A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

Cardiotonic steroids (CTS) are a group of steroid compounds derived from certain plants and animals. CTS are selective inhibitors of Na,K-ATPase, so for a long time they were widely used for medical purposes to treat heart failure and some other diseases. However, over time, doctors gradually began to refuse this group of drugs due to their narrow therapeutic range and a number of serious side effects. However, in parallel with the rise and fall of interest in CTS as a drug, interest in them as a single class of high-affinity Na,K-ATPase inhibitors has only increased. Numerous data on the effect of CTS on signaling cascades and cell viability made impelling a search for a rationale for the existence of such a subtle biological regulator. A large number of studies devoted to the potential use of CTS in the treatment of neurodegenerative, oncological, immune and other diseases "revitalized" the already "written off" group of the drugs. If initially the role of exogenous (mainly plant origin) CTS was studied, then by the 90s of the XX century the study of the role of endogenous CTS and their regulatory effects became a popular trend in biology and physiology. The role of endogenous CTS was studied in details in the pathogenesis of cardiovascular diseases [1]. A large number of researchers have unanimously stated that endogenous CTS are very complex regulators of the development of pathological processes; however, the exact cause-and-effect relationship that would unambiguously explain the processes of synthesis, utilization, and the role of endogenous CTS has not yet been established. The effects of CTS in the frame of various regulatory schemes have been described, but the predominant number of studies was devoted to arterial hypertension, heart and renal failure, cancer [2–4], aging [5,6], and neuroinflammation. The effects of both endo- and exogenous CTS on blood cells and have been studied to a much lesser extent.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

It is well known that X-ray crystallography is based on X-ray diffraction (XRD) by atoms and molecules. The diffraction pattern arises as a result of scattering of incident radiation, which makes it possible to determine the structure of the scattering substance. With the advent of ultrashort radiation sources, the theory and interpretation of X-ray diffraction analysis remained the same. This work shows that when an attosecond laser pulse is scattered on a DNA molecule, including during its nicking and bending, the pulse duration is an important characteristic of the scattering. In this case, the diffraction pattern changes significantly compared to the previously known scattering theory. The results obtained must be used in XRD theory to study DNA structures, their mutations and damage, since the previously known theory can produce large errors and, therefore, the DNA structure can be “deciphered” incorrectly.

Indole and indole-3-lactate are known dominant microbial tryptophan catabolites (MICT). In obesity, the fecal indole concentration corresponds to the normal one, and that of indole-3-lactate significantly decreases along with other MICT, while it increases in blood plasma. During the analysis of the «enzymatic landscape» of the intestinal microbiota we find an almost twofold increase in the correlation between the concentrations of fecal MICT and the «enzymatic landscape», with indole-3-lactate having the closest relationships with the “enzymatic landscape” of all MICT. Here, we report statistically significant correlations of indole-3-lactate and the gut microbial enzymes for fructose, amino sugars, nucleotides, polyamines metabolism, and sulfoglycolysis. We also demonstrate that indole-3-lactate producing microbiota representatives increase three-fold in obesity. The phenotype of the microbiotic population is thus represented by completely different genera and species of microorganisms in obese individuals compared to healthy donors.

The analysis of methods of cleaning and processing of saponite-bearing technogenic waters of diamond mining enterprises of the Arkhangelsk region is carried out. The perspective of the electrochemical separation method for extracting saponite from man-caused waters, providing a targeted change in its structural-texture, physico-chemical and mechanical properties, is shown. The possible directions of realization of saponite and products of its modification in various branches of industry are considered.

X-ray diffraction (XRD) analysis of complex poly-atomic systems, especially of biomolecules, using ultra-short laser pulses (USP), is currently one of the most important fields of modern physics. The basis for interpreting and "deciphering" experimental data is the well-known theory of X-ray scattering, where the main parameter of USPs - its duration - is not taken into account. In the present work it is shown that for scattering of attosecond USPs on DNA and RNA trinucleotides the pulse length is the most important scattering parameter. In this case the diffraction pattern significantly changes with respect to the previously known scattering theory. The results obtained are extremely important in XRD when using attosecond pulses to study trinucleotides of DNA and RNA because using the previously known scattering theory which does not take into account the duration of USPs one can not correctly interpret and therefore "decode" DNA and RNA structures.

Recent advances in recording and real-time analysis of surface electromyographic signals (sEMG) have fostered the use of sEMG human-machine interfaces for controlling personal computers, prostheses of upper limbs, and exoskeletons among others. Despite a relatively high mean performance, sEMG-interfaces still exhibit strong variance in the fidelity of gesture recognition among different users. Here we systematically study the latent factors determining the performance of sEMG-interfaces in synthetic tests and in an arcade game. We show that the degree of muscle cooperation and the amount of the body fatty tissue are the decisive factors in synthetic tests. Our data suggest that these factors can only be adjusted by a long-term training, which promotes fine-tuning of low-level neural circuits driving the muscles. A short-term training has no effect on synthetic tests, but significantly increases the game scoring. This implies that it works at a higher decision-making level, not relevant for synthetic gestures. We propose a procedure that enables quantification of the gestures’ fidelity in a dynamic gaming environment. For each individual subject the approach allows identifying “problematic” gestures that decrease gaming performance. This information can be used for optimizing the training strategy and for adapting the signal processing algorithms to individual users, which could be a way for a qualitative leap in the development of future sEMG-interfaces.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

Cutaneous melanoma (CM) is a candidate for screening programs, since its prognosis is excellent when diagnosed in an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and expert assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a “nevometer” to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels defining a nevus score. Cohen’s weighted kappa-coefficient was estimated to measure the level of agreement. In the total sample, agreement between self-assessments and expert-assessments was moderate (raw agreement: 50.29%, weighted κ=0.596). Self-assessed nevus counts were higher than those determined by experts (mean differ-ence: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants’ eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and expert-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

We describe a multi-resolution approach for audio classification and illustrate its application to the open data set for environmental sound classification. The proposed approach utilizes a multi-resolution based ensemble consisting of targeted feature extraction of approximation (coarse scale) and detail (fine scale) portions of the signal under the action of multiple transforms. This is paired with an automatic machine learning engine for algorithm and parameter selection and the LSTM algorithm, capable of mapping several sequences of features to a predicted class membership probability distribution. Initial results show an improvement in multi-class classification accuracy.

Scattering of ultrashort X-ray pulses (USP) is an important component of the diffraction analysis of matter using modern USP sources. Usually, the specific scattering of such USPs is not taken into account to determine the structure of a substance. Taking into account the specifics of scattering on complex structures will give more accurate results when deciphering complex structures. In this work, it is shown that when X-ray USPs are scattered on diamond with NV centers, it is necessary to take into account the pulse duration. The results obtained can be very different from the widely used theory of diffraction analysis, which confirms the need to take into account the specifics of USP scattering when diagnosing complex structures. It is also shown that scattering spectra are quite sensitive to the concentration of NV centres in the diamond structure and this can be used in diffraction analysis.

Regulatory cystathionine β-synthase (CBS) domains are widespread in proteins; however, difficulty in structure determination prevents a comprehensive understanding of the underlying regulation mechanism. Tetrameric microbial inorganic pyrophosphatase containing such domains (CBS-PPase) is allosterically inhibited by AMP and ADP and activated by ATP and cell alarmones diadenosine polyphosphates. Each CBS-PPase subunit contains a pair of CBS domains but binds cooperatively only one molecule of the mono-adenosine derivatives. We used site-directed mutagenesis of Desulfitobacterium hafniense CBS-PPase to identify the key elements determining the direction of the effect (activation or inhibition) and the “half-of-the-sites” ligand binding stoichiometry. Seven amino acid residues were selected in CBS1 domain based on the available X-ray structure of the regulatory domains and substituted by alanine and other residues. The interaction of 11 CBS-PPase variants with the regulating ligands was characterized by activity measurements and isothermal titration calorimetry. Lys100 replacement reversed the effect of ADP from inhibition to activation, whereas Lys95 and Gly118 replacements made ADP activator at low concentrations but inhibitor at high concentrations. Replacements of these residues for alanine increased the stoichiometry of mono-adenosine phosphate binding twofold. These findings identify several key protein residues and suggest “two non-interacting pairs of interacting regulatory sites” concept in CBS-PPase regulation.

The intensive development of nanodevices acting as two-state systems has motivated the search for nanoscale molecular structures whose long-term conformational dynamics are similar to the dynamics of bistable mechanical systems such as Euler arches and Duffing oscillators. Collective synchrony in bistable dynamics of molecular-sized systems has attracted immense attention as a potential pathway to amplify the output signals of molecular nanodevices. Recently, pyridin-furan oligomers of helical shape that are a few nanometers in size and exhibit bistable dynamics similar to a Duffing oscillator have been identified through molecular dynamics simulations. In this article, we present the case of dynamical synchronization of these bistable systems. We show that two pyridine-furan springs connected by a rigid oligomeric bridge spontaneously synchronize vibrations and stochastic resonance enhances the synchronization effect.

The genus Euonymus (L.) consists of shrubs or woody plants, distributed mainly in the Northern Hemisphere. To date, from Euonymus spp. several hundreds of different secondary metabolites have been isolated and identified. In addition, fatty oil was found in the fruits of some species of these plants, which accumulates not only in the seeds, but also in the arils. This study presents the research of unique long-term (ten-year-old) suspension cell cultures of Euonymus maximoviczianus Prokh. which were obtained from arils of unripe capsules. Suspension cells retain the ability to form oil droplets containing neutral lipids, both in the dark and in the light, the cells are able to synthesize very-long-chain fatty acids (VLCFAs), and can synthesize delphinidin-3-O-hexoside, cyanidin-3-O-hexoside, and peonidin-3-O-hexoside. Here, we research of the fatty acid, VLCFA, and anthocyanin biosynthesis dynamics in the subcultivation, as well as the influence of methyl jasmonate (MeJa) on these processes in the dark- and under-light-grown cell cultures. In the darkness, the formation of VLCFAs is more intense, and the biosynthesis of anthocyanins is significantly activated in the light. MeJA substantially enhances the biosynthesis of anthocyanins in the light and, surprisingly, the formation of VLCFAs in the darknss. In connection with the commonality of the cytosolic pool of malonyl-CoA, which is necessary both for the biosynthesis of VLCFAs and dihydroflavonols (and, ultimately, anthocyanins), the competition of these biosynthetic pathways is discussed.

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

The Einstein-Lovelock theory contains an infinite series of corrections to the Einstein term with an increasing power of the curvature. It is well-known that for large black holes the lowest (Gauss-Bonnet) term is the dominant one, while for smaller black holes higher curvature corrections become important. We will show that if one is limited by positive values of the coupling constants, then the dynamical instability of black holes serves as an effective cut-off of influence of higher curvature corrections in the 4D Einstein-Lovelock approach: the higher is the order of the Lovelock term, the smaller is the maximal value of the coupling constant allowing for stability, so that effectively only a first few orders can deform the observable values seemingly. For negative values of coupling constants this is not so, and, despite some suppression of higher order terms also occurs due to the decreasing threshold values of the coupling constant, this does not lead to an noticeable opportunity to neglect higher order corrections. In the case a lot of orders of Lovelock theory are taken into account, so that the black-hole solution depends on a great number of coupling constants, we propose a compact description of it in terms of only two or three parameters encoding all the observable values.

The approach based on molecular modeling was developed to study dNTP derivatives characterized by new polymerase-specific properties. For this purpose, the relative efficiency of PCR amplification with modified dUTPs was studied using Taq, Tth, Pfu, Vent, Deep Vent, Vent (exo-), and Deep Vent (exo-) DNA polymerases. The efficiency of PCR amplification with modified dUTPs was compared with the results of molecular modeling using the known 3D structures of KlenTaq polymerase–DNA–dNTP complexes. The dUTPs were C5-modified with bulky functional groups (the Cy5 dye analogs) or lighter aromatic groups. Comparing the experimental data and the results of molecular modeling revealed the decrease of PCR efficiency in the presence of modified dUTPs with an increase in the number of non-covalent bonds between the substituents and the DNA polymerase (about 15% decrease per one extra non-covalent bond). Generalization of the revealed patterns to all the studied polymerases of the A and B families is discussed herein. The number of non-covalent bonds between the substituents and polymerase amino acid residues is proposed to be a potentially variable parameter for regulating enzyme activity.

Here we compile a detailed record of eddies and examine their intra-annual variability over the Spitsbergen Bank in the northwestern Barents Sea using spaceborne Sentinel-1 A/B synthetic aperture radar (SAR) data acquired in 2018. Analysis of 3070 SAR images enabled to register 1758 eddy manifestations in the marginal ice zone (MIZ) and 1631 signatures in the open water (OW). Submesoscale and small mesoscale eddies were observed within a range 0.2-40 km with the range of MIZ eddies being twice larger than that of OW eddies. We note a strong seasonal variability of eddy diameters and the ratio of cyclones to anticyclones. The eddies were present in all seasons showing an approximate parity in eddy generation intensity in the surface layer between winter and summer. The peak eddy activity is observed during the first (January to March) and third (July-September) quarters of the year. A well-pronounced seasonality of SAR-derived eddy intensity correlates with that of eddy kinetic energy in the surface layer of the Eurasian Arctic. Eddies were detected most frequently in Storfjorden, south of Edge Island, near Hopen Island and along the entire eastern flank of the Spitsbergen Bank. Very low eddy activity was observed in the central part of the bank. The MIZ eddies were recorded during eight months of the year peaking in February, and being spatially limited by a 200-m isobath. The OW eddies were widely dispersed across the study domain peaking in August and tending to accumulate in regions of relatively weak surface currents. In summer, about 20-25% of them were observed within the Barents Sea Polar Front.

Sumatriptan is a serotonin receptor agonist approved by FDA in 1992 to treat migraines. Its’ solid form used in commercially available drugs Imitrex, Treximet, Onzetra Xsail and Zembrace symtouch is sumatriptan succinate. Herein we report on crystal structure of sumatriptane succinate hemi(ethanol solvate), HSum+·HSucc–·0.5EtOH, its comparison with previously reported solids containing derivatives of sumatriptan.

Various bat species often occupy the same habitats. Cohabitation should induce different preferences in spatial or trophic components of the bat ecological niche, to reduce their competition. This determines the differences in the trematode fauna of Myotis spp. The purpose of our research was to study the biodiversity of trematodes in syntopic populations of five Myotis species in the Samarskaya Luka National Park. In 2005–2007 we studied 867 bat specimens by the methods of complete helminthological dissection. In total, 11 trematode species were found in Myotis bats. Only three trematode species, Plagiorchis koreanus, Prosthodendrium chilostomum and Parabascus duboisi were revealed in all studied Myotis spp. Prosthodendrium cryptolecithum was recorded for the first time in Russia. Digenean species diversity is higher in Myotis daubentonii and M. dasycneme. The trematode fauna of M. brandtii, M. nattereri and M. mystacinus is less diverse. The determining factor in the infection of bats by trematodes is feeding on semi-aquatic insects, possible second intermediate hosts of these parasites. Our results confirm the data that the ecological niches of the five Myotis species partially overlap. An analysis of the trematode fauna in Myotis spp. showed that in the Samarskaya Luka there may be weak competition for food items among bats.

The nonlocality (superdiffusion) of turbulence is expressed in the empiric Richardson t3 scaling law for the mean square of the mutual separation of a pair of particles in a fluid or gaseous medium. The development of the theory of nonlocality of various processes in physics and other sciences based on the concept of Lévy flights resulted in the idea of Shlesinger and colleagues about the possibility of describing the nonlocality of turbulence using a linear integro-differential equation with a slowly falling kernel. The close approach developed by us made it possible to establish the closeness of the superdiffusion parameter of plasma density fluctuations moving across a strong magnetic field in a tokamak to the Richardson law. In this paper, we show the possibility of a universal description of the characteristics of nonlocality of transfer in a stochastic medium (including turbulence of gases and fluids) using the Biberman-Holstein approach to the transfer of excitation of a medium by photons, generalized to take into account the finiteness of the velocity of excitation carriers. This approach enables us to propose a scaling that generalizes Richardson's t3 scaling law to the combined regime of Lévy flights and Lévy walks.

Ultrafast chip nanocalorimetry opens up remarkable possibilities in materials science by allowing samples to be cooled and heated at extremely high rates. Due to heat transfer limitations, controlled ultrafast cooling and heating can only be achieved for tiny samples in calorimeters with a micron-thick membrane. Even if ultrafast heating can be controlled under quasi-adiabatic conditions, ultrafast controlled cooling can be performed if the calorimetric cell is located in a heat-conducting gas. It was found that the maximum possible cooling rate increases as 1/r0 with decreasing radius r0 of the hot zone of the membrane. The possibility of increasing the maximum cooling rate with decreasing r0 was successfully implemented in many experiments. In this regard, it is interesting to answer the question: what is the maximum possible cooling rate in such experiments if r0 tends to zero? Indeed, on submicron scales, the mean free path of gas molecules lmfp becomes comparable to r0, and the temperature jump that exists at the membrane/gas interface becomes significant. Considering the limitation associated with thermal resistance at the membrane/gas interface and considering the transfer of heat through the membrane, we show that the controlled cooling rate can reach billions of K/s, up to 1010 K/s.

Optimum design and accurate control of the internal structure of the laser target materials remain an important goal for various laser physics experiments, especially for generating high flux photon and neutron beams. The low-density material is considered to be one of the most difficult for X-ray study due to its high transparency and imperceptible contrast. To produce clear visualization of foam containing sparse structures we used a high-quality monochromatic X-ray beam of synchrotron radiation source PETRA-III at DESY. The X-ray beam parameters allow tomographic scanning with application of phase contrast retrieval algorithms. A series of 3D images of foam-suspended glass microsphere inside the plastic cylinder were obtained with the quality high enough to observe the internal structure and to visualize uniformity, displacement and surface roughness on both sides of the microsphere. The main object under investigation was a CH-plastic capillary including 10 mg/cc CHO-foam with the centered glass microsphere. The results of this work demonstrate that tomographic visualization based on a high quality X-ray radiation and phase contrast analysis is an effective and useful technique for development of new laser targets containing structured low density materials.

