstums-inhibierende Wirkung gegen die verschiedenen Tumor-Zelllinien aufweist. Zudem übertrifft es aufgrund einer geringeren Anfälligkeit gegenüber dem ABC-Transportprotein P-gp die Wirkung von Doxorubicin an mehrfachresistenten KB-V1/VBL Zervixkarzinom-Zellen um das 3-Fache. Die lange Fettsäureseitenkette dient dabei als eine Art Anker. Die Wirkungsweise von Doxorubicin und seinen Derivaten ist vorwiegend apoptotisch, wobei sowohl klassische Wege als auch alternative Wege über das Endoplasmatische Retikulum und die Generierung von reaktiven Sauerstoffradikalen (ROS) und Ceramiden beteiligt sind. Weiterhin konnte auch für die meisten Derivate die zelluläre DNA als Haupt-Target identifiziert werden. Die Interkalation der Derivate in die DNA führt aufgrund der Blockierung von DNA-bindenden Enzymen zu einem Verbleib der Zellen in der DNA-Replikation-Phase und somit zur Auslösung der Apoptose. Auch einfache Verbindungen wie das p-Benzochinon Thymochinon – Bestandteil des Schwarzkümmel-Extraktes (Nigella sativa) – sind aufgrund von antioxidativen und antitumoralen Effekten potentielle Kandidaten zur Weiterentwicklung zum Chemotherapeutikum. Durch die Funktionalisierung von Thymochinon mit verschiedenen gesättigten und ungesättigten bzw. Terpen-terminierten Fettsäuren sollte die geringe antitumorale Wirkung verbessert werden; die Derivate sollten wiederum mithilfe geeigneter biochemischer Arbeitsmethoden charakterisiert werden. Es konnten einige Derivate identifiziert werden, die die Wirkung und Selektivität der Ausgangsverbindung bei Weitem überschreiten: Einerseits zeigt das DHA-Thymochinon mit Langzeit-IC50-Werten im nano-molaren Bereich überdurchschnittliche Effektivität bei gleichzeitig verbesserter Tumorselektivität. Andererseits weist das (–)-Mentholderivat die geringste MDR-Sensitivität, also die geringste Anfälligkeit gegenüber ABC-Transportern auf. Die Wirkungsweise von Thymochinon und seinen Derivaten ist vorwiegend apoptotisch; es werden sowohl klassische als auch alternative Wege der Apoptose-Initiation angesprochen. Als Haupt-Wirkort von konnten DNA- bzw. RNA-reiche Regionen im Zellkern identifiziert werden.
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Biphasic, Homogeneous, and Heterogeneous Hydrocarbon Conversion Reactions with Novel Aluminum Chloride Based Catalyst Systems
(2011)
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Matthias Dötterl
- The aim of this thesis was the development of novel cocatalysts for nickel catalyzed olefin dimerization and oligomerization reactions. For this purpose, cheap and air stable Lewis acidic chloroaluminate ionic liquids were the starting point for our investigations. Chloroaluminate melts are immiscible with hydrocarbon phases, and thus, biphasic oligomerization reactions allow a simple product separation by decantation. Unmodified chloroaluminate melts containing excess aluminum chloride predominantly catalyze non selective, cationic olefin oligomerization reactions. We found that the addition of triphenylamine, triphenylphosphine, or triphenylbismuth donors efficiently suppressed these side reactions to yield an ideal cheap and air stable ionic liquid cocatalyst for common nickel complexes used for olefin dimerization reactions. Especially triphenylbismuth was able to buffer slightly acidic chloroaluminate melts as well as highly acidic compositions. For nickel catalyzed dimerization reactions, we found that high buffering levels led to very high selectivities to give dimers, while systems with lower buffer contents were less selective but extremely active. Further, the melting points of acidic chloroaluminate melts were reduced upon addition of BiPh3. Thus, room temperature ionic liquid compositions derived from 100 different organic halide salts were screened towards their performances in nickel catalyzed selective propene dimerization reactions. Amines and BiPh3 used for such systems can be easily recovered by acid base extraction. Subsequently, an optimized composition was successfully employed to dimerize ethene, propene, 1-butene, and 1-hexene with high activities and selectivities. In order to minimize leaching effects and to investigate the interactions of a donor additive with the ionic liquid, a cationic para-trimethylammonium substituted triphenylphosphine derivative was synthesized and its interaction with the ionic liquid was monitored by means of 31P NMR spectroscopy. The concept of buffering highly Lewis acidic aluminum chloride centers was also transferred to binary homogeneous systems. In combination with stoichiometric amounts of BiPh3 or N-methylpyrrole buffer, aluminum chloride readily dissolved in toluene and methylene chloride to form a highly efficient, cheap and air stable cocatalyst for nickel catalyst precursors. Furthermore, the Lewis acidities of these binary homogeneous cocatalyst solutions could be tuned precisely by the choice of the solvent and the type and amount of buffer. Also, buffer addition efficiently suppressed isomerization reactions of the 1-olefinic products. The interaction of BiPh3 and N-methylpyrrole with AlCl3 was monitored by 27Al NMR spectroscopy. Further, the concept of buffering highly Lewis acidic aluminum species was extended to heterogeneous systems. The Lewis acidities of EtAlCl2 or Et2AlCl modified silicas were reduced by the addition of BiPh3 or N-methylpyrrole buffers. Buffered surface modified silica cocatalysts were successfully employed to activate nickel complexes for highly selective olefin dimerization reactions. Also, surface modified silica proved to be an ideal substrate for the formation of supported ionic liquid phase (SILP) cocatalyst systems used in nickel catalyzed olefin dimerization reactions. Buffered aluminum based cocatalysts were also able to activate a nickel diimine complex for biphasic, homogeneous, and heterogeneous ethene polymerization reactions. The polymer yields, molecular weights and polydispersities of the polyethylenes could be influenced by varying the solvent or the type and amount of buffer. We developed the first air stable cocatalyst systems solely based on aluminum chloride. With the right combination of solvent, type and amount of buffer, and process parameters, tailor-made homogeneous, heterogeneous and biphasic cocatalysts for numerous catalyst precursors can be designed. The systems proved to be highly active, long term stable and very selective for olefin dimerization or polymerization reactions. Due to the cheap components and the possibility to recycle buffers or halide salts, these new systems provide promising alternatives to established alkylaluminum based cocatalyst systems.
