No description available.

Dynamic properties of Josephson junctions are interesting due to the emission of high frequency radiation (up to THz range) from Josephson junctions, closely related to fluxon dynamics. A better understanding of this dynamics can help to improve the Josephson devices used for applications. Josephson junctions can also be of great use as T-shaped multiple Josephson junctions in Josephson electronic circuits. In general, T-junctions consist of two attached Josephson transmission lines: a main Josephson transmission line (MJTL) along the -axis, and an additional Josephson transmission line (AJTL) along the -axis. These junctions can use to create fluxons (solitons) in junctions without applied magnetic field, (called flux cloning phenomenon). This work is devoted to contributing to a clarification of the dynamic behaviour of solitons (fluxons) in 2D extended conventional T-shaped Josephson junctions (extended means an AJTL is larger than MJTL). A conventional T-junction is a MJTL along the x-axis which divides into two Josephson transmission lines along the x- and y-axes. In addition, we also attempt to elucidate further the concept of flux cloning in rotated T-junctions, which are 90 degrees anticlockwise rotation of conventional T-junction. In rotated Tjunction, a MJTL along the x-axis divide into two Josephson transmission lines along the y-axis. We find the first evidence of moving semifluxon and observe for the first time new phenomena of semifluxons and anti-semifluxons in both extended conventional and rotated T-junctions. We numerically study the electrodynamics behaviour of solitons in the standard Tshaped Josephson junction (conventional T-junction) in a magnetic field. Therefore, we describe theoretically how flux cloning circuits exist and give an opportunity for use as flux flow oscillators operating without applied magnetic field. The results that emerge give further support to the flux cloning mechanism.

Lymphatic valves (LVs) are cusped luminal structures that permit the movement of lymph in only one direction and are therefore critical for proper lymphatic vessel function. Congenital valve aplasia or agenesis can, in some cases, be a direct cause of lymphatic disease. Knowledge about the molecular mechanisms operating during the development and maintenance of LVs may thus aid in the establishment of novel therapeutic approaches to treat lymphatic disorders. In this study, we examined the role of Connexin43 (Cx43), a gap junction protein expressed in lymphatic endothelial cells (LECs), during valve development. Mouse embryos with a null mutation in Cx43 (Gja1) were previously shown to completely lack mesenteric LVs at embryonic day 18. However, interpreting the phenotype of Cx43(-/-) mice was complicated by the fact that global deletion of Cx43 causes perinatal death due to heart defects during embryogenesis. We have now generated a mouse model (Cx43(∆LEC)) with a lymphatic-specific ablation of Cx43 and show that the absence of Cx43 in LECs causes a delay (rather than a complete block) in LV initiation, an increase in immature valves with incomplete leaflet elongation, a reduction in the total number of valves, and altered lymphatic capillary patterning. The physiological consequences of these lymphatic changes were leaky valves, insufficient lymph transport and reflux, and a high incidence of lethal chylothorax. These results demonstrate that the expression of Cx43 is specifically required in LECs for normal development of LVs.

In the present work we study transmission of electron through vibrat- ing molecular junction interacting with leads using a method of nonequilibrium Green functions. Our Green functions use combination of first quantization to treat vibrational levels and second quantization to treat electron processes. We treat the change of vibrational potential of junction induced by charging of junc- tion, we find a spectral function and a magnitude of current through the junction. We confirm the effect of Fermi sea and Frack-Condon factors on sharpening of peaks. We study these processes on model motivated by biphenyl molecule, in- troducing double well potential and study an effect of quasidegenerate energy levels. We present the shift of peaks, resulting from an increase of moment of inertia, to positions determined by Franck-Condon factors.

