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Shipping emissions control is critical to air quality management and improved public health for coastal port cities and regions with heavy marine traffic. However, Asian port cities have been slow in introducing regulations on marine fuels for two main reasons – firstly, due to a lack of information and therefore appreciation on the air quality and public health benefits that could be derived; and secondly, due to sensitivity as to whether there may be negative impacts on port competitiveness and trade opposition. Hong Kong, one of the top-ten international container ports in the world, has been proactive in reducing shipping emissions in the past decade. The Ocean Going Vessels Fuel at Berth regulation, enforced since July 2015 in Hong Kong, is the first marine fuel control regulation for ocean going vessels in Asia. This regulation has been adopted nationally by China for its coastal ports, followed by the establishment of domestic emission control areas in its coastal waters that will come into force in 2019. This paper describes the decade-long journey where scientific research led to evidence-based policy changes. New insights and understanding arising from the research enabled cross-sectoral engagement and dialogue among the key stakeholders in government, industry and civil society, which resulted in the political consensus needed for a change in policy and legislation. Similar evidence-based policy formulation, together with public-private sectors dialogue could be useful to other jurisdictions in pursuing a “win-win” path to improve environmental protection and public health through regulating shipping emissions. The same combination of science-to-engagement-to-policy approach could also become part of a knowledge-and-consensus-building process for other environmental policy areas as well. [ABSTRACT FROM AUTHOR]

Abstract: A new exhaust emission inventory of ocean-going vessels (OGVs) was compiled for Hong Kong by using Automatic Identification System (AIS) data for the first time to determine typical main engine load factors, through vessel speed and operation mode characterization. It was found that in 2007, container vessel was the top emitting vessel type, contributing 9,886, 11,480, 1,173, 521 and 1166 tonnes of SO2, NO x , PM10, VOC and CO, respectively, or about 80%–82% of the emissions. The top five, which also included ocean cruise, oil tanker, conventional cargo vessel and dry bulk carrier, accounted for about 98% of emissions. Emission maps, which add a new spatial dimension to the inventory, show the key emission hot spots in Hong Kong and suggest that a significant portion of emissions were emitted at berth. Scientific evidence about the scale and distribution of ship emissions has contributed in raising public awareness and facilitating stakeholder engagement about the issue. Fair Winds Charter, the world's first industry-led voluntary emissions reduction initiative, is a perfect example of how careful scientific research can be used in public engagement and policy deliberation to help drive voluntary industry actions and then government proposals to control and regulate marine emissions in Hong Kong and the Pearl River Delta region. [Copyright &y& Elsevier]

The Fair Winds Charter is a good example of public-private-NGO sector collaboration that can create the framework for future legislation covering emissions throughout the Pearl River Delta (PRD). The Fair Winds Charter is the first agreement of its kind. The Charter calls on regional governments to regulate the shipping sector. This report explains the importance of stakeholder engagement in increasing policy understanding and acceptance, the value of data and cross-disciplinary research in air quality and public health for developing a compelling case for policy change; and how the science and stakeholder engagement stimulated regulatory change under the public-private- NGO umbrella of engagement. [ABSTRACT FROM AUTHOR]

The article focuses on the civil society in Hong Kong, China. It notes that many residents engaged in civil society activities as citizen wealth grows and social awareness rises. It offers an overview of the non-governmental groups (NGOs) including human rights, law, philanthropy, and culture. It also mentions that the city has emerged as a more cosmopolitan society with many people concerned with social issues including pollution, equal rights, and quality education.

The article examines the role that Hong Kong plays in the process of modernization in China. It argues that the role of Hong Kong is that of a transforming catalyst. Beijing from time to time has to put aside its normal instincts in dealing with the affairs of this city. This creates opportunities with potentially far-reaching consequences, though questions have often been raised as to whether two systems will survive as Hong Kong becomes more integrated into one China. In conclusion, Hong Kong has a gradual transforming effect on China's modernization.

The new Principal Officials Accountability System (POAS), a proto-ministerial system, was established at the start of the Second Term of Office of the Chief Executive of the Hong Kong Special Administrative Region (HKSAR). This paper examines the setting-up of the POAS and reviews how it has functioned during its first year of life. Both the design and implementation of the POAS were characterized by undue haste. The establishing of the POAS intensified the debate on a range of matters as new ministers, senior civil servants and residents have come to terms with the detail of this novel arrangement. Discussions about political reform are set to intensify in the years to come. This article reviews the origins and deeper need for the POAS in Hong Kong before looking at the fundamentals of the new system. The nature of 'accountability' is then discussed prior to examining Hong Kong's experience with the POAS in action during its first year. The article also discusses the potential of the POAS to contribute to Hong Kong's overall political development. [ABSTRACT FROM AUTHOR]

Reveals the changes in the notions of democracy and the conception of citizenship through a study of elections and political participation in Greater China. Definition of democracy and democratic participation in the context of liberal democracies; Form of government in China; System of governance adopted by the Kuomintang and the Chinese Community Party; Discussion of the political system in Taiwan and Hong Kong; Impact of the functional constituencies system on Hong Kong.

