G protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant and well-studied protein targets, yet unanswered questions in the field leave significant gaps in our understanding of their nuanced structure and function. 3D pharmacophore models are powerful computational tools in silico drug discovery, presenting myriad opportunities for the integration of GPCR structural biology and cheminformatics. This review highlights success stories in the application of 3D pharmacophore modeling to de novo drug design, discovery of biased and allosteric ligands, scaffold hopping, QSAR analysis, hit-to-lead optimization, GPCR de-orphanization, mechanistic understanding of GPCR pharmacology and elucidation of ligand-receptor interactions. Furthermore, advances in the incorporation of dynamics and machine learning will be highlighted. The review will analyze challenges in the field of GPCR drug discovery, detailing how 3D pharmacophore modeling can be used to address them. Finally, we will present opportunities afforded by 3D pharmacophore modeling in the advancement of our understanding and targeting of GPCRs.

Machine learning methods have widely been applied to detect anomalies in machine and cutting tool behavior during lathe or milling. However, detecting anomalies in the workpiece itself did not get the same attention by researchers. That is why in this article, the authors present a pub-licly available multivariate time series dataset which was recorded during milling of 16MnCr5. Due to artificially introduced, though realistic anomalies in the workpiece the dataset can be ap-plied for anomaly detection. By using a convolutional autoencoder as a first model good results in detecting the location of the anomalies in the workpiece were achieved. Furthermore, milling tools with two different diameters where used which led to a dataset eligible for transfer learn-ing. The objective of this article is to provide researchers with a real-world time series dataset of the milling process which is suitable for modern machine learning research topics like anomaly detection and transfer learning.

This paper presents a comparison of two methods to represent variable blade inertia in two codes for aero-servo-elastic simulations of wind turbines: the nonlinear aeroelastic multi-body model HAWC2 and the nonlinear geometrically exact beam model BeamDyn for OpenFAST. The main goal is to enable these tools to simulate the dynamic behavior of a wind turbine with variable blade inertia. However, in order to simulate the structural response of wind turbines with variable blade inertias, the source code of load simulation tools need to be modified. This is due to the fact that, currently, state-of-the-art load simulation tools for wind turbines are unable to simulate variable rotor blade inertias. The validity of the modified codes is proven based on a simple beam model. The validation shows very good agreement between the modified codes of HAWC2, BeamDyn and an analytical calculation. The add-on of variable blade inertias is applied to reduce the mechanical loads of a 5 megawatt reference wind turbine with an integrated hydraulic-pneumatic flywheel in its rotor blades.

In this work, the wetting and evaporation behaviour of non-polar solvent droplets on thin soluble coatings is investigated experimentally. The wetting process on spin coated polymer layers by the solvent is captured using shadowgraphy. Initial spontaneous dynamic wetting as well as later stages of wetting are recorded and evaluated. Furthermore, structures obtained by wetting and subsequent evaporation of solvents on polymer coatings are studied by confocal microscopy. The solubility of the substrate has been varied by using polymers with different molecular masses. We observe that initial spreading dynamics does not depend on the molar mass in the studied range. However, we find a strong influence of the molar mass on the late stage wetting dynamics and on the surface structure after solvent evaporation.

For evaluating probabilities of arbitrary random events with respect to a given multivariate probability distribution, specific techniques are of great interest. An important two-dimensional high risk limit law is the Gauss-exponential distribution whose probabilities can be dealt with based upon the Gauss-Laplace law. The latter will be considered here as an element of the newly introduced family of (p,q)-spherical distributions. Based upon a suitably defined non-Euclidean arc-length measure on (p,q)-circles we prove geometric and stochastic representations of these distributions and correspondingly distributed random vectors, respectively. These representations allow dealing with the new probability measures similarly like with elliptically contoured distributions and more general homogeneous star-shaped ones. This is demonstrated at hand of a generalization of the Box-Muller simulation method. En passant, we prove an extension of the sector and circle number functions.

Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanism by which spiders respond to heavy metals at the molecular level. In this study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. Ultimately, 3450 cDNA simple sequence repeats were identified and validated as potential molecular markers in the unigenes. A total of 2939, 2491 and 3759 DEGs were detected among the three libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanism underlying spiders' responses to heavy metal stress.

Periodontitis is microbial infection affecting periodontium, the tooth supporting structure and affects >743 million people worldwide. Neural crest-derived stem cells (NCSCs) hold the promise to regenerate the damaged periodontium. These cells have been identified within adult adipose tissue, periodontal ligament, and palatal tissue. Typical enzymatic isolation protocols are expensive, time consuming and often not clinically compliant. Enzyme-free, mechanical dissociation has been suggested as an alternative method of generating cell suspensions required for cell separation and subsequent expansion ex vivo. In our study, samples of rat skeletal muscle tissue were used to appraise the suitability of a novel mincing method of mechanical dissociation against enzymatic digestion with collagenase and dispase. Skeletal muscle is readily available and has been shown to contain NCSC populations. We used a Rigenera-Human Brain Wave^® prototype mincer to produce a suspension of skeletal muscle-derived cells modeling NCSCs. We have compared the resulting cell cultures produced via mechanical dissociation and enzymatic dissociation, producing single cell suspensions suitable for Magnetic Cell Sorting (MACs) and Fluorescence-activated cell sorting (FACS). Despite the Countess Automated Cytometry data demonstrating that cell suspensions produced by mechanical dissociation (n=24) contain on average 26.8 times as many viable cells as enzymatic cell suspensions (n=18), enzymatic suspensions produced more successful cell cultures. Spheroids and subsequently adherent cells formed from 4 enzymatic cell suspensions (44.4%) vs. 1 mechanical cell suspension (8.3%). Enzymatic digestion protocols formed spheroids faster and more plentifully than mechanical cell suspensions. Adherent cells and spheroids isolated via both methods appear morphologically similarly to NCSCs from our previous studies.

Influenza in pregnancy is associated with elevated morbidity and mortality. Influenza vaccines are safe and effective in pregnancy. There are no Mexican surveys in physicians on knowledge, beliefs, and practices towards influenza and influenza immunization during pregnancy. A 32 questions cross-sectional and descriptive survey was conducted addressing general knowledge of influenza, as well as beliefs and practices regarding influenza vaccination during pregnancy among Mexican physicians responsible for prenatal care, traditionally Obstetricians (OBGYNs), and Family Physicians (FPs). A total of 206 surveys were available, 98 (47.6%) from OBGYNs, and 108 (52.4%) from FPs representing an estimated 2,472 daily pregnancy consultations. 54 from 206 (26.2%) weren´t aware that influenza is more severe during pregnancy, 106 from 206 (51.5%) ignored the potential side effects of influenza infection on the fetus, and 56.8% did not know when to vaccinate pregnant women. Pregnancy as a risk factor for developing influenza complications was known only by 99 from 206(48.1%), and 6.1 % believed that vaccination does not confer protection to the fetus. Current beliefs of Mexican OBGYNs and FPs for both influenza morbidity and mortality, and the importance of influenza vaccination during pregnancy, is suboptimal. Understanding drivers for beliefs should be assessed to improve influenza vaccination recommendations, as knowledge alone is not sufficient.

Greenhouse gas (GHG) emissions from human activities have climbed significantly above pre-pandemic levels and reached record highs that unequivocally accelerate global warming. Industry has a significant impact on climate change, emitting at least 21 % of global GHGs and making little overall progress toward its reduction until now. Reducing industry’s emissions requires coordinated action along the value chains in order to promote mitigation options, such as energy and material efficiency, circular material flows, and transformative changes within production processes. The authors analyzed the GHG emissions generated during the manufacturing of three different products of automotive suppliers located in Austria. Despite previous efforts toward an environmentally compatible fabrication, additional and significant reduction potentials were identified. These measures for product carbon footprint (PCF) reduction included the sourcing of low-carbon materials (which are already available on the market), more extensive use of renewable energy, and changes towards more resource efficient manufacturing processes and machinery. Depending on the materials used, the PCF can be reduced by up to 80 %. The findings serve to prepare for future PCF reporting regulations and illustrate reduction potentials to achieve future market advantages, especially when PCFs become an awarding criterion.

Considering the negative impacts of climate changes along with the rapid increase in population in Islamic dominated states, e.g., the Middle East, water tension among upstream and downstream states is increasing. Despite the importance of water management in Islamic culture, the role of religion has been under-valued and under-emphasized by the scholars. The paper has sought to compare and contrast Islamic water management principles (IWMP) with international water law principles (IWLP). The findings from this analysis show not only that IWMP are in conformity with IWLP, but that in many cases, IWMP can be more effective. For instance, where international water accords between riparian states of a shared river basin are poorly developed and lack enforcement mechanisms under IWLP, those upstream states can abuse their geographical locations depriving those downstream-ers. In contrast, IWMPs stress the equitable and reasonable use of water resources among upstream and downstream users of a shared watercourse. Moreover, although IWLPs emphasize the conservation and preservation of ecosystems and the environment at the basin level, the inter-basin states especially those upstream can pose significant harm to the ecosystems. On the other side, Islam as the religion of peace, has placed much emphasis on the preservation of nature. For example, the verse, “.... And waste not by excess, for Allah loves not the wasters” [Quran, 7:31], illustrates the importance of the sustainable use of water and the environment. It is argued that if Islamic Water Management Principles are incorporated into the management instrument of Islamic States, the issue of equitable and sustainable use of water among Muslim-dominated riparian states (e.g., Iran, Afghanistan, etc.) will be solved.

