Context. The properties of the smallest subunits of cometary dust contain information on their origin and clues to the formation of planetesimals and planets. Compared to interplanetary dust ...particles or particles collected during the Stardust mission, dust collected in the coma of comet 67P/Churyumov-Gerasimenko (67P) during the Rosetta mission provides a resource of minimally altered material with known origin whose structural properties can be used to further the investigation of the early solar system. Aims. The cometary dust particle morphologies found at comet 67P on the micrometer scale are classified, and their structural analysis is extended to the nanometer scale. Methods. We present a novel method for achieving the highest spatial resolution of imaging obtained with the MIDAS Atomic Force Microscope on board Rosetta. 3D topographic images with resolutions down to 8 nm were analyzed to determine the subunit sizes of particles on the nanometer scale. Results. Three morphological classes can be determined: (i) fragile agglomerate particles of sizes larger than about 10 μm comprised of micrometer-sized subunits that may themselves be aggregates and show a moderate packing density on the surface of the particles. (ii) A fragile agglomerate with a size of about a few tens of micrometers comprised of micrometer-sized subunits that are suggested to be aggregates themselves and are arranged in a structure with a fractal dimension lower than two. (iii) Small micrometer-sized particles comprised of subunits in the size range of hundreds of nanometers that show surface features that are again suggested to represent subunits. Their differential size distributions follow a log-normal distribution with means of about 100 nm and standard deviations between 20 and 35 nm. Conclusions. The properties of the dust particles found by MIDAS represent an extension of the dust results of Rosetta to the micro- and nanometer scale. All micrometer-sized particles are hierarchical dust agglomerates of smaller subunits. The arrangement, appearance, and size distribution of the smallest determined surface features are reminiscent of those found in chondritic porous interplanetary dust particles. They represent the smallest directly detected subunits of comet 67P.
Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. ...Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.e. >125 times less compared to the mean expression of all other genes over lesional skin sections. Nevertheless, cytokine expression is limited to lesional skin and presented in a disease-specific pattern. Leveraging a density-based spatial clustering method, we identify specific responder gene signatures in direct proximity of cytokines, and confirm that detected cytokine transcripts initiate amplification cascades of up to thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and heterogeneous infiltrates of ncISD, only a low number of cytokine transcripts and their translated proteins promote disease by initiating an inflammatory amplification cascade in their local microenvironment.
Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is ...known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN-) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype. This OPN-TGF-β1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-β1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN-MZF1-TGF-β1 pathway.
Primary amines are one of the most predominant functional groups found in organic molecules. These entities help form the chemical architecture of natural products, bioactive molecules, synthetic ...building blocks and catalysts. Due to their ubiquitous presence, the development of strategies for the construction of C-C or C-X bonds through deaminative processes is of high importance. Deaminative methods offer new possibilities on the retrosynthetic rationale, and enable late-stage-functionalization of complex structures. As a result of the recent development of photoinduced processes, a variety of photo-mediated deaminative protocols employing 2,4,6-triphenyl-pyridinium salts - Katritzky Salts - as activating agents have been recently realized. This review covers the most recent developments of deaminative strategies by using Katritzky Salts as alkyl radical reservoirs, with particular concern on photoinduced processes applied to organic synthesis.
Primary amines are one of the most predominant functional groups found in organic molecules. This review covers the most recent developments on photocatalytic deaminative strategies by using Katritzky Salts as alkyl radical reservoirs.
A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical ...management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.
A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation ...in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. Although epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 has an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing.
The Interior Exploration using Seismic Investigations, Geodesy and Heat Transport mission, to be launched in 2018, will perform a comprehensive geophysical investigation of Mars in situ. The Seismic ...Experiment for Interior Structure package aims to detect global and regional seismic events and in turn offer constraints on core size, crustal thickness, and core, mantle, and crustal composition. In this study, we estimate the present‐day amount and distribution of seismicity using 3‐D numerical thermal evolution models of Mars, taking into account contributions from convective stresses as well as from stresses associated with cooling and planetary contraction. Defining the seismogenic lithosphere by an isotherm and assuming two end‐member cases of 573 K and the 1073 K, we determine the seismogenic lithosphere thickness. Assuming a seismic efficiency between 0.025 and 1, this thickness is used to estimate the total annual seismic moment budget, and our models show values between 5.7 × 1016 and 3.9 × 1019 Nm.
