205 research outputs found

    The Effects of Fiber Orientation and Volume Fraction of Fiber on Mechanical Properties of Additively Manufactured Composite Material

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    Additive manufacturing (AM) also known as 3D printing has tremendous advancements in recent days with a vast number of applications in industrial, automotive, architecture, consumer projects, fashion, toys, food, art, etc. Composite materials are widely used in structures with weight as a critical factor especially in aerospace industry. Recently, additive manufacturing technology, a rapidly growing innovative technology, has gained lot of importance in making composite materials. The properties of composite materials depend upon the properties of constituent’s matrix and fiber. There is lot of research on effect of fiber orientation on mechanical properties of composite materials made using conventional manufacturing methods. It will be interesting and relevant to study the relationship between the fiber orientation and fiber volume with mechanical properties of additively manufactured composite materials. This thesis work presents experimental investigation of mechanical behavior like tensile strength and fatigue life with variation in fiber orientation and fiber volume fraction of 3D printed composite materials. The aim is to study the best combination of volume fraction of fiber and fiber orientation that has better fatigue strength for additive manufactured composite materials. Using this study, we can decide the type of orientation and volume percent for desired properties. This study also finds the range of fatigue limits of 3d printed composite materials

    Single nucleotide polymorphism rs13079080 is associated with differential regulation of the succinate receptor 1 (SUCNR1) gene by miRNA-4470.

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    Item does not contain fulltextOxidative stress is a feature of many common diseases. It leads to excessive formation and subsequent release of the mitochondrial metabolite succinate, which acts as a signalling molecule through binding the succinate receptor (SUCNR1). Recently, a potential role for SUCNR1 was proposed in age-related macular degeneration (AMD), a common cause of vision loss in the elderly associated with increased oxidative stress. Here, we evaluated the potential effect of genetic variants in SUCNR1 on its expression through differential micro-RNA (miRNA) binding to target mRNA, and investigated the relevance of altered SUCNR1 expression in AMD pathogenesis. We analysed common SUCNR1 SNPs for potential miRNA binding sites and identified rs13079080, located in the 3'-UTR and binding site for miRNA-4470. Both miRNA-4470 and SUCNR1 were found to be expressed in human retina. Moreover, using a luciferase reporter assay, a 60% decrease in activity was observed when miRNA-4470 was co-expressed with the C allele compared to the T allele of rs13079080. Finally, genotyping rs13079080 in an AMD case-control cohort revealed a protective effect of the TT genotype on AMD compared to the CC genotype (p = 0.007, odds ratio = 0.66). However, the association was not confirmed in the case-control study of the International AMD Genomics Consortium. Our study demonstrates that the T allele of rs13079080 in SUCNR1 disrupts a binding site for miRNA-4470, potentially increasing SUCNR1 expression and consequently increasing the capacity of sensing and dealing with oxidative stress. Therefore, it would be worthwhile assessing the relevance of rs13079080 in other oxidative stress-associated diseases in future studies.1 november 201

    Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

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    Contains fulltext : 175039.pdf (publisher's version ) (Open Access)BACKGROUND: Age-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits. METHODS: For each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression. RESULTS: Of the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27-20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 x 10-16 to 1.9 x 10-3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 x 10-7 to 3.0 x 10-4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis. CONCLUSIONS: We demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common

    Depictions of Thailand in Australian and Thai writings:Reflections of the Self and Other

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    This thesis offers both an examination of the depiction of Thailand in Australian novels, short stories and poems written in the 1980s and after, and an analysis of modern Thai novels and short stories that reflect similar themes to those covered in the Australian literature. One Australian film is also examined as the film provides an important framework for the analysis of some of the short stories and novels under consideration. The thesis establishes a dialogue between Thai and Australian literatures and demonstrates that the comparison of Australian representations of Thailand with Thai representations challenges constructively certain dominant political and social ideologies that enhance conservatism and the status quo in Thailand. The author acknowledges that the discussion of the representations of Thailand in contemporary Australian novels and short stories needs to take into account the colonial legacy and the discourse of Orientalism that tends to posit the ‘East’ as the ‘West’’s ‘Other’. Textual analysis is thus informed by post-colonial and cross-cultural theories, starting from Edward Said’s powerful and controversial critique of Western representation of the East in Orientalism. The first part of the thesis examines Australian crime stories and shows how certain Orientalist images and perceptions persist and help reinforce the image of the East and its people as the antithesis of the West. From Chapters Three through Six, however, more literary works by Australian authors are examined. The important finding is that most of the Australian authors under consideration attempt, though not always successfully, to resist and challenge the Eurocentric stereotypes of Asia and Asians that dominated Australian literature in earlier periods. This difference between contemporary Australian authors and their predecessors seems to reflect modern Australia’s endeavor to distinguish itself from the rest of the Western world and to redefine its relationship with Asia. As literary representations cannot be separated from socio-political contexts, the thesis also includes discussion of the Thai social and political history and, where appropriate, shows how colonialism and neo-colonialism exert their impact on modern Thailand

    Illness Self-Schema in Systemic Lupus Erythematosus

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    Systemic lupus erythematosus (SLE) is a relatively rare autoimmune disease with no known aetiology or cure. In addition to numerous physical symptoms, those living with SLE have also been shown to experience significant emotional and psychosocial difficulties. There has been little psychological research into SLE despite the rapidly increasing interest in health psychology and quality of life issues over the last two decades. One such issue that has commanded particular attention is that of cognitive bias in individuals with chronic pain and/or chronic illness. Cognitive bias toward illness-related information is theorised to indicate the presence of an illness self-schema, and is a valuable tool of investigation as it permits access to a level of cognitive structure that is inaccessible via self-report instruments. The primary focus of the present study is to investigate recall bias for pain- and illness-related words in SLE patients. This bias is explored relative to the recall of neutral words and depression-related words, and also relative to the responses of rheumatoid arthritis (RA) patients and healthy controls. Two hypotheses are proposed: firstly, that bias is related to disease activity; and secondly, that bias is related to the combination of illness and depression. The findings provide support for the second hypothesis, with the additional caveat that the nature of the pain/illness stimuli used is important in determining the presence of cognitive bias. No recall bias for illness-related words as a whole was found in any of the groups, nor was there evidence of a recall bias in the SLE and RA patients when they were divided according to depression status. However, when the illness words were examined separately according to �sensory pain� and �disability-related� words, a clear bias for disability words was found in the depressed patient group. It is concluded that there is a relationship between depression in chronically ill individuals, and the way in which such individuals process disability-related words. In accordance with the schema-enmeshment model (Pincus & Morley, 2001), it is suggested that both a pain-schema and an illness-schema exist, and it is when these two schemas become enmeshed with the self-schema that depression occurs in chronic pain/chronically ill patients. The cognitive bias assessment paradigm adopted in this study-one that is typically used in similar investigations-is lengthy, requires sophisticated equipment and can be difficult to interpret on an individual level. The present study investigates the relationship between cognitive biases in SLE patients and a recently-developed task, PRISM, which appears to symbolise the enmeshment of illness-, pain- and self-schemas. Analyses confirmed that recall of negative illness words was the only independent predictor of PRISM scores. This suggests that PRISM, a quick and easy task to administer, may have considerable usefulness as a clinical tool to assess information relevant to the enmeshment of illness- and self-schema. A greater understanding of schema and the processing styles of chronically ill patients will allow for more effective psychological treatment such that quality of life can be improved

    PRPH2 mutation update: in silico assessment of 245 reported and 7 novel variants in patients with retinal disease

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    Mutations in PRPH2, encoding peripherin-2, are associated with the development of a wide variety of inherited retinal diseases (IRDs). To determine the causality of the many PRPH2 variants that have been discovered over the last decades, we surveyed all published PRPH2 variants up to July 2020, describing 720 index patients that in total carried 245 unique variants. In addition, we identified seven novel PRPH2 variants in eight additional index patients. The pathogenicity of all variants was determined using the ACMG guidelines. With this, 107 variants were classified as pathogenic, 92 as likely pathogenic, one as benign, and two as likely benign. The remaining 50 variants were classified as variants of uncertain significance. Interestingly, of the total 252 PRPH2 variants, more than half (n = 137) were missense variants. All variants were uploaded into the Leiden Open source Variation and ClinVar databases. Our study underscores the need for experimental assays for variants of unknown significance to improve pathogenicity classification, which would allow us to better understand genotype-phenotype correlations, and in the long-term, hopefully also support the development of therapeutic strategies for patients with PRPH2-associated IRD.Ophthalmic researc

    Macular Dystrophy and Cone-Rod Dystrophy Caused by Mutations in the RP1 Gene: Extending the RP1 Disease Spectrum.

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    To describe the clinical and genetic spectrum of RP1-associated retinal dystrophies. In this multicenter case series, we included 22 patients with RP1-associated retinal dystrophies from 19 families from The Netherlands and Japan. Data on clinical characteristics, visual acuity, visual field, ERG, and retinal imaging were extracted from medical records over a mean follow-up of 8.1 years. Eleven patients were diagnosed with autosomal recessive macular dystrophy (arMD) or autosomal recessive cone-rod dystrophy (arCRD), five with autosomal recessive retinitis pigmentosa (arRP), and six with autosomal dominant RP (adRP). The mean age of onset was 40.3 years (range 14-56) in the patients with arMD/arCRD, 26.2 years (range 18-40) in adRP, and 8.8 years (range 5-12) in arRP patients. All patients with arMD/arCRD carried either the hypomorphic p.Arg1933* variant positioned close to the C-terminus (8 of 11 patients) or a missense variant in exon 2 (3 of 11 patients), compound heterozygous with a likely deleterious frameshift or nonsense mutation, or the p.Gln1916* variant. In contrast, all mutations identified in adRP and arRP patients were frameshift and/or nonsense variants located far from the C-terminus. Mutations in the RP1 gene are associated with a broad spectrum of progressive retinal dystrophies. In addition to adRP and arRP, our study provides further evidence that arCRD and arMD are RP1-associated phenotypes as well. The macular involvement in patients with the hypomorphic RP1 variant suggests that macular function may remain compromised if expression levels of RP1 do not reach adequate levels after gene augmentation therapy
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