Eine computermodellgestützte Analyse der elektrophysiologischen Effekte von Gap-Junction-Lateralisierung und zellulärer Hypertrophie in kardialem Gewebe

Die vorliegende Dissertation befasst sich mit Entstehungsmechanismen kardialer Arrhythmien auf der Grundlage pathologisch veränderten Myokards. Es wurde eine systematische Analyse der elektrophysiologischen Veränderungen, die als Folge von Gap-Junction- Lateralisierung und zellulärer Hypertrophie auftreten, durchgeführt. Die Analyse beruht auf einem mathematischen Computermodell, das zur Simulation der Aktionspotentialausbreitung innerhalb einer Einzelzellschicht humaner ventrikulärer Kardiomyozyten entwickelt wurde. Ausgehend von bestehenden Einzelzellmodellen wurde ein räumlich und zeitlich hoch aufgelöstes Multizellmodell generiert und in der Programmiersprache Object Pascal implementiert. Nach Validierung des Modells wurde es zur gezielten, an experimentellen Daten orientierten Manipulation geometrischer Eigenschaften der Zellen (Länge, Durchmesser) und des Zellverbandes (Anordnung der Zellen untereinander) sowie der Gap-Junction-Verteilung genutzt. Die Analyse der elektrophysiologischen Effekte im Vergleich zur Kontrolle fand sowohl unter Normalbedingungen als auch unter Bedingungen, die pathologischen Veränderungen entsprechen (Entkopplung der Gap-Junctions, verringerte Aktivität des schnellen Natriumkanals, erhöhte Inhomogenität), statt. Es zeigte sich, dass ein größerer Zelldurchmesser bzw. erhöhte laterale Gap-Junction-Leitfähigkeit (Simulation von kardialer Hypertrophie bzw. Connexin- Lateralisierung) die Entstehungswahrscheinlichkeit eines unidirektionalen Leitungsblocks erhöhte. Die Erregungsausbreitungsgeschwindigkeit in hypertrophierten Zellen war zudem weniger stabil als in normalen Zellen. Beide Effekte gehören zu den Hauptursachen der Entstehung und Aufrechterhaltung ventrikulärer Arrhythmien. Die Ergebnisse der Arbeit erklären somit Ursachen des erhöhten Arrhythmierisikos in pathologisch veränderten und hypertrophierten Herzen und liefern eine theoretische Grundlage für zukünftige Studien

Concurrent optimization of airframe and engine design parameters

An integrated system for the multidisciplinary analysis and optimization of airframe and propulsion design parameters is being developed. This system is known as IPAS, the Integrated Propulsion/Airframe Analysis System. The traditional method of analysis is one in which the propulsion system analysis is loosely coupled to the overall mission performance analysis. This results in a time consuming iterative process. First, the engine is designed and analyzed. Then, the results from this analysis are used in a mission analysis to determine the overall aircraft performance. The results from the mission analysis are used as a guide as the engine is redesigned and the entire process repeated. In IPAS, the propulsion system, airframe, and mission are closely coupled. The propulsion system analysis code is directly integrated into the mission analysis code. This allows the propulsion design parameters to be optimized along with the airframe and mission design parameters, significantly reducing the time required to obtain an optimized solution

Braid group actions on derived categories of coherent sheaves

Published versio

Fructose Alters Cell Survival and Gene Expression in Microglia and Neuronal Cells Lines

Purpose: Microglia are macrophages that are found primarily in the CNS and play a crucial role in maintaining a healthy brain by engulfing invading microorganisms, releasing inflammatory mediators, and pruning dead cells. Microglia can become activated in response to certain stimuli which causes them to transition into a pro-inflammatory state, and can sometimes become chronically activated which can result in neuronal damage. Studies have shown a causal relationship between this activation and sugars such as fructose and glucose. We sought to understand the role of sugars in microglial activation and the subsequent effects on neuron health. Methods: Rat microglia (HAPI) and neuronal (B35) cell lines were treated with varying concentrations of fructose (25 mM, 12.5 mM, and 6.25 mM) or glucose (25 mM and 12.5 mM)as a positive control to determine their effects on the cells. Following treatment and incubation for 3 or 24 hours, the cells were analyzed using an MTT assay to measure cell survival or real-time polymerase chain reaction (RT-PCR) to measure gene expression levels. Effects of fructose were measured in HAPI microglia after direct treatment with the sugar. The genes investigated by the RT-PCR in the HAPI cells included: glucose transporter 5 (GLUT5), and the inflammatory markers high mobility group box 1 (HMGB1), and prostaglandin E receptor 2 (Ptger2). To evaluate the effects of microglial activation on neuronal function, the B35 neurons were treated either directly with sugars or with the supernatant collected from fructose-treated HAPI microglia. This allows examination of the effects of soluble neuron-injury factors released by microglia. The genes investigated by RT-PCR in B35 neurons included nuclear factor-κB (NFκB) and enolase 2 (Eno2). Results: Cell survival assays showed that 24-hour direct fructose treatment increased B35 cell survival by up to 13%, while groups treated with microglia supernatant increased cell survival by up to 33%. In HAPI microglia, 3 hours of treatment with fructose caused GLUT5 expression to be suppressed by up to 32% in all treatment groups except for 6.25 mM fructose, while Ptger2 and HMGB1 expression was increased by as much as 65% and 15%, respectively. After 24-hours of treatment with fructose, the HAPI microglia showed a maximum of 80% increased expression of HMGB1, while Ptger2 expression was mostly unchanged. In B35 neurons, 3 hours of treatment with fructose caused a decrease of up to 26% in NFκB and an increase of up to 46% in Eno2 expression. Conclusion: Cell survival results indicate that the microglia may provide a short term protective effect on the B35 neurons. However, data from the gene expression assays show evidence of cellular dysfunction in neurons and pro-inflammatory activity in microglia which may lead to neuronal death on a longer timeline. As seen in the gene expression results, microglia had increased expression of pro-inflammatory genes and B35 neuronal cells had increased expression of markers of cellular damage. Future studies will further explore the effects of fructose on expression of other genes and examine the effects on neuron survival at later time points