We have drawn a few interesting conclusions while studying reaction products of Ph₂Si(OH)₂ with Al(ⁱBu)₃ and tetraisobutylalumoxane. In the first place, this is the production (at Ph₂Si(OH)₂ and Al(ⁱBu)₃ equimolar ratio) of oligomer siloxyalumoxane structure with alternating four- and six-member rings, as well as isobutyl and phenyl groups migration between aluminum and silicon due to the formation of intramolecular four-member cyclic complex [Ph₂(OH)SiO]Al(ⁱBu)₂ → [(ⁱBu)Ph(OH)SiO]Al(ⁱBu)Ph. Ph₂Si(OH)₂ interaction with Al(ⁱBu)₃ not only starts from intramolecular complex production, but the chain is terminated for the same reason, which in the case of Ph₂Si(OH)₂ reaction with tetraisobutylalumoxane results in failure of obtaining high-polymer siloxyalumoxane compounds. When Al(ⁱBu)₃ interacts with α- and γ-diols, no oligomer compounds are produced. Al(ⁱBu)₃ reaction with α, γ-diols results in monomer compounds that are likely to have cyclic structure. Notably at Al(ⁱBu)₃ interaction with α-diol only double excess of Al(ⁱBu)₃ allows full replacement of hydrogen in α-diol hydroxyl groups by aluminum alkyl residue with 1,3-bis(diisobutylalumoxymethyl)-1,1,3,3-tetramethyldisiloxane production. At equimolar ratio of initial reagents the second isobutyl radical at Al does not interact with the second hydroxyl group of α-diol, apparently due to the steric hindrance and 1-(diisobutylalumoxymethyl)-3-(hydroxymethyl)-1,1,3,3-tetramethyl-disiloxane is produced. Al(ⁱBu)₃ reactions with γ-diol also result in monomer compounds but the presence of a chain consisting of three СН₂-groups between Si and hydroxyl group facilitates interaction between the second hydroxyl group of γ-diol and the second isobutyl radical Al(ⁱBu)₃. Tetraisobutylalumoxane reaction with α- and γ-diols results in oligomer compounds.

Alectinib hydrochloride is an anticancer medication used for the first-line treatment of non-small cell lung cancer. Although it has been approved for medical use ten years ago, and three polymorphs of this substance were proposed based on X-ray diffraction patterns, their crystal structures remained unknown to date. The main problem was preparation of high quality single crystals due to very low solubility of the salt. Herein we report on molecular and crystal structure of form I of alectinib hydrochloride as obtained by powder X-ray diffraction data from laboratory source. The refinement revealed that the nitrogen atom of the morpholinyl ring is protonated. The chloride anion interacts with the H(N) atoms of the morpholine and benzo[b]carbazole rings to form infinite H-bonded chains.

Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, closo-dodecaborate anion represents a high-boron containing residue with remarkable chemical stability and low toxicity, suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5'-, 3'-, or both terminal positions of DNA, RNA, 2'-O-Me RNA, and 2'-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3'-end of all oligomers stabilized their complementary complexes, while analogous 5'-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2'-O-methyl and 2'-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized DNA/DNA duplex but gave a strong stabilization of the duplex with RNA target. According to CD spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

Currently, the most promising work seems to be aimed not so much at the development of new drugs, but rather at creating ways of targeted delivery of existing drugs. In this paper, we show that polymeric micelles based on chitosan, heparin grafted with lipoic and oleic acids residues demonstrate the potential for doxorubicin delivery to tumors due to pH-, glutathione-sensitivity. Smart delivery systems use the Aikido principle, i.e. they target tumor cells according to their features. Natural polysaccharides (heparin and chitosan) provide the pH sensitivity of micelles: the release of doxorubicin (Dox) is enhanced in a slightly acidic environment (model tumor microenvironment). Fatty acid residues are necessary for the formation of micelles and solubilization of cytostatics in a hydrophobic core. Lipoic acid residues formed a labile S-S cross-linking between polymer chains (the first method), and also covalently attached doxorubicin molecules through glutathione-sensitive S-S bridges (the second option) – determine Redox sensitivity of micelles to tumors. The characterization of polymeric micelles and prodrugs (Dox-polymer) was carried out using FTIR spectroscopy. The release of doxorubicin from micelles occurs slowly (20% / 6h) in an environment with a pH of 7.4 and the absence of glutathione, while in a slightly acidic environment and in the presence of 10 mM glutathione, the rate increases up 6 times, with an increase in the effective concentration up to 5 times after 7 h. The permeability of free doxorubicin, micellar formulations (covalent S-S crosslinked and not) into Raji, K562, A875 cancer cells was studied using confocal laser scanning microscopy (CLSM), demonstrated an increase in the permeability of micellar formulations based on Dox. Thus, we have presented micellar formulations of doxorubicin for targeted delivery to tumor, what is important in the aspects of reducing non-target toxicity, increasing the selectivity of cytostatics against tumors and overcome multidrug resistance.

Amorphous germanium films on non-refractory glass substrates were annealed by ultrashort near-infrared (1030 nm, 1.4 ps) and mid-infrared (1500 nm, 70 fs) laser pulses. Crystallization of germanium irradiated at a laser energy density (fluence) range from 25 to 400 mJ/cm2 under single-shot and multi-shot conditions was investigated using Raman spectroscopy. The dependence of the fraction of the crystalline phase on the fluence was obtained for picosecond and femtosecond laser annealings. The regimes of almost complete crystallization of germanium films over the entire thickness are obtained (from the analysis of Raman spectra with excitation of 785 nm laser). The possibility of scanning laser processing is shown, which can be used to create films of micro and nanocrystalline germanium on flexible substrates.

Dehydroaromatization of methane (MDA) is of great interest as a promising process for processing natural and associated petroleum gases, the main component of which is methane. The rapid loss of catalyst activity because of coke formation hinders the introduction of the DHA methane process into industry. Therefore, the aim of the research was to find ways to improve Mo/ZSM-5 catalysts for MDA. The paper presents the results of the synthesis of high-silica zeolites of the ZSM-5 type with a microporous and micro-mesoporous structure, the preparation of Mo/ZSM-5 catalysts based on them, and the study of the physicochemical and catalytic properties of the obtained samples during the non-oxidative conversion of methane into aromatic hydrocarbons. Zeolite catalysts were investigated by IR spectroscopy, X-ray diffraction, TPD-NH3, SEM, HR-TEM, N2-adsorption. It was found that the addition of carbon black at the stage of synthesis of zeolite type ZSM-5 does not lead to structural changes, the obtained samples have a crystallinity equal to 100%. The creation of the micro-mesoporous structure in Mo/ZSM-5 catalysts lead to an increase in their activity and stability in the process of methane dehydroaromatization. The highest conversion of methane is observed on a 4.0%Mo/ZSM-5 catalyst prepared based on of zeolite synthesized using 1.0% carbon black, and is 13.0% in 20 minutes of reaction, while the benzene yield reaches 7.0%. It has been shown by HR-TEM that a more uniform distribution of the active metal component is observed in a zeolite catalyst with a micro-mesoporous structure than in a microporous zeolite.

Regulation at the level of translation plays an essential role in modulating gene expression. Given the importance of knowledge about translationally active mRNAs as an indicator of translation efficiency, it is crucial for researchers to have at their disposal organised sources of functional information on translation - plant translatomic maps similar to transcription maps. The development of a general experimental and computational methodology for constructing translatome maps is essential to address this challenge. In this manuscript, we discuss what researchers can do to design plant translatome maps, namely, we review: (i) experimental methods to obtain translationally active mRNA fractions, considering their advantages and limitations; (ii) additional methodological approaches to obtain complete pools of translationally active mRNAs; (iii) sequencing methods to qualitatively and quantitatively assess different mRNA fractions; and (iv) multivariate analyses of sequencing results by bioinformatics methods, including metrics for assessing mRNA translational activity.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The effect of aqueous extracts of the biomass of the adult Ulomoides dermestoides beetle on the delayed effects of the defoliant paraquat causing parkinsonism in experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP⁺. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.

The article is devoted to the research of economic cycles and crises, which are studied within the framework of the theory of long waves by N. D. Kondratiev (K-waves) using the mathematical apparatus of fractional calculus. The object of the study is the mathematical model of S.V. Dubovsky 3 and some of its modifications, which describe the dynamics of the economic system, characterizing the interaction between the efficiency of new technologies and the efficiency of capital productivity. Modifications in the model are determined by the following points: the mathematical model takes into account the dependence of the rate of accumulation on capital productivity, there is an external harmonic influence - the influx of investments and new technological solutions, the economic system has heredity, including time-dependent, which leads to a delayed effect - the system’s response to impact. The property of heredity in the mathematical model is taken into account using fractional derivatives of constant and variable orders. Mathematical model S.V. Dubovsky and its modifications are studied numerically using the Adams-Bashforth-Moulton algorithm. Oscillograms and phase trajectories are constructed, and an interpretation of the simulation results is given.

In the current work, in continuation of our recent research [1] we synthesized and studied new chimeric compounds comprising the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP) connected by alkyl linkers of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly decrease membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP on bacterial ribosomes differ from that of CHL. By simulating the dynamics of complexes of CAM-Cn-TPP with bacterial ribosomes, we have proposed a possible explanation for the specificity of the action of these analogs on the translation process. CAM-C10-TPP and CAM-C14-TPP stronger inhibit the growth of the Gram-positive bacteria in comparison to the CHL and suppress some strains of CHL-resistant bacteria. Thus, we have shown that TPP derivatives of CHL are dual-acting compounds that target the ribosomes and the cellular membranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds contributes to the inhibitory effect on bacteria. Moreover, since the mitochondria of eukaryotic cells have qualities similar to those of their prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cells with these compounds.

The need for multi-gene analysis in evolutionary and taxonomic studies is generally accepted. However, sequencing of multiple genes is not always possible. For various reasons, short mito-chondrial DNA barcodes are the only source of molecular information for some species in many genera, although multilocus data are available for other species of the same genera. In particular, such a situation exists in the species-rich butterfly subgenus Polyommatus (Agrodiaetus). Here, we analysed partitioning of this subgenus into species groups by using three data sets. The first data set was represented by short mitochondrial DNA barcodes for all analysed samples. The second and third data sets were represented by combination of short mitochondrial DNA barcodes for a part of the taxa with longer mitochondrial sequences COI+tRNA-Leu+COII (data set 2) and with longer mitochondrial COI+tRNA-Leu+COII and nuclear 5.8S rDNA+ITS2+28S rDNA sequences (data set 3) for the remaining species. We show that DNA barcoding approach (data set 1) failed to reveal the taxonomic structure resulting in numerous polytomies in the phylogenetic tree ob-tained. Combined analysis of the mitochondrial and nuclear sequences (data sets 2 and 3) re-vealed the species groups and position within these species groups even for the taxa for which only short DNA barcodes were available.