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Thu Annelise Nguyen / Preclinical animal models of mammary carcinoma formation are vital for the advancement of cancer research, specifically in drug development. Two different types of animal models were utilized to determine the efficacy of combinational treatment of common antineoplastic drugs and the new class of primaquines that act as gap junction enhancers (PQs) at attenuating mammary tumor growth. The classic xenograft mouse model was used to show that PQs could increase the efficacy of cisplatin and paclitaxel. Combinational treatment induced an upregulation of connexin and caspase expression in the isolated tumor. Next the transgenic PyVT mouse model was characterized by multiple factors, including hormone receptor status, molecular markers for survival and proliferation, tissue histopathology, and secondary metastases during multiple stages of tumor development. This model showed limited therapeutic response to the antineoplastic drugs tested. PQ1 effectively attenuated tumor growth at all stages of tumorigenesis in the PyVT model, while PQ7 was determined to be an effective chemopreventive compound rather than chemotherapeutic. The PQs altered the expression profiles of connexins during tumorigenesis. Together the results indicate that PQs have an anticancer effect that is more efficient at attenuating tumor growth than the common antineoplastic compounds. Lastly the PyVT mouse model was used to determine the efficacy of antineoplastic compounds on male mammary carcinoma development. Interestingly, the antineoplastic compound that attenuated female mammary carcinoma growth did not produce a therapeutic response in the males and vice versa, suggesting a need for further studies into the male response to therapy.

Previous work has shown D1/D2 requisite synergism can still occur in the striatum in the absence of action potentials. Some nonclassical communication such as gap junctions may be allowing the segregated dopamine (DA) receptors to interact to produce stereotyped motor activity. Connexin-32 (Cx32) and connexin-36 (Cx36) were targeted for study due to their abundance in neural tissues and presence in the striatum. Mice lacking either the Cx32 or Cx36 gene and their respective wildtype littermates were compared on a climbing behavior task used to gauge their dopaminergic activity after receiving either saline, D1 agonist, D2 agonist, or both D1 and D2 agonists. The results showed that D1/D2 requisite synergism was still intact in both strains of mice. The Cx32 WT mice displayed significantly greater scores than the KO mice in the D1/D2 treatment. The Cx36 mice did not display a significant genotype difference, but a trend was observed with the KO females having larger scores relative to WT females or to males of either genotype.

No description available.

Skin wound healing presents a challenging and expensive clinical problem with nearly 20 million wounds requiring intervention leading to an annual cost of more than $8 million. Tissue engineered skin substitutes are valuable not only as a clinical therapy for chronic wounds and severe traumas, but also as in vitro 3D model systems to investigate wound healing and skin pathogenesis. However, these substitutes are limited by a lack of topography at the dermal-epidermal junction (DEJ). In contrast, the native DEJ is characterized by a series of dermal papillae which project upward into the epidermal layer and create physical topographic microniches that support keratinocyte stem cell clustering. In this thesis, we created novel 3D skin model systems to investigate the role of microtopography in regulating keratinocyte function and cell fate using scaffolds containing precisely engineered topographic features. We hypothesized that the microtopography of the DEJ creates distinct keratinocyte microniches that promote epidermal morphogenesis and modulate keratinocyte stem cell clustering which can be harnessed to create a more robust skin substitute that expedites wound closure. Using photolithographic techniques, we created micropatterned DEJ analogs and micropatterned dermal-epidermal regeneration matrices (µDERM) which couple a dermal support matrix to a micropatterned DEJ analog. We found that the incorporation of microtopography into our in vitro skin model resulted in a thicker, more robust epidermal layer. Additionally, we identified three distinct functional keratinocyte niches: the proliferative niche in narrow channels, the synthetic niche in wide channels and the keratinocyte stem cell niche in narrow channels and corner topographies. Ultimately, incorporation of both narrow and wide channels on a single construct allowed us to recreate native keratinocyte stem cell patterning in vitro. These model systems will allow us to investigate the role of cellular microniches in regulating cellular function and epidermal disease pathogenesis as well as to identify topographic cues that enhance the rate of wound healing.

