Prostate cancer is the most common cancer in men in the western world. Although early stage prostate cancer is treatable late stage, more specifically, metastatic and drug resistant prostate cancers are mostly incurable. The failure of current treatments obligates the research community to explore novel areas in prostate cancer biology and find better therapeutic targets. Emerging evidences show that non-coding RNAs specifically long non-coding RNAs (lncRNAs) play regulatory roles in various cellular processes and are frequently dysregulated in cancer including prostate cancer. These aberrantly expressed lncRNAs mostly with unexplored genetic information may drive cancer progression. Previous studies done in our laboratory showed a tumor suppressor role of a cluster of small non-coding RNAs or microRNA (miRNA) miR-17-92a in PC-3 prostate cancer cells. To learn the underlying mechanism, transcriptome analysis with or without expression of miR-17-92a was conducted in our laboratory. RNA-sequencing data analysis identified reduced expression of a set of lncRNAs and oncogenes, and up regulation of several tumor suppressor genes upon expression of miR-17-92a cluster miRNAs. One of the down regulated intergenic lncRNAs, PAINT (Prostate Cancer Associated Intergenic Non-coding Transcript) (LINC00888), was selected for determining its functional role in prostate cancer. TCGA and GEO profiles analyses revealed up regulation of PAINT in prostate tumors with higher Gleason Scores, in highly aggressive metastatic prostate cancer cell lines, and upon androgen deprivation therapy of prostate cancer cells. This observation was supported by our studies on expression analysis of PAINT in prostate tumor tissues using RNA in-situ hybridization in tissue microarrays (TMA) containing tissues from different stages of prostate cancer and normal prostate tissues, which showed higher expression of PAINT in prostate cancer tissues compared to normal tissues. Furthermore, late stage (stage III and stage IV) prostate tumors showed significant overexpression of PAINT compared to early stage (stage II) prostate cancer tissues. We examined the functional relevance of PAINT in promoting tumor progression next using different prostate cancer cell lines. Silencing of PAINT using siRNAs showed decreased cell proliferation, reduced S-phase progression and activation of pro-apoptotic proteins PARP and Caspase-3. Silencing of PAINT also showed decreased cell migration and increased expression of the epithelial marker, E-cadherin while reduced expression of mesenchymal markers Slug and Vimentin. Ectopic expression of PAINT reversed the effects observed upon silencing of PAINT. Increased cell proliferation, cell cycle progression and cell migration were noted in prostate cancer cells overexpressing PAINT. Additionally, cancer promoting phenotype such as larger colony formation and higher expression of mesenchymal marker Slug, was detected upon overexpression of PAINT. Our study also determined the therapeutic benefit of inhibition of expression showing an increased sensitivity of metastatic prostate cancer cells to the chemotherapeutic agent docetaxel (DTX) and selective Aurora kinase inhibitor VX-680. Taken together, our study establishes an oncogenic function of PAINT, its clinical relevance as a marker for advanced stage prostate cancer and its potential as a therapeutic target for metastatic prostate cancer.

Phenylethanolamine N-methyltransferase (Pnmt) is the enzyme that N-methylates norepinephrine to produce the stress hormone/neurotransmitter, epinephrine, which is abundantly expressed in adrenal glands. Developmental studies have also identified Pnmt expression in the embryonic heart and several areas of the brain, including brainstem, cerebellum, and hypothalamus. Thus, we hypothesize that selective ablation of Pnmt+ cells will have detrimental effects on cardiovascular, neuromuscular, and metabolic processes. To uncover the importance of Pnmt+ cells in vivo, we generated a novel Diphtheria Toxin A (DTA) suicide model (Pnmt+/Cre; R26+/DTA) to selectively ablate Pnmt-expressing (Pnmt+) cells in mice. Appearing normal at birth, Pnmt-Cre/DTA mice began to develop apparent cardiovascular, neurological, and metabolic impairments soon thereafter. To measure cardiac function, we performed quantitative echocardiography, electrocardiography (ECG), and blood pressure measurements. Key findings from these assessments indicated decreased left-ventricular performance, slowed atrioventricular conduction, and increased pulse pressure in the Pnmt-Cre/DTA ablation mice. These mice also showed signs of motor control deficits as early as one month, which progressively worsened with age. To assess these effects, we performed standard motor tests including hind-limb clasping, grip strength, and rotarod balance tests. Moreover, we found that the Pnmt-Cre/DTA mice ceased to gain weight shortly after puberty. The motor and metabolic deficits apparent in these animals suggested potential neurological impairments, and we thus undertook immunohistochemical staining experiments to determine the localization of Pnmt+ cells in the brain. Staining revealed Pnmt expression in the Purkinje cells of the cerebellum (motor), paraventricular nucleus of the hypothalamus (metabolic), and surprisingly extensive staining in the cerebral cortex. These results demonstrate that Pnmt+ cell contributions in the brain are much more extensive than previously thought. Overall, this work opens new pathways that will have substantial impacts on our understanding of the roles Pnmt+ cells play in normal development and disorders affecting cardiovascular, motor, and metabolic functions.

