High strain rate effect on tensile ductility and fracture of AM fabricated Inconel 718 with voided microstructures

The paper describes Electromagnetic Ring Expansion Tests (ERET) performed on Laser Melting Powder Bed Fusion (LPBF) Inconel 718 stress relieved test pieces, to establish the effect of a randomly dispersed spherically voided microstructure on tensile ductility, fracture, and fragmentation at high strain rate (10-3 < e < 104 s-1). An empirical model to predict porosity type and growth rates as a function of laser energy density was established, to select the LPBF process parameters to fabricate test pieces under stable conduction and keyhole melting. The size, shape, distribution of macro and keyhole pores in the test pieces obtained for ERET testing were characterised. At high strain rate the number of ring fragments for the highest porosity doubled, accompanied by a reduction in true strain at maximum uniform elongation and fracture strain. The trend for reducing fracture strain with increasing porosity at high strain rate was described by a decaying power law. Overall, there was a significant positive strain rate effect on tensile ductility at lower porosities attributed strain rate hardening (Hart, 1967) [1]. Fracture surfaces containing the highest porosity identified four different void coalescence mechanisms that helped explain the influence of larger pores on the stress state in the alloy.The AM of IN718 and tensile testing was funded by the UoD, College of Science and Engineering Research Excellence Framework (REF) funding for the Director of IISE (P. Wood) and AM Researcher (U. Gunputh). The support of G. Williams for IN718 sample preparation and M. Pawlik for tensile testing is acknowledged. A. Rusinek acknowledges the program UC3M-Santander Chair of Excellence in additive manufacturing. The expanding ring tests investigations were funded by the Polish Ministry of Science and Higher Education, Centre for Research and Development under research grant No. TECHMATSTRATEG2/410049/12/NCBR/2019

Machinability of INCONEL718 alloy with a porous microstructure produced by laser melting powder bed fusion at higher energy densities

Products produced by additive manufacturing (AM) seek to exploit net shape manufacturing by eliminating or minimizing post-process stages such as machining. However, many applications which include turbo machinery components with tight dimensional tolerances and a smooth surface finish will require at least a light machine finishing stage. This paper investigates the machinability of the additively fabricated INCONEL718 (IN718) alloy produced by laser melting powder bed fusion (LM-PBF) with different levels of spherical porosity in the microstructure. The literature suggests that the band width for laser energy density, which combines the various scan process parameters to obtain a low spherical type porosity in the LM-PBF IN718 alloy (~1%), has wide breadth. With the increasing laser energy density and above a threshold, there is a rapid increase in the spherical pore size. In this paper, three tube samples each with different levels of spherical porosity were fabricated by varying the laser energy density for LM-PBF of the IN718 alloy within the stable and higher energy density range and the porosity measured. A low laser energy density was avoided due to balling up, which promotes highly irregular lack of fusion defects and poor consolidation within the alloy microstructure. An orthogonal turning test instrumented, with a three-component dynamometer to measure the cutting forces, was performed on AM produced IN718 tube samples under light cut conditions to simulate a finish machining process. The orthogonal turning tests were also performed on a tube sample obtained from the wrought extruded stock. The machining process parameters, which were studied include varying the cutting speed at three levels, at a fixed feed and under dry cut conditions for a short duration to avoid the tool wear. The results obtained were discussed and a notable finding was the higher rate of built-up-edge formation on the tool tip from the AM samples with a higher porosity and especially at a higher cutting speed. The paper also discusses the mechanisms that underpin the findings.N/

Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability

Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types

Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing

This research was supported by the Australian Research Council (DP160102400), the Australian National Health and Medical Research Council (1078037, 1078901, 1103418, 1107258, 1127440 and 1113400), and the Sylvia & Charles Viertel Charitable Foundation. Riccardo Marioni was supported by Alzheimer’s Research UK Major Project Grant [ARUK-PG2017B-10]. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping and DNA methylation profiling of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” ((STRADL) Reference 104036/Z/14/Z).Peer reviewedPublisher PD

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

An evaluation of market segmentation in the top 100 companies of Mauritius

To be successful, businesses have to view their markets as consisting of distinct customer groups, each with their own distinct set of requirements and then deliver targeted offers to the customer groups they select to serve. Market segmentation is an essential prerequisite for commercial success. THe aim of this study was to evaluate the importance being attributed to market segmentation, targeting and positioning by the Top Hundred Companies of Mauritius. Questionnaires relating to market segmentation were adminstered to marketing managers of these companies. The findings were that most of the companies has a formal marketing planning system and marketing managers also believed that market segmentation is important. However, segmentation and product positioning were carried out informally. It was also found that the most commonly used segmentation variables were region, income, age, lifestyle and attitude towards the product. However, religion was not a very popular segmentation variable even though Mauritius is a multicultural country. Mauritian companies encountered numerous difficulties when trying to implement market segmentation

An examination of the consumer buying behaviour of single-parent households

With the rise in single-parent families, there is a need to determine whether there is a resulting change in family consumer behaviour and if marketers need to alter their strategies accordingly. The methodology used was a literature search on single parent families. Some of the interesting findings emerging from the literature review were that the single-mother family was the second most common type in the US; single mothers and married mothers behaved similarly in their buying behaviours, however single mothers took their children shopping more frequently; single mothers and single fathers were very different when it comes to product choice regarding food and beverages; children of single parents had more influence in the decision-making process than children of dual parents. They also shopped for the family more often; Working single parents and dual earners showed a similar behaviour when it came to grocery shopping and using convenience foods. Unemployed single parents differed to both in their buying behaviour; Single-parent families valued certain products more highly than intact families, such as holidays, traditions and family pets. It was concluded that the change in consumer behaviour due to the increase in single-parent families was minimal and inconsistent. Rather, there were similarities amongst members of the same socioeconomic class, rather than family type. Marketers would be unwise to adjust their strategies until more conclusive evidence is discovered. Instead, marketers could look at segmenting the group based on socioeconomic factors, particularly employment status as well as the quality of inter-family relationships

Developing a service quality questionnaire for the hotel industry in Mauritius

The evaluation of customer satisfaction is a primary goal for any service firm that would like to survive in this increasingly competitive market. Keeping tourists satisfied and delighted is even more important for the Mauritian tourism industry given that the destination faces fierce competition abroad. Developing a measure of hotel service quality is an important precursor to attracting and retaining tourists and hence ensuring the survival of hotels. SERVQUAL has been proposed as a generic measure of service quality that may be applicable to hotel services. The purpose of this study is to investigate whether SERVQUAL dimensions are pertinent to the hotel industry. Results from this study verify SERVQUAL dimensions, but demonstrate additional dimensions that are specific to the hotel sector