The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, the study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it’s the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease.

G4v is a four-vector theory of gravitation proposed by Mead (2015, 2023a,b) which reinterprets several major results commonly celebrated for the tensor-based approach of General Relativity (GR). Here, we show that G4v obeys the correspondence principle, an important test of any relativistic theory. We derive the non-relativistic Lagrangian and Energy expressions at the limit of low speeds and potentials, complete with the correct terms for potential energy (something traditional Special Relativity is incapable of achieving). G4v could represent a new interpretation of the gravitational field with essentially the same mathematics as electromagnetism (Mead 2023a). It is also possible to interpret G4v as a very interesting (and useful) approximation of the Einstein field equations (Mead 2023b).

In this paper, COMSOL Multiphysics software was used to simulate and analyze the process of cleaning oily sludge by high-speed stirring rotor. The physical phenomena such as velocity field, pressure field, heat dissipation and cavitation generated by the rotor during the process of the oily sludge cleaning were analyzed. The results showed that in the process of cleaning the oily sludge by high-speed stirring rotor, the shear force, heat dissipation and pressure increased with the enhance in the rotor speed. Cavitation occurs in the impeller area of the rotor because of the change of pressure, so the cavitation bubbles were formed. Shear force, heat dissipation and cavitation contributed to the separation of oil phase in oily sludge. Meanwhile, the simulation results were verified by experiments.

In any region of a space, the gravitational field cannot be eliminated. The speed of light in a vacuum has never been observed and cannot be observed with current technology. Till now, only the speed of light in a gravitational field has been observed. It results in that all the observed speed of light are always being varied by the gravity. Here, it is presented that light could be dispersion in a gravitational field analogous to the dispersion of light in the Newtonian prism experiment. The relativistic mass density on the surface of a neutron star is on the level of 10¹⁷kg/m³ while on the surface of the Earth is only 10^-7kg/m³, the effect of the gravitational field acting on the speed of light by a neutron star is much larger than that by the Earth. Therefore, the dispersion of light in strong gravitational field could be generally observed from the image of a star and it should have been observed through the double-image gravitational lensing and the spectroscopic binary system. And, it should affect the observed numbers, spectrogram, size and distance of the celestial objects.

Trypanosomes are the extracellular protozoan parasites that cause human African trypanosomiasis disease in humans and nagana disease in animals. The disease is endemic in African countries where tsetse flies which act as a vector for the transmission of disease are present. The animals infected by these parasites become useless or workless and disease can become fatal if not treated. Old drugs used for treatment have many side effects and some are responsible for death in 5% of the patients. The parasite possesses a major surface protein known as variant surface glycoprotein. The immune system of the host develops antibodies against this antigen but due to antigenic variation, parasites evade the immune response. Currently, no vaccine is available that provides complete protection. Only partial protection using certain antigens in murine models was investigated. The tools of molecular biology and immunology have enabled a novel approach to the development of vaccines against trypanosomes. Immunization is the sole method for the control of disease because the eradication of the vector from endemic areas is an impossible task. Genetic vaccines can carry multiple genes encoding different antigens of the same parasite or different parasites. DNA immunization induces the activation of both cellular immune response and humoral immune response along with the generation of memory. This review highlights the importance of DNA vaccines and advances in the development of DNA vaccines against T. brucei.

The visual span refers to the number of letters readers can identify in a single fixation without using linguistic skills. Proponents of the visual span hypothesis postulate an influence of early visual processing on reading speed. Given the slowness of reading Arabic texts, the present work aims to study the development of the visual span and its effects on reading speed in the Arabic-speaking context. Thirty-four subjects participated in the study. The trigram task and the rapid serial visual presentation (RSVP) paradigm were used to estimate visual span size and reading speed. In line with our initial assumptions, the results showed a significant effect of grade level on reading speed (F(2,31) = 30.93, p<0.001), visual span size (F(2,31) = 20.57, p<0.001). In good alignment with previous work, our results show that visual span size could explain around 40% of the reading speed variability. Interestingly, our analyses revealed a narrowing of visual span size in our Arabic sample. The results of study 2, suggest that the poor performance in the trigram task is due to poor visual attention capacities in our Arabic readers

We appeal the science community to review the basic definition of wavelength dependent cosmic red shift. We would like to emphasize the point that, the true cosmic red shift must be defined as the ratio of loss in energy of photon to the energy of photon at galaxy. In terms of wavelength, photon red shift must be defined as the ratio of change in wavelength to the observed wavelength of photon. Considering the recent paper pertaining to cosmic halt authored by Cosmin Andrei, Anna Ijjas, and Paul J. Steinhardt and reviewed by Saul Perlmutter, in this paper we propose a very simple model of the universe having early stage light radius of proton seems to be equal to half the product of reduced Planck’s constant and current speed expansion and current stage quantum halt accompanied by continuous light speed rotation. In this context, representing early cosmic expansion and rotation as an outward spiral, it seems possible to consider Hubble’s law as a representation of current cosmic light speed rotation having no further expansion. To understand the current cosmic halt, we are proposing very simple and very strange atomic and nuclear relations that constitute Hubble parameter and gravitational constant. Qualitatively and quantitatively, gravitational potential energy of proton and electron separated by a distance of root mean square radius of proton. Based on uncertainty condition, it needs further study, observations and analysis. We have extended our analysis towards the microscopic coupling constants. Thus, instead of considering the cosmological variable nature of elementary physical constants, we consider the case of current or nearby cosmic halt by means of considering the equality of current cosmic variable physical constants having similar dimensions of fixed elementary physical constants and their combinations. In this connection, it is very interesting to note that, our estimated cosmic age of (2/H0) is matching with recent estimates proposed by Rajendra P Gupta and published in MNRAS.

The high-speed railway operation environment monitoring network system has a wide variety of sensors and inconsistent business requirements, which have certain requirements for data transmission delay and network life. Most of the previous research focuses only on prolonging network lifetime or reducing data transmission delays when designing or optimizing routing protocols, without co-designing the two. In addition, due to the harsh operating environment of high-speed railways, when the network changes dynamically, the traditional routing algorithm will generate unnecessary redesigns and lead to high overhead. Based on the actual needs of high-speed railway operation environment monitoring, this paper proposes a novel Double Q-values adaptive model combined with the existing reinforcement learning method, which considers the energy balance of the network and real-time data transmission, and constructs energy saving and delay. The two-dimensional reward avoids the extra overhead of maintaining a global routing table while capturing network dynamics. In addition, the adaptive weight coefficient is used to ensure the adaptability of the model to each business of the high-speed railway operation environment monitoring system. Finally, simulations and performance evaluations are carried out and compared with previous studies.Finally, simulations and performance evaluations are carried out and compared with previous studies. The results show that the proposed routing algorithm successfully extends the network’s life cycle and gets good real-time data performance. It also saves energy and has fewer delays than the other three routing protocols in different situations.

The wind observations for multiple levels (40–200 m) have been conducted for a long time (2016–2020) on Jeju Island of South Korea. This study aims at understanding the vertical and temporal characteristics of lower atmosphere. Jeju Island is a region located at mid-latitude and is affected by seasonal monsoon wind. The maximum wind speed appears in the lower layer during day time and is delayed in the upper layer during latter time in diurnal cycle. In summer season, the surface layer increases up to 160 m during day time via dominant solar radiation effect, which is higher than those for other seasons. However, the maximum wind speed in winter season appears irregularly among altitudes, and the surface layer is ~100 m, which is lower than that in summer season. It can be attributed to the increase in the mean wind speed in diurnal cycle caused by the strong northwestern wind for winter season. These results imply that the relationship between near-surface and higher altitudes is primarily affected by solar radiation and seasonal monsoon winds. These results are expected to contribute to site selection criteria for wind farms and to the assessment concerning planetary boundary layer modeling.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

Proliferating cell nuclear antigen (PCNA) is the key regulator of human DNA metabolism. One important interaction partner is p15, involved in DNA replication and repair. Targeting the PCNA-p15 interaction is a promising therapeutic strategy against cancer. Here, a Förster resonance energy transfer (FRET)-based assay for the analysis of PCNA-p15 interaction was developed. Next to the application as screening tool for the identification and characterization of PCNA-p15 interaction inhibitors, the assay is also suitable for the investigation of mutation-induced changes in their affinity. This is particularly useful for analysing disease associated PCNA or p15 variants at the molecular level. Recently, the PCNA variant C148S has been associated with Ataxia-telangiectasia-like disorder type 2 (ATLD2). ATLD2 is a neurodegenerative disease based on defects in DNA repair due to an impaired PCNA. Incubation time dependent FRET measurements indicated no effect on PCNAC148S-p15 affinity, but on PCNA stability. The impaired stability and increased aggregation behaviour of PCNAC148S was confirmed by intrinsic tryptophan fluorescence, DSF and AF4 measurements. The analysis of the disease associated PCNA variant demonstrated the versatility of the interaction assay as developed.

The quantile estimation of extreme wind speed is needed in various environmental fields such as climatology, design of structures, renewable energy sources and agricultural operations. These calculations are crucial for the coding of wind speed. In this study, the required wind speed series of 16 stations in Khyber Pakhtunkhwa, Pakistan, was obtained from the NASA official website and measured in meters per second (m/s) at a 10-meter distance. A Regional Frequency Analysis of 16 AMWS stations was performed using L-moments. The quantile estimates of extreme wind speed are needed for various areas of interest using Regional Frequency Analysis (RFA) and extreme value theory. These calculations are crucial for the coding of wind speed. The data was taken from the NASA official website at a 10-meter distance and measured in meter per second (m/s). A Regional Frequency Analysis of AMWS using L-moments is performed utilizing wind speed data from sixteen sites (16) in Pakistan's Khyber Pakhtunkhwa province. There are no sites that are found to be discordant. The wards method is used to construct a homogenous region and make two homogenous regions from 16 sites. The heterogeneity test justifies that both clusters are homogeneous. The most appropriate probability distribution from the Generalized Normal (GNO), Generalized Logistic (GLO), Pearson Type-3 (P3), Generalized Pareto (GPA), and Generalized Extreme Value (GEV) distributions are chosen to calculate regional quantiles. According to the L-moments diagram and Z statistics, GEV for Cluster- Ι and GLO for Cluster- ΙΙ are the best suggestions from the others. Both clusters’ robustness is measured utilizing Relative Bias (RB) and Relative Root Mean Square Error (RRMSE). Overall, GEV distribution is fit for cluster-Ι, and the GLO distribution is fit for cluster-ΙΙ. Utilizing the site mean and median as index parameters, we can also find at-site quantiles from regional quantiles. The study’s quantile estimates can be employed in codified structural designs with policy consequences.

