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- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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- Holtslag, A. A. M., et al.
(författare)
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STABLE ATMOSPHERIC BOUNDARY LAYERS AND DIURNAL CYCLES : Challenges for Weather and Climate Models
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:11, s. 1691-1706
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Tidskriftsartikel (refereegranskat)abstract
- The representation of the atmospheric boundary layer is an important part of weather and climate models and impacts many applications such as air quality and wind energy. Over the years, the performance in modeling 2-m temperature and 10-m wind speed has improved but errors are still significant. This is in particular the case under clear skies and low wind speed conditions at night as well as during winter in stably stratified conditions over land and ice. In this paper, the authors review these issues and provide an overview of the current understanding and model performance. Results from weather forecast and climate models are used to illustrate the state of the art as well as findings and recommendations from three intercomparison studies held within the Global Energy and Water Exchanges (GEWEX) Atmospheric Boundary Layer Study (GABLS). Within GABLS, the focus has been on the examination of the representation of the stable boundary layer and the diurnal cycle over land in clear-sky conditions. For this purpose, single-column versions of weather and climate models have been compared with observations, research models, and large-eddy simulations. The intercomparison cases are based on observations taken in the Arctic, Kansas, and Cabauw in the Netherlands. From these studies, we find that even for the noncloudy boundary layer important parameterization challenges remain.
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- Magnusson, JP, et al.
(författare)
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A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse
- 2014
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 346:6206, s. 237-241
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Tidskriftsartikel (refereegranskat)abstract
- Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies.
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