Thesis (M.S.)--University of California, Berkeley, 1963. / "UC-37 Instruments" -t.p. "TID-4500 (19th Ed.)" -t.p. Includes bibliographical references (p. 50).

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 97-101). Also available in electronic version.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Accumulating evidence suggests a prominent role of the arrestin-dependent signaling pathway in triggering most of the deleterious side effects observed using δ-OR targeting drugs. Numerous small molecules targeting the δ-OR receptors have been developed but their pharmacological properties, including their functional selectivity, have been poorly characterized. The absence of functionally selective opioid drugs, and the lack of knowledge of the pharmacological profile and signaling properties of the δ-OR receptor, limits its therapeutic exploitation. The development of functionally selective modulator toward the canonical G protein pathway could importantly increase the therapeutic potential of this receptor while decreasing its deleterious effects. An approach to fine-tune the functional selectivity of a GPCR is by using allosteric modulators. These allosteric modulators would reduce problems associated with drugs targeting the orthosteric site by not chronically activating the receptor. The overall goal of the proposed research is to study the molecular mechanism by which sodium-channel inhibitors allosterically regulates the delta opioid receptor (δ-OR) signaling and functional selectivity. Additionally, the signaling features of the δ-OR signal transduction triggered by biased receptor activation have been investigated. A combination of approaches, including functional studies, molecular modeling and mutagenesis, were used to study the general mechanism underlying the activation and tuning of the δ-OR signal transduction behavior. Thus, this work suggests the druggability of the allosteric sodium pocket by using sodium channel inhibitors. The current research represent discovery of two different allosteric profiles for the β-arrestin recruitment and one allosteric profile for the G-protein pathway at activated DOR and would serve as scaffold for further refinement of modulators with the desired pharmacological profile.

University of Macau / Faculty of Science and Technology / Department of Electrical and Computer Engineering

Magister Scientiae (Medical Bioscience) - MSc(MBS) / A functional sperm is critical for successful fertilization in order to deliver an intact genome to the site of fertilization. It is often characterized by high motility and normal morphology. Moreover, sperm hyperactivated motility is imperative for both detachment from the oviductal wall and for penetration into the zona pellucida, subsequently resulting in fertilization. Several semen parameters such as volume, colour, sperm morphology and sperm concentration are used to clinically discriminate between fertile and sub-fertile males. Additionally, several sperm functional tests assess sperm function and a male’s fertility potential. A sperm feature that is not currently assessed clinically, but could possibly discriminate between fertility and infertility, is hyperactivation. The aim of this project was to investigate motility degrees (good, medium and poor) of sperm subpopulations and induce hyperactivation in each subpopulation, as well as to sperm in semen, by addition of caffeine and procaine. This was achieved by separating three sperm subpopulations from a semen sample using the Puresperm density gradient separating technique. Sperm subpopulations were exposed to 5mM caffeine and 2 mM procaine respectively for 15, 30, 60, 90 and 120 minutes. Sperm in semen was exposed to caffeine and procaine using a flush technique and analysed at 0, 5, 15, 30, 45 and 60 minutes. Sperm displaying hyperactivation was determined using cut-offs for curvilinear velocity, linearity and amplitude of lateral head displacement. The results indicate significant differences in overall percentage motility, sperm kinematic parameters and hyperactivation among the three subpopulations (p<0.05). Procaine and caffeine both induced hyperactivation in subpopulations, although the most pronounced effect of procaine was evident after 15-30 minutes compared to caffeine (60-90 minutes) in subpopulations. Maximum hyperactivation of sperm in semen was seen after 15- 30 minutes in both procaine and caffeine. Moreover, caffeine had significantly higher stimulating effect than procaine. The results suggest that the existence and distinct motility characteristics of subpopulations should be considered in future during clinical assessment of male fertility, especially when assessing hyperactivation. The immediate and higher stimulation response of sperm with the flush technique indicates that the technique may be an ideal sperm functional test compared to the separation technique. The separation technique may be used to categorize sperm subpopulation of a patient in terms of motility (high motile or low motile) and to stimulate such subpopulations with chemicals for use in assisted reproduction technologies.

No description available.

Electrostatic self-assembly was used to fabricate several samples of polymers known to have non-linear optical behavior. These samples characteristics were measured with interferometry and their electro-optic coefficients determined to be on the order that of LiNbO3. The self-assembled samples are shown to have an enhanced polar order compared to that of more traditional poled polymers. Furthermore, this polar order is intrinsic and thus doesn't require electric field poling and does not decay with time. The self-assembly process is therefore shown to possess great potential for the fabrication of high-speed electro-optic modulators for commercial and military applications. / Master of Science

Alpha7 Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in essential physiological functions and play a role in disorders such as Alzheimer’s disease. MD-354 (3-chlorophenylguanidine; 21), the first small–molecule negative allosteric modulator (NAM) at alpha7 nAChRs, served as a lead in developing structure–activity relationships for NAMs at a7 nAChRs. MD-354 (21) also binds at 5-HT3 receptors. Analogs of MD-354 with structural features detrimental to 5-HT3 receptor affinity were evaluated in patch-clamp recordings and an aniline N-methyl analog resulted in a more potent and selective NAM than MD-354. A new N-methyl series of compounds was synthesized in which the 3-position was replaced with different substituents considering their electronic, lipophilic, and steric nature. Comparative studies were initiated to investigate whether or not the MD-354 series and the N-methyl series bind in the same manner; 3D models of the extracellular domain of human alpha7 nAChRs were developed, allosteric sites identified, and docking studies conducted.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.