This work is the first in literature to tackle the difficult open problem of determining the upper bound and threshold theorem for the TDCDP (time-dependent controller parameter) of the (Fokker Planck Kolmogorov) probability density function. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to information theory, graph theory, data science, finance, economics, and beyond. So, this by default adds more taste and credibility to this study. This leads by nature to introducing a different flavor to this ground-breaking research by highlighting the impact of Fokker Planck Kolmogorov(FPK) to revolutionize crypocurrency,which have received its name because it uses encryption to verify transactions, a new debatable digital payment system that doesn't rely on banks to verify transactions. It’s a peer-to-peer system that can enable anyone anywhere to send and receive payments. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

This study aimed to evaluate the discrepancies between genetic and visual coat color assignment in the Sarcidano Horse and to elucidate potential reasons. Individual DNA from 90 Sarcidano Horses was used for genetic assignment of coat color to explore the correspondence with individual forms containing phenotypical traits. The MC1R exon 1 and ASIP exon 3 have been genotyped and sequenced to obtain a picture of the coat color distribution in this breed. Surprisingly, once we compared the genetic results with the individual forms reporting the phenotypic data for each subject, a certain degree of non-correspondence between the phenotypic and genetic data in relation to coat color emerged. From the genetic analysis, Chestnuts (n = 58) resulted the most common Sarcidano Horse (n = 58), followed by a quite large number of Blacks (n = 28) and a very small number of Bays (n = 4), whereas phenotypic distribution resulted in 38 Chestnuts, 40 Bays, only 2 Blacks, and 10 Grays (without the possibility of recognizing the true color they carried). Chestnut resulted a very representative coat color, while many horses that visually identified as Bays were genetically Blacks. This discrepancy, that could be due to a variety of individual and external factors, including age, time of year, living situation and dietary condition, suggesting the importance of accurate coat color identification to ensure adequate features registration and reliable prediction of offspring’s coat color.

We are introducing a highly efficient 48-channel ultrasound beamforming system ideal for ultrasound endoscopy applications. The system includes a transmitter and a receiver, which allow for low-area, high-resolution imaging acquisition. The transmitter uses a charge redistribution HV (high voltage) scheme to generate three-level pulses that actuate the transducer, implemented with the standard CMOS process for optimal cost and power savings. Meanwhile, the receiver features a sub-array structure and a delay generator that reduces area usage. To achieve high-resolution ultrasound imaging acquisition with low computational power, we developed the Shift Coherence Factor (SCF) algorithm, which is hardware-friendly. This approach delivers a lateral resolution over 20% better than the conventional delay and sum (DAS) algorithm, with a contrast ratio of over 30 dB. The system was implemented in a 180 nm standard CMOS process with an area of 24.98 mm2, power consumption of 8.23 mW per channel, achieving a delay resolution of 8.33 ns, and a low-area implementation of 0.52 mm2 per channel. The system offers high-quality imaging acquisition with minimal additional area and power consumption, which has great potential for 3D imaging or catheterized ultrasound systems.

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium’s dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. Aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, being the effect pronounced also when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin treated cells, which were unable to form colonies, were actually ROS+/PI–. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.

The application of distributed fiber optic strain and temperature measurement can be utilized to address a multitude of measurement tasks across a diverse range of fields, particularly in the context of structural health monitoring in the domains of building construction, civil engineering, and special foundation engineering. However, a comprehensive understanding of the influences on the measurement method and the sensors is essential to prevent misinterpretations or measurement deviations. In this context, this study investigated the effects of moisture exposure, including various salt solutions and a high pH value, on a distributed strain measurement using Rayleigh backscattering. Three fiber optic sensors with different coating materials and one uncoated fiber were exposed to five different solutions for 24 hours. The study revealed significant discrepancies in deformation between the three coating types depending on the surrounding solution. Furthermore, in contrast to the prevailing literature, which predominantly describes swelling effects, a negative deformation was observed in a magnesium chloride solution. The findings of this study indicate that corresponding effects can impact the precision of measurement, potentially leading to misinterpretations. Conversely, these effects could be used to conduct large-scale monitoring of chemical components using distributed fiber optic sensing.

This paper presents the development and implementation of a Pan-Tilt-Zoom (PTZ) camera interfaced with a Jetson processor hosting Artificial Intelligence (AI) algorithms, designed to address the challenges of traditional biometric capture for first-time passport photos of young children. The system enhances the accuracy, efficiency, and adaptability of facial biometric capture by recognizing and accommodating the dynamic and diverse behaviors of children. Utilizing AI, the system detects faces and analyzes facial features using 68 landmark points, ensuring high-quality images that meet ISO standards. These technical specifications, implementation process, and performance evaluations of the developed system are provided in this paper, demonstrating the potential of the proposed AI Face-Capture to advance biometric identification and verification for young children.

Air pollution has recently gained much attention from the general population. Despite pollution control being an issue in both urban and rural regions, most of the available research has concentrated on urban districts. Hence, investigations into how urban-rural transition affects PM2.5 are warranted within the framework of urban-rural integration. Using the Yellow River Basin as a case study, this study employed the entropy method and Analytic Hierarchy Process (AHP) to uncover the extent of urban-rural transformation. It then used the spatial autocorrelation method to investigate the spatiotemporal features of PM2.5 and the spatial econometric model to investigate the mechanisms that influence the relationship between urban-rural transformation and PM2.5. The results are as follows: (1) Over time, there was a discernible upward tendency in the change in urban-rural areas. The development has progressed from asymmetrical north-east and south-west elevations to a more balanced pattern of north-east, middle-east, and west-west elevations. (2) The PM2.5 concentration increased steadily, then fluctuated, and finally decreased. Notably, the general pattern has not changed much, and it is high in the east and low in the west. (3) Different subsystems of the urban-rural transformation have different impacts on air pollution at different stages. The influence of industrial transformation (IT) on PM2.5 showed an inverted “N-shaped” curve of negative-positive-negative changes, and the industrial structure played a leading role in the spatiotemporal evolution of PM2.5. Currently, an inverted "U-shaped" curve forms the left side of the impact of population transition (PT) on PM2.5. Land development (LT) has a "U-shaped" curve for its effect on PM2.5. This research provides a new perspective on the topic of PM2.5 and its connection to urban-rural integration, which is crucial to understanding the dynamics of this shift. To achieve its goal of high-quality development, it supports regional initiatives to reduce PM2.5 emissions in the Yellow River Basin. Moreover, it can provide a reference for decision-makers in the world’s densely populated areas that suffer from serious air pollution.

Einstein was skeptical of part of quantum mechanics, and he believed that Heisenberg’s uncertainty principle did not reflected the full depth of reality. He famously stated, ”God does not play dice with the universe.” However, since quantum mechanics has passed so many experimental tests, most physicists today assume that Einstein was wrong. Nevertheless, we will demonstrate that Heisenberg’s uncertainty principle must be modified to unify gravity with quantum mechanics. This modification leads to the Certainty-Uncertainty principle where the certainty part is strongly linked to gravity. This means Einstein likely was right in his intuition also on this point. The key is to understand that the de Broglie wavelength is not the actual wavelength of matter but merely a derivative of the true matter wavelength, namely the Compton wavelength. Furthermore, one must understand that the gravitational constant, first introduced in 1873, is simply a composite constant needed to rectify the in- complete definition of kilogram mass introduced into Newtonian gravity in 1873.