Solar dynamic power systems for space station

The Parabolic Offset Linearly Actuated Reflector (POLAR) solar dynamic module was selected as the baseline design for a solar dynamic power system aboard the space station. The POLAR concept was chosen over other candidate designs after extensive trade studies. The primary advantages of the POLAR concept are the low mass moment of inertia of the module about the transverse boom and the compactness of the stowed module which enables packaging of two complete modules in the Shuttle orbiter payload bay. The fine pointing control system required for the solar dynamic module has been studied and initial results indicate that if disturbances from the station are allowed to back drive the rotary alpha joint, pointing errors caused by transient loads on the space station can be minimized. This would allow pointing controls to operate in bandwidths near system structural frequencies. The incorporation of the fine pointing control system into the solar dynamic module is fairly straightforward for the three strut concentrator support structure. However, results of structural analyses indicate that this three strut support is not optimum. Incorporation of a vernier pointing system into the proposed six strut support structure is being studied

Heegaard Floer homology of certain mapping tori

We calculate the Heegaard Floer homologies$HF^+(M,s) for mapping tori M associated to certain surface diffeomorphisms, where s is any Spin^c structure on M whose first Chern class is non-torsion. Let gamma and delta be a pair of geometrically dual nonseparating curves on a genus g Riemann surface Sigma_g, and let sigma be a curve separating Sigma_g into components of genus 1 and g-1. Write t-gamma, t_delta, and t_sigma for the right-handed Dehn twists about each of these curves. The examples we consider are the mapping tori of the diffeomorphisms t_gamma^m circ t_delta^n for m,n in Z and that of t_sigma^{+-1}.Comment: Published by Algebraic and Geometric Topology at http://www.maths.warwick.ac.uk/agt/AGTVol4/agt-4-31.abs.htm

Modular Change in Platform Ecosystems and Routine Mirroring in Organizations

Organizational routines involve modular digital technologies that are part of larger platform ecosystems that often transcend organizational boundaries. Change in organizational routines is thus interwoven with innovation and associated change in digital platforms. To get at this “embedded” routine change, we use the concept of modular operators to conceptualize how changes to digital technologies in platform ecosystems are mirrored in changes in the organizational routines in which these technologies are implicated. We distinguish between enabling and constraining impacts and develop a set of propositions to move towards a theory of “routine mirroring.” We use the Industrial Internet of Things (IIoT) as a base example

Shift in Perspective: Case Study of Motivational Factors in an Online Innovation Community

New product innovations are necessary to attract consumers for companies to survive in the market in the long term in our fast-moving world. One way to gain access to such new creative solutions is through online communities whose members exchange ideas on virtual platforms (Antikainen & Väätäjä, 2010). This explorative research paper investigates the motivational reasons of users who engage themselves on innovation platforms. The aim is to provide practice-oriented design recommendations to support community managers in establishing or improving innovation communities in companies. The improved conditions have a positive influence on the creativity of individual users and thus contribute to the increased innovative power of the entire online community. The study focuses on LEGO Ideas as an example of an online innovation community with members from all over the world. Within the community LEGO models are designed, discussed, re-designed and finally rated by enthusiasts. The best-rated models are then produced as innovative products. The designers of the models receive a share of the sales revenues. The article specifically addresses the following research question: What key factors motivate online community innovators’ engagement? [Aus: Introduction

Cascading Digital Options and the Evolution of Digital Infrastructures: The Case of IIoT

Digital infrastructures provide a space where possibilities for innovation continuously emerge. They are not stable entities but are evolving. Their boundaries are subject to constant negotiation among multiple organizational actors as well as changing connections of digital technologies, operations, and users. In this paper, we explore the evolution of an Industrial Internet of Things (IIoT) infrastructure in a leading manufacturing company. We find that the IIoT infrastructure provided actionable spaces upon which organizational actors discovered opportunities for improving process performance which, in turn, led to investment decisions. We explain this process through the lens of digital options theory and highlight how IIoT infrastructure provides the material foundation for the identification of digital options, how the realization of digital options leads to the emergence of more digital options, and how these “cascading” digital options are implicated in the evolution of IIoT infrastructure. We discuss theoretical and practical implications