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The Role Of Map Kinase Cascade In Msp Signaling Response, Youfeng Yang Jan 2010

The Role Of Map Kinase Cascade In Msp Signaling Response, Youfeng Yang

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The MSP domain is an evolutionarily conserved immunoglobulin-like structure of about 120 amino acids (Miller et al., 2001). A P56S missense mutation in the MSP domain of the human vapb gene is associated with a dominantly inherited form of Amyotropic Lateral Sclerosis (ALS) or Spinal Muscular Atrophy (SMA) (Nishimura et al., 2004). In C. elegans, secreted MSP binds to the VAB-1 Eph receptor and other receptors on oocyte and ovarian sheath cell surfaces (Miller et al., 2003). We have recently shown that the P56S mutation prevents secretion of the VAPB MSP domain, suggesting that the signaling function is important in …

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Cardiovascular Endothelial Regeneration On An Electrospun Scaffold, Xing Zhang Jan 2010

Cardiovascular Endothelial Regeneration On An Electrospun Scaffold, Xing Zhang

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A bi-layer electrospun nano-fibrous scaffold comprising synthetic polymers and natural proteins was constructed as the prototype of an arterial substitute for coronary ar-tery disease. This scaffold featured a highly porous microstructure analogous to native extracellular matrix. Uni-axial tensile test suggested that its excellent mechanical strength could restore normal blood flow immediately after implantation. Subsequent biocompati-bility study demonstrated that scaffolding materials, either traditional or degraded, were non-toxic to the regenerated human endothelium on the luminal layer. Moreover, this re-generated endothelium possessed critical functions, such as the formation of tight junc-tions, the secretion of prostacyclin, and the prevention of platelet adhesion. Thereafter, …

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Effect Of Overexpressing Apolipoprotein A-I In An Animal Model Of Alzheimer's Disease, Terry L. Lewis Jan 2010

Effect Of Overexpressing Apolipoprotein A-I In An Animal Model Of Alzheimer's Disease, Terry L. Lewis

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Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoprotein (HDL) in circulation and is expressed mainly by the liver and intestine. The levels of apoA-I/HDL are inversely related to the incidence of cardiovascular disease. Because of the connections between heart disease and Alzheimer's disease (AD), it is conceivable that high levels of apoA-I/HDL may be protective against AD. However, the limited literature shows mixed results on the role of apoA-I/HDL in the development of AD. It is hypothesized that increased expression of human apoA-I will ameliorate the behavioral deficits and characteristic amyloid-ß (Aß) plaque formation in a …

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Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels Jan 2010

Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels

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Current pneumococcal vaccines containing pneumococcal capsular polysaccharide antigens protect against infection by pneumococci. However, this protection is limited to strains expressing the capsule types included in the vaccine. Since the introduction of these vaccines, the increase in incidence of infection by serotypes not targeted by the vaccine, a process called "serotype replacement," and the growing antibiotic resistance of replacement strains both stress the need for vaccines with broader protection. The alpha-helical region of a protein present on all clinical isolates of pneumococci, Pneumococcal Surface Protein A (PspA), elicits protective immunity. Downstream of the alpha-helical region is a highly conserved region …

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Characterization Of Explanted Endovascular Stents: A Study Of In-Vivo Corrosion And The Role Of Vascular Calcification In Stent Fracture, Dina Halwani Jan 2010

Characterization Of Explanted Endovascular Stents: A Study Of In-Vivo Corrosion And The Role Of Vascular Calcification In Stent Fracture, Dina Halwani

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The electrochemical and mechanical stability of endovascular stents in-vivo is essential for their biocompatibility. Limited information is available regarding the condition of stents following interaction with vascular tissue, as a result, twenty seven stented vessels containing 45 stents (33 bare metal and 12 drug eluting) were retrieved during autopsy and vascular surgery. The stent/tissue components were carefully separated using a rigorous tissue dissolution protocol. Stent surfaces were characterized using 3D digital optical and scanning electron microscopy. Transferred metallic elements in dissolved tissue were measured using mass spectroscopy. Histopathologic assessment of stented tissue, when available, was also performed. Fifteen out of …

