Naresuan University Journal
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Early stages of insulin fibrillogenesis examined with ion mobility mass spectrometry and molecular modelling
No full textA prevalent type of protein misfolding causes the formation of beta-sheet-rich structures known as amyloid fibrils. Research into the mechanisms of fibril formation has implications for both disease prevention and nanoscale templating technologies. This investigation into the aggregation of insulin utilises ion mobility mass spectrometry coupled with molecular modelling to identify and characterise oligomers formed during the 'lag' phase that precedes fibril growth. High resolution mass spectrometry and collision induced dissociation is used to unequivocally assign species as m/z coincident multimers or confomers, providing a robust analytical approach that supports the use of molecular dynamics to atomistically resolve the observed oligomers. We show that insulin oligomerises to form species In where
The Prevalence of Tree Nut Allergy: A Systematic Review.
No full textTree nuts are one of the most common foods causing acute allergic reactions and nearly all tree nuts have been associated with fatal allergic reactions. Despite their clinical importance, tree nut allergy epidemiology remains understudied and the prevalence of tree nut allergy in different regions of the world has not yet been well characterised. We aimed to systematically review the population prevalence of tree nut allergy in children and adults. We searched three electronic databases (OVID MEDLINE, EMBASE and PubMed) from January 1996 to December 2014. Eligible studies were categorised by age, region and method of assessment of tree nut allergy. Of the 36 studies identified most were in children (n = 24) and from Europe (n = 18), UK (n = 8) or USA (n = 5). Challenge-confirmed IgE-mediated tree nut allergy prevalence was less than 2 % (although only seven studies used this gold standard) while probable tree nut allergy prevalence ranged from 0.05 to 4.9 %. Prevalence estimates that included oral allergy syndrome (OAS) reactions to tree nut were significantly higher (8-11.4 %) and were predominantly from Europe. Prevalence of individual tree nut allergies varied significantly by region with hazelnut the most common tree nut allergy in Europe, walnut and cashew in the USA and Brazil nut, almond and walnut most commonly reported in the UK. Monitoring time trends of tree nut allergy prevalence (both overall and by individual nuts) as well as the prevalence of OAS should be considered given the context of the overall recent rise in IgE-mediated food allergy prevalence in the developed world
Manufacturing Technology for Implementing Geological Disposal - Electroforming of Copper Canisters
No full textExisting capability and further development needs for implementing electroforming as a viable manufacturing process to produce KBS-3 type copper canisters is discussed. Large copper cylinders with dimensions similar to the Swedish KBS-3 design can readily be produced. The challenge lies in controlling the electro-deposition process to conform to compositional and mechanical requirements of the produced copper layers, illustrated with examples of the effect of electrolyte additives on the carbon and oxygen content, and the grain size of the electroformed layer. Challenges to up-scale the process to manufacture KBS-3 type prototypes are briefly discussed, with possible ways to introduce a robust manufacturing route
Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls
No full textThe ethics weathervane
No full textBackgroundGlobal collaboration in genomic research is increasingly both a scientific reality and an ethical imperative. This past decade has witnessed the emergence of six new, interconnected areas of ethical consensus and emphasis for policy in genomics: governance, security, empowerment, transparency, the right not to know, and globalization.DiscussionThe globalization of genomic research warrants an approach to governance policies grounded in human rights.SummaryA human rights approach activates the ethical principles underpinning genomic research. It lends force to the right of all citizens to benefit from scientific progress, and to the right of all scientists to be recognized for their contributions
Equivalence of Brownian dynamics and dynamic Monte Carlo simulations in multicomponent colloidal suspensions
