A strategy for transforming St. James United Methodist Church: a study in the relationship between church growth and church health

https://place.asburyseminary.edu/ecommonsatsdissertations/1515/thumbnail.jp

Magnetic Resonance Rheology on Phantoms and Human Brains

In this thesis first systematic measurements on phantoms and human brains using Magnetic Resonance Rheology (MRR) are presented and means to evaluate the acquired data are investigated. MRR is a novel technique designed to image the mechanical properties of human brain tissue by performing a creep relaxation experiment inside a Magnetic Resonance Imaging (MRI) scanner. Using a lifting device inside the head coil the head is basically dropped a distance of approximately 1 mm. The response of the brain tissue to this shock excitation is then measured using motion sensitive phase imaging techniques. Hydrogels with varying stiffness inside PMMA containers with different sizes were used as phantoms emulating the soft brain tissue inside the hard skull to investigate the response to the excitation. Homogeneous phantoms were measured to investigate the response to the shock excitation and to determine the influence of size, stiffness and boundary conditions of the probe. An oscillation in the phase could be observed in response to the excitation and its frequency allowed distinguishing between different phantom configurations. Additionally, different kinds of inhomogeneous phantoms were investigated to evaluate the feasibility to spatially resolve substructures in the mechanical properties of the phantom material. For local structures depicting the phase strain proved to be a useful tool to identify the inclusions. The results from the phantom measurements were transferred to the in vivo measurement of ten healthy volunteers to evaluate the experimental set-up under real conditions. These measurements showed that the brain responses to excitation as expected with a distinct oscillation in each hemisphere. The frequencies extracted showed mostly comparable values over the ten volunteers. In both the phase and the phase strain images similar localized features were visible, some corresponding to anatomical structures like sulci. These result show that in vivo MRR measurements of the human brain are feasible and comparable and though there is room for improvement concerning the reproducibility of the excitation between different measurement sets, MRR appears to be an interesting tool to investigate human brain tissue

Patient-Centered Medicine and Self-Help Groups in Germany: Self-Help Friendliness as an Approach for Patient Involvement in Healthcare Institutions

Collaboration between laypersons and professionals is closely linked to the concept of patient centeredness. Patient centeredness means meeting the needs of individual patients as well as reacting to patients’ demands on the collective level. The support of self-help groups and their integration into healthcare institutions represent a major policy approach to fulfilling this requirement. Here, we first deal with the concept of patient centeredness in general, and the understanding of concept and use in Germany. We also provide a short definition of self-help friendliness (SHF) and discuss the success achieved in implementing it in Germany so far. We then clarify the closely related concepts of patient centeredness, patient participation and patient involvement SHF is seen as a strategy for increasing both patient centeredness and patient participation in healthcare services. We subsequently describe the involvement of self-help groups and patient associations in a series of empirical studies and practice-oriented projects carried out between 2004 and 2013. The last section contains a general discussion of the SHF approach as a means of systematically increasing sustainable patient centeredness and patient participation in healthcare services. Finally, we address the chances for future development in Germany and the transferability of SHF to other countries

Modeling Wnt/β-catenin target gene expression in APC and Wnt gradients under wild type and mutant conditions

The Wnt/β-catenin pathway is involved in the regulation of a multitude of physiological processes by controlling the differential expression of target genes. In certain tissues such as the adult liver, the Wnt/β-catenin pathway can attain different levels of activity due to gradients of Wnt ligands and/or intracellular pathway components like APC. How graded pathway activity is converted into regionally distinct patterns of Wnt/β-catenin target gene expression is largely unknown. Here, we apply a mathematical modeling approach to investigate the impact of different regulatory mechanisms on target gene expression within Wnt or APC concentration gradients. We develop a minimal model of Wnt/beta-catenin signal transduction and combine it with various mechanisms of target gene regulation. In particular, the effects of activation, inhibition, and an incoherent feedforward loop (iFFL) are compared. To specify activation kinetics, we analyze experimental data that quantify the response of β-catenin/TCF reporter constructs to different Wnt concentrations, and demonstrate that the induction of these constructs occurs in a cooperative manner with Hill coefficients between 2 and 5. In summary, our study shows that the combination of specific gene regulatory mechanisms with a time-independent gradient of Wnt or APC is sufficient to generate distinct target gene expression patterns as have been experimentally observed in liver. We find that cooperative gene activation in combination with a TCF feedback can establish sharp borders of target gene expression in Wnt or APC gradients. In contrast, the iFFL renders gene expression independent of gradients of the upstream signaling components. Our subsequent analysis of carcinogenic pathway mutations reveals that their impact on gene expression is determined by the gene regulatory mechanism and the APC concentration of the cell in which the mutation occurs

