'International relations theory in flux in view of China's "Peaceful Rise"'

This paper will first explore some essential theoretical backgrounds, which contribute to the understanding of the theory of hegemonic stability (a core strand of IPE theory) with a view to examine some empirical challenges of US hegemonic power after the Second World War. Secondly, it will go on to look at the notion of neo-liberalist regional development in East Asia to understand in what ways China’s entitlement creed has been increasingly instrumental in modifying the region institutional context. Third, it attempts to apply the constructivist approach in trying to locate the culturally embedded soft power entitlement of which China has been trying to capitalize on

International Relations Theory in Flux in View of China’s ‘Peaceful Rise’

This paper will first explore some essential theoretical backgrounds, which contribute to the understanding of the theory of hegemonic stability (a core strand of IPE theory) with a view to examine some empirical challenges of US hegemonic power after the Second World War. Secondly, it will go on to look at the notion of neo-liberalist regional development in East Asia to understand in what ways China’s entitlement creed has been increasingly instrumental in modifying the region institutional context. Third, it attempts to apply the constructivist approach in trying to locate the culturally embedded soft power entitlement of which China has been trying to capitalize on

In Searching the Meaning of Chineseness in Greater China

Among the people in Greater China (People’s Republic of China [PRC], Taiwan and Hong Kong), needless to say, economic incentive, political relations and business relations all conjure up an ethos of relations, if not close bonds, among Hong Kong, Taiwan and the PRC. The rise of China matters to everyone who lives in Greater China. Hong Kong is already part of China. Taiwan, according to the PRC, cannot be independent without running the risk of a war. Yet, my question is that are those Chinese the same in Greater China? Do they have different identities? If living with China is inevitable, do they need to search for a new identity to face the challenges? Keywords: Chineseness, Greater China, identity, national boundaries, Hong Kong, Taiwa

The immunomodulatory and cytotoxic effects of different forms of recombinant adenylate cyclase toxin

This thesis describes the small- and large-scale purification of four different recombinant forms of CyaA, namely; fully functional enzymically-active, acylated and invasive CyaA; an acylated and invasive CyaA form lacking adenylate cyclase (AC) enzymic activity (CyaA*); and the non-acylated, poorly-invasive forms of these toxins, proCyaA and proCyaA*, respectively. Only proCyaA and CyaA showed AC enzymic activity. Only CyaA and CyaA* were haemolytic towards sheep erythrocytes and cytotoxic towards mouse J774.2 macrophage-like cells. Both haemolysis and cytotoxicity by CyaA and CyaA* only occurred in the presence of calcium. CyaA was cytotoxic towards J774.2 cells at low concentrations (50% killing at 0.1 ?g protein/ml) and this paralleled low levels of caspase 3/7 activity, a measure of apoptotic activity. At higher toxin concentrations of CyaA (> 0.5 ?g protein/ml), caspase 3/7 activity declined despite high levels of cell killing measured by the cytotoxicity assay. This may have been due to the onset of necrotic killing at higher concentrations. CyaA* could only kill J774.2 cells at a toxin concentration greater than 0.5 ?g protein/ml and the effect was more calcium-dependent than that of CyaA. Cell killing by CyaA* also occurred in the absence of apoptosis. These data suggested that CyaA killed J774.2 cells by two different mechanisms, involving apoptosis at low concentrations (which was cAMP dependent) and necrosis by pore-formation at higher concentrations. ProCyaA and proCyaA* showed no apoptotic, cytotoxic or haemolytic activities. CyaA inhibited the zymosan stimulated oxidative burst of J774.2 cells. ProCyaA and CyaA* were ~500-fold less active at inhibiting the zymosan-stimulated oxidative burst of J774.2 cells compared with native CyaA. Thus, inhibition of the zymosan-stimulated oxidative burst by CyaA was a result of both invasive and AC enzymic activities. This also indicated that proCyaA was able to invade cells, albeit at a very low level, but that any increase in intracellular cAMP levels created by intracellular proCyaA was unable to induce apoptosis. Circular dichroism (CD) was used to assess any differences in the secondary structure of the four CyaA forms. There were similar changes in tertiary structure of all the CyaA forms as shown by intrinsic tryptophan fluorescence and near UV CD studies in the absence and presence of 1 mM CaCl2. Similar conformational changes in protein secondary structure of all four CyaA forms, at 0.5 mg protein/ml, were observed by far UV CD in the absence and presence of 1 mM CaCl2. However, at 0.05 mg protein/ml, the spectral amplitude of CyaA was decreased by 2-fold suggesting that CyaA was able to adopt two stochiometric forms. Preliminary analytical ultracentrifugation (AUC) studies indicated that CyaA did not exist as a single molecular species in solution. At 3 mg protein/ml, different oligomeric forms of CyaA (monomers, dimers and trimers) as well as the presence of degradation products (20 - 80 kDa) were present. Further optimisation of AUC studies is required to overcome the problem of non-ideality (caused by either a repulsion between charged molecules (proteins) that is not shielded by solvent counter-ions or by size-exclusion effects arising from extended/elongated conformations) which may have interfered with the analyses. (Abstract shortened by ProQuest.)

