Interactive Physics and Characteristics of Photons and Photoelectrons in Hyperbranched Zinc Oxide Nanostructures

As is commonly known, the world is full of technological wonders, where a multitude of electronic devices and instruments continuously help push the boundaries of scientific knowledge and discovery. These new devices and instruments of science must be utilized at peak efficiency in order to benefit humanity with the most advanced scientific knowledge. In order to attain this level of efficiency, the materials which make up these electronics, or possibly more important, the fundamental characteristics of these materials, must be fully understood. The following research attempted to uncover the properties and characteristics of a selected family of materials. Herein, zinc oxide (ZnO) nanomaterials were investigated and subjected to various, systematical tests, with the aim of discovering new and useful properties. The various nanostructures were grown on a quartz substrate, between a pair of gold electrodes, and subjected to an electrical bias which produced a measurable photocurrent under sufficient lighting conditions. This design formed a novel photodetector device, which, when combined with a simple solar cell and a methodical set of experimental trials, allowed several unique phenomena to be studied. Under various conditions, the device photocurrent as a function of applied voltage, as well as transmitted light, were measured and compared between devices of different ZnO morphologies. Zinc oxide is an absorber of ultraviolet (UV) light. UV absorbing materials and devices have uses in solar cells, long range communications, and astronomical observational equipment, hence, a better understanding of zinc oxide nanostructures and their properties can lead to more efficient utilization of UV light, improved solar cell technology, and a better understanding of the basic science in photon-to-electricity conversion

BUILDING TOOLS FOR IMPROVED MODULATION OF THE HUMAN GABAA RECEPTOR, A CENTRAL NERVOUS SYSTEM TARGET FOR THE TREATMENT OF ANXIETY

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market. The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABAA receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABAA receptor interaction suggests that constraining the isobutenyl group relative to the 5,6 membered ring system of VA could improve its binding specificity and affinity to the GABAA receptor. In planta, valerena-1,10-diene (VLD) is synthesized from farnesyl pyrophosphate (FPP) valerenadiene synthase (VDS), a sesquiterpene synthase. VLD is then carboxylated at one of its isobutenyl terminal methyl groups to yield VA. Our first objective was to engineer the VDS enzyme for altered product specificity and a more chemically constrained VLD scaffold. Using computational homology modelling and phylogenetic sequence analysis of characterized sesquiterpene synthases, amino acid residues in or near the active site and potentially impinging on catalytic specificity of VDS were identified. Residues were mutated via site-directed mutagenesis and mutants evaluated in vivo and in vitro. While wild type VDS’ products were 66 % VLD, 5 % allo-aromadendrene, and 29 % bicyclogermacrene (BCG), mutant Y535F yielded solely BCG. VDS with alanine or serine substituted for asparagine at position 455 lost all its ability to produce any of the wild type products and instead yielded a suite of seven new products dominated by germacrene-D-ol (≥ 40 %). To install a carboxylic acid functional group onto the sesquiterpene hydrocarbon scaffolds, we focused on the development of a host platform harboring an endomembrane system suitable for the expression of eukaryotic cytochrome P450 enzymes (P450s). As an example, plasmid co-expression of VDS, Lactuca sativa germacrene-A oxidase, and Artemisia annua cytochrome P450 oxidoreductase yielded an average 2mg/L of VA. For biological evaluation of sesquiterpene analogs, HEK293 cells transiently transfected with the human GABAA receptor subunit genes ⍺1, β3, and 2L, as well as a HEK293 cell line stably expressing the same GABA subunit genes, were optimized for sensing changes in membrane potential using a fluorescent bioassay. Effective concentration of test compounds and absolute magnitude of membrane depolarization in the transiently transfected cells gave the greatest responsiveness as determined for -aminobutyric acid (EC50 = 808 ± 206 nM, Emax = 13,309 ± 953 AFU’s), clonazepam (EC50 = 15 ± 8 nM, Emax = 4,211 ± 334 AFU’s), and VA (EC50 = 2,397 ± 341 nM, Emax = 5,935 ± 104 AFU’s). Abscisic acid, gibberellic acid, and cyclopartheniol demonstrated little to no detectable activity for modulating the human GABAA receptor

Evidence for changes in Holocene vegetation and lake sedimentation in the Markham Valley, Papua New Guinea

The past stability of vegetation patterns in the Markham Valley (6°30’S, 146°30’E), a lowland grassland area of Papua New Guinea, is investigated by pollen analysis of lake deposits and related palaeoecological techniques.¶ The predominantly organic sediments of Lake Wanum (alt. 35 m) span the last 9600 years. A 14C chronology supports the calculation of annual pollen deposition, sediment accumulation, and carbonised particle influx rates. At Yanamugi lake (alt. 170 m), 14C assays of the calcareous muds are influenced by variable ‘hard- water error’. A tentative chronology is based on palaeomagnetic and tephra correlations.¶ ..

Constituent order in the Tibetan noun phrase

This paper gives a schematic presentation of the order of constituents in the Tibetan noun phrase as revealed by an investigation of a corpus of Classical Tibetan texts

A Constraint Grammar POS-Tagger for Tibetan

This paper describes a rule-based part-of speech tagger for Tibetan, implemented in Constraint Grammar and with rules operating over sequences of syllables rather than words

Cellular transduction mechanisms of adeno-associated viral vectors

Recombinant adeno-associated viral vectors (rAAV) are regarded as promising vehicles for therapeutic gene delivery. Continued development and new strategies are essential to improve the potency of AAV vectors and reduce the effective dose needed for clinical efficacy. In this regard, many studies have focused on understanding the cellular transduction mechanisms of rAAV, often with the goal of exploiting this knowledge to increase gene transfer efficiency. Here, we provide an overview of our evolving understanding of rAAV cellular trafficking pathways through the host cell, beginning with cellular entry and ending with transcription of the vector genome. Strategies to exploit this information for improving rAAV transduction are discussed

A Rule-based Part-of-speech Tagger for Classical Tibetan

This paper reports on the development of a rule-based part-of-speech tagger for Classical Tibetan. Far from being an obscure tool of minor utility to scholars, the rule-based tagger is a key component of a larger initiative aimed at radically transforming the practice of Tibetan linguistics through the application of corpus and computational methods