| 1. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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- Tinetti, Giovanna, et al.
(author)
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The EChO science case
- 2015
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Journal article (peer-reviewed)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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| 7. |
- Leleu, A., et al.
(author)
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Six transiting planets and a chain of Laplace resonances in TOI-178
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
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Journal article (peer-reviewed)abstract
- Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at the possible presence of a near 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152 to 2.87 Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02 to 0.177 times the Earth's density between planets c and d. Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 (H = 8.76 mag, J = 9.37 mag, V = 11.95 mag) allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes. -0.070 -0.13 -0.23 -0.061 +0.073 +0.14 +0.28 +0.055
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| 18. |
- Salganik, E., et al.
(author)
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Temporal evolution of under-ice meltwater layers and false bottoms and their impact on summer Arctic sea ice mass balance
- 2023
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In: Elementa: Science of the Anthropocene. - 2325-1026. ; 11:1
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Journal article (peer-reviewed)abstract
- Low-salinity meltwater from Arctic sea ice and its snow cover accumulates and creates under-ice meltwater layers below sea ice. These meltwater layers can result in the formation of new ice layers, or false bottoms, at the interface of this low-salinity meltwater and colder seawater. As part of the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC), we used a combination of sea ice coring, temperature profiles from thermistor strings and underwater multibeam sonar surveys with a remotely operated vehicle (ROV) to study the areal coverage and temporal evolution of under-ice meltwater layers and false bottoms during the summer melt season from mid-June until late July. ROV surveys indicated that the areal coverage of false bottoms for a part of the MOSAiC Central Observatory (350 by 200 m2) was 21%. Presence of false bottoms reduced bottom ice melt by 7-8% due to the local decrease in the ocean heat flux, which can be described by a thermodynamic model. Under-ice meltwater layer thickness was larger below first-year ice and thinner below thicker second-year ice. We also found that thick ice and ridge keels confined the areas in which under-ice meltwater accumulated, preventing its mixing with underlying seawater. While a thermodynamic model could reproduce false bottom growth and melt, it could not describe the observed bottom melt rates of the ice above false bottoms. We also show that the evolution of under-ice meltwaterlayer salinity below first-year ice is linked to brine flushing from the above sea ice and accumulating in the meltwater layer above the false bottom. The results of this study aid in estimating the contribution of underice meltwater layers and false bottoms to the mass balance and salt budget for Arctic summer sea ice.
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| 19. |
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| 20. |
- Unat, D., et al.
(author)
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Trends in Data Locality Abstractions for HPC Systems
- 2017
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In: IEEE Transactions on Parallel and Distributed Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-2183 .- 1045-9219. ; 28:10, s. 3007-3020
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Journal article (peer-reviewed)abstract
- The cost of data movement has always been an important concern in high performance computing (HPC) systems. It has now become the dominant factor in terms of both energy consumption and performance. Support for expression of data locality has been explored in the past, but those efforts have had only modest success in being adopted in HPC applications for various reasons. them However, with the increasing complexity of the memory hierarchy and higher parallelism in emerging HPC systems, locality management has acquired a new urgency. Developers can no longer limit themselves to low-level solutions and ignore the potential for productivity and performance portability obtained by using locality abstractions. Fortunately, the trend emerging in recent literature on the topic alleviates many of the concerns that got in the way of their adoption by application developers. Data locality abstractions are available in the forms of libraries, data structures, languages and runtime systems; a common theme is increasing productivity without sacrificing performance. This paper examines these trends and identifies commonalities that can combine various locality concepts to develop a comprehensive approach to expressing and managing data locality on future large-scale high-performance computing systems.
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| 25. |
- Hanlon, Killian S., et al.
(author)
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High levels of AAV vector integration into CRISPR-induced DNA breaks
- 2019
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels of AAV integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide AAV mapping in mouse brain shows no overall increase of AAV integration except at the CRISPR/Cas9 target site. To allow detailed characterization of integration events we engineer a miniature AAV encoding a 465 bp lambda bacteriophage DNA (AAV-lambda 465), enabling sequencing of the entire integrated vector genome. The integration profile of AAV-465 lambda in cultured cells display both full-length and fragmented AAV genomes at Cas9 on-target sites. Our data indicate that AAV integration should be recognized as a common outcome for applications that utilize AAV for genome editing.
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| 26. |
- Chamberlain, E. J., et al.
