One of the relevant goals in forging technologies is simplifying the existing process and developing new processes that can retain the original or very close to the original dimensions and billet shape after the end of the deformation cycle. This study attempts to develop a forging equipment design that provides alternating cyclic loading; the alternate cyclic forging (ACF) method is proposed. To preliminary evaluate the ACF and study the plastic deformation behavior, numerical simulation via finite element modeling (FEM) was conducted using DEFORM-3D. The main attention was paid to the metal flow characteristics, effective strain and stress distribution, and the forging load. The ACF results in non-uniform metal flow with the formation of diagonal and vortex flows were demonstrated. Maximum effective strains and stresses zones are localized at two points of the billet contact with the surface of the tooling container and at two points of the interface between the punches. It was also assumed that reducing the contact area between the punch and the billet using separate semi-cylindrical punches can reduce the forging load. Preliminary finite element analysis (FEA) results of the proposed process after four successive steps of the deformation cycle confirmed the feasibility of its general implementation.

This article delves into the complex landscape of Bitcoin halving events, analyzing the historical context and implications of these pivotal occurrences within the cryptocurrency ecosystem and on its sustainability within the landscape of financial technologies. Through an examination of past halving events in 2012, 2016, and 2020, this study meticulously scrutinizes the conditions and prices of Bitcoin before and after each halving. By synthesizing data and trends from previous events, this article aims to uncover patterns and insights that illuminate the impact of Bitcoin halving on market dynamics and sustainability, movement of the price level, reached peaks and price troughs. Furthermore, this research presents a comparative analysis of past halving events, drawing parallels and distinctions to elucidate the evolving nature of Bitcoin's price movements and market sentiment surrounding these milestone events. Looking towards the future, this study estimates predictions and expectations for the upcoming Bitcoin halving. By unraveling the intricate relationship between Bitcoin halving events and market behavior, this article seeks to provide a comprehensive understanding of the broader implications for Bitcoin's trajectory and the evolving landscape of the cryptocurrency market and its sustainability.

Bicycle transport stands at the forefront of sustainable mobility initiatives, a cornerstone of European Union policy. While support for cycling is crucial, its advancement hinges upon the presence of high-quality, secure infrastructure for cyclists. Safety emerges as a paramount concern, influencing the viability of cycling as a mode of transportation, yet its perception varies among user demographics. Considering this, this article endeavours to examine and contrast cycling infrastructure across various European nations, alongside analysing statistics pertaining to fatal traffic accidents involving cyclists. In our paper, we have chosen the Netherlands as a representative of building quality cycling infrastructure with many years of experience, and two countries that are developing conditions for cyclists, Slovakia and Poland. We have applied a correlation between the length of the transport infrastructure and the number of cyclists killed. The findings point to the substantial correlation between the quality of cycling infrastructure and the incidence of accidents. This correlation underscores the pressing need for robust infrastructure development and safety measures to bolster cycling as a safe and viable transportation option. We have employed the Shapiro-Wilk test for normal distribution to verify the input data and process the Pearson correlation to investigate the correlation between cycling infrastructure and road accident fatalities of cyclists.

The purpose of the study is to establish compliance of the design of the modernized car with the requirements for safe operation. An option has been proposed for upgrading a passenger wagon to a Mobile Diagnostic Complex for transporting a combined vehicle equipped with appropriate flaw detection equipment intended for rail diagnostics. The authors have established the most optimal option for locating the diagnostic vehicle on board the Mobile Diagnostic Complex (MDC) wagon, taking into account the additional load from the vehicle. To achieve this goal, the article developed a three-dimensional model of the supporting structure of the wagon body, proposed a methodology and presented the results of a study of the stress-strain state of the wagon body, taking into account the additional weight of the wagon. The article develops a methodology for studying the natural frequencies of vibrations of the wagon body and develops a three-dimensional model of the wagon for calculating dynamic indicators in the Universal Mechanism software package. Taking into account the previously carried out strength calculations, as well as in order to maintain the factory life cycle indicators of the supporting structure of the wagon body, it is recommended to use the model in the first version.

The design complexity of the new generation of civil aero-engines results in higher demands on engines’ components, higher component temperature, higher heat generation, and, finally, critical thermal management issues. This paper will propose a methodological approach to create physics-based models for heat loads developed by sources as well as a systematic sensitivity analysis to identify the effects of design parameters on the thermal behaviour of civil aero-engines. The ranges and levels of heat loads generated by heat sources (e.g., accessory gearbox, bearing, pumps, etc.) and heat absorption capacity of heat sinks (e.g., engine fuel, oil, and air) are discussed systematically. The practical research challenges for thermal management system design and development for the new and next generation of turbofan engines will then be addressed through a sensitivity analysis of the heat load values as well as the heat sinks flow rates. The potential solutions for thermal performance enhancements of propulsion systems will be proposed and discussed accordingly.

The process involved in preparing driving simulator tests is a labor intensive one, and the nature of this complexity depends on the sophistication of the tests to be carried out, as well as the number of participants. Which has an impact on the duration of the research itself. The very solution of using driving simulators is a research tool that has been in use for many years and with great success. They are used in a very wide range of areas of human functioning. They replicate in a very realistic way the conditions that can occur in the external environment, offer the possibility of repetition of particular conditions and insight into certain behaviors that could be very difficult to initiate in real life. This article also describes the dis- ease of using simulators to conduct research activities, along with the workflow from assumptions to finalizing the research. An algorithm is also presented for the study of individual participants, with examples for separate research scenarios concerning driver behavior in the vicinity of pedestrian crossings.

In this study, we investigate the growth of EV ownership among Swedish households. Through detailed socio-economic data and the Swedish vehicle register, we are able compare characteristics of households that bought an EV in 2016 with those that became EV owners in 2020. We are thus able to describe and analyse the transition from the early EV owners to the early majority. Unlike many prior studies in the field, which are based on surveys or interviews, this study relies on registry data, thereby encompassing all car owners in Sweden. In this study, we have also scrutinized the significance of ownership mode by distinguishing between households that have chosen to purchase a car and those that have chosen to lease one. The results show that the demand for EVs has reached new consumer groups, e.g. both younger and older car buyers, and that the option to lease a car privately has broadened the market for new cars in general, and for EV’s in particular.

