There is a growing interest in the synthesis of functional materials by supramolecular assembly. Special attentions are recently attracted to understand the assembly mechanism, the incorporation of desired functionalities, and the applications. This research is to study three functional assembly systems, i.e. bridged silsesquioxanes, organic hybrid materials, and polymer aggregates By incorporating functional organic moieties into ordered silica network, self-assembly of bridged silsesquioxanes ((RO)3Si-R' -Si(OR)3) proves efficient to produce advanced organic/inorganic materials. The present research introduces four functional organic components, i.e. polydiacetylene (PDA), oligothiophene, perylenediimide and porphyrin, into the silica framework, and the resultant assemblies show interesting structures and great applications as optoelectronic devices and sensors. Particularly, this thesis demonstrates the first example to synthesize responsive mesoporous PDA systems, the first example to fabricate oligomer thin films through a simple sol-gel process, the first mechanism study on the molecular assembly at multi-length scales, and the first assembly system of macroscopically helical fibers with chiral micropores, mesopores and macropores PDA systems have been known to switch their color between blue and red when exposed to temperature, inorganic ions, organic solvents, pH and salt changes or mechanical stress, which endow them with potential applications as sensor materials. This thesis reports the first example to synthesize PDA nanocomposites that switch their colors under UV irradiation at room temperature, induced by the unique configuration change of incorporated azobenzene derivatives Environment-responsive polymer aggregates have attracted increasing attentions in recent years because of their potential applications in numerous fields, e.g. drug delivery vehicles. This thesis focuses on self-assembly of homopolymer with small organic molecules (such as poly (4-vinylpyridine), or poly (allylamine), with diacetylenic acids) or two homopolymers (sulfonated poly (ether ether ketones), and PAA) in common solvents, resulting in the formation of microsized hollow spheres or nanoparticles, respectively. Both of them indicate potential applications as controlled and targeted delivery vehicles / acase@tulane.edu

DNA chimeras are constructs comprised of oligonucleotides (ODNs) bearing synthetic motifs. The rationale for building and exploring this class of compounds is that by combining the unique properties of DNA with tasked synthetic fragments, systems capable of controlled functional operations can be realized. The choice of synthetic fragment determines the chimera's specific function with regard to what it is designed to interface with. The core ODN scaffold provides the chimera with a mechanism by which it can associate and respond to stimuli. This dissertation explores strategies by which DNA chimeras can act as selective protein antagonists, protein detection agents, and high fidelity molecular switches. In particular two systems are defined which are capable of stimuli responsive protein binding. The first system describes a chimera that exhibits the capacity of switching between bidentate and monodentate protein binding modes. This system is chronicled in chapter two, as well as in a communication in J. Am. Chem. Soc. (2008). The second system details the development of a host-guest functionalized DNA chimera. This system features digital protein binding characteristics, significant stabilization towards thermal denaturation, and a high degree of sequence selectivity with regard towards ODN hybridization. This system is chronicled in chapter three, as well as in a communication in J. Am. Chem. Soc. (2011). Further, a method for using chimeras as a protein detection agent is detailed in chapter four, which was published in Supramol. Chem. (2009) / acase@tulane.edu

Ontologies are clearly the most important feature of the Semantic Web, as demonstrated in Chapter 1. Ontology Merging is the key operation that will be needed for the effective operation of the Semantic Web, and this is the focus of Chapter 2. In Chapter 3, we prove that the development of Ontologies with the explicit goal of facilitating Ontology Merging is hugely beneficial to the Semantic Web In Chapter 4, we prove that well formed formulations of Nodes, Levels, Paths, Subtrees, Trees and Ontologies leads to easier development of intelligent ontology merge operations and algorithms. In Chapter 5, we show that an explicit specification of various ontology types leads to a cluster of efficient ontology merge algorithms. The results of the experiments show that the Ontology formulations and Ontology Merge algorithms developed in this work are realizable in polynomial time / acase@tulane.edu

NafionRTM/ceramic nanocomposite membranes are prepared by a solid state method for fuel cell applications. Nanocomposite powders from NafionRTM pellets and a zirconium phosphate ceramic are formed by mechanical attrition. The powders are consolidated into membrane form by mechanical pressing and hot isostatic pressing. Cross-sectional analysis by scanning electron microscopy (SEM) indicates that the ceramic particles exist in agglomerates that are evenly dispersed across the membrane. Dynamic mechanical analysis (DMA) and tensile testing found the membranes to be mechanically equivalent, and in some cases superior, to a commercial extruded membrane. Increasing ceramic content is accompanied by an increase in modulus and shift in the alpha transition to higher temperature. Evaluation of membrane hydration by thermal gravimetric analysis (TGA) indicates that the prepared membranes have increased water uptake when compared to a commercially available membrane. However, as distribution of the ceramic is improved, the hydration of the sample is reduced. Low temperature differential scanning calorimetry (DSC) indicates that the additional water contributes to an increase in both freezing and nonfreezing water contents in the membranes. Proton conductivity, measured by the 4-probe method at 60°C in water as well as with varying relative humidity and temperature, revealed that the prepared membranes have conductivities that are comparable to but somewhat lower than the commercial membranes. An increase in conductivity is seen with decreased particle size and improved dispersion of the ceramic / acase@tulane.edu

Snell (dw/dw) and Ames (df/di) dwarf mice lack prolactin (PRL), growth hormone (GH) and thyroid stimulating hormone (TSH), and exhibit deficient PRL-inhibitory tuberoinfundibular dopaminergic (TIDA) neuron numbers. Studies in dw/dw and df/df demonstrate neurotrophic actions of PRL on TIDA neurons. Daily ovine PRL treatment maintains normal TIDA neuron numbers in df/df when initiated at 12 days (d) of age, but not later. However, PRL and PRL receptor knockout mice exhibit normal TIDA neuron numbers. The studies presented here further define the neurotrophic PRL effect on TIDA neuron development, by addressing species specificity and importance of age and duration, and investigate whether GH can assume the PRL effect in PRL deficiency. Homologous PRL or low doses of heterologous PRL, administered beginning at 3d, maintains the maximum TIDA neuron numbers observed in dw/dw development. High doses of heterologous PRL induce TIDA neuron differentiation in early postnatal development. However, increased hypothalamic cell proliferation is observed in response to homologous, but not heterologous PRL. These data indicate high dose heterologous PRL-induced TIDA neuron recruitment is not due to stimulation of neurogenesis, but to phenotype change in pre-existing hypothalamic neurons. However, bromodeoxyuridine (BrdU) was not administered throughout PRL treatment, so the mechanism of neurogenesis cannot be excluded. Long-term, homologous PRL induces TIDA neuron differentiation in adult dw/dw in a duration-dependent fashion, suggesting the existence of PRL-sensitive potential TIDA neurons in adult dw/dw. No differences in cell proliferation were observed, but neurogenesis as a mechanism of long-term, homologous PRL-induced TIDA neuron recruitment cannot be excluded because BrdU was not administered throughout the PRL regimen. Also, dw/dw exhibit deficient periventricular (PeN) DA (A14) neuron numbers. A 14 neuron numbers were increased to near-normal in response to homologous PRL in early postnatal development, but not in the adult, suggesting a critical developmental period for PRL effect on A 14 neurons. Heterologous GH, administered beginning at 3d, induced increased, but not normal-sized, TIDA neuron numbers in WE. These findings suggest that GH effects on TIDA neurons are less potent than those of PRL, although GH has a minimal effect on TIDA neuron development. Surprisingly, GH did not affect PeN somatostatin (SRIH) cell number, which is decreased in dwarfs, indicating that PRL and/or TSH are important in early PeN SRIH neuron development, unless this lack of effect is only seen with porcine GH. The findings presented here better define neurotrophic effects of PRL on TIDA neurons and suggest a minimal effect of GH in TIDA neuron development / acase@tulane.edu