No full textWe propose a simple but powerful theoretical framework to quantitatively compare Brownian dynamics (BD) and dynamic Monte Carlo (DMC) simulations of multicomponent colloidal suspensions. By extending our previous study focusing on monodisperse systems of rodlike colloids, here we generalize the formalism described there to multicomponent colloidal mixtures and validate it by investigating the dynamics in isotropic and liquid crystalline phases containing spherical and rodlike particles. In order to investigate the dynamics of multicomponent colloidal systems by DMC simulations, it is key to determine the elementary time step of each species and establish a unique timescale. This is crucial to consistently study the dynamics of colloidal particles with different geometry. By analyzing the mean-square displacement, the orientation autocorrelation functions, and the self part of the van Hove correlation functions, we show that DMC simulation is a very convenient and reliable technique to describe the stochastic dynamics of any multicomponent colloidal system. Our theoretical formalism can be easily extended to any colloidal system containing size and/or shape polydisperse particles
Characterization of a real-time tracer for isoprene epoxydiols-derived secondary organic aerosol (IEPOX-SOA) from aerosol mass spectrometer measurements
No full textSubstantial amounts of secondary organic aerosol (SOA) can be formed from isoprene epoxydiols (IEPOX), which are oxidation products of isoprene mainly under low-NO conditions. Total IEPOX-SOA, which may include SOA formed from other parallel isoprene oxidation pathways, was quantified by applying positive matrix factorization (PMF) to aerosol mass spectrometer (AMS) measurements. The IEPOX-SOA fractions of organic aerosol (OA) in multiple field studies across several continents are summarized here and show consistent patterns with the concentration of gas-phase IEPOX simulated by the GEOS-Chem chemical transport model. During the Southern Oxidant and Aerosol Study (SOAS), 78% of PMF-resolved IEPOX-SOA is accounted by the measured IEPOX-SOA molecular tracers (2-methyltetrols, C5-Triols, and IEPOX-derived organosulfate and its dimers), making it the highest level of molecular identification of an ambient SOA component to our knowledge. An enhanced signal at C5H6O+ (m/z 82) is found in PMF-resolved IEPOX-SOA spectra. To investigate the suitability of this ion as a tracer for IEPOX-SOA, we examine fC(5)H(6)O (fC(5)H(6)O = C5H6O+ / OA) across multiple field, chamber, and source data sets. A background of similar to 1.7 +/- 0.1 parts per thousand (parts per thousand = parts per thousand) is observed in studies strongly influenced by urban, biomass-burning, and other anthropogenic primary organic aerosol (POA). Higher background values of 3.1 +/- 0.6 parts per thousand are found in studies strongly influenced by monoterpene emissions. The average laboratory monoterpene SOA value (5.5 +/- 2.0 parts per thousand) is 4 times lower than the average for IEPOX-SOA (22 +/- 7 parts per thousand), which leaves some room to separate both contributions to OA. Locations strongly influenced by isoprene emissions under low-NO levels had higher fC(5)H(6)O (similar to 6.5 +/- 2.2 parts per thousand on average) than other sites, consistent with the expected IEPOX- SOA formation in those studies. fC(5)H(6)O in IEPOX- SOA is always elevated (12-40 parts per thousand) but varies substantially between locations, which is shown to reflect large variations in its detailed molecular composition. The low fC(5)H(6)O (<3 parts per thousand) reported in non-IEPOX-derived isoprene-SOA from chamber studies indicates that this tracer ion is specifically enhanced from IEPOX- SOA, and is not a tracer for all SOA from isoprene. We introduce a graphical diagnostic to study the presence and aging of IEPOX- SOA as a triangle plot of f(CO2) vs. fC(5)H(6)O. Finally, we develop a simplified method to estimate ambient IEPOX- SOA mass concentrations, which is shown to perform well compared to the full PMF method. The uncertainty of the tracer method is up to a factor of similar to 2, if the fC(5)H(6)O of the local IEPOX- SOA is not available. When only unit mass-resolution data are available, as with the aerosol chemical speciation monitor (ACSM), all methods may perform less well because of increased interferences from other ions at m/z 82. This study clarifies the strengths and limitations of the different AMS methods for detection of IEPOX- SOA and will enable improved characterization of this OA component
The role of steroid hormones in breast cancer stem cells
No full textBreast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity