660 research outputs found

    In situ monitoring the effects of Ti6Al4V powder oxidation during laser powder bed fusion additive manufacturing

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    Making laser powder bed fusion (L-PBF) additive manufacturing process sustainable requires effective powder recycling. Recycling of Ti6Al4V powder in L-PBF can lead to powder oxidation, however, such impact on laser-matter interactions, process, and defect dynamics during L-PBF are not well understood. This study reveals and quantifies the effects of processing Ti6Al4V powders with low (0.12 wt%) and high (0.40 wt%) oxygen content during multilayer thin-wall L-PBF using in situ high speed synchrotron X-ray imaging. Our results reveal that high oxygen content Ti6Al4V powder can reduce melt ejections, surface roughness, and defect population in the built parts. With increasing oxygen content in the part, there is an increase in microhardness due to solid solution strengthening and no significant change in the microstructure is evident

    In situ characterisation of surface roughness and its amplification during multilayer single-track laser powder bed fusion additive manufacturing

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    Surface roughness controls the mechanical performance and durability (e.g., wear and corrosion resistance) of laser powder bed fusion (LPBF) components. The evolution mechanisms of surface roughness during LPBF are not well understood due to a lack of in situ characterisation methods. Here, we quantified key processes and defect dynamics using synchrotron X-ray imaging and ex situ optical imaging and explained the evolution mechanisms of side-skin and top-skin roughness during multi-layer LPBF of Ti-6Al-4V (where down-skin roughness was out of the project scope). We found that the average surface roughness alone is not an accurate representation of surface topology of an LPBF component and that the surface topology is multimodal (e.g., containing both roughness and waviness) and multiscale (e.g., from 25 µm sintered powder features to 250 µm molten pool wavelength). Both roughness and topology are significantly affected by the formation of pre-layer humping, spatter, and rippling defects. We developed a surface topology matrix that accurately describes surface features by combining 8 different metrics: average roughness, root mean square roughness, maximum profile peak height, maximum profile valley height, mean height, mean width, skewness, and melt pool size ratio. This matrix provides a guide to determine the appropriate linear energy density to achieve the optimum surface finish of Ti-6Al-4V thin-wall builds. This work lays a foundation for surface texture control which is critical for build design, metrology, and performance in LPBF

    Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

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    Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al

    Identification of KasA as the cellular target of an anti-tubercular scaffold

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    Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis β-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related β-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis
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