The most common site of prostate cancer (PC) metastasis is the bone resulting in painful bone disease and complications. The majority of prostate cancer lesions exhibit an osteoblastic i.e. bone formation, and one factor that may play an important role in the activation of osteoblasts are bone morphogenetic proteins (BMP). BMPs are members of the transforming growth factor-beta superfamily that are implicated in the homing of prostate cancer cells to the bone. Although it has been reported that BMP expression by PC cell lines is increased, the factors involved in the activation of BMPs is not clearly understood. We demonstrate that a number of BMPs are activated by nuclear factor kappa B (NF-kappaB) in PC cells. Two androgen independent (AI) prostate carcinoma PC-3 and DU-145 cells have constitutive NF-kappaB activity, whereas LNCaP, an androgen dependent (AD) cell line does not -- suggesting that this family of transcription factors is a potentially important molecular target for therapies designed to prevent PC progression. Using an adenoviral superrepressor construct we determined that activation of NF-kappaB has the ability to modulate PC cell invasion through Matrigel. To investigate the mechanism by which NF-kappaB enhances the invasive properties of PC cells, we examined if stimulation of NF-kappaB with and endogenous activator, TNFalpha, in PC cells enhanced BMP expression. Semiquantitative PCR from LNCaP and its osteotropic subline C4-2B revealed that BMPs 2 and 4 are activated by NF-kappaB in both cell lines - suggesting a possible role for these BMPs in tumor cell clonal expansion in an autocrine fashion. We determined that BMP-2 and BMP-4 are transcriptionally regulated by NF-kappaB and inhibition of Akt lowers the promoter activity. We also demonstrate that targeted disruption of NF-kappaB lowers the phosphorylation of Smad proteins, downstream molecules in the BMP signaling cascade. Therefore, the transcription factor NF-kappaB promotes PC bone metastasis by activating bone morphogenetic proteins and cross-signaling with the Smad pathway / acase@tulane.edu

In this paper we make use of the the concept of covering spaces for homogeneous continua as pioneered by Rogers and refined by Maciaas. For a continuum X embedded essentially into the product of the circle S1 and the Hilbert cube Q , we examine the structure of the space X˜ which is the preimage of X under a standard covering map p : RxQ→S1xQ . We show that the compactification of components of X˜ must be decomposable, and are aposyndetic whenever X is. We also demonstrate the conditions under which higher order forms of aposyndesis are inherited by the components of X˜ as well. We conclude by examining the continuum component structure of X˜ and develop several theorems that allow us to determine the cardinality of the collection of continuum components / acase@tulane.edu

Layered ruthenates in the Ruddlesden-Popper series (Sr,Ca) n+1RunO3n+1 exhibit exceptionally rich ground state properties, such as unconventional spin-triplet superconductivity, orbital ordering, and metamagnetic quantum criticality. These unusually rich ground states headline the complex interplay between the charge, spin, lattice and orbital degrees of freedom in ruthenates, and provide fantastic opportunities to study novel quantum phenomena tuned by non-thermal parameters like chemical doping, pressure, and magnetic field We focus on two particular layered ruthenates, each with rich ground state properties. First, Sr4Ru3O10 exhibits an itinerant ferromagnetic ground state, but moderate in-plane magnetic fields induce a metamagnetic transition. The presence of both ferromagnetism and metamagnetism in this material is puzzling and has been the subject of extensive study. The other material studied here, Ca3Ru2O 7 orders antiferromagnetically at 56 K and exhibits a metal-insulator transition at 48 K. With the application of magnetic field this material shows spin-flop transition causing giant magnetoresistance. Neutron scattering studies have revealed a rich magnetic phase diagram with four different magnetic phases In this dissertation we aim to elucidate the orbital dependence of the magnetism in Sr4Ru3O10 and the nature of the complex coupling between spin and charge in Ca3Ru2O 7. In order to achieve these aims we developed a directional angle-resolved magnetotransport technique, as magnetoresistivity anisotropy is a powerful analysis tool. With this technique we revealed the metamagnetism in Sr 4Ru3O10 to be orbital selective, i.e. the metamagnetism and ferromagnetism arise from different orbitals. In Ca3Ru 2O7 we studied the nature of the effects of ferromagnetic and antiferromagnetic coupling on c-axis transport throughout the different magnetic phases in this material by analyzing the magnetoresistivity anisotropy, and have observed a complex interplay between the charge and spin degrees of freedom that were dependent on both temperature and magnetic field By utilizing a relatively simple technique we have probed the nature of the magnetism in two materials. In addition to revealing important physics in these two materials, our results suggest possible avenues of investigation in other ruthenates and strongly correlated systems using the developed technique / acase@tulane.edu

