@misc{Dandekar1991, author = {Dandekar, Thomas}, title = {Yeast U3 localization and correct sequence (snR17a) and promotor activity (snR17b) identified by homology search}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29781}, year = {1991}, abstract = {No abstract available}, language = {en} } @article{DandekarRibesTollervey1989, author = {Dandekar, Thomas and Ribes, V. and Tollervey, David}, title = {Schizosaccharomyces pombe U4 small nuclear RNA closely resembles vertebrate U4 and is required for growth}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29771}, year = {1989}, abstract = {No abstract available}, language = {en} } @article{DandekarArgos1994, author = {Dandekar, Thomas and Argos, Patrick}, title = {Amiloride-sensitive epithelial Na\(^+\) channel is made of three homologous subunits}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29734}, year = {1994}, abstract = {No abstract available}, language = {en} } @phdthesis{Osmanovic2008, author = {Osmanovic, Jelena}, title = {Changes in gene expression of brain insulin system in STZ icv - damaged rats - relevance to Alzheimer disease}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29603}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Ratten, die intrazerebroventricular (icv) mit Streptozotocin (STZ) behandelt werden, eignen sich gut als Tiermodelle f{\"u}r die sporadische Alzheimererkrankung (sAD). In der hier vorgelegten Arbeit wurden Ver{\"a}nderungen bez{\"u}glich der Insulinkonzentration sowie einiger Bestandteile der Insulinrezeptor (IR) - Signalkaskade in Rattengehirnen, welche icv mit STZ behandelt wurden, zu verschiedenen Zeitpunkten untersucht. Die Auswirkungen von STZ auf die zerebrale IR-Signalkaskade wurden dann mit denen von chronisch erh{\"o}hten Corticosteronkonzentrationen verglichen. In dieser Studie wurde im Hippocampus eine verminderte mRNA-Expression von Insulin, der IR sowie des insulinabbauenden Enzyms (IDE) nachgewiesen; bez{\"u}glich der tau-mRNA-Expression konnten jedoch in diesem Gehirnareal der mit STZ behandelten Ratten keine Ver{\"a}nderungen beobachtet werden. Die Resultate der Insulin-, IR- und IDE-mRNA-Expression fielen bei den mit Corticosteron behandelten Ratten {\"a}hnlich aus Im Gegensatz hierzu nahm die tau-mRNA-Expression bei Ratten, die mit Corticosterone behandelt wurden, zu, was auch f{\"u}r eine sAD kennzeichnend ist. Sowohl bei den mit STZ als auch bei den mit Corticosteronen behandelten Ratten konnten Verhaltensanomalien beobachtet werden. Die in dieser Arbeit erzielten Resultate deuten darauf hin, dass viele Merkmale einer sAD experimentell durch eine Beeintr{\"a}chtigung des Insulin/IR-Signalwegs sowie eine chronische Erh{\"o}hung der Corticosteronkonzentration hervorgerufen werden k{\"o}nnen. Dies untermauert wiederum unsere Hypothese, dass es sich bei sAD um eine neuroendokrine St{\"o}rung handelt, die mit gehirnspezifischen Fehlfunktionen in der Insulin/IR-Signalkaskade einhergeht, welche zum Teil durch erh{\"o}hte Corticosteronkonzentrationen ausgel{\"o}st werden k{\"o}nnen. Auf Grund der in dieser Arbeit erzielten Resultate stellt sich die Frage, ob \&\#61538;-Amyloid (A\&\#61538;) ein Ausl{\"o}ser oder eine Konsequenz einer sAD darstellt. Die hier vorgelegte Arbeit last den Schlus zu, dass bei sAD-Tiermodellen ein Zusammenhang zwischen prim{\"a}ren Fehlfunktionen im zerebralen Insulinsystem und dadwol sekund{\"a}r ausgeloster A\&\#61538;-Pathologie besteht. Weiterf{\"u}bende Untersuchungen wird aber notwendig um diese Aussagen zu best{\"a}tigen.}, subject = {Insulin}, language = {en} } @phdthesis{Fischer2008, author = {Fischer, Stefan Martin}, title = {Regulation and functional consequences of MCP-1 expression in a model of Charcot-Marie-Tooth 1B disease}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29189}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Charcot-Marie-Tooth 1B (CMT1B) is a progressive inherited demyelinating disease of human peripheral nervous system leading to sensory and/or motor function disability and is caused by mutations in the P0 gene. Mice heterozygously deficient for P0 (P0+/-) are an adequate model of this human disorder showing myelin degeneration, formation of onion bulbs, remyelination and a reduced motor conduction velocity of around 30m/s similar to patients. Previously, it had been shown that T-lymphocytes and macrophages play a crucial role during pathogenesis in peripheral nerves of P0+/- mice. Both, T-lymphocytes and macrophages increase in number in the endoneurium and deletion of T-lymphocytes or deletion of a macrophage-directed cytokine ameliorates the disease. In this study the monocyte