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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
101

Preoptic Regulatory Factor 2 Inhibits Proliferation and Enhances Drug Induced Apoptosis in Neural Stem Cells

Ma, Shuang 24 April 2009 (has links)
No description available.
102

Synthesis and switchability study of amidine-containing vinyl monomers and their polymers

Li, Meng 04 1900 (has links)
<p>In this thesis work, two new CO<sub>2</sub>-responsive monomers have been synthesized. These amidine-containing monomers were prepared in a simple and effective one-step reaction, giving a very high yield (98.5 %) of product. Furthermore, there was no complicated further purification required to obtain the highly pure product. The CO<sub>2</sub> switchability, conductivity and partitioning of the monomers were measured. It was confirmed that the monomers could be protonated CO<sub>2</sub> in the present of trace amount of water and reversibly switched back and forth to their natural forms by N<sub>2</sub> at room temperature.</p> <p>The polymers having different molecular weights were prepared from one monomer via conventional free radical polymerization method. The polymers also showed the reversible switchability property with CO<sub>2</sub> and N<sub>2</sub> stimuli. This was confirmed by the results of conductivity and partitioning tests. Temperature showed a major influence on the conductivity of the monomer and polymers. The effect of molecular weight on the polymer switchability of was further investigated through conductivity tests and potentiometric titration. The conductivity decreased with the increased molecular weight. The apparent equilibrium constant (pK<sub>a</sub>)<sub> </sub>decreased with the degree of protonation (δ) suggesting that the basicity of the polymers is strongly depended on the value of δ.</p> / Master of Applied Science (MASc)
103

Asymmetric Synthesis of Nitrogen Containing Bioactive Compounds via the Utilization of Enantiopure p-Toluenesulfinimines

Xu, Peng January 2013 (has links)
The research objective of this thesis research was to develop new methods for the asymmetric synthesis of amine derivatives using p-toluenesulfinimines. Enantiopure sulfinimines are versatile chiral building blocks for the asymmetric synthesis of alkaloids. Sulfinimines were prepared by the condensation of (S)- or (R)-p-toluenesulfinamide with aldehydes and ketones in good to excellent yields, which were prepared from the commercially available Anderson reagent. The first research project was the development of a new method for the preparation of enantiopure anti-anti- α-lkyl β-amino ketones and was accomplished by the stereoselective α-alkylation of enolates of sulfinimine derived β-amino esters. The anti- α-lkyl β-amino esters were transformed to their corresponding Weinreb amides by reacting with lithium dimethyl hydroxyl amine without epimerization. Reactions of the Weinreb amides with Grignard and organolithium reagents afforded the corresponding anti- α-lkyl β-amino ketones in modest yields and high optical purity. The modest yields are the results of competition between addition and reduction of the Weinreb amide. anti- α-lkyl β-amino ketones are important chiral building blocks for the asymmetric synthesis of nitrogen-containing biologically active molecules, such as pyrrolidines, piperidines and other alkaloids. To further illustrate the utility of sulfinimine -derived enantiopure N-sulfinyl anti- α-lkyl β-amino ketones, they was applied to the asymmetric synthesis of the unknown anti-C5, C6 derivative of 2,3,4,6-tetrasubsituted indolizidine 221-T. The key step in the synthesis was the stereoselective construction of the piperidine ring of the 5,6,8-tri-substituted indolizidine and was realized via the use of an acid-catalyzed intramolecular Mannich cyclization. The indolizidine was readily transformed in to the key intermediate 7-hydroxyl-2,3,4,6-tetrasubsituted indolizidine in high stereoselectivity and yield. Changing the sequence of chemical operation steps avoided the production of the side product β-pyrrole ketone. Reduction of the intermediate piperdinone, followed by ring-closing metathesis and reductive catalytic hydrogenation afford the bicyclic indolizidine with overall 76% yield of 3 steps. The C-2 branched cocaine analogs are thought to have varied bioactivities and potent therapeutical uses compared to other positions of substituted cocaine analogs. However, reports on the synthesis of such analogs are few. The first example of preparation of a cocaine analog having a dimethylphosphonate group at the C-2 position was reported. The key step in forming the required isoxazolidine intermediate, which controls the required cis stereochemistry at C-2 and C-3, was a novel microwave induce stereoselective [3+2] intramolecular cycloaddition of an α,β-unsaturated pyrrolidine nitrone. The use of the microwave irradiation techniques significantly reduce the time required for isoxazolidine formation from 96 hours to five hours. / Chemistry
104

The versatile biomedical applications of bismuth-based nanoparticles and composites: therapeutic, diagnostic, biosensing, and regenerative properties

