A very high parking occupancy can negatively influence the traffic performance of an area by causing very long cruising times. A very low parking occupancy, on the other hand, is inefficient from a space utilization perspective. Thus, this paper proposes a framework to compute the optimal parking occupancy rate over a given time horizon based on a macroscopic traffic and parking model. This rate is set high enough to ensure an efficient usage of the parking infrastructure. However, it should also guarantee a high likelihood of finding parking in order to eliminate the drivers’ time wasted in cruising for parking and the added congestion it causes. The model outputs are based on small data collection efforts and low computational costs, and they can be generated without complex simulation software using a simple numerical solver. Multiple vehicle types are included into our methodology allowing us to generate insights about the optimal parking occupancy with or without differentiated parking (i.e., parking for specific vehicles, such as fuel and electric vehicles). In times of a modal shift towards electric vehicles, cities can use our model to evaluate how much parking supply (with battery charging opportunities) they would like to dedicate to electric vehicles in order to achieve optimal traffic and parking results, and whether a differentiated or semi-differentiated parking policy is desirable. We illustrate our framework in a case study of a central area within the city of Zurich, Switzerland, showing the traffic and parking impacts (e.g., average searching time for parking, total revenue created by parking fees, optimal parking occupancy rate) for different proportions of fuel and electric vehicles in the parking demand and/or supply. Our results confirm that optimal occupancy rates are between and for most realistic scenarios. We then discuss how these rates might change depending on various demand and supply relationships, and according to different parking policies. We show that equal proportions between electric vehicles in the demand and their parking spaces in the supply lead to the best traffic performance in the area. We also provide the tools for cities to analyze their loss in performance if they do not react, e.g., to an increasing demand for electric vehicles over time. Moreover, we illustrate how some of these risks can be mitigated by having more flexible parking policies, e.g., allowing electric vehicles to use parking spaces for fuel vehicles.

Looking at different operating climatic conditions, the electrical behavior predicting photovoltaic modules gets very important. For the estimation of output power from photovoltaic (PV) plants this is a very essential and basic aspect. In this paper, the relationship between the I-V curve and the irradiation spectrum is discussed by combining the single diode model. An explicit elementary analytical model with two defined shape parameters is discussed and improved with three approximations and second order Taylor expansion. Then, the explicit elementary analytical model is investigated under varying conditions leveraging the four parameters I_ph, I₀, R_s and R_sh from the single diode model. The relationship between the physical parameters and the condition parameters are discussed and applied to extract the shape parameters at different scenarios. Considering the aging effect, the process of calculation to predict the I-V curve under different splitting spectra is simplified as follow: (1) two shape parameters are gotten from the I-V data at measurement reference conditions (MRC); (2) the short circuit current, open circuit voltage and shape parameters under any splitting spectrum can be calculated based on the relationship provided in article; (3) the performance of PV panel can be predicted with parameters. The validation of this model was experimentally proven leveraging monocrystalline silicon photovoltaic module with different splitting films. Results showed that the model accurately predicts the I-V characteristics for the examined PV modules at different irradiance spectra and cell temperatures. Moreover, the presented model performs superior compared to other investigated models when looking at accuracy and simplicity.

The semi-enclosed estuary is very susceptible to changes in the physical and environmental characteristics of the inflow from the land and the coastal sea weather and so the continuous and comprehensive monitoring is necessary for managing the estuary. Nevertheless, the standard procedure or schematic framework has not been proposed appropriately to determine how many instruments are necessary and where they need to be deployed to detect critical changes. Therefore, the present work proposes a systematical strategy for the deployments of the monitoring array by using the combination of the graphical optimization with the objective mapping technique. In order to reflect the spatiotemporal characteristics of the bay, the representative variables and eigenvectors are determined by the Empirical Orthogonal Function (EOF), and the cosine angle among them are calculated for a design index of optimization. At the recommended locations, the sampled representative variables are interpolated to reconstruct their spatiotemporal distribution and compared with the distributions of the true values. Analysis confirms that the selected locations, even with a small number of points, can be used for on-site monitoring. Also, the present framework suggests how to determine installable regions for real-time monitoring stations, which reflect the global and local characteristics of the semi-enclosed estuary.

The activity of prioritizing software requirements should be done as efficiently as possible. Selecting the most stable requirements for the most important customers for the development company can be a positive factor when we consider that the available resource does not always encompass the implementation of all requirements. Quantitative methods for reaching software prioritization in releases are many in the field of Search-Based Software Engineering (SBSE). However, we show that it is possible to use qualitative Verbal Decision Analysis (VDA) methods to solve this same type of problem. Moreover, we will use the ZAPROS III-i methods to prioritize requirements considering the opinion of the decision-maker, who will participate in this process. Finally, the results obtained in the VDA structured methods were quite satisfactory when compared to the methods using SBSE. A comparison of results between quantitative and qualitative methods will be made and discussed later.

We propose the Hamiltonian formalism of Bianchi type 1 cosmological model for perfect fluid. We have considered both the equation of state parameter ω and the cosmological constant Λ as the function of volume V(t) which is defined by the product of three scale factors of the Bianchi type 1 line element. We propose a Lagrangian for the anisotropic Bianchi type-1 model in view of a variable mass moving in a variable potential . We can decompose the anisotropic expansion in terms of expansion and shearing motion by Lagrangian mechanism. We have considered a canonical transformation from expanding scale factor to scalar field ø which helps us to give the proper classical definition of that scalar field in terms of scale factors of the mentioned model. This definition helps us to explain the cosmological inflation. We have used large anisotropy(as in the cases of Bianchi models) and proved that cosmic inflation is not possible in such large anisotropy. Therefore we can conclude that the extent of anisotropy is less in case of our universe. Otherwise the inflation theory which explained the limitations of Big Bang cannot be resolved.Part II is contained with some analysis of the lagrangian ; derived in Part I ; on the quintessence model.

We construct a family of two-step optimal fourth order iterative methods for finding single root of non-linear equations. We generalize these methods to simultaneous iterative methods for determining all the distinct as well as multiple roots of single variable non-linear equations. Convergence analysis is present for both cases to show that the order of convergence is four in case of single root finding method and is twelve for simultaneous determination of all roots of non-linear equation. The computational cost, Basin of attraction, efficiency, log of residual and numerical test examples shows, the newly constructed methods are more efficient as compared to the existing methods in literature.

The extended finite element method (XFEM) is now widely used in crack simulations and the direction of propagation of the XFEM crack in SS-304 has been quite interesting. This paper discusses the direction,θ(+ve in anti-clockwise direction), of the XFEM crack (under mode-I) propagation based on the von Mises stress-field around the crack-tip for static loading under the light water reactors (LWRs) conditions. The Mises core region from the crack-tip is chosen for β=〖90〗^o, the angle between the load and the initial crack. Experimental data for LWRs’environment is obtained and the simulations have been carried out applying three different static loads and results for the direction of the crack are calculated by measuring the stress-field around the crack-tip. It has been found that the direction of the XFEM varies inversely as the stress-field around the crack tip is increased. The computational results have been compared with the numerical results based on the minimum strain energy density criterion[S-criterion].

Over the last decades, the energy market around the world has reshaped due to accommodating the high penetration of renewable energy resources. Although renewable energy sources have brought various benefits, including low operation cost of wind and solar PV power plants, and reducing the environmental risks associated with the conventional power resources, they have imposed a wide range of difficulties in power system planning and operation. Naturally, classical optimal power flow (OPF) is a nonlinear problem. Integrating renewable energy resources with conventional thermal power generators escalates the difficulty of the OPF problem due to the uncertain and intermittent nature of these resources. To address the complexity associated with the process of the integration of renewable energy resources into the classical electric power systems, two probability distribution functions (Weibull and lognormal) are used to forecast the voltaic power output of wind and solar photovoltaic, respectively. Optimal power flow, including renewable energy, is formulated as a single-objective and multi-objective problem in which many objective functions are considered, such as minimizing the fuel cost, emission, real power loss, and voltage deviation. Real power generation, bus voltage, load tap changers ratios, and shunt compensators values are optimized under various power systems’ constraints. This paper aims to solve the OPF problem and examines the effect of renewable energy resources on the above-mentioned objective functions. A combined model of wind integrated IEEE 30-bus system, solar PV integrated IEEE 30-bus system, and hybrid wind and solar PV integrated IEEE 30-bus system are performed using the equilibrium optimizer technique (EO) and other five heuristic search methods. A comparison of simulation and statistical results of EO with other optimization techniques showed that EO is more effective and superior.

We study the application of Optimal Control Theory to Ion Cyclotron Resonance. We test the validity and the efficiency of this approach for the robust excitation of an ensemble of ions with a wide range of cyclotron frequencies. Optimal analytical solutions are derived in the case without any pulse constraint. A gradient-based numerical optimization algorithm is proposed to take into account limitation in the control intensity. The efficiency of optimal pulses is investigated as a function of control time, maximum amplitude and range of excited frequencies. A comparison with adiabatic and SWIFT pulses is done. On the basis of recent results in Nuclear Magnetic Resonance, this study highlights the potential usefulness of optimal control in Ion Cyclotron Resonance.