Fragile X syndrome (FXS) is an intellectual developmental disorder characterized, inter alia, by deficits in short-term processing of neural information such as sensory processing and working memory. The primary cause of FXS is the loss of fragile X messenger ribonucleoprotein (FMRP), which is profoundly involved in synaptic function and plasticity. Short-term synaptic plasticity (STSP) may play important roles in functions that are affected by FXS. Recent evidence points to a crucial involvement of presynaptic calcium sensor synaptotagmin-7 in STSP. However, how the loss of FMRP affects STSP and synaptotagmin-7 have been insufficiently studied. Further-more, males and females are affected differently by FXS, but the underlying mechanisms remain elusive. The aim of the present study is to investigate possible changes in STSP and the expres-sion of synaptotagmin-7 along the hippocampus of adult males and females in the Fmr1 knock-out (KO) rat model of FXS. We found that paired-pulse ratio and frequency facilita-tion/depression, two forms of STSP, as well as the expression of synaptotagmin-7, are normal in adult KO males, but paired-pulse ratio is increased in the ventral hippocampus of KO females. Furthermore, we found no gender-related but robust region-dependent difference in STSP. AM-PA receptors are similarly expressed in the two hippocampal segments of the two genotypes and in both genders. Also, basal excitatory synaptic transmission is higher in males compared with females. Interestingly, we found more than twofold higher levels of synaptotagmin-7, not syn-aptotagmin-1, in the dorsal compared with the ventral hippocampus in males of both genotypes and in wild type females. These results point to the susceptibility of the female ventral hippo-campus to FMRP loss. Importantly, the different levels of synaptotagmin-7 that parallel the higher score of synaptic facilitation in the dorsal vs ventral hippocampus suggest that synapto-tagmin-7 may play a pivotal role in defining the striking difference in STSP along the long axis of the hippocampus.

The signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arose during the acute phase of COVID19 by an increased breakdown of haematocytes, to which the liver responds by reducing the production of albumin, in order to prevent a too large decrease in haematocrit.In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID. My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the intravenous administration of donor blood products, starting with albumin concentrate. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable. I suspect that most Long COVID patients will exhibit a high serum ferritin level as a result of internal haemolysis, and haematocrit and albumin values at the high and low extremes of the reference range because the liver can not keep up with the recovery of the red bone marrow.

Undoubtedly, there is a potential impact of large language models like ChatGPT in revolutionizing information retrieval and knowledge discovery, particularly in the context of the vast amount of electronic material available. On another strong note, the current work offers a first time ever mathematical approach to accurately fine tune perplexity AI, which sets a giant step ahead towards accurate next generations AI. Having started this world leading discovery, the upper and lower bounds of perplexity AI, namely , , respectively, are obtained for the first-time ever. Concluding remarks combined with emerging open problems and next research phase are provided.

Intestinal parasitic infections pose a significant public health challenge in Northern Nigeria, with prevalence rates ranging from 20% to 70%. Traditional diagnostic methods, primarily microscopic examination of stool samples, face limitations such as low sensitivity and high costs. This research addresses these challenges by proposing an Artificial Intelligence (AI)-based platform for the identification and counting of intestinal parasites. A total of 651 samples were collected from the 7 Northern State of Nigeria along with questionnaire collecting data on demographic, socio-economic, hygiene habits and environmental factors. Leveraging the You Only Look Once (YOLO) V8 model, trained on a dataset of 360 pre-processed and 467 annotated images, the AI model demonstrated promising performance metrics. Information-Theory-Based approaches including (CIFE, CMIM, DISR and ICAP) were used on various machine learning models (Naïve Bayes, Random Forest, Support Vector Machine and Decision Tree) to analyse the risk factors associated with the parasitic disease. The precision-recall curve, average precision, mean average precision, and F1 score indicated reliable detection and classification across various parasite classes. The accuracy (97%) and AUC (99%) scores shows that CIFE with Random Forest has the best performance indicating the significant risk factors associated with the parasitic diseases. The model exhibited a well-balanced trade-off between precision and recall, showcasing its potential as a cost-effective and accessible tool for improving the diagnosis and treatment of intestinal parasitic infections in resource-limited settings.

This research challenges the traditional perspective on consumer behavior, which focuses on external factors shaping the sequential stages of decision-making. Instead, it proposes a paradigm shift by treating the decision-making process itself as an independent variable, exploring its impact on various outcomes like purchasing behavior, brand loyalty, and post-purchase satisfaction. This novel approach offers deeper insights into the intricacies of consumer behavior, particularly in the digital age. By uncovering the reciprocal relationships between the decision-making process and other variables, the research provides a more nuanced understanding of how consumers navigate today's complex landscape. It further delves into how variations in the decision-making process across diverse consumer groups influence various outcomes, recognizing the unique characteristics and needs of different demographics. The research also acknowledges the interplay of psychological, social, and contextual factors that shape both the decision-making process and its downstream effects, offering a comprehensive understanding of the multifaceted influences on consumer behavior. Ultimately, by studying the decision-making process as an independent variable, this research aims to equip businesses and researchers with valuable insights, enabling them to better navigate the ever-evolving world of consumer behavior.

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

Remediation of IT issues encoded into domain-specific or user-defined alerts occurring in cloud environments and customer ecosystems in a vast majority of cases suffers from accurate recommendations which could be timely supplied for recovery of performance degradations. That, of course, is hard to realize through furnishing those abnormality definitions with an appropriate expert knowledge which varies from one environment to another. At the same time, in a large proportion of support cases, the reported problems under Global Support Services (GSS) or Site Reliability Engineering (SRE) treatment ultimately go down to the product teams making them waste costly development hours on investigating self-monitoring metrics of our solutions. Therefore, the mean-time-to-resolution (MTTR) rates of problems/alerts are significantly impacted from lack of a systematic approach towards adopting AI Ops. That would imply building, maintaining, and continuously improving/annotating a data store of insights that ML models are trained and generalized across the whole customer base and corporate cloud services. Our ongoing study is in line with such a vision and validates an approach that learns the alert resolution patterns in such a global setting and explains them using interpretable AI methodologies. The knowledge store of causative rules is then applied in predicting potential sources of the application degradation reflected in an active alert instance. In this communication, we share our experiences with a prototype solution and up to date analysis demonstrating how root conditions are discovered with a high accuracy for a specific type of problem. It is validated against the historical data of resolutions performed by heavy manual development efforts. We also offer a Dempster-Shafer theory-based rule verification framework for experts as a what-if analysis tool to test their hypotheses about underlying environment.

This paper presents a methodology for the integration of Building Information Modeling (BIM) and Life Cycle Cost Analysis (LCCA) to assess the economic implications of designing aging-in-place (AIP) homes at the conceptual stage. With the global increase in the aging population, there is an increased demand for housing solutions tailored to the needs of elderly individuals. Focusing on the importance of the early phase of design, this study aims to improve the process of making efficient decisions by providing a comprehensive assessment of the life cycle costs associated with AIP homes. The study introduces a semi-automated model for the economic evaluation of AIP homes, enabling the estimation of costs throughout the houses’ entire life cycle, from design and construction to operation, maintenance, and eventual renovation or disposal. The said model facilitates the exploration of the long-term economic feasibility of design’s related decisions with an emphasis on the importance of considering the life cycle costs early during the design process to optimize the functionality and economic viability. By investing in accessible and universal design features upfront, the initial costs for modifications can lead to long-term savings by reducing the need for extensive retrofits. The model can easily do comparison between different design alternatives in terms of their lifecycle costs, allowing designers to assess the financial impact of using important features in their design such as wider doorways, accessible bathrooms, and elevators. Overall, this study provides valuable insights for designers and homeowners about the economic aspects of designing AIP homes as a support for efficient decision-making during the early stages of the design process.

In order to solve the problem of large eddy current loss and high temperature rise caused by large amount of permanent magnet, a new type of combined magnetic pole permanent magnet motor is proposed in this paper. The sinusoidal distribution subdomain model of non-uniform air gap rotor is established by using Laplace equation, and the analytical expression of eddy current loss of rotor in uniform air-gap and non-uniform air-gap is derived. The effect of rotor eccentricity on eddy current loss is obtained. According to the characteristics of distributed winding of non-uniform air gap combined pole permanent magnet motor, equivalent treatment is performed to obtain the equivalent thermal conductivity, so as to establish equivalent thermal network model of motor, calculate the temperature value of each component of the motor, and verify the correctness of the thermal network model through the method of magnetothermal bidirectional coupling. Finally, an experimental platform is set up to carry out temperature rise experiments on the two prototypes respectively. Experimental results show that the non-uniform air-gap rotor structure can effectively reduce the rotor eddy current loss and motor temperature rise, and also verify the accuracy of the analytical model calculation results.

Soccer is the leading cause of all sports-related ocular injuries in Europe and Israel and leads to blindness at a disproportionately high rate, especially among children (Thompson et al., 2019). With soccer being the most popular sport in the world, it is surprising the only solution to ocular injuries are sports glasses which can cause direct damage to the eye and impair peripheral vision by 15%, calling for an alternative (Smith & Jones, 2020). This work, based on an imported facial model, focuses on both the qualitative and quantitative aspects of building a personalized, low-cost (through optimizing material needed), superior apparatus to conventional sports glasses. The quantitative side examines a modified and model-validated (through a SRS of thirty unique extrapolated points) multivariate linear regression equation, based on horizontal and vertical rotation angles (n=60) trained with residual and computer simulation data, that can accurately extrapolate and quantify ocular impact from all horizontal and vertical rotation angles and a modified Hertzian Contact Stress Equation to determine the thickness of the apparatus using the elasticity modulus, impact force, and geometrical facial and soccer-ball features. The qualitative side examines where firstly, ocular impact is most prevalent, and secondly, where most impact is seen from rotating the ball horizontally and vertically through analysis of Pearson’s Correlation Coefficient at the supraorbital, medial canthus, infraorbital, and lateral canthus regions from both regression equations as well as a cost-benefit analysis for comparison with conventional sports glasses. The findings discovered in this work lay the groundwork for future research to build a customized low-cost ocular injury prevention device which can simultaneously ensure complete ocular safety while enhancing athletic performance for over 250,000,000 players (Johnson & Garcia, 2022).

The continuous flowing spacetime forms a spacetime group G, one of its fundamental groups is the Poincare group PO(1,3), and the matter and interaction fields are representations of its intrinsic spacetime group. As a kind of quantized space-time unit, space-time group elements generate both space-time manifolds and matter. Matter and fields are aggregates of the quantum space-time within them and determine their type: the Lorentz group SO(1,3) represents a rotating spacetime corresponding to visible matter and the translation group P^1,3 represents a translational spacetime corresponding to dark matter and dark energy. The aggregation mode of space-time degrees of freedom in matter reveals that charge conjugation symmetry is the inverse symmetry of internal time of charged particles, and the external parity breaking of neutrinos is also due to their internal spatial aggregation mode.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

The ocean of the planet Earth, which is as thin as a cicada's wings, play a role of catalyst to the evolving of the ancient plates. The ocean and the ancient plates of the planet Earth formed a magic Whirlpool of the Cross “十” shape with double whirl arms. The central core of the Cross “十” shape Ocean-Plate Whirlpool is the Hint Black Hole (HBH) located at the Northwestern Pacific Ocean floor which is decorated with invisible geological age distribution of clam shell. The double whirl arms of ancient plates are distinguished to be left and right at Bering Strait and just formed the ring of fire of the Pacific Ocean.The Cross “十” shape Ocean-Plate Whirlpool of the planet Earth was born at the equatorial area about 66 Ma ago and is rotating anticlockwise and drifting northward by a mini footprint of spiral at s speed of as slow as a snail moves. Obviously, it would come to an end at the North Pole about 100 Ma in the future. So, the lifespan of the Cross “十” shape Ocean-Plate Whirlpool would be about 166 Ma, from birth to death on the planet Earth.What is hidden behind of the evolving of the oceans and the ancient plates is the golden law of geometrical progression of ladder pagoda of attributes evolving of them, which is “1➨2➨4➨2➨1”, including upgrading and downgrading process. It seems to hint that what is happening on the planet Earth, including the top-level species of human race, is actually unique in the Milky Way galaxy in essence.The property roles of expanding and shrinking are existing in the Cross “十” shape Ocean-Plate Whirlpool by face to face and the exchange of property roles took place tens of millions of years ago. And that situation would happen again tens of millions of years in the future. It seems a giant circle of evolving of the exchange of property roles would be drawn by the Cross “十” shape Ocean-Plate Whirlpool in her lifetime.

Recent developments in microfluidics and biomaterials have enabled the creation of organs-on-chips (OoCs), which provide a controlled and lifelike in vitro microenvironment resembling an actual organ. Organ-on-a-chip technology offers a tremendous opportunity for efficient, cost-effective, and ethical drug testing and research. However, the high throughput and large quantities of data these complex microenvironments produce make it difficult for researchers to effectively analyze the data and draw valuable conclusions. Convolutional Neural Networks (CNNs) are most aptly positioned to address many of OoC’s challenges because of their ability to interpret microscopic images and facilitate the analytical process. Despite the growing field of AI, there have been a limited number of studies summarizing the various applications of CNNs in OoCs. This review aims to provide 1) an overview of the technology involved with CNNs and OoCs 2) an insight into the state-of-the-art applications of CNNs in OoCs including device parameters, predicting and tracking cell trajectories, super-resolution image segmentation, and image classification, and 3) an overview of existing challenges and opportunities ahead for clinical translation of this technology. Various applications of CNNs have been classified by the type of task. Different CNN models such as Faster R-CNNs, fully convolutional networks (FCNs), and Mask R-CNNs are explained and highlighted. This review article can be used as a resource for a better understanding of the potential of CNNs in biomedical research and clinical applications, particularly OoCs.

Due to Motor Neurone Diseases, a large population remains disabled worldwide, negatively impacting their independence and quality of life. This typically involves a weakness in the hand and forearm muscles, making it difficult to perform fine motor tasks such as writing, buttoning a shirt, or gripping objects. This project presents a vision-enabled rehabilitation hand exoskeleton to assist disabled persons in their hand movements. The design goal was to create an accessible tool to help with a simple interface requiring no training. This prototype is built on a commercially available glove where a camera and embedded processor were integrated to help open and close the hand, using air pressure, thus grabbing an object. An accelerometer is also implemented to detect the characteristic hand gesture to release the object when desired. This passive vision-based control differs from active EMG-based designs as it does not require individualized training. Continuing the research will reduce the cost, weight, and power consumption to facilitate mass implementation.

The existence of semantic inaccuracy §2 articles by A. Einstein “On the electrodynamics of moving bodies”, illustrating the principle of the relativity of simultaneity. In a sentence “The observers co-moving with the moving rod would thus find that the two clocks do not run synchronously while the observers in the system at rest would declare them synchronous”, the preposition “not” must be moved and placed before the word “synchronous”, at the end of the sentence. The criterion for synchronism of the clocks on the rod is the time it takes for the beam to travel from clock A to clock B and back, and for observers on the rod it will be the same both when the rod is at rest and when the rod is moving. Otherwise, observers on the rod would have had at their disposal an experiment that would allow them to determine whether the rod is moving or at rest, which contradicts the first postulate of the Special Theory of Relativity. The inaccuracy is found unchanged in modern editions in English and Russian, and can become a source of difficulties when teaching the basics of the Special Theory of Relativity based on primary sources, as well as make it difficult to understand the author’s logic when studying independently. Nobel laureate R. Feynman, having expanded and modified A. Einstein's thought experiment, eliminated the inaccuracy described in the article.

The automotive industry has witnessed a significant push towards increased fuel efficiency and reduced carbon emissions. Among many factors influencing overall vehicle efficiency, aerodynamic drag is a critical consideration, accounting for a substantial portion of fuel consumption. Our investigation focused on the drag coefficients of three prominent 2023 passenger car models – the Toyota Corolla, Hyundai Elantra, and Kia Soul. Using ANSYS Fluent to perform computational fluid dynamics, we demonstrated an inverse correlation between drag force and gas mileage, underlining the significance of aerodynamic design in fuel efficiency. Notably, the Hyundai Elantra emerged as the most aerodynamically efficient of the three vehicles, followed closely by the Toyota Corolla. In contrast, the boxier-designed Kia Soul exhibited significantly higher drag coefficients and drag forces, rendering it the least efficient of the trio. These findings emphasize the importance of environmental factors in car design. Shaping aerodynamic profiles directly impacts fuel efficiency, stability, and overall performance.

Background. Chronic kidney disease (CKD) is a progressive condition with limited treatment options that often lead to significant morbidity. Recent studies suggest that oxyhydrogen nanobubbles (HHOnb) may offer therapeutic benefits due to their antioxidative and anti-inflammatory properties. This case series examines the effects of intravenous HHOnb therapy on three patients with varying stages of CKD.Methods. Three patients with CKD underwent a series of ten HHOnb infusions over a period of two to three months. The patients, aged 43 to 70, presented with additional comorbidities including hypertension, diabetes mellitus, and polycystic kidney disease. Clinical parameters, including glomerular filtration rate (GFR), serum creatinine, blood pressure, and uric acid levels, were monitored alongside subjective health improvements.Results. Patient A. A 70-year-old woman with CKD grade 3a experienced a reduction in serum creatinine from 0.98 mg/dL to 0.82 mg/dL and an improvement in GFR from 59 mL/min/1.73 m² to 73.2 mL/min/1.73 m². She reported reduced leg swelling and increased vitality. Patient B. A 52-year-old man with CKD grade 4 and class III obesity showed a decrease in serum creatinine from 3.0 mg/dL to 2.86 mg/dL, an increase in GFR from 23 mL/min/1.73 m² to 24.4 mL/min/1.73 m², and improved sleep quality. Blood pressure reduced from 167/82 mmHg to 145/85 mmHg. Patient C. A 43-year-old man with CKD grade 4 and massive polycystic kidney disease reported reduced fatigue and normalized urination. His serum creatinine decreased from 3.26 mg/dL to 3.09 mg/dL, and his GFR improved from 22 mL/min/1.73 m² to 23.6 mL/min/1.73 m².Conclusion. Intravenous HHOnb therapy demonstrated potential benefits in improving renal function and overall health in CKD patients. These findings suggest that HHOnb could be a promising complementary treatment for CKD, though larger, controlled studies are needed to confirm its efficacy and safety.

In the dynamic landscape of the telecommunications industry, understanding and mitigating customer churn is paramount for maintaining competitive advantage and sustaining revenue streams. This comprehensive literature review delves into the intricacies of customer churn prediction, a crucial aspect in fortifying the bond between telecom businesses and their customers. The review methodically analyzes 11 articles published between 2000 and March 2024, spotlighting the strategic role of Customer Relationship Management and the prevalence of high churn rates that necessitate a shift from customer acquisition to retention strategies. Furthermore, the review navigates through the challenges inherent in churn prediction, including the complexities of managing large, imbalanced, and noisy datasets and the intricacies involved in model selection and optimization. Despite these challenges, the paper highlights the superior capability of machine learning techniques in handling complex datasets to provide accurate predictions, albeit acknowledging their practical complexities. The main aim of the study is to provide an overview, serving as a knowledge base for researchers interested in machine learning techniques within the realm of telecommunications.

The classical propositional calculus (zero-order logic, classical propositional logic), is the most fundamental two-valued logical system. In this paper we present a proof of inconsistency of the classical propositional calculus. Then, we get right away the conclusion that the metatheory of the classical propositional calculus is inconsistent.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

Comprising the largest population cohort on this planet, Gen Z presents a future-oriented consumer segment driven by climate change and food. This study sought to investigate Gen Zs’ perceptions to-ward plant-based foods and diets, and explore the relationship between attitude components, meal preparation involvement, personal and lifestyle factors, and perceived barriers in adopting a plant-based diet with willingness to adopt green-eating practices. Using cross-sectional data from uni-versity students in Greece, India and UK, various tools were employed to determine the factors influ-encing youths’ consumer behavior toward animal-protein substitutes. PCA indicated the underlying dimensions of students’ viewpoints on plant-based foods, whereas hierarchical and k-means clustering provided the cluster structure. An ordered probit model was estimated to delineate Gen Zs’ willingness to adopt plant-based diets and distinguish among mostly unwilling, somewhat willing and mostly willing youths. Our findings identified two consumer segments, namely proponents and opponents toward plant-based foods and diets, with statistically significant differences in the perceived health benefits of plant-based diets, attachment to animal-based proteins, perceived exclusion of ani-mal-based foods, dissatisfaction with plant-based foods attributes and demand for ensuring adequate protein intake. The ordered probit model estimates showed that there is a rather «homogeneity» in the factors influencing youths’ intention to adopt plant-based diets, with attitude components, meal prep-aration indicators, perceived barriers to eating “green” and personal factors, viz. self-assessed knowledge on healthy eating and physical activity, being strongly associated with students’ willingness to switch to plant-based diets in all three countries. Mapping potential obstacles and enablers in terms of shifting to more green-eating behaviors, our findings could add information to better understand the factors affecting food choice and youths’ transition to a more sustainable lifestyle.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

