Sacrificial form: the libretti in English 1940-2000

This thesis focuses on the genre of libretto, the sung words for music theatre. The “little book” which accompanies every operatic performance is not just an extended program note to the spectacle, but in fact a substantial literary form in its own right. However, despite the immense influence of Wagner, the output from librettists in an operatic collaboration, has been serious ignored; indeed in opera the aesthetic function of language is frequently diminished and foreshortened, because it is often re-directed by and within the music. The result is that librettists are often seen as offering words to be “decomposed” by composers in the process of operatic collaboration. Opera, in the English language, finally achieved its rightful status, alongside its European counterparts, during the second half of the twentieth century. The thesis is intended to encompass something of the vast diversity of this genre and discusses a number of individual works as constituting legitimate literary artefacts in their own right. There will be five chapters featured in the thesis and each chapter is devoting to a specific theme

Generation of functional scFv intrabody to abate the expression of CD147 surface molecule of 293A cells

<p>Abstract</p> <p>Background</p> <p>Expression of intracellular antibodies (intrabodies) has become a broadly applicable technology for generation of phenotypic knockouts <it>in vivo</it>. The method uses surface depletion of cellular membrane proteins to examine their biological function. In this study, we used this strategy to block the transport of cell surface molecule CD147 to the cell membrane. Phage display technology was introduced to generate the functional antibody fragment to CD147, and we subsequently constructed a CD147-specific scFv that was expressed intracellularly and retained in the endoplasmic reticulum by adenoviral gene transfer.</p> <p>Results</p> <p>The recombinant antibody fragments, Fab and scFv, of the murine monoclonal antibody (clone M6-1B9) reacted specifically to CD147 by indirect enzyme-linked immunosorbent assays (ELISA) using a recombinant CD147-BCCP as a target. This indicated that the Fab- and scFv-M6-1B9 displaying on phage surfaces were correctly folded and functionally active. We subsequently constructed a CD147-specific scFv, scFv-M6-1B9-intrabody, in 293A cells. The expression of CD147 on 293A cell surface was monitored at 36 h after transduction by flow cytometry and demonstrated remarkable reduction. Colocalization of scFv-M6-1B9 intrabody with CD147 in the ER network was depicted using a 3D deconvolution microscopy system.</p> <p>Conclusion</p> <p>The results suggest that our approach can generate antibody fragments suitable for decreasing the expression of CD147 on 293A cells. This study represents a step toward understanding the role of the cell surface protein, CD147.</p

A Direct Approach to Sparse Discriminant Analysis in Ultra-high Dimensions

1 online resource (PDF, 27 pages

Human mobility increased with vaccine coverage and attenuated the protection of COVID-19 vaccination: a longitudinal study of 107 countries

Background: The World Health Organization has raised concerns that vaccinated people may reduce physical and social distancing more than necessary. With imperfect vaccine protection and the lifting of mobility restrictions, understanding how human mobility responded to vaccination and its potential consequence is critical. We estimated vaccination-induced mobility (VM) and examined whether it attenuates the effect of COVID-19 vaccination on controlling case growth. Methods: We collected a longitudinal data set of 107 countries between 15 February 2020 and 6 February 2022 from Google COVID-19 Community Mobility Reports, the Oxford COVID-19 Government Response Tracker, Our World in Data, and World Development Indicators. We measured mobility in four categories of location: retail and recreational places, transit stations, grocery stores and pharmacies, and workplaces. We applied panel data models to address unobserved country characteristics and used Gelbach decomposition to evaluate the extent to which VM has offset vaccination effectiveness. Results: Across locations, a 10-percentage-point (pp) increase in vaccine coverage was associated with a 1.4-4.3 pp increase in mobility (P < 0.001). VM was greater in lower-income countries (up to 7.9 pps; 95% confidence interval (CI) = 5.3 to 10.5, P < 0.001) and in earlier stages of vaccine rollouts (up to 19.2 pps; 95% CI = 15.1 to 23.2%, P < 0.001). VM decreased the effectiveness of vaccines in controlling case growth by 33.4% in retail and recreation places (P < 0.001), 26.4% in transit stations (P < 0.001), and 15.4% in grocery stores and pharmacies (P = 0.002). Conclusions: VM provides support for the Peltzman effect; it attenuates but does not completely counter vaccine effectiveness. Our study findings suggest strategies for mitigating the unintended consequences of VM, including reducing short-term mobility responses after vaccination, prioritizing mobility in grocery-type places and workplaces, and accelerating rollouts at earlier stages of vaccination, especially in lower-income countries

Functional Effects of let-7g Expression in Colon Cancer Metastasis.

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment

MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing.

The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC