81 research outputs found

    NO activation of guanylyl cyclase

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    Sick-leave track record and other potential predictors of a disability pension. A population based study of 8,218 men and women followed for 16 years

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    <p>Abstract</p> <p>Background</p> <p>A number of previous studies have investigated various predictors for being granted a disability pension. The aim of this study was to test the efficacy of sick-leave track record as a predictor of being granted a disability pension in a large dataset based on subjects sampled from the general population and followed for a long time.</p> <p>Methods</p> <p>Data from five ongoing population-based Swedish studies was used, supplemented with data on all compensated sick leave periods, disability pensions granted, and vital status, obtained from official registers. The data set included 8,218 men and women followed for 16 years, generated 109,369 person years of observation and 97,160 sickness spells. Various measures of days of sick leave during follow up were used as independent variables and disability pension grant was used as outcome.</p> <p>Results</p> <p>There was a strong relationship between individual sickness spell duration and annual cumulative days of sick leave on the one hand and being granted a disability pension on the other, among both men and women, after adjustment for the effects of marital status, education, household size, smoking habits, geographical area and calendar time period, a proxy for position in the business cycle. The interval between sickness spells showed a corresponding inverse relationship. Of all the variables studied, the number of days of sick leave per year was the most powerful predictor of a disability pension. For both men and women 245 annual sick leave days were needed to reach a 50% probability of transition to disability. The independent variables, taken together, explained 96% of the variation in disability pension grantings.</p> <p>Conclusion</p> <p>The sick-leave track record was the most important predictor of the probability of being granted a disability pension in this study, even when the influences of other variables affecting the outcome were taken into account.</p

    Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

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    BACKGROUND: The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. METHODOLOGY/PRINCIPAL FINDINGS: To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. CONCLUSION/SIGNIFICANCE: Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure

    The functional significance of microRNA-145 in prostate cancer

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    BackgroundMicroRNAs (miRNAs) are small noncoding RNAs that have important roles in numerous cellular processes. Recent studies have shown aberrant expression of miRNAs in prostate cancer tissues and cell lines. On the basis of miRNA microarray data, we found that miR-145 is significantly downregulated in prostate cancer.Methods and resultsWe investigated the expression and functional significance of miR-145 in prostate cancer. The expression of miR-145 was low in all the prostate cell lines tested (PC3, LNCaP and DU145) compared with the normal cell line, PWR-1E, and in cancerous regions of human prostate tissue when compared with the matched adjacent normal. Overexpression of miR-145 in PC3-transfected cells resulted in increased apoptosis and an increase in cells in the G2/M phase, as detected by flow cytometry. Investigation of the mechanisms of inactivation of miR-145 through epigenetic pathways revealed significant DNA methylation of the miR-145 promoter region in prostate cancer cell lines. Microarray analyses of miR-145-overexpressing PC3 cells showed upregulation of the pro-apoptotic gene TNFSF10, which was confirmed by real-time PCR and western analysis.ConclusionOne of the genes significantly upregulated by miR-145 overexpression is the proapoptotic gene TNFSF10. Therefore, modulation of miR-145 may be an important therapeutic approach for the management of prostate cancer

    Taxonomic distribution and origins of the extended LHC (light-harvesting complex) antenna protein superfamily

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    <p>Abstract</p> <p>Background</p> <p>The extended light-harvesting complex (LHC) protein superfamily is a centerpiece of eukaryotic photosynthesis, comprising the LHC family and several families involved in photoprotection, like the LHC-like and the photosystem II subunit S (PSBS). The evolution of this complex superfamily has long remained elusive, partially due to previously missing families.</p> <p>Results</p> <p>In this study we present a meticulous search for LHC-like sequences in public genome and expressed sequence tag databases covering twelve representative photosynthetic eukaryotes from the three primary lineages of plants (Plantae): glaucophytes, red algae and green plants (Viridiplantae). By introducing a coherent classification of the different protein families based on both, hidden Markov model analyses and structural predictions, numerous new LHC-like sequences were identified and several new families were described, including the red lineage chlorophyll <it>a/b</it>-binding-like protein (RedCAP) family from red algae and diatoms. The test of alternative topologies of sequences of the highly conserved chlorophyll-binding core structure of LHC and PSBS proteins significantly supports the independent origins of LHC and PSBS families via two unrelated internal gene duplication events. This result was confirmed by the application of cluster likelihood mapping.</p> <p>Conclusions</p> <p>The independent evolution of LHC and PSBS families is supported by strong phylogenetic evidence. In addition, a possible origin of LHC and PSBS families from different homologous members of the stress-enhanced protein subfamily, a diverse and anciently paralogous group of two-helix proteins, seems likely. The new hypothesis for the evolution of the extended LHC protein superfamily proposed here is in agreement with the character evolution analysis that incorporates the distribution of families and subfamilies across taxonomic lineages. Intriguingly, stress-enhanced proteins, which are universally found in the genomes of green plants, red algae, glaucophytes and in diatoms with complex plastids, could represent an important and previously missing link in the evolution of the extended LHC protein superfamily.</p

