| 1. |
- Deans, Andrew R, et al.
(author)
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Finding Our Way through Phenotypes.
- 2015
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In: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
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Journal article (peer-reviewed)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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| 2. |
- Simone, Roberto, et al.
(author)
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G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology invitro and invivo.
- 2018
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In: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 10:1, s. 22-31
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Journal article (peer-reviewed)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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| 3. |
- Földváry Ličina, Veronika, et al.
(author)
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Development of the ASHRAE Global Thermal Comfort Database II
- 2018
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In: Building and Environment. - : Elsevier BV. - 0360-1323. ; 142, s. 502-512
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Journal article (peer-reviewed)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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| 4. |
- Navin Cristina, Tina J, et al.
(author)
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Identification of diabetes, heart disease, hypertension and stroke in mid- and older-aged women : Comparing self-report and administrative hospital data records
- 2016
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In: Geriatrics & Gerontology International. - : Wiley. - 1444-1586 .- 1447-0594. ; 16:1, s. 95-102
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Journal article (peer-reviewed)abstract
- AIM: To estimate the prevalence of diabetes, heart disease, hypertension and stroke in self-report and hospital data in two cohorts of women; measure sensitivity and agreement between data sources; and compare between cohorts.METHODS: Women born between 1946-1951 and 1921-1926 who participated in the Australian Longitudinal Study on Women's Health (ALSWH); were New South Wales residents; and admitted to hospital (2004-2008) were included in the present study. The prevalence of diabetes, heart disease, hypertension and stroke was estimated using self-report (case 1 at latest survey, case 2 across multiple surveys) and hospital records. Agreement (kappa) and sensitivity (%) were calculated. Logistic regression measured the association between patient characteristics and agreement.RESULTS: Hypertension had the highest prevalence and estimates were higher for older women: 32.5% case 1, 45.4% case 2, 12.8% in hospital data (1946-1951 cohort); 57.8% case 1, 73.2% case 2, 38.2% in hospital data (1921-1926 cohort). Agreement was substantial for diabetes: κ = 0.75 case 1, κ = 0.70 case 2 (1946-1951 cohort); κ = 0.77 case 1, κ = 0.80 case 2 (1921-1926 cohort), and lower for other conditions. The 1946-1951 cohort had 2.08 times the odds of agreement for hypertension (95% CI 1.56 to 2.78; P < 0.0001), and 6.25 times the odds of agreement for heart disease (95% CI 4.35 to 10.0; P < 0.0001), compared with the 1921-1926 cohort.CONCLUSION: Substantial agreement was found for diabetes, indicating accuracy of ascertainment using self-report or hospital data. Self-report data appears to be less accurate for heart disease and stroke. Hypertension was underestimated in hospital data. These findings have implications for epidemiological studies relying on self-report or administrative data. Geriatr Gerontol Int 2015
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| 5. |
- Parkinson, Dilworth Y., et al.
(author)
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Real-Time Data-Intensive Computing
- 2016
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In: Proceedings Of The 12Th International Conference On Synchrotron Radiation Instrumentation (SRI2015). - : Author(s). - 9780735413986
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Conference paper (peer-reviewed)abstract
- Today users visit synchrotrons as sources of understanding and discovery-not as sources of just light, and not as sources of data. To achieve this, the synchrotron facilities frequently provide not just light but often the entire end station and increasingly, advanced computational facilities that can reduce terabytes of data into a form that can reveal a new key insight. The Advanced Light Source (ALS) has partnered with high performance computing, fast networking, and applied mathematics groups to create a "super-facility", giving users simultaneous access to the experimental, computational, and algorithmic resources to make this possible. This combination forms an efficient closed loop, where data-despite its high rate and volume-is transferred and processed immediately and automatically on appropriate computing resources, and results are extracted, visualized, and presented to users or to the experimental control system, both to provide immediate insight and to guide decisions about subsequent experiments during beamtime. We will describe our work at the ALS ptychography, scattering, micro-diffraction, and micro-tomography beamlines.
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| 6. |
- Saunders, Gary, et al.
(author)
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Leveraging European infrastructures to access 1 million human genomes by 2022
- 2019
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In: Nature reviews genetics. - : Springer Nature. - 1471-0056 .- 1471-0064. ; 20:11, s. 693-701
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Journal article (peer-reviewed)abstract
- Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.
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| 7. |
- Schunemann, Holger J., et al.
(author)
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Methods for Development of the European Commission Initiative on Breast Cancer Guidelines Recommendations in the Era of Guideline Transparency
- 2019
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In: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 171:4, s. 273-280
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Journal article (peer-reviewed)abstract
- Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission ( EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE ( Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.
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| 8. |
- Zhang, Yunyan, et al.
(author)
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Highly Strained III-V-V Coaxial Nanowire Quantum Wells with Strong Carrier Confinement
- 2019
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 13:5, s. 5931-5938
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Journal article (peer-reviewed)abstract
- Coaxial quantum wells (QWs) are ideal candidates for nanowire (NW) lasers, providing strong carrier confinement and allowing close matching of the cavity mode and gain medium. We report a detailed structural and optical study and the observation of lasing for a mixed group-V GaAsP NW with GaAs QWs. This system offers a number of potential advantages in comparison to previously studied common group-V structures (e.g., AlGaAs/GaAs) including highly strained binary GaAs QWs, the absence of a lower band gap core region, and deep carrier potential wells. Despite the large lattice mismatch (∼1.7%), it is possible to grow defect-free GaAs coaxial QWs with high optical quality. The large band gap difference results in strong carrier confinement, and the ability to apply a high degree of compressive strain to the GaAs QWs is also expected to be beneficial for laser performance. For a non-fully optimized structure containing three QWs, we achieve low-temperature lasing with a low external (internal) threshold of 20 (0.9) μJ/cm2/pulse. In addition, a very narrow lasing line width of ∼0.15 nm is observed. These results extend the NW laser structure to coaxial III-V-V QWs, which are highly suitable as the platform for NW emitters.
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