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392 result(s) for "Stepanyan, S."
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Thermostable enzyme isoforms, continuously producing monocomponent superoxide radicals, from human postoperative serous fluids: isolation and properties
Free radicals are generated in the body through endogenous and exogenous systems, with their overproduction linked to chronic diseases such as cancer. Interestingly, chemotherapeutic drugs utilize free radicals to induce apoptosis in cancer cells, highlighting their dual nature. This study explores the therapeutic potential of free-radical-generating compounds in solid tumor treatment. Using a patented universal method, superoxide (O 2 − )-producing enzymatic systems were isolated for the first time from serous fluids of patients with breast cancer, gastric cancer, and liver cirrhosis. These enzymes were qualitatively and quantitatively characterized and found to continuously produce monocomponent O 2 − under aerobic in vitro conditions. The enzyme complexes consist of flavin adenine dinucleotide (FAD), a reduced nicotinamide adenine dinucleotide phosphate (NADPH)-containing protein component (NPC), and Fe(III) ions. Their stable O 2 − production mechanism was elucidated, and characteristic optical absorption and fluorescence excitation spectra were recorded. The concentrations of monocomponent O 2 − were quantified in moles (mol/ml) for each serous fluid type. These findings suggest that liquid-phase O 2 − could be used to selectively destroy cancer cells by predetermining effective concentrations. Furthermore, since O 2 − -producing enzymes can oxidize adrenaline, they may help reduce elevated adrenaline levels in tumor cells. Future animal studies will assess their efficacy in eliminating metastatic cells, particularly in the postoperative period. This novel approach may offer a promising adjunct therapy in oncology.
TRPA1-Mediated Accumulation of Aminoglycosides in Mouse Cochlear Outer Hair Cells
Aminoglycoside ototoxicity involves the accumulation of antibiotic molecules in the inner ear hair cells and the subsequent degeneration of these cells. The exact route of entry of aminoglycosides into the hair cells in vivo is still unknown. Similar to other small organic cations, aminoglycosides could be brought into the cell by endocytosis or permeate through large non-selective cation channels, such as mechanotransduction channels or ATP-gated P2X channels. Here, we show that the aminoglycoside antibiotic gentamicin can enter mouse outer hair cells (OHCs) via TRPA1, non-selective cation channels activated by certain pungent compounds and by endogenous products of lipid peroxidation. Using conventional and perforated whole-cell patch clamp recordings, we found that application of TRPA1 agonists initiates inward current responses in wild-type OHCs, but not in OHCs of homozygous Trpa1 knockout mice. Similar responses consistent with the activation of non-selective cation channels were observed in heterologous cells transfected with mouse Trpa1 . Upon brief activation with TRPA1 agonists, Trpa1 -transfected cells become loaded with fluorescent gentamicin–Texas Red conjugate (GTTR). This uptake was not observed in mock-transfected or non-transfected cells. In mouse organ of Corti explants, TRPA1 activation resulted in the rapid entry of GTTR and another small cationic dye, FM1-43, in OHCs and some supporting cells, even when hair cell mechanotransduction was disrupted by pre-incubation in calcium-free solution. This TRPA1-mediated entry of GTTR and FM1-43 into OHCs was observed in wild-type but not in Trpa1 knockout mice and was not blocked by PPADS, a non-selective blocker of P2X channels. Notably, TRPA1 channels in mouse OHCs were activated by 4-hydroxynonenal, an endogenous molecule that is known to be generated during episodes of oxidative stress and accumulate in the cochlea after noise exposure. We concluded that TRPA1 channels may provide a novel pathway for the entry of aminoglycosides into OHCs.