The transportation sector is seeing an increased adoption rate of electric vehicles (EV), which comprise battery electric vehicles (BEV), hybrid electric vehicles (HEV) and plug-in hybrid electric vehicles (PHEV). This mode of transportation is likely to displace automobiles powered by internal combustion engines (ICE) in the nearest future, as indicated by the current trend. Each of the key EC components is home to a variety of technologies that are either currently in use or will be in the near future. Electric vehicles have the potential to have a significant impact on a variety of fields, including the economy, the energy infrastructure, and the natural environment. As a result of the production of carbon dioxide gas from the combustion of fossil fuels, transportation is the sector that is responsible for the second-highest amount of greenhouse gas emissions. Electric vehicles, often known as EVs, are getting a lot of attention as a potentially game-changing solution to this issue. It is possible for electric vehicles to produce fewer emissions of carbon dioxide (CO2) than conventional automobiles due to the fact that an electric motor serves as the vehicle's propeller rather than an internal combustion engine. EVs have the potential to become zero-emission vehicles if they are paired with renewable energy sources. This document presents an overview of the numerous types of EV drive circuits, covering their design as well as the benefits and drawbacks associated with each type. The current state of battery technology, particularly that pertaining to the batteries utilized in electronic vehicles, is discussed in this paper. This article also discusses electric motor efficiency, power density, fault tolerance, dependability, cost, and the best electric motor for EVs. Then, a thorough study of future EV implementation's obstacles and prospects is done. Charging times and battery performance are examples of technological challenges, but government regulation of EVs continues to be a substantial non-technical hurdle.

Due to the special terrain of Urumqi (in the valley area), which often triggers strong foehn weather, and causes huge losses to local people's lives and social economy. This study uses in-situ surface meteorological variables (including the hourly temperature, pressure, humidity, wind, etc.) from the Urumqi Meteorological Station (downstream station, DS) and the Dabancheng Meteorological Station (upstream station, US) in the Middle Tianshan Valley and NCEP/NCAR reanalysis data from 2008 to 2022. A dataset of the foehn weather process at DS in the past 15 years is established and the variation patterns of each meteorological variable during the process of foehn is analyzed. Based on the physical mechanism of the occurrence of foehn, a three-element identification standard for foehn in Urumqi is established by comparing and analyzing the variation of wind direction (WD), wind speed (WS), and the difference of potential temperature (Δθ) between DS and US during the period of foehn and non-foehn from 2013 to 2022, namely: 94°≤ 2-minute average WD ≤168°, 2-minute average WS ≥2.0 m/s, and Δθ between DS and US ≥ 0.29 K. According to the test and evaluation, the three-element identification standard has an accuracy of 82.96%, and a hit rate of 89.50% for the occurrence of foehn in Urumqi from 2008 to 2012. Moreover, the hit rate of foehn identification is 100% for strong wind or above (i.e., 2-minute average WS ≥10.8 m/s) WS. In addition, combined with two predictors of sea-level pressure difference (ΔP) and Δθ between DS and US, forecasting foehn can be more accurately predicted than a single forecasting factor. When ΔP ≤ -12 hPa and Δθ≥5 K, the probability of the occurrence of foehn is more than 90%. This study provides certain reference and application value for the weather forecasting operation of foehn.

Aiming at the prediction of environmental vibrations induced by elevated high-speed railway, a machine-learning method is developed by combining random forest algorithm and Bayesian optimization, which using the dataset from on-site experiments . When it comes to achieving a rapid and effective prediction of environmental vibration, there is few research on com-parisons and verifications of different algorithms, and neither on parameter tuning and optimi-zation of machine learning algorithms. In this paper, a field experiment is firstly carried out to measure the ground vibrations caused by high-speed trains running on bridge, and then the en-vironmental vibration characteristics are analyzed in view of ground accelerations and weighted vibration levels. Subsequently, three machine-learning algorithms of linear regression, support vector machine and random forest are developed by using experimental database, and their prediction performance are discussed. Finally, two optimization models for the hyperparameter set of random forest algorithm are further compared. It turns out that the integrated random forest algorithm has higher accuracy in predicting environmental vibration than linear regression and support vector machine; the Bayesian optimization has excellent performance and high efficiency in achieving efficient and in-depth optimization of parameters, and can be combined with the RF machine learning algorithm to effectively predict the environmental vibrations induced by the high-speed railway.

Outbreaks of Anticarsia gemmatalis (Hübner, 1818) (Lepidoptera: Erebidae), a major pest of soybean, can be controlled below economic thresholds with methods that do not involve the application of synthetic insecticides. Formulations based on natural isolates of the Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) (Baculoviridae: Alphabaculovirus), played a significant role in integrated pest management programs in the early 2000s, but a new generation of chemical insecticides and transgenic soybean, have displaced AgMNPV-based products over the past decade. However, the marked genotypic variability present among and within alphabaculovirus isolates suggests that highly insecticidal genotypic variants can be isolated and used to reduce virus production costs or overcome isolate-dependent host resistance. This study aimed to select novel variants of AgMNPV with suitable insecticidal traits that could comple-ment the existing AgMNPV active ingredients. Three distinct AgMNPV isolates were compared by restriction endonuclease profile and in terms of their occlusion body (OB) pathogenicity. One isolate was selected (AgABB51) from which eighteen genotypic variants were plaque purified and characterized in terms of their insecticidal properties. The five most pathogenic variants varied in OB pathogenicity although none of them was faster-killing or had higher OB production characteristics than the wild-type isolate. We conclude that the AgABB51 wild-type isolates ap-pear to be genotypically structured for fast speed-of-kill and high OB production, both of which would favor transmission. Interactions among the component variants are likely to influence this insecticidal phenotype.

This article addresses the problem of contact voltage increase caused by the low frequency oscillation of the train-grid system in the phase-separation process of the EMU. The article establishes the EMU-contact line-traction substation model, reveals the mechanism of low-frequency oscillation, and obtains the relationship between the separation phase angle of the pantograph with line and low-frequency oscillations. Methods to suppress the over-voltage during the low-frequency oscillation are proposed. The study shows that when the power phase angle of the pantograph-line separation is within the range of 60°~90° and 240°~270°, the voltage amplitude in the neutral zone is larger, the maximum amplitude can reach 52.2kV, and low-frequency oscillation will occur in the neutral zone. When low frequency oscillation occurs, the contact line voltage in the neutral zone is mainly 1/3 power frequency (16.7Hz). After installing an RC suppression device in the neutral zone, when the EMU enters the neutral zone, the absolute value of the voltage peak drops to below 20 kV. Compared with the situation where the suppression device is not connected, the absolute value of the voltage peak is reduced by nearly 60%. The study provides a basis for the design of the neutral zone of the contact line and the selection of the high-voltage equipment of the EMU.

Most of the fishing currently practiced in Japan is done by small vessels with a small number of fishermen (one or two). One of the most common fishing methods is longline fishing. However, this method requires the vessel to operate at a constant low speed because the depth of the hook must be kept constant while adjusting the speed of the fishing boat to the tidal current. In addition, because the vessel must maneuver and fish at the same time, automation is desired. Thus, we propose a robotic system that can control the depth of the trap at a constant depth even when the speed of the vessel and the current change, and that can successfully fish without the need for skilled fishermen. Fishing can be conducted regardless of the speed of the vessel, whereas currently it is controlled by the speed of the vessel and the tidal current. Therefore, it may contribute to proposing new fishing methods as well as the existing ones. This can contribute to the shortage of successors to the fishing industry and to the revitalization of the fishing industry.

Development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods are either methods with adjustable parameters or machine learning algorithms, both requiring a database of experimentally measured folding and binding free energy changes. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residue on the above-mentioned thermodynamics characteristics, i.e., the mutations are not introduced at random and do not necessarily represent mutations originating from single nucleotide variant (SNV). Thus, the reported performance of the leading algorithms assessed on these databases or other limited cases, may not be applicable for predicting the effect of SNVs seen in the human population. Indeed, we demonstrate that the SNVs and non-SNVs are not equally presented in the corresponding databases and the distribution of the free energy changes are not the same. Furthermore, the Pearson correlation coefficients (PCCs) obtained on cases involving SNVs are less impressive than for non-SNVs, indicating that caution should be used in applying them to reveal the effect of human SNVs. All methods are found to underestimate the energy changes by roughly a factor of 2.

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

This study aims at better understanding the damage and fracture kinetics in flax fibres elements at both the unitary and bundle scales using an experimental setup allowing optical observation at high recording rate in the course of tensile loading. Defects issues from flax unitary fibre extraction are quantitated using polarized light microscopy. Tensile loading is conducted according to a particular setup adapted to fibres of 10 to 20 µm in diameter and 10 mm in length. Optical recording using high speed camera is performed during loading up to the failure at acquisition speed ranging from 108,000 to 270,000 frames per second. Crack initiation in polymer layers of fibre elements, propagation as well as damage mechanisms are captured. The results show different failure scenarios depending on the fibre element nature. In particular, fractured fibres underline either a fully transverse failure propagation or a combination of transverse and longitudinal cracking with different balances. Image recordings with high time resolution down to 3.7 μs suggest unstable system and transverse crack speed higher than 4 m/s and a slower propagation for longitudinal crack deviation.

In today's human society, diesel generators (DGs) are highly applied into the human energy and electricity supply system due to its technical, operational and economic advantages. This paper proposes an intelligent nonlinear $H_2/H_{\infty}$ robust controller based on the chaos particle swarm gravity search optimization algorithm (CPSOGSA), which controls the speed and excitation of a DG. In this method, firstly, establish the nonlinear mathematical model of the DG and then design the nonlinear $H_2/H_{\infty}$ robust controller based on this. The direct feedback linearization and the $H_2/H_{\infty}$ robust control theory are combined and applied. Based on the design of the integrated controller for DG speed and excitation, the system's performance requirements are transformed into a standard robust $H_2/H_{\infty}$ control problem. The parameters of the proposed solution controller are optimized by using the proposed CPSOGSA. The introduction of CPSOGSA completes the design of an intelligent nonlinear $H_2/H_{\infty}$ robust controller for DG. The simulation is implemented in MATLAB/Simulink, and the results are compared with the PID control method. The obtained results prove that the proposed method can effectively improve the dynamic accuracy of the system and the ability to suppress disturbances and improve the stability of the system.

The theory of special relativity has reexamined and reconstructed the concepts of space and time, which are indispensable for describing physical laws, consequently instigating a major revolution in physics in general. Although the correctness of the special theory of relativity has been con-firmed by many observations and experiments, it is unclear why the "principle of relativity" and the "principle of the constant speed of light," which form the basis of the idea, are valid. Moreo-ver, although special relativity has advanced our understanding of time, our understanding of the fundamental question, "What is time?" is still limited. The theory of special relativity regards space as a four-dimensional construct consisting of one-dimensional time and three-dimensional space. This paper proposes an alternative framework, wherein real space is uniform and isotropic four-dimensional space, and elementary particles are waves that propagate through this four-dimensional space at a constant speed. This new perspective provides evidence to support two of Einstein’s key principles—the "principle of relativity" and the "principle of the constant speed of light." Furthermore, this model clarifies what time is and why time flows at a constant rate from the past to the future.

We derive a quantum speed limit for unitary evolution for the case of mixed quantum states using the stronger uncertainty relation for mixed quantum states. This bound can be optimized over different choices of Hermitian operators for a better bound. We illustrate this with some examples and show its better performance with respect to three existing bounds for mixed quantum states.

The emergence of the SARS-CoV-2 Variant of Concern (VOC) Omicron has been characterized by an explosive number of cases in almost every part of the world. The dissemination of different sub-lineages and recombinant genomes also led to several posterior waves in many countries. The circulation of this VOC and its major sub-lineages (BA.1 to BA.5) was monitored in community cases and in international travelers returning to Venezuela, by a rapid partial sequencing method. The specific sub-lineage assignment was performed by complete genome sequencing. Epidemic waves of SARS-CoV-2 cases were observed among international travelers during 2022, a situation not seen before December 2021. The succession of the Omicron VOC sub-lineages BA.1 to BA.5 occurred sequentially, except for BA.3, which was almost not detected. However, the sub-lineages generally circulated two months earlier in international travelers than in community cases. The diversity of Omicron sub-lineages found in international travelers was related to the one found in the USA, consistent with the most frequent destination of international travel from Venezuela this year. These differences are compatible with the delay observed in Latin American countries in the circulation of the different lineages of the Omicron VOC.

In this work, we introduce a scalable and efficient GPU-accelerated methodology for volumetric particle advection and finite-time Lyapunov exponent (FTLE) calculation, focusing on the analysis of Lagrangian Coherent Structures (LCS) in large-scale Direct Numerical Simulation (DNS) datasets across incompressible, supersonic, and hypersonic flow regimes. LCS play a significant role in turbulent boundary layer analysis, and our proposed methodology offers valuable insights into their behavior in various flow conditions. Our novel owning-cell locator method enables efficient, constant-time cell search, and the algorithm draws inspiration from classical search algorithms and modern multi-level approaches in numerical linear algebra. The proposed method is implemented for both multi-core CPUs and Nvidia GPUs, demonstrating strong scaling up to 32,768 CPU cores and up to 62 Nvidia V100 GPUs. By decoupling particle advection from other problems, we achieve modularity and extensibility, resulting in consistent parallel efficiency across different architectures. Our methodology was applied to calculate and visualize the FTLE on four turbulent boundary layers at different Reynolds and Mach numbers, revealing that coherent structures grow more isotropic proportional to the Mach number, and their inclination angle varies along the streamwise direction. We also observed increased anisotropy and FTLE organization at lower Reynolds numbers, with structures retaining coherency along both spanwise and streamwise directions. Additionally, we demonstrated the impact of lower temporal frequency sampling by upscaling with an efficient linear upsampler, preserving general trends with only 10% of the required storage. In summary, we present a particle search scheme for particle advection workloads in the context of visualizing LCS via FTLE that exhibits strong scaling performance and efficiency at scale. Our proposed algorithm is applicable across various domains requiring efficient search algorithms in large structured domains. While this manuscript focuses on the methodology and its application to LCS, an in-depth study of the physics and compressibility effects in LCS candidates will be explored in a future publication.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC with peritoneal metastasis exhibits a poor prognosis due to the lack of diagnostic biomarkers and effective therapy. A comprehensive analysis of malignant ascites identified the genomic alterations and significant amplifications of cancer driver genes, including CD44. CD44 and its splicing variants are overexpressed in tumors, and play crucial roles in the acquisition of invasiveness, stemness, and resistance to treatments. Therefore, the development of CD44-targeting monoclonal antibodies (mAbs) is important for GC diagnosis and therapy. In this study, we immunized mice with CD44v3–10-overexpressed PANC-1 cells and established several dozens of clones that produce anti-CD44v3–10 mAbs. One of the clones (C44Mab-94; IgG1, kappa) recognized the variant-8-encoded region and peptide, indicating that C44Mab-94 is a specific mAb for CD44v8. Furthermore, C44Mab-94 could recognize CHO/CD44v3–10 cells, oral squamous cell carcinoma cell line (HSC-3), or GC cell lines (MKN45 and NUGC-4) in flow cytometric analyses. C44Mab-94 could detect the exogenous CD44v3–10 and endogenous CD44v8 in western blotting and stained the formalin-fixed paraffin-embedded gastric cancer cells in immunohistochemistry. These results indicate that C44Mab-94 is useful for detecting CD44v8 in various applications and is expected to be useful for the application of GC diagnosis and therapy.

Introduction and objectives: arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. Methods: A descriptive observational study that included 8 initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p. (Glu259Glyfs*77) variant in PKP2 gene. The genetic testing employed next-generation sequencing for the index cases, and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. Results: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years, and a median follow-up of 39 [24-59] months. Worthy of note are the high incidence of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9% respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (4 patients 16.7%) and biventricular (4 patients 16.7%); we found no statistical differences in any of the variables analysed. Conclusions: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in 8 families of our geographical area in Malaga (Andalusia, Spain), where we can establish a founder effect and describe the clinical and risk characteristics.

This study aims to focus on using the Volterra series and machine learning for forecasting random and chaotic wind speed regimes, since the calm weather is mostly noticed at the local site, making the dataset selection difficult. A novel method is proposed to predict Volterra kernels up to the third order, using a forward-back propagation neural network with 12-month measurements at Fujairah site (UAE). Both daily and monthly wind speed data sets are investigated for forecasting. The three dominant hourly and daily kernels are extracted for each day and each month. Predicted future Volterra kernels are estimated from past values using both statistical analysis and individual neuro networks for each of the Volterra kernel coefficients. Due to the random nature of wind speed at the local site, a two-layer with 4 neurons per layer neuro network is used to locate the most variable and intense speed during 8-hours in the day. Forecasted wind speed is determined with errors arising from different sources such as the utilization of only 3rd-order Volterra kernels and the difficulty of machine training of the employed shallow network. Nevertheless, this work depicts a useful algorithm to forecast chaotic and random wind speed regimes. Computational time is a trade of the complexity of Volterra mathematical analysis.

Background: In regenerative dentistry the graft material influences the success. It should act as an osteoconductive scaffold, providing a mineral substrate during resorption and inducing the activity of osteoinductive cells capable of producing new bone, platelet growth factors, and cell differentiation factors inducing the differentiation of undifferentiated mesenchymal cells into. Given that dentin shares many biochemical characteristics with bone tissue, it has recently attracted considerable interest as a biomaterial for bone repair. The aim of this study is to compare two grinder types in order to determine the optimal method for producing dentinal particles using a mechanical grinder. Materials and methods: A sample of 40 natural human teeth without restorations, prostheses or root canal treatments was used and divided into two groups subjected to two different grinder speeds (high-speed and low-speed). The high-speed showed a greater dispersion (53.5+-9.89% of the tooth) due to the pulverisation (highly thin granules) of part of the tooth. The low-speed grinder does not pulverize the dentin and the percentage of tooth loss is 9.16+/-2.34%. Conclusion: The low-speed gringer allows to save a major part of the tooth and to have a maximum quantity of graft material but requires more time. Further studies must be promoted to optimise the grinding procedures.

Since the onset of coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time that also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we have summarized the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, bringing up-to-date hints for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are located in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

pump as turbine (PAT); computational fluid dynamics; variable rotational nominal speed; OpenFoam.

Distracted driving is the leading cause of accidents, the cause of these distractions may include drowsiness, using cell phone, smoking a cigarette, etc. The proposed paper aims at monitoring the attentiveness of the driver and alerting the driver when his/her alertness goes below a certain threshold. It uses image processing using OpenCV (Computer Vision) and You Look Only Once (YOLO) algorithm to detect the eyes and object respectively and sounds an alarm when the driver is either drowsy or using his cell phone or smoking a cigarette.

Small hydro-power systems seem to be the best solution for energy generation through the use of pump as turbine (PAT) due to its low cost and lesser environmental hazards associated with it. Recently, PAT applications are gaining global attention in energy generation but its operation is not fully understood. The performance and flow behavior is affected by several operational conditions. This study seeks to investigate the effects of rotational speed on flow behavior and performance of a PAT. Rotational speed is an important physical parameter that affects the operation of a PAT. A selected centrifugal pump model of four blades and splitters was used for the study. Numerical simulations were carried out using k-ε turbulence model to solve the three-dimensional (3D) equations in both pump and PAT modes. The outcomes were then validated using experimental results in the pump mode to obtain overview flow physiognomies. The results predicted that the efficiency increases as the rotational speed increases in the pump mode whereas in turbine mode, higher rotational speed cannot convert hydraulic energy into mechanical energy. Thus, a rotational speed of 1500 rpm performed the highest efficiency of 69.8% at QBEP among the other rotational speeds selected. Moreover, the head performance in the turbine mode increases as the flow rate increases. This research provides useful information which will help improve PAT performance as well as selecting PAT for small hydro-power site.

As one of the fastest-growing new energy sources, wind power technology has attracted widespread attention from all over the world. In order to improve the quality of wind power generation, wind speed prediction is an indispensable task. In this paper, an error correction based Variational Mode Decomposition and Broad Learning System (VMD-BLS) hybrid model is proposed for wind speed prediction. First, the wind speed is decomposed into multiple components by the VMD algorithm, and then an ARMA model is established for each component to find the optimal number of sequence divisions. Second, the BLS model is used to predict each component, and the prediction results are summed to obtain the wind speed forecast value. However, in some traditional methods, there is always time lag, which will reduce the forecast accuracy. To deal with this, a novel error correction technique is developed by utilizing BLS. Through verification experiment with actual data, it proves that the proposed method can reduce the phenomenon of prediction lag, and can achieve higher prediction accuracy than traditional approaches, which shows our method’s effectiveness in practice.

Aiming to diminish the defects caused by high-speed pulsed GMAW welding, such as non-penetration, non-fusion, humping and undercut, the paper proposed an improved twin-wire double-pulsed high-speed welding process by introducing the impact of additional shielding gas on the welding pool and the effects of different shielding gas flowrates on the microstructure and mechanical properties of the welded seam was investigated. The 2205 duplex stainless steel plate was used as the base material for the butt welding test, and the welded seams were subjected to tensile test, metallographic analysis, hardness analysis, and nondestructive testing. The results indicate that as the flowrate of additional shielding gas increases in the range of 8 L/min~16 L/min, the width of the welded seam increases and the height of reinforcement decreases gradually. However, a grooved seam with a lower middle region and higher sides will appear when the gas flowrate becomes excessively large. The test results indicate that the jet impact force is relatively moderate when the flowrate of the additional shielding gas is 12 L/min and thus, is optimal for the welded seam.

With the aim to improve cladding coating quality and prevent cracking, this paper established an extreme high-speed laser cladding thermo-mechanical coupling simulation model to study the evolution of the temperature field and residual stress distribution. Process parameters that impacted the macroscopic morphology of single-pass coatings were investigated. Numerical calculations and temperature field simulations were performed based on the process parameter data to validate the effect of the temperature gradient and cooling rate on the coating structure and the residual stress distribution. The results showed that a good coating quality could be achieved using a laser power of 2400 W, a cladding rate of 20 m/min, and a powder feeding rate of 20.32 g/min. The coatings’ cross-sectional morphology corresponded well with the temperature distribution predicted by numerical modeling of the melt pool. The microstructure of the molten coatings is affected by the temperature gradient and cooling rate, which vary greatly from the bottom to the middle to the top. Maximum residual stress appears between the bonding region of the coatings and the substrate, and the coatings themselves have significant residual stress in the form of tensile strains that are mostly distributed in the direction of the laser cladding speed.

