Machine-Part cell formation through visual decipherable clustering of Self Organizing Map

Machine-part cell formation is used in cellular manufacturing in order to process a large variety, quality, lower work in process levels, reducing manufacturing lead-time and customer response time while retaining flexibility for new products. This paper presents a new and novel approach for obtaining machine cells and part families. In the cellular manufacturing the fundamental problem is the formation of part families and machine cells. The present paper deals with the Self Organising Map (SOM) method an unsupervised learning algorithm in Artificial Intelligence, and has been used as a visually decipherable clustering tool of machine-part cell formation. The objective of the paper is to cluster the binary machine-part matrix through visually decipherable cluster of SOM color-coding and labelling via the SOM map nodes in such a way that the part families are processed in that machine cells. The Umatrix, component plane, principal component projection, scatter plot and histogram of SOM have been reported in the present work for the successful visualization of the machine-part cell formation. Computational result with the proposed algorithm on a set of group technology problems available in the literature is also presented. The proposed SOM approach produced solutions with a grouping efficacy that is at least as good as any results earlier reported in the literature and improved the grouping efficacy for 70% of the problems and found immensely useful to both industry practitioners and researchers.Comment: 18 pages,3 table, 4 figure

Naloxone inhibits immune cell function by suppressing superoxide production through a direct interaction with gp91phox subunit of NADPH oxidase

<p>Abstract</p> <p>Background</p> <p>Both (-) and (+)-naloxone attenuate inflammation-mediated neurodegeneration by inhibition of microglial activation through superoxide reduction in an opioid receptor-independent manner. Multiple lines of evidence have documented a pivotal role of overactivated NADPH oxidase (NOX2) in inflammation-mediated neurodegeneration. We hypothesized that NOX2 might be a novel action site of naloxone to mediate its anti-inflammatory actions.</p> <p>Methods</p> <p>Inhibition of NOX-2-derived superoxide by (-) and (+)-naloxone was measured in lipopolysaccharide (LPS)-treated midbrain neuron-glia cultures and phorbol myristate acetate (PMA)-stimulated neutrophil membranes by measuring the superoxide dismutase (SOD)-inhibitable reduction of tetrazolium salt (WST-1) or ferricytochrome c. Further, various ligand (³H-naloxone) binding assays were performed in wild type and gp91<it>^phox-/-</it>neutrophils and transfected COS-7 and HEK293 cells. The translocation of cytosolic subunit p47<it>^phox</it>to plasma membrane was assessed by western blot.</p> <p>Results</p> <p>Both (-) and (+)-naloxone equally inhibited LPS- and PMA-induced superoxide production with an IC50 of 1.96 and 2.52 μM, respectively. Competitive binding of ³H-naloxone with cold (-) and (+)-naloxone in microglia showed equal potency with an IC50 of 2.73 and 1.57 μM, respectively. ³H-Naloxone binding was elevated in COS-7 and HEK293 cells transfected with gp91^{<it>phox</it>}; in contrast, reduced ³H-naloxone binding was found in neutrophils deficient in gp91^{<it>phox </it>}or in the presence of a NOX2 inhibitor. The specificity and an increase in binding capacity of ³H-naloxone were further demonstrated by 1) an immunoprecipitation study using gp91^{<it>phox </it>}antibody, and 2) activation of NOX2 by PMA. Finally, western blot studies showed that naloxone suppressed translocation of the cytosolic subunit p47^{<it>phox </it>}to the membrane, leading to NOX2 inactivation.</p> <p>Conclusions</p> <p>Strong evidence is provided indicating that NOX2 is a non-opioid novel binding site for naloxone, which is critical in mediating its inhibitory effect on microglia overactivation and superoxide production.</p

A feasibility study for NOn-Traditional providers to support the management of Elderly People with Anxiety and Depression: the NOTEPAD study Protocol