The article presents investigations of rail vehicle bogie of Y25 type. The Y25 bogie family is one of the most commonly used freight car bogie designs. In addition to several significant advantages characterising this design, it also has several disadvantages observed since the beginning of more than fifty years of operation in several types of cargo vehicles. One of these defects observed in real systems is "unsatisfactory running stability", particularly at long straight tracks. The article used commercial engineering software VI-Rail to create a model of the gondola car (type 412W Eaos) with two Y25 bogies. The car model was tested empty and loaded (maximum permissible load). Motion along straight and curved tracks with different radii values was analysed. The vehicle velocity was changed from a few m/s to the maximum values for which stable solutions of the model existed. For each route, a non-linear critical velocity was determined, defining the maximum operating velocity of the modelled car. The model solutions were recorded, while just one was selected to present the results - the first wheelset lateral displacement ylw. The opinion about the "imperfect running quality" in curved tracks was confirmed. The possible appearance of self-exciting wheelset vibrations in the modelled car's operating velocity range in the laden state was also observed. The research results on the impact of the bogie suspension parameters change on the vehicle model stability are presented. The crucial parameter in the bogie suspension was indicated. Reducing its value by several percent about the nominal value increases the critical velocity of the car to values higher than the maximum operating velocity of the modelled vehicle.

Electrical contacts are important circuit components with diverse industrial applications, and their failure can lead to multiple unwanted effects. Hence, the behavior of electrical contacts is a widely studied topic in scientific literature based on various approaches, tools, and techniques. The present study proposes a numerical modeling and simulation approach based on the Holm contact theory to study the dependence between the electric potential and the temperature within an electrical contact. Structured in 5 sections, the research was conducted using COMSOL Multiphysics software and its solid-state mechanics, electric current, and heat transfer modules in order to highlight contact behavior from mechanical, electrical and thermal points of view: the von Mises stress, contact force, the electric field amplitude, the variation of the electrical potential along the current path, the temperature gradient, and dependence of temperature along the contact elements edges were obtained by simulation and graphically represented. The results are in line with the expectations and with past research that was studied in the literature review.

Cars are a highly inefficient mode of urban transport with significant negative impacts. Electric vehicles make it possible to eliminate direct CO2 emissions (though the total over a vehicle’s entire life cycle greatly offsets the advantages) but leave unchanged – or even aggravate – all the other negative effects on the quality of urban environments. Three visions for urban transport were presented: automobility, multimodality and accessibility. The first dominates North American cities, the second European one. The anomalies of these two visions have been examined. The automobility cities cannot manage the congestion and the attempts are self- defeating. The anomalies of multimodality city are related to the public space consumption for mobility and the impossibility to plan spatial proximity. The sustainable vision, that resolve the anomalies, is represented by the accessibility city in the Triple Access System (TAS) version which, however, still has a long way to go to be accepted and implemented.

The development of transport infrastructure is a key element of economic growth, social connectivity, and sustainable development. Many countries have historically underinvested in transport infrastructure, necessitating more efficient strategic planning in transport infrastructure investment projects implementation. This article addresses the selecting and scheduling of transport infrastructure projects, specifically within the context of drawing available resources from pre-allocated funds within a multi-annual budget investment program. The current decision-making process is largely based on expert judgment, lacking quantitative decision support methods. The authors propose a genetic algorithm as a decision-support tool that frames the problem as an NP-hard 0-1 multiple knapsack problem. The proposed genetic algorithm is unique for its matrix-encoded chromosomes, specially designed genetic operators, and a customized repair operator, which is implemented to address the large number of invalid chromosomes generated during the GA computation. The goal is to maximize the impact of allocated funds over a seven-year programming period, while respecting constraints specified by the funding authorities. In computational experiments, proposed GA is compared to an exact solution and is proved to be efficient in terms of quality of obtained solutions and computational time, highlighting its potential for enhancing strategic decision-making in transport infrastructure development.

Let Vn(d) denote the least number such that every collection of nd-cubes with total volume 1 in d-dimensional (Euclidean) space can be packed parallelly into some d-box of volume Vn(d). We show that V3(d)=r1−dd if d≥11 and V3(d)=1r+1rd+1r−rd+1 if 2≤d≤10, where r is the only solution of the equation 2(d−1)kd+dkd−1=1 on 22,1 and (k+1)d(1−k)d−1dk2+d+k−1=kddkd+1+dkd+kd+1 on 22,1, respectively. The maximum volume is achieved by hypercubes with edges x, y, z such that x=2rd+1−1/d, y=z=rx if d≥11, and x=rd+(1r−r)d+1−1/d, y=rx, z=(1r−r)x if 2≤d≤10. We also proved that only for dimensions less than 11 there are two different maximum packings, and for all dimensions greater than 10 the maximum packing has the two smallest cubes the same.

Polar auxin transport (PAT) and auxin efflux carriers are known components controlling leaf complexity and venation patterns in some model plant species. Evidence indicates that PAT generates auxin converge points (CPs) that in turn lead to local leaf formation and internally into major vein formation. However, the role of PAT in more diverse leaf arrangements and vein patterns is largely unknown. We used pharmacological inhibition of PAT in developing pinnate tomato, trifoliate clover, palmate lupin, and bipinnate carrot leaves and observed dosage-dependent reduction to simple leaves in these eudicots. Leaf venation patterns changed from craspedodromous (clover, carrot), semi-craspedodromous (tomato) and brochidodromous (lupin) to more parallel patterning with PAT inhibition. The visualization of auxin responses in transgenic tomato plants showed that discrete and separate CPs in control plants were replaced by diffuse convergence areas near the margin. These effects indicate that PAT plays a universal role in the formation of different leaf and vein patterns in eudicot species via a mechanism that depends on the generation as well as separation of auxin CPs. Computer simulations indicate that variations in PAT can alter the number of CPs, corresponding leaf lobe formation and position of major leaf veins along the leaf margin in support of experimental results.

Traffic Inspection (TI) work in this article is positioned as a specific module of road traffic with its primary function oriented towards monitoring and controlling safe traffic and the execution of significant events within a particular geographic area. Exploratory research on the significance of event execution in simple, complicated and complex traffic flow and process situations is related to the activities of monitoring and controlling functional states and performance of categorical variables, which include objects and locations of road infrastructure, communication infrastructure and networks of traffic inspection resources. It is emphasized that the words “work” and “traffic” have the semantic status as synonyms (in one world language), which is explained in the design of the Agent-based model of the complexity of content and contextual structure of TI work at the singular and plural level with 12 points of interest (POI) in the thematic research. An Event Execution Log (EEL) was created for on-site data collection with eight variables, seven of which are independent (event type, activities, objects, locations, host, duration-period and periodicity of the event) and one dependent (significance of the event) variable. The structured data set includes 10,994 input-output vectors in 970 categories collected in the EEL created by 32 human agents (traffic inspectors) over a 30-day period. An algorithmic presentation of the methodological research procedure for preprocessing and final data processing in the ensemble of machine learning models for classification and selection of TI tasks is given. Data cleaning was performed on the available dataset to increase data consistency for further processing. Vector elimination was carried out based on the Location variable, such that the total number of vectors equals the number of unique categories of this variable, which is 636. The main result of this research is the Classification modeling of the significance of events in TI work based on machine learning techniques and the Stacking ensemble. The created machine learning models for event significance classification modeling have high accuracy values. To evaluate the performance metrics of the Stacking ensemble of models, the confusion matrix, Precision, Recall, ND F1-score are used.

