343 research outputs found

    Graphical workstation capability for reliability modeling

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    In addition to computational capabilities, software tools for estimating the reliability of fault-tolerant digital computer systems must also provide a means of interfacing with the user. Described here is the new graphical interface capability of the hybrid automated reliability predictor (HARP), a software package that implements advanced reliability modeling techniques. The graphics oriented (GO) module provides the user with a graphical language for modeling system failure modes through the selection of various fault-tree gates, including sequence-dependency gates, or by a Markov chain. By using this graphical input language, a fault tree becomes a convenient notation for describing a system. In accounting for any sequence dependencies, HARP converts the fault-tree notation to a complex stochastic process that is reduced to a Markov chain, which it can then solve for system reliability. The graphics capability is available for use on an IBM-compatible PC, a Sun, and a VAX workstation. The GO module is written in the C programming language and uses the graphical kernal system (GKS) standard for graphics implementation. The PC, VAX, and Sun versions of the HARP GO module are currently in beta-testing stages

    Neural Generalized Predictive Control: A Newton-Raphson Implementation

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    An efficient implementation of Generalized Predictive Control using a multi-layer feedforward neural network as the plant's nonlinear model is presented. In using Newton-Raphson as the optimization algorithm, the number of iterations needed for convergence is significantly reduced from other techniques. The main cost of the Newton-Raphson algorithm is in the calculation of the Hessian, but even with this overhead the low iteration numbers make Newton-Raphson faster than other techniques and a viable algorithm for real-time control. This paper presents a detailed derivation of the Neural Generalized Predictive Control algorithm with Newton-Raphson as the minimization algorithm. Simulation results show convergence to a good solution within two iterations and timing data show that real-time control is possible. Comments about the algorithm's implementation are also included

    Pressure visualization (PreViz) package version 1.0 user's guide

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    The Pressure Visualization (PreViz) package is a software tool which merges a wireframe model of the test aircraft with pressure data represented as a series of displacement vectors normal to the aircraft's skin. The PreViz package automates much of the researcher's data reduction effort, reduces the time required to review large amounts of pressure data, presents the data more clearly than tabular listings, and provides a wireframe description for a black and white graphic suitable for a technical publication (the actual graphic images must be created by a local package since PreViz has no graphics capability). Although designed for pressure data, the PreViz package works equally well for any surface property (such as structural loading or skin temperature). Written in ANSI-standard FORTRAN 77 and self-contained, PreViz executes in UNIX, VAX/VMS, and CDC/NOS host environments

    Educazione Fisica per Bambini con Sindrome di Charge: Ricerca per la Pratica

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    I bambini affetti da sindrome di Charge mostrano spesso un significativo ritardo nell o sviluppo motorio, che influisce sull a loro performance in diverse abilità motorie e attività fisiche. Lo scopo di questo studio era determinare lo stato dell ’educazione fisica offerta ai bambini affetti da questa sindrome. Le principali aree di interesse erano: (1) setting dell ’educazione fisica; (2) modalità di comunicazione; (3) modifiche; (4) lezioni di successo; (5) lezioni di educazione fisica problematiche. Ventisei genitori di bambini con sindrome di Charge, di età compresa tra 6 e 19 anni, hanno compilato un questionario durante una conferenza internazionale rivolta all e famiglie di soggetti affetti da questa sindrome, che è stato utilizzato come principale fonte di raccolta dati, per comprendere meglio la prospettiva dei genitori sull e esperienze di educazione fisica dei loro bambini con sindrome di Charge. I dati contenuti nell e risposte dei genitori al questionario sono stati usati per fornire indicazioni pratiche per la programmazione di attività di educazione fisica. I risultati hanno rivelato che il tipo di inserimento nell ’educazione fisica influisce sul successo dei bambini e sull a soddisfazione dei genitori rispetto al programma di educazione fisica. Inoltre, i bambini che avevano la possibilità di usufruire di personale di sostegno, come un assistente dell ’insegnante, un educatore o un coadiutore durante l’educazione fisica, avevano maggiore successo. Sono state utilizzate svariate modalità di comunicazione con i bambini con sindrome di Charge. Le lezioni di educazione fisica di successo, secondo quanto riportato dai genitori, erano nuoto, monopattino, bowling, scherma, T-ball , danza, roccia, hockey su pista, hockey su prato e ginnastica artistica. Le lezioni in cui i bambini facevano più fatica erano quell e relative ad abilità motorie fondamentali, come saltare la corda, correre, saltell are, e tutte le lezioni di sport che implicavano l’uso di una pall a che si muoveva velocemente. In conclusione, le modalità di inserimento in educazione fisica, la comunicazione e le modifiche devono essere definitive in modo individualizzato, tenendo conto dell e caratteristiche di ogni singolo bambino con sindrome di Charge. Inoltre, il personale di supporto deve essere appositamente formato sull e esigenze speciali di ogni bambino e sull e aree base di insegnamento del programma di educazione fisica. Vengono infine inclusi nell ’articolo alcuni suggerimenti per migliorare i programmi di educazione fisica, in modo da favorire il coinvolgimento del bambino con la classe e aumentare il successo nell e singole lezioni svolte

    Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

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    The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs

    Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland:Scottish Family Health Study (GS:SFHS)

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    The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD

    Congenital Heart Disease–Causing Gata4 Mutation Displays Functional Deficits In Vivo

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    Defects of atrial and ventricular septation are the most frequent form of congenital heart disease, accounting for almost 50% of all cases. We previously reported that a heterozygous G296S missense mutation of GATA4 caused atrial and ventricular septal defects and pulmonary valve stenosis in humans. GATA4 encodes a cardiac transcription factor, and when deleted in mice it results in cardiac bifida and lethality by embryonic day (E)9.5. In vitro, the mutant GATA4 protein has a reduced DNA binding affinity and transcriptional activity and abolishes a physical interaction with TBX5, a transcription factor critical for normal heart formation. To characterize the mutation in vivo, we generated mice harboring the same mutation, Gata4 G295S. Mice homozygous for the Gata4 G295S mutant allele have normal ventral body patterning and heart looping, but have a thin ventricular myocardium, single ventricular chamber, and lethality by E11.5. While heterozygous Gata4 G295S mutant mice are viable, a subset of these mice have semilunar valve stenosis and small defects of the atrial septum. Gene expression studies of homozygous mutant mice suggest the G295S protein can sufficiently activate downstream targets of Gata4 in the endoderm but not in the developing heart. Cardiomyocyte proliferation deficits and decreased cardiac expression of CCND2, a member of the cyclin family and a direct target of Gata4, were found in embryos both homozygous and heterozygous for the Gata4 G295S allele. To further define functions of the Gata4 G295S mutation in vivo, compound mutant mice were generated in which specific cell lineages harbored both the Gata4 G295S mutant and Gata4 null alleles. Examination of these mice demonstrated that the Gata4 G295S protein has functional deficits in early myocardial development. In summary, the Gata4 G295S mutation functions as a hypomorph in vivo and leads to defects in cardiomyocyte proliferation during embryogenesis, which may contribute to the development of congenital heart defects in humans

    Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

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    Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p
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