The weakness of the dispersion-managed link combined with optical phase conjugation to compensate for optical signal distortion caused by chromatic dispersion and nonlinear Kerr effect of standard single mode fiber is its limited structural flexibility. We propose dispersion map that can simultaneously compensate for the distorted wavelength division multiplexed signal while increasing the configurational flexibility. Each residual dispersion per span (RDPS) in the former half of the proposed link is randomly determined, and in the latter half, the arrangement order of RDPS is the same as or inverted in the former half. We confirm that the dispersion maps in which the RDPS distribution pattern in the latter half is opposite to the arrangement order in the former half are more effective in compensation, and rather, the compensation effect is better than in the dispersion map of the conventional scheme. The notable result of this paper is that the increase of flexibility can be achieved through random arrangement of RDPS in the former half, and the compensation improvement can be achieved by through inverse arrangement in the latter half which make the distribution profile of each half link roughly symmetric with respect to the midway optical phase conjugator.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

This article discuss the estimation of electrical stresses input that is required to determine lifetime degradation of the HV cables installed within overhead transmission lines (OHTL’s). Abort from lightning effects, these electrical stresses are mainly generated due to repetitive switching operation of the transmission line that produces transient overvoltage (TOV) stress and high frequency stress. The transient overvoltage (TOV) due to switching-off the transmission line at the interface points between the cable and OHTL is estimated using artificial neural network (ANN). PSCAD software is used to build the transmission line model for 749 different case in order to build the required database for ANN training. Two different algorithm input to train ANN with one hidden layer and one output layer using different number of nodes are modeled in MATLAB. The results performance is continuously compared and evaluated till acceptable Regression is achieved to insure the error is less than +/-1.5%. The high frequency due to switching-on the transmission line is also recorded and analyzed. The results show that this new method is efficient, accurate and useful as there is no cable monitoring system is available for each HV cable installed within the transmission line.

A groundbreaking integrated predictive model, termed Cyber Forensics Behavioral Analysis (CFBA), has been developed in an environment characterized by rapidly evolving and increasingly sophisticated cyber threats. This model merges Cyber Behavioral Sciences with Digital Forensics to enhance the prediction accuracy and effectiveness of cyber threats originating from specific Autonomous System Numbers (ASNs). It has been observed that traditional cybersecurity strategies, predominantly focused on technical aspects, must be improved in addressing the complex landscape of cyber threats. Consequently, a novel approach has been proposed in this research, combining technical expertise with insights into the behavior of cybercriminals, thereby addressing a significant gap in existing methodologies. A mixed-methods approach has been employed in the study, integrating quantitative and qualitative research methods. This approach has created a comprehensive framework incorporating digital forensics, cybersecurity, computer science, forensic psychology, and the cyber behavioral sciences which incorporates disciplines scuch as cyberpsychology and forensic cyberpsychology. The study is anchored around four key concepts: (1) Forensic Cyberpsychology, which focuses on understanding psychological aspects of cybercriminal behavior; (2) Digital Forensics, involving the collection and analysis of digital evidence from cyber incidents; (3) Predictive Modeling, which utilizes historical data and patterns to anticipate potential cyber threats; and (4) the Cyber Behavioral Analysis Metric (CBAM) and Cyber Behavioral Score (CBS), tools designed for evaluating and scoring ASNs based on their behavior in terms of cybersecurity threat risks. Challenges encountered in the development of this integration have been significant. Initial setbacks included the misalignment of traditional cyber defense methods with the evolving nature of cyber threats and the absence of a holistic approach in pre-existing models. Through the narrative of these challenges and the subsequent development of the CFBA model, the research highlights the necessity for an interdisciplinary approach to cybersecurity. The outcomes of this study are not merely theoretical but provide practical, actionable tools and frameworks that markedly improve the precision of predicting cyber threats, especially from ASNs. The CFBA model represents a significant shift in cybersecurity strategies, highlighting the importance of integrating behavioral insights with technical knowledge. The study emphasizes the need for ongoing research and collaboration in cybersecurity, advocating for an approach that is as comprehensive and multifaceted as the cyber threats it seeks to mitigate. This research has been conducted to contribute significantly to cybersecurity, offering new perspectives and methodologies in a rapidly changing domain.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

BackgroundThe use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. ObjectivesThis aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of EMA (0.0875 μg/ml) and WHO (0.012 μg/ml) ADI doses of erythromycin proceeded by isolation of S. pneumoniae colonies on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.   Results Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA. Conclusion In our in vivo model, even single dose of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

Recently, Gohar et al. introduced a novel, local, and well-behaved fractional calculus. It possesses all the classical properties, and Its locality imposes simplicity and accuracy in modeling fractional order systems. In this article, we further develop the definitions and extend the classical properties of Gohar fractional calculus to address some of the open problems in Calculus. The fractional Gronwall's integral inequality, Taylor power series expansion, and Laplace transform are defined and applied to overcome some of the limitations in the classical integer-order calculus. The fractional Laplace transform is applied to solve Bernoulli-type logistic and Bertalanffy nonlinear fractional differential equations, and the criteria under which it can be applied to solve linear differential equations are investigated.

Throughout this paper the impact of anxiety on adolescent athlete’s is highlighted through analyzing neurological and psychological aspects involved in sports performance. The neuroanatomy and neuropsychology of the human brain plays a major role in developing athlete’s that has only begun to be analyzed within recent years. Especially in young athletes, there are numerous factors that affect performance on the field that originate from the environment and training the adolescent athlete is involved in. Sports performance is viewed as a major physical factor such as training and lifting weights, however the psychological aspect of sports performance often goes unnoticed. Athletes can begin to develop mental fatigue and anxiety which inevitably can decrease their ability to perform. The athlete’s internal suffering begins to go unnoticed, as the only tangible factor is watching their performance decrease. This causes the athlete to push themselves further in training resulting in greater mental fatigue. This paper emphasizes the numerous factors neurologically that play a role in athletic performance which should be focused on in adolescent athletes as they navigate the challenges and competition that are apparent within athletics. It is critical to understand the processes and hormonal changes the body undergoes with training and playing a sport, this information can change the way adolescent sports are approached and advanced.

Improper lifting measures of long-span spatial steel structures during construction process may delay the construction period and even cause safety accidents. Few studies on long-span spatial steel structures considered time-varying mechanical characteristic during construction process. In order to achieve safe and efficient installation in a long-span spatial steel structure, this research presents a time-varying mechanical analysis of the synchronous and asynchronous integral lifting and a single and interlaced point’s asynchronous integral lifting analysis method of a long-span spatial steel structure. The results showed that in the case of asynchronous lifting of single point, the displacement influence on other members is related to the distance. The closer the distance from the lifting point, the greater the influence. In asynchronous integral lifting, the lifting point with large lifting force is first installed to the specified position, and the lifting point with small lifting force is installed to the specified position.

In our recent publications, based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. In this paper, we make an attempt to understand and estimate the maximum binding energy associated with any mass number. It can be expressed as, for A > 4, $\left(BE\right)_A\cong \left[A-0.000935A^2-A^{1/3}-A^{-1/2}\right]$ MeV. We are working on refining the 4^th term with even-odd corrections, shell corrections and other microscopic corrections. Proceeding further, stable mass numbers and super heavy mass numbers can be understood with a relation of the form, $\left[\textrm{RoundOff}\left(\left(Z+2.9464\right)^{1.2}-1.7165\right)\right]\pm\left[0,1\right]\pm\left(2n\right)$ where $n \cong 0,1,2$. It needs a review with respect to even-odd proton numbers and other microscopic corrections.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

The document sets out three differentiated proposals for the transport of medicines through RPAS with their respective regulations, adapted to different operational categories: open category, special category and military scope. In the open category, an economical and efficient solution is prioritized for urban and rural areas, complying with weight and height regulations, in addition to guaranteeing the stability and quality of medications during transportation. The special category allows more complex operations and in more adverse conditions, such as densely populated areas and long routes, incorporating advanced security measures and training for personnel. In the military field, RPAS are used in conflict zones and hard-to-reach areas, ensuring the safe and rapid delivery of medical supplies under extreme conditions. Success stories in different countries are highlighted, demonstrating significant improvements in delivery times and risk reduction for health personnel.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Epoxy asphalt (EA) concrete is widely used in constructing long-span steel bridge pavements (SBDPs). This study aims to derive a fatigue damage evolution law, conducting an experimental investigation of SBDP. First, a general theoretical form of the fatigue damage evolution law of materials is established based on the thermal motion of atoms. Then, fatigue experiments demonstrate that this evolution law well represents the known damage–life relationships of SBDP. Taking into account the experimental relationships between damage and fatigue life under symmetrical cyclic loadings with different overload amplitudes and temperature variations, a detailed damage evolution law is deduced. Finally, the role of damage accumulation is discussed on the basis of the proposed damage evolution law for the extreme situation of heavy overload and severe environments. The results show that both heavy loading and falling temperatures increase the fatigue damage of SBDP considerably; therefore, SBDP should avoid heavy loading combined with winter temperatures. EA shows a fatigue life two to three times longer than that of modified matrix asphalt (SMA) or guss asphalt (GA). For the same thickness, EA pavement is demonstrated to be more suitable for an anti-fatigue design of large-span SBDP under high traffic flows and low temperatures.

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.

Long-span steel structure trusses are widely used in factory buildings, but with the growth of service time and the increase of dynamic load fatigue, a considerable part of the long-span truss with dynamic load appears serious transverse cracks at the bottom of the middle span and oblique deformation of the abdomen in the operation process. The U-shaped cracks at the bottom and belly, as well as the mid-span down deflection of the main truss, reduced the functional function of the factory building truss structure, and had to limit the original crane load, which affected the normal safety and durability of the structure. Therefore, the application principle of the variable axial force cable system in the long-span factory building truss structure and 3D3S software modeling [1] were used. Analyzing and studying the reinforcement method of large-span powerhouse truss can provide practical experience for subsequent similar projects. In view of the above phenomenon, the large-span powerhouse trusses of Hongcheng Powerhouse 1 and No.2 located in Tonglu, Zhejiang Province are used as the research object, and the variable axial force cable method is proposed to strengthen and lift the load. Considering the span of large-span powerhouse truss, the cable system with 22m controlling force of 400kN is proposed to be selected for powerhouse 1, and the cable system with variable axial force of 24m is proposed to be selected for Powerhouse 2. The force model of large-span truss is established by using the finite element method commonly used to analyze the force of truss. Under two working conditions, The influence of reinforcement effect is analyzed and compared from three aspects: stiffness, bearing capacity and stability. And the phenomenon of uneven stress distribution is analyzed. The stress distribution characteristics of each node are understood by simulating the most disadvantageous node plates with the greatest internal force before and after reinforcement.

This study delves into the intricate interplay between cosmology and gravity in dilaton-based models, enhancing our understanding. Exploring boundary theories coupled to gravity, we derive a four-dimensional effective theory from the cosmological constant. Dilaton gravity is then scrutinized, revealing elegant solutions and insights into brane embedding. The analysis extends to probe scalar fields, employing the WKB approximation in both conformal and non-conformal cases. In summary, this work contributes to a nuanced understanding of the complex relationship between cosmology and gravity in dilaton-based frameworks.

We introduce the linear subgroup of volume-preserving diffeomorphism as the underlying symmetry to construct an action within the effective field theory framework and the Schwinger-Keldish formalism. The formulated action is posited to effectively incorporate dissipative effects into the Navier-Stokes equations.

Immune disorders, characterized by dysregulation at cellular and inflammatory levels, result from a complex interplay of genetics and environmental factors that lead to an abnormal immune response against autoantigens, triggering tissue damage. Recent research highlights reactive antibodies as key players in autoimmune diseases and graft rejection, but the complexity of their determination limits their use in clinic. Hence, we studied the specific binding profile of serological antibodies against a panel of cellular membranes in order to determine whether this antigenic panel could be used to diagnose specific immune disorders in humans. For this purpose, cell membrane microarrays of spleen, liver, and kidney tissues of monkey, rat, and human were developed, and human sera were analyzed, including healthy controls, patients with autoimmune disorders, and kidney transplant patients. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and Human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in the serum of patients as potential biomarkers of immune disorders.

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

MicroRNAs are small non-coding RNAs that are implicated in several physiological processes such as cell development, proliferation, differentiation, apoptosis, immune response and angiogenesis. In the last couple of decades, several studies on miRNA profiling in OSCC have tried to associate miRNAs with clinical characteristics such as relapse, metastasis, and survival, however, the results have been found to vary considerably, sometimes even being contradictory. The main objective of our study was to analyse and verify miRNA expression in oral squamous cell carcinoma in a Spanish population. Second, we attempted to associate the identified deregulated miRNAs with molecular pathways. 8 Oral Squamous Cell Carcinoma patients and 8 healthy control samples were analysed by a microarray Affymetrix® miRNA 4.1 array plate and validated with 8 more cases using RT-qPCR. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways. Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Only miR-497-5p and miR-4417 maintained its deregulated expression after validation with qPCR. Among the molecular pathways in which deregulated miRNAs could be implicated, the most statistically significant pathway was ‘proteoglycans in cancer’. No relationship was found between miR-497-5p or miR-4417 expression and clinical or pathological parameters except of nodular affectation (high miR-4417 expression in patients with nodular affectation, p = 0.035) and radiotherapy (diminished miR-497-5p expression in patients who needed radiotherapy, p = 0.05). We have verified the altered expression of miR-497-5p and miR-4417 in Oral Squamous Cell Carcinoma samples and related the deregulated miRNAs with the ‘proteoglycans in cancer’ pathway.

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blind, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3,100 median cell-culture infectious dose [CCID50] measles, ~4,300 CCID50 rubella); high dose MR-HD-MAPs (~9,300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1,000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8°C for at least 24 months. When MR HD-MAPs stored at 2–8°C for 24 months were transferred to 40°C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates at day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7% respectively for measles and 37.5%, 25.0% and 35.7% respectively for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.