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance with growing evidence of its underlying molecular mechanisms and its interaction with the immune cell control. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 consecutive human papilloma virus (HPV)-negative OSCC lesions and correlated to tumor specific parameters, the intratumoral immune cell response and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was seen in OSCC sections when compared to non-neoplastic cells. Based on the expression levels of HLA-I APM components three main OSCC subgroups were detected and categorized into HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh phenotypes. In the HLA-Ihigh/APMhigh group, the highest frequency of intratumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3 cells was found. Despite being associated with the highest T cell infiltration, patients within this group presented the most unfavorable survival, which was most evident in stage T2 tumors. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

The prevention, mitigation and treatment of movement impairments, ideally, requires early diagnosis or identification. As the human movement system has physiological and functional redundancy, movement limitations do not promptly arise at the onset of physical decline. A such, prediction of movement limitations is complex: it is unclear how much decline can be tolerated before movement limitations start. Currently, the term ‘homeostatic reserve’ or ‘physiological reserve’ is used to refer to the redundancy of the human biological system, but these terms do not describe the redundancy in the muscle architecture of the human body. The result of functional redundancy is compensation. Although compensation is an early predictor of movement limitations, clear definitions are lacking and the topic is underexposed in literature. The aim of this article is to provide a definition of compensation and emphasize its importance. Compensation is defined as an alteration in the movement trajectory and/or altering muscle recruitment to complete a movement task. Compensation for capacity is the result of a lack in neuromusculoskeletal reserve, where reserve is defined as the difference between the capacity (physiological abilities of the neuromusculoskeletal system) and the task demand. Compensation for movement objectives is a result of a shift in weighting of movement objectives, reflecting changing priorities. Studying compensation in biomechanics requires altered protocols in experimental set-ups, musculoskeletal models that are not reliant on prescribed movement, and inclusion of alternative movement objectives in optimal control theory.

The bending performance of a basalt-polypropylene fiber-reinforced concrete (HBPFRC) was characterized by testing 24 400×100×100 mm3 prismatic specimens in a four-point bending test JSCE-SF4 configuration. The type and content of both fibers was varied in order to guarantee different target levels of post-cracking flexural performance. The results evidenced that mono-micro basalt fiber reinforced concrete (BFRC) allows the increase of the flexural strength (pre-cracking stage), while macro polypropylene fiber reinforced concrete can effectively improve both bearing capacity and ductility of the composite for a wide crack width range. Compared with the plain concrete specimens, flexural toughness and equivalent flexural strength of macro polypropylene fiber-reinforced concrete (PPFRC) and the hybrid fiber-reinforced concrete (HFRC) increased by 3.7~7.1 times and 10%~42.5%, respectively. From both technical and economic points of view, the optimal mass ratio of basalt fiber to polypropylene fiber resulted to be 1:2, with a total content of 6 kg/m3. This HFRC is seen as a suitable material to be used in sewerage pipes where cracking control (crack formation and crack width control) is of paramount importance to guarantee the durability and functionality of the pipeline as well as the ductility of the system in case of local failures.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for the patients' dichotomization in the continuous gene expression. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the median or quantiles of gene expression value to perform the analyses. There are also few clinicopathological features available on their pre-processed data sets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustment with confounders, the clinical tumor stage and the surgical margin involvement are independent risk factors for patients' prognosis. According to the resulting tables with Bonferroni-adjusted P value under the optimal cutoff and the hazard ratio, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with the patients' overall survival. We validated this discovery by using the other independent HNSCC dataset (GSE65858). Thus, we suggest the transcriptomic analysis could help for biomarker discovery.

The practice of quantified-self sleep tracking is increasingly common nowadays among healthy individuals as well as patients with sleep problems. However, existing sleep-tracking technologies only support simple data collection and visualization, and are incapable of providing actionable recommendations that are tailored to users' physical, behavioral and environmental context. Here we coined the term context-aware sleep health recommender system (CASHRS) as an emerging multidisciplinary research field that bridges ubiquitous sleep computing and context-aware recommender systems. In this paper, we presented a narrative review to analyze the type of contextual information, the recommendation algorithms, the context filtering techniques, the behavior change techniques, the system evaluation, and the challenges in peer-reviewed publications that meet the characteristics of CASHRS. Analysis results identified current research trends, the knowledge gap, and future research opportunities in CASHRS.

In the last two decades, variably doped strontium barium niobate (SBN) has attracted a lot of scientific interest mainly due to its specific non-linear optical response. Comparably, the parental compound, i.e., undoped SBN, appears to be less studied so far. Here, two different cuts of single-crystalline nominally pure strontium barium niobate in the composition Sr0.61Ba0.39Nb2O6 (SBN61) are comprehensively studied and analyzed with regard to their photoconductive responses. We present conductivity measurements under systematically varied illumination conditions along either the polar z-axis or perpendicular to it (x-cut). Apart from a pronounced photoconductivity (PC) already under daylight and a large effect upon super-bandgap illumination in general, we observe (i) distinct spectral features when sweeping the excitation wavelength over the sub-bandgap region as then discussed in the context of deep and shallow trap states, (ii) extremely slow long-term relaxation for both light-on and light-off transients in the range of hours and days, (iii) a critical dependence of the photoresponse on the pre-illumination history of the sample, and (iv) a current-voltage hysteresis depending on both the illumination and the electrical-measurement conditions in a complex manner.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

In this paper, we have used magnetron sputtering to grow the high-quality GeSn layer on Ge (100) with Sn compositin up to 7%. The crystallinity of the GeSn layer is pretty good, and the strain relaxation degree of the GeSn layer is evaluated to be approximately 50%. The root mean square (RMS) value is 0.8 nm, and the averaged TDDs in the GeSn layer is 8.7×109 cm-2, which is obtained from the rocking curve of GeSn layer along (004) plane. PL measurement result shows the significant optical emission from the deposited high-quality GeSn layer, which also means that magnetron sputtering is an optional way to achieve the higher Sn composition GeSn luminescent material. To verify whether our deposited GeSn can used for optoelectronic devices, we fabricate the simple vertical p-i-n diode, and the room temperature current-voltage (I-V) characteristic was obtained. This result paves the way for future sputtered-GeSn optimization, which is critical for the optoelectronic application.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

The II law of thermodynamics is most often given in three supposedly equivalent formulations: two Clausius (I and II) and one Kelvin. The most general and indisputable entropy formulation belong to Clausius (II). The earlier Clausius I principle determines the natural direction heat flow between bodies at different temperatures. On the other hand, the Kelvin principle states that it is impossible to completely convert heat into work. The author argues that the Kelvin principle is a weaker statement (or more strictly non-equivalent) than Clausius I principle, and the latter is a weaker statement than Carnot principle, which is equivalent to Clausius II principle. As a result, the Kelvin principle and the Clausius I principle are not exhaustive formulations of the II law of thermodynamics. At the same time, it turns out that the Carnot principle becomes such a formulation. Apart from providing a complete set of proof and disproof, the author, indicates where the methodological errors were made in the alleged proof of the equivalence of the Kelvin principle and both Clausius principles.

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

Microgrid is one of the promising green transition technologies that will provide enormous benefit to the seaport, as a solution to the major concerns in this sector, namely energy crisis, economical and environmental pollution. However, finest design of the microgrid is a challenging task considering different objectives, constraints and uncertainties involved. To ensure the optimal operation of the system, determining the right configuration framework and size for each component in the seaport microgrid at the minimum cost is a vital decision at the design stage. This paper aims to design a hybrid system of seaport microgrid with optimally sized component .The selected case study is the Port of Aalborg, Denmark. The proposed grid-connected structure consists of renewable energy sources (photovoltaic system and wind turbines), an energy storage system and cold ironing as seaport’ loads. The architecture is then optimized by utilizing HOMER to meet the maximum load demand by considering a few parameters such as solar global horizontal irradiance, temperature and wind resources. Then, the best configuration framework is analyzed in terms of economic feasibility, energy reliability and environmental impact.

Chinese divination of I Ching has a history of thousands of years. The six lines changes in 64 hexagrams have exceeded one billion scenarios, and the inherent laws among them have not been well revealed to this day. By using big data's technology and coin toss method, this paper simulates the change of 64 hexagrams, and explores the probability and proportion of each hexagram during the change from the perspective of quantification, as well as the maximum and minimum conversion rate of hexagram change. This paper summarizes the basic characteristics and the basic law of hexagram change, and accordingly constructs the spatial form of hexagram change, and reveals the hidden secrets of the ancient Book of changes (I Ching). To achieve this goal, we randomly toss three coins 600 million times to generate 100 million hexagrams. According to the basic rules of hexagram divination, we calculate the hexagram changes. The results showed that: (1) Changes of things are mostly simple changes. The probability of 1 billion randomly generated hexagrams from one to three dynamic lines is close to 80%. (2) About 17% of the 64 hexagrams have no dynamic lines, which means that a significant proportion of the 64 hexagrams are invariant. (3) Small probability changing hexagram certainty and large probability changing hexagram uncertainty. (4) After generating one billion hexagrams at random, the topographic map with the probability of changing hexagrams has axial symmetry and fractal geometric characteristics, and the fractal characteristics are mainly manifested in that the changes on both sides of the symmetry are presented based on the triangle background. These results reflect the obvious characteristics and internal regularity of the changes in the 64 hexagrams of the I Ching. This article provides new ideas for scientific exploration of the internal laws of the 64 hexagrams in the I Ching.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMPK activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here we report an enlarged and extended study of mitochondrial function and associated cellular stress-signalling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction of reactive O2 species (ROS) levels in premutation cells and revealed for the first time that TORC1 activities are reduced. Extensive correlation, multiple regression and Principal Components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signalling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK activation and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration and ATP steady state levels. In addition the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells, but may presage the previously reported activation of TORC1 in FXS cells.

This paper introduces a closed-loop control strategy for maintaining consistency of liquid temperature in commercial Drop on Demand (DoD) inkjet printing. No additional sensors or additional actuators are installed in the printhead while achieving the consistency in liquid temperature. To this end, this paper presents a novel in situ sensing-actuation policy at every individual liquid-nozzle, where the jetting mechanism has three distinct roles. It is used for jetting liquid droplet onto the print media based on the print-job. It is used as a soft sensor to estimate the real-time liquid temperature of the jetting nozzle. While not jetting liquid, it is used as a heating actuator to minimize the gradient of liquid temperature among nozzles. The soft sensing based in situ controller is implemented in an experimentally validated digital twin that models the thermo-fluidic processes of the printhead. The digital twin is scalable and flexible to incorporate an arbitrary number of liquid-nozzles, making the control strategy applicable for future designs of the printhead.