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch's membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent “age pigment” lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing simultaneously both types of pigments - melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of oxidative degradation of pigment granules are considered. A mechanism has been proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy its melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.

We review a modern differential geometric description of the fluid isotropic motion and featuring it the diffeomorphism group structure, modelling the related dynamics, as well as its compatibility with the quasi-stationary thermodynamical constraints. There is analyzed the adiabatic liquid dynamics, within which, following the general approach, there is explained in detail, the nature of the related Poissonian structure on the fluid motion phase space, as a semidirect Banach groups product, and a natural reduction of the canonical symplectic structure on its cotangent space to the classical Lie-Poisson bracket on the adjoint space to the corresponding semidirect Lie algebras product. We also present a modification of the Hamiltonian analysis in case of the isotermal liquid dynamics. We study the differential-geometric structure of the adiabatic magneto-hydrodynamic superfluid phase space and its related motion within the Hamiltonian analysis and invariant theory. In particular, we construct an infinite hierarchies of different kinds of integral magneto-hydrodynamic invariants, generalizing those before constructed in the literature, and analyze their differential-geometric origins. A charged liquid dynamics on the phase space invariant with respect to an abelian gauge group transformation is also investigated, some generalization of the canonical Lie-Poisson type bracket is obtained.

If we accept that human body is a dissipative structure, then the recovery of the body should be considered as a redirection of the enegy flows. The recovery of vertebral cartilage through redirecting of inner dissipative flow requires the understanding of how is this case the fact of reversibility can be proven. We proposed the approach, that according to the collected data, satisfies all the scientific requirements.

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. For several cancers, breast and prostate in particular, bone is the primary site of metastasis. Efforts to treat bone metastases have been stymied by a lack of models to study the progression and cellular players and signaling pathways driving bone metastasis. In this review, we examine the newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic and in silico computational models bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cell enter and escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

We propose a promising model of discrete spacetime based on nonassociative geometry and complex networks. Our approach treats space as a simplicial 3-complex (or complex network), built from "atoms" of spacetime and entangled states forming n-dimensional simplices (n=1,2,3). At large scales, a highly connected network is a coarse, discrete representation of a smooth spacetime. We show that for high temperatures, the network describes disconnected discrete space. At the Planck temperature, the system experiences the phase transition, and for low temperatures, the space becomes a triangulated discrete space. We show that the cosmological constant depends on the universe’s topology. The "foamy" structure, analogous to Wheeler’s "spacetime foam," significantly contributes to the effective cosmological constant, which is determined by the Euler characteristic of the universe.

: Electric air conditioning and heating systems capacity is growing rapidly. So does the nameplate capacity of PV power plants. While demand in cooling has a positive correlation with solar irradiationirradiance, the demand in heating has an opposite relation. In this study, different approaches of to design (aggregation; energy storagethermal, battery and implicit systems storage) and control (frequency conversion; variable and adaptive load) and their effects on the efficiency of an off-grid active thermal stabilisation system based on a solar-powered heat pump are analysed. The case considered is permafrost thermal stabilisation system in Norway. It is shown that proper layout and control of the system with an adaptive load can reduce the capital expenses expenditures and the total cost of ownership by 30-40%. Increase in the efficiency capacity factor and cooling stability of the systems with the aggregated and threshold power consumervariable load due to the principle of aggregation is studied. The downside of that is the increase in compressors operation time by 50% with variable load and by 25% per unit with aggregation which means more frequent replacement in terms of motor-hours. But The the feasibility of this approaches considered are applicable for a wide range of solar-powered facilities, but the results are is quite case sensitive and depends on the prices for low-power heat pumps. The prospects of using the excess refrigerant and soil for thermal energy storage instead of traditional electrochemical batteries are considered.

To investigate the process and chemistry of reaction zone formation, we conducted detailed petrographic observations and major-trace element analysis of rocks and minerals of lherzolite xenoliths from basanites of Tumusun volcano (Baikal Rift Zone). The reaction zones gradually disappear from contact toward center of xenoliths. This indicates their formation as a result of lherzolite-basanite interaction. The influence of basanite melt on major-trace element composition of secondary minerals of reaction zones is notable only at distance up to 100-200 μm from the contact. The major-trace element composition of secondary clinopyroxenes from orthopyroxene reaction zone indicates their formation from a melt formed by dissolution of orthopyroxene and influenced by element diffusion from basanite melt. Inside xenoliths the secondary minerals have Mg# values equal to or higher than Mg# of primary minerals. The secondary clinopyroxenes inherit their depleted or enriched REE pattern from primary pyroxenes. The major-trace element variations in secondary clinopyroxenes testify melt heterogeneity. Secondary clinopyroxene has slightly higher LILE and similar abundances of other trace elements compared to unreacted part of clinopyroxene grain. This is consistent with model developed from experimental studies: due to the interaction with basanite, incongruent dissolution of orthopyroxene occurs to form a melt which circulates in lherzolite and leads to pyroxenes and spinel dissolution. Non-dissolved centers of minerals are homogenous and similar in major-trace element composition to primary minerals. The process of peridotite-basanite interaction is not isochemical: even the centers of large xenoliths become enriched in LILE.

Graphene quality for use in biosensors was assessed in fabricated chips by a set of methods that includes atomic force microscopy (AFM), Raman spectroscopy, and low-frequency noise. It is shown that local areas of residues on the graphene surface, which arisen due to the interaction of graphene with a photoresist at the initial stage of chips development, leads to a spread of chips resistance (R) within 1-10 kΩ and to an increase in the root mean square (RMS) roughness up to 10 times that can significantly impair reproducibility of graphene parameters in biosensors chips. It was observed that the control of the photoresist residues after photolithography (PLG) by AFM and subsequent additional cleaning allow reducing the spread of R values in chips to 1–1.6 kΩ and obtaining RMS roughness similar to the roughness in pristine graphene before PLG. Monitoring of the spectral density of low-frequency voltage fluctuation (SU), which provides integral information about the defect system and quality of the material, makes it possible to identify chips with low graphene quality and with inhomogeneously distributed compressive stresses areas by the type of frequency dependence SU (f).

The article presents a new approach to the analysis of the stability of automatic systems with discrete links.In almost all modern automatic control systems, there are links that break signals in time. These are power controlled switches - transistors or thyristors operating in a pulsed mode and digital links in regulators.Time discretization significantly affects the stability of processes in the automatic control system. The theoretical analysis of such systems is rather complicated and requires a significant change in engineering approaches to analysis. In connection with the improvement of digital controllers and a significant increase in their performance, in recent years this problem has practically not been remembered. However, its mathematical "content" has not changed since the 80s of the 20th century, when discreteness began to play a major role among the problems hindering progress in automatic control systems, in terms of the transition to digital systems.In this paper, a new approach is proposed, which consists in interpreting the sampling operation by a link with the proposed frequency characteristic, which determines the suppression of input high-frequency signals. This link greatly simplifies engineering calculations and demonstrates the new capabilities of sampling systems. These possibilities include the rational distribution of digitalization resources - the number of bits and the sampling interval between the regulator channels, depending on the frequency range of the efficiency of these channels. Theoretical statements have been verified and confirmed by simulation. It is shown how this approach makes it possible to formulate new principles of construction of seemingly well-known controllers - PID controllers and variable structure systems (VSS).

This paper considers two types of Protestant ethnic groups of some areas of Urals and Western Siberia. The first type consist of representatives of members of different ethnic groups consisting of well-educated professionals, incorporated into industrial society and associated with the intellectualism of Protestantism. The second type is represented by the indigenous peoples of the Polar Urals and Western Siberia, who use the Protestant religious organizations as tool for restoring life-sustaining elements of the native peoples’ traditional economy. I employed the inductive approach and the comparison method; during the fieldwork I used ethnographic participant observations, sociological structured interviews and closed-ended questionnaires. The empirical data have been collected in the Southern, Middle and Polar Urals and Western Siberia.

Rapid emergence of evasive SARS-CoV-2 variants is an on-going challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform on the sufficiency of the breadth of antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. Traditional analysis of neutralization titers against WT, Alpha, Beta, Delta, Omicron BA.1 and BA.4/BA.5 showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

There are various approaches to managing polyethylene terephthalate waste, including methods for recycling PET. However, at present, only the cleanest wastes that can already be efficiently recycled using known methods are considered in the scientific literature. The study aims to look at other forms of polyethylene terephthalate waste that pose a challenge: low quality PET flakes, polyester tire cord, PET dust and prepolymer waste. The waste was characterized by FTIR spectroscopy, viscosimetry, differential scanning calorimetry, laser diffraction and sieve analysis. The findings describe the composition and properties of various forms of polyethylene terephthalate waste. Low quality PET flake waste and polyethylene terephthalate dust have been shown to be suitable for all chemical recycling methods. When recycling waste polyester tire cord, it is difficult to completely separate the rubber, so its presence in the final product must be taken into account. The most promising way to process a prepolymer is its depolymerization by hydrolysis, alcoholysis or glycolysis to produce monomers for the synthesis of PET, similar in properties to the primary one.

As the problem of air pollution becomes more urgent, the precise determination of the characteristics of air pollution and the associated mechanisms of transport of pollutants becomes an increasingly urgent task. The simulation results of the Copernicus Atmospheric Monitoring Service (CAMS) [18] were used as initial data sets. The area of the Crimean Peninsula (within coordinates 44.50 latitude, 33.50 longitude) in 23 - 26 January, 2019 was chosen for the study. That time concentrations of pollutants (aerosol particles with a diameter of 2.5 (PM2.5) and 10 micrometers (PM10)) steadily increased and reached the maximum value. Four kinds of meteorological data sets were used in the work. The first and second data sets were the global NCEP/NCAR and (ERA-5) re-analyses. The third and fourth meteorological data sets were obtained using the Weather tracking and Forecasting model (WRF) as domains on high-resolution grids: 9 km and 2 km. The analysis of meteorological data sets was carried out to analyze the nature of the air masses movement in the studied region. Using the HYSPLIT model simulation was carried out to determine area of the sources of negative impact. The emissions transfer from the supposed sources of negative impact on the Crimea region is analyzed. The sensitivity of simulation the inverse and direct trajectories of air masses transfer was studied based a set of simulation results. On the basis of HYSPLIT model the simulation was carried out separately using meteorological data sets having different spatial and temporal resolutions. In general, the simulation results allowed us to conclude that the HYSPLIT model in combination with high-resolution meteorological input data of the WRF model are good to identify the sources of possible negative effects on atmospheric air located at long distances from the study site.

An approach to estimating the objective function value of minimization maximum lateness problem is proposed. It is shown how to use transformed instances to define a new continuous objective function. After that, using this new objective function, the approach itself is formulated. We calculate the objective function value for some polynomially solvable transformed instances and use them as interpolation nodes to estimate the objective function of the initial instance. What is more, two new polynomial cases, that are easy to use in the approach, are proposed. In the end of the paper numeric experiments are described and their results are provided.

The possibilities of applying various methods to study Coleoptera give unexpected and original results. The studies were carried out with the help of fermental crown traps in 2018-2020 on the territory of eight regions in the central part of European Russia. The biodiversity of Coleoptera that fall into crown traps includes 294 species from 45 families. The number of species attracted to the fermenting bait is about a third of the total number of species in the traps (this is 97.4% of the number of all caught specimens). The largest number of species that have been found in traps belong to the families Cerambycidae, Elateridae and Curculionidae. The most actively attracted species mainly belong to the families Cerambycidae, Nitidulidae and Scarabaeidae. Species of these families are equally attracted by baits made of beer, white and red wines. To identify the Coleoptera biodiversity of a particular biotope, two-year studies are sufficient, which should be carried out throughout the vegetation season. Especially good results can be obtained from studies of rare species that are actively attracted by such baits. It is possible to study the verti-cal-horizontal distribution of Coleoptera fauna in individual biotopes.

The Schelling model of segregation allows for a general description of residential movements in an environment modeled by a lattice. The key factor is that occupants change positions until they are surrounded by a designated minimum number of similarly labeled residents. An analogy to the Ising model has been made in previous research, primarily due the assumption of state changes being dependent upon the adjacent cell positions. This allows for concepts produced in statistical mechanics to be applied to the Schelling model. Here is presented a methodology to estimate the entropy of the model for different states of the simulation. A Monte Carlo estimate is obtained for the set of macrostates defined as the different aggregate homogeneity satisfaction values across all residents, which allows for the entropy value to be produced for each state. This produces a trace of the estimated entropy value for the states of the lattice configurations to be displayed with each iteration. The results show that the initial random placements of residents have larger entropy values than the final states of the simulation when the overall homogeneity of the residential locality is increased.

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [¹²³I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [¹²³I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [¹²³I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220 – age]. Approximately one minute before reaching this level, [¹²³I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [¹²³I]IAZA and total radioactivity (total[¹²³I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [¹²³I]IAZA data from healthy volunteers rest. Following exercise stress, both [¹²³I]IAZA and total[¹²³I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t_1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t_1/2β of 195 and 290 min, respectively]. Total body clearance (CL_TB) and the steady state volume of distribution (V_ss) were 0.647 L/kg and 185 mL/min, respectively, for [¹²³I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[¹²³I]. The t_1/2β, CL_TB and V_ss values were comparable to those reported previously for rested volunteers. The t_1/2α was approximately 4-fold shorter for [¹²³I]IAZA and approximately 3-fold shorter for total[¹²³I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [¹²³I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t_1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [¹²³I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [¹²³I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

Acute vertigo and dizziness are frequent presenting symptoms in patients on the emergency department. With a broad differential diagnosis and symptoms/signs often subtle and transient, the diagnostic approach to the dizzy patient remains challenging. Previous work emphasized the value of combining structured history-taking and a targeted examination focusing on subtle oculomotor signs. Here I review different bedside algorithms proposed for the acutely dizzy patient. Comparing area-under-the-curve ROC-characteristics and sensitivity/specificity, highest diagnostic accuracy was observed for algorithms focusing on subtle oculomotor signs. Both the HINTS+ bedside-exam and the STANDING algorithm have demonstrated higher diagnostic accuracy for identifying strokes than early (<24-48h after symptom-onset) MRI-DWI. Importantly, HINTS and STANDING require moderate training to allow reliable application. Thus, for physicians lacking dedicated training, other approaches are needed. Various scores that rely on vascular risk-factors, clinical symptoms and focal neurologic findings have been proposed (e.g., ABCD2-score, PCI-score, TriAGe+-score). While these scores are more readily applicable for frontline providers, they provide intermediate diagnostic accuracy at best and often lack external validation, thus are an insufficient substitute for algorithms assessing subtle oculomotor findings. Providing dedicated training in HINTS+ or STANDING techniques will be key to improve the diagnostic accuracy and to avoid unnecessary brain imaging.

Excessive activation of frog eggs, so called overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit with a low frequency, in natural populations of spawned frog eggs. Currently, cytological and biochemical events of the spontaneous process are not characterized. In the present study, we demonstrate that spontaneous overactivation of Xenopus frog eggs, similarly to oxidative stress- and mechanical stress-induced overactivation, is characterized by the fast and irreversible contraction of the egg’s cortical layer, increase in the egg size, depletion of intracellular ATP, drastic increase in the intracellular ADP/ATP ratio, and degradation of M phase-specific cyclin B2. These events manifest in eggs in the absence of caspase activation within just one hour of triggering overactivation. Importantly, large amounts of ATP and ADP leak from the overactivated eggs, indicating that plasma membrane integrity is compromised in these cells. The rapture of the plasma membrane and acute depletion of intracellular ATP define explicitly necrotic cell death. Finally, we report that egg overactivation can occur in the frog’s genital tract. Our data argue that mechanical stress may be a key factor promoting egg overactivation during natural spawning in frogs.

The [PSI⁺] nonsense-suppressor determinant of Saccharomyces cerevisiae is related to formation of heritable amyloids of the Sup35 (eRF3) translation termination factor. [PSI⁺] amyloids have variants in amyloid structure and in the strength of suppressor phenotype. Appearance of [PSI⁺], its propagation and manifestation depend primarily on chaperones. Besides chaperones, the Upf1/2/3, Siw14 and Arg82 proteins restrict [PSI⁺] formation, while Sla2 can prevent the [PSI⁺] toxicity. Here, we identify two more non-chaperone proteins involved in [PSI⁺] detoxification. We show that simultaneous lack of the Pub1 and Upf1 proteins causes lethality of [PSI⁺] cells with a strong, but not with weak suppressor phenotype. This lethality results from excessive depletion of the Sup45 (eRF1) termination factor due to its sequestration into Sup35 polymers. We also show that Pub1 acts to restrict excessive Sup35 prion polymerization, while Upf1 interferes with Sup45 binding to Sup35 polymers. These data allow considering the Pub1 and Upf1 proteins as a novel [PSI⁺] detoxification system.

Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans, and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational program, Domain Analysis and Motif Matcher (DAMM), that predicts target specificity in choanoflagellate PDZ domains by analyzing peptide-binding cleft sequence identity as compared to human PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with &lt;100 M affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contributes to investigations into choanoflagellate signaling and how it informs metazoan evolution.

The results of an LA-ICP-MS U-Pb dating and Hf isotope study of zircon crystals separated from small eclogite xenoliths found in Devonian kimberlites within the Prypyat horst, Ukraine, are reported. The studied area is located in the Central Belarusian Suture Zone, which represents a Paleoproterozoic belt extending along the boundary between the Sarmatian and Fennoscandian segments of the East European Platform. Four laser ablation sites on two zircon grains yielded Paleoproterozoic U-Pb ages between 1954 ± 24 Ma and 1735 ± 54 Ma. In contrast, three of four Hf sites revealed negative εHf values and Paleoarchean to Mesoarchean model ages, excluding the possibility that the eclogite xenoliths represent segments of a Paleoproterozoic subducted slab or younger mafic melts crystallized in the subcontinental lithospheric mantle. A single laser ablation Hf spot yielded a positive εHf value (+3) and a Paleoproterozoic model age. Two models for eclogite origin can be proposed. The first foresees the extension of the Archean lower-crustal or lithospheric roots beneath the Central Belarus Suture Zone for over 200 km from the nearest known outcrop of Archean rocks. The second model is that the Central Belarus Suture Zone represents a rifted-out fragment of the Kola-Karelian craton that was accreted to Sarmatia before the actual collision of these two segments of Baltica.

Tuberculosis (TB) is a leading infectious disease with serious antibiotic resistance. The benzothiazinone (BTZ) scaffold PBTZ169, an inhibitor of the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1) in Mycobacterium tuberculosis (Mtb), showed anti-TB potential in animal model and piloted clinical tests. Although highly potent, the BTZ type DprE1 inhibitors in general shows extremely low aqueous solubility, which adversely affect the drug like property. To improve the compounds physiochemical properties, we generated a series of BTZ analogues. Several optimized compounds had MIC values against Mtb in single digit nanomolar. The representative compound 37 displayed improved solubility and bioavailability compared to the lead compound. Additionally, compound 37 shows Mtb-killing ability in an acute infection mouse model.