Distracted driving is a major cause of road traffic crashes in Yaoundé. Partly due to scarcity of enforcement, lack of evidence and investigation of distraction safety performance indicator (SPI), hindering evidence-based intervention. This study aimed to address this evidence gap by evaluating the distraction SPI using proven methodology. Data on distracted driving (handheld mobile device; interaction; eating/smoking/drinking) were collected from roadside observation on 36 randomly selected road sections carefully spread to cover the city. SPI were computed and weighted with traffic volume to ensure representativeness of values. A total of 41,004 drivers were observed (38,248 in car; 1,116 in van; 977 in truck; 663 in bus). The prevalence of distracted driving in Yaoundé is 13.69% for the three distractions type combined. The prevalence is 7.84% for interaction, 4.89% for handled mobile device usage and 0.96% for eating/smoking/drinking. Leveraging these insights, a seven year (2024 - 2030) fighting strategy aiming at halving the prevalence was developed. The strategy contains intervention including on legislation/enforcement, which have been proven effective. This study, pioneer in Yaoundé, provide stakeholders with evidence of the issue and measures to implement and can also serve when developing road safety strategy.Future research should consider investigation at national level.

Speeding is a significant global issue, with disparities in speed outcome and speed research between low- and middle-income countries (LMICs) and high-income countries (HICs). This study aims to address speed research gaps by examining the prevalence of self-reported speeding and factors influencing drivers' speeding behavior (SB) using the Theory of Planned Behavior (TPB). An online survey involving 387 anonymous drivers was conducted in Yaoundé. Results showed that all drivers reported exceeding speed limits, with 81% exceeding by 5km/h, 12% by 10km/h, and 7% by more than 10km/h in urban areas. On highways, 54% reported exceeded the limit by more than 10km/h. Age, driver's license, and gender showed significant associations with speed limits non-compliance. The study results suggests that the TPB can be useful in assessing speeding behavior, as the inclusion of TPB variables led to a more than 50% proportionate increase in SB variance. Structural equation modeling revealed attitude towards speeding as the strongest predictor of speeding intention (SI), along with certain demographics indirectly influencing SB through SI. Perceived behavioral control (PBC) and SI directly influenced SB. These findings emphasize the potential of interventions targeting attitude, intentions, and perceived behavioral control to modify speeding behavior and improve road safety.

In Yaoundé, Cameroon, excessive and inappropriate speeding remains a major public health concern. Part of the problem are the unsafe speed limits, lack of evidence, and effective evaluation of speeding safety performance indicators (SSPIs), and the absence of speed management, hindering the city's ability to mitigate the risks associated with speeding. This study aimed to address this knowledge gap by assessing SSPIs using a well-defined methodology and suggesting speed management strategies. Data on speed, traffic volumes and road attributes were collected from a random selection of 16 representative road sections in Yaoundé. Seven SSPIs were calculated, and weights were assigned to evaluate city-level SSPIs. The findings showed that 66.8% of drivers drive within the speed limit, generally operating at speeds of 54 km/h with a speed variation of 26 km/h. Based on the speed analysis, evidence-based strategies are proposed, and implementing these strategies could potentially reduce fatalities and serious injuries by 16% to 84% across study locations, as indicated by Elvik's model. These findings have significant policy implications for reducing speeding in Yaoundé, and the methodological approach can be replicated in other urban settings. Future research should extend SSPI evaluation to the national level and test the effectiveness of the recommended strategies.

The transition to sustainable mobility is a recognized socio-economic and environmental challenge, particularly among young adults in low- and middle-income countries (LMICs). This paper addresses the lack of comprehensive research on mobility patterns for LMICs by examining the travel patterns of students, staff, and lecturers at the National Advanced School of Public Works, Yaoundé (NASPW) to understand transport mode choices and barriers to the use of public and active transport modes. Data was collected through online questionnaires from 425 participants. Findings revealed that most students (27.5%) used multiple modes of transport, with moto-taxis being the most common (21%). Lecturers primarily used private cars (50%), while staff relied on taxis or multiple modes (33%). Accessibility, vehicle speed, and flexibility appeared as the most important reasons for the preferred modes of transport. Barriers included long waiting times and traffic congestion for public transport, and distance and inadequate infrastructure for active mobility. The usage of public transportation was encouraged by its affordability and reduced travel time, whilst active options were preferred due to their cost savings and health benefits. To promote sustainable mobility for campus travel, it is crucial to encourage active modes, develop mass transport systems, and raise awareness through symposiums and conferences among students and staff.

In order to achieve the elimination of the negative impacts of transport on road safety, the European Union is taking various measures resulting from its commitment to improve road safety. One of the instruments for achieving the objectives set is social legislation for the work of drivers in road freight and passenger transport. In line with the objective of improving the quality of working conditions for road transport drivers and road safety, the European Union applies Regulation (EC) No 561/2006 on the harmonisation of certain social legislation relating to road transport, which lays down rules on driving times, breaks and rest periods for drivers operating in road freight and passenger transport. The main objective of the paper is to assess the impact of social legislation on road transport safety by means of real research and to identify the factors influencing the violation of the legislation depending on the type of transports carried out in domestic or international road freight transport.

Warming of the climate system is unequivocal, and many of the observed changes are unprecedented over five decades to millennia. Globally the atmosphere and ocean is increasingly getting warmer, the amount of ice on the earth is decreasing over the oceans, and the sea level has risen. According to Intergovernmental Panel on Climate Change, the total increasing temperature globally averaged combined land and surface between the average of the 1850-1900 period and the 2003 to 2012 period is 0.78 °C (0.72 to 0.85). But should we prepare for such the relatively small change? The importance is not the mean of the warming but the considerable likelihood of climate change that could trigger extreme natural hazards. The impact and the risk of climate change associated with railway infrastructure have not been fully addressed in the literature due to the difference in local environmental parameters. On the other hand, the current railway network in Malaysia, over the last decade, has been significantly affected by severe weather conditions such as rainfall, lightning, wind and very high temperatures. Our research findings point out the extremes that can lead to asset system failure, degraded operation and ultimately, delays to train services. During the period of flood, the embankment of the track can be swept away and bridge can be demolished, while during drought, the embankment of the track can suffer from soil desiccation and embankment deterioration, high temperature increases the risk of track buckling and high winds can result in vegetation or foreign object incursion on to the infrastructure as well as additional quasi-static burden exerted. This review is of significant importance for planning and design of the newly proposed high speed rail link between Malaysia and Singapore.

Micro (nano) plastics are emerging pollutants and their gradual accumulation in soil due to factors such as improper wastewater processing, plastic film abuse and atmospheric deposition could pose a significant threat to the environment. However, there is limited research on the uptake and transposition of micro (nano) plastics by terrestrial plants and the effects of microplastics on terrestrial plant growth. Therefore, the sources of plastics in soil as well as the uptake and transposition pathways of micro (nano) plastics in terrestrial plants are systematically summarized in this study. The effects of micro (nano) plastics on plants and their mechanisms are thoroughly discussed, which mainly affect the growth and development of plants by blocking roots, triggering oxidative damage and altering the nature of the soil and the microbial community as well as the combined toxic effects with other pollutants. Future research should strengthen the in-situ experiments to study the mechanisms by which soil micro (nano) plastics affect the uptake and transposition of individual plants and plant growth. It should also focus on the factors affecting the uptake of micro-(nano) plastics, the behaviour of micro-(nano) plastics in soil and plant uptake, transposition processes and their mechanisms and combined effects of micro-(nano) plastics and pathogens on plants. Moreover, new detection technologies should be developed to monitor their impacts on ecosystems to better manage their potential risks to the environment.

Mobility hubs (MHs), where various transport modes converge, are increasingly being implemented as a key policy strategy to promote sustainable travel behavior. The existing literature is rich with proposals for various types of MHs and their suitable siting locations. However, studies comparing the role of land use patterns on the performance of different types of MHs are scarce. This study aims to fill this gap by analyzing transit patronage and active mode share as performance indicators of MHs. It compares the effects of land use patterns on the performance of different types of MHs classified by the nature of transport integration (e.g., train-tram-bus, train-tram, and train-bus) in different contexts (e.g., city center and suburb) in the Greater Melbourne Area, Australia. Results show that MHs, irrespective of their type, significantly enhance the use of both transit and active transport services compared to a unimodal train station, with maximum usage observed in a train-tram-bus hub, followed by train-tram and train-bus hubs. However, the underlying land use patterns significantly affect their performance. While the size of commercial land use consistently and positively influences transit patronage across MH types, certain land use patterns (e.g., intersection density, cultural centers, care facilities) exert their influence in specific types of MHs. These findings suggest that MH typologies should be designed in tandem with supportive land uses to maximize sustainable travel behavior.

The aim of the article is to verify differences in the perception of selected factors of sustainability among small and medium-sized enterprises (SMEs) in Central Europe. The subjects of analysis are factors such as corporate social responsibility (CSR), business risk sources (market, financial, personnel, and operational), reputation and social media, national support, social changes, and crisis events in business. The questionnaire was completed by 1,090 SMEs from the business environments of Visegrad Group countries. Statistical hypotheses were verified using Z-scores for two population properties. The most negatively perceived factors among owners and managers in the SME segment are national support and legislative changes. The most positively perceived factor is reputation and social media. The country of doing business is a significant factor. The perception of crisis events in business is most negative among Czech SMEs. More than 80% of Hungarian SMEs perceive their companies as sustainable. In comparison with Slovak and Polish SMEs, Hungarian perceptions are more positive in the context of sustainability. The country of doing business is the strongest factor in evaluating CSR indicators. The positive perception of CSR in Czech SMEs (43.9%) is lower than in other countries.

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding the impacts of the interactions in both systems is crucial for governments, system operators, regulators and operational planners, particularly, to ensure security of supply for the overall energy system. Although simulation has been widely used in the assessment of gas systems as well as power systems, there is a significant gap in simulation models that are able to address the coupling of both systems. In this paper, a simulation framework that models and simulates the gas and power network in an integrated manner is proposed. The framework consist of a transient model for the gas system and a steady state model for the power system based on AC-Optimal Power Flow. The gas and power system model are coupled through an interface which uses the coupling equations to establish the data exchange and coordination between the individual models. The bidirectional interlink between both systems considered in this studies are the fuel gas offtake of gas fired power plants for power generation and the power supply to LNG terminals and electric drivers installed in gas compressor stations and underground gas storage facilities. The simulation framework is implemented into an innovative simulation tool named SAInt (Scenario Analysis Interface for Energy Systems) and the capabilities of the tool are demonstrated by performing a contingency analysis for a real world example. Results indicate how a disruption triggered in one system propagates to the other system and affects the operation of critical facilities. In addition, the studies show the importance of using transient gas models for security of supply studies instead of successions of steady state models, where the time evolution of the line pack is not captured correctly.

In Yaoundé, Cameroon, where walking is a leading transport mode, pedestrian safety remains an issue as they account for a fair share of road traffic casualties, partly due to the lack of walking policies and data on pedestrian facilities safety, hindering targeted intervention. This study investigated road segments using the Pedestrian Safety Index (PSI) and the Global Walkability Index (GWI) across 12 key roads frequented by diverse pedestrian groups, especially students. The indexes were graded from E to A and analyzed using description and rank correlation analysis. Only one segment (R7) achieved a grade C, while the remainder scored D or E, indicating poor pedestrian safety conditions and unpleasant walking experience. The strong correlation coefficient (0.69) between the PSI and GWI at a 99% significance level validated the safety assessment, providing confidence in the safety results. Leveraging these findings, a seven-year (2024-2030) safety strategy was developed aiming to upgrade all roads to grade B. This strategy contains interventions including engineering improvement, proven effective. The study offers evidence for city officials to improve pedestrian safety and informs walking policies development and upcoming projects implementation. Future research should include more road segments and validate indexes with crash or conflict data.

Commuting to work by private vehicle is one of the main sources of air pollution in cities, mainly from NO2 and particulate matter (PM2.5 and PM10). With the spread of telework, traffic congestion during peak hours is reduced on certain days of the week, improving air quality. This study an-alyzes the relationship between the improvement of air quality improvement and urban traffic resulting from teleworking activities after the COVID-19 pandemic in Madrid, Spain. The article considers road traffic and teleworking before the COVID-19 pandemic (2018 and 2019), during the pandemic (2020 and 2021) and in the period after (2022 and 2023) in the city center and the in-fluence on certain environmental factors. Daily NO2, PM2.5, PM10, and O3 concentration data were collected at air quality stations in Madrid municipality, traffic data and some meteorological variables such as wind speed, precipitation and temperature were considered. When conducting correlation and regression analysis among the variables it shows a clear association between NO2 and traffic before the pandemic, which is lower for both PM and O3. This correlation was main-tained during the pandemic, except for O3, whose association increased during this period and then decreased in the later period due to various motives. These results seem to indicate the ex-istence of a relevant relationship between urban mobility and air quality and an especially rele-vant relationship with telework, suggesting the need for policies aimed at promoting sustainable mobility in the future.

The 5-hydroxymethylfurfural (HMF) is a six-carbon heterocyclic organic compound with two substituents an aldehyde group and an alcohol group. It is formed from saccharides as a result of two reactions: the Maillard reaction and the caramelization of saccharides. It has both a negative and a positive effect on the human body, which makes it, even more, an attractive research object. The objective of the study was to determine HMF content in honey samples available on the Polish market using three varied methods and compare the results obtained. The methodology used included: two spectrophotometric methods (by White and Winkler) and the HMF determination method based on the LC-MS/MS technique developed uniquely for this study. The determined HMF content in all tested honey samples did not exceed the applicable standard. All results are within the scope of the European Council Directive 2001/110/EC of 20 December 2001, i.e. they do not exceed HMF content in honey, which is 40 mg/kg.