The food system represents a key industry for Europe and particularly Germany. However, it is also the single most significant contributor to climate and environmental change. A food system transformation is necessary to overcome the system's major and constantly increasing challenges in the upcoming decades. One possible facilitator for this transformation are radical and disrup-tive innovations that start-ups develop. There are many challenges for start-ups in general and food start-ups in particular. Various support opportunities and resources are crucial to ensure the success of food start-ups. One aim of this study is to identify how the success of start-ups in the food system can be supported and further strengthened by players in the innovation ecosystem in Germany. There is still room for improvement and collaboration toward a thriving innovation ecosystem. A successful innovation ecosystem is characterised by a well-organised, collaborative, and supportive environment with a vivid exchange between the members in the ecosystem. The interviewees confirmed this, and although the different actors are already cooperating, there is still room for improvement. The most common recommendation for improving cooperation is learning from other countries and bringing the best to Germany.

Low-frequency electromagnetic induction (EMI) is a non-invasive geophysical method that is based on the induction of electromagnetic (EM) waves into the subsurface to quantify changes in electrical conductivity. In this study we present an open (design details and software are accessible) and modular system for the collection of EMI data. The instrument proposed allows to adjust the separations between the transmitter and up to four receiving antennas as well as the acquisition frequency (in the range between 3 and 50 kHz) to permit measurements with variable depth of investigation. The sensor provides access to raw data and the software described in this study allows control of the signal processing chain. The design specifications permit apparent conductivity measurements in the range of between 1 mS/m and 1000 mS/m, with a resolution of 1.0 mS/m and with a sampling rate of up to 10 samples per second. The sensor allows for a synchronous acquisition of a time stamp and a location stamp for each data sample. The sensor has a mass of less than 5 kg, is portable and suitable for 1-person operation, provides 4 hours of operation time on one battery charge, and provides sufficient rigidity for practical field operations.

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

Rotary drilling for oil and natural gas uses drilling fluid for lubrication of the bit, to seal off unstable shale layers, and floating out rock cuttings. Drilling fluid is a water-clay chemical mixture. Produced water is a water-sand chemical mixture. Land farming is a common disposal technique of drilling fluid and produced water. In the land farming process, amendments of fluid are repeatedly applied to the soil surface. Plant growth and soil chemical properties may be altered by additions of drilling fluid, because of alkalinity, salinity, trace elements, and petroleum residue contained in waste. The objective of this study was to determine the change in soil pH, electrical conductivity (EC), total nitrogen and carbon, and extractable nutrient levels following the land application of drilling fluid and produced water. The study was a comparison of three plots with similar soil properties and conditions. The three study plots had various levels of drilling fluid and produced water applications. The data show a major difference from field-to-field for EC, Na, and Cl levels. The EC and salt levels increased with additional applications of drilling fluid and produced water. The percent total nitrogen values and plant available P levels were very low in all fields. High EC and salt values, coupled with low N and P levels, would be detrimental to plant growth and development. To successfully vegetate this land-farm site, application of N and P fertilizer would be required. This study will help to give a better understanding of practical ways to land-farm drilling fluid and produced water in a fashion that both minimizes environmental issues and is economically feasible. Salinity changes to soil were expected to be high; there are excessive amounts of sodium and chloride in spent drilling fluid and produced water.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

The energy transition towards renewable and more decentral power production triggers the need for grid and storage expansion on all voltage levels. Today's power system planning focuses on certain voltage levels or spatial resolutions. In this work we present an open source software tool eGo which is able to optimize grid and storage expansion throughout all voltage levels in a developed top-down approach. System costs are minimized by applying a linear optimal power flow considering the grid infrastructure of the extra-high and high-voltage (380 to 110 kV) level. Hence, the common differentiation of transmission and distribution grid is partly dissolved, integrating the high-voltage level into the optimization problem. Consecutively, optimized curtailment and storage units are allocated in the medium voltage grid in order to lower medium and low voltage grid expansion needs, that are consequently determined. Here, heuristic optimization methods using the non-linear power flow were developed. Applying the tool on future scenarios we derived cost-efficient grid and storage expansion for all voltage levels in Germany. Due to the integrated approach storage expansion and curtailment can significantly lower grid expansion costs in medium and low voltage grids and at the same time serve the optimal functioning of the overall system. Nevertheless, the cost-reducing effect for the whole of Germany was marginal. Instead, the consideration of realistic, spatially differentiated time series lead to substantial overall savings.

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

Starting with BitTorrent and then Bitcoin, decentralized technologies have been on the rise over the last 15+ years, gaining significant momentum in the last 2+ years with the advent of platform ecosystems such as the Blockchain platform Ethereum. New projects have evolved from decentralized games to marketplaces to open funding models to decentralized autonomous organizations. The hype around cryptocurrency and the valuation of innovative projects drove the market cap of cryptocurrencies to over a trillion dollars at one point in 2017. These high valued technologies are now enabling something new: globally scaled, decentralized business models. Despite their valuation and the hype, these new business ecosystems are frail. This is not only because the underlying technology is rapidly evolving, but also because competitive markets see a profit opportunity in exponential cryptocurrency returns. This extracts value from these ecosystems, which could lead to their collapse, if unchecked. In this paper, we explore novel ways for decentralized economies to protect themselves from, and coexist with competitive markets at a global scale utilizing decentralized technologies such as Blockchain.

Vitamin E is a group of eight compounds divided into two subgroups: four tocopherols (α-, β-, γ-, and δ-) and four tocotrienols (α-, β-, γ-, and δ-). α-Tocopherol is considered the most biologically active form. This review paper summarizes the current knowledge and historical progression of vitamin E research, with particular emphasis on its role in animal nutrition. Early studies in the 1920s identified vitamin E’s role in preventing neonatal mortality in rats. Over the following decades, scientists discovered the compound’s chemical structure and its importance for the immune system, skin health, anti-inflammatory properties, hormonal balance, and other bodily functions. Production of vitamin E products has evolved, starting with isolating the vitamin from natural sources and advancing to synthesizing it with greater efficiency and standardized potency units. Early animal studies focused on reproductive health and growth disorders, but further research demonstrated the importance of vitamin E in preventing encephalomalacia in domestic fowl and muscular dystrophy in rabbits and other animals. Today, vitamin E is commonly used as a feed additive to meet animals’ requirements and assure immune function and overall health. Despite much knowledge on vitamin E’s role in animal nutrition, many questions remain unanswered, and current research aims to determine optimal supplementation levels, interactions with other nutrients, impacts on gene expression, cell signaling and communication, and effects of supranutritional dosages in livestock. Vitamin E has a long and fascinating history in scientific research, with significant advancements in understanding its chemical structure and biological activity. In animal nutrition, vitamin E continues to play an important role in improving animal health, and ongoing research will continue to expand our understanding of its benefits and mechanisms of action.

Image registration has an imperative role in medical imaging. In this work, a grey-wolf optimizer (GWO) based non-rigid demons registration is proposed to support the retinal image registration process. A comparative study of the proposed GWO-based demons registration framework with cuckoo search, firefly algorithm, and particle swarm optimization- based demons registration is conducted. In addition, a comparative analysis of different demons registration methods, such as Wang’s demons, Tang’s demons, and Thirion’s demons which are optimized using the proposed GWO is carried out. The results established the superiority of the GWO-based framework which achieved 0.9977 correlation, and fast processing compared to the use of the other optimization algorithms. Moreover, GWO-based Wang’s demons performed better accuracy compared to the Tang’s demons and Thirion’s demons framework. It also achieved the best less registration error of 8.36×10^-5.

Stable half-sandwich iron(II) dihalido complexes of the type [Fe(5-Cp’)X2] are extremely scarce, being limited to congeners containing the bulky C5H2-1,2,4-tBu3 ligand. We have extended this to homologues [Fe(5-Cp*)X2] (X = Cl – I) containing the particularly popular C5Me5 (Cp*) ligand. Corresponding ionic compounds ER4[Fe(5-Cp*)X2] are easily accessible from FeX2, MCp* (M = Li, K) and a suitable halide source R4EX (E = N, P) in THF. The new compounds NnPr4[Fe(5-Cp*)X2] (X = Cl, Br), NnPr4[Fe(5-Cp*)BrCl] and PPh4[Fe(5-Cp*)X2] (X = Cl, Br, I) have been structurally characterised by single-crystal X-ray diffraction. NnPr4[Fe(5-Cp*)Cl2] reacts readily with CO to afford [Fe(5-Cp*)Cl(CO)2], indicating the synthetic potential of ER4[Fe(5-Cp*)X2] in FeCp* half-sandwich chemistry.

