A model for the Josephson junction is constructed based on two macroscopic angular momentum vectors. These vectors, which interact via a Heisenberg-like Hamiltonian, are defined using Anderson's pseudospin concept in superconductivity. Along with this, a new state vector, which affords a more complete description of the constant-charge-imbalance mode of the junction, is explicitly constructed. The resulting equations of motion lead directly to the basic Josephson results and at the same time provide a simple physical picture for the dynamical behavior of the junction. Both the Anderson (n,(phi)) and Feynman two-state models of the junction are shown to be equivalent to a restricted form of the angular momentum approach. The process of formulating the junction problem in terms of pseudo-angular-momentum together with the above identification constitutes a microscopic derivation of the Feynman method. A perturbation theory calculation is carried out within the full pseudo-angular-momentum equations of motion to determine how this approach differs from the earlier ones.

No description available.

No description available.

Forming and maintaining an intact epidermal permeability barrier (EPB) is necessary to mammalian health and dysregulation of this process can result in serious complications. Tight junctions (TJs) and their integral proteins the Claudins (Cldns) have both structural and signaling importance to the skin barrier and the latter is most likely mediated via Cldn tail interaction with cytoplasmic proteins. Given that the family member Cldn6 is known to be important to EPB function, we set out to determine the contribution of its cytoplasmic tail domain to TJ-mediated homoeostasis. Using transgenic mouse models, we overexpressed epidermal-targeted tail truncation mutants and assessed EPB formation and maintenance. We then used yeast 2-hybrid and quantitative proteomic approaches to identify proteins that interact with this tail region and to assess the downstream effects of overexpressing these proteins in human keratinocytes in culture. We demonstrate that a 10 amino acid region in the cytoplasmic tail is required for efficient epidermal maturation and injury repair and that our mouse models may be applicable to postnatal epidermal maturation and human skin aging studies. We show that in addition to the known interacting partner ZO1, the C-terminal tail of Cldn6 also binds FIZ1 (Flt3 interacting zinc finger protein-1), which we characterize for the first time as a mitogenic factor for keratinocytes. FIZ1 stimulates autocrine pathways involving secreted heparin-binding factors IGFBP3 and DKK1, sensitization to IGF signaling, MAP/ERK activation and increased G1 progression. Specific transcription factors, protein kinases and signaling scaffolds that we identified as novel FIZ1-binding partners likely mediate this signaling. Our studies on the Cldn6 cytoplasmic tail support the importance of this region for epidermal maturation and for maintenance of skin homeostasis throughout life. They also delineate the potential for tail interactors such as ZO1 and FIZ1 to act in concert with Cldns in TJ-based signaling networks to regulate the balance between proliferation and differentiation in keratinocytes. These findings provide new insight into the role of the Cldn6 cytoplasmic tail and will ultimately aid in the development of new diagnostic tools and therapeutic approaches for the treatment of skin conditions rooted in barrier defects.

Transepithelial barriers represent important mechanisms by which epithelial cells delimit tissue compartments and maintain distinct extracellular environments. Such cellular barriers are key in regulating organ and tissue homeostasis and their dysregulation leads to a wide variety of pathologies. Novel tight junctions termed tricellular junctions (TCJs) appear to provide this barrier activity at the molecular level. Despite their proposed key role in barrier function, our understanding of these junctions is limited, with only a few molecules localized to tricellular junctions having been reported. Here we add to this understanding by identifying a LIG family member, Kek6, in Drosophila that represents the first example of a molecule uniquely excluded from TCJs. LIGs represent transmembrane molecules with Leucine-rich repeats and Immunoglobulin domains whose expression is often enriched in the developing nervous system. Data on Kek6 confirms this nervous system expression. Investigation into the mechanism which controls Kek6€™s unique exclusion from TCJs has proved that it is not solely mediated by the C-terminal intracellular PDZ domain-binding site. Although PDZ domain-binding sites of various proteins have been implicated as important for protein localization, it is thought that it is the extracellular domain of Kek6 that is the part of the protein which is responsible for its unique localization pattern. Shown here, it is believed that Kek6 participates in a stabilizing homophilic interaction which may support the hypothesis that the extracellular domain is required for localization. Kek6 expression in one cell is not sufficient for expression in the bicellular junctions. Adjacent cells must both express Kek6 in order for Kek6 to be stably localized to the bicellular junction. Studies on the potential relationship between Kek6 and Gliotactin, the Drosophila protein which localizes to TCJs, revealed that there is no direct relationship between these two proteins but does not eliminate the potential of unidentified shared interactors. Further investigation of Kek6 will allow for the elucidation of the role of Kek6 in TCJs which will help further develop the junction biology field. In addition to the information provided on Kek6, this study reports the first localization and functional knowledge of Kek3. Misexpression of Kek3 leads to cross vein defects and reduction/loss of bristles revealing that Kek3 may be a modulator of BMP signaling. Although family member Kek5 has been previously identified as a modulator of BMP signaling, the mechanism of this function is still under investigation but it is believed that Kek3 is acting through a different mechanism.

No description available.

This thesis addresses the problem of road intersection safety with regard to a mixed population of automated vehicles and non-automated road users. The work derives and evaluates safety-critical scenarios at road junctions, which can pose a particular safety problem involving automated cars. A simulation and evaluation framework for car-to-car accidents is presented and demonstrated, which allows examining the safety performance of automated driving systems within those scenarios. Given the recent advancements in automated driving functions, one of the main challenges is safe and efficient operation in complex traffic situations such as road junctions. There is a need for comprehensive testing, either in virtual testing environments or on real-world test tracks. Since it is unrealistic to cover all possible combinations of traffic situations and environment conditions, the challenge is to find the key driving situations to be evaluated at junctions. Against this background, a novel method to derive critical pre-crash scenarios from historical car accident data is presented. It employs k-medoids to cluster historical junction crash data into distinct partitions and then applies the association rules algorithm to each cluster to specify the driving scenarios in more detail. The dataset used consists of 1,056 junction crashes in the UK, which were exported from the in-depth On-the-Spot database. The study resulted in thirteen crash clusters for T-junctions, and six crash clusters for crossroads. Association rules revealed common crash characteristics, which were the basis for the scenario descriptions. As a follow-up to the scenario generation, the thesis further presents a novel, modular framework to transfer the derived collision scenarios to a sub-microscopic traffic simulation environment. The software CarMaker is used with MATLAB/Simulink to simulate realistic models of vehicles, sensors and road environments and is combined with an advanced Monte Carlo method to obtain a representative set of parameter combinations. The analysis of different safety performance indicators computed from the simulation outputs reveals collision and near-miss probabilities for selected scenarios. The usefulness and applicability of the simulation and evaluation framework is demonstrated for a selected junction scenario, where the safety performance of different in-vehicle collision avoidance systems is studied. The results show that the number of collisions and conflicts were reduced to a tenth when adding a crossing and turning assistant to a basic forward collision avoidance system. Due to its modular architecture, the presented framework can be adapted to the individual needs of future users and may be enhanced with customised simulation models. Ultimately, the thesis leads to more efficient workflows when virtually testing automated driving at intersections, as a complement to field operational tests on public roads.

Electro-transmittance of molecular junctions was characterized electrically and studied optically at 410nm and 532nm. Between 1kHz and 100kHz there was no qualitative difference between the control samples and the molecular junction samples, however there were difficulties with reproducibility of the quantitative behaviour, so no hard conclusions could be drawn. A microfluidic capacitor device was designed and fabricated to study the electrical double layer, using standard microfabrication techniques. A complimentary flux corrected transport simulation was written using the same experimental geometry and the results of this study found qualitative agreement between the simulation and experiment. The experiment produced results about the concentration dependence of the double layer formation time which allows an estimate of the required frequency of an AC electrical signal for which the electrical double layer doesnt have time to form, and its effects can be ignored.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 100-102).

During spermatogenesis, developing germ cells must migrate across the blood-testis barrier (BTB) and enter the adluminal compartment for further development. Throughout this process, extensive junction restructuring occurs at Sertoli-Sertoli and Sertoli-germ cell interfaces. Cytokines are known to play crucial roles in regulating testicular cell junction dynamics at different regulatory levels. However, the mechanism of cytokine-mediated regulation on newly identified junction molecules remains unclear. In this dissertation, the molecular mechanisms on how cytokines regulate the junction proteins of immunoglobulin superfamily (IgSF) including coxsackievirus and adenovirus receptor (CAR), nectin-like molecule-2 (Necl-2) and Necl-4 in testicular cells were studied. CAR is expressed on Sertoli and germ cells. It mediates both homophilic and heterophilic interaction for Sertoli-germ cell adhesion. It was found that combined treatment of interferon-γ (IFN-γ) and tumor necrosis factor α (TNFα) reduced CAR mRNA and protein levels, and caused the disappearance of CAR from germ cell interface. IFN-γ+TNFα promoted CAR protein degradation via ubiquitin-proteasome pathway. In addition, IFN-γ+TNFα reduced CAR mRNA through regulating the binding of NF-κB subunits and SP/KLF proteins to CAR promoter. Collectively, these results demonstrated for the first time the potential mechanism utilized by IFN-γ+TNFα to exert their effects during testicular inflammation. Necl-2 is exclusively expressed by spermatogenic cells in the testis. In this study, it was demonstrated that transforming growth factor-β1 (TGF-β1) down-regulated Necl-2 mRNA and protein levels, and caused the disappearance of Necl-2 from cell surface. Using inhibitors and shRNAs, it was found that TGF-β1 induced Necl-2 protein degradation through clathrin-dependent endocytosis. Endocytosis assay further confirmed that TGF-β1 accelerated the internalization of Necl-2 to cytosol. Moreover, TGF-β1 repressed Necl-2 gene transcription in Smad-dependent manner. Taken together, these results unraveled the mechanism of how TGF-β1 regulates Necl-2 expression to achieve timely junction restructuring during spermatogenesis. Necl-4 has been detected in Sertoli cells, but little is known about its regulation in the testis. It was found that TNFα down-regulated Necl-4 mRNA and protein levels. Inhibitor studies suggested that both caveolin-dependent endocytosis and ubiquitin-proteasome pathway were involved in TNFα-induced Necl-4 protein degradation. Co-immunoprecipitation indicated that Necl-4 was physically associated with Par3, Par6, aPKC and Cdc42 which are the major components of polarity complex in mouse testis. Further study was shown that TNFα reduced the expression of Par3, and altered the binding between Necl-4 and Par complex in Sertoli cells. These results suggested that Necl-4-mediated cell adhesion could be disrupted by TNFα via reducing its expression and altering its interaction with Par complex. Studies reported herein suggest that junction proteins of the IgSF are precisely regulated by cytokines at transcriptional and post-translational levels. These results further enrich current understanding on how junction dynamics are regulated during spermatogenesis. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy