Dartmouth Digital Library Program

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MicroRNA-10b promotes pancreatic cancer cell invasion by suppressing TIP30 and enhancing EGF and TGF-[beta] actions / by Haoxu Ouyang
MicroRNA-10b (miR-10b) is considered a marker of disease aggressiveness in pancreatic ductal adenocarcinoma (PDAC), in view of the fact that lower levels of miR-10b are associated with better response to neoadjuvant therapy, likelihood of surgical...
Dartmouth Dissertations

Estradiol regulation of innate immune protection in the human female reproductive tract / by Mickey Vinay Patel.
Estradiol is a key regulator of immune protection in the female reproductive tract (FRT). Its concentration varies during the menstrual cycle, leading to changes in innate immune protection. In this thesis, I demonstrate the multiple levels at...
Dartmouth Dissertations

Endogenous leukocyte activation by chimeric antigen receptor T cell immunotherapy / by Paul Spear.
Many protocols for adoptive T cell therapy (ACT) include preparative conditioning strategies to deplete host lymphocytes prior to T cell infusion. Total body irradiation and high-dose chemotherapy regimens not only relieve immunosuppression, but...
Dartmouth Dissertations

Role of the Menin-MLL1 interaction in normal hematopoiesis and leukemia / by Bin Li.
Leukemia represents a small percentage of human cancer, accounting for about 5% of all cases of cancer in adults, but, interestingly, for about 50% of all cases of cancer in children. The behavior of leukemia is often regulated by the chromosomal...
Dartmouth Dissertations

Computational methods for the discovery and application of protein sequence-structure-function relationships / by Lu He.
Proteins are ubiquitous in cells and are essential to a wide range of biological processes. Since existing proteins occupy only a small portion of the space of possible amino acid composition, understanding their sequence-structure-function...
Dartmouth Dissertations

The role of cell stress signalling in the induction of [gamma]-globin gene expression / by Emily K. Schaeffer.
Increased fetal hemoglobin (HbF) expression is beneficial for [beta]-hemoglobinopathy patients; however, most inducing agents do not possess the ideal combination of efficacy, safety and availability. Better understanding the mechanisms involved in...
Dartmouth Dissertations

Novel techniques for the investigation of GPCR structure and function / by Joshua A. Weiner.
G protein coupled receptors (GPCRs) make up somewhere between 30-50% of all current drug targets, yet the structural characterization of these receptors has been moderate at best. Until recently, structural data were almost nonexistent and...
Dartmouth Dissertations

Involvement GP39 and CD40 interactions in the generation of immune responses to allogeneic antigens.
T cells. Antigen presenting cells. CD antigens. Ligands (Biochemistry). Cell interaction. Immune response -- Regulation.
Dartmouth Dissertations

Functional studies of human IgG Fc receptors.
Immunoglobulin G. Immunoglobulins.
Dartmouth Dissertations

Dendritic cell Fcγ receptor expression and function
Fc receptors. Dendritic cells. Immune recognition.
Three types of Fc receptors for IgG, FcyRI (CD64), FcyRII (CD32), and FcyRIII (CD 16) are expressed differentially on blood leukocytes. In particular, CD64 and CD32 are constitutively expressed on mononuclear phagocytes of the human myeloid system....
Dartmouth Dissertations

Hepatic toxicity and compensatory hyperplasia in a rat model of aflatoxin bi-induced liver cancer
Liver -- Cancer -- Etiology. Hepatotoxicology. Aflatoxins -- Toxicology. Taurine. Liver -- Cancer -- Animal models.
A hypothesis that chronic aflatoxin Bi- (AFBi) induced hepatotoxicity and the resulting compensatory cell proliferation are critical for the growth of preneoplastic lesions was investigated. A commonly utilized protocol which consists of 10 doses...
Dartmouth Dissertations

The interplay between BCL2 family members in response to pharmacologically induced apoptosis
Apoptosis.; Cancer cells -- Growth -- Regulation. ; Cellular signal transduction. ; Apoptosis Regulatory Proteins -- pharmacology. ; Proto-Oncogene Proteins c-bcl-2 -- pharmacology. ; bcl2-Associated Death Protein -- pharmacology. ; Vinblastine --...
Dartmouth Dissertations

High-throughput analysis of antigen-specific antibody effector function from polyclonal Ig / by Eric Brown
Antibodies are known to be a primary correlate of protection in almost all current vaccines, and thus evaluating the antibody response is of critical importance in attempting to predict the efficacy of novel vaccine candidates. Historically...
Dartmouth Dissertations

Innate immune mechanisms contributing to LP-BM5 murine retroviral pathogenesis and immunodeficiency / by Megan Ashley O''Connor
LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), and is characterized by profound and broad immunosuppression of T- and B-cell responses. Adaptive immune response to LP-BM5 infection, including the pathogenic role of CD4+ T-cells and...
Dartmouth Dissertations

Determinants of the il-1β response to Pseudomonas aeruginosa / by Yash R. Patankar
IL-1β is a potent proinflammatory cytokine produced in response to Pseudomonas aeruginosa infection. While it is appreciated that IL-1β is a critical modulator of the host response to P. aeruginosa infection, the host and bacterial determinants...
Dartmouth Dissertations

Probing a receptor-binding domain of interleukin-2 by combinatorial cassette mutagenesis.
Interleukin-2. ; Mutagenesis.
Dartmouth Dissertations

Regulation of dendritic cell biology in vitro and in vivo with biological response modifiers.
Dendritic cells. Biological response modifiers. Immune response -- Regulation. T cells. CD antigens. Dendritic Cells -- Immunology. Receptors
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that regulate antigen-specific T cell activation or tolerance. The maturation state of DCs is critical since immature DCs are believed to induce T cell tolerance whereas mature...
Dartmouth Dissertations

Development and application of a genetically-structured simulation for bacteriophage T7.
Viral genetics -- Mathematical models. ; Bacteriophages -- Growth -- Computer simulation. ; Recombinant viruses. ; Bacteriophage T7.
Dartmouth Dissertations

Glutaredoxins and CPF: the backbone dynamics, resonance assignments, secondary structure, and isotopic labeling of DNA and proteins.
Genetic transcription -- Regulation. ; Glutaredoxin. ; Vaccinia -- Genetics. ; Escherichia coli -- Genetics. ; DNA-protein interactions.
Dartmouth Dissertations

Uterine epithelial cell release of MIP3, TNF and TGF in response to Escherichia coli, Lactobicillus rhamnosus and pathogen associated molecular patterns (PAMP) and the influence of estradiol on cytokine release.
Epithelial cells. Estradiol -- Physiological effect. Tumor necrosis factor. Transforming growth factors-beta. Cytokines -- Pathophysiology. Escherichia coli. Lactobacillus rhamnosus. Uterus -- Pathophysiology.
The research presented in this thesis tested the hypothesis that uterine epithelial cells (UEC) are selectively responsive to bacteria and pathogen associated molecular patterns (PAMP) and that responses are influenced by estradiol (E 2 ). We...
Dartmouth Dissertations

An effective distributed caching strategy for partial result reuse for discrete optimization problems.
Evolutionary computation. ; Cache memory. ; Mathematical optimization. ; Protein folding -- Computer simulation.
Evolutionary Computation (EC) is one of the most advanced computational techniques. It has been frequently and successfully used to find good solutions to many complicated optimization problems with limited computational resources. EC is the...
Dartmouth Dissertations

Mechanism of cleavage of the TcpA prepilin by the type 4 prepilin peptidase, TcpJ, of Vibrio cholerae.
Vibrio cholerae -- Molecular genetics. ; Peptidase -- Pathophysiology. ; Proteolytic enzymes.
Type 4 prepilins and prepilin-like-proteins are secreted by a wide range of bacterial species and are required for a variety of functions including type 4 pilus (Tfp) formation, toxin and other enzyme secretion, gene transfer, and biofilm...
Dartmouth Dissertations

Investigation of trans-acting factors in AURE-mediated mRNA turnover.
Messenger RNA -- Metabolism. ; Trans-Activation (Genetics). ; RNA-protein interactions. ; Adenosine. ; Uridine. ; Lactate dehydrogenase. ; Genetic regulation. ; RNA-Binding Proteins. ; Protein processings Post-transcriptional. ; Hippel-Lindau...
Post-transcriptional pathways provide a major means of regulating eukaryotic gene expression. Reiterations of the AU-rich element (AURE) located within the 3' UTR of many labile cytokine and proto-oncogene mRNA serve as signals for rapid...
Dartmouth Dissertations

Investigation into the syntheses and reactions of 2-nitroindoles and 3-nitroindoles and discovery of novel syntheses of the pyrrolo[3,4-b]indole and pyrrolo[2,3-b]indole ring systems.
Carbazole -- Synthesis. ; Indole. ; Pyrroles.
A new synthetic approach to both pyrrolo[2,3- b]indoles and pyrrolo[3,4- b]indoles by the reaction of 3-nitro-1-(substituted)indoles with functionalized isocyanides is presented. The reaction between 3-nitro-1-(phenylsulfonyl)indole (185) and ethyl...
Dartmouth Dissertations

Dose dependent effects of sodium arsenite on NF-κB and interleukin-8 in bronchial epithelial cells.
Epithelial cells. ; NF-kappa B (DNA-binding protein). ; Interleukin-8. ; Arsenic compounds -- Physiological effect.
Dartmouth Dissertations

Biophysical and ligand-binding characterization of the interleukin-2 receptor ß-subunit ectodomain.
Interleukin-2. ; T cells -- Receptors. ; Ligand binding (Biochemistry).
Dartmouth Dissertations

Distinct neuroimmune interactions in acute inflammatory pain and persistent neuropathic pain.
Pain -- Immunological aspects. ; Inflammation -- Immunological aspects. ; Nervous system -- Diseases -- Immunological aspects. ; Neuroimmunology.
Chronic neuropathic pain is a debilitating condition that exacts an emotional and physical toll on its sufferers and their family as well as an enormous monetary toll on society. Neuropathic pain can arise following nerve injury induced by trauma,...
Dartmouth Dissertations

Mutational studies of simian virus 40 large T antigen.
Tumor antigens. ; SV40 (Virus).
Dartmouth Dissertations

Novel diphosphate surrogates: synthesis of potential inhibitors of cholesterol biosynthesis.
Cholesterol -- Synthesis -- Inhibitors. ; Anticholesteremic agents -- Synthesis. ; Pyrophosphates.
Dartmouth Dissertations

Coordination chemistry and DNA-binding studies of a non-classical zinc finger motif.
Coordination compounds. ; Zinc-finger proteins. ; DNA-binding proteins. ; DNA-protein interactions.
Dartmouth Dissertations

Characterization of Saccharomyces cerevisiae genes RAT8, RAT9/NUP85 and RAT10/NUP145.
Messenger RNA -- Physiological transport. ; Saccharomyces cerevisiae -- Genetics.
Dartmouth Dissertations

Coupling of termination, 3' processing and mRNA export.
Messenger RNA -- Genetic aspects. ; Transcription factors. ; Genetic transcription -- Regulation. ; RNA-protein interactions. ; Saccharomyces cerevisiae -- Genetics.
Dartmouth Dissertations

Solution structure determination of core binding factor ß(1-141) and map of CPFα binding site.
Transcription factors -- Structure. ; Genetic transcription. ; DNA-binding proteins.
Core binding factor (CBF) is a heterodimeric transcription factor that is essential for a number of developmental process including hemotopoiesis and bone development. CBFs contain a DNA-binding CBFα. subunit and a non-DNA binding CBFß. subunit...
Dartmouth Dissertations

Biochemical characterization of prion conversion.
Prion diseases. Prions. Proteolytic enzymes -- Pathophysiology. Proteins -- Conformation.
Prion diseases are infectious neurodegenerative disorders characterized by a conformational change of the host-encoded prion protein. The normal nonpathogenic isoform of the prion protein (PrPc) is primarily composed of α-helices and very low...
Dartmouth Dissertations

Effects of mitomycin C and other DNA crosslinking agents on gene expression: modulation of cancer cell multidrug resistance in cell culture and in vivo.
Mitomycin C -- Genetic aspects. ; DNA damage. ; Drug resistance in cancer cells. ; Cancer -- Chemotherapy -- Genetic aspects.
Our laboratory is concerned whether the distribution of chemically-induced DNA damage is non-random at the level of individual genes. Using changes in gene expression as a marker for DNA damage, we have previously demonstrated that genotoxic...
Dartmouth Dissertations

CD8 T cell responses to murine gamma-herpesvirus 68: viral persistence shapes the immune response.
T cells. Immunologic memory. Latent virus diseases -- Immunological aspects. Herpesvirus diseases. Cell-mediated cytotoxicity. CD8-Positive T-Lymphocytes -- immunology. T-Lymphocytes
Vaccines are one the greatest advances in public health. Vaccines work by priming cells of the adaptive immune system in such a way that they remember that they have encountered a specific antigen before. This then allows those cells to respond...
Dartmouth Dissertations

Modulation antigen presentaton by Fcγ receptor-targeting and glucocorticoids.
Antigen presenting cells. ; Major histocompatibility complex. ; Fc receptors. ; Glucocorticoids. ; Immune recognition.
Dartmouth Dissertations

The role of Mediator and TFIIH in CTD-dependent transcription.
Saccharomyces cerevisiae -- Genetics. ; Genetic transcription -- Regulation. ; RNA -- Genetic aspects.
The C terminal domain (CTD) of Rpb1, a sub-unit of RNA Pol II, in Saccharomyces cerevisiae, contains 26 repeats of a heptapeptide sequence that is highly conserved in all eukaryotes. The CTD affects the implementation and co-ordination of...
Dartmouth Dissertations