Angiogenesis, a complex multi-step process resulting in the formation of new blood vessels, is essential for the growth and metastasis of solid tumors as well as for the progression of other diseases. The balance between vascular endothelial cell (EC) survival and apoptosis is a major determinant of tumor angiogenesis. Recent clinical studies suggest that the pharmacological agent flavopiridol (FP) may be an effective therapeutic option for the treatment of cancer; however, the mechanism by which FP inhibits cancer progression is not understood. At high (micromolar) concentrations, FP is a broad inhibitor of cyclin-dependent kinases, but at low (nanomolar) concentrations, FP is a specific inhibitor of the positive-acting transcription elongation factor (P-TEFb). Recent reports suggest that P-TEFb, that was initially thought to be a global transcription elongation factor affecting the expression of all genes, may be required for the expression of some genes but not others. [1, 2] Accordingly, PrFEF-b, that is composed of cyclindependent kinase 9 (Cdk9) and cyclin T, binds to the transcription factor nuclear factorkappa B (NF-kappaB) and is required for transcription of NF-kappaB-dependent genes such as Interleukin-8 (IL-8). [3] We hypothesize that P-TEFb and NF-ICB are required for Bel-2 expression and survival in EC during angiogenesis Here, we show that NF-kappaB and Cdk9 knase activity are activated by angiogenic stimuli in primary Human Umbilical Vein Endothelial Cells (HUVEC). Inhibition of P-TEFb and NF-kappaB decreases expression of the pro-survival factor, B-cell Leukemia-2 (Bcl-2) correlating with decreased HUVEC survival in vitro and with inhibition of invasion and vessel formation in vivo. Inhibition of P-TEFb decreases Bcl-2 protein and mRNA expression yet increases p21 expression, suggesting that some genes are more sensitive to P-TEFb inhibition than are others. The studies discussed herein provide invaluable insight into the mechanism of action of P-TEFb and NF-kappaB in EC, and more importantly, in mechanisms of gene expression critical for differential regulation of tumor-associated angiogenesis / acase@tulane.edu

Sweet almond beta-glucosidase is a retaining, family 1, glycosidase that catalyzes the efficient hydrolysis of a broad range of substrates. The catalytic activity of the enzyme relies on two glutamic acid residues in the active site, one protonated and the other deprotonated. The hydrolysis of p-nitrophenyl beta-D-glucoside was found to rely on two groups with pKas of 4.00 and 7.10 with a (kcat/K M)lim value of 30,902 M-1 sec-1 , in agreement with the active site containing two carboxylic acid residues Hydrolysis and binding studies for a number of glucosides were carried out over a wide temperature range to determine thermodynamic parameters for the catalyzed reactions. These studies were used to determine what effects the enthalpy and entropy of activation have on increasing the rate of the reaction during catalysis. Results indicate that the significant rate improvement is due primarily to a more favorable enthalpy of activation for the catalyzed reaction resulting in rate enhancements between 1012-10 14 times faster than the spontaneous reactions at 25°C. The relative order of the first-order rate constants roughly follows the order predicted based on a Bronsted coefficient of -1, calculated under the assumption that the generally accepted mechanism is the correct mechanism for the substrates studied / acase@tulane.edu