Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Optical “fingerprints” are widely used in chemometrics-assited recognition of samples of different nature. An emerging trend in this area is the transition from obtaining "static" spectral data to reactions occurring over time. The indicator reactions are usually carried out in aqueous solutions; in this study we have developed the reactions that occur in an organic solvent, which makes it possible to recognize fat-soluble samples. In this capacity, we used 5W40, 10W40 and 5W30 motor oils of 4 manufacturers, totally 6 samples. The procedure involved mixing of the dye, sample, and reagents (HNO3, HCl, or t-butyl hydroperoxide) in ethanolic solution in a 96-well plate and measuring absorbance or near-IR fluorescence intensity every several minutes during 20–55 min. The obtained photographic images were processed by linear discriminant analysis (LDA) and k-nearest neighbors algorithm (kNN). The discrimination accuracy was evaluated by using the validation procedure. Reaction of oxidation of a dye with nitric acid allowed to recognize all 6 samples with 100% accuracy by LDA. Merging data of 4 reactions that did not provide complete discrimination ensured an accuracy of 93% by kNN technique. The developed indicator systems have good prospects for the discrimination of other fat-soluble samples. Overall, the results confirm the viability of the kinetic-based discrimination strategy.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

In this paper, we present sums and partial sums of Horadam sequences via generating functions which extends a recent result of Prodinger.

In this paper, closed forms of the sum formulas $\sum_{k=0}^{n}x^{k}W_{k}^{3}$ and $\sum_{k=1}^{n}x^{k}W_{-k}^{3}$ for the cubes of generalized Fibonacci numbers are presented. As special cases, we give sum formulas of Fibonacci, Lucas, Pell, Pell-Lucas, Jacobsthal, Jacobsthal-Lucas numbers.

The excessive intake of sodium (Na) and insufficient intake of potassium (K) are major concerns to prevent hypertension. Using low-Na/K seasonings (reducing 25% of the NaCl and adding K salt) may improve the dietary Na/K ratio and help prevent hypertension. To devise an intervention study using low-Na/K seasonings at a company cafeteria, we calculated the Na and K contents of the meals served at the cafeteria and estimated changes in the intakes when suitable low-Na/K seasonings were used. We also considered using milk as a good source of K. We used an ingredient list of a company cafeteria and calculated Na and K contents in each dish. The average amounts of NaCl and K per use were 5.04 g and 718 mg, respectively. Seasonings contributed 70.9% of the NaCl. With the use of low-Na/K seasonings, an estimated reduction in NaCl of 0.8 g/day and an estimated increase in K of 308 mg/day was achieved. An additional serving (200 mL) of milk, NaCl was reduced by 0.57 g/day and K was increased by 610 mg/day, with an overall decrease in the dietary Na/K ratio from 3.20 to 2.40. The use of low-Na/K seasonings and dairy may improve the dietary Na/K ratio among cafeteria users and help prevent hypertension.

The article analyzes existing materials and structures with quadratic-nonlinear optical properties that can be used to generate a difference frequency in the terahertz and sub-terahertz frequency ranges. The principle of constructing a nonlinear optical-radio converter, based on an optical focon (a focusing cone), is proposed. Based on the assumption that this focon can be implemented from the metal-organic framework (MOF), we propose a technique for modeling its parameters. The mathematical model of the process of propagation and nonlinear interaction of waves inside the focon is based on a simplification of the nonlinear wave equation. Within the framework of the developed model, the following parameters are approximately determined: the 3D gradient of the linear refractive index and the function determining the geometric profile of the focon, which provide a few-mode-based generation of the difference frequency.

Two clear-air over-the-horizon propagation mechanisms affecting Automatic Identification System (AIS) detection range are considered. Comparison results are presented between the path loss due to tropospheric ducting and path loss due to tropospheric scattering (troposcatter) for the AIS frequencies. The calculations are based on the well-known parabolic equation approximation to the wave equation, in which a simple troposcatter formula is incorporated. In most studied cases the ducting assures significantly greater reduction of path loss than troposcatter even when the AIS frequencies are not well trapped in the duct. Emphasis is placed on elevated trapping layers and some features that may make ducting propagation less favorable in terms of increasing the AIS detection range are discussed.

K-band radar waves have high penetration and low attenuation coefficients. However, the wavelength of this radar wave is relatively short; thus, designing and preparing both broadband and wide-angle radar wave absorbers in this band presents considerable challenges. In this study, a resin-based K-band radar wave absorber with a biomimetic lotus leaf structure was designed and formed by UV curing. Here, microscale lotus leaf papillae and antireflection structures were prepared using a DLP 3D printer, and the contact angle between the material and water droplets was increased from 56° to 130°. In addition, the influence of the geometric parameters of the lotus leaf antireflection structure on the electromagnetic absorption performance and mechanical strength was investigated. After simulation optimization, the maximum electromagnetic loss of the lotus leaf structure 3D printed sample was −32.3 dB, and the electromagnetic loss was below −10 dB in the 20.8–26.5 GHz frequency range. When the radar incidence angle was 60°, the maximum electromagnetic loss was still less than −10 dB. The designed lotus leaf structure has a higher mechanical energy absorption per unit volume (337.22 KJ/m3) and per unit mass (0.55 KJ/Kg) than commonly used honeycomb lightweight structures during the elastic deformation stage, and we expect that the designed structure can be used as an effective lightweight material for K-band radar stealth.

Introduction of Cl- and O- atoms into C4-vinyl carbocations was studied by X-ray diffraction analysis and IR spectroscopy. Chlorine atoms are weak electron acceptors in ordinary molecules, but within vinyl carbocations, manifest themselves as strong electron donors that accept a positive charge. The attachment of a Cl atom directly to a C=C bond leads to an increase in the e-density on it, exceeding that of the common double bond. The positive charge should be concentrated on the Cl atom, and weak δ- may appear on the C=C bond. More distant attachment of the Cl atom—to a C atom adjacent to the C=C bond—has a weaker effect on it. If two Cl atoms are attached to the Сγ atom of the vinyl cation, as in Cl2СγСδHСαHCH3, then the cation switches to the allyl type with two practically equivalent and almost uncharged СγСδСα bonds. When such a strong nucleophile as the O atom is introduced into the carbocation, a protonated ester molecule with a C-O(H+)-C group and a C=C bond forms. Nonetheless, in the future, there is still a possibility of obtaining carbocations with a non-protonated C-O-C group.

This paper aims to investigate appropriate mathematical models devoted to optimization of some cleaning processes related to pharmaceutical contaminants removal. In our previous recent works has been reported that a possibility for removal from water sources of this type of micropollutants is to rehabilitate the existing cleaning plants by introducing efficient techniques such as adsorption on granulated active carbon filters, micro-, nano- or ultrafiltration. To have such processes under a better control and to pass from small to large scale treatment stations, specific mathematical models are necessary. Starting from Navier-Stokes equations and imposing proper boundary conditions, some mathematical physics problems are obtained for which adequate solving methods via variational methods and surjectivity results are proposed. The importance of these solution characterizations consists in their continuation in a numerical method and the possibility to visualize the result by using CFD program.

At the beginning of the 21st century, it became obvious that radical changes had taken place in the concept of living matter and, in particular, in the concept of the organization of intracellular space. The accumulated data testify to the essential importance of phase transitions of biopolymers (first of all, intrinsically disordered proteins and RNA) in the spatiotemporal organization of the intracellular space. Of particular interest is the stress-induced reorganization of the intracellular space. Examples of organelles formed in response to stress are nuclear A-bodies and nuclear stress granules. The formation of these organelles is based on LLPS of intrinsically disordered proteins and non-coding RNA. Despite the overlapping composition and similar mechanism of formation, these organelles have different functional activities and physical properties. In this review, we will focus our attention on these MLOs and describe their functions, structure, and mechanism of formation.

In this paper, we present the interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles and cytisine and salsoline alkaloids. It has been shown that the reaction results in the one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction is affected by the presence of a base and the order in which the reagents are added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity has been carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking shows that the compounds have insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increases the affinity of these substrates for target proteins selected.

this review summarizes current knowledge of the hydrogen sulfide role in cardiovascular system, the proposed mechanisms of its action and the prospects for its applicability in the treatment of cardiovascular diseases. Hydrogen sulfide was recently recognized as gasotransmitter – simple signaling molecule which freely penetrates the cell membrane and regulates a number of biological functions. In humans endogenous H2S is generated via enzymatic and non-enzymatic pathways and its content varies in different tissues and is strictly regulated. In cardiovascular system H2S is produced by myocardial, vascular and blood cells and regulates a number of vital functions. Numerous experimental data prove that endogenously generated as well as exogenously administered H2S exerts a wide range of actions in cardiovascular system, including vasodilator/vasoconstrictor effects, regulation of blood pressure, pro-apoptotic and anti-proliferative effects in the vascular smooth muscle cells, influence on angiogenesis and erythropoiesis, myocardial cytoprotection in ischemia-reperfusion injury, oxygen sensing, inhibition of platelet aggregation and blood coagulation, modification of erythrocyte microrheological properties (aggregability and deformability). Understanding of molecular mechanisms of H2S action and molecular crosstalk between H2S, NO, and CO is essential for the development of its diagnostic and therapeutic potential.

Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia less than 50% of patients remain in a long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder which requires therapy in majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first line as well as relapsed setting. Rituximab is the preferred therapy for steroid refractory wAIHA and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of the rituximab and current literature its role in management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.

: Intracellular tripeptide glutathione is an important agent of cell survival in hypoxia. Glutathione covalently binds to SH-groups of hemoglobin cysteine residues, protecting them from irreversible oxidation and changes its affinity to oxygen. Reduced glutathione (GSH) can also form a non-covalent complex with hemoglobin. Previously, we showed that hemoglobin tetramer has four noncovalent binding sites of glutathione GSH molecules inside, two of which are released during hemoglobin transition to deoxy form. In this study, we characterized the conserved cysteine residues and residues of non-covalent glutathione binding sites in the sequences of a number of hypoxia tolerant and hypoxia-sensitive mammals. The alpha subunit of all species considered was found to have no conserved cysteines, whereas the beta subunit contains Cys94 residue, which is conserved across species and whose glutathionylation changes the affinity of hemoglobin for oxygen 5-6-fold. In addition, the key residues of noncovalent glutathione binding sites in both alpha and beta subunits are absolutely conserved in all species considered, suggesting a common mechanism of hemoglobin redox regulation for both hypoxia-sensitive and hypoxia-tolerant mammals. The solvent accessibility of all HbA and HbB residues in oxy- and deoxy- forms was analyzed. The key residue betaCys94 is solvent accessible only in the deoxy form.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

In the paper, the authors generalize the notion "k-Mittag-Leffler function'', establish some integral transforms of the generalized k-Mittag-Leffler function, and derive several special and known conclusions in terms of the generalized Wright function and the generalized k-Wright function.

The formation and functioning of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, maintenance of genome stability, response to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML-bodies for their tendency to spontaneous liquid-liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs), and remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SOMYylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected.

This paper will explore analogs of groups formed by the transformations of two ropes as presented by Minh-Tam Quang Trinh.1 The two operations acting on these ropes are T and S, defined as twists and clockwise turns, respectively. These actions intertwine the ropes, creating tangles. T and S also have the ability to untangle the rope when used in certain combinations. In the two-rope case, these actions expressed as a group presentation were shown to be isomorphic to SL₂(Z). We explored the analog of these opera- tions, T and S, and conjectured the corresponding group to which they are isomorphic. Partial proofs for this conjecture are included and future work would include proving our conjecture as well as generalizing results to k ropes.

High-throughput screening technologies continues to produce large amounts of multiomics data from different populations and cell types for various diseases, such as cancer. However, analysis of such data encounters difficulties due to cancer heterogeneity, further exacerbated by human biological complexity and genomic variability. There is a need to redefine the drug discovery development pipeline, bringing an Artificial Intelligence (AI)-powered informational view that integrates relevant biological information and explores new ways to develop effective anticancer approaches. Here, we show SynPred, an interdisciplinary approach that leverages specifically designed ensembles of AI-algorithms, links omics and biophysical traits to predict synergistic anticancer drug synergy. SynPred exhibits state-of-the-art performance metrics: accuracy – 0.85, precision – 0.77, recall – 0.75, AUROC – 0.82, and F1-score - 0.76 in an independent test set. Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application available online at http://www.moreiralab.com/resources/synpred/ was constructed to predict synergistic anticancer drug combinations requiring only the upload of the two drug SMILES to be tested, allowing easy access by non-expert researchers.

Radical changes in the idea of the organization of the intracellular space that occurred in the early 2010-s made it possible to consider the formation and functioning of the so-called membrane-less organelles (MLOs) based on a single physical principle: the liquid-liquid phase separation (LLPS) of biopolymers. Weak nonspecific inter- and intramolecular interactions of disordered polymers, primarily of intrinsically disordered proteins and RNA, play a central role in the initiation and regulation of these processes. On the other hand, in some cases, the "maturation" of MLOs can be accompanied by the "liquid-gel” phase transition, where other types of interactions can play a significant role in reorganization of their structure. In this work, we conducted a bioinformatics analysis of the propensity of the proteomes of two membrane-less organelles formed in response to stress in the same compartment, nucleolus, for spontaneous phase separation and looked at their intrinsic disorder predispositions. These nucleolar MLOs, amyloid bodies (A-bodies) formed in the response to acidosis and heat shock and nuclear stress bodies (nSBs), are characterized by the partially overlapping composition, but show different functional activities and morphologies. We show that the proteomes of these nucleolar biocondensates are differently enriched in proteins, many of with high potential for spontaneous LLPS that correlates with different morphology and function of these organelles. The results of these analyses allowed us to evaluate the role of weak interactions in the formation and functioning of these important organelles.

In this work α-synuclein amyloid fibrils, formation of which is a biomarker of the Parkinson’s disease, were investigated with the use of fluorescent probe thioflavin T (ThT). Experimental conditions of the protein fibrillogenesis were chosen so that a sufficient number of continuous measurements can be performed to characterize and analyze all stages of this process. The reproducibility of fibrillogenesis and the structure of the obtained aggregates (that is a critical point for their further investigation) were proved using a wide range of physical-chemical methods. For determination of ThT—α-synuclein amyloid fibrils binding parameters sample and reference solutions were prepared with the use of equilibrium microdialysis. By absorption spectroscopy of these solutions ThT—fibrils binding mode with the binding constant about 10⁴ M⁻¹ and stoichiometry of ThT per protein molecule about 1:8 was observed. Fluorescence spectroscopy of the same solutions with the subsequent correction of the recorded fluorescence intensity on the primary inner filter effect allowed to determine another mode of ThT binding to fibrils with the binding constant about 10⁶ M⁻¹ and stoichiometry about 1:2500. Analysis of photophysical characteristics of the dye molecules bound to the sites of different binding modes allowed to assume the possible localization of these sites. Obtained differences in the ThT binding parameters to amyloid fibrils formed from α-synuclein and other amyloidogenic proteins, as well as in the photophysical characteristics of the bound dye, confirmed the hypothesis of amyloid fibrils polymorphism.

Background and Objectives: Fibrillinopathies have different phenotypic expression: Marfan- like skeleton features, MLSF; mitral valve prolapse syndrome, MVPS; MASS phenotype, M= mitral valve prolapse, MVP, A= aortic root dilation, S= skeletal features, and the second S= (cutaneous) striae; Marfan syndrome, MS. These are inherited connective tissue diseases, provoked by a mutation of the encoding gene for a protein(fibrillin 1, FBN1) which has major importance in the formation of elastic fibers.The study had the following main objectives: the correlation between disc displacement, DD( a major sign for temporomandibular joint dysfunction, TMD) on magnetic resonance imaging, MRI, and aortic Z score(a major sign for aortic root dilation) on echocardiography; the predictive value of DD towards aortic Z score. DD had 2 types of severity: DD with reduction(the mild type, DDwR) , and DD without reduction( the severe type, DDwoR). Materials and Methods: The type of fibrillinopathy was precised by clinical exam( systemic score), ophthalmic exam(for ectopia lentis), and echocardiography(aortic Z score, MVP). Medical treatment consisted in betablockers, BB(for patients with tachycardia), or angiotensin II receptor blockers, ARB. Surgical treatment was addressed to aortic root aneurysm, and severe MR. DD benefited by dental conservatory treatment, or surgical restoration.Results: DD- Z score had a powerful correlation in MASS(Rho= 0.787, p< 0.01), and in MS patients(Rho=0.819, p< 0.01). For the entire sample, both DDwR- Z score, and DDwoR- Z score had a moderate correlation(Rho= 0.469, and respectively 0.669). Muchmore, DD was an important predictor for Z score. DDwoR had a double power of prediction for Z score, comparative with DDwR(B coefficient= 1.661 for DDwR, and 3.281 for DDwoR). Conclusions: TMD had a powerful correlation with aortic root dilation, in MASS, and MS patients from the sample. Likewise, TMD was a major predictor for aortic root dilation, in the entire sample. We can utilize in clinical practice, an extracardiac finding, TMD, obtained by a non-invasive technique, MRI, for cardiac severity stratification of fibrillinopathies.

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K⁺ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K⁺ ions are at least 10,000 times more permeant than Na⁺ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na⁺ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

Abstract The aim of the present review is to discuss the roles of vitamin K and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. Adequate vitamin K status is required for carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanism, such as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through dietary adequacy of vitamin K (phylloquinone or menaquinone). Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3 we find that an adequate supply of vitamin K on top of an optimal vitamin D status seems to add to the benefit for maintaining bone health. More research related to synergism and possible mechanisms of vitamins D3 and K interaction in bone health is needed.

