PHA synthases (PhaC) are grouped into four classes based on the kinetics and mechanisms of reaction. The grouping of PhaC enzymes into four classes is dependent on substrate specificity, according to the preference in forming short chain length (scl) or medium chain length (mcl) polymers: class I, class III, and class IV produce scl-PHAs depending on propionate, butyrate, valerate and hexanoate precursors, while class II phaC synthesize mcl-PHAs based on the alkane (C6 to C14) precursors. PHA synthases of class I, in particular PhaC_Cs from Chromobacterium USM2 and PhaC_Cn/RePhaC1 from Cupriavidus necator/R. eutropha, have been analysed and the crystal structures of the C-domains have been determined. PhaC_Cn/RePhaC1 was also studied by small angle X-ray scattering (SAXS) analysis. Models have been proposed for dimerization, catalysis mechanism, substrate recognition and affinity, product formation and product egress route. The assays based on amino acid substitution by mutagenesis have been useful to validate the hypothesis on the role of amino acids in catalysis and in accommodation of bulky substrates, for the synthesis of PHB co-polymers and medium chain length-PHA polymers with optimized chemical properties.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

In the last decade, the genetic engineering world has been shaken up by a relatively new genetic editing tool based on RNA-guided Nucleases (RGNs): the CRISPR/Cas9 system. Since the first report in 1987 and its characterization in 2007 as a bacterial defense mechanism, the interest and research on this system have grown exponentially. CRISPR systems provide immunity to bacteria against invading genetic material; however, with specific modifications in sequence and structure, it becomes a precise editing system that makes it possible to genetically modify almost any organism. There are diverse approaches regarding the refinement of these modifications, such as constructing more accurate nucleases, understanding the cellular context and facing the epigenetic conditions, or re-designing guide RNAs (gRNAs). Considering the critical importance for the correct CRISPR/Cas9 systems performance, our scope will emphasize in the latter approach. Hence, we present an overview of the past and the most recent guide RNA web-based design tools, highlighting their computational architecture and gRNA characteristics evolution through the years. Our study concisely explains the computational approaches that use machine learning techniques, deep neural networks, and large datasets of gRNA/target interactions to make possible both predictions and classifications directed to design, optimize, and create promising gRNAs suitable for future gene therapies.

This review explores the integration of Virtual and Mixed Reality in medical training. The advent of immersive technologies has revolutionized traditional methodologies, offering immersive, interactive, and flexible learning environments. This study aims to assess the impact, efficacy, and potential of Extended Reality (XR) in medical education. Methods included a comprehensive analysis of current Metaverse’s applications in various medical fields, including surgery, diagnostics, and patient care. Results indicate a significant enhancement in learning outcomes, practical skills, and student engagement. Conclusions suggest that Virtual Reality is a valuable tool for medical training, providing realistic simulations and improving both theoretical knowledge and practical skills. The intersection of virtual reality and cognitive neuroscience presents an exciting frontier for understanding the human brain's response to immersive environments. This review explores how VR impacts learning, with a particular focus on the activation and engagement of the prefrontal cortex during immersive experiences. It delves into various studies that highlight the transformative potential of VR in educational settings and therapeutic applications, demonstrating how VR can facilitate deeper and more effective learning experiences. The review will present a dedicated section on the current methodologies used to analyze the brain's response while immersed in a virtual environment.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

All types of sports are potential application scenarios for automatic and real-time visual object and event detection. In rink hockey, the popular roller quad skate variant of hockey team sports, it is of great interest to automatically track player’s movements and positions, player’s sticks and, also, making other judgments, such as being able to locate the ball. In this work, we introduce a real-time pipeline composed by an object detection model, created specifically for rink hockey games, followed by a knowledge-based event detection module. Even in the presence of occlusions and quick motions, our deep learning object detection model effectively identifies and tracks, in real-time, important visual elements such as: ball; players; sticks; referees; crowd; goalkeeper; and goal. Using a curated dataset composed by a collection of videos of rink hockey, comprising 2525 annotated frames, we trained and evaluated the algorithm performance and compare it to state of the art object detection techniques. Our object detection model, based on YOLOv7, presents a global accuracy of 80%, and presents a good performance in terms of accuracy and speed, according to our results, making it a good choice for rink hockey applications. In our initial tests, the event detection module successfully detected one important event type in rink hockey games, the occurrence of penalties.

In this study, the application of the main algorithms used for SDM, namely Boosted Regression Tree (BRT), Generalized Linear Model (GLM), Multivariate Adaptive Regression Splines (MARS), Maximum Entropy (MAXENT) and Random Forest (RF), were considered in order to simulate the citrus probability of distribution in a Mediterranean area, based on presence data and a random background sample, and in relation to several predictors. The predictors were grouped under 19 bioclimatic variables, elevation described through a Digital terrain model, soil physical properties, and irrigation. Sensitivity analysis was carried out by: modifying the values of the main models’ parameters; and reducing the input presence points.

The Romani are the main European ethnic minority. The Romani people’s situation of social vulnerability and their difficulties in accessing the health system, make their health indicators worse than those of the non-Romani population. The present study will delve into the health beliefs and experiences with health services and their professionals through the perspectives of Romani women. In this qualitative study, 16 women of different ages were interviewed in a city located in the South of Spain. Four themes emerged from the analysis of data: the construction of the identity of Romani women, difficulties in life, health and disease beliefs and barriers in the access to the health system. We conclude that every project for the improvement of the health of the Romani community must take into account the active participation of Romani women and must consider the principles of Cultural Safety, by delving into the intercultural training of health professionals and addressing the social determinants of health which affect the Romani collective.

Digital twins are an emerging technology that could be harnessed for the digitalization of the industry. Steel industry systems contain a large number of electro-hydraulic components, as proportional valves. An input-output model for a novel water proportional cartridge valve is derived from physical modelling based on fluid mechanics, dynamics, and electrical principles. The valve is a two-stage valve with two 2/2-way water proportional valves as the pilot stage and a marginally stable poppet-type cartridge valve as the main valve. The orifice equation, which is based on Bernoulli principles, is approximated by a polynomial which makes parameter estimation easier and makes modelling possible without measuring pressure of the varying control volume situated in the pilot stage part of the valve. Data were collected when the valve was operating as a component in a closed-loop system as part of a press-mill machine in a steel manufacturing plant. Parameter estimation was made by convex optimization with physical constraints to overcome problems caused by poor system excitation. For comparison, a simple linear model was derived and the least squares method used for parameter estimation. A thorough estimation of the parameters relative errors is presented. The model contains 5 parameters related to the design parameters of the valve. The modelled position output is in good agreement with experimental data for training and test data. The model can be used for real time monitoring of the valve’s status by the model parameters. One of the model parameters varies linearly with production cycles. Thus, aging of the valve can be monitored.

Knowledge of the motivations of managers to practice Corporate Social Responsibility (CSR) is a critical issue for those who promote its adoption. The understanding of these reasons is complicated by the fact that there are different ways of defining this responsibility, raising the question of whether there is any relationship between reasons for adopting it and how to define it. To address this issue, a classification of these reasons was constructed and related to a classification of the different ways of defining CSR. A self-administered questionnaire was applied to a non-probability sample of Social Responsibility managers, which included indicators for both classifications. It was found that these managers present all types of motives, with proactive outweighing reactive motives and that there is a significant degree of correlation between the ways of defining CSR and the reasons for doing so. This suggests that managers present coherence in their objectives (motives) and means (practices of Social Responsibility.

Scales are widely used in many agricultural applications, ranging from weighing crops at harvest to determine crop yields to regularly weighing animals to determine growth rate. In agricultural research applications, there is a long history of measuring crop water use (evapotranspiration) using a particular type of scale called weighing lysimeters. Typically, weighing lysimeters require very accurate data logging systems that tend to be expensive. Recent developments in open-source technologies, such as micro-controllers and Internet of Things (IoT) platforms, created opportunities for developing effective and affordable ways to monitor crop water use and transmit the data to the Internet in near real-time. Therefore, this study aimed to create an affordable Internet of Things (IoT) scale system to measure crop evapotranspiration. A scale system to monitor crop evapotranspiration was developed consisting of an Arduino-compatible microcontroller with cell phone communication, electronic load cells, an Inter-Integrated Circuit (I2C) multiplexer, and analog-to-digital converters (ADC). The system was powered by a LiPo battery, charged by a small (6 W) solar panel. The IoT scale system was programmed to collect data from the load cells at regular time intervals and send the data to the ThingSpeak.com IoT platform. The system performed successfully during indoor and outdoor experiments conducted in 2023 at the Clemson University Edisto Research and Education Center, Blackville, SC. The results from the experiments showed that the IoT scale system could accurately measure crop evapotranspiration using the weighing lysimeter technique.

Some of the barriers preventing Virtual Reality (VR) from being widely adopted are the cost and unfamiliarity of VR systems. Here we propose that in many cases the specialized controllers shipped with most VR head-mounted displays can be replaced by a regular smartphone, cutting the cost of the system, and allowing users to interact in VR using a device they are already familiar with. To achieve this, we developed SmartVR Pointer, an approach that uses smartphones as a replacement for the specialized controllers for two essential operations in VR: selection and navigation by teleporting. In SmartVR Pointer a camera mounted on the head-mounted display (HMD) is tilted downwards so that it points to where the user will naturally be holding their phone in front of them. SmartVR Pointer supports three selection modalities: tracker-based,gaze-based, and combined/hybrid. In the tracker-based SmartVR pointer selection we use image-based tracking to track a QR code displayed on the phone screen and them map the phone’s position to a pointer shown within the field of view of the camera in the Virtual Environment. In the gaze-based selection modality the user places the pointer using their gaze and taps on the phone for selection. The combined technique is a hybrid between head-gaze-based interaction in VR and smartphone-based Augmented Reality. It allows the user to control a VR pointer that behaves like a mouse pointer by moving their smartphone to select objects within the virtual environment, and to interact with the selected objects using the smartphone’s touch screen. The touchscreen is used for selection and dragging. SmartVR Pointer is simple and requires no calibration and no complex hardware assembly or disassembly. We demonstrate successful interactive applications of SmartVR Pointer in a VR environment with a demo where the user navigates in the virtual environment using teleportation points on the floor and then solves a Tetris-style key-and-lock challenge.

In this article, the evolution in space and in time of the coronavirus pandemic is studied by utilizing a neural network with a self-organizing nature for the spatial analysis of data, and a fuzzy fractal method for capturing the temporal trends of the time series of the countries. Self-organizing neural networks possess the capability for clustering countries in the space domain based on their similar characteristics with respect to their coronavirus cases. In this form enabling finding the countries that are having similar behavior and thus can benefit from utilizing the same methods in fighting the virus propagation. To validate the approach, publicly available datasets of coronavirus cases worldwide have been used. In addition, a fuzzy fractal approach is utilized for the temporal analysis of time series of the countries. Then, a hybrid combination of both the self-organizing maps and the fuzzy fractal approach is proposed for efficient COVID-19 forecasting of the countries. Relevant conclusions have emerged from this study, that may be of great help in putting forward the best possible strategies in fighting the virus pandemic. A lot of the existing works concerned with the Coronavirus have look at the problem mostly from the temporal viewpoint that is of course relevant, but we strongly believe that the combination of both aspects of the problem is relevant to improve the forecasting ability. The most relevant contribution of this article is the proposal of combining neural networks with a self-organizing nature for clustering countries with high similarity and the fuzzy fractal approach for being able to forecast the times series and help in planning control actions for the Coronavirus pandemic.

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is currently known that AMH introgressed with archaic hominins once they left the African continent. Current out of African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.

