Enforcing ?-Regular Properties in Markov Chains by Restarting

Restarts are used in many computer systems to improve performance. Examples include reloading a webpage, reissuing a request, or restarting a randomized search. The design of restart strategies has been extensively studied by the performance evaluation community. In this paper, we address the problem of designing universal restart strategies, valid for arbitrary finite-state Markov chains, that enforce a given ?-regular property while not knowing the chain. A strategy enforces a property ? if, with probability 1, the number of restarts is finite, and the run of the Markov chain after the last restart satisfies ?. We design a simple "cautious" strategy that solves the problem, and a more sophisticated "bold" strategy with an almost optimal number of restarts

Generisches Simulationsmodell für Stückgutspeditionsanlagen auf Basis der Anforderungen von KMUs

Simulation can be used to plan and optimize less-than-truckload (LTL) terminals. To develop simulation models, specific expertise in this field is needed, which often requires high financial investments for acquisition of this knowledge. Due to limited financial resources, SMEs are often incapable to get to this expertise. The objective of the paper is to develop a generic model for LTL terminal planning that can be used without simulation expertise and that can be adapted to individual SME layouts. Therefore, based on focus group interviews with SMEs, a catalog of requirements is developed, including input variables and design criteria. Key performance indicators (KPIs) are defined to evaluate the results. A feasibility study for implementing a generic model based on the identified requirements is then performed. The implementation is done by modeling the I-layout of an LTL terminal

Integration of the DLBCL-specific B-cell receptor antigen ARS2 in Fab- and IgG1- antibody therapy formats

