A robust design methodology suitable for application to one-off products

Robust design is an activity of fundamental importance when designing large, complex, one-off engineering products. Work is described which is concerned with the application of the theory of design of experiments and stochastic optimization methods to explore and optimize at the concept design stage. The discussion begins with a description of state-of-the-art stochastic techniques and their application to robust design. The content then focuses on a generic methodology which is capable of manipulating design algorithms that can be used to describe a design concept. An example is presented, demonstrating the use of the system for the robust design of a catamaran with respect to seakeeping

Angiotensin II and NADPH Oxidase Increase ADMA in Vascular Smooth Muscle Cells

Asymmetric dimethylarginine inhibits nitric oxide synthase, cationic amino acid transport and endothelial function. Patients with cardiovascular risk factors often have endothelial dysfunction associated with increased plasma asymmetric dimethylarginine and markers of reactive oxygen species. We tested the hypothesis that reactive oxygen species, generated by nicotinamide adenine dinucleotide phosphate oxidase, enhance cellular asymmetric dimethylarginine. Incubation of rat preglomerular vascular smooth muscle cells with angiotensin II doubled the activity of nicotinamide adenine dinucleotide phosphate oxidase, but decreased the activities of dimethylarginine dimethylaminohydrolase by 35% and of cationic amino acid transport by 20% and doubled cellular (but not medium) asymmetric dimethylarginine concentrations (p<0.01). This was blocked by tempol or candesartan. Cells stably transfected with p22(phox) had a 50% decreased protein expression and activity of dimethylarginine dimethylaminohydrolase despite increased promoter activity and mRNA. The decreased DDAH protein expression and the increased asymmetric dimethylarginine concentration in p22(phox) transfected cells were prevented by proteosomal inhibition. These cells had enhanced protein arginine methylation, a 2-fold increased expression of protein arginine methyltransferase-3 (p<0.05), and a 30% reduction in cationic amino acid transport activity (p<0.05). Asymmetric dimethylarginine was increased from 6±1 to 16±3μmol·l(−1) (p<0.005) in p22(phox) transfected cells. Thus, angiotensin II increased cellular asymmetric dimethylarginine via type 1 receptors and reactive oxygen species. Nicotinamide adenine dinucleotide phosphate oxidase increased cellular asymmetric dimethylarginine by increasing enzymes that generate it, enhancing the degradation of enzymes that metabolize it, and reducing its cellular transport. This could underlie increases in cellular asymmetric dimethylarginine during oxidative stress

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

Digital Drugs: an anatomy of new medicines

Medicines are digitalized as aspects of their regulation and use are embodied in or draw from interlinked computerized systems and databases. This paper considers how this development changes the delivery of health care, the pharma industry, and regulatory and professional structures, as it reconfigures the material character of drugs themselves. It draws on the concept of assemblage in presenting a theory-based analysis that explores digital drugs’ ontological status including how they embody benefit and value. The paper addresses three interconnected domains – that of use of drugs (practice), of research (epistemology) and of regulation (structures)

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

The roles of the formal and informal sectors in the provision of effective science education

For many years, formal school science education has been criticised by students, teachers, parents and employers throughout the world. This article presents an argument that a greater collaboration between the formal and the informal sector could address some of these criticisms. The causes for concern about formal science education are summarised and the major approaches being taken to address them are outlined. The contributions that the informal sector currently makes to science education are identified. It is suggested that the provision of an effective science education entails an enhanced complementarity between the two sectors. Finally, there is a brief discussion of the collaboration and communication still needed if this is to be effective

Quasielastic (e,e′p) reaction on 12C,56Fe, and 197Au

We report the results from a systematic study of the quasielastic (e,e′p) reaction on 12C, 56Fe, and 197Au performed at Jefferson Lab. We have measured nuclear transparency and extracted spectral functions (corrected for radiation) over a Q2 range of 0.64–3.25 (GeV∕c)2 for all three nuclei. In addition, we have extracted separated longitudinal and transverse spectral functions at Q2 of 0.64 and 1.8 (GeV∕c)2 for these three nuclei (except for 197Au at the higher Q2). The spectral functions are compared to a number of theoretical calculations. The measured spectral functions differ in detail but not in overall shape from most of the theoretical models. In all three targets the measured spectral functions show considerable excess transverse strength at Q2=0.64 (GeV∕c)2, which is much reduced at 1.8 (GeV∕c)2

Separated spectral functions for the quasifree 12C(e,e′p) reaction

A separation of the longitudinal and transverse 12C(e,e′p) cross sections in the quasifree region has been performed in parallel kinematics at Q2 of 0.64 and 1.8 GeV2 for initial proton momentum <80 MeV. The separated transverse and longitudinal spectral functions at Q2=0.64GeV2 show significant differences for missing energy between 25 and 60 MeV indicating a breakdown in the single nucleon knockout picture. The transverse spectral functions exhibit definite momentum transfer dependence

Chromosomal location of human genes encoding major heat-shock protein HSP70

The HSP70 family of heat-shock proteins constitutes the major proteins synthesized in response to elevated temperatures and other forms of stress. In eukaryotes members of the HSP70 family also include a protein similar if not identical to bovine brain uncoating ATPase and glucose-regulated proteins. An intriguing relation has been established between expression of heat-shock proteins and transformation in mammalian cells. Elevated levels of HSP70 are found in some transformed cell lines, and viral and cellular gene products that are capable of transforming cells in vitro can also stimulate transcription of HSP70 genes. To determine the organization of this complex multigene family in the human genome, we used complementary approaches: Southern analysis and protein gels of Chinese hamster-human somatic cell hybrids, and in situ hybridization to human chromosomes. We demonstrate that functional genes encoding HSP70 proteins map to human chromosomes 6, 14, 21, and at least one other chromosome .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45535/1/11188_2005_Article_BF01534692.pd