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A self-taught photographer of the natural world, Sergey Gorshkov won the prestigious Wildlife Photographer of the Year competition in 2020, for his photo of a tiger hugging a tree in [...]

Current proteomics approaches rely almost exclusively on using the positive ionization mode, resulting in inefficient ionization of many acidic peptides. This study investigates protein identification efficiency in the negative ionization mode using the DirectMS1 method. DirectMS1 is an ultrafast data acquisition method based on accurate peptide mass measurements and predicted retention times. Our method achieves the highest rate of protein identification in the negative ion mode to date, identifying over 1000 proteins in a human cell line at a 1% false discovery rate. This is accomplished using a single-shot 10 min separation gradient, comparable to lengthy MS/MS-based analyses. Optimizing separation and experimental conditions was achieved by utilizing mobile buffers containing 2.5 mM imidazole and 3% isopropanol. The study emphasized the complementary nature of data obtained in positive and negative ion modes. Combining the results from all replicates in both polarities increased the number of identified proteins to 1774. Additionally, we analyzed the method’s efficiency using different proteases for protein digestion. Among the four studied proteases (LysC, GluC, AspN, and trypsin), trypsin and LysC demonstrated the highest protein identification yield. This suggests that digestion procedures utilized in positive-mode proteomics can be effectively applied in the negative ion mode. Data are deposited to ProteomeXchange: PXD040583.

One-dimensional systems exhibiting a continuous symmetry can host quantum phases of matter with true long-range order only in the presence of sufficiently long-range interactions1. In most physical systems, however, the interactions are short-ranged, hindering the emergence of such phases in one dimension. Here we use a one-dimensional trapped-ion quantum simulator to prepare states with long-range spin order that extends over the system size of up to 23 spins and is characteristic of the continuous symmetry-breaking phase of matter2,3. Our preparation relies on simultaneous control over an array of tightly focused individual addressing laser beams, generating long-range spin–spin interactions. We also observe a disordered phase with frustrated correlations. We further study the phases at different ranges of interaction and the out-of-equilibrium response to symmetry-breaking perturbations. This work opens an avenue to study new quantum phases and out-of-equilibrium dynamics in low-dimensional systems.

One of the key steps in data dependent acquisition (DDA) proteomics is detection of peptide isotopic clusters, also called “features”, in MS1 spectra and matching them to MS/MS-based peptide identifications. A number of peptide feature detection tools became available in recent years, each relying on its own matching algorithm. Here, we provide an integrated solution, the intensity-based Quantitative Mix and Match Approach (IQMMA), which integrates a number of untargeted peptide feature detection algorithms and returns the most probable intensity values for the MS/MS-based identifications. IQMMA was tested using available proteomic data acquired for both well-characterized (ground truth) and real-world biological samples, including a mix of Yeast and E. colidigests spiked at different concentrations into the Human K562 digest used as a background, and a set of glioblastoma cell lines. Three open-source feature detection algorithms were integrated: Dinosaur, biosaur2, and OpenMS FeatureFinder. None of them was found optimal when applied individually to all the data sets employed in this work; however, their combined use in IQMMA improved efficiency of subsequent protein quantitation. The software implementing IQMMA is freely available at https://github.com/PostoenkoVI/IQMMAunder Apache 2.0 license.

Abstract: We study the Weber integral transforms \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$W_{k,k\pm1}$$\end{document}, which have a nontrivial kernel, so that the spectral expansion contains not only the continuous part of the spectrum but also the zero eigenvalue corresponding to the kernel. The inversion formula, the spectral decomposition, and the Plancherel–Parseval equality are derived. These transforms are used in an explicit formula for the solution of the classical nonstationary Stokes problem on the flow past a circular cylinder.

The proteogenomic search pipeline developed in this work has been applied for reanalysis of 40 publicly available shotgun proteomic datasets from various human tissues comprising more than 8000 individual LC–MS/MS runs, of which 5442 .raw data files were processed in total. This reanalysis was focused on searching for ADAR-mediated RNA editing events, their clustering across samples of different origins, and classification. In total, 33 recoded protein sites were identified in 21 datasets. Of those, 18 sites were detected in at least two datasets, representing the core human protein editome. In agreement with prior artworks, neural and cancer tissues were found to be enriched with recoded proteins. Quantitative analysis indicated that recoding the rate of specific sites did not directly depend on the levels of ADAR enzymes or targeted proteins themselves, rather it was governed by differential and yet undescribed regulation of interaction of enzymes with mRNA. Nine recoding sites conservative between humans and rodents were validated by targeted proteomics using stable isotope standards in the murine brain cortex and cerebellum, and an additional one was validated in human cerebrospinal fluid. In addition to previous data of the same type from cancer proteomes, we provide a comprehensive catalog of recoding events caused by ADAR RNA editing in the human proteome.

Abstract: The study in this work focuses on the properties and structure of the material in the heat-affected zone that occurs during laser metal cutting, depending on the positioning of the workpiece on the pallet: above the protrusion and between the protrusions of the pallet. Significant differences in properties and structure in these areas are demonstrated. Recommendations on the positioning of the workpiece relative to the pallet protrusions are given. Material properties in the cutting zone above the pallet protrusion and between the protrusions differ significantly. Microhardness values in the zone above the pallet protrusions at the edge are approximately 50% lower than in the zone between the protrusions. As the analysis moves deeper into the sample, the difference decreases. The magnesium concentration is nearly two times lower in the zone above the protrusions than between the protrusions. In the surface layers of the workpiece above the protrusions, the sizes of inclusions are larger than in the depth. This is due to additional quenching of the metal in the workpiece located between the protrusions and prolonged contact with the bath of liquid metal due to difficulties in its removal during cutting on the pallet protrusion. Removing the defective layer by milling to a depth of 0.5 mm neutralizes the difference in the material properties in the zone above the pallet protrusion, between the protrusions, and in the depth.

Quantum many-body systems away from equilibrium host a rich variety of exotic phenomena that are forbidden by equilibrium thermodynamics. A prominent example is that of discrete time crystals1–8, in which time-translational symmetry is spontaneously broken in periodically driven systems. Pioneering experiments have observed signatures of time crystalline phases with trapped ions9,10, solid-state spin systems11–15, ultracold atoms16,17and superconducting qubits18–20. Here we report the observation of a distinct type of non-equilibrium state of matter, Floquet symmetry-protected topological phases, which are implemented through digital quantum simulation with an array of programmable superconducting qubits. We observe robust long-lived temporal correlations and subharmonic temporal response for the edge spins over up to 40 driving cycles using a circuit of depth exceeding 240 and acting on 26 qubits. We demonstrate that the subharmonic response is independent of the initial state, and experimentally map out a phase boundary between the Floquet symmetry-protected topological and thermal phases. Our results establish a versatile digital simulation approach to exploring exotic non-equilibrium phases of matter with current noisy intermediate-scale quantum processors21.

In 1688 two sculptural fragments, a head of bearded man and a head of an unbearded youth, arrived in Copenhagen, sent from Athens as a gift to King Christian 5. They were placed in the Royal Kunstkammer, their provenance given as the Temple of Artemis in Ephesos, one of the Seven Wonders of the World. Almost a hundred and fifty years later, in the early 1820’s they were noticed and studied by two scholars independently visiting the Kunstkammer. However, both concluded that the two heads belonged to one of the metopes decorating the south side of the Parthenon temple on the Acropolis in Athens, showing fighting between Greeks and the mythical Centaurs, part man and part horse. In the 1830’s another sculptural fragment, a horse’s hoof, obtained through the German archaeologist and state antiquary of Greece, Ludwig Ross, reached Copenhagen. It was forwarded by the Danish consul to Athens, C.T. Falbe, as a gift to King Christian 8. The inventory reads: ‘… was found on the Acropolis near the Parthenon temple and is supposed to belong to one the Centaurs on the metopes.’ The present paper focuses solely on the head of the Centaur.

With sodium-ion batteries (SIBs) finding widespread application, the demand grows for hard carbon, the most popular anode material for SIBs. Hydrothermal carbonization facilitates the production of hard carbon with desired characteristics from various sources. Despite the considerable volume of literature addressing this subject, there is a notable absence of investigations elucidating the relationship between synthesis conditions and the electrochemical characteristics of the product. Here we study systematically the influence of hydrothermal carbonization parameters on hard carbon characteristics and emphasize the potential of hard carbon as an anode material for SIBs. The initial Coulombic efficiency (ICE) is significantly affected by the particle size of the glucose-derived hard carbon, which, in turn, depends on glucose concentration in the initial solution, pH, and stirring regime. By optimizing the hydrothermal carbonization parameters, the ICE up to 91% and a good reversible capacity of ∼300 mAh g−1in a half cell are achieved. Full cells with Na3(VO)2(PO4)2F cathode material demonstrate ICE of about 80% and reversible capacity of up to 100 mAh g−1cath. Considering the effective performance of pouch-cell SIB prototypes based on Na3(VO)2(PO4)2F and hard carbon, hydrothermal carbonization of glucose yields hard carbon with the necessary characteristics required for its successful application in SIBs.

The grain of rye (Secale cerealeL.) used for baking contains a large amount of non-starch polysaccharides, making it an excellent component of functional foods. But rye grain intended for alcohol production and forage use should have a reduced content of these polysaccharides. A comprehensive parameter that can predict the best field of application for winter rye grain is the viscosity of its wholemeal water extract. However, our understanding of the genetic background underlying this key trait and associated features of rye grain is poor. By analyzing six Russian winter rye cultivars, we identified the most contrasting forms and characterized the peculiarities of their water-soluble carbohydrates capable of influencing the viscosity of water extracts. Then, using phylogenetic and transcriptomic analyses, we identified in the rye genome many genes encoding putative glycosyltransferases and glycosylhydrolases responsible for the synthesis and degradation of arabinoxylans, mixed-linkage glucans, cellulose, and some other polysaccharides. We determined the dynamics of mRNA abundance for these genes at three stages of kernel development. Comparisons of gene expression levels in two contrasting cultivars revealed specific members of multigene families that may serve as promising targets for manipulating non-starch polysaccharide content in rye grain. High-viscosity cultivars were characterized by up-regulation of many glycosyltransferases involved in the biosynthesis of arabinoxylans and other cell-wall polysaccharides, whereas low-viscosity cultivars showed up-regulation of several genes encoding polysaccharide-degrading enzymes.

ABSTRACTIntroductionSARS-CoV-2 is a highly infectious and deadly coronavirus whose study requires the use of a biosafety level 3 (BSL-3) containment facility to investigate viral biology and pathogenesis, which limits the study of live virus and slows progress toward finding suitable treatments for infection. While vaccines from several companies have proven very effective in combating the virus, few treatments exist for those who do succumb to the viral-induced systemic disease called COVID-19.Areas CoveredThis short review focuses on fluorescent quantum dot-based modeling of SARS-CoV-2. New BSL-2 viral models are essential for finding small molecules and biologics that may be effective in stopping viral infection, as well as treating already infected individuals. Nanoparticles are invaluable tools for biological research as they can be used to both model pathogens and serve as a platform for developing vaccines.Expert opinionVisualizing viral activity with fluorescent quantum dots enables both biochemical and cell-based assays to detect virus-host receptor interactions, cellular activity after binding to the cell plasma membrane, screening for interventions using small-molecule drug repurposing, and testing of novel biologics. Quantum dots can also be used for diagnostic assays, vaccine development, and importantly, pan-antiviral drugs to address variants that may escape the immune response.

Effective small molecule therapies to combat the SARS-CoV-2 infection are still lacking as the COVID-19 pandemic continues globally. High throughput screening assays are needed for lead discovery and optimization of small molecule SARS-CoV-2 inhibitors. In this work, we have applied viral pseudotyping to establish a cell-based SARS-CoV-2 entry assay. Here, the pseudotyped particles (PP) contain SARS-CoV-2 spike in a membrane enveloping both the murine leukemia virus (MLV) gag-pol polyprotein and luciferase reporter RNA. Upon addition of PP to HEK293-ACE2 cells, the SARS-CoV-2 spike protein binds to the ACE2 receptor on the cell surface, resulting in priming by host proteases to trigger endocytosis of these particles, and membrane fusion between the particle envelope and the cell membrane. The internalized luciferase reporter gene is then expressed in cells, resulting in a luminescent readout as a surrogate for spike-mediated entry into cells. This SARS-CoV-2 PP entry assay can be executed in a biosafety level 2 containment lab for high throughput screening. From a collection of 5,158 approved drugs and drug candidates, our screening efforts identified 7 active compounds that inhibited the SARS-CoV-2-S PP entry. Of these seven, six compounds were active against live replicating SARS-CoV-2 virus in a cytopathic effect assay. Our results demonstrated the utility of this assay in the discovery and development of SARS-CoV-2 entry inhibitors as well as the mechanistic study of anti-SARS-CoV-2 compounds. Additionally, particles pseudotyped with spike proteins from SARS-CoV-2 B.1.1.7 and B.1.351 variants were prepared and used to evaluate the therapeutic effects of viral entry inhibitors.

Proteome characterization relies heavily on tandem mass spectrometry (MS/MS) and is thus associated with instrumentation complexity, lengthy analysis time, and limited duty cycle. It was always tempting to implement approaches that do not require MS/MS, yet they were constantly failing to achieve a meaningful depth of quantitative proteome coverage within short experimental times, which is particularly important for clinical or biomarker-discovery applications. Here, we report on the first successful attempt to develop a truly MS/MS-free method, DirectMS1, for bottom-up proteomics. The method is compared with the standard MS/MS-based data-dependent acquisition approach for proteome-wide analysis using 5 min LC gradients. Specifically, we demonstrate identification of 1 000 protein groups for a standard HeLa cell line digest. The amount of loaded sample was varied in a range from 1 to 500 ng, and the method demonstrated 10-fold higher sensitivity. Combined with the recently introduced Diffactoapproach for relative protein quantification, DirectMS1 outperforms most popular MS/MS-based label-free quantitation approaches because of significantly higher protein sequence coverage.

Many-body open quantum systems balance internal dynamics against decoherence and measurements induced by interactions with an environment1,2. Quantum circuits composed of random unitary gates with interspersed projective measurements represent a minimal model to study the balance between unitary dynamics and measurement processes3–5. As the measurement rate is varied, a purification phase transition is predicted to emerge at a critical point akin to a fault-tolerant threshold6. Here we explore this purification transition with random quantum circuits implemented on a trapped-ion quantum computer. We probe the pure phase, where the system is rapidly projected to a pure state conditioned on the measurement outcomes, and the mixed or coding phase, where the initial state becomes partially encoded into a quantum error correcting codespace that keeps the memory of initial conditions for long times6,7. We find experimental evidence of the two phases and show numerically that, with modest system scaling, critical properties of the transition emerge.

The Ln 2 NiO 4+δ -based layered phases have attracted much attention as components for high-performance protonic ceramic fuel cells (PCFCs) and electrolysis cells (PCECs) enabling energy conversion with good efficiency and low pollution. The present paper aims at rationally engineering the Cu-doped Pr 2 NiO 4+δ materials and analysing their electrode behaviour for reversible protonic ceramic cells operating in both PCFC and PCEC modes. Complex oxides of Pr 2 Ni 1– x Cu x O 4+δ (x = 0, 0.1, 0.2 and 0.3) were synthesised using the citrate-nitrate method. The obtained materials were characterised considering their crystalline structures, as well as thermal, thermomechanical and electrotransport properties. A special interest was focused on the quality of an electrode/electrolyte interface governing the electrochemical performance of the cells fabricated. It is shown that a copper doping of x = 0.2 has a positive impact on the thermomechanical compatibility of the Ba(Ce,Zr)O 3 -based electrolytes, providing a better adhesion to these electrolytes at low-temperature sintering and resulting in a decrease of the polarisation resistance of the air electrodes. A reversible protonic ceramic cell demonstrates a power density of ~340 mW cm–2 and a hydrogen output flux of ~3.8 ml cm−2 min−1 at 750 °C. The presented results propose modernised alkaline-earth-element-free and cobalt-free electrodes that can be successfully used in the electrochemical cells based on the-state-of-the-art proton-conducting electrolytes. • Pr 2 Ni 1– x Cu x O 4+ δ phases (where x = 0, 0.1, 0.2 and 0.3) were successfully prepared • Links between composition, defect structure and properties were elucidated • Pr 2 Ni 0.8 Cu 0.2 O 4+ δ (PNC0.2) shows the best thermomechanical characteristics • PNC0.2 exhibits also the improved electrochemical properties • PNC0.2 is a promising oxygen electrode candidate for SOFCs, SOECs or rSOCs. [ABSTRACT FROM AUTHOR]

Thermalization is a ubiquitous process of statistical physics, in which a physical system reaches an equilibrium state that is defined by a few global properties such as temperature. Even in isolated quantum many-body systems, limited to reversible dynamics, thermalization typically prevails1. However, in these systems, there is another possibility: many-body localization (MBL) can result in preservation of a non-thermal state2,3. While disorder has long been considered an essential ingredient for this phenomenon, recent theoretical work has suggested that a quantum many-body system with a spatially increasing field—but no disorder—can also exhibit MBL4, resulting in ‘Stark MBL’5. Here we realize Stark MBL in a trapped-ion quantum simulator and demonstrate its key properties: halting of thermalization and slow propagation of correlations. Tailoring the interactions between ionic spins in an effective field gradient, we directly observe their microscopic equilibration for a variety of initial states, and we apply single-site control to measure correlations between separate regions of the spin chain. Furthermore, by engineering a varying gradient, we create a disorder-free system with coexisting long-lived thermalized and non-thermal regions. The results demonstrate the unexpected generality of MBL, with implications about the fundamental requirements for thermalization and with potential uses in engineering long-lived non-equilibrium quantum matter.

Purpose: The purpose of this paper is to provide the high-pass (HP) negative group delay (NGD) circuit based (RL) network. Synthesis and experimental investigation of HP-NGD circuit are developed. Design/methodology/approach: The research work methodology is organized in three phases. The definition of the HP-NGD ideal specifications is introduced. The synthesis method allowing to determine the RL elements is developed. The validation results are discussed with comparison between the calculated model, simulation and measurement. Findings: This paper shows a validation of the HP-NGD theory with responses confirming NGD optimal frequency, value and attenuation of about (9 kHz, −1.12 µs, −1.64 dB) and (21 kHz, −0.92 µs, −4.81 dB) are measured. The tested circuits have experimented NGD cut-off frequencies around 5 and 11.7 kHz. Research limitations/implications: The validity of the HP-NGD topology depends on the coil self-inductance resonance. The HP-NGD effect is susceptible to be penalized by the parasitic elements of the self. Practical implications: The NGD circuit is usefully exploited in the electronic and communication system to reduce the undesired delay effect context. The NGD can be used to compensate the delay in any electronic devices and system. Social implications: Applications based on the NGD technology will be helpful in the communication, transportation and security research fields by reducing the delay inherent to any electronic circuit. Originality/value: The originality of the paper concerns the synthesis formulations of the RL elements in function of the expected HP-NGD optimal frequency, value and attenuation. In addition, an original measurement technique of HP-NGD is also introduced. [ABSTRACT FROM AUTHOR]

AbstractTwo influenza A nucleoprotein variants (wild-type: G102R; and mutant: G102R and E292G) were studied with regard to macro-molecular interactions in oligomeric form (24-mers). The E292G mutation has been previously shown to provide cold adaptation. Molecular dynamics simulations of these complexes and trajectory analysis showed that the most significant difference between the obtained models was distance between nucleoprotein complex strands. The isolated complexes of two ribonucleoprotein variants were characterized by transmission electron microscopy and differential scanning fluorimetry (DSF). Presence of the E292G substitution was shown by DSF to affect nucleoprotein complex melting temperature. In the filament interface peptide model, it was shown that the peptide corresponding in primary structure to the wild-type NP (SGYDFEREGYS) is prone to temperature-dependent self-association, unlike the peptide corresponding to E292G substitution (SGYDFGREGYS). It was also shown that the SGYDFEREGYS peptide is capable of interacting with a monomeric nucleoprotein (wild type); this interaction’s equilibrium dissociation constant is five orders of magnitude lower than for the SGYDFGREGYS peptide. Using small-angle neutron scattering (SANS), the supramolecular structures of isolated complexes of these proteins were studied at temperatures of 15, 32, and 37 °C. SANS data show that the structures of the studied complexes at elevated temperature differ from the rod-like particle model and react differently to temperature changes. The data suggest that the mechanism behind cold adaptation with E292G is associated with a weakening of the interaction between strands of the ribonucleoprotein complex and, as a result, the appearance of inter-chain interface flexibility necessary for complex function at low temperature.Communicated by Ramaswamy H. Sarma

AbstractThe Russian government adopted “anti-gay propaganda” laws in 2013, prompting an exodus of LGBT+ individuals who sought asylum in Western countries. Little is known about this new and diverse group of immigrants and their post-migration experiences in the U.S. An interpretive phenomenological analysis (IPA) was used to analyze nine semi-structured interviews. Four major themes emerged: “being a new asylum seeker: challenges ranked,” “reconciling multipolar identities,” “a sense of safety and freedom vs. a shock of nonsupport and discrimination,” and “belonging: new communities and their challenges.” The study calls for counselors to gain knowledge of immigration policies and new immigrant LGBT+ communities to address the within-group diversity, immigration and asylum challenges, language barriers, and general institutional barriers to services faced by these populations.

The article deals with the determination of the efficiency of a multi-bladed tool equipped with inserts made of oxide-carbide cutting ceramics, depending on the microstructural parameters of the tool material. The microstructural parameters of the oxide-carbide cutting ceramic, which affect the performance of the tool, are proposed to be determined according to the electrical resistance of the tool material. In order to implement the method for determining the working capacity of the instrument, a basic design of the device for measuring the electrical resistance of the material of the instrument is proposed. The device for measuring the electrical resistance of ceramic plates consists of a body made of a dielectric material, with channels for supplying a conductive material and a groove for installing a case with a test sample. During the test, the channels are filled with a liquid conductive material, which fills the cavity formed by the channel of the case, the groove of the case and the plate itself under test. To ensure uniform filling of the cavity, after the introduction of the liquid conductive material, metal balls are installed into the channels, which are made in such a size as to ensure free sliding along the channel, but not to let the liquid pass into the upper part of the channel. The tested ceramic plate is installed in the walls of the removable case. The walls of the removable case include electrodes, which, when the device is in operation, are inserted into a cavity with a liquid conductive material at one end, and are connected to an ohmmeter at the other. Using a device for measuring the electrical resistance of ceramic plates, it is possible to determine the operability of the tool and guarantee its operation without rejection for a certain period of time, which was confirmed by experimental research in the milling of workpieces of machine parts made of gray cast iron. Experimental studies in multi-edge machining with cutters with different values ​​of electrical resistance of ceramic plates made it possible to plot graphs of the dependence of the quality of machining during milling on the operability of the tool and on the time of the machining process.

Particles subject to confinement experience an attractive potential that increases without bound as they separate. A prominent example is colour confinement in particle physics, in which baryons and mesons are produced by quark confinement. Confinement can also occur in low-energy quantum many-body systems when elementary excitations are confined into bound quasiparticles. Here we report the observation of magnetic domain-wall confinement in interacting spin chains with a trapped-ion quantum simulator. By measuring how correlations spread, we show that confinement can suppress information propagation and thermalization in such many-body systems. We quantitatively determine the excitation energy of domain-wall bound states from the non-equilibrium quench dynamics. We also study the number of domain-wall excitations created for different quench parameters, in a regime that is difficult to model with classical computers. This work demonstrates the capability of quantum simulators for investigating high-energy physics phenomena, such as quark collision and string breaking.

The possibility of distributed wide-range strain and temperature measurements in a 100 km long optical fiber using tunable-wavelength low-coherence optical time-domain reflectometer (OTDR) is demonstrated. The specified distance range is provided by employing two narrowband microelectromechanical system (MEMS) spectral filters tuned synchronously as well as by taking advantage of Raman amplification and amplification by remotely pumped erbium-doped fiber segments built into the fiber under test. With the time of a single measurement of 10 min and the spatial resolution of about 1 m, the measurement range reached 1000 µ? in strain units, which is equivalent to the temperature range of 110°C.

We have analyzed the physical mechanisms responsible for the formation of an ordered sequence of nanoclusters synthesized on a nanowire in the diffusion mode of deposition of free atoms. The results were obtained using a kinetic Monte Carlo model, which takes into account only the interaction between the nearest atoms of the crystal lattice. Nevertheless, this model describes the correlations between the elements of the system at distances significantly exceeding their sizes. We show that the long-range spatial correlation between the synthesized clusters is due to two factors: first, the surface diffusion in the metastable system of deposited atoms which leads to the formation of primary nuclei, and second, the shadow effect arising when growing nanoclusters become rather large. It is these processes that are the “tools” through which individual clusters suppress the development of their neighboring nuclei in the competition for survival and form high self-ordering at the final stage of synthesis. Numerical experiments were carried out for one-dimensional systems with a diamond-like lattice structure. The features of manifestation of self-ordering effects are investigated in detail depending on the orientation of the basic nanowire, temperature, and the rate of supply of free atoms into the system. The observed variety of morphologies of one-dimensional systems at the final stage of synthesis is in good agreement with numerous experimental data obtained during the synthesis of nanoclusters on silicon and germanium nanowires. On the basis of the obtained results, optimal synthesis modes are proposed for increasing the regularity in the localization of synthesized nanoclusters.

We report the results of theoretical and experimental studies of a digital system for regulating and stabilising the frequency of a four-frequency Zeeman laser gyroscope (ZLG), in which generation occurs simultaneously on two longitudinal modes with orthogonal circular polarisations; therefore, four light waves propagate in the optical ring resonator. In contrast to a two-frequency Zeeman laser gyroscope, a four-frequency ZLG does not use the intensity modulation signal of one of the light waves, which appears when an alternating magnetic field is applied to the active medium, to analyse the frequency detuning of longitudinal modes from the centre of the active-medium gain contour. At the same time, it is possible to construct a digital perimeter adjustment system (PAS), which allows the resonator perimeter to be adjusted so that the magnetic components of the zero drift of the gyroscope for two longitudinal generation modes are equal and opposite in sign. Due to this, almost complete compensation for the magnetic component of the zero drift of the gyroscope is realised in a four-frequency ZLG. The use of the digital system makes it possible to provide a higher accuracy of the resonator perimeter adjustment than that in a two-frequency ZLG, even with a relatively small bit capacity of the PAS digital-to-analogue conversion (DAC), and to fully take advantage of the capabilities of a four-frequency ZLG to reduce the magnetic sensitivity.

