| 1. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 2. |
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| 3. |
- 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. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 5. |
- Askarian, Fatemeh, et al.
(författare)
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Staphylococcus aureus Membrane-Derived Vesicles Promote Bacterial Virulence and Confer Protective Immunity in Murine Infection Models
- 2018
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus produces membrane-derived vesicles (MVs), which share functional properties to outer membrane vesicles. Atomic force microscopy revealed that S. aureus-derived MVs are associated with the bacterial surface or released into the surrounding environment depending on bacterial growth conditions. By using a comparative proteomic approach, a total of 131 and 617 proteins were identified in MVs isolated from S. aureus grown in Luria-Bertani and brain-heart infusion broth, respectively. Purified S. aureus MVs derived from the bacteria grown in either media induced comparable levels of cytotoxicity and neutrophil-activation. Administration of exogenous MVs increased the resistance of S. aureus to killing by whole blood or purified human neutrophils ex vivo and increased S. aureus survival in vivo. Finally, immunization of mice with S. aureus-derived MVs induced production of IgM, total IgG, IgG1, IgG2a, and IgG2b resulting in protection against subcutaneous and systemic S. aureus infection. Collectively, our results suggest S. aureus MVs can influence bacterial-host interactions during systemic infections and provide protective immunity in murine models of infection.
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| 6. |
- Bröms, Jeanette E., et al.
(författare)
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A functional VipA-VipB interaction is required for the type VI secretion system activity of Vibrio cholerae O1 strain A1552
- 2013
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Ingår i: BMC Microbiology. - London, England : BioMed Central. - 1471-2180. ; 13, s. 96-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many Gram-negative bacteria rely on a type VI secretion system (T6SS) to infect eukaryotic cells or to compete against other microbes. Common to these systems is the presence of two conserved proteins, in Vibrio cholerae denoted VipA and VipB, which have been shown to interact in many clinically relevant pathogens. In this study, mutagenesis of a defined region within the VipA protein was used to identify residues important for VipB binding in V. cholerae O1 strain A1552. Results: A dramatically diminished interaction was shown to correlate with a decrease in VipB stability and a loss of hemolysin co-regulated protein (Hcp) secretion and rendered the bacterium unable to compete with Escherichia coli in a competition assay. Conclusions: This confirms the biological relevance of the VipA-VipB interaction, which is essential for the T6SS activity of many important human pathogens.
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| 7. |
- Collin, Betty, 1976, et al.
(författare)
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The origin of vibrio cholerae influences uptake and persistence in the blue mussel Mytilus edulis
- 2012
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Ingår i: Journal of Shellfish Research. - : National Shellfisheries Association. - 0730-8000 .- 1943-6319. ; 31:1, s. 87-92
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Tidskriftsartikel (refereegranskat)abstract
- Vibrio cholerae may cause diarrheal diseases and wound infections, both of which have the potential to be fatal. Transmission to humans is often linked to consumption of contaminated shellfish/drinking water or dermal exposure to water (e.g. when swimming). In this study, we investigated whether different isolates of Vibrio cholerae differ in terms of accumulation, persistence, and viability when encountering blue mussels (Mytilus edulis). Mussel uptake and elimination of three different V. cholerae strains were compared: one fatal clinical non-O1/O139 isolate, one highly potent El Tor biotype, and one marine strain isolated from blue mussels. The results showed that the uptake of the marine strain was significantly higher than the clinical strain, but the elimination process of the marine strain was also more efficient. The El Tor strain was not at all ingested by the mussels. In addition, the survival of bacteria when incubated together with M. edulis hemocytes was tested in vitro. The viability of clinical strains was unaffected by the presence of hemocytes, and the marine strains were even more resistant and able to multiply. We conclude that the highly virulent El Tor biotype was not taken up by the mussels and could thereby escape the mussels' elimination process. The potentially fatal non-O1/O139 V. cholerae strain may accumulate in low numbers, but could be very persistent in mussels.
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| 8. |
- Fan, Lizhou, et al.
(författare)
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Promoting the Fe(VI) active species generation by structural and electronic modulation of efficient iron oxide based water oxidation catalyst without Ni or Co
- 2020
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Ingår i: Nano Energy. - : Elsevier BV. - 2211-2855 .- 2211-3282. ; 72
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Tidskriftsartikel (refereegranskat)abstract
- Fe is considered as a promising alternative for OER catalysts owing to its high natural abundance and low cost. Due to the low conductivity and sluggish catalytic kinetics, the catalytic efficiency of Fe-rich catalysts is far from less abundant Ni, Co-rich alternatives and has been hardly improved without the involvement of Ni or Co. The lower activity of Fe-rich catalysts renders the real active center of state-of-the-art NiFe, CoFe catalyst in long-term scientific debate, despite of detection of Fe-based active intermediates in these catalysts during catalytic process. In the present work, we fabricated a series of sub-5 nm Fe1-yCryOx nanocatalysts via a simple solvothermal method, achieving systematically promoted high-valent Fe(VI) species generation by structural and electronic modulation, displaying highly active OER performance without involvement of Ni or Co. Detailed investigation revealed that the high OER activity is related to the ultrasmall nanoparticle size that promotes abundant edge- and corner-site exposure at catalyst surface, which involves in OER as highly reactive site; and the incorporated Cr ions that remarkably accelerate the charge transfer kinetics, providing an effective conduit as well as suitable host for high-valent active intermediate. This work reveals the structural prerequisites for efficient Fe-rich OER catalyst fabrication, inspiring deeper understanding of the structure-activity relationship as well as OER mechanism of Fe-based catalysts.
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| 9. |
- Jers, Carsten, et al.
(författare)
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The Global Acetylome of the Human Pathogen Vibrio cholerae V52 Reveals Lysine Acetylation of Major Transcriptional Regulators
- 2018
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : FRONTIERS MEDIA SA. - 2235-2988. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Protein lysine acetylation is recognized as an important reversible post translational modification in all domains of life. While its primary roles appear to reside in metabolic processes, lysine acetylation has also been implicated in regulating pathogenesis in bacteria. Several global lysine acetylome analyses have been carried out in various bacteria, but thus far there have been no reports of lysine acetylation taking place in the important human pathogen Vibrio cholerae. In this study, we analyzed the lysine acetylproteome of the human pathogen V. cholerae V52. By applying a combination of immuno-enrichment of acetylated peptides and high resolution mass spectrometry, we identified 3,402 acetylation sites on 1,240 proteins. Of the acetylated proteins, more than half were acetylated on two or more sites. As reported for other bacteria, we observed that many of the acetylated proteins were involved in metabolic and cellular processes and there was an over-representation of acetylated proteins involved in protein synthesis. Of interest, we demonstrated that many global transcription factors such as CRP, H-NS, IHF, Lrp and RpoN as well as transcription factors AphB, TcpP, and PhoB involved in direct regulation of virulence in V. cholerae were acetylated. In conclusion, this is the first global protein lysine acetylome analysis of V. cholerae and should constitute a valuable resource for in-depth studies of the impact of lysine acetylation in pathogenesis and other cellular processes.
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| 10. |
- Kim, Dae-Kyum, et al.
(författare)
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EVpedia: A Community Web Portal for Extracellular Vesicles Research
- 2015
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 31:6, s. 933-939
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
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