Here we investigate how the local properties of particles in a thermal bath may influence the thermodynamics of the bath, and consequently alter the statistical mechanics of subsystems that comprise the bath. We are guided by the theory of small-system thermodynamics, which is based on two primary postulates: that small systems can be treated self-consistently by coupling them to an ensemble of similarly small systems, and that a large ensemble of small systems forms its own thermodynamic bath. We adapt this “nanothermodynamics” to investigate how a large system may subdivide into an ensemble of smaller subsystems, causing internal heterogeneity across multiple size scales. For the semi-classical ideal gas, maximum entropy favors subdividing a large system of “atoms” into an ensemble of “regions” of variable size. The mechanism of region formation could come from quantum exchange symmetry that makes atoms in each region indistinguishable, while decoherence between regions allows atoms in separate regions to be distinguishable by their distinct locations. Combining regions reduces the total entropy, as expected when distinguishable particles become indistinguishable, and as required by a theorem in quantum mechanics for sub-additive entropy. Combining large volumes of small regions gives the usual entropy of mixing for a semi-classical ideal gas, resolving Gibbs paradox without invoking quantum symmetry for atoms that may be meters apart. Other models presented here are based on Ising-like spins, which are solved analytically in one dimension. Focusing on the bonds between the Ising-like spins we find similarity in the equilibrium properties of a two-state model in the nanocanonical ensemble and a three-state model in the canonical ensemble. Thus, emergent phenomena may alter the thermal behavior of microscopic models, and the correct ensemble is necessary for fully-accurate predictions. Another result using Ising-like spins involves simulations that include a nonlinear correction to Boltzmann’s factor, which mimics the statistics of indistinguishable states by imitating the dynamics of spin exchange on intermediate lengths. These simulations exhibit 1/f-like noise at low frequencies (f), and white noise at higher f, similar to equilibrium thermal fluctuations found in many materials.

The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite’s strong dependence on this pathway and significant structural differences of its glycolytic enzymes compared to their human counterpart, glycolysis is considered as a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK), containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion which lines the active site. Moreover, we propose that this insertion plays a role upon ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both Sglutathionylation and Snitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.

Studies over the past three years have substantially expanded the involvements of eIF3 in mRNA translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting, and degradation. At the same time, eIF3 subunits appear to have specific functions that probably vary between different tissues and individual cells. Considering the broad functions of eIF3 in protein homeostasis, it comes as little surprise that eIF3 is increasingly implicated in major human diseases and first attempts at therapeutically targeting eIF3 have been undertaken. Much remains to be learned, however, about subunit- and tissue-specific functions of eIF3 in protein synthesis and disease and their regulation by environmental conditions and posttranslational modifications.

In order to assess the degradation state of rolling bearings and accurately grasp the remaining life information of rolling bearings, a bearing remaining life prediction method based on the grey wolf optimization algorithm to improve the BP neural network model is proposed. The method consists of two steps, firstly, using the craggy value and root mean square value to determine the first failure time of rolling bearings so as to approximate the input features, and secondly, using the Grey Wolf optimization algorithm to optimize the BP neural network to construct the degradation model of the bearings through machine learning. The method reduces the prediction error compared with conventional techniques, indicating that the method can effectively simulate the bearing degradation process and predict the remaining useful life (RUL) of the bearing.

Plasmodium vivax causes the second highest number of malaria morbidity and mortality cases in humans. Several biological traits of this parasite species, including the formation of dormant stages (hypnozoites) that persist inside the liver for prolonged periods of time, present an obstacle for intervention measures and create a barrier for the elimination of malaria. Research into the biology of hypnozoites requires efficient systems for parasite transmission, liver stage cultivation and genetic modification. However, P. vivax research is hampered by the lack of an in vitro blood stage culture system, rendering it reliant on in vivo derived, mainly patient material, for transmission and liver stage culture. This has also resulted in a limited capability for genetic modification, creating a bottleneck in investigations into the mechanisms underlying the persistence of the parasite inside the liver. This bottleneck can be overcome through optimal use of the closely related and experimentally more amenable nonhuman primate (NHP) parasite Plasmodium cynomolgi as model system. In this review we discuss the genetic modification tools and liver stage cultivation platforms available for studying P. vivax persistent stages and highlight how their combined use may advance our understanding of hypnozoite biology.

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

The integration of diverse distributed generation (DG) units, encompassing both Renewable Energy Sources (RES) and non-RES technologies delves into voltage levels, current distributions, and power flows, aiming to optimize and effectively manage the distribution network. An RES-based DGs such as photovoltaic systems and wind turbines, alongside non-RES units like fuel cells and micro turbines. This study proposes a hybrid approach the Multi-Objective Genetic Algorithm - Grey Wolf Optimizer (MOGA-GWO). By merging the strengths of multi-objective genetic algorithms with the efficiency of the Grey Wolf Optimizer, this advanced algorithm seeks semi-optimal solutions for multi-objective optimization problems. The algorithm aims to improve convergence speed without compromising solution quality, offering a promising solution for optimizing the characteristics of DG and RES integration in distribution networks compared to Cuckoo Search and Simulation Annealing Techniques. Key algorithmic operations include individual representation, initialization, fitness function computation, selection, crossover, mutation, and ending conditions. The DG optimal power flow problem is explored with a focus on minimizing generation costs, improving voltage profiles, minimizing losses, enhancing reliability, integrating renewable energy, reducing environmental impact, managing congestion, and ensuring compliance with operational constraints. Beyond traditional considerations, the study emphasizes neglected objectives and constraints, such as cyber-security concerns, real-time operation, regulatory frameworks, social acceptance, lifecycle environmental impact, grid resilience, data privacy, aging infrastructure compatibility, and economic viability.

In Latvia, livestock depredation by wolves has increased during the last two decades. Most attacks had occurred in summer and autumn within wolf hunting season. Cumulative numbers of wolf attacks and number of affected sheep per year at regional forest management units were analyzed in relation to estimated wolf density, extent of culling and proportion of juveniles, as well as sheep density and estimated number of wild prey. The response variables (cumulative number of attacks and cumulative number of affected sheep) were modelled by a negative binomial regression, testing effects of every covariate separately and building models from the significant covariates. Depredation level was related to sheep density and estimated wolf population size. No reducing effect was found for culling, and even greater depredation rate was expected at higher proportions of culled wolves. Estimated number of wild prey or proportion of juvenile wolves had an insignificant effect. However, greater numbers of affected sheep were expected at higher red deer density, suggesting increased opportunistic livestock depredation when the red deer may locally outcompete the preferred wolf prey – roe deer.

The question of building sustainable in a geographical locality is inexorably linked to cost. In 2011, one of the authors built a sustainable house that was (at the time) the highest certified sustainable home based on the National Association of Home Builder’s standards for sustainable construction. This Texas house has been used for residential and research purposes for the past decade. In this case study, the authors evaluate components of the construction and their effectiveness as well as unseen secondary and tertiary effects. Some of the specific components discussed are home site placement; rainwater harvesting (100% of residential requirements); aerobic septic system; grid-tied solar array power; electric car charging; geothermal heating and cooling; reclaimed wood framing; spray foam installation; selection of windows, fixtures, and appliances; on-demand electric water heaters for guest areas; generator backups; and use of local items. Electric bills and water system improvements are discussed in detail, as improvements were made as part of residential and research requirements. This case study suggests that the financial outlay is worth the extra up-front costs if residents in this geographical area and climate will occupy the residence 7 years.

Background: As the opioid epidemic continues, understanding the geospatial, temporal and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and admission rates using geospatial analysis, demand analysis, and explanatory models, respectively. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high opioid admissions in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. High rates of admission (claims per 10,000 population) exist in the Appalachian area and on the Northeastern seaboard. Explanatory models suggest that hospital overall workload and financial variables might be used for allocating opioid-related treatment funds effectively. Gradient-boosted random forest models accounted for 87.8% of the variability of claims on blinded 20% test data. Conclusions: Based on the GIS analysis, opioid admissions appear to have spread geographically, while higher frequency rates are still found in some regions. Interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement. Based on GIS analysis, the opioid epidemic is likely to spread or diffuse through the country, and interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement.

Keeping the bus voltage within acceptable limits depends on dispatching reactive power. Power quality improves as a result of creating an effective power flow system, which also helps to reduce power loss. Therefore, Optimal Reactive Power Dispatch (ORPD) studies aim at designing appropriate system configurations to enable a reliable operation of power systems. Establishment of such a configuration is handled through control variables in power systems. On the other hand, installing Distributed Generation Unit (DGU) into a power system can have an important effect on power quality and power loss minimization. In this paper, Grey Wolf Optimization (GWO method is applied to ORPD problem for the first time, to find optimal placement of newly installed DGUs at the power system. Active power loss and voltage minimization have been minimized by optimizing the control variables while keeping them within their upper and lower bounds, and by finding the optimal placement of a newly installed DGU in power system. On the basis of IEEE 30 bus and IEEE 118 bus systems, performance of the suggested approach is investigated. A comparison is also performed among the proposed method and some other methods. Test results demonstrate that the resulting configuration contributes to growing the rate of renewable integration to a power system. The results also indicate that the suggested optimization approach applied to ORPD problem has improved power system performance in terms of both on power loss and voltage deviation. The promising results highlight the potential of the GWO algorithm to facilitate the integration of renewable power sources, and its role in promoting sustainable energy solutions.

