Molecular pharmacology of DNA topoisomerase II drugs

Ph. D. ThesisTopoisomerase II (TOP2) is an important anti-cancer drug target. This study demonstrates that proteasomal inhibition by MG132 or PS341 potentiates the effect of TOP2 poisons on cell growth inhibition. Mitoxantrone was potentiated the most. The presence of the proteasome inhibitor MG132 prolonged the half-life of drug-induced DNA-TOP2 complexes stabilised by mitoxantrone or etoposide. Genotoxicity was measured in K562 cells using in vitro micronucleus assays for combinations of a proteasome inhibitor (MG132 or PS341) and mitoxantrone and for each agent alone. Combinations that potentiated the cytotoxicity reduced the genotoxicity. This suggests that combining a proteasome inhibitor with a TOP2 drug has the potential to reduce late toxicities such as therapy related leukaemia. The genotoxicity of six TOP2 poisons was determined by high throughput in vitro micronucleus assays in three Nalm-6 cell lines with differing TOP2 levels. Lower genotoxicity was observed in TOP2B knock-out and TOP2A knock-down cells, suggesting both TOP2A and TOP2B have a role in genotoxicity triggered by TOP2 poisonsBloodwis

What has China done for the global refugee problem in the past 20 years? : should China do more?

published_or_final_versionInternational and Public AffairsMasterMaster of International and Public Affair

Interpretation of Chinese modern poetry in light of a proposed theory of Shiyi

Modern Chinese poetry has since its inception been subjected to unfavourable comments as compared to classical Chinese poetry, which can be construed as the result of the alleged unintelligibility problem encountered in interpretation of poetry. This thesis attempts to find out if it is justified to attribute modern poetry’s poorer reception to the alleged unintelligibility problem. Accordingly, a purported criterion of poetry assessment, shiyi 詩意 (literally “poeticalness”), as well as a theoretical framework based on shiyi, is formulated primarily in light of Dan Sperber and Deirdre Wilson’s relevance theory and Paul Ricoeur’s hermeneutics. Whereas relevance theory is a cognitive pragmatic approach focusing on recovery of meanings of an utterance by tracing the authorial intention through relevance, Ricoeur’s hermeneutics sees textual interpretation as relying on a hermeneutical circle through which a reader produces a world of the text, itself also a means by which the reader attains or enriches self-understanding. To incorporate the speaker-centred relevance theory, Ricoeur’s comparatively reader-oriented model, as well as other related text-focused approaches into the proposed framework, the central concept of shiyi is put forward with a view to bridging the distance between emphasis on author, reader and text. The framework formulated should be more applicable to literary texts and less vulnerable to the intriguing authorship problematic. In addition, a “subtlety-unintelligibility continuum” is posited and developed within the framework to identify and account for the differences in shiyi, as well as to provide a clear characterisation of shiyi. The framework thus represents an interface between the linguistic, the philosophical and the literary perspectives. The overall objectives of this thesis are: (1) to prove that the proposed theory of shiyi and its underlying framework are theoretically and practically valid by putting the framework to the test through thoroughly analysing a number of representative modern Chinese poems, and (2) to justify or refute the propriety of attributing modern poetry’s poorer reception to the alleged unintelligibility problem based on findings of the analysis of poetry mentioned in (1)

China

Economic development processes in post-1949 China can be divided into two periods. In the first, 1950-70, the economy was extensively and intensively controlled by the state with a priority for developing heavy industries. In the second, since the 80s and known as the \u27reform period,\u27 the Chinese economy has increasingly been integrated with the world economy and relying on light (rural) industries as the prime motor of economic growth. Yet, in both these periods, Chinese policymakers shared the same \u27developmental\u27 philosophy in which social costs, that is the reproduction costs of human labour and nature, are largely ignored. The following is a critical sketch of government policies and their impact on the domestic population in these two periods

Capacity Estimation for Vehicle-to-Grid Frequency Regulation Services with Smart Charging Mechanism

Due to various green initiatives, renewable energy will be massively incorporated into the future smart grid. However, the intermittency of the renewables may result in power imbalance, thus adversely affecting the stability of a power system. Frequency regulation may be used to maintain the power balance at all times. As electric vehicles (EVs) become popular, they may be connected to the grid to form a vehicle-to-grid (V2G) system. An aggregation of EVs can be coordinated to provide frequency regulation services. However, V2G is a dynamic system where the participating EVs come and go independently. Thus it is not easy to estimate the regulation capacities for V2G. In a preliminary study, we modeled an aggregation of EVs with a queueing network, whose structure allows us to estimate the capacities for regulation-up and regulation-down, separately. The estimated capacities from the V2G system can be used for establishing a regulation contract between an aggregator and the grid operator, and facilitating a new business model for V2G. In this paper, we extend our previous development by designing a smart charging mechanism which can adapt to given characteristics of the EVs and make the performance of the actual system follow the analytical model.Comment: 11 pages, Accepted for publication in IEEE Transactions on Smart Gri

Call for quality epilepsy neuroimaging—An illustrative case of missed epileptic substrate

No. 779