This paper presents a method for producing a gravity field through an electromagnetic field. The electromagnetic field can produce a positive or negative gravity field. The relationship between gravity force and electromagnetic is unknown. Former studies by theoretical physics predict the relationship between these two forces. Based on the general balance theory in six dimensions of space and time, the electromagnetic field was studied from this viewpoint. Three-dimensional waves oscillate in the fourth dimension and electromagnetic waves distort space-time. Aggregating these distortions can behave like a positive or negative gravity field. Consequently, the production of energy is possible from gravitational fields.

The G2 gas cloud motion data and the scarcity of observations on the event horizon-scale distances have challenged the comprehensiveness of the central supermassive black hole model. In addition, the Planck Legacy 2018 release has preferred a positively curved early Universe with a confidence level higher than 99%. This study investigates the impact of the background curvature and its evolution over the conformal time on the formation and morphological evolution of central compact objects and the consequent effect on their host galaxies. The formation of a galaxy from the collapse of a supermassive gas cloud in the early Universe is modeled based on interaction field equations as a 4D relativistic cloud-world that flows and spins through a 4D conformal bulk of a primordial positive curvature considering the preference of the Planck release. Owing to the curved background, this scenario of galaxy formation reveals that the core of the galaxy undergoes a forced vortex formation with a central event horizon leading to opposite vortices (traversable wormholes) that spatially shrink while evolving in the conformal time. It indicates that the galaxy and its core are formed in the same process whereas the surrounding gas clouds form the spiral arms due to the frame-dragging induced by the fast-rotating core. It demonstrates that the accretion flow onto the central supermassive compact object only occurs at the central event horizon of the two opposite vortices while their other ends eject the relativistic jets. This can elucidate the relativistic jet formation and explain the G2 gas cloud motion if its orbit is around one of the vortices but at a distance from the central event horizon. The gravitational potential of the early curved bulk could contribute to galaxy formation while the present spatial flatness deprives the potential of bulk which could lead to galaxy quenching. The formation of a galaxy and its core simultaneously could explain the growth of the supermassive compact galaxy core to a mass of ~10⁹ M_⊙ at just 6% of the current Universe age.

This article presents the results of reviewing the predictive capacity of Google trends for national elections in Chile. The electoral results of the elections between Michelle Bachelet and Sebastián Piñera in 2006, Sebastián Piñera and Eduardo Frei in 2010, Michelle Bachelet and Evelyn Matthei in 2013, Sebastián Piñera and Alejandro Guillier in 2017, and Gabriel Boric and José Antonio Kast in 2021 were reviewed. The time series analysed were organised on the basis of relative searches between the candidacies, assisted by R software, mainly with the gtrendsR and forecast libraries. With the series constructed, forecasts were made using the ARIMA technique to check the weight of one presidential option over the other. The ARIMA analyses were performed on 3 ways of organising the data: the linear series, the series transformed by moving average and the series transformed by Hodrick-Prescott. The result indicates that the method offers optimal pre-dictive ability.

The distributed acoustic sensing (DAS) has great potential for monitoring natural-resource reservoirs and borehole conditions. However, the large volume of data and complicated wavefield add challenges to processing and interpretation. In this study, we demonstrate that seismic interferometry based on deconvolution is a convenient tool for analyzing this complicated wavefield. We extract coherent wave from the observation of a borehole DAS system at the Brady geothermal field in Nevada. Then, we analyze the coherent reverberating waves, which are used for monitoring temporal changes of the system. These reverberations are tirelessly observed in the vertical borehole DAS data due to cable or casing ringing. The deconvolution method allows us to examine the wavefield at different boundary conditions. We interpret the deconvolved wavefields using a simple 1D string model. The velocity of this wave varies with depth, observation time, temperature, and pressure. We find the velocity is sensitive to disturbances in the borehole related to increasing operation intensity. The velocity decreases with rising temperature, which potentially suggests that the DAS cable or the casing are subjected to high temperature. This reverberation can be decomposed into distinct vibration modes in the spectrum. We find that the wave is dispersive, and the the fundamental mode propagate with a large velocity. The method can be useful for monitoring borehole conditions or reservoir property changes. For the later, we need better coupling than through only friction in the vertical borehole to obtain coherent energy from the formation.

The Albufera of Valencia is a coastal lagoon located in the western area of the Mediterranean Sea, in the Iberian Peninsula. It has an area of 23.1 km2 and an average depth of only 1 m, with a maximum depth of 1.6 m. This lagoon is the rest of an original and more extensive wetland of about 220 km2, mostly dedicated to rice cultivation nowadays. Surface water is supplied through several main and many secondary canals for a total of 64 water entry points and three exit points to the sea. It is difficult to evaluate the renewal rate due to the lack of reliable measurements of the inflow or outflow, as well as continuous measurements. Between 1988 and 2018 several procedures have been used, synthesizing in this work the result, in which it is observed a decrease of the inflow in these thirty years, and therefore the residence time is increasing. There is a temporal variation during the year of renewal influenced by rainfall and cultivation periods. Likewise, it is observed that the natural hydrological zoning of the lagoon causes a spatial heterogeneity with small areas with more renewal, practically weekly, and large extensions with little renewal during months. It is impossible to know this information if flow measurements are not taken in each of the main watercourses.

We have shown in previous work that the equivalence of the Heisenberg and Schrödinger pictures of quantum mechanics requires the use of the Born and Jordan quantization rules. In the present work we give further evidence that the Born--Jordan rule is the correct quantization scheme for quantum mechanics. For this purpose we use correct short-time approximations to the action functional, initially due to Makri and Miller, and show that these lead to the desired quantization of the classical Hamiltonian.

Algaecides are chemicals that cause serious health problems. Conventional paints contain algaecides to improve the algae resistance on the paint film. Present research has suggested an environmental friendly paint formulation that focuses on developing algae resistance without having algaecides. In this research, Algae growth on newly developed paint is modeled by incorporating dirt resistance of paint and natural phenomena including humidity, temperature and time respectively. The fitted Model revealed explained variation of 59.65% in the average algae growth, of which, Dirt Resistance, Humidity and temperature and some of their interactions play significant role in this variation. Model suggests that the proposed newly developed paint without algaecides is more resilient to algae growth and significantly decreased the average algae growth rate by 0.53% as compared to conventional paints. Keeping the effect of all other factors constant, if dirt resistance of paint (D_c value) increases by one percent, average algae growth decreases by 12.98%; when temperature increases by 1^oC, average algae growth decreases by 22.4%; a positive unit change in the joint linear effect dirt resistance, temperature and humidity caused a decrease in average algae growth by 0.0031%. It was also observed that the individual effect of humidity variable was inversely related with average algae growth. However the combination of humidity and temperature, humidity and dirt resistance, humidity and time, and the quadratic effect of humidity were found to increase the average algae growth rate. The cubic effect of temperature variable by one degree centigrade resulted in decrease of average algae growth by 0.000907%.

Landslide is a sliding movement of rock mass, debris and soil along the slope under the action of gravity. Small Baseline Subset (SBAS) is an established method for the investigation and monitoring of landslide moments. This study focuses on monitoring the long-temporal displacement of mountainous terrain in Danba County, Sichuan Province via SBAS technique, based on 31 scenes of L-band ALOS/PALSAR data from Feb. 2007 to Oct. 2010.The results show that the largest velocity rates in LOS direction are ±120 mm/yr and maximum accumulated displacement is up to -300, which indicates fast movement of the mountainous terrain during the observation time. These results get good consistency against the results of previous study. This demonstrates the strong potential of SBAS technique for monitoring the landslides geohazard.

In nonlinear self-consistent system, Lorenz system (Lorenz equations) is a classic case with chaos solutions which are sensitively dependent on the initial conditions. As it is difficult to get the analytical solution, the numerical methods and qualitative analytical methods are widely used in many studies. In these papers, Runge-Kutta method is the one most often used to solve these differential equations. However, this method is still a method based on explicit time scheme, which would be the main reason for the chaotic solutions to Lorenz system. In this work, numerical experiments based on implicit time scheme and explicit scheme are setup for comparison, the results show that: in implicit time scheme, the numerical solutions (counterexamples) are without chaos; for an original volume, the volume shrinks exponentially fast to 0 in common.

A time interval only description necessarily needs its own independent definitions, without one moment time coordinates to it. In this paper derived are time interval only set properties, including commutation relations, addition, multiplication and derivatives. Time interval only set commutation relations, consistent with one moment time set properties, are introduced by defining correspondence relations for these sets. Time development and equilibrium within the time interval description depend on the well-known ‘mean velocity theorem’ and the time interval version of the Legendre transform. In contrast, usually applied is only the traditional vector and one moment time coordinate kinematic approach from Newton’s laws. The main results of this paper are correspondences and time interval only set commutation relations. All other properties are derived from these results, while for the time interval only set, different from the one moment time set the canonical property is not valid. The time interval only description can be applied assuming spherical symmetric star-source radiation propagation, with finite time intervals for realistic measurement events. From time development with (a-)symmetry of time intervals, and from Curie’s principle, change can be described with a set theoretic approach. Time interval only set properties include the time interval only version of Noether charges and structure constants. A time interval only description for wave propagation, including group-velocity, for zero and non-zero mass wave particles, relates to the properties of the time interval only set. A second result in terms of the time interval only description is propagation wave energy equivalence with gravitation energy, derived from time interval only set commutation relations. A time interval approach, however including one moment time description dependence, was introduced in earlier publications of this author. In part 1 investigated are the time interval only set and its properties, a forthcoming part 2 to application of the time interval only description to specific groups of stars as emission sources.

