Naresuan University Journal
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Nation, Ethnicity and Race on Russian Television:Mediating Post-Soviet Difference
No full textRussia, one of the most ethno-culturally diverse countries in the world, provides a rich case study on how globalisation and associated international trends are disrupting, and causing the radical rethinking of approaches to, inter-ethnic cohesion. The book highlights the importance of television broadcasting in shaping national discourse and the place of ethno-cultural diversity within it. It argues that television’s role here has been reinforced, rather than diminished, by the rise of new media technologies. Through an analysis of a wide range of news and other television programmes, the book shows how the covert meanings of discourse on a particular issue can diverge from the overt significance attributed to it, just as the impact of that discourse may not conform with the original aims of the broadcasters. The book discusses the tension between the imperative to maintain security through centralised government and overall national cohesion that Russia shares with other European states, and the need to remain sensitive to, and to accommodate, the needs and perspectives of ethnic minorities and labour migrants. It compares the increasingly isolationist popular ethnonationalism in Russia, which harks back to "old-fashioned" values, with the similar rise of the Tea Party in the United States and the UK Independence Party in Britain. Throughout, this extremely rich, well-argued book complicates and challenges received wisdom on Russia’s recent descent into authoritarianism. It points to a regime struggling to negotiate the dilemmas it faces, given its Soviet legacy of ethnic particularism, weak civil society, large native Muslim population and overbearing, yet far from entirely effective, state control of the media
Picomolar Inhibition of Plasmepsin V, an Essential Malaria Protease, Achieved Exploiting the Prime Region
No full textMalaria is an infectious disease caused by Plasmodium parasites. It results in an annual death-toll of ~ 600,000. Resistance to all medications currently in use exists, and novel antimalarial drugs are urgently needed. Plasmepsin V (PmV) is an essential Plasmodium protease and a highly promising antimalarial target, which still lacks molecular characterization and drug-like inhibitors. PmV, cleaving the PExEl motif, is the key enzyme for PExEl-secretion, an indispensable parasitic process for virulence and infection. Here, we describe the accessibility of PmV catalytic pockets to inhibitors and propose a novel strategy for PmV inhibition. We also provide molecular and structural data suitable for future drug development. Using high-throughput platforms, we identified a novel scaffold that interferes with PmV in-vitro at picomolar ranges (~ 1,000-fold more active than available compounds). Via systematic replacement of P and P' regions, we assayed the physico-chemical requirements for PmV inhibition, achieving an unprecedented IC50 of ~20 pM. The hydroxyethylamine moiety, the hydrogen acceptor group in P2', the lipophilic groups upstream to P3, the arginine and other possible substitutions in position P3 proved to be critically important elements in achieving potent inhibition. In-silico analyses provided essential QSAR information and model validation. Our inhibitors act ‘on-target’, confirmed by cellular interference of PmV function and biochemical interaction with inhibitors. Our inhibitors are poorly performing against parasite growth, possibly due to poor stability of their peptidic component and trans-membrane permeability. The lowest IC50 for parasite growth inhibition was ~ 15μM. Analysis of inhibitor internalization revealed important pharmacokinetic features for PExEl-based molecules. Our work disclosed novel pursuable drug design strategies for highly efficient PmV inhibition highlighting novel molecular elements necessary for picomolar activity against PmV. All the presented data are discussed in respect to human aspartic proteases and previously reported inhibitors, highlighting differences and proposing new strategies for drug development
Clinical evaluation of respiration-induced attenuation uncertainties in pulmonary 3D PET/CT.
No full textAtherosclerosis in rheumatoid arthritis: is it all about inflammation?
No full textRheumatoid arthritis (RA) has long been associated with increased cardiovascular risk, but despite substantial improvements in disease management, mortality remains high. Atherosclerosis is more prevalent in RA than in the general population, and atherosclerotic lesions progress at a faster rate and might be more prone to rupture, causing clinical events. Cells and cytokines implicated in RA pathogenesis are also involved in the development and progression of atherosclerosis, which is generally recognized as an inflammatory condition. The two diseases also share genetic and environmental risk factors, which suggests that patients who develop RA might also be predisposed to developing cardiovascular disease. In RA, inflammation and atherosclerosis are closely linked. Inflammation mediates its effects on atherosclerosis both through modulation of traditional risk factors and by directly affecting the vessel wall. Treatments such as TNF inhibitors might have a beneficial effect on cardiovascular risk. However, whether this benefit is attributable to effective control of inflammation or whether targeting specific cytokines, implicated in atherosclerosis, provides additional risk reduction is unclear. Further knowledge of the predictors of cardiovascular risk, the effects of early control of inflammation and of drug-specific effects are likely to improve the recognition and management of cardiovascular risk in patients with RA
Measurement of differential production cross sections and forward-backward ratios in p + Pb collisions with the ATLAS detector
No full textGraphene oxide selectively targets cancer stem cells, across multiple tumor types: implications for non-toxic cancer treatment, via "differentiation-based nano-therapy".
No full textTumor-initiating cells (TICs), a.k.a. cancer stem cells (CSCs), are difficult to eradicate with conventional approaches to cancer treatment, such as chemo-therapy and radiation. As a consequence, the survival of residual CSCs is thought to drive the onset of tumor recurrence, distant metastasis, and drug-resistance, which is a significant clinical problem for the effective treatment of cancer. Thus, novel approaches to cancer therapy are needed urgently, to address this clinical need. Towards this end, here we have investigated the therapeutic potential of graphene oxide to target cancer stem cells. Graphene and its derivatives are well-known, relatively inert and potentially non-toxic nano-materials that form stable dispersions in a variety of solvents. Here, we show that graphene oxide (of both big and small flake sizes) can be used to selectively inhibit the proliferative expansion of cancer stem cells, across multiple tumor types. For this purpose, we employed the tumor-sphere assay, which functionally measures the clonal expansion of single cancer stem cells under anchorage-independent conditions. More specifically, we show that graphene oxide effectively inhibits tumor-sphere formation in multiple cell lines, across 6 different cancer types, including breast, ovarian, prostate, lung and pancreatic cancers, as well as glioblastoma (brain). In striking contrast, graphene oxide is non-toxic for "bulk" cancer cells (non-stem) and normal fibroblasts. Mechanistically, we present evidence that GO exerts its striking effects on CSCs by inhibiting several key signal transduction pathways (WNT, Notch and STAT-signaling) and thereby inducing CSC differentiation. Thus, graphene oxide may be an effective non-toxic therapeutic strategy for the eradication of cancer stem cells, via differentiation-based nano-therapy