Ziel der Arbeit war es, unterschiedliche Antikörper oder antikörperähnlichen Konstrukte zu entwickeln, die auf der Grundlage des BAR (B-cell receptor antigens for reverse targeting)-Konzepts spezifisch diffus großzellige B-Zell Lymphome (DLBCL) binden und diese zerstören können. Das BAR-Konzept basiert auf der spezifischen Bindung von Autoantigenen an die B-Zell Rezeptoren (BCR) der Lymphomzellinien. In dieser Arbeit wurde das arsenite resistance protein 2 (ARS2) als Autoantigen verwendet, welches spezifisch den B-Zell Rezeptor von diffus großzelligen B-Zell Lymphomen vom activated b-cell type (ABC-Typ) bindet. Zunächst wurden drei Fab-Konstrukte mit unterschiedlichen Ausschnitten der ARS2 Sequenz an Stelle der variablen Domänen der Leicht- und Schwerkette in einen pCES-1 Vektor kloniert. Dieser wurde anschließend in Bakterien transformiert. Nach erfolgreicher Expression und anschließender Isolation der Konstrukte mit Hilfe des Histidin (His)-Tags, was durch eine Wester Blot Analyse bestätigt werden konnte, wurde mittels Durchflusszytometrie die Bindung auf diffus großzelligen B-Zell Lymphom Zelllinen überprüft. Das Fab-Konstrukt mit den ARS2 Aminosäuren (AA) 343-466 konnte erfolgreich und spezifisch auf der U2932 Zelllinie binden. Im nächsten Schritt wurde dieses Konstrukt an ein Toxin, in diesem Fall das ETA-Toxin, gekoppelt. Dazu wurde die für das Fab-Konstrukt codierende Sequenz ausgeschnitten und in einen pCES-1 Vektor kloniert, der das ETA-Toxin bereits beinhaltet. Anschließend konnte der Vektor erfolgreich in Bakterien transformiert werden. Das Konstrukt konnte nun erfolgreich exprimiert und mithilfe des Histidin-Tags isoliert werden, was mittels Western Blot Analyse bestätigt werden konnte. Nach durchflusszytometrischer Bestätigung der erfolgreichen Bindung auf den U2932 Zellen, wurde zur Untersuchung der Zytotoxizität ein Laktatdehydrogenase (LDH)-Zytotoxizitätsassay durchgeführt. Es konnte keine spezifische Lyse detektiert werden. In einer anschließenden durchflusszytometrischen Untersuchung konnte gezeigt werden, dass es zu keiner Internalisierung des BAR Fab-ETA Konstrukts durch die Zellen gekommen ist. Als weiteres Therapieformat wurde nun ein BAR Schwerketten-Konstrukt, welches aus der konstanten Domäne 1 der Schwerkette, der ARS2 Domäne (AA 343-466) und der ETA-Sequenz besteht, konstruiert. Dazu wurde die leichte Kette aus dem pCES-1 Vektor, der für das Fab-ETA-Konstrukt codiert, herausgeschnitten. Anschließend wurde der Vektor in Bakterien transformiert, das Konstrukt erfolgreich exprimiert und mithilfe des Histidin-Tags isoliert, was wiederum durch eine Western Blot Analyse bestätigt werden konnte. Durchflusszytometrisch konnte zunächst die Bindung auf den U2932 Zellen gezeigt werden. Im Anschluss konnte ebenfalls die Internalisierung durch die Zellen durchflusszytometrisch bestätigt werden. Mit Hilfe des LDH-Zytotoxizitätsassay konnte nun eine spezifische Lyse auf den U2932 Zellen detektiert werden. Schließlich wurde nun ein BAR-Antikörper im Sinne eines vollständigen IgG1 Antikörpers mit zwei ARS2 Domänen (AA 343-466), anstelle der variablen Domänen konstruiert. Zunächst wurden die passenden Sequenzen für das ARS2 und für die Leicht- und Schwerketten in einen TA-Vektor kloniert. Darauffolgend wurde nun die codierende Sequenz als Ganzes in einen pSfi-FLAG-Vektor kloniert. Dieser wurde dann in HEK-293T Zellen transfeziert. Das Konstrukt konnte anschließend exprimiert werden und erfolgreich mithilfe des FLAG-Tags isoliert werden, was durch eine Western Blot Analyse validiert werden konnte. Nun konnte im Anschluss durchflusszytometrisch gezeigt werden, dass der BAR-Antikörper erfolgreich und spezifisch auf den U2932 Zellen bindet. Mit Hilfe des LDH-Zytotoxizitätsassay konnte ohne zugegebene Effektorzellen auf den U2932 Zellen eine spezifische Lyse von 19% bei einer Konstruktkonzentration von 0,5 µg/ml ermittelt werden. Mit hinzugegebenen Effektorzellen, in diesem Fall peripheral blood mononuclear cells (PBMCs), kam es auf den U2932 Zellen zu einer spezifischen Lyse von 86% bei einer Konstruktkonzentration von 1 µg/ml.The aim of the thesis was to design different types of antibodies or antibody-like constructs based on the B-cell receptor antigens for reverse targeting (BAR) concept, which are able to bind to and to destroy diffuse large cell B-cell lymphoma (DLBCL) cells specifically. The B-cell receptor antigens for reverse targeting concept is based on the specific binding of autoantigens to their B-cell receptor (BCR) on lymphoma cells. In this thesis we worked with the arsenite resistance protein 2 (ARS2) which binds to diffuse large B-cell lymphoma from the activated B-cell type (ABC-type) specifically. First, we designed three different Fab-constructs with different sections of the ARS2 protein at the place of the variable regions of the light and heavy chain. The sequences were cloned into an pCES-1 vector. Next the vector was transformed into bacteria. In the next step the construct was expressed and isolated successfully with the help of the histidine (his)-tag. This was confirmed by a western blot analysis. Now flow cytometry was used to verify the binding of the three constructs to the U2932 cell line. The Fab-construct with the aminoacids (AA) 343-466 could bind to the U2932 cells successfully. The next step was to link the Fab-construct to a toxin, in this case the ETA-toxin. Therefore, the Fab-construct coding sequence was cloned into a pCES-1 vector containing the ETA-toxin sequence. After transformation into bacteria the construct could be expressed and isolated with the help of the histidine-tag, which was proved by western blot analysis. After confirming the binding of the BAR Fab-ETA-construct to the U2932 cells by flow cytometry, the lactatdehydrogenase (LDH)-cytotoxicity assay was accomplished to look for the specific cytotoxicity of the construct. There was not any specific cytotoxicity on the U2932 cells. A following flow cytometry demonstrated that the construct has not been internalized by the cells. The next build construct was a BAR heavy chain construct, which contains of the constant domain 1 of the heavy chain, the ars2 sequence (AA 343-466) and the ETA sequence. To build that construct, the light chain was cut out of the pCES-1 vector who coded for the fab-ETA-construct. Subsequently the vector was transformed into bacteria and the construct was expressed and isolated successfully with the help of the histidine-tag. That could be proved by a western blot analysis. Afterwards, the binding to the U2932 cells and also the internalization could be shown by two different flow cytometric analysis. Now a specifical lysis on the U2932 cells could be recognized by the LDH cytotoxicity assay. Finally, we built a BAR antibody in the meaning of a IgG1 antibody with two ARS2 domains at the place of the variable domains. First, the sequences for the ARS2 and for the light and heavy chains were cloned into a TA vector. Next the whole coding sequence was cloned into a pSfi-FLAG vector, which was transfected into HEK-293T cells then. Afterwards, the construct could be expressed and isolated successfully with the help of the FLAG-tag. This fact was proved by western blot analysis. Now in the flow cytometry the binding of the antibody construct to the U2932 cells was confirmed. The LDH-cytotoxicity assay has come to the result that without addition of effector cells the specific lysis is maximum 19% by a construct concentration of 5 µg/ml. With addition of peripheral blood mononuclear cells (PBMCs) as effector cells, there could be detected a specific lysis of maximum 86 % by a construct concentration of 1 µg/ml at the U2932 cells