The collaboration of multimodal transport documents is the foundation for conducting multimodal transport operations. Blockchain technology can effectively address trust issues and information sharing difficulties in current multimodal transport document collaboration. However, in current blockchain-based electronic document research, the bottleneck problem lies in the collaboration of multiparty in multimodal transport under the "one-bill coverage system". We design a blockchain platform architecture for multimodal transport, reshaping collaboration processes for different modes of transport based on the blockchain platform. It proposes a collaboration model for multimodal transport under the "one-bill coverage system" and performs model solving and case analysis. The obtained collaboration strategies are embedded into the platform's application layer. Finally, using Solidity language, it writes smart contracts related to multimodal transport under the "one-bill coverage system " and deploys and executes them on the Remix platform.

Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

Walking School Buses (WSBs) provide a safe alternative to being driven to school. Children benefit from the contribution the exercise provides towards their daily exercise target, it gives children practical experience with respect to road safety and helps to relieve traffic congestion around the entrance to their school. Walking routes are designed largely based in road safety considerations, catchment need and the availability of parent support. However, little attention is given to the air pollution exposure experienced by children during their journey to school, despite the commuting microenvironment being an important contributor to a child’s daily air pollution exposure. This study aims to quantify the air pollution exposure experienced by children walking to school and those being driven by car. A school was chosen in Bradford, UK. Three adult participants carried out the journey to and from school each carrying a P-Trak ultrafine particle (UFP) count monitor. One participant travelled the journey to school by car while the other two walked, each on opposite sides of the road for the majority of the journey. Data collection was carried out over a period of two weeks, for a total of five journeys to school in the morning and five on the way home at the end of the school day. Results of the study suggest that car commuters experience lower levels of air pollution dose due to lower exposures and reduced commute times. The largest reductions in exposure for pedestrians can be achieved by avoiding close proximity to traffic queuing up to intersections, and, where possible, walking on the side of the road opposite the traffic, especially during the morning commuting period. Major intersections should also be avoided as they were associated with peak exposures. Steps to ensure that the phasing of lights is optimized to minimize pedestrian waiting time would also help reduce exposures. If possible, busy roads should be avoided altogether. By the careful design of WSB routes, taking into account air pollution, children will be able to experience the benefits that walking to school brings while minimizing their air pollution exposure during their commute to and from school.

The rise in population density, vehicle ownership, and urban development has significantly influenced travel demand and altered travel patterns, leading to traffic congestion in rapidly growing urban centers like Accra, Ghana. The traditional approach of expanding roadways to accommodate rising traffic is no longer environmentally sustainable. Instead, emphasis has shifted towards travel demand management (TDM) strategies as a more sustainable solution. This study aimed to investigate a range of TDM strategies that can be adopted in Accra to improve traffic flow through the lenses of everyday road users. The study employed a questionnaire survey and a stratified sampling technique to gather data from 615 respondents for relative importance index (RII) ranking, and Chi-square statistical analysis. The findings reveal that the topmost preferred strategies were mass transit improvements, walking and cycling improvements, and alternative work schedules. Notably, mass transit improvements emerged as the most preferred strategy. The study also unveiled a statistically significant correlation between variables such as age, education level, marital status, income level, and mode of transportation with all selected TDM preferences. However, no significant relationship was found between gender and car ownership with all selected TDM preferences. The study provides valuable insights regarding road users’ preferences for TDM strategies that can aid in planning future urban mobility systems to proactively manage travel demand, alleviate congestion, and promote sustainable transportation options for the city’s residents.

In wheeled vehicles, there exists a challenge concerning the alignment of the front wheels during turns. When both wheels are turned to the same extent, the inner wheel experiences lateral slippage on the road surface, resulting in reduced steering efficiency. Such problems can be solved by using the Ackermann principle. There are two approaches: through the steering mechanism or by employing autonomous wheel control. From a technical standpoint, it is achievable to synthesize a steering mechanism that fulfills the Ackermann condition, ensuring as accurately as possible for any given turning radius. This research paper focuses on synthesizing a steering mechanism, specifically a two-circuit linkage that links the left and right wheels. The structure and kinematics of this mechanism are being investigated. Following the principles of Ackermann, an objective function for the kinematic synthesis of the mechanism has been formulated. The synthesis process of the mechanism is conducted using the analytical method of interpolation in four parameters. A dedicated method has been developed, and kinematic analysis of the mechanism using the synthesized parameters has been performed. The simulation results have demonstrated high accuracy in achieving the desired implementation of the Ackermann condition.

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research indicates that they share both distinctive and common pathways. Moreover, they exhibit intriguing intersections with mechanotransduction, a process that involves cells sensing and responding to mechanical forces. This review article describes the intricate interplay between mechanical forces and CI, shedding light on how these forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs) emerge as sensitive players in both CI and the mechanotransduction process. This article presents methods for identifying these TAFs and profiling the associated changes in chromatin structure, offering valuable insights into CI and mechanotransduction regulation. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

Firefighters Protective Clothing consist of several layers of different properties and functions. The layers create barriers against dangerous outer factor. However, they are also barriers to transport of sweat produced by human organism. It causes that very often sweat in the form of vapor is not transferred effectively from the human organism through the FPC to environment. This leads to sweat condensation on the skin of the FPC user causing his discomfort. In order to ensure as good as possible physiological comfort of firefighter while firefighting and other rescue actions it is necessary to take into consideration the transport of condensed sweat in the multilayer textile set creating the FPC. In the presented work four variants of multilayer textile sets for the FPC have been tested in the aspect of liquid moisture transport. Measurement was performed by means of the Moisture Management Tester (MMT290) – innovative instrument manufactured by the SDL Atlas. Obtained results showed that the transfer of sweat in liquid form occurs only in the inner, next to skin layer of the multilayer sets for the FPC.

this paper focuses on a scientific study of the restoration, rehabilitation and reuse of the great throne hall, the most important hall in al-jawhara palace. it also aims to study the most important factors and forces of damage that affected the great throne hall, natural, biological, and human, and the resulting damage. field tests were performed, laboratory tests to determine fracture stress, liquidity and spandex limits tests, chemical analysis on soil samples and geoelectrical testing of the soil, and the results did not show caves or voids in the ground until a depth of 10.00 m, construc-tion materials were studied and tested using x-ray, (xrd), mechanical tests (tensile, shear, com-pression), and a study of the effect of seismic loads on the walls; the results showed horizontal and vertical cracks; based on the study and analysis of these cracks, it was possible to present modern techniques in restoration and reinforcement methods, and in conclusion, the researcher's recommendations.

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this paper, we show the existing knowledge on the inhibition of this protein in different types of cancer and discuss the importance it could have in the development of new therapies directed against this pathology.

The targeted compounds in this research, resveratrol analogs 1–14 were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. Molecular docking of these compounds was conducted to visualize the ligand-active site complexes' structure and identify the non-covalent interactions responsible for the complex's stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.

Atopic dermatitis (AD) is a chronic inflammatory disorder presenting a dysregulated immune response and derangement of the epidermal barrier lipids. The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signal axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D-epidermal equivalents. We used tofacitinib, a low-molecular-mass JAK inhibitor, to screen for the JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4, and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase, and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitate and caused a depletion of triglycerides. This depletion was associated with altered PC profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very long chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by halted homeostasis of FA metabolism.

Maritime transport has adapted to recent political and economic shifts by addressing stringent pollution reduction requirements, redrawing transport routes for safety, reducing onboard technical incidents, managing data security risks and transitioning to autonomous vessels. The integration of AI-based technologies for fault diagnosis and decision-making, coupled with proper personnel training, has become essential for optimal ship operation, with AI-assisted predictive maintenance emerging as the key strategy to ensure onboard systems function within desired parameters and enhance equipment availability. This study proposes a machine-learning algorithm for evaluating onboard systems performance by analyzing sensor data and mapping it to fault patterns to estimate functional states, validated through tests on a seawater cooling system from an oil tanker, demonstrating operational efficiency and reliability. The immediate advantage is reduced time for fault diagnosis by rapidly assessing the system using operational data, the algorithm enabling real-time monitoring and fault data management to minimize efforts as part of predictive maintenance assisted by machine learning tools.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

As it turns out, both isotope scaling and density limits are phenomena closely linked to fluid closure. The necessity to include ion viscosity arises for both phenomena. Thus, we have added ion viscosity to our model. The experimental isotope scaling has been successfully recovered in our fluid model through parameter scans. Although ion viscosity typically exerts a small effect, the density limit is manifested by increasing the density by approximately tenfold from the typical experimental density. In our case, this increase originates from the density in the Cyclone base case. Notably, these phenomena would not manifest with a gyro-Landau fluid closure. The isotope scaling is nullified by the addition of a gyro-Landau term, while the density limit results from permitting ion viscosity to become comparable to the gyro-Landau term. The mechanism of zonal flows, demonstrated analytically for the Dimits upshift, yields insights into the isotope scaling observed in experiments. In our approach, ion viscosity is introduced in place of the Landau fluid resonances found in some fluid models. This implies that the mechanism of isotope scaling operates at the level of fluid closure in connection with the generation of zonal flows. The strength of zonal flows in our model has been verified, particularly in connection with the successful simulation of the nonlinear Dimits shift. Consequently, a role is played by our approach in the temperature perturbation part of the Reynolds stress.

Cisplatin is a widely used anticancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas increased Bcl-2 expression. Moreover, in cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor interacting protein kinase (RIPK) and mixed lineage kinase domain like (MLKL) were identified. In vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted by co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anticancer adjuvant.

This paper introduces a three-layer system, proposing a comprehensive model of granular mixture transport over a mobile sloped bed in a steady flow. This system, consisting of the bottom, contact and upper zones, provides complete, continuous sediment velocity and concentration vertical profiles. The model considers gravity’s effect on sediment transport in the bottom (dense) layer, a crucial factor often overlooked in previous studies. The induced movement in the mobile sublayer of the dense layer causes an increase in velocity at the upper boundary of this layer, significantly affecting the vertical distributions of velocity and concentration above this layer. We described the interactions between fractions and an intensive sediment mixing and sorting process in the contact layer. The proposed shear variation, with an increase in its maximum value at the bed, adds to the novelty of our approach. The data sets used for the model’s validation cover various conditions, including slopes, grain diameters, densities and grain mobility conditions, from incipient motion to a fully mobilised bed. This extensive validation process instils confidence in the theoretical description and its applicability to real-world scenarios.

The maneuverability of ships is influenced by several factors, including ship design, size, propulsion system, hull shape, and external conditions such as wind, waves, and currents. The size, shape, and arrangement of the hull, rudder, and propeller are decisive for maneuverability. Hydrodynamic forces such as bank effect and squat significantly impact the maneuverability of large ships in narrow channels. With the increasing trend of building ever-larger ships, the demand to evaluate the maneuvering performance of the ship at the design stage has become more critical than ever. Both experimental and computational methods are used to obtain accurate maneuvering characteristics of vessels. In this study, the methods for predicting ship maneuvering characteristics are analyzed using a systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA). This article contributes to a deeper understanding of the hydrodynamic capabilities of ships and identifies possible future challenges in the field of ship hydrodynamics. The findings inform educators and the shipping industry about the importance of predicting the maneuvering performance of ships, with an emphasis on the education and training of seafarers needed to make timely decisions in critical situations.

Land transportation is contributing to global greenhouse gas (GHG) emissions significantly. Switching from gasoline-powered vehicles to electric vehicles (EVs) is the most practical way to decarbonize land transportation. Some regions of the world have seen significant advancements in the adoption of electric vehicles, largely due to government policies through subsidies and other rules and laws that globally made the cost of acquisition and ownership more advantageous for EV owners compared to their internal combustion engine (ICE) counterparts. The success of EV adoption in Norway, China, the United States of America (USA), the European Union (EU), and India has been linked to the favorable government policies. At present, China is the largest EV market in the world, enjoying a better advantage than any other market. It also has the highest manufacturing capacity and the largest number of EVs in operation. Norway has the highest EV penetration rate, with over 90% of newly registered cars, and one of the lowest costs of ownership globally. In this review, we present the current state of EV technology and performance, together with consumer perspectives and barriers, EV regulations in the regions with the highest penetration rates, and the decarbonization of land transportation. China is competing with the USA for leadership in manufacturing and technology, especially in the areas of artificial intelligence (AI) and batteries. In order to achieve the goal of decarbonizing road transportation, we proposed that a number of factors, including government energy policies and regulatory standard development, necessary infrastructure investments and developments, AI incorporation in EVs, innovation in EV and battery technologies, and consumer perspectives, play a crucial role.

Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining cancer cell response to chemotherapy. Whether REV1 inhibition would similarly sensitize cancer cells to radiation treatment is unknown. This study reports a lack of radiosensitization in response to REV1 inhibition by small molecule inhibitors in ionizing radiation-exposed cancer cells. Instead, REV1 inhibition unexpectedly triggers autophagy, which is a known biomarker of radioresistance. Collectively, we report a possible role of REV1 TLS protein in determining cancer treatment outcomes depending upon the type of DNA damage inflicted. Furthermore, we discover REV1 inhibition directly triggers autophagy, an uncharacterized REV1 phenotype, with significant bearing on cancer treatment regimens.