The effect of the addition of maleated polyethylene (MAPE) to compounds of natural rubber (NR) and Teline monspessulana flour (TMF) previously mercerized was investigated. Two factors were analyzed: A. concentration of MAPE with five levels 2; 4; 6; 8; 10 phr (parts per hundred rubber), B. concentration of TMF with two levels 25 and 40 phr. The effect of MAPE on compatibility between NR and HTM was evaluated by tensile testing the compounds. The mixing was performed in a laboratory scale mill. The test tubes were obtained by cutting or die-cutting crosslinked peroxide sheets, these were obtained during the compression molding process. Analysis indicate that the MAPE coupling agent improved the compatibility between HTM and NR, this effect was evidenced by the values of tensile strength and elongation at break. However, the gel content determination indicates that the addition of 10 phr of MAPE crosslinking decreases due to competition with coupling reaction MAPE - HTM.

The objective of this research is to develop an experimental-theoretical analysis about the influence of the cooling medium and the geometry of the welding bead profile in fatigue life and associated parameters with structural integrity of welded joints. A welded joint with cruciform geometry is considered using SMAW, plates in structural steel ASTM A36 HR of 8 mm of thickness and E6013 electrode input. A three-dimensional computational model of the cruciform joint was created using the finite element method. For this model, the surface undulation of the cord and differentiation in the mechanical properties of the fusion zone were considered, the heat-affected zone (HAZ) and base material, respectively. In addition, an initial residual stress field which was established experimentally was considered. The results were a set of analytical expressions for the weld magnification factor Mk. It was found that values for the latter decrease markedly in function of the intensity of the cooling medium used in the post welding cooling phase, mainly due to the effect of the residual compressive stresses. The obtained models of behavior of the weld magnification factor are compared with the results from other researchers with some small differences, mainly due to the inclusion of the cooling effect of the post weld and the variation of the leg of the weld bead. The obtained analytical equations in the present research for Mk can be used in management models of life and structural integrity for this type of welded joint.

In this review, we aimed to understand the relationship between SARS-CoV-2 infection and preeclampsia severity in infected pregnant women. Pregnant women with SARS- CoV-2 infection have been shown to have a significantly increased risk of maternal death, ICU admission, preterm delivery, and stillbirth compared with those without infection. The risk of preeclampsia also increases in pregnant women infected with SARS-CoV-2, particularly in those with severe symptoms. We emphasize the im-portance of specialized clinical management to prevent poor pregnancy outcomes in this situation. The association between COVID-19 and preeclampsia (PE) is likely due to multiple mechanisms, including the direct effects of the virus on trophoblast function and the arterial wall, acute atherosis, local inflammation leading to pla-cental ischemia, exaggerated inflammatory responses in pregnant women, SARS-CoV-2-related myocardial injury, cytokine storm, and thrombotic microan-giopathy. Emphasis has been placed on the potential impact of COVID-19 on pregnant women, specifically in relation to thrombotic complications, placental dysfunction, and cardiovascular dysfunction. Undoubtedly, one of the diagnostic tools to differentiate between COVID-19-induced preeclampsia-like syndrome and true preeclampsia is the use of biomarkers, such as the sFlt-1/PlGF ratio. We wish to highlight the potential for COVID-19-induced myocardial injury in pregnant women and the associated in-crease in maternal mortality rate. Vaccination against COVID-19 in the general population and in pregnant women in particular, drastically reduced the severity of the disease. There is an urgent need to continue the follow-up of these women and their children to detect the appearance of sequelae of the disease or peristent COVID 19

The applicability of the distance aggregation problem has attracted the interest of many authors. Motivated by this fact, in this paper we face the modular quasi-(pseudo-)metric aggregation problem. We characterize those functions that allow merging a collection of modular quasi-(pseudo-)metrics into a single one. Specifically, a description of such functions in terms of triangle triplets is given and, in addition, the relationship between modular quasi-(pseudo-)metric aggregation functions and modular (pseudo-)metric aggregation functions is discussed. Such characterizations are illustrated with appropriate examples. A few methods to construct modular quasi-(pseudo-)metrics are yielded. Several properties of modular quasi-(pseudo-)metric aggregation functions are explored and used to develop quick tests for discarding candidate functions to aggregate modular quasi-(pseudo-)metrics. Moreover, a characterization of those modular quasi-(pseudo-)metric aggregation functions that preserve modular quasi-(pseudo-)metrics is also provided. Furthermore, the relationship between modular quasi-(pseudo-)metric aggregation functions and quasi-(pseudo-)metric aggregation functions is studied in such a way that significative differences are displayed.

Sufficient evidence is currently available to demonstrate the reality of the warming of our planet's climate system. Global warming has different effects on climate at the regional and local levels. The detection of changes in extreme events using instrumental data provides further evidence of such warming and allows for the characterization of its local manifestations. The present study analyzes changes in temperature and precipitation extremes in the Mexican state of Zacatecas using climate change indices developed by the Expert Team on Climate Change Detection, Monitoring and Indices (ETCCDI). We studied a 40-year period (1976-2015) using annual and seasonal time scales. Maximum and minimum temperature data were used, as well as precipitation statistics from the Mexican climatology database (CLICOM) provided by the Mexican meteorological service. Weather stations with at least 80% of data availability for the selected study period were selected; these databases were subjected to quality control, homogenization, and data filling using Climatol, which runs in the R programming language. These homogenized series were used to obtain daily grides of the three variables at a resolution of 1.3 km. Results reveal important changes in temperature-related indices, such as the increase in maximum temperature and the decrease in minimum temperature. Irregular variability was observed in the case of precipitation, which could be associated with low-frequency oscillations such as the Pacific Decadal Oscillation and the El Niño–Southern Oscillation. The possible impact of these changes in temperature and the increased irregularity of precipitation could have a negative impact on the agricultural sector, especially given that the state of Zacatecas is the largest national bean producer. The most important problems in the short term will be related to the difficulty of adapting to these rapid changes and the new climate scenario, which will pose new challenges in the future.

This study explores into a comprehensive examination of an optical cavity system that integrates Raman and Yb-doped gain media, with a focus on understanding their interactions. The research implies a characterization of each gain medium within the cavity while subjecting them to diverse co-pumping conditions with the other. When the Raman-lasing cavity is co-pumped by exciting the Yb-doped section, the resulting composite laser exhibits significant threshold reductions and there is an optimal co-pumping regime that enhances energy transfer from pump to Stokes. As for the complementary cavity, where the Yb-doped gain is influenced by the co-pumped Raman gain, at moderate pump powers a light-controlling-light behavior phenomenon arises. Within this regime, the 1064-nm signal suppresses the Yb-generated 1115-nm signal, suggesting potential applications in intracavity optical modulation. For higher pump levels, a cooperative effect emerges whereby both lasers mutually enhance each other. Minor variations in the primary 974-nm pump power, even by just a few milliwatts, result in significant capabilities for switching or modulating the Stokes signal. Under these conditions of mutual enhancement, the hybrid optical system validates notable improvements regarding energy transfer efficiency and threshold reduction. This research provides valuable insights into the intricate dynamics of optical cavity systems and reveals promising avenues for applications in advanced optical modulation technologies.

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B₁₂ (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.

The Eliezer and Gray physical interpretation of the Ermakov-Lewis invariant is applied as a guiding principle for the derivation of the special relativistic analog of the Ermakov-Milne-Pinney equation and associated first integral. The special relativistic extension of the Ray-Reid system and invariant is obtained. General properties of the relativistic Ermakov-Milne-Pinney are analyzed. The conservative case of the relativistic Ermakov-Milne-Pinney equation is described in terms of a pseudo-potential, reducing the problem to an effective Newtonian form. The non-relativistic limit is considered as well. A relativistic nonlinear superposition law for relativistic Ermakov systems is identified. The generalized Ermakov-Milne-Pinney equation has additional nonlinearities, due to the relativistic effects.

In recent years, new metaheuristic algorithms have been developed taking as reference the inspiration on biological and natural phenomena. This nature-inspired approach for algorithm development has been widely used by many researchers in solving optimization problem. These algorithms have been compared with the traditional ones algorithms and have demonstrated to be superior in complex problems. This paper attempts to describe the algorithms based on nature, that are used in fuzzy clustering. We briefly describe the optimization methods, the most cited nature-inspired algorithms published in recent years, authors, networks and relationship of the works, etc. We believe the paper can serve as a basis for analysis of the new are of nature and bio-inspired optimization of fuzzy clustering.

Carbon footprint mitigation actions have become a key issue for companies involved in urban freight transport. The electrification of the delivery fleets is one of the crucial sustainable actions carried out. To this end, it is necessary to explore several fleet renewal strategies over a finite planning horizon evaluating different types of electric powertrains for light commercial vehicles. The primary goal of this purpose-built analysis is to assist and boost the fleet managers' decisions when transitioning to alternative-fuelled vans, intending to maximize cost savings and reduce greenhouse gas emissions inventory. The model presented in this work is a Multi-Objective Linear Programming hybrid analysis taking into account the vehicle and energy supply infrastructure costs and the emissions reported in each inventory scope following the Greenhouse Gas Protocol sustainability guidelines. From this perspective, the conducted research offers a novel approximation to fleet management problems enabling a break-down cost analysis and an evaluation of the annual emissions company report. The comprehensive numerical simulations carried out over different study scenarios in Spain demonstrate that the optimization approach does not only show effective fleet renewal strategies but also identifies critical factors that impact the fleet's competitiveness, offering valuable insights for fleet managers and policymakers to meet carbon footprint reductions in a cost-effectively way.

Tetranychid outbreaks have been detected since 2016 in southern highbush blueberries (SHB); however, it was not until 2019 when the southern red mite (SRM), Oligonychus ilicis (Acari: Tetranychidae) was confirmed as the pest causing severe bronzing and stunting, in multiple Florida and Georgia commercial blueberry plantings. There is little known about the management of SRM in SHB and only three miticides (fenazaquin, fenpyroximate, and acequinocyl), have recently been registered for use in SHB between 2019 and 2020. Similarly, there is no knowledge regarding the existence of natural enemies of SRM in SHB. This is the first report of naturally occurring predatory mites (Amblyseius sp. and Neoseiulus ilicis) associated with SRM in SHB. Predatory mites were recorded in treated bushes after evaluating the performance of seven miticides used to manage SRM populations including spiromesifen, acequinocyl, sulfur, sulfur + molasses, bifenazate, fenpyroximate, and fenazaquin. Miticide efficacy was rated based on the number of SRM recorded on collected leaves and plant damage ratings using an arbitrary index (from 0= no bronzing to 4= 100% bronzing). Additionally, the presence or absence of predatory mites per sample was recorded. Fenpyroximate used as the standard miticide, significantly reduced mite numbers seven days after application, as well as acequinocyl and fenazaquin. Only plants treated with fenpyroximate or fenazaquin showed significantly less bronzing compared with the control plants. Overall, fenpyroximate and fenazaquin demonstrated the best performance for managing O. ilicis on SHB and safe to naturally occurring predatory mites. Lastly, the level of growers’ awareness regarding SRM was assessed using surveys in 2020 to design adequate educational materials available to the grower community.

A E. Crassipes is considered a problem in different aquatic ecosystems, due to its abundance could become a solution to design and build economic and efficient treatment plants, and especially for the production of biofuels such as bioethanol. The objective of this research is to design and implement a sustainable development process between phytoremediation and bioethanol production with E. crassipes, evaluating the incidence of chromium adhered to the biomass of this plant in the production of bioethanol. Materials and methods: A system was installed to evaluate the phytoremediation with E crassipes with water loaded with chromium, determining the effectiveness of this plant to remove this heavy metal even if it is alive in a body of water. After this process, we proceeded to bring the biomass loaded with chromium to bioreactors to evaluate the production of bioethanol, assessing three types of biomass, one without chromium adhered and the other two with chromium adhered to its plant structure. There was an impact of the ethanol production of the E crassipes due to the presence of chromium, but this production can be taken into account for the assembly of an integral system of phytoremediation and bioethanol production, making the most of this biomass.