Hepatitis B surface antigen (HBsAg) is the most clinically relevant serological marker of hepatitis B virus (HBV) infection. Its detection in blood is extremely important for identification of asymptomatic individuals or chronic HBV carriers, screening blood donors, and early seroconversion. Rapid point-of-care HBsAg tests are predominantly qualitative, and their analytical sensitivity does not meet the requirements of regulatory agencies. We present a highly sensitive lateral flow assay based on superparamagnetic nanoparticles for rapid quantification (within 30 min) of polyvalent HBsAg in serum. The demonstrated limit of detection (LOD) of 80 pg mL−1in human serum is better than both the FDA recommendations for HBsAg assays (which is 0.5 ng mL−1) and the sensitivity of traditional laboratory-based methods such as enzyme linked immunosorbent assays. Along with the attractive LOD at lower concentrations and the wide linear dynamic range of more than 2.5 orders, the assay features rapidity, user-friendliness, on-site operation and effective performance in the complex biological medium. These are due to the combination of the immunochromatographic approach with a highly sensitive electronic registration of superparamagnetic nanolabels over the entire volume of a 3D test structure by their non-linear magnetization and selection of optimal antibodies by original optical label-free methods. The developed cost-efficient bioanalytical technology can be used in many socially important fields such as out-of-lab screening and diagnosis of HBV infection at a point-of-demand, especially in hard-to-reach or sparsely populated areas, as well as highly endemic regions.

The Corsica–Sardinia lithospheric block is traditionally viewed as a region of notoriously low seismicity. Earthquake catalogs report only three moderate earthquakes in the range of magnitudes 5.0–5.1. The scarcity of documented seismicity in the region does not allow for the reliable assessment of the seismic hazard. In this paper, we make an attempt to evaluate the seismic potential of the Corsica–Sardinia region employing the morphostructural zoning (MSZ) that allows for the identification of locations of potential earthquakes. The MSZ delineates the hierarchical system of morphostructural blocks, the network of lineaments bounding the blocks, and the loci of nodes formed around intersections of lineaments. Nodes are treated as earthquake controlling structures. We have used the existing criteria of seismicity defined earlier for seismogenic (M5+) nodes in Iberia and the Western Alps with the goal to identify seismogenic nodes capable of generating earthquakes M5+ in the Corsica–Sardinia block. We test the criteria of seismicity for these regions relying on modern models of the Mediterranean geodynamics that view the eastern margin of Iberia and Provence adjacent to the Western Alps as locations of the Corsica–Sardinia block before drifting. Due to a common tectonic evolution the structure of the Corsica–Sardinia block is roughly similar in the basic features to the structural setting of Iberia and southern France. Out of the 81 nodes delineated by MSZ (deliberately ignoring the available earthquake catalogue) we identify 24 nodes capable of earthquakes M5+ using the criteria of seismicity defined for Iberia. Nodes hosting three documented M5+ earthquakes are assigned to seismogenic ones and most of the nodes accommodating smaller events with magnitudes 4.0–4.9 are also classified as seismogenic by pattern recognition. Applying the criteria of seismicity defined for the Western Alps, we have properly identified only two nodes hosting the documented M5+ earthquakes and missed practically all the nodes with smaller events. The performed analysis reveals that the criteria of seismicity defined for Iberia are more pertinent for the identification of seismogenic nodes in Corsica–Sardinia, because they recognize as seismogenic the nodes marked by documented earthquakes. Our study suggests that the seismic potential of the Corsica–Sardinia block can be specified as low-to-moderate. The defined locations of seismogenic nodes provide key information for knowledgeable long-term seismic hazard assessment of the region.

In this paper we consider a prime graph of finite groups. In particular, we expect finite groups with prime graphs of maximal diameter.

COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.

The Orbitrap mass analyzer can provide high mass accuracy and throughput, which has significantly improved proteome research and made this type of instrumentation one of the most frequently applied in proteomics. The efficient use of Orbitrap mass spectrometers requires training. Students in the field of proteomics can benefit from a deeper understanding of the Orbitrap technology to comprehend mass spectral interpretation, troubleshooting, and judgment of experimental settings. Unfortunately, the cost of high-end mass spectrometers limits the implementation of this type of equipment in educational laboratories. Guided by these concerns, we developed an eLearning web application called HUMOSaimed to help teach Orbitrap mass spectrometry. Although a typical proteomics experiment includes the use of several different technologies, such as liquid chromatography, mass spectrometry, and bioinformatics, the learning objectives of HUMOSare focused on mass spectrometry. HUMOSmodels a mass spectrum of a peptide mixture, allowing us to investigate the influence of mass spectral acquisition parameters. By changing the parameters and observing the differences, students can learn more about the mass spectral resolution, duty cycle, throughput of the analysis, ion accumulation, and spectral dynamic range and get familiar with advanced spectral acquisition methods, such as BoxCar. HUMOSis an open-source software published under the Apache license; the live installation is available at http://humos.bmb.sdu.dk.

