The G-protein coupled receptor (GPCR) Cysteine (C)-X-C Receptor 4 (CXCR4) plays an important role in prostate cancer metastasis. CXCR4 is regarded as a plasma membrane receptor, that it transmits signals that support transformation, progression and metastasis. Due to the central role of CXCR4 in tumorigenesis, therapeutic approaches such as antagonists and monoclonal antibodies have focused on receptors the located at the plasma membrane. An emerging concept for GPCRs is that they can localize to the nucleus where they may retain function and mediate nuclear signaling. Herein, we demonstrate that CXCR4 is highly expressed in high grade metastatic prostate cancer tissues. Increased expression of CXCR4 is also detected in several prostate cancer cell lines as compared to normal prostate epithelial cells. Our studies identify a nuclear pool of CXCR4 and also define a mechanism for nuclear targeting of CXCR4. A classical nuclear localization sequence (cNLS), "RPRK", in CXCR4 can contribute to nuclear localization. In addition, CXCR4 interacts with the nuclear transport receptor, Transportin βi, to promote nuclear accumulation of CXCR4. Importantly, Gαi immunoprecipitation and calcium mobilization studies indicate that nuclear CXCR4 is functional and can participate in G-protein signaling revealing that the nuclear pool of CXCR4 can retain function. Localization of functional CXCR4 to the nucleus may be a mechanism by which prostate cancer cells evade treatment, thus contributing to increased metastatic ability and poorer prognosis after tumors have been treated with therapy that targets plasma membrane CXCR4. This study addresses the mechanism of nuclear targeting for CXCR4 and demonstrates that CXCR4 can retain function within the nucleus and provides important new information to illuminate what have previously been primarily clinical observations of nuclear CXCR4.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [118]-127).

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (p. [32]-37).

Thesis (Ph. D.)--University of Washington, 1998. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 205-223). Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 1998. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

As a good and competent surgical simulator, it should provide surgeons with visual, tactile and behavioral illusion of reality. In literature, methods for object deformation range from non-physically based models to physically based models. Early works of non-physically based models focused on pure geometrical models that were originally employed in computer-aided design. These methods could be used to produce vivid deformable effects in computer animation. However, the soft tissue simulation in surgical applications requires more realistic models based on physical properties of human tissues. As a result, the mass-spring model and the finite element model have become the most popular representations for deformable organs in surgical simulation. Our research focuses on the real-time soft tissue deformable model based on the finite element method for surgical application. / Extended from the hybrid condensed finite element model, an interactive hybrid condensed model with hardware acceleration by the graphics processing unit (GPU) is proposed. Two methods are developed in order to map the data onto the GPU in accordance with the application data structure. The performance of the primary calculation task in the solver is enhanced. Furthermore, an improved scheme is presented to conduct the newly applied forces induced by dragging or poking operations in the non-operational region. / In the thesis, new approaches to establish a physically based model for soft tissue deformation and cutting in virtual-reality-based simulators are proposed. A deformable model, called the hybrid condensed finite element model, based on the volumetric finite element method is presented. By this method, three-dimensional organs can be represented as tetrahedral meshes, divided into two regions: the operational region and the non-operational one. Different methods treat the regions with different properties in order to balance the computational time and the level of the simulation realism. The condensation technique is applied to only involve the calculation of the surface nodes in the non-operational region while the fully calculation of the volumetric deformation is processed in the operational part. This model guarantees the smooth simulation of cutting operation with the exact cutting path when users manipulate a virtual scalpel. Moreover, we discuss the relevant aspects on what affect the efficiency of implementing the finite element method, as well as the issues considered for choosing the effective solving method to our problem. Three numerical methods have been examined in our model. / Surgical simulator, which benefits from virtual reality techniques, presents a realistic and feasible approach to train inexperienced surgeons within a safe environment. It plays more and more important role in medical field and also changes the world of surgical training. Especially, the minimally invasive microsurgery, which offers patients various attractive advantages over the traditional surgery, has been widely used in otolaryngology, gastroenterology, gynecology and neurology in the last two decades. / Through the combination of these approaches, a physically based model which allows users to freely perform the soft tissue cutting and detecting, such as poking or dragging operations, with soft tissue deformation is achieved in real-time. / Wu Wen. / "August 2006." / Adviser: Pheng Ann Heng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1745. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 112-127). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Degenerative suspensory ligament desmitis (DSLD) is a debilitating disease of connective tissues seen in many breeds but has become prevalent in the Peruvian Pasohorse. DSLD is believed to be a genetic disorder caused by one primary founder and most likely has a recessive mode of inheritance although a dominant or co-dominant mode of inheritance has not been ruled out. A genome scan using 259 microsatellite markers was used to test for linkage disequilibrium between one or more markers and DSLD. Two groups of Peruvian Pasohorses were selected from one population including the US and Canada. The only difference between the two groups of horses besides the size of the two groups was the presence of DSLD in the affected group and the absence of DSLD in the unaffected group. It was assumed that differences seen between the two groups in homozygosity and or common allele frequency could be an indication of linkage to DSLD. As a connective tissue disorder, there were a large number of candidate genes forDSLD to consider, yet no identical human or animal model exists. The genome scan identified five chromosomal regions where statistically significant differences were seen between affected and unaffected sample populations that could be indications of linkage to DSLD. Those chromosomes were: ECA 6, 7, 11, 14, and 26. Sequencing of a portion of the G domain in the Chondroitin Sulfate Proteoglycan2 (CSPG2) gene has mostly ruled out that segment of chromosome 14 as having linkage to DSLD. Further research needs to be conducted in the regions of ECA 6,7,11 and 26 where statistically significant differences were seen between the affected and unaffected groups, especially on ECA 6 and 11 since possible candidate genes are located in those regions based on the human comparative map.