Collective states in social systems with interacting learning agents

We consider a social system of interacting heterogeneous agents with learning abilities, a model close to Random Field Ising Models, where the random field corresponds to the idiosyncratic willingness to pay. Given a fixed price, agents decide repeatedly whether to buy or not a unit of a good, so as to maximize their expected utilities. We show that the equilibrium reached by the system depends on the nature of the information agents use to estimate their expected utilities.Comment: 18 pages, 26 figure

Dataset of characterised construction safety risks and related treatments

The Safety Risk Library [1] is a structured database [2] that integrates knowledge drawn from multiple sources to address the problem of information disaggregation in the construction industry. This knowledge base maps construction safety risk scenarios to treatment suggestions that help designers implement the concept of prevention through design. In the context of the Safety Risk Library, risk scenarios are characterised by six data categories based on a formalised ontology [3]. To build the first iteration of the Safety Risk Library, nine different risk scenarios were identified and mapped to relevant risk treatments in focus groups. Subsequently, the Safety Risk Library was pilot tested in six construction projects, and user feedback and input were used to expand the list of risk scenarios and treatment prompts. Additionally, public press releases reporting construction accidents were analysed to identify and characterise risk scenarios, which were then mapped to appropriate treatment suggestions and included in the Safety Risk Library. This dataset can assist construction industry stakeholders in identifying, characterising, communicating and mitigating safety risks in construction projects. It can also be integrated into building information modelling environments to assist designers to implement prevention through design

Inhibition of lactate transport by MCT-1 blockade improves chimeric antigen receptor T-cell therapy against B-cell malignancies

BACKGROUND: Chimeric antigen receptor (CAR) T cells have shown remarkable results against B-cell malignancies, but only a minority of patients have long-term remission. The metabolic requirements of both tumor cells and activated T cells result in production of lactate. The export of lactate is facilitated by expression of monocarboxylate transporter (MCTs). CAR T cells express high levels of MCT-1 and MCT-4 on activation, while certain tumors predominantly express MCT-1. METHODS: Here, we studied the combination of CD19-specific CAR T-cell therapy with pharmacological blockade of MCT-1 against B-cell lymphoma. RESULTS: MCT-1 inhibition with small molecules AZD3965 or AR-C155858 induced CAR T-cell metabolic rewiring but their effector function and phenotype remained unchanged, suggesting CAR T cells are insensitive to MCT-1 inhibition. Moreover, improved cytotoxicity in vitro and antitumoral control on mouse models was found with the combination of CAR T cells and MCT-1 blockade. CONCLUSION: This work highlights the potential of selective targeting of lactate metabolism via MCT-1 in combination with CAR T cells therapies against B-cell malignancies