Naresuan University Journal
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Microstructure and mechanical characteristics of a laser welded joint in SA508 nuclear pressure vessel steel
No full textSA508 steels are typically used in civil nuclear reactors for critical components such as the reactor pressure vessel. Nuclear components are commonly joined using arc welding processes, but with design lives for prospective new build projects exceeding 60 years, new welding technologies are being sought. In this exploratory study, for the first time, autogenous laser welding was carried out on 6 mm thick SA508 Cl.3 steel sheets using a 16kW fiber laser system operating at a power of 4kW. The microstructure and mechanical properties (including microhardness, tensile strength, elongation, and Charpy impact toughness) were characterized and the microstructures were compared with those produced through arc welding. A three-dimensional transient model based on a moving volumetric heat source model was also developed to simulate the laser welding thermal cycles in order to estimate the cooling rates included by the process. Preliminary results suggest that the laser welding process can produce welds that are free of macroscopic defects, while the strength and toughness of the laser welded joint in this study matched the values that were obtained for the parent material in the as-welded condition
Measurement of jet charge in dijet events from sqrt(s)=8 TeV pp collisions with the ATLAS detector
No full textKeyway Root Crack Arrest in an AGR Graphite Brick
No full textThe graphite bricks in an advanced gas-cooled reactor (AGR) core are subject to fast neutron irradiation which leads to significant dimensional and material properties changes. These changes vary across the relatively thick (~100mm) wall section of a typical graphite moderator brick due to the fluence and temperature profiles leading to the generation of internal stresses. In the carbon dioxide cooled environment of an AGR, the graphite also suffers weight loss due to the radiolytic oxidation which further alters the material properties. In early life the brick bore is under tension whilst the periphery is under compression. This state is reversed later in life leading to tensile stresses on the periphery and at the keyways. The keyway near 90° corners cause stress concentrations and are possible locations for crack initiation. Circular methane holes within the brick may provide locations for crack arrest before a crack could reach the brick bore, preventing detection of the crack during a routine inspection. There is a limit put on the number of cracked bricks that may be tolerated as part of the operating safety case. It is therefore desirable to ensure that keyway root cracked bricks are not missed during inspection. In this paper, the possibility of keyway root crack arrest at the methane holes is investigated. Numerical finite element models of different crack propagation scenarios are analysed. The stress levels are then used to predict the likelihood of the arrest of a keyway root crack before reaching the bore of a graphite fuel brick where a crack can be visually detected
TREM2 analysis and increased risk of Alzheimer's disease.
No full textImportant insights into the pathogenic mechanism of Alzheimer's disease (AD) have arisen from the identification of genetic risk factors. Recently, a variant in the TREM2 gene (rs75932628), causing a C-to-T base-pair change that results in the substitution of histidine for arginine at amino acid position 47 (R47H) in the TREM2 protein, has been associated with an increased risk of AD. We, therefore, genotyped samples from a cohort of 474 AD patients and 608 healthy controls, from the northwest region of the UK, using allelic discrimination assays, to replicate the results of the previous studies. We show a significant association of the T allele of the rs75932628 variant of TREM2 with AD (allelic odds ratio 11.08, 95% confidence interval 2.55-48.09, and Yates' corrected p value = 0.000146). TREM2 is an innate immune receptor that regulates microglial cytokine production and phagocytosis, implying that dysregulation of these processes may be involved in AD pathology, with implications for disease management
The Cryo-EM Structure of the CorA channel from Methanocaldococcus jannaschii in low magnesium conditions.
No full textCorA channels are responsible for the uptake of essential magnesium ions by bacteria. X-ray crystal structures have been resolved for two full-length CorA channels, each in a non-conducting state with magnesium ions bound to the protein: These structures reveal a homo-pentameric quaternary structure with approximate 5-fold rotational symmetry about a central pore axis. We report the structure of the detergent solubilized Methanocaldococcus jannaschii CorA channel determined by Cryo-electron microscopy and Single Particle Averaging, supported by Small Angle X-ray scattering and X-ray crystallography. This structure also shows a pentameric channel but with a highly asymmetric domain structure. The asymmetry of the domains includes differential separations between the trans-membrane segments, which reflects mechanical coupling of the cytoplasmic domain to the trans-membrane domain. This structure therefore reveals an important aspect of the gating mechanism of CorA channels by providing an indication of how the absence of magnesium ions leads to major structural changes
Variability in the effect of 5-HTTLPR on depression in a large European population: the role of age, symptom profile, type and intensity of life stressors.
No full textBACKGROUND: Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity. METHODS: In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models. RESULTS: The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (≤30) individuals. LIMITATIONS: Our study is cross-sectional and applies self-report questionnaires. CONCLUSIONS: Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups
Triggered doxorubicin release in solid tumours from thermosensitive liposome-peptide hybrids: critical parameters and therapeutic efficacy
No full textTemperature-sensitive vesicles designed by inclusion of leucine zipper peptides within a lipid bilayer (Lp-Peptide hybrids) encapsulating Doxorubicin have been reported. Intravenous administration of these constructs prolonged blood circulation kinetics and increased tumour accumulation in vivo with local mild hyperthermia. In this study, the biological activity of the Doxorubicin-loaded Lp-Peptide hybrid vesicles was further investigated at the cellular level and in vivo compared to lysolipid-containing temperature-sensitive liposomes (LTSL) and traditional temperature-sensitive liposomes (TTSL). Lp-Peptide vesicles were not toxic to cell cultures at 37 ºC, while effective cancer cell toxicity was observed after 1 h of heating at 42 ºC. The activity of Lp-Peptide vesicles in vivo was studied using two different heating protocols to obtain tumour intravascular or interstitial drug release. Lp-Peptide vesicle treatment allowing intravascular Doxorubicin release showed equally effective tumour growth retardation and survival to that of LTSL treatment. The Lp-Peptide vesicles also offered therapeutic responses using the alternative heating protocol to maximise drug release within the tumour interstitium. Matching the drug release kinetics of temperature-sensitive vesicles with the heating protocol applied is considered the most critical factor to determine therapeutic efficacy in the clinical translation of such modalities
Eosinophilic oesophagitis.
No full textEosinophilic oesophagitis (EoE) is an antigen-driven pan-oesophagitis that is defined by the presence of at least 15 eosinophils per high power field on oesophageal histology in conjunction with upper gastrointestinal symptoms. EoE is closely associated with atopic disorders, in particular with food allergy, and as for other atopic diseases in childhood, there is a strong preponderance of male patients who have this disorder. The mechanisms leading to EoE have been characterised at the molecular level. Eotaxin-3, interleukin-5 and interleukin-13 are the key effector molecules in EoE pathogenesis. EoE presents with a diverse range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infancy, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnosis may also be ascertained as an incidental finding in patients undergoing gastroscopy for other suspected conditions, including coeliac disease. EoE is different from gastro-oesophageal reflux disease and does not improve in response to proton pump inhibitors. Therefore, EoE needs to be distinguished from so-called PPI-responsive oesophageal eosinophilia. The long-term prognosis of EoE remains poorly defined, and complications mainly relate to subepithelial remodelling and fibrosis that may result in dysmotility, dysphagia and oesophageal strictures. The treatment of EoE involves elimination diets and topical swallowed aerosolised corticosteroids, while biological therapies targeting molecular mechanisms have so far been unsuccessful. In children, elemental diets have proved highly effective, but multiple food elimination diets are more sustainable in the long term. Further randomised, controlled trials on dietary or pharmacological interventions are needed to inform the optimal long-term management of EoE