Late Antique Plague Ships: Sixth-Century C.E. Trade Routes and Their Role in Transmitting the Justinianic Plague

The major European epidemic of bubonic plague in the sixth century C.E. – named for the ruling Byzantine emperor, Justinian – devastated the empire at the same time that outside pressures in the form of Goths, Vandals, Persians and others were also eroding the territory held by the Byzantines. While far less documentation survives the period between 550-750 C.E. than does for the periods before and after, we do have numerous references to specific plague outbreaks with which it is possible to reconstruct a transmission path and timeline. The combination of geographical information systems (GIS) tools, literary references, modern archaeological finds and DNA analysis of excavated sixth-century C.E. graves creates an opportunity past researchers of this plague have not had for linking individual outbreaks. Synthesizing this data gives us a more detailed path of transmission than has previously been available and more clearly illustrates the relationships between various cities and countries through which the plague moved during the epidemic. Although several authors have done outstanding work tracing the path of the plague through specific regions, no prior work has combined all known literary references to the Justinianic plague for the specific purpose of mapping its course. This thesis attempts to do just that by combining the plague outbreak information with trading data, evidence from shipwrecks, ancient road information, archaeological finds, and other materials to present a plausible transmission scenario. This synthesis reveals, in many cases, a startlingly clear relationship between cities during phases of the epidemic. While epidemiological work has strongly suggested that waterborne transmission was required for the speed of the spread, it is evident when all available information is mapped. Holes in our information are similarly highlighted, and present opportunities for focused plague-related research and/or excavation. This thesis presents a fresh look at old data, but also opens the door for new questions and lines of inquiry

Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes

BACKGROUND: Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/β-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/β-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. RESULTS: Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/β-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. CONCLUSIONS: Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter- and intracellular processes, such as Dkk feedback, diffusion and Wnt/β-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression

Sources of dynamic variability in NF-κB signal transduction: a mechanistic model

The transcription factor NF-{kappa}B (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF-{kappa}B signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF-{kappa}B. By applying mathematical modelling and bifurcation analyses, we show that NF-{kappa}B is capable of exhibiting different types of dynamics in response to the same stimulus. We identified the total NF-{kappa}B concentration and the I{kappa}B{alpha} transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF-{kappa}B. Both parameters might vary as a result of cell-to-cell variability. The regulation of the IκBα transcription rate constant, e.g. by co-factors, provides the possibility of regulating the NF-{kappa}B dynamics by crosstalk

A modelling approach to quantify dynamic crosstalk between the pheromone and the starvation pathway in baker's yeast

Cells must be able to process multiple information in parallel and, moreover, they must also be able to combine this information in order to trigger the appropriate response. This is achieved by wiring signalling pathways such that they can interact with each other, a phenomenon often called crosstalk. In this study, we employ mathematical modelling techniques to analyse dynamic mechanisms and measures of crosstalk. We present a dynamic mathematical model that compiles current knowledge about the wiring of the pheromone pathway and the filamentous growth pathway in yeast. We consider the main dynamic features and the interconnections between the two pathways in order to study dynamic crosstalk between these two pathways in haploid cells. We introduce two new measures of dynamic crosstalk, the intrinsic specificity and the extrinsic specificity. These two measures incorporate the combined signal of several stimuli being present simultaneously and seem to be more stable than previous measures. When both pathways are responsive and stimulated, the model predicts that (a) the filamentous growth pathway amplifies the response of the pheromone pathway, and (b) the pheromone pathway inhibits the response of filamentous growth pathway in terms of mitogen activated protein kinase activity and transcriptional activity, respectively. Among several mechanisms we identified leakage of activated Ste11 as the most influential source of crosstalk. Moreover, we propose new experiments and predict their outcomes in order to test hypotheses about the mechanisms of crosstalk between the two pathways. Studying signals that are transmitted in parallel gives us new insights about how pathways and signals interact in a dynamical way, e.g., whether they amplify, inhibit, delay or accelerate each other