chemoattractant protein-1 (MCP-1) was identified as an early regulated cytokine before onset of disease is visible at the age of six months. MCP-1 mRNA and protein expression could be detected in femoral quadriceps and sciatic nerves of P0+/- mice already at the age of one month but not in cutaneous saphenous nerves which are never affected by the disease. MCP-1 was shown to be expressed by Schwann cells and to mediate the immigration of immune cells into peripheral nerves. Deletion of MCP-1 in P0+/- mice accomplished by crossbreeding P0 and MCP-1 deficient mice revealed a substantial reduction of immune cells in peripheral nerves of P0+/-/MCP-1+/- and P0+/-/MCP-1-/- mice at the age of six months. In twelve months old mice reduction of immune cells in peripheral nerves is accompanied by amelioration of demyelinating disease in P0+/-/MCP-1+/- and aggravation of demyelinating disease in lumbar ventral roots of P0+/ /MCP-1-/- mice in comparison to P0+/ /MCP 1+/+ mice. Furthermore, activation of the MEK1/2-ERK1/2 signalling cascade could be demonstrated to take place in Schwann cells of affected peripheral nerves of P0+/- mice overlapping temporarily and spatially with MCP-1 expression. An animal experiment using a MEK1/2-inhibitor in vivo, CI-1040, revealed that upon reduction of ERK1/2 phosphorylation MCP-1 mRNA expression is diminished suggesting that the activation of the MEK1/2-ERK1/2 signalling cascade is necessary for MCP-1 expression. Additionally, peripheral nerves of P0+/- mice showing reduced ERK1/2 phosphorylation and MCP-1 mRNA expression also show reduced numbers of macrophages in the endoneurium. This study shows a molecular link between a Schwann cell based mutation and immune cell function. Inhibition of the identified signalling cascade might be a putative target for therapeutic approaches.}, subject = {Schwann-Zelle}, language = {en} } @phdthesis{Seiberlich2008, author = {Seiberlich, Nicole}, title = {Advances in Non-Cartesian Parallel Magnetic Resonance Imaging using the GRAPPA Operator}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28321}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Magnetic Resonance Imaging (MRI) is an imaging modality which provides anatomical or functional images of the human body with variable contrasts in an arbitrarily positioned slice without the need for ionizing radiation. In MRI, data are not acquired directly, but in the reciprocal image space (otherwise known as k-space) through the application of spatially variable magnetic field gradients. The k-space is made up of a grid of data points which are generally acquired in a line-by-line fashion (Cartesian imaging). After the acquisition, the k-space data are transformed into the image domain using the Fast Fourier Transformation (FFT). However, the acquisition of data is not limited to the rectilinear Cartesian sampling scheme described above. Non-Cartesian acquisitions, where the data are collected along exotic trajectories, such as radial and spiral, have been shown to be beneficial in a number of applications. However, despite their additional properties and potential advantages, working with non-Cartesian data can be complicated. The primary difficulty is that non-Cartesian trajectories are made up of points which do not fall on a Cartesian grid, and a simple and fast FFT algorithm cannot be employed to reconstruct images from non-Cartesian data. In order to create an image, the non-Cartesian data are generally resampled on a Cartesian grid, an operation known as gridding, before the FFT is performed. Another challenge for non-Cartesian imaging is the combination of unusual trajectories with parallel imaging. This thesis has presented several new non-Cartesian parallel imaging methods which simplify both gridding and the reconstruction of images from undersampled data. In Chapter 4, a novel approach which uses the concepts of parallel imaging to grid data sampled along a non-Cartesian trajectory called GRAPPA Operator Gridding (GROG) is described. GROG shifts any acquired k-space data point to its nearest Cartesian location, thereby converting non-Cartesian to Cartesian data. The only requirements for GROG are a multi-channel acquisition and a calibration dataset for the determination of the GROG weights. Chapter 5 discusses an extension of GRAPPA Operator Gridding, namely Self-Calibrating GRAPPA Operator Gridding (SC-GROG). SC-GROG is a method by which non-Cartesian data can be gridded using spatial information from a multi-channel coil array without the need for an additional calibration dataset, as required in standard GROG. Although GROG can be used