291 research outputs found

    Impact of the 1872 Education (Scotland) act, on Scottish working class education up to 1899

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    Plunge milling time optimization via mixed-integer nonlinear programming

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    International audiencePlunge milling is a recent and efficient production mean for machining deep workpieces, notably in aeronautics. This paper focuses on the minimization of the machining time by optimizing the values of the cutting parameters. Currently, neither Computer-Aided Manufacturing (CAM) software nor standard approaches take into account the tool path geometry and the control laws driving the tool displacements to propose optimal cutting parameter values, despite their significant impact. This paper contributes to plunge milling optimization through a Mixed-Integer NonLinear Programming (MINLP) approach, which enables us to determine optimal cutting parameter values that evolve along the tool path. It involves both continuous (cutting speed, feed per tooth) and, in contrast with standard approaches, integer (number of plunges) optimization variables, as well as nonlinear constraints. These constraints are related to the Computer Numerical Control (CNC) machine tool and to the cutting tool, taking into account the control laws. Computational results, validated on CNC machines and on representative test cases of engine housing, show that our methodology outperforms standard industrial engineering know-how approaches by up to 55% in terms of machining time

    Cutting Conditions and Surface Integrity During Dry Plunge-milling of a Wrought Magnesium Alloy

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    AbstractPlunge milling is a machining process used to remove material rapidly in roughing operations. It is known to offer significant increases in productivity as compared with conventional milling, especially in the case of deep milled workpieces. However, high productivity also entails the increase in machining conditions so it would be expected that plunge milling has more impact on surface integrity than conventional machining. In this study the authors consider the case of a dry plunge milling process applied to a wrought Mg-Zr-Zn-RE alloy. First, the study involves obtaining surfaces through experimental design. Second, plunge milling conditions are correlated with surface integrity factors, such as roughness, microstructure and microhardness. This study suggests plunge milling conditions to offer a trade-off between surface integrity and chip flow

    Specific and complete human genome amplification with improved yield achieved by phi29 DNA polymerase and a novel primer at elevated temperature

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    <p>Abstract</p> <p>Backgrounds</p> <p>Whole genome amplification (WGA) is a practical solution to eliminate molecular analysis limitations associated with genomic DNA (gDNA) quantity. Different methods have been developed to amplify the whole genome, including primer extension preamplification (PEP), degenerate oligonucleotide primed PCR (DOP-PCR), and multiple displacement amplification (MDA). Each of these methods has its own merits and limitations.</p> <p>Findings</p> <p>Effects of primer length and composition on amplification quality and quantity were explored in this study at two different temperatures (30°C & 40°C). New primer designs combined with elevated amplification temperature has significantly improved MDA as measured by amplification yield, genome coverage, and allele drop out (ADO) analysis. A remarkable finding was the comprehensive amplification, at 30°C & 40°C, of the human whole genome via the use of GGGCAGGA*N*G hotspot recombination consensus primer. Amplification was characterized by Affymetrix 10K SNP chip analysis. Finally, the use of new primer designs has suppressed the template-independent DNA amplification (TIDA) both at 30°C and 40°C.</p> <p>Conclusion</p> <p>The use of new primers in this study combined with elevated incubation temperatures in MDA has remarkably improved the specificity, amplification yield, and suppressed TIDA.</p

    Mycobacterium bovis shedding patterns from experimentally infected calves and the effect of concurrent infection with bovine viral diarrhoea virus

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    Concurrent infection of cattle with bovine viral diarrhoea virus (BVDV) and Mycobacterium bovis is considered to be a possible risk factor for onward transmission of bovine tuberculosis (BTB) in infected cattle and is known to compromise diagnostic tests. A comparison is made here of M. bovis shedding (i.e. release) characteristics from 12 calves, six experimentally co-infected with BVDV and six infected with M. bovis alone, using simple models of bacterial replication. These statistical and mathematical models account for the intermittent or episodic nature of shedding, the dynamics of within-host bacterial proliferation and the sampling distribution from a given shedding episode. We show that while there are distinct differences among the shedding patterns of calves given the same infecting dose, there is no statistically significant difference between the two groups of calves. Such differences as there are, can be explained solely in terms of the shedding frequency, but with all calves potentially excreting the same amount of bacteria in a given shedding episode post-infection. The model can be thought of as a process of the bacteria becoming established in a number of discrete foci of colonization, rather than as a more generalized infection of the respiratory tract. In this case, the variability in the shedding patterns of the infected calves can be explained solely by differences in the number of foci established and shedding being from individual foci over time. Should maximum exposure on a particular occasion be a critical consideration for cattle-to-cattle transmission of BTB, cattle that shed only intermittently may still make an important contribution to the spread and persistence of the disease

    Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency

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    Inactivating mutations in chromodomain helicase DNA binding protein 7 (CHD7) cause CHARGE syndrome, a severe multiorgan system disorder of which Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a minor feature. Recent reports have described predominantly missense CHD7 alleles in IGD patients, but it is unclear if these alleles are relevant to causality or overall genetic burden of Kallmann syndrome (KS) and normosmic form of IGD. To address this question, we sequenced CHD7 in 783 well-phenotyped IGD patients lacking full CHARGE features; we identified nonsynonymous rare sequence variants in 5.2% of the IGD cohort (73% missense and 27% splice variants). Functional analyses in zebrafish using a surrogate otolith assay of a representative set of these CHD7 alleles showed that rare sequence variants observed in controls showed no altered function. In contrast, 75% of the IGD-associated alleles were deleterious and resulted in both KS and normosmic IGD. In two families, pathogenic mutations in CHD7 coexisted with mutations in other known IGD genes. Taken together, our data suggest that rare deleterious CHD7 alleles contribute to the mutational burden of patients with both KS and normosmic forms of IGD in the absence of full CHARGE syndrome. These findings (i) implicate a unique role or preferential sensitivity for CHD7 in the ontogeny of GnRH neurons, (ii) reiterate the emerging genetic complexity of this family of IGD disorders, and (iii) demonstrate how the coordinated use of well-phenotyped cohorts, families, and functional studies can inform genetic architecture and provide insights into the developmental biology of cellular systems
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