Focuses on the relationship between Hong Kong and the Commonwealth. Commonwealth's position on Hong Kong's transition from British to Chinese rule; Effects of Hong Kong's economic growth; History of British rule in Hong Kong; Challenges in Hong Kong's transition in 1997.

This article represents a first attempt to pull together relevant materials with the aim of providing a broad-brush view of how climate change may affect Greater Pearl River Delta (GPRD) region (Hong Kong, Macau and the Pearl River Delta). Among the various consequences of climate change, rising sea levels are a matter of great concern for the GPRD region, which is made vulnerable both by its physical geography (the southern part of the delta lies between - 0.3m to 0.4m relative to mean sea level (MSL)) and its urban development. More in-depth research and modeling remain to be done so that the authorities, business and civil society can better understand climate impacts on the region, but this article shows that climate change could have a big impact on the regional economy, which represents nearly 10% of China's GNP. The paper concludes with a discussion of the measures that government and businesses will need to consider in order to adapt to these future conditions. [ABSTRACT FROM AUTHOR]

Retinoic acid receptor-related orphan nuclear receptor γ (RORγ) orchestrates a pro-inflammatory gene expression programme in multiple lymphocyte lineages including T helper type 17 (Th17) cells, γδ T cells, innate lymphoid cells and lymphoid tissue inducer cells. There is compelling evidence that RORγ-expressing cells are relevant targets for therapeutic intervention in the treatment of autoimmune and inflammatory diseases. Unlike Th17 cells, where RORγ expression is induced under specific pro-inflammatory conditions, γδ T cells and other innate-like immune cells express RORγ in the steady state. Small molecule mediated disruption of RORγ function in cells with pre-existing RORγ transcriptional complexes represents a significant and challenging pharmacological hurdle. We present data demonstrating that a novel, selective and potent small molecule RORγ inhibitor can block the RORγ-dependent gene expression programme in both Th17 cells and RORγ-expressing γδ T cells as well as a disease-relevant subset of human RORγ-expressing memory T cells. Importantly, systemic administration of this inhibitor in vivo limits pathology in an innate lymphocyte-driven mouse model of psoriasis. [ABSTRACT FROM AUTHOR]

Circadian rhythms govern a wide variety of physiological and metabolic functions in many organisms, from prokaryotes to humans. We previously reported that silent information regulator 1 (SIRT1), a NAD+-dependent deacetylase, contributes to circadian control. In addition, SIRT1 activity is regulated in a cyclic manner in virtue of the circadian oscillation of the coenzyme NAD+. Here we used specific SIRT1 activator compounds both in vitro and in vivo. We tested a variety of compounds to show that the activation of SIRT1 alters CLOCK:BMAL1-driven transcription in different systems. Activation of SIRT1 induces repression of circadian gene expression and decreases H3 K9/K14 acetylation at corresponding promoters in a time-specific manner. Specific activation of SIRT1 was demon- strated in vivo using liver-specific SIRT1-deficient mice, where the effect of SIRT1 activator compounds was shown to be dependent on SIRT1. Our findings demonstrate that SIRT1 can fine-tune circadian rhythm and pave the way to the development of pharmacological strategies to address a broad range of therapeutic indications. [ABSTRACT FROM AUTHOR]

Chronic inflammation is a major contributing factor in the pathogenesis of many age-associated diseases. One central protein that regulates inflammation is NF-κB, the activity of which is modulated by post-translational modifications as well as by association with co-activator and co-repressor proteins. SIRT1, an NAD+-dependent protein deacetylase, has been shown to suppress NF-κB signaling through deacetylation of the p65 subunit of NF-κB resulting in the reduction of the inflammatory responses mediated by this transcription factor. The role of SIRT1 in the regulation of NF-κB provides the necessary validation for the development of pharmacological strategies for activating SIRT1 as an approach for the development of a new class of anti-inflammatory therapeutics. We report herein the development of a quantitative assay to assess compound effects on acetylated p65 protein in the cell. We demonstrate that small molecule activators of SIRT1 (STACs) enhance deacetylation of cellular p65 protein, which results in the suppression of TNFα-induced NF-κB transcriptional activation and reduction of LPS-stimulated TNFα secretion in a SIRT1-dependent manner. In an acute mouse model of LPS-induced inflammation, the STAC SRTCX1003 decreased the production of the proinflammatory cytokines TNFα and IL-12. Our studies indicate that increasing SIRT1-mediated NF-κB deacetylation using small molecule activating compounds is a novel approach to the development of a new class of therapeutic anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Abstract: The design and development of a series of highly selective pyrrolidine carboxamide 11β-HSD1 inhibitors are described. These compounds including PF-877423 demonstrated potent in vitro activity against both human and mouse 11β-HSD1 enzymes. In an in vivo assay, PF-877423 inhibited the conversion of cortisone to cortisol. Structure guided optimization effort yielded potent and stable 11β-HSD1 selective inhibitor 42. [Copyright &y& Elsevier]