Shahbazi, M-A., Faghfouri, L., Ferreira, M.P.A., Figueiredo, P., Maleki, H., Sefat, Farshid, Hirvonen, J., Santos, H.A. 24 April 2020 (has links)
Yes / Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical, chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR) absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery, biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive discussion focusing on challenges and future opportunities is presented. / M.-A. Shahbazi acknowledges financial support from the Academy of Finland (grant no. 317316). P. Figueiredo acknowledges the Finnish Cultural Foundation for its financial support (decision no. 00190246). H. A. Santos acknowledges financial support from the HiLIFE Research Funds, the Sigrid Juse´lius Foundation, and the Academy of Finland (grant no. 317042). / Research Development Fund Publication Prize Award winner, Jan 2020.
105

Novel Monomer Design for Next-Generation Step-Growth Polymers

Wolfgang, Josh David 16 July 2021 (has links)
Facile monomer synthesis provided routes towards novel step-growth polymers for emerging applications. Adjustment of reaction conditions enabled green synthetic strategies, and promising scalability studies offered impetus for industrial funding. Engineering thermoplastics, such as linear polyetherimides (PEIs), had carefully targeted molecular weights for analysis of the effect of molecular weight and regiochemistry on the thermomechanical and rheological properties of PEIs. The design of linear, high performance PEIs comprising 3,3'- and 4,4'-bisphenol-A dianhydride (bis-DA) and m-phenylene diamine (mPD) provided an opportunity to elucidate the influence of dianhydride regiochemistry on thermomechanical and rheological properties. This unique pair of regioisomers allowed the tuning of the thermal and rheological properties for high glass transition temperature polyimides for engineering applications. The selection of the dianhydride regioisomer influenced the weight loss profile, entanglement molecular weight, glass transition temperature (Tg), tensile strain-at-break, zero-shear melt viscosity, average hole-size free volume, and the plateau modulus prior to viscous flow during dynamic mechanical analysis (DMA). The 3,3'-PEI composition interestingly exhibited a ~20 °C higher Tg than the corresponding 4,4'-PEI analog. Moreover, melt rheological analysis revealed a two-fold increase in Me for 3,3'-PEI, which pointed to the origin of the differences in mechanical and rheological properties as a function of PEI backbone geometry. The frequently studied 4,4'-PEI exhibited exceptional thermal, mechanical, and rheological properties, yet the 3,3'-PEI regioisomer lacked significant study in the industrial and academic sectors due to its 'inferior' properties, namely poor mechanical properties. Introduction of long-chain branching (LCB) into PEIs provided a unique comparison between a commercially relevant PEI (Ultem® 1000) and a regioisomer infrequently found in the literature. Thermal stability remained consistent for each regioisomer, and Tgs for the 3,3'- and 4,4'-LCB-PEIs agreed well with prior literature. Rheological analysis demonstrated typical shear thinning and low-shear viscosity trends for LCB systems. The targeted molecular weights for the 3,3'-LCB-PEIs were well below the Me cutoff for "high molecular weight," and for this reason the rheological properties demonstrated inconsistent trends. Further study of PEIs led to the incorporation of ionic endgroups. These provided physical crosslinks, which enhanced mechanical and rheological properties of branched PEIs compared to their non-ionic analogs. The Tgs decreased with an increase in branching concentration for the phenyl-terminated PEI, while it remained unchanged for the ionically-endcapped PEIs. The divalent salts demonstrated higher mechanical strength and melt viscosities compared to the monovalent salt and the non-ionic PEIs. Interestingly, the zinc-endcapped PEI series exhibited decreased high-shear viscosities compared to the other PEIs, lending to promising industrial applications for the zinc-endcapped branched and linear PEIs for high temperature applications. Additional engineering thermoplastics in the form of bio-based polyureas exhibited mechanical properties similar to those of non-bio-based polyureas. The isocyanate-free synthetic route incorporated an essential urea degradation mechanism at elevated temperatures to produce isocyanic acid, which then reacted with amines to produce linear polyurea thermoplastics. Urea provided a sustainable and bio-friendly reagent for high molecular weight, isocyanate-free polyureas. Poly(propylene glycol) triamine enabled the long-chain branching of thermoplastic polyureas. Differential scanning calorimetry (DSC) showed no change in Tg for the series; however, melting peaks decreased in intensity as the branching concentration increased, indicating a reduction in crystallinity. Tensile testing eluded to a decrease in ultimate stress values for higher branching concentrations, while melt rheology showed significant differences in melt viscosities. Viscosities increased markedly with an increase in branching concentration, signifying greater entanglement and stronger physical crosslinks for the branched polyureas. Further analysis of possible isocyanate-free routes led to the use of 1,1'-carbonyldiimidazole (CDI) to generate polyureas and polyurethanes. CDI, known in the literature for its use in amidation and functionalization reactions, enabled the production of well-defined and stable polyurethane monomers. The functionalization of butanediol with CDI yielded an electrophilic biscarbamate monomer, bis-carbonylimidazolide (BCI), suitable for further step-growth polymerization in the presence of amines. The reaction of this novel monomer with aliphatic diamines produced thermoplastic polyurethanes with high thermal stability, tunable glass transition temperatures based on incorporation of flexible polyether segments, and creasable thin films. It is envisioned that CDI functionalized diols will afford access to various polymeric backbones without the use of toxic isocyanate-containing strategies. Additionally, non-isocyanate polyurethane (NIPU) foams were produced from BCI monomers without the need of blowing agents, catalysts, or solvents. These materials offered an alternative to existing foaming technology, which typically employed isocyanates. Polyurethanes were foamed through a CO2 thermal decomposition mechanism involving the BCI monomers. We investigated two series of polyurethane foams with a tunable Tg range from ~0 °C to ~110 °C. We found that the incorporation of aromatic amines vastly altered the foam thermomechanical properties, and the resulting foams were closed-cell in nature. / Doctor of Philosophy / Step-growth polymers play a significant role in commercial and industrial applications. On-going work in this field focuses on sustainability, biodegradability, and improved processability. This dissertation encompasses the improvement and innovation of current and novel engineering thermoplastics and foams. The careful purification and step-growth synthetic strategies herein, afforded targeted molecular weights for analysis of linear and long-chain branched (LCB) polyetherimides (PEIs). Further analysis of LCB-PEIs, with monovalent and divalent ionic endgroups, provided an opportunity to study the effect of ionic interactions and physical crosslinks at high temperatures (>300 °C). The long branches improved the melt processability compared to linear analogues at equivalent molecular weights. The challenge to investigate polyurethanes using non-isocyanate methodologies offered an opportunity to apply fundamental small-molecule, organic synthesis to macromolecular science. 1,1'-Carbonyldiimidazole (CDI) provided a platform to generate polymeric chains from industrially relevant monomers. Additional testing serendipitously discovered the generation of CO2 upon thermal degradation of the novel monomers. Harnessing the release of CO2, during the gelation of polyurethanes, provided an isocyanate-, catalyst-, and solvent-free synthetic route towards polyurethane foams that boasts scalability and industrial relevance.
106