Dielectric barrier discharge for multi-point plasma-assisted ignition at high pressures
Nanosecond surface dielectric barrier discharge (nSDBD) is an efficient tool for a multi-point plasma-assisted ignition of combustible mixtures at elevated pressures. The discharge develops as a set of synchronously propagated from the high-voltage electrode charged channels (streamers), with a typical density up to a few streamers per millimetre of the length of the electrode. In combustible mixtures, nSDBD initiates numerous combustion waves propagating from the electrode. Very little is known about nSDBD at high pressures. This work presents a comparative experimental study of the surface dielectric barrier discharge initiated by high-voltage pulses (U=±(20-60) kV) of different polarities in air at elevated pressures (P=1-6 atm). Discharge morphology, deposited energy and velocity of the discharge front propagation are analysed. Differences between the discharges of positive and negative polarity, as well as the changes in the discharge morphology with changing of a gas mixture composition,
A small proton charge radius from an electron–proton scattering experiment
Elastic electron–proton scattering (e–p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, r p . In 2010, a new method using muonic hydrogen atoms 1 found a substantial discrepancy compared with previous results 2 , which became known as the ‘proton radius puzzle’. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen 3 , 4 . Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e–p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e–p experiments and enabled measurements at very small forward-scattering angles. Our result, r p  = 0.831 ± 0.007 stat  ± 0.012 syst  femtometres, is smaller than the most recent high-precision e–p measurement 5 and 2.7 standard deviations smaller than the average of all e–p experimental results 6 . The smaller r p we have now measured supports the value found by two previous muonic hydrogen experiments 1 , 7 . In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant 8 —one of the most accurately evaluated fundamental constants in physics. A magnetic-spectrometer-free method for electron–proton scattering data reveals a proton charge radius 2.7 standard deviations smaller than the currently accepted value from electron–proton scattering, yet consistent with other recent experiments.
Modified structure of protons and neutrons in correlated pairs
The atomic nucleus is made of protons and neutrons (nucleons), which are themselves composed of quarks and gluons. Understanding how the quark–gluon structure of a nucleon bound in an atomic nucleus is modified by the surrounding nucleons is an outstanding challenge. Although evidence for such modification—known as the EMC effect—was first observed over 35 years ago, there is still no generally accepted explanation for its cause 1 – 3 . Recent observations suggest that the EMC effect is related to close-proximity short-range correlated (SRC) nucleon pairs in nuclei 4 , 5 . Here we report simultaneous, high-precision measurements of the EMC effect and SRC abundances. We show that EMC data can be explained by a universal modification of the structure of nucleons in neutron–proton SRC pairs and present a data-driven extraction of the corresponding universal modification function. This implies that in heavier nuclei with many more neutrons than protons, each proton is more likely than each neutron to belong to an SRC pair and hence to have distorted quark structure. This universal modification function will be useful for determining the structure of the free neutron and thereby testing quantum chromodynamics symmetry-breaking mechanisms and may help to discriminate between nuclear physics effects and beyond-the-standard-model effects in neutrino experiments. Simultaneous high-precision measurements of the EMC effect and short-range correlated abundances for several nuclei reveal a universal modification of the structure of nucleons in short-range correlated neutron–proton pairs.
Investigation of the torque electric drive of the enclosing structure at low temperatures
The article deals with the study of a torque electric drive at low negative air temperatures used as part of the enclosing structure of a ventilated underground building. The increasing of the efficiency of the torque electric drive of the enclosing structure is analyzed, a simulation model of the torque electric drive is developed and a model of the control system of the enclosing structure in the language of MATLAB&Simulink is designed. A software model in the form of Arduino software package was developed to study the drive operation of the ventilated underground of building enclosure structure in the permafrost zone.