Adenosine-to-inosine RNA editing is an enzymatic post-transcriptional modification which modulates immunity and neural transmission in multicellular organisms. In particular, it involves editing of mRNA codons with the resulting amino acid substitutions. We identified such sites for developmental proteomes of Drosophila melanogasterat the protein level using available data for 15 stages of fruit fly development from egg to imago and 14 time points of embryogenesis. In total, 40 sites were obtained, each belonging to a unique protein, including four sites related to embryogenesis. The interactome analysis has revealed that the majority of the editing-recoded proteins were associated with synaptic vesicle trafficking and actomyosin organization. Quantitation data analysis suggested the existence of a phase-specific RNA editing regulation with yet unknown mechanisms. These findings supported the transcriptome analysis results, which showed that a burst in the RNA editing occurs during insect metamorphosis from pupa to imago. Finally, targeted proteomic analysis was performed to quantify editing-recoded and genomically encoded versions of five proteins in brains of larvae, pupae, and imago insects, which showed a clear tendency toward an increase in the editing rate for each of them. These results will allow a better understanding of the protein role in physiological effects of RNA editing.

The first step of SARS-CoV-2 infection is binding of the spike protein’s receptor binding domain to the host cell’s ACE2 receptor on the plasma membrane. Here, we have generated a versatile imaging probe using recombinant Spike receptor binding domain conjugated to fluorescent quantum dots (QDs). This probe is capable of engaging in energy transfer quenching with ACE2-conjugated gold nanoparticles to enable monitoring of the binding event in solution. Neutralizing antibodies and recombinant human ACE2 blocked quenching, demonstrating a specific binding interaction. In cells transfected with ACE2-GFP, we observed immediate binding of the probe on the cell surface followed by endocytosis. Neutralizing antibodies and ACE2-Fc fully prevented binding and endocytosis with low nanomolar potency. Importantly, we will be able to use this QD nanoparticle probe to identify and validate inhibitors of the SARS-CoV-2 Spike and ACE2 receptor binding in human cells. This work enables facile, rapid, and high-throughput cell-based screening of inhibitors for coronavirus Spike-mediated cell recognition and entry.

Cryptic peptides (cryptides) are biologically active peptides formed after proteolysis of native precursors present in animal venoms, for example. Proteolysis is an overlooked post-translational modification that increases venom complexity. The tripeptide KPP (Lys-Pro-Pro) is a peptide encrypted in the C-terminus of Ts14—a 25-mer peptide from the venom of the Tityus serrulatusscorpion that has a positive impact on the cardiovascular system, inducing vasodilation and reducing arterial blood pressure of hypertensive rats among other beneficial effects. A previous study reported that KPP and its native peptide Ts14 act via activation of the bradykinin receptor B2 (B2R). However, the cellular events underlying the activation of B2R by KPP are unknown. To study the cell signaling triggered by the Ts14 cryptide KPP, we incubated cardiac myocytes isolated from C57BL/6 mice with KPP (10–7mol·L–1) for 0, 5, or 30 min and explored the proteome and phosphoproteome. Our results showed that KPP regulated cardiomyocyte proteins associated with, but not limited to, apoptosis, muscle contraction, protein turnover, and the respiratory chain. We also reported that KPP led to AKT phosphorylation, activating AKT and its downstream target nitric oxide synthase. We also observed that KPP led to dephosphorylation of phospholamban (PLN) at its activation sites (S16 and T17), leading to reduced contractility of treated cardiomyocytes. Some cellular targets reported here for KPP (e.g., AKT, PLN, and ERK) have already been reported to protect the cardiac tissue from hypoxia-induced injury. Hence, this study suggests potential beneficial effects of this scorpion cryptide that needs to be further investigated, for example, as a drug lead for cardiac infarction.

Modern methods of machining of bed slideways with the required parameters of accuracy and quality of the processed surfaces are considered in order to increase productivity in the treatment of the surface of machine stands. To improve productivity, the finishing sanding operation has been replaced with finishing milling to ensure the required roughness, flatness and parallelism. The method of replacement of technological operations as exemplified by processing of a bed made of gray cast iron of grade “СЧ-20” is studied. The priority method of increasing the productivity of the processing of machine slideways of metal-cutting equipment, based on the use of cutting ceramics during the processing of the bed as a final technological operation, is determined. Based on the microstructural characteristics of oxide-carbide cutting ceramics, a uniform method of equipping cutters with cutting inserts with equal lifespan is used to increase productivity and achieve the required surface finish. This method of the milling cutter layout allows for longer life and provides the required margin of tool accuracy as well as allows predicting premature wear of the cutting tool. The results of the work are the identification of the patterns of influence of structural parameters of cutting ceramics on the quality of machine slideways of metal-cutting equipment in the selective formation of instrumentation. Studies have shown that the quality of machining depends on the microstructure characteristics of each insert used in the machining process when using interchangeable multi-sided oxide carbide ceramic inserts. The increase in productivity and quality of machining is achieved by monitoring the microstructure of the cutting oxide-carbide ceramics.

The greatest power of a prime pdividing the natural number nwill be denoted by np. For a set of primes πand a natural number nwe will denote nπ=∏p∈πnp. Let Gbe a finite group with trivial center, and p,q>5be distinct prime divisors of |G|. We prove that if for every nonunity conjugacy classes size α, it is true that α{p,q}∈{pn,qm,pnqm}, where nand mdepend only on pand q, then |G|{p,q}=pnqm, and CG(g)∩CG(h)=1for every p-element gand every q-element h.

Abstract: The specific features of resistive switching, which was initiated by triangular pulses with a high-frequency sine signal imposed on them, in experimental memristor prototypes based on thin films of yttria-stabilized zirconia were examined. It was found that memristors switched by these complex signals have lower switching voltage, higher ratio of currents in low- and high-resistance states, and better long-term current stability than memristors switched by triangular pulses without the sine signal. This improvement of switching parameters is associated with resonance activation of migration of oxygen ions via vacancies in the alternating external electric field.