Currently Single Board Computers (SBCs) are sufficiently powerful to run Real-Time Operating Systems (RTOSs) and applications with real-time attributes and requirements. SBCs serve as a foundation in Industrial Internet of Things (IIoT). The NXP Semiconductors produces a series of SBCs based on ARM-processors for a variety of industrial applications. The continuous increase in real-time data generated by IoT devices adds further research issues about the efficiency of such systems and applications. The purpose of this research was to investigate the timing performance of an NXP TWR-K70F120M device with μClinux OS on running concurrently tasks with real-time features and constraints. A custom-built multithreaded application with specific compute-intensive sorting and matrix operations was developed and applied to obtain measurements in specific timing metrics, including task’s execution time, threads waiting time, and response time, under different threads variations. The performance of this device was additionally benchmarked and validated against favorite platforms, a Raspberry Pi4 and BeagleBone AI SBCs. The experimental results showed that this device stands well both in terms of timing and efficiency metrics. Execution times were quite lower than the others, by approximately 56% in the case of two threads, and by 29% in the case of thirty-two threads configurations.

This paper presents sufficient conditions for almost global stability of nonlinear switched systems consisting of both stable and unstable subsystems. Techniques from the stability analysis of switched systems have been combined with the multiple Lyapunov density approach - recently proposed by the authors for the almost global stability of nonlinear switched systems composed of stable subsystems. By using slow switching for stable subsystems and fast switching for unstable subsystems lower and upper bounds for mode-dependent average dwell times are obtained. In addition to that, by allowing each subsystem to perform slow switching and using some restrictions on total operation time of unstable subsystems and stable subsystems, we have obtained a lower bound for an average dwell time.

In recent years, the individualized demand of customers brings small batches and diversification of orders towards enterprises. The application of enabling technologies in factory, such as the Industrial Internet of Things (IIoT) and Cloud Manufacturing (CMfg), enhances the ability of customer requirement automatic elicitation and the manufacturing process control. The job shop scheduling problem with random job arrival time dramatically increases the difficulty in process management. Thus, how to collaboratively schedule the production and logistics resources in the shop floor is very challenging, and it has a fundamental and practical significance of achieving the competitiveness for an enterprise. To address this issue, the real-time model of production and logistics resources is built firstly. Then, the task entropy model is built based on the task information. Finally, the real-time self-adaption collaboration of production and logistics resources is realized. The proposed algorithm is carried out based on a practical case to evaluate its effectiveness. Experimental results show that our proposed algorithm outperforms three existing algorithms.

Multi-gap Resistive Plate Chamber has been attracting increasing attention and has been studied in recent decades because of its good efficiency, high time resolution and relatively low cost. It has become a new standard technology for the Time of Flight system in particle and high energy physics experiments. In this paper, we introduce the operation principle and structure of the MRPC detector and review the applications on the Time of Flight system in several famous experiments, such as STAR, CBM and SoLID. The performances including time resolution and particle identification are discussed in detail. Some recent advances and perspectives with regard to the future development of the next generation MRPC are also outlined.

Hand and arm gesture recognition using radio frequency (RF) sensing modality proves valuable in man-machine interface and smart environment. In this paper, we use time series analysis method for accurately measuring the similarity of the micro-Doppler (MD) signatures between the training and test data, thus providing improved gesture classification. We characterize the MD signatures by the maximum instantaneous Doppler frequencies depicted in the spectrograms. In particular, we apply the dynamic time warping (DTW) method and compare its performance with that of the long short-term memory (LSTM) network. Both methods take into account the values as well as the temporal evolution and trends of time series data. It is shown that the DTW method achieves high gesture classification rates and is robust to time misalignment.

After developed the formulation of a "general relativity" in C⁴ [2], we proceed with the formulation of a Hamilton-Jacobi equation in C⁴. We argue that in this consideration, the usual problems of the ADM formalism, do not exist, due to the complex time as it exists in our consideration. Specically, we can derive a suitable dispersion relation in order to work with and nd a generalised super Hamiltonian

Understanding the dynamics of humoral immune responses throughout the COVID-19 pandemic is crucial for optimizing vaccine strategies. This study aimed to investigate the impact of infection and vaccine-induced immunity on the Albanian population from August 2021 to August 2022. Two independent samples from the Albanian general population were analyzed using an ELISA method to assess IgG class anti-Spike (S1) and anti-Nucleocapsid (N) SARS-CoV-2 antibodies. The results revealed a robust immune response among vaccinated individuals with prior COVID-19 infection who received only one vaccine dose. In the 2022 cohort, most individuals who received one vaccine dose achieved comparable seropositivity and antibody levels to those who received two doses. However, individuals aged 61 and over required two or three vaccine doses to reach the same level of immune response as the younger population. Notably, the time elapsed since infection or vaccination did not significantly impact the immune response. These findings highlight the importance of hybrid immunity and suggest that one vaccine dose may be sufficient for most individuals with prior COVID-19 infection. However, additional doses are necessary for optimal protection in older individuals. This study provides unique insights into humoral immune response dynamics that can be used to refine ongoing COVID-19 population vaccination strategies for middle-income countries with low vaccination coverage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

A green, fast and selective approach for the synthesis of mono-substituted closo-decaborate derivatives [2-B10H9COR]n– has been established via a nucleophilic addition reaction between the carbonyl derivative of closo-decaborate [2-B10H9CO]– and the corresponding Grignard reagent RMgX, where R is the ethyl, iso-propyl, pentyl, allyl, vinyl, and propynyl groups. This approach is accomplished under mild conditions with 70–80% yields. The significance of these derivative is their ability to constitute building blocks for polymeric integration via the allyl, vinyl and propynyl substituents. All products were characterized by 11B, 1H, and 13C NMR, elemental analysis and mass spectrometry.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different biopertinent activities specially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold a clinical promise against acute myeloid leukemia.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with ACE2 receptor located in endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease leading to irreversible tissue damage and death of patients with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated to the interaction of SARS CoV-2 with ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally, it exerts unique “off target” steroidal effects that include gynecomastia, impotence and loss of libido in males and menstrual irregularity in females. Together, these have led to a poor tolerability and limited use despite positive results in many randomized, controlled clinical trials. We review the off-target effects of spironolactone that may summate with its MRA action to provide an advantageous profile for prevention or treatment of patients with COVID-19. Methods: Literature review using PubMed Central. Results: The blockade by spironolactone of the androgen receptor should diminish the expression of transmembrane protease serine 2 (TMPRSS2) that has an androgen promoter while its MRA action should enhance the expression of protease nexin1 (PN1) that inhibits furin and plasmin. TMPRSS2, furin and plasmin cooperated to process the SARS-CoV-2 spike protein to increase its high affinity binding to the angiotensin converting enzyme 2 (ACE2) and thereby promote viral cell entry. Its actions as an MRA may reduce inflammation and preserve pulmonary, cardiac and vascular functions. Its anti-plasmin action may combat hemostatic dysfunction. Conclusion: The hypothesis that the off-target effects of spironolactone summate with its MRA actions to provide special benefits for COVID-19 is worthy of direct investigation and clinical trial.

Today, there is a time series analysis that has gained significant popularity across various industries to provide effective solutions for any specific challenges. Artificial intelligence logic is generally used to solve time-series problems with the help of various frameworks that are available for the development of AI-based applications. Currently, there is a significant framework in Python that is driven by its comprehensive libraries and their practical implementations. Time series analysis can be built with the help of some specific models that give results to differentiate the efficiency and domains of great work. This paper focuses on three diverse libraries of Python to predict the Gulf stock exchange market. These libraries are prediction models that are helpful in predicting future values. These models utilized include SARIMA (Seasonal Auto-Regressive Integrated Moving Average), Neural Prophet Model, and Fb Prophet model. Each model is trained using the provided datasets, which are followed by evaluation parameters such as MSE, RMSE, recall, MDAPE, accuracy, precision, etc. The main purpose of using these three models for stock market prediction is to find the better-suited models. In the past few decades, the stock market industry has seemed to have promising growth after 2022 onwards. This paper will help us make a significant decision about model usage for addressing such complex challenges. Especially, the research findings indicate that all three models demonstrate in different domains. SARIMA can perform well in overall prediction tasks, while the Prophet model works great with smaller datasets that contain seasonality trends.

The paper deals with one new property of the linear time-optimal control problems with real eigenvalues of the system, no matter of the number of eigenvalue multiplicity. This property unveils a prospective of synthesizing the time-optimal control without the need of describing the switching hyper-surfaces. The already chrestomathy example of the time-optimal control of a double integrator is resolved by the new technique and compared with the classical synthesis.

A correct system design can be systematically obtained from a specification model of a real-time system that integrates hybrid measurements in a realistic industrial environment, this has been carried out through complete Matlab / Simulink / Stateflow models. However, there is a widespread interest in carrying out that modeling by resorting to Machine Learning models, which can be understood as Automated Machine Learning for Real-time systems that present some degree of hybridization. An induction motor controller which must be able to maintain a constant air flow through a filter is one of these systems and it is discussed in the paper as a study case of closed-loop control system. The article discusses a practical application of ML methods that demonstrates how to replace such closed loop in industrial control systems with a Simulink block generated from neural networks to show how the proposed procedure can be applied to derive complete hybrid system designs with artificial neural networks (ANN). In the proposed ANN-based method to design a real-time hybrid system with continuous and discrete components, we use a typical design of a neural network, in which we define the usual phases: training, validation, and testing. The generated output of the model is made up of reference variables values of the cyber-physical system, which represent the functional and dynamic aspects of model. They are used to feed Simulink/Stateflow blocks in the real target system.

Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signaling pathways to foster drug resistance, cancer stem cell survival, metastasis, inflammation, epithelial mesenchymal transition, and angiogenesis. All-trans retinoic acid (ATRA) and chemotherapy have been the standard treatments for acute promyelocytic leukemia (APL), but clinical studies have shown that arsenic trioxide (ATO), alone or in combination with ATRA, can improve outcomes. ATO exerts cytotoxic effects in a variety of ways by inducing oxidative stress, genotoxicity, altered signal transduction, and/or epigenetic modification. In the present study, we showed that ATO increased ROS production and apoptosis ratios in ATRA-differentiated NB4 leukemia cells and that these responses were enhanced when TG2 was deleted. The combined ATRA+ATO treatment also increased the amount of nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, an adaptive regulator of cellular oxidative stress response, and proteolytic activity of calpain, resulting in TG2 degradation and reduced survival of WT leukemia cells. We further showed that upon ATO treatment, the induced TG2 protein expression was degraded in the MCF-7 epithelial cell line, and primary peripheral blood mononuclear cells, thereby sensitizing these cell types to apoptotic signals.

In this research article we solve the problem of synchronization and anti-synchronization of chaotic systems described by discrete and time-delayed variable fractional order differential equations. To guarantee the synchronization and anti-synchronization of these systems, we use the well-known PID control theory and the Lyapunov-Krasovskii stability theory for discrete systems of variable fractional order.We illustrate the results obtained through simulation with examples, in which it can be seen that our results are satisfactory, thus achieving synchronization and anti-synchronization of chaotic systems of variable fractional order with discrete time delay.

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

Objective: Spontaneous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA vaccination causes a marked increase in antibody titer because of the combined effect of vaccine and infection (“hybrid immunity”). In this study, we discuss the significance of the mRNA vaccine booster inoculation that has been repeatedly performed in Japan.Methods: We describe the temporal trends of antibody titers in cases in which antibody titers were markedly increased by hybrid immunization.Results: The antibody titer increased with hybrid immunization and tended to decrease with time. However, several cases maintained high antibody titers for approximately one year after coronavirus disease 2019 (COVID-19 diagnosis), even without booster vaccination.Conclusions: Most Japanese patients naturally infected with COVID-19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid-immunized cases is highly questionable regarding cost-effectiveness and risk-benefit.

Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis - inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, Multiple Sclerosis, Diabetes. In this review, we discuss the therapeutic potential of regulating BCL-2 family connections and their relevance to health and disease.

BA.2, a sublineage of Omicron BA.1, is now prominent in many parts of the world. Early reports indicate that BA.2 is more infectious than BA.1. To gain insight into BA.2 mutation profile and the resulting impact of mutations on interaction with receptor and/or monoclonal antibodies, we analyzed available se-quences, structures of Spike/receptor, and Spike/antibody complexes, and conducted molecular dynamics simulations. The results showed that BA.2 has 50 high-prevalent mutations compared to 48 in BA.1. Seventeen BA.1 mutations are not present in BA.2. Instead, BA.2 has 19 unique mutations and a signature Delta variant mutation (G142D). Intriguingly, the BA.2 has 28 signature mutations in Spike, compared to 30 in BA.1. This is due to two revertant mutations S446G and S496G in the receptor-binding domain (RBD), making BA.2 somewhat similar to Wuhan-Hu-1 (WT), which has G446 and G496. The molecular dynamics simulations showed that the RBD consisting of G446/G496 is more stable than S446/S496 containing RBD. Thus, our analyses suggest that BA.2 has evolved with novel mutations (i) to maintain receptor binding similar to WT, (ii) evade the antibody binding greater than BA.1, and (iii) acquire mutation of the Delta variant that may be associated with the high infectivity.

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways, however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following the SARS-CoV-2 infection, while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection pandemic with similarities to the influenza virus.

With the emergence of the novel corona virus SARS-CoV-2 since December 2019, more than 43 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases leading to over 1 million deaths globally. Despite the collaborative and concerted research efforts that has been made, no effective treatment for COVID-19 (corona virus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to achieve this through the use of angiotensin converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2. However, through this review, we present another perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, shedding and its cellular trafficking pathways including internalization are not well elucidated. Therefore, hereby we present an overview on the fate of newly synthesized ACE2, its post translational modifications, what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Extensive understanding of these processes is necessary to evaluate the potential use of ACE2 as a credible therapeutic target.

COVID-19 (coronavirus disease 2019) is a public health emergency of international concern caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of this time, there is no known effective pharmaceutical, phytopharmaceutical or traditional medicine for cure or prevention of COVID-19, although it is urgently needed. In this review, based on the current understanding of the disease molecular mechanisms of novel Coronavirus SARS-CoV-2 and its closest relative SARS-CoV and other human Coronaviruses, I have identified some naturally occurring plant based substances and Ayurvedic medicinal herbs that could feasibly be tested as a matter of urgency for prevention as well as therapeutic option for COVID-19 in India and other parts of the world. I conclude that dried rhizome of Curcuma longa L. i.e. turmeric, and its active ingredient curcumin may be effective in preventing as well as cure the COVID-19 pandemic due to its proven antiviral activities, this however need to be tested by appropriate clinical trials as research priority.

The rodent collecting duct (CD) expresses a 24p3/NGAL/lipocalin-2 (Lcn2) receptor (Slc22a17) apically to possibly mediate high-affinity reabsorption of filtered proteins by endocytosis, yet its functions remain uncertain. Recently, we showed that hyperosmolarity/-tonicity upregulates Slc22a17 in cultured mouse inner medullary CD cells, whereas activation of toll-like receptor 4 (TLR4) via bacterial lipopolysaccharides (LPS) downregulates Slc22a17. This is similar to the upregulation of Aqp2 by hyperosmolarity/-tonicity and arginine vasopressin (AVP) and downregulation by TLR4 signaling that occur via the transcription factors Nfat5 (TonEBP or OREBP), cAMP-responsive element binding protein (CREB), and nuclear factor-kappa B, respectively. The aim of the study was to determine the effects of osmolarity/tonicity via Nfat5, AVP via CREB and TLR4 signaling on the expression of Slc22a17 and its ligand Lcn2 in the mouse (m) cortical collecting duct cell line mCCD(cl.1). Normosmolarity/-tonicity was 300 mosmol/l whereas addition of 50-100 mmol/l NaCl for up to 72 h induced hyperosmolarity/-tonicity (400-500 mosmol/l). RT-PCR, qPCR, immunoblotting and immunofluorescence microscopy detected Slc22a17 and Lcn2 expression. RNAi silenced Nfat5, and the pharmacological agent 666-15 blocked CREB. Activation of TLR4 occurred with LPS. Similar to Aqp2, hyperosmotic/-tonic media and AVP upregulated Slc22a17 via activation of Nfat5 and CREB, respectively, and LPS/TLR4 signaling downregulated Slc22a17. Conversely, though Nfat5 mediated hyperosmolarity/-tonicity induced downregulation of Lcn2 expression, AVP reduced Lcn2 expression and predominantly apical Lcn2 secretion evoked by LPS, but through a posttranslational mode of action that was independent of cAMP signaling. In conclusion, the hyperosmotic/-tonic upregulation of Slc22a17 in mCCD(cl.1) cells via Nfat5 and by AVP via CREB suggests a contribution of Slc22a17 to adaptive osmotolerance, whereas Lcn2 downregulation could counteract increased proliferation and permanent damage of osmotically stressed cells.

We develop a renormalizable model of Quantum General Relativity (QGR). We do this by building on earlier work with quantum electrodynamics (QED). Working with the Feynman path integral (FPI) approach to QED, we generalize the paths from varying in space to varying in space and time. This gives the standard results plus dispersion in time of order attoseconds or left. Over longer times, the dispersion in time averages out, but at attosecond times it should be detectable with current technology. As an unexpected but welcome side-effect, the approach caused the usual loop integrals to be finite. Since the usual UV divergences are significantly harder to renormalize in QGR than in QED, and since using paths in time plus space is definitely more in keeping with the general spirit of GR, we here apply the same approach to QGR. We show that with an appropriate choice of gauge (trace-reversed de Donder gauge) we can extend the earlier results to include QGR. Sub-attosecond measurements of individual gravitons are not within our reach, but at least the ultraviolet divergences in QGR are contained in the same way. We have therefore a renormalizable model of QGR

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Rainfall, or more generally the precipitation process (flux), is a clear example of chaotic variables resulting from a highly nonlinear dynamical system, the atmosphere, represented by a set of physical equations such as the Navier-Stokes equations, energy balances and hydrological cycle among others. As a generalization of the Euclidean (ordinary) measurements, chaotic solutions of these equations are characterized by fractal dimensions, which are non-integer values that represent the complexity of variables like the precipitation. However, observed precipitation is measured as an aggregate variable over time, thus physical analysis of the observed fluxes is very limited. Therefore, this review aims to go through the different approaches used in the identification and analysis of the complexity of the observed precipitation, taking advantage of its geometry footprint. To address the review, it ranges from classical perspectives of fractal-based techniques to new perspectives at temporal and spatial scales as well as for classification of climatic features, including monofractal dimension, multifractal approaches, Hurst exponent, Shannon entropy and time scaling in intensity-duration-frequency curves.

