Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study

Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution.

Macrophage uptake of oxidized and acetylated low-density lipoproteins and generation of reactive oxygen species are regulated by linear stiffness of the growth surface

Macrophages are key players in the development of atherosclerosis: they scavenge lipid, transform into foam cells, and produce proinflammatory mediators. At the same time, the arterial wall undergoes profound changes in its mechanical properties. We recently showed that macrophage morphology and proinflammatory potential are regulated by the linear stiffness of the growth surface. Here we asked whether linear stiffness also regulates lipid uptake by macrophages. We cultured murine bone marrow-derived macrophages (BMMs) on polyacrylamide gels modeling stiffness of healthy (1kPa) and diseased (10-150kPa) blood vessels. In unprimed BMMs, increased linear stiffness increased uptake of oxidized (oxLDL) and acetylated (acLDL) low density lipoproteins and generation of reactive oxygen species, but did not alter phagocytosis of bacteria or silica particles. Macrophages adapted to stiff growth surfaces had increased mRNA and protein expression of two key lipoprotein receptors: CD36 and scavenger receptor b1. Regulation of the lipoprotein receptor, lectin-like receptor for ox-LDL, was more complex: mRNA expression decreased but surface protein expression increased with increased stiffness. Focal adhesion kinase was required for maximal uptake of oxLDL, but not of acLDL. Uptake of oxLDL and acLDL was independent of rho-associated coiled coil kinase. Through pharmacologic inhibition and genetic deletion, we found that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, plays an inhibitory role in the uptake of acLDL, but not oxLDL. Together, these results implicate mechanical signaling in the uptake of acLDL and oxLDL, opening up the possibility of new pharmacologic targets to modulate lipid uptake by macrophages in vivo.

Epitaxial Growth and Structural Characterizations of MnBi2Te4 Thin Films in Nanoscale

The intrinsic magnetic topological insulator MnBi2Te4 has attracted much attention due to its special magnetic and topological properties. To date, most reports have focused on bulk or flake samples. For material integration and device applications, the epitaxial growth of MnBi2Te4 film in nanoscale is more important but challenging. Here, we report the growth of self-regulated MnBi2Te4 films by the molecular beam epitaxy. By tuning the substrate temperature to the optimal temperature for the growth surface, the stoichiometry of MnBi2Te4 becomes sensitive to the Mn/Bi flux ratio. Excessive and deficient Mn resulted in the formation of a MnTe and Bi2Te3 phase, respectively. The magnetic measurement of the 7 SL MnBi2Te4 film probed by the superconducting quantum interference device (SQUID) shows that the antiferromagnetic order occurring at the Néel temperature 22 K is accompanied by an anomalous magnetic hysteresis loop along the c-axis. The band structure measured by angle-resolved photoemission spectroscopy (ARPES) at 80 K reveals a Dirac-like surface state, which indicates that MnBi2Te4 has topological insulator properties in the paramagnetic phase. Our work demonstrates the key growth parameters for the design and optimization of the synthesis of nanoscale MnBi2Te4 films, which are of great significance for fundamental research and device applications involving antiferromagnetic topological insulators.

Technological features of the method of liquid-phase epitaxy when growing InP/GaInAsP heterostructures

Semiconductor devices of quantum electronics based on InP/GaInAsP heterostructures require the creation of non-defective chips for emitting devices and photodetectors. The production of such chips is impossible without a thorough technological study of the growth processes of epitaxial structures. One of the important problems in relation to the growth of such structures is the growth defects associated with the process of dissociation of indium phosphide on the surface during their growth. The aim of the work was the investigation of the process and mechanism of destruction (dissociation) of the surface of indium phosphide substrates in the range of growth temperatures of structures, as well as the study of methods andtechniques that allow minimize the process of dissociation of surface of indium phosphide.The work provides studies of the growth processes of InP/GaInAsP heterostructures, from the liquid phase, taking into account the degradation processes of the growth surface and the mechanisms for the formation of dissociation defects.The schemes of the dissociation process of the InP on the surface of the substrate and the formation of the defective surface of the substrate were analysed. At the same time, technological methods allowing to minimize the dissociation of the surface compound during the process of liquid-phase epitaxy were shown. The original design of a graphite cassette allowing to minimize the dissociation of the indium phosphide substrate in the process of liquid-phase epitaxy was proposed

CoFlame: A refined and validated numerical algorithm for modeling sooting laminar coflow diffusion flames

Mitigation of soot emissions from combustion devices is a global concern. For example, recent EURO 6 regulations for vehicles have placed stringent limits on soot emissions. In order to allow design engineers to achieve the goal of reduced soot emissions, they must have the tools to so. Due to the complex nature of soot formation, which includes growth and oxidation, detailed numerical models are required to gain fundamental insights into the mechanisms of soot formation. A detailed description of the CoFlame FORTRAN code which models sooting laminar coflow diffusion flames is given. The code solves axial and radial velocity, temperature, species conservation, and soot aggregate and primary particle number density equations. The sectional particle dynamics model includes nucleation, PAH condensation and HACA surface growth, surface oxidation, coagulation, fragmentation, particle diffusion, and thermophoresis. The code utilizes a distributed memory parallelization scheme with strip-domain decomposition. The public release of the CoFlame code, which has been refined in terms of coding structure, to the research community accompanies this paper. CoFlame is validated against experimental data for reattachment length in an axi-symmetric pipe with a sudden expansion, and ethylene–air and methane–air diffusion flames for multiple soot morphological parameters and gas-phase species. Finally, the parallel performance and computational costs of the code is investigated.

CoFlame: A refined and validated numerical algorithm for modeling sooting laminar coflow diffusion flames

Mitigation of soot emissions from combustion devices is a global concern. For example, recent EURO 6 regulations for vehicles have placed stringent limits on soot emissions. In order to allow design engineers to achieve the goal of reduced soot emissions, they must have the tools to so. Due to the complex nature of soot formation, which includes growth and oxidation, detailed numerical models are required to gain fundamental insights into the mechanisms of soot formation. A detailed description of the CoFlame FORTRAN code which models sooting laminar coflow diffusion flames is given. The code solves axial and radial velocity, temperature, species conservation, and soot aggregate and primary particle number density equations. The sectional particle dynamics model includes nucleation, PAH condensation and HACA surface growth, surface oxidation, coagulation, fragmentation, particle diffusion, and thermophoresis. The code utilizes a distributed memory parallelization scheme with strip-domain decomposition. The public release of the CoFlame code, which has been refined in terms of coding structure, to the research community accompanies this paper. CoFlame is validated against experimental data for reattachment length in an axi-symmetric pipe with a sudden expansion, and ethylene–air and methane–air diffusion flames for multiple soot morphological parameters and gas-phase species. Finally, the parallel performance and computational costs of the code is investigated.

A STUDY OF NAIL CHANGES AND DISORDERS IN ELDERLY AT SKMCH MUZAFFARPUR, BIHAR

Background: Nail changes associated with ageing are common in the elderly and include characteristic modications of color, contour, growth, surface, thickness and histology. No cutaneous examination is complete without a careful clinical evaluation of the nails. Objective: The aim of present work is to assess the nail changes and disorders in elderly people compared with control age group (20 - 30 years old). Material and methods: This case-controlled, cross-sectional study was performed in the outpatient of Dermatology and Venereology and Leprosy Department at Sri Krishna Medical College and Hospital Muzaffarpur in the period from August 2020 to March 2021. The study included 200 subjects, of which 100 patients were above 50 years old (study group), and the other 100 subjects were from 20 - 30 years old (control group). A detailed history from each subject was recorded to detect the onset, duration and progression of nail changes and/or disorders, their occupation and any environmental exposure. A careful examination of the nails was carried out to assess the type of nail changes, site and symmetry. Any patient with systemic disease, dermatological disease or with suspected drug intake was excluded from the study. The present work has shown Results: that many nail changes were more frequent among older age individuals than younger age group with signicant statistical difference (p = 0.043 - 0.000) like dull opaque appearance, rough lusterlessness, longitudinal ridg-ing, altered thickness, ragged cuticle, altered contour, subungual hyperkeratosis and scaling nail folds. Chromonychia was not statistically signicant (14% of study group versus 16% of the control) with p = 0.692. Longitudinal melanonychia was signicantly higher in the study group (6% versus 0% of the control) with p = 0.013, while punctate leukonychia was signicantly higher in the control group (16% versus 4% of study group) with p = 0.005. Conclusion: Some changes of the nail are signicantly correlated with advanced age like dull opaque nails, rough lusterlessness, longitudinal ridging. Therefore, these signs can be regarded as indicative of ageing of healthy people.

The Early Steps of Molecule-to-Material Conversion in Chemical Vapor Deposition (CVD): A Case Study

Transition metal complexes with β-diketonate and diamine ligands are valuable precursors for chemical vapor deposition (CVD) of metal oxide nanomaterials, but the metal-ligand bond dissociation mechanism on the growth surface is not yet clarified in detail. We address this question by density functional theory (DFT) and ab initio molecular dynamics (AIMD) in combination with the Blue Moon (BM) statistical sampling approach. AIMD simulations of the Zn β-diketonate-diamine complex Zn(hfa)2TMEDA (hfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionate; TMEDA = N,N,N′,N′-tetramethylethylenediamine), an amenable precursor for the CVD of ZnO nanosystems, show that rolling diffusion of this precursor at 500 K on a hydroxylated silica slab leads to an octahedral-to-square pyramidal rearrangement of its molecular geometry. The free energy profile of the octahedral-to-square pyramidal conversion indicates that the process barrier (5.8 kcal/mol) is of the order of magnitude of the thermal energy at the operating temperature. The formation of hydrogen bonds with surface hydroxyl groups plays a key role in aiding the dissociation of a Zn-O bond. In the square-pyramidal complex, the Zn center has a free coordination position, which might promote the interaction with incoming reagents on the deposition surface. These results provide a valuable atomistic insight on the molecule-to-material conversion process which, in perspective, might help to tailor by design the first nucleation stages of the target ZnO-based nanostructures.