Designing supramolecular liquid-crystalline hybrids from pyrenyl-containing dendrimers and arene ruthenium metallacycles

Pitto-Barry, Anaïs, Barry, Nicolas P.E., Russo, V., Heinrich, B., Donnio, B., Therrien, B., Deschenaux, R. 24 November 2014 (has links)
Yes / The association of the arene ruthenium metallacycle [Ru4(p-cymene)4(bpe)2(donq)2][DOS]4 (bpe = 1,2-bis(4-pyridyl)ethylene, donq = 5,8-dioxydo-1,4-naphtoquinonato, DOS = dodecyl sulfate) with pyrenyl-functionalized poly(arylester) dendrimers bearing cyanobiphenyl end-groups is reported. The supramolecular dendritic systems display mesomorphic properties as revealed by polarized optical microscopy, differential scanning calorimetry and small-angle X-ray scattering measurements. The multicomponent nature of the dendrimers and of the corresponding host–guest supramolecules (i.e., end-group mesogens, dendritic core, pyrene unit, aliphatic spacers, and metallacycle) leads to the formation of highly segregated mesophases with a complex multilayered structure due to the tendency of the various constitutive building-blocks to separate in different organized zones. The pyrenyl dendrimers exhibit a multilayered smectic A-like phase, thereafter referred to as LamSmA phase to emphasize this unaccustomed morphology. As for the corresponding Ru4–metallacycle adducts, they self-organize into a multicontinuous thermotropic cubic phase with the Im3̅m space group symmetry. This represents a unique example of liquid-crystalline behavior observed for such large and complex supramolecular host–guest assemblies. Models of their supramolecular organizations within both mesophases are proposed. / R.D. thanks the Swiss National Science Foundation (Grant No 200020-140298) for financial support.
107

RAFT dispersion polymerization : a method to tune the morphology of thymine-containing self-assemblies

Kang, Y., Pitto-Barry, Anaïs, Maitland, A., O'Reilly, R.K. 11 June 2015 (has links)
Yes / The synthesis and self-assembly of thymine-containing polymers were performed using RAFT dispersion polymerization. A combination of microscopy and scattering techniques was used to analyze the resultant complex morphologies. The primary observation from this study is that the obtained aggregates induced during the polymerization were well-defined despite the constituent copolymers possessing broad dispersities. Moreover, a variety of parameters, including the choice of polymerization solvent, the degree of polymerization of both blocks and the presence of an adenine-containing mediator, were observed to affect the resultant size and shape of the assembly. / University of Warwick, National Science Foundation (U.S.) (NSF), Engineering and Physical Sciences Research Council (EPSRC)
108