Tungsten and its alloys are considered as a key component in high temperature environment. Self-passivating W-Si-xY alloys with different Y contents made from the powders milled for different times were prepared by mechanical alloying (MA) and spark plasma sintering (SPS). Their microstructures and oxidation resistance were investigated. It is found that the oxidation resistance of the alloys with low Y contents (0Y and 2Y) made from 20 h-milled powders is worse than that of the alloys made from 4 h-milled powders. It is because the protective WO3/SiO2 composite layer is discontinuous. While the alloys with high Y contents (4Y and 6Y) made from 4 h and 20 h-milled powders show good oxidation resistance. Even, the thickness of the oxide layer of the alloys with 4Y and 6Y made from 20 h-milled powders after oxidation at 1000 ℃ for 2 h is 84.0 μm and 70.7 μm, less than that made from 4 h-milled powders. This is due to the size and distribution of W5Si3, Y2Si2O7 aggregates and W-Y-O melt. The synergistic effects of Y contents and milling time on the microstructures and oxidation resistance of the alloys are revealed.

The Hwangdo tidal flat is an intertidal landform located in Cheonsu Bay, Taean-gun, Chungcheongnam-do, on the west coast of Korea. The topographical characteristics of the semi-enclosed bay on the eastern side of the study area include waterways, sandbars, small islands, and tidal flats. In this study, data were acquired from tide gauges installed on the Hwangdo Bridge, and the height of the ellipsoid was measured using a real-time kinematics global positioning system (RTK-GPS). Digital elevation model (DEM) using Matrice 300 drone data were also acquired after processing. The geochemical sediment characteristics in the study area were analyzed, together with tidal-flat exposure-time characteristics based on environmental factors. Sediment data (n = 107) collected from October 25 to 28, 2022 (Korean local time) were used to classify sediment particles according to Folk and Ward (1957). Sedimentary facies ranged from coarse sand (sand:mud ratio = 9:1) to sandy silt (sZ) followed by muddy sand (mS) and slightly gravelly sandy mud ((g)sM). Total organic carbon (TOC) in the surface sediments were also characterized based on a particle-size analysis. The mean change in tidal height measured at Hwangdo Bridge during the sampling period was ~7.53 m (minimum: –3.86 m, maximum: +3.67 m). Based on the Boryeong's sea level measurement tide data in 2022, the tidal area in the drone images ranged from 6.362 m² (0.006 km²) at DEM +4.0 to 4,841,078 m² (4.841 km²) at DEM –4.0 m, indicating an increase in the tidal-flat area according to the tidal level of up to ~800-fold. The daily average exposure time was 9.0 h (minimum: 1.5 h, maximum: 17.9 h). Based on the results of multivariate analysis using exposure times and a geochemical dataset, four groups were identified: upper, middle, and lower intertidal zones and regions with a relatively high organic-matter concentration. A determination of the main characteristics of the Hwangdo tidal flat according to their spatial distribution showed that, among various environmental factors, changes in the sand or clay sediment composition were determined by community factors. The results of this study demonstrate the four statistically processed groups of marine environmental characteristics in the Hwangdo tidal flats. Changes in sedimentary patterns, rather than in the exposure time, accounted for the differences in the sediment compositions of the upper, middle, and lower stations, a response that is expected to continue.

Knowledge of permafrost’s ice and unfrozen water content is critical for predicting the permafrost behavior during ice–water–ice transition. This is especially relevant when ice and permafrost are melting in many regions under the influence of global warming. It is well-known that only a part of the formation's pore water turns into ice at 0 ^oC. After the further lowering the temperature, the water phase transition continues, but at gradually decreasing rates. Thus, the porous space is filled with ice and unfrozen water. The laboratory data show that frozen formations' mechanical, thermal, and rheological properties strongly depend on the moisture content. Hence, porosity and temperature are essential parameters of permafrost. In this paper, it is shown how, and by combining research in three fields: (1) geophysical exploration, (2) numerical modeling, and (3) temperature logging, it is possible to estimate in-situ the porosity of permafrost. To demonstrate the procedure, five examples of numerical modeling (where all input parameters are specified) are given. This investigation is the first attempt to analyze the permafrost’s porosity in situ quantitively.

The aim of this study was to compare the effectiveness of propofol-based sedation and midazo-lam sedation in same-day bidirectional endoscopy (BDE) in children. The charts of children (≤15 years old) who had undergone same-day BDE were retrospectively reviewed. Demographic data, indications, sedatives and their dosages, clinical outcomes, endoscopic findings, adverse events, and patient time requirements were compared in cases with propofol-based and midazolam se-dation. A total of 91 children [51 boys, mean age 13 years (range 9-15)] were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was given in 51 (propofol-based sedation group) while midazolam alone or in combination with pentazocine was given in 40 (midazolam sedation group). The mean doses of propofol, midazolam and pentazocine were 96 mg (range 40–145 mg), 4.1 mg (range 3–5 mg) and 7.5 mg in the propofol group while the mean doses of midazolam and pentazocine were 6.2 mg (range 4–10 mg) and 15 mg in the midazolam group, respectively. The total procedure times and endoscopic findings between the two groups were similar, but the median patient time requirement in the propofol group was significantly shorter than that of the midazolam group (7.3 h vs. 8.4 h, P<0.001). No adverse events occurred in either group. Propofol-based sedation shortened patient time requirements in same-day BDE compared with midazolam sedation in children.

In this paper we exploit concepts from Information Theory to improve the classical Chvatal’s greedy algorithm for the Set Covering Problem. In particular, we develop a new greedy procedure, called Surprisal-Based Greedy Heuristic (SBH), incorporating the computation of a “surprisal” measure when selecting the solution columns. Computational experiments, performed on instances from the OR-Library, show that SBH yields a 2.5% improvement in terms of the objective function value over the Chvatal’s algorithm while retaining similar execution times, making it suitable for real-time applications. The new heuristic was also compared with Kordalewski’s greedy algorithm, obtaining similar solutions with much lower times on large instances, and Grossmann and Wool’s algorithm for unicost instances, where SBH obtained better solutions.

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

Deep-learning-based speech enhancement techniques have been recently grown in interest, since their impressive performance can potentially benefit a wide variety of digital voice communication systems. However, such performance has been evaluated mostly in offline audio processing scenarios (i.e. feeding the model, in one go, a complete audio recording, which may extend several seconds). It is of great interest to evaluate and characterize the current state-of-the-art in applications that process audio online (i.e. feeding the model a sequence of segments of audio data, concatenating the results at the output end). Although evaluations and comparisons between speech enhancement techniques have been carried out before, as far as the author knows, the work presented here is the first that evaluates the performance of such techniques in relation to their online applicability. Meaning, this work measures how the output signal-to-interference ratio (as a separation metric), the response time and memory usage (as online metrics) are impacted by the input length (the size of audio segments), in addition to the amount of noise, amount and number of interferences, and amount of reverberation. Three popular models were evaluated, given their availability on public repositories and online viability: MetricGAN+, Spectral Feature Mapping with Mimic Loss, and Demucs-Denoiser. The characterization was carried out using a systematic evaluation protocol based on the Speechbrain framework. Several intuitions are presented and discussed, and some recommendations for future work are proposed.

This study presents the developments regarding the time-domain-induced polarisation method, as a supporting tool for resistivity soundings during investigations of coastal detrital aquifers that are salinised by marine intrusion. The interpretation of resistivity measurements in such aquifers, which have variable hydrochemistry and lithology, involves uncertainties owing to the presence of low-resistivity lithologies, such as clays. To reduce these uncertainties, the use of other geophysical parameters is necessary; hence, this study focuses on induced polarisation, since it can be measured simultaneously with resistivity. In detail, we propose the determination of induced polarisation using 1D techniques, while developing a different algorithm for processing the induced polarisation data. The aim is to extend the results of this phenomenon, using instead of chargeability, the concepts of polarisability and decay time, which are extracted from the decay curve, given that they represent more intrinsic properties of the various analysed subsurface media. We present results obtained by applying this methodology to a Quaternary aquifer of the Costa del Sol in the SE Iberian Peninsula (in the province of Almería) during two different campaigns, one before and one after winter (i.e., in October and February, respectively). The results reveal the position of the saline front during each campaign, while reflecting the seasonal movement of the marine intrusion.

Inspired by recent developments in wave propagation and scattering experiments with parity-time (PT) symmetric materials, we discuss reciprocity and representation theorems for 3D inhomogeneous PT-symmetric materials and indicate some applications. We start with a unified matrix-vector wave equation which accounts for acoustic, quantum-mechanical, electromagnetic, elastodynamic, poroelastodynamic, piezoelectric and seismoelectric waves. Based on the symmetry properties of the operator matrix in this equation, we derive unified reciprocity theorems for wave fields in 3D arbitrary inhomogeneous media and 3D inhomogeneous media with PT-symmetry. These theorems form the basis for deriving unified wave field representations and relations between reflection and transmission responses in such media. Among the potential applications are interferometric Green’s matrix retrieval and Marchenko-type Green’s matrix retrieval in PT-symmetric materials.

In this work, the hypothesis that the universe is made up of 4-dimensional spheres of space, whose diameter is the Planck length, allows us to calculate most of the constants used in current physical theories. Calculated constants include: elementary charge, fine structure constant, electron mass, Planck constant, gravitational constant, electrical constant, Boltzmann constant, mass and charge of up and down quarks, muon mass, and Higgs boson. All of these depend on the speed of light and the Planck length, which shows that all the constants are related and not due to chance.

