Automotive leaf spring design and manufacturing process improvement using failure mode and effects analysis (FMEA)

Nowadays human safety and comfort are the most considerable parameters in designing and manufacturing of a vehicle, that is why every organization ensures the quality and reliability of components used in the vehicle. Leaf spring is also a component of vehicle which plays an important role in human safety and comfort. It acts as a structural member and an integral part of suspension system. It is important to eliminate the failures in designing and manufacturing process of leaf springs because of its importance in functionality and safety of vehicle. In this research, failure mode and effects analysis has been used to analyze and reduce the risks of 42 possible failures that can occur in automotive leaf spring. It starts from determining, classifying, and analyzing all potential failures and then rating them with the help numeric scores. The four numeric scores namely severity, occurrence, detection, and Risk Priority Number (RPN) are used to find the high potential failures of semi-elliptical leaf springs. In the end, actions are recommended for RPN greater than 250, to increase quality and reliably of product. </jats:p

Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues

PURPOSE: There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism. METHODS: Rats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins. RESULTS: Both oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake. CONCLUSIONS: Oral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world

Extensive Anti-CoA Immunostaining in Alzheimer’s Disease and Covalent Modification of Tau by a Key Cellular Metabolite Coenzyme A

Alzheimer’s disease (AD) is a neurodegenerative disorder, accounting for at least two-thirds of dementia cases. A combination of genetic, epigenetic and environmental triggers is widely accepted to be responsible for the onset and development of AD. Accumulating evidence shows that oxidative stress and dysregulation of energy metabolism play an important role in AD pathogenesis, leading to neuronal dysfunction and death. Redox-induced protein modifications have been reported in the brain of AD patients, indicating excessive oxidative damage. Coenzyme A (CoA) is essential for diverse metabolic pathways, regulation of gene expression and biosynthesis of neurotransmitters. Dysregulation of CoA biosynthesis in animal models and inborn mutations in human genes involved in the CoA biosynthetic pathway have been associated with neurodegeneration. Recent studies have uncovered the antioxidant function of CoA, involving covalent protein modification by this cofactor (CoAlation) in cellular response to oxidative or metabolic stress. Protein CoAlation has been shown to both modulate the activity of modified proteins and protect cysteine residues from irreversible overoxidation. In this study, immunohistochemistry analysis with highly specific anti-CoA monoclonal antibody was used to reveal protein CoAlation across numerous neurodegenerative diseases, which appeared particularly frequent in AD. Furthermore, protein CoAlation consistently co-localized with tau-positive neurofibrillary tangles, underpinning one of the key pathological hallmarks of AD. Double immunihistochemical staining with tau and CoA antibodies in AD brain tissue revealed co-localization of the two immunoreactive signals. Further, recombinant 2N3R and 2N4R tau isoforms were found to be CoAlated in vitro and the site of CoAlation mapped by mass spectrometry to conserved cysteine 322, located in the microtubule binding region. We also report the reversible H_{2}O_{2}-induced dimerization of recombinant 2N3R, which is inhibited by CoAlation. Moreover, CoAlation of transiently expressed 2N4R tau was observed in diamide-treated HEK293/Pank1β cells. Taken together, this study demonstrates for the first time extensive anti-CoA immunoreactivity in AD brain samples, which occurs in structures resembling neurofibrillary tangles and neuropil threads. Covalent modification of recombinant tau at cysteine 322 suggests that CoAlation may play an important role in protecting redox-sensitive tau cysteine from irreversible overoxidation and may modulate its acetyltransferase activity and functional interactions

Distributed manufacturing: scope, challenges and opportunities

This discussion paper aims to set out the key challenges and opportunities emerging from distributed manufacturing (DM). We begin by describing the concept, available definitions and consider its evolution where recent production technology developments (such as additive and continuous production process technologies), digitization together with infrastructural developments (in terms of IoT and big-data) provide new opportunities. To further explore the evolving nature of DM, the authors, each of whom are involved in specific applications of DM research, examine through an expert panel workshop environment emerging DM applications involving new production and supporting infrastructural technologies. This paper presents these generalizable findings on DM challenges and opportunities in terms of products, enabling production technologies, and the impact on the wider production and industrial system. Industry structure and location of activities are examined in terms of the democratizing impact on participating network actors. The paper concludes with a discussion on the changing nature of manufacturing as a result of DM, from the traditional centralized, large scale, long lead-time forecast driven production operations, to a new DM paradigm where manufacturing is a decentralized, autonomous near end-user driven activity. A forward research agenda is proposed that considers the impact of DM on the industrial and urban landscape.The Cambridge–Hamied Visiting Lecture Scheme and UKIERIThis is the author accepted manuscript. The final version is available from Taylor & Francis via https://doi.org/10.1080/00207543.2016.119230

Publisher Correction: Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease)

Correction to: Scientific Reports https://doi.org/10.1038/s41598-018-27107-8, published online 19 June 201

Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment

Delivering access to sufficient food, energy and water resources to ensure human wellbeing is a major concern for governments worldwide. However, it is crucial to account for the ‘nexus’ of interactions between these natural resources and the consequent implications for human wellbeing. The private sector has a critical role in driving positive change towards more sustainable nexus management and could reap considerable benefits from collaboration with researchers to devise solutions to some of the foremost sustainability challenges of today. Yet opportunities are missed because the private sector is rarely involved in the formulation of deliverable research priorities. We convened senior research scientists and influential business leaders to collaboratively identify the top forty questions that, if answered, would best help companies understand and manage their food-energy-water-environment nexus dependencies and impacts. Codification of the top order nexus themes highlighted research priorities around development of pragmatic yet credible tools that allow businesses to incorporate nexus interactions into their decision-making; demonstration of the business case for more sustainable nexus management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance. Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation.This work was supportedby the Economic and Social Research Council [Grant Number ES/L01632X/1] and is part of the Nexus Network Initiative. WJS is funded by Arcadia

New methodologies and algorithms for the design of variable structure control systems

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Intronic SNP rs3811647 of the human transferrin gene modulates its expression in hepatoma cells

Peer Reviewe