As companies increasingly undergo digital transformation, the role of talent management pro-cesses becomes pivotal in enhancing overall organizational performance. The research addresses the significance of talent management in corporate digital transformation, examining whether variations in the digitalization of these processes can be attributed to company size. A qualitative approach was employed, utilizing a questionnaire, collecting responses from 202 organizations across diverse sectors. Findings reveal disparities in digitalization throughout the talent man-agement process, with pronounced presence in the attracting, selecting, and rewarding phases, but diminishing in deployment and development, further declining in planning. A positive cor-relation between company size and adoption of specific digital platforms was observed. Larger enterprises exhibit greater utilization of digital platforms in talent deployment and development. Moreover, corporate communication tools are consistently utilized in the rewarding phase, irre-spective of company size. These findings offer practical insights for organizations to optimize their digitalization strategies based on their scale, thereby contributing to more effective and tailored digitalization endeavors. The uniqueness of this research lies in its exploration of the in-fluence of company size on the digitalization of talent management processes and its potential to explain variations across different stages of these processes.

The analysis and simulation of water quality in distribution networks is a complex issue of great concern today. The analysis of the evolution of water age, as a simple indicator of water quality in the network, is of great interest in both design and operation phases. Understanding the factors that have the strongest influence on water quality is key to developing adequate strategies aimed at preserving it. This paper firstly analyses the factors with biggest influence in the tanks water age, to support the selection of the most appropriate configuration from the point of view of water quality during design phases. Then, the main considerations when modelling tanks following the different mixing models considered in Epanet have been presented. Also, a real tank behaviour has been characterised through field measurements and Epanet simulations in order to determine the best fitted mixing model.

When there is uncertainty in the value of parameters of the input random components of a stochastic simulation model, two-level nested simulation algorithms are used to estimate the expectation of performance variables of interest. In the outer level of the algorithm (n) observations are generated for the parameters, and in the inner level (m) observations of the simulation model are generated with the value of parameters fixed at the value generated in the outer level. In this article, we consider the case in which the observations at both levels of the algorithm are independent, showing how the variance of the observations can be decomposed into the sum of a parametric variance and a stochastic variance. Next, we derive central limit theorems that allow us to compute asymptotic confidence intervals to assess the accuracy of the simulation-based estimators for the point forecast and the variance components. Under this framework, we derive analytical expressions for the point forecast and the variance components of a Bayesian model to forecast sporadic demand; and we use these expressions to illustrate the validity of our theoretical results by performing simulation experiments using this forecast model.

Food allergies have increased significantly in recent decades, with shellfish being a leading cause of food allergy and anaphylaxis worldwide, affecting both children and adults. The prevalence of shellfish allergies is estimated to be approximately 0.5-2.5% of the general population, varying significantly by geographical location, age, and consumption habits. Although mollusk consumption has risen, the prevalence of mollusk allergies remains unknown. While extensive research has focused on crustacean allergies, mollusk allergies, particularly those related to gastropods, have received comparatively less attention. Clinical manifestations of shellfish allergy range from localized symptoms to life-threatening systemic reactions, such as anaphylaxis. Notably, severe bronchospasm is a predominant clinical feature in cases involving gastropods. Several allergens have been identified in mollusks, including paramyosin, tropomyosin, and sarcoplasmic calcium-binding protein. In gastropods, documented allergens include tropomyosin, paramyosin, the heavy chain of myosin, and Der p 4 amylase. Diagnosis typically involves a thorough clinical history, skin testing, in vitro quantification of immunoglobulin (Ig) E, and confirmation through oral challenge, although the latter is reserved for selected cases. This review highlights the limited research on gastropod allergy, the identified allergens to date, and the necessity for further investigations to better understand the implications of shellfish allergy within this class.

There is an urgent need to develop new therapies for cancer treatment due to high rates of resistance and tumor relapse. Moreover, chemotherapy and radiation weaken the immune system and leave patients susceptible to sudden death from infections and organ failure since antineoplastic drugs lack specificity. Hence, scientists worldwide continue the search for natural alternatives with anticancer activities and fewer side effects. In this regard, traditional medicine offers strategies for preventing and treating numerous diseases and nowadays scientific studies worldwide highlight some of the mechanisms underlying their potential as an effective alternative for the management of cancer. In Mexico, Mayan healers have been prescribed mainly medicinal plants for more than 2,000 years. Furthermore, their ethnomedical knowledge has led to drug discovery or the development of herbal remedies. Medicinal plants from the genus of Cissus remain an important element of all indigenous medical systems in Mexico including the Mayan tribes in Yucatan, particularly for the management of gastrointestinal illnesses, sores, cutaneous diseases, and tumors. In this review, we present the reported bioactivities against cancer cells of the extract and compounds from the species of Cissus with a particular focus on recent studies on the phytochemistry of C. trifoliata which is widely distributed in Mexican territory and used for tumor management in traditional medicine.

This article analyzes laws, normative reforms and regulations surrounding the practices and mechanisms of control over the consumption, cultivation and commercialization of cannabis. On the one hand, I investigate regulatory practices that deny rights for the consumption of cannabis classified as recreational. On the other hand, I study regulatory practices that extend rights for the production, consumption and commercialization of cannabis classified as medicinal and industrial. The empirical moment is composed of four stages and methodological tools. First, I conduct an analysis of state policies. Then, I analyze nine laws and codes on cannabis regulation from 1970 to the present. Next, I perform five semi-structured interviews. Finally, I develop two life stories of former people deprived of their liberty for cannabis cultivation and trade. In this way, I trace forms of regulation on multiple demands, knowledge, interests and beliefs. This research focuses on state regulation. Cannabis regulatory regimes are conceived as constructions of political, social and economic truths, meanings and rights. In sum, the answer to the question of how collective demands around cannabis are regulated in Ecuador stipulates that state action reinforces stigmatization and criminalization. In addition, it legitimizes moral entrepreneurs and counter-movements around cannabis.

In this work, we report the magnetocaloric effect (MCE) in a quantum dot corresponding to an electron interacting with an antidot, under the effect of an Aharonov-Bohm flux subjected to a parabolic confinement potential. We use the Bogachek and Landman model, which additionally allows the study of quantum dots with Fock-Darwin energy levels for vanishing antidot radius and flux. We find that the Aharonov-Bohm flux (AB-flux) strongly controls the oscillatory behaviour of the MCE, thus acting as a control parameter for the cooling or heating of the magnetocaloric effect. We propose a way to detect AB-flux by measuring temperature differences.

The combined influence of the North Atlantic Oscillation (NAO) and the East Atlantic (EA) patterns on the covariability of temperatures and precipitation in 35 stations of the Iberian Peninsula during the period 1950-2019 is analysed in this work. Four EA-NAO composites were defined from teleconnection patterns positive and negative phases: EA+NAO+, EA+NAO-, EA-NAO+, and EA-NAO-. Daily data of maximum and minimum temperature were used to obtain seasonal means (TX, and TN, respectively), and the covariability of these variables with accumulated seasonal rainfall (R) was studied comparing results obtained for different NAO and EA composites. Main results indicate slight differences in the spatial coverage of correlation coefficients between R and temperature variables, except in spring when the generalized negative relationship between R and TX under EA+NAO+ and EA-NAO- disappears under EA-NAO+ and EA+NAO- composites. This result may be useful to interpret and discuss historical reconstructions of Iberian climate.

This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.

Several review articles about megachurch studies have been published recently concentrating their work on USA, Europe, and other parts of the world, with just a few references about Latin American megachurches. For that reason, this article aims to identify some of the characteristics of Latin American Evangelical megachurches by looking at relevant literature, especially that produced in the region, in Spanish and Portuguese, which is usually overlooked by researchers in Global North. Since this research field is still limited in Latin America, areas, where further work is necessary, are identified. Three general catalysts for the emergence of megachurches in the region, church growth methodologies, Pentecostalization, and theologies of growth, serve as guides to organize the review process. The discussion shows several potential areas of research in a variety of fields such as theology, ecclesiology, organizational theory, leadership, gender studies, and ethics, are proposed from the review.

Given the importance of the development of urban infrastructure and environmental impacts produced by the civil construction waste (CCW), it is important to correct the handling of CCW with objective solutions that are more environmentally friendly. In that sense the present study aimed to determine indicators that make it possible to estimate the amount of CCW generated from construction sites in the city of Londrina, Parana State, Brazil. The generation of CCW was estimated in a general way, regarding the composition of its mixture, correlated to the gross areas of the buildings studied and their generated volumes of RCC. This generating rate was evaluated in a general way and specifies two types of sites: the new residential and new non-residential constructions. The data required for the development of these indicators was obtained through extensive survey and interviews carried out at the environment secretariat of the City Hall. The generating rate of CCW obtained for non-residential buildings was 0.2052m3/m2 or 170.44kg/m2, for new residential sites was 0.2054m3/m2 or 170.60kg/m2 and for new commercial or non-residential construction sites, it was 0.20453 m3/m2 or 169.85kg/m2. It was also possible to estimate the amount generated annually per inhabitant in the municipality, which is 0.60m3/inhabit.year or 498.55kg/inhabit.year.

The world is facing an energy crisis. Governments are seeking to provide universal energy access and guarantee energy security while trying to mitigate climate change. One possible solution is energy transitions towards low carbon energy systems. Among other things (physical infrastructure, public policy and regulatory enablers and knowledge and capacities) changes in the energy systems require a well informed and participative citizenship. Within this context the concept of energy literacy appears. Energy literacy is the understanding of how energy is generated, transported, stored, distributed and used, awareness about its environmental and social impacts and the knowledge to use it efficiently in the different sectors of the economy. This paper provides a systematic literature review in the Web of Science’s Core Collection. Most of the work done around energy literacy addresses its evaluation among different groups, particularly students at different levels, and the construction, application and evaluation of tools for improving energy literacy. Other frequently studied issues are the influence of energy literacy in decision making, its drivers and conceptual research about the topic. Energy enables citizens to effectively contribute to energy efficiency and sustainable development, nevertheless energy literacy is not strongly correlated to energy consumption habits.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

Weeds are unwanted and invasive plants that proliferate and compete for resources such as space, water, nutrients, and sunlight, affecting the quality and productivity of the desired crops. Weed detection is crucial for the application of precision agriculture methods and for this purpose machine learning techniques can be used, specifically convolutional neural networks (CNN). This study focuses on the search for CNN architectures and technology used to detect and identify weeds in different crops; 61 articles applying CNN architectures and technology were analyzed in the last five years (2019-2023). The results show the used of different devices to acquire the image for training, such as digital cameras, smartphones, and drone cameras. Additionally, the YOLO family and algorithms are the most widely adopted architectures, followed by VGG, ResNet, Faster R-CNN, AlexNet, and MobileNet, respectively. This study provides an update on CNNs that will serve as a starting point for researchers wishing to implement these weed detection and identification techniques.

Mandarins occupy the third group among citrus produced in Brazil. Primarily aimed at the fresh fruit market, commercial orchards have suffered significant losses in production, due to the high incidence of diseases, such as alternaria brown spot (ABS) and huanglongbing (HLB). The fact that 80% of the orchards are composed of two varieties, Ponkan mandarin and Murcott tangor, are highly susceptible to both diseases, demand intensive chemical control of the diseases in the field, which has resulted in a significant increase in production costs and a negative environmental impact. A total of one hundred and seventy-three mandarin accessions, including several species and hybrids, belonging to the Collections of the Instituto Agronômico de Campinas (IAC), were evaluated in the field, in an endemic location for the diseases. Evaluations of the incidence and severity of the diseases showed that there is a range of genotypes tolerant to ABS with potential to replace the current commercial varieties, mainly within the clementina and Willow leaf mandarin groups. Although with differences in incidence and susceptibility to HLB, there are no varieties tolerant to this disease, which significantly impacts the loss of fruit quality.