The role of glia in neuropathic pain: a journey into the tetrapartite synapse.
Neuroglia -- Effect of drugs on. Astrocytes. Opioids -- Physiological effect. Central nervous system -- Pathophysiology. Nerves
Neuropathic pain is a debilitating condition that affects millions of individuals worldwide. Unfortunately, opioids are only partially effective in treating neuropathic pain while entraining tolerance and a myriad of side effects from the high...
Dartmouth Dissertations

The role of retinoic acid on CD4+ T cell biology.
T cells.; Tretinoin -- Physiological effect. ; CD4-Positive T-Lymphocytes -- immunology.
Dartmouth Dissertations

Characterization of metal ion binding to zinc finger peptides and metal ion competition reactions between metallothionein and Sp1 zinc finger #3.
Zinc-finger proteins. ; Metallothionein. ; Binding sites (Biochemistry).
Dartmouth Dissertations

Cellular and molecular effects of chromium on the activity and expression of fibrinolytic proteins in epithelial cells.
Chromium -- Therapeutic use. ; Fibrinolysis. ; Epithelial cells. ; Pulmonary fibrosis.
Transition metals play critical roles in biological systems as essential components of metalloproteins and metalloenzymes, as diagnostic probes and pharmaceuticals, and in some instances, as sources of toxicity. Cellular concentrations vary...
Dartmouth Dissertations

Cholesterol trafficking and the etiology of NPC disease.
Cholesterol -- Physiological transport. ; Cholesterol -- Genetic aspects. ; Purkinje cells. ; Neurogenetics. ; Neimann-Pick Diseases -- etiology.
Niemann-Pick type C (NPC) disease is a fatal autosomal recessive pediatric neurovisceral disorder characterized clinically by progressive neurodegeneration in the central nervous system (CNS) and hepatosplenomegaly. Biochemically, it is...
Dartmouth Dissertations

Substrate recognition by the phenylalanine-adenylating domain of gramicidin synthetase, and redesign of nonribosomal peptide synthetases by modulation of substrate specificity.
Peptides -- Synthesis -- Mathematical models. ; Peptides -- Physiological effect. ; Peptides -- Biotechnology. ; Gramicidins. ; Immunospecificity. ; Site-specific mutagenesis. ; Binding sites (Biochemistry). ; Phenylalanine. ; Peptide Biosynthesis.
Non-ribosomal peptide synthetases (NRPS) are a family of enzymes that assemble a variety of pharmacologically interesting polypeptides from canonical and non-canonical amino acids. The identity and connectivity of the monomers in the final product...
Dartmouth Dissertations

3D structure determination of reduced human glutaredoxin: Biophysical and biochemical characterization of CBFß proteins.
Transcription factors. ; Glutaredoxin -- Structure. ; DNA-protein interactions.
Dartmouth Dissertations

Characterization of CTL responses to the murine AIDS defective retrovirus.
Retroviruses. ; AIDS (Disease). ; Mouse leukemia viruses. ; Diseases -- Causes and theories of causation. ; Antineoplastic antibiotics. ; MHC antibodies.
Dartmouth Dissertations

Multiple pathways for macromolecular transport through the nuclear pore complex in Saccharomyces cerevisiae.
Saccharomyces cerevisiae -- Genetics. ; Messenger RNA -- Genetic aspects. ; Proteins -- Synthesis. ; Heat shock proteins.
Dartmouth Dissertations

Complete configuration space analysis for structure determination of symmetric homo-oligomers by NMR.
Proteins -- Structure -- Data processing. Proteins -- Analysis -- Data processing. Nuclear magnetic resonance spectroscopy. Oligomers -- Analysis -- Data processing.
Symmetric homo-oligomers (protein complexes with similar subunits arranged symmetrically) play pivotal roles in complex biological processes such as ion transport and cellular regulation. Structure determination of these complexes is necessary in...
Dartmouth Dissertations

Protein spatial dynamics during homotypic vacuole fusion.
Membrane proteins -- Physiological transport. ; Membrane fusion. ; Tonoplasts. ; Biological transport -- Regulation. ; Saccharomyces cerevisiae -- Molecular aspects.
Membrane docking and fusion are essential steps in intracellular vesicular trafficking. The underlying molecular mechanisms are highly conserved between organisms. Yeast homotypic vacuole fusion has become a paradigm in studying this fundamental...
Dartmouth Dissertations

Regulation of innate immunity of mouse uterine epithelial cells by keratinocyte growth factor and estradiol.
Epithelial cells. Uterus -- Physiology. Keratinocytes -- Physiological effect. Estradiol -- Physiological effect. Growth factors -- Physiological effect. Chemokines.
The mucosal immune system of the female reproductive tract (FRT) balances the dual functions of protection against invading pathogens and adaptation of the endometrial environment for successful fertilization and implantation. Growth factors are...
Dartmouth Dissertations

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