Formation of Power-law Energy Spectra in Space Plasmas by Stochastic Acceleration due to Whistler-Mode Waves

A non-relativistic Fokker-Planck equation for the electron distribution function is formulated incorporating the effects of stochastic acceleration by whistler-mode waves and Coulomb collisions. The stationary solution $f$ to the equation, subject to a zero-flux boundary condition, is found to be a generalized Lorentzian (or kappa) distribution, which satisfies $f\propto v^{-2(\kappa+1)}$ for large velocity $v$, where $\kappa$ is the spectral index. The parameter $\kappa$ depends strongly on the relative wave intensity $R$. Taking into account the critical energy required for resonance of electrons with whistlers, we calculate a range of values of $R$ for each of a number of different space plasmas for which kappa distributions can be expected to be formed. This study is one of the first in the literature to provide a theoretical justification for the formation of generalized Lorentzian (or kappa) particle distribution functions in space plasmas.Comment: 14 page-Latex, 1 ps-figure, agums.st

Rapid acceleration of electrons in the magnetosphere by fast-mode MHD waves

During major megnetic storms, enhanced flux of relativistic electrons in the inner magnetosphere have been observed to correleated with ULF waves. The enhancements can take place over a period of several hours. In order to account for such a rapid generation of relativistic electrons, we examine the mechanism of transit-time acceleration of electrons by low-frequency fast-mode MHD waves, here the assumed form of ULF waves. Calcaulations of the acceleration timescales in the model show that fast-mode waves in the Pc4 to Pc5 frequency range, with typically observed wave amplitudes 10--20 nT, can accelerate the seed electrons to energies of order MeV in a period of a few hours.Comment: 9 pages, 3 figures, Accepted to J. Geophys. Re

Particle Simulation of the Generation of Plasmaspheric Hiss

We have conducted a one‐dimensional electromagnetic particle simulation with a parabolic magnetic field to reproduce whistler‐mode hiss emissions in the plasmasphere. We assume a bi‐Maxwellian distribution with temperature anisotropy for energetic electrons injected into the plasmasphere and find that hiss emissions are generated with spectrum characteristics typical of those observed by spacecraft near the magnetic equator. The hiss emissions contain fine structures involving rising tone and falling tone elements with variation in frequencies. The amplitude profile of the spectra agrees with the optimum wave amplitude derived from the nonlinear wave growth theory. The simulation demonstrates that hiss emissions are generated locally near the magnetic equator through linear and nonlinear interactions with energetic electrons with temperature anisotropy. The coherent hiss emissions efficiently scatter resonant electrons of 2.5–80 keV into the loss cone

Comprehensive Assessment of Restoration Seedings to Improve Restoration Success

Restoration projects rely on seedling establishment and persistence to foster invasion resistance and improve resilience to environmental stress and disturbance (James et al. 2010; Chambers et al. 2014). However, few studies have comprehensively evaluated the landscape-level performance of seeded species or the factors that control their short-term establishment and long-term persistence (Hardegree et al. 2011; Knutson et al. 2014). Assessing the role of these factors across physiographic regions that experience high temporal and spatial variability in environmental conditions will reveal the effectiveness of various pre-seeding land treatments and enhance our capacity to select appropriate restoration species for specific ecological sites based on their seeding establishment and persistence

Potent acyl-CoA synthetase 10 inhibitors kill <i>Plasmodium falciparum</i> by disrupting triglyceride formation

Identifying how small molecules act to kill malaria parasites can lead to new chemically validated targets. By pressuring Plasmodium falciparum asexual blood stage parasites with three novel structurally-unrelated antimalarial compounds (MMV665924, MMV019719 and MMV897615), and performing whole-genome sequence analysis on resistant parasite lines, we identify multiple mutations in the P. falciparum acyl-CoA synthetase (ACS) genes PfACS10 (PF3D7_0525100, M300I, A268D/V, F427L) and PfACS11 (PF3D7_1238800, F387V, D648Y, and E668K). Allelic replacement and thermal proteome profiling validates PfACS10 as a target of these compounds. We demonstrate that this protein is essential for parasite growth by conditional knockdown and observe increased compound susceptibility upon reduced expression. Inhibition of PfACS10 leads to a reduction in triacylglycerols and a buildup of its lipid precursors, providing key insights into its function. Analysis of the PfACS11 gene and its mutations point to a role in mediating resistance via decreased protein&nbsp;stability

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A)

GWAS and Meta-Analysis Identifies 49 Genetic Variants Underlying Critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A)

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A)