Melanoma is the deadliest form of skin cancer due to its high propensity to metastasize and resistance to current therapies. We have created a spontaneous mouse model of metastatic melanoma (Dct-Grm1/K5-Edn3) where metastasis to the lungs is 80% penetrant. The primary tumors of these mice present cellular heterogeneity with cells at varying levels of differentiation. The main goal of this study was to determine the metastatic potential of the primary tumor resident Tyrosinase positive cells and evaluate the dynamic phenotypic changes as those cells move from the primary tumors to the sites of metastasis. To accomplish this aim I crossed the Dct-Grm1/K5-Edn3 mice to CreERT2/mT/mG mice to indelibly label Tyrosinase cell populations within the primary tumor with Green Fluorescent Protein (GFP) by topical application of 4-hydroxytamoxifen (4HT) at the tumor site. In vivo lineage tracing and characterization of GFP+ cells were performed in the metastatic lesions. In the 4HT treated Dct-Grm1/ K5-Edn3/Tyr-CreERT2/mT/mG mice, primary tumor derived Tyrosinase positive cells or their progeny (GFP+) established successful metastases in the distant organs indicating the tumorigenic capacity of the differentiated cell populations. Numerous metastatic melanoma cells were identified in the vasculature of the metastatic organs and established close association with the vascular endothelium. The intravascular cells lost pigmentation and did not express melanocytic markers; however, they mimicked endothelial cell properties and gained the expression of CD31 (also known as platelet endothelial cell adhesion molecule PECAM-1) and vascular endothelial (VE)-Cadherin. In the lung metastatic foci, GFP+ cells resumed pigmentation production and lost the expression of endothelial cell markers. Evidence from other metastatic organs in the mice further supported the phenotypic plasticity of metastatic melanoma cells. The in vivo lineage tracing system established in the melanoma mouse model revealed tumor phenotypic plasticity and will be a powerful model to evaluate and help us understand the etiology and pathogenesis of melanoma metastasis. Further characterization of those more aggressive cells in melanoma will allow for the development of new prognostic tests and novel therapeutic strategies to eliminate metastasis.

This report describes the case of a 56-year-old man who presented with blurry vision, increased intraocular pressure, and conjunctival injection after posterior chamber intraocular lens implantation. Initially post-operative endophalmitis and foreign body inflammation were considered as differential diagnoses, but after further examination pan-uveitis was diagnosed. Uveitis is an ocular finding that may indicate several diseases, one of which is Behçet’s Disease. During the interview, the patient mentioned a history of apthous ulcers and genital ulcers which then lead to the clinical diagnosis of Behçet’s Disease. This report emphasizes that Behçet’s Disease is rare in Caucasians. Therefore, is frequently misdiagnosed in North America due to variable presentations and by not exploring the option when analyzing differential diagnoses. Early diagnosis and intervention will prevent the development of blindness and fatality due to complications of the disease.