| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 3. |
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| 4. |
- van der Lee, S. J., et al.
(författare)
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A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- 2019
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
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Tidskriftsartikel (refereegranskat)abstract
- The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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| 6. |
- dos Remedios, C. G., et al.
(författare)
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The Sydney Heart Bank : improving translational research while eliminating or reducing the use of animal models of human heart disease
- 2017
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Ingår i: Biophysical Reviews. - : Springer Nature. - 1867-2450 .- 1867-2469. ; 9:4, s. 431-441
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Tidskriftsartikel (refereegranskat)abstract
- The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5–10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent’s Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170–180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.
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| 7. |
- Batistoni, P., et al.
(författare)
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14 MeV calibration of JET neutron detectors-phase 2 : in-vessel calibration
- 2018
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 58:10
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Tidskriftsartikel (refereegranskat)abstract
- A new DT campaign (DTE2) is planned at JET in 2020 to minimize the risks of ITER operations. In view of DT operations, a calibration of the JET neutron monitors at 14 MeV neutron energy has been performed using a well calibrated 14 MeV neutron generator (NG) deployed, together with its power supply and control unit, inside the vacuum vessel by the JET remote handling system. The NG was equipped with two calibrated diamond detectors, which continuously monitored its neutron emission rate during the calibration, and activation foils which provided the time integrated yield. Cables embedded in the remote handling boom were used to power the neutron generator, the active detectors and pre-amplifier, and to transport the detectors' signal. The monitoring activation foils were retrieved at the end of each day for decay gamma-ray counting, and replaced by fresh ones. About 76 hours of irradiation, in 9 days, were needed with the neutron generator in 73 different poloidal and toroidal positions in order to calibrate the two neutron yield measuring systems available at JET, the U-235 fission chambers (KN1) and the inner activation system (KN2). The NG neutron emission rates provided by the monitoring detectors were in agreement within 3%. Neutronics calculations have been performed using MCNP code and a detailed model of JET to derive the response of the JET neutron detectors to DT plasma neutrons starting from the response to the NG neutrons, and taking into account the anisotropy of the neutron generator and all the calibration circumstances. These calculations have made use of a very detailed and validated geometrical description of the neutron generator and of the modified. MNCP neutron source subroutine producing neutron energy-angle distribution for the neutrons emitted by the NG. The KN1 calibration factor for a DT plasma has been determined with +/- 4.2%' experimental uncertainty. Corrections due to NG and remote handling effects and the plasma volume effect have been calculated by simulation modelling. The related additional uncertainties are difficult to estimate, however the results of the previous calibration in 2013 have demonstrated that such uncertainties due to modelling are globally <= +/- 3%. It has been found that the difference between KN1 response to DD neutrons and that to DT neutrons is within the uncertainties in the derived responses. KN2 has been calibrated using the Nb-93(n,2n)Nb-92m and Al-27(n,a)Na-24 activation reactions (energy thresholds 10 MeV and 5 MeV respectively). The total uncertainty on the calibration factors is +/- 6% for Nb-93(n,2n)Nb-92m and +/- 8% Al-27(n,a)Na-24 (1 sigma). The calibration factors of the two independent systems KN1 and KN2 will be validated during DT operations. The experience gained and the lessons learnt are presented and discussed in particular with regard to the 14 MeV neutron calibrations in ITER.
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| 8. |
- Collet, T. H., et al.
(författare)
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The Sleep/Wake Cycle is Directly Modulated by Changes in Energy Balance
- 2016
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 39:9, s. 1691-1700
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: The rise in obesity has been paralleled by a decline in sleep duration in epidemiological studies. However, the potential mechanisms linking energy balance and the sleep/wake cycle are not well understood. We aimed to examine the effects of manipulating energy balance on the sleep/wake cycle. Methods: Twelve healthy normal weight men were housed in a clinical research facility and studied at three time points: baseline, after energy balance was disrupted by 2 days of caloric restriction to 10% of energy requirements, and after energy balance was restored by 2 days of ad libitum/free feeding. Sleep architecture, duration of sleep stages, and sleep-associated respiratory parameters were measured by polysomnography. Results: Two days of caloric restriction significantly increased the duration of deep (stage 4) sleep (16.8% to 21.7% of total sleep time; P = 0.03); an effect which was entirely reversed upon free feeding (P = 0.01). Although the apnea-hypopnea index stayed within the reference range (< 5 events per hour), it decreased significantly from caloric restriction to free feeding (P = 0.03). Caloric restriction was associated with a marked fall in leptin (P < 0.001) and insulin levels (P = 0.002). The fall in orexin levels from baseline to caloric restriction correlated positively with duration of stage 4 sleep (Spearman rho = 0.83, P = 0.01) and negatively with the number of awakenings in caloric restriction (Spearman rho = -0.79, P = 0.01). Conclusions: We demonstrate that changes in energy homeostasis directly and reversibly impact on the sleep/wake cycle. These findings provide a mechanistic framework for investigating the association between sleep duration and obesity risk.
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| 9. |
- Gregor, L., et al.
(författare)
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GliderTools: A Python Toolbox for Processing Underwater Glider Data
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Underwater gliders have become widely used in the last decade. This has led to a proliferation of data and the concomitant development of tools to process the data. These tools are focused primarily on converting the data from its raw form to more accessible formats and often rely on proprietary programing languages. This has left a gap in the processing of glider data for academics, who often need to perform secondary quality control (QC), calibrate, correct, interpolate and visualize data. Here, we present GliderTools, an open-source Python package that addresses these needs of the glider user community. The tool is designed to change the focus from the processing to the data. GliderTools does not aim to replace existing software that converts raw data and performs automatic first-order QC. In this paper, we present a set of tools, that includes secondary cleaning and calibration, calibration procedures for bottle samples, fluorescence quenching correction, photosynthetically available radiation (PAR) corrections and data interpolation in the vertical and horizontal dimensions. Many of these processes have been described in several other studies, but do not exist in a collated package designed for underwater glider data. Importantly, we provide potential users with guidelines on how these tools are used so that they can be easily and rapidly accessible to a wide range of users that span the student to the experienced researcher. We recognize that this package may not be all-encompassing for every user and we thus welcome community contributions and promote GliderTools as a community-driven project for scientists.
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| 10. |
- Hendricks, A. E., et al.
(författare)
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Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).
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