Key Points
We compute the cumulative seismic moment due to convective and cooling stresses from 3‐D thermal evolution models of Mars
The annual seismic moment budget calculated from our models is between 5.7 × 1016 and 3.9 × 1019 Nm
A new, self‐consistent model for the spatial distribution of seismicity is derived from 3‐D thermal evolution models
Biologic agents (also termed biologicals or biologics) are therapeutics that are synthesized by living organisms and directed against a specific determinant, for example, a cytokine or receptor. In ...inflammatory and autoimmune diseases, biologicals have revolutionized the treatment of several immune‐mediated disorders. Biologicals have also been tested in allergic disorders. These include agents targeting IgE; T helper 2 (Th2)‐type and Th2‐promoting cytokines, including interleukin‐4 (IL‐4), IL‐5, IL‐9, IL‐13, IL‐31, and thymic stromal lymphopoietin (TSLP); pro‐inflammatory cytokines, such as IL‐1β, IL‐12, IL‐17A, IL‐17F, IL‐23, and tumor necrosis factor (TNF); chemokine receptor CCR4; and lymphocyte surface and adhesion molecules, including CD2, CD11a, CD20, CD25, CD52, and OX40 ligand. In this task force paper of the Interest Group on Biologicals of the European Academy of Allergy and Clinical Immunology, we review biologicals that are currently available or tested for the use in various allergic and urticarial pathologies, by providing an overview on their state of development, area of use, adverse events, and future research directions.
Brown carbon aerosol consists of light‐absorbing organic particulate matter with wavelength‐dependent absorption. Aerosol optical extinction, absorption, size distributions, and chemical composition ...were measured in rural Alabama during summer 2013. The field site was well located to examine sources of brown carbon aerosol, with influence by high biogenic organic aerosol concentrations, pollution from two nearby cities, and biomass burning aerosol. We report the optical closure between measured dry aerosol extinction at 365 nm and calculated extinction from composition and size distribution, showing agreement within experiment uncertainties. We find that aerosol optical extinction is dominated by scattering, with single‐scattering albedo values of 0.94 ± 0.02. Black carbon aerosol accounts for 91 ± 9% of the total carbonaceous aerosol absorption at 365 nm, while organic aerosol accounts for 9 ± 9%. The majority of brown carbon aerosol mass is associated with biomass burning, with smaller contributions from biogenically derived secondary organic aerosol.
Key Points
Aerosol optical extinction in the southeastern U.S. is dominated by scattering
Black carbon is a more significant absorber than organic carbon at 365 nm
Biomass burning makes the largest contribution to organic aerosol absorption
Abstract
We investigate the interplay of magnetization and lattice vibrations in rare-earth orthoferrites
R
FeO
3
, with a specific focus on non-symmetry-breaking anomalies. To do so, we study the ...magnetization, magnon excitations and lattice dynamics as a function of temperature in NdFeO
3
, TbFeO
3
, EuFeO
3
and GdFeO
3
. The magnetization shows distinct temperature anomalous behavior for all investigated rare-earth orthoferrites, even in the compounds with no phase transitions occurring at those temperatures. Through spin–phonon coupling, these magnetic changes are mirrored by the FeO
6
rotation mode for all the studied
R
FeO
3
, revealing a common magnetostructural effect associated with the octahedra rotations. The
R
3+
oscillation modes evidence a Fe
3+
/R
3+
spins cross-talk for the NdFeO
3
and TbFeO
3
cases. Our work sheds light into the common magnetostructural coupling in rare-earth orthoferrites, and the important role of magnetic anisotropy and spin–orbit coupling strength of the
R
–Fe interactions on the spin-reorientation transition at high temperatures.
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