:Peat substrate is made from peat from drained peatlands, which is a limited resource. A realistic estimate is that 50% of the world’s wetlands have been lost. Peat is used in horticulture, especially for the cultivation of vegetables in greenhouses. The consequences of peatland exploitation are an in-crease in the greenhouse effect and a decrease in carbon stocks. Wood fiber can be used as an al-ternative to peat. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the growing container. This study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) variety “Dirigent H” developed in the Netherlands, were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) con-ventional fertilization (CF); (2) N13; (3) N23; (4) N30. The experiment was carried out in three repli-cations. As the amount of wood fiber increased, the humidity and pH of the growing medium in-creased. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in 50/50 and 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat sub-strate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

The objective of this study was aimed to study the sensory processes of the “human-computer interaction” model when classifying visual images with an incomplete set of signs based on the analysis of early, middle, late and slow components of event-related potentials (ERPs). 26 healthy subjects (men) aged 20-22 years were investigated. ERPs in 19 monopolar sites according to the 10/20 system were recorded. Discriminant and factor analysis were applied. The component N450 is the most specialized indicator of the perception of unrecognizable (oddball) visual images. The amplitude of the ultra-late components N750 and N900 is also higher under conditions of presentation of the oddball image, regardless of the location of the registration points. The results of the study are discussed in the light of the paradigm of the P300 wave application in brain-computer interface systems, as well as with the peculiarities in brain pathology. Promising directions for the development of studies of the “Brain Computer Interface” (BCI) P300 systems are to increase the throughput of information flows. To extend the application of the P300 ERPs to multiple modalities, the underlying physiological mechanisms and responses of the brain for a particular sensory system and mental function must be carefully examined.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary & safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

The article deals with issues related to social and moral education and development of preschool children. The theoretical understanding of the current state of this field is reflected in the modern normative documents "On education in the Russian Federation", the state educational standards. Analysis of theoretical and practice-oriented research in this area shows that the phrase "moral education" today is gradually replaced by "social and moral education", "social and moral development". This trend is found in preschool pedagogy (work L. V. Abramova, R. S. Bure, S. M. Zyryanova, N.A. Karataeva, G. M. Kiseleva, I. F. Sleptsova, etc.). It is the study of social and moral representations of preschool children that many relevant diagnostic methods are aimed at: to explain the actions of children, their relationship with each other and adults, to assess these actions (i.e. to correlate the situation with the moral norm). The presented research was based on the method of research of moral representations of children of senior preschool age, developed by G. A. Uruntaeva and Yu.A. Afon'kina. The analysis of the results showed that children of senior preschool age willingly included in the retelling of the actions described in the situation, but find it difficult to assess what is happening from a moral point of view. It is obvious that psychological and pedagogical work is necessary in this direction, taking into account the age characteristics of children, as well as social and moral guidelines relevant to the current situation of development of society.

Sudden cardiac arrest (SAC) is a leading cause of mortality. In recent years, though, many lives have been saved through the use of defibrillators by random bystanders. As a result, defibrillators have been popping up in various locations. In this work we propose a state mandate demanding the presence of a defibrillator at every pharmacy store and argue that it could greatly enhance and augment the impact of the defibrillator network. We support our claim via detailed calculations of the immediate (a defibrillator readily available) and partial (a defibrillator available at a reasonable distance) population coverage achievable by the implementation of our proposal, taking the Argolis area in Peloponnese Greece as a case study. Our findings indicate that, in addition to other benefits, the use of pharmacies to establish a defibrillator network could bring an eight-fold increase in the immediate population coverage of defibrillators and would provide immediate / partial access to a defibrillator to 18 / 24 incidents of SCA per year that would otherwise lead to death, potentially leading to the saving of numerous lives. Alternative scenaria are also discussed.

The intricacies of translational strategies make this stage of the implementation of genetic information one of the most difficult to understand and, at the same time, perhaps the most interesting. It also becomes clear that all this variety of strategies is not just a consequence of a long evolutionary history but is of paramount importance for fine-tuning gene expression and metabolic modulation. This is especially true for those organisms that demonstrate predominantly biochemical and physiological reactions with a lack of behavioural ones. Plants are just such a group of organisms. Overcoming unfavourable environmental conditions occupies a key place in plant physiology. This is especially true with the changing conditions of global warming and the irretrievable loss or depletion of natural ecosystems. Conceptually, the response of plants to abiotic stress is a set of complex and intricate strategies. This is dictated both by a variety of abiotic factors that provoke stressful conditions and by a variety of molecular genetic mechanisms that make it possible to fine-tune the metabolic pathways through which the plant organism overcomes non-standard and non-optimal conditions. In the presented review, we tried to focus on the state-of-the-art in the field of translational regulation in plants under abiotic stress conditions. Various regulatory elements and patterns are considered in relative chronological order. We also considered it necessary to pay attention to key high-performance methods for studying the dynamics of genetic information at the stage of translation.

Stress is one of the important factors affecting the growth and development of plants. In recent years, a large body of data on transcriptional changes in response to stress in plants has been obtained. Despite the fact that the important role of the regulation of translation in response to stress has been proven in plants, knowledge in this area remains extremely scarce. In this review, we focused on mRNA translation in the cytoplasm of higher plants. Most of the current research on the effects of translation has been done in yeast and mammalian systems. Translation factors and mechanisms are mostly conserved among eukaryotes; however, some differences are known to exist among plants. A comprehensive understanding of the complex apparatus of translation and its regulation in plants is required. In this work, we have tried to update modern ideas about the regulation of translation under conditions of abiotic stress.

In interepidemic periods, a sapronoses typically employs a variety of mechanisms for maintaining viability of its causative agent in terrestrial parasitic systems, associated with different adaptive strategies utilized by its populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses use resistant cell forms, which is a viable but nonculturable (VBNC) state, and persistence. Implementation of these strategies is conditioned by effects of various stress factors of the habitat and is characterized by decreased metabolism, alteration of the morphology and physiology of bacterial cell, and cessation of its replication. It is important that the resistant forms of cells retain virulence and, as favorable conditions come, turn back into the active vegetative form again. The discovery of the genetic modules of bacterial toxin–antitoxin systems in recent years has made it possible to identify a number of complicated regulatory molecular mechanisms responsible for maintaining the pathogenic potential of resistant forms of causative agents of natural-focus sapronoses in interepidemic periods.

This article presents the results of research on the influence of polymetallic dust aerial emissions on the pollution levels in the soil and plants by heavy metals which have been under impact of the “Severonickel” smelter complex on the Kola peninsula (Russia) for many years. Research using soil- and bio-indicators was carried out at fixed measuring points in the years 1980-1999 (high aerotechnogenic emissions) and 2000-2019 (low aerotechnogenic emissions). The organic horizon (forest litter) of the Al-Fe-humus podzol, leaves of Vaccinium myrtillus L., V. vitis-idaea L., V. uliginosum L., Empetrum hermaphroditum Hagerup and one-year old Scots pine needles Pinus sylvestris L. as well as tree rings of Pinus sylvestris L. were used for bioindication research. The content of heavy metals was determined by the AAS method. During these time periods, the volume of atmospheric emissions of sulfur dioxide decreased 5 fold, polymetallic dust by 3.5 times, while the level of forest litter pollution by heavy metals in the buffer zone increased by 2 times, and did not change significantly in the impact zone. The decrease in atmospheric emissions of pollutants led to a 1.5- fold increase in the width of the annual rings of pine trunks in the impact zone, while in the buffer zone the differences were insignificant. At present, the content of Ni and Cu in the leaves of the wild dwarf-shrubs and pine needles in the impact zone has decreased by 5 times compared with 1980-1999 due to a decrease in polymetallic dust on the leaf surface.

Recent data suggest that K-Ras4B (hereafter K-Ras) can drive cancer cell stemness via calmodulin (CaM)-dependent, non-canonical Wnt-signalling. Here we examined whether another Ca2+-binding protein, the CaM-related centrin1, binds to K-Ras and could mediate some K-Ras functions that were previously ascribed to CaM. While CaM and centrin1 appear to distinguish between peptides that were derived from their classical targets, they both bind to K-Ras in cells. Cellular BRET-data suggest that CaM engages more with K-Ras than centrin1 and that the interaction with the C-terminal membrane anchor of K-Ras is sufficient for this. Surprisingly, binding of neither K-Ras nor its membrane anchor alone to CaM or centrin1 is sensitive to inhibition of prenylation. In support of an involvement of the G-domain of K-Ras in cellular complexes with these Ca2+-binding proteins, we find that oncogenic K-RasG12V displays increased engagement with both CaM and centrin1. This is abrogated by addition of the D38A effector-site mutation, suggesting that K-RasG12V is held together with CaM or centrin1 in complexes with effectors. When treated with CaM-inhibitors the BRET-interaction of K-RasG12V with centrin1 was also disrupted in the low micromolar range, comparable to that with CaM. While CaM predominates in regulating functional membrane anchorage of K-Ras, it has a very similar co-distribution with centrin1 on mitotic organelles. Given these results, a significant overlap of the CaM- and centrin1-dependent functions of K-Ras is suggested.

With increasing interest in the use of additive manufacturing techniques in the construction industry, static rheological properties of fresh concrete have necessarily come into focus. In particular, the knowledge and control of static yield stress (SYS) and its development over time are crucial for mastering formwork-free construction, e.g. by means of layered extrusion. Furthermore, solid understanding of the influences of various concrete constituents on the initial SYS of the mixture and the structural build-up rate is required for purposeful material design. This contribution is concentrated on the effect of aggregates on these rheological parameters. The volume fraction of aggregates was varied in the range of 35 to 55 % by volume under condition of constant total surface area of the particles. The total surface area per unit volume of cement paste was equal to 5.00, 7.25 and 10.00 m²/l, conditioned on the constant volume fraction of aggregates. Both variations were enabled by changing the particle size distributions of the aggregates while holding the cement paste composition constant for all concrete mixtures. To characterise the SYS and the structural build-up, constant shear rate tests with a vane-geometry rotational rheometer were performed. It was found that in the ranges under investigation the variation in volume fraction had a more pronounced effect on the static rheological properties of concrete than did the variation in surface area. An accurate mathematical description of the relationship between the initial SYS of concrete and the relative volume fraction of aggregate based on the Chateau-Ovarlez-Trung model was proposed. Challenges in deriving a similar relationship for the structural build-up rate of concrete were highlighted.

