Doctor of Philosophy

dissertationThis dissertation consists of two essays. Each essay measures how changes in particular market rules and structure affect financial market outcomes. The essays assess two of the most debated regulatory issues that have arisen in recent years, speculative trading and transparency, respectively. The implication of the empirical results obtained in both essays is that the financial market reacts to regulatory changes and that regulations designed to improve the financial market do not necessarily yield the expected outcome. Both studies provide useful policy implications in terms of improving the quality of financial markets. In the first essay, I evaluate how increased speculator participation in the commodity futures market affects market outcomes, including trades' price impacts, price volatility, and market quality. The results indicate that speculators either have no effect or stabilize prices during periods of substantial price movement. Speculators on average sell during periods of large price appreciation, consistent with the interpretation that speculators' trades dampen rather than accentuate price increases. My analysis also reveals that futures speculation reduces spot price volatility and that futures speculation either has no effect or improves liquidity and short-term efficiency in the commodity market. Recent policy changes under the Dodd-Frank Act aim to regulate speculative trading in the futures market to bring order to the commodity markets. My study suggests that these regulatory changes may well be counterproductive to that goal. The second essay examines the effect of enhanced transparency on firm value and liquidity by studying the introduction and subsequent discontinuation of the NextPrime and NextEconomy market segments on the Euronext stock market. I document positive effects on firm value and liquidity for the firms that opted into the segments, thereby committing to enhanced transparency and improved reporting quality. However, when similar market regulations were imposed on all listed firms, I document negative valuation effects, on average. My analysis offers an important implication regarding rules governing market transparency: firms' self-regulation to improve transparency can be more effective than marketwide mandatory regulation

Improvement of photon extraction efficiency of GaN-based LED using micro and nano complex polymer structures

A micro- and nanoscale complex structure made of a high refractive index polymer (n = 2.08) was formed on the ITO electrode layer of an edge-emitting type GaN blue light-emitting diode (LED), in order to improve the photon extraction efficiency by suppressing total internal reflection of photons. The nanoimprint lithography process was used to form the micro- and nanoscale complex structures, using a polymer resin with dispersed TiO2 nano-particles as an imprint resin. Plasma processing, such as reactive ion etching, was used to form the micro- and nano-scale complex structure; thus, plasma-induced damage to the LED device can be avoided. Due to the high refractive index polymeric micro- and nanostructure on the ITO layer, the electroluminescence emission was increased up to 20%, compared to an identical LED that was grown on a patterned sapphire substrate to improve photon extraction efficiency

High-resolution crystal structure of the non-specific lipid-transfer protein from maize seedlings

AbstractBackground: The movement of lipids between membranes is aided by lipid-transfer proteins (LTPs). Some LTPs exhibit broad specificity, transferring many classes of lipids, and are termed non-specific LTPs (ns-LTPs). Despite their apparently similar mode of action, no sequence homology exists between mammalian and plant ns-LTPs and no three-dimensional structure has been reported for any plant ns-LTP.Results We have determined the crystal structure of ns-LTP from maize seedlings by multiple isomorphous replacement and refined the structure to 1.9 å resolution. The protein comprises a single compact domain with four α-helices and a long C-terminal region. The eight conserved cysteines form four disulfide bridges (assigned as Cys4–Cys52, Cys14–Cys29, Cys30–Cys75, and Cys50–Cys89) resolving the ambiguity that remained from the chemical determination of pairings in the homologous protein from castor bean. Two of the bonds, Cys4–Cys52 and Cys50–Cys89, differ from what would have been predicted from sequence alignment with soybean hydrophobic protein. The complex between maize ns-LTP and hexadecanoate (palmitate) has also been crystallized and its structure refined to 1.8 å resolution.Conclusion The fold of maize ns-LTP places it in a new category of all-α-type structure, first described for soybean hydrophobic protein. In the absence of a bound ligand, the protein has a tunnel-like hydrophobic cavity, which is large enough to accommodate a long fatty acyl chain. In the structure of the complex with palmitate, most of the acyl chain is buried inside this hydrophobic cavity

Crystal structure of xenotropic murine leukaemia virus-related virus (XMRV) ribonuclease H

RNase H (retroviral ribonuclease H) cleaves the phosphate backbone of the RNA template within an RNA/DNA hybrid to complete the synthesis of double-stranded viral DNA. In the present study we have determined the complete structure of the RNase H domain from XMRV (xenotropic murine leukaemia virus-related virus) RT (reverse transcriptase). The basic protrusion motif of the XMRV RNase H domain is folded as a short helix and an adjacent highly bent loop. Structural superposition and subsequent mutagenesis experiments suggest that the basic protrusion motif plays a role in direct binding to the major groove in RNA/DNA hybrid, as well as in establishing the co-ordination among modules in RT necessary for proper function.Molecular and Cellular Biolog

Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model

Background Mesenchymal stem cells (MSCs) are used for the treatment of osteoarthritis (OA), and MSC genetic engineering is expected to enhance cartilage repair. Here, we aimed to investigate the effect of MSCs overexpressing platelet-derived growth factor (PDGF) or heme oxygenase-1 (HO-1) in chondrocytes and synovial cells with an OA phenotype and assess the in vivo efficacy of intra-articular injections of these MSCs in canine OA models. Methods Canine adipose-derived MSCs were transfected with canine PDGF (PDGF-MSCs) or HO-1 (HO-1-MSCs) using lentiviral vectors. Canine chondrocytes or synovial cells were stimulated with lipopolysaccharide (LPS) to mimic the inflammatory OA model and then co-cultured with MSCs, PDGF-MSCs, or HO-1-MSCs for 24 h and 72 h. The mRNA levels of pro-inflammatory, extracellular matrix-degradative/synthetic, or pain-related factors were measured after co-culture by real-time PCR. Furthermore, a surgery-induced canine OA model was established and the dogs were randomized into four groups: normal saline (n = 4), MSCs (n = 4), PDGF-MSCs (n = 4), and HO-1-MSCs (n = 4). The OA symptoms, radiographic OA severity, and serum matrix metallopeptidase (MMP)-13 levels were assessed before and 10 weeks after treatment, to evaluate the safety and efficacy of the modified MSCs. Results PDGF or HO-1 overexpression significantly reduced the expression of pro-inflammatory factors, MMP-13, and nerve growth factor elicited by LPS and increased that of aggrecan and collagen type 2 in chondrocytes (P < 0.05). In addition, the expression of aggrecanases was significantly downregulated in synovial cells, whereas that of tissue inhibitor of metalloproteinases was upregulated (P < 0.05). Furthermore, the co-cultured MSCs highly expressed genes that contributed to the maintenance of joint homeostasis (P < 0.05). In vivo studies showed that OA symptoms improved after administration of all MSCs. Also, PDGF-MSCs significantly improved limb function and reduced pain (P < 0.05). The results of the radiographic assessment and serum MMP-13 levels did not vary significantly compared to those of the control. Conclusions Genetically modifying PDGF and HO-1 in MSCs is an effective strategy for treating OA, suggesting that PDGF-MSCs can be novel therapeutic agents for improving OA symptoms

Effectiveness of electroacupuncture on anxiety: a systematic review and meta-analysis of randomized controlled trials

This systematic review and meta-analysis aimed to comprehensively evaluate the effectiveness of electroacupuncture (EA) for patients with anxiety. Randomized controlled trials (RCTs) on the treatment of anxiety by EA up to November 2022 were searched and collected from nine databases. Hamilton Anxiety Rating Scale (HAMA), self-rating anxiety scale (SAS), and adverse reactions were used as outcome indicators. The quality of relevant articles was evaluated using the Cochrane Collaboration’s risk of bias tool. The quality of evidence for each outcome was classified as “low risk,” “unclear risk,” or “high risk.” RevMan 5.0 was used for data analysis. A total of 633 articles were identified from nine electronic databases; 37 RCTs were included, which measured anxiety changes by using EA alone compared to the control group. For the main outcome, EA significantly reduced the HAMA score [Mean difference (MD):−1.13 (95% CI:−2.55–0.29), I2:80%], and the quality of evidence was moderate. EA significantly reduced the SAS score (MD:−3.47 (95% CI,−6.57−−0.36), I2:88%), and the quality of evidence was moderate. Our meta-analysis shows that EA reduces HAMA and SAS. This study suggests that EA can relieve anxiety. For various uses, additional research is needed on its effect when combined with other treatments.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=345658, identifier (CRD42022345658)

Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation

DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next-generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short-term calorie restriction (CR) on the methylome of aged rat kidney. Whole-genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats was analyzed by methylated DNA immunoprecipitation and next-generation sequencing (MeDIP-Seq). CpG islands and repetitive regions were hypomethylated, but 5&apos;-UTR, exon, and 3&apos;-UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short-term CR could partially ameliorate age-related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease-related genes during aging may indicate increases in susceptibility to age-related diseases. Therefore, the CR-induced epigenetic changes that ameliorate age-dependent aberrant methylation may be important to CR&apos;s health-and life-prolonging effects.ope

Synthesis of High Crystalline Al-Doped ZnO Nanopowders from Al 2

High crystalline Al-doped ZnO (AZO) nanopowders were prepared by in-flight treatment of ZnO and Al2O3 in Radio-Frequency (RF) thermal plasma. Micron-sized (~1 μm) ZnO and Al2O3 powders were mixed at Al/Zn ratios of 3.3 and 6.7 at.% and then injected into the RF thermal plasma torch along the centerline at a feeding rate of 6.6 g/min. The RF thermal plasma torch system was operated at the plate power level of ~140 kVA to evaporate the mixture oxides and the resultant vapor species were condensed into solid particles by the high flow rate of quenching gas (~7000 slpm). The FE-SEM images of the as-treated powders showed that the multipod shaped and the whisker type nanoparticles were mainly synthesized. In addition, these nanocrystalline structures were confirmed as the single phase AZO nanopowders with the hexagonal wurtzite ZnO structure by the XRD patterns and FE-TEM results with the SAED image. However, the composition changes of 0.3 and 1.0 at.% were checked for the as-synthesized AZO nanopowders at Al/Zn ratios of 3.3 and 6.7 at.%, respectively, by the XRF data, which can require the adjustment of Al/Zn in the mixture precursors for the applications of high Al doping concentrations