Screen viewing time is the total time spent by a child on any digital/electronic device. The objective of the present study was to determine the incidence and predictors of excessive screen viewing time in children in Ujjain, India. This cross-sectional, community-based study was conducted through house-to-house survey by using the three-stage cluster sampling method in 36 urban wards and 36 villages of Ujjain district, India. Excessive screen viewing time was defined as screen viewing for &gt; 2 h/day. The prevalence of excessive screen viewing time was 17.83%. Risk factors identified using the multivariate logistic regression model were: age (OR: 1.5, P &lt; 0.001); mobile phone use before bedtime (OR: 3.17, P = 0.008); parents’ perception about the child habituated to screen (OR: 14.03, P &lt; 0.001); television in bedroom (OR: 48.69, P &lt; 0.001); morning mobile screen viewing time (OR: 9.27, P &lt; 0.001); not reading books other than textbooks (OR: 9.71, P &lt; 0.001); and lack of outdoor play for &gt;2 h (OR: 4.20, P &lt; 0.001). Presence of eye pain was a protective factor for excessive screen viewing time (OR: 0.12, P = 0.011). The study identified multiple modifiable risk factors for excessive screen viewing time.

Multi-objective optimization (MOO) is an optimization involving minimization or maximization of several objective functions more than the conventional one objective optimization, which is useful in many fields. Many of the current methodologies addresses challenges and solutions that attempt to solve simultaneously several Objectives with multiple constraints subjoined to each. Often MOO are generally subjected to linear inequality, equality and or bounded constraint that prevent all objectives from being optimized at once. This paper reviews some recent articles in area of MOO and presents deep analysis of Random and Uniform Entry-Exit time of objectives. It further break down process into sub-process and then provide some new concepts for solving problems in MOO, which comes due to periodical objectives that do not stay for the entire duration of process lifetime, unlike permanent objectives which are optimized once for the entire process duration. A methodology based on partial optimization that optimizes each objective iteratively and weight convergence method that optimizes sub-group of objectives are given. Furthermore, another method is introduced which involve objective classification, ranking, estimation and prediction where objectives are classified based on their properties, and ranked using a given criteria and in addition estimated for an optimal weight point (pareto optimal point) if it certifies a coveted optimal weight point. Then finally predicted to find how far it deviates from the estimated optimal weight point. A Sample Mathematical Tri-Objectives and Real world Optimization was analyzed using partial method, ranking and classification method, the result showed that an objective can be added or removed without affecting previous or existing optimal solutions. Therefore suitable for handling time governed MOO. Although this paper presents concepts work only, it’s practical application are beyond the scope of this paper, however base on analysis and examples presented, the concept is worthy of igniting further research and application.

Reservoir computing is a machine learning method that uses the response of a dynamical system to a certain input in order to solve a task. As the training scheme only involves optimising the weights of the responses of the dynamical system, this method is particularly suited for hardware implementation. Furthermore, the inherent memory of dynamical systems which are suitable for use as reservoirs mean that this method has the potential to perform well on time series prediction tasks, as well as other tasks with time dependence. However, reservoir computing still requires extensive task dependent parameter optimisation in order to achieve good performance. We demonstrate that by including a time-delayed version of the input for various time series prediction tasks, good performance can be achieved with an unoptimised reservoir. Furthermore, we show that by including the appropriate time-delayed input, one unaltered reservoir can perform well on six different time series prediction tasks at a very low computational expense. Our approach is of particular relevance to hardware implemented reservoirs, as one does not necessarily have access to pertinent optimisation parameters in physical systems but the inclusion of an additional input is generally possible.

This paper describes a polynomial time algorithm for solving graph isomorphism and automorphism. We introduce a new tree data structure called Walk Length Tree. We show that such tree can be both constructed and compared with another in polynomial time. We prove that graph isomorphism and automorphism can be solved in polynomial time using Walk Length Trees.

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

P versus NP is considered as one of the most fundamental open problems in computer science. This consists in knowing the answer of the following question: Is P equal to NP? It was essentially mentioned in 1955 from a letter written by John Nash to the United States National Security Agency. However, a precise statement of the P versus NP problem was introduced independently by Stephen Cook and Leonid Levin. Since that date, all efforts to find a proof for this problem have failed. Another major complexity class is NP-complete. It is well-known that P is equal to NP under the assumption of the existence of a polynomial time algorithm for some NP-complete. We show that the Monotone Weighted Xor 2-satisfiability problem (MWX2SAT) is NP-complete and P at the same time. Certainly, we make a polynomial time reduction from every directed graph and positive integer k in the K-CLOSURE problem to an instance of MWX2SAT. In this way, we show that MWX2SAT is also an NP-complete problem. Moreover, we create and implement a polynomial time algorithm which decides the instances of MWX2SAT. Consequently, we prove that P = NP.

Traditional applications of Interferometric Synthetic Aperture Radar (InSAR) data involved inverting an interferogram stack to determine the average displacement velocity. While this approach has useful applications in continuously deforming regions, much information is lost by simply fitting a line through the time series. Thanks to regular acquisitions across most of the the world by the ESA Sentinel-1 satellite constellation, we are now in a position to explore opportunities for near-real time deformation monitoring. In this paper we present a simple statistical approach for detecting offsets and gradient changes in InSAR time series. Our key assumption is that 5 years of Sentinel-1 data is sufficient to calculate the population standard deviation of the detection variables. Our offset detector identifies statistically significant peaks in the first, second and third difference series. The gradient change detector identifies statistically significant movements in the second derivative series. We exploit the high spatial resolution of Sentinel-1 data and the spatial continuity of geophysical deformation signals to filter out false positive detections that arise due to signal noise. When combined with near-real time processing of InSAR data these detectors, particularly the gradient change, could be used to detect incipient ground deformation associated with geophysical phenomena, for example from landslides or volcanic eruptions.

The necessity of the dark energy and dark matter in the present universe could be a consequence of the antimatter elimination assumption in the early universe. In this research, I derive a new model to obtain the cosmic horizon radius and the potential cosmic topology utilising a new construal of space geometry inspired by large-angle correlations of the cosmic microwave background (CMB). A version of the Big Bounce theory is utilised to avoid the Big Bang singularity and inflationary constraints, and to tune the initial conditions of the curvature density. The mathematical derivation of a positively curved universe governed by only gravity revealed two cosmic horizon solutions. Although the positive horizon is conventionally associated with the evolution of the matter universe, the negative horizon solution could imply additional evolution in the opposite direction. This possibly suggests that the matter and antimatter could be evolving in opposite directions as distinct sides of the universe, as in the visualised Sloan Digital Sky Survey. The cosmic horizon radius is found to be accountable for the universal space curvature. By implementing this model, we find a decelerated stage of expansion during the first 10 Gyr, which is followed by a second stage of an accelerated expansion; potentially matching the tension in Hubble parameter measurements. In addition, the model predicts a final time-reversal stage of spatial contraction leading to the Big Crunch of a cyclic universe. The predicted density is 1.14. Other predictions are (1) a calculable flow rate of the matter side towards the antimatter side at the accelerated stage; conceivably explaining the dark flow observation, (2) a time-dependent spacetime curvature over horizon evolution, which could influence the galactic rotational speed; possibly explaining the high speed of stars, and (3) evolvable spacetime internal voids at the accelerated stage, which could contribute in continuously increasing the matter and antimatter densities elsewhere in both sides respectively. These findings may indicate the existence of the antimatter as a distinct side, which influences the evolution of the universe instead of the dark energy or dark matter.

We employ another approach to quantize electromagnetic fields in the coordinate space, instead of the mode (or Fourier) space, such that local features of photons can be efficiently, physically, and more intuitively described. To do this, coordinate-ladder operators are defined from mode-ladder operators via the unitary transformation of systems involved in arbitrary inhomogeneous dielectric media. Then, one can expand electromagnetic field operators through the coordinate-ladder operators weighted by non-orthogonal and spatially-localized bases, which are propagators of initial quantum electromagnetic (complex-valued) field operators. Here, we call them QEM-CV-propagators. However, there are no general closed form solutions available for them. This inspires us to develop a quantum finite-difference time-domain (Q-FDTD) scheme to numerically time evolve QEM-CV-propagators. In order to check the validity of the proposed Q-FDTD scheme, we perform computer simulations to observe the Hong-Ou-Mandel effect resulting from the destructive interference of two photons in a 50/50 quantum beam splitter.

The Aβ cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction and neuronal injury followed by Aβ have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aβ, the change of tau, NfL and NG is the main alternation and connection to others. The neuro-inflammation, synaptic dysfunction and neuronal injury function is exhibited prior the structural and metabolic changes in the brain following Aβ deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aβ deposition, several factors favor one or the other. There is an interaction between the proteins that CSF SNAP-25, VILIP-1 and YKL-40 can predict the brain amyloid burden. The Aβ cascade hypothesis could be the pathway, but not all subjects are converted to AD, even with very high elevated Aβ. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.

The study of order patterns of three equally spaced values $x_t,x_{t+d},x_{t+2d}$ in a time series is a powerful tool. The lag $d$ is changed in a wide range so that differences of frequencies of order patterns become autocorrelation functions. Similar to a spectrogram in speech analysis, four ordinal autocorrelation functions are used to visualize big data series, as for instance heart and brain activity over many hours. The method applies to real data without preprocessing, outliers and missing data do not matter. On the theoretical side, we study properties of order correlation functions and show that the four autocorrelation functions are orthogonal in a certain sense. An analysis of variance of a modified permutation entropy can be performed with four variance components associated with the functions.