The fast fashion industry has a significant impact on the environment at every stage of the product life cycle. There is a lack of research in the literature on the impact of fast fashion on the environment through logistics and transport. In this area, the greatest environmental impact is caused by air emissions, which is very important from the point of view of climate change. Therefore, this article deals with the analysis of the carbon footprint resulting from the fast fashion logistics process. The identification and assessment of fast fashion companies' sustainability efforts in the area of transport-related emissions and sustainable transformation strategies was conducted using a case study method for selected brands (H&M Group; Inditex, Shein). The study uses secondary data available in non-financial reports from 2023. After analyzing the data and content in non-financial reports on transport-related emissions, sev-eral important conclusions emerge. As a dominant practice, companies emphasize their reliance on external frameworks and standards, in particular the Global Reporting Initiative and the Task Force on Climate-related Financial Disclosures. Companies prioritize reducing emissions from significant factors, such as production processes. The data disclosed in the reports (scope 1, 2, 3) are not clearly formulated, but they can be used to calculate the level of CO2 emission reduction/increase. The ar-ticle contains recommendations for companies to improve their reporting by including additional indicators expressing the efficiency of transport-related emissions.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

We study the electron tunneling (ET) and local Andreev reflection (AR) processes in a quantum dot (QD) coupled to the left and right ferromagnetic leads with noncollinear ferromagnetisms. In particular, we consider that the QD is also side-coupled to a nanowire hosting Majorana bound states (MBSs) at its ends. Our results show that when one mode of the MBSs is coupled simultaneously to both spin-up and spin-down electrons on the QD, the height of the central peak is quite different from that if the MBS is coupled to only one spin component electrons. The ET and AR conductances which are mediated by the dot-MBS hybridization strongly depend on the angle between the left and right magnetic moments in the leads, which result in sign change of the angle-dependent tunnel magnetic resistance. This result is very different from case when the QD is coupled to regular fermonic mode, and can be used for detecting the existence of MBSs, a current challenge in condensed matter physics under extensive investigations.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition with a high mortality rate for which there are no effective therapeutics. The failure of the alveolar-capillary barrier, composed of lung endothelial (EC) and alveolar epithelial (AEC) cells, is a critical factor leading to excessive inflammation and edema characteristics of acute lung injury (ALI). Phosphodiesterases (PDE) are enzymes well-recognized for their roles in regulating endothelial permeability and inflammation. Although PDE inhibitors are used as therapeutics for inflammatory diseases like COPD (chronic obstructive pulmonary disease), their efficacy in treating ARDS has not yet been established. In this study, we investigate the effects of ensifentrine, an FDA-approved novel dual PDE 3/4 inhibitor, on lung endothelial and epithelial dysfunction caused by methicillin-resistant S. aureus (MRSA), a pathogen involved in bacterial ARDS. Human primary lung endothelial cells and alveolar epithelial cell lines (A549 and immortalized AEC) were treated with heat-killed MRSA, and their responses were assessed in the presence or absence of ensifentrine. Ensifentrine given either pre- or post exposure attenuated MRSA-induced increased lung endothelial permeability. VE-cadherin junctions, which serve to stabilize the EC barrier, were disrupted by MRSA; however, ensifentrine effectively prevented this disruption. Pre-treatment with ensifentrine protected against MRSA-induced EC pro-inflammatory signaling by inhibiting the expression of VCAM-1, ICAM-1, and by reducing the IL-6 release. In AEC, MRSA caused upregulation of ICAM-1, activation of NF-kB and production of IL-8, all of which were inhibited by ensifentrine. These results indicate that dual inhibition of phosphodiesterases 3 and 4 by ensifentrine is barrier protective and attenuates MRSA-induced inflammation in both lung endothelial and epithelial cells. The PDE3/4 inhibitor ensifentrine may represent a promising novel strategy for the treatment of ALI.

In this paper we derive a unified perspective for Optimal Transport (OT) theory and Mean Field Control (MFC) theory to analyse the learning process for Neural Networks algorithms in a high-dimensional framework. We consider Mean Field Neural Networks in the context of MFC theory, specifically the mean field formulation of OT theory that allows the development of highly efficient algorithms while providing a powerful tool in the context of explainable Artificial Intelligence.

Anterior-tooth (ANT) contacts induce short latency reflex inhibition of human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint-targeting muscle force into a single bite-point, the pivoting food particle. See-saw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food-crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. Compression/distraction strains of food-crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food-fulcrum send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units, via Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back-tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw-muscle units. The inhibitory feed from ANT temporarily blocks the excitatory potential of masticatory motor efferent neurons to protect the ANT and jaw-joints from inadvertent strains. The inhibitory inputs from ANT alternate with the excitatory inputs from BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food-crushing. The Vmes exists in all jawed vertebrates, and its’ evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCR) override the coexisting bilaterally executed feed for jaw muscles from the central nervous system. Hypothesis: The Vmes-mediated UFCR combine neural inputs from tooth contacts with concomitant feedback from muscle stretch receptors for the control of mammalian food-crushing bite force.

An optical fiber scale sensor based on the detection principle of surface plasmon resonance (SPR) was developed for the rapid, high-sensitivity real-time evaluation of scale precipitation from geothermal fluids. The optical fiber SPR scale sensor was fabricated by depositing a gold thin film on the surface of an optical fiber with an exposed core. The optimal gold film thickness of the sensor was determined to be 30 nm, which achieved a refractive index sensitivity of 2140 nm per refractive index unit. A field test was conducted using geothermal brine from the Obama Binary Geothermal Power Plant in Unzen, Nagasaki Prefecture. A conventional optical fiber scale sensor and the SPR sensor were simultaneously assessed using raw and pH-adjusted brines. For the SPR sensor, a peak shift of 0.27 nm/min was observed at a response time of 1 min, whereas no change in transmittance was observed for the conventional sensor until 180 min. After the experiments, scanning electron microscopy–energy-dispersive spectroscopy analysis was conducted on the sensors, and findings showed that the deposition of Mg–SiO2 scale did not significantly differ between the two sensors. The developed SPR sensor achieved faster scale precipitation detection (tens of minutes to hours) than the conventional sensor.