Cluster of differentiation 44 (CD44) promotes tumor progression through the recruitment of growth factors, and the acquisition of stemness, invasiveness, and drug resistance. CD44 has multiple isoforms including CD44 standard (CD44s) and CD44 variants (CD44v), which have common and unique functions in tumor development. Therefore, the elucidation of each CD44 isoform’s function in tumor is essential for the establishment of CD44-targeting tumor therapy. We have established various anti-CD44s and anti-CD44v monoclonal antibodies (mAbs) through immunization of CD44v3–10-overexpressed cells. In this study, we established C44Mab-6 (IgG1, kappa), which recognized the CD44 variant 3-encoded region (CD44v3) determined by enzyme-linked immunosorbent assay. C44Mab-6 reacted with CD44v3–10-overexpressed Chinese hamster ovary (CHO)-K1 cells (CHO/CD44v3–10) or some cancer cell lines (COLO205 and HSC-3) by flow cytometry. The apparent KD of C44Mab-6 for CHO/CD44v3–10, COLO205, and HSC-3 was 1.5 × 10−9 M, 6.3 × 10−9 M, and 1.9 × 10−9 M, respectively. C44Mab-6 could detect the CD44v3–10 in western blotting, and stained the formalin-fixed paraffin-embedded tumor sections in immunohistochemistry. These results indicate that C44Mab-6 is useful for detecting CD44v3 in various experiments, and expected for the application of tumor diagnosis and therapy.

The connectivity level of last-generation vehicles is constantly on the rise. The combined use of Vehicle-To-Everything (V2X) connectivity and autonomous driving can provide remarkable benefits through the optimization of the route and speed trajectory. In this framework, this paper focuses on vehicle eco-driving optimization in a connected environment. The virtual test rig of a premium segment passenger car was used for generating the simulation scenarios. The benefits, in terms of energy and time savings, that the introduction of V2X communication, integrated with cloud computing, can have in a real-world scenario were assessed. The Reference Scenario is a pre-defined Real Driving Emissions (RDE) compliant route, while the simulation scenarios were generated by assuming two different penetration levels of V2X technologies. The associated energy minimization problem is formulated and solved by means of a global optimization algorithm, i.e., Dynamic Programming (DP). The optimization framework includes information coming from the surrounding environment, e.g., traffic lights state, speed limits, distance to travel, etc. The simulations show that introducing a smart infrastructure along with optimizing the vehicle speed in a real-world route can potentially reduce the required energy by 54% while shortening the travel time by 38%. Finally, a sensitivity analysis is performed on the bi-objective optimization cost function to find a set of Pareto optimal solutions, between energy and travel time minimization.

The androgen/androgen receptor (AR)-signaling axis plays a central role in the development and growth of prostate cancer (PCa) cells. Upon androgen-binding the AR dimerizes with another AR, translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. In consequence treatments for locally advanced or metastatic PCa are commonly based on androgen deprivation therapies (ADT). Unfortunately, the clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. In the clinic failure of ADT is often characterized by the synthesis of a C-terminally truncated, constitutively active AR splice variant, termed AR-V7. In contrast to AR, the constitutively active AR-V7 does no longer need androgenic stimuli for nuclear entry and/or dimerization. The goal of the present study was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology (NanoBiT) structural complementation assay under androgen stimulation and deprivation conditions. Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 localize in the nucleus. However, after 15 min of androgen stimulation, all AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers localized in the nucleus. In this way, we can show an androgen-regulated interaction between AR-FL and AR-V7 at forming heterodimers that localize in the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus. Treatment with enzalutamide diminished the luminescence of AR-FL homodimers and AR-FL/AR-V7 heterodimers but not AR-V7/AR-V7 homodimers.

Based on four major cosmological and astrophysical coincidences, it seems possible to develop a new model of Hubble-Hawking Universe having light speed expansion. Considering the analysis of 740 super novae data, it is possible to consider a constant rate of cosmic expansion. As there is no physical reasoning for the observed speed of light and all the cosmological observations are completely based on speed of light-by considering ‘light speed expansion’ as a characteristic nature of the universe, big bang, inflation, dark energy, quintessence and lambda term like ideal and unidentified concepts can be reviewed and relinquished at fundamental level and a practical model of expanding universe can be developed with ease and clarity. In this context, we would like to emphasize the point that, traditional definition of cosmic red shift is absolutely wrong. In terms of energy of photon, true cosmic red shift must be defined as - ratio of loss of energy in photon to the energy of photon at galaxy. We encourage the reader to see Figure 1 and Table 1 pertaining to light travel distances prepared with $\left(\frac{z}{1+z}\right)\left(\frac{c}{H_0}\right)\cong z_{new}\left(\frac{c}{H_0}\right)$. For data comparison, readers are encouraged to visit https://cosmocalc.icrar.org/ and http://www.atlasoftheuniverse.com/cosmodis.c. It may be noted that, considering 200 million solar masses as a cut off for ordinary gravity, dark matter can be considered as an effect of power law based super gravity of galactic baryonic mass. It is well believed that, Hawking’s findings about black holes are the most important contributions to physics in recent decades. Hence, we appeal the science community to recommend our Hubble-Hawking model for further research and study.

Imaginary dimensions in physics require an imaginary set of base Planck units and some negative parameter $c_n$ corresponding to the speed of light in vacuum $c$. Fresnel coefficients for the normal incidence of electromagnetic radiation on monolayer graphene introduce the second, negative fine-structure constant $\alpha_2^{-1} \approx -140.178$ as a fundamental constant of nature and this constant introduces these imaginary base Planck units along with this negative parameter $c_n \approx -3.06 \times 10^8~\text{[m/s]}$. Neutron stars and white dwarfs, considered as \emph{objects} emitting perfect black-body radiation, are conjectured to possess energy exceeding their mass-energy equivalence ratios, wherein the imaginary parts of two complex energies inaccessible for direct observation make storing excess of these energies possible. With this assumption, black holes are fundamentally uncharged; charged micro neutron stars and white dwarfs with masses lower than $5.7275 \times 10^{-10}~[\text{kg}]$ cannot be observed; and the radii of white dwarfs' cores are limited to $R_{WD} < 6.7933~G M_{WD}/c^2$, where $M_{WD}$ is a white dwarf mass. This sets the bounds on charged blackbody objects' minimum masses and maximum radii.

Cluster of differentiation 44 (CD44) has been investigated as a cancer stem cell (CSC) marker, and plays critical roles in tumor malignant progression. The splicing variants are overexpressed in many carcinomas, especially squamous cell carcinomas, and play critical roles in the promotion of tumor metastasis, the acquisition of CSC properties, and resistance to treatments. Therefore, each CD44 variant (CD44v) function and distribution in carcinomas should be clarified for the establishment of novel tumor diagnosis and therapy. In this study, we immunized mice with a CD44 variant (CD44v3−10) ectodomain and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C44Mab-34; IgG1, kappa) recognized a peptide which covers both variant 7 and 8-encoded region, indicating that C44Mab-34 is a specific mAb for CD44v7/8. Moreover, C44Mab-34 reacted with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells or oral squamous cell carcinoma (OSCC) cell line (HSC-3) by flow cytometry. The apparent KD of C44Mab-34 for CHO/CD44v3–10 and HSC-3 was 1.4 × 10−9 M and 3.2 × 10−9 M, respectively. C44Mab-34 could detect CD44v3–10 in western blotting, and stained the formalin-fixed paraffin-embedded OSCC in immunohistochemistry. These results indicate that C44Mab-34 is useful for detecting CD44v7/8 in various applications, and expected for the application of OSCC diagnosis and therapy.

Adaptive Cruise Control (ACC) is useful in the most dangerous maneuvers such as braking and acceleration. This study assesses how ACC modifies traffic flows by analysing the differences be-tween manual and autonomous driving in connected and autonomous vehicles (CAVs). Using a platoon of 80 vehicles, tested in pairs on the road, it was possible to define the speed trends during braking and acceleration and the reaction times to the driving maneuvers (PRT, TH, TCC) with a kinematic data detector. The interactions between the CAV and the driver, have been studied in-novatively, i.e through gaze analysis. Situations of potential danger, characterized by the braking of the vehicle that precedes the car with the driver equipped with the eye tracker tool, have been recreated, considering the influence of the driver’s ACC experience. Results statistically confirmed that with the ACC switched on the reaction times are greater than manual driving (2.4/3.8 sec); this can lead to a reduction in road safety, further motivated by the rapid decrease in speed. The interpolation between automated and human data, finally, has allowed the detection of some criticalities of the system that are fundamental in order to reach the second level of automation.

The Sun is a frame at relative rest in which sunlight travels at the emitted speed c. Earth travels at the revolving speed v in this frame. The reflection of light as a mechanical phenomenon applies to the modified Michelson interferometer employed by Miller in his experiments with light from the Sun. Unlike the Tomaschek experiments, which use light from stars that may travel in the Universe at velocities different from that of the Sun, the fringe shifts in the Miller experiments are predictable. Based on Michelson's derivation, Miller expected in his experiments at Mount Wilson a 1.12 fringe shift and observed a fringe shift of 0.08 in 1921 and 0.088 in 1925. The reflection of light as a mechanical phenomenon predicts zero fringe shift for Miller's experiment agreeing only with his observations at the Cleveland laboratory in 1924.

The continuously developing project aims to build an informatics system enabling analysis of spatial and temporal parameters of movement activities occurring in the sport of speed climbing. The monitoring system (climbing information speed system – CISS) is to be used for conducting comprehensive scientific research in the field of speed climbing. The system enables the evaluation of the training process of climbers at various levels of competition. The study analysis was based on video. The video recording with a camera positioned at a short distance (10 m) from the wall. The marker was positioned closest to the centre of mass (gravity) BMC. Results: development of a system for data collection and analysis of the climbing run based on video recording (application of the Kanade-Lucas-Tomasi (KLT) algorithm). Our results showed that used devices can measure a wide range of specific internal and external variables during speed climbing. Some of the analyzed parameters were significantly correlated with speed climbing time. These results could be a theoretical basis for future research and for training program’s preparation.

While genetic testing is becoming mainstream in the management of patients with potentially inherited cardiovascular disease, the prevalence of uncertain results severely limits its utility. One promising approach is to generate variant effect maps that report the function of all possible variants in a gene prospectively. The proactive clinical application of these maps is nascent, and it requires careful integration with current American College of Medical Genetics guidelines for variant interpretation. Here, we describe three pediatric cases of cardiac arrest or sudden cardiac death with variants of uncertain significance in calmodulin genes. We demonstrate the prospective clinical utility of a calmodulin variant effect map to inform variant interpretation, and therefore diagnosis and family care, in each case. This study was approved by the Stanford University and Vanderbilt University Medical Center IRBs. Consent was waived based on low risk of de-identified retrospective data collection per the IRB.

The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures and for this propose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanism leading to the creation of genomic heterogeneity by altering the number of chromosomes as well as changing their structures. In this review we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, human genome shows induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as whole genome doubling to more discrete changes as indels as well as the recent discovered complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double strand breaks (DSB) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar pattern observed during tumorigenesis. Then, we will also list several diseases associated to CIN resulting in fertility issue, miscarriage, genetic rare diseases and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and the resistance to conventional chemotherapy. CD44 has been known as a cancer stem cell marker, and plays tumor promotion and drug resistance in various cancers. Especially, the splicing variants are overexpressed in many carcinomas, and play essential roles in the cancer stemness, invasiveness or metastasis, and resistance to treatments. Therefore, the understanding of each CD44 variant (CD44v) function and distribution in carcinomas is essential for the establishment of CD44-targeting tumor therapy. In this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells, and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C44Mab-3; IgG1, kappa) recognized peptides of the variant 5-encoded region, indicating that C44Mab-3 is a specific mAb for CD44v5. Moreover, C44Mab-3 reacted with CHO/CD44v3–10 cells or pancreatic cancer cell lines (PK-1 and PK-8) by flow cytometry. The apparent KD of C44Mab-3 for CHO/CD44v3–10 and PK-1 was 7.1 × 10−10 M and 1.9 × 10−9 M, respectively. C44Mab-3 could detect the exogenous CD44v3–10 and endogenous CD44v5 in western blotting, and stained the formalin-fixed paraffin-embedded pancreatic cancer cells, but not normal pancreatic epithelial cells in immunohistochemistry. These results indicate that C44Mab-3 is useful for detecting CD44v5 in various applications, and expected for the application of pancreatic cancer diagnosis and therapy.

Can a gravitational lens magnify gravity ? The answer to this question is the subject of this article. Light is deflected as it passes through curved spacetime caused by a mass distribution. This phenomenon, known as "gravitational lensing," has been extensively studied and is well understood. According to the general theory of relativity, the same deflection is expected for gravitational waves, because they also propagate at the speed of light. But this applies to gravitational fields as well. Thus, gravitational fields, which extend through curved spacetime, are also deflected correspondingly. This effect is referred to as "Gravitationally Lensed Gravity". It leads to the fact that the gravitational field strength originating from an object in the background of a gravitational lens is enhanced in the same way as its light intensity. If the background object is visible to an observer several times due to the gravitational lens, each of the images also exerts a corresponding gravitational attraction on her ! For the first time, a proof of the existence of this amazing effect is given. In a simple thought experiment the contraction of a spherically symmetric gravitational lens is discussed. The proof is essentially based on Birkhoff's theorem. According to this theorem, during the contraction additional null geodesics between the background object and the observer come into existence. To these null geodesics also contributions to the gravitational field are to be assigned. In the literature, similar descriptions can be found for the gravitational self-interaction of a particle in a curved spacetime background. The article is organized as follows: In the introduction, the historical origin of the idea of the "Gravitationally Lensed Gravity" is briefly outlined. In the second chapter, the subsequently required basic principles and essential features of general relativity are explained. In the third chapter I analyze different arrangements of masses and describe the observations to be expected. The arrangements show step by step the transition from the classical "Newtonian limit" in a flat spacetime background to the "Gravitationally Lensed Gravity" in a curved spacetime background. Due to its clarity, the simple scenario may also serves as a suitable test case for the mathematical methods of general relativity. The concluding outlook provides references to current questions in astrophysics, especially the question of the existence of Dark Matter. Here, the general theory of relativity offers much simpler explanations with the "Gravitationally Lensed Gravity".

The SARS-CoV-2 Hydra with many heads (variants) has been causing the COVID-19 pandemic for 3 years. The appearance of every new head (SARS-CoV-2 variant) causes a new pandemic wave. The last in the series is the XBB.1.5 “Kraken” variant. In the general public (social media) and in the scientific community (scientific journals), during the last several weeks since the variant has appeared, the question was raised of whether the infectivity of the new variant will be greater. This article attempts to provide the answer. Analysis of thermodynamic driving forces of binding and biosynthesis leads to the conclusion that infectivity of the XBB.1.5 variant could be increased to a certain extent. The pathogenicity of the XBB.1.5 variant seems to be unchanged compared to the other Omicron variants.

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

SARS-CoV-2 resembles the ancient mythical creature Hydra. Just like with the Hydra, when one head is cut, it is followed by appearance of two more heads, suppression of one SARS-CoV-2 variant causes appearance of newer variants. Unlike Hydra that grows identical heads, newer SARS-CoV-2 variants are usually more infective, which can be observed as time evolution of the virus at hand, which occurs through acquisition of mutations during time. The appearance of new variants is followed by appearance of new COVID-19 pandemic waves. With the appearance of new pandemic waves and determining of sequences, in the scientific community and general public the question is always raised of whether the new variant will be more virulent and more pathogenic. The two variants characterized in this paper, BA.5.2 and BF.7, have caused a pandemic wave during the late 2022. This paper gives full chemical and thermodynamic characterization of the BA.5.2 and BF.7 variants of SARS-CoV-2. Having in mind that Gibbs energy of binding and biosynthesis represent the driving forces for the viral life cycle, based on the calculated thermodynamic properties we can conclude that the newer variants are more infective than earlier ones, but that their pathogenicity has not changed.

CD44 has been known as a marker of tumor initiating cells, and plays pro-tumorigenic functions in many cancers. The splicing variants play critical roles in malignant progression of cancers by promoting the stemness, cancer cell invasion or metastasis, and resistance to chemo- and radiotherapy. To understand each CD44 variant (CD44v) function is essential to know the property of cancers and establishment of the therapy. However, the function of the variant 4-encoded region has not to be elucidated. Therefore, specific monoclonal antibodies (mAbs) against the variant 4 are indispensable for basic research, tumor diagnosis, and therapy. In this study, we established anti-CD44 variant 4 (CD44v4) monoclonal antibodies (mAbs) by immunizing mice with a peptide containing the variant 4-encoded region. We next performed flow cytometry, western blotting, and immunohistochemistry to characterized them. One of the established clones (C₄₄Mab-108; IgG₁, kappa) reacted with CD44v3-10-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44v3-10). The K_D of C₄₄Mab-108 for CHO/CD44 v3-10 was 3.4 × 10⁻⁷ M. In western blot analysis, C₄₄Mab-108 detected CD44v3-10 in the lysate of CHO/CD44v3-10 cells. Furthermore, C₄₄Mab-108 stained formalin-fixed paraffin-embedded oral squamous carcinoma tissues in immunohistochemistry. These results indicated that C₄₄Mab-108 is useful to detect CD44v4 in various applications.

RNA viruses exhibit a great tendency to mutate. Starting from 2019, the wild type that was labeled Hu-1 has during the last 3 years evolved to produce several dozen new variants, as a consequence of mutations. Mutations cause changes in empirical formulas of new virus strains, which lead to change in thermodynamic properties of biosynthesis and binding. These changes cause changes in the rate of reactions of binding of virus antigen to the host cell receptor and the rate of virus multiplication in the host cell. Changes in thermodynamic and kinetic parameters lead to changes in biological parameters of infectivity and pathogenicity. SARS-CoV-2 has starting from in 2019, until today, evolved towards increase in infectivity and maintaining constant pathogenicity, or for some variants a slight decrease in pathogenicity. In the case of Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants pathogenicity is identical as in the Omicron BA.2.75 variant. On the other hand, infectivity of the Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants is greater than those of previous variants. This will most likely result in the phenomenon of asymmetric coinfection, that is circulation of several variants in the population, some being dominant.

1) We shall discuss what modern interpretations say about the Heisenberg's uncertainties. These interpretations explain that a quantity begins to 'lose' meaning when a conjugate property begins to 'acquire' definite meaning. We know that a quantity losing meaning means that it has no fixed value and has an uncertainty . In this paper we look deeper into this interpretation and the outcome reveals more evidence of the quantity losing meaning. Newer insights appear. 2) We consider two extreme cases of hypothetical processes nature undergoes, without interference by a measurement: One, a system collapses to an energy eigenstate under the influence of a Hamiltonian instantaneously at a time $t$. This is thus what would happen if we would measure the system's energy. Next, when a particle becomes localised to a point at a time $t_0$ under the influence of a Hamiltonian. This is thus what would happen if we would measure the system's position. We shall prove that both these situations cannot arise under ordinary circumstances and thus measurement processes cannot be modelled by physical Hamiltonians.

A significant proportion of SARS-CoV-2 infections in Africa are identified as asymptomatic, facilitating the silent spread of the virus especially in populated urban cities. With the surge of the highly transmissible Omicron variant, the inclusion of asymptomatics in epidemiological surveys is key in estimating true infections and seroprevalence in the population. The aim of the study was to determine seroprevalence, active infection and circulating variants in Accra, the capital city of Ghana during the Omicron wave. The study was a cross-sectional survey conducted in 22 municipalities in December 2021. Naso-oropharyngeal swabs and serum samples were collected from 1027 individuals aged 5 years and above, for detection of infection by RT-qPCR and estimation of total antibodies using the WANTAI ELISA kit. Our results show 10% SARS-CoV-2 prevalence, with the Omicron and Delta variants accounting for 44.1% and 8.8% of infections, respectively. Omicron was most prevalent (48.9.%) among the 20–39-year-olds. Asymptomatic individuals accounted for 75.2% of infections. Seropositivity within the population was 86.8%, with the 60+ year group having significantly higher likelihood of exposure (OR 10.22: 95% CI: 3.51-29.73; p<0.001). This high seroprevalence appears to have been as a result of increased vaccination among this group (OR 2.7: 95% CI 1.78-4.09, p < 0.001). The high seropositivity of SARS-CoV-2 in the capital could be a good indication of herd immunity among the population and while the low infection rate supports the role of vaccination in reducing viral transmission.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Omicron BA.2.75 may become the next globally dominant strain of COVID-19 in 2022. BA.2.75 sub-variant has acquired more mutations (9) in spike protein and other genes of SARS-CoV-2 than any other variant. Thus, its chemical composition and thermodynamic properties have changed comparing to earlier variants. In this paper Gibbs energy of binding and antigen-receptor binding rate is reported for the BA.2.75 variant. Gibbs energy of binding (driving force of binding) of Omicron BA.2.75 variant is more negative than that of the competing variants BA.2 and BA.5.

The prediction of an extremely severe cyclonic storm (ESCS) is one of the challenging issues due to increasing intensity and its life period. In this study, an ESCS Fani that developed over Bay of Bengal region during 27 April - 4May, 2019 and made landfall over Odisha coast of India is investigated to forecast the storm track, intensity and structure. Two numerical experiments (changing two air-sea flux parameterization schemes; namely FLUX-1 and FLUX-2) are conducted with the Advanced Research version of the Weather Research and Forecasting (ARW-WRF) model by using a moving nest with fine horizontal resolution about 3 km. The high resolution (25 km) NCEP operational Global Forecast System (GFS) analysis and forecast datasets are used to derive the initial and boundary conditions, the ARW model initialized at 00 UTC 29 April 2019 and forecasted for 108 hours. The forecasted track and intensity of Fani is validated with available India Meteorological Department (IMD) best-fit track datasets. Result shows that the track, landfall (position and time) and intensity in terms of minimum sea level pressure (MSLP) and maximum surface wind (MSW) of the storm is well predicted in the moving nested domain of the WRF model using FLUX-1 experiment. The track forecast errors on day-1 to day-4 are ~ 47 km, 123 km, 96 km, and 27 km in FLUX-1 and ~54 km, 142 km, 152 km and 166 km in Flux-2 respectively. The intensity is better predicted in FLUX-1 during the first 60 h followed by FLUX -2 for the remaining period. The structure in terms of relative humidity, water vapor, maximum reflectivity and temperature anomaly of the storm is also discussed and compared with available satellite and Doppler Weather Radar observations.

Viral variant analysis is a bedrock of the disease surveillance. When combined with temporospatial analysis variant analysis can further the knowledge of disease spread in a study area. This paper suggests a method to perform the analysis in an operational setting which will allow for real-time surveillance of viral variants and allow local public health professionals to rapidly respond to changes in the evolution of the disease. This method includes three main subprocesses: preprocessing, analysis, and rendering. This method can be performed across multiple software platforms. A use case is given in which it was found that this method helped a hospital system understand the spread of SARS-CoV-2 in Northeast, Ohio.

In our recently published papers, considering Planck mass based light speed growing black hole universe and scaled Hawking’s black hole temperature formula, we have developed a simple procedure for estimating the current Hubble parameter and current cosmic mass. In addition to that, without considering galactic dark matter, starting from 10 km/sec to 500 km/sec, we have tried to fit the observed galactic flat rotation speeds with a concept of super gravity of galactic baryonic mass. To estimate the equivalent mass of currently hypothecated galactic dark matter, we have introduced a timely increasing cosmological reference mass unit. Its current magnitude seems to be around 200 million solar masses. In this paper, considering 200 million solar masses as a characteristic representation of cosmic weak interaction mass unit, we have developed a simple formula for its estimation. We would like to appeal that, weak interaction boosts the gravity of galaxies in proportion with their virtual dark mass as (galactic baryonic mass)^3/2 / (200 million solar masses)^1/2. With further study- dark matter existence and physical properties can be understood in a theoretical approach.

Lynch syndrome (LS) is an inherited disorder in which affected individuals have a significantly higher-than-average risk of developing colorectal and non-colorectal cancers, often before the age of 50 years. In LS, mutations in DNA repair genes lead to a dysfunctional post-replication repair system. As a result, the unrepaired errors in coding regions of the genome produce novel proteins, called neoantigens. Neoantigens are recognised by the immune system as foreign and trigger an immune response. Due to the invasive nature of cancer screening tests, universal cancer screening guidelines unique for LS (including colonoscopy) are poorly adhered to by LS variant heterozygotes (LSVH). Currently, it is unclear whether immunogenomic components produced as a result of neoantigen formation can be used as novel biomarkers in LS. We hypothesize that: (i) LSVH produce measurable and dynamic immunogenomic components in blood, and (ii) these quantifiable immunogenomic components correlate with cancer onset and stage. Here, we discuss feasibility and propose the potential to: (a) identify personalised novel immunogenomic biomarkers, (b) reduce invasive cancer screening tests and thus increase non-invasive cancer surveillance, (c) improve compliance and adherence to recommended cancer screening guidelines in LSVH.

Immune escape is observed with SARS-CoV-2 Omicron (Pango lineage B.1.1.529), the predominant circulating strain worldwide. Booster dose was shown to restore immunity against Omicron infection, however, real world data comparing mRNA (BNT162b2; Comirnaty) and inactivated vaccine (CoronaVac; Sinovac) homologous and heterologous boosting is lacking. A retrospective study was performed to compare the rate and outcome of COVID-19 in healthcare workers (HCWs) with various vaccination regime during a territory-wide Omicron outbreak in Hong Kong. During the study period 1 Feb – 31 Mar 2022, 3167 HCWs were recruited, 871 HCWs reported 746 and 183 episodes of significant household and non-household close contact. 737 HCWs acquired COVID-19 which were all clinically mild. Time dependent Cox regression showed that, comparing with 2-dose vaccination, 3-dose vaccination reduced infection risk by 31.7% and 89.3% in household contact and non-household close contact respectively. Using 2-dose BNT162b2 as reference, 2-dose CoronaVac recipient had significantly higher risk of being infected (HR 1.69 P<0.0001). Three-dose BNT162b2 (HR 0.4778 P<0.0001) and 2-dose CoronaVac + BNT162b2 booster (HR 0.4862 P=0.0157) were associated with lower risk of infection. Three-dose CoronaVac and 2-dose BNT162b2 + CoronaVac booster were not significantly different from 2-dose BNT162b2. The mean time to achieve negative RT-PCR or E gene cycle threshold 31 or above was not affected by age, number of vaccine dose taken, vaccine type and timing of the last dose. In summary, we have demonstrated lower risk of breakthrough SARS-CoV-2 infection in HCWs given BNT162b2 as booster after 2 doses of BNT162b2 or CoronaVac.

For the first time in history, we have witnessed the origin and development of a pandemic. To handle the accelerated accumulation of viral mutations and to comprehend the virus' evolutionary adaptation in humans, an unparalleled program of genetic sequencing and monitoring of SARS-CoV-2 variants has been undertaken. Several scientists have theorized that, with the Omicron surge producing a more contagious but less severe disease, the end of COVID-19 is near. However, by analyzing the behavior shown by this virus for 2 years, we have noted that pandemic viruses do not always show a decreased virulence. Instead, it appears there is an evolutionary equilibrium between transmissibility and virulence. We have termed this concept “intermittent virulence”. The present work analyzes the temporal and epidemiological behavior of SARS-CoV-2 and suggests that there is a high possibility that new virulent variants will arise in the near future, although it is improbable that SARS-CoV-2´s virulence will be the same as was seen during the pandemic phase.

Mixture of abramis brama (freshwater bream), carassius carassius (crucian carp), and sander lucioperca (pike perch) scales was used for the preparation of fish scale powder containing about 26.5 wt. % of removed when heating components preferably of organic nature, and 63.5 wt. % of mineral components. Fish scale powder enriched with inorganic components was prepared from washed, dried, and ground fish scale mixture using vibration sieving. Inorganic powders consisting of hydroxyapatite and magnesium whitlockite were obtained via heat treatment of this fish scale powder at 800-1000 oC. Particles of these inorganic powders consisted of sintered grains with dimensions less than 100 nm after heat treatment at 800 oC, less than 200 nm after heat treatment at 900 oC, and 100-500 nm after heat treatment at 1000 oC. Fish scale powder enriched with inorganic components as well as heat-treated inorganic powders consisting of hydroxyapatite and magnesium whitlockite can be recommended for the production of different materials such as ceramics or composites.

This paper presents the implementation of a control strategy based on fuzzy logic artificial intelligence (AI) for speed regulation of an electromagnetic frequency regulator (EFR) prototype, aiming to eliminate the dependence on knowledge of physical parameters in the most diverse operating conditions. Speed multiplication is one of the most important steps in power generation wind. Gearboxes are generally used for this purpose. However, they have a reduced lifespan and a high failure rate and are still noise sources. The search for new ways to match the speed (and torque) between the turbine and the generator is an important research area to increase the energy, financial and environmental efficiency of wind systems. The EFR device is an example of an alternative technology that this team of researchers has proposed. It counts the fact of taking advantage of the main advantages of an induction machine with the rotor in a squirrel cage positively. In the first studies, the EFR control strategy consisted of the conventional PID controllers, which has several limitations widely discussed in the literature. This strategy also limits the EFR's performance, considering its entire operating range. The simulation program was developed using the Matlab/Simulink platform, while the experimental results were obtained in the laboratory emulating the EFR-based system. The EFR prototype used has 2 poles, a nominal power of 2.2 kW, and a nominal frequency of 60 Hz. Experimental results were presented to validate the efficiency of the proposed control strategy.

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic, however, the need for orally available antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using 5 two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were conducted three times and in triplicate. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p<0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p<0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p=0.01) and 13.08 (p<0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro.

Short Linear Motifs (SLiMs) are short linear sequences that can mediate protein-protein interaction. Mimicking eukaryotic SLiMs to compete with extra or intracellular binding partners or to sequester host proteins is the crucial strategy of viruses to pervert the host system. The evolved proteins in viruses facilitate minimal protein-protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about the SARS-CoV-2 SLiMs is known, especially across the SARS-CoV-2 variants. Through ELM database-based sequence analysis of spike protein from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant including LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants.

Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The eCDC and the WHO recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the PCR-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor a possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490-509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariant when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.1 NTD and a BA.2 RBD, which can only be detected by using specially designed PCR primers. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.

The fault diagnosis of the gearbox is primarily based on the analysis of the harmonic response. However, the generation mechanism of the harmonic response of the gear pair is still not distinctly explained in a healthy gearbox. Therefore, this paper is dedicated to establishing a dynamic model of the gearbox for this issue. In this model, the contact force of the bearing and the meshing stiffness of the gear pair are determined by the Hertz theory and the potential energy method, then the shaft motion is used as the connection to establish the coupling relationship between the gear pair and the bearing. After this dynamic model is confirmed by experiments and existing models, the coupling relationship inside the gearbox and the harmonic response of the gear pair are studied using this model. The result demonstrates that a closed control loop is formed due to the vibration transmission between the gear pair, the bearing and the shaft, and there is a strong coupled vibration between the gear pair and the bearing in the gearbox. Due to the generation of the center distance error, misalignment angle and disorganized meshing process of the gear pair, the meshing stiffness is altered, which excites the harmonic response of the gear pair. When the speed of the gearbox is increased, although the vibration amplitude of the gearbox is increased, the system predominantly vibrates at the fundamental frequency, and the harmonic of the gear pair is also shifted to the low frequency band.

Triple X syndrome (TXS, also known as trisomy X or 47,XXX) has been associated with impaired overall neurocognitive functioning in children and relatively young adults. However, neurocognitive functioning in adults with TXS is poorly understood. The aim of this study was, therefore, to examine cognitive functioning in adults with TXS. Methods: In this cross-sectional study, data were collected from 34 adult women with TXS (mean age = 32.9; SD = 13.1) and 31 controls (mean age = 34.9; SD = 13.7). General intellectual functioning, semantic/verbal memory, visual/episodic memory, psychomotor speed, and attention and executive functioning were then compared between these two groups. Results: We found that general intellectual functioning was significantly lower in the TXS group compared to the control group. In addition, women with TXS had more attention problems and lower psychomotor speed, particularly motor processing speed. When the analyses were adjusted for IQ, the strength of these associations decreased. The women in the TXS group also scored significantly lower at free recall in the verbal memory test, but not in immediate or delayed recognition. Finally, visual/episodic memory and executive functioning did not differ significantly between groups. Conclusions: Our analysis revealed that women with TXS score lower in general intellectual functioning and have impairments in motor processing speed and attention compared to controls, but do not differ with respect to executive functioning. These results offer new insights for improving the support of adults with TXS both at school and in the workplace.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T&gt;C(p.Met1Thr) and c.449+5G&gt;A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G&gt;A. An in vitro minigene assay demonstrated that variant c.449+5G&gt;A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

In this study, we analyzed sequences of SARS-CoV-2 isolates of the Delta variant in Mexico, which completely replaced other previously circulating variants in the country due to its transmission advantage. Among Delta sublineages detected, 81.5 % were classified as AY.20, AY.26, and AY.100. According to publicly available data, these sublineages only reached a world prevalence of less than 1%, suggesting a possible Mexican origin. The signature mutations of these sublineages are described, and phylogenetic analyses and haplotype networks were used to track their spread across the country. Other frequently detected sublineages include AY.3, AY.62, AY.103, and AY.113. Over time, the principal sublineages showed different geographical distributions, with AY.20 predominant in Central Mexico, AY.26 in the North, and AY.100 in the Northwest and South/Southeast. This work describes the circulation, from May to November 2021, of the primary sublineages of the Delta variants associated to the third wave of the COVID-19 pandemic in Mexico and reinforces the importance of SARS-CoV-2 genomic surveillance for timely identification of emerging variants that may impact public health.