    Leveraging analytics to produce compelling and profitable film content

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    Producing compelling film content profitably is a top priority to the long-term prosperity of the film industry. Advances in digital technologies, increasing availabilities of granular big data, rapid diffusion of analytic techniques, and intensified competition from user generated content and original content produced by Subscription Video on Demand (SVOD) platforms have created unparalleled needs and opportunities for film producers to leverage analytics in content production. Built upon the theories of value creation and film production, this article proposes a conceptual framework of key analytic techniques that film producers may engage throughout the production process, such as script analytics, talent analytics, and audience analytics. The article further synthesizes the state-of-the-art research on and applications of these analytics, discuss the prospect of leveraging analytics in film production, and suggest fruitful avenues for future research with important managerial implications

    Sorry, Your Order Has a Substitution : The Effects of Substitution Policy in Online Grocery Retailing

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    Post-purchase out-of-stock (OOS) often happens in an online store context, where products appear to be available at the time a consumer makes an order and checks out, but then become OOS when the order is to be dispatched. To mitigate negative responses from consumers, online grocery retailers often provide consumers a substitution alternative to the OOS item. This paper investigates the effects of two substitution policies where we focus on different matching strategies of the substitution with the OOS item. In policy one, we measure the effect of matching on the dominant attribute (brand vs. flavour). In policy two, we test the effect of matching with a product from the consumers’ past purchase portfolio. We investigate these two substitution policies and their interaction in two categories that differ on the level of differentiation (i.e., the degree to which distinctions are objectively measurable – vertical differentiation/VD vs. not easy to evaluate – horizontal differentiation/HD). Our dependent variable is the probability to accept the substitute. The study employs a computer-simulated purchase experiment, using two product categories: margarine (VD) and cereals (HD). 2,113 UK consumers representative of general UK shopper profile participated. Findings show that in the margarine category where brand is the dominant attribute, the same brand substitution is more likely to be accepted than the same flavour substitution. In contrast, in the cereal category where flavour is more likely to be the dominant attribute, same flavour substitution is more likely to be accepted than same brand substitution. The results also show that, in both categories, matching the substitution product with a product from consumers’ past purchase portfolio is more likely to be accepted than offering a substitute that consumers have not bought before. We also found a significant interaction between the two policy types but for cereals only. The effects of two substitution policies are mediated by perceived fairness of the substitution. The paper discusses contributions and implication for future research

    Evidence-based Kernels: Fundamental Units of Behavioral Influence

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    This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

    Scenes, saliency maps and scanpaths

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    The aim of this chapter is to review some of the key research investigating how people look at pictures. In particular, my goal is to provide theoretical background for those that are new to the field, while also explaining some of the relevant methods and analyses. I begin by introducing eye movements in the context of natural scene perception. As in other complex tasks, eye movements provide a measure of attention and information processing over time, and they tell us about how the foveated visual system determines what to prioritise. I then describe some of the many measures which have been derived to summarize where people look in complex images. These include global measures, analyses based on regions of interest and comparisons based on heat maps. A particularly popular approach for trying to explain fixation locations is the saliency map approach, and the first half of the chapter is mostly devoted to this topic. A large number of papers and models are built on this approach, but it is also worth spending time on this topic because the methods involved have been used across a wide range of applications. The saliency map approach is based on the fact that the visual system has topographic maps of visual features, that contrast within these features seems to be represented and prioritized, and that a central representation can be used to control attention and eye movements. This approach, and the underlying principles, has led to an increase in the number of researchers using complex natural scenes as stimuli. It is therefore important that those new to the field are familiar with saliency maps, their usage, and their pitfalls. I describe the original implementation of this approach (Itti & Koch, 2000), which uses spatial filtering at different levels of coarseness and combines them in an attempt to identify the regions which stand out from their background. Evaluating this model requires comparing fixation locations to model predictions. Several different experimental and comparison methods have been used, but most recent research shows that bottom-up guidance is rather limited in terms of predicting real eye movements. The second part of the chapter is largely concerned with measuring eye movement scanpaths. Scanpaths are the sequential patterns of fixations and saccades made when looking at something for a period of time. They show regularities which may reflect top-down attention, and some have attempted to link these to memory and an individual’s mental model of what they are looking at. While not all researchers will be testing hypotheses about scanpaths, an understanding of the underlying methods and theory will be of benefit to all. I describe the theories behind analyzing eye movements in this way, and various methods which have been used to represent and compare them. These methods allow one to quantify the similarity between two viewing patterns, and this similarity is linked to both the image and the observer. The last part of the chapter describes some applications of eye movements in image viewing. The methods discussed can be applied to complex images, and therefore these experiments can tell us about perception in art and marketing, as well as about machine vision
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