The Combined Inversion of Surface and AeRosols (CISAR) algorithm for the joint retrieval of surface and aerosol single scattering properties has been further developed in order to extend the retrieval to clouds and overcome the need for an external cloud mask. Pixels located in the transition zone between pure cloud and pure aerosol are often discarded by both aerosol and cloud algorithms, despite being essential for studying aerosol-cloud interactions, which still represent the largest source of uncertainty in climate predictions. The proposed approach aims at filling this gap and deepening the understanding of aerosol properties in cloudy environments. The new CISAR version is applied to Sentinel-3A/SLSTR observations and evaluated against different satellite products and ground measurements. The spatial coverage is greatly improved with respect to algorithms processing only pixels flagged as clear sky by the SLSTR cloud mask. The continuous retrieval of aerosol properties without any safety zone around clouds opens new possibilities for studying aerosol properties in cloudy environments.

The prim objective of commenced article is to determine q-sumudu transforms of a product of unified family of q-polynomials with basic (or q-) analogue of fox’s H-function and q-analog of I-functions. Specialized cases of the leading outcome are further evaluated as q-sumudu transform of general class of q-polynomials and q-sumudu transforms of the basic analogues of Fox’s H-function and I-functions.

The increasing penetration of renewable energy sources in power grids highlights the role of battery energy stor- age systems (BESSs) in enhancing the stability and reliability of electricity. A key challenge with the renewables’, specially the BESSs, integration into the power system is the lack of proper dynamic model for stability analysis. Moreover, a proper control design for the power system is a complicated issue due to its complexity and inter-connectivity. Thus, the application of decentralized control to improve the stability of a large- scale power system is inevitable, especially in distributed energy sources (DERs). This paper presents an optimal distributed hybrid control design for the interconnected systems to suppress the effects of small disturbances in the power system employing utility-scale batteries based on existing battery models. The results show that i) the smart scheduling of the batteries’ output reduces the inter-area oscillations and improves the stability of the power systems; ii) the hybrid model of the battery is more user-friendly compared to the Western electricity coordinating council (WECC) model in power system analysis.

Streptococcus mutans is well known for having virulence factors associated with its cariogenic role, such as glucosyltransferases, which have been used as targets for the virtual screening of molecules with inhibitory capacity. The Antigen I/II of S. mutans is involved in the adhesion to the surface of the tooth and the bacterial co-aggregation in the biofilm formation, despite that, this protein has not been used as a target in a virtual strategy search for inhibitors. In this study we identified in silico and evaluated in vitro molecules with adhesion inhibitory potential on S. mutans Ag I/II. A virtual screening of 883,551 molecules was conducted, cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity, and molecular dynamics simulation were also performed. We have found three molecules (ZI-187, ZI-939, ZI-906) that were not cytotoxic and inhibited the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides three new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates and provides a new computational line for the search and selection of safe inhibitory molecules against different pathogens.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

The purpose of this paper is to find the time optimal control to a target set for semilinear stochastic functional differential equations involving time delays or memories under general conditions on a target set and nonlinear terms even though the equations contain unbounded principal operators. Our research approach is construct a fundamental solution for corresponding linear systems and establish variations of constant formula of solutions for given stochastic equations. The existence result of time optimal controls for one point target set governed by the given semilinear stochastic equation is also established.

The use of crime mapping has been used by the police to inform deployment of resources for many decades. Such approaches are commonly used to underpin crime control strategies designed to prevent or reduce acquisitive crimes such as domestic burglary. In recent decades there has been a shift away from simple hot spot identification to more complex geospatial mapping methodologies, such as near repeat analysis which was developed through research regarding burglary victimisation. One of these newly emerging methodologies is built upon the ecological, optimal forager theory (OFT). Research using this theory to examine domestic burglary offending intimated potential for positive results in predicting areas at risk of future crime. This led to a number of police services using crime analysis methodologies built upon OFT to underpin their deployment of resources in an effort to prevent or reduce domestic burglary through increased capable guardianship. However, to date, there has been no detailed examination of how the police services implemented such approaches. As such, this study seeks to fill this gap by examining OFT strategies implemented within 5 police services. By interviewing participants directly involved in the programs the study gathers views and perspectives of its relative success. As a result, we identify that participants felt the strategies produced limited impact on recorded burglary crime. We discuss how despite some positive by-products of the strategies, failure to comprehensively apply the theoretical foundations of OFT, and a variety of implementation failures have undermined the various programs, ultimately impacting their effectiveness.

Demand responsive transport (DRT) is operated according to flexible routes, dispatch intervals, and dynamic demand, is attracting a lot of attention. The biggest characteristic of DRT service is that the vehicle routes and schedules are operated optimally based on real-time travel requests of using passengers without fixed operating schedules. Today, the smart-city era has arrived, particularly because of progress in the wireless communications technology and technology related to location information service and real-time passenger demands and requests, and services that change the vehicles’ operating schedules in real-time according to dynamic demand have attracted more attention. In this study, we analyze the effects of the DRT system to solve the first mile/last mile problem based on a proposed DRT routing algorithm considering real-time travel behavior. The algorithm is modified from the dynamic vehicle routing problem (DVRP), in which a DRT-based routing algorithm tends to minimize users’ cost and providers’ operation cost. So far, the DVRP has only been able to serve a single request per vehicle at a time. However, this needs to be extended for the purpose of DRT, wherein several passengers board a vehicle at the same time. The routing algorithm can serve multiple requests at a time and schedule picks ups, drop offs, and rides according to the requests and as calculated by the dispatch algorithm. The basic principle of routing is as follows. The DRT vehicle moves on an attractive path and picks up a passenger if boarding is requested, but it does not simply hang around as a DVRP would. In this step, if another DRT vehicle is present near another passenger, the vehicle that would minimize that passenger’s total travel time picks up the passenger. The optimal routing algorithm developed in this study is applied to the activity-based model; that is, a microscopic traffic demand estimation method is implemented through an activity-based model by using an open-source, activity-based model package called Multi-Agent Transport Simulation (MATSim). MATSim is used for the simulation, because it combines a multi-modal traffic flow simulation with a scoring model for agents, and it provides co-evolutionary algorithms that can alter agents’ daily routines. This process is applied to a type of mode choice and route choice repeatedly over several iterations until some form of user equilibrium has been reached. This study analyzed the feasibility of implementing the DRT service by analyzing the benefits for the users and cost of the operator from the effects of increasing public transportation use and providing personalized mobility service based on DRT implementation by the introduction of DRT will be analyzed according to the scale of DRT supply. Through the simulation, the DRT is expected to provide convenient, fast, and cost-effective mobility services to customers; provide an optimal vehicle scale to providers; and, ultimately, achieve a safe and efficient transportation system.

Optimal conditions for maximum efficacy of photoinitiated polymerization are theoretically presented. Analytic formulas are shown for the crosslink time, crosslink depth and efficacy function. The roles of photoinitiator (PI) concentration, diffusion depth and light intensity on the polymerization spatial and temporal profiles, for both uniform and non-uniform cases, are presented. For optimal efficacy, a strategy via controlled PI concentration is proposed, where re-supply of PI in high light intensity may achieve a combined-efficacy similar to low light intensity, but has a much faster procedure. A new criterion of efficacy based on the polymerization (crosslink) [strength] and [depth] is introduced. Experimental data are analyzed for the role of PI concentration and light intensity on the gelation time and efficacy.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Mehtods: In Trypanosoma cruzi, the causal agent of the Chagas disease, an NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that are clearly detached from the other Trypanosomatidae such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that an NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids.

Enhancing the effectiveness of search and rescue operation at sea is always a duty of utmost importance of the coastal states. The search area for distressed objects can be determined by using Monte Carlo simulation, combined with the Median-Filter. Once the search area has been identified, the success of search and rescue operations depends on the sweeping ability of search and rescue vessel at the probability area of the distress object with the minimum time. This is the important element to the success of the search and rescue operation as it minimizes the risk and cost for Search and rescue team. In this article, the authors study and propose the use of Bacterial Foraging Optimization Algorithm (BFOA) to calculate the optimal search and co-ordination route for many search and rescue vessels in Vietnam sea. The simulation results show that it is quite consistent with reality and BFOA can be effectively applied to determine a quick search.

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing HLA-E monomeric heavy chain (HC) (Open Conformers, OCs). Two of the mAbs (TFL-006 and TFL-007) bound to the HC’s coated on a solid matrix. The binding was inhibited by a peptide 117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by 2-microglobulin -m) in intact HLA-I trimers (Closed Conformers, CCs). Identical HLA-I polyreactivity is observed in IVIg administered to lower anti-HLA antibodies (Abs) in HLA-sensitized patients, but the mechanism is unknown. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might mimic the immunomodulatory functions of IVIg. We tested the relative binding affinity of the mAbs and IVIg for both OCs- and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells, (b) the production of anti-HLA-II antibody (Ab) by B-memory cells, and anti-HLA-I Ab by immortalized B-cells, and (c) the upregulation of CD4+, CD25+, and Fox P3+ T-regs. The mAbs bound only to OCs, whereas IVIg is bound to both CCs and OCs. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells, anti-HLA Ab production by B-cells and expanded the T-regs, better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal therapeutic IVIg-mimetic.

In the new period, the state has made every effort to promote the new urbanization of public sports service. Entropy method, coupled coordination model, cold hot spot analysis is used to explore the dynamic relationship between public sports services and the development of new urbanization in China from 2008 to 2017. The results show that: (1) The development of the internal subsystem of public sports service is not balanced, the sports financial investment system grows rapidly, but the development of professional sports talent team is slow. (2) The imbalance of regional development cannot be ignored, and the public sports service level shows a decreasing gradient from east to west. (3) The regional development features are different. The eastern region is dominated by the coordinated development of sports public service and urbanization, while the central region is mainly in the type of public sports service lag, while the western region has multiple complex characteristics of low-level coordination and public sports service lag. Therefore, it is proposed that the construction of modern public sports service system should be investigated in the context of the development of new urbanization. It should be promoted from the following aspects: promoting the extension of public sports service to rural areas, engendering the "citizen's right" of sports health to the migrant population, conforming to the trend of mass sports intelligence, developing green sports and revitalizing idle sports assets in cities.

In this paper, the design and control of a hydraulic system based tire changer machine have been analyzed and simulated using Matlab/Simulink Toolbox successfully. The machine have a displacement input which is a leg pedal displacement in order to push the piston of the pump to fed the motor with a pressured hydraulic fluid to rotate the tire with an angular speed to mount and dismount it. Augmentation based H_∞ and H₂ optimal synthesis controllers have been used to improve the performance of the machine. Comparison of the proposed controllers for tracking a reference input speed have been done using two reference inputs (step and random) signals. Finally the comparative simulation results proved the effectiveness of the proposed tire changer with H synthesis controller in improving the settling time and percentage overshoot.

Considerable attention has been given to the research field of bioorganometallic chemistry, which is a hybrid chemistry field between biology and organometallic chemistry. The introduction of biomolecules, which have hydrogen bonding sites and chiral centers, into organometallic compounds is considered to be a promising strategy to construct chirality-organized bioorganometallic conjugates. This feature paper sketches an outline of induction of helical chirality into bioorganometallic conjugates. Topics covered include control of the helical chirality of 1,n’-disubstituted ferrocene moieties in ferrocene-dipeptide conjugates and the chirality induction of the Au(I)–Au(I) axis in the dinuclear organogold(I)-uracil conjugates.

Recently, the mapping industry has been focusing on the possibility of large-scale mapping from unmanned aerial vehicles (UAVs) owing to advantages such as easy operation and cost reduction. In order to produce large-scale maps from UAV images, it is important to obtain precise orientation parameters. For this, various techniques have been developed and are included in most of the commercial UAV image processing software. For mapping, it is equally important to select images that can cover a region of interest (ROI) with the fewest possible images. Otherwise, to map the ROI, one may have to handle too many images, and commercial software does not provide information needed to select images, nor does it explicitly explain how to select images for mapping. For these reasons, stereo mapping of UAV images in particular is time consuming and costly. In order to solve these problems, this study proposes a method to select images intelligently. We can select a minimum number of image pairs to cover the ROI with the fewest possible images. We can also select optimal image pairs to cover the ROI with the most accurate stereo pairs. We group images by strips, and generate the initial image pairs. We then apply an intelligent scheme to iteratively select optimal image pairs from the start to the end of an image strip. According to the results of the experiment, the number of images selected is greatly reduced by applying the proposed optimal image–composition algorithm. The selected image pairs produce a dense 3D point cloud over the ROI without any holes. For stereoscopic plotting, the selected image pairs were map the ROI successfully on a digital photogrammetric workstation (DPW), and a digital map covering the ROI is generated. The proposed method should contribute to time and cost reductions in UAV mapping.

Probability is an open question in the ontological interpretation of quantum mechanics. It has been discussed in some trajectory interpretations such as Bohmian mechanics and stochastic mechanics. New questions arise when the domain of probability extends to the complex space, including the generation of complex trajectories, the definition of the complex probability, the relation of the complex probability to the real quantum probability, and so on. The complex treatment proposed here applies the optimal quantum guidance law to derive the stochastic differential (SD) equation governing the particle’s random motions in the complex plane. The ensemble of the complex quantum random trajectories (CQRTs) solved from the complex SD equation is used to construct the probability distribution ρc(t,x,y) of the particle’s position over the complex plane z=x+iy. The correctness of the obtained complex probability is confirmed by the solution of the complex Fokker-Planck equation. The significant contribution of the complex probability is that it can be used to reconstruct both quantum probability and classical probability, and to clarify their relationship. Although quantum probability and classical probability are both defined on the real axis, they are obtained by projecting complex probability onto the real axis in different ways. This difference explains why the quantum probability cannot exactly converge to the classical probability when the quantum number is large.

The radial distribution networks are designed for unidirectional power flows and are passive in nature. However, with the penetration of Distributed Generation (DG), the power flow becomes bidirectional and the network becomes active. The integration of DGs into distribution network creates many issues with: system stability, protection coordination, power quality, islanding, proper placement and sizing etc. Among these issues, the two most significant are optimal sizing and placement of DGs and their protection coordination in utility network. The proper coordination of relays with high penetration of DGs placed at optimal location increases the availability and reliability of the network during abnormal operating conditions.This research addresses most of the available methods for efficient sizing and placement of DGs in distribution system (numerical, analytical and heuristic) as well as the developed protection coordination techniques for utility networks in the presence of DGs (Artificial Intelligence (AI), adaptive and non-adaptive, multi-agent, hybrid). This paper indicates the possible research gaps and highlights the applications possibilities and methods’ limitations in the area of DGs.

Solar radiation is closely related to the energy buildings consume for cooling, heating, and lighting purposes. Glazing is the only material of the building envelope that transmits solar radiation and needs to be appropriately designed to reduce energy cㅈonsumption. Currently, smart glass technology is being actively investigated and developed for effective solar radiation control. Among the various types of smart glass, electrochromic glazing is one of the most promising technologies, as it can adjust transmittance on its own, has a wider transmittance range in both the clear and darkened states, and consumes less electricity. Considering the importance of solar radiation adjustment in electrochromic glazing technology, this study attempted to develop an optimal control method for electrochromic glazing. Toward this goal, the solar radiation incident on vertical surfaces and outdoor temperature conditions were controlled in three regions with different climatic characteristics, and the annual cooling, heating, and lighting loads, discomfort glare, and interior illumination were analyzed. This approach enabled the optimal conditions with respect to visual comfort to be determined. Subsequently, the EDPI (Energy and daylight performance index) was used to optimize control conditions for each region, thereby producing integrated evaluations from results with different units and properties. The proposed control method will be utilized to develop a control algorithm and a control system to reduce building energy consumption.

Based on the Expected Utility Theory and Regret Theory, the Extended Regret Theory (ERT) is proposed in this paper to study the optimal pricing strategy of retailers in e-commerce environment. Taking the diversity of sales channels and the uncertainty of consumers in e-commerce environment into consideration, author of the paper designs an extended regret utility function which comprehensively considers both pessimistic and optimistic attitudes of decision makers in retailing industry to describe their regret-avoidance behavior. According to the sensitivity analysis, it is found that the optimal retail price decreases as the consumer price sensitivity coefficient increases, yet does not show variation with changes of the consumers pessimism degree. Moreover, the optimal retail price(s) obtained under EUT, ERT and combination of EUT and ERT represent the same.

The present work studies a swelling porous-elastic system with viscoelastic damping. We establish a general and optimal decay estimate which generalizes some recent results in the literature. Our result is established without imposing the usual equal-wave-speed condition associated with similar problems in literature.

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.

Abstract: The increased penetration of renewables in distribution power systems has motivated researchers to take significant interest in local energy transactions. The major goal of Local Energy Markets (LEM) is to promote the participation of small consumers in energy transactions and providing an opportunity for transactive energy systems. Such energy transactions in LEM are considered as a bi-level optimization problem in which all agents at upper and lower levels try to maximize their profits. But typical bi-level problem is very complex as it is inherently nonlinear, discontinued and strongly NP-hard. So, this article proposes the application of hybridized Cross Entropy Covariance Matrix Adaptation Evolution Strategy (CE-CMAES) to tackle such a complex bi-level problem of LEM. The proposed CE-CMAES secured the 1st rank in Testbed-2 entitled, “Bi-level optimization of end-users’ bidding strategies in local energy markets (LM)” at international competitions on Smart Grid Problems, held at GECCO 2020 and WCCI 2020. CE method is used for global exploration of search space and CMAES is used for local exploitation as its adaptive step-size mechanism prevents its premature convergence. A practical distribution system with renewable energy penetration is considered for simulation. The comparative analysis shows that the overall cost, mean fitness and Ranking Index (R.I) obtained from CE-CMAES are superior to those obtained from the state-of-the-art participated algorithms. Wilcoxon Signed Rank Statistical test also proves that CE-CMAES is statistically different from the tested algorithms.

In this paper we study the normal bases for Galois ring extension ${{R}} / {Z}_{p^r}$ where ${R}$ = ${GR}$(p^r, n). We present a criterion on normal basis for ${{R}} / {Z}_{p^r}$ and reduce this problem to one of finite field extension $\overline{R} / \overline{Z}_{p^r}=F_{q} / F_{p} (q=p^n)$ by Theorem 1. We determine all optimal normal bases for Galois ring extension.

The sudden onset of the Covid-19 pandemic disrupted the modern multi-national interconnected society and led the countries and societies to enforce unprecedented restrictions on movement. Among myriad containment measures, the policy of trace and quarantine found universal adoption among countries; the swift adoption of the policy was soon met with widespread criticism and opposition activists who questioned the utility and the risk associated with such a large scale collection of data and infringement on the movement of individuals. Consequently, one often tends to be either pro- or anti-trace and quarantine; the ensuing polarizing and politicized left little room for nuance. In this work, we undertake a methodology study to understand the nuances of the impact of different implementations of trace and quarantine. To this end, we design a user-friendly and intuitive tool that can be employed by experts to model the disease dynamics and societal structure. We focus on the study of the cost of policy with respect to quarantine degree, which captures the distance between the person required to quarantine after a person is detected to be infected. Our study results in a surprising conclusion: the cost is not necessarily monotone with respect to the degree of quarantine. Our analysis indicates that governments must curb the urge to adopt simplistic policy and the optimal policy of trace and quarantine for a country strongly depends on its societal structure and disease dynamics.

Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)‐dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to Class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action potential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax) and conduction velocity (CV), and decreased AP duration (APD) and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that quinidine and disopyramide may be more effective against Pitx2-induced AF than propafenone by prolonging WL.

The paper deals with the modelization and optimization of an integrated multi-component energy system. On-off operation and presence-absence of components must be described by means of binary decision variables, besides equality and inequality constraints; furthermore, the synthesis and the operation of the energy system should be optimized at the same time. In this paper a hierarchical optimization strategy is used, adopting a genetic algorithm in the higher optimization level, to choose the main binary decision variables, whilst a MILP algorithm is used in the lower level, to choose the optimal operation of the system and to supply the merit function to the genetic algorithm. The method is then applied to a distributed generation system, which has to be designed for a set of users located in the center of a small town in the North-East of Italy. The results show the advantage of distributed cogeneration, when the optimal synthesis and operation of the whole system are adopted, and significant reduction in the computing time by using the proposed two-level optimization procedure.

Abstract: The effect of collagen type 1 (Col I) oxidation on Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) remodeling is described as a model for acute oxidative stress. Morphologically, remodeling was presented by a mechanical rearrangement of adsorbed FITC-Col I and a trend for its organization in a fibril-like pattern - a process strongly abrogated in oxidized samples, but without visible changes in cell morphology. The cellular proteolytic activity was quantified in multiple samples utilizing fluorescence de-quenching (FRET effect). In the presence of ADMSCs a significant increase of native FITC-Col I fluorescence was observed, almost absent in the oxidized samples. Parallel studies in cell-free systems confirmed the enzymatic de-quenching of native FITC-Col I by Clostridial collagenase, again showing significant inhibition in oxidized samples. The structural changes in the oxidized Col I was further studied by Differential Scanning Calorimetry: an additional endotherm at 33.6°C along with the typical for native Col I at 40.5°C with sustained enthalpy (∆H) was observed in oxidized samples. Collectively, it has been evidenced that remodeling of Col I by ADMSCs is altered upon oxidation due to the intrinsic changes in the protein structure, thus presenting a novel mechanism for the control of stem cells' behavior toward collagen.

This survey reports on the DNA identification and occurrence of Culex torrentium and Cx. pipiens s.s. in Belgium. These native disease vector mosquito species are morphologically difficult to separate and the biotypes of Cx. pipiens s.s. are morphologically indistinguishable. Culex torrentium and Cx. pipiens s.s. were identified using the COI and ACE2 loci. We recorded 1,248 Cx. pipiens s.s. and 401 Cx. torrentium specimens from 24 locations in Belgium (collected between 2017 and 2019). Culex pipiens biotypes pipiens and molestus, and their hybrids, were differentiated by fragment size analysis of the CQ11 locus (956 pipiens and 227 molestus biotype specimens, 29 hybrids). Hybrids were observed at 13 out of 16 sympatric sites. These results confirm that both species are widespread in Belgium, but while Cx. torrentium revealed many COI haplotypes, Cx. pipiens s.s. showed only one abundant haplotype. This latter observation may either reflect a recent population-wide demographic or range expansion, or a recent bottleneck, possibly linked to a Wolbachia infection. Finally, new evidence is provided for the asymmetric but limited introgression of the molestus biotype into the pipiens biotype.

Human Perrault syndrome (PRLTS) is defined by autosomal recessive inheritance with primary ovarian insufficiency and early hearing loss. Most PRLTS disease proteins modulate mitochondrial transcription or translation. Among the genetic causes are ClpP mutations, which trigger also complete azoospermia, whose cellular and molecular underpinnings are unknown. Here, the ClpP-null mouse model was studied by global transcriptomics, proteomics, RT-qPCR, immunoblots, tissue fractionation, testis histology, and was crossed with STING/IFNAR mutants. Spermatogenesis showed accumulated early spermatocytes, versus deficits of desynapsis and kinetochore factors; excess Dazl/Stra8 and acetylSMC3, versus deficient SHCBP1L, were molecular correlates. Spermiogenesis showed few round spermatids, tsHMG/TFAM in elongated spermatids was absent; transcripts for tail/acrosome factors were downregulated from start. Nuclear anomalies included a failed Rec8 induction, early BRDT deficiency, histone H3 cleavage, and cGAMP increase, among antiviral responses typical of ClpP-mutants. However, deletion of downstream innate immune signals STING/IFNAR failed to reestablish fertility. As mitochondrial triggers, we observed accumulation of ClpX, with PTCD1, POLDIP2, GRSF1, ALKBH7, DNAJA3, AURKAIP1, VWA8, and Perrault proteins ERAL1, PEO1, HARS2, partially showing nuclear redistribution. ClpP-depletion is known to cause extra-mitochondrial release of mispacked mtDNA/mtRNA/protein complexes. Now we define nuclear inflammatory responses and meiotic arrest as consequences, similar to observations in mito-mice and mutator-mice.

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

Fish schooling implies an awareness of the swimmers for their companions. In flow mediated environments, in addition to visual cues, pressure and shear sensors on the fish body are critical for providing quantitative information that assists the quantification of proximity to other swimmers. Here we examine the distribution of sensors on the surface of an artificial swimmer so that it can optimally identify a leading group of swimmers. We employ Bayesian experimental design coupled with two-dimensional Navier Stokes equations for multiple self-propelled swimmers. The follower tracks the school using information from its own surface pressure and shear stress. We demonstrate that the optimal sensor distribution of the follower is qualitatively similar to the distribution of neuromasts on fish. Our results show that it is possible to identify accurately the center of mass and even the number of the leading swimmers using surface only information.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

In this paper, a horizontally moving suspended mass pendulum base is designed and controlled using robust control theory. H infinity optimal loop shaping with first and second order desired loop shaping function controllers are used to improve the performance of the system using Matlab/Simulink Toolbox. Comparison of the H infinity optimal loop shaping with first and second order desired loop shaping function controllers for the proposed system have been done to track the desired angular position of the pendulum using step and sine wave input signals and a promising result has been obtained succesfully.

In this paper, modelling designing and simulation of a simple voltage amplidyne system is done using robust control theory. In order to increase the performance of the voltage amplidyne system with H ∞ optimal control synthesis and H ∞ optimal control synthesis via ∞-iteration controllers are used. The open loop response of the voltage amplidyne system shows that the system can amplify the input 7 times. Comparison of the voltage amplidyne system with H ∞ optimal control synthesis and H ∞ optimal control synthesis via ∞-iteration controllers to track a desired step input have been done. Finally, the comparative simulation results prove the effectiveness of the proposed voltage amplidyne system with H ∞ optimal control synthesis controller in improving the percentage overshoot and the settling time.

With the rapid spread of carbon trading in the global economy, the interactions of prices between carbon (or clean/renewable energy) and traditional fossil energies such as coal and oil have raised growing attention, but little research have discussed their dynamic volatility spillover and time-varying correlation. The purpose of this study is to investigate these issues, for the weekly data of EUA futures, Biofuel and Brent oil prices from 25 October 2009 to 5 July 2020. We employ the VAR-GARCH model with the BEKK specification. Our results are summarized as follows. At first, we identified the sudden changes and the volatility persistence in the three markets, and also confirmed that the volatility of the markets has changed significantly over time. Secondly, we find that there are a weak volatility spillover effect among the three markets, while a strong spillover effect between the EUA and Brent oil markets. Lastly, in financial markets, the EUA can be used as a hedging portfolio for the Biofuel and Brent oil markets. These results can help investors to well compose their portfolios and manage their investment risks, and help potential pollutant emission sources to join in carbon market in a cost-effective way.

This paper mainly analyzes the design and control of the rotational inverted pendulum, and presents a state space expression. Since the system is highly unstable a feedback control system is used. Augmentations with weighting functions based mixed sensetivity and H2 optimal control methods are used to make the system stable for uprise position. The rotational inverted pendulum have been simulated and compared with the proposed controllers and a promising results have been analyzed sussesfuly.

Over the last decades, the energy market around the world has reshaped due to accommodating the high penetration of renewable energy resources. Although renewable energy sources have brought various benefits, including low operation cost of wind and solar PV power plants, and reducing the environmental risks associated with the conventional power resources, they have imposed a wide range of difficulties in power system planning and operation. Naturally, classical optimal power flow (OPF) is a nonlinear problem. Integrating renewable energy resources with conventional thermal power generators escalates the difficulty of the OPF problem due to the uncertain and intermittent nature of these resources. To address the complexity associated with the process of the integration of renewable energy resources into the classical electric power systems, two probability distribution functions (Weibull and lognormal) are used to forecast the voltaic power output of wind and solar photovoltaic, respectively. Optimal power flow, including renewable energy, is formulated as a single-objective and multi-objective problem in which many objective functions are considered, such as minimizing the fuel cost, emission, real power loss, and voltage deviation. Real power generation, bus 13 voltage, load tap changers ratios, and shunt compensators values are optimized under various power systems’ 14 constraints. This paper aims to solve the OPF problem and examines the effect of renewable energy resources 15 on the above-mentioned objective functions. A combined model of wind integrated IEEE 30-bus system, solar 16 PV integrated IEEE 30-bus system, and hybrid wind and solar PV integrated IEEE 30-bus system are performed 17 using the equilibrium optimizer technique (EO) and other five heuristic search methods. A comparison of 18 simulation and statistical results of EO with other optimization techniques showed that EO is more effective 19 and superior.