A highly dirt resistant paint for building facades without chemicals harmful to nature and environment, is developed which resolves the unattractive disfigurement of building walls caused by dirt. The experimentation is scientifically and statistically planned with the aid of computer programming. It consists of a sequence of phases which include the selection of appropriate raw materials, adopting of Basic Language computer programming to generate a target population of paint formulations. The average PVC percentage is computed using theory and found to be 54.98% for the target population of 543143 paint formulations hence verifies the literature results. Experimentation and statistical analysis are performed to compare the classical conventional agitator with latest lab equipment like Nano mill and it is concluded that Nano mill performs better on the average than conventional agitator in preparation of paint formulations. Hence the sample of paint formulations is prepared on Nano mill and tested in laboratory using advanced available technology for the analysis and comparison of paint properties to determine the best paint formulation. The results are analyzed using Analysis Of Variance Technique (ANOVA) and it is concluded that the paint formulation named “O3” has the highest dirt resistance on the average. The final selected formula O3 is compared with three other competitor paints in market under natural environment for a period of almost one year. A regression model is also constructed to study the effect of environmental factors like time, temperature and humidity on dirt resistance of paints. It is found that O3 formulation is the best environment friendly which performs equally well with one competitor paint and has higher dirt resistance than two other competitor paint formulations containing harmful chemicals. The regression model of dirt resistance on variables including time, temperature and humidity shows that these factors are significantly affecting the dirt resistance of a given paint at 5% level of significance. 95.34% variation in the dirt resistance of a given paint is due to and explained by the given factors. The regression model is useful to predict the average dirt resistance of a given paint with a certain level of confidence. The project exemplifies the work of an applied research from conceptualization to successful commercialization for the paint industry.

The current work investigates how adding a battery of optimal capacity to a grid-connected photovoltaic (PV) system can improve its economic feasibility. Also, the effect of different parameters on the feasibility of the PV system was evaluated. The OBC was determined for different saving targets of the annual electricity consumption of the chosen building. For this aim, real electricity consumption data of a residential building in Landskrona, Sweden, was used as energy consumption profile. Solar World SW325XL, which is a monocrystalline solar panel, was selected as PV panels. The calculations were performed under the metrological and economic conditions of southern Sweden. Different working parameters (WP)were considered (prices of the battery, feed-in tariffs, and saving targets). The performed calculations show that the optimal battery capacity (OBC), in which the payback time (PBT) of the system is maximized, strongly depends on the WP. The proper selection of the battery can considerably increase the economic feasibility of the PV system in southern Sweden. However, in some cases, using battery can have a negative impact on the PBT of the system. The results show that the electricity price, the module price, the inverter price, and the inverter lifetime have the highest effect on the PBT.

Operational weather and also flood forecasting has been performed successfully for decades and is of great socioeconomic importance. Up to now, forecast products focus on atmospheric variables, such as precipitation, air temperature and, in hydrology, on river discharge. Considering the full terrestrial system from groundwater across the land surface into the atmosphere, a number of important hydrologic variables are missing especially with regard to the shallow and deeper subsurface (e.g. groundwater), which are gaining considerable attention in the context of global change. In this study, we propose a terrestrial monitoring/forecasting system using the Terrestrial Systems Modeling Platform (TSMP) that predicts all essential states and fluxes of the terrestrial hydrologic and energy cycles from groundwater into the atmosphere. Closure of the terrestrial cycles provides a physically consistent picture of the terrestrial system in TSMP. TSMP has been implemented over a regional domain over North Rhine-Westphalia and a continental domain over European in a real-time forecast/monitoring workflow. Applying a real-time forecasting/monitoring workflow over both domains, experimental forecasts are being produced with different lead times since the beginning of 2016. Real-time forecast/monitoring products encompass all compartments of the terrestrial system including additional hydrologic variables, such as plant available soil water, groundwater table depth, and groundwater recharge and storage.

Reducing sedentary behaviours can help prevent non-communicable diseases, particularly among young adolescents with long term illnesses or disabilities (LTID). Much of young people’s voluntary sedentary time is related to screen-time behaviours (STBs) such as TV viewing, playing computer games, and using the computer for other activities. Although public health data on adolescents’ STB is growing, information about adolescents with LTID is currently lacking in a European context. The purpose of this study is to compare time on STBs between adolescents with and without LTID in European Countries through the HBSC 2013/14 study. Young adolescents (n = 61,329; boys 47.8%) from 15 European countries reported the time spent on TV viewing, playing computer games, and using the computer for other purposes on weekdays and the weekend. STBs were dichotomised based on international recommendations of less than 2 h per day, and Chi-square tests of independence were performed to investigate differences. STB time was combined to produce a sum score as dependent variable in multiple analysis of covariance with age and family affluence as covariates. There were statistically significant differences in computer gaming among boys and other computer use among girls for both weekdays and weekends, whereby adolescents with LTID reported higher use. In addition, both boys and girls with LTID spent more time on STBs than their same sex peers without LTID (Boys, F = 28.17, p < 0.001; Girls, F = 9.60, p = 0.002). The results of this study indicate a need for preventive strategies to address high levels of STB among young adolescents with LTID and reduce the risk of poor health outcomes associated with higher levels of sedentary behaviour.

Bijective Analysis of 4D Minkowski space-time model confirms that 4D space-time where time would be 4th dimension of space does not exist. In 4D manifold, time is the duration of a physical event which runs in space. An event does not have the duration in time, duration itself is time. It means that any given physical phenomena can only be symmetric in space; not in time.

Prolonged sedentary behaviour (SB) has shown to be detrimental to health. Nevertheless, population levels of SB are high and interventions to decrease SB are needed. This study aimed to explore the effect of an individualized consultation intervention aimed at reducing SB and increasing breaks in SB among college employees. A pre-experimental study design was used. Participants (n=36) were recruited at a college in Massachusetts, USA. SB was measured over 7 consecutive days using an activPAL3 accelerometer. Following baseline measures, all participants received an individualized SB consultation which focused on limiting bouts of SB >30 minutes, participants also received weekly follow-up e-mails. Post-intervention measures were taken after 16 weeks. Primary outcome variables were sedentary minutes/day and SB bouts >30 minutes. Differences between baseline and follow-up were analyzed using paired t-tests. The intervention did not change daily sedentary time (-0.48%; p>0.05). The number of sedentary bouts >30 minutes decreased significantly by 0.52 bouts/day (p=0.015). In this study a consultation based SB intervention was successful in reducing number of bouts >30 minutes of SB. However, daily sedentary time did not reduce significantly. These results indicate that consultation-based interventions may be effective if focused on a specific component of SB.

Flower bud formation and flowering in chrysanthemum occur under short day conditions (SD), but the molecular basis for the switch to reproductive growth is less well understood than in model plants. Here, a spontaneous mutant able to flower under long days is described. In an attempt to reveal the pathway(s) involved in the formation of flower buds under contrasting daylengths, transcriptome sequencing was carried out in plants grown both under SD and under long day conditions (LD). A number of differentially transcribed genes involved in the various known flowering pathways were identified. Both circadian clock genes and CmFTL3 were up-regulated under SD, thereby inducing floral bud formation and flowering. The gibberellin (GA) signalling pathway-related genes GA20ox and GID1 were up-regulated in the mutant under LD, while the catabolic gene GA2ox and GAI was down-regulated, thereby inducing the transcription of CmFTL1, SOC1 and LFY. The GA content of the leaf was higher in the mutant than in the wild type under LD. When treated with GA, the mutant flowered earlier under both SD and LD, but there was no other detectable phenotype difference between the two lines. The indication was that the photoperiod pathway majorly regulates flower bud formation and flowering time in chrysanthemum under SD. GA signalling pathway only plays a subsidiary role for flowering. However, the GA signalling pathway predominated for flowering under LD.

Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process. The benefits offered by the LIF experimental technique have been demonstrated and some frequent problems in its application analysed. The mixing time results for configurations with and without baffles for three types of impellers and four different rotational speeds have been presented. The false shorter mixing times in the non-baffled configurations have been observed and this phenomena explained by the existence of two segregated zones in the reactor and confirmed by additional experiments. The precise measurements in these cases have been shown as difficult using the LIF technique, particularly for higher rpms. The experimental data has been compared to the preliminary simulation results obtained from the Smoothed Particle Hydrodynamics method and the standard k-ε turbulence model with the modest success. The shortcomings of the SPH model have been recognized and the directions for the future work discussed.

Due to a simple crane limited capacity; there is an urgent need to use high capacity cranes such as tower cranes. However, with regard to their high expense, we have to take into consideration selecting what type of cranes to be utilized which has been discussed by many researchers. In this research, a proposed technique was created to select the suitable type of crane and best place for crane erection, in addition to minimum radius for requested crane in order to minimize cost. To fulfill that target, a computer program is designed to numerate these problems, demonstrating an example explaining how to apply program and the result donated best place.

The stock beta coefficient literature extensively discusses the proper methods for the estimation of beta as well as its use in asset valuation. However, there are relatively few references with respect to the appropriate time horizon that investors should utilize when evaluating the risk-return relationship of a stock. We examine the appropriate time horizon for beta estimation differentiating our results by sector according to the Industry Classification Benchmark. We employ data from the NYSE and we estimate varying lengths of beta employing data from 30 to 250 trading days. The constructed beta series is then examined for the presence of breaks using the endogenous structural break literature. Results show evidence against the use of betas that employ more than 90 trading days of data provisional to the sector under study.

While the COVID-19 outbreak was reported to first originate from Wuhan, China, it has been declared as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 by WHO, and it has spread to over 180 countries by the time of this paper was being composed. As the disease spreads around the globe, it has evolved into a worldwide pandemic, endangering the state of global public health and becoming a serious threat to the global community. To combat and prevent the spread of the disease, all individuals should be well-informed of the rapidly changing state of COVID-19. In the endeavor of accomplishing this objective, a COVID-19 real-time analytical tracker has been built to provide the latest status of the disease and relevant analytical insights. The real-time tracker is designed to cater to the general audience without advanced statistical aptitude. It aims to communicate insights through various straightforward and concise data visualizations that are supported by sound statistical foundations and reliable data sources. This paper aims to discuss the major methodologies which are utilized to generate the insights displayed on the real-time tracker, which include real-time data retrieval, normalization techniques, ARIMA time-series forecasting, and logistic regression models. In addition to introducing the details and motivations of the utilized methodologies, the paper additionally features some key discoveries that have been derived in regard to COVID-19 using the methodologies.