Hu Xiaoling. / "May 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Gemin5 是運動神經元綜合體(SMN Complex)的其中一個組件，這綜合體的主要功能是控制小型胞核核糖核蛋白(UsnRNPs)的合成。這些小型胞核核糖核蛋白組合成剪接核糖核酸前體(pre-mRNA)的剪接體(Spliceosome)，使核糖核酸分子可以用來翻譯成蛋白質。失去運動神經元綜合體功能引致脊髓肌肉萎縮症。果蠅是其中一個用作研究人類疾病重要的生物。更重要的是，部分組成運動神經元綜合體的組件也存在於果蠅。是次研究是利用遺傳方式在果蠅內研究Gemin5 的同源基因-- rigor mortis (rig) 的作用。果蠅帶有rig 突變基因表現神經肌肉接頭(neuromuscular junction)上的缺陷和異常的運動行為。這表明，rig 的功能可能與神經退化性疾病有關。為了進一步了解rig 的功能途徑(functional pathway)，已進行了一個利用移除突變體的基因過濾實驗，研究鎖定了 12 個染色體部份可能和rig 有基因上的相互作用，進一步研究與rig 有相互作用的基因有助於了解rig 的功能及研究脊髓肌肉萎縮症的發病機制。 / Gemin5 is a component of the Survival of Motor Neuron (SMN) complex, which is a protein complex regulating biogenesis of various Uridine-enriched small nuclear ribonucleoproteins (UsnRNPs). These UsnRNPs form the molecular machinery spliceosome, which mediates pre-messenger RNA splicing, an important mechanism before an mRNA molecule can be used to translate proteins. Loss-of-function of the SMN complex is now known to cause the neurodegenerative disease, Spinal Muscular Atrophy. Drosophila is one of the well-characterized model organisms for studying human diseases. More importantly, components of the SMN complex are also found in Drosophila. Here, I studied the function of rigor mortis (rig), the Gemin5 orthologue, in Drosophila using a genetic approach. Drosophila carrying mutations in the rig gene show defects in the neuromuscular junction (NMJ) and display abnormal motor behavior. This suggests that the function of rig may link to the neurodegenerative disease. To further characterize the function of rig, a genetic screen was carried out. Twelve chromosomal regions encoding possible rig-interacting genes were identified. Further characterization of these rig-interacting genes may help us better understand the function of rig. / Detailed summary in vernacular field only. / Cheng, Yat Pang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 120-125). / Abstracts also in Chinese. / ABSTRACT --- p.i / ABSTRACT IN CHINESE --- p.ii / ACKNOWLEDGEMENT --- p.iii / LIST OF ABBREVIATIONS --- p.iv / LIST OF FIGURES --- p.v / LIST OF TABLES --- p.vi / TABLE OF CONTENTS --- p.vii / Chapter CHAPTER 1. --- INTRODUCTION / Chapter 1.1 --- Introduction of rigor mortis / Chapter 1.1.1 --- Orthologue of Gemin5 in Drosophila --- p.1 / Chapter 1.1.2 --- Published Phenotypic Analyses of rig Mutants --- p.1 / Chapter 1.2 --- Introduction of Gemin5 / Chapter 1.2.1 --- Introduction of Gemins --- p.4 / Chapter 1.2.2 --- Structural Properties of Gemin5 --- p.4 / Chapter 1.2.3 --- Gemin5-interacting partners --- p.7 / Chapter 1.2.4 --- Gemin5 as a Component of the Survival of Motor Neuron (SMN) Complex --- p.7 / Chapter 1.2.5 --- Function of the SMN Complex and Spinal Muscular Atrophy --- p.11 / Chapter 1.3 --- Drosophila as a Model Organism / Chapter 1.3.1 --- Advantages of Using Drosophila as a Model Organism --- p.11 / Chapter 1.3.2 --- Neuromuscular Junction of Drosophila --- p.15 / Chapter 1.4 --- Aim of the Present Study --- p.19 / Chapter CHAPTER 2. --- MATERIALS AND METHODS / Chapter 2.1 --- Drosophila Culture / Chapter 2.1.1 --- Culture Medium --- p.20 / Chapter 2.1.2 --- Drosophila Stocks and Crosses Maintenance --- p.20 / Chapter 2.1.3 --- Larvae Collection --- p.21 / Chapter 2.1.3.1 --- Reagents --- p.21 / Chapter 2.1.3.2 --- Procedures --- p.21 / Chapter 2.2 --- Cell culture / Chapter 2.2.1 --- Reagents --- p.23 / Chapter 2.2.2 --- Drosophila S2R⁺ Cell Culture --- p.24 / Chapter 2.2.3 --- Establishment of Stable S2R⁺ Cells --- p.24 / Chapter 2.3 --- Genomic Polymerase Chain Reaction (PCR) / Chapter 2.3.1 --- Reagents --- p.25 / Chapter 2.3.2 --- Genomic DNA Extraction from a Single Larva --- p.26 / Chapter 2.3.3 --- Primer Design --- p.26 / Chapter 2.3.4 --- Polymerase Chain Reaction (PCR) --- p.27 / Chapter 2.4 --- Behavioral Assay / Chapter 2.4.1 --- Stable S2R⁺ Cell Staining --- p.29 / Chapter 2.4.1.1 --- Reagents --- p.29 / Chapter 2.4.1.2 --- Procedures --- p.30 / Chapter 2.4.2 --- Larvae Staining --- p.31 / Chapter 2.4.2.1 --- Reagents --- p.31 / Chapter 2.4.2.2 --- Larvae Dissection --- p.32 / Chapter 2.4.2.3 --- Larval Muscle Staining --- p.33 / Chapter 2.4.2.4 --- Larval Neuromuscular Junction Staining --- p.33 / Chapter 2.5 --- Microscopy / Chapter 2.5.1 --- Light Microscopy --- p.34 / Chapter 2.5.1.1 --- Microscopic Observation of Larval Movement --- p.34 / Chapter 2.5.1.2 --- Quantification of Larval Contraction Rate --- p.34 / Chapter 2.5.1.3 --- Quantification of Larval Travelling Distance --- p.34 / Chapter 2.5.2 --- Fluorescence Microscopy --- p.35 / Chapter 2.5.2.1 --- Microscopic Observation of Larval Muscle --- p.35 / Chapter 2.5.2.2 --- Microscopic Observation of Stable S2R⁺ Cells --- p.35 / Chapter 2.5.3 --- Confocal Microscopy --- p.36 / Chapter 2.5.3.1 --- Microscopic Observation of Larval Neuromuscular Junction --- p.36 / Chapter 2.5.3.2 --- Quantification of Larval Neuromuscular Junction --- p.36 / Chapter 2.6 --- Generation of transgenic fly lines expressing rig transgene / Chapter 2.6.1 --- Polymerase Chain Reaction --- p.36 / Chapter 2.6.2 --- Agarose Gel Electrophoresis --- p.38 / Chapter 2.6.2.1 --- Reagents --- p.38 / Chapter 2.6.2.2 --- Procedures --- p.39 / Chapter 2.6.3 --- Restriction Digestion --- p.39 / Chapter 2.6.4 --- Ligation Reaction --- p.39 / Chapter 2.6.5 --- Bacterial Transformation --- p.40 / Chapter 2.6.5.1 --- Reagents --- p.40 / Chapter 2.6.5.2 --- Procedures --- p.40 / Chapter 2.6.6 --- Bacterial Glycerol Stock for Long-term Storage --- p.41 / Chapter 2.7 --- Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and Immunoblotting / Chapter 2.7.1 --- Reagents --- p.41 / Chapter 2.7.2 --- Lysate Preparation of Stable S2R⁺ Cells, Adult Fly Heads and Larvae --- p.44 / Chapter 2.7.2.1 --- Stable S2R+ Cells --- p.44 / Chapter 2.7.2.2 --- Adult Fly Heads --- p.44 / Chapter 2.7.2.3 --- Larvae --- p.45 / Chapter 2.7.3 --- SDS-Polyacrylamide Gel Electrophoresis --- p.45 / Chapter 2.7.4 --- Immunoblotting --- p.45 / Chapter CHAPTER 3. --- PHENOTYPIC CHARACTERIZATION OF RIG MUTANT / Chapter 3.1 --- Introduction --- p.48 / Chapter 3.2 --- Re-balancing of rig Mutant Fly Lines Over the Cy; Tb Compound Balancer for Genotype Identification --- p.48 / Chapter 3.3 --- Verification of Model Genotype --- p.49 / Chapter 3.4 --- rig Mutant Larvae Displayed Abnormal Motor Behavior / Chapter 3.4.1 --- Contraction Rate of rig Mutant Larvae --- p.54 / Chapter 3.4.2 --- Traveling Distance of rig Mutant Larvae --- p.56 / Chapter 3.5 --- rig Mutant Larvae Showed Normal Body Wall Musculature --- p.58 / Chapter 3.6 --- rig Mutant Larvae Displayed Defects in the Neuromuscular Junction / Chapter 3.6.1 --- rig Mutant Larvae Showed Branching Defects --- p.60 / Chapter 3.6.2 --- rig Mutant Larvae Showed Fewer Boutons Number --- p.62 / Chapter 3.7 --- rig Mutant Larvae Showed Normal Active Zone Pattern --- p.64 / Chapter 3.8 --- Discussion --- p.66 / Chapter CHAPTER 4. --- A GENETIC SCREEN TO IDENTIFY GENES THAT INTERACT GENETICALLY WITH RIG / Chapter 4.1 --- Introduction --- p.71 / Chapter 4.2 --- Candidates and Design of the Screen --- p.72 / Chapter 4.3 --- Re-balancing of Deletion Lines Over the Cy; Tb Compound Balancer --- p.75 / Chapter 4.4 --- Identification of Chromosomal Regions That Genetically Interact With rig --- p.75 / Chapter 4.5 --- Identification of NMJ Genes That Genetically Interact With rig --- p.80 / Chapter 4.6 --- Discussion --- p.83 / Chapter CHAPTER 5. --- ATTEMPTS TO INVESTIGATE RIG FUNCTION IN PRE-AND POST-SYNAPTIC REGIONS OF THE NMJ / Chapter 5.1 --- Introduction --- p.89 / Chapter 5.2 --- Transgenic Rescue Experiment by Transgenic Expression of rig in rig Mutant / Chapter 5.2.1 --- Design of the Rescue Experiment --- p.90 / Chapter 5.2.2 --- Construct of pUAST-rig-FLAG --- p.93 / Chapter 5.2.3 --- Construct of the pUAST-myc-rig --- p.98 / Chapter 5.3 --- Tissue Specific Knockdown of rig expression --- p.102 / Chapter 5.4 --- Discussion --- p.105 / Chapter CHAPTER 6. --- ESTABLISHMENT OF AN INDUCIBLE S2R⁺ CELL MODEL FOR RIG OVEREXPRESSION / Chapter 6.1 --- Introduction --- p.108 / Chapter 6.2 --- Detection of Rig Protein in S2R⁺ Cells by Immunoblotting --- p.111 / Chapter 6.3 --- Detection of Rig Protein in S2R⁺ Cells by Immunostaining --- p.111 / Chapter 6.4 --- Detection of RNA in Immunopurified Rig Protein --- p.113 / Chapter 6.5 --- Discussion --- p.115 / Chapter CHAPTER 7. --- GENERAL DISCUSSION --- p.117 / References --- p.120 / Appendices --- p.126