Electron-beam energy reconstruction for neutrino oscillation measurements
Neutrinos exist in one of three types or ‘flavours’—electron, muon and tau neutrinos—and oscillate from one flavour to another when propagating through space. This phenomena is one of the few that cannot be described using the standard model of particle physics (reviewed in ref.  1 ), and so its experimental study can provide new insight into the nature of our Universe (reviewed in ref.  2 ). Neutrinos oscillate as a function of their propagation distance ( L ) divided by their energy ( E ). Therefore, experiments extract oscillation parameters by measuring their energy distribution at different locations. As accelerator-based oscillation experiments cannot directly measure E , the interpretation of these experiments relies heavily on phenomenological models of neutrino–nucleus interactions to infer E . Here we exploit the similarity of electron–nucleus and neutrino–nucleus interactions, and use electron scattering data with known beam energies to test energy reconstruction methods and interaction models. We find that even in simple interactions where no pions are detected, only a small fraction of events reconstruct to the correct incident energy. More importantly, widely used interaction models reproduce the reconstructed energy distribution only qualitatively and the quality of the reproduction varies strongly with beam energy. This shows both the need and the pathway to improve current models to meet the requirements of next-generation, high-precision experiments such as Hyper-Kamiokande (Japan) 3 and DUNE (USA) 4 . Electron scattering measurements are shown to reproduce only qualitatively state-of-the-art lepton–nucleus energy reconstruction models, indicating that improvements to these particle-interaction models are required to ensure the accuracy of future high-precision neutrino oscillation experiments.
Investigation of the possibility of replacing high-lead glasses in fusible glass solders by less toxic glasses
The possibility of partial or complete replacement of PbO in fusible glass solders by less toxic components is investigated. It is found that it is impossible to find a full-fledged replacement for glasses in the lead-borate eutectic, used as the glass base in glass soldering compositions for sealing glass ceramic packages of integrated microcircuits at temperatures 390 – 420°C, within the systems PbO – P 2 O 5 – ZnO – B 2 O 3 ,V 2 O 5 – P 2 O 5 – ZnO – B 2 O 3 , and TeO 2 – PbO – V 2 O 5 – Bi 2 O 3 with different additives and total mass content of class-I hazard components not exceeding 70%.
Dielectric barrier discharge for multi-point plasma-assisted ignition at high pressures
Nanosecond surface dielectric barrier discharge (nSDBD) is an efficient tool for a multi-point plasma-assisted ignition of combustible mixtures at elevated pressures. The discharge develops as a set of synchronously propagated from the high-voltage electrode charged channels (streamers), with a typical density up to a few streamers per millimetre of the length of the electrode. In combustible mixtures, nSDBD initiates numerous combustion waves propagating from the electrode. Very little is known about nSDBD at high pressures. This work presents a comparative experimental study of the surface dielectric barrier discharge initiated by high-voltage pulses (𝓤 = ±(20-60) kV) of different polarities in air at elevated pressures (P = 1–6 atm). Discharge morphology, deposited energy and velocity of the discharge front propagation are analysed. Differences between the discharges of positive and negative polarity, as well as the changes in the discharge morphology with changing of a gas mixture composition, are discussed.
Electron-beam energy reconstruction for neutrino oscillation measurements
Neutrinos exist in one of three types or 'flavours'--electron, muon and tau neutrinos--and oscillate from one flavour to another when propagating through space. This phenomena is one of the few that cannot be described using the standard model of particle physics (reviewed in ref. .sup.1), and so its experimental study can provide new insight into the nature of our Universe (reviewed in ref. .sup.2). Neutrinos oscillate as a function of their propagation distance (L) divided by their energy (E). Therefore, experiments extract oscillation parameters by measuring their energy distribution at different locations. As accelerator-based oscillation experiments cannot directly measure E, the interpretation of these experiments relies heavily on phenomenological models of neutrino-nucleus interactions to infer E. Here we exploit the similarity of electron-nucleus and neutrino-nucleus interactions, and use electron scattering data with known beam energies to test energy reconstruction methods and interaction models. We find that even in simple interactions where no pions are detected, only a small fraction of events reconstruct to the correct incident energy. More importantly, widely used interaction models reproduce the reconstructed energy distribution only qualitatively and the quality of the reproduction varies strongly with beam energy. This shows both the need and the pathway to improve current models to meet the requirements of next-generation, high-precision experiments such as Hyper-Kamiokande (Japan).sup.3 and DUNE (USA).sup.4.