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Exploration Of The Crosslinks Between Saccadic And Vergence Eye Movement Pathways Using Motor And Visual Perturbations, Kevin Paul Schultz Jan 2010

Exploration Of The Crosslinks Between Saccadic And Vergence Eye Movement Pathways Using Motor And Visual Perturbations, Kevin Paul Schultz

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ANCOVA models to be non-orthogonal, we get similar results to the ANCOVA with

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Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom Jan 2010

Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom

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We have investigated the set of all poxvirus proteins for information about the origins of protein coding genes of the Poxviridae family of viruses. A global assessment of all poxvirus proteins for levels of similarity to proteins of other organisms, including eukaryotes, viruses, and prokaryotes, has suggested trends and relationships informative about poxvirus evolution and poxvirus interactions with hosts. Our research has focused on the poxvirus proteins subset this assessment identified as likely to have evolutionary histories involving horizontal gene transfer (HGT). We have used phylogenetic reconstructions to individually determine the sources of more than 70 horizontally transferred genes present …

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Bone Properties Surrounding Ha-Coated Custom Osseous Integrated Dental Implants, Maribel Ibañez Baker Jan 2009

Bone Properties Surrounding Ha-Coated Custom Osseous Integrated Dental Implants, Maribel Ibañez Baker

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No abstract provided.

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Examination Of The Capacity Of The Cathelicidins To Control Bacillus Anthracis Pathogenesis, Mark W. Lisanby Jan 2009

Examination Of The Capacity Of The Cathelicidins To Control Bacillus Anthracis Pathogenesis, Mark W. Lisanby

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cillus anthracis is a gram-positive, spore forming bacterium that causes infection through three routes: cutaneous, gastrointestinal and pulmonary. Historically, anthrax pathogenesis was thought to be initiated via the uptake of spores by resident macrophages, which then transited to the regional lymph nodes. While en-route, the spores germinated and developed into bacilli within the phagolysosome, escaped into the cytoplasm, killed the cell and eventually the host. Following the recent use of B. anthracis as a biological weapon, researchers began to reevaluate anthrax pathogenesis in order to develop novel treatments. One aspect of anthrax pathogenesis that saw renewed interest was the intracellular …

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Klf4 And Retinoid Receptor Signaling In Cancer, Wen Jiang Jan 2009

Klf4 And Retinoid Receptor Signaling In Cancer, Wen Jiang

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The fight against cancer has generated wide interest in understanding the genetic mechanisms behind the disease. One group of oncogenes – transcription factors – offers many opportunities for treatment or prevention. Among these transcription factors is KLF4, which functions in post-mitotic epithelial cells to promote differentiation. KLF4 has tumorigenic activity in both in vitro and in vivo models. In analyzing transcripts that were induced by KLF4, we noted the induction of multiple nuclear receptors, including retinoid receptors. Retinoids are well-established as chemopreventive agents, but the mechanisms by which they act to prevent cancer remain unclear. Previous studies have shown that …

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Pathological Modification Of Tau Induce Toxicity And Facilitate Cell Death, Tori A. Matthews Jan 2009

Pathological Modification Of Tau Induce Toxicity And Facilitate Cell Death, Tori A. Matthews

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eimer’s disease (AD) is a progressive neurodegenerative disorder characterized by two major pathophysiological hallmarks, beta-amyloid (A��) plaques and tau tangles. In AD and other tau associated neurodegenerative disorders, termed tauopathies, a critical role in promoting neuronal degeneration has been demonstrated for hyperphosphorylated forms of tau. Recent findings suggest that cleavage of tau in the carboxyl-terminal region (Asp421) may also promote deleterious effects of tau on neuronal health. In the first half of my study, the relationship between Asp421 cleaved tau and a common AD associated stressor (endoplasmic reticulum [ER] stress) was investigated using an inducible cortical neuronal model. Cells expressing …