Abstract: PC-1 (NPP-1) inhibitors may be useful as therapeutics for the treatment of CDDP (calcium pyrophosphate dehydrate) deposition disease and osteoarthritis. We have identified a series of potent quinazolin-4-piperidin-4-ethyl sulfamide PC-1 inhibitors. The series, however, suffers from high affinity binding to hERG potassium channels, which can cause drug-induced QT prolongation. We used a hERG homology model to identify potential key interactions between our compounds and hERG, and the information gained was used to design and prepare a series of quinazolin-4-piperidin-4-methyl sulfamides that retain PC-1 activity but lack binding affinity for hERG. [Copyright &y& Elsevier]

Abstract: The key role of kinases in signal transduction and cell growth regulation has been a long standing interest among academics and the pharmaceutical industry. Recombinant enzymes have been used to understand the mechanism of action as well as to screen for chemical inhibitors. The baculo-insect system has been the primary method used to obtain soluble and active kinases, usually producing a mixture of the kinase in various phosphorylation states in different conformations. To obtain a homogenous preparation of non-phosphorylated kinases is critical for biochemical, biophysical and kinetic studies aimed at understanding the mechanism of kinase activation. Taking advantage of the eukaryotic expression property of insect cells, we were able to obtain high yield expression of non-phosphorylated protein tyrosine kinases BTK, JAK3 and Eph2A through coexpression with the tyrosine phosphatase YopH, which suggests that this method can be applied to protein tyrosine kinases in general. We have demonstrated that the fully non-phosphorylated BTK obtained with this method is suitable for various biochemical and kinetic studies. [Copyright &y& Elsevier]

Air quality has deteriorated in Hong Kong over more than 15 yr. As part of a program of public accountability, photographs on Poor and Better visibility days were used as representations of the relationships among visibility, air pollution, adverse health effects, and community costs for health care and lost productivity. Coefficients from time-series models and gazetted costs were used to estimate the health and economic impacts of different levels of pollution. In this population of 6.9 million, air quality improvement from the annual average to the lowest pollutant levels of Better visibility days, comparable to the World Health Organization air quality guidelines, would avoid 1335 deaths, 60,587 hospital bed days, and 6.7 million doctor visits for respiratory complaints each year. Direct costs and productivity losses avoided would be over US$240 million a year. The dissemination of these findings led to increased demands for pollution controls from the public and legislators, but denials of the need for urgent action arose from the government. The outcome demonstrates the need for more effective translation of the scientific evidence base into risk communication and public policy. [ABSTRACT FROM AUTHOR]

Polo-like kinase 1 (Plk1) is an attractive target for the development of anticancer agents due to its importance in regulating cell-cycle progression. Overexpression of Plk1 has been detected in a variety of cancers, and expression levels often correlate with poor prognosis. Despite high interest in Plk1-targeted therapeutics, there is currently no structure publicly available to guide structure-based drug design of specific inhibitors. We determined the crystal structures of the T210V mutant of the kinase domain of human Plk1 complexed with the nonhydrolyzable ATP analogue adenylylimidodiphosphate (AMPPNP) or the pyrrolo-pyrazole inhibitor PHA-680626 at 2.4 and 2.1 Å resolution, respectively. Plk1 adopts the typical kinase domain fold and crystallized in a conformation resembling the active state of other kinases. Comparison of the kinetic parameters determined for the (unphosphorylated) wild-type enzyme, as well as the T210V and T210D mutants, shows that the mutations primarily affect the kcat of the reaction, with little change in the apparent Km for the protein or nucleotide substrates (kcat = 0.0094, 0.0376, and 0.0049 s-1 and Km(ATP) = 3.2, 4.0, and 3.0 μM for WT, T210D, and T210V, respectively). The structure highlights features of the active site that can be exploited to obtain Plk1-specific inhibitors with selectivity over other kinases and Plk isoforms. These include the presence of a phenylalanine at the bottom of the ATP pocket, combined with a cysteine (as opposed to the more commonly found leucine) in the roof of the binding site, a pocket created by Leu132 in the hinge region, and a cluster of positively charged residues in the solvent-exposed area outside of the adenine pocket adjacent to the hinge region. [ABSTRACT FROM AUTHOR]

Discusses the 2004 Air & Waste Management Association (AWMA) Critical Review of megacities and their effects on air quality and pollution-control policies. Comparison of city pollution levels in developing and developed countries; Recommendations for emission control; Factors hindering pollution control efforts.