to grid undersampled datasets, it is important to note that this method uses parallel imaging only for gridding, and not to reconstruct artifact-free images from undersampled data. Chapter 6 introduces a simple, novel method for performing modified Cartesian GRAPPA reconstructions on undersampled non-Cartesian k-space data gridded using GROG to arrive at a non-aliased image. Because the undersampled non-Cartesian data cannot be reconstructed using a single GRAPPA kernel, several Cartesian patterns are selected for the reconstruction. Finally, Chapter 7 discusses a novel method of using GROG to mimic the bunched phase encoding acquisition (BPE) scheme. In MRI, it is generally assumed that an artifact-free image can be reconstructed only from sampled points which fulfill the Nyquist criterion. However, the BPE reconstruction is based on the Generalized Sampling Theorem of Papoulis, which states that a continuous signal can be reconstructed from sampled points as long as the points are on average sampled at the Nyquist frequency. A novel method of generating the "bunched" data using GRAPPA Operator Gridding (GROG), which shifts datapoints by small distances in k-space using the GRAPPA Operator instead of employing zig-zag shaped gradients, is presented in this chapter. With the conjugate gradient reconstruction method, these additional "bunched" points can then be used to reconstruct an artifact-free image from undersampled data. This method is referred to as GROG-facilitated Bunched Phase Encoding, or GROG-BPE.}, subject = {NMR-Tomographie}, language = {en} } @phdthesis{Heymer2008, author = {Heymer, Andrea}, title = {Chondrogenic differentiation of human mesenchymal stem cells and articular cartilage reconstruction}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29448}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Articular cartilage defects are still one of the major challenges in orthopedic and trauma surgery. Today, autologous chondrocyte transplantation (ACT), as a cell-based therapy, is an established procedure. However, one major limitation of this technique is the loss of the chondrogenic phenotype during expansion. Human mesenchymal stem cells (hMSCs) have an extensive proliferation potential and the capacity to differentiate into chondrocytes when maintained under specific conditions. They are therefore considered as candidate cells for tissue engineering approaches of functional cartilage tissue substitutes. First in this study, hMSCs were embedded in a collagen type I hydrogel to evaluate the cartilaginous construct in vitro. HMSC collagen hydrogels cultivated in different culture media showed always a marked contraction, most pronounced in chondrogenic differentiation medium supplemented with TGF-ß1. After stimulation with chondrogenic factors (dexamethasone and TGF-ß1) hMSCs were able to undergo chondrogenesis when embedded in the collagen type I hydrogel, as evaluated by the temporal induction of cartilage-specific gene expression. Furthermore, the cells showed a chondrocyte-like appearance and were homogeneously distributed within a proteoglycan- and collagen type II-rich extracellular matrix, except a small area in the center of the constructs. In this study, chondrogenic differentiation could not be realized with every hMSC preparation. With the improvement of the culture conditions, e.g. the use of a different FBS lot in the gel fabrication process, a higher amount of cartilage-specific matrix deposition could be achieved. Nevertheless, the large variations in the differentiation capacity display the high donor-to-donor variability influencing the development of a cartilaginous construct. Taken together, the results demonstrate that the collagen type I hydrogel is a suitable carrier matrix for hMSC-based cartilage regeneration therapies which present a promising future alternative to ACT. Second, to further improve the quality of tissue-engineered cartilaginous constructs, mechanical stimulation in specific bioreactor systems are often employed. In this study, the effects of mechanical loading on hMSC differentiation have been examined. HMSC collagen hydrogels were cultured in a defined chondrogenic differentiation medium without TGF-ß1 and subjected to a combined mechanical stimulation protocol, consisting of perfusion and cyclic uniaxial compression. Bioreactor cultivation neither affected overall cell viability nor the cell number in collagen hydrogels. Compared with non-loaded controls, mechanical loading promoted the gene expression of COMP and biglycan and induced an up-regulation of matrix metalloproteinase 3. These results