Simulationsgestützte Analyse eines Wertstroms als Beitrag zu nachhaltigen Produktions- und Logistiksystemen von KMUs

In crises, small and medium-sized enterprises (SMEs) are under more significant pressure than large companies. However, SMEs are more adaptable to changes caused by external influences. To leverage this strength, the focus is on increasing transparency, identifying bottlenecks in the material flow, and evaluating a defined target state of the material flow based on company-specific key performance indicators (KPIs) for sustainable production. Varieties of different methods are suitable for determining these KPIs. In this paper, a simulation-based analysis is performed to determine such indicators. For this purpose, an application example from practice illustrates these methods' applicability to increase the SMEs' adaptability to external influencing factors. First, a value stream analysis of the current state of the material flow is performed. Based on the results, suggestions for changes are given and implemented in a new optimized value stream. A simulation study compares the new value stream with the current one

Sammelrezension: Defizite in der UN-Friedenspraxis

Sammelrezension: 1) Laura J. Shepherd: Gender, UN Peacebuilding, and the Politics of Space. Locating Legitimacy. Oxford: Oxford University Press 2017. ISBN 9780190086862. 2) Sabrina Karim, Kyle Beardsley, 2019: Equal Opportunity Peacekeeping: Women, Peace and Security in Post-Conflict States. Oxford: Oxford University Press 2019. ISBN 9780190093532

Excitation transfer in disordered spin chains with long-range exchange interactions

We examine spin excitation or polarization transfer via long-range interacting spin chains with diagonal and off-diagonal disorder. To this end, we determine the mean localization length of the single-excitation eigenstates of the chain for various strengths of the disorder. We then identify the energy eigenstates of the system with large localization length and sufficient support at the chain boundaries that are suitable to transfer an excitation between the sender and receiver spins connected to the opposite ends of the chain. We quantify the performance of two transfer schemes involving weak static couplings of the sender and receiver spins to the chain, and time-dependent couplings realizing stimulated adiabatic passage of the excitation via the intermediate eigenstates of the chain which exhibits improved performance.Comment: minor correction

What can we learn from diffusion about Anderson localization of a degenerate Fermi gas?

Disorder can fundamentally modify the transport properties of a system. A striking example is Anderson localization, suppressing transport due to destructive interference of propagation paths. In inhomogeneous many-body systems, not all particles are localized for finite-strength disorder, and the system can become partially diffusive. Unravelling the intricate signatures of localization from such observed diffusion is a long-standing problem. Here, we experimentally study a degenerate, spin-polarized Fermi gas in a disorder potential formed by an optical speckle pattern. We record the diffusion in the disordered potential upon release from an external confining potential. We compare different methods to analyze the resulting density distributions, including a new method to capture particle dynamics by evaluating absorption-image statistics. Using standard observables, such as diffusion exponent and coefficient, localized fraction, or localization length, we find that some show signatures for a transition to localization above a critical disorder strength, while others show a smooth crossover to a modified diffusion regime. In laterally displaced disorder, we spatially resolve different transport regimes simultaneously which allows us to extract the subdiffusion exponent expected for weak localization. Our work emphasizes that the transition toward localization can be investigated by closely analyzing the system's diffusion, offering ways of revealing localization effects beyond the signature of exponentially decaying density distribution.Comment: 18 pages, 11 figure