205 resultados para Regulatory optimization


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Since independent regulatory agencies (IRAs) became key actors in European regulatory governance in the 1990s, a significant share of policy-making has been carried out by organizations that are neither democratically elected nor directly accountable to elected politicians. In this context, public communication plays an important role. On the one hand, regulatory agencies might try to use communication to raise their accountability and thereby to mitigate their democratic deficit. On the other hand, communication may be used with the intent to steer the behavior of the regulated industry when more coercive regulatory means are unfeasible or undesirable. However, empirical research focusing directly on how regulators communicate is virtually non-existent. To fill this gap, this paper examines the public communication of IRAs in four countries (the United Kingdom, Germany, Ireland, and Switzerland) and three sectors (financial services, telecommunications, and broadcasting). The empirical analysis, based on qualitative interviews and a quantitative content analysis, indicates that the organization of the communication function follows a national pattern approach while a policy sector approach is helpful for understanding the use of communication as a soft tool of regulation.

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The impact of transnational private regulation on labour standards remains in dispute. While studies have provided some limited evidence of positive effects on 'outcome standards' such as wages or occupational health and safety, the literature gives little reason to believe that there has been any significant effect on 'process rights' relating primarily to collective workers' voice and social dialogue. This paper probes this assumption by bringing local contexts and worker agency more fully into the picture. It outlines an analytical framework that emphasizes workers' potential to act collectively for change in the regulatory space surrounding the employment relationship. It argues that while transnational private regulation on labour standards may marginally improve workers access to regulatory spaces and their capacity to require the inclusion of enterprises in them, it does little to increase union leverage. The findings are based on empirical research work conducted in Sub-Saharan Africa.

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The subdivision of cell populations in compartments is a key event during animal development. In Drosophila, the gene apterous (ap) divides the wing imaginal disc in dorsal vs ventral cell lineages and is required for wing formation. ap function as a dorsal selector gene has been extensively studied. However, the regulation of its expression during wing development is poorly understood. In this study, we analyzed ap transcriptional regulation at the endogenous locus and identified three cis-regulatory modules (CRMs) essential for wing development. Only when the three CRMs are combined, robust ap expression is obtained. In addition, we genetically and molecularly analyzed the trans-factors that regulate these CRMs. Our results propose a three-step mechanism for the cell lineage compartment expression of ap that includes initial activation, positive autoregulation and Trithorax-mediated maintenance through separable CRMs.

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A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

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Successful generation of high producing cell lines requires the generation of cell clones expressing the recombinant protein at high levels and the characterization of the clones' ability to maintain stable expression levels. The use of cis-acting epigenetic regulatory elements that improve this otherwise long and uncertain process has revolutionized recombinant protein production. Here we review and discuss new insights into the molecular mode of action of the matrix attachment regions (MARs) and ubiquitously-acting chromatin opening elements (UCOEs), i.e. cis-acting elements, and how these elements are being used to improve recombinant protein production. These elements can help maintain the chromatin environment of the transgene genomic integration locus in a transcriptionally favorable state, which increases the numbers of positive clones and the transgene expression levels. Moreover, the high producing clones tend to be more stable in long-term cultures even in the absence of selection pressure. Therefore, by increasing the probability of isolating a high producing clone, as well as by increasing transcription efficiency and stability, these elements can significantly reduce the time and cost required for producing large quantities of recombinant proteins.

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Computed tomography (CT) is a modality of choice for the study of the musculoskeletal system for various indications including the study of bone, calcifications, internal derangements of joints (with CT arthrography), as well as periprosthetic complications. However, CT remains intrinsically limited by the fact that it exposes patients to ionizing radiation. Scanning protocols need to be optimized to achieve diagnostic image quality at the lowest radiation dose possible. In this optimization process, the radiologist needs to be familiar with the parameters used to quantify radiation dose and image quality. CT imaging of the musculoskeletal system has certain specificities including the focus on high-contrast objects (i.e., in CT of bone or CT arthrography). These characteristics need to be taken into account when defining a strategy to optimize dose and when choosing the best combination of scanning parameters. In the first part of this review, we present the parameters used for the evaluation and quantification of radiation dose and image quality. In the second part, we discuss different strategies to optimize radiation dose and image quality at CT, with a focus on the musculoskeletal system and the use of novel iterative reconstruction techniques.

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Computed tomography (CT) is a modality of choice for the study of the musculoskeletal system for various indications including the study of bone, calcifications, internal derangements of joints (with CT arthrography), as well as periprosthetic complications. However, CT remains intrinsically limited by the fact that it exposes patients to ionizing radiation. Scanning protocols need to be optimized to achieve diagnostic image quality at the lowest radiation dose possible. In this optimization process, the radiologist needs to be familiar with the parameters used to quantify radiation dose and image quality. CT imaging of the musculoskeletal system has certain specificities including the focus on high-contrast objects (i.e., in CT of bone or CT arthrography). These characteristics need to be taken into account when defining a strategy to optimize dose and when choosing the best combination of scanning parameters. In the first part of this review, we present the parameters used for the evaluation and quantification of radiation dose and image quality. In the second part, we discuss different strategies to optimize radiation dose and image quality of CT, with a focus on the musculoskeletal system and the use of novel iterative reconstruction techniques.

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Mapping the microstructure properties of the local tissues in the brain is crucial to understand any pathological condition from a biological perspective. Most of the existing techniques to estimate the microstructure of the white matter assume a single axon orientation whereas numerous regions of the brain actually present a fiber-crossing configuration. The purpose of the present study is to extend a recent convex optimization framework to recover microstructure parameters in regions with multiple fibers.

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Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants-including variants that do not reach genome-wide significance-often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).