Most patients diagnosed with End Stage Renal Disease (ESRD) undergo hemodialysis. Traditional hemodialysis treatment requires patients spending three to five hours every other day while yielding the high waste level accumulated between treatments. These limitations in the current technology have spurred the development of a portable renal replacement system. The portable system will not only free the patients from visiting the clinic but also allow more frequent treatment that will lead to lower average waste level. To realize a portable system, the size and weight of hemodialysis system components should be reduced. This work analyzes the working principle of the pump and proposes a DC-motor and cam driven finger pump design. In addition, an analytical pump model is created for the optimization of the pump design. In vitro experiment conducted using the pump measured Creatinine levels over time, and the results validitate the design for the portable renal replacement system. The proposed pump design is smaller than 188 cm³ and consumes less than 4W while providing a flow rate of more than 100ml/min (the optimum flow rate for a portable system) for both blood and dialysate flows. The smallest pump of a portable renal replacement system in the literature uses check valves, which considerably increase the overall manufacturing cost and possibility of clogging. Compared to that pump, the proposed pump design achieved reduction in size by 40% and savings in energy consumption by 65% with the removal of valves. This simple and reliable design substantially enables development of a portable renal replacement system.

Military historians have been debating the U.S. Army's World War II replacement system for decades, but no one has completed a detailed study of the War Department's policies and practice. Authors have focused primarily on how combat units overcame the system's limitations, but they have not conducted an in-depth examination of its creation, structure, and function. Nor did they question why infantry divisions had to devise their own replacement policies in the first place. The extant literature is too celebratory of the army and utilizes ultimate victory as a measure of efficiency and effectiveness. Such a myopic view has prevented these earlier studies from evaluating how the replacement system affected the overall course of the European war. This dissertation breaks new ground by presenting a comprehensive overview of the replacement system--from the War Department down to the squad, and from the last days of World War I through the post-World War II years. It will elucidate a process of failed administration and implementation at the highest levels of the War Department and army, but it will also relate a "grassroots" story of success at the divisional level and below. The War Department's managerial approach to the utilization of military manpower was both inefficient and wasteful. The army largely overlooked the impact of individuality, morale, psyche, experience, and training on a soldier's performance. Its insistence on rushing men to the line once combat operations began meant that it often neglected to train, orient, and equip replacements in a manner conducive to their favorable and effective integration into combat units. The GIs at the front, both veterans and replacements alike, suffered for this oversight. / History

The thesis contains 3 repairable systems and 2 replacement systems: First a repairable system is considered with Markovian deterioration and imperfect repair, carried out at fixed times. We look for optimal strategies under certain conditions. Two optimality criteria are considered: expected discounted cost and long-run average cost. Conditions are found under which the optimal policy is a control-limit policy as used by Derman or Ross. We explicitly explain how to derive this optimal policy; numerical examples are given, too. The special case of unbounded cost is also studied. With the first model the state space is numerable but with the second it is not. With the fourth model the system occurs a shock process and is only inspected after such a shock. Models 3 and 5 are replacement systems with Morkovian deterioration and finite state space {0,...,N}. A system in state N is considered to be in a very serious situation. Hence there is the condition, e.g. stipulated by law, that the percentage of all replaced machines in state N in the group of all replaced machines may not be larger than 100 epsilon for a fixed epsilon in [0,1]. We prove that a generalized control limit policy maximizes the expected running time of a machine and we explain explicitly how to derive this optimal policy. Illustrated numerical examples are given.

Eukaryotische DNA ist in Chromatin verpackt, einem Komplex aus DNA und Proteinen. Das ermöglicht Transkriptionsregulation von Genen durch Modulation ihrer Zugänglichkeit. Histone sind evolutionär konservierte Chromatinproteine, die durch posttranslationale Modifikationen (PTMs) modifiziert sind. Das legt nahe, dass deren Primärstruktur und ihre PTMs funktionellen Beschränkungen unterliegen. Genetische Ansätze zur Entschlüsselung von Struktur-Funktions-Beziehungen für Histone waren auf Einzeller und D. melanogaster beschränkt. Das Histon-Ersatz-System in D. melanogaster, bei dem Histontransgene verwendet werden, um endogene Histone zu ersetzen, war nicht für systematische Untersuchung dieser Beziehungen ausgelegt. In meiner Arbeit habe ich die Funktion von Threonin 11 in Histon H3 (H3T11) untersucht, das phosphoryliert werden kann. Ich analysierte zwei Mutationen in H3T11 (H3T11A und H3T11E) und stellte fest, dass beide zur Derepression von Transposons führen. H3T11E hat in Gegenwart von Wildtyp-Histon H3 einen dominanten Phänotyp mit transkriptomweiten Folgen. Dazu gehören Induktion von Immun-Genen und Unterdrückung von mit DNA-Stoffwechsel in Verbindung stehenden Genen. Die Mutationen wurden unter der Prämisse charakterisiert, ein Analyse-Schema für eine große Anzahl von Histon-Ersatz-Stämmen zu entwickeln und Probleme zu identifizieren, die die Analyse beeinträchtigen. Dabei habe ich das Verfahren zur Erzeugung von Histon-Ersatz-Stämmen optimiert. Dazu gehören die optionale Verwendung größerer Histon-Transgene und zuverlässigere Produktion und optimierte Rekombinations-Strategie dieser. Ich habe das Klonierungsverfahren gestrafft und eine Plasmid-Bibliothek erstellt, die es erlaubt, 178 verschiedene mutierte Histon-H3-Transgene zu erzeugen. Mit den Änderungen am Produktionsschema, ist diese Bibliothek eine wertvolle Ressource und wird dazu beitragen, die Funktion von Histon H3 und seiner PTMs während der Entwicklung eines Vielzellers besser zu verstehen. / Eukaryotic DNA is packaged into chromatin, a complex composed of DNA and proteins. This enables transcriptional regulation of genes through modulation of their accessibility. Histones are chromatin proteins, modified by post-translational modifications (PTMs) and their sequences are conserved in evolution. This suggests functional constraints for the primary structure of histones and their PTMs. Genetic approaches to decipher structure-function relationships for histone proteins were restricted to unicellular organisms and D. melanogaster. The histone replacement system in D. melanogaster, which uses histone transgenes to replace endogenous histones, was not adapted for systematic interrogation of such relationships. Here, I investigated the function of threonine 11 in histone H3 (H3T11), which can be phosphorylated. I analyzed two mutations in H3T11 (H3T11A and H3T11E) and found that both lead to de-repression of transposable elements. I also found that H3T11E, has a dominant phenotype in the presence of wildtype histone H3 with transcriptome-wide consequences. These include induction of immune-related genes and repression of genes associated with DNA metabolism. I characterized both mutations under the premise of establishing an analysis scheme suitable for a large set of histone replacement strains and identifying problems that interfere with this analysis. As a consequence, I optimized the procedure to generate histone replacement strains. These include an option to incorporate larger histone transgenes, a more reliable production of transgenes and an optimized strategy to recombine them. I streamlined the cloning procedure and created a plasmid library allowing for the generation of 178 distinct mutant histone H3 transgenes. Together with my amendments to the production scheme, this library provides a valuable resource to the field and will help to better understand the function of histone H3 and its PTMs during the development of a multicellular organism.