circumstantiate that hMSCs are sensitive to mechanical forces, but their differentiation to chondrocytes could not be induced. Further studies are needed to identify the specific metabolic pathways which are altered by mechanical stimulation. Third, for the development of new cell-based therapies for articular cartilage repair, a reliable cell monitoring technique is required to track the cells in vivo non-invasively and repeatedly. This study aimed at analyzing systematically the performance and biological impact of a simple and efficient labeling protocol for hMSCs. Very small superparamagnetic iron oxide particles (VSOPs) were used as magnetic resonance (MR) contrast agent. Iron uptake was confirmed histologically with prussian blue staining and quantified by mass spectrometry. Compared with unlabeled cells, VSOP-labeling did neither influence significantly the viability nor the proliferation potential of hMSCs. Furthermore, iron incorporation did not affect the differentiation capacity of hMSCs. The efficiency of the labeling protocol was assessed with high resolution MR imaging at 11.7 Tesla. VSOP-labeled hMSCs were visualized in a collagen type I hydrogel indicated by distinct hypointense spots in the MR images, resulting from an iron specific loss of signal intensity. This was confirmed by prussian blue staining. In summary, this labeling technique has great potential to visualize hMSCs and track their migration after transplantation for articular cartilage repair with MR imaging.}, subject = {Gelenkknorpel}, language = {en} } @phdthesis{Ceteci2008, author = {Ceteci, Fatih}, title = {Analysis of the role of the E-(Epithelial) Cadherin in murine lung tumorigenesis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29396}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Beim humanen nichtkleinzelligen Bronchialkarzinom ist die schrittweise Progression vom gutartigen Tumor zur malignen Metastasierung weitestgehend ungekl{\"a}rt. In einem transgenen Mausmodell f{\"u}r das humane nichtkleinzellige Bronchialkarzinom, in dem in Lungenepithelzellen eine onkogene Mutante der Proteinkinase C-RAF exprimiert wird, k{\"o}nnen einzelne Schritte im Prozess der malignen Progression entschl{\"u}sselt werden. Die durch C-RAF induzierten Adenome zeichnen sich durch eine hohe genomische Stabilit{\"a}t in den Tumorzellen, durch starke interzellul{\"a}re Adh{\"a}sionskontakte zwischen den Tumorzellen und das Fehlen einer malignen Progression aus. Hier wurde demzufolge untersucht, ob die Aufl{\"o}sung der E-Cadherin-vermittelten Zellkontakte zwischen den einzelnen Tumorzellen eine Metastasierung ausl{\"o}sen k{\"o}nnte. Es wurden zwei genetische Ans{\"a}tze verfolgt, um die Rolle der Tumorzelladh{\"a}sion im C-RAF Modell zu bewerten, die konditionelle Eliminierung des E-Cadheringens Cdh1 sowie die regulierbare transgene Expression von dominant-negativem E-Cadherin. Die Aufl{\"o}sung der E-Cadherin-vermittelten Zelladh{\"a}sion f{\"u}hrte zur Neubildung von Tumorgef{\"a}ßen, welche in der fr{\"u}hen Phase der Gef{\"a}ßbildung durch Wiederherstellung des Zellkontakts reversibel war. Die vaskularisierten Tumore wuchsen schneller, bildeten invasive Fronten aus und f{\"u}hrten zur Ausbildung von Mikrometastasen. Es konnte gezeigt werden, dass Beta-Catenin f{\"u}r die Induktion der Angiogenesefaktoren VEGF-A und VEGF-C in Lungentumorzellinien des Menschen und der Maus essentiell war. Lungentumorzellen aus den in situ Tumoren mit aufgel{\"o}sten E-Cadherin-vermittelten Zellkontakten exprimierten Gene endodermaler und anderer Zellabstammung, was epigenetische Reprogrammierung in Tumorzellen als den Mechanismus bei der malignen Progression vermuten l{\"a}sst.}, subject = {E-cadherin}, language = {en} } @phdthesis{Qiu2008, author = {Qiu, Liyan}, title = {Structural and functional analysis of crossveinless 2 / BMP-2 /Chordin interaction}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29249}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {No abstract available}, language = {en} } @phdthesis{Martin2008, author = {Martin, R{\"u}diger}, title = {Resilience, Provisioning, and Control for the Network of the Future}, doi = {10.25972/OPUS-2504}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28497}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {The Internet sees an ongoing transformation process from a single best-effort service network into a multi-service network. In addition to traditional applications like e-mail,WWW-traffic, or file transfer, future generation networks (FGNs) will carry services with real-time constraints and stringent availability and reliability requirements like