Abstract: A new method for constructing exact solutions of the General Relativity equations for a dusty matter with fractal property is proposed. This method allows to find the solution of the GR-equations in terms of matter velocities : the connection coefficients and the Ricci tensor of space-time are expressed in terms of matter velocities; the metric tensor and the matter density are found as functions of velocity from the GR-equations. The connection coefficients and the Ricci tensor are invariant with respect to the discrete scaling transformation of velocity , where is constant. Therefore, the found solution can be used to simulate the fractal properties of the cosmic web in terms of matter velocities. This solution includes isotropic and anisotropic distributions of matter density. In an isotropic case, there is a class of exact solutions including both the well-known Friedmann’s solution and a solution with a periodic distribution of the matter density in space. This last solution may be used to simulate the quasi-periodic distribution of matter in the cosmic web. It is possible that, the cosmic web and its fractal properties are the space-time primary properties. These properties are described with a deformation tensor of the space-time.

Huge filaments with scales from several hundred megaparsecs to gigaparsecs are detected in the distribution of galaxies and clusters, quasars, gamma-bursters. The hypothesis on the nature of the huge filaments as regions of space-time deformation is proposed. An anisotropic deformation of the local region is described by the strain tensor, it depends on the velocities of matter. Galaxies get an extra velocity in the region, which leads to the formation of filamentary structures. The class of exact solution of the GR equations is constructed by introducing the special definition of the Christoffel symbols as function of the velocity of matter. With a definition of these symbols, the motion matter equation turns into identity. For the sake of simplicity, an ideal fluid is considered.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

The cruise ship industry has become a well-implemented industry in the Baltic Sea area, and each year, the number of cruise ship passengers rises steadily. Efficient waste management in cruising ports around the Baltic Sea is a crucial element in minimizing environmental impacts. This research involves the four selected ports of Copenhagen, Helsinki, Stockholm and Tallinn. The study applies statistics and interview data to the analysis of waste management systems for cruise ship-generated waste. The interview data involves 14 executives and professionals responsible for environmental issues and decision making in their respective ports. The interviews highlighted the need for standardized environmental legislation and related procedures, which would result in coherent measurement systems. These systems would enable transparent environmental monitoring, thus maintaining the ports’ competitiveness. A common environmental legislation would support the emerging waste management system for the whole Baltic Sea area. We suggest that ports should focus on handling specific types of wastes and collaborate as a spatial network. Specialization to allow discharge of certain fractions of waste is essential. The paper concludes by addressing demands for future research, particularly vessel- and customer behavior focused studies.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Nearest-neighbour clustering is a simple yet powerful machine learning algorithm that finds natural application in the decoding of signals in classical optical-fibre communication systems. Quantum k-means clustering promises a speed-up over the classical k-means algorithm; however, it has been shown to currently not provide this speed-up for decoding optical-fibre signals due to the embedding of classical data, which introduces inaccuracies and slowdowns. Although still not achieving an exponential speed-up for NISQ implementations, this work proposes the generalised inverse stereographic projection as an improved embedding into the Bloch sphere for quantum distance estimation in k-nearest-neighbour clustering, which allows us to get closer to the classical performance. We also use the generalised inverse stereographic projection to develop an analogous classical clustering algorithm and benchmark its accuracy, runtime and convergence for decoding real-world experimental optical-fibre communication data. This proposed `quantum-inspired' algorithm provides an improvement in both the accuracy and convergence rate with respect to the k-means algorithm. Hence, this work presents two main contributions. Firstly, we propose the general inverse stereographic projection into the Bloch sphere as a better embedding for quantum machine learning algorithms; here, we use the problem of clustering quadrature amplitude modulated optical-fibre signals as an example. Secondly, as a purely classical contribution inspired by the first contribution, we propose and benchmark the use of the general inverse stereographic projection and spherical centroid for clustering optical-fibre signals, showing that optimizing the radius yields a consistent improvement in accuracy and convergence rate.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Clustering, or otherwise known as cluster analysis, is a learning problem that takes place without any human supervision. This technique has often been utilized, much efficiently, in data analysis, and serves for observing and identifying interesting, useful, or desired patterns in the said data. The clustering technique functions by performing a structured division of the data involved, in similar objects based on the characteristics that it identifies. This process results in the formation of groups, and each group that is formed, is called a cluster. A single said cluster consists of objects from the data, that have similarities among other objects found in the same cluster, and resemble differences when compared to objects identified from the data that now exist in other clusters. The process of clustering is very significant in various aspects of data analysis, as it determines and presents the intrinsic grouping of objects present in the data, based on their attributes, in a batch of unlabeled raw data. A textbook or otherwise said, good criteria, does not exist in this method of cluster analysis. That is because this process is so different and so customizable for every user, that needs it in his/her various and different needs. There is no outright best clustering algorithm, as it massively depends on the user’s scenario and needs. This paper is intended to compare and study two different clustering algorithms. The algorithms under investigation are k-mean and mean shift. These algorithms are compared according to the following factors: time complexity, training, prediction performance and accuracy of the clustering algorithms.

For each $t\in(-1,1)$, exact values of the least upper bounds $$ H(t)=\sup_{\E X=t,\,\E X^2=1} \frac{\E\abs{X}^3}{\E \abs{X-t}^3},\quad \sup_{\E X=t,\,\E X^2=1} \frac{L_1(X)}{L_1(X-t)} $$ are obtained, where $L_1(X)=\E|X|^3/(\E X^2)^{3/2}$ is the non-cental Lyapunov ratio. It is demonstrated that these values are attained only at two-point distributions. As a corollary, S.\,Shorgin's conjecture is proved that states that the exact value is $$ \sup\frac{L_1(X)}{L_1(X-\E X)}= \frac{\sqrt{17 + 7\sqrt7}}{4} = 1.4899\ldots, $$ where the supremum is taken over all non-degenerate distributions of the random variable $X$ with the finite third moment. Also, in terms of the central Lyapunov ratio $L_1(X-\E X)$, an analog of the Berry--Esseen inequality is proved for Poisson random sums of independent identically distributed random variables with the constant $$ 0.3031\cdot H\left(\frac{\E X}{\sqrt{\E X^2}}\right) \left(1-\frac{(\E X)^2}{\E X^2}\right)^{3/2} \le 0.3031\cdot \frac{\sqrt{17 + 7\sqrt7}}{4}<0.4517.$$ where $\Law(X)$ is the common distribution of the summands.

Sugarcane (Saccharum spp.) is a crop of great industrial and alimentary importance, essential for the production of numerous products. Given its significance, genetic improvement programs exist that involve a rigorous study process, from material selection to the development of new varieties, requiring at least seven selection phases. This study modeled the growth curve of the sucrose percentage (SP) in 33 hybrids and six control varieties (MEX 69-290, ITV 92-1424, CP 72-2086, COLMEX 94-8, COLMEX 95-27, RB 85-5113) during the plant and ratoon periods in the experimental fields of the Melchor Ocampo Sugar Mill, Jalisco, Mexico. For clustering the materials, k-means, k-medoids, and Density-based spatial clustering of applications with noise (DBSCAN) algorithms were used, considering four maturity types among the control varieties. The DBSCAN algorithm proved to be the most effective, as the means between groups were not statistically equal. The hybrids identified as candidates for subsequent phases due to their high SP were COSTA JAL, ATEMEX 99-48, ATEMEX 99-1, ATEMEX 99-61, MEX 70-486, MEX 80-1521, ITSAMEX 07-44814, ITSAMEX 06-6395, and ITSAMEX 07-1903. These results are crucial for improving the productivity and sustainability of the crop, with significant implications for the sugar industry.

In the particular configuration of the scalar field K-essence in the Wheeler-DeWitt quantum equation, for some age in the Bianchi type I anisotropic cosmological model, a fractional differential equation for the scalar field arises naturally. The order of the fractional differential equation is $\beta=\frac{2\alpha}{2\alpha - 1}$. This fractional equation belongs to different intervals, depending on the value of the barotropic parameter; when $\omega_{X} \in [0,1]$, the order belongs to the interval $1\leq \beta \leq 2$, and when $\omega_{X}\in[-1,0)$, the order belongs to the interval $0<\beta \leq 1$. In the quantum scheme, we introduce the factor ordering problem in the variables $(\Omega,\phi)$ and its corresponding momenta $(\Pi_\Omega, \Pi_\phi)$, obtaining a linear fractional differential equation with variable coefficients in the scalar field equation, then the solution is found using a fractional power series expansion. The corresponding quantum solutions are also given. We found the classical solution in the usual gauge N obtained in the Hamiltonian formalism and without a gauge. In the last case, the general solution is presented in a transformed time $T(\tau)$, however in the dust era we found a closed solution in the gauge time $\tau$.

The main objective of this paper is to introduce k-fractional derivative operator by using the definition of k-beta function. We establish some results related to the newly defined fractional operator such as Mellin transform and relations to k-hypergeometric and k-Appell's functions. Also, we investigate the k-fractional derivative of k-Mittag-Leffler and Wright hypergeometric functions.

This article explores the question of the rate of digital progress in the context of the labor market. Specific features of the current situation are indicated: temporality of socio-technological transformations, which is becoming less and less compatible with the harmonious development of man and society; the pace at which machines acquire intelligence; total devaluation of mental labor; unresolved issue of the role of man in the world of intelligent machines; the criticality of the problem of the labor market, due to its global nature, social significance and the rate of socio-technological changes. It is emphasized that these circumstances in the short term threaten the sustainable development of the global society, whose reactions to the transformation of technological and socio-economic infrastructure are significantly lagging behind. It is concluded that there is an urgent need to strengthen social responsibility, determined by the new ethics of relations between humans and machines with AI, supplemented by the primacy of the dignity of the social role of humans. The authors point out the urgent need to revise ideas about work as the main purpose of a person and about realization in the profession as the main factor that determines the self-esteem of an individual and his social status.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

:. Background and Objectives: Pulmonary embolism, PE, incidence had been increasing in the last ten years. Computed thoracic pulmonary angiography, CTPA, had a major role in confirming PE di-agnosis.The main purpose of the study was to establish the prognostic value of a CTPA parameter: pulmonary artery obstruction index, PAOI, for PE risk assessment . A second objective of the re-search was to investigate the predictive accuracy of biomarkers (D-dimer, and cardiac Troponin T, c-TnT ), and PAOI, in 7-day mortality. The third objective of the study was the relationship between PAOI, and these biomarkers, in different etiologies of PE. Materials and Methods: The study com-prised 109 patients with PE, hospitalized, and treated between February 2021, and August 2022. They had different etiologies: deep vein thrombosis, DVT; persistent atrial fibrillation, AF; chronic obstructive pulmonary disease, COPD, exacerbation; Covid; and cancers. The investigations were the following: clinical examination; D-dimer testing, as a mandatory method for PE suspicion( values ≥ 500 µg/L were highly suggestive for PE); c-TnT , as a marker of myocardial injury(values ≥ 14 ng/L were abnormal); CTPA, with right ventricle dysfunction, RVD, signs, and PAOI. Treat-ments were according to PE risk: systemic thrombolysis (in high risk , and hemodynamic instability); low weight molecular heparins, LWMH, after systemic thrombolysis, or in high risk PE, with he-modynamic stability; direct oral anticoagulants, DOAC (in low, and intermediate risk). Results: The relationship PAOI- D-dimer, and PAOI- c-TnT, had very strong statistical correlation, for the entire sample, and for DVT, AF, COPD, Covid subgroups ( Rho = 0.815-0.982). PAOI had a high predic-tive accuracy for intermediate , and high risk together (area under curve, AUC=0.948), and high risk PE (AUC= 0.993). For 7-day mortality, D-dimer , and c-TnT had high predictive accura-cy(AUC=0.921, and 0.979). PAOI had statistical significance for 7-day mortality in Covid (p=0.045), and cancer (p=0.038) patients. Conclusions: PAOI was an important tool for PE risk as-sessment. D-dimer , and c-TnT were valuable predictors, for 7-day mortality in PE. PAOI, and D-dimer; PAOI, and c-TnT were strongly correlated, for the entire PE sample, and for DVT, AF, COPD, and Covid patients.

The powdered sorbents were applied in a batch system under "static" conditions and showed a much higher adsorption capacity than the granular one. These type of sorbents are more suitable for small quantities of water with a high concentration of arsenic. The possibilities of using all the tested methods for arsenic removal have been evaluated, and a scheme of the technological process has been proposed.

We describe our investigations of the surface physicochemical and biological properties of polylactic acid modified by silver, argon and carbon ion implantation to doses of 1 × 10¹⁴, 1 × 10¹⁵ and 1 × 10¹⁶ ion/cm² at energies of 20 keV (for C and Ar) and 40 keV (for Ag). X-ray analysis shows enhancement of coherent scattering regions and lattice constant increase after ion implantation. Secondary electron mass-spectrometry indicates that Ag concentration in the subsurface layer is less than 80%, but at a depth of 500 nm does not exceed 1–2%. The silver forms metal particles in the subsurface layer rather than making additional chemical bonds with polymer atoms. Atomic force microscopy reveals that the higher the irradiation dose the larger the surface roughness of the samples. Ag-irradiated samples implanted to a dose of 1 × 10¹⁶ ions/cm² have the highest roughness, 190 nm. Our investigation of the cytotoxicity of two individual donor macrophages shows that Ag-implanted polylactic acid has no negative impact on immune system cells and could be a promising material for biomedical application.

Nanoporous membranes promise energy-efficient water desalination. Hexagonal boron nitride (h-BN), like graphene, exhibits outstanding physical and chemical properties, making it a promising candidate for water treatment. We employed Car–Parrinello molecular dynamics simulations to establish accurate modeling of Na+ and Cl- permeation through hydrogen passivated nanopores in graphene and h-BN membranes. In these complex systems the classical potentials cannot properly account for the physics at play. We demonstrate that ion separation works well for the h-BN by imposing a barrier of 0.13 eV and 0.24 eV for Na+ and Cl- permeation respectively, compared to the graphene where the Cl- ion faces a negative barrier of 0.68 eV and is prone toward blockade and Na+ permeation is associated with a slightly negative barrier of 0.03 eV. From the change in the solvation shell, we get the following trend: Na/h-BN > Na/G > Cl/G > Cl/h-BN. We argue that the trend in the permeation barrier changes to Cl-h-BN > Na-h-BN > Na-G > Cl-G due to a combination of several interactions, including the distortion of the water network induced by the ions, the ion-water interaction, and the ion-nanopore interaction. Overall, the desalination performance of h-BN surpasses that of their graphene counterparts.

The visualization of hyperspectral images in display devices, having RGB colour composition channels is quite difficult due to the high dimensionality of these images. Thus, principal component analysis has been used as a dimensionality reduction algorithm to reduce information loss, by creating uncorrelated features. To classify regions in the hyperspectral images, K-means clustering has been used to form clusters/regions. These two algorithms have been implemented on the three datasets imaged by AVIRIS and ROSIS sensors.

Concept Knowledge (C-K) theory has been used in engineering and science-based research for more than a decade. Design of an Information Technology (IT) artefact is mostly pragmatic in nature. Design Science Research (DSR) methodology applied and studied in many Information Systems (IS) research. Many sub design decisions involved through the design of an IT artefact from a concept (idea) to a working prototype. A DSR artefact is based on a combination of decisions made during several sub-design stages. Artefacts are built based on the selection of elements in each sub-design space. Recording the design decisions on each sub-design space would be beneficial for future researchers. By knowing the design decisions on each sub-design space, researchers would be able to try different combinations of the design. C-K theory provides the ability to capture the design processes’ several sub-design spaces. In this paper, we discuss the DSR research methodology by looking at the stages proposed in the literature, and the application of C-K theory in an IT-based DSR. This paper also proposed a C-K theory-based protocol called Concept Tree for tracking and reporting artefact design steps. The application of C-K theory in DSR is exhibited using the implementation of the Concept Tree for a prototype design IT artefact.

In this paper, some convexity properties and some inequalities for the (p,k)-analogue of the Gamma function, Г_p,k(x) are given. In particular, a (p,k)-analogue of the celebrated Bohr-Mollerup theorem is given. Furthermore, a (p,k)-analogue of the Riemann zeta function, ζ_p,k(x) is introduced and some associated inequalities are derived. The established results provide the (p,k)-generalizations of some known results concerning the classical Gamma function.

Motivated by important applications to the analysis of complex noise-induced phenomena, a problem of the constructive description of randomly forced equilibria for nonlinear systems with multiplicative noise is considered. Using apparatus of the first approximation systems, we construct an approximation of mean square deviations that explicitly takes into account the presence of multiplicative noise. This approximation is compared with the widely used approximation based on the stochastic sensitivity technique. The general mathematical results are illustrated with the example of the van der Pol oscillator with hard excitement.

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close to the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li embedded into various matrices. The one-dimensional lattice built of the identical metallic micro-elements m_eff connected by ideal springs k_1 representing various media such as polydimethylsiloxane and soda-lime glass is treated. The optical and acoustical branches of longitudinal modes propagating through the lattice are elucidated for various ratios ω_1/ω_p . The 1D lattice built of the thin metallic wires giving rise to the low frequency plasmons is treated. The possibility of the anti-resonant propagation, strengthening the effect of the negative mass occurring under  = p = 1 is addressed.

Voronoi entropy for the random patterns and patterns demonstrating various elements of symmetry are calculated. The symmetric patterns are characterized by the values of the Voronoi entropy very close to those inherent to random ones. This contradicts the idea that the Voronoi entropy quantifies the ordering of the seed points, constituting the pattern. The extension of the Shannon-like formula embracing symmetric patterns is suggested. Analysis of Voronoi diagrams enables revealing of the elements of symmetry of the pattern.

This paper presents a new semi-explicit algorithm for parameters estimation in a time-fractional generalization of dual-phase-lag heat conduction model with the Caputo fractional derivatives. It is shown that this model can be derived from a general linear constitutive relation for the heat transfer by conduction when the heat conduction relaxation kernel contains the Mittag-Leffler function. The model can be used to describe heat conduction phenomena in a material with power-law memory. The proposed algorithm of parameters estimation is based on the time integral characteristics method. The explicit representations of the thermal diffusivity and the fractional analogues of the thermal relaxation time and the thermal retardation are obtained via a Laplace transform of the temperature field and utilized in the algorithm. An implicit relation is derived for the order of fractional differentiation. In the algorithm, this relation is resolved numerically. An example illustrates the proposed technique.

To meet the dual-carbon objective, China's economy needs to move from a carbon-intensive to a green economy. Green technology innovation and renewable energy development are key to promoting green economic growth. The study uses 2010–2022 provincial panel data from 30 Chinese provinces. The super-efficient SBM model measures the province's green economic growth index. A panel fixed-effects model is used to experimentally evaluate how green technology innovation and renewable energy development affect green economic growth. Green financing moderates and a panel threshold model tests the threshold effect of renewable energy development on green economic growth. The results demonstrate that (1) China's green economic growth is rising and has a "U" shape. (2) all selected variables significantly impact green economic growth. However, population density, government intervention, and industrial structure are inversely associated with GEG. Green economic growth is significantly boosted by the moderate role of green finance in the development of renewable energy and green technological innovation. (3) Renewable energy development has a single threshold non-linear effect on green economic growth, depending on its development level and green technological innovation. Considering China's current condition and research findings, this study examines the green energy transition to promote green economic growth and high-quality economic development. Meanwhile, puts forward some important policy recommendations.

The current study aims to produce a material that has a dual effect of healing and anti-inflammatory. For this target k-carrageenan/polyacrylamide hydrogel film loaded with cetrimide (k-CAR/PAAm/CI) was performed by manual casting technique. Definite concentrations of k-CAR and AAm was heated at 80°C for 2 hours, CI and glycerol were added. The solution was cast without using initiator and cross-linker. The reaction of the sulfonic acid group -SO3H of k-CAR with -CONH2 group of PAAm lead to the formation of a sulfonamide (-SO2NH-) linkage. The characteristics of the produced films were investigated by FTIR, TGA, contact angle, and mechanical properties. Improvement in the thermal stability was performed in k-CAR/PAAm/CI2 film containing 1.5% CI compared to the film has 0.5% CI (k-CAR/PAAm/CI1). The contact angle measurement proved the films are hydrophobic that enhanced by increasing CI content. The tensile strength and elongation percent values are considered adequate for materials used in wound care. k-CAR/PAAm/CI2 (1.5% CI) film showed superior antimicrobial activity against P. aeruginosa, moderate activity against S. aureus, and low activity against E. coli. The film k-CAR/PAAm/CI2 was effectively inhibiting the heat-induced hemolysis and may offer a promising approach for the development of effective wound dressings.

The recyclability of polystyrene, acrylonitrile butadiene styrene, polystyrene and polyvinylchloride waste and using them as a source for 3D printing were studied. Filaments of about 3 mm in diameter were extruded successfully with a small-size extruder. The processed filaments were tested on a broad range of parameters - glass transition temperature, tensile properties and a pyrolysis scenario were obtained. The measured parameters were compared with parameters of virgin counterparts presented in the literature. In order to estimate the toxicity of the recycled material, elemental analysis of the samples was done.

For this research we are selected three indicators of wheat: yield (t/ha), producer price (USD/t) and share of the harvested area under wheat in relation to the total land area of country (%). The mentioned indicators were analyzed for the period 2006-2021 in thirty-two European countries. The purpose of the research is to determine which of the mentioned indicators achieve average annual growth/decrease rates, what is the correlation between them, how European countries are grouped with their similarities and differences. The research examines the impact of the COVID-19 pandemic on the mentioned indicators in a two time phases: Phase I, before the pandemic (2006-2019); Phase II, during the pandemic (2020-2021). The methodological approach to the research topic involved the application of descriptive statistics, as the method of principal components analysis (abbr. PCA) with graphics. A positive correlation exists only between the yield of wheat and the share of the harvested area under wheat in the total area of the land (0.291). PCA method showed that countries are grouped differently depending on the observed indicator and the analyzed time phase.

This paper is focused on the analysis of methods used to assess effectiveness and efficiency of the occupational safety and health management system (OSHMS) in a company. It reviews current Russian and international occupational safety and health standards. The paper details the method outlined in International Standard GOST 12.0.230.3-2016 “Occupational safety standards system. Management systems for occupational safety. Evaluation of effectiveness and efficiency” based on the data collected during the external audit of OSHMS function efficiency in a Russian mining company. Effectiveness and efficiency indicators were determined, and a generalized desirability coefficient was calculated. Weaknesses of the method proposed in GOST 12.0.230.3-2016 were identified and mathematical and linguistic solutions were proposed to improve it. Harrington function was used to determine a numerical and linguistic score. The performed calculation demonstrated that the company needed strategic management decisions to improve the current situation. Practical approaches were offered to enhance the company's systems-based occupational safety and health performance..

The modern paradigm of studying the processes of carcinogenesis and vital activity of tumor tissues implies increased attention to constituents of tumor microenvironment (TME) and their interactions. These interactions between the cells in TME can be mediated via protein junctions of different types. Connexins (Cnxs) are one of the major contributors to intercellular communication. They form gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc. between neighboring tumor cells as well as between tumor and stromal cells. Cnx hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, Cnxs were reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. Pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization and functionality as well as channel assembly and non-channel functions. In this review we have summarized the data on the Cnxs contribution in TME and to the cancer initiation and progression.

There are experimental evidences that chronic social defeat stress is accompanied by development of anxiety- and depression-like state as well as downregulation of serotonergic genes in the midbrain raphe nuclei of male mice. The study was aimed at investigating the effect of chronic lithium chloride (LiCl) administrations on anxiety behavior and the expression of serotonergic genes in the midbrain raphe nuclei of affected mice. The pronounced anxiety in male mice was caused by chronic social defeat stress in daily agonistic interactions. After 6 days of social stress, defeated mice were treated with saline or LiCl (100 mg/kg, i.p. two weeks) against the background of continuing agonistic interactions. The level of anxiety was assessed using behavioral tests. The effect of chronic treatment with LiCl on the expression of serotonergic genes in the midbrain rapher nuclei was also studied. Mild anxiolytic effects of LiCl were found on communication in the partition test. Anxiogenic-like effects assessed using the elevated plus-maze and social interaction tests were found. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei. The effects of chronic LiCl treatment depends on the method of treatment, psychoemotional state, and experimental context (tests).

Serine proteases regulate cell functions through G protein-coupled protease-activated receptors (PARs). Cleavage of one peptide bond of the receptor amino terminus results in the formation of a new N-terminus ("tethered ligand") that can specifically interact with the second extracellular loop of the PAR receptor and activate it. Activation of PAR1 by thrombin (canonical agonist) and activated protein C (APC, noncanonical agonist) was described as biased agonism. Here we have supposed that synthetic peptide analogues to the PAR1 tethered ligand liberated by APC could have neuroprotective effects like APC. To verify this hypothesis a model of the ischemic brain impairment based on glutamate (Glu) excitotoxicity in primary neuronal cultures of neonatal rats has been used. It was shown that nanopeptide NPNDKYEPF-NH2 (AP9) effectively reduced the neuronal death induced by Glu. The influence of AP9 on cell survival was comparable to that of APC. Both APC and AP9 reduced the dysregulation of intracellular calcium homeostasis in cultured neurons induced by excitotoxic Glu (100 µM) or NMDA (200 µM) concentrations. PAR1 agonist synthetic peptides might be a noncanonial PAR1-agonist and a basis of novel neuroprotective drugs for disorders related to Glu excitotoxicity such as brain ischemia, trauma and some neurodegenerative diseases.

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.

While lidar-based forest inventory methods have been widely demonstrated, prediction of tree diameters with lidar is not well understood. The performance metrics typically used in studies for prediction of diameters can be difficult to interpret and may not support comparative inferences between sampling designs or study areas. We evaluate a variety of lidar and k nearest neighbor (k-NN) strategies for prediction of tree diameter distributions using two indices which are easier to interpret and compare. The indices are based on the coefficient of determination (R²), and root mean square deviation (RMSD). These indices facilitate comparisons with alternative (non-lidar) inventory strategies, and with other project areas. We evaluate k nearest neighbors (k-NN) dbh density (relative frequency by dbh class) prediction strategies with lidar for 190 training plots distribute across the 800 km² Savannah River Site in South Carolina, USA. We evaluate the performance of k-NN with respect to distance metrics, number of neighbors, predictor sets, and response sets. Amongst the examined strategies we found Mahalanobis distance with k = 3 neighbors performed best according to a number of criteria.

Topological interlocking assembly (TIA) and computational architecture treat form as an emergent property of a material system, where the final shape results from the interplay of geometries and geometric interdependencies influenced by material, structural, and fabrication constraints. This paper posits that TIA is an ideal pedagogical tool for introducing students to computational architecture, its theoretical foundations and design principles. Specifically, defining TIA as a material system provides a robust educational approach for engaging students with computation, fostering design processes through bottom-up, hands-on investigations and procedural logic, understanding generative geometric rules, and exploring the flexibility of parametric variations. The methodology is illustrated through a Design Workshop and study unit from the Bachelor’s and Master’s programs at the Faculty for the Built Environment, University of Malta. The paper presents four investigations of defining a material system based on TIA - of tetrahedra, cones, octahedra, and osteomorphic blocks—as case studies to demonstrate how these exercises introduce students to computational thinking, parametric design, and fabrication techniques. Finally, the paper discusses the advantages and limitations of this pedagogical methodology.

This study delves into the impact of artificial intelligence on students’ learning.The paper pioneers the use of kmeans classification to reduce the dimensionality of features before the classification process, which minimizes redundant information and computational overhead. This step is not commonly found in prior research.Firstly, a random forest model is established with “whether AI assistance was used to complete the paper” as the output, and various features as inputs. The analysis of the predictive accuracy when changing input features reveals the degree of influence of each feature on using AI to complete the paper. After feature selection, the remaining 6 features can still effectively predict the use of AI to complete the paper, indicating the representativeness of the extracted indicators. Subsequently, the PCA-K-means algorithm is employed to classify the use of artificial intelligence. PCA algorithm is used for dimensionality reduction of the extracted features to better characterize students’ use of AI. Three representative variables are selected, and the contribution of each feature is computed based on the factor loading matrix. Finally, the K-means algorithm is used to classify students based on the three dimensional features, showing that students can be effectively classified into 2 categories. The results indicate that the majority of students support the use of AI technology to enhance their abilities, although some students may only intend to use AI to cope with exams and similar tasks.

The primary purpose of this research article is to study the famous K$\ddot{o}$the's Conjecture for the special cases - when a ring $\mathfrak{R}$ is commutative, and when $\mathfrak{R}$ is an Algebra over a field. Furthermore, some open problems involving tensor product of Algebras over a field has also been discussed extensively along with their proofs. Subsequently, an equivelent statement of K$\ddot{o}$the's problem in terms of algebra of matrices has been established.

(1) Background: Vitamin K deficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and increased risk of vascular calcifications. A method to indirectly measure Vitamin K status is measuring the blood level of Vitamin K dependent proteins (VKDP)- osteocalcin (OC) and matrix GLA protein (MGP). The aim of this study is to correlate the level of OC and MGP with markers of CKD mineral bone disorder (CKD-MBD). (2) Methods: We conducted a single-center cross-sectional study that included 45 CKD G5D patients and measured blood biochemistry, complete blood count and intact osteocalcin and matrix GLA protein. (3) Results: We found a strong statistically significant correlation of OC with the markers of CKD-MBD such as: iPTH , serum calcium and serum phosphorus and a strong indirect statistically significant correlation with abdominal circumference. There was also a statistically significant correlation of MGP with markers of inflammation (CRP). Higher levels of MGP were found in patients treated with vitamin K antagonists, non-calcium based phosphate binders and vitamin D receptor activator- paricalcitol. (4) Conclusions: In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP is associated to CKD-MBD. The use of medication such as phosphate binders, that reduce vitamin K absorbtion, Vitamin D that increases Vitamin K requirements and also vitamin K antagonists, seem to have an influence on the blood level of VKDPs.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li.

This paper explores the application of the generalized double reduction method to the (1+1)-dimensional Kaup-Boussinesq (K-B) system, which models nonlinear wave propagation. Double reduction method is a structured and systematic approach in the analysis of partial differential equations (PDEs). We first identify the Lie point symmetries of the K-B system and construct four non-trivial conservation laws using the multiplier method. The association between the Lie point symmetries and the conservation laws is established, and the generalized double reduction method is then applied to transform the B-K system into second-order differential equations or algebraic equations. The reduction process allowed us to derive two exact solutions for the K-B system, illustrating the method’s effectiveness in handling nonlinear systems. This work highlights the effectiveness of the generalized double reduction method in simplifying and solving nonlinear nonlinear systems of PDEs, contributing to a deeper understanding of the systems.

Salinity, resulting from climate change and excessive mineral fertilization, burdens farmers and negatively impacts soil and water ecosystems in the Northeastern Nile Delta. Organic and biological approaches are crucial for addressing these issues. This study examined the effects of individual and combined inoculations with cyanobacteria, yeast, and Arbuscular Mycorrhizal Fungi (AMF), with or without K-humate, on enhancing salinity tolerance, increasing yield, and improving crop quality of wheat and faba bean. The aim was to reduce NPK mineral fertilizer application rates to 25% of recommended doses. An economic evaluation was also conducted. In a preliminary laboratory experiment, the interactive effects of these microbiomes on the production of plant antioxidant enzymes and soil enzymes were investigated under salinity stress. Results showed that co-inoculation, especially with K-humate, yielded superior outcomes compared to individual inoculations. The laboratory experiment findings were confirmed by a field trial conducted in saline-alkaline soil in the Northeastern Nile Delta region. The study found that the integrated inoculation of cyanobacteria, yeast, and mycorrhizae with K-humate, along with 25% mineral NPK fertilization enhanced microbial activity, including AMF colonization, spore density, and total bacteria, cyanobacteria, and yeast counts in the plant rhizosphere. It also increased soil enzyme activity, improving soil fertility compared to individual or mineral control treatments. This integration resulted in wheat yields of 2.77 tons/ha and faba bean yields of 4.75 tons/ha. Crop quality improved, with higher levels of nitrogen, potassium, phosphorus, and protein in wheat grains and faba bean seeds. Microbiomes inoculation increased potassium uptake over sodium, enhancing the potassium/sodium ratio and salt stress tolerance. This approach reduces reliance on costly mineral fertilizers by up to 75%, enabling economically viable cultivation in marginal lands. These sustainable practices optimize resource utilization, maximize economic efficiency, and preserve natural resources.

Water quality control employs techniques mostly targeting individual analytes; group detection is also practiced, but the choice of group methods is limited, which supports interest in developing such methods. We have examined an interaction of hypochlorite with a chlorine-containing heptamethine carbocyanine dye in the presence of 30 organic and inorganic model analytes that were found to induce diverse color changes in the system. The main supposed mechanisms are retardation of the dye oxidation with hypochlorite (presumably by scavenging chlorine radicals) and substitution of chlorine atom in the dye by the most nucleophilic analytes (amines, amino acids, proteins, DNA, phenol). The grass-green substitution product is more contrastingly visible against the dark-purple hypochlorite oxidation product of the dye than against the original emerald-green dye. The indicator reaction is monitored photographically for 10–40 min and the images are processed using principal component analysis (PCA) or linear discriminant analysis (LDA), allowing for data convolution for the complex color transitions. Nitrogen compounds are discriminated from the others, and more reactive analytes (tryptophan, cysteine, bovine serum albumin, and DNA) are detected in the presence of less reactive ones in natural water. The system is promising for the development of group assays for dissolved organic matter and discrimination of water samples.

The work analyses the way in which symptoms and life themes manifest in middle-aged adults diagnosed with major recurrent depression. Specifically, the relationships between symptoms, life themes, and life themes - symptoms have been analyzed. For this purpose, Spearman correlation, and the methods of Latent Semantic Indexing (LSI) were used. Seven symptoms and twenty-six life themes were identified in the patients analyzed as well as similarities of symptoms/life themes (at patient level), the ranking of the importance of symptoms on each life theme (at the level of the group of patients), the rankings of the similarities of life themes in relation to different symptoms or various groups of symptoms (at the level of the group of patients), and dysfunctional cycles of symptoms and life themes (at patient level). The findings only refer to the patients analyzed. Although our findings cannot be generalized, there is a possibility that some of them may also be encountered in other patients. However, the design of the work can be used to initiate other similar studies.

Real time condition monitoring and precision health assessment system is a mandatory need for effective maintenance program in industrial sector. Rapid advancement in the information technology and other engineering technologies have invited more proactive attention from research and development in industrial sectors and particularly in condition monitoring of machines and related Industrial processes. In this work, drill bit condition monitoring techniques have been developed based on wavelet analysis and artificial neural networks (ANN) for automatic drill bit fault detection and classification. An experimental work has been conducted to capture the vibration signals for analysis. In this experiment, the CNC drill machine is used with high carbon steel drill bit and mild steel material as work piece. The cutting condition parameters are kept constant and the wear level is varied from 0.2 to 0.6 mm. The Data Acquisition system (DAQ) with Lab VIEW software is used to capture the vibration signals for drill bit with different wear conditions using accelerometer. The captured vibrations data are analyzed using continuous wavelet transform (CWT) with Morlet wavelet and Daubechies wavelet as a prime function. In general, the CWT coefficient is used to generate the inputs features to ANN for automatic tool condition classification, with two outputs (0, 1) for healthy and (1, 0) for faulty. The outcome of ANN showed 98% of accuracy in the wear prediction and this results show the effectiveness of the combed WT and ANN for automatic classification of tool wear conditions with high success rate.

Embracing Fourth Industrial Revolution(4IR) techniques is a need for a long-term sustainability and to do automation in the processes of Industrial and education sector. Rapid advancement in the information technology and other engineering technologies demand more proactive steps in the education institutes. In the post pandemic world, there is an increasing demand of changes in teaching and learning methodologies with the support of modern digital technologies. So, all of the teaching institutes need to have a significant step change in the areas of learning and teaching. The impact of 4 IR is more on the education sectors compared to previous generation’s industrial revolution. Keeping track of key technologies can be quite a challenge as they keep evolving at a very fast pace. Fourth Industrial revolution is the current technological digital revolution in which major focus is on cyber physical and biological systems such as Artificial Intelligence, Robotics, Internet on Things, Virtual Reality etc., The educators and institutions should establish the pedagogies and teaching with the aid of Industry 4.0 techniques to evolve education 4.0. So, it is very important to understand the challenges and competencies required about the implementation of 4IR by the faculty members and students who are currently studying in Higher Education Institutes (HEIs). This paper aim is to do a systematic review about industry 4.0 techniques and its application in relate to the online learning and teaching, change in pedagogies, enhancement of data management in HEIs, digital and virtual laboratories etc.

Several long-term monitoring of aerosol datasets from the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Terra/Aqua, Multi-angle Imaging SpectroRadiometer (MISR), Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) are used to derive the dust aerosol optical depth (DOD) in Central Asia based on the Angstrom exponent parameter and/or the particle shape. All sensors agree very well on the interannual variability of DOD. The seasonal analysis of DOD and dust occurrences identified the largest dust loading and the most frequent dust occurrence in the spring and summer, respectively. No significant trend is found during the research period in terms of both DOD and the dust occurrence. Further analysis of Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) aerosol products on a case-by-case basis in most dust months of 2007 suggested that the vertical structure is varying in terms of the extension and the dust loading from one event to another, although dust particles of most episodes have similar physical characteristics (the particle shape and size). Our analysis on the vertical structure of dust plumes, the layer-integrated color ratio and depolarization ratio indicates a varied climate effect (e.g., the direct radiative impact) by mineral dust, dependent on the event being observed in Central Asia.

In this paper, closed forms of the sum formulas $\sum_{k=0}^{n}W_{k}^{2}$ \ for the squares of generalized Tetranacci numbers are presented. We also present the sum formulas $\sum_{k=0}^{n}W_{k+1}W_{k},$ $\sum_{k=0}^{n}W_{k+2}W_{k},$ and $\sum_{k=0}^{n}W_{k+3}W_{k}.$ As special cases, we give summation formulas of the of Tetranacci, Tetranacci-Lucas and some other fourth order linear recurrance sequences.

The Lagrangian and Eulerian structure and dynamics of a strong wind event in the Tokar Gap region are described using a WRF model hindcast for 2008. Winds in the Tokar Gap reach 25 m s-1 and remain coherent as a jet far out over the Red Sea, whereas equally strong wind jets occurring in neighboring gaps are attenuated abruptly by a jump-like hydraulic transition that occur just offshore of the Sudan coast. The transition is made possible by the supercritical nature of the jets, which are fed by air that spills down from passes at relatively high elevation. By contrast, the spilling flow in the ravine-like Tokar Gap does not become substantially supercritical and therefore does not undergo a jump, and also carries more total horizontal momentum. The Tokar Wind Jet carries some air parcels across the Red Sea and into Saudi Arabia, whereas air parcel trajectories in the neighboring jets ascend as they cross through the jumps, then veer sharply to the southeast and do not cross the Red Sea. The mountain parameter Nh/U is estimated to lie in the rage 1.0-4.0 for the general region, a result roughly consistent with a primary gap jet having a long extension, and supercritical jets spilling down from higher elevation passes. The strong event is marked by the formation of a cyclonic cell near the upstream entrance to the Tokar Gap, a feature absent from the more moderate events that occur throughout the summer. The cell contains descending air parcels that are fed into the primary and secondary jets. An analysis of the Bernoulli function along air parcel trajectories reveals an approximate balance between the loss of potential energy and gain of internal energy and pressure, with surprisingly little contribution from kinetic energy, along the path of the descending flow. All jets attain the critical wind speed nominally required to loft dust into the atmosphere, though only the Tokar Gap has a broad, delta region with plentiful deposits of silt.

The purpose of this article was to check the relashionship of different types of physical activities, BMI, smoking and alcohol consumption (with control for age, sex and level of education) on health (physical and mental). The study was based on Belgium epidemiological data (10661 participants from 19 to 81 years old for whom we have health indicators over a period of 11 years) together with questionnaires about alcohol, tobacco consumption and the frequency of different types of physical activities. Descriptive statistics and regression analysis of epidemiological data was performed with use of STATA v.14. Our results indicate that the different categories of physical activities (PA) had some differences on health indicators impacts. Our findings confirm that leading a healthy life style (all types of physical activities and weight maintenance) is an important issue since it has a significant relationship with physical and mental health indicators, but outdoor physical activities and practicing leisure sport in group have shown slightly higher magnitude in association on general health. Magnitude of association of PA with physical and mental health indicators was similar to those observed with smoking and alcohol consumption.

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.

Propagation of electromagnetic (EM) waves inside and on the surface of the human body is the subject of active research in area of biomedical applications. This research area is the basis for wireless monitoring of biological object parameters and characteristics. Much attention has been paid to radio-frequency identification systems, which are intended for biomedical applications. Solutions to the following problems are crucial to achieve the stated goals in the area of wireless monitoring: EM wave propagation inside regular and multilayer biological media, through the interface between different media, and on-body surface wave propagation. The biological object monitoring is based on a consideration of the followingprocesses: a) propagation of the EM wave in a biological medium considered as the dielectric with a high dielectric permittivity and substantial conductivity; b) penetration of the EM wave through the biological medium–air interface (wave reflection and refraction); c) propagation of the EM wave in a multi-layer biological medium; d) propagation of the EM wave along the plane or curved surface of biological objects.

The paper proves the existence of a family of axisymmetric equilibrium figures as solutions of a stationary problem with unknown boundaries for the Navier–Stokes equations corresponding to the slow rotation of a viscous compressible two-layer liquid mass about some axis. It is assumed that the liquids are barotropic, capillary and have different viscosities, the internal fluid being bounded by a closed surface. This interface does not intersect with the external boundary of the cloud. The proof is based on implicit function theorem and carried out in the Hölder spaces.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

Tracking temperature changes in certain geographic regions is a current task in modern research on Earth's climate changes. One of the global problems in solving this task is related to the large volume of measured data and the search for appropriate methods for effective determination of changes. The purpose of this research is to track climate temperature changes using a machine learning-based automated change detection method. The presented method includes training of a two-level structure of neural networks, with measured temperatures for a ten-year period of time for a certain geographical region. In the testing phase, the neural structure classifies measured temperatures for two three-year periods, before and after the ten-year time period, respectively, for the same geographic region. An algorithm was developed to visualize the studied regions by creating a map with their geographic coordinates. The classification results in the neural structure outputs are presented and analyzed as possible temperature changes. Suggestions for continuing and expanding the research in the future are discussed.

Microbiocontrol of Mycogone perniciosa is focused on casing soil antagonists use. Since no industrial producer strains of polyfunctional biologics were used in previous studies, research goal was to characterize Bacillus subtilis B-10 and M-22 effect on mycopathogen and reveal its control possibilities. Interactions between producer strains and M. perniciosa were evaluated using well method and spraying. Mycoparasite colony area and its lysis zone were determined. Biological efficacy was characterized by lysis zone proportion in total area occupied by the micromycete mycelium. Statistical processing included W-test, ANOVA, means (M) and standard errors (±SEM) calculation. The significance was assessed by t-test. M. perniciosa development suppressing by producer strains was established, indicates a prolonged B-10 and M-22 effect on mycopathogen. High biological efficacy of both strains at the early stages of mycopathogen development by introducing into the wells and spraying was shown: B-10 – 50.9–99.6 % and M-22 – 57.5–99.2 % respectively (p ≤ 0.05). Significant differences between producer strains were not revealed, although during the first exposure day to developed M. perniciosa colonies M-22 has shown greater activity. Preventive treatment high efficiency when producer strains completely suppressed mycoparasite development, permit recommending them both to introduce when preparing casing for M. perniciosa control.

The article presents a new scalable iterative method for linear programming called the “apex method”. The key feature of this method is constructing a path close to optimal on the surface of the feasible region from a certain starting point to the exact solution of linear programming problem. The optimal path refers to a path of minimum length according to the Euclidean metric. The apex method is based on the predictor-corrector framework and proceeds in two stages: quest (predictor) and target (corrector). The quest stage calculates a rough initial approximation of linear programming problem. The target stage refines the initial approximation with a given precision. The main operation used in the apex method is an operation that calculates the pseudoprojection, which is a generalization of the metric projection to a convex closed set. This operation is used both in the quest stage and in the target stage. A parallel algorithm using a Fejér mapping to compute the pseudoprojection is presented. An analytical estimation of the parallelism degree of this algorithm is obtained. Also, an algorithm implementing the target stage is given. The convergence of this algorithm is proven. An experimental study of the scalability of the apex method on a cluster computing system is described. The results of applying the apex method to solve problems from the Netlib-LP repository are presented.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.