Congenital heart disease (CHD) is the most commonly detected congenital anomaly and affects up to 1 % of all live-born neonates. Current guidelines support the use of Chromosomal Microarray Analysis (CMA) and Next Generation Sequencing (NGS) as diagnostic approaches to identify genetic causes. The aim of our study was to evaluate the diagnostic yield of CMA and NGS in a cohort of neonates with both isolated and syndromic CHD. The present study included 188 infants under 28 days of age with abnormal echocardiography findings hospitalized at the Department of Neonatology, UMC Ljubljana, between January 2014 and December 2023. Phenotypic data were obtained for each infant by retrospective medical chart review. We established the genetic diagnosis of 22 distinct syndromes in 17% of neonates. The most common genetic diagnoses were 22q11.2 microdeletion (22.7%) and CHARGE syndromes (22.7%), Noonan syndrome (9.1%), and Williams syndrome (9.1%). In addition, we detected variants of uncertain significance in 4.8% of neonates. Timely genetic diagnosis is important for the detection of syndrome-related comorbidities, prognosis, reproductive genetic risks and, when appropriate, genetic testing of other family members.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% Whale Oil) were topically applied to the back of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptomic analysis also showed that 20% WO may have lower stress- and inflammation-related responses than 3% MXD. Therefore, whale oil can be expected to be used as a safe hair growth agent.

Drug hypersensitivity reactions (DHR) to platinum-based compounds (PC) are on the rise, and their personalized and safe management is essential to enable first-line treatment of these cancer patients. This study aimed to evaluate the usefulness of basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PC. 24 patients with DHR to PC (20 oxaliplatin and four carboplatin) were evaluated: 13 patients diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients diagnosed as non-allergic with negative STs and DPTs, and five patients classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarrays were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control group were negative for the sIgE- and BAT-microarrays. Our experience indicates that sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PC and may provide an advance in decision-making for drug provocation testing.

Autoantibodies (Abs) to thyroid antigens are associated with autoimmune thyroid disease (AITD), although sometimes they have no clear clinical significance. The aim of this study was to evaluate the avidity of thyroid Abs in the sera of AITD patients and non-AITD Abs carriers. A multiplex microarray-based assay was developed to detect the avidity of thyroid disease-associated Abs, including Abs to thyroperoxidase (TPO), thyroglobulin (Tg), pendrin, thyroid hormones T3 and T4, pyruvate kinase, and carbonic anhydrase 2. The method is based on indirect multiplex assay with an additional step involving the chaotrope destruction of the autoantibody-antigen complexes. The avidity index (AI) is then calculated. The method was tested on clinical cohort (n =117) and then confirmed by studies with another independent cohort (n =123). For the confirmation study, the median AI for AbTg was 29.9% among healthy Abs carriers, 52.6% for AITD patients, and 92.7% for non-AITD type 1 diabetes (T1D) patients. Median AI for AbTPO were 39.9% in healthy carriers, 73.4% in AITD patients, 83.2% in T1D patients, and 98.5% in AITD patients with thyroid neoplasm. The presence of high-avidity AbTg in T1D patients was also confirmed by a modified ELISA. Identification of high-avidity autoantibodies to thyroid proteins in non-thyroid T1D patients requires further studies.

The hexaploid bread wheat Triticum aestivum L. (2n = 6x = 42) and the tetraploid durum wheat Triticum durum (2n = 4x = 28) are two commercially the most important wheat species worldwide. These two species are components of the same gene pool, which evolved under different conditions, which made it possible to acquire different adaptations to a wider range of environmental conditions. Identification and characterization of introgressed fragments of one species in the genome of another can help in the search for new loci responsible for economically valuable traits. SNP microarrays provide information on the genotypes of thousands of positions throughout the genome. This information can be used to obtain the distribution of alleles of one species in the genome of another and to determine the location of introgressed fragments. In our work, we used genotyping data from the SNP microarray to identify durum wheat chromosome fragments containing bread wheat alleles in the offspring from crossing bread and durum wheat. We have studied the distribution of the genetic material of bread wheat in 15 combinations from crosses of bread and durum wheat. Introgressed fragments of bread wheat into the durum wheat genome were identified on chromosomes 1A, 1B, 4A, 5B, 6B, and 7A. The introgressed fragments showed polymorphism in different breeding lines. A functional enrichment analysis of genes in the introgression fragments was performed, which showed the presence of statistically significant enrichment of genes responsible for various molecular functions, biological processes and cellular components. The obtained data can be used to identify new QTL of economically valuable traits for obtaining durum wheat varieties with improved agronomic traits.

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT responsible for protection remains to be clarified. Here, we have mapped the B-cell linear epitopes of the three chains of the CT protein (CTP) prepared by Spot synthesis. The immunoreactivity of sera from mice immunized with an oral, inactivated vaccine (Schankol†™) was measured against membrane-bound peptides for mapping. Results: Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three epitopes, TQTGFVRHDDGYVST (aa 66-77, Vc/TxA-3), KNGAIFQVE VPGSQN (aa 64-78, Vc/TxB-11), and LNDEHK (aa 90-95, Vc/TxP-16), were chosen to synthesize a multiple antigen peptide that was used to coat ELISA plates to screen immunized mouse sera as a test for an in vitro diagnostics for cholera. Conclusion: Vaccination with inactive CT-generated antibodies against multiple linear epitopes and the selected epitopes can be used to construct immunological reagents for rapid serological diagnosis of cholera with high sensitivity and specificity.

Many fundamental molecular techniques (PCR, Microarray, Southern and northern hybridization, siRNA, CRISPR/Cas9 etc.) developed so far shows errors. I wish to highlight these molecular techniques are developed on basis of Watson-Crick DNA model, ignoring the concept of parallel stranded DNA. Through this opinion article, I wish to highlight specificity and accuracy of these molecular techniques can be enhanced by considering both parallel and anti parallel hybridization of DNA. Hopefully my views will also solve issue of irreproducibility in life science research.

Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on the tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer, and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be up-regulated in multiple cancer types. In this study, EphaA2 and EphB4 are evaluated as target for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be an especially promising candidate for IGOS of colorectal cancer.

Molecular mechanisms associated with the pathogenesis of Vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle and pigs. To gain more insight on the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory and immunosuppressive genes. Overall, the interferon (IFN) response appeared suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFNb. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrants further investigation

Background: transcriptome data provide a valuable resource for the study of cancer molecular mechanisms, but technical biases, samples’ heterogeneity and small sample sizes result in poorly reproducible lists of regulated genes. Additionally, the presence of multiple cellular components contributing to cancer development complicate the interpretation of bulk transcriptomic profiles. Methods: we collected 48 microarray datasets of laser capture microdissected breast tumors, and performed a meta-analysis to identify robust lists of genes differentially expressed in these tumors. We created a database with carefully harmonized metadata to be used as a resource for the research community. Results: combining the results of multiple datasets improved the statistical power, and the analysis of stroma and epithelium separately allows identifying genes with different contribution in each compartment. Conclusions: our database can profitably help biomarkers’ discovery and is readily accessible through a user-friendly web interface (https://aurorasavino.shinyapps.io/metalcm/).

