Fire is the primary disturbance factor in many terrestrial ecosystems. Wildfire alters vegetation structure and composition, affects carbon storage and biogeochemical cycling, and results in the ...release of climatically relevant trace gases including CO2, CO, CH4, NOx, and aerosols. One way of assessing the impacts of global wildfire on centennial to multi-millennial timescales is to use process-based fire models linked to dynamic global vegetation models (DGVMs). Here we present an update to the LPJ-DGVM and a new fire module based on SPITFIRE that includes several improvements to the way in which fire occurrence, behaviour, and the effects of fire on vegetation are simulated. The new LPJ-LMfire model includes explicit calculation of natural ignitions, the representation of multi-day burning and coalescence of fires, and the calculation of rates of spread in different vegetation types. We describe a new representation of anthropogenic biomass burning under preindustrial conditions that distinguishes the different relationships between humans and fire among hunter-gatherers, pastoralists, and farmers. We evaluate our model simulations against remote-sensing-based estimates of burned area at regional and global scale. While wildfire in much of the modern world is largely influenced by anthropogenic suppression and ignitions, in those parts of the world where natural fire is still the dominant process (e.g. in remote areas of the boreal forest and subarctic), our results demonstrate a significant improvement in simulated burned area over the original SPITFIRE. The new fire model we present here is particularly suited for the investigation of climate–human–fire relationships on multi-millennial timescales prior to the Industrial Revolution.
A duality for the S matrix Arkani-Hamed, N.; Cachazo, F.; Cheung, C. ...
The journal of high energy physics,
03/2010, Volume:
2010, Issue:
3
Journal Article
Peer reviewed
Open access
We propose a dual formulation for the S Matrix of
= 4 SYM. The dual provides a basis for the “leading singularities” of scattering amplitudes to all orders in perturbation theory, which are sharply ...defined, IR safe data that uniquely determine the full amplitudes at tree level and 1-loop, and are conjectured to do so at all loop orders. The scattering amplitude for
n
particles in the sector with
k
negative helicity gluons is associated with a simple integral over the space of
k
planes in n dimensions, with the action of parity and cyclic symmetries manifest. The residues of the integrand compute a basis for the leading singularities. A given leading singularity is associated with a particular choice of integration contour, which we explicitly identify at tree level and 1-loop for all NMHV amplitudes as well as the 8 particle N
2
MHV amplitude. We also identify a number of 2-loop leading singularities for up to 8 particles. There are a large number of relations among residues which follow from the multi-variable generalization of Cauchy’s theorem known as the “global residue theorem”. These relations imply highly non-trivial identities guaranteeing the equivalence of many different representations of the same amplitude. They also enforce the cancellation of non-local poles as well as consistent infrared structure at loop level. Our conjecture connects the physics of scattering amplitudes to a particular subvariety in a Grassmannian; space-time locality is reflected in the topological properties of this space.
An abnormal neutrophil subset has been identified in the PBMC fractions from lupus patients. We have proposed that these low-density granulocytes (LDGs) play an important role in lupus pathogenesis ...by damaging endothelial cells and synthesizing increased levels of proinflammatory cytokines and type I IFNs. To directly establish LDGs as a distinct neutrophil subset, their gene array profiles were compared with those of autologous normal-density neutrophils and control neutrophils. LDGs significantly overexpress mRNA of various immunostimulatory bactericidal proteins and alarmins, relative to lupus and control neutrophils. In contrast, gene profiles of lupus normal-density neutrophils do not differ from those of controls. LDGs have heightened capacity to synthesize neutrophils extracellular traps (NETs), which display increased externalization of bactericidal, immunostimulatory proteins, and autoantigens, including LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity to kill endothelial cells and to stimulate IFN-α synthesis by plasmacytoid dendritic cells. Affected skin and kidneys from lupus patients are infiltrated by netting neutrophils, which expose LL-37 and dsDNA. Tissue NETosis is associated with increased anti-dsDNA in sera. These results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.
Understanding excited carrier dynamics in semiconductors is crucial for the development of photovoltaics and efficient photonic devices. However, overlapping spectral features in optical pump-probe ...spectroscopy often render assignments of separate electron and hole carrier dynamics ambiguous. Here, ultrafast electron and hole dynamics in germanium nanocrystalline thin films are directly and simultaneously observed by ultrafast transient absorption spectroscopy in the extreme ultraviolet at the germanium M
edge. We decompose the spectra into contributions of electronic state blocking and photo-induced band shifts at a carrier density of 8 × 10
cm
. Separate electron and hole relaxation times are observed as a function of hot carrier energies. A first-order electron and hole decay of ∼1 ps suggests a Shockley-Read-Hall recombination mechanism. The simultaneous observation of electrons and holes with extreme ultraviolet transient absorption spectroscopy paves the way for investigating few- to sub-femtosecond dynamics of both holes and electrons in complex semiconductor materials and across junctions.
Planetary cores consist of liquid metals (low Prandtl number Pr) that convect as the core cools. Here, we study nonlinear convection in a rotating (low Ekman number Ek) planetary core using a fully ...3D direct numerical simulation. Near the critical thermal forcing (Rayleigh number Ra), convection onsets as thermal Rossby waves, but as Ra increases, this state is superseded by one dominated by advection. At moderate rotation, these states (here called the weak branch and strong branch, respectively) are smoothly connected. As the planetary core rotates faster, the smooth transition is replaced by hysteresis cycles and subcriticality until the weak branch disappears entirely and the strong branch onsets in a turbulent state at Ek<10^{-6}. Here, the strong branch persists even as the thermal forcing drops well below the linear onset of convection (Ra=0.7Ra_{crit} in this study). We highlight the importance of the Reynolds stress, which is required for convection to subsist below the linear onset. In addition, the Péclet number is consistently above 10 in the strong branch. We further note the presence of a strong zonal flow that is nonetheless unimportant to the convective state. Our study suggests that, in the asymptotic regime of rapid rotation relevant for planetary interiors, thermal convection of liquid metals in a sphere onsets through a subcritical bifurcation.
Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such as systemic lupus ...erythematosus (SLE), a condition characterized by aberrant type I IFN signaling, has not been determined. Here, we identify a nonredundant role for IFN-λ in immune dysregulation and tissue inflammation in a model of TLR7-induced lupus. IFN-λ protein is increased in murine lupus and IFN-λ receptor (Ifnlr1) deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys without effects on autoantibody production. Single-cell RNA sequencing in mouse spleen and human peripheral blood revealed that only mouse neutrophils and human B cells are directly responsive to this cytokine. Rather, IFN-λ activates keratinocytes and mesangial cells to produce chemokines that induce immune cell recruitment and promote tissue inflammation. These data provide insights into the immunobiology of SLE and identify type III IFNs as important factors for tissue-specific pathology in this disease.
Objective
Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date ...targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized.
Methods
MRL/lpr lupus‐prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium‐dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice.
Results
Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium‐dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies.
Conclusion
Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage.
Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-α-producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine ...deiminase inhibition is a strategy that can decrease in vivo NET formation.
To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis.
Apolipoprotein-E (Apoe)(-/-) mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-α in diseased arteries. Apoe(-/-) mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-α expression.
Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses.
The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic ...event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.
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