This article discusses the outcomes of a quantitative analysis of the competitiveness of grain and its recycling in the countries-members of the Eurasian Economic Union (EEU) through econometric panel data models. The analysis is based on the data of public authorities’ statistics of the countries-members of the EEU, as well as the United Nations Comtrade Database which is a repository of official international trade statistics. The results of the analysis allow to assess the level of competitiveness of produced agro-food products in the countries-members of the EEU and determine the extent to which various factors affect it. The research conclusions can be used to develop and adjust the agreed with the agro-food policy in the EEU.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

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

Generalized distributions have been studied a lot recently because of their flexibility and relia-bility in modeling lifetime data. The two-parameter exponentially-modified logistic distribution is a new flexible modified distribution that was introduced recently. It is regarded as a strong competitor for widely used classical symmetrical and non-symmetrical distributions such as normal, logistic, lognormal, and log-logistic. In this study, the unknown parameters of the dis-tribution are estimated using the maximum likelihood method. The Grey Wolf Optimization al-gorithm, which is a new meta-heuristic algorithm, is applied in order to solve the nonlinear like-lihood equations of the study model. The performance of the Grey Wolf Optimization method is compared to that of the other meta-heuristic algorithms used in this study, which include the Whale Optimization Algorithm, the Sine Cosine Algorithm, and the Particle Swarm Optimiza-tion Algorithm. The efficiencies of maximum likelihood estimates for all algorithms are com-pared via an extensive Monte-Carlo simulation study. The likelihood estimates for the location α and scale β parameters of the exponentially-modified logistic distribution developed with the Grey Wolf Optimization algorithm are the most efficient among others, according to simulation findings. Four real datasets are analyzed to show the flexibility of this distribution.

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

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

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

Leishmaniasis in wild canids is a vector-borne disease caused in Europe by the protozoan parasite Leishmania infantum. To date, there is limited information on clinical signs and laboratory abnormalities in wolves due to leishmaniasis. The current clinical case report described a female Iberian wolf (Canis lupus signatus) housed in semi-captivity conditions at the Centro del Lobo Ibérico “Félix Rodríguez de la Fuente”, in Robledo de Sanabria, Zamora (Spain) with an interdigital ulcerous wound at the right forepaw, hyper-gammaglobulinemia, and abnormal liver blood parameters. Definitive serodiagnosis of leishmaniasis was established using antileishmanial serum antibodies and PCR analysis of different biological samples. A gold standard anti-L. infantum treatment protocol consisting in intramuscular meglumine antimoniate and oral allopurinol combination was installed. However, the presence of pain at the site of injection due to meglumine antimoniate administration forced its substitution by oral miltefosine. A progressive reduction of the levels of anti-L. infantum serum antibodies and the concentrations of gamma-globulin fraction was detected after antileishmanial treatment as well as a decline of liver GPT. To our knowledge, this is the first case of leishmaniasis diagnosed in a wolf housed in semi-captivity conditions treated and successfully cured.

Neurogenesis in the adult brain plays a major role in the cognitive ability of animals including learning and memory. Poria cocos (Schw.) Wolf (P. cocos) has been known as a traditional Chinese edible medicinal herb with the potential effect to improve learning and memory. However, the effect mechanisms are still elusive. In this study, significant neuronal differentiation-promoting activities of the ethanol extracts of P. cocos (EEPC) were tested in Neuro-2a cells and mouse cortical neural stem/progenitor cells (NSPCs). Subsequently, 97 compounds of EEPC were identified using UHPLC-Q-Exactive-MS/MS. After investigation of neuronal differentiation-promoting activities of 4 major compounds (Ethyl palmitoleate, L-(-)-Arabitol, Choline and Adenosine), only Choline has significant neuronal differentiation-promoting activity. In summary, we investigated the neuronal differentiation-promoting activity and chemical compositions of EEPC, the study of the neuronal differentiation-promoting effect of ether extract of P. cocos indicated P. cocos’s positive effect on learning and memory functions. This is the first investigation of the neuronal differentiation-promoting effect of ether extract of P. cocos based on similar research references.

The accurate prediction of the solar Diffuse Fraction (DF), sometimes called the Diffuse Ratio, is an important topic for solar energy research. In the present study, the current state of Diffuse Irradiance research is discussed and then three robust, Machine Learning (ML) models, are examined using a large dataset (almost 8 years) of hourly readings from Almeria, Spain. The ML models used herein, are a hybrid Adaptive Network-based Fuzzy Inference System (ANFIS), a single Multi-Layer Perceptron (MLP) and a hybrid Multi-Layer Perceptron-Grey Wolf Optimizer (MLP-GWO). These models were evaluated for their predictive precision, using various Solar and Diffuse Fraction (DF) irradiance data, from Spain. The results were then evaluated using two frequently used evaluation criteria, the Mean Absolute Error (MAE) and the Root Mean Square Error (RMSE). The results showed that the MLP-GWO model, followed by the ANFIS model, provided a higher performance, in both the training and the testing procedures.

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

Micronutrient deficiencies are a major public health problem. Beans are an important plant-based source of iron, zinc and copper, but their absorption is reduced in the presence of anti-nutrients such as phytates, polyphenols and tannins. Soaking and discarding the soaking water before cooking is unanimously recommended, but this can result in mineral loss. Data on the consequences for mineral bioaccessibility is still limited. This study aimed to evaluate iron, zinc and copper bioaccessibility in black beans cooked (regular pan, pressure cooker) with and without the soaking water. Minerals were quantified by ICP-MS, myo-inositol phosphates (InsP₅, InsP₆) by HPLC ion-pair chromatography, total polyphenols using Folin-Denis reagent and condensed tannins using Vanillin assay. Mineral bioaccessibility was determined by in vitro digestion and dialysis. All treatments resulted in a statistically significant reduction of total polyphenols (30%) and condensed tannins (20%). Only when discarding the soaking water a loss of iron (6%) and copper (30%) was observed, and InsP₆ was slightly decreased (7%) in one treatment. Bioaccessibility of iron and zinc were low (about 0.2% iron and 35% zinc), but copper presented high bioaccessibility (about 70%). Cooking beans under pressure without discarding the soaking water resulted in the highest bioaccessibility levels among all household procedures. Discarding the soaking water before cooking did not improve the nutritional quality of the beans.

Six bacterial strains with differing abilities to produce varying concentrations of Indole Acetic Acid were tested individually and in consortia for plant growth promoting and fitness related traits of Cicer arietinum. In all experiments the presence of the nitrogen fixer Mesorhizobium ciceri resulted in increased biomass production. In the absence of this strain, IAA Psedomonas putida and Bacillus megaterium hinder plant growth and fitness related traits. The application of mixes of the three strains always resulted in better plant performance when M. ciceri was present. Whereas P. putida has a noticeable plant growth-promoting effect B. megaterium resulted less effective. The low levels of IAA produced by the selected strains had a significantly greater positive effect on plant biomass accumulation, flower, pods and seed production as well as on total plant nitrogen and nitrogen concentration in seed than high IAA producer strains.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

An accurate outbreak prediction of COVID-19 can successfully help to get insight into the spread and consequences of infectious diseases. Recently, machine learning (ML) based prediction models have been successfully employed for the prediction of the disease outbreak. The present study aimed to engage an artificial neural network-integrated by grey wolf optimizer for COVID-19 outbreak predictions by employing the Global dataset. Training and testing processes have been performed by time-series data related to January 22 to September 15, 2020 and validation has been performed by time-series data related to September 16 to October 15, 2020. Results have been evaluated by employing mean absolute percentage error (MAPE) and correlation coefficient (r) values. ANN-GWO provided a MAPE of 6.23, 13.15 and 11.4% for training, testing and validating phases, respectively. According to the results, the developed model could successfully cope with the prediction task.

Development of load-bearing polymer composite constructions in civil engineering, such as industrial chimneys and gas ducts, requires filling some research gaps. These gaps are related to long-term behavior under mechanical and temperature loads, cyclic ones as well. Such conditions mean that viscoelasticity should be considered. First of all, viscoelastic parameters should be calculated, based on the used inner structure model. Then, due to the high working temperatures, thermal aging should be considered as well. This research is devoted to effects of thermal aging on viscoelastic behavior of polymers. Two sets of experiments were conducted: creep tensile tests and cyclic heating in constrained state. The Kelvin-Voigt viscoelasticity model was used to determine the rheological parameters of binder from experimental creep curves. Thermally-aged binder turned out to lose its viscous properties and became elastic. Cyclic heating was used to compare the behavior of normal and thermally-aged binder and to evaluate the possibility of temperature stress accumulation. Similar to creep tests, cyclic heating showed that aged binder lost viscosity and worked almost perfectly elastic. Non-aged binder was prone to stress accumulation much more. As a result, the rheological behavior of aged and non-aged binder was compared and showed a significant difference. In addition, the influence of temperature stress accumulation on stress—strain state was evaluated and turned out to be significant as well. The obtained results can be further used to predict the mechanical behavior of structures made of polymer composites operating for a long time at elevated temperatures, including those exceeding the glass transition temperature.

The recent past has witnessed a growing interest in technologies for creating chatbots. Advances in Large Language Models for natural language processing are underpinning rapid progress in chatbot development, and experts predict revolutionary changes in the labour market as many manual tasks are replaced by virtual assistants in a range of business functions. As the new technology becomes more accessible and advanced, more companies are exploring the possibilities of implementing virtual assistants to automate routine tasks and improve service. This article reports on qualitative inductive research undertaken within a chatbot development team operating in a major international enterprise. The findings identify critical success factors for chatbot projects, and, based on the in-depth case study, a model is put forward to aid the manageability of chatbot implementation. The presented model can serve as an exemplar guide for researchers and practitioners working on the design, development and implementation of virtual assistants. It is flexible and applicable in a wide range of business contexts, linking strategic business goals with execution steps. It is particularly applicable for teams with no experience of chatbot implementation, reducing uncertainty and managing decisions and risks throughout the project lifecycle, thereby increasing the likelihood of project success.

Stairs are among the key elements in architectural composition, both aesthetically and spatially. They are also one of the main innovations in architecture and building, allowing pedestrians to bridge considerable height differences with relative efficiency. It is therefore surprising that, in spite of all stair regulations in building codes, stairs are responsible for a huge number of accidents – second only to motorcars. The extent of safety failures suggests that user interaction with stairs is poorly understood by designers and policy makers. This is not unrelated to the lack of research into the design and use of stairs. Templer’s seminal work is the exception but it dates from 1992 and since then little has been done to understand the relation between architectural design and stair performance, including safety. To redress this, we can build on affordance-based analyses of stair climbability, which establish a clear connection between the form of a stair and the perception of action possibilities and dangers by all kinds of users. By doing so affordances establish a comprehensive and consistent framework for the analysis of architectural designs, which utilizes both domain and psychological knowledge, including as a foundation for computational applications.

Accurate and stable cost forecasting of substation projects is of great significance to ensure the economic construction and sustainable operation of power engineering projects. In this paper, a forecasting model based on the improved least squares support vector machine (ILSSVM) optimized by wolf pack algorithm(WPA) is proposed to improve the accuracy and stability of the cost forecasting of substation projects. Firstly, the optimal features are selected through the data inconsistency rate (DIR), which helps reduce redundant input vectors. Secondly, the wolf pack algorithm is used to optimize the parameters of the improved least square support vector machine. Lastly, the cost forecasting method of WPA-DIR-ILSSVM is established. In this paper, 88 substation projects in different regions from 2015 to 2017 are chosen to conduct the training tests to verify the validity of the model. The results indicate that the new hybrid WPA-DIR-ILSSVM model presents better accuracy, robustness and generality in cost forecasting of substation projects.

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

Machine learning (ML) is growing in popularity for various particle accelerator applications including anomaly detection such as faulty beam position monitor or RF fault identification, for non-invasive diagnostics, and for creating surrogate models. ML methods such as neural networks (NN) are useful because they can learn input-output relationships in large complex systems based on large data sets. Once they are trained, methods such as NNs give instant predictions of complex phenomenon, which makes their use as surrogate models especially appealing for speeding up large parameter space searches which otherwise require computationally expensive simulations. However, quickly time varying systems are challenging for ML-based approaches because the actual system dynamics quickly drifts away from the description provided by any fixed data set, degrading the predictive power of any ML method, and limits their applicability for real time feedback control of quickly time-varying accelerator components and beams. In contrast to ML methods, adaptive model-independent feedback algorithms are by design robust to un-modeled changes and disturbances in dynamic systems, but are usually local in nature and susceptible to local extrema. In this work, we propose that the combination of adaptive feedback and machine learning, adaptive machine learning (AML), is a way to combine the global feature learning power of ML methods such as deep neural networks with the robustness of model-independent control. We present an overview of several ML and adaptive control methods, their strengths and limitations, and an overview of AML approaches. A simple code for the adaptive control algorithm used here can be downloaded from: https://github.com/alexscheinker/ES_adaptive_optimization

We study the Kelvinons: monopole ring solutions to the Euler equations, regularized as the Burgers vortex in the viscous core. There is finite anomalous dissipation in the inviscid limit. However, in the anomalous Hamiltonian, some terms are growing as logarithms of Reynolds number; these terms come from the core of the Burgers vortex. In our theory, the turbulent multifractal phenomenon is similar to asymptotic freedom in QCD, with these logarithmic terms summed up by an RG equation. The small effective coupling does not imply small velocity; on the contrary, velocity is large compared to its fluctuations, which opens the way for a quantitative theory. In the leading order in the perturbation theory in this effective coupling constant, we compute running multifractal dimensions for high moments of velocity circulation, in good agreement with the data for quantum Turbulence and available data for classical Turbulence. The logarithmic dependence of fractal dimensions on the loop size comes from the running coupling in anomalous dimensions. This slow logarithmic drift of fractal dimensions would be barely observable at Reynolds numbers achievable at modern DNS.

The creative potential of homo sapiens is the biological basis of his spirituality. To take into account factor of spirituality in analysis of global problems of demography and ecology used analogies of chemical kinetics. Stable in the historical time, population of people was modeled by open thermodynamic system, equilibrium state of which depends on climate and geophysics. The demography of creative potential was divided into two geographical zones - north and south. Process of society sapientation was formalized by introducing into logistic equation of Verhulst, in addition to a couple of parents, at least one more teacher from among educated people. Stationary solution of the modified kinetic equations determines optimal demography for sustainable development of population in accordance with its education index. The solution of the demographic, energy and environmental problems of mankind is determined by the level of world creative potential, the growth of which is currently limited by the consumption paradigm.

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

The impact of organizational accreditation and professional certification and the evidence-based measurable impact of those for both academic programs and affiliates is one of specific interest to universities and individuals in the healthcare management field [1]. The authors’ analysis examined the impact of hiring graduates from higher education programs that held external accreditation from the Commission on Accreditation of Healthcare Management Education (CAHME). Graduates’ affiliation with the American College of Healthcare Executives (ACHE) professional healthcare leadership organization was also assessed as an independent variable. Study outcomes focused on these graduates’ respective healthcare organization’s performance measures (cost, quality, and access) to assess the researchers’ inquiry into the perceived value of a CAHME-accredited graduate degree in healthcare administration and a professional ACHE affiliation [2]. The results from this study found no effect of CAHME accreditation or ACHE affiliation on healthcare organization performance outcomes. The study findings support the need for future research surrounding healthcare administration professional graduate degree program characteristics and leader development affiliations, as perceived by various industry stakeholders.

Autonomous driving navigation relies on diverse approaches, each with advantages and limitations depending on various factors. For HD maps, modular systems excel, while end-to-end methods dominate mapless scenarios. However, few leverage the strengths of both. This paper innovates by proposing a hybrid architecture that seamlessly integrates modular perception and control modules with data-driven path planning. This innovative design leverages the strengths of both approaches, enabling a clear understanding and debugging of individual components while simultaneously harnessing the learning power of end-to-end approaches. Our proposed architecture achieved 1st and 2nd place in the 2023 CARLA Autonomous Driving Challenge’s SENSORS and MAP tracks, respectively. These results demonstrate the architecture’s effectiveness in both map-based and mapless navigation.

Interdisciplinary research into the underlying neural processes of music therapy (MT) and subjective experiences of patients and therapists are largely lacking. The aim of the current study was to assess the feasibility of newly developed procedures (including EEG/ECG hyperscanning, synchronous audio-video monitoring, and qualitative interviews) to study the personal experiences and neuronal dynamics of moments of interest during MT with stroke survivors. The feasibility of our mobile set-up and procedures as well as their clinical implementation in a rehabilitation centre and an acute hospital ward were tested with four phase C patients. Protocols and interviews were used for the documentation and analysis of the feasibility. Recruiting patients for MT sessions was feasible, although data collection on three consecutive weeks was not always possible due to organisational constraints, especially in the hospital with acute ward routines. Research procedures were successfully implemented, and according to interviews, none of the patients reported any burden, tiredness or increased stress due to the research procedures, which lasted approx. 3 hours (ranging from 135min to 209min) for each patient. Implementing the research procedures in a rehabilitation unit with stroke patients was feasible and only small adaptations were made for further research.

This research is completed in development of researches devoted to relations between elastic modulus (MoE) and thermal expansivity (CTe) of different materials. This study experimentally confirmed the relation of MoE and CTe for thermosetting polymers and FRPs both under normal and heating temperatures. As the thermosetting polymers, the epoxy compositions were used and glass fiber and mineral additives for FRP. The experiment was based on dilatometric and elastic deformations’ testing. Also, the relaxation model of MoE/CTe was proposed, that is based on physical properties of polymers’ supramolecular structures. The comparative analyzing of MoE/CTes’ different models is done. The most accurate models are determined, and the relaxation model has demonstrated the high accuracy.

In healthy humans, taste sensitivity varies widely, influencing food selection and nutritional status. Chemosensory reductions have been associated with numerous pathological disorders or pharmacological interventions. Reliable psychophysical methods are crucial resources to analyze the taste function during routine clinical assessment. However, in the daily clinical routine, they are often considered to be too time-consuming. We used the Supervised Learning (SL) regression method to analyze with high precision the overall taste status of healthy controls (HC) and patients with chemosensory loss and to characterize the combination of responses that best can predict the overall taste status of two groups. Random Forest regressor allowed us to achieve our objective. The analysis of the order of importance and impact of each parameter on the prediction of overall taste status in the two groups showed that salty (low concentration) and sour (high concentration) stimuli specifically characterized healthy subjects, while bitter (high concentration) and astringent (high concentration) stimuli identified patients with chemosensory loss. The identification of these distinctions appears to be of interest to the health system since they may allow the use of specific stimuli during routine clinical assessments of taste function reducing the commitment in terms of time and costs.

Knowledge about laminar-turbulent transition on operating multi-megawatt wind turbine blades needs sophisticated equipment like hot-films or microphone arrays. Contrarily thermographic pictures can easily be taken from the ground and temperature differences indicate different states of the boundary layer. The accuracy however, still is an open question, so that an aerodynamic glove known from experimental research on aero-planes was used to classify the boundary-layer state of a 2 megawatt wind turbine blade operating in the orthern part of Schleswig-Holstein, Germany. State-of-the-art equipment for measurering static surface pressure was used for monitoring the lift distribution. To distinguish laminar and turbulent parts of the boundary layer (suction side only) 48 microphones were applied together with ground-based thermographic cameras from two teams. Additionally, an optical camera mounted on the hub was used to survey vibrations. During start-up (from 0 to 9 rpm) extended, but irregularly shaped regions of a laminar boundary layer were observed which had the same extension measured both with microphones and Thermography. When an approximately constant rotor rotation (9 rpm corresponding to approximately 6 m/s wind-speed) was achieved, a flow transition was visible at the expected position of 40 % chord length on the rotor blade, which was fouled with dense turbulent wedges and an almost complete turbulent state on the glove was detected. In all observations, quantitative determination of the flow transition positions from thermography and microphones agree well within their accuracy.

In the work, the nuclei structure was modeled by a system of shells consisting of combinations of spherical and annular vortices. Having connected the spin and the magnetic moments of the nuclei with the dynamics of the outer shell of the nucleus, we determined its type and carried out a semiempirical calculation of the parameters of its structure for stable and unstable nuclear isotopes in the sequence of the order number Z from 1 to 37. Comparison of the obtained nuclear sizes with the radii of the electron shells of atoms made it possible to reveal a definite correlation. On the basis of it, it was concluded that the periodic law of Mendeleyev can determine the patterns in the change in the structure of the atomic nucleus.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

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

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

This is the second paper in a cycle investigating the exact solution of loop equations in decaying turbulence. We perform numerical simulations of the Euler ensemble, suggested in the previous work, as a solution to the loop equations. We designed novel algorithms for simulation, which take a small amount of computer RAM so that only the CPU time grows linearly with the size of the system and its statistics. This algorithm allows us to simulate systems with billions of discontinuity points on our fractal curve, dual to the decaying turbulence. For the vorticity correlation function, we obtain \textbf{quantum fractal laws} with regime changes between universal discrete values of indexes. The traditional description of turbulence with fractal or multifractal scaling laws does not apply here. The measured conditional probabilities of fluctuating variables are smooth functions of the logarithm of scale, with statistical errors being negligible at our large number of random samples $T = 167,772,160$ with $N = 200,000,000$ points on a fractal curve. The quantum jumps arise from the analytical distribution of scaling variable $X = \frac{\cot^2(\pi p/q)}{q^2}$ where $\frac{p}{q}$ is a random fraction. This distribution is related to the totient summatory function and is a discontinuous function of $X$. In particular, the energy spectrum is a devil's staircase with tilted uneven steps with slopes between $-1$ and $-2.03$. The logarithmic derivative of energy decay $n(t)$ as a function of time is jumping down the stairs of universal levels between $1.50$ and $1.53$. The quantitative verification of this quantization would require more precise experimental data.

Long-range interactions are relevant for a large variety of quantum systems in quantum optics and condensed matter physics. In particular, the control of quantum-optical platforms promises to gain deep insights in quantum-critical properties induced by the long-range nature of interactions. From a theoretical perspective, long-range interactions are notoriously complicated to treat. Here, we give an overview of recent advancements to investigate quantum magnets with long-range interactions focusing on two techniques based on Monte Carlo integration. First, the method of perturbative continuous unitary transformations where classical Monte Carlo integration is applied within the embedding scheme of white graphs. This linked-cluster expansion allows to extract high-order series expansions of energies and observables in the thermodynamic limit. Second, stochastic series expansion quantum Monte Carlo which enables calculations on large finite systems. Finite-size scaling can then be used to determine physical properties of the infinite system. In recent years, both techniques have been applied successfully to one- and two-dimensional quantum magnets involving long-range Ising, XY, and Heisenberg interactions on various bipartite and non-bipartite lattices. Here, we summarise the obtained quantum-critical properties including critical exponents for all these systems in a coherent way. Further, we review how long-range interactions are used to study quantum phase transitions above the upper critical dimension and the scaling techniques to extract these quantum critical properties from the numerical calculations.

The evolution of manual grooming and its implications have received little attention in the quest to understand the origins of simian primates and their social and technical intelligence. All simians groom manually, whereas prosimians groom orally despite comparable manual dexterity between some members of the two groups. Simians also exhibit a variable propensity for the manipulation of inanimate, non-food objects, which has culminated in tool making and tool use in some species. However, lemuriform primates also seem capable of tool use with training. Furthermore, lemuriforms appear to understand the concept of a tool and use their own body parts as “tools”, despite not using inanimate objects. This suggests that prosimian primates are pre-adapted for proprioceptive object manipulation and tool use, but do not express these cognitive abilities by default. This essay explores the paleontological, anatomical, cognitive, ethological, and neurological roots of these abilities and attempts to explain this behavioural divide between simians and prosimians. Common misconceptions about early primate evolution and captive behaviours are addressed, and chronological inconsistencies with Machiavellian Intelligence are examined. A “licking to picking” hypothesis is also proposed to explain a potential link between manual grooming and object manipulation, and to reconcile the inconsistencies of Machiavellian Intelligence. Bayesian decision theory, the evolution of the parietal cortex and enhanced proprioception, and analogies with behavioural changes resulting from artificial selection may help provide new insights into the minds of both our primate kin and ourselves.

Driver drowsiness is one of the leading causes of traffic accidents. This paper proposes a new method for classifying driver drowsiness using deep convolution neural networks trained by wavelet scalogram images of electrocardiogram (ECG) signals. Three different classes were de-fined for drowsiness based on video observation of driving tests performed in a simulator for manual and automated modes. The Bayesian optimization method is employed to optimize the hyperparameters of the designed neural networks, such as the learning rate and the number of neurons in every layer. To assess the results of the deep network method, Heart Rate Variability (HRV) data is derived from the ECG signals, some features are extracted from this data, and finally, random forest and k-nearest neighbors (KNN) classifiers are used as two traditional methods to classify the drowsiness levels. Results show that the trained deep network achieves balanced accuracies of about 77% and 79% in the manual and automated modes, respectively. However, the best obtained balanced accuracies using traditional methods are about 62% and 64%. We conclude that designed deep networks working with wavelet scalogram images of ECG signals significantly outperform KNN and random forest classifiers which are trained on HRV-based features.

Objective: To compare the overall survival (OS) and surgical outcomes between open and minimally invasive surgery (MIS) in a large cohort of women with Type II endometrial cancer. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, carcinosarcoma) between January 2010 and December 2014. Primary outcome was the comparison of OS between MIS and the open approach. Secondary outcomes included the length of hospital stay, readmission rate, 30- and 90-day mortality. Multivariable logistic regression and inverse propensity weighting analyses were performed. Results: A total of 12,905 patients with Type II, Stage I-III endometrial cancer who underwent hysterectomy were identified. Among these patients, 7,123 (55.2%) underwent MIS. The utilization of MIS increased from 39% to 64% over the four-year period. In propensity-score-weighted analysis, MIS was associated with superior OS (101.7 vs. 86.7 months, p=0.0003 by the log-rank test), with a hazard ratio of 0.9 (CI 0.857-0.954, p=0.0002). MIS was also associated with improved perioperative outcomes, including a shorter length of stay (1 vs. 4 days, p<0.001), lower 30-day readmission rate (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p<0.001). The time interval between surgery and initiation of chemotherapy was shorter in the MIS group (38 vs. 41 days, p<0.001).The increase in MIS adoption correlated with a decrease in 90-day postoperative mortality (2.8% to 2.2%, r=-0.89; p=0.003) and 12-month overall mortality (51% to 38%, r=-0.95, p=0.006). Conclusions: In an epidemiologic study, MIS is associated with improved overall survival and superior perioperative outcomes compared to open surgery in women with Type II endometrial cancer.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

Guessing effects frequently occur in testing data in educational or psychological applications. Different item response models have been proposed to handle guessing effects in dichotomous test items. However, it has been pointed out in the literature that the oftenemployed three-parameter logistic model poses implausible assumptions regarding the guessing process. The four-parameter guessing model has been proposed as an alternative to circumvent these conceptual issues. In this article, the four-parameter guessing model is compared with alternative item response models for handling guessing effects through a simulation study and an empirical example. It turned out that model selection for item response models should be rather based on the AIC than the BIC. However, the RMSD item fit statistic used with typical cutoff values was found to be ineffective in detecting misspecified item response models. Furthermore, sufficiently large sample sizes are required for sufficiently precise item parameter estimation. Moreover, it is argued that the criterion of statistical model fit should not be the sole criterion of model choice. The item response model used in operational practice should be valid with respect to the meaning of the ability variable and the underlying model assumptions. In this sense, the four-parameter guessing model could be the model of choice in educational large-scale assessment studies.

The comparison of group means in latent variable models plays a vital role in empirical research in the social sciences. The present article discusses extensions of invariance alignment and Haberman linking concerning the choice of linking functions for comparisons of many groups. Robust linking functions are proposed for invariance alignment and robust Haberman linking that are particularly suited to item response data under partial invariance. In a simulation study, it is shown that both linking approaches have comparable performance, and in some conditions, the newly proposed robust Haberman linking outperforms invariance alignment.

The results of measuring the capacity of a thin-film solid-state lithium-ion battery (SSLIB) Ti|Si@O@Al|LiPON|LiCoO₂|Ti at different charge currents are reported. It is shown that the dependence of the capacity on the current density follows the Peukert's law, which is characterized by a low value of the Peukert’s exponent in the region of low currents and a high value of the exponent in the region of high currents. A capacity model for a SSLIB based on the balance of diffusion and migration currents is proposed and the dependence of the capacity on the charge current is derived. The obtained dependence is well approximated by Peukert's law with an exponent of 1.39, which is intermediate between the exponents for lithium-ion batteries with liquid electrolyte and SSLIBs.

The paper proposes a game theory model of price oligopoly with a heterogeneous product, where total demand depends linearly on the minimum market price. This model develops the Bertrand oligopoly for the case of imperfect price elasticity of demand. The most interesting result is an asymmetric Nash equilibrium with different prices and sales in the situation of symmetric oligopolists. The asymmetry is explained by the fact that a decrease in the minimum market price leads not only to a reallocation of consumers among firms, but also to an increase in total demand. Modifications of a two-stage game with a leader and followers and the price discrimination model are also considered. Microeconomic substantiation of the model is given on the basis of the spatial differentiation approach.

In the first part of this article, we discuss and generalize the complete convergence introduced by Hsu and Robbins (1947) to the r-complete convergence introduced by Tartakovsky (1998). We also establish its relation to the r-quick convergence first introduced by Strassen (1967) and extensively studied by Lai (1976). Our work is motivated by various statistical problems, mostly in sequential analysis. As we show in the second part, generalizing and studying these convergence modes is important not only in probability theory but also to solve challenging statistical problems in hypothesis testing and changepoint detection for general stochastic non-i.i.d. models.

This paper presents one of the approaches to solution of the problem of the repulsion origin in gravity. The approach is based on the property of compactness characteristic for a self-gravitating object in General Relativity. Here we understand compactness as estimation of the upper boundary for mass such an object in a static two--dimensional sphere. Repulsion originates when this boundary is violated. The main hypothesis is formulated in the form of the principle of maximal mass within a two-dimensional static sphere. It is demonstrated that the principle is true for Schwarzschild black holes on absorption of the matter in the process of accretion, both in the classical case and with due regard for quantum-gravitational corrections. The results have been extended to black holes with the Schwarzschild-de Sitter metric in the early Universe. The applicability of the principle suggested is analyzed for the early and for the present Universe.

The invariant mass of free particles is used to derive a bound-state equation for several particle atomic systems at rest. This relativistic-kinematic bound-state equation is applied to the hydrogen and helium atoms. The derived equation has the well-known solutions for the single-electron bound states of the hydrogen atom, and the two-electron states of the helium atom. For the hydrogen atom, existence of the two-particle bound states, for which the electron and the proton kinetic energies are of the same order of magnitude, is predicted. The three-particle bound states with the same feature of the kinetic energies can exist in the helium atom. Radiative operators for processes involving the hydrogen two-particle bound states, are obtained. It is discussed that these new two- and three-particle bound states should be optically inactive.

We consider the Dirac electron as a nonperturbative particle-like solution consistent with its own Kerr-Newman (KN) gravitational and electromagnetic field. We develop the earlier models of the KN electron regularized by Israel and López, and consider the non-perturbative electron model as a bag model formed by Higgs mechanism of symmetry breaking. The López regularization determines the unique shape of the electron in the form of a thin disk with a Compton radius reduced by 4π. In our model this disk is coupled with a closed circular string which is placed on the border of the disk and creates the caused by gravitation frame-dragging string tension produced by the vector potential of the Wilson loop. Using remarkable features of the Kerr-Schild coordinate system, which linearizes the Dirac equation, we obtain solutions of the Dirac equation consistent with the KN gravitational and electromagnetic field, and show that this solution takes the form of a massless relativistic string. Parallelism of this model with quantum representations in Heisenberg and Schrodinger pictures explains remarkable properties of the stringy electron model in the relativistic scattering processes.

Quantification of physical activity (PA) depends on the type of measurement and analysis method making it difficult to compare adherence to PA guidelines. Therefore, test-retest reliability, criterion validity, and stability for self-reported (i.e. questionnaire and diary) and device-based measured (i.e. accelerometry with 10/60 second epochs) PA was compared in 32 adults and 32 children from the SMARTFAMILY study to examine if differences in these measurement tools are systematic. PA was collected during two separate measurement weeks and the relationship for each quality criteria was analyzed using Spearman correlation. Results showed the highest PA values for questionnaires followed by 10-second and 60-second epochs measured by accelerometers. Levels of PA were lowest when measured by diary. Only accelerometry demonstrated reliable, valid, and stable results for the two measurement weeks, the questionnaire yielded mixed results and the diary showed only few significant correlations. Overall, higher correlations for the quality criteria were found for moderate than for vigorous PA and the results differed between children and adults. Since the differences were not found to be systematic, the choice of measurement tools should be carefully considered by anyone working with PA outcomes, especially if vigorous PA is the parameter of interest.

The paper presents the results of experimental studies and mathematical modeling of the effect of stress accumulation in thermosetting epoxy polymer "hot" curing on anhydride hardener. Stress accumulation occurs under cyclic thermomechanical action in a locked rod, similar effects are observed, for example, in thermoplastic elements subjected to the combined effect of mechanical loads and variable temperatures. Experimental results have shown that under cyclic thermomechanical loading during exploitation it is possible to accumulate residual stresses in the thermosetting polymer. A multi-element structural mathematical model with memory for thermomechanical load, which allows to consider the accumulation of residual thermal stresses, has been proposed. The results of modeling and experiment are compared. Based on the results, corrections are made in the approach to the application of this model to thermosetting polymers such as the epoxy resin under study. Considering the corrections, a good agreement (the difference is from 1 to 6%) with the results of experimental determination of stresses under complex cyclic thermomechanical load was obtained.

There are several well-known methods for determining enzyme catalytic activity, including spectral techniques and electrochemical approaches. However, at present, there is no definitive solution to the challenges associated with the fluorescent approach in, for instance, systems of reverse micelles, non-aqueous media, and model biomembranes. We propose the use of the fluorescent resonant energy transfer (FRET) technique, which can enhance the selectivity of fluorescent detection of enzyme activity by shifting the maximum emission wavelength to the longer-wavelength range and reducion the influence of medium components. As fluorescence donors, we have used derivatives of 4-methylumbelliferone (MUmb) and 7-amino-4-methylcoumarin (AMC), which also serve as substrates for hydrolases such as chymotrypsin, phosphatase, and asparaginase. During the catalytic depletion of substrates, an accumulation of a highly fluorescent product is observed. This product can be specifically detected using the fluorescent marker rhodamine 6G (R6G), which emits light in the red region of the spectrum (550–600 nm) with high quantum yield. A significant FRET effect is observed when forming AOT reverse micelles. This is due to the proximity of fluorophores within the hydrophobic core of the micelle, which is shorter than in a buffer solution. This approach have practical implications for visualizing intracellular processes. The FRET technique can be used to determine intracellular enzymatic activity by detection with confocal laser scanning microcopy (CLSM), as demonstrated with L-asparaginase, a clinically important anti-leukemia medication. The approach suggested will allow researchers to study enzyme activity within cells. This has the potential to revolutionize medicine by improving drug development and shedding light on previously unknown aspects of cellular metabolism.

Power sources that can consistently deliver high levels of energy over extended periods are crucial for various space applications. Among the many methods of energy generation, direct heat-to-electricity conversion without intermediate steps or moving components shows particular promise but also presents significant challenges. The aim of this research is to address these challenges by enhancing the energy efficiency of thermionic conversion, which transforms thermal energy into electrical energy, through the development and utilization of a novel class of emission nanomaterials known as multilayer carbyne-enriched 3D-shaped nano-interfaces. By manipulating the topological, physicochemical, and functional characteristics of these interfaces, we seek to optimize their thermionic conversion capabilities. Building on the recent discovery of collective atomic vibrations called phonon waves within transition domains of multilayer nanostructures, we have devised a new approach to enhance the efficiency of thermionic energy converters. This involves unlocking the predictive functionality of 2D-ordered linear-chain carbon-based multilayer emitters through the excitation and fine-tuning of collective atomic vibrations and nanoarchitecture. To achieve this, we propose employing a combination of techniques that leverage interface effects, enable phonon wave propagation, facilitate energy exchange, and capitalize on synergistic effects offered by the multilayer nano-enhanced interfaces. The resulting devices for thermionic energy conversion have the potential to significantly surpass the efficiency of existing plasma thermionic converters by several orders of magnitude. Moreover, these electricity-generating sources based on thermionic conversion represent fundamental options for the advancement of Lunar and Martian research missions, opening up possibilities for sustainable energy production in extraterrestrial environments.

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

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

A new generation of nano-technologies is expanding solid propulsion capabilities and increasing their relevance for versatile and manoeuvrable micro-satellites with safe high-performance propulsion. We propose the innovative concept, connected with application of new synergistic effect of the energetic materials performance enhancement and reaction zones programming for the next generation small satellite multimode solid propulsion system. The main idea of suggested concept is manipulating by the self-organized wave patterns excitation phenomenon, by the properties of the energetic materials reaction zones and by localization of the energy release areas. This synergistic effect can be provided through application of the functionalized carbon-based nanostructured metamaterials as a nano-additives along with simultaneous manipulating by their properties through the electrostatic field. Mentioned effect will be controlled through predictive programming both by the spatial structure and physics-chemical properties of the functionalized carbon-based nano-additives and through the electromagnetic control of the self-organized wave pattern excitation and micro- and nano- scale oscillatory networks in the energetic material reaction zones. Suggested new concept makes it possible to increase the energetic material regression rate and increase the thrust of the solid propulsion system with minimal additional energy consumption.