2,3,5,6-Tetramethyl-1,4-diisocyanobenzene (1), 1,4-diisocyanobenzene (2), and 1,4-dicyanobenzene (3) were co-crystallized with 1,3,5-triiodotrifluorobenzene (1,3,5-FIB) to give three cocrystals, 1·1,3,5-FIB, 2·2(1,3,5-FIB), and 3·2(1,3,5-FIB), which were studied by XRD. Common feature of the three structures is the presence of I···Cisocyanide or I···Nnitrile HaBs occurred between an iodine -hole and the isocyanide C- (or the nitrile N-) atom. The diisocyanide and dinitrile cocrystals, 2·2(1,3,5-FIB) and 3·2(1,3,5-FIB), are isostructural thus providing a basis for accurate comparison of the two types of noncovalent linkages of CN/NC groups in the composition of structurally similar entities and in one crystal environment. The bonding situation was studied by a set of theoretical methods. Diisocyanides are more nucleophilic than the dinitrile and they exhibit stronger binding to 1,3,5-FIB. In all structures, the HaBs are mostly determined by the electrostatic interactions, but the dispersion and induction components also provide a noticeable contribution and make the HaBs attractive. Charge transfer has a small contribution (<5%) to the HaB and it is higher for the diisocyanide than for the dinitrile systems. At the same time, diisocyanide and dinitrile structures exhibit typical electron-donor and -acceptor properties in relation to the HaB donor.

We investigated the magnetic properties of antiferromagnetic (AFM) topological insulator MnBi$_2$Te$_4$ with partial substitution of Mn atoms by non-magnetic elements (A$_x^{IV}$ = Ge, Pb, Sn). Samples with various element concentrations (10-80%) were studied using SQUID magnetometry. The results demonstrate that, for all substitutes the type of magnetic ordering remains AFM, while the Nèel temperature (T$_N$) and spin-flop transition field (H$_{SF}$) decrease with increasing A$_x^{IV}$ = Ge, Pb, Sn concentration. The rate of decrease varies among the elements, being highest for Pb, followed by Sn and Ge. This behavior is attributed to combined effects of magnetic dilution and lattice parameter increase on magnetic properties, most prominent in (Mn$_{1−x}$Pb$_x$)Bi$_2$Te$_4$. Besides this, the linear approximation of experimental data of T$_N$ and H$_{SF}$ suggests higher magnetic parameters for pure MnBi$_2$Te$_4$ than observed experimentally, indicating the possibility of their non-monotonic variation at low concentrations and the potential for enhancing magnetic properties through doping MnBi$_2$Te$_4$ with small amounts of nonmagnetic impurities. Notably, the (Mn$_{1−x}$Pb$_x$)Bi$_2$Te$_4$ sample with 10% Pb substitution indeed exhibits increased magnetic parameters, which is also validated by local analyses using ARPES. Our findings shed light on tailoring the magnetic behavior of MnBi$_2$Te$_4$-based materials, offering insights for potential applications in device technologies.

Nanoparticles (NPs) have various applications in medicine, cosmetics, optics, catalysis, environmental purification, and other areas nowadays. With an increasing annual production of NPs, the risks of their harmful influence to the environment and human health is rising. Currently, our knowledge about the mechanisms of interaction between NPs and living organisms is limited. Additionally, poor understanding of how physical and chemical characteristic and different conditions influence the toxicity of NPs restrict our attempts to develop the standards and regulations which might allow us to maintain the safe living conditions. The marine species and their habitat environment are under continuous stress due to anthropogenic activities which result in the appearance of NPs in the aquatic environment. Our study aimed to evaluate and compare biochemical effects caused by the influence of different types of carbon nanotubes, carbon nanofibers, and silica nanotubes on four marine microalgae species. We have evaluated the changes in growth-rate, esterase activity, membrane polarization, and size changes of microalgae cells using flow cytometry method. Our results demonstrated that toxic effects caused by the carbon nanotubes strongly correlated with the content of heavy metal impurities in the NPs. More hydrophobic carbon NPs with less ordered structure had a higher impact on the red microalgae P. purpureum because of higher adherence between the particles and mucous covering of the algae; silica NPs caused significant inhibition of microalgae growth-rate predominantly produced by mechanical influence.

Juvenile idiopathic arthritis (JIA) is a disease with unknown causes within all forms of arthritis in children under 16 years of age. The diagnosis is made when another joint pathology is excluded. Difficulties in early and differential diagnosis lead to the rapid disability of patients and an unfavourable life prognosis. Therefore, timely diagnosis is necessary to prevent irreversible damage to the joints and preserve their function. Due to the widespread use of new technologies, modern multimodal imaging has gained recognition, which includes X-ray, ultrasound, and MRI. The combination of methods plays a key role in confirming the diagnosis, monitoring disease activity, prognosis during the course, and outcome in children with JIA. Each method has its own advantages and disadvantages. The introduction of the method of passive microwave radiometry (MWR), in combination with other imaging methods, makes it possible to expand the possibilities of screening the disease in the preclinical and early clinical phases.

Companies are increasingly focusing on sustainable business practices. Internal and external stakeholders’ expectations manifest in legal requirements, national and international standards, and market and customer expectations, among other things, must be considered. In addition to profit maximization as the usual target for corporate management, management must consider environmental sustainability aspects such as resource efficiency, greenhouse gas intensity, and a company's emissions behavior. In addition, social aspects relating to the company's employees, the immediate urban environment, the situation in the supply chain, and effects on the market environment must increasingly be considered. Specifically, companies are faced with the chal-lenge of dealing with conflicting objectives regarding the various aspects of sustainability and, if necessary, weighing them up against each other. These trade-offs must be made against the company's socio-economic and ecological environment, corporate strategy, and sustainability goals. This paper provides an overview of current approaches and research gaps on this topic through a literature review. It shows a lack of methods and frameworks to specifically deal with trade-offs and conflicts of goals.

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.

Domestic abuse and stalking in higher education (HE) have been overlooked in research in comparison to sexual harassment and sexual violence. This article reports on survey data from 725 students at a UK university using measures of ‘dating violence’ – physical and psychological violence from an intimate partner – and stalking from a US survey instrument (the Administrator Researcher Campus Climate Collaborative (ARC3) survey). According to this measure, 26% of respondents had been subjected to ‘dating violence’ and 16% to stalking behaviours. However, these findings need to be contextualised within a critical discussion of the use of the ARC3 survey tool in the UK context. The ARC3 questions on ‘dating violence’ focus on physical and ‘psychological violence’; the questions therefore omit further types of domestic abuse under UK definitions. In relation to stalking, US definitions – as captured in the ARC3 survey instrument – define specific behaviours. By contrast, in the UK stalking involves behaviours that engender fear or distress in a pattern of behaviour over time. These differences mean that the ARC3 modules on stalking and ‘dating violence’ would need to be significantly adapted to be suitable for use in the UK context.

We develop a quantitative microscopic theory of decaying Turbulence by studying the dimensional reduction of the Navier-Stokes loop equation for the velocity circulation. We have found an infinite dimensional manifold of solutions of the Navier-Stokes loop equation\cite{M93, M23PR} for the Wilson loop in decaying Turbulence in arbitrary dimension $d >2$. This family of solutions corresponds to a fractal curve in complex space $\mathbb C^d$, described by an algebraic equation between consecutive positions plus a nonlinear periodicity condition. We derive the constrained SDE for the evolution of the fractal curve at a fixed moment of physical time as a function of an auxiliary stochastic time. We expect this stochastic process to cover our fixed manifold of the solutions of the decaying Turbulence. The energy density of the fluid decays as $\mathcal E_0/t$, where $\mathcal E_0$ is an initial dissipation rate. Presumably, we have found a new phase of extreme Turbulence yet to be observed in real or numerical experiments.

The development of magnesium calcium phosphate bone cements (MCPCs) have garnered big attention. MCPCs are bioactive and biodegradable and have appropriate mechanical and antimicrobial properties for use in reconstructive surgery. In this study, the cement powders based on a (Ca + Mg)/P = 2 system doped with Zn2+ at 0.5 and 1.0 wt.% were obtained and investigated. After the mixing with a cement liquid, structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behaviour of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn2+ 1.0-wt.%-substituted powders. The Zn2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter up to 8 mm. Biological assays confirmed that the developed cements are cytocompatible and promising as a potential bone substitute in reconstructive surgery.

Carbonization of a biopolymer (lignin) in self-propagating high-temperature synthesis (SHS) led to the production of 2D graphene structures. With the help of modern analytical methods (Raman spectroscopy, X-ray diffraction) and electron microscopy, the resulting product was confirmed to have a few-layer 2D graphene structure. The predicted photovoltaic properties of the resulting few-layer graphene were implemented for laser ignition of a model pyrotechnic composition based on porous silicon. A phenomenological model of the formation mechanism of 2D graphene structures under the conditions of the SHS process is proposed.

Calcium sulfate (CS) materials containing terbium ions at 0, 1.0, or 2.0 mol.% were obtained by mechanochemical synthesis. According to X-ray diffraction data, the powder materials are characterized by the presence of a CaSO4×0.5H2O phase, while Tb3+ is incorporated into the lattice at ≤1.0 mol.%. Specific surface area enlarged from 2.1 to 22.5 m2/g as crystallite size decreased from 68 to 31 nm and the Tb3+ concentration increased up to 1.0 mol.%. Thermal analysis showed that terbium slightly raises the temperature of CaSO4×2H2O-to-CaSO4 transition. The presence of Tb3+ did not affect the solubility of the CS cements. Furthermore, after 7 days of soaking of the materials in a simulated body fluid, a calcium phosphate layer formed corresponding to a hydroxyapatite phase, in contrast to the pure cements. Luminescent properties were studied by excitation at 276 nm. The recorded emission peaks of the CS materials indicated that the luminescence of the samples is green and blue, with the most intense luminescence observed for samples containing 1.0 mol.% Tb3+. The developed materials can find applications in medicine as bioimplants for the regeneration and restoration of bone tissue with a possibility of noninvasive monitoring of the bone restoration process.

In this article, we discuss problems that exist in modern SCADA systems and present a Controls-kt (formerly DataForge-controls) software development kit, that allows both to create a control system from scratch and provide integration with existing systems via Magix specification and connector.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

Radio astronomical observations at millimeter and submillimeter wavelengths are a very important tool of astrophysical research. However, there is a huge area in the northern Eurasia, including the whole Russian territory, which lacks sufficiently large radio telescopes effectively operating at these wavelengths. In this review we describe our long-term efforts to find suitable sites for such radio telescopes in this area, that is, sites with good atmospheric transparency at millimeter and submillimeter waves. We describe methods and instruments used for measurements and evaluations of the atmospheric opacity. They include special radiometric systems, which are used for estimations of the atmospheric opacity from the sky brightness measurements. Evaluation of the precipitable water vapor from such measurements by the artificial neural network is discussed. Alternative approaches use global atmospheric models and signals of the Global Navigation Satellite Systems. To date, a long-term radiometric monitoring has been performed at several candidate sites and atmospheric conditions for many sites have been evaluated using global atmospheric models. Several sites with the best atmospheric transparency at millimeter and submillimeter wavelengths have been selected. They can be effectively used for astronomical observations at least in the major atmospheric transparency windows at 1.3 mm and 0.85 mm. These results can be also used for space communications and radar systems.

A pattern of NK cell heterogeneity in each individual determines proliferative and functional responses of NK cells to activating stimuli. Obtaining the progeny of a single cell by cloning original population is one of the ways to study the NK cell heterogeneity. In this work, we used single cell sorting into a plate and stimulation by IL-2 and gene-modified K562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21) that led to generation of phenotypically confirmed and functionally active NK cell clones. We applied two models of clone cultivation, which differently affected their phenotype, lifespan and functional activity. The first model, which included weekly restimulation of clones with K562-mbIL21 and IL-2, resulted in the generation of relatively short-lived (5-7 weeks) clones of highly activated NK cells. HLA-DR expression in the expanded NK cells correlated strongly with IFN-γ production. The second model, in which NK cells were restimulated mainly with IL-2 alone, produced long-lived clones (8-14 weeks) that expanded up to 10⁷ cells with lower ability to produce IFN-γ. Our method is applicable for studying variability in phenotype, proliferative and functional activity of the certain NK cell progeny in response to the stimulation, which may help in selecting NK cells best suited for clinical use.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

The existence of multiple copies of genes is a well-known phenomenon. A gene family is a set of sufficiently similar genes, formed by gene duplication. In earlier works conducted on limited number of completely sequenced and annotated genomes it was found that size of gene family and size of genome are positively correlated. Additionally, it was found that several atypical microbes deviated from the observed general trend. In this study, we reexamined these associations on a larger dataset consisting of 1484 prokaryotic genomes and using several ranking approaches. We applied ranking methods in such a way that genomes with lower number of paralogs would have lower rank. Until now only simple ranking methods were used; we applied the Kemeny optimal aggregation approach as well. Regression and correlation analysis were utilized in order to accurately quantify and characterize the relationships between measures of paralog indices and genome size. In addition, boxplot analysis was employed as a method for outlier detection. We found that, in general, all paralog indexes positively correlate with an increase of genome size. As expected, different groups of atypical prokaryotic genomes were found for different types of paralog quantities.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

The acylation of unsymmetrical N-benzylbispidinols in aromatic solvents without external base led to formation of supramolecular gels, which possess different thickness and stability depending on the substituents in para-positions of benzylic group and nature of acylating agent as well as on the nature of the solvent used. Structural features of the native gels as well as of their dried forms were studied by complementary techniques including FT IR- and ATR-spectroscopy, AFM, TEM, SEM, SAXS. Structures of the key crystalline compounds were established by X-ray diffraction. Analysis of obtained data allowed speculating on the crucial structural and condition factors that governed the gel formation. The most important factors were: (i) absence of base, either external or internal; (ii) presence of HCl; (iii) presence of carbonyl and hydroxyl groups to allow hydrogen bonding; (iv) presence of two (hetero)aromatic rings at both sides of the molecule. The hydrogen bonding involving amide carbonyl, hydroxyl at 9th position and, very probably, ammonium N-H+ and Cl- anion appear to be responsible for the formation of infinite molecular chains required for the first step of gel formation. Subsequent lateral cooperation of molecular chains into fibers occured, presumably, due to the aromatic pi-pi-stacking interactions. sc-CO2 drying of the gels gave rise to aerogels morphology different from that of air dried samples.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Because of their high biocompatibility, stability, ability to negotiate biological barrier passage, and functionalization properties, biological nanoparticles have been actively investigated for many medical applications. Biological nanoparticles, including natural extracellular vesicles (EVs) and synthetic extracellular vesicle-mimetic nanovesicles (EMNVs) represent novel drug delivery vehicles that can accommodate different payloads. In this study, we investigated EVs and EMNVs for their physical, biological and delivery properties and we showed that EMNVs have similar delivery properties compared to EVs. In addition, these nanotherapeutics were analyzed for their cytostatic properties in combination with the FDA-approved drug hydroxychloroquine (HCQ), which increased their cytostatic thanks to its lysosome-destabilizing properties. Altogether, these data demonstrated that, at least in vitro, the use of synthetic biomimetic particles is comparable to the natural counterparts, while their synthesis is significantly faster and more cost effective. In addition, we highlighted the benefits of combining biological nanoparticles with a lysosome destabilizing agent that increased the delivery properties of the particles.

Polynomial recurrence bounds for a class of stochastic differential equations with a gradient type drift and an additive Wiener process are studied without Lyapunov functions.

Porous coatings on prosthetic implants encourage implant fixation. Enhanced fixation may be achieved using a magneto-active porous coating that can deform elastically in vivo on application of an external magnetic field, straining in-growing bone. Such coating, made of 444 ferritic stainless steel fibres, was previously characterised in terms of its mechanical and cellular responses. In this work, co-cultures of human osteoblasts and endothelial cells were seeded into a novel fibrin-based hydrogel embedded in a 444 ferritic stainless steel fibre network. Albumin was successfully incorporated into fibrin hydrogels improving the specific permeability and the diffusion of fluorescently-tagged dextrans without affecting their Young’s modulus. The beneficial effect of albumin was demonstrated by upregulation of osteogenic and angiogenic gene expression. Furthermore, mineralisation, extracellular matrix production and formation of vessel-like structures were enhanced in albumin-enriched fibrin hydrogels compared to fibrin hydrogels. Collectively, the results indicate that the albumin-enriched fibrin hydrogel is a promising bio-matrix for bone tissue engineering and orthopaedic applications.

It is well known that the basis of diffraction analysis of matter is scattering, including scattering of ultrashort laser pulses. In the theory of scattering of ultrashort pulses the pulse duration parameter is usually not taken into account, which leads to some error. This error may be more significant than the considered effects in the scattering of the pulse on the studied structure. In this paper it is shown that the pulse duration parameter should be taken into account when scattering X-ray pulses on oriented diamonds with NV-centers. It is shown that the scattering spectra can be used to judge the orientation of NV centers in the diamond structure. The obtained results may be very different from the widely used theory of diffraction analysis, which confirms the necessity of taking into account the pulse duration parameter in the diagnosis of complex structures.

A university campus is a place full of memorable experiences and a sense of place. It is an environment that potentially creates a social and intellectual exchange of ideas and brings together diverse people. Campus planning is one essential need for any higher institution and is an instrument used for directing, promoting, and securing orderly physical development of an institution Campus planning present unique opportunities for demonstrating and popularizing contemporary tendencies in urban planning. The purpose of this study is to explore the overall concepts of the campus planning and architecture of the Kwame Nkrumah University of Science and Technology (Knust) And University of Ghana (Legon). The Study was based mainly on two methods; Documentary research and qualitative Observation to have in depth knowledge about the campuses. Through field observation, the study was limited to the spatial organization and planning, site layout and master planning, land use, use of space, and architectural details. The study adopts A Comparative Analysis Approach and found out that Campus Planning Concept varies and unique to campuses and in developing a campus plan, it involves a time-consuming dynamic process and besides, there are neither shortcuts nor one approach or generic solution to that. The study also revealed that Iconic and unique buildings are usually found on university campuses.

