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Träfflista för sökning "WFRF:(Parkinson David) "

Sökning: WFRF:(Parkinson David)

  • Resultat 1-10 av 19
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1.
  • Bacon, David J., et al. (författare)
  • Cosmology with Phase 1 of the Square Kilometre Array Red Book 2018 : Technical specifications and performance forecasts
  • 2020
  • Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 37
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from z = 0.35 to 3; and a deep, high-redshift HI IM survey over 100 deg2 from z = 3 to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to z = 3 with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to z = 6. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
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2.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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3.
  • Deans, Andrew R, et al. (författare)
  • Finding Our Way through Phenotypes.
  • 2015
  • Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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4.
  • Simone, Roberto, et al. (författare)
  • G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology invitro and invivo.
  • 2018
  • Ingår i: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 10:1, s. 22-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA-binding proteins and through toxic dipeptide repeat proteins generated by repeat-associated non-ATG translation. GGGGCC repeat RNA folds into a G-quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy. We performed a screen that identified three structurally related small molecules that specifically stabilise GGGGCC repeat G-quadruplex RNA We investigated their effect in C9orf72 patient iPSC-derived motor and cortical neurons and show that they significantly reduce RNA foci burden and the levels of dipeptide repeat proteins. Furthermore, they also reduce dipeptide repeat proteins and improve survival invivo, in GGGGCC repeat-expressing Drosophila Therefore, small molecules that target GGGGCC repeat G-quadruplexes can ameliorate the two key pathologies associated with C9orf72 FTD/ALS These data provide proof of principle thattargeting GGGGCC repeat G-quadruplexes has therapeutic potential.
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5.
  • Ackermann, M., et al. (författare)
  • THE FIRST FERMI-LAT CATALOG OF SOURCES ABOVE 10 GeV
  • 2013
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 209:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a catalog of gamma-ray sources at energies above 10 GeV based on data from the Large Area Telescope (LAT) accumulated during the first 3 yr of the Fermi Gamma-ray Space Telescope mission. The first Fermi catalog of > 10 GeV sources (1FHL) has 514 sources. For each source we present location, spectrum, a measure of variability, and associations with cataloged sources at other wavelengths. We found that 449 (87%) could be associated with known sources, of which 393 (76% of the 1FHL sources) are active galactic nuclei. Of the 27 sources associated with known pulsars, we find 20 (12) to have significant pulsations in the range > 10 GeV (> 25 GeV). In this work we also report that, at energies above 10 GeV, unresolved sources account for 27% +/- 8% of the isotropic. gamma-ray background, while the unresolved Galactic population contributes only at the few percent level to the Galactic diffuse background. We also highlight the subset of the 1FHL sources that are best candidates for detection at energies above 50-100 GeV with current and future ground-based gamma-ray observatories.
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6.
  • Cheeseman, Luke, et al. (författare)
  • When Concurrency Matters : Behaviour-Oriented Concurrency
  • 2023
  • Ingår i: Proceedings of the ACM on Programming Languages. - : Association for Computing Machinery (ACM). - 2475-1421. ; 7:OOPSLA2, s. 1531-1560
  • Tidskriftsartikel (refereegranskat)abstract
    • Expressing parallelism and coordination is central for modern concurrent programming. Many mechanisms exist for expressing both parallelism and coordination. However, the design decisions for these two mechanisms are tightly intertwined. We believe that the interdependence of these two mechanisms should be recognised and achieved through a single, powerful primitive. We are not the first to realise this: the prime example is actor model programming, where parallelism arises through fine-grained decomposition of a program’s state into actors that are able to execute independently in parallel. However, actor model programming has a serious pain point: updating multiple actors as a single atomic operation is a challenging task. We address this pain point by introducing a new concurrency paradigm: Behaviour-Oriented Concurrency (BoC). In BoC, we are revisiting the fundamental concept of a behaviour to provide a more transactional concurrency model. BoC enables asynchronously creating atomic and ordered units of work with exclusive access to a collection of independent resources. In this paper, we describe BoC informally in terms of examples, which demonstrate the advantages of exclusive access to several independent resources, as well as the need for ordering. We define it through a formal model. We demonstrate its practicality by implementing a C++ runtime. We argue its applicability through the Savina benchmark suite: benchmarks in this suite can be more compactly represented using BoC in place of Actors, and we observe comparable, if not better, performance.
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7.
  • Földváry Ličina, Veronika, et al. (författare)
  • Development of the ASHRAE Global Thermal Comfort Database II
  • 2018
  • Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323. ; 142, s. 502-512
  • Tidskriftsartikel (refereegranskat)abstract
    • Recognizing the value of open-source research databases in advancing the art and science of HVAC, in 2014 the ASHRAE Global Thermal Comfort Database II project was launched under the leadership of University of California at Berkeley's Center for the Built Environment and The University of Sydney's Indoor Environmental Quality (IEQ) Laboratory. The exercise began with a systematic collection and harmonization of raw data from the last two decades of thermal comfort field studies around the world. The ASHRAE Global Thermal Comfort Database II (Comfort Database), now an online, open-source database, includes approximately 81,846 complete sets of objective indoor climatic observations with accompanying “right-here-right-now” subjective evaluations by the building occupants who were exposed to them. The database is intended to support diverse inquiries about thermal comfort in field settings. A simple web-based interface to the database enables filtering on multiple criteria, including building typology, occupancy type, subjects' demographic variables, subjective thermal comfort states, indoor thermal environmental criteria, calculated comfort indices, environmental control criteria and outdoor meteorological information. Furthermore, a web-based interactive thermal comfort visualization tool has been developed that allows end-users to quickly and interactively explore the data.
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8.
  • Garg, Manik, et al. (författare)
  • Tumour gene expression signature in primary melanoma predicts long-term outcomes
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10−5) and overall survival (HR = 1.61, p = 1.67 × 10−4), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC = 7.03 × 10−4), or published prognostic signatures (pAUROC < 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = −0.75, p < 2.2 × 10−16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
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9.
  • Giorgi Rossi, Paolo, et al. (författare)
  • Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative
  • 2021
  • Ingår i: British Journal of Cancer. - : Springer. - 0007-0920 .- 1532-1827. ; 124:9, s. 1503-1512
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question “Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?”Methods: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS).Results: Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests.Conclusions: The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).
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10.
  • Jacobs, Alan M., et al. (författare)
  • The Qualitative Transparency Deliberations : Insights and Implications
  • 2021
  • Ingår i: Perspectives on Politics. - 1537-5927 .- 1541-0986. ; 19:1, s. 171-208
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process-the Qualitative Transparency Deliberations (QTD)-involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups' final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency's promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports-the full versions of which can be found in the Supplementary Materials-offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate-as understood by relevant research communities-to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.(1)
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