Keywords: Olfaction; Rehabilitation; Hyposmia; Anosmia

Uranium isotopes actively investigated as mechanistic or time scale tracers of natural processes. This paper describes the occurrence and redistribution of U in the Vendian aquifer of the paleo valley at NW Russia. Forty-four rock samples were collected from boreholes, and twenty-five groundwater samples. The U, Fe concentration, and 234U/238U activity ratio were determined in the samples. We estimated the 14C and 234U-238U residence time of groundwater in an aquifer. It has been established that the processes of chemical weathering of Vendian deposits led to the formation of a strong oxidation zone, developed above -250 m.a.s.l. The inverse correlation between the concentrations of uranium and iron is a result of removal of U from paleo valley slopes in oxidizing conditions and accumulation of U at the bottom of the paleo valley in reducing conditions, and accumulation of Fe on the slopes and removal from bottom. Almost all U on the slopes replaced by a newly formed hydrogenic U with a higher 234U/238U activity ratio. After that dissolution and desorption of hydrogenic U was occurred from the slopes during periods without any glaciations and marine transgressions. Elevated concentrations of U preserved in not oxidized lenses at the paleo valley bottom.

This article shows that the recently proposed latent D-scoring model of Dimitrov is statistically equivalent to the two-parameter logistic item response model. An analytical derivation and a numerical illustration are employed for demonstrating this finding. Hence, estimation techniques for the two-parameter logistic model can be used for estimating the latent D-scoring model. In an empirical example using PISA data, differences of country ranks are investigated when using different metrics for the latent trait. In the example, the choice of the latent trait metric matters for the ranking of countries. Finally, it is argued that an item response model with bounded latent trait values like the latent D-scoring model might have advantages for reporting results in terms of interpretation.

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

Arylmagnesium and -calcium reagents are easily accessible, however, ether degradation processes limit the storability especially of the calcium-based heavy Grignard reagents. Ortho-bound substituents with phosphanyl donor sites usually block available coordination sites and stabilize such complexes. The reaction of bromo-2,6-bis(diphenylphosphanylmethyl)benzene (1a) with magnesium in tetrahydrofuran yields [Mg{C₆H₃-2,6-(CH₂PPh₂)₂}₂] (2) after recrystallization from 1,2-dimethoxyethane. However, the similarly performed reduction of bromo- (1a) and iodo-2,6-bis(diphenylphosphanylmethyl)benzene (1b) with calcium leads to ether cleavage and subsequent degradation products. α-Deprotonation of THF yields 1,3-bis(diphenylphosphanylmethyl)benzene. Furthermore, the insoluble THF adducts of dimeric calcium diphenylphosphinate halides, [(thf)₃Ca(X)(µ-O₂PPh₂)]₂ [X = Br (3a), I (3b)], precipitate verifying ether decomposition and cleavage of P-C bonds. Ether adducts of calcium halides [such as [(dme)₂(thf)CaBr₂] (4)] form supporting the initial Grignard reaction and a subsequent Schlenk-type dismutation reaction.

In the last decades the primordial black holes ({\bf pbhs}) have attracted much attention of cosmologists and astrophysicists. This is associated with origination of such black holes in the early Universe as a result of a gravitational collapse of the high-density matter, making them natural ''detectors'' of the processes involved. In inflationary cosmology of particular importance are {\bf pbhs} originated during the pre-inflationary period. And, since they are small and generated at the energies close to the Planck energies, for them we should take into consideration the quantum-gravitational corrections ({\bf qgcs}). In turn, these corrections change (shift) the inflationary parameters. The paper presents a study of the above-mentioned shifts with regard to these corrections for different scenarios. It is shown that probabilities of occurrence of the {\bf pbhs} under study with due regard for the given {\bf qgcs} are rising as compared to the semiclassical consideration. Besides, high-energy deformations of Friedmann Equations created on the basis of these corrections have been derived for different patterns. Conclusion contains the general remarks concerning the above-mentioned {\bf qgcs} for cosmological parameters and perturbations due to inflation; the steps for their investigation are outlined and the key problems of such a study are formulated.

Response of tomato and eggplant to continuous lighting (CL) and abnormal light/dark (L/D) cycles was studied to elucidate the role of the absence of the dark period in the diurnal cycle in the development of leaf injuries under CL. Four light treatments were set: 16/8 h (control), 24/0 h (CL), 6/6 h, and 24/24 h (abnormal L/D cycles). These light treatments provided average daily light integrals of 17.3, 25.9, 13.0 and 13.0 mol m-2 day-1, respectively. Results of this work have shown that in both tomato and eggplant abnormal L/D cycles caused photoinhibition and leaf injuries similar to those in CL-grown plants. Induced defense mechanisms were not strong enough to contend against oxidative stress caused by light treatments that provided plants with even smaller DLI than 16/8 h photoperiod did. Half time during abnormal L/D cycles were dark periods. Despite these facts, abnormal L/D cycles were injurious. It is concluded that photooxidative stress induced by CL can not be attributed to excessive DLI or the continuity of light itself (the absence of dark periods). Therefore, we believe that the hypothesis suggesting circadian asynchrony to be the main triggering factor of CL-induced leaf injuries is the most plausible among many others proposed.

A critical quality attribute of therapeutic monoclonal antibodies (mAbs) is the terminal sugar molecules of the N-linked glycan attached to the fragment crystalizable (Fc) region. There exists naturally-occurring heterogeneity in the N-linked glycan structure of mAbs, and such heterogeneity has a significant influence on the clinical safety and efficacy of mAb drugs. We previously proposed a constraint-based modeling method called glycosylation flux analysis (GFA) to characterize the rates (fluxes) of intracellular glycosylation reactions and applied the method to examine the N-linked glycosylation of immunoglobulin G (IgG) in fed-batch Chinese hamster ovary (CHO) fed-batch cultivations. In this work, we significantly improved the computational efficiency of the GFA, and employed the method to analyze the glycosylation of IgG in continuous perfusion CHO cultivations. Perfusion cell cultures have several advantages over the traditional (fed-)batch operation, including higher productivity per unit volume of reactor and more consistent product quality. The GFA showed that as in the fed-batch cultivation, the dynamical changes of IgG glycan heterogeneity in the perfusion culture are mainly attributed to alterations in the galactosylation flux activity. Furthermore, a regression analysis of the galactosylation flux activity using random forest regression linked the dynamics of galactosylation activity with the cell-specific productivity of IgG and the extracellular ammonia concentration.

Energy system models have become indispensable to shape future energy systems by providing insights into different trajectories. However, sustainable systems with high shares of renewable energy are characterized by growing cross-sectoral interdependencies and decentralized structures. To capture important properties of increasingly complex energy systems, sophisticated and flexible modelling tools are needed. At the same time open science becomes increasingly important in energy system modelling. This paper presents the Open Energy Modelling Framework (oemof) as a novel approach in energy system modelling, representation and analysis. The framework forms a toolbox to construct comprehensive energy system models and has been published open source under a free license. With a collaborative development based on open processes the framework seeks for a maximum level of participation and transparency to facilitate open science principles in energy system modelling. Based on a generic graph based description of energy systems it is well suited to flexibly model complex cross-sectoral systems and incorporate various modelling approaches. This makes the framework a multi-purpose modelling environment for modelling and analyzing different systems ranging from an urban to a transnational scale.

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

Within the framework of the previously proposed formulation of the quantum theory of gravity in terms of world histories, it was suggested that the universe has its own mass. This quantity is analogous to the mass of a particle in relativistic mechanics. The mass of the universe is a distribution of non-zero values of gravitational constraints, which arises and changes in time as a consequence of the initial conditions for fundamental dynamic variables. A formulation of the Euclidean quantum theory of gravity is also proposed to determine the initial state, which can be the source of the universe’s own mass. Being unrelated to ordinary matter, the distribution of its own mass affects the geometry of space and forms a dedicated frame of reference. The existence of selected reference systems is taken into account by the corresponding modification of the system of quantum gravitational constraints. A variant of such a modification of the Wheeler-De Witt equation is the operator representation of gravitational constraints, which, together with the state of the universe, determines the parameters of the reference system in the form of a distribution of the spinor field on a spatial section.

One of the important features of polymethine (cyanine) dyes is isomerization around one of C–C bonds of the polymethine chain. In this review, spectral properties of the isomers, photoisomerization and thermal back isomerization of carbocyanine dyes, mostly meso-substituted carbocyanine dyes, are considered. meso-Alkyl-substituted thiacarbocyanine dyes are present in polar solvents mainly as cis isomers and, hence, exhibit no photoisomerization, whereas in nonpolar solvents, in which the dyes are in the trans form, photoisomerization takes place. In contrast, the meso-substituted dyes 3,3′-dimethyl-9-phenylthiacarbocyanine and 3,3′-diethyl-9-(2-hydroxy-4-methoxyphenyl)thiacarbocyanine occur as trans isomers and exhibit photoisomerization in both polar and nonpolar solvents. The behavior of these dyes may be explained by the fact that the phenyl ring of the substituent in their molecules can be twisted at some angle, removing the substituent from the plane of the molecule and reducing its steric effect on the conformation of the trans isomer. In some cases, photoisomerization of cis isomers of meso-substituted carbocyanine dyes is also observed (for some meso-alkyl-substituted dyes complexed with DNA and chondroitin-4-sulfate; for 3,3′-diethyl-9-methoxythiacarbocyanine in moderate polarity solvents). The cycle photoisomerization–thermal back isomerization of cyanine dyes can be used in various systems of information storage and deserves further investigation using modern research methods.