Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics
. Dozens of recent studies have begun to describe ITH by ...single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH
. Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell-cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.
The dynamics of quantized magnetic vortices and their pinning by materials defects determine electromagnetic properties of superconductors, particularly their ability to carry non-dissipative ...currents. Despite recent advances in the understanding of the complex physics of vortex matter, the behavior of vortices driven by current through a multi-scale potential of the actual materials defects is still not well understood, mostly due to the scarcity of appropriate experimental tools capable of tracing vortex trajectories on nanometer scales. Using a novel scanning superconducting quantum interference microscope we report here an investigation of controlled dynamics of vortices in lead films with sub-Angstrom spatial resolution and unprecedented sensitivity. We measured, for the first time, the fundamental dependence of the elementary pinning force of multiple defects on the vortex displacement, revealing a far more complex behavior than has previously been recognized, including striking spring softening and broken-spring depinning, as well as spontaneous hysteretic switching between cellular vortex trajectories. Our results indicate the importance of thermal fluctuations even at 4.2 K and of the vital role of ripples in the pinning potential, giving new insights into the mechanisms of magnetic relaxation and electromagnetic response of superconductors.
The aspects of adaptating the moisture circulation system at the catchments of small watercourses to climate change based on the observational data from the Kamennaya Step’ water balance station are ...considered. It is demonstrated that the transformation of the moisture circulation system results from the changes in the balance between the groundwater recharge and leakage with a decrease in the contribution of cryogenic factors to the river basin water regime formation. It is suggested that the transition period in the moisture circulation restructuring in river basins can be divided into two periods: with predomination of groundwater recharge and with predomination of its leakage. The length of the transformation phase in the steppe zone depending on the cryogenic factor is about 40 years. The final stabilization of the hydrological regime will depend on setting the groundwater balance under the specific hydrogeological conditions and anthropogenic load.
Soil hydrocarbon-contamination represents an environmental threat even at remote locations such as Antarctica. In order to restore these soils, bioremediation, and biostimulation in particular, have ...proven to be an effective approach. However, large scale bioremediation schemes under the extreme environmental conditions of this continent provide a big uncertainty upon the robustness and reproducibility of these treatments. In this work, we compared the efficiency of two consecutive year field assays using 0.5 ton biopiles at Carlini Station, in order to identify those factors that affect the reproducibility of the pre-optimized biostimulation. First year field assay (biopiles I) reached >75% of hydrocarbon removal, while second year (biopiles II) only removed 55% of the total hydrocarbons. Several biological and physicochemical variables were statistically analyzed for both years' biopiles in order to identify the source of these differences. Total sunlight hours resulted to be the key factor driving removal efficiency in these treatments by increasing soil temperature inside the biopiles, and therefore, total biological activity and degrading bacterial counts in soil. This work represents the first study on the reproducibility of field assays in extreme environments such as Antarctica, and it provides a novel input to the scarce knowledge on field hydrocarbon bioremediation practices in cold regions.
•Efficiency in these on-site bioremediation processes showed to be strongly dependent on hydrocarbons initial concentration.•Removal percentages for the second year biopiles were lower than those observed for the first experiment.•The temperature on both, uncovered and biopiled-covered soils, showed a clear correlation with the removal efficiency.•Such temperatures depend stronger on total sunlight hours than on air temperature.
Results are provided for a study of an aluminized coating corrosion resistance on the surface of alloys of the Fe–Cr–Al system (fechrals) and austenitic corrosion-resistant steel 12Kh18N10T under ...conditions of a temperate climate humid atmosphere containing chlorides. Coatings are applied by immersion in a melt. A study of corrosion during variable immersion of specimens in a 3% aqueous solution of sodium chloride show that coatings of the Fe–Cr–Al system prepared by aluminizing withstand long-term exposure to the environment (corrosion rate is 0.0003 g/(m
2
·day). An aluminized coating on a steel 12Kh18N10T surface has twice as good corrosion resistance indicators than for a coating on a Kh15Yu5 substrate.
The state of stress in locked-coil rope elements is subjected to finite element simulation under joint tension and torsion. The axial forces and torques in the cross sections of the layers are found ...to be redistributed when a rope turns under an external torque, which leads to a decrease in the safety factor of the rope, a violation of the compatibility of the axial and radial displacements of the layers, and a violation of the structural integrity of the rope in the form of breaks in the outer layer wires.
Abstract
Finite element simulation of tensile deformation of titanium-aluminum composite D20 – AD1 – VT6 was carried out. The joint boundary had a wave profile and local melts. 3D modeling of ...deformation of the composite D20 – AD1 – VT6 with a wave profile of the welded joint was carried out using the SIMULIA / Abaqus software. The relative thickness of the AD1 interlayer and the area of the melt were varied during the simulation. To determine for metal hardening during plastic deformation and the failure deformations for aluminum and aluminum alloy both Johnson-Cook deformation and fracture models was used. The influence of the size of the local melting zone and thickness of the soft interlayer on the distribution of stresses and strains in the composite is shown. The wave profile of the boundaries junction leads initially to localization of plastic deformation in the aluminum interlayer in the zone of free surfaces of the sample near the interface with the titanium alloy. A change in the length of vortices with areas of local melting near the tops of the wave profile from 0.3 to 0.8 mm had little effect on the profile of the curves “equivalent stress-absolute elongation of the sample”.
The change in the transverse strains of the layers in a spiral rope during tension at the stage of elastic deformation is studied by finite element simulation. The influence of the presence of gap ...between the wires in the outer layers and its value on the compatibility of operation of the layers in the radial direction and the preservation of the structural integrity of the rope during operation is revealed.
It was shown that the optical and dielectric properties of polyimides (PIs) are affected by both the presence of an alicyclic fragment and the non-coplanarity of the structural elements of the ...polymer chain. The combination of these factors contributed to an increase of the transparency of the PIs in the optical range and a decrease of the dielectric constant. It was determined that the introduction of 20 mol.% adamantane-containing diamine into the PI structure contributed to its more complete amorphization and increased its transparency.
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