599 research outputs found
Application of the x-ray measurement model to image processing of x-ray radiographs
A computational model has been developed at which simulates the film response to the interaction of x-rays with a sample[1,2]. By using a CAD model as a virtual part, film densities of the radiograph are predicted. The number of photons which reach the film is based on the thickness of the part, part geometry, and the material absorption coefficient. Also taken into consideration are the x-ray beam characteristics, film properties, and the experimental configuration. The model generated images can vary in size and resolution, depending on the user chosen parameters. Noise is calculated using a Gaussian noise distribution and adjusted for the film type. The result of this simulation is a two-dimensional numerically generated digital image, which represents a radiograph of the part. This result can be used to analyze the flaws in an actual radiograph with the same set-up and exposure parameters
Evidences for a quasi 60-year North Atlantic Oscillation since 1700 and its meaning for global climate change
The North Atlantic Oscillation (NAO) obtained using instrumental and
documentary proxy predictors from Eurasia is found to be characterized by a
quasi 60-year dominant oscillation since 1650. This pattern emerges clearly
once the NAO record is time integrated to stress its comparison with the
temperature record. The integrated NAO (INAO) is found to well correlate with
the length of the day (since 1650) and the global surface sea temperature
record HadSST2 and HadSST3 (since 1850). These findings suggest that INAO can
be used as a good proxy for global climate change, and that a 60-year cycle
exists in the global climate since at least 1700. Finally, the INAO ~60-year
oscillation well correlates with the ~60- year oscillations found in the
historical European aurora record since 1700, which suggests that this 60-year
dominant climatic cycle has a solar-astronomical origin
Genomic screen for loci associated with tobacco usage in Mission Indians
BACKGROUND: The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California. METHODS: A structured diagnostic interview was used to define two tobacco use phenotypes: 1) any regular tobacco usage (smoked daily for one month or more) and 2) persistent tobacco usage (smoked at least 10 cigarettes a day for more than one year). Heritability was determined and a linkage analysis was performed, using genotypes for a panel 791 microsatellite polymorphisms, for the two phenotypes using variance component methods implemented in SOLAR. RESULTS: Analyses of multipoint variance component LOD scores for the two tobacco use phenotypes revealed two scores that exceeded 2.0 for the regular use phenotype: one on chromosomes 6 and one on 8. Four other loci on chromosomes 1,7,13, and 22 were found with LOD scores between 1.0 and 1.5. Two loci of interest were found on chromosomes 1 and 4 for the persistent use phenotype with LOD scores between 1.3–1.5. Bivariate linkage analysis was conducted at the site on chromosome 4 for persistent tobacco use and an alcohol drinking severity phenotype previously identified at this site. The maximum LOD score for the bivariate analysis for the region was 3.4, however, there was insufficient power to exclude coincident linkage. CONCLUSION: While not providing evidence for linkage to specific chromosomal regions these results identify regions of interest in the genome in this Mission Indian population, for tobacco usage, some of which were identified in previous genome scans of non-native populations. Additionally, these data lend support for the hypothesis that cigarette smoking, alcohol dependence and other consumptive behaviors may share some common risk and/or protective factors in this Mission Indian population
Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence
o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (≥ 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified
SIRT2 Ablation Has No Effect on Tubulin Acetylation in Brain, Cholesterol Biosynthesis or the Progression of Huntington's Disease Phenotypes In Vivo
Huntington's disease (HD) is a devastating neurodegenerative disorder for which there are no disease-modifying treatments. The molecular pathogenesis of HD is complex and many mechanisms and cellular processes have been proposed as potential sites of therapeutic intervention. However, prior to embarking on drug development initiatives, it is essential that therapeutic targets can be validated in mammalian models of HD. Previous studies in invertebrate and cell culture HD models have suggested that inhibition of SIRT2 could have beneficial consequences on disease progression. SIRT2 is a NAD[superscript +]-dependent deacetylase that has been proposed to deacetylate α-tubulin, histone H4 K16 and to regulate cholesterol biogenesis – a pathway which is dysregulated in HD patients and HD mouse models. We have utilized mice in which SIRT2 has been reduced or ablated to further explore the function of SIRT2 and to assess whether SIRT2 loss has a beneficial impact on disease progression in the R6/2 mouse model of HD. Surprisingly we found that reduction or loss of SIRT2 had no effect on the acetylation of α-tubulin or H4K16 or on cholesterol biosynthesis in the brains of wild type mice. Equally, genetic reduction or ablation of SIRT2 had no effect on HD progression as assessed by a battery of physiological and behavioural tests. Furthermore, we observed no change in aggregate load or levels of soluble mutant huntingtin transprotein. Intriguingly, neither the constitutive genetic loss nor acute pharmacological inhibition of SIRT2 affected the expression of cholesterol biosynthesis enzymes in the context of HD. Therefore, we conclude that SIRT2 inhibition does not modify disease progression in the R6/2 mouse model of HD and SIRT2 inhibition should not be prioritised as a therapeutic option for HD.American Parkinson Disease Association, Inc. (Fellowship)Johnson & Johnson. Pharmaceutical Research & Development (Fellowship
The P2Y4 receptor forms homo-oligomeric complexes in several CNS and PNS neuronal cells
It is well established that several cell surface receptors interact with each other to form dimers and oligomers, which are essential for their activation. Since little is known about the quaternary structure of P2Y receptors, in the present work, we investigated the expression of the G-protein-coupled P2Y4 subunit as monomeric or higher-order complex protein. We examined both endogenously expressed P2Y4 subtype with the aid of specific anti-P2Y4 antiserum, and heterologously transfected P2Y4-tagged receptors with the use of antitag antibodies. In both cases, we found the P2Y4 receptor displaying molecular masses corresponding to monomeric, dimeric and oligomeric structures. Experiments performed in the absence of reducing agents demonstrated that there is a strict correlation among the multiple protein bands and that the multimeric forms are at least partially assembled by disulphide bonds. The direct demonstration of P2Y4 homodimerisation comes instead from co–transfection and differential co–immunoprecipitation experiments, with the use of differently tagged P2Y4 receptors and antitag antibodies. The structural propensity of the P2Y4 protein to form homo-oligomers may open the possibility of a novel regulatory mechanism of physiopathological functions for this and additional P2Y receptors