— In a smart healthcare system," Human Activity Recognition (HAR)" is considered as an efficient approach in pervasive computing from activity sensor readings. The "Ambient Assisted Living (AAL)" in the home or community helps the people to provide independent care and enhanced living quality. However, many AAL models are restricted to multiple factors that include both the computational cost and system complexity. Moreover, the HAR concept has more relevance because of its applications, such as content-based video search, sports play analysis, crowd behavior prediction systems, patient monitoring systems, and surveillance systems. This paper attempts to implement the HAR system using a popular deep learning algorithm, namely "Recurrent Neural Network (RNN)" with the activity data collected from smart activity sensors over time, and it is publicly available in the "UC Irvine Machine Learning Repository (UCI)". The proposed model involves three processes: (1) data collection, (b) optimal feature learning, and (c) activity recognition. The data gathered from the benchmark repository was initially subjected to optimal feature selection that helped to select the most significant features. The proposed optimal feature selection method is based on a new meta-heuristic algorithm called "Colliding Bodies Optimization (CBO)". An objective function derived from the recognition accuracy has been used for accomplishing the optimal feature selection. The proposed model on the concerned benchmark dataset outperformed the conventional models with enhanced performance.

This work aims to develop an autonomous system for the unmanned aerial vehicle (UAV) to land on a moving platform such as the automobile or marine vessels, providing a promising solution for a long-endurance flight operation, a large mission coverage range, and a convenient recharging ground station. Different from most state-of-the-art UAV landing frameworks which rely on UAV’s onboard computers and sensors, the proposed system fully depends on the computation unit situated on the ground vehicle/marine vessel to serve as a landing guidance system. Such novel configuration can therefore lighten the burden of the UAV and computation power on the ground vehicle/marine vessel could be enhanced. In particular, we exploit a sensor fusion-based algorithm for the guidance system to perform UAV localization, whilst a control method based upon trajectory optimization is integrated. Indoor and outdoor experiments are conducted and the result shows that a precise autonomous landing on a 43 X 43 cm platform could be performed.

In this study, the thermal behavior of a PCM-based heat sink in the presence of horizontal fins was numerically investigated. These types of heat sink can be effective in electronic cooling applications. Independent variables included aspect ratio (AR), number of horizontal fins (n) and their length (LR), while the objective function was defined to maximize the safe operation time (tmax). The incorporation of horizontal fins has a positive effect (thermal conductivity enhancement) as well as a negative effect (latent heat reduction). Based on the results, the optimal number of horizontal fins was five. As the number of fins rises up to five, the incremental effect of thermal conductivity improvement (positive effect) was superior to the decremental effect of the latent heat reduction (negative effect), hence the objective function (tmax) improved. However, with a further increase in the number of fins upon five, the negative effect prevailed over the positive effect and therefore the safe operation time diminished.

In this paper, the design and performance investigation of the permanent magnet machines have been done to increase the mechanical and electrical outputs improvement of the systems. A permanent magnet Dc motor (PMDM) and generator (PMDG) have been modelled and designed to improve the angular position and generated current respectively. In this work, augmentation based H 2 optimal and H infinity synthesis controllers have been designed as a controller for the two systems and a comparison between the proposed controller for tracking a reference inputs and a promising results have been obtained.

Manufacturers of photovoltaic modules do not provide all the information necessary to predict their performance under different climatic conditions. This forces the development of mathematical models of behavior and the application of mathematical methods for the calculation of their associated parameters. A toolbox called PVMSim implemented in MATLAB/GUI is proposed in this paper. PVMSIm provides models allowing the simulation of photovoltaic modules. A two-diode model is used to represent the effect of irradiance and temperature on the V-I and V-P characteristic curves. The accuracy of PVMSim has been vaildated by applying the models to two mono-crystalline and multi-crystalline solar modules of different power ratings and manufacturers. The model PVMSim model accuracy was verified against the manufacturer’s datasheet. This paper shows that this tool is useful for designers and professionals who require an intuitive graphical interface for fast and accurate modeling, simulation and sizing of photovoltaic systems.

Cell migration is essential for physiological, pathological and biomedical processes such as, in embryogenesis, wound healing, immune response, cancer metastasis, tumour invasion and inflammation. In light of this, quantifying mechanical properties during the process of cell migration is of great interest in experimental sciences, yet few theoretical approaches in this direction have been studied. In this work, we propose a theoretical and computational approach based on the optimal control of geometric partial differential equations to estimate cell membrane forces associated with cell polarisation during migration. Specifically, cell membrane forces are inferred or estimated by fitting a mathematical model to a sequence of images, allowing us to capture dynamics of the cell migration. Our approach offers a robust and potentially accurate framework to compute geometric mechanical membrane forces associated with cell polarisation during migration and also yields geometric information of independent interest, we illustrate one such example that involves quantifying cell proliferation levels which are associated with cell division, cell fusion or cell death.

Pericentromeric regions of chromosomes enriched in tandemly repeated satellite DNA although representing a significant part of eukaryotic genomes are still understudied mainly due to interdisciplinary knowledge gaps. Recent studies suggest their important role in genome regulation, karyotype stability and evolution. Thus, the idea of satellite DNA as a junk part of the genome was refuted. Integration of data about molecular composition, chromosome behaviour and details of in situ organization of pericentromeric regions is of great interest. The objective of this work was a cytogenetic analysis of the interactions of pericentromeric regions non-homologous chromosomes in mouse spermatocytes using immuno-FISH. We analysed two events: the associations between cerntomeric regions of X chromosome and autosomes, and associations between centromeric regions of autosomal bivalents forming chromocenters. We conclude that X chromosome form temporary synaptic associations with different autosomes in early meiotic prophase I which normally can be found at pachytene-diplotene without signs of pachytene arrest. These associations are formed between the satellite DNA-enriched centomeric regions of X chromosome and different autosomes but not involve the satellite-poor centromeric region of Y-chromosome. We suggest the mechanism of X chromosome competitive replacement from such associations during synaptic correction. We showed that centromeric region of the X chromosome remains free of γH2Ax-dependent chromatin inactivation, while Y chromosome is completely inactivated. This findings highlights the predominant role of associations between satellite DNA-enriched regions of different chromosomes including X. We assume that X-autosome temporary associations is a manifestation of an additional synaptic disorders checkpoint. These associations are normally corrected before the late diplotene. We revealed that the intense spreading conditions applied to the spermatocytes I nuclei did not lead to destruction of stretched chromatin fibers i.e. elongated chromocenters enriched in satellite DNA. Revealed by us tight associations between pericentromeric regions of different autosomal bivalents and X chromosome may represent the basis for repeat stability maintenance in autosomes an X chromosome. The consequences of our findings are discussed. We obtained the preparations of mouse spermatocytes nuclei in the meiotic prophase I using two approaches: standard and extremely intense surface spread techniques. Using immuno-FISH we visualized tandemly repeated mouse Major and Minor satellite DNA located in the pericentromeric regions of chromosomes and performed a morphological comparison of the standard- and intensely spreaded meiotic nuclei. Based on our results, we assume the remarkable strength of the chromocenter-mediated associations, “chromatin “bridges”, between different bivalents at the pachytene and diplotene stages. We have demonstrated that the chromocenter “bridges” between the centromeric ends of meiotic bivalents are enriched in both tandemly repeated Major and Minor satellite DNA. Association of centromeric regions of autosomal bivalents and X-chromosome but not with Y-chromosome correlates with the absence of Major and Minor satellites on Y-chromosome. We suggest that revealed tight associations between pericentromeric regions of bivalents may represent the network-like system providing dynamic stability of chromosomal territories, as well as add new data for the hypothesis of ectopic recombination in these regions which supports sequence homogeneity between non-homologous chromosomes and does not contradict the meiotic restrictions imposed by the crossing-over interference near centromeres. We conclude that nuclear architecture in meio-sis may play an essential role in contacts between the non-homologous chromosomes providing the specific characteristics of pericentromeric DNA.

In this paper, modelling designing and simulation of a Ward Leonard layout system is done using robust control theory. In order to increase the performance of the Ward Leonard layout system with H infinity optimal control synthesis and H infinity optimal control synthesis via gamma-iteration controllers are used. The open loop response of the Ward Leonard layout system shows that the system needs to be improved. Comparison of the Ward Leonard layout system with H∞ optimal control synthesis and H infinity optimal control synthesis via gamma-iteration controllers to track a desired step speed input have been done. Finally, the comparative simulation results prove the effectiveness of the proposed Ward Leonard layout system with H infinity optimal control synthesis controller in improving the percentage overshoot and the settling time.

In this paper we analyze and propose new method and algorithm of selecting the optimal labor time as a function of skills following our main references Mirrlees (1971), Saez (2001) and Stancheva (2014). The optimal labor time is a situation when the utility function of individual reaches a maximum. One of the main differences with Saez (2001) is our algorithm for creation the skill distribution.

In this paper, an electromechanical mass lifter system is designed, analyzed and compare using optimal and robust control theories. LQR and μ -synthesis controllers are used to improve the lift displacement by comparison method for tracking the desired step and sinusoidal wave signals input. Finally, the comparison simulation result prove the effectiveness of the electromechanical mass lifter system with μ -synthesis controller for improving the rise time, percentage overshoot, settling time and peak value of tracking the desired step displacement signal and improving the peak value for tracking the desired sinusoidal displacement signal with a good performance.

Mesenchymal stem cells (MSCs) are involved in the process of extracellular matrix (ECM) remodeling where collagens play a pivotal role. We recently demonstrated that the remodeling of adsorbed collagen type I might be disordered upon oxidation following its fate in the presence of human adipose-derived MSC (ADMSCs). With the present study, we intended to learn more about the effect of polyphenolic antioxidant Epigallocatechin gallate (EGCG) attempting to mimic the conditions of oxidative stress in vivo and its putative prevention by antioxidants. Collagen Type I was isolated from mouse tail tendon (MTC) and labeled with FITC before oxidizing according to Fe2+/H2O2 protocol. FITC-collagen remodeling by ADMSC was assessed morphologically before and after EGCG pretreatment and confirmed via detailed morphometry analysis measuring the anisotropy index (AI) and fluorescence intensity (FI) in selected regions of interest (ROI), namely: outside the cells; over the cells and central (nuclear perinuclear) region, whereas the pericellular proteolytic activity was measured by de-quenching of fluorescent collagen probes (FRET effect). Here we provide morphological evidence that MTC undergoes significant reorganization by the adhering ADMSC along with the substantial activation of pericellular proteolysis, and further confirm that both processes are suppressed upon collagen oxidation. An important observation was that this abrogated remodeling cannot be prevented by the EGCG pretreatment. Conversely, the detailed morphometry analysis showed that oxidized FITC-collagen rather tends to accumulate beneath the cells and around the cell’s nuclei suggesting the activation of alternative routes for its removal, such as internalization and/or transcytosis. Morphometry analysis also revealed that both processes are supported by EGCG pretreatment.

