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| 2. |
- 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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| 4. |
- Bandaru, S V Ravikumar, et al.
(författare)
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Multi-nozzle spray cooling of a reactor pressure vessel steel plate for the application of ex-vessel cooling
- 2021
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Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Spray cooling is a versatile technology for various cooling applications involving high surface heat fluxes. Experimental facility was built to study heat transfer performance of an upward multi-nozzle array of water sprays impacting a surface of heated plate made of reactor vessel grade steel. The effect of inclination angles of the steel surface on the cooling performance was investigated to assess heat transfer in complex semispherical/ semielliptical geometry of large reactor lower head and to address possible application of spray cooling in severe accident management (SAM) of light water reactors (LWRs) based on In-vessel melt retention with external reactor vessel cooling (IVR-ERVC). Joule heating of SA302B steel foil of 0.15 mm thickness and surface area of 96 cm2 enabled prototypic heat fluxes to be evacuated during reactor accident. A 2×3 array of full jet narrow-coned pressure-swirl spray nozzles was used to reproduce multi-nozzle cooling. The tests were conducted as a series of consequent steady states realized at stepwise increasing power and surface heat fluxes up to the maximum values of 29 kW and 2.97 MW/m2 limited in the specific facility design. Seven surface inclinations, between 0o and 90o were tested and no significant variations in spray cooling performance with the inclination of the heated surface was found. The results indicated a promising prospect of using a multi-nozzle array system for cooling of large surface area of reactor lower head. Much higher heat fluxes can be safely extracted by spray cooling in comparison with the critical heat fluxes that appeared at RPV water pool cooling at natural convection. The maximum value of heat flux at direct spray impact zones and its drop-off slightly from the center to the periphery of the spray cone was detected in the tests. The water flow rate and liquid subcooling significantly influenced maximum steel surface temperature but had no noticeable effects on surface temperature uniformity. The spray-to-spray interaction had no observable effects on local surface temperatures, however, the colliding zones where four spray cones have visible effects on local surface temperatures due to poor liquid momentum. The results also showed that more uniform liquid film distribution could be obtained for some inclinations because of improved liquid drainage, which in turn leads to maintaining low surface temperatures.
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| 5. |
- Bandaru, S V Ravikumar, et al.
(författare)
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Upward-facing multi-nozzle spray cooling experiments for external cooling of reactor pressure vessels
- 2020
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Ingår i: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310 .- 1879-2189. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- Cooling by water spray is a well-known technology that can reach significantly higher Critical Heat Flux (CHF) compared to other cooling methods. For the light water reactor safety, the in-vessel retention (IVR) by external reactor vessel cooling (ERVC) is a comprehensive severe accident management strategy to arrest and confine the corium in the lower head of the reactor pressure vessel. Heat fluxes up to 1.5 MW/m2 have already been assumed attainable in low-power nuclear reactors while cooling required in high-power reactors is expected to reach 2.5 MW/m2. Instead of reactor lower head flooding and relying on cooling due to natural convection, a viable and more efficient alternative is to spray the external surface of the vessel. Given all the advantages of spray cooling reported in the literature, a lab-scale experimental facility was built to validate the efficiency of multi-nozzle spray cooling of a downward-facing heated surface inclined at different angles up to 90o. The facility employed a 2×3 matrix of spray nozzles to cool the FeCrAl alloy foil with an effectively heated surface area of 96 cm2 using water as the coolant. Heat loads and surface inclinations were varied parameters in the test matrix. The results show that no significant variations in spray cooling performance concerning the inclination of the heated surface. A surface heat flux of 2.5 MW/m2 was achieved at every inclination of the downward-facing surface. The results also indicate that more uniform liquid film distribution could be obtained for some inclinations, which in turn leads to maintaining low surface temperature. The obtained surface heat flux margin by spray cooling indicates that it is feasible to adopt IVR-ERVC strategy for a large power reactor.
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| 7. |
- Chen, Xin, 1980, et al.
(författare)
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Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response
- 2023
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Ingår i: Advanced Functional Materials. - 1616-3028 .- 1616-301X. ; 33:45
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, with the aggregation of misfolded amyloid-β (Aβ) peptides in the brain being one of its histopathological hallmarks. Recently, graphene oxide (GO) nanoflakes have attracted significant attention in biomedical areas due to their capacity of suppressing Aβ aggregation in vitro. The mechanism of this beneficial effect has not been fully understood in vivo. Herein, the impact of GO on intracellular Aβ42 aggregates and cytotoxicity is investigated using yeast Saccharomyces cerevisiae as the model organism. This study finds that GO nanoflakes can effectively penetrate yeast cells and reduce Aβ42 toxicity. Combination of proteomics data and follow-up experiments show that GO treatment alters cellular metabolism to increases cellular resistance to misfolded protein stress and oxidative stress, and reduces amounts of intracellular Aβ42 oligomers. Additionally, GO treatment also reduces HTT103QP toxicity in the Huntington's disease (HD) yeast model. The findings offer insights for rationally designing GO nanoflakes-based therapies for attenuating cytotoxicity of Aβ42, and potentially of other misfolded proteins involved in neurodegenerative pathology.
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| 8. |
- Du, Yuxuan, et al.
(författare)
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Complementary Simulations to Determine Heat Transfer Coefficients and the Maximum Heat Flux in Multi-Nozzle Spray Cooling Experiments
- 2022
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Ingår i: International Conference on Nuclear Engineering, Proceedings, ICONE. - : ASME International.
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Konferensbidrag (refereegranskat)abstract
- For Light Water Reactor (LWR) safety, spray cooling during severe accidents is one of the promising approaches to achieve In-Vessel Retention of corium by External Reactor Vessel Cooling (IVR-ERVC). To study the efficiency of multi-nozzle spray cooling (nozzles of 2×3 matrix) on a downward-facing FeCrAl heated surface, a lab-scale experimental facility was built. It should be emphasized, however, that a direct measurement of Heat Transfer Coefficient (HTC) on the sprayed side is challenging due to the strong interference of water flow and intrusiveness of standard instrumentation methods. In this paper, a 3D numerical model has been established with the same geometric and material parameters as the foil sample in a multi-nozzle upward spray cooling. Given the experimental temperature profiles on the sample's dry side measured by an IR camera, the complementary numerical simulations have revealed the HTCs and corresponding temperature profiles on the sprayed side, which enabled the prediction of the maximum heat fluxes (MHFs). The maximum heat fluxes for the given spray cooling conditions can reach up to 3.25 MWm2, which is more than adequate for what is required for a successful IVR-ERVC for high-power reactors. At the same time, the maximum temperature on the dry side at the highest input power is still much lower than the expected failure temperature of the sample material.
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| 9. |
- Fusai, Giuseppe Kito, et al.
(författare)
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Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries
- 2023
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Ingår i: British Journal of Surgery. - : OXFORD UNIV PRESS. - 0007-1323 .- 1365-2168.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries. Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).
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| 10. |
- Futo, M., et al.
(författare)
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Embryo-Like Features in Developing Bacillus subtilis Biofilms
- 2021
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Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:1, s. 31-47
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Tidskriftsartikel (refereegranskat)abstract
- Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.
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