The rapid emergence and worldwide detection of the SARS-CoV-2 omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and more strong vaccine breakthrough ability. Also known as B.1.1.529, Omicron has four sub-variants, BA.1, BA.2, BA.3, and BA.4. Among them, BA.1 is the currently prevailing sub-variant, BA.2 is found to be able to alarmingly re-infect patients initially infected by omicron BA.1. BA.3 sub-variants is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today emerging is the BA.4, herein described and first detected in Italy, harboring a new mutation, specifically a deletion in the ORF 1 ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants pointed out that the deletion was not present previously and was never reported until now. Therefore, we can speculate that omicron BA.4; will become a new dominating “variant of concern” and might also break vaccine protection . On the other hand, we show that other proteins are mutated in the BA.4 in particular, seven mutations are recognized in the nucleocapsid (N) protein, the capability of five different types of rapid antigenic tests to recognize it.

Lethal congenital contracture syndrome 11 (LCCS11) is a form of arthrogryposis multiplex congenita (AMC) which is associated with mutations in the gliomedin gene (GLDN) and has been known to be severely life-shortening, mainly due to respiratory insufficiency. Patients with this condition have been predominantly treated by pediatricians as they usually do not survive beyond childhood. In this case report we present a young adult who developed severe progressive respiratory insufficiency as a teenager due to diaphragmatic hypomotility and was diagnosed with LCCS11 following the finding of compound heterozygous pathogenic variants in GLDN. This case demonstrates the importance of screening for neuromuscular diseases in well-child visits and follow-ups of patients at risk for gross and fine motor function developmental delay. It also underscores the significance of including LCCS11 and other axonopathies in the differential diagnosis of juvenile onset of respiratory insufficiency, highlights that patients with this condition may present to adult practitioners and questions whether the nomenclature of this condition with various phenotypes should be reconsidered due to the stigmatizing term ‘lethal’.

Genomic surveillance represents an important strategy for understanding evolutionary mechanisms, transmission profile, and infectivity of different SARS-CoV-2 variants. We assessed the epidemiological profile of 366 individuals who tested positive for SARS-CoV-2 from 29 municipalities in Rondônia between December 2021 to March 2022. Samples were collected, RNA was ex-tracted and screened using RT-qPCR for Alpha, Beta, Gamma, Delta and Omicron VOCs and viral quantification was performed. Sequences were analyzed for phylogeny, mutations and lineages. Of the samples analyzed, 93.71% were positive for the Omicron variant and 6.28% were positive for the Delta variant. The symptoms observed were cough, sore throat, and fever, with a mean duration of 5 days; no hospitalizations or deaths were reported. We noted that among the positive individuals, 51% had been immunized with two doses, 22% received three doses, 13% received one dose, and 13% were not immunized. Just 242 samples were amenable to analysis for alignment and phylogenetic characterization; corresponding to variants BA.1 and BA.1.1; a total of 120 mutations were identified, 36% of which were found in the S gene. In conclusion, there was a high frequency of mutations in the SARS-CoV-2 genome, but no record of clinical severity, demonstrating the positive effect of vaccination.

Emission, propagation, and reflection of light as mechanical phenomena in inertial frames are based on the behavior of balls at the limit when their mass is zero. The kinematics of massless balls is like that of balls with mass. Light as a wave or particle is a massless entity. Therefore, it is natural to apply the kinematics of the massless balls to light. Consequently, the kinematics of light depends on its kinetics of electromagnetic nature and its kinematics of mechanical nature in its interactions of emission and reflection with the matter. The study of the physics phenomena in the frame at absolute rest includes those in the inertial frames. Considering this and applying the emission, propagation, and reflection of light as mechanical phenomena in the vacuum of the frame at absolute rest, this study derives formulas for the speed of the wavefront of a ray of light reflected by a fixed and moving mirror when the light comes from a fixed and moving source. The derived formulas apply to the modified Michelson interferometer, employed independently by R. Tomaschek and D. C. Miller in their experiments.

A gravitational lens is mass-curved spacetime. Light that propagates freely, locally always on the fastest way, follows curved paths in it. The same applies to all effects propagating with the speed of light, also to gravity itself. They all have to follow the curvature of spacetime. A gravitational lens not only enhances the light from background objects but concurrently also their gravitational effect ! The "Gravitationally Lensed Gravity" (GLG) is a still scarcely noticed peculiar feature of general relativity. In [1] I presented a thought experiment to make the existence of this effect plausible. Here these considerations are described in terms of future and past light cones or null cones commonly used in relativity theory to illustrate the causal structure of spacetime. In the framework of general relativity, the GLG effect can be understood as a consequence of the folding of the past null cone by a gravitational lens. Starting from the basic ideas of the theory, the terms are introduced and applied. The extensive description on textbook level should be understandable also for beginners. In order not to obstruct the view on the essential physical relations, I avoid a mathematical formalism and use instead diagrams and figures, based on realistic numerical calculations, to reinforce my logical argumentation. Experts will recognize many long-known facts, but may still be surprised by the resulting conclusions. First, I present some particular aspects of the historical evolution of the concept of gravitational lensing and give a brief overview of the work of other authors on the subject GLG. I then explain the limitations of the applicability of the "Newtonian Limit" and move on to the key role of the speed of gravity in understanding GLG. Finally, I use a simple example to illustrate the possible significance of the GLG effect. With this work I intend to elicit greater interest in "Gravitationally Lensed Gravity" and to initiate a broader discussion about it.

Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?

SARS-CoV-2 Omicron variants contain many mutations in its spike receptor binding domain, the target of all authorized monoclonal antibodies (mAbs). Determining the extent to which Omicron variants reduced mAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated February 22, 2022, of the in vitro activity of authorized mAbs against the Omicron variants. Thirty-three studies were eligible including 33 containing Omicron BA.1 susceptibility data and five that also contained Omicron BA.2 susceptibility data. The first two authorized mAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were inactive against the Omicron BA.1 and BA.2 variants. In 24 studies, sotrovimab (third authorized mAb) displayed a median 4.1-fold (IQR: 2.4-7.6) reduced activity against Omicron BA.1 and, in four studies, a median 26-fold (IQR:16-35) reduced activity against Omicron BA.2. In 18 studies, cilgavimab and tixagevimab independently displayed median reductions in activity of >300-fold against Omicron BA.1, while in ten studies, the cilgavimab/tixagevimab combination (fourth authorized mAb preparation) displayed a median 63-fold (IQR: 26-145) reduced activity against Omicron BA.1. In two studies, cilgavimab was approximately 100-fold more susceptible to BA.2 than to BA.1. In two studies, bebtelovimab, the most recently authorized mAb, was fully active against both the Omicron variants. Disparate results between assays were common as evidenced by a median 42-fold range (IQR: 25-625) in IC50 between assays for the eight authorized individual mAbs and three authorized mAb combinations. Highly disparate results between published assays indicates a need for improved mAb susceptibility test standardization or inter-assay calibration.

Mechanical power and motion are often transmitted by the gear-rotor-bearing system. When there are fitting clearances between the housing and outer ring in bearings, complex vibration responses will be generated, which makes the operating status difficult to identify. Therefore, for analyzing dynamic responses, a dynamic model of gear-rotor-bearing systems with bearing fitting clearances is proposed. In the model, the bearing system with fitting clearances and gear pair system are combined, and the coupling relationship is determined by the gyroscopic mo-tion of the shaft. The friction force and collision force caused by fitting clearances are also con-sidered, which are simulated by the Coulomb friction model and Hertz theory. The result shows that the meshing stiffness will also be excited by the bearing displacement. When there are fit-ting clearances on the bearing, the amplitude modulation of the bearing outer raceway to the system time-domain response is intensified, and the multiple harmonic frequency of bearings and gear pairs are generated on the spectrum, as well as defect frequencies of gear pairs. As the fitting clearance is increased, the higher multiple harmonic responses will be caused. Although the response amplitude of the gearbox is increased by raising the input speed, multiple harmon-ic responses are suppressed, which makes the system mainly vibrate at the fundamental fre-quency. Then, the dynamic model and the vibration analysis are experimentally verified.

Rapid antigen detection tests (RAD) are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC) presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One-hundred and twenty samples were selected and tested with both RT-qPCR and five commercial RAD commonly sold in Belgian pharmacies. Of these, direct whole genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron. Sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) were comparable and ranged from 70.0% to 77.1% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct &gt; 25), poor performances were observed for the Delta strains (20.0 to 40.0%) and, even more so, for Omicron strains (0.0 to 23.1%). Two devices failed to detect all samples (n = 13) containing Omicron strains with a low viral load. The poor performance observed with low viral loads is an important limitation of RAD, which is not sufficiently highlighted in the instruction for use of these devices.

In this report, we describe the course and successful treatment of complicated infective endocarditis (IE). A patient presented with a high-grade irregular fever with chills lasting at least 2 months, dyspnoea, chest pain, fatigue, weight loss, and night sweats during the previous 3 months. Above cardiac congenital disorders, he was found to have Granulicatella adiacens infective aortic valve endocarditis, presumably transmitted from the oral cavity niche. Validated metagenomic 16S rDNA next generation sequencing was used to perform taxonomic identification, allowing for specific adequate antibiotic therapy instead of empiric therapy. This paper highlights the critical role of rapid taxonomic identification of nutritionally variant streptococci crucial and the benefit of proper IE treatment to avoid relapses or fatal complications.

The 2019 Coronavirus Disease (COVID-19) is a major cause of morbidity and mortality worldwide. Since late November 2021, Omicron variant has emerged as the primary cause of COVID-19 and caused a huge increase in the reported incidence around the world. To date, 32-34 spike mutations have been reported, 15 of which were located in the receptor-binding domain that interacts with the cell surface of the host cells, while the rest were located in the N-terminal domain and around the Furin cleavage site. At present, both the genomic and clinical profiles of this novel variant are being investigated. Here, we aim to discuss the recent reports on the transmissibility and severity of Omicron variant from both the genetic and clinical perspectives. Afterward, we also take the chance to deliver our personal view on the topic.