There are many problems based on solving non-autonomous differential equations of the form x¨(t)+ω2(t)x(t)=0, where x(t) represents the coordinate of a material point and ω is the angular frequency. The inverse problem involves finding the bounded coefficient ω. Continuity of the function ω(t) is not required. The trajectory x(t) is unknown, but the initial and final values of the phase variables are given. The variation principle of minimum time for the entire dynamic process allows for the determination of the optimal solution {x(t),ω(t)}. Thus, the inverse problem is an optimal control problem. No simplifying assumptions were made.

There are no theorems (proven theories) in the biological sciences. We propose that the 3 31 nt minihelix tRNA evolution theorem be universally accepted as one. The 3 31 nt minihelix theorem completely describes evolution of type I and type II tRNAs from ordered precursors (RNA repeats and inverted repeats). Despite diversification of tRNAome sequences, statistical tests overwhelmingly support the theorem. Furthermore, the theorem relates the dominant pathway for the origin of life on Earth, specifically, how tRNAomes and the genetic code may have coevolved. Alternate models for tRNA evolution (i.e., 2 minihelix, convergent and accretion models) are falsified. In the context of the pre-life world, tRNA was a molecule that via mutation could modify anticodon sequences and teach itself to code. We relate the clearest history to date of the chemical evolution of life on Earth. From analysis of tRNA evolution, ribozyme-mediated RNA ligation was a primary driving force in evolution of complexity during the pre-life to life transition on Earth.

Noise reduction is the major issue in the loudspeaker for the application of the musical instruments and related areas. In this paper, a noise disturbance control of a loudspeaker with optimal and robust controllers has been done successfully. The noise of the loudspeaker has been analyzed by simply track a reference cone displacement with the actual cone displacement. Static output feedback and H infinity optimal loop shaping controllers have been used to compare the actual and reference cone displacements by using a sine wave and random cone displacement signals and a promising results have been analyzed.

Although many policosanols from different sources, such as sugar cane, rice bran, and insects, have been marketed worldwide, there has been no comparative study of the in vivo efficacy using a hyperlipidemic animal model. This study compared the efficacy of treating dyslipidemia with four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran) in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and high cholesterol diet (HCD, final 4%, wt/wt) in a tetrabit, the Raydel policosanol group and Xi’an Natural policosanol group showed the highest survivability of approximately 81%, whereas the Xi’an Realin policosanol group and Shaanxi policosanol group showed 57% and 67% survivability, respectively. Among five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p<0.001 versus HCD control) and triglyceride (TG, p<0.001 versus HCD control) with the highest percentage of high-density lipoproteins (HDL)-C in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes. In the ovary, the Raydel policosanol group also showed the highest contents of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testis, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis with the least interstitial area and reactive oxygen species (ROS) production in testicular cells. In conclusion, 12 weeks of Raydel policosanol consumption resulted in remarkable improvement of the blood lipid profile, amelioration of inflammation in the liver, and enhancement of the cell morphology in the ovary and testis with the highest survivability under the HCD.

Malaria is a critical fevered illness caused by Plasmodium parasites transmitted among people through the bites of infected female Anopheles mosquitoes. Public awareness about the disease is important for the control of disease. This article proposes a mathematical model to study the dynamics of malaria disease transmission with the influence of awareness-based control interventions. We found two equilibria of the model, namely the disease-free and endemic equilibrium. Disease-free equilibrium is stable globally if basic reproduction number (R0) is less than unity (R0&lt;1). Some basic mathematical properties of the proposed model, such as nonnegativity and boundedness of solutions, the feasibility of the equilibrium points and their stability properties, have been studied. Finally, we adopted optimal control to minimize the cost of disease control and solve the problem by formulating Hamiltonian functional. The optimal use of insecticides for controlling the mosquito population is determined. Numerical simulations have been provided for the confirmation of the analytical results. We conclude that media awareness with optimal control approach is best for cost-effective malaria disease management.

Understanding surface water evaporation in tropical catchments is pivotal for effective water management, but limited research exists on stable isotopic (δ2H and δ18O) assessment of water evaporation losses. Our study bridges that gap, examining stable isotopes in meteoric water and surface waters across tropical regions, both humid and semi-arid. Using the Craig-Gordon model, we calibrated evaporation-to-inflow (E/I) ratios, identifying distinct E/I variations between seasons and regions. Notably, the semi-arid region consistently exhibited higher E/I ratios due to climatic characteristics. By integrating the Hamiltonian Monte Carlo and the No-U-Turn Sampler, we were able to quantify uncertainties in isotopic and meteorological parameters, resulting in E/I estimates within 68% and 95% confidence intervals. Our Bayesian model insights are critical for freshwater resource optimization and hydrological modeling in tropical regions.

This study proposes a novel flexible bus dispatching system where a fleet of fully automated modular bus units, together with conventional buses, serves the passenger demand. These modular bus units can either operate individually or combined (forming larger modular buses with a higher passenger capacity). This provides enormous flexibility to manage the service frequencies and vehicle allocation, reducing thereby the operating cost and improving passenger mobility. We develop an optimization model used to determine the optimal composition of bus units and the optimal service frequency at which the buses (both conventional and modular) are dispatched across each bus line. We explicitly account for the dynamics of traffic congestion and complex interactions between the modes at the network level based on the recently proposed three-dimensional macroscopic fundamental diagram (3D-MFD). To the best of our knowledge, this is the first application of the 3D-MFD and modular bus units for the frequency setting problem in the domain of bus operations. Numerical results show the improvements in the total system cost made by adapting the number of combined modular bus units and their dispatched frequencies to the evolution of both, the car and the passenger demand. A comparison with the commonly used approach that considers only the bus system (neglecting the complex multimodal interactions and congestion propagation) reveals the value of the proposed modeling framework.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

In this paper we analyze and propose new method and algorithm of selecting the optimal labor time as a function of skills following our main references Mirrlees (1971), Saez (2001) and Stancheva (2014). The optimal labor time is a situation when the utility function of individual reaches a maximum. One of the main differences with Saez (2001) is our algorithm for creation the skill distribution

Cardiac vascular diseases, especially acute myocardial infarction (AMI), are one of the leading causes of death worldwide. Therefore cardio-specific biomarkers such as cardiac Troponin I (cTnI) play an essential role in diagnostics. In order to enable rapid and accurate measurement of cTnI with the potential of online measurements, a proof of concept of a chemiluminescence-based biosensor is presented. A flow cell was designed and combined with a sensitive CMOS camera allowing an optical readout. In addition, a microfluidic setup was established, and cTnI was determined selectively. The biomarker cTnI was expressed in E. coli, and its characterization and correct folding were investigated by different analytical methods. This recombinant cTnI was used for enzyme-linked immunosorbent assays (ELISA), calibrated against commercially available recombinant cTnI, and applied for the biosensor measurements. Based on chemiluminescence detection, the biosensor was successfully tested, and the cTnI biomarker could be reproducibly determined in buffer, spiked blood serum, and plasma.

Every month teachers face the dilemma of what exercises should their students practice, and what their consequences are on long-term learning. Since teachers prefer to pose their own exercises, this generates a large number of questions, each one attempted by a small number of students. Thus, we couldn’t use models based on big data such as deep learning. Instead, we developed a simple to understand state-space model that predicts end-of-year national test scores. We used 2,386 online fourth-grade mathematic questions designed by teachers and each attempted by some of the 500 students in 24 low socioeconomic schools. We found that the state-space model predictions improved month-by-month and that in most months it outperformed linear regression models. Moreover, the state-space estimator provides for each month a direct mechanism to simulate different practice strategies and compute their impact on the end-of-year standardized national test. We built iso-impact curves based on two critical variables: the number of questions solved correctly in the first attempt and the total number of exercises attempted. This allows the teacher to visualize the trade-off between asking students to do exercises more carefully or doing more exercises. To the best of our knowledge, this model is the first of its kind in education. It is a novel tool that supports teachers drive whole classes to achieve long-term learning targets.

Hasselmann and coauthors proposed the discrete interaction approximation (DIA) as the best tool replacing the nonlinear evolution term in a numerical wind-wave model. Much later, Polnikov and Farina radically improved the original DIA by means of location all the interacting four wave vectors, used in the DIA configuration, exactly at the nodes of the numerical frequency-angular grid. This provides nearly two-times enhancing the speed of numerical calculation for the nonlinear evolution term in a wind-wave model. For this reason, the proposed version of the DIA was called as the fast DIA (FDIA). In this paper we demonstrate all details of the FDIA concept for several frequency-angular numerical grids of high resolution, with the aim of active implementation the FDIA in modern versions of world-wide used wind-wave models.

The average age of in-service bridges has increased in recent years in the United States. To address this issue, structural health monitoring and damage identification approaches can be employed to prioritize maintenance/replacement of aging bridges. Among the damage identification and operational health monitoring approaches, finite element (FE) model updating methods can offer a solution to evaluate the mechanics-based characteristics of bridges. However, in a real-world setting, unidentifiability and mutual dependency between model parameters, modeling errors, especially due to boundary conditions, as well as ill-conditioning of updating algorithms can pose challenges to the application of FE model updating methods. To address these challenges, this study presents a two-step FE model updating approach. In the first step, modal-based model updating is used to estimate linear model parameters mainly related to the stiffness of boundary conditions and material properties. In the second step, in order to refine parameter estimation accounting for nonlinear response behavior of the bridge, a time-domain model updating is carried out. In this step, boundary conditions are fixed at their final estimates using modal-based model updating. To prevent the convergence of updating algorithm to local solutions, the initial estimates for nonlinear material properties are selected based on their corresponding final estimates in the modal-based model updating. To validate the applicability of the two-step FE model updating approach, a series of forced-vibration experiments are designed and carried out on a pair of decommissioned and deteriorated prestressed bridge I-girders. After carrying out the two-step FE model updating, the final estimates of concrete compressive strength are shown to provide reasonable assessment of the damage extent in the girders.

Aiming at the problem of low charging efficiency caused by the scattered sensor nodes in traditional wireless rechargeable sensor networks (WRSNs), a UAV-assisted WRSN Online Charging Strategy Based on Dynamic Queue and Improved K-means (UOCS) is proposed. The scheme assumes that the energy consumption of nodes is unpredictable, and only generates charging requests when the energy is lower than a threshold, and performs on-demand responses to nodes that issue charging requests. The scheme combines the characteristics of one-to-one charging of UAVs, the selection and allocation timing of waiting queues and the number of UAVs, and the improved K-means partitioning based on space-time coordination(SPKM), which simplifies the problem of coordinated charging of multiple UAVs and maximizes energy. Using the efficiency and charging success rate, the optimal charging trajectory can be found under the constraint that the node will not starve to death due to power shortage. Finally, a simulation comparison experiment is carried out with the existing UAV charging scheduling strategy. UOCS achieves the optimal node survival rate with low algorithm complexity.

In this paper we present AWEbox, a Python toolbox for modeling and optimal control of multi-aircraft systems for airborne wind energy (AWE). AWEbox provides an implementation of optimization-friendly multi-aircraft AWE dynamics for a wide range of system architectures and modeling options. It automatically formulates typical AWE optimal control problems based on these models, and finds a numerical solution in a reliable and efficient fashion. To obtain a high level of reliability and efficiency, the toolbox implements different homotopy methods for initial guess refinement. The first type of methods produces a feasible initial guess from an analytic initial guess based on user-provided parameters. The second type implements a warmstart procedure for parametric sweeps. We investigate the software performance in two different case studies. In the first case study we solve a single-aircraft reference problem for a large number of different initial guesses. The homotopy methods reduce the expected computation time by a factor of 1.7 and and the peak computation time by a factor of 8, compared to when no homotopy is applied. Overall, the CPU timings are competitive to timings reported in the literature. When the user initialization draws on expert a priori knowledge, homotopies do not increase expected performance, but the peak CPU time is still reduced by a factor of 5.5. In the second case study, a power curve for a dual-aircraft lift-mode AWE system is computed using the two different homotopy types for initial guess refinement. On average, the second homotopy type, which is tailored for parametric sweeps, outperforms the first type in terms of CPU time by a factor of 3. In conclusion, AWEbox provides an open-source implementation of efficient and reliable optimal control methods that both control experts and non-expert AWE developers can benefit from.

Should our planet be visited by an extraterrestrial civilization, the prevailing assumption would undoubtedly be that the extraterrestrial civilization is Type I i.e. its capacity for interstellar travel results from its technological development. This assumption is dangerous for it unnecessarily leads to the Extraterrestrial Tandem Hypothesis (ETH): the belief than an extraterrestrial civilization technologically capable of interstellar travel must also be technologically compatible with the inexorably rapid annihilation of life on Earth. Such a state of things would compromise the planet’s capacity to stage a confident defense should the extraterrestrials prove belligerent. The presumption of Type I extraterrestrials (on the premise of the capacity for interstellar travel alone) is unfounded as extraterrestrials may be Type II i.e. capable of interstellar travel by virtue of natural intrinsic or extrinsic factors. This paper advances, most importantly, that the fundamental policy of first contact should be the employment of various strategies toward the evaluation of the technological capacity of visiting extraterrestrials. This evaluation must be particularly devoted to the detection of Type II extraterrestrials masquerading as Type I (using concealment and Wizard of Oz strategies). Integral to this detection are the concepts of the precedence relation and The Extraterrestrial Exclusion Principle (EEP). A precedence relation is a qualitative relation expressing the relative difficulty of producing a technological action. The Extraterrestrial Exclusion Principle states that a Type I extraterrestrial life form is excluded from certain actions. Such actions are lower in precedence than interstellar travel and may be described as in violation of the EEP or EEP forbidden. EEP actions reveal extraterrestrials to be Type II. As an example, the value of the Hawking Warning is subjected to EEP analysis. Furthermore, a hypothetical conundrum in linguistics termed the Kryptonian Linguistic Paradox (KLP) is discussed as a case of an EEP forbidden act. Finally, the paper explores the limitations of the stated fundamental policy of first contact.

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

We obtain exact solutions to the field equations for 5 dimensional LRS Bianchi type-I spacetime in $f(R,T)$ theory of gravity where specifically the following three cases are considered: (i) $f(R,T)=\mu(R+T)$, (ii) $f(R,T)=R \mu + R T \mu^2$ and (iii) $f(R,T)=R+\mu R^2+\mu T$ where $R$ and $T$ respectively the Ricci scalar and trace of the energy-momentum tensor. It is found that the equation of state (EOS) parameter $w$ is governed by the parameter $\mu$ involved in the $f(R,T)$ expressions. We fine-tune the parameter $\mu$ to obtain effect of phantom energy in the model, however we also restrict this parameter to obtain a stable model of the universe. It is noted that the model isotropizes at finite cosmic time.

How to optimally allocate COVID-19 vaccines and scarce public goods is a crucial and sensitive question to scholars, policy-makers, and practitioners. The ethical dimensions and principles of vaccine allocation between groups are widely agreed upon, whereas the ethical dimensions and principles of vaccine distribution between countries at the peak of the COVID-19 pandemic are highly controversial. This article aims to investigate how vaccines were globally allocated across countries and propose an optimal allocation mechanism for vaccines and scarce public goods. The results show that, to a certain extent, the global allocation of COVID-19 vaccines was fair and effective. Countries with more cases and deaths obtained more vaccines and vaccinations. Wealthier countries might receive more vaccinations but also suffer more severe consequences of COVID-19. Though COVAX could miss its initial vaccine delivery targets, the facility should be considered successful in its core goals and plays a critical role in controlling the pandemic. The study proposes a fair and effective mechanism of vaccine allocation that combines the roles of markets and interventions of international organizations and national governments with three degrees: emergency, priority, and market.

The present work concerns with presenting an explicit formula for new shifted wavelet (NSW) functions. Wavelet functions have many applications and advantages in both applied and theoretical fields. They are formulated with different orthogonal polynomials to construct new techniques for treating some problems in sciences, and engineering. A new important differentiation property of NSW in terms of NSW themselves is obtained and proved in this paper. Then it is utilized together with the state parameterization technique to find solution of optimal control problem (OCP) approximately. The suggested method converts the OCP into a quadratic programming problem, which can be easily determined on computer. As a result, the approximate solution closes with the exact solution even with a small number of NSW utilized in estimation. The error bound estimation for the proposed method is also discussed. Some test numerical examples are solved to demonstrate the applicability of the suggested method. For comparison, the exact known solutions against the obtained approximate results are listed in Tables.

In this study, we construct a new Atangana-Baleanu fractional model for whooping cough disease to predict future dynamics of the disease, as well as to suggest strategies to eliminate the disease in an optimal way. We prove that the proposed model has a unique solution which is positive and bounded. To measure contagiousness of the disease, we determine the reproduction number R0 and use it to examine the local and global stability at equilibrium points that have symmetry. Through sensitivity analysis, we determine parameters of the model that are most sensitive to R0. The ultimate aim of this research is to analyze different disease prevention approaches in order to find the most suitable one. For this, we include the vaccination and quarantine compartments in the proposed model and formulate an optimal control problem to assess the effect of vaccination and quarantine rates on disease control in three distinct scenarios. Firstly, we study the impact of vaccination strategy and conclude findings with presentation of graphical results. Secondly, we examine the impact of quarantine strategy on whooping cough infection with possible elimination from the society. Lastly, we implement vaccination and quarantine strategies together to visualize their combine effect on infection control. In addition to the study of an optimal control problem, we examine the effect of fractional order on disease dynamics as well as the impact of constant vaccination and quarantine rates on disease transmission and control. We determine that the optimal control strategy with the three controls is more effective in reducing the spread of whooping cough infection. Implementation of Toufik-Atangana type numercial scheme both for the state and adjoint equations is another contribution of this article.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on their animal model’s data verified by molecular docking, multitarget interactions in network pharmacology, and dynamic simulation assays. The GC-MS characterized tamarind products were administered to the cholesterol-induced hypertensive Wistar albino rat models. Two-week-intervened animals were dissected to collect serum and organs which were respectively subjected to the analyses of hypertension-linked markers and tissue architectures. Lead biometabolites of tamarinds interacted with eight target receptors in molecular docking and dynamic simulation studies and they were tested for multitarget interactions using network pharmacological analyses. Results showed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), Troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour over the sweet tamarind flesh extracts, but seed extracts had a smaller influence. Among the tamarind’s biometabolites, Gamma-sitosterol (ϒ-sitosterol) was found to be the best ligand in managing hypertension via the possible ligand-receptor interactions with the guanylate cyclase which displayed the best drug-likeliness through the highest binding energy -9.3 Kcal. Multitargeted interactions-based degree algorithm and phylogenetic tree of pathways showed 14 targeted genes, of which NR3C1, REN, PPARG, and CYP11B1 hub genes, were consistently modulated by the ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 to 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be supplemented to be a more prospective antihypertensive target or nutraceuticals affirming through advanced preclinical and clinical studies.