| 1. |
- Fenstermacher, M.E., et al.
(författare)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
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.
|
|
| 2. |
- Murray, Alison E., et al.
(författare)
-
Roadmap for naming uncultivated Archaea and Bacteria
- 2020
-
Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
-
Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
|
|
| 3. |
|
|
| 4. |
- Ebersole, Charles R., et al.
(författare)
-
Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
-
Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
|
|
| 5. |
- Gorini, Giacomo, et al.
(författare)
-
Engagement of monocytes, NK cells, and CD4(+) Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition
- 2020
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 16:3
-
Tidskriftsartikel (refereegranskat)abstract
- The ALVAC-HIV/gp120/alum regimen tested in 8,197 human volunteers (61.4% males, 38.6% females) in the RV144 trial decreased the risk of HIV infection similarly in both sexes. The ALVAC-SIV/gp120/alum vaccine also reduced the risk of intrarectal SIVmac251 acquisition in both female and male vaccinated macaques at an average of 44% per exposure. In the current work, we tested whether this vaccine modality could also reduce the risk of intravaginal SIVmac251 exposure. In order to detect correlates of risk, we administered the virus by the intravaginal route and tested another vaccine regimen based on the vaccinia derivative poxvirus NYVAC in parallel. We demonstrate here that the ALVAC-SIV/gp120/alum regimen decreases the risk of vaginal SIVmac251 acquisition (50% vaccine efficacy) and, importantly, we confirmed that subsets of monocytes and CD4(+) T cells are correlates of risk of acquisition. In addition, we uncovered cytotoxic vaginal NKG2A(+) cells and gut-homing alpha(4)beta(7) positive plasmablasts as novel correlates of risk of intravaginal virus acquisition. In contrast, NYVAC-SIV vaccination induced high levels of activated T cells and did not protect against SIVmac251 acquisition. We examined the contrasting immune responses to better understand the correlate of protection and found that the unique ability of ALVAC-SIV to activate early interferon responses and the inflammasome during priming differentiates the two poxvirus vectors. This work demonstrates the reproducibility of the efficacy observed in the ALVAC-based regimen and defines novel correlates of risk in the rigorous SIVmac251 macaque model, establishing a benchmark for future improvement of this vaccine approach. The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIVmac251. Here, we demonstrate that the ALVAC-SIV/gp120/alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIVmac251 and we confirm that CD14(+) classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14(+) cells and/or their gene expression correlates with blood Type 1 CD4(+) T helper cells, alpha(4)beta(+)(7) plasmablasts, and vaginal cytocidal NKG2A(+) cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4(+)Ki67(+)CD38(+) and CD4(+)Ki67(+)alpha(4)beta(+)(7) T cells, higher SIV envelope-specific IFN-gamma producing cells, equivalent ADCC, and did not decrease the risk of SIVmac251 acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A(+) cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.
|
|
| 6. |
- Yamauchi, M., et al.
(författare)
-
Plasma-neutral gas interactions in various space environments : Assessment beyond simplified approximations as a Voyage 2050 theme
- 2022
-
Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508.
-
Tidskriftsartikel (refereegranskat)abstract
- In the White Paper, submitted in response to the European Space Agency (ESA) Voyage 2050 Call, we present the importance of advancing our knowledge of plasma-neutral gas interactions, and of deepening our understanding of the partially ionized environments that are ubiquitous in the upper atmospheres of planets and moons, and elsewhere in space. In future space missions, the above task requires addressing the following fundamental questions: (A) How and by how much do plasma-neutral gas interactions influence the re-distribution of externally provided energy to the composing species? (B) How and by how much do plasma-neutral gas interactions contribute toward the growth of heavy complex molecules and biomolecules? Answering these questions is an absolute prerequisite for addressing the long-standing questions of atmospheric escape, the origin of biomolecules, and their role in the evolution of planets, moons, or comets, under the influence of energy sources in the form of electromagnetic and corpuscular radiation, because low-energy ion-neutral cross-sections in space cannot be reproduced quantitatively in laboratories for conditions of satisfying, particularly, (1) low-temperatures, (2) tenuous or strong gradients or layered media, and (3) in low-gravity plasma. Measurements with a minimum core instrument package (< 15 kg) can be used to perform such investigations in many different conditions and should be included in all deep-space missions. These investigations, if specific ranges of background parameters are considered, can also be pursued for Earth, Mars, and Venus.
|
|
| 7. |
- Amano, Tatsuya, et al.
(författare)
-
Transforming Practice : Checklists for Delivering Change
- 2022
-
Ingår i: Transforming Conservation : A Practical Guide to Evidence and Decision Making - A Practical Guide to Evidence and Decision Making. - 9781800648562 - 9781800648586 ; , s. 367-386
-
Bokkapitel (refereegranskat)abstract
- Delivering a revolution in evidence use requires a cultural change across society. For a wide range of groups (practitioners, knowledge brokers, organisations, organisational leaders, policy makers, funders, researchers, journal publishers, the wider conservation community, educators, writers, and journalists), options are described to facilitate a change in practice, and a series of downloadable checklists is provided.
|
|
| 8. |
- Chirinos, Julio A., et al.
(författare)
-
Reduced Apolipoprotein M and Adverse Outcomes across the Spectrum of Human Heart Failure
- 2020
-
Ingår i: Circulation. - 0009-7322. ; , s. 1463-1476
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61]; P<0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58-0.67]; P<0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69-0.88]; P<0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76-0.94]; P=0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated (R=0.81, P<0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
|
|
| 9. |
- Drago, Victoria N., et al.
(författare)
-
Neutron diffraction from a microgravity-grown crystal reveals the active site hydrogens of the internal aldimine form of tryptophan synthase
- 2024
-
Ingår i: Cell Reports Physical Science. - 2666-3864. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- Pyridoxal 5′-phosphate (PLP), the biologically active form of vitamin B6, is an essential cofactor in many biosynthetic pathways. The emergence of PLP-dependent enzymes as drug targets and biocatalysts, such as tryptophan synthase (TS), has underlined the demand to understand PLP-dependent catalysis and reaction specificity. The ability of neutron diffraction to resolve the positions of hydrogen atoms makes it an ideal technique to understand how the electrostatic environment and selective protonation of PLP regulates PLP-dependent activities. Facilitated by microgravity crystallization of TS with the Toledo Crystallization Box, we report the 2.1 Å joint X-ray/neutron (XN) structure of TS with PLP in the internal aldimine form. Positions of hydrogens were directly determined in both the α- and β-active sites, including PLP cofactor. The joint XN structure thus provides insight into the selective protonation of the internal aldimine and the electrostatic environment of TS necessary to understand the overall catalytic mechanism.
|
|
| 10. |
- Hollmann, E M, et al.
(författare)
-
Estimate of pre-thermal quench non-thermal electron density profile during Ar pellet shutdowns of low-density target plasmas in DIII-D
- 2021
-
Ingår i: Physics of Plasmas. - : AIP Publishing. - 1089-7674 .- 1070-664X. ; 28:7
-
Tidskriftsartikel (refereegranskat)abstract
- The radial density profile of pre-thermal quench (pre-TQ) early-time non-thermal (hot) electrons is estimated by combining electron cyclotron emission and soft x-ray data during the rapid shutdown of low-density (ne≲1019m−3) DIII-D target plasmas with cryogenic argon pellet injection. This technique is mostly limited in these experiments to the pre-TQ phase and quickly loses validity during the TQ. Two different cases are studied: a high (10 keV) temperature target and a low (4 keV) temperature target. The results indicate that early-time, low-energy (∼10 keV) hot electrons form ahead of the argon pellet as it enters the plasma, affecting the pellet ablation rate; it is hypothesized that this may be caused by rapid cross field transport of argon ions ahead of the pellet or by rapid cross field transport of hot electrons. Fokker-Planck modeling of the two shots suggests that the hot electron current is quite significant during the pre-TQ phase (up to 50% of the total current). Comparison between modeled pre-TQ hot electron current and post-TQ hot electron current inferred from avalanche theory suggests that hot electron current increases during the high-temperature target TQ but decreases during the low-temperature target TQ. The uncertainties in this estimate are large; however, if true, this suggests that TQ radial loss of hot electron current could be larger than previously estimated in DIII-D.
|
|