The idea of an extension of life for CubeSats is proposed to reduce space debris in a low-earth orbit. In this work, a gripper is designed for geometry-based grasping in berthing tasks. The grasping operation is outlined for square- and rectangle-profiled CubeSats. Equilibrium conditions are used to choose fingertips shape and parameters for grasping the CubeSat body. A design scheme is proposed to provide the required accuracy. A design concept is developed into a lab prototype by using low-cost 3D printing technique, and a mock-up grasping task that is representative of the berthing operation is evaluated with the lab prototype. Center-mass hanging setup for the prototype and grasped body is used to evaluate the impact of grasping, partially replicating the conditions in space by reducing the effect of gravity on the system.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Zika virus (ZIKV) is a widespread mosquito-borne pathogen. Phylogenetically, two lineages of the ZIKV are distinguished: African and Asian-American. The latter became the cause of the 2015-2016 pandemic with severe defeat to newborns. In West African countries the African lineage has been found, but there is evidence of the emergence of Asian-American lineage in Cape Verde and Angola. This highlights the need not only to monitor the ZIKV, but also to sequence the isolates. In this article, we present a case report of Zika fever in a pregnant woman from Guinea, identified in 2018. Viral RNA was detected by qRT-PCR in serum sample. In addition, seroconversion of anti-Zika IgM and IgG antibodies was detected in repeated blood samples. Subsequently, the virus was isolated in C6/36 cell line. The detected ZIKV belonged to the African lineage, the Nigerian sublineage. The strains with the closest sequences were isolated from mosquitoes in Senegal in 2011 and 2015. In addition, we conducted serological screening of 116 blood samples collected from patients presenting to the hospital of Faranah with fevers during the period 2018-2021. As a result, it was found that IgM-positive patients occurred each year, seroprevalence varied between 5.6% and 17.1%.

The Rasch model is one of the most prominent item response models. In this article, different item parameter estimation methods for the Rasch model are compared through a simulation study. The type of ability distribution, the number of items, and sample sizes were varied. It is shown that variants of joint maximum likelihood estimation and conditional likelihood estimation are competitive to marginal maximum likelihood estimation. However, efficiency losses of limited-information estimation methods are only modest. It can be concluded that in empirical studies using the Rasch model, the impact of the choice of an estimation method with respect to item parameters is almost negligible for most estimation methods. Interestingly, this sheds a somewhat more positive light on old-fashioned joint maximum likelihood and limited information estimation methods.

Camouflage evaluation typically involves human visual search and detection experiments that are time-consuming and expensive. Hence, there is a need for models that compute camouflage effectiveness from digital imagery. Convolutional neural networks are a powerful tool for automatic object detection and recognition. We investigated whether such a network (YOLO) can also provide a measure of camouflage effectiveness that is related to human perception. To this end, human performance measures of camouflage effectiveness such as detection time and target conspicuity were obtained in observer experiments and compared with the performance of the (standard, i.e. pre-trained) YOLO-V4-tiny algorithm. YOLO provides the probability that a detected object is correctly classified, and this is adopted as our measure of camouflage effectiveness. We compared the YOLO-predicted classification probability for a person in camouflage clothing moving through rural and urban scenes to human detection performance. Overall, camouflage effectiveness predicted by YOLO correlates with human observer performance. At close distances, YOLO’s classification performance appears sensitive to high-contrast shape-breaking elements of a camouflage pattern. This suggests that YOLO may be adapted to assess camouflage effectiveness for a wide range of applications, such as evaluating or optimizing one’s signature and predicting optimal hiding locations in a given environment. Further research is required to fully establish YOLO’s limitations and applicability for this purpose.

In the present article, we study the possibilities of machine learning for estimation of seeing at the Maidanak Astronomical Observatory (38∘40′24′′N, 66∘53′47′′E) using only Era-5 re-analysis data. Seeing is usually associated with the integral of the turbulence strength Cn2(z) over the height z. Based on the seeing measurements accumulated over 13 years we created ensemble models of multi-layer neural networks under the machine learning framework, including training and validation. For the first time in the world, we have simulated optical turbulence (seeing variations) during night-time with deep neural networks trained on a 13-year database of astronomical seeing. A set of neural networks for simulations of night-time seeing variations have been obtained. For these neural networks the linear correlation coefficient ranges from 0.48 to 0.68. We show that modeled seeing with neural networks is well described through meteorological parameters, which include wind speed components, air temperature, humidity and turbulent surface stresses. One of the fundamental new results is that the structure of small-scale (optical) turbulence over the Maidanak Astronomical Observatory does not depend or depends negligibly on the vortex component of atmospheric flows.

Porous ferroelectric lead zirconate-titanate (PZT) films are a promising material for various electronics applications. This study focuses on understanding how structure-directing agent (polyvinylpyrrolidone) can change structure and electrical properties of porous PZT films prepared by chemical solution deposition. The films with various porosity up to ~ 40 vol.% and pore connectivity changing from 3-0 to 3-3 were prepared and studied by capacitance-voltage, dielectric hysteresis, transient current, photocurrent, and local current techniques. We have found that the linear decrease in the material volume in a porous film is not the only factor governing film properties. The key role in changing electrical properties plays the creation of new internal grain boundaries. This research expands the understanding of physical phenomena in porous ferroelectric films and may enable the development of new materials and devices.

A class of controlled plants, whose dynamics is governed by a vector system of ordinary differential equations with a partially known right-hand side, is considered. The state variables and their velocities are assumed to be measurable. The aim is to design a controller which minimizes a loss function under certain constraints which arguments is the current state of the controlled plant. The designed control action is admitted to be a function of the current sub-gradient only, which supposed to be measurable on-line. The control design is based on ASG (Average Sub-Gradient method) — version of Integral Sliding Mode (ISM) concept, aimed to minimize on average a given convex (not obligatory strongly convex) cost function of the current state under a set of given constraints. An optimization type algorithm is developed and analyzed using ideas of SDM technique. The main results consist in proving the reachability of the "desired regime" (nonstationary analogue of sliding surface) from the beginning of the process and obtaining an explicit upper bound for the averaged loss function decrement, that is, the averaged in time functional convergence is proven and the rate of such convergence is estimated.

This review explores the complex interrelationships between emotion, attention, and behavior, drawing upon empirical evidence from psychological, neuroscientific, and clinical studies. It delves into the neural mechanisms that underlie these interactions, with a focus on key brain regions such as the prefrontal cortex and amygdala. Clinical cases involving stroke and attention-deficit/hyperactivity disorder (ADHD) are examined to illustrate the real-world implications of these cognitive interactions. The review also discusses the impact of effective emotion regulation strategies and the role of attention as a cognitive mechanism that influences both emotion and behavior. Neuroimaging studies, particularly functional MRI, are highlighted for their role in providing a deeper understanding of these intricate relationships. The review concludes by emphasizing the importance of this triadic relationship in adaptive functioning and its broader implications for mental health, interpersonal relationships, and quality of life.

This work describes the synthesis and X-ray diffraction properties of spirocyclic compounds based on 8-azaspiro[5.6]dodec-10-ene. Diasteriomerically pure pyrrole derivatives were prepared from the spirocyclic 1,2,3-triazole using a coupling reaction. The resulting compounds were characterized via 1H and 13C NMR spectroscopy and HRMS, and the crystallographic characteristics of one of them were studied by X-ray diffraction.

A closed chain of oscillators can be considered as a model of ring-shaped ecosystems, such as atolls or coastal zones of inland reservoirs. As an oscillator model, we use the logistic map that often referred to as an archetypical example of how complex dynamics can arise from very simple nonlinear equations. We investigate the influence of the model parameters both on the nature of oscillations in the oscillator ring and on the spatial structures that arise in this case. Namely, we demonstrate a variety of emerging spatial structures depending on the initial conditions.

The development of sustainable tourism in the territory requires the monitoring of all diverse aspects of the tourism sector and the creation of information technologies that provide the collection, analysis, processing and visualization of relevant information. The aim of this work is to describe the concept of the tourism monitoring service in Irkutsk Oblast as part of the Lake Baikal area, define methods and software of implementing this service, and present individual results of its prototyping. The creation of a service includes the development and software implementation of methods for collecting, processing and visualizing data, as well as ensuring the use of the functionality of existing cloud platforms for the main information processes. Data collection methods are based on Application Programming Interface and web scraping technologies, processing methods include statistical methods and artificial intelligence methods, visualization methods are based on Business Intelligent systems methods. In this paper described the concept of service, justified methods of data analysis and visualization, built an ontological model, defined the content of dashboards, implemented a prototype of a service, and demonstrated the results of data collection, processing and presentation obtained from the research. Currently, information has been collected and processed for the following tourist attractions: 685 accommodation facilities, 16 services, 809 catering establishments, 352 attractions, 94 tourist routes and excursions. The proposed technology (methods and software) of the territory tourism monitoring service has demonstrated its effectiveness.

Excessive activation of frog eggs (overactivation) is a pathological process that renders eggs unfertilizable. Its physiological inducers are unknown. Previously, oxidative stress was shown to cause time- and dose-dependent overactivation of Xenopus laevis frog eggs [1]. Here, we demonstrate that the oxidative stress-induced egg overactivation is a calcium-dependent phe-nomenon which can be attenuated in the presence of the selective calcium chelator BAPTA. Degradation of cyclin B2, which is known to be initiated by calcium transient in fertilized or parthenogenetically activated eggs, can also be observed in the overactivated eggs. Decline in mitochondrial membrane potential, ATP depletion and termination of protein synthesis manifest in the eggs within one hour of triggering overactivation. These intracellular events occur in the absence of caspase activation. Furthermore, plasma membrane integrity is compromised in the overactivated eggs, as evidenced by ATP leakage and egg swelling. In sum, our data demonstrate that oxidative stress-induced overactivation of frog eggs causes fast and dramatic disruption of cellular homeostasis, resulting in robust and expedited cell death by a calcium-dependent non-apoptotic mechanism.

We present a very computationally light and fast approximation algorithm and then verify it with genetic algorithm and simulated annealing. We show that our algorithm is on par with GA and SA in terms of output produced while having a tightly bounded time complexity. Our algorithm works best when there is a strong positive correlation between the reliability of a component and its cost. We present two algorithms with the same essence. One of them is system cost bounded and the other is target reliability bounded. Our proposed algorithm works on a subsystem level redundancy instead of component level redundancy.