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Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena Jan 2009

Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena

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Rapid bone loss occurs during prolonged periods of weightlessness experienced by astronauts during spaceflights which leads to osteopenia and increased fracture risk upon return to earth. Spaceflight studies have shown that the bone loss occurs as a result of both a decrease in bone formation and an increase in bone resorption, however, the molecular mechanisms still need to be elucidated. Previous studies from our laboratory and other groups have indicated that modeled microgravity leads to inhibition of osteoblastogenesis and a stimulation of adipogenesis of human mesenchymal stem cells in osteogenic medium which is most likely mediated by a decrease in …

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Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck Jan 2009

Immunotherapy Of Cancer Employing Γδ-T Cells: A Study Examining Their Utility And Feasibility, Benjamin Hester Beck

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Unlike antigen-specific alpha beta-T cells, gamma delta-T cells can recognize and lyse cancerous cells rapidly upon encounter in a manner that does not require the recognition of tumor-specific antigens. Given the well-documented capacity of gamma delta-T cells to innately kill malignant cells, efforts are now underway to exploit the antitumor properties of gamma delta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gamma delta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively-transferred gamma delta-T cells would be employed therapeutically against breast …

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Identification Of New Strategies For The Treatment Of Glioblastoma Multiforme Utilizing A Pharmacogenomic Approach: Genetic Profiles Associated With Patient Prognosis And Outcome To Capecitabine Treatment, Jessica Marie Grunda Jan 2009

Identification Of New Strategies For The Treatment Of Glioblastoma Multiforme Utilizing A Pharmacogenomic Approach: Genetic Profiles Associated With Patient Prognosis And Outcome To Capecitabine Treatment, Jessica Marie Grunda

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Glioblastoma multiforme (GBM) is the most lethal form of primary brain neoplasm with average patient survival between 9 and 15 months even with the most aggressive treatment modalities. Unfortunately, this poor outcome has not appreciably changed in the past 50 years emphasizing the lack of traditional `trial and error' methods in identifying an efficacious treatment for GBM. Pharmacogenomics is greatly impacting cancer research through the development of personalized medicine and rationally designed treatment paradigms for the development of more efficacious and less toxic treatment modalities. The main objective of this research was to utilize a pharmacogenomic approach to identify new …

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The Role Of The Ss2-Integrin Family On T Cell Subsets, Jillian E. Wohler Jan 2009

The Role Of The Ss2-Integrin Family On T Cell Subsets, Jillian E. Wohler

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Members of the ß2-integrin family of adhesion molecules, CD11a, CD11b, and CD11c, have all been shown to play a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). CD11d had yet to be studied in demyelinating disease and its functions remained unclear. We report here that CD11d is the only member of the ß2-integrin family of adhesion molecules that fails to protect against the development of EAE. Surprisingly, the EAE studies suggested that CD11a, CD11b, and CD11c were all contributing to T cell activity during disease development by mechanisms beyond the migration of these cells into the CNS. However, the …

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Monosodium L-Glutamate Exposure Adversely Affects Early Development In The Sea Urchin Lytechinus Variegatus, Dorothy B. Moseley Jan 2009

Monosodium L-Glutamate Exposure Adversely Affects Early Development In The Sea Urchin Lytechinus Variegatus, Dorothy B. Moseley

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No abstract provided.

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Mechanism Of Centaurin Alpha -1 Control Of Neuronal Differentiation, Donna Monique Hill Jan 2009

Mechanism Of Centaurin Alpha -1 Control Of Neuronal Differentiation, Donna Monique Hill

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No abstract provided.