Thesis (Ph. D.)--University of Virginia, 1994. / Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xiii, 202 p.; also includes graphics. Includes abstract and vita. Advisor: Ian M. Sheldon, Dept. of Agricultural, Environmental and Development Economics. Includes bibliographical references (p. 197-202).

Thesis (Ph. D.)--Ohio State University, 2004. / Includes bibliographical references (p. 197-202). Also available online.

Thesis (M. Sc. (Urb. Plan.))--University of Hong Kong, 1994. / Includes bibliographical references (leaves 137-142).

Class of 2010 Abstract / OBJECTIVES: (1) To characterize the long-term performance of the biotechnology sector and the overall market using a Sharpe Ratio analysis (excess return/volatility; α/SD). The null hypothesis tested in this paper is the generalized Sharpe ratio characteristic of the biotechnology sector is identical to that of the overall market. METHODS: 337 companies were identified using Standard Industry Classification code 2836 (Biological Products, (No Diagnostic Substances)) lists from the Center for Research and Security Prices (CRSP) and S&P CompuStat databases. Market data on equity and return were derived from securities price data from the CRSP database. Market data were used to characterize the following measures: Mean Excess Return, Mean Excess Return minus 1% of top earners (trimmed), Volatility (SD),Sharpe Ratio and 1% Adjustment RESULTS: The study finds the biotech industry earned excess returns of 13.84% over time when compared to the overall market ( 5.10%). However, these returns are highly concentrated: When the top 1% of sector earners are removed from analysis, excess return declines below the risk free rate (return of -0.05%) suggesting significant barriers to risk diversification. CONCLUSIONS: The results show the biotechnology sector experiences higher volatility compared with the overall market, as well as higher excess returns. The results justify a rejection of the null hypothesis – that the generalized Sharpe ratio of the biotechnology sector is identical to that of the overall market