This study presents the substantiation, development, and analysis of a technique for planning the autonomous vehicle (AV) motion reference parameters. The trajectory plan, speed and acceleration distributions, including other AV's kinematic parameters, are determined using sequential optimization. The study objectives are based on an analysis of the fundamental problems of AV motion planning summarized in this area's latest publications. The proposed approach combines the basic principles of the finite element method (FEM) and nonlinear optimization with nonlinear constraints. First, the generalization on representing an investigated function by finite elements (FE) is briefly described. A one-dimension FE with two nodes and three degrees of freedom (DOF) in a node was chosen as the basic one, corresponding to the 5th-degree polynomial. Next, a method for determining the motion trajectory is presented. The following are considered: formation of a restricted space for the AV's allowable maneuvering, the geometry of motion trajectory and its relation with vehicle steerability parameters, cost functions and their influences on the desirable trajectory's nature, compliance of nonlinear restrictions of the node parameters with the motion area boundaries. At the second stage, a technique for optimizing AV speed and acceleration redistribution is presented. The model considers possible combinations of cost functions, conditions of limiting the kinematic parameters with the tire slip critical speed, maximum speed level, maximum longitudinal acceleration, and critical lateral acceleration. In the simulation section, several variants of trajectories were searched and compared. Several versions of distributing the longitudinal speed and acceleration curves are determined, and their comparative analysis is fulfilled. At the end of the paper, the advantages and drawbacks of the proposed technique are noted. The conclusion is made regarding the options for improving the method in further studies.

Plant geneticists and breeders have used marker technology since the 1980s in quantitative trait locus (QTL) identification. Marker-assisted selection is effective for large-effect QTL but has been challenging to use with quantitative traits controlled by multiple minor effect alleles. Therefore, genomic selection (GS) was proposed to estimate all markers simultaneously, thereby capturing all their effects. However, breeding programs are still struggling to identify the best strategy to implement it into their programs. Traditional breeding programs need to be optimized to implement GS effectively. This review explores the optimization of breeding programs for variety release based on aspects of the breeder’s equation. Optimizations include reorganizing field designs, training populations, increasing the number of lines evaluated, and leveraging the large amount of genomic and phenotypic data collected across different growing seasons and environments to increase heritability estimates, selection intensity, and selection accuracy. Breeding programs can leverage their phenotypic and genotypic data to maximize genetic gain and selection accuracy through GS methods utilizing multi-trait and, multi-environment models, high-throughput phenotyping, and deep learning approaches. Overall, this review describes various methods that plant breeders can utilize to increase genetic gains and effectively implement GS in breeding .

Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of FOXC1. The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, congenital heart anomalies, and cystic kidney disease. Whole exome sequencing revealed a novel variant [c.313_314insA; p.(Tyr105*)] in FOXC1 that disrupts the alpha-helical region of the DNA-binding forkhead box domain. In vitro studies using a heterologous cell system revealed aberrant cytoplasmic localization of FOXC1 harboring the Tyr105* variant, likely precluding downstream transcription function. Meta-analysis of the literature highlighted the intrafamilial variability related to FOXC1 truncating alleles. This study highlights the clinical variability in ASD and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.

Covid-19 has caused infections and deaths worldwide. While research in the field of Data Science has contributed good predictions of positive Covid-19 case numbers, this study's review of literature shows there is little research in the use of variants of the virus in predictions. We set out to define and evaluate novel variant features. We find that features relating to variant trends, thresholds and amino acid substitutions are especially powerful in two tasks. In the first task, predicting Covid-19 case numbers, accuracy improved from 71.53% without variant features to 82.12% with variant features. In the second task, predicting transmission severity of variants between two classes, we created a method to build some variable ensembles through selecting appropriate models that are generated with variant features. The test results showed that our ensembles are more accurate and reliable. One particular ensemble of 14 models correctly classified 90.91% of variants, outperforming other models including the popular Random Forest ensemble. In addition, as the variant features have represented more underlying information about Covid-19 pathophysiology, our ensemble methods use only a few data samples to achieve an accurate prediction. The ensemble of 14 models uses only 50 cases of each variant, an ability that could be exploited for early detection of highly infectious variants. These research findings may benefit public health professionals, policy makers, and the research community in the collective efforts to overcome this disease.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Fanconi anemia (FA) is a rare genetic disorder caused by pathogenic variants (PV) in at least 22 genes, which cooperate in the FA/BRCA pathway to maintain genome stability. PV in FANCA, FANCC, and FANCG account for most cases (~90%). This study evaluated the chromosomal, molecular, and phenotypic findings of a novel founder FANCG PV, identified in three patients with FA from the Mixe community of Oaxaca, Mexico. All patients presented chromosomal instability and a homozygous PV, FANCG: c.511-3_511-2delCA, identified by next-generation sequencing analysis. Bioinformatics predictions suggest that this deletion disrupts a splice acceptor site promoting the exon 5 skipping. Analysis of Cytoscan 750K arrays for haplotyping and global ancestry supported the Mexican origin and founder effect of the variant, reaffirming the high frequency of founder PV in FANCG. The degree of bone marrow failure and physical findings (described through the acronyms VACTERL-H and PHENOS) were used to depict the phenotype of the patients. Despite having a similar frequency of chromosomal aberrations and genetic constitution, the phenotype showed a wide spectrum of severity. The identification of a founder PV could help for a systematic and accurate genetic screening of patients with FA suspicion in this population.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

Magnesium nanoparticles of various mean diameters (53 – 239 nm) were synthesized herein via Pulsed Laser Ablation in Liquid (PLAL) from millimeter sized magnesium powders within iso-propyl alcohol. It was observed via a 3x3 full factorial DOE that the processing parameters can control the nanoparticle distribution to produce three size-distribution types (bimodal, skewed and normal). Ablation times of 2, 5, and 25 minutes where investigated. An ablation time of 2 minutes produced a bimodal distribution with the other types seen at higher periods of processing. Mg nanoparticle UV-Vis absorbance at 204 nm increased linearly with increasing ablation time, indicating an increase in nanoparticle count. The colloidal density (mg/ml) generally increased with increasing nanoparticle mean diameter as noted via increasing UV-vis absorbance. High la-ser scan speeds (within the studied range of 3000 - 3500 mm/s) tend to increase the nanoparticle count/yield. For the first time, the effect of scan speed on colloidal density, UV-vis absorbance and nanoparticle diameter from metallic powder ablation was investigated and is reported herein. The nanoparticles formed dendritic structures after being drop cast on aluminum foil as observed via FESEM analysis. Dynamic light scattering was used to measure the size of the nanoparticles. Magnesium nanoparticles have promising use in the fabrication of wearables, such as in conductive tracks or battery electrodes, owing to their low heat capacity, high melting point and bio-compatibility.

Improving the operational reliability of nuclear power plants, combined heat and power plants (CHP), as well as oil and gas pipelines is a priority task in the development of a variable-speed drive for lock valves used at these facilities. The paper analyzes technical requirements for such devices; the motor has been selected, its electrical equilibrium and moment equations have been obtained; recommendations for the selection of the kinematic drive scheme have been formulated. Based on the theoretical data obtained, a prototype has been developed, manufactured and tested.

In the present paper, the so-called Einstein’s causality is scrutinized and proven to be an illusion, a sort of mathematical fallacy. Causality as a well-established universal principle was and is absolutely valid for subluminal, luminal and superluminal signals under any natural and/or artificial circumstances. It is also shown that conceptually special relativity theory (SRT) is inapplicable to superluminality of physical phenomena since SRThas the light speed in vacuum as an upper limiting speed in its own proper domain of applications, and also because SRT is crucially based on the concept of inertial reference frames (IRFs) which are related to each other by Lorentz transformations, that is why the relative velocity of any two IRFs must be smaller than light speed.

An axiomatic theory is proposed that reconciles the existence of an absolute scale for time (Planck time) and special relativity. According to this theory speed of light c becomes a variable which is proposed to be taken as the fifth dimension.

The search algorithm based on symbiotic organisms’ interactions is a relatively recent bio-inspired algorithm of the swarm intelligence field for solving numerical optimization problems. It is meant to optimize applications based on the simulation of the symbiotic relationship among the distinct species in the ecosystem. The modified SOS algorithm is developed to solve independent task scheduling problems. This paper proposes a modified symbiotic organisms search based scheduling algorithm for efficient mapping of heterogeneous tasks to access cloud resources of different capacities. The significant contribution of this technique is the simplified representation of the algorithm's mutualism process, which uses equity as a measure of relationship characteristics or efficiency of species in the current ecosystem to move to the next generation. These relational characteristics are achieved by replacing the original mutual vector, which uses an arithmetic mean to measure the mutual characteristics with a geometric mean that enhances the survival advantage of two distinct species. The modified symbiotic organisms search algorithm (G_SOS) aimed to minimize the task execution time (Makespan), response, degree of imbalance and cost and improve the convergence speed for an optimal solution in an IaaS cloud. The performances of the proposed technique have been evaluated using a Cladism toolkit simulator, and the solutions are found to be better than the existing standard (SOS) technique and PSO.

Due to the renewed variation in government and political systems inside and outside countries, and with the high tariffs at borders, the latter have become an outlet for terrorism and smugglers. Therefore, each country seeks to develop its own protection system, and the technologies used in these systems vary according to the severity and the importance of the installations to be protected, it is found that some of them are expensive and unnecessary, but other have good and variable levels of efficiency. Consequently, the idea of designing a surveillance system that can monitor and control access becomes indispensable. In the same context, this work is of crucial strategic and geopolitical importance. It combines pre-existing alarm and monitoring methods and revolutionary Internet of Things (IoT) application products, of which Wireless Sensor Networks (WSN) and Optical Fiber Sensors (OFS) are part of this application. This article presents the distribution of wireless radar nodes accompanying with a Bragg fiber sensor to identify each rolling intruder incoming the zone to be monitored, from the determination of its speed, weight and wheelbase distance.

Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used in addition with other control measures. However, only a limited number of vaccine strains are commercially available which often have a restricted spectrum of activity against the different FMD virus strains in circulation. As a result, when new strains emerge, it is important to measure the efficacy of the current vaccine strains against these new variants. This is important for countries where FMD is endemic but also for countries that hold an FMD vaccine bank to be prepared for emergency vaccination. The emergence and spread of the O/ME-SA/Ind-2001 lineage of viruses posed a serious threat to countries which had OIE-endorsed FMD control plans and had not reported FMD for many years. In vitro vaccine matching results showed a poor match (r1-value &lt;0.3) to the more widely used vaccine strain O Manisa and less protection in a challenge test. This paper describes the use of O3039 vaccine strain as an alternative either alone or in combination with the O Manisa vaccine strain with virulent challenge by a O/ME-SA/Ind-2001d sub-lineage virus from Algeria (O/ALG/3/2014). The experiment included challenge at 7 days post vaccination (to study protection and emergency use) and 21 days post vaccination (as would be done in standard potency studies). The results indicated that the O3039 vaccine strain alone as well as the combination with O Manisa is effective against this strain of the O/ME-SA/Ind/2001d lineage offering protection from clinical disease even after 7 days post vaccination and with reduction in viraemia and virus excretion.