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

Keywords: Requirements prioritization, Next release plan, Software product planning, Decision support, MoSCoW, AHP, K-Menas, GMM, BIRCH, PAM, Hierarchical, Clustering, Clusters Evaluation

Air passenger traffic prediction is crucial for the effective operation of civil aviation airports. Despite some progress in this field, the prediction accuracy and methods need further improvement. This paper proposes an integrated approach to the prediction of air passenger index as follows. Firstly, the air passenger index is defined and classified by the K-means clustering method. Based on the mutual information (MI) principle, the information entropy is used to analyze and select the key influencing factors of air passenger travel. By incorporating the MI principle into the support vector regression (SVR) framework, this paper presents an innovative MI-SVR machine learning model used to predict the air passenger index. Finally, the proposed model is validated by passenger throughput data of the Shanghai Pudong International Airport, China. The experimental results prove the model feasibility and effectiveness by comparing them with conventional methods, such as ARIMA, LSTM, and other machine learning models, outperformed by the MI-SVR model. Besides, it is shown that the prediction effect of each model could be improved by introducing influencing factors based on mutual information. The main findings are considered instrumental to the airport operation and air traffic optimization.

Air passenger traffic prediction is crucial for the effective operation of civil aviation airports. Despite some progress in this field, the prediction accuracy and methods need further improvement. This paper proposes an integrated approach to the prediction of air passenger index as follows. Firstly, the air passenger index is defined and classified by the K-means clustering method. Based on the mutual information (MI) principle, the information entropy is used to analyze and select the key influencing factors of air passenger travel. By incorporating the MI principle into the support vector regression (SVR) framework, this paper presents an innovative MI-SVR machine learning model used to predict the air passenger index. Finally, the proposed model is validated by passenger throughput data of the Shanghai Pudong International Airport, China. The experimental results prove the model feasibility and effectiveness by comparing them with conventional methods, such as ARIMA, LSTM, and other machine learning models, outperformed by the MI-SVR model. Besides, it is shown that the prediction effect of each model could be improved by introducing influencing factors based on mutual information. The main findings are considered instrumental to the airport operation and air traffic optimization.

This paper presents work done as part of a transformation effort towards a greener and more sustainable Aluminium manufacturing plant. The effort includes reducing the carbon footprint by minimising waste and increasing operational efficiency. The contribution of this work includes the reduction of waste through the implementation of autonomous, real-time quality measurement and classification at an Aluminium casthouse. Data is collected from the MV20/20 which uses ultrasound pulses to detect molten Aluminium inclusions, which degrade the quality of the metal and cause subsequent metal waste. The sensor measures cleanliness, inclusion counts and distributions from 20 - 160 microns. The contribution of this work is in the development of business analytics to implement condition-based monitoring through anomaly detection, and to classify inclusion types for samples that failed. For anomaly detection, multivariate K-Means and DBSCAN algorithms are compared as they have been proven to work in a wide range of datasets. For classification, a two-stage classifier is implemented. The first stage classifies the success or failure of the sample, while the second stage classifies the inclusion responsible for the failed sample. The algorithms considered include logistic regression, support vector machine, multi-layer perceptron and radial basis function network. The multi-layer perceptron offers the best performance using k-fold cross-validation, and is further tuned using grid search to explore the possibility of an even better performance. The results reveal that the model has achieved a global maximum in performance. Recommendations include the integration of additional sensor systems and the improvements in quality assurance practices.

The internet of things and growing demand for smaller and advanced devices has created the problem of high heat production in the electronic equipment which greatly reduces the work performance and life of the electronic instruments. Thermal interface materials (TIMs) are placed in between heat generating micro-chip and the heat dissipater to conduct all the produced heat to the heat sink. Development of suitable TIMs with excellent thermal conductivity (TC) in both in-plane and through-plane directions is a very important need at present. For efficient thermal management, polymer composites are potential candidates. But in general their thermal conductivity is low compared to that of metals. The filler integration into the polymer matrix is one of the two approaches used to increase the thermal conductivity of polymer composites and is also easy to scale up for industrial production. Another way to achieve this is to change the structure of polymer chains, which fall out of the scope of this work. In this review, considering the first approach, the authors have summarized recent development in many types of fillers with different scenarios by providing multiple cases with successful strategies to improve through-plane thermal conductivity (TPTC) (K⊥). For better understanding of TC the comprehensive background is also presented. In the end, it is given a detailed conclusion which provides drawbacks of some filler, multiple significant routes recommended by other researchers to build Thermally Conductive Polymer Composites, future aspects along with direction so that the researchers can get a guideline to design an effective polymer based Thermal interface materials. A number of methods to improve the effective (out-plane) thermal conductivity of polymer composites are also discussed.

Satellite-based data classification performance remains a challenge for research community in the field of land use/land cover mapping. Here we investigated supervised per-pixel classifications performance under different scenarios, based on single and seasonal multispectral data combina-tions of different sensors (Landsat-8 OLI and Sentinel-2 MSI). In case of Landsat, seasonal spectral indices (EVI and NDMI) were included. A typical Mediterranean watershed with a complex landscape comprised of various forest and wetland ecosystems, crops, artificial surfaces, and lake water was selected to test our approach. All available geospatial data from national databases (Forest Map, LPIS, Natura2000 habitats, cadastral parcels, etc.) are used as ancillary data for clas-sification training and validation. We examined and compared the performance of ML, RF, KNN and SVM classifiers under different scenarios for land use/land cover mapping, according to Co-pernicus Land Cover nomenclature. In total, eight land use/land cover classes were identified in Landsat-8 OLI and nine in Sentinel-2 MSI for an acceptable overall accuracy over 85%. A com-parison of the overall classification accuracies shows that Sentinel-2 overall accuracy was slightly higher than Landsat-8 (96.68% vs. 93.02%). Respectively, the best-performed algorithm was ML in Sentinel-2 while in Landsat-8 was KNN. However, machine-learning algorithms have similar results regardless the type of sensor. We concluded that best classification performances achieved using seasonal multispectral data. Future research should be oriented towards integrating time-series multispectral data of different sensors and geospatial ancillary data for land use/land cover mapping.

Shown is the derivation of Lorentz-Einstein k-factor in SRT as an amplitude-term of oscillation-differential equations of second order.This case is shown for classical Lorentz-factor as solution of an equation for undamped oscillation as well as the developed theorem as a second solution for advanced SRT of fourth order with an equation for damped oscillation-states.This advanced term allows a calculation for any velocities by real rest mass.Also accelerated coordinate -frames are discussed.

Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

This study investigates the application of regression neural networks, in particular the fitrnet model, in predicting the hardness of steels. The experiments involve extensive tuning of hyperparameters using Bayesian optimization and employ 5-fold and 10-fold cross-validation schemes. The trained models are rigorously evaluated, and their performances are compared using various metrics such as mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2). The results provide valuable insights into the effectiveness of the models and their ability to generalize to unseen data. In particular, Model 4208 (8-85-141-1) emerges as the top performer with an impressive RMSE of 1.0790 and an R² of 0.9900. The research paper contains an illustrative example that demonstrates the practical application of the developed model in determining the hardenability band for a specific steel grade and shows the effectiveness of the model in predicting and optimizing heat treatment results.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

A quantum hybrid (QH) intelligent approach that blends the adaptive search capability of the quantum-behaved particle swarm optimisation (QPSO) method with the intuitionistic rationality of traditional fuzzy k-nearest neighbours (Fuzzy k-NN) algorithm (known simply as the Q-Fuzzy approach) is proposed for efficient feature selection and classification of cells in cervical smeared (CS) images. From an initial multitude of seventeen (17) features describing the geometry, colour, and texture of the CS images, the QPSO stage of our proposed technique is used to select the best subset features (i.e. global best particles) that represent a pruned down collection of seven (7) features. Using a dataset of almost 1000 images, performance evaluation of our proposed Q-Fuzzy approach assesses the impact of our feature selection on classification accuracy by way of three experimental scenarios that are compared alongside two other approaches: The All-features (i.e. classification without prior feature selection) and another hybrid technique combining the standard PSO algorithm with the Fuzzy k-NN technique (P-Fuzzy approach). In the first and second scenarios, we further divided the assessment criteria in terms of classification accuracy based on the choice of best features and those in terms of the different categories of the cervical cells. In the third scenario, we introduced new QH hybrid techniques, i.e. QPSO combined with other supervised learning methods, and compared the classification accuracy alongside our proposed Q-Fuzzy approach. Furthermore, we employed statistical approaches to establish qualitative agreement with regards to the feature selection in scenarios 1 and 3. The synergy between the QPSO and Fuzzy k-NN in the proposed Q-Fuzzy approach marginally improves classification accuracy as manifest in the reduction in number cell features, which is crucial for effective cervical cancer detection and diagnosis.

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

: Drought monitoring and early detection have improved greatly in recent decades through the development and refinement of numerous indices and indicators. However, a lack of guidance, based on user experience, exists as to which drought monitoring tools are most appropriate in a given location. This review paper summarizes the results of targeted user engagement and the published literature to improve the understanding of drought across North America, and to enhance the utility of drought monitoring tools. Workshops and surveys were used to assess and make general conclusions about the perceived performance of drought indicators, indices and impacts information used for monitoring drought in the five main Köppen climate types (Tropical, Temperate, Continental, Polar Tundra, Dry) found across Canada, Mexico, and the United States. In Tropical, humid Temperate, and southerly Continental climates, droughts are perceived to be more short-term (less than 6 months) in duration rather than long-term (more than 6 months). In Polar Tundra climates, Dry climates, Temperate climates with dry warm seasons, and northerly Continental climates, droughts are perceived to be more long-term than short-term. In general, agricultural and hydrological droughts were considered to be the most important drought types. Drought impacts related to agriculture, water supply, ecosystem, and human health were rated to be of greatest importance. Users identified the most effective indices and indicators for monitoring drought across North America to be the U.S. Drought Monitor (USDM) and Standardized Precipitation Index (SPI) (or another measure of precipitation anomaly), followed by the Normalized Difference Vegetation Index (NDVI) (or another satellite-observed vegetation index), temperature anomalies, crop status, soil moisture, streamflow, reservoir storage, water use (demand), and reported drought impacts. Users also noted the importance of indices that measure evapotranspiration, evaporative demand, and snow water content. Drought indices and indicators were generally thought to perform equally well across seasons in Tropical and the colder Continental climates, but their performance was perceived to vary seasonally in Dry, Temperate, Polar Tundra, and the warmer Continental climates, with improved performance during warm and wet times of the year. The drought indices and indicators, in general, were not perceived to perform equally well across geographies. This review paper provides guidance on when (time of year) and where (climate zone) the more popular drought indices and indicators should be used. The paper concludes by noting the importance of understanding how drought, its impacts, and indicators are changing over time as the climate warms, and by recommending ways to strengthen the use of indices and indicators in drought decision-making.

Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli, thus exerting crucial neuroprotection for cerebellar ataxias and corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. Earliest changes were detected at 3 months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, impacting communication and excitability of cerebellar neurons. Discovery of such risk versus progression markers improves the assessment of pre-symptomatic treatments in SCA2 and related disorders.

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine co-releasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play key roles in the regulation of pain, locomotive movement, and respiratory rhythms. Herein, we first describe GABAergic and glycinergic transmission and inhibitory networks, which consist of three types of terminals, in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many of GABAergic neurons convert to co-releasing state. The co-releasing neurons and terminals remain in the dorsal horn, whereas many of co-releasing ones ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7,389 participants and 53 variables. Initially, unsupervised K-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (Light-GBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised K-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

In this paper we introduce the New/Generalized two parameter Gamma function and Pochhammer symbol. We named them, as Generalized p - k Gamma Function and Generalized p - k Pochhammer symbol and denoted as $ _{p}^{a}\Gamma_{k}(x) $ and $ _{p}^{a}(x)_{n,k} $ respectively. We prove the several identities for $ _{p}^{a}\Gamma_{k}(x) $ and $ _{p}^{a}(x)_{n,k} $ those satisfied by the classical Gamma function. Also we provide the integral representation for the $ _{p}^{a}\Gamma_{k}(x) $

Keywords: Electrical power systems, Support vector machines, Random Forest, Machine learning, Wavelet transform, Transmission lines fault, Electrical power quality, Short circuit, Classification of faults, Localization of faults, Decision trees, Ensemble learning, K-nearest neighbors.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.