A comparative study of paragenesis, geochemistry and fluid inclusions of selected primary tin deposits of West Malaysia

Imperial Users onl

Reasoning about Action: An Argumentation - Theoretic Approach

We present a uniform non-monotonic solution to the problems of reasoning about action on the basis of an argumentation-theoretic approach. Our theory is provably correct relative to a sensible minimisation policy introduced on top of a temporal propositional logic. Sophisticated problem domains can be formalised in our framework. As much attention of researchers in the field has been paid to the traditional and basic problems in reasoning about actions such as the frame, the qualification and the ramification problems, approaches to these problems within our formalisation lie at heart of the expositions presented in this paper

A Novel Taxonomy of Opportunities and Risks in Massively Multiplayer Online Role Playing Games

The explosion and rapid embrace of Massively Multiplayer Online Role Playing Games (MMORPG) has provided players with unique, fully immersive three dimensional environments in which they can express themselves in a myriad of ways. Players can develop unique skill sets, share knowledge, explore and experiment with various identities and network with like-minded individuals. Evidence suggests however, that these opportunities are accompanied with a number of risks including addiction, desensitisation and threats to the privacy of personal information. This paper presents a novel Taxonomy of opportunities and risks in the specific context of Massively Multiplayer Online Role Playing Games

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple negative breast cancer cells

Ethnopharmacological Relevance: Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. Aim of The Study: Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been reported the cytotoxicity of this plant towards MDA-MB-231 triple-negative breast cancer cells. The present study was designed to investigate the mode of cell death and signalling pathways of MDA-MB-231 cells treated with dichloromethane Dillenia suffruticosa root extract (DCM-DS). Methods: Extraction of Dillenia suffruticosa root was performed by the use of sequential solvent procedure. The cytotoxicity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using an inverted light microscope and flow cytometry analysis using Annexin-V/PI. Cell cycle analysis and measurement of reactive oxygen species level were performed by using flow cytometry. The cells were treated with DCM-DS and antioxidants α-tocopherol or ascorbic acid to evaluate the involvement of ROS in the cytotoxicity of DCM-DS. Effect of DCM-DS on the expression of antioxidant, apoptotic, growth, survival genes and proteins were analysed by using GeXP-based multiplex system and Western blot, respectively. The cytotoxicity of compounds isolated from DCM-DS was evaluated towards MDA-MB-231 cells using MTT assay. Results: DCM-DS induced apoptosis, G2/M phase cell cycle arrest and oxidative stress in MDA-MB-231 cells. The induction of apoptosis in MDA-MB-231 cells by DCM-DS is possibly due to the activation of pro-apoptotic JNK1 and down-regulation of anti-apoptotic ERK1, which in turn down-regulates anti-apoptotic BCL-2 to increase the BAX/BCL-2 ratio to initiate the mitochondrial apoptotic pathway. The cell cycle arrest in DCM-DS-treated MDA-MB-231 cells is possibly via p53-independent but p21-dependent pathway. A total of 3 triterpene compounds were isolated from DCM-DS. Betulinic acid appears to be the most major and most cytotoxic compound in DCM-DS. Conclusion: The data suggest the potential application of DCM-DS in the treatment of triple-negative breast cancer

Evidence of many-body localization in 2D from quantum Monte Carlo simulation

We use the stochastic series expansion quantum Monte Carlo method, together with the eigenstate-to-Hamiltonian mapping approach, to map the localized ground states of the disordered two-dimensional Heisenberg model, to excited states of a target Hamiltonian. The localized nature of the ground state is established by studying the spin stiffness, local entanglement entropy, and local magnetization. This construction allows us to define many body localized states in an energy resolved phase diagram thereby providing concrete numerical evidence for the existence of a many-body localized phase in two dimensions.Comment: 8 pages, 6 figure

Statin use and risk of developing diabetes: results from the Diabetes Prevention Program

Objective Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations. Research design and methods During the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose. Lipid profile was measured annually, with statin treatment determined by a participant’s own physician outside of the protocol. Statin use was assessed at baseline and semiannual visits. Results At 10 years, the cumulative incidence of statin initiation prior to diabetes diagnosis was 33%–37% among the randomized treatment groups (p=0.36). Statin use was associated with greater diabetes risk irrespective of treatment group, with pooled HR (95% CI) for incident diabetes of 1.36 (1.17 to 1.58). This risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy. Conclusions In this population at high risk for diabetes, we observed significantly higher rates of diabetes with statin therapy in all three treatment groups. Confounding by indication for statin use does not appear to explain this relationship. The effect of statins to increase diabetes risk appears to extend to populations at high risk for diabetes. Trial registration number NCT00038727; Results

Superconductivity in a layered cobalt oxyhydrate Na0.31_{0.31}CoO2⋅_{2}\cdot1.3H2_{2}O

We report the electrical, magnetic and thermal measurements on a layered cobalt oxyhydrate Na$_{0.31}$CoO$_{2}\cdot$1.3H$_{2}$O. Bulk superconductivity at 4.3 K has been confirmed, however, the measured superconducting fraction is relatively low probably due to the sample's intrinsic two-dimensional characteristic. The compound exhibits weak-coupled and extreme type-II superconductivity with the average energy gap $\Delta_{a}(0)$ and the Ginzburg-Landau parameter $\kappa$ of $\sim$ 0.50 meV and $\sim$ 140, respectively. The normalized electronic specific heat data in the superconducting state well fit the $T^{3}$ dependence, suggesting point nodes for the superconducting gap structure.Comment: 4 pages, 3 figure

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.

The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported. Here we report on the identification of a novel PALB2 variant, c.104T>C (p.L35P), that segregates in a family with a strong history of breast cancer. Functional analyses showed that L35P abrogates the PALB2-BRCA1 interaction and completely disables its abilities to promote HR and confer resistance to platinum salts and PARP inhibitors. Whole-exome sequencing of a breast cancer from a c.104T>C carrier revealed a second, somatic, truncating mutation affecting PALB2, and the tumor displays hallmark genomic features of tumors with BRCA mutations and HR defects, cementing the pathogenicity of L35P. Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development. Our findings establish L35P as the first pathogenic missense mutation in PALB2 and directly demonstrate the requirement of the PALB2-BRCA1 interaction for breast cancer suppression