Naresuan University Journal
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Modeling infectious disease dynamics in the complex landscape of global health
No full textDespite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health
Synthetic biology for the directed evolution of protein biocatalysts:navigating sequence space intelligently
No full textAbstractThe amino acid sequence of a protein affects both its structure and its function. Thus, the ability to modify the sequence, and hence the structure and activity, of individual proteins in a systematic way, opens up many opportunities, both scientifically and (as we focus on here) for exploitation in biocatalysis. Modern methods of synthetic biology, whereby increasingly large sequences of DNA can be synthesised de novo, allow an unprecedented ability to engineer proteins with novel functions. However, the number of possible proteins is far too large to test individually, so we need means for navigating the 'search space' of possible protein sequences efficiently and reliably in order to find desirable activities and other properties. Enzymologists distinguish binding (Kd) and catalytic (kcat) steps. In a similar way, judicious strategies have blended design (for binding, specificity and active site modelling) with the more empirical methods of classical directed evolution (DE) for improving kcat (where natural evolution rarely seeks the highest values), especially with regard to residues distant from the active site and where the functional linkages underpinning enzyme dynamics are both unknown and hard to predict. Epistasis (where the 'best' amino acid at one site depends on that or those at others) is a notable feature of directed evolution. The aim of this review is to highlight some of the approaches that are being developed to allow us to use directed evolution to improve enzyme properties, often dramatically. We note that directed evolution differs in a number of ways from natural evolution, including in particular the available mechanisms and the likely selection pressures. Thus, we stress the opportunities afforded by techniques that enable one to map sequence to (structure and) activity in silico, as an effective means of modelling and exploring protein landscapes. Because known landscapes may be assessed and reasoned about as a whole, simultaneously, this offers opportunities for protein improvement not readily available to natural evolution on rapid timescales. Intelligent landscape navigation, informed by sequence-activity relationships and coupled to the emerging methods of synthetic biology, offers scope for the development of novel biocatalysts that are both highly active and robust
Effect of solution casting temperature on properties of nafion composite membrane with surface modified mordenite for direct methanol fuel cell.
No full textIncompatibility between organic polymer and inorganic filler has been addressed as critical area of Nafion and mordenite composite membrane fabrication for direct methanol fuel cell (DMFC) application. It possibly brings about void leading to high methanol crossover. Incompatibility at the surface of the filler can be improved by using silane coupling agent. In this study, two coupling agents were used in order to improve interfacial property between filler and polymer matrix, including gamma-glycidoxypropyl trimethoxysilane (GMPTS) and 3-mercaptopropyl triethoxysilane (MPTES). Surfaced modified mordenite was used in Nafion/mordenite composite membranes fabrication by using solution casting method. Properties of composite membranes were investigated, including chemical resistance, water uptake, ion-exchange capacity (IEC), proton conductivity and methanol permeability. It was found that properties of the composite membrane were greatly affected by casting temperature in casting method. In this work, the most suitable solution casting temperature was 100 °C. The obtained membrane gave 0.59% soluble, 1.38% water uptake and 0.10 meq g− 1 IEC. With type of silanes, membrane fabricated with MPTES treated mordenite showed better properties than that of GMPTES giving 60% higher proton conductivity and 85% lower methanol permeability at 30 °C
Barriers and facilitators to recruitment in mental health services:Care coordinators' expectations and experience of referring to a psychosis research trial
No full textOBJECTIVE: High-quality research trials are necessary to provide evidence for the effective management of mental health difficulties, but successful recruitment can be challenging. DESIGN: This qualitative study examines the perceived barriers and facilitators to referring mental health service users to research trials. Seven care coordinators (n = 7) who facilitated the recruitment of participants to a cognitive behaviour therapy - informed psychosis intervention trial were interviewed. METHOD: Demographic information was collected by questionnaire and a semi-structured guide was used to explore barriers and facilitators to referring to a partially randomized participant preference trial. Qualitative data were thematically analysed. RESULTS: Four key themes, each with a number of sub-themes, were identified: (1) engage the care coordinator in the recruitment process, (2) barriers to referring to research studies, (3) facilitators to referring to research studies; (4) organisational constraints impact on implementing research outcomes into routine clinical practice. CONCLUSIONS: Understanding the barriers and facilitators to recruitment in mental health research could improve recruitment strategies. Our findings highlight the need for researchers' to closely consider their