The purpose of the present study was to develop an experimental model for studying of the intra-articular knee movements depending on the work of the knee joint and applied muscle groups in isometric stretching conditions with different tens. The experimental procedure includes ultrasound examination of a knee joint after isometric stretching of healthy men (n=32). The changes in millimeters of the distances between the femur and tibia were measured with ultrasound sonographer at three stages. The first stage was performed on ten (n=10) healthy men at five different sitting and upright positions. In the second and third experimental model stages the lower limbs loading was on 22 participants. Our hypothesis which was confirmed, was that as a result of increasing extraloads on the participants back (2, 5, 10, 15, 17, 20 kg), a intra-articular decrease in the femur-tibia cartilage surface distance wiil be observed. The accuracy of the created experimental model was improved over its three stages from 30% to 9%. Quantitative model data can help to create a mathematical model for the mechanical effects during deformation of the knee joint bone cartilage, as well as to outlines the some future tasks: increasing loading weights; enlarge participant groups; comparison men and women; healthy and pathology comparison.

Chymotrypsin is an important proteolytic enzyme in human digestion system that cleaves milk proteins, through hydrolysis reaction, which makes it interesting subject to study activity of milk proteases. In this work, we compared detection of chymotrypsin by spectrophotometric, dynamic light scattering (DLS) and quartz crystal microbalance (QCM) methods and determined the limit of chymotrypsin detection (LOD), 0.15 ± 0.01 nM for spectrophotometric, 0.67 ± 0.05 nM for DLS and 1.40 ± 0.30 nM for QCM methods, respectively. We discuss peculiarities and give perspective for implementation of detection methods and note that while the optical detection methods are simple to implement, the QCM method is more robust for sample preparation. We give an overview on methods and instruments for detection of chymotrypsin and other milk proteases.

This paper investigates reachable set estimation and state-feedback controller design for linear time-delay control system with bounded disturbances. First, by constructing an appropriate Lyapunov-Krasovskii functional, we obtained a delay-dependent condition, which determed the admissible bounding ellipsoid for the reachable set of the system we considered. Then, a sufficient condition in form of liner matrix inequalities is given to solve the problem of controller design with reachable set estimation. Finally, by minimizing the volume of the ellipsoid and solving the liner matrix inequality, we obtain the desired ellipsoid and controller gain. A comparative numerical example is given to verify the usefulness of our result.

Positive invariant set is an important concept of dynamic systems. The purpose of this paper is to study the sufficient and necessary conditions that the set of ellipsoids and the Lorenz cone are positive invariant sets of discrete time systems. By means of nonlinear programming and induced norm, the problem of positive invariance is formulated as an optimization problem, and the equivalent dual form optimization is also presented using the dual optimization method. Our results provide more alternative methods for determining the positive invariance of quadratic form convex sets from the point of view of optimization and dual optimization. The effectiveness of this method is demonstrated by numerical examples.

Characterized in biomedical terms, stretching exercises have been defined as movements applied by external and/or internal forces – to increase muscle and joint flexibility, decrease muscle stiffness, to elevate joint range of motion (ROM), to increase the length of the morpho-functional unit “muscle-tendon”, to improve joint, muscle and tendon movements, contraction and relaxa-tion. The present review examines and summarizes the initial and recent literature data related to the biomechanical, physiological and therapeutic effects of static stretching (SS) on flexibility and other physiological characteristics of the main structural and functional unit “joint-ligaments-tendon-muscle”. The healing and therapeutic effects of SS, soon combined with other rehabilitation techniques (massage, foam rolling – with and without vibrations; hot/cold therapy, etc.) are discussed in relationship to creation of individual (patient-specific) or group programs for treatment and prevention of joint injuries as well as for improving performance in sports. From a theoretical point of view, the role of SS as positively affecting the composition of the connective tissue matrix is pointed out: type I-III collagen synthesis, hyaluronic acid and glucosaminoglycans (GAGs) turnover – under influence of the transforming growth factor beta-1 (TGF-β-1). Different variables as collagen type, biochemistry, elongation and elasticity are used as molecular biomarkers. Recent studies evaluated that the static progressive stretching therapy could prevent/reduce the development of arthrogenic contractures, joint capsule fibrosis, muscle stiffness and need new clinical applications. Combined stretch techniques are proposed and ap-plied in medicine and sports, depending on their long- and short-term effects on variables such as ROM, EMG activity, muscle stiffness, etc. The results obtained are of theoretical and practical interest for development of new experimental, mathematical and computational models and creation of efficient therapeutic programs. The healing SS effects on the main structural and functional unit – “joint-ligament-tendon-muscle” need further investigations, which could clarify and evaluate benefits of SS in prophylaxis and treatment of joint injuries - in healthy and ill in-dividuals, in older adults, as compared to young, active and well-trained persons, as well as to professional athletes.

This paper secures the analytical soliton solutions of the perturbed NLSE gives to (1). The existence criteria have been demonstrated and the wave speed of the soliton befall out. To achieve all the results obtained we used the mathematical technique. In view of the results obtained, some new additional one have been reported in left-handed metamaterials.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections represent major a public health concern and require comprehensive understanding of their genetic make-up. This study investigated the first occurrence of IMP-carrying MDR P. aeruginosa strains from Bulgaria. Whole genome sequencing identified a novel plasmid-mediated blaIMP-100 allele located in a In1300-like integron embedded in a novel putative transposon. Two other closely related chromosomal blaIMP variants IMP-13 and IMP-84 were also detected. The IMP-producers were resistant to last-line drugs including cefiderocol (CFDC) (2 out of 3) and susceptible to colistin. The blaIMP-13/84 cassettes were situated in a In320 integron inserted in a Tn5051-like transposon as previously reported. Lastly, the p47825-IMP plasmid rendered PAO1 transformant resistant to CFDC, suggesting a transferable CFDC resistance. A variety of virulence factors associated with adhesion, antiphagocytosis, iron uptake, quorum-sensing, as well as secretion systems, toxins, and proteases were confirmed, suggesting significant pathogenic potential consistent with the observed strong biofilm formation. Emergence of IMP-producing MDR P. aeruginosa is alarming as they remain unsusceptible even to last geneneration drugs like CFDC. Newly detected IMP-100 was even located in an CFDC-resistant XDR strain.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

We apply utilized the extended form of the auxiliary equation method to obtain extensively reliable exact travelling wave solutions of perturbed Gerdjikov–Ivanov equation (GIE) that is widely used as a model in the field theory of quanta and non-linear optics. The method is based on a simple first order second degree ODE. The new form of the approach gives more solutions to the governing equation efficiently.

We demonstrate the use of a nanotechnology-based approach for the investigation of enzymatic activity of a single molecule of horseradish peroxidase with a solid-state nanopore. The artificial 5 nm solid-state nanopore has been formed in a 40-nm-thick silicon nitride structure. Single molecule of HRP has been entrapped into the nanopore. The activity of horseradish peroxidase (HRP) enzyme molecule inserted in the nanopore has been monitored by recording the time dependence of the ion current through the nanopore in the course of the reaction of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) oxidation reaction. We have found that in the process of ABTS oxidation in the presence of 2.5 mM hydrogen peroxide, individual HRP enzyme molecules are able to retain activity for approximately 700 seconds before a decrease in the ion current through the nanopore, which can be explained by structural changes of the enzyme.

In recent years, there has been an increasing demand for personalized experiences in various domains, including the cultural and educational sectors. Museums, as custodians of art, history, and scientific knowledge, are seeking innovative ways to engage their visitors and provide tailored content that enhances their understanding and appreciation of the exhibits. This article presents ExhibitXplorer, a distributed architecture service that leverages geofencing, artificial intelligence, and microservices to enable personalized content delivery in museums. By combining implicit and explicit segmentation of museum visitors and utilizing the GPT API for content generation, ExhibitXplorer offers a dynamic experience to different visitor segments, including researchers, students, casual visitors, and children. The system utilizes push notifications triggered by visitor location changes, allowing seamless delivery of personalized information both indoors and outdoors. Tests were conducted to evaluate the user experience of visitors to an outdoor ethnographic museum. The results showed that 55% of the test participants were satisfied and 45% very satisfied with the way personalized content was delivered.

In this work we have critically reviewed the processes in high-temperature sublimation growth of graphene in Ar atmosphere using enclosed graphite crucible. Special focus is put on buffer layer formation and free charge carrier properties of monolayer graphene and quasi-freestanding monolayer garphene on 4H-SiC. We show that by introducing Ar at different temperatures, TAr one can shift to higher temperatures the formation of the buffer layer for both n-type and semi-insulating substrates. A scenario explaining the observed suppresed formation of buffer layer at higher TAr is proposed and discussed. Increased TAr is also shown to reduce the sp3 hybridization content and defect densities in the buffer layer on n-type conductive substrates. Growth on semi-insulating substrates results in ordered buffer layer with significantly improved structural properties, for which TAr plays only a minor role. The free charge density and mobility parameters of monolayer graphene and quasi-freestanding monolayer graphene with different TAr and different environmental treatment conditions are determined by contactless terahertz optical Hall effect. An efficient annealing of donors on and near the SiC surface takes place in intrinsic monolayer graphene grown at 2000∘C, and which is found to be independent of TAr. Higher TAr leads to higher free charge carrier mobility parameters in both intrinsically n-type and ambient p-type doped monolayer graphene. TAr is also found to have a profound effect on the free hole parameters of quasi-freestanding monolayer graphene. These findings are discussed in view of interface and buffer layer properties in order to construct a comprehensive picture of high-temperature sublimation growth and provide guidance for growth parameters optimization depending on the targeted graphene application.

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

OSI model used to be common network model for years. In the case of ad hoc networks with dynamic topology and difficult radio communications conditions, gradual departure is happening from the classical kind of OSI network model with a clear delineation of layers (physical, channel, network, transport, application) to the cross-layer approach. The layers of the network model in ad hoc networks strongly influence each other. Thus, the cross-layer approach can improve the performance of an ad hoc network by jointly developing protocols using interaction and collaborative optimisation of multiple layers. The existing cross-layer methods classification is too complicated, because it’s based on the whole manifold of network model layers combinations, regardless their importance. In this work, we review ad hoc networks cross-layer methods, propose the new useful classification of cross-layer methods, and show future research directions in ad hoc networks cross-layer methods development. The proposed classification can help to simplify the goal-oriented cross-layer protocol development.

Two Iron Age settlements, Tuzusai and Taldy Bulak 2 (ca. 500 BCE to 1 CE), located in Southeastern Kazakhstan on the Talgar alluvial fan north of the Tian Shan range, have yielded a small collection of bone, antler/horn, bronze, and stone artifacts with affinity to nomadic art of the first millennium BCE. Both settlements date within the period of late Saka culture. Two pieces have decorative ornamentations with zoomorphic imagery: a small carved fragment of a with carved images of a wing and an ear and a perforated bone disk with the carving of three birds’ heads. The other artifacts include objects associated with Saka weaponry or nomadic economy such as the two antler/horn psalia (cheek pieces) and a bronze amulet. A carnelian bead will also be described as an imported object. These special finds are found on the occupation floors of mud brick houses and pit houses of settlements, not in grave or burial contexts. The objects are placed in stratigraphic sequence in the settlement sites. Then the method for placing these objects within the chronological framework of “animal-style art” is through comparisons with similar objects found throughout Eurasia—a method used in Soviet and Post-Soviet archaeology. The results show that functional and stylistic elements of the six objects indicate that the Talgar settlements were part of a larger world-system of trade and communication along the early Silk Route(s).

In this paper, the authors consider the influence of the type of power supply and the internal parameters of the DC-DC converter on the stability of the system at constant power load. The stability of the system under consideration is important in the design and development of the power supply system for an autonomous consumer. Such a typical system can be a DC microgrid. In the work, when analyzing the stability of the system, the power source is not considered an ideal voltage source, but the active-inductive nature of the voltage source is taken into account, which is equivalent to using a synchronous machine with permanent magnets. The Rauss-Hurwitz algebraic criterion was used as a criterion for analyzing the stability of the system. This will make it possible to build and analyze the areas and boundaries of the system's stability. As a result, the areas and boundaries of the stability of the system were presented. The general trend towards the behavior of the zone of instability of the system was given. At the same time, dependences describing the boundaries of instability are presented, which are combinations of parameters of the DC-DC converter, beyond which the system becomes unstable. The presented definitions of the instability limits can be used as a corrective device of the control system to ensure the stability of the system in the upper limits of the power consumption.

This study investigates the effectiveness of a range of timber-based solutions for seismic and energy retrofitting of existing masonry buildings. These solutions are designed not only to prevent structural collapse during earthquakes but also to create integrated interventions that enhance thermo-physical performance and reduce emissions in existing buildings. Various case scenarios were considered and both mechanical and energetic behavior post-intervention were evaluated. Timber-engineered products serve as foundational components for the retrofit approach, encompassing one-dimensional vertical elements (strong-backs) and various types of panels (cross-laminated timber panels, laminated veneer lumber panels, and oriented strand board panels). The analyzed retrofit techniques share a common principle, involving the attachment of these timber-based elements to the building's wall surfaces through mechanical point-to-point connections. The proposed solutions integrate strong-backs and timber panels with membranes and insulation layers, yielding cohesive and highly effective interventions. Finite element modeling was employed to analyze the mechanical and thermal responses of the retrofitted walls. A comprehensive comparative analysis of various techniques was conducted to determine the most effective solution for each specific scenario.

Abstract: The aim of this study was to identify and quantify polyphenolic compounds in skin extracts from four Bulgarian grape varieties and compare to those of seed extracts. The values of total phenolic contents (TPC), flavonoids, anthocyanins, procyanidins, ascorbic acid in grape skin extracts were determined. The antioxidant capacities of skin extracts were evaluated by DPPH, ABTS, FRAP and CUPRAC methods. The TPC values of skin extracts were 2-3 times lower than those of seed extracts. The significant difference between total parameters values of individual grape varieties were also found. According to the TPC and antioxidant capacity of skin extracts the different grape varieties were in the following order: Marselan ≥ Pinot Noir ˃ Cabernet Sauvignon ˃ Tamyanka. The individual compounds in the grape skin extracts were determined by RP-HPLC and compared with those of seed extracts. The determined composition of skin extracts was significant different from seed extracts composition. Qualitative and quantitative evaluation of the procyanidins and catechins in the skins were carried out. A correlation between phenolic contents, individual composition and antioxidant capacity of different extracts was found. The studied grape extracts have a potential to be applied as natural antioxidants in the pharmaceutical and food industries.

In this paper a combined Laplace transform (LT) and boundary element method (BEM) is used to find numerical solutions to problems of anisotropic functionally graded media which are governed by the transient diffusion-convection-reaction equation. First, the variable coefficients governing equation is reduced to a constant coefficients equation. Then, the Laplace-transformed constant coefficients equation is transformed a boundary-only integral equation. Using a BEM, the numerical solutions in the frame of Laplace transform may then be obtained from this integral equation. Then the solutions are inversely transformed numerically using the Stehfest formula. Some problems considered are those of compressible or incompressible flow, and of media which are quadratically, exponentially and trigonometrically graded materials. The results obtained show that the analysis used to transform the variable coefficients equation into the constant coefficients equation is valid, and the mixed LT-BEM is easy to implement for obtaining the numerical solutions. The numerical solutions are verified by showing their accuracy and steady state. For symmetric problems, the symmetry of solutions is also justified. Moreover, the effect of the anisotropy and inhomogeneity of the material on the solutions are also shown, as to suggest that it is important to take the anisotropy and inhomogeneity into account when doing experimental studies.

Nanoparticles of graphene and carbon nanotubes are attractive materials for improvement of mechanical and barrier properties and functionality of biodegradable polymers for food packaging applications. However, the increase of the manufacture and consumption increases the probability of exposure of human and environment to such nanomaterials, this rising questions about the risks of nanomaterials since they can be toxic. For a risk assessment, it is crucial to know whether airborne nanoparticles of graphene and carbon nanotubes can be released from nanocomposites into the environment at their end-life, or they remain embedded in the matrix. In this work the release of graphene and carbon nanotubes from the poly(lactic) acid nanocomposite films were studied for the scenarios of: (i) biodegradation of matrix polymer at the disposal of wastes; and (ii) combustion and fire of nanocomposite wastes. Thermogravimetric analysis in air atmosphere, TEM, AFM and SEM were used to verify the release of nanoparticles from nanocomposite films. The three factors model was applied for the quantitative and qualitative risk assessment to the release of graphene and carbon nanotubes from nanocomposite wastes for these scenarios. Safety concern is discussed in respect to the existing regulations for nanowastes stream.

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

Floating Offshore Wind Turbine (FOWT) is an innovative technology with little industry guidance for its hull design. Various FOWT floaters with different hull shapes claim to support the same turbines. Structural integrity and material expense analyses of different pontoon shapes were conducted, and it was found that some configurations, such as those with every two columns connected by both pontoon and bracing, have advantages over others. However, it is important to note that the choice of pontoon shape should be based on the wave loading conditions the floater will be exposed to. While a T-shaped pontoon provides a cost-effective solution under certain wave loading scenarios, it may not be the best option for all conditions. Specifically, ring pontoon designs with full bracing were found to be necessary for withstanding certain wave loads. Therefore, it is important to consider different Dominant Load Parameters (DLP) and ensure that a FOWT floater can withstand all applicable DLPs. An uneven hexahedral column shape, which combines the best attributes of square and round shapes, is proposed as a better alternative to cylindrical columns. It offers ease of manufacture and reasonably low drag. Bracing is found to be necessary for withstanding the wind turbine’s incurred moment and forces. The conclusion is that platform design should prioritize manufacturing costs and strength over maximizing hydrodynamic performance.

This study delves into the therapeutic potential of two natural compounds, Amentoflavone and Bilobetin, by investigating their interactions with the BPIFB4 protein. BPIFB4, a member of the BPI fold-containing superfamily, has been associated with various biological processes, particularly in longevity and cardioprotection( LAV-BPIFB4). Molecular docking analyses revealed promising binding energies for Amentoflavone and Bilobetin with BPIFB4, suggesting favorable interactions.Additionally by pKCSM database are showed the predicted toxicity properties of Amentoflavone and Bilobetin respectively.This research contributes to the growing body of knowledge on natural compounds and their therapeutic implications in the context of vital biological processes. However, these findings underscore the need for further investigations, including in vivo studies and clinical trials, to validate the observed effects and explore the translational potential of Amentoflavone and Bilobetin in promoting cardiovascular health and longevity.

We review recent progress in high-speed orbital angular momentum (OAM) multiplexed free-space optical communication systems. The outdoor atmospheric turbulence is emulated by an indoor turbulence emulator, which is based on split-step beam propagation method. Adaptive optics, channel coding, Huffman coding combined with LDPC coding, and spatial offset are used for turbulence mitigation; while OAM multiplexing and wavelength-division multiplexing (WDM) are applied to boost aggregate capacity.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

The pentose phosphate pathway (PPP) is one of three major pathways involved in glucose metabolism, regulated by glucose-6-phosphate dehydrogenase (G6PD), controlling NADPH formation. NADPH, in turn, regulates the balance of oxidative stress and reactive oxygen species (ROS) levels. G6PD dysfunction, affecting PPP, is implicated in neurological disorders, including epilepsy. However, PPP's role in epileptogenesis and ROS production during epileptic activity remains unclear. To clarify these points, we conducted electrophysiological and imaging analyses on mouse hippocampal brain slices. Using the specific G6PD inhibitor G6PDi-1, we assessed its effects on mouse hippocampal slices, examining intracellular ROS, glucose/oxygen consumption, and ROS production during synaptic stimulation and in the 4AP epilepsy model. G6PDi-1 increased basal intracellular ROS levels and reduced synaptically induced glucose consumption but had no impact on ROS production from synaptic stimulation. In the 4AP model, G6PDi-1 didn't significantly alter spontaneous seizure frequency or H2O2 release amplitude but increased the frequency and peak amplitude of interictal events. These findings suggest that short-term PPP inhibition has a minimal impact on synaptic circuit activity.

This paper discusses the preliminary results of archaeological surveys conducted in the Juuku Region of north-central Kyrgyzstan on the south side of Lake Issyk kul. Our goal was to document ancient and contemporary agropastoral systems over a four millenia time period. During the surveys about 350 loci were identified as settlements, burial mounds, graves, single artifact finds, and artifact scatters (ceramic). The areas of Juuku Valley survey included two discrete polygons: Polygon 1, Lower Juuku at 1750 to 1950 m asl in elevation and Polygon 2, Chak Juuku or Upper Eastern Branch Juuku Valley at 2060 to 2100 m asl in elevation. Three radiometric dates and preliminary archaeobotanical studies were conducted at three exposed profile cuts. The methods included here are: (1) pedestrian surveys; (2) use of digital maps (Google Earth, Encarta); (3) placing archaeological loci within known chronological time periods; (4) AMS dating of charcoal samples collected from profile deposits; and (5) preliminary identification of plant remains found from archaeobotanical samples. The results of our research represent the first step toward inventorying and interpreting archaeological data in the Juuku Valley derived from field studies.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell, in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi, and tumors. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic center of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

Glycerol has found its applications as a heat-transfer fluid in heat exchangers, and as a compo-nent of functional solutions in biosensor analysis. Flowing non-aqueous fluids are known to be able to induce electromagnetic fields due to triboelectric effect. These triboelectrically generated electromagnetic fields can affect biological macromolecules. Horseradish peroxidase (HRP) is widely employed as a convenient model object for studying how external electric, magnetic, and electromagnetic fields affect enzymes. Herein, we have studied whether the flow of glycerol in a ground-shielded cylindrical coil affects the HRP enzyme incubated at a 2 cm distance near the coil’s side. Atomic force microscopy (AFM) has been employed in order to study the effect of glycerol flow on HRP at the nanoscale. Increased aggregation of HRP on mica has been observed after the incubation of the enzyme near the coil. Moreover, the enzymatic activity of HRP has also been affected. The results reported can find their application in biotechnology, food technology and life sciences application, considering the development of triboelectric generators, en-zyme-based biosensors and bioreactors with surface-immobilized enzymes. Our data can also be of interest for scientists studying triboelectric phenomena.

An extended classification of active RC- and RLC- filters with Sallen-Key architectures, including those created in the last three years, is proposed. This makes it possible to formulate new design directions for an extended family of active RC- and RLC- Sallen-Key filters (PF, LPF, HPF, RF) for the tasks of high-speed and ultra-fast analog-to-digital signal conversion.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

The paper investigates the issues of transliteration of Russian toponyms in a city environment and studies the efficiency of the Technical Reference Manual for the Standardization of Geographical Names published by the United Nations group of experts. The paper demonstrates the feasibility of the UN and Russian official transliteration standards and compares the suggested theoretical models with the practical applications found on the street signs, labels, maps, and other sources of navigation. The author presents a comprehensive account of practical transcription methods used in Moscow and offers a solution to a number of issues and discrepancies between popular transliteration models and their real-life application.

Therapies targeting amyloid, such as monoclonal antibodies like Lecanemab, Aducanumab, and Donanemab, have garnered FDA approval but remain controversial due to limited clinical benefits and significant side effects against Alzheimer. The present theorical work utilized Virtual Screening and Docking techniques to explore potential small natural molecules' interactions with the KIBRA protein, a promising target for drug development. Kibra protein is considered a biomarker for synaptic dysfunction and cognitive decline. Employing Autodock Vina and Pyrx software, on several natural compounds and found Hypericin to exhibit the lowest binding energy of approximately -9 kcal/mol. Previous studies have highlighted Hypericin's strong affinity for Alzheimer's Disease-associated targets like ABAD and BACE1. These findings suggest Hypericin could be as a potential therapeutic agent for Alzheimer's Disease. Further research is warranted to validate its efficacy and safety for clinical use.

Reservoir computing (RC) systems can efficiently forecast chaotic time series using nonlinear dynamical properties of an artificial neural network of random connections. The versatility of RC systems has motivated further research on both hardware counterparts of traditional RC algorithms and more efficient RC-like schemes. Inspired by the nonlinear processes in a living biological brain and using solitary waves excited on the surface of a flowing liquid film, in this paper we experimentally validate a physical RC system that substitutes the effect of randomness for a nonlinear transformation of input data. Carrying out all operations using a microcontroller with a minimal computational power, we demonstrate that the so-designed RC system serves as a technically simple hardware counterpart to the `next-generation’ improvement of the traditional RC algorithm.

This study investigates the potential antimicrobial utility of the natural substance Amentoflavone against four dangerous bacterial strains—Mycobacterium tuberculosis, Helicobacter pylori, Haemophilus influenzae, and Pseudomonas aeruginosa. Utilizing molecular docking studies, are assessed the binding interactions between Amentoflavone and key protein targets crucial for the viability of these bacteria. The findings suggest promising binding affinities, particularly in the active sites of Aminoglycoside 2'-N-acetyltransferase, Thioredoxin Reductase, N-acetylneuraminate Lyase, and Glucose-1-phosphate Thymidylyltransferase in the respective bacterial strains. While these in silico results provide initial insights, further in vitro and in vivo experiments are essential to validate the biological relevance and efficacy of Amentoflavone as a potential antimicrobial agent against these bacterial pathogens.

The study focused on Molecular Docking simulations using Autodock Vina in conjunction with the Pyrx program to investigate potential drugs and natural compounds against the Bcr-Abl oncoprotein. From initial virtual screening of 200 compounds, 11 potential candidates were selected for further evaluation. Additional investigations included toxicity prediction using the pKCSM server. Among the compounds, Diosmin and Hesperidin showed high maximum tolerated doses in humans and low toxicity. Conversely, only Eltrombopag among the selected drugs exhibited excellent parameters, albeit with a potential risk of liver damage at high dosages. These findings underscore the need for comprehensive evaluation of efficacy and safety in the development of potential treatments targeting the Bcr-Abl oncoprotein.

This study employs molecular docking experiments to investigate the binding interactions of Hypericin with key proteins implicated in Alzheimer's disease (AD). Hypericin demonstrated a significant binding energy of -10.1 kcal/mol with ABAD (3-hydroxyacyl-CoA dehydrogenase type II). The analysis revealed multiple binding interactions, including hydrogen bonds with arginine 6, serine 7, and glutamic acid 140, as well as hydrophobic bonds involving leucine 11, aspartic acid 142, and aspartic acid 86. These findings illuminate the intricate molecular interactions between Hypericin and ABAD, suggesting its potential as a lead compound for further therapeutic development in the context of Alzheimer's disease. Additionally, a parallel docking investigation was conducted for Beta-secretase 1 (BACE1), a protein pivotal in the generation of beta-amyloid peptides—a hallmark of Alzheimer's disease. Inhibiting BACE1 activity is considered a promising therapeutic strategy for AD. Computational analyses suggest that Hypericin may serve as a potential inhibitor of BACE1. Molecular Docking results reveal a robust binding affinity between Hypericin and BACE1, supported by a significant binding energy score of -10.3 kcal/mol. Notably, both ABAD and BACE1 exhibit high binding affinity with Hypericin. This theoretical exploration provides an initial understanding of the intricate molecular pathways involved in Alzheimer's disease and proposes Hypericin as a potential therapeutic compound for mitigating its progression.

Docking results suggest that Amentoflavone has a higher affinity for investigated Serine/threonine-protein kinases, indicating potential interactions that may influence the activities of these kinases. The negative values of the binding energies signify strong and stable interactions, suggesting that Amentoflavone could be a key molecule in modulating the functions of these kinases, which play crucial roles in cellular processes such as cell cycle regulation and apoptosis.

Giant unilamellar vesicles (GUVs) are membrane model used to study membrane properties. Electroformation is one of the methods used to produce GUVs. During electroformation protocol dry lipid film is formed. Drying of the lipid film induce Cholesterol (Chol) demixing artifact, in which Chol forms anhydrous crystals, where these crystals does not participate in formation of vesicles. This leads to a lower Chol concentration in the vesicle bilayers compared to the Chol concentration in the initial lipid solution. To address this problem, we propose novel electroformation protocol that includes rapid solvent exchange, plasma cleaning and spin-coating methods to produce GUVs. We tested the protocol focusing on vesicles with high Chol content using different spin-coating durations and vesicle types deposition. Additionally, we compared the novel protocol using completely dry lipid film. The optimal spin-coating duration for vesicles made out of phosphatidylcholine/Chol mixture was 30 s. Mulitlamellar vesicles (MLVs), large unilamellar vesicles (LUVs) obtained by extrusion of MLVs through 100 nm membrane pores and LUVs obtained by extrusion of previously obtained LUVs through 50 nm membrane pores were deposited on electrode for 1.5/1 Chol/phosphatidylcholine lipid mixture and the results were compared. Electroformation using all three deposited vesicle types gave a high GUVs yield, but deposition of LUVs obtained by extrusion of MLVs through 100 nm membrane pores gave the most reproducible results. Using deposition of these LUVs, we produced GUVs with high yield for 6 different Chol concentrations (from 0 % to 71.4%). Using protocol that includes dry lipid film GUVs yield was lower and Chol demixing artifact was induced, proving that the lipid film should never undergo drying when Chol content is high.

A new low-pass filter (LPF) circuit with independent adjustment of various, incl. digitally controlled, pole frequency resistors, pole quality factor and transmission coefficient. The proposed low-pass filter is based on the use of the properties of a multi-differential operational amplifier that performs the functions of a signal adder. The peculiarity of the filter is that it has three inputs, with respect to which different transmission coefficients are implemented, incl. inverting (-1) and non-inverting (+1). To check these properties of a low-pass filter in the Micro-Cap environment, computer simulation of a specific circuit was performed on a multi-differential operational amplifier AD 8130. Mathematical expressions are given for the main parameters of the proposed low-pass filter, which allow parametric synthesis of elements of a specific circuit under given restrictions on the used element base.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi and tumours. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic centre of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

Statistical denoising techniques have been well studied, however many challenges still remain. This 9 article focuses on determining the least necessary number of significant samples in a statistical pop-10 ulation sampling, while minimizing the impact on the statistical detection of the fiber Bragg grating 11 (FBG) power spectra. This is achieved by using Bayesian decision making, small population statis-12 tics while excluding false detection. First, we investigate the impact of two-sided sliding window 13 technique applied near the cell under the test. The window size varies from 8 to 60 samples. The 14 considered maximum size of population sampling is connected with the number of wavelength 15 samples within the bandwidth of the symmetrical FBG power spectra peaks. Regarding the sym-16 metry of FBG power spectra peaks and the possible reduction of computational demands, we inves-17 tigate the impact of a one-sided sliding window. This enables to achieve less processing latency for 18 real time applications thus brings benefits to FBG-based fiber optical sensing. Both, two- and one-19 sided small population sampling techniques are then experimentally verified. Detection results are 20 analyzed in depth via calculating detection thresholds by using the small size window sliding along-21 side the waveband. From results achieved, it was found that the normality three-sigma rule does 22 not need to be followed while using the small population sampling. Experimental demonstrations 23 and analyses showed that the proposed concept of denoising and statistical threshold detection 24 based on the sliding window does not depend on the prior knowledge of probability distribution 25 functions of the FBG power spectra peaks level and background noise. We have also found that the 26 thresholds’ adaptability mainly depends on the statistical numerical characteristics of the above ad-27 ditive mixture of the FBG power spectra peaks signals and background noise.

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

A new circuit of a low-pass filter (LPF) is considered, which is switched on at the input of analog-to-digital converters to limit the spectrum of input signals. The peculiarity of the proposed low-pass filter is the independent adjustment of the pole frequency, the quality factor of the pole and the transmission coefficient by different resistors. Computer simulation performed in the Micro-Cap environment confirms these properties of the LPF. The basic mathematical expressions are obtained, which make it possible to carry out the parametric synthesis of the LPF circuit. It is shown that the sensitivity of the LPF transmission coefficient to changes in the parameters of the frequency-setting elements of the circuit is close to zero and depends only on the ratio of the resistances of the two resistors in the feedback circuit.

The Simplified Spherical Harmonic (SPN) approximation was first introduced as a three-dimensional (3-D) extension of the plane-geometry Spherical Harmonic (PN) equations. A third order SPN (SP3) solver, recently implemented in the Nodal Expansion Method (NEM), has shown promising performance in the reactor core neutronics simulations. This work is focused on the development and implementation of the transport corrected interface and boundary conditions in NEM SP3 solver, following recent published work on the rigorous SPN theory for piecewise homogeneous regions. A streamlined procedure has been developed to generate the flux zero and second order/moment discontinuity factors (DFs) of the generalized equivalence theory to eliminate the error introduced by pin-wise homogenization. Moreover, several color set models with varying size and configuration are later explored for their capability of generating DFs that can produce results equivalent to that using the whole-core homogenization model for more practical implementations. The new developments are tested and demonstrated on the C5G7 benchmark. The results show that the transport corrected SP3 solver shows general improvements to power distribution prediction compared to the basic SP3 solver with no DFs or only zero order/moment DFs. The complete equivalent calculations using the DFs can almost reproduce transport solutions with high accuracy. The use of equivalent parameters from larger size color set models show better prediction in the whole-core calculations. By coupling different color set models DFs can offer the best accuracy at both eigenvalues and power distributions.

This study presents a pre-processing approach adopted for the radar reflectivity data assimilation and results of simulations with the Harmonie numerical weather prediction model. The method shows an improvement of precipitation prediction within the radar location area in both the rain rates and spatial pattern presentation. With the assimilation of radar data, the model simulates larger water content in the middle troposphere within the layer from 1 to 6 km, with major variations at 2.5–3 km; it also reproduces better the mesoscale belt and cell patterns of precipitation fields.

Sustainability is a characteristic manifested in the ability to maintain the necessary level of performance for construction companies when risk factors arise during the implementation of investment and construction projects. The risk factors that arise during the implementation of in-vestment and construction projects differ in nature, degree of influence, and other characteristics. Ignoring these factors and measures to manage them often leads to critical consequences in the form of disruptions in the timing of work. Risk is a combination of the probability and consequences of the occurrence of adverse events. The article considers the concept of risk as a potential possibility of occurrence of adverse situations and related consequences when exposed to these factors. Risk factors are characterized by surprise, discreteness of changes, the presence of threshold values, upon reaching which a transition to a different mode of operation is required. The article discusses the risk factors arising at the construction stage, their classification. A methodology has been developed that includes conducting a survey in the form of a questionnaire in order to collect information about risk factors that affect the implementation of investment and construction projects. Experts with experience in the construction sector were involved in the survey. The processing of the survey results made it possible to assess the significance of various risk factors in investment and construction projects. Thus, statistical and expert methods were used in the study. The results showed that financial, technical, legal, economic, managerial and natural factors have the greatest impact on investment and construction projects. It is recommended to pay special attention to the listed factors when developing measures aimed at preventing risks and their consequences. The methodology described in the study can be used by construction companies in strategic planning. The analysis of the stability of construction companies, depending on their use of various ways to counteract risk factors, allowed us to develop a number of practical recommendations to reduce the impact of the studied factors on achieving the goals of investment and construction projects.

In this work, the possibility of fabrication magneto-optical ceramics by vacuum sintering of compacts prepared by electrophoretic deposition (EPD) from suspensions of (Ho0.95La0.05)2O3 (HoLa) nanopowders made by self-propagating high-temperature synthesis and (Y0.9La0.1)2O3 (YLa) nanopowders made by laser synthesis was systematically investigated. The processes of the formation of bulk one- and two-layer compacts by the EPD method from non-aqueous suspensions of nanopowders was studied. The use of acetylacetone and polyvinyl butyral (PVB) was shown to make it possible to obtain stable alcohol suspensions of the nanopowders characterized by high zeta potential values (+29…+80 mV) and to carry out a stable EPD process. One-layer compacts were made from the YLa and HoLa nanopowders with a density of 30–43%. It was found out that the introduction of PVB into the suspension leads to a decrease in the mass and thickness of the green bodies deposited, but does not significantly affect their density. A possibility to make two-layers (YLa/HoLa) compacts with a thickness of up to 2.6 mm and a density of up to 46% was demonstrated. Sintering such compacts in a vacuum at a temperature of 1750°C for 10 hours leads to the formation of ceramics with a homogeneous boundary between the YLa/HoLa layers and thickness of the interdiffused ions layer of about 30 μm.

Epidemics are the most common natural phenomena that have occurred throughout the entire history of human society. Depending on the type of disease and the development of the collective immunity that society had acquired by then, the consequences of epidemics were usually very severe. Precisely because of this, the aim of the paper is a scientific description of the way in which the prescribed preventive measures should be applied from the epidemiological, security, economic, legal and other aspects, so that the society, through the mechanisms of the state, can defend and rehabilitate the consequences of an epidemic of an infectious disease. Eliminating the epidemic's impacts is a very difficult issue. In particular, there is an infectious illness epidemic that is spreading uncontrolled throughout society on the one hand. In order to introduce a quarantine that restricts the epidemic's progress and, if the quarantine lasts long enough, to end the epidemic, contact between members of the social group must be broken. On the other side, the cessation of communication between members of a social group also signifies the cessation of all facets of life in that society, including economic ties, education, growth of culture, scientific research, etc.