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“Voyeurizing The Voyeurs”: An Analysis Of The Gaze Of The Nonhuman Other In Chris Marker's Film Sans Soleil, Michele Forman Jan 2009

“Voyeurizing The Voyeurs”: An Analysis Of The Gaze Of The Nonhuman Other In Chris Marker's Film Sans Soleil, Michele Forman

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No abstract provided.

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Effects Of Cyclic Strain On Tgf-Ss1 Activation And Phenotype Modulation The Aortic Valve Interstitial Cells, Michael P. Nilo Jan 2009

Effects Of Cyclic Strain On Tgf-Ss1 Activation And Phenotype Modulation The Aortic Valve Interstitial Cells, Michael P. Nilo

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No abstract provided.

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Riverfish, James Samuel Owens Jan 2009

Riverfish, James Samuel Owens

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No abstract provided.

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The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud Jan 2009

The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud

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An understanding of the molecular mechanisms involved in the generation of protective antibody responses to polysaccharides associated with pathogenic microorganisms is of importance for improving vaccine design. The heavy chain third complementarity-determining region (HCDR3) of an antibody molecule is at the center of its antigen-binding site and plays a determinative role in antigen recognition. The goal of this dissertation was to investigate the role of HCDR3 diversity and composition on the antibody response to the polysaccharide α 1→3 Dextran (DEX). In the first study, we investigated the role of TdT, a DNA polymerase that plays a major role in generating …

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The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams Jan 2009

The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams

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Insulin resistance and hyperglycemia are common findings in patients following acute illnesses or injuries, such as surgical trauma, thermal injury, infection, hemorrhage, and sepsis. Insulin has three main target tissues: liver, skeletal muscle, and adipose tissue. Insulin resistance in the liver results in an increase in gluconeogenesis. In skeletal muscle, insulin resistance causes a decrease in insulin-stimulated glucose uptake. However, little is known about the contribution that adipose tissue makes to the insulin resistant state. The goals of the research presented in this dissertation were to: 1) determine whether insulin resistance developed in adipose tissue following acute trauma and hemorrhage; …

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Analysis Of Cystic Kidney Disease-Related Genes In Caenorhabditis Elegans, Corey L. Williams Jan 2009

Analysis Of Cystic Kidney Disease-Related Genes In Caenorhabditis Elegans, Corey L. Williams

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Cilia are evolutionarily conserved, membrane-bound, microtubule-based organelles found on a diverse array of cell types in eukaryotic organisms. Inherited diseases of cilia protein dysfunction include Nephronophthisis (NPHP), Joubert Syndrome (JBTS), Meckel-Gruber Syndrome (MKS), and Bardet-Biedl Syndrome (BBS). Important insight in the basic cell biological functions of BBS and NPHP proteins has been gained from analysis in the nematode Caenorhabditis elegans. My goal in this dissertation was to model MKS protein function in cilia biology utilizing the powerful genetic malleability of C. elegans. mks-1 and mks-3, the C. elegans homologs of two MKS-associated proteins in humans, were selected for this analysis. …

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Oxidation Of Mercury During Selective Catalytic Reduction Of Nitric Oxide, Giang Tong Jan 2009

Oxidation Of Mercury During Selective Catalytic Reduction Of Nitric Oxide, Giang Tong

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A promising method for mercury removal from the gaseous products of coal combustion is the catalytic oxidation of elemental mercury to water-soluble mercuric chloride during selective catalytic reduction of NOx by ammonia, followed by removal of the oxidized mercury during wet flue gas desulfurization. Measurements of the mercury species distribution and sulfate formation at the outlet of a 310 mm long square cell monolithic V2O5-WO3/TiO2 commercial SCR catalyst showed the following trends: (1) Mercury oxidation was highly sensitive to HCl at the low levels characteristic of Powder River Basin subbituminous coals (0-5 ppmv). (2) Mercury oxidation was inhibited by NH3, …

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Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang Jan 2009

Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang

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Adenovirus (Ad) is the most commonly used viral vector in gene therapy applications to date for a broad range of diseases. Although Ad-based viral vectors have many advantages in a variety of gene therapy designs, the commonly used adenoviral vectors have several key shortcomings. Those shortcomings include (1) inefficient transduction in cell types devoid of Ad’s native receptors and the incapability of gene delivery to targets behind physical barriers; (2) restricted accessibility to the central nerve system due to the existence of the blood-brain barrier (BBB); (3) lack of a useful strategy and platform to generate multi-functionality displaying Ad vectors …

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Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith Jan 2009

Axonal Trafficking Of Bmp Signals In Drosophilia Motoneurons, Rebecca Burt Smith

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The Drosophila Bone Morphogenetic Protein (BMP) Glass bottom boat (Gbb) is a ligand for the BMP type II receptor, Wishful thinking (Wit). Mutations in either of these proteins impair synaptic growth at the neuromuscular junction (NMJ). Gbb is a retrograde signal (from target to innervating neuron) that is essential for proper NMJ development and function. Tissue-specific rescue of pathway mutants and immunolocalization experiments indicate that the receptor-ligand interaction occurs at the NMJ, and results in the nuclear accumulation of the phosphorylated form of the transcription factor Mad, indicating that retrograde transport along the axon is critical for pathway activation. We …

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The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai Jan 2009

The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai

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Several reports have suggested that Mycoplasma pneumoniae (Mp) can contribute importantly to the expression of symptoms in asthmatic human subjects. As a foundation for understanding the interactions between Mp and asthma susceptibility, we first studied the mechanisms by which the host normally eliminated Mp. Mice were inoculated with 4x106 Mp intranasally. Twenty-four hours after inoculation with Mp, subpopulations of CD11b+ macrophages/monocytes had been recruited into the lungs. The clearance of Mp was impaired both in macrophage-depleted and in macrophage-deficient mice. Furthermore, mice deficient in MyD88, a major adaptor for TLR signaling, showed dramatically defective clearance of Mp, associated with reduced …

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Mouse Model Of Cooley's Anemia, Yongliang Huo Jan 2009

Mouse Model Of Cooley's Anemia, Yongliang Huo

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β thalassemia major or Cooley’s anemia (CA) is a heterogeneous group of inherited disorders characterized by deficient β globin chain production. Newborns with CA are healthy because of the high fetal hemoglobin (HbF) levels present in their red blood cells (RBCs). As HbF levels decline during the first year of life, patients develop severe anemia that necessitates regular blood transfusion to maintain life. CA has been difficult to model in the mouse due to the lack of a fetal hemoglobin equivalent in the mouse. By utilizing a human fetal to adult delayed hemoglobin switching cassette, I hypothesize that a CA …

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Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang Jan 2009

Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang

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Embryonic stem (ES) cells are pluripotent and, therefore, can differentiate into most if not all somatic cell types. Because of this characteristic, ES cells have great potential for medical therapies. Since the first cloned mammal, Dolly the sheep, was published in 1996 (1), several groups have successfully cloned other animals by the same nuclear transfer method (2). Isogenic ES cell lines can also be established from donor cells by the same technique (3). However, to date there has been no report of successful derivation of human ES cells by nuclear transfer. Based on the cell fusion (4) and nuclear transfer …

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The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng Jan 2009

The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng

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Zinc is an essential cation for life that is involved in numerous physiology and pathophysiology processes. Despite its wide use as a cytoprotective agent in medications, its cellular and molecular mechanisms of action have not been well established. In order to define the potential therapeutic benefit of zinc, I used several Cystic Fibrosis (CF) and non-CF human airway epithelial cell lines as models in my studies. Extracellular zinc caused release calcium from the endoplasmic reticulum though zinc-sensitive Gq-coupled receptor(s) that may subsequently modulate ion channels. In addition, zinc also exhibited anti-inflammatory effects. Zinc inhibited pro-inflammatory molecular TNFα-induced cytokine and chemokine …

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