Ho Wing Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 110-123). / Abstracts in English and Chinese. / Chapter 1 --- Introduction / Chapter 1.1 --- Bioconversion --- p.1 / Chapter 1.2 --- Functional foods & quality improvement in fermentation Edible mushroom --- p.2 / Chapter 1.3 --- Substrates --- p.4 / Chapter 1.4 --- Edible mushroom --- p.6 / Chapter 1.5 --- Nutritional value of food and feed --- p.9 / Chapter 1.6 --- Protein digestibility --- p.16 / Chapter 1.7 --- Problem caused by fungal contamination --- p.17 / Chapter 1.8 --- Antioxidant --- p.18 / Chapter 1.9 --- Research objectives --- p.20 / Tables and figures --- p.21 / Chapter 2 --- Materials and Methods / Chapter 2.1 --- Materials --- p.32 / Chapter 2.2 --- Sample preparation --- p.33 / Chapter 2.3 --- Fungal growth measurement --- p.34 / Chapter 2.4 --- Proximate compositions --- p.34 / Chapter 2.4.1 --- Moisture determination --- p.34 / Chapter 2.4.2 --- Ash determination --- p.35 / Chapter 2.4.3 --- Crude lipid determination --- p.35 / Chapter 2.4.4 --- Dietary fiber determination --- p.36 / Chapter 2.4.5 --- Crude protein determination --- p.38 / Chapter 2.4.6 --- Carbohydrate determination --- p.38 / Chapter 2.4.7 --- Glucose determination --- p.39 / Chapter 2.4.8 --- Chitin determination --- p.40 / Chapter 2.4.9 --- Phytic acid determination --- p.41 / Chapter 2.5 --- In vitro protein digestibility --- p.42 / Chapter 2.6 --- Aflatoxin determination --- p.43 / Chapter 2.7 --- Antioxidant ability --- p.45 / Chapter 2.7.1 --- Ferric reducing antioxidant powder (FRAP) assay --- p.45 / Chapter 2.7.2 --- Trolox equivalent antioxidant capacity (TEAC) assay --- p.46 / Chapter 2.8 --- Statistical analysis --- p.47 / Table --- p.48 / Chapter 3 --- Results / Chapter 3.1 --- Mycelia growth --- p.49 / Chapter 3.1.1 --- Growth diameter --- p.49 / Chapter 3.1.2 --- Chitin content --- p.50 / Chapter 3.2 --- Weigh loss in sample preparation --- p.51 / Chapter 3.3 --- Proximate composition --- p.52 / Chapter 3.3.1 --- Moisture --- p.52 / Chapter 3.3.2 --- Ash --- p.52 / Chapter 3.3.3 --- Crude lipid --- p.53 / Chapter 3.3.4 --- Dietary fiber --- p.54 / Chapter 3.3.5 --- Crude protein --- p.55 / Chapter 3.3.6 --- Carbohydrate content --- p.56 / Chapter 3.3.7 --- Glucose content --- p.56 / Chapter 3.3.8 --- Phytic acid --- p.56 / Chapter 3.4 --- In vitro protein digestibility (IVPD) --- p.57 / Chapter 3.5 --- Aflatoxin --- p.53 / Chapter 3.6 --- Antioxidant ability --- p.58 / Chapter 3.6.1 --- Ferric reducing antioxidant powder (FRAP) assay --- p.58 / Chapter 3.6.2 --- Trolox equivalent antioxidant capacity (TEAC) assay --- p.60 / Tables and figures --- p.62 / Chapter 4 --- Dissusions / Chapter 4.1 --- Mycelia growth --- p.89 / Chapter 4.2 --- Weigh loss in sample preparation --- p.90 / Chapter 4.3 --- Proximate composition --- p.90 / Chapter 4.3.1 --- Moisture --- p.90 / Chapter 4.3.2 --- Ash --- p.91 / Chapter 4.3.3 --- Crude lipid --- p.92 / Chapter 4.3.4 --- Dietary fiber --- p.93 / Chapter 4.3.5 --- Crude protein --- p.96 / Chapter 4.3.6 --- Glucose concentration --- p.98 / Chapter 4.3.7 --- Phytic acid --- p.99 / Chapter 4.4 --- In vitro protein digestibility (IVPD) --- p.101 / Chapter 4.5 --- Aflatoxin --- p.102 / Chapter 4.6 --- Antioxidant activity --- p.103 / Chapter 4.7 --- Bioconversion ability --- p.105 / Chapter 4.8 --- Best substrate --- p.105 / Chapter 4.9 --- Functional foods --- p.106 / Chapter 4.10 --- Limitation of the methodology and future development --- p.107 / Table --- p.108 / Chapter 5 --- Conclusion --- p.109 / References

Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1989. / Includes bibliographical references (leaves 159-172) / Microfiche. / xvii, 172 leaves, bound ill. 29 cm

Biotechnology is one of the most important emerging technologies of the 21st century and has already attracted worldwide interest. Biotechnology has been touted as the next revolution in the high technology industry following the computer-telecommunications boom. Modern biotechnology is now widely applied to almost all areas of human life, such as medicine, pharmaceuticals, agriculture, food products, energy, and environmental ecology. However, biotechnology can be said to be still in its early developmental stage and both developed and developing countries recognize its potential contribution. / Thesis (DBA(DoctorateofBusinessAdministration))--University of South Australia, 2005.