Voice over IP (VoIP), video conferencing, virtual private networks (VPNs) for finance, other real-time business applications, tele-medicine, or tele-robotics. Hence, quality of service (QoS) guarantees and resilience to failures are crucial characteristics of an FGN architecture. At the same time, network operations must be efficient. This necessitates sophisticated mechanisms for the provisioning and the control of future communication infrastructures. In this work we investigate such echanisms for resilient FGNs. There are many aspects of the provisioning and control of resilient FGNs such as traffic matrix estimation, traffic characterization, traffic forecasting, mechanisms for QoS enforcement also during failure cases, resilient routing, or calability concerns for future routing and addressing mechanisms. In this work we focus on three important aspects for which performance analysis can deliver substantial insights: load balancing for multipath Internet routing, fast resilience concepts, and advanced dimensioning techniques for resilient networks. Routing in modern communication networks is often based on multipath structures, e.g., equal-cost multipath routing (ECMP) in IP networks, to facilitate traffic engineering and resiliency. When multipath routing is applied, load balancing algorithms distribute the traffic over available paths towards the destination according to pre-configured distribution values. State-of-the-art load balancing algorithms operate either on the packet or the flow level. Packet level mechanisms achieve highly accurate traffic distributions, but are known to have negative effects on the performance of transport protocols and should not be applied. Flow level mechanisms avoid performance degradations, but at the expense of reduced accuracy. These inaccuracies may have unpredictable effects on link capacity requirements and complicate resource management. Thus, it is important to exactly understand the accuracy and dynamics of load balancing algorithms in order to be able to exercise better network control. Knowing about their weaknesses, it is also important to look for alternatives and to assess their applicability in different networking scenarios. This is the first aspect of this work. Component failures are inevitable during the operation of communication networks and lead to routing disruptions if no special precautions are taken. In case of a failure, the robust shortest-path routing of the Internet reconverges after some time to a state where all nodes are again reachable - provided physical connectivity still exists. But stringent availability and reliability criteria of new services make a fast reaction to failures obligatory for resilient FGNs. This led to the development of fast reroute (FRR) concepts for MPLS and IP routing. The operations of MPLS-FRR have already been standardized. Still, the standards leave some degrees of freedom for the resilient path layout and it is important to understand the tradeoffs between different options for the path layout to efficiently provision resilient FGNs. In contrast, the standardization for IP-FRR is an ongoing process. The applicability and possible combinations of different concepts still are open issues. IP-FRR also facilitates a comprehensive resilience framework for IP routing covering all steps of the failure recovery cycle. These points constitute another aspect of this work. Finally, communication networks are usually over-provisioned, i.e., they have much more capacity installed than actually required during normal operation. This is a precaution for various challenges such as network element failures. An alternative to this capacity overprovisioning (CO) approach is admission control (AC). AC blocks new flows in case of imminent overload due to unanticipated events to protect the QoS for already admitted flows. On the one hand, CO is generally viewed as a simple mechanism, AC as a more complex mechanism that complicates the network control plane and raises interoperability issues. On the other hand, AC appears more cost-efficient than CO. To obtain advanced provisioning methods for resilient FGNs, it is important to find suitable models for irregular events, such as failures and different sources of overload, and to incorporate them into capacity dimensioning methods. This allows for a fair comparison between CO and AC in various situations and yields a better understanding of the strengths and weaknesses of both concepts. Such an advanced capacity dimensioning method for resilient FGNs represents the third aspect of this work.}, subject = {Backbone-Netz}, language = {en} }