Determination of indoor location based on fine time measurement (FTM) of the round trip time (RTT) of a signal between an initiator (smartphone) and a responder (Wi-Fi access point) enables a number of applications. However, the accuracy currently attainable — standard deviations of 1–2 meter in distance measurement under favorable circumstances — limits the range of possible application. A first responder, for example, may not be able to unequivocally determine on which floor someone in need of help is in a multi-story building. The error in location depends on several factors, including the bandwidth of the RF signal, delay of the signal due to the high relative permittivity of construction materials, and the geometry-dependent “noise gain” of location determination. Errors in distance measurements have unusual properties that are exposed here for the first time. Improvements in accuracy depend on understanding all of these error sources. This paper introduces “frequency diversity,” a method for doubling the accuracy of indoor location determination using weighted averages of measurements with uncorrelated errors obtained in different channels. The properties of this method are verified experimentally with a range of responders. Finally, different ways of using the distance measurements to determine indoor location are discussed and the Bayesian grid update method shown to be more useful than others, given the non- Gaussian nature of the measurement errors.

The COVID-19 pandemic has created huge damage to society and brought panics around the world. Such panics can be ascribed to the seemingly deceptive features of the COVID-19: compared to other deadly viral outspreads, it has medium transmission and mortality rates. As a result, the severity of the causative coronavirus, SARS-CoV-2, was deeply underestimated by the society at the beginning of the COVID-19 outbreak. Based on this, in this review, we define the viruses with features similar to those of SARS-CoV-2 as the Panic Zone viruses. To contain those viruses, accurate and fast diagnosis followed by effective isolation and treatment of patients are pivotal at the early stage of virus breakouts. This is especially true when there is no cure or vaccine available for a transmissible disease, which is the case for current COVID-19 pandemic. As of January 2021, more than two hundred kits for the COVID-19 diagnosis on the market are surveyed in this review, while emerging sensing techniques for SARS-CoV-2 are also discussed. It is of critical importance to rationally use these kits for the efficient management and control of the Panic Zone viruses. Therefore, we discuss guidelines to select diagnostic kits at different outbreak stages of the Panic Zone viruses, SARS-CoV-2 in particular. While it is of utmost importance to use nucleic acid-based detection kits with low false negativity (high sensitivity) at the early stage of an outbreak, the low false positivity (high specificity) gains its importance at later stages of the outbreak. When a society is set to reopen from the lock-down stage of the COVID-19 pandemic, it becomes critical to have antibody based immunoassay kits with high specificity to identify people who can safely return to the society after their recovery of SARS-CoV-2 infections. Given that the emergence of mutant viruses at the beginning of 2021 has complicated current battle against the COVID-19, we also discussed approaches and guidelines to detect viral mutants in the middle of the second wave of the pandemic that started at the end of 2020. Finally, since a massive attack from a viral pandemic requires a massive defense from the whole society, we urge both government and private sectors to research and develop more affordable and reliable point-of-care testing (POCT) kits, which can be used massively by the general public (and therefore called as massive POCT) to contain Panic Zone viruses in future.

The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as ‘long- COVID’, emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review provides a summary of the primary effects of long COVID on the cardiovascular, nervous, and respiratory systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

To control the COVID-19 pandemic, many countries implemented vaccination and imposed societal restrictions both at the national level and for international travel. As a check of the corona status, a COVID pass has been issued. A COVID pass could be obtained when fully vaccinated against COVID-19, having recovered from a documented COVID-19 episode, or a recent (24-48 hours) negative SARS-CoV-2 antigen test. A global analysis of SARS-CoV-2 immune status (determined by past infection and/or vaccination), vaccination rates, as well as societal restrictions in controlling the COVID-19 pandemic is presented.

The Puuc Biocultural State Reserve (PBSR is an unique model for tropical dry forest conservation in Mexico. Preserving forest biodiversity and carbon within the PBSR depends on the mainte-nance of low impact productive activities coordinated by multiple communal and private land-owners. In this study, we used state-of-the-art remote sensing data to investigate past spatial patterns in forest clearing dynamics and its relation to forest carbon density and forest plant species richness and diversity in the context of the forest conservation goals of the PBSR. We used a Landsat-based continuous change detection product for the 2000-2021 period and compared it to carbon density and tree species richness models generated from ALOS-2 PALSAR 2 imagery and national scale forest inventory data. The estimated error-adjusted area of detected annual forest clearings from the year 2000 until the year 2021 was 230,511 ha in total (+19,979 ha). The analysis of annual forest clearing frequency and area suggests that although forest clearing was significantly more intensive outside of the PBSR than within the PBSR during the entire 2000-2021 period, there is no evidence suggesting that the frequency and magnitude of forest clearing has changed over the years after the creation of the PBSR in 2011. An emergent hotspot analysis shows, however, that high spatiotemporal clustering of forest clearing events (hotspots) during the 2012-2021 pe-riod was less common than prior to 2011 and these more recent hotspots have been confined to areas outside the PBSR. After comparing forest clearing events to carbon density and tree species richness models, results show that land owners outside the PBSR often clear forests with lower carbon density and species diversity than land owners inside the PBSR. This suggests that, compared to land owners outside the PBSR, land owners within the PBSR might be practicing longer fallow periods allowing forests to attain higher carbon density and tree species richness and hence better soil nutrient recovery after land abandonment. In conclusion, our results show that the PBSR effectively acted as a stabilizing forest management scheme during the 2012-2021 period minimizing the impact of productive activities by lowering the frequency of forest clearing events and preserving late secondary forests within the PBSR. We recommend the continuation of efforts for providing alternative optimal field data collection strategies and modeling techniques to spatially predict key tropical forest attributes. The combination of these models with contin-uous change detection datasets will allow to reveal underlying ecological processes and generate information better adapted to forest governance scales.

Background & aims. The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. Methods. LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T cell responses were measured before and two months following the fourth vaccine dose, and anti-SARS-CoV-2-s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. Results. Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2-s-RBD antibodies. The mean antibody titer was 8944 UI/ml. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T cell response. Two patients (one positive for T cell response) developed a self-limited SARS-CoV-2 infection. Conclusions. Suspending MMF prior to the fourth dose of anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.

This work is mainly focused on improving the differential evolution algorithm with the utilization of shadowed and general type 2 fuzzy systems to dynamically adapt one of the parameters of the evolutionary method. In this case, the mutation parameter is dynamically moved during the evolution process by using a shadowed and general type-2 fuzzy systems. The main idea of this work is to make a performance comparison between using shadowed and general type 2 fuzzy systems as controllers of the mutation parameter in differential evolution. The performance is compared with the problem of optimizing fuzzy controllers for a D.C. Motor. Simulation results show that general type-2 fuzzy systems are better when higher levels of noise are considered in the controller.

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection or inflammation of the ENS highlights its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI disorders such as short bowel syndrome with neuronal pathophysiology. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances, and ultimately change our approach to GI disorders.

SARS-CoV-2, the causal agent of the globally spreading COVID-19, is capable of infecting variable animals besides human being. We evaluated the potential susceptibility of important livestock, pets and aquatic mammals by performing a multi-species sequence analysis of ACE2 based on the reported affected and unaffected animals. We identified a triple amino acid pattern of ACE2, at position 30, 31 and 34, that might be associated with SARS-CoV-2 infection and H34 might be an indicator of the susceptibility to COVID-19.

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2, predicting potential intermediate hosts of SARS-CoV-2.

Thermally-assisted-occupation density functional theory (TAO-DFT) has been an efficient electronic structure method for studying the ground-state properties of large electronic systems with multi-reference character over the past few years. To explore the time-dependent (TD) properties of electronic systems (e.g., subject to an intense laser pulse), in this work, we propose a real-time (RT) extension of TAO-DFT, denoted as RT-TAO-DFT. Besides, we employ RT-TAO-DFT to study the high-order harmonic generation (HHG) spectra and related TD properties of molecular hydrogen H2 at the equilibrium and stretched geometries, aligned along the polarization of an intense linearly polarized laser pulse. The TD properties obtained with RT-TAO-DFT are compared with those obtained with the widely used time-dependent Kohn-Sham (TDKS) method. In addition, issues related to the possible spin-symmetry breaking effects in the TD properties are discussed.

With simple but rigorous arguments we prove that the ordinary second quantization of bosonic and fermionc fields is formally equivalent to constraining the elementary degrees of freedom of the classical fields to have intrinsically periodic dynamics in time. This result confirms and extends the formal equivalence obtained in previous papers for general Hamiltonian systems in terms of canonical quantization, for elementary relativistic particles also in terms of the Feynman Path Integrals, as well as other remarkable correspondences of both phenomenological and theoretical fundamental interest.

We construct admissible circulant Laplacian matrix functions as generators for strictly increasing random walks on the integer line. These Laplacian matrix functions refer to a certain class of Bernstein functions. The approach has connections with biased walks on digraphs. Within this framework, we introduce a space-time generalization of the Poisson process as a strictly increasing walk with discrete Mittag-Leffler jumps subordinated to a (continuous-time) fractional Poisson process. We call this process ‘space-time Mittag-Leffler process’. We derive explicit formulae for the state probabilities which solve a Cauchy problem with a Kolmogorov-Feller (forward) difference-differential equation of general fractional type. We analyze a “well-scaled” diffusion limit and obtain a Cauchy problem with a space-time convolution equation involving Mittag-Leffler densities. We deduce in this limit the ‘state density kernel’ solving this Cauchy problem. It turns out that the diffusion limit exhibits connections to Prabhakar general fractional calculus. We also analyze in this way a generalization of the space-time fractional Mittag-Leffler process. The approach of construction of good Laplacian generator functions has a large potential in applications of space-time generalizations of the Poisson process and in the field of continuous-time random walks on digraphs.

