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Currently, there is a lack of substantial integration in considering both natural and heritage environment with respect to managing change in either heritage conservation or environment protection. The failure of achieving harmonious environmental management can hence often be seen, leading to conflicting situation or even irreversible loss. This study therefore seeks to develop a framework/methodology for 'Harmonious Environmental Management of Cultural Heritage and Nature (i.e. water environment particularly)', to simultaneously mitigate the existing knowledge gaps in both domains, through a holistic view that is scarce in literature. The study primarily examines the issues from values-based theory, minimal intervention theory, the dichotomy between culture and nature, and the conduct of Heritage Impact Assessment (HIA), all play critical roles in managing change whilst they are either narrow in considerations or confined to some extents, leading to the inadequacy in application and the incapability to catch up with the latest revolution of heritage conservation that features broadening the lens to people and nature, rather than merely the fabric. The research proposes some novel perspectives and approaches, through the explorations from the sphere of philosophy, theory, practice, to application sphere, presented respectively as four chapters. Moreover, it covers different temporal (past, present and future) and spatial (regional and global) scales, as follows: 1) for the past, the regional pluralism of heritage conservation is echoed. It explores the philosophy of ancient Chinese regarding the interaction between people, nature and built world, as well as accommodating changes, as the underlying core concept-harmony-for the rest chapters; 2) for the present, a more comprehensive intervention approach featuring matrix thinking covering heritage, nature and people sphere is developed. Followed by examining the emerging issues in conducting HIA that has troubled the world: 3) the incompatibility of HIA within Environmental Impact Assessment (EIA), which portrays four patterns of statutory system from global lens, and proposes a HIA approach in response to the troublesome discourse; and 4) for the future, a participatory decision-making support method is developed for environmental planning involving water cultural heritage and nature, which is also a manifestation of the applicability of the proposed matrix approach. The integrated method tackles a real dilemma case in a historic town of Taiwan, with a scarce function of scenario forecasting to address the condition of the context. This part is presented as a more pragmatic and quantitative complement to the conceptual developments in the previous parts, for rounding out the whole exploration towards harmonious change management.

Pulmonary hypertension (PH) is characterized by structural remodelling of pulmonary arteries and arterioles, the result, at least in part, of excessive cell proliferation, resistance to cell death and hyperactive inflammatory reactions. Currently available treatments targeting the hyper-proliferative and pro-inflammatory pathology are limited. Epigenetic programming, dynamically regulated by histone acetylation, is an important mechanism for cell proliferation and survival. Aberrant changes of histone acetylation, modulated by histone deacetylase (HDAC), are shown in many proliferative and inflammatory disorders, especially cancer, and may contribute to the phenotypical changes in remodelling and overall to the development of PH. Hypothetically, HDAC inhibitors have therapeutic potential by reversing the imbalance of acetylation. I examined the correlations between HDAC expression and PH development, followed by evaluation of the pharmacological effects and possible mechanisms of two HDAC inhibitors, class I inhibitor valproic acid (VPA) and pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), on animal models and cellular systems. Altered HDAC expression, specifically increased HDAC1 and HDAC5 along with elevation of anti-apoptotic marker Bcl-2, were found in lungs from patients with idiopathic pulmonary arterial hypertension and chronically hypoxic rats. In in vivo studies, VPA and SAHA ameliorated the established PH in both hypoxia- and monocrotalineinduced PH rat models, by reducing pulmonary arterial pressure, right ventricular hypertrophy and pulmonary vascular muscularization, in parallel with increasing histone acetylation. In in vitro studies, VPA and SAHA inhibited stimulated cell growth of pulmonary artery smooth muscle cells and cytokine release from endothelial cells. Biochemical analysis indicated these two inhibitors exert anti-proliferative effects comprising cell cycle arrest by upregulation of p21 and apoptotic induction by downregulation of Bcl-2. Collectively, this study shows the contribution of abnormal HDAC activity to vascular pathology of PH and provides a preclinical basis to further explore the therapeutic potential of HDAC inhibitors in human PH.