ZnO films with Ti atoms incorporated (TZO) in a wide range (0-18 at. %) have been grown by reactive co-sputtering on silicon and glass substrates. The influence of the titanium incorporation in the ZnO matrix on the structural and optical characteristics of the samples has been determined by Rutherford backscattering spectroscopy (RBS), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The results indicate that the samples with low Ti content (< 4 at. %) exhibit the wurtzite-like structure, with the Ti+4 ions substitutionally incorporated into the ZnO structure, forming Ti-doped ZnO films. In particular, very low concentration of Ti (<0.9 at. %) leads to a significant increase of the crystallinity of the TZO samples. Higher Ti contents give rise to a progressive amorphization of the wurtzite-like structure so samples with high Ti content (≥18at. %), displays an amorphous structure indicating the XPS analysis a predominance of Ti-O-Zn mixed oxides. The energy gap, obtained from absorption spectrophotometry, increases from 3.2 eV for pure ZnO films to 3.6 eV for those with the highest Ti content. Ti incorporation in the ZnO samples below 0.9 at. % rises both, the blue (380 nm) and green (550 nm) bands of the photoluminescence (PL) emission, thereby indicating a significant improvement of PL efficiency of the samples.

The increasing number of registered road crashes involving cyclists during the last decade, and the high proportion of road crashes resulting in severe injuries and fatalities among cyclists constitutes a global issue for community health, urban development, and sustainability. Nowadays, the incidence of many risk factors for road crashes of cyclists remains largely unexplained. Given the importance of this issue, the present study has been conducted with the aim of determining relationships between infrastructural, human factors and safety outcomes of cyclists. Objectives: This study aimed, first, to examine the relationship between key infrastructural and human factors present in cycling, bicycle-user characteristics, and their self-reported experience with road crashes. And second, to determine whether a set of key infrastructural and human factors may predict their self-reported road crashes. Methods: For this cross-sectional study, a total of 1064 cyclists (38.8% women, 61.2% men; M = 32.8 years of age) from 20 different countries across Europe, South America and North America, participated in an online survey composed of four sections: demographic data and cycling-related factors, human factors, perceptions on infrastructural factors, and road crashes suffered. Results: The results of this study showed significant associations between human factors, infrastructural conditions and self-reported road crashes. Also, a logistic regression model found that self-reported road crashes of cyclists could be predicted through variables such as age, riding intensity, risky behaviors, and problematic user/infrastructure interactions. Conclusions: The results of this study suggest that self-reported road crashes of cyclists are influenced by features related to the user and their interaction with infrastructural characteristics of the road.

The microstructure of the coating during hot-dip galvanizing under industrial conditions of two structural steels, a low-silicon ASTM A36 steel and a high-silicon Q345B steel, both of commercial quality, have been characterized for industrial-relevant times. For both cases it is noted that the formation of the Fe-Zn phases begins in early stages during the heating of the steel, a situation in which all the phases are in the solid state. The characterization was carried out through traditional metallographic techniques including SEM-EDS and DRX equipment. The evolution in time of the microstructure of both steels is examined, being able to observe that the mechanism by which silicon accelerates the formation of Fe-Zn phases in galvanizing is related to the change in the energy of the interfaces caused by a silicon accumulation in the liquid phase in contact with the ζ layer. These results provided us with a deeper understanding of the phase evolution in the hot-dip galvanizing of high silicon steels.

Single Image Super Resolution (SSIR) is a problem in computer vision where the goal is 1 to create high-resolution images from low-resolution ones. It has important applications in fields 2 such as medical imaging and security surveillance. While traditional methods such as interpolation 3 and reconstruction-based models have been used in the past, deep learning techniques have recently 4 gained attention due to their superior performance and computational efficiency. This article proposes 5 an Autoencoder based Deep Learning Model for SSIR, in particular, a light model that uses fewer 6 parameters without compromising performance. The down-sampling part of the Autoencoder 7 mainly uses 3 by 3 convolution and has no subsampling layers. The up-sampling part uses transpose 8 convolution and residual connections from the down sampling part. The model is trained using a 9 subset of the VILRC ImageNet database. The model is evaluated using quantitative metrics PSNR, 10 SSIM as well as qualitative measures such as perceptual quality. PSNR and SSIM figures as high as 11 76.06 and 0.93 are reported.

Alternaria brown spot (ABS) is a disease caused by the fungus Alternaria alternata f. sp. citri, which results in lesions on fruits, leaves, and branches of several mandarin varieties and their hybrids. Due to the high cost of fungicide application, alternative methods for controlling ABS need to be studied. Therefore, this study aimed to evaluate the use of essential oils (EOs) from different mandarin varieties to mitigate the effects of ABS. The inhibitory effect of different concentrations (1, 2, 4, 8, and 16 μL mL-1) of Fremont IAC 543 mandarin, IAC 2019Maria mandarin, Murcott IAC 221 tangor, and Late IAC 855 willowleaf. EOs on the in vitro mycelial growth of the fungus A. alternata was evaluated. Additionally, the curative and preventive effects of these EOs on ABS symptoms on detached leaves of Murcott IAC 221 tangor were also assessed. The EO of IAC 2019Maria mandarin induced less mycelial growth, and consequently, greater inhibition of the growth of the fungus A. alternata at a concentration of 16 μL mL-1. This EO was more effective in control than the other oils tested. In the detached leaf experiment, both the curative and preventive treatments at a concentration of 16 μL mL-1 showed lower values of disease severity.

The Cobb angle is critical in assessing adolescent idiopathic scoliosis (AIS) patients. This study aimed to evaluate the error in selecting the cranial and caudal limit vertebrae on AIS digital X-rays of experienced and novice observers and its correlation with the error in measuring the Cobb angle and determining the length of the scoliotic curves. Using the TraumaMeter v.873 software, eight raters (four experienced and four novices) independently evaluated 68 scoliotic curves on 42 AIS X-rays across three sessions one month apart according to Hopkins’ criteria of absolute reliability. Two spine specialist experts using the Cobb method established the gold standard measurements. The percentage of error in the selection of the cranial vertebrae (the most-tilted vertebra above the apex) is higher than in the caudal vertebrae (the most-tilted vertebrae below the apex) (44.7%, CI95% 41.05-48.3 compared to 35%, CI95% 29.7-40.4). The error in the choice of the most tilted vertebrae, in number of vertebrae per scoliotic curve, was MBE (mean bias error) =0.45, CI95% 0.38-0.52 in the cranial and MBE=0.35, CI% 0.69-0.91 in the caudal. The percentage of errors in the choice of boundary vertebrae is lower for the experienced than for the novices, both in cranial and caudal. The experienced chose at least one boundary vertebrae incorrectly in 52% of the meas-urements and the novices in 65.1%. The error in the Cobb angle did not depend on the number of boundary vertebrae chosen incorrectly (r=0.198, p=0.111). Of the 50% of Cobb angle measurements closest to the actual value, 55.4% (454) were obtained by incorrectly selecting at least one boundary vertebra. There was a positive correlation (r=0.673, p=0.000) between the error in selecting the boundary vertebrae and the error in determining the length of the scoliotic curves. The error in quantifying the length of scoliotic curves was MBE=0.43, CI95% 0.35-0.51 vertebrae per curve. We can conclude that errors in selecting boundary vertebrae are common among experienced and novice observers, with a greater frequency of error in the cranial vertebrae. There is no correlation between the error in selecting the boundary vertebrae and the error in measuring the Cobb angle. Contrary to the consensus, the accuracy of determining the length of the scoliotic curve is limited by the Cobb method’s reliance on the correct selection of boundary vertebrae. Inappropriate choice of boundary vertebrae leads to an estimated error in determining the length of the scoliotic curves of 0.805 vertebrae for each boundary vertebra chosen incorrectly.

Macromolecular assemblies, such as protein complexes, undergo continuous structural dynamics, including global reconfigurations critical for their function. Two fast analytical methods are widely used to study these global dynamics, namely elastic network model normal mode analysis and principal component analysis of ensembles of structures. These approaches have found wide use in various computational studies, driving the development of complex pipelines in several software packages. One common one has been conformational sampling through hybrid simulations incorporating all-atom molecular dynamics and global modes of motion. However, wide functionality is only available for experienced programmers with limited capabilities for other users. We have, therefore, integrated one popular and extensively developed software for such analyses, the ProDy Python application programming interface, into the Scipion workflow engine. This enables a wider range of users to access a complete range of macromolecular dynamics pipelines beyond the core functionalities available in its command-line applications and the normal mode wizard in VMD. The new protocols and pipelines can be further expanded and integrated into larger workflows together with other software packages for cryo-electron microscopy image analysis and molecular simulations. We present the resulting plugin, Scipion-EM-ProDy, in detail, highlighting the rich functionality made available by its development.

Corneal biomechanics is a hot topic in ophthalmology. The biomechanical properties of the cornea (BMPs) have important implications in the management and diagnosis of corneal diseases such as ectasia and keratoconus. In addition, the characterization of BMPs is crucial to model the predictability of a corneal surgery intervention, the outcomes of refractive surgery or follow-up of corneal diseases. The biomechanical behavior of the cornea is governed by viscoelastic properties that allow, among other structural implications, the damping of excess of intraocular pressure and reduce damage to the optic nerve. Currently, the most versatile and complete methods to measure corneal viscoelasticity are based on air-puff corneal applanation. However, those methods lack the ability to directly measure corneal viscosity. The aim of this work is to propose a new methodology based on the analysis of corneal air-puff measurements through the Standard Linear Solid model (SLSM) to provide analytical expressions to separately calculate the elastic and time-dependent (corneal retardation time and viscosity) properties. The results shown the mean values of elasticity (E), viscosity (Ƞ) and corneal retardation time (τ) in a sample of 200 young and healthy subjects. The influence of elasticity and viscosity on viscoelasticity, high-order corneal aberrations and optical transparency is investigated. Finally, the SLSM fed back from experimental E and Ƞ values was employed to compare the creep-relaxation response between normal, an ocular hypertension patient and Ortho-K user.

The vehicular ad hoc network (VANET) when augmented with internet is called internet of vehicles (IoV). In the IoV, vehicles have on board units (OBUs), use communication technologies and customized software to communicate with infrastructure around them. The vehicles can have permanent connectivity and global network awareness based on cloud computing. IoV technologies are still being assessed to ensure that the network is protected from attacks, supports a dynamic vehicular mobility scenarios and meets the low latency communication requirements between the vehicles and the surrounding infrastructure. To meet these strict Quality of Service (QoS) demands, Unmanned Aerial Vehicles (UAVs) play a vital role in IoV ecosystems. An UAV can serve as a mobile roadside unit (mRSU) to transmit data between vehicles, stationery RSUs and other UAVs. The UAVs have better line of sight (LOS) connections which result in better channel states and lower path loss than fixed RSUs. Although the inclusion of UAVs in vehicular networks has improved the system performance by providing better resource management and routing solutions, the traditional optimization techniques with their limitations are often not applicable. Therefore, in recent years, research community is integrating Artificial Intelligence (AI) and Machine Learning (ML) into UAV based IoV ecosystem to better manage resource allocation, routing and mobility management issues to optimize the overall network performance. In this survey paper we review the existing research done in AI/ML based UAV-IoV networks and communications with focus on resource management and routing from year 2019 to 2023. We have studied different AI techniques, their training attributes and architectures in various research works. The limitations of AI-based approaches in terms of required computational resources, availability of real world data and AI models’ complexity for the UAV-IoV environment are also discussed. Finally, the future directions for UAV-IoV research opportunities that can leverage the full potential of AI are presented.