Membrane insertion and secretion of the Engrailed-2 (EN2) transcription factor by prostate cancer cells may induce antiviral activity in the stroma

Punia, N., Primon, Monika, Simpson, G.R., Pandha, H.S., Morgan, Richard 26 March 2019 (has links)
Yes / Engrailed-2 (EN2) is a homeodomain-containing transcription factor that has roles in boundary formation and neural guidance in early development, but which is also expressed in a range of cancers. In addition to transcriptional regulation, it is secreted by cells and taken up by others through a mechanism that is yet to be fully elucidated. In this study, the distribution of EN2 protein in cells was evaluated using immunofluorescence with a set of antibodies raised against overlapping epitopes across the protein, and through the use of an EN2-GFP construct. MX2 expression in primary prostate tumors was evaluated using immunohistochemistry. We showed that EN2 protein is present in the cell membrane and within microvesicles that can be secreted from the cell and taken up by others. When taken up by normal cells from the stroma EN2 induces the expression of MX2 (MxB), a protein that has a key role in the innate immune response to viruses. Our findings indicate that EN2 secretion by tumors may be a means of preventing viral-mediated immune invasion of tissue immediately adjacent to the tumor. / The Ringrose Family Trust supported this study through a studentship awarded to N.P.
109

New Roles for Arginine Methylation in RNA Metabolism and Cancer

Goulet, Isabelle 05 October 2011 (has links)
Because it can expand the range of a protein’s interactions or modulate its activity, post-translational methylation of arginine residues in proteins must be duly coordinated and ‘decoded’ to ensure appropriate cellular interpretation of this biological cue. This can be achieved through modulation of the enzymatic activity/specificity of the protein arginine methyltransferases (PRMTs) and proper recognition of the methylation ‘mark’ by a subset of proteins containing ‘methyl-sensing’ protein modules known as ‘Tudor’ domains. In order to gain a better understanding of these regulatory mechanisms, we undertook a detailed biochemical characterization of the predominant member of the PRMT family, PRMT1, and of the novel Tudor domain-containing protein 3 (TDRD3). First, we found that PRMT1 function can be modulated by 1) the expression of up to seven PRMT1 isoforms (v1-7), each with a unique N-terminal region that confers distinct substrate specificity, and by 2) differential subcellular localization, as revealed by the presence of a nuclear export sequence unique to PRMT1v2. Second, our findings suggest that TDRD3 is recruited to cytoplasmic stress granules (SGs) in response to environmental stress potentially by engaging in methyl-dependent protein-protein interactions with proteins involved in the control of gene expression. We also found that arginine methylation may serve as a general regulator of overall SG dynamics. Finally, we uncovered that alteration of PRMT1, TDRD3, and global arginine methylation levels in breast cancer cells may be closely associated with disease progression and poor prognosis. Therefore, further studies into the pathophysiological consequences ensuing from misregulation of arginine methylation will likely lead to the development of novel strategies for the prevention and treatment of breast cancer.
110

New Roles for Arginine Methylation in RNA Metabolism and Cancer

Goulet, Isabelle 05 October 2011 (has links)
Because it can expand the range of a protein’s interactions or modulate its activity, post-translational methylation of arginine residues in proteins must be duly coordinated and ‘decoded’ to ensure appropriate cellular interpretation of this biological cue. This can be achieved through modulation of the enzymatic activity/specificity of the protein arginine methyltransferases (PRMTs) and proper recognition of the methylation ‘mark’ by a subset of proteins containing ‘methyl-sensing’ protein modules known as ‘Tudor’ domains. In order to gain a better understanding of these regulatory mechanisms, we undertook a detailed biochemical characterization of the predominant member of the PRMT family, PRMT1, and of the novel Tudor domain-containing protein 3 (TDRD3). First, we found that PRMT1 function can be modulated by 1) the expression of up to seven PRMT1 isoforms (v1-7), each with a unique N-terminal region that confers distinct substrate specificity, and by 2) differential subcellular localization, as revealed by the presence of a nuclear export sequence unique to PRMT1v2. Second, our findings suggest that TDRD3 is recruited to cytoplasmic stress granules (SGs) in response to environmental stress potentially by engaging in methyl-dependent protein-protein interactions with proteins involved in the control of gene expression. We also found that arginine methylation may serve as a general regulator of overall SG dynamics. Finally, we uncovered that alteration of PRMT1, TDRD3, and global arginine methylation levels in breast cancer cells may be closely associated with disease progression and poor prognosis. Therefore, further studies into the pathophysiological consequences ensuing from misregulation of arginine methylation will likely lead to the development of novel strategies for the prevention and treatment of breast cancer.

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