BACKGROUND: Anxiety and depression are common among older people, with up to 20% reporting such symptoms, and the prevalence increases with co-morbid chronic physical health problems. Access to treatment for anxiety and depression in this population is poor due to a combination of factors at the level of patient, practitioner and healthcare system. There is evidence to suggest that older people with anxiety and/or depression may benefit both from one-to-one interventions and group social or educational activities, which reduce loneliness, are participatory and offer some activity. Non-traditional providers (support workers) working within third-sector (voluntary) organisations are a valuable source of expertise within the community but are under-utilised by primary care practitioners. Such a resource could increase access to care, and be less stigmatising and more acceptable for older people. METHODS: The study is in three phases and this paper describes the protocol for phase III, which will evaluate the feasibility of recruiting general practices and patients into the study, and determine whether support workers can deliver the intervention to older people with sufficient fidelity and whether this approach is acceptable to patients, general practitioners and the third-sector providers. Phase III of the NOTEPAD study is a randomised controlled trial (RCT) that is individually randomised. It recruited participants from approximately six general practices in the UK. In total, 100 participants aged 65 years and over who score 10 or more on PHQ9 or GAD7 for anxiety or depression will be recruited and randomised to the intervention or usual general practice care. A mixed methods approach will be used and follow-up will be conducted 12 weeks post-randomisation. DISCUSSION: This study will inform the design and methods of a future full-scale RCT. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN16318986 . Registered 10 November 2016. The ISRCTN registration is in line with the World Health Organization Trial Registration Data Set. The present paper represents the original version of the protocol. Any changes to the protocol will be communicated to ISRCTN

Relativistic Binaries in Globular Clusters

Galactic globular clusters are old, dense star systems typically containing 10\super{4}--10\super{7} stars. As an old population of stars, globular clusters contain many collapsed and degenerate objects. As a dense population of stars, globular clusters are the scene of many interesting close dynamical interactions between stars. These dynamical interactions can alter the evolution of individual stars and can produce tight binary systems containing one or two compact objects. In this review, we discuss theoretical models of globular cluster evolution and binary evolution, techniques for simulating this evolution that leads to relativistic binaries, and current and possible future observational evidence for this population. Our discussion of globular cluster evolution will focus on the processes that boost the production of hard binary systems and the subsequent interaction of these binaries that can alter the properties of both bodies and can lead to exotic objects. Direct {\it N}-body integrations and Fokker--Planck simulations of the evolution of globular clusters that incorporate tidal interactions and lead to predictions of relativistic binary populations are also discussed. We discuss the current observational evidence for cataclysmic variables, millisecond pulsars, and low-mass X-ray binaries as well as possible future detection of relativistic binaries with gravitational radiation.Comment: 88 pages, 13 figures. Submitted update of Living Reviews articl

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early

Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts

Objective: We aimed to explore the precise molecular mechanism of early and invasive tumor growth in a small-for-size graft after liver transplantation and to identify the distinct molecular signature linked to acute-phase injury and late-phase tumor invasiveness. Summary background data: Acute phase small-for-size liver graft injury plays an important role in tumor recurrence after liver transplantation. For prevention of such recurrence, understanding of its underlying mechanism will be important in developing novel therapeutic strategies. Methods: An orthotopic rat liver transplantation model was applied using whole grafts and small-for-size (50%) grafts. The recipients were injected with hepatoma cell lines via the portal vein to mimic tumor recurrence after liver transplantation. Tumor invasive properties were compared between the tumor developed from small and whole graft. Gene signatures of acute phase graft injury (days 1 and 3) and late phase tumor recurrence (days 14 and 21) were screened using cDNA microarray analysis and further confirmed by quantitative RT-PCR. The potential gene candidate CXCL10 was singled out for further functional studies to investigate its role in tumor progression. Results: A number of genes linked to inflammatory responses and tumor invasiveness were found over-expressed in small-for-size liver grafts and/or tumors developed in small liver grafts by cDNA microarray screening. Real-time RT-PCR also confirmed that the gene CXCL10 was over-expressed not only in small-for-size graft at the early phase, but also in tumor from small-for-size graft at the late phase after liver transplantation. In vitro functional studies further confirmed that CXCL10 promoted tumor-invasion-related properties and tumor-associated macrophage activation. Conclusion: CXCL10 over-expression, the distinct gene signature of acute-phase graft injury and tumor invasiveness in small-for-size liver grafts, may contribute to early tumor recurrence after liver transplantation. CXCL10 and its downstream signals may be potential therapeutic targets in the prevention of tumor recurrence after liver transplantation using small-for-size graft. © 2010 Lippincott Williams & Wilkins.link_to_subscribed_fulltex