Peri-implant diseases are defined as pathological inflammatory reactions in the tissue surrounding the osseointegrated implants. They are classified into two categories: mucositis - defined as peri-implant soft tissue inflammation and peri-implantitis - bone loss in the peri-implant region. A clinical case of a 61-years-old woman with an implant in the 46 anatomical position and a 5-year follow-up is presented. A probe depth of 5mm and a bone defect length of 35% was observed. The Implacure® Protocol was applied, with the main objective of eliminating the biofilm present on the exposed implant surface. There are multiple approaches to treat peri-implant diseases. While non-surgical treatment is essential for mucositis control, the treatment of peri-implantitis surgical treatment should be considered. Regenerative bone reconstruction promotes bone repair in the defect area and reduces bleeding during probing. To achieve that, autologous fibrin combined with Cerasorb M® was used. The proposed approach in the exposed clinical case involves the application of Implacure® Protocol, whose combination of the physical decontamination technique, together with the use of chlorhexidine and orthophosphoric acid, added with the combination Piperacillin + Tazobactam together with hyaluronic acid, provide a base that allows to regenerate bone using platelet-rich fibrin with Cerasorb M® and increase the survival time of the implant.

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

In the field of forensic imaging, it is important to be able to extract a “camera fingerprint” from one or a small set of images known to have been taken by the same camera (image sensor). Ideally, that fingerprint would be used to identify an individual source camera. Camera fingerprint is based on certain kind of random noise present in all image sensors that is due to manufacturing imperfections and thus unique and impossible to avoid. PRNU (Photo-Response Non-Uniformity) has become the most widely used method for SCI (Source Camera Identification). In this paper, we design a set of “attacks” to a PRNU based SCI system and we measure the success of each method. We understand an attack method as any processing that alters minimally image quality and that is designed to fool PRNU detectors (or, generalizing, any camera fingerprint detector). The PRNU based SCI system was taken from an outstanding reference that is publicly available.

The current study aims to develop a methodology for obtaining topology-optimal structures made of short fiber-reinforced polymers, which include the fluid-structure interaction. Accounting for the molding process during the internal iterations of topology optimization makes it possible to enhance the weight efficiency of structures—a crucial aspect, especially in aerospace. Anisotropy is considered through the fiber orientation tensor, which is modeled by solving the plastic molding equations for non-Newtonian fluids, and then introduced as a variable of the stiffness matrix during the structural analysis. The materials used were non-linearly modeled using an exponential-and-linear hardening law. The evaluation of weight efficiency in structures composed of short-reinforced composite materials using a dimensionless criterion is addressed. Experimental verification was performed to confirm the validity of the developed methodology. The evidence illustrates that considering anisotropy leads to stiffer structures and structural elements should be oriented in the direction of maximal stiffness. The load-carrying factor can be expressed in terms of failure criteria. The presented multidisciplinary methodology can be used to improve the quality of the design of structures made of short fiber-reinforced composites (SFRC) where high stiffness, high strength, and minimum mass are the primary required structural characteristics.

Based on recent contributions regarding the treatment of unsteady hydraulic conditions into the state-of-the-art of scour literature, the theoretically derived probability distribution of bridge scour is introduced. The model is derived assuming a rectangular hydrograph shape with a given duration, and random flood peak following a Gumbel distribution. A model extension for a more complex flood event is also presented, assuming a synthetic exponential hydrograph shape. The mathematical formulation can be extended to any flood-peak probability distribution. The aim of the manuscript is to move forward the current approaches adopted for the bridge design coupling hydrological, hydraulic, and erosional models in a mathematical closed form.

Climate changes caused by anthropogenic actions can directly and indirectly affect living beings, including parasites and their hosts. Changes such as water temperature, pH, distribution of nutrients in the aquatic environment are some examples that can interfere with the fish community, whether in open water or in production systems. In this review, we will show how climate change can affect the adaptation of hosts and parasites in the aquatic environment and how these parasites can be used for environmental monitoring.

Forecasting streamflow accurately is essential to achieve an efficient integrated water resources management strategy and provide consistent support to water decision-makers. We present a simple, low-cost and robust approach for forecasting monthly and yearly streamflow during the hydrological year in course, applicable to headwater catchments. It combines the use of regression analysis techniques, the two-parameter Gamma continuous cumulative probability distribution function and the Monte Carlo method. It is based on a probabilistic comparison of the progression of the current hydrological year with the historic observed series. The methodology has been successfully applied to two headwater reservoirs within the Guadalquivir River Basin in southern Spain. The root-mean-square error and correlation coefficient were used to measure the accuracy of the model and the results showed good levels of reliability. The outputs are the probabilistic monthly and yearly streamflow and 80% confidence interval. Further reductions in prediction errors may be achieved from increasing the number of observed years. These risk-based predictions are of great value, especially, before the intensive irrigation campaign starts (usually in April), when Water Authorities are to take responsible management decisions about the best allocation of the available water volume between the different water users and environmental needs.

In this article the galactic rotation curve is analyzed as an effect of an accelerated reference frame. This phenomenon is the strongest evidence for the so called dark matter. We show that a non-inertial reference frame could explain the experimental data. We also show that general relativity is not enough to complete explain that which encouraged alternatives paths such as the MOND approach. Considering the effect of dark matter as a realization of accelerated reference frames is a simple but powerful hypothesis.

Introduction: Biofuels, biohydrogen and bioethanol have properties that stand out from other fossil fuels, are colorless, odorless, and insipid, therefore, they are free of contaminants. Its production can be generated from the biomass of the aquatic plant Eichhornia crassipes, since this alternative is timely and viable due to its high energy composition. This plant is a problem in wetlands, rivers and other hydrosystems, due to its abundance and dominance over other species of aquatic plants, and which in effect causes an ecological imbalance. Objective: To evaluate the production of biohydrogen and bioethanol from the biomass of the E. crassipes plant. Materials and methods: Lignocellulosic material was used, realizing different physical, chemical and biological processes such as: reduction of size, lignin removal, acid hydrolysis, fermentation and distillation. a laboratory scale production system was designed and built where two bioreactors were used in the process. Results and discussion: the production of bioethanol and biohydrogen showed a production index of more than 40 mg of bioethanol per gram of bio-mass of E. crassipes and in relation to biohydrogen, 65 mmol / L was obtained. Conclusion: With the biomass of E. crassipes it is possible to obtain a high index of bio-fuel production, since it is possible to take advantage of its physical characteristics and its high proliferation in hydrosystems, in this way it constitutes an optimal alternative to produce biohydrogen and bioethanol at a high scale.

Our study utilized density functional theory (DFT) to explore a 2D MoP2 surface for hydrogen storage. Optimization determined a gravimetric capacity for pristine MoP2 of 5.72%, with an adsorption energy of ‒ 0.13 eV/molecule. For this surface with 12.5% Mo vacancies, we achieved 6.02% and ‒ 0.14 eV/molecule. We then introduced a novel criterion to test the attraction forces in hydrogen storage at a given temperature. This involved a first-principles molecular dynamics approach at various temperatures. To determine the number of molecules adsorbed on the surface at temperature T1, we conducted an FPMD calculation at T1, using the optimization as the initial system configuration. Subsequently, we performed a second FPMD calculation at a temperature T2 (with T2 ‹‹ T1), using the stable configuration of the first FPMD calculation as the initial configuration. If there were attraction forces on the molecules, they would move towards the surface. We identified as adsorbed molecules at temperature T1, only those that moved back toward the surface at temperature T2. The defective surface gave the best gravimetric capacity, ranging from 5.27% at 300 K to 6.02% at 77 K. The latter met the requirement from the US-DOE, indicating the potential practical application of our research in hydrogen storage.

Cosmic strings can arise from spontaneous phase transitions during the inflationary period and are describable as disclination topological defects in spacetime. Analytical integration of the geodesic equations for a particle around a cosmic string reveals distinct orbit patterns dependent on the disclination intensity $\beta_{0}$. After its interaction with the cosmic string, the particle's behavior becomes random. To categorize these patterns, we describe the geodesic motion as iterated maps of a discrete parameter. Through the stabilization values of these functions, we correlate the scattering angle and the number of loops for the particle with $\beta_{0}$. Therefore, we interpret the gravitational field mathematically as an instructor of a particle's next position, given its previous one. We find that the radial function in the small displacement limit is similar to the logistic map. This leads us to conjecture the potential of the discrete parameter being a multiple of Planck's time, suggesting a method for the geometric discretization of spacetime around a cosmic string.

Millions of people worldwide have an inadequate intake of selenium (Se) and zinc (Zn), and agronomic biofortification may minimise these problems. To evaluate the efficacy of combined foliar Se and Zn fertilisation in bread making wheat (Triticum aestivum L.), foliar Se (as NaSeO4) and soil and foliar Zn applications (as ZnSO4·7H2O) were tested individually and in all combinations. A 2-year field experiment was established in southern Spain under semiarid Mediterranean conditions, by following a split-split-plot design. The study year (2017/2018, 2018/2019) was considered as the main-plot factor, soil Zn application (50 kg Zn ha-1, nil Zn) as a subplot factor, and foliar application (nil, 10 g Se ha-1, 8 kg Zn ha-1, 10 g Se ha-1 + 8 kg Zn ha-1) as a sub-subplot factor. The best treatment to increase both Zn and Se concentration in both straw, 12.3- and 2.7-fold respectively, and grain, 1.2- and 4.1-fold respectively was the combined foliar application of Zn and Se. This combined Zn and Se application also increased on average the yield of grain, main product of this crop, by almost 26%. Therefore, bread-making wheat seems to be a very suitable crop to be used in biofortification programs with Zn and Se to alleviate their deficiency in both, people when using its grain and livestock when using its straw.

Software defect prediction models enable test managers to predict defect-prone modules and assist with delivering quality products. A test manager would be willing to identify the attributes that can influence defect prediction and should be able to trust the model outcomes. The objective of this research is to create software defect prediction models with a focus on interpretability. Additionally, it aims to investigate the impact of size, complexity, and other source code metrics on the prediction of software defects. This research will also assess the reliability of cross-project defect prediction. Well-known machine learning techniques such as support vector machines, k-nearest neighbors, random forest classifiers, and artificial neural networks were applied to publicly available PROMISE datasets. The interpretability of this approach has been demonstrated by SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanations (LIME) techniques. The developed interpretable software defect prediction models showed reliability on independent and cross-project data. Finally, the results demonstrate that static code metrics can contribute to the defect prediction models, and the inclusion of explainability assists in establishing trust in the developed models.

The theory of the origin of carcinomas suggests that neoplasias from epithelial tissues are the consequence of the reactivation of developmental programs. It proposes a model in which the epithelial cells undergo cellular transitions due to replicative senescence and inflammation towards a mesenchymal-undifferentiated phenotype with cancerous behavior. The conserved pattern of histological progression and the molecular biology of carcinomas is congruent with the view of cancer as a developmental disease. In support of the theory, the experimental literature regarding the molecular, cellular, and histopathological mechanisms associated with epithelial carcinogenesis were aligned according to the premises of the hypothesis. Thereby identified a generic process in the carcinogenesis of the breast, endometrium, prostate, colon, lung, pancreas, bladder, liver, and cervix. Then, is provided a methodology overview of modeling in systems biology derived from previous research testing the hypothesis. The results illustrate the value of the complex systems approach to recover behavior that cannot be inferred only by traditional methods. Specifically, the model suggests that the consistency in the cell types and the directionality of the observed cellular transitions during epithelial carcinogenesis arise from structural constraints in the molecular networks associated with the carcinomas. Overall, the results of the dynamical analysis agree with the premises of the hypothesis and provide an insightful perspective of the potential mechanisms underlying the cellular plasticity displayed during epithelial carcinogenesis. In an era of big data and yet few advances in the underlying causes of chronic diseases, the manuscript also aims to inspire molecular biologists to integrate existing empirical evidence with systems biology modeling in the pursuit of understanding.