The development of the automotive industry leads to the improvement of the designs of automatic transmissions and drives and to the development of methods for monitoring and diagnosing their condition. The trend of improving transmissions comes down mainly to the endless improvement of existing designs of CVTs and variators, which inevitably leads to the complication of designs and methods for their control and diagnostics.There is a need to create a fundamentally new simplified gearbox based on the scientific achievements of mechanics. However, the created structures remained inoperable due to the lack of theoretical justification.The adaptive gear variator developed by the author, which has CVT functions, is a mechanism with two degrees of freedom and with an additional constraint of a fundamentally new type, called a force - speed constraint. The force - speed constraint imposes a force restriction on the movement of links, while maintaining the number of degrees of freedom in the kinematics. Monitoring the state of the developed gearbox in the form of a non-switchable gear variator is greatly simplified, since the largest number of faults occur in the control system, and there is no control system in the gear variator. It seems possible to apply the digital twin method to diagnose the developed simplified CVT.The proposed article is devoted to a theoretical description of a fundamentally new adaptive gearbox, created on the basis of the latest achievements in mechanics, with the prospect of developing a simplified monitoring and diagnostic system for it

The performance of the nanoribbon biosensor upon the use of two different types of molecular probes — the antibodies and the aptamers against HCVcoreAg — has been tested. The sensor chips employed are based on “silicon-on-insulator structures”. Two different HCVcoreAg preparations have been tested: recombinant b-galactosidase-conjugated HCVcoreAg (“Virogen”, USA) and recombinant HCVcoreAg (“Vector-Best”, Russia). Upon the detection of either type of the antigen preparation, the lowest concentration of the antigen detectable in buffer with pH 5.1 has been found to be approximately equal, amounting to ~10^–14 M. This value has been found to be similar upon the use of either type of molecular probes.

Qualitative comparative analysis (QCA) was developed by Charles Ragin in 1987 for the comparative analysis of small data sets. The method has become widespread in sociological and economic research. There are examples of successful use of QCA in the field of medicine and epidemiology. The purpose of this review is to describe the key stages of QCA with a discussion the application of this method to the analysis of medical and epidemiological data.

In a 24-week-long experiment, 31 rats were assigned to one of 3 groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. Both groups experienced significantly increased caloric intake but did not gain weight above the Control group level. Adipocytes in subcutaneous and visceral adipose depots of both groups had smaller size compared to control and higher density in tissue. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated that in both experimental groups high tissue respiration is associated with better biochemical profile and closer to control adipose tissue morphology. Increased tissue respiration in adipose depots could be an important mechanism of resilience to excessive caloric intake.

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.

This comparative study aims to investigate environmental awareness, knowledge, and safety among students in Montenegro and North Macedonia, considering the unique socio-cultural and environmental contexts of both countries. A mixed-methods approach involving surveys and interviews was employed to gather data from students in educational institutions across Montenegro and North Macedonia. The study assessed various factors, including students' awareness of environmental issues, their perceived level of knowledge, and their attitudes towards safety measures. A comprehensive series of 400 face-to-face interviews was carried out and these interviews encompassed 200 students from Montenegro and an equal number from North Macedonia, taking place at two esteemed academic institutions: The University of Montenegro in Podgorica and The University of St. Clement of Ohrid, Bitola, Republic of North Macedonia. Our hypothetical conceptual framework proposes that a combination of variables, including gender (H1), age (H2), year of study (H3), and rate of study (H4), significantly influences the attitudes of students from Montenegro and North Macedonia towards environmental awareness, safety, and knowledge. Research findings indicate significant variations in environmental awareness and knowledge perception among students in the two countries. While both Montenegro and North Macedonia face environmental challenges, differences in educational systems and socio-economic factors contribute to distinct attitudes and behaviors towards environmental issues and safety practices. This study sheds light on the importance of understanding regional differences in environmental awareness and knowledge perception among students. By identifying areas of strength and areas needing improvement, policymakers and educators can develop targeted interventions to enhance environmental education and foster a culture of sustainability in both Montenegro and North Macedonia.

The structural evolution and phase composition of multi-block thermoplastic polyurethanes, with different nature of the soft segments based on poly(butylene adipate) (PBA), were analyzed during in-situ thermal treatments. A combination of synchrotron small- and wide-angle X-ray scattering, differential scanning calorimetry, thermogravimetric analysis, and FTIR spectroscopy was used to determine the influence of macrodiol nature and crystallization conditions on the polymorphic behavior of PBA. Using a new synthesis scheme, a relatively high degree of crystallinity for urethane blocks was achieved, which depends on the diisocyanate type in the structure of the soft segment. The hard segment domains impose geometrical constraints on PBA, thereby altering its crystallization process compared to the neat oligomer. Thus, crystallization after annealing at a low temperature (80 °C) is fast, predominantly yielding a metastable β-phase. When heated to 180 °C, which is higher than the hard-segment melting temperature, a phase-separated structure is observed. Subsequent crystallization is slower, favoring the formation of the stable α-PBA modification. The phase separation can be observed even after the hard block melting. A notably slow crystallization from an isotropic melt was documented after the disruption of phase separation at 230 °C.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

The response of plasmonic metal particles to an electromagnetic wave undergoes significant features at the nanoscale level. Different properties of the internal composition of a metal, such as its ionic background and the free electron gas, begin to manifest more prominently. As the dimensions of the nanostructures decrease, the classical local theory gradually becomes inadequate. Therefore, Maxwellʹs equations need to be supplemented with a relationship determining the dynamics of current density which is the essence of nonlocal plasmonic models. In this field of physics, the standard (linearized) hydrodynamic model (HDM) has been widely adopted with great success, serving as the basis for a variety of simulation methods. However, ongoing efforts are also being made to expand and refine it. Recently, the GNOR (general nonlocal optical response) modification of the HDM has been used, with the intention of incorporating the influence of electron gas diffusion. Clearly, from the classical description of fluid dynamics, a close relationship between viscosive damping and diffusion arises. This offers a relevant motivation for introducing the GNOR modification in an alternative manner. The standard HDM and its existing GNOR modification also do not include the influence of interband electron transitions in the conduction band and other phenomena that are part of many refining modifications of the Drude‐Lorentz and other models of metal permittivity. In this article, we present a modified version of GNOR‐HDM that incorporates the viscosive damping of the electron gas and a generalized Drude‐Lorentz term. In the selected simulations, we also introduce Landau damping which corrects the magnitude of the standard damping constant of the electron gas based on the size of the nanoparticle. We have chosen a spherical particle as a suitable object for testing and comparing HD models and their modifications because it allows finding precise analytical solutions for the interaction and, simultaneously, it is a relatively easily fabricable nanostructure in practice. Our contribution also includes our own analytical method for solving the HDM interaction of a plane wave with a spherical particle. This method forms the core of calculations of the characteristic quantities, such as the extinction cross‐sections and the corresponding components of electric fields and current densities.

Hippocampus plays a crucial role in spatial and episodic memory. The acquisition of new memories is impossible without participation of the hippocampus. There are two main functional states or “modes” of the hippocampal activity, theta and non-theta state. They have different behavioral correlates and clearly different spectral content of the LFPs and neuronal spiking. Hippocampal theta state is present under active exploratory behavior, locomotion, cognitive situations requiring attention and REM sleep. Slow-wave sleep and quiet wakefulness (immobility, eating, grooming) represent the non-theta hippocampal state. The nodal point for the regulation of hippocampal activity is the MS. The activation or suppression of different types of MS cells appears to be responsible for controlling hippocampal theta and non-theta states. Functional coupling between MS neurons and hippocampal interneurons varies in a state-dependent manner.

The literature was scoped to help place mass spectrometric (MS) platforms in the spotlight of the life sciences, as a tool of OMICS and OMICS 2.0 technologies. Moreover, today’s appliances are so handy, that they literally place a whole lab on a single chip. Methods of OMICS (and the most recently developed term OMICS 2.0) are tackled, having in mind their aptness for educational purposes, as well as their feasibility. This same topic was highlighted in many reviews that have been periodically published. The author’s initial interest was the forensic application of MS, but since these interests changed, terms such as “biosensors” were also examined, so the review included means of discovery of efficient biomarkers and clinical therapeutic targets. Aside from simply reviewing the research status and the future perspectives, this article tackles terms such as Society 5.0 and OMICS 2.0. However, within the framework of this review, physical chemistry, bioinformatics, or specific software solutions were not specifically studied. Since the topic of generating permanent collections of digital content for retrospective analysis was also reviewed, the need for loads of data – cloud storage was discussed in the context of MS. These large quantities of data are easier to operate with if generated by MS, rather than by any other commercially available assay. In this manner, the review has strengthened an in-depth understanding of the applications of MS.

The growing need to use renewable sources and the current difficulty in spreading the electricity grid in a widespread manner raise the question of how to respond to the need for more electricity immediately. The idea behind this study is to power a horizontal axis wind turbine with the air flow generated for cooling a stationary internal combustion engine. The power extracted from this solution is significantly lower than that of the internal combustion engine (about 0.3%) and could be advantageous only in limited contexts. Installation costs are limited because many elements deriving from wind variability can be removed or simplified.

The deregulated markets have replaced the traditional way of trading electricity from the producers to the consumer, via government-owned organizations and regulated tariffs. Nowadays, electricity prices are determined by the offer-demand mechanism and consumers can negotiate tariffs with their supplier of choice. For classic wholesale suppliers, the tariffs are a result of the transactions performed on the wholesale market and the energy mix available in certain geographical regions. In parallel with becoming eligible and participating in retail electricity markets, the consumers use increasingly local generation sources based mostly on renewable energy technologies such as PV panels, and become prosumers. They want to be able to sell back to the market the generation surplus, in order to obtain the maximum benefits from their initial investment. Currently, several trading mechanisms for prosumers are available, ranging from the simplest, selling back the surplus to an aggregator at fixed tariffs, to more complex market schemes. This paper proposed a two-tier local market model for prosumers and consumers connected in microgrids, based on the blockchain technologies and other technologies and concepts such as remote sensing, smart grids, crowdsourcing and energy poverty.

The deregulated markets have replaced the traditional way of trading electricity from the producers to the consumer, via government-owned organizations and regulated tariffs. Nowadays, electricity prices are determined by the offer-demand mechanism and consumers can negotiate tariffs with their supplier of choice. For classic wholesale suppliers, the tariffs are a result of the transactions performed on the wholesale market and the energy mix available in certain geographical regions. In parallel with becoming eligible and participating in retail electricity markets, the consumers use increasingly local generation sources based mostly on renewable energy technologies such as PV panels, and become prosumers. They want to be able to sell back to the market the generation surplus, in order to obtain the maximum benefits from their initial investment. Currently, several trading mechanisms for prosumers are available, ranging from the simplest, selling back the surplus to an aggregator at fixed tariffs, to more complex market schemes. This paper proposed a two-tier local market model for prosumers and consumers connected in microgrids, based on the blockchain technologies and other technologies and concepts such as remote sensing, smart grids, crowdsourcing and energy poverty.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

Emerging of mass-spectroscopy with inductively-coupled plasma (ICP-MS) made possible to study the microelement composition of crude oil and its derivatives (with the limit of detection at the ppt level). We have studied the crude oil composition of some West Siberian and Tatarstan oilfields with the ICP-MS method to detect 50 rare, rare-earth, and other microelements. The elemental composition is reasonably comparable to their concentrations in ultrabasites whereas the contents of most of the elements are low to the limit. On the diagrams of rare-earth elements, one can see the prevalence of light lanthanides and positive europium anomaly. The study shows that crude oils have a specific microelement composition that stands out from other geological systems.

Lettuce (Lactuca sativa) is a leafy vegetable that provides a valuable source of phytonutrients for a healthy human diet. Assessment of plant growth and composition is vital for determining crop yield and overall quality, however, classical laboratory analyses are slow and costly. Therefore, new, less expensive, more rapid, and non-destructive approaches are being developed, including those based on (hyper)spectral reflectance. Additionally, it is also important to determine how plant phenotypes respond to fertilizer treatments and whether these differences in response can be detected from analyses of hyperspectral image data. In the current study, we demonstrate the suitability of hyperspectral imaging in combination with machine learning models to estimate the content of chlorophyll (SPAD), anthocyanins (ACI), glucose, fructose, sucrose, vitamin C, β-carotene, N, P, K, dry matter content, and plant fresh weight. The implemented five classification and regression machine learning models showed high accuracy in classifying the lettuces by the applied fertilizers treatments and estimating nutrient concentrations. To reduce the input (predictor data, i.e., hyperspectral data) dimension, 13 principal components were found and applied in models. The implemented artificial neural network models of the machine learning algorithm demonstrated high accuracy (r = 0.85 ... 0.99) in estimating fresh leaf weight, and contents of chlorophyll, anthocyanins, N, P, K, and β-carotene. The four applied classification models of machine learning demonstrated 100% accuracy in classifying the studied baby leaf lettuces by phenotype when certain fertilizer treatments were applied.

Despite the remarkable success of Carnot’s heat engine cycle in founding the discipline of thermodynamics two centuries ago, false viewpoints of his use of the caloric theory in the cycle still linger, limiting his legacy. An action revision of the Carnot cycle can correct this, showing that the heat flow powering external mechanical work is compensated internally with configurational changes in the thermodynamic or Gibbs potential of the working fluid, differing in each stage of the cycle quantified by Carnot as caloric. Action (@) is a property of state having the same physical dimensions as angular momentum (mrv=mr2ω). However, this property is scalar rather than vectorial, including a dimensionless phase angle (@=mr2ωδφ). We have recently confirmed with atmospheric gases that their entropy is a logarithmic function of the relative vibrational, rotational and translational action ratios with Planck’s quantum of action ħ. The Carnot principle shows that the maximum rate of work (puissance motrice) possible from the reversible cycle is controlled by the difference in temperature of the hot source and the cold sink, the colder the better. This temperature difference between the source and the sink also controls the isothermal variations of the Gibbs potential of the working fluid, that Carnot identified as reversible temperature-dependent but unequal exchanges in caloric. Importantly, the engine’s inertia ensures that heat from work performed adiabatically in the expansion phase is all restored to the working fluid during the adiabatic recompression, less the net work performed. This allows both the energy and the thermodynamic potential to return to the same values at the beginning of each cycle, a point strongly emphasized by Carnot. Our action revision equates Carnot’s calorique, or the non-sensible heat later described by Clausius as ‘work-heat’ exclusively to negative Gibbs energy (-G) or quantum field energy. This action field complements the sensible energy or vis-viva heat as molecular kinetic motion and its recognition should have significance for designing more efficient heat engines or better understanding of the heat engine powering the Earth’s climates.

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using Nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results & conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

The spectral properties of a one-dimensional photonic crystal bounded by a resonant absorbing nanocomposite layer with the near-zero permittivity have been studied. The problem of calculating the transmittance, reflectance, and absorptance spectra of such structures at the normal and oblique incidence of light has been solved. It is shown that, depending on the permittivity sign near zero, the nanocomposite is characterized by either metallic or dielectric properties. For the first time, the possibility of simultaneous formation of the Tamm plasmon polariton at the photonic crystal/metallic nanocomposite interface and the localized state similar to the defect mode with the field intensity maximum inside the dielectric nanocomposite layer is demonstrated. Specific features of field localization at the Tamm plasmon polariton and defect mode frequencies are analyzed.

This study employs molecular docking simulations using Autodock Vina with the Pyrx program to investigate the binding interactions between Human prostate-specific antigen (PSA) and natural compounds, namely Amentoflavone, Ginketin, Rutin, and Hypericin. The evaluation reveals excellent binding energy values, averaging around -10 kcal/mol, suggesting robust and favorable interactions between the selected compounds and PSA. The results provide valuable insights into the potential therapeutic applications of these natural compounds in the context of prostate cancer treatment or management. Further experimental validation is warranted to confirm these findings and explore the viability of these compounds as promising candidates for innovative therapeutic strategies. This research contributes to the growing body of knowledge in the field of molecular docking and its applications in drug discovery and bioinformatics.

Parkinson's disease is a neurodegenerative disorder resulting from progressive damage to specific brain regions. Key symptoms encompass involuntary movements (tremor), slowness of movements (bradykinesia), and muscle rigidity. Although the precise cause remains uncertain, a combination of genetic and environmental factors is believed to contribute to its development. This study focuses on the interaction of the E3 ubiquitin-protein ligase parkin with natural compounds. Docking investigations revealed that Amentoflavone exhibited an excellent binding energy score of approximately -10 kcal/mol. The E3 ubiquitin-protein ligase parkin displayed a robust binding affinity with docked amentoflavone, evident from a high binding energy of -10 kcal/mol. Nonetheless, additional biological studies are crucial not only to validate its potential efficacy against Parkinson's and assess safety in terms of toxicity but also to perform further computational analyses confirming these preliminary assessments.

This study employs molecular docking techniques to investigate a spectrum of targets within Escherichia coli (E. coli), with a specific focus on four key proteins: Beta-lactamase, MccE protein, Penicillin G acylase, and DNA polymerase II. The research explores the binding interactions of various natural compounds, emphasizing Hypericin. Through computational analyses, the study aims to unveil the potential interactions between these compounds and essential proteins in E. coli. Notably, Hypericin demonstrates remarkable binding energy scores of approximately -10.5 kcal/mol within the Ligand Binding Site of the specified proteins. This observation suggests Hypericin's potential as a potent modulator of E. coli targets, prompting further investigation into its antimicrobial properties and therapeutic applications.

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

PIM1is involved in critical cellular processes, playing a key role in the regulation of the cell cycle, apoptosis, transcriptional activation, and broader signal transduction pathways . The exploration of PIM1inhibitors, such as small molecules or antibodies, represents a promising avenue in cancer research for developing novel treatment strategiess. Its significance in oncogenic signaling has led to extensive research on PIM1 as a target in cancer studies. Docking studies have revealed a robust interaction between hypericin and PIM1, suggesting a strong binding affinity (-12.5 kcal/mol). This research aims to explore the molecular dynamics of the hypericin-PIM1 interaction, identifying potential binding sites and elucidating the impact on PIM1-mediated cellular processes, such as cell cycle regulation and apoptosis. The findings may contribute valuable insights into developing hypericin-based therapies targeting PIM1, paving the way for novel and effective strategies in cancer research.

Heat Shock Proteins play a crucial role in maintaining cellular integrity during thermal stress conditions, acting as chaperones and participating in the regulation of cellular responses. The focus was to contribute valuable insights into the potential role of hypericin in modulating these heat shock proteins and its implications for anti-tumoral properties. This study employs computational methods, specifically molecular docking, to investigate the potential biological interactions between the chaperone proteins HSP90 and HSC70 and Hypericin, a natural compound recognized for its anti-tumor properties. Despite the limited existing studies in this domain, this research aims to uncover structural insights into the binding mechanisms between Hypericin and these heat shock proteins. In the docking assessments, hypericin demonstrated notable binding energy results, exhibiting a binding energy of -10.5 kcal/mol with Heat Shock Cognate 71 kDa protein and -11.2 kcal/mol with Heat Shock Protein HSP90-alpha.

BACE1 is involved in the production of beta-amyloid peptides, and inhibiting its activity is a potential therapeutic strategy for managing Alzheimer's disease, as excessive beta-amyloid accumulation is a characteristic feature of the disease.Computational results suggest that hypericin has the potential to act as an inhibitor of BACE1. The Molecular Docking results indicate a high binding affinity between hypericin and BACE1, with a notable binding energy score of -10.3 kcal/mol. Additionally, the formation of various chemical bonds, including hydrogen bonds and hydrophobic bonds, further supports the idea that hypericin may effectively interact with the active site of BACE1. It's important to note that while the in silico Molecular Docking results are promising, further in vitro and in vivo studies would be necessary to validate and better understand the inhibitory potential of hypericin against BACE1. Additionally, the practical application of hypericin as a BACE1 inhibitor in a therapeutic context would require careful consideration of factors such as bioavailability, safety, and efficacy.

The assessment of Histone deacetylases in conjunction with Curcumin, conducted through the Mcule Database employing the Autodock Vina algorithm, involves an examination of molecular interactions. This analysis includes the calculation of binding energies, revealing the strength and stability of the interactions between Curcumin and various Histone deacetylase targets. The comparison encompasses diverse aspects such as binding energies, specific binding sites, interactions across different targets, structural details, and potential implications for biological activity. The results imply that Curcumin shows heightened affinity for Histone deacetylase 4 in comparison to other investigated histone deacetylases.

Understanding the genetic architecture of a disease is crucial for development of valid diagnostic and therapeutic interventions. The analysis of genomic variations associated with pathological conditions is the starting point for uncovering disease-causing pathways (candidate processes). However, the complexity of intergenic and genetic-environmental interactions hinders the identification of pathogenic values of genomic changes. Furthermore, heredity, epigenetics and somatic mosaicism make the interpretation of genomic data even more sophisticated. To succeed, a variety of bioinformatic techniques are applied. Here, reviewing own and literature data, knowledge-based prioritization of genomic variations is described. Theoretical basis of the knowledge-based prioritization is given with a special regard to gene ontology, heuristics, hermeneutics (genomic hermeneutics) and analytics. Practical and methodological issues of prioritization using ontology- or pathway-based systems analysis are considered in the light of optimistic and realistic scenarios of cumulative phenotypic effects of the variome (the whole set of genomic variations in an individual or specific set of genomic variations for a phenotypic outcome). In the present communication, copy number variants (CNVs) in children with neurodevelopmental diseases are used as a practical foundation for the prioritization, inasmuch as these genome variations are systematically overlooked in the so-called NGS era. Nonetheless, it is highly likely that the prioritization is applicable to almost all types of genomic variations (e.g. chromosome abnormalities, gene mutations, functional synonymous variants etc.). The present methodology seems to be a valuable addition to current biomedical science widening the opportunities for medical genomics and genetics.

Information cascades (tree-like structures formed by posts, comments, likes, replies, etc.) constitute the spine of the public online information environment, reflecting its various trends, evolving with it and, importantly, affecting its development. While users participate in online discussions, they display their views and thus contribute to the growth of cascades. At the same time, users’ opinions are influenced by cascades’ elements. The current paper aims to advance our knowledge regarding this social phenomenon by developing an agent-based model in which agents participate in a discussion around a post on the Internet. Agents display their opinions by writing comments on the post and liking them (i.e., leaving positive assessments). The result of these processes is dual: on the one hand, agents develop an information cascade; on the other hand, they update their views. Our purpose is to understand how agents’ activity, openness to influence, and cognitive constraints (that condition the amount of information individuals are able to proceed with) affect opinion dynamics. We also control for social contagions (when people’ perception of a message may depend not only on the message’s opinion, but also on how other individuals perceive this object, with more positive evaluations increasing the probability of adoption) and ranking algorithms that steer the order in which agents learn new messages. Among other things, we demonstrated that replies to disagreeable opinions are extremely effective for promoting your own position. In contrast, likes have a tiny effect on this issue.

The question does P = NP has confounded mathematicians and computer scientists alike for over 50 years and although there is an almost unanimous agreement that it in fact does not, there still is no absolute proof. In this paper, I attempt to prove to that P does not equal NP.

Chemical versatility of organic semiconductors provides nearly unlimited opportunities for tuning their electronic properties. However, despite decades of research, relationship between molecular structure, molecular packing and charge mobility in these materials remains poorly understood. This reduces the search for high-mobility organic semiconductors to the inefficient trial-and-error approach. For clarifying the abovementioned relationship, investigations of the effect of small changes in the chemical structure on OSs properties are particularly important. In this study, we address computationally the impact of substitution of C-H atom pairs by nitrogen atoms (N-substitution) on molecular properties, molecular packing and charge mobility of crystalline oligoacenes. Besides of decreasing frontier molecular orbital levels, N-substitution dramatically alters molecular electrostatic potential yielding pronounced electron-rich and electron-deficient areas. These changes in the molecular electrostatic potential strengthen face-to-face and edge-to-edge interactions in the corresponding crystals and result in the crossover from the herringbone packing motif to π-stacking. When the electron-rich and electron-deficient areas are large, sharply defined and, probably, have certain symmetry, charge mobility increases up to 3-4 cm2V-1s-1. The results obtained highlight the potential of azaacenes for application in organic electronic devices and are expected to facilitate rational design of organic semiconductors for steady improvement of organic electronics.

The gravel road pavement has a lower construction cost but poorer performance than the asphalt surface. It also emits dust and deforms under the impact of vehicle loads and ambient air factors. The resulting ripples and ruts are constantly deepening, increasing vehicle vibrations and fuel consumption, reducing safe driving speed and comfort. In this article, existing pavement quality evaluation indexes are analysed, and a methodology for their adaptation for roads with gravel pavement is proposed. This article reports the measured wave depth and length of the gravel pavement profile by the straightedge method of a 160 m long road section in three road exploitation stages. The measured pavement elevation was processed according to ISO 8608, and vehicle frequency response has been investigated using simulations in MATLAB/Simulink. The applied International Roughness Index (IRI) analysis showed that a speed of 30-45 km/h instead of 80 km/h provides the objective results of IRI calculation on the flexible pavement due to a decreasing velocity of vehicle's unsprung mass on a more deteriorated road pavement state. The influence of the corrugation phenomenon of gravel pavement has been explored, identifying specific driving safety and comfort cases. Finally, an increase in the Dynamic Load Coefficient (DLC) at a low speed of 30 km/h on the most deteriorated pavement and a high speed of 90 km/h on the middle-quality pavement demonstrates the demand for timely gravel pavement maintenance and the complicated prediction of a safe driving speed for drivers.

Clausius’ virial theorem set a basis for relating kinetic energy in a body of independent material particles to its potential energy, pointing to their complementary role with respect to the second law of maximum entropy. In action mechanics, expressing the entropy of ideal gases as a capacity factor for sensible heat or enthalpy plus the configurational work to sustain the relative translational, rotational and vibrational action yields algorithms for estimating chemical reaction rates and positions of equilibrium. All properties of state including entropy, work potential as Helmholtz and Gibbs energies and activated transition state reaction rates can be estimated, using easily accessible molecular properties, such as atomic weights, bond lengths, moments of inertia and vibrational frequencies. Understanding how Clausius’ virial theorem balances the internal kinetic energy with field potential energy justifies partitioning between thermal and statistical properties of entropy, yielding a more complete view of the evolutionary nature of the second law of thermodynamics. The ease of performing these operations is illustrated by three important chemical gas phase reactions, the reversible dissociation of the hydrogen molecules, lysis of water to hydrogen and oxygen and the reversible formation of ammonia from nitrogen and hydrogen. Employing the ergal also introduced by Clausius to define the reversible internal work to overcome molecular interactions plus the configurational internal work of negative Gibbs energy as a function of volume or pressure may provide a practical guide for managing risk in industrial processes and climate change at the global scale.

Using the fluorescent method in the modification of Krasnoyarsk State University, we study development (as chlorophyll content, ∑CHL) and photosynthetic activity of phytoplankton in seven large flat reservoir of the Volga River cascade (Russia) in August 2915–2017. In period of maximal warming of water, average ∑CHL varied in limits of 19.4–33.7 μg L–1 in the Upper Volga, 8.5–27.8 μg L–1 in the Middle Volga, and 5.2–11.3 μg L–1 in the Lower Volga. Photosynthetic activity coefficient (PhAC) varied mostly in limits of 0.12–0.59 with average of 0.22–0.38 and only in 2017 decreased to minimal <0.10 and average <0.20. The average PhAC values shows the normal physiological state of the phytoplankton of the Upper Volga during all periods of observation, occasional decrease of PhAC in the Middle Volga, and low photosynthetic activity in the Lower Volga. A decrease in the average ∑Chl and PhAC in 2017 was under cyclonic windy weather with a large amount of precipitation, low solar radiation, and large volume of flow. Trend towards a decrease in ∑CHL, like decrease in PhAC from the Upper Volga to the Lower Volga is explained by increasing in the flow rate and volume of runoff downstream the Volga River.

The antioxidant potential (capacity and activity) of aqueous fullerene dispersions (AFD) of non-functionalized C₆₀, C₇₀, and Gd@C₈₂ endofullerene (in micromolar concentration range) was estimated based on chemiluminescence measurements of the model of luminol and generation of organic radicals by 2,2’-azobis(2-amidinopropane) dihydrochloride (ABAP). The antioxidant capacity was estimated by the TRAP method, from the concentration of half-suppression, and from the suppression area in the initial period. All three approaches agree and show that the antioxidant capacity of AFDs increased in the row Gd@C₈₂ < C₇₀ < C₆₀. Mathematical modeling of the long-term kinetics data was used for antioxidant activity estimation. The effect of C₆₀ and C₇₀ is found to be quenching of the excited product of luminol with ABAP-generated radical and not an actual antioxidant effect; quenching constants differ insignificantly. Apart from quenching with a similar constant, the AFD of Gd@C₈₂ exhibits actual antioxidant action. The antioxidant activity in Gd@C₈₂ is 300-fold higher than quenching constants.