Unstaged cancer in the United States: a population-based study
<p>Abstract</p> <p>Background</p> <p>The current study examines unstaged disease for 18 cancer sites in the United States according to the influence of age, sex, race, marital status, incidence, and lethality.</p> <p>Methods</p> <p>Analyses are based on 1,040,381 male and 1,011,355 female incident cancer cases diagnosed during 2000 through 2007. Data were collected by population-based cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program.</p> <p>Results</p> <p>The level of unstaged disease was greater in more lethal cancers (e.g., liver, esophagus, and pancreas) compared with less deadly cancers (i.e., colon, urinary bladder, and female breast). Unstaged disease increased with age and is greater among non-married patients. Blacks compared with whites experienced significantly higher levels of unstaged cancers of the stomach, rectum, colon, skin (melanoma), urinary bladder, thyroid, breast, corpus, cervix, and ovaries, but lower levels of unstaged liver, lung and bronchial cancers. Males compared with females experienced significantly lower levels of unstaged cancers of the liver, pancreas, esophagus, and stomach, but significantly higher levels of unstaged lung and bronchial cancer and thyroid cancer. The percent of unstaged cancer significantly decreased over the study period for 15 of the 18 cancer sites.</p> <p>Conclusion</p> <p>Tumor staging directly affects treatment options and survival, so it is recommended that further research focus on why a decrease in unstaged disease did not occur for all of the cancer sites considered from 2000 to 2007, and why there are differential levels of staging between whites and blacks, males and females for several of the cancer sites.</p
Asteroseismology and Interferometry
Asteroseismology provides us with a unique opportunity to improve our
understanding of stellar structure and evolution. Recent developments,
including the first systematic studies of solar-like pulsators, have boosted
the impact of this field of research within Astrophysics and have led to a
significant increase in the size of the research community. In the present
paper we start by reviewing the basic observational and theoretical properties
of classical and solar-like pulsators and present results from some of the most
recent and outstanding studies of these stars. We centre our review on those
classes of pulsators for which interferometric studies are expected to provide
a significant input. We discuss current limitations to asteroseismic studies,
including difficulties in mode identification and in the accurate determination
of global parameters of pulsating stars, and, after a brief review of those
aspects of interferometry that are most relevant in this context, anticipate
how interferometric observations may contribute to overcome these limitations.
Moreover, we present results of recent pilot studies of pulsating stars
involving both asteroseismic and interferometric constraints and look into the
future, summarizing ongoing efforts concerning the development of future
instruments and satellite missions which are expected to have an impact in this
field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume
14, Issue 3-4, pp. 217-36
Effective lifestyle interventions to improve type II diabetes self-management for those with schizophrenia or schizoaffective disorder: a systematic review
<p>Abstract</p> <p>Background</p> <p>The prevalence of type II diabetes among individuals suffering from schizophrenia or schizoaffective disorders is more than double that of the general population. By 2005, North American professional medical associations of Psychiatry, Diabetes, and Endocrinology responded by recommending continuous metabolic monitoring for this population to control complications from obesity and diabetes. However, these recommendations do not identify the types of effective treatment for people with schizophrenia who have type II diabetes. To fill this gap, this systematic evidence review identifies effective lifestyle interventions that enhance quality care in individuals who are suffering from type II diabetes and schizophrenia or other schizoaffective disorders.</p> <p>Methods</p> <p>A systematic search from Medline, CINAHL, PsycINFO, and ISI Web of Science was conducted. Of the 1810 unique papers that were retrieved, four met the inclusion/exclusion criteria and were analyzed.</p> <p>Results</p> <p>The results indicate that diabetes education is effective when it incorporates diet and exercise components, while using a design that addresses challenges such as cognition, motivation, and weight gain that may result from antipsychotics.</p> <p>Conclusions</p> <p>This paper begins to point to effective interventions that will improve type II diabetes management for people with schizophrenia or other schizoaffective disorders.</p
Host-Detrimental Role of Esx-1-Mediated Inflammasome Activation in Mycobacterial Infection
The Esx-1 (type VII) secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium marinum. However, the molecular events and host-pathogen interactions underlying Esx-1-mediated virulence in vivo remain unclear. Here we address this problem in a non-lethal mouse model of M. marinum infection that allows detailed quantitative analysis of disease progression. M. marinum established local infection in mouse tails, with Esx-1-dependent formation of caseating granulomas similar to those formed in human tuberculosis, and bone deterioration reminiscent of skeletal tuberculosis. Analysis of tails infected with wild type or Esx-1-deficient bacteria showed that Esx-1 enhanced generation of proinflammatory cytokines, including the secreted form of IL-1β, suggesting that Esx-1 promotes inflammasome activation in vivo. In vitro experiments indicated that Esx-1-dependent inflammasome activation required the host NLRP3 and ASC proteins. Infection of wild type and ASC-deficient mice demonstrated that Esx-1-dependent inflammasome activation exacerbated disease without restricting bacterial growth, indicating a host-detrimental role of this inflammatory pathway in mycobacterial infection. These findings define an immunoregulatory role for Esx-1 in a specific host-pathogen interaction in vivo, and indicate that the Esx-1 secretion system promotes disease and inflammation through its ability to activate the inflammasome
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