The origin of cancer remains one of the most important enigmas in modern biology. The prevailing paradigm has failed to grasp a comprehensive view of the disease. Naturally, therapies developed under the current assumptions are inadequate and cancer is practically an incurable disease. Meanwhile, descriptive studies continuously extend the molecular complexity of cancer without an equivalent advancement in its understanding. Furthermore, they tend to accumulate inconsistencies inexplicable under the classical view. This paper presents a compelling theory of the origin of carcinomas. By hypothesis, a series of generic events in epithelial tissues promoted by cellular aging and inflammation enables the reactivation of developmental programs. The origin of carcinomas in vivo is described as the time-ordered cell state transitions undergone by epithelial cells in the hyperplasia due to replicative senescence and inflammation towards a mesenchymal undifferentiated endogenous cell state with cancerous behavior. In support of the theory, the molecular, cellular, and histopathological evidence is critically reviewed. A plausible model for the origin of carcinomas is presented to explain the mechanism underlying carcinogenesis from an evolutive and developmental perspective. The implications of the hypothesis in the current strategies for cancer prevention and treatment are discussed along with rational alternatives and some predictions for possible experimental validation.

Plastics are naturally hydrophobic materials so, in order to employ flotation for the separation of plastic mixtures, the use of appropriate wetting agents is mandatory. In this work, the effect of pretreatment with alkaline solutions of sodium hydroxide on the floatability of four plastics (PET, PS, PMMA and PVC) was studied. The influence of NaOH concentration, treatment time and temperature of the alkaline solution, and influence of particle size was analyzed. Results showed that alkaline treatment had a strong effect on PET floatability, some effect on floatability of PMMA and PVC and no effect on floatability of PS. Plastics floatability decreased with the increase of NaOH concentration, temperature and treatment time of the alkaline solution. Based on flotation behavior of simple plastics, flotation separation after alkaline treatment of bi-component mixtures of PET with PS and PVC was achieved efficiently. The best separation was obtained for PET/PS mixture, a floated with a grade of 98% in PS and a sunk with a grade of 100% in PET. PET/PMMA mixture led to the worst separation. For PET/PMMA and PET/PVC mixtures, flotation separation improved with the decrease of the particles size.

Introduction Acalypha indica (AI) is an Ayurvedic medicinal plant. Some of this plant’s phytochemicals have been reported to cause oxidative stress in red blood cells. However, we know very little about those chemicals due to a dearth of literature. We present a case in which a patient with a previously unidentified glucose-6-phosphate dehydrogenase (G6PD) deficiency experienced acute hemolysis after ingesting fresh AI plant leaves. Case Presentation A 65-year-old man presented with jaundice, pallor, and haematuria following ingestion of the "Kuppamenia mallum" dish. His peripheral blood picture showed bite cells and Heinz bodies. A positive Brewer's test raised the clinical suspicion of G6PD deficiency. Low values of the G6PD level assessment at the follow-up visit confirmed the diagnosis. Conclusion Although AI is regarded as a medicinal plant, acute hemolysis can also occur after consumption in G6PD-deficient patients. This case emphasises the need for further research to identify the phytochemicals and their concentrations that can induce toxicity.

An exploding demand for processing capabilities related to the emergence of the IoT, AI and big data, has led to the quest for increasingly efficient ways to expeditiously process the rapidly increasing amount of data. These ways include different approaches like improved devices capable of going further in the more Moore path, but also new devices and architectures capable of going beyond Moore and getting more than Moore. Among the solutions being proposed, Stochastic Computing has positioned itself as a very reasonable alternative for low-power, low-area, low-speed, and adjustable precision calculations; four key-points beneficial to edge computing. On the other hand, chaotic circuits and systems appear to be an attractive solution for (low-power, green) secure data transmission in the frame of edge computing and IoT in general. Classical implementations of this class of circuits require intensive and precise calculations. This paper discusses the use of the SC framework for the implementation of nonlinear systems, showing that it can provide results comparable to those of classical integration, with much simpler hardware, paving the way for relevant applications.

In this paper is presented the design and syntheis of a dynamic output feedback neural network controller for a non-holonomic mobile robot. First the dynamic model of a non-holonomic mobile robot is presented, in which these constraints are considered for the mathematical derivation of a feasable representation for this kind of robot. Then two control strategies are provided based on kinematic control for this kind of robot. The first control strategy is based on driftless control, this means, that considering that the velocity vector of the mobile robot is orthogonal to its restriction a dynamic output feedback and neural network controller is designed in order that the control action would be zero only when the velocity of the mobile robot is zero. The Lyapunov stability theorem is implemented in order to find a suitable control law. Then another control strategy is designed for trajectory tracking purposes, which similar to the driftless controller, a kinematic control scheme is provided but suitable to implement in more sophisticated hardware. In both control strategy a dynamic control law is provided along with a feedforward neural network controller, so in this way, by the Lyapunov theory the stability and convergence to the origin of the mobile robot position coordinates is ensured. Finally, two numerical experiment are presented in order to validate the theoretical results synthetized in this research study. Discussions and conclusions are provided in order to analyze the results found in this research study.

Autotaxin (ATX) is a secreted lysophospholipase D, catalysing the conversion of lysophosphatidylcholine (LPC) to bioactive lysophosphatidic acid (LPA). LPA acts through two families of G protein-coupled receptors (GPCRs) controlling key cellular responses, and is implicated in many physiological processes and pathologies. ATX has therefore been established as an important drug target in the pharmaceutical industry. Structural and biochemical studies of ATX have shown that it has a bimetallic nucleophilic catalytic site, a substrate-binding (orthosteric) hydrophobic pocket that accommodates the lipid alkyl chain, and an allosteric tunnel that can accommodate various steroids and LPA. Here we first review what is known about ATX-mediated catalysis, crucially in light of allosteric regulation. We then present the known ATX catalysis-independent functions, including binding to cell-surface integrins and proteoglycans. In light of these data we then discuss the four types of ATX inhibitors, as classified depending on their binding to the orthosteric and/or the allosteric site. Finally, we analyse the binding mode of known members of all four types and discuss how mechanistic differences might differentially modulate the activity of the ATX-LPA signalling axis, and clinical applications including cancer.

In this work, we report the magnetocaloric effect (MCE) in two systems of non-interactive particles, the first corresponds to the Landau problem case and the second, the case of an electron in a quantum dot subjected to a parabolic confinement potential. In the first scenario, we realize that the effect is totally different from what happens when the degeneration of a single electron confined in a magnetic field is not taken into account. In particular, when the degeneracy of the system is negligible, the magnetocaloric effect cools the system, while in the other case, when the degeneracy is strong, the system heats up. For the second case, we study the competition between the characteristic frequency of the potential trap and the cyclotron frequency to find the optimal region that maximizes the ΔT of the magnetocaloric effect, and due to the strong degeneration of this problem, the results are in coherence with those obtained for the Landau problem. Finally, we consider the case of a transition from a normal MCE to an inverse one and back to normal as a function of temperature. This is due to the competition between the diamagnetic and paramagnetic response when the electron spin in the formulation is included.

Androgen receptor signaling is crucial for prostate cancer growth and is positively regulated in part by intratumoral CYP3A5. As African American (AA) men often carry the wild type CYP3A5 and express high level of CYP3A5 protein, we blocked the wild type CYP3A5 in AA origin prostate cancer cells and tested its effect on androgen receptor signaling. q-PCR based profiler assay identified several AR regulated genes known to regulate AR nuclear translocation, cell cycle progression and cell growth. CYP3A5 processes several commonly prescribed drugs and many of these are CYP3A5 inducers or inhibitors. In this study, we test the effect of these commonly prescribed CYP3A5 inducers/inhibitors on AR signaling. The results show that the CYP3A5 inducers promoted AR nuclear translocation, downstream signaling and cell growth whereas CYP3A5 inhibitors abrogated them. The observed changes in AR activity is specific to alterations in CYP3A5 activity. Both the inducers tested demonstrated increased cell growth of prostate cancer cells, whereas the inhibitors showed reduced cell growth. Further, characterization and utilization of the observation that CYP3A5 inducers and inhibitors alter AR signaling may provide guidance to physicians prescribing CYP3A5 modulating drugs to treat comorbidities in elderly patients undergoing ADT, particularly AA.

Dendroclimatology has gained relevance during the XXI century. We analyze the state of-the-art of dendroclimatology in Latin America during the past 28 years (1990 to 2019), identifying the current state and recent advances in the application of dendroclimatology in this region. We carried out a systematic review in ScienceDirect, Web of Science, and Scopus databases using Boolean operators to logically connect the keywords “dendrochronology,” “dendroclimatology,” “trend,” “climatic variability,” and “climatic variability trend”, for each country. Dendroclimatological research conducted in the region focused on climatic reconstruction and the evaluation of new tree species with dendrochronological potential, which increase in 2010, then there was a gap between 1995 and 1996, later increase to present. Dendroclimatological studies in Latin America have been mainly developed in temperate climate zones (82.4 %) followed by tropical or subtropical areas (17.6 %). Dendroclimatological research in Latin America has provided advances in the study of climate variability by defining response functions of tree rings to climate. The generated information allows for a better understanding of the spatial and temporal dynamics of climatic variability and about its effects on ecosystems and society. We also call for increased dendroclimatological research based on subtropical and tropical forests limited studied until today.

This study proposes a methodology for identifying time intervals in which time-of-use (ToU) energy tariffs can be set. This is achieved by analyzing the variability in electric power demand and esti-mating the potential for demand flexibility. The proposed methodology is as follows: first, data preprocessing is performed, focusing on the organization and cleaning of individual consumption records. Subsequently, the data are processed and classified by using consumption variability analysis and clustering techniques. Then, representative clusters are selected and time intervals are analyzed to identify periods of high electric power consumption variability. This methodology was tested with real data from smart meters in the Colombian electrical system, in which time intervals with potential for settinh ToU tariffs were ultimately identified. This work promotes the implementation of demand response strategies that enhance sustainability and facilitate the transition to a more resilient energy landscape both nationally and internationally. The findings are expected to contribute to the formulation of tariff schemes that encourage con-scious changes in electric energy consumption patterns.

The abilities of quantitative description of noise are restricted due to its origin and only the statistical and spectral analysis methods can be applied while an exact time evolution cannot be defined or predicted. It emphasizes the challenges faced in many applications including communication systems where noise can play, on one hand, a vital role impacting signal-to-noise ratio but possessing, on the other hand, unique properties such as infinite entropy (infinite information capacity), exponentially decaying correlation function and so on. Despite the deterministic nature of chaotic systems, the predictability of chaotic signals is limited for a short time window putting them close to random noise. In this article, we propose and experimentally verify an approach to achieve Gaussian-distributed chaotic signals by processing the outputs of chaotic systems. The mathematical criteria, on which the main idea of the study is based on, is the Central Limit Theorem which states that the sum of a large number of independent random variables with similar variances approaches a Gaussian distribution. The study involves more than 40 mostly three-dimensional continuous-time chaotic systems (Chua’s, Lorenz’s, Sprott’s, memristor-based, etc.) whose output signals are analyzed according to criteria that encompass the probability density functions of a chaotic signal itself and its envelope and phase, statistical and entropy-based metrics such as skewness, kurtosis, and entropy power. We found that two chaotic signals of Chua’s and Lorenz’s systems exhibited superior performance across the chosen metrics. Furthermore, our focus extended to determining the minimum number of independent chaotic signals necessary to yield a Gaussian-distributed combined signal. The analytic and experimental results indicate that the sum of at least three non-Gaussian chaotic signals closely approximates Gaussian distribution. It allows generation of reproducible Gaussian-distributed deterministic chaos by modeling simple chaotic systems.