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

Long-acting (LA) drug-delivery system (DDS) successes are linked to their abilities to harness biocompatible polymers and materials for sustained and predictable release of therapeutic agents over an extended period of time. For human immune deficiency virus type one (HIV-1) infections, LA DDSs hold great promise in closing the gaps of daily oral therapy for treatment and prevention. Examples are Cabenuva, Apretude and Sunlenca, which have been shown to be safe and effective. Alternative promising drug delivery technologies such as implants, prodrugs, vaginal rings, and microarray patches are being explored to further meet patients’ needs. We posit that improved physicochemical properties of the formulation payloads and material chemistry design with optimal drug release kinetics holds the potential to optimize release profiles. Furthermore, for the treatment and prevention of HIV-1 infection, the landscape of LA medicines now in clinical or preclinical development offers hope that the strategic design of polymers will further improve upon controlled delivery of drugs to simplify dosing schedules.

Autoantibodies against type 1 interferons (IFN-I) are highly specific marker for type 1 autoimmune polyglandular syndrome (APS-1). Moreover, determination of antibodies to IFN-ω and IFN-α2 allows a short-term diagnosis in patients with isolated and atypical forms of APS-1. In this study, a comparison of three different methods, namely, multiplex microarray-based, cell-based and enzyme-linked immunosorbent assays for detection of antibodies against omega-interferon and alpha2-interferon was carried out. A total of 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies, non-autoimmune endocrine disorders and healthy individuals were analyzed. In the APS-1 patient cohort (n=18), there was good agreement between the results of anti- IFN-I antibody tests performed by three methods, with 100% specificity and sensitivity for microarray-based assay. Although only the cell-based assay can determine the neutralizing activity of autoantibodies, the microarray-based assay can serve as a highly specific and sensitive screening test to identify anti- IFN-I antibody positive patients.

Trio-based exome sequencing and high-resolution HLA typing were employed to analyze three patients with autoimmune adrenal insufficiency (AAI), including those with autoimmune polyglandular syndrome (APS) type 2, as well as their parents. Benign or likely benign variants of the AIRE gene were identified in all participants of the study. These variants, coupled with clinical data and the results of antibody studies to type I interferons, helped to exclude APS-1. Patients with APS-2, in contrast to patient with AAI, inherited distinct variants of unknown significance in the CLEC16A gene, which is associated with autoimmune diseases including AAI. Various risk alleles in other genes associated with autoimmunity were identified in all patients. HLA typing of second class loci revealed alleles related to APS types 2, 3, and 4. Nevertheless, the frequencies of the haplotypes identified are substantial in the healthy Russian population, precluding from regarding these alleles as genetic determinants linked to APS development. Immunological examination can detect antibody carriers and predict the risk of autoimmune disease development. In the future, to identify genetic predictors of autoimmune endocrinopathies, it is recommended to analyze the whole genome of patients and their relatives, examining clinically relevant variants in non-coding regions.

Diabetes mellitus is a chronic disease that affects millions of people worldwide. Article focuses on detecting the presence of diabetes in patients using microarray gene data obtained from the pancreas. Handle the high-dimensional nature of the data, four different dimensionality reduction techniques, namely Bessel Function, Discrete Cosine Transform (DCT), Least Square Linear Regression (LSLR), and Artificial Algae Algorithm (AAA) are used. After reduced the data, Meta-heuristic algorithms are applied like Dragonfly Optimization Algorithm (DOA) and Elephant Herding Optimization Algorithm (EHO) for feature selection. Ten classification techniques are using to classify the data in both the format like without feature selection method and with feature selection method. The classification techniques are Non-Linear Regression (NLR), Linear Regression (LR), Gaussian Mixture Model (GMM), Expectation Maximum (EM), Bayesian Linear Discriminant Classifier (BLDC), Logistic Regression (LoR), Softmax Discriminant Classifier (SDC), Support Vector Machine (SVM) with linear kernel, Support Vector Machine (SVM) with polynomial kernel, and Support Vector Machine (SVM) with Radial Basis Function (RBF) kernel. Results showed that the AAA with SVM(RBF) achieved an accuracy of 90% without feature selection. However, when feature selection was applied, with EHO of AAA with SVM(RBF) exhibited the highest accuracy of 95.714%, followed closely by with DOA of AAA with SVM (RBF) at 94.28%.

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.

Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM’s concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.

Thousands of antibodies for diagnostic and other analytical purposes are on the market. However, it is often difficult to identify duplicates, reagent changes, and to assign the correct original publications to an antibody. This slows down scientific progress and might even be a cause of irreproducible research and a waste of resources. Recently, activities were started to suggest the sole use of recombinant antibodies in combination with the open communication of their sequence. In this case, such uncertainties should be eliminated. Unfortunately, this approach seems to be rather a long-term vision since the development and manufacturing of recombinant antibodies remain quite expensive in the foreseeable future. Also, nearly all commercial antibody suppliers may be reluctant to publish the sequence of their antibodies, since they fear counterfeiting. De-novo sequencing of antibodies is also not feasible today for a reagent user without access to the hybridoma clone. Nevertheless, it seems to be crucial for any scientist to have the opportunity to identify an antibody undoubtedly to guarantee the traceability of any research activity using antibodies from a third party as a tool. For this purpose, we developed a method for the identification of antibodies based on a MALDI-TOF-MS fingerprint. To circumvent lengthy denaturation, reduction, alkylation, and enzymatic digestion steps, the fragmentation was performed with a simple formic acid hydrolysis step. Eighty-nine unknown monoclonal antibodies were used for this study to examine the feasibility of this approach. Although the molecular assignment of peaks was rarely possible, antibodies could be easily recognized in a blinded test, simply from their mass-spectral fingerprint. A general protocol is given, which could be used without any optimization to generate fingerprints for a database. We want to propose that in most scientific projects relying critically on antibody reagents, such a fingerprint should be established to prove and document the identity of the used antibodies and to assign a specific reagent to a datasheet of a commercial supplier, a public database record or an antibody ID.

The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence a risky venture. We think that it is crucial to improve the screening process to eliminate most of the immanent deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and simultaneous performance of competition experiments. The latter can directly be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones and blank supernatant has been designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the IgG concentration, which is unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration is not possible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media had been used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system, we conclude that this approach should be preferable to most other protocols leading to many of false positives, causing expensive and lengthy confirmation steps to weed out the poor clones.

Microarray gene expression-based detection and classification of medical conditions have been prominent in research studies over the past few decades. However, extracting relevant data from the high-volume microarray gene expression with inherent nonlinearity and inseparable noise components raises significant challenges during data classification and disease detection. So, this paper proposes a two-level strategy involving feature extraction and selection methods before the classification step. The feature extraction step utilizes Short Term Fourier Transform (STFT), and the feature selection step employs Particle Swarm Optimization (PSO) and Harmonic Search (HS) metaheuristic methods. The classifiers employed are Non-Linear Regression, Gaussian Mixture Model, Softmax Discriminant, Naive Bayes, SVM (Linear), SVM (Polynomial), and SVM (RBF). The two-level extracted relevant features are compared with raw data classification results, including Convolutional Neural Network (CNN) Methodology. Among the methods, STFT with PSO feature selection and SVM (RBF) classifier produced the highest accuracy of 94.47%.

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.