Novel Driver Strength Index highlights important cancer genes in TCGA PanCanAtlas patients

Background Cancer driver genes are usually ranked by mutation frequency, which does not necessarily reflect their driver strength. We hypothesize that driver strength is higher for genes preferentially mutated in patients with few driver mutations overall, because these few mutations should be strong enough to initiate cancer. Methods We propose formulas for the Driver Strength Index (DSI) and the Normalized Driver Strength Index (NDSI), the latter independent of gene mutation frequency. We validate them using TCGA PanCanAtlas datasets, established driver prediction algorithms and custom computational pipelines integrating SNA, CNA and aneuploidy driver contributions at the patient-level resolution. Results DSI and especially NDSI provide substantially different gene rankings compared to the frequency approach. E.g., NDSI prioritized members of specific protein families, including G proteins GNAQ, GNA11 and GNAS, isocitrate dehydrogenases IDH1 and IDH2, and fibroblast growth factor receptors FGFR2 and FGFR3. KEGG analysis shows that top NDSI-ranked genes comprise EGFR/FGFR2/GNAQ/GNA11–NRAS/HRAS/KRAS–BRAF pathway, AKT1–MTOR pathway, and TCEB1–VHL–HIF1A pathway. Conclusion Our indices are able to select for driver gene attributes not selected by frequency sorting, potentially for driver strength. Genes and pathways prioritized are likely the strongest contributors to cancer initiation and progression and should become future therapeutic targets

Applications of Nanostructural NiTi Alloys for Medical Devices

New nanostructural shape memory alloy (55.91 wt% of Ni and 44.03 wt% of Ti) for the production of minimally invasive implantation medical devices (stents) was tested for corrosion resistance under static conditions by dipping it into solutions with various acidities (pH from 1.68 to 9.18) for 2 years, for static mechanical properties and for biocompatibility. The material for investigations was 280‐μm wires before and after thermal treatment at 450°C for 15 min in air and surface mechanical treatment. The characteristic image and size of grains were determined using the transmission electron microscope (TEM), and the phase composition; surface morphology; and the layer‐by‐layer composition were investigated using an X‐ray diffractometer; a scanning electron microscope (SEM); and an Auger spectrometer. The nickel release from the investigated nanostructural nitinol is less in comparison with data for microstructural nitinol in a solution of any acidity. Dissolution in the alkali medium is absent. A significant retardation of the nickel ion release (and insignificant concentration as a whole) and the absence of titanium ion release in the weakly acidic and neutral solutions with polished samples are observed. A simultaneous 7–11% increase in strength and plasticity in comparison with microstructural nitinol was attained. Toxicity of samples has not been revealed

Function of the ribosomal E-site: a mutagenesis study

Ribosomes synthesize proteins according to the information encoded in mRNA. During this process, both the incoming amino acid and the nascent peptide are bound to tRNA molecules. Three binding sites for tRNA in the ribosome are known: the A-site for aminoacyl-tRNA, the P-site for peptidyl-tRNA and the E-site for the deacylated tRNA leaving the ribosome. Here, we present a study of Escherichia coli ribosomes with the E-site binding destabilized by mutation C2394G of the 23S rRNA. Expression of the mutant 23S rRNA in vivo caused increased frameshifting and stop codon readthrough. The progression of these ribosomes through the ribosomal elongation cycle in vitro reveals ejection of deacylated tRNA during the translocation step or shortly after. E-site compromised ribosomes can undergo translocation, although in some cases it is less efficient and results in a frameshift. The mutation affects formation of the P/E hybrid site and leads to a loss of stimulation of the multiple turnover GTPase activity of EF-G by deacylated tRNA bound to the ribosome

Using of Magnetron Sputtering for Biocompatible Composites Creating

Biocompatible composites obtained using the magnetron sputtering for the production of minimally invasive implantation medical devices (stents) were investigated. Nano- and microdimensional surface layers of Ta, Ti, Ag, and Cu on flat and wire NiTi, Cu, Ti, and SiO2 substrates were created. The phase composition, surface morphology, and the layer-by-layer composition were investigated on an X-ray diffractometer, SEM, and Auger spectrometer. It was shown that the thickness and the structure of surface layers were affected by the sputtering distance, time, power, and the bias voltage at the substrate. The presence of the transition layer that contains both substrate and target elements and provides high adhesion of the surface layer to the substrate has been demonstrated. The material was tested for corrosion resistance under static conditions by dipping into solutions with various acidities (pH from 1.68 to 9.18) for 2 years, static mechanical properties, and biocompatibility in vitro and in vivo. A slight corrosive dissolution was observed only in a medium with a pH of 1.56. Dissolution in the other media is absent. An increase in strength and plasticity in comparison with substrate was attained depending on the nature of the sputtered substance and substrate. Toxicity of samples has not been revealed

Reactive SPS of Al2O3–RE:YAG (RE = Ce; Ce+Gd) composite ceramic phosphors

Ultrafine-grained Al2O3–rare earth:yttrium aluminium garnet (Al2O3–RE:YAG) (RE = Ce; Ce+Gd) composite ceramics were obtained for the first time by reactive spark plasma sintering (SPS) using commercially available initial oxide powders. The effect of key sintering parameters (temperature, dwell time, and external pressure (Pload)) on densification peculiarities, structural-phase states, and luminescent properties of composites was studied comprehensively. Differences in phase formation and densification between Ce-doped and Ce,Gd-codoped systems were shown. Parameters of reactive SPS, at which there is partial melting with the formation of near-eutectic zones of the Al2O3–YAG system/coexistence of several variations of the YAG-type phase, were established. Pure corundum–garnet biphasic ceramics with an optimal balance between microstructural and luminescence performance were synthesized at 1425 ℃/30 min/30–60 MPa. The external quantum efficiency (EQE) of the phosphor converters reached 80.7% and 72% with close lifetime of ~63.8 ns, similar to those of commercial Ce:YAG materials, which is promising for further applications in the field of high-power white light-emitting diodes (WLEDs) and laser diodes (LDs)

KINETICAL PHENOMENA IN DENSE VAPOURS OF METALS

The work covers the dense stationary and pulse-made vapours of metals. The aim of the worh is to investigate the processes of plasma excitation and formation, laser generation, laser radiation scattering and fluorescence in the dense vapours of metals. The characteristics of discharge in the dense vapours of copper have been analysed. The increments of developing four-wave instability of the intensive laser beams in the three-level medium and also the resonance fluoroscence spectra in the strong laser field have been modelled numerically. The generation in the dense vapours of metals has been obtained firstly, the characteristics of erosion UV-laser plasma and also the breakdown thresholds in the vapours of a namber of the metallic targets have been measured, the effects of resonance breakdown on the surface, instabilities of the laser beams in the resonance media and multicomponent fluorescence have been discovered. The investigation results can be introduced in the some research instiutesAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

Theoretical-Probability Model of Metal Removal During Magnetic-Abrasive Treatment

The work is devoted to the issue of calculating material removal during magnetic abrasive processing. Cutting grains have random dimensional characteristics, are randomly located on the surface of the tool, the workpiece has an irregular profile. The cutting parts of the grain tops partially remove the chips, and partially elastically-plastic deform the metal. Part of the vertices falls into the risks on the surface of the workpiece formed by the previous machining, and part -into the risks from passing through the previous vertices. This process is determined by the probability of the contact of the top of the grain with the metal. The developed stochastic models make it possible to predict the removal of metal from the treated surface depending on the time and parameters of the operation, which creates the prerequisites for their use in the design of polishing operations

Theoretical-Probability Model for Calculating Roofness in Magnetic Abrasive Machining

The work is devoted to the problem of calculating the surface roughness during magnetic abrasive processing. Cutting grains have random dimensional characteristics, are randomly located on the surface of the tool, the workpiece has an irregular profile. The cutting parts of the grains partially remove the chips and partially elastoplastically deform the metal. Some of the vertices fall into the marks on the surface of the workpiece formed by the previous processing, and some - on the marks from the passage of the previous vertices. This process is determined by the probability of contact of the top of the grain with the metal. The developed probabilistic-theoretical model makes it possible to predict the removal of metal from the treated surface depending on the time and parameters of the operation, which creates the prerequisites for their use in the design of polishing operations

Direct numerical simulation of two-phase gas dynamic flows with phase transition for water and for liquid sodium

In this paper the results of the calculation for one-dimensional problems with water, as well as, a two-dimensional calculation simulating an experimental study of heat transfer and resistance in the vertical pipe with boiling sodium subject to forced lift conditions are presented

Direct numerical simulation of two-phase gas dynamic flows with phase transition for water and for liquid sodium

In this paper the results of the calculation for one-dimensional problems with water, as well as, a two-dimensional calculation simulating an experimental study of heat transfer and resistance in the vertical pipe with boiling sodium subject to forced lift conditions are presented