recruitment strategies as service users are not always given the choice to participate in research. Several key recommendations are made based on these findings in order to maximize successful recruitment to research studies. Overall, we recommend that researchers' adopt a flexible, tailor-made approach for each clinical team to ensure a collaborative relationship is developed between research staff and clinicians. PRACTITIONER POINTS: A qualitative approach to understanding recruitment challenges provides a useful opportunity to explore the barriers and facilitators to recruiting participants to research studies. These findings have practical implications that highlight the need for a collaborative partnership between researchers and clinical services. Understanding the challenges and issues related to recruitment can help researchers consider strategies to overcome recruitment issues. More research with a larger sample, across a broader population and in different mental health services is required
Cancer-associated protein kinase C mutations reveal kinase's role as tumor suppressor
No full textProtein kinase C (PKC) isozymes have remained elusive cancer targets despite the unambiguous tumor promoting function of their potent ligands, phorbol esters, and the prevalence of their mutations. We analyzed 8% of PKC mutations identified in human cancers and found that, surprisingly, most were loss of function and none were activating. Loss-of-function mutations occurred in all PKC subgroups and impeded second-messenger binding, phosphorylation, or catalysis. Correction of a loss-of-function PKCβ mutation by CRISPR-mediated genome editing in a patient-derived colon cancer cell line suppressed anchorage-independent growth and reduced tumor growth in a xenograft model. Hemizygous deletion promoted anchorage-independent growth, revealing that PKCβ is haploinsufficient for tumor suppression. Several mutations were dominant negative, suppressing global PKC signaling output, and bioinformatic analysis suggested that PKC mutations cooperate with co-occurring mutations in cancer drivers. These data establish that PKC isozymes generally function as tumor suppressors, indicating that therapies should focus on restoring, not inhibiting, PKC activity.</p
The influence of polar additives on chromonic mesophase formation of Edicol Sunset Yellow
No full textClass meets Land: the social mobilisation of land as catalyst for urban change
No full textThe paper explores the active yet neglected role that local class struggle over land plays in negotiating new forms of urbanity. Unfashionably shifting research focus from global elites and the “creative classâ€� to local industrial elites and industrial workers, we show that socially embodied local struggles over land are as relevant to globalised urbanisations as they had been to industrial capitalism, and need to be brought back squarely into geographical analysis. We focus empirically on the closely-knitted histories of the Pirelli company, Pirelli’s workers, and Pirelli’s industrial space at Bicocca (north-east Milan). As we unfold Bicocca’s transformation from workers’ village (19th century), to radical industrial action hub (1960s-1970s), and finally to trendy mixed-use space (1990s-2000s), we show how, for over a century, social struggles over land remain the terrain on which new forms of urbanity are fought, and highlight two important points. First, class struggle over the economic, social, and symbolic role of industrial land was not the outcome of, but an essential precondition for urban restructuring. Second, the industrial working class and traditional elites were not passive recipients, but active producers of urban chang
Studying the build-up of stresses in nuclear grade graphite using X-ray tomography
No full textGraphite is used as a moderating material in British Magnox Nuclear Reactors and Advanced Gas-Cooled Reactors (AGRs). Channels are cut into the graphite components through which coolant, fuel rods and control rods travel during reactor operation. Significant stresses can build up in the graphite components as a result of thermal and irradiation-induced deformation and dimensional change. Large amounts of deformation may inhibit the flow of coolant and the movement of fuel rods and control rods, potentially preventing the reactor from shutting down safely. Hence a detailed understanding of graphite’s response to reactor conditions is needed to guarantee safe and efficient reactor operation. Of particular interest is the variation of the graphite’s pore structure, which can have a significant effect on the strength of moderator components.A series of experiments were performed to investigate how the pore structures of various nuclear grade graphites respond to stresses. Axial compressive loading was used to simulate the build-up of stresses in graphite samples. X-ray tomography was performed on the samples during in-situ application of a range of loads to study variation of the interior microstructure of the samples. Image analysis software was used to define the interior pore structure of the samples and calculate properties including pore volumes, pore shapes and total porosity. The observed changes to the microstructure were used to explain the behaviour of the bulk material, and the consequences for the UK’s aging graphite moderated reactor fleet were discussed.This research is particularly important and timely due to the large numbers of nuclear reactors in the UK that are aging or operating beyond their original lifespans, and due to the ongoing concerns of cracks in graphite components being found during recent inspections