Expansins are cell wall (CW) proteins that mediate the CW loosening and regulate salt tolerance in a positive or negative way. The transcription of Populus trichocarpa expansin A6 (PtEXPA6) was downregulated upon prolonged duration of salt stress (48 h) after a transient increase induced by NaCl (100 mM). The role of PtEXPA6 in salt tolerance was determined by transferring the PtEXPA6 gene into the hybrid species Populus alba × P. tremula var. glandulosa clone 84K (84K) and Populus tremula × P. alba INRA '717-1B4' (717-1B4). The PtEXPA6-transgenic poplars of 84K and 717-1B4 showed a greater reduction in photosynthesis, stem height and diameter growth under salt stress and a reduced capacity for ROS scavenging by antioxidant enzymes, which is associated with excessive Na+ accumulation in roots and shoots. NMT flux recordings showed that the radial translocation of Na+ salt into the root xylem and real-time Na+ translocation from roots to leaves were greater in PtEXPA6-transgenic poplars than in wild-type poplars. Analysis of comparative contractility and comparative extensibility of intact root tips indicated that PtEXPA6 increased the CW loosening in the transgenic poplars of 84K and 717-1B4. Noteworthy, the PtEXPA6-promoted CW loosening was shown to facilitate radial and longitudinal transport of Na+ in transgenic poplars. We conclude that overexpression of PtEXPA6 leads to CW loosening that facilitates radial translocation of Na+ into the root xylem and subsequent Na+ translocation from roots to leaves, resulting in excessive Na+ accumulation and consequently reduced salt tolerance in transgenic poplars.

Это исследование сосредоточено на разработке системы искусственного зрения для гибкого дельта-робота-манипулятора и ее интеграции с межмашинной связью для оптимизации взаимодействия устройств в реальном времени. Эта интеграция направлена ​​на увеличение скорости роботизированной системы и улучшение ее общей производительности. Предлагаемое сочетание системы искусственного зрения с межмашинной связью позволяет обнаруживать и распознавать цели с высокой точностью в режиме реального времени в ограниченном пространстве, предназначенном для позиционирования, дальнейшей локализации и выполнения производственных процессов, таких как сборка или сортировка деталей. . В данном исследовании RGB-изображения используются в качестве входных данных для алгоритма MASK-R-CNN, а результаты обрабатываются в соответствии с особенностями прототипа дельта-манипулятора робота. Данные, полученные от MASK-R-CNN, адаптированы для использования в системе управления дельта-роботом с учетом ее уникальных характеристик и требований к позиционированию. Технология M2M позволяет манипулятору робота быстро реагировать на изменения, например, на перемещение объектов или изменение их положения, что имеет решающее значение для задач сортировки и упаковки. Система была протестирована в условиях, близких к реальным, чтобы оценить ее производительность и надежность.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

Energy from biogas is one of the most promising renewable energy sources. Significant, for technical, economic, and environmental reasons, is the construction of agricultural microgas plants next to households specialising in cattle rearing. The availability of free substrate makes it possible not only to produce one's electricity and heat but also to produce a more environmentally and human-friendly manure. The operation of biogas plants is, unfortunately, associated with technical problems. This paper presents the results of a study of the quality of electricity generated in an agricultural biogas plant built at a farm specialising in dairy cows, where the owner reported a problem with the voltage in the power supply network. Therefore, selected power quality parameters occurring at the connection point of the biogas plant were analysed in detail. As the authors' research showed, in the case in question, the agricultural biogas plant was connected via a cable with too small a conductor cross-section, which resulted in significant voltage exceedances, making it impossible to switch on the second of the biogas plant's generators. Replacement of the feed-in cable has enabled both generators to run, but significant fluctuations in the feed-in voltage values were still noticeable. Analysis of the subsequent measurements revealed the need for changes in the design of the digester itself. The proposal for change is to replace the two current digester mixers (each rated at 9 kW) with more mixers of lower power. The new mixers would operate in an alternating system, where only one would always be activated.

Candida albicans, a prominent constituent of the human microbiota, poses a significant health threat due to its opportunistic pathogenicity and adept biofilm-forming capabilities. This research delves into the antifungal attributes and biofilm inhibition potential of Tea Tree Oil (Melaleuca alternifolia) cultivated in Vietnam. Renowned for its bioactive compounds, including terpinen-4-ol, 1,8-cineole, and terpinolene, the essential oil of Melaleuca alternifolia, commonly referred to as tea tree oil (TTO), is scrutinized for its impact on Candida albicans. The study meticulously determines the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of TTO against Candida albicans in both planktonic and biofilm states. Additionally, it assesses the biofilm-forming capacity of Candida albicans and establishes the Minimum Biofilm Inhibitory Concentration (MBIC) and Minimum Biofilm Eradication Concentration (MBEC) of TTO. Employing a liquid culture dilution method within a defined concentration range of 0.1 μL/mL to 10 μL/mL, the experimental approach adheres to established protocols. The outcomes reveal a noteworthy MIC and MIC₈₀ of 0.1 μL/mL and 2 μL/mL, respectively, and an MFC of 10 μL/mL for TTO against Candida albicans. Furthermore, TTO exhibits an MBIC of 2 μL/mL, showcasing its efficacy in inhibiting biofilm formation. However, the MBEC of TTO remains uncertain, possibly due to insufficient concentration tested, which may not effectively disrupt over 50% of the pre-formed biofilm mass within 24 hours. These results underscore the promising potential of TTO as a potent antifungal agent and biofilm inhibitor against Candida albicans, offering valuable insights for the innovation of novel therapeutic strategies in the realm of fungal infections.

Structural health monitoring has been studied by a number of researchers as well as various industries to keep up with the increasing demand for preventive maintenance routines. This work presents a novel method for reconstruct prompt, informed strain/stress responses at the hot spots of the structures based on strain measurements at remote locations. The structural responses measured from usage monitoring system at available locations are decomposed into modal responses using empirical mode decomposition. Transformation equations based on finite element modeling are derived to extrapolate the modal responses from the measured locations to critical locations where direct sensor measurements are not available. Then, two numerical examples (a two-span beam and a 19956-degree of freedom simplified airfoil) are used to demonstrate the overall reconstruction method. Finally, the present work investigates the effectiveness and accuracy of the method through a set of experiments conducted on an aluminium alloy cantilever beam commonly used in air vehicle and spacecraft. The experiments collect the vibration strain signals of the beam via optical fiber sensors. Reconstruction results are compared with theoretical solutions and a detailed error analysis is also provided.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

The rehabilitation of the road embankments alongside the irrigation canal, which is constructed on a Bangkok soft clay foundation, has resulted from land use growth for several decades. As a result, the embankment is always confronted with the problem of instability. Numerous articles have demonstrated that rapid drawdown of the water level in the canal could be one of the most significant reasons, whereas vehicle cyclic loading may potentially contribute to some effect of the embankment failure. To explore and assess the effects of the influence factors, the finite element method (FEM) and conventional and dynamic triaxial approaches were employed. The study also investigated the consequences of varying thicknesses of soft clay and cyclic loading with different magnitudes and frequencies. Consequently, cyclic loading can lead to an augmentation in strain distribution and excess pore water pressure. Likewise, more significant deformation and excess pore water pressure were induced by a lower frequency and deeper thickness of soft clay compared to a higher frequency and thinner thickness. In brief, vehicle repetitive loading is one of the primary factors contributing to embankment failure, with the threshold stress being approximately three-fourths of the undrained shear strength. In contrast, threshold strain is approximately one to two-fold of the monotonic strain condition.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

Integrating advