When deformed beyond their elastic limits, crystalline solids flow plastically via particle rearrangements localized around structural defects. Disordered solids also flow, but without obvious ...structural defects. We link structure to plasticity in disordered solids via a microscopic structural quantity, “softness,” designed by machine learning to be maximally predictive of rearrangements. Experimental results and computations enabled us to measure the spatial correlations and strain response of softness, as well as two measures of plasticity: the size of rearrangements and the yield strain. All four quantities maintained remarkable commonality in their values for disordered packings of objects ranging from atoms to grains, spanning seven orders of magnitude in diameter and 13 orders of magnitude in elastic modulus. These commonalities link the spatial correlations and strain response of softness to rearrangement size and yield strain, respectively.
Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert ...working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.
Magnetic reconnection is a fundamental physical process in plasmas whereby stored magnetic energy is converted into heat and kinetic energy of charged particles. Reconnection occurs in many ...astrophysical plasma environments and in laboratory plasmas. Using measurements with very high time resolution, NASA's Magnetospheric Multiscale (MMS) mission has found direct evidence for electron demagnetization and acceleration at sites along the sunward boundary of Earth's magnetosphere where the interplanetary magnetic field reconnects with the terrestrial magnetic field. We have (i) observed the conversion of magnetic energy to particle energy; (ii) measured the electric field and current, which together cause the dissipation of magnetic energy; and (iii) identified the electron population that carries the current as a result of demagnetization and acceleration within the reconnection diffusion/dissipation region.
We use 2009-2011 space-borne methane observations from the Greenhouse Gases Observing SATellite (GOSAT) to estimate global and North American methane emissions with 4 degree 5 degree and up to 50 km ...50 km spatial resolution, respectively. GEOS-Chem and GOSAT data are first evaluated with atmospheric methane observations from surface and tower networks (NOAA/ESRL, TCCON) and aircraft (NOAA/ESRL, HIPPO), using the GEOS-Chem chemical transport model as a platform to facilitate comparison of GOSAT with in situ data. This identifies a high-latitude bias between the GOSAT data and GEOS-Chem that we correct via quadratic regression. Our global adjoint-based inversion yields a total methane source of 539 Tg a-1 with some important regional corrections to the EDGARv4.2 inventory used as a prior. Results serve as dynamic boundary conditions for an analytical inversion of North American methane emissions using radial basis functions to achieve high resolution of large sources and provide error characterization. We infer a US anthropogenic methane source of 40.2-42.7 Tg a-1, as compared to 24.9-27.0 Tg a-1 in the EDGAR and EPA bottom-up inventories, and 30.0-44.5 Tg a-1 in recent inverse studies. Our estimate is supported by independent surface and aircraft data and by previous inverse studies for California. We find that the emissions are highest in the southern-central US, the Central Valley of California, and Florida wetlands; large isolated point sources such as the US Four Corners also contribute. Using prior information on source locations, we attribute 29-44 % of US anthropogenic methane emissions to livestock, 22-31 % to oil/gas, 20 % to landfills/wastewater, and 11-15 % to coal. Wetlands contribute an additional 9.0-10.1 Tg a-1.
The global burden of atmospheric methane has been increasing over the past decade, but the causes are not well understood. National inventory estimates from the U.S. Environmental Protection Agency ...indicate no significant trend in U.S. anthropogenic methane emissions from 2002 to present. Here we use satellite retrievals and surface observations of atmospheric methane to suggest that U.S. methane emissions have increased by more than 30% over the 2002–2014 period. The trend is largest in the central part of the country, but we cannot readily attribute it to any specific source type. This large increase in U.S. methane emissions could account for 30–60% of the global growth of atmospheric methane seen in the past decade.
Key Points
We identify a large increase in U.S. methane emissions over the past decade
Increase occurred during a time when emission inventories indicate no change in U.S. emissions
The U.S. could account for 30‐60% of the global increase in atmospheric methane over the past decade
Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 ...July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvénic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site.
Classical and Type II Cepheids are used to reinvestigate specific properties of the Galaxy. A new Type II reddening-free Cepheid distance parametrization is formulated from Large Magellanic Cloud ...(LMC) Cepheids (OGLE), with uncertainties typically no larger than 5–15 per cent. A distance to the Galactic centre of R0= 7.8 ± 0.6 kpc is derived from the median distance to Type II Cepheids in the bulge (OGLE), R0= 7.7 ± 0.7 kpc from a distance to the near side of the bulge combined with an estimated bulge radius of 1.3 ± 0.3 kpc derived from planetary nebulae. The distance of the Sun from the Galactic plane inferred from classical Cepheid variables is Z⊙= 26 ± 3 pc, a result dependent on the sample's distance and direction because of the complicating effects of Gould's Belt and warping in the Galactic disc. Classical Cepheids and young open clusters delineate consistent and obvious spiral features, although their characteristics do not match conventional pictures of the Galaxy's spiral pattern. The Sagittarius–Carina arm is confirmed as a major spiral arm that appears to originate from a different Galactic region than suggested previously. Furthermore, a major feature is observed to emanate from Cygnus–Vulpecula and may continue locally near the Sun. Significant concerns related to the effects of metallicity on the VI-based reddening-free Cepheid distance relations used here are allayed by demonstrating that the computed distances to the Galactic centre, and to several globular clusters (M54, NGC 6441, M15 and M5) and galaxies (NGC 5128 and NGC 3198) which likely host Type II Cepheids: agree with literature results to within the uncertainties. An additional empirical test is proposed to constrain any putative metallicity dependence of Cepheid distance determinations through forced matches of distance estimates to a particular galaxy using both Type II and classical Cepheids.
The evolution of galaxies is connected to the growth of supermassive black holes in their centers. During the quasar phase, a huge luminosity is released as matter falls onto the black hole, and ...radiation-driven winds can transfer most of this energy back to the host galaxy. Over five different epochs, we detected the signatures of a nearly spherical stream of highly ionized gas in the broadband x-ray spectra of the luminous quasar PDS 456. This persistent wind is expelled at relativistic speeds from the inner accretion disk, and its wide aperture suggests an effective coupling with the ambient gas. The outflow's kinetic power larger than 1046 ergs per second is enough to provide the feedback required by models of black hole and host galaxy coevolution.
ObjectivesTristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway ...mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP.MethodsThe expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP.ResultsTTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation.ConclusionsThe phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.
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