(author)
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Impacts of sea ice melting procedures on measurements of microbial community structure
- 2022
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In: Elementa. - : University of California Press. - 2325-1026. ; 10:1
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Journal article (peer-reviewed)abstract
- Microorganisms play critical roles in sea ice biogeochemical processes. However, microbes living within sea ice can be challenging to sample for scientific study. Because most techniques for microbial analysis are optimized for liquid samples, sea ice samples are typically melted first, often applying a buffering method to mitigate osmotic lysis. Here, we tested commonly used melting procedures on three different ice horizons of springtime, first year, land-fast Arctic sea ice to investigate potential methodological impacts on resulting measurements of cell abundance, photophysiology, and microbial community structure as determined by 16S and 18S rRNA gene amplicon sequencing. Specifically, we compared two buffering methods using NaCl solutions (“seawater,” melting the ice in an equal volume of 35-ppt solution, and “isohaline,” melting with a small volume of 250-ppt solution calculated to yield meltwater at estimated in situ brine salinity) to direct ice melting (no buffer addition) on both mechanically “shaved” and “non-shaved” samples. Shaving the ice shortened the melting process, with no significant impacts on the resulting measurements. The seawater buffer was best at minimizing cell lysis for this ice type, retaining the highest number of cells and chlorophyll a concentration. Comparative measurements of bacterial (16S) community structure highlighted ecologically relevant subsets of the community that were significantly more abundant in the buffered samples. The results for eukaryotic (18S) community structure were less conclusive. Taken together, our results suggest that an equivalent-volume seawater-salinity buffered melt is best at minimizing cell loss due to osmotic stress for springtime Arctic sea ice, but that either buffer will reduce bias in community composition when compared to direct melting. Overall, these findings indicate potential methodological biases that should be considered before developing a sea ice melting protocol for microbiological studies and afterwards, when interpreting biogeochemical or ecological meaning of the results.
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| 28. |
- Hall, CL, et al.
(author)
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Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents-'Online Remote Behavioural Intervention for Tics' (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e027583-
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Journal article (peer-reviewed)abstract
- Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms.Methods and analysisThis parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9–17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02).Ethics and disseminationThe findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079).Trial registration numbersISRCTN70758207andNCT03483493; Pre-results.
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| 34. |
- Chamberlain, Aaron K, et al.
(author)
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Ultrastructural organization of amyloid fibrils by atomic force microscopy
- 2000
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In: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 79:6, s. 3282-3293
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Journal article (peer-reviewed)abstract
- Atomic force microscopy has been employed to investigate the structural organization of amyloid fibrils produced in vitro from three very different polypeptide sequences. The systems investigated are a 10-residue peptide derived from the sequence of transthyretin, the 90-residue SH3 domain of bovine phosphatidylinositol-3'-kinase, and human wild-type lysozyme, a 130-residue protein containing four disulfide bridges. The results demonstrate distinct similarities between the structures formed by the different classes of fibrils despite the contrasting nature of the polypeptide species involved. SH3 and lysozyme fibrils consist typically of four protofilaments, exhibiting a left-handed twist along the fibril axis. The substructure of TTR(10-19) fibrils is not resolved by atomic force microscopy and their uniform appearance is suggestive of a regular self-association of very thin filaments. We propose that the exact number and orientation of protofilaments within amyloid fibrils is dictated by packing of the regions of the polypeptide chains that are not directly involved in formation of the cross-beta core of the fibrils. The results obtained for these proteins, none of which is directly associated with any human disease, are closely similar to those of disease-related amyloid fibrils, supporting the concept that amyloid is a generic structure of polypeptide chains. The detailed architecture of an individual fibril, however, depends on the manner in which the protofilaments assemble into the fibrillar structure, which in turn is dependent on the sequence of the polypeptide and the conditions under which the fibril is formed.
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| 36. |
- Ernst, R. E., et al.
(author)
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Long-lived connection between southern Siberia and northern Laurentia in the Proterozoic
- 2016
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In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 9:6, s. 464-469
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Journal article (peer-reviewed)abstract
- Precambrian supercontinents Nuna-Columbia (1.7 to 1.3 billion years ago) and Rodinia (1.1 to 0.7 billion years ago) have been proposed. However, the arrangements of crustal blocks within these supercontinents are poorly known. Huge, dominantly basaltic magmatic outpourings and intrusions, covering up to millions of square kilometres, termed Large Igneous Provinces, typically accompany (super) continent breakup, or attempted breakup and offer an important tool for reconstructing supercontinents. Here we focus on the Large Igneous Province record for Siberia and Laurentia, whose relative position in Nuna-Columbia and Rodinia reconstructions is highly controversial. We present precise geochronology - nine U-Pb and six Ar-Ar ages - on dolerite dykes and sills, along with existing dates from the literature, that constrain the timing of emplacement of Large Igneous Province magmatism in southern Siberia and northern Laurentia between 1,900 and 720 million years ago. We identify four robust age matches between the continents 1,870, 1,750, 1,350 and 720 million years ago, as well as several additional approximate age correlations that indicate southern Siberia and northern Laurentia were probably near neighbours for this 1.2-billion-year interval. Our reconstructions provide a framework for evaluating the shared geological, tectonic and metallogenic histories of these continental blocks.
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| 37. |
- Hollis, Chris, et al.
(author)
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Online remote behavioural intervention for tics in 9- to 17-year-olds : the ORBIT RCT with embedded process and economic evaluation
- 2023
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In: Health Technology Assessment. - 1366-5278. ; 27:18, s. 1-120
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Journal article (peer-reviewed)abstract
- BACKGROUND: Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online.OBJECTIVE: To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders.DESIGN: Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation.SETTING: Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals.PARTICIPANTS: Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months.INTERVENTIONS: Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control).OUTCOME: Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation.RESULTS: Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval -0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes.HARMS: Two serious, unrelated adverse events occurred in the control group.LIMITATIONS: We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services.CONCLUSION: Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months.FUTURE WORK: Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice.TRIAL REGISTRATION: This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete.FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.
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