Strukturqualität in deutschen Intensivstationen: Reevaluation der Strukturdatensätze des DIVI-Registers

Seitdem im Jahr 2000 im Zuge eines zunehmenden ökonomischen Drucks die Forderung zur Pflichtimplementierung von qualitätssichernden Maßnahmen in der Medizin gesetzlich verankert wurde, ist verstärkt versucht worden, Intensiveinheiten bezüglich ihrer Basisdaten zu erfassen sowie einen nationalen Referenzwert bezüglich intensivmedizinischer Qualität zu erarbeiten. Der Gedanke hinter der Erfassung war, dass es mit Hilfe der Basisdaten und eines nationalen Referenzwerts möglich sein sollte, das Leistungsspektrum und die Leistungsfähigkeit der Intensiveinheiten abzubilden und untereinander vergleichbar zu machen, um somit bestehende Ressourcen einer effizienteren Nutzung zuführen zu können. Intensiveinheiten standen bis dahin insbesondere deswegen im Zentrum der Aufmerksamkeit, weil der sehr kostenintensive Bereich der Intensivmedizin einen großen Anteil der bestehenden Ressourcen für sich beansprucht hatte, ohne dass sich nach Einführung des Abrechnungssystems mittels Fallpauschalen (Diagnosis Related Groups, DRG) eine adäquate Abbildung der intensivmedizinischen Leistungen darstellen ließ. Konsens bestand darüber, dass ohne einen nationalen Referenzwert oder eine Referenzgruppe eine Vergleichbarkeit der Leistungsfähigkeit unterschiedlicher Intensiveinheiten nicht erfolgen kann und ohne eine mögliche Vergleichbarkeit eine Aussage bezüglich der Qualität und einer möglichen Effizienzoptimierung der Bereiche nicht möglich ist. Einen wichtigen Beitrag zur Erfassung der Basisdaten und Erarbeitung eines nationalen Referenzwerts leistete die Querschnittstudie bzgl. der Erfassung der Strukturqualität deutscher Intensiveinheiten der Jahre 1999-2000 unter der Leitung der Deutschen Interdisziplinären Vereinigung für Intensivmedizin (DIVI)1. Die dort gewonnenen Ergebnisse konnten zur Gründung eines Nationalen Intensivmedizinregisters genutzt werden, und dieses wiederum fand unter anderem Verwendung bei der Planung neuer und Optimierung bestehender Qualitätsstrukturen deutscher Intensiveinheiten. Die vorliegende Arbeit aktualisiert den damaligen Basisdatensatz und ergänzt ihn stellenweise, damit im Folgenden eine deutlich gezieltere Aussage bezüglich der Qualität und einer Effizienzoptimierung der Bereiche möglich ist

Methodische Untersuchungen zur Beurteilung der proteolytischen Aktivität, der Proteolyse und der Desmolyse bei der Silierung eiweißreicher Grünfutterleguminosen

Der Proteinabbau während der Silierung muss negativ bewertet werden, vor allem bei den als schwer silierbar geltenden Grünfutterleguminosen. Um das zu erwartende Ausmaß des Proteinabbaus vor der Silierung einschätzen und beeinflussen zu können, wurde eine In-vitro-Methode zur Bestimmung der proteolytischen Aktivität konzipiert sowie ein Parameter für die Abbauanfälligkeit des Pflanzenproteins festgelegt. Die Wirkung von Einflussfaktoren auf den Proteinabbau während der Fermentation wurde unter In-vitro-Bedingungen quantifiziert. Außerdem wurden Parameter zur Charakterisierung der Proteinqualität von Silagen festgelegt, mit denen die Proteolyse und Desmolyse beurteilt werden können