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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
- Kamnitsas, Konstantinos, et al.
(författare)
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Transductive Image Segmentation : Self-training and Effect of Uncertainty Estimation
- 2021
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Ingår i: Domain Adaptation and Representation Transfer, and Affordable Healthcare and AI for Resource Diverse Global Health - 3rd MICCAI Workshop, DART 2021, and 1st MICCAI Workshop, FAIR 2021, Held in Conjunction with MICCAI 2021, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030877217 ; 12968 LNCS, s. 79-89
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Konferensbidrag (refereegranskat)abstract
- Semi-supervised learning (SSL) uses unlabeled data during training to learn better models. Previous studies on SSL for medical image segmentation focused mostly on improving model generalization to unseen data. In some applications, however, our primary interest is not generalization but to obtain optimal predictions on a specific unlabeled database that is fully available during model development. Examples include population studies for extracting imaging phenotypes. This work investigates an often overlooked aspect of SSL, transduction. It focuses on the quality of predictions made on the unlabeled data of interest when they are included for optimization during training, rather than improving generalization. We focus on the self-training framework and explore its potential for transduction. We analyze it through the lens of Information Gain and reveal that learning benefits from the use of calibrated or under-confident models. Our extensive experiments on a large MRI database for multi-class segmentation of traumatic brain lesions shows promising results when comparing transductive with inductive predictions. We believe this study will inspire further research on transductive learning, a well-suited paradigm for medical image analysis.
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| 6. |
- Bouvier, Laura, et al.
(författare)
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Evidence for extremely rapid magma ocean crystallization and crust formation on Mars
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 558, s. 586-589
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Tidskriftsartikel (refereegranskat)abstract
- The formation of a primordial crust is a critical step in the evolution of terrestrial planets but the timing of this process is poorly understood. The mineral zircon is a powerful tool for constraining crust formation because it can be accurately dated with the uranium-to-lead (U–Pb) isotopic decay system and is resistant to subsequent alteration. Moreover, given the high concentration of hafnium in zircon, the lutetium-to-hafnium (176Lu–176Hf) isotopic decay system can be used to determine the nature and formation timescale of its source reservoir (1,2,3) Ancient igneous zircons with crystallization ages of around 4,430 million years (Myr) have been reported in Martian meteorites that are believed to represent regolith breccias from the southern highlands of Mars (4,5) These zircons are present in evolved lithologies interpreted to reflect re-melted primary Martian crust4, thereby potentially providing insight into early crustal evolution on Mars. Here, we report concomitant high-precision U–Pb ages and Hf-isotope compositions of ancient zircons from the NWA 7034 Martian regolith breccia. Seven zircons with mostly concordant U–Pb ages define 207Pb/206Pb dates ranging from 4,476.3 ± 0.9 Myr ago to 4,429.7 ± 1.0 Myr ago, including the oldest directly dated material from Mars. All zircons record unradiogenic initial Hf-isotope compositions inherited from an enriched, andesitic-like crust extracted from a primitive mantle no later than 4,547 Myr ago. Thus, a primordial crust existed on Mars by this time and survived for around 100 Myr before it was reworked, possibly by impacts (4,5) to produce magmas from which the zircons crystallized. Given that formation of a stable primordial crust is the end product of planetary differentiation, our data require that the accretion, core formation and magma ocean crystallization on Mars were completed less than 20 Myr after the formation of the Solar System. These timescales support models that suggest extremely rapid magma ocean crystallization leading to a gravitationally unstable stratified mantle, which subsequently overturns, resulting in decompression melting of rising cumulates and production of a primordial basaltic to andesitic crust (6,7).
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| 7. |
- Bregu, Endri, et al.
(författare)
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Reactive control of autonomous drones
- 2016
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Ingår i: MobiSys 2016 - Proceedings of the 14th Annual International Conference on Mobile Systems, Applications, and Services. - New York, NY, USA : Association for Computing Machinery, Inc. - 9781450342698 ; , s. 207-219
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Konferensbidrag (refereegranskat)abstract
- Aerial drones, ground robots, and aquatic rovers enable mobile applications that no other technology can realize with comparable flexibility and costs. In existing platforms, the low-level control enabling a drone's autonomous movement is currently realized in a time-triggered fashion, which simplifies implementations. In contrast, we conceive a notion of reactive control that supersedes the time-triggered approach by leveraging the characteristics of existing control logic and of the hardware it runs on. Using reactive control, control decisions are taken only upon recognizing the need to, based on observed changes in the navigation sensors. As a result, the rate of execution dynamically adapts to the circumstances. Compared to time-triggered control, this allows us to: i) attain more timely control decisions, ii) improve hardware utilization, iii) lessen the need to overprovision control rates. Based on 260+ hours of real-world experiments using three aerial drones, three different control logic, and three hardware platforms, we demonstrate, for example, up to 41% improvements in control accuracy and up to 22% improvements in flight time.
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| 8. |
- Condon, Daniel J., et al.
(författare)
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U-Th-Pb Geochronology
- 2021. - 2nd
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Ingår i: Encylopedia of Geology, 2nd Edition. - : Elsevier. - 9780081029091 ; , s. 26-46
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Bokkapitel (refereegranskat)
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| 9. |
- Dunkley, Daniel J., et al.
(författare)
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Two Neoarchean tectonothermal events on the western edge of the North Atlantic Craton, as revealed by SIMS dating of the Saglek Block, Nain Province, Labrador
- 2020
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Ingår i: Journal of the Geological Society. - : Geological Society of London. - 0016-7649 .- 2041-479X. ; 177:1
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Tidskriftsartikel (refereegranskat)abstract
- The Saglek Block forms the northern part of the Nain Province and underwent widespread metamorphism at c. 2.7 Ga, producing the dominant gneissosity and intercalation of supracrustal sequences. Zircon dating of gneiss samples collected along 80 km of the Labrador coast from Ramah Bay in the north to Hebron Fjord in the south confirms the widespread extent of high-grade metamorphism between 2750 and 2700 Ma. In addition, a distinct event between 2550 and 2510 Ma produced felsic melt with peritectic garnet in metavolcanic gneiss and granoblastic recrystallization in mafic granulite. Ductile deformation of granite emplaced at c. 2550 Ma indicates that this later event involved a degree of tectonism during high-T metamorphism. Such tectonism may be related to a hypothesized post-2.7 Ga juxtaposition of the predominantly Eoarchean Saglek Block against the Mesoarchean Hopedale Block, along a north–south boundary that extends from the coast near Nain to offshore of Saglek Bay. Evidence of reworking of c. 2.7 Ga gneisses by c. 2.5 Ga tectonothermal activity has been found elsewhere on the margins of the North Atlantic Craton, of which the Nain Province represents the western margin. In particular, a recent suggestion that c. 2.5 Ga metamorphic ages along the northern margin of the North Atlantic Craton in SW Greenland may record the final assembly of the craton could also apply to the western margin as represented by the rocks of the Nain Province.Supplementary material: Plots and geochemical data are available at https://doi.org/10.6084/m9.figshare.c.4567934
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| 10. |
- El Albani, Abderrazak, et al.
(författare)
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Large colonial organisms with coordinated growth in oxygenated environments 2.1 Gyr ago
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7302, s. 100-104
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Tidskriftsartikel (refereegranskat)abstract
- The evidence for macroscopic life during the Palaeoproterozoic era (2.5-1.6 Gyr ago) is controversial(1-5). Except for the nearly 2-Gyr-old coil-shaped fossil Grypania spiralis(6,7), which may have been eukaryotic, evidence for morphological and taxonomic bio-diversification of macroorganisms only occurs towards the beginning of the Mesoproterozoic era (1.6-1.0 Gyr)(8). Here we report the discovery of centimetre-sized structures from the 2.1-Gyr-old black shales of the Palaeoproterozoic Francevillian B Formation in Gabon, which we interpret as highly organized and spatially discrete populations of colonial organisms. The structures are up to 12 cm in size and have characteristic shapes, with a simple but distinct ground pattern of flexible sheets and, usually, a permeating radial fabric. Geochemical analyses suggest that the sediments were deposited under an oxygenated water column. Carbon and sulphur isotopic data indicate that the structures were distinct biogenic objects, fossilized by pyritization early in the formation of the rock. The growth patterns deduced from the fossil morphologies suggest that the organisms showed cell-to-cell signalling and coordinated responses, as is commonly associated with multicellular organization(9). The Gabon fossils, occurring after the 2.45-2.32-Gyr increase in atmospheric oxygen concentration(10), may be seen as ancient representatives of multicellular life, which expanded so rapidly 1.5 Gyr later, in the Cambrian explosion.
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