In the field of robotics education, introductory courses would ideally utilize heavy industrial arms for hands-on learning. This would provide students with valuable experience in joint programming, which involves direct control of each joint motor in the arm to accomplish desired path planning and differential movements. This practice requires consideration of the physical dynamics of the arm. However, the use of heavy industrial arms has several drawbacks. They are large and expensive, require specialized maintenance, can pose safety risks, and they typically do not allow for direct control of the joint motors. One solution is to use a small, lightweight, toy-like arm. While these are cost-effective and provide direct access to the joint motors without posing safety risks, their lightweight construction means they exhibit minimal dynamic behavior, which limits their educational value. Another solution involves a robotic arm simulator that uses a virtual arm. However, a virtual arm doesn't offer the same level of hands-on engagement and excitement as a physical arm. We propose a hybrid solution that combines a small physical arm with a virtual arm. This approach provides students with the experience of working with an industrial arm, but without the associated difficulties. We demonstrate how this approach successfully improved the completion rate of joint programming assignments, offering a promising solution for practical robotics education.

New data on the climate in southern Spain from 1792 to 1808 are analyzed in this work. The data source is the newspaper Correo Mercantil de España y sus Indias, where summaries of the weather conditions in Spain were published at weekly resolution. The study is focused on southern provinces, providing 2788 new records, some of them corresponding to areas without data previously recorded. The analysis indicates the predominance of cold-dry winters, cold-wet springs, warm-dry summers, and variable conditions in autumn, from west (cold-wet) to east (warm-dry). Some examples of these situations are presented.

This study introduces an innovative optimization method to identify the optimal configuration of a sparse symmetric 2D array for applications in security, particularly multistatic imaging. Utilizing Genetic Algorithms (GA) in a sophisticated optimization process, the research focuses on achieving the most favorable antenna distribution while mitigating the common issue of secondary lobes in sparse arrays. The main objective is to determine the ideal configuration from specific design parameters, including hardware specifications such as number of radiating elements, minimum spacing, operating frequency range, and image separation distance. The study employs a cost function based on the the point spread function (PSF), the system response to a point source, with the goal of minimizing the secondary lobe levels and maximizing their separation from the main lobe. Advanced simulation algorithms based on Physical Optics (PO) are used to validate the presented methodology and results.

Condition monitoring of bearings is an open issue. The use of the stator current to monitor induction motors has been validated as a very advantageous and practical way to detect several types of faults. Nevertheless, for bearing faults the use of vibrations or sound generally offers better results in the accuracy of the detection although with some disadvantages related to the sensors used for monitoring. To improve the performance of bearing monitoring, it is proposed to take advantage of more information available in the current spectra, beyond the usually employed, incorporating the amplitude of a significant number of sidebands around the first eleven harmonics, growing exponentially the number of fault signatures. This is especially interesting for inverter-fed motors. But, in turn, this leads to the problem of overfitting when applying a classifier to perform the fault diagnosis. To overcome this problem, and still exploit all the useful information available in the spectra, it is proposed to use shrinkage methods, which have been lately proposed in machine learning to solve the overfitting issue when the problem has much more variables than examples to classify. A case study with a motor is shown to prove the validity of the proposal

Twin pregnancies are highly undesirable in dairy cattle; they compromise the health and wellbeing of a cow, and its incidence dramatically impairs the farm economy. Recently, a genomic prediction for twin pregnancies has been developed. The objective of this study was to assess cow, environmental and management risk factors affecting the incidence of twin pregnancies in high-producing dairy cows in their first lactation, with special emphasis placed on the genomic prediction values for twin pregnancy. Our study population of primiparous cows proved valuable in identifying factors other than genomic predictive values influencing the twin pregnancy rate. The odds ratio for twin pregnancy was 0.85 (p &lt;0.0001) for each unit of a prediction value increase, 3.5 (p = 0.023) for cows becoming pregnant during the negative photoperiod, and 0.33 (p = 0.016) for cows producing ≥42 kg of milk at AI, compared to the remaining cows producing &lt;42kg of milk. As a general conclusion, the practical implication of our findings is that genomic prediction values can identify the risk of twin pregnancy at herd level. Given the cumulative effect of genomic selection, selecting for animals with reduced genetic risk of twin pregnancies can contribute to reduce its incidence in dairy herds.

One of the most important defining characteristics of groundwater quality is pH as it fundamentally controls the amount and chemical form of many organic and inorganic solutes in groundwater. Groundwater data are frequently characterized by a wide degree of variability of the factors which possibly influence pH distribution. For this reason, it is challenging to link the spatio-temporal dynamics of pH to a single environmental factor by the ordinary least squares regression technique of the conditional mean. In this study, quantile regression was used to estimate the response of pH to nine environmental factors (As, Cd, Fe, Mn, Pb, turbidity, electrical conductivity, total dissolved solids and nitrates). Results of 25%, 50%, 75% quantile regression and ordinary least squares (OLS) regression were compared. The standard regression of the conditional means (OLS) underestimated the rates of change of pH due to the selected factors in comparison with the regression quantiles. The effect of arsenic increased for sampling locations with higher pH values (higher quantiles) likewise the influence of Pb and Mn. However, the effects of Cd and Fe decreased for sampling locations in higher quantiles. It can be concluded that these detected heterogeneities would be missed if this study had focused exclusively on the conditional means of the pH values. Consequently, quantile regression provides a more comprehensive account of possible spatio-temporal relationships between environmental covariates in groundwater. This study is one of the first to apply this technique on groundwater systems in sub-Saharan Africa. The approach is useful and interesting and has broad application for other mining environments especially tropical low-income countries where climatic conditions can drive rapid cycling or transformations of pollutants. It is also pertinent to geopolitical contexts where regulatory; monitoring and management capacities are weak and where mining pollution of groundwater largely occur.

This study investigates the power production and blade fatigue of a three-turbine array subjected to active yaw control (AYC) in full-wake and partial-wake configurations. A framework of two-way coupled large-eddy simulation (LES) and aeroelastic blade simulation is applied to simulate the atmospheric boundary-layer (ABL) flow through the turbine array and the structural responses of the turbine blades. Mean power outputs and blade fatigue loads are extracted from the simulation results. By exploring the feasible AYC decision space, we find that (a) in the full-wake configuration, the local power-optimal AYC strategy with positive yaw angles endures less flapwise blade fatigue and more edgewise blade fatigue than the global power-optimal strategy; (b) in the partial-wake configuration, applying positive AYC in certain inflow wind directions achieves higher optimal power gains than that in the full-wake scenario and reduces the blade fatigue from the non-yawed benchmark. Through a theoretical analysis based on the blade element momentum theory, we reveal that the aforementioned differences in flapwise blade fatigue between the positively and negatively yawed turbine are due to the differences in the azimuthal distributions of the local relative velocity on blade sections, resulting from the combined effects of vertical wind shear and blade rotation. Furthermore, the difference in the blade force between the positively and negatively yawed front-row turbine induces different wake velocity and turbulence distributions, causing different fatigue loads on the downwind turbine exposed to the wake.

The primary sources of particulate matter are linked to human activity. Certain particulate emissions, particularly those of a finer nature, can significantly impact human health, making them one of the most concerning pollutants. Ultrafine particles (UFP), which have a diameter of less than 100 nm, are of particular concern due to their impact on human health and the difficulty in controlling them. The concentration of ultrafine particles (UFP) in the workplace is a growing concern and is classified as an emerging risk. Workers may be exposed to UFP through inhalation, skin absorption, ingestion, or a combination of these routes. This study aims to determine the levels of UFP exposure among workers in environments with varying direct particle emission patterns. Measurements were conducted to compare the results with the levels recommended by the WHO. The study monitored industrial workplaces with direct particulate matter emissions, such as a carpentry and a bakery, as well as social sector sites without or almost without direct particle emissions, such as a school and a health clinic. One conclusion drawn from this study is that all tasks and occupations are susceptible to high levels of UFP, exceeding WHO recommended values in virtually all monitored environments. Therefore, monitoring and controlling UFP is crucial. Further in-depth studies on this subject are also necessary..

The growing awareness of the biological effects of artificial light on humans has stimulated ample research. It is now widely accepted that asynchrony between artificialand natural light-dark cycles can elicit severe detrimental health effects. New research has been devoted to lighting solutions that dynamically change their color to mimic spectral changes of daylight and to account for human needs. However, in some situations, the visual properties of light must be preserved: For example professional TV video editors and shift workers who must work under standardized lighting conditions to do color correction in post-production. We have investigated the possibility to tune circadian effects using white lights that are spectrally different but nonetheless have similar color coordinates thus appear as a similar white tone. Our simulation results indicate that it is possible to modulate circadian light effects by combining LEDs for neutral white (4000 K), a widely used white tone for indoor lighting in europe. The results also show that the solutions combining single-color LEDs do however not meet the quality criteria from the visual point of view because their color rendering ability decays to unacceptable low levels. Combining narrowband LEDs with a broadband white LED improves the color rendering quality and we show how far circadian light effects can be tuned according to common theoretical models. The aim is to reflect daylight situations with artificial lighting, thus having a high melatonin suppression in the morning and low melatonin suppression in the evening. As a consequence our aim is to show what maximum and minimum circadian effect is possible with the same set of LEDs.

Artificial intelligence’s rapid advancement has enabled various applications, including intelligent video surveillance systems, assisted living, and human-computer interaction. These applications often require one core task: video-based human action recognition. Research in human video-based human action recognition is vast and ongoing, making it difficult to assess the full scope of available methods and current trends. This survey provides an in-depth exploration of the vision-based human action recognition field, comprehensively offering the available techniques and their evolution, highlighting the cutting-edge ideas driving its development. We also analyze the most used keywords in research papers over the past years to identify trends and predict possible future directions. Hence, this concise survey helps researchers understand the breadth of existing approaches, evaluate current research trends, and stay up-to-date on potential developments.

In August 2020, the World Health Assembly launched a global initiative to eliminate cervical cancer by 2030, setting three primary targets. One key goal is to achieve a 70% screening coverage rate for cervical cancer, primarily relying on the precise analysis of Papanicolaou (Pap) or digital Pap smears. However, the responsibility of reviewing Pap smear samples to identify potentially cancerous cells primarily falls on pathologists, a task known to be exceptionally challenging and time-consuming. This paper proposes a solution to address the shortage of pathologists for cervical cancer screening. It leverages the OpenAI-GYM API to create a deep reinforcement learning environment utilizing liquid-based Pap smear images. By employing the Proximal Policy Optimization algorithm, autonomous agents navigate Pap smear images, identifying cells with the aid of rewards, penalties, and accumulated experiences. Furthermore, the use of a pre-trained convolutional neuronal network like Res-Net54 enhances the classification of detected cells based on their potential for malignancy. The ultimate goal of this study is to develop a highly efficient, automated Papanicolaou analysis system, ultimately reducing the need for human intervention in regions with limited pathologists.

Three-dimensional matrices are a new strategy used to tackle type I diabetes; a chronic metabolic disease characterized by the destruction of beta pancreatic cells. Type I collagen is an abundant extracellular matrix (ECM), component that has been used to support cell growth. However, pure collagen possesses some difficulties including low stiffness and strength, and high susceptibility to cell-mediated contraction. Therefore, we developed a collagen hydrogel with a poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN), functionalized with vascular endothelial growth factor (VEGF) to mimic the pancreatic environment for the sustenance of beta-pancreatic cells. We analyzed the physicochemical characteristic of the hydrogels and found that they were successfully synthesized. The mechanical behavior of the hydrogels improved with the addition of VEGF, and the swelling degree and the degradation were stable over time. In addition, it was found that 5 ng/mL VEGF-functionalized collagen/PEGDA IPN hydrogels sustained and enhanced viability, proliferation, respiratory capacity and functionality of beta pancreatic cells. Hence, this is a potential candidate for future preclinical evaluation, which may be favorable for diabetes treatment.

The main objective of this study was to study the effect of occupational stress on turnover intentions, as well as whether this relationship is mediated by burnout levels and moderated by motivation. The sample of this study consisted of 603 participants, all employees of the Portuguese Tax and Customs Authority, which is part of the Ministry of Finance and belongs to the Direct State Administration. The results indicate that occupational stress (with managers, with career and remuneration and with work overload) has a positive and significant effect on turnover intentions and that this relationship is mediated by burnout. Motivation (intrinsic and identified) has a negative and significant effect on turnover intentions. Intrinsic motivation moderates the rela-tionship between occupational stress (with managers, with colleagues, with career and pay and with family problems) and turnover intentions. These results indicate that among the dimensions of occupational stress, the most critical are stress with managers, work overload and career and pay. These are factors that the Direct State Administration should be concerned about in trying to minimize their causes.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity that may ultimately result in cancer. The process is described as the result of dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potential cancerous behavior. In support of the hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic model for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed against recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. Subsequently, is proposed an epigenetic landscape for their progression and a potential mechanism to restrain the degree of dedifferentiation and malignant behavior. Finally, is suggested a novel understanding of the involution and carcinogenesis of tissues associated with aging as a perspective that might inspire integrative approaches in the study and management of chronic diseases.

In this paper we use the additive thermodynamic formalism to obtain new bounds of the Hausdorff and box-counting dimension of certain non conformal hyperbolic repellers defined by piecewise smooth expanding maps on a $d$-dimensional smooth manifold $M$.

Inherited retinal dystrophies (IRDs) are a global problem that is largely unaddressed, especially in Africa. Black indigenous Africans are rarely represented in research that develop genetic tests and genetic therapies for IRDs yet their genomes are more diverse. The aim of this literature review is to synthesize information on the IRD genetic research conducted among indigenous black Africans to identify challenges and opportunities for progress. PubMed was searched to identify empirical publications reporting the genetic analysis of IRDs among indigenous Africans. A total of 10 articles were selected for the review. Based on the information in the articles, the main genetic testing methods in use include next-generation, whole exome, and Sanger sequencing. The main IRDs characterized by the genetic tests include retinitis pigmentosa, Leber Congenital Amaurosis, Stagardt disease, and cone dystrophy. Examples of implicated genes include MERTK, GUCY2D, ABCA4, and KCNV2 for the four IRDs respectively. Research activities on the genetics of IRDs are generally scanty in Africa. Even in South Africa and North Africa where some research activities were noted, only a few indigenous black Africans were in the study cohorts. There is an urgent need for genetic research on IRDs, especially in East, Central, and West Africa.

ABSTRACT The work is focused on determining the energy transfer from EV’s to grid for different operating conditions. The study has been simulated on a scaled model and later validated through experimental tests on batteries of 20 kWh, 40 kWh, 60 kWh and 80 kWh for EV’s energy rates from 130 Wh/km to 180 Wh/km. Tests have been developed to evaluate the energy transfer from driving distance between 0 and 50 km. Results have proved there is a linear dependence between energy transfer and energy rate. Experimental and simulated values have been correlated showing a 99.6% accuracy. The ratio of energy transfer to battery energy capacity depends not only on this latter parameter, but also on the energy rate of the electric vehicle. Experimental tests have shown a variation from a minimum transfer ratio of 54.1% for the highest electric vehicle energy rate and lowest battery energy capacity and power transfer to grid rate to a maximum of 88.6% for the highest power transfer to grid rate and battery energy capacity and lowest electric vehicle energy rate.

This study aims to evaluate the land surface temperature (LST) and the thermal characteristics of the Urban Canopy Layer (UCL) of the urban canyon in Avenida Rio Branco in the Central Business District (CBD) of Rio de Janeiro during summer. In order to conduct this evaluation, two methods were employed: 1) TIRS Landsat-8 sensor for data selection and processing (latest generation, 2011-2020); ; 2) field survey using nine sampling points — seven along two mobile transects, one fixed point, and one vertical measurement point, which required the use of a RPA (Remotely Piloted Aircraft). Three categories of analysis were established for the field survey based on the prevailing synoptic situations: stability, instability, and post-instability. The CBD is characterized by extensive areas with surface heat islands, in which temperatures were higher than 38.9°C; the areas with milder LSTs were Campo do Santana, Avenida Rio Branco, and one of the Mixed-Use Zones (Praça Mauá). With respect to Rio Branco Avenue, the LST niches of lowest elevation were derived through building shadowing; however, the orbital data diverged from the observation data of the ten field-study days. In situ data revealed that the characteristics urban morphology of Avenida Rio Branco is susceptible to the formation of heat islands, presenting heat islands of very strong magnitude (over 6.1°C) in atmospheric stability, strong magnitude (4.1-6.0°C) in atmospheric instability, and moderate magnitude (2.1°C-4.0°C) in post-atmospheric instability. Despite the synoptic situation, thermal cores were concentrated at 1 pm. The intersection between Avenida Rio Branco, Rua do Ouvidor, and Praça Mauá stored most of the solar energy received during the day due to the greater sky obstruction caused by the verticalization. Finally, vertical analysis demonstrated the formation of a thermal inversion on the night of the highest mean air temperature (29.5°C), probably, due to the roughness and number of buildings in the urban canyon.

The research explores the impact of financial indicators on the credit ratings of companies listed on the S&amp;P 500, employing a Sys-GMM Model to address endogeneity concerns. The study investigated three independent variables categorized as market and survival factors alongside with seven control variables sourced from leverage, liquidity, interest coverage, profitability, market, survival, and macroeconomic domains. The sample comprised 2398 observations from Capital IQ Pro, spanning nine years (2013 to 2021) and encompassing 240 public companies. The findings suggest that neither Tobin's Q (TQ) and Total Shareholder Return (TSR) lack significant correlations with credit ratings, implying that stock market performance and total shareholder return do not directly impact credit ratings. In contrast, the Altman Z-score (AZS) emerged as a significant predictor, indicating its importance in assessing credit risk. These insights enhance understanding of financial indicators' impact on credit ratings, aiding financial institutions and companies in prudent lending and financing decisions.

Taxes on the consumption of certain products have played a key role in public revenue analysis in European countries. This work aims to assess the differences in tax planning on new non-combustion products across some European territories. Through theoretical analysis, the paper has three distinct aspects. Firstly, we show the taxpayer profile in different countries. Secondly, the study analyzes the risks for the health system and the individual. Thirdly, the design of the land tax is based on previous experience and planning in Europe. This paper concludes with a case study for different countries: 1) Spain “vapers” and “smokers”, where the analysis is based on micro-data from the European Health Interview Survey 2020. 2) Sweden with the analysis of snus, shows it as a practice to reach economic savings while decreasing economic costs thanks to the nudging of consumers towards better products. The results show taxation and, specially, land taxation, should consider differences in planning in the case of new products, such as the non-combustion products, given the user per capita income and the potential lower health risks involved.

The Covid-19 pandemic has produced a change in the way of living, socializing and a modification in Health Systems around the world. A multicentre retrospective study was carried out to study orofacial trauma in one of the regions most affected during the first wave of the pandemic, with the participation of the five main tertiary hospitals in Madrid. The aim of this study is to evaluate the epidemiology of orofacial surgical trauma during the 1 year of COVID pandemic and compared to de prior year. Age, sex, mechanism, localization, and treatment were studied. P-value <0.05 was considered statically significative. Reduction of 39.36% (<0.001) in maxillofacial fractures was observed, without significance change in sex, localization or treatment. Significant increase in age (35,92 vs. 40,26) (p = 0.006) was observed. Significant decline in mechanism was noted (p = 0.025), decreasing personal violence (41% vs 35%) and sports (14% vs 8%); increasing in falls (27% vs 35%), precipitation (2 vs 5%), and traffic accidents (12% vs 13%). The mandible was the most frequent fractured bone. The COVID pandemic has produced epidemiological variations in orofacial trauma, making it necessary to monitor social and legal changes that may require reorganization to adjust to population needs.

This article addresses the emergence of a niche for sustainable agricultural production in the province of García Rovira, Colombia. It examines the intervention of the Colombian planning regime, which implements agendas for sustainable territorial development. However, these agendas are not adequately aligned with provincial realities, resulting in a productive decline. From a multi-level perspective, a niche of production linked to the landscape is identified, highlighting sustainable practices and innovation. The study seeks to understand how planning influences the emergence of such niches and what factors boost their transition to sustainability. Through a mixed methodology, growing sectors are highlighted, and the profiles of the producers involved are outlined. The main conclusion is that the planned intervention is inefficient, as the niche of sustainable production emerges without its clear influence. Therefore, it is proposed to re-evaluate planning using alternative analysis frameworks to detect emerging productive dynamics, serving as a basis for future plans.

Using first-principles molecular dynamics (FPMD), we performed numerical simulations at 300 K to explore the interaction of a 2D MoS2 surface and a platinum atom, calculating the optical properties of the resulting material. The pristine MoS2 is a semiconductor with a gap of around 1.8 eV. The Pt atom is chemisorbed by the surface with an adsorption energy of −1.718 eV. With the adsorption of the Pt atom, the material remains a semiconductor, and its energy band gap reduces to 1.04 eV. But changes in the material's energy band structure imply substantial changes in its optical properties. The energy band structure of the 2D MoS2 with a sulfur vacancy VS shows that the material becomes a conductor, and there are significant changes in its optical properties. We also found that the Pt atom chemisorbs in a sulfur vacancy of the material, with an adsorption energy of −4.1164 eV. After the adsorption of Pt atoms in the sulfur vacancy, the material becomes a semiconductor with a band gap of 1.06 eV, and the changes in the optical absorption and reflectivity are significant.

Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. However, few genera of FLA are linked to human infections. Within these genera, Acanthamoeba spp., classified by genotypes (T1-T23), being T1, T2, T4, T5, T10, T12, and T18 as capable of causing granulomatous amoebic encephalitis (GAE) in immunocompromised patients mostly and Acanthamoeba keratitis related to genotypes T2, T3, T4, T5, T6, T10, T11, T12 and T15 in apparently healthy patients. Meanwhile, Naegleria fowleri is the causative agent of an acute infection called primary amoebic meningoencephalitis (PAM), while Balamuthia mandrillaris, like some Acanthamoeba genotypes, causes GAE, differing from the latter in the description of numerous cases in patients immunocompetent. Finally, other FLA related to the pathologies mentioned above have been reported; Sappinia pedata is responsible for one case of amoebic encephalitis; Vermamoeba vermiformis has been found in cases of ocular damage, and its extraordinary capacity as endo-cytobiont for microorganisms of public health importance such as Legionella pneumophila, Bacillus anthracis, Pseudomonas aeruginosa, among others. In this review, issues related to the epidemiology of each one are addressed, updating their geographic distribution and cases reported in recent years for pathogenic FLA.

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.