The independent set, IS, on a graph $G=(V,E)$ is $V^{*}\subseteq V$ such that no two vertices in $V^{*}$ have an edge between them. The MIS problem on G seeks to identify an IS with maximum cardinality, i.e. MIS. $V^{*}\subseteq V$ is a vertex cover, i.e. VC of $G=(V,E)$ if every $e\in E$ is incident upon at least one vertex in $V^{*}$ . $V^{*}\subseteq V$ is dominating set, DS, of $G=(V,E)$ if $\forall v\in V$ either $v\in V^{*}$ or $\exists u\in V^{*}$ and $(u,v)\in E$ . The MVC problem on G seeks to identify a vertex cover with minimum cardinality, i.e. MVC. Likewise, MCV seeks a connected vertex cover, i.e. VC which forms one component in G, with minimum cardinality, i.e. MCV. A connected DS, CDS, is a DS that forms a connected component in G. The problems MDS and MCD seek to identify a DS and a connected DS i.e. CDS respectively with minimum cardinalities. MIS, MVC, MDS, MCV and MCD on a general graph are known to be NP-complete. Polynomial time algorithms are known for bipartite graphs, chordal graphs, cycle graphs, comparability graphs, claw-free graphs, interval graphs and circular arc graphs for some of these problems. We introduce a novel graph class, layered graph, where each layer refers to a subgraph containing at most some k vertices. Inter layer edges are restricted to the vertices in adjacent layers. We show that if $k=\Theta (log\mid V\mid )$ then MIS, MVC and MDS can be computed in polynomial time and if $k=O\left({(log\mid V\mid )}^{\alpha }\right)$ , where $\alpha <1$ , then MCV and MCD can be computed in polynomial time. If $k=\Theta \left({(log\mid V\mid )}^{1+ϵ}\right)$ , for $ϵ>0$ , then MIS, MVC and MDS require quasi-polynomial time. If $k=\Theta (log\mid V\mid )$ then MCV, MCD require quasi-polynomial time. Layered graphs do have constraints such as bipartiteness, planarity and acyclicity.

New exact solutions to conformable time fractional EW and modified EW equations are constructed by using Sine-Gordon expansion approach. The fractional traveling wave transform and homogeneous balance have significant roles in the solution procedure. The predicted solution is of the form of some finite series of multiplication of powers of cos and sin functions. The relation among trigonometric and hyperbolic functions in sense of Sine-Gordon expansion gives opportunity to construct the solutions in terms of hyperbolic functions.

Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rate during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare maternal and obstetric complications between women who seroconverted in the first versus the third trimester. This is an observational, cohort study carried out at Hospital Universitario de Torrejón, in Madrid, Spain, during the first peak of the COVID-19 pandemic. All consecutive singleton pregnancies with a viable fetus attending their 11-13 weeks scan between January 1st and May 15th, 2020, were included and monthly follow up until delivery. Antibodies against SARS-CoV-2 (IgA and IgG) were analyzed on stored serum samples obtained from the first and third trimester routine antenatal bloods in 470 pregnant women. Antibodies against SARS-CoV-2 were detected in 31 (6.6%) women in the first trimester and in 66 (14.0%) in the third trimester, including 48 (10.2%) that were negative in the first trimester (seroconversion during pregnancy). Although the rate of infection was significantly higher in the third versus the first trimester (p = 0.003), no significant differences in maternal or obstetric complications were observed in women testing positive in the first versus the third trimester.

Despite the remarkable success of SARS CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS CoV-2 challenge. The SARS CoV-2 MAPS vaccine generated robust neutralizing antibodies as well as Th1, Th17 and cytotoxic CD8 T-cell responses in NHPs. Furthermore, MAPS-immunized NHPs had significantly lower viral loads in the nasopharynx and lung compared to control animals. Taken together, these findings support the use of the MAPS platform to make a SARS CoV-2 vaccine. The nature of the platform also could enable its use for the inclusion of different variants in a single vaccine.

Wastewater surveillance for SARS-CoV-2 has garnered extensive public attention during the COVID-19 pandemic as a proposed complement to existing disease surveillance systems. Over the past year, methods for detection and quantification of SARS-CoV-2 viral RNA in untreated sewage have advanced, and concentrations in wastewater have been shown to correlate with trends in reported cases. Despite the promise of wastewater surveillance, for these measurements to translate into useful public health tools, it is necessary to bridge the communication and knowledge gaps between researchers and public health responders. Here we describe the key uses, barriers, and applicability of SARS-CoV-2 wastewater surveillance for supporting public health decisions and actions, including establishing ethical consideration for monitoring. Overall, while wastewater surveillance to assess community infections is not a new idea, by addressing these barriers, the COVID-19 pandemic may be the initiating event that turns this emerging public health tool into a sustainable nationwide surveillance system.

To date, uncertainty remains about how long the protective immune responses against SARS-CoV-2 persists and reports of suspected reinfection began to be described in recovered patients months after the first episode. Viral evolution may favor reinfections, and the recently described spike mutations, particularly in the receptor binding domain (RBD) in SARS-CoV-2 lineages circulating in the UK, South Africa, and most recently in Brazil, have raised concern on their potential impact in infectivity, immune escape and reinfection. We report a case of reinfection from distinct SARS-CoV-2 lineages presenting the E484K mutation in Brazil, a variant associated with escape from neutralizing antibodies.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the current coronavirus pandemic is an infectious disease that initially confirmed in China in late December 2019. In this study, we analyzed 131 complete sequences of SARS-CoV-2 from Asia. Our results show that there are fifteen major mutations in Asia which most of them are co-evolved. There were five groups based on co-mutations which three of them resulted in clade G including (241C>T, 3037C>T, 14408C>T, and 23403A>G), (28881G>A, 28882G>A, 28883G>C and 23403A>G) and (25563G>T and 23403A>G). Co-mutations in (8782C>T and 28144T>C) and (1397G>A, 28688T>C, 29742G>T and 11083G>T) were clustered in clade S and a new clade outside of GISAID classification, respectively. Sequences with a mutation in 26144G>T had low variability without any co-mutation which formed clade V. In this study, we showed that Most of the circulated viruses in Asia collected in five co-mutation groups which may affect the transmissibility and vaccine designing strategies.

Coronaviruses (CoVs) are a well-known group of viruses in veterinary medicine. We currently know four genera of Coronavirus, alfa, beta, gamma and delta. Wild, farmed and pet animals are infected with CoVs belonging to all four genera. Seven human respiratory coronaviruses have still been identified, four of which cause upper respiratory tract diseases, specifically, the common cold, and the last three that have emerged cause severe acute respiratory syndromes, SARS-CoV-1, MERS-CoV and SARS-CoV-2. In this review we briefly describe animal coronaviruses and what we actually know about SARS-CoV-2 infection in farm and domestic animals.

The outbreak of COVID-19 has caused a global public health crisis. The spread of SARS-CoV-2 by contact is widely accepted, but the relative importance of aerosol transmission for the spread of COVID-19 is controversial. Here we characterize the distribution of SARA-CoV-2 in 123 aerosol samples, 63 masks, and 30 surface samples collected at various locations in Wuhan, China. The positive percentages of viral RNA included 21% of the aerosol samples from an intensive care unit and 39% of the masks from patients with a range of conditions. A viable virus was isolated from the surgical mask of one critically ill patient while all viral RNA positive aerosol samples were cultured negative. The SARS-CoV-2 detected in masks from patients, ambient air, and respirators from health workers compose a chain of emission, transport, and recipient of the virus. Our results indicate that masks are effective in protecting against the spread of viruses, and it is strongly recommended that people throughout the world wear masks to break the chain of virus transmission and thus protect themselves and others from SARS-CoV-2.

There is an urgent need to advance safe and affordable COVID-19 vaccines for low- and middle-income countries of Asia, Africa and Latin America. Such vaccines rely on proven technologies such as recombinant protein-based vaccines to facilitate its transfer for emerging market vaccine manufacturers. Our group is developing a two-pronged approach to advance recombinant protein-based vaccines to prevent COVID-19 caused by SARS CoV2 and other coronavirus infections. One vaccine is based on a yeast-derived (Pichia pastoris) recombinant protein comprised of the receptor binding domain (RBD) of the SARS-CoV formulated on alum and referred to as the CoV RBD219-N1 Vaccine. Potentially this vaccine could be used as a heterologous vaccine against COVID-19. A second vaccine specific for COVID-19 is also being advanced using the corresponding RBD of SARS-CoV-2. The first antigen has already undergone cGMP manufacture and is therefore “shovel ready” for advancing into clinical trials, following vialing and required GLP toxicology testing. Evidence for its potential efficacy to cross-protect against SARS-CoV-2 includes cross-neutralization and binding studies using polyclonal and monoclonal antibodies. Evidence in support of its safety profile include our internal assessments in a mouse challenge model using a lethal mouse adapted SARS strain, which show that SARS-CoV RBD 291N1 (when adsorbed to Alhydrogel®) does not elicit eosinophilic lung pathology. Together these findings suggest that recombinant protein-based vaccines based on the RBD warrant further development to prevent SARS, COVID-19 or other coronaviruses of pandemic potential.