The results of mathematical modeling of electrical soundings with the AMNB (Schlumberger, Wenner) arrays and the proposed combined AMN + NMA array above horizontally layered medium and including a ball medium are presented. It is shown that the combined array has two main advantages: the current penetration depth is greater at the same position of outer electrodes of the considered arrays; edge effects are smaller due to bilateral measurements with respect to the central receiving electrode; a geoelectric inhomogeneity is delineated at the pseudosections of the apparent resistivity. The quantitative interpretation of the sounding curves obtained with the AMN + NMA array can be carried out by an existing software for inversing of data of the symmetric Wenner (AMNB) array with electrode spacing equal to 1/3 of supplying dipole. The results of application of the new technique of electrical soundings by the combined array in the study of state of the dam on sedimentation tank of liquid chemicals are presented. On the geoelectric sections and the pseudosections of the apparent resistivity, areas of increased electrical conductivity in body and base of the dam are detected. Filtration of water from the reservoir occurs through these areas. Soundings with the AMN + NMA array are expedient for studying of a geological medium at small depths where the medium is horizontally-heterogeneous, and also for solving of engineering-geological problems.

Biological functions of many proteins are governed by post-translational modifications (PTMs). In particular, the rich PTM complement in histones controls the gene expression and chromatin structure with major health implications via a combinatoric language. Deciphering that “histone code” is the great challenge for proteomics given an astounding number of possible proteoforms, including isomers with different PTM positions. These must be disentangled on the top- or middle-down level to preserve the key PTM connectivity, which condensed-phase separations failed to achieve. We reported the capability of ion mobility spectrometry (IMS) methods to resolve such isomers for model histone tails. Here, we advance to biological samples, showing middle-down analyses of histones from mouse embryonic stem cells via online chromatography to fractionate proteoforms with distinct PTM sets, differential or field asymmetric waveform IMS (FAIMS) to resolve the isomers, and Orbitrap mass spectrometry with electron transfer dissociation to identify the resolved species.

Protein arginine methyltransferase 5 (PRMT5) has emerged as a promising cancer drug target, and three PRMT5 inhibitors are currently in clinical trials for multiple malignancies. In this study, we investigated the role of PRMT5 in human acute myeloid leukemia (AML). Using an enzymatic dead version of PRMT5 and a PRMT5-specific inhibitor, we demonstrated the requirement of the catalytic activity of PRMT5 for the survival of AML cells. We then identified PRMT5 substrates using multiplexed quantitative proteomics and investigated their role in the survival of AML cells. We found that the function of the splicing regulator SRSF1 relies on its methylation by PRMT5 and that loss of PRMT5 leads to changes in alternative splicing of multiple essential genes. Our study proposes a mechanism for the requirement of PRMT5 for leukemia cell survival and provides potential biomarkers for the treatment response to PRMT5 inhibitors.

Stem cell engineeringthe manipulation and functionalization of stem cells involving genetic modificationcan significantly expand their applicability for cell therapy in humans. Toward this aim, reliable, standardized, and cost-effective methods for cell manipulation are required. Here we explore the potential of magnetic multilayer capsules to serve as a universal platform for nonviral gene transfer, stem cell magnetization, and magnetic cell separation to improve gene transfer efficiency. In particular, the following experiments were performed: (i) a study of the process of internalization of magnetic capsules into stem cells, including capsule co-localization with established markers of endo-lysosomal pathway; (ii) characterization and quantification of capsule uptake with confocal microscopy, electron microscopy, and flow cytometry; (iii) intracellular delivery of messenger RNA and separation of gene-modified cells by magnetic cell sorting (MACS); and (iv) analysis of the influence of capsules on cell proliferation potential. Importantly, based on the internalization of magnetic capsules, transfected cells became susceptible to external magnetic fields, which made it easy to enrich gene-modified cells using MACS (purity ∼95%), and also to influence their migration behavior. In summary, our results underline the high potential of magnetic capsules in stem cell functionalization, namely (i) to increase gene-transfer efficiency and (ii) to facilitate enrichment and targeting of transfected cells. Finally, we did not observe a negative impact of the capsules used on the proliferative capacity of stem cells, proving their high biocompatibility.

Charging of analytes is a prerequisite for performing mass spectrometry analysis. In proteomics, electrospray ionization is the dominant technique for this process. Although the observation of differences in the peptide charge state distribution (CSD) is well-known among experimentalists, its analytical value remains underexplored. To investigate the utility of this dimension, we analyzed several public data sets, comprising over 250,000 peptide CSD profiles from the human proteome. We found that the dimensions of the CSD demonstrate high reproducibility across multiple laboratories, mass analyzers, and extensive time intervals. The general observation was that the CSD enabled effective partitioning of the peptide property space, resulting in enhanced discrimination between sequence and constitutional peptide isomers. Next, by evaluating the CSD values of phosphorylated peptides, we were able to differentiate between phosphopeptides that indicate the formation of intramolecular structures in the gas phase and those that do not. The reproducibility of the CSD values (mean cosine similarity above 0.97 for most of the experiments) qualified CSD data suitable to train a deep-learning model capable of accurately predicting CSD values (mean cosine similarity − 0.98). When we applied the CSD dimension to MS1- and MS2-based proteomics experiments, we consistently observed around a 5% increase in protein and peptide identification rate. Even though the CSD dimension is not as effective a discriminator as the widely used retention time dimension, it still holds the potential for application in direct infusion proteomics.