Background: Despite the fact that bone reconstructive surgeries are widely practiced worldwide, the search for an ideal bone replacement matetrial is still an open issue. We aimed to provide an overview of the current status of research and developments in this field with a focus on sapphire materials; Methods: A literature search and review was conducted using the PubMed, Scopus, and Embase databases. We searched for literature using the following keywords: bone implants; biocompatible materials; bone replacement material; sapphire implants; Results: Sapphire has a unique combination of mechanical, physical and chemical characteristics thanks to wich it has an excelent biocompatability and biointegrity.Unlike other materials it is incredibly strong and has a high endurance. The successful experience of using this material in medical instrument engineering, dentistry and cardiac surgery shows its benefits; Conclusions: We consider that sapphire is a perspective material for bone replacement implants and researchers should look in this direction.

We offered the circuit of a discrete analog filter (DAF) low frequencies of second-order on switchable capacitors, which differs from the known ones in that three capacitors with one terminal are connected to a common bus, and the frequency of the DAF pole depends not only on the ratio of the capacitances of the frequency-setting capacitors, but also on the ratio of resistances two additional resistors in the feedback. This allows at constant values ​​of the capacitances and a fixed switching frequency of electronic switches, control the pole frequency by changing the resistance ratio of additional resistors. Computer simulation of the developed circuit was performed in the Micro-Cap environment. It has been established that the DAF has a transmission coefficient close to minus one at very low frequencies and a transmission coefficient close to zero at higher frequencies.

Transmission electron microscopy methods were used to analyze the cementite substructure in the head of special-purpose long rails of DT400IK category made of hypereutectoid steel after long-term operation on an experimental track on the Russian Railways ring (the passed tonnage is 187 million tonnes). It is noted that the study of various aspects of cementite – its structure, morphology, chemical composition, crystal lattice defects is relevant. The steel structure is represented by three morphological components at a distance of 10 mm from the sample surface: lamellar perlite, fractured and fragmented perlite. The volume fraction of lamellar perlite in the material is 65%. It is shown that after operation, the cementite plates are bent and separated by ferrite bridges. In the plates of ferrite and cementite, a dislocation substructure is formed which is of chaotically distributed and network type in ferrite and of ordered type in cementite. An increased density of dislocations at ferrite-cementite interfaces compared to the volume of ferrite plates was noted. Two possible mechanisms of deformation transformation of lamellar perlite grains are indicated: fracture of cementite plates and carbon pulling out from the lattice of the carbide phase. It is indicated that in the dissolution of cementite plates, the interfacial boundaries “α-phase-cementite” play an important role. The removal of carbon from cementite plates occurs most intensively near defects in ferrite and cementite. The formed nanosized particles of tertiary cementite are unevenly distributed in the ferrite plates, most of them are observed at the locations of ferrite subgrains and interfacial boundaries. This results in non-uniform diffraction contrast in dark-field images of cementite plates. Nanosized particles of cementite can be taken out into the interlamellar space of pearlite colonies in the process of dislocation slip, or they are formed as a result of deformation decomposition, which is less likely. Fragmentation of ferrite and cementite plates is revealed and azimuthal components of total misorientation angles are estimated. The mechanisms of mass transfer of carbon atoms over interstitial sites, deformation vacancies, dislocation tubes, grain boundaries and fragments are considered. According to all the established patterns of the cementite substructure transformation, a comparison with the results for rails made of hypoeutectoid steel was performed.

Grid refinement is used to save computing costs while preserving high precision of fluid simulation. In the Lattice Boltzmann Method, grid refinement often uses interpolated values. We found a method, where interpolation in space and time is not required. For this purpose, we used the moment matching condition and rescaling the non-equilibrium part of populations, and developed the recalibration procedure that allows to transfer information between different LBM stencils in the simulation domain. Then, we build non-uniform lattice which uses stencils with different shapes on the transition. The resulting procedure is verified on the 2D Poisselle flow and the advected vortex benchmark. In prospect, grids with adaptive geometry can be built with the use of the proposed method.

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

This paper discusses approaches to the numerical integration of the coupled nonlinear Schrödinger equations system in case of few-mode wave propagation. The wave propagation assumes the propagation of up to nine modes of light in an optical fiber. In this case, the light propagation is described by the non-linear coupled Schrödinger equation system, where propagation of each mode is described by own Schrödinger equation with other modes interactions. In this case, the non-linear coupled Schrödinger equation system solving becomes increasingly complex, because each mode affects the propagation of other modes. The suggested solution is based on the direct numerical integration approach, which is based on a finite-difference integration scheme. The well-known explicit finite-difference integration scheme approach fails, due to the non-stability of the computing scheme. Due to this fact, the combined explicit/implicit finite-difference integration scheme, based on the implicit Crank–Nicolson finite-difference scheme, is used. It allows ensuring the stability of the computing scheme. Moreover, this approach allows separating the whole equation system on the independent equation system for each wave mode at each integration step. Additionally, the algorithm of numerical solution refining at each step and the integration method with automatic integration step selection are used. The suggested approach has performance gains (or resolutions) up to three or more orders of magnitude in comparison with the split-step Fourier method due to the fact that there is no need to produce direct and inverse Fourier transforms at each integration step. The main advantage of the proposed method is the ability to calculate the propagation of an arbitrary number of modes in the fiber.

The opinion dynamics literature argues that the way people perceive social influence depends not only on the opinions of interacting individuals, but also on the individuals’ non-opinion characteristics, such as age, education, gender, or place of residence. The current paper advances this line of research by studying longitudinal data that describe the opinion dynamics of a large sample (~30,000) of online social network users, all citizens of one city. Using these data, we systematically investigate the effects of users’ demographic (age, gender) and structural (degree centrality, the number of common friends) properties on opinion formation processes. We revealed that females are less easily influenced than males. Next, we found that individuals that are characterized by similar ages have more chances to reach a consensus. Besides, we report that individuals who have many common peers find an agreement more often. We also demonstrated that the impacts of these effects are virtually the same, and despite being statistically significant, are far less strong than that of opinion-related features: knowing the current opinion of an individual and, what is even more important, the distance in opinions between this individual and the person that attempts to influence the individual is much more valuable. Next, after conducting a series of simulations with an agent-based model, we revealed that accounting for non-opinion characteristics may lead to not very sound but statistically significant changes in the macroscopic predictions of the populations of opinion camps, primarily among the agents with radical opinions (≈ 3% of all votes). In turn, predictions for the populations of neutral individuals are virtually the same. Besides, we demonstrated that the accumulative effect of non-opinion features on opinion dynamics is seriously moderated by whether the underlying social network correlates with the agents’ characteristics. After applying the procedure of random shuffling (in which the agents and their characteristics were randomly scattered over the network), the macroscopic predictions have changed by ≈ 9% of all votes. What is interesting, the population of neutral agents was again not affected by this intervention.

Sulfur, peroxide and combined sulfur and peroxide curing systems were applied for cross-linking of unfilled and carbon black filled rubber compounds based on ethylene-propylene-diene-monomer rubber. The results revealed that the type of curing system influenced the course and shape of curing isotherms. This resulted in the change of curing kinetics of rubber compounds. The cross-link density of vulcanizates cured with combined vulcanization systems was lower than that for vulcanizates cured only in the presence of sulfur or peroxide system. The results revealed good correlation between the cross-link density as well as the structure of the formed cross-links and physical-mechanical characteristics of the materials. It can be stated that by proper combination of vulcanization systems it is possible to modify tensile behavior of vulcanizates in targeted manner. On the other side, dynamical-mechanical properties were found not be significantly influenced by the composition of curing system.

Four-wire low voltage microgrids supply one-phase consumers with continuously changing electricity demand. For addressing climate change concerns, governments implemented incentive schemes for residential consumers, encouraging the installation of home PV panels for covering self-consumption needs. In the absence of sufficient storage capacities, the surplus is sold back by these entities, called prosumers, to the grid operator or in local markets, to other consumers. While these initiatives encourage the proliferation of green energy resources, and ample research is dedicated to local market designs for prosumer-consumer trading, the main concern of distribution network operators is the influence of power flows generated by prosumer surplus injection on the operating states of microgrids. The change in power flow amount and direction can greatly influence the economic and technical operating conditions of radial grids. This paper proposes a metaheuristic algorithm for prosumer surplus management that optimizes the power surplus injections using the automated control of three-phase inverters, with the aim of improving the active power losses and balancing the phase voltage profiles. A case study is performed on two real distribution networks with distinct layouts and load profiles and the algorithm shows its efficiency in both scenarios.

A growing number of households benefit from the government subsidies to install renewable generation facilities such as PV panels, used to gain independence from the grid and provide cheap energy. In the Romanian electricity market, these prosumers can sell their generation surplus only at regulated prices, back to the grid. A way to increase the number of prosumers is to allow them to make higher profit by selling this surplus back into the local network. This would also be an advantage for the consumers, who could pay less for electricity exempt from network tariffs and benefitting from lower prices resulting from the competition between prosumers. One way of enabling this type of trade is to use peer-to-peer contracts traded in local markets, run at microgrid (μG) level. This paper presents a new trading platform based on smart peer-to-peer (P2P) contracts for prosumers energy surplus trading in a real local microgrid. Several trading scenarios are proposed, which give the possibility to perform trading based on participants’ locations, instantaneous active power demand, maximum daily energy demand and the principle of first come first served implemented in an anonymous blockchain trading ledger. The developed scheme is tested on a low-voltage (LV) microgrid model to check its feasibility of deployment in a real network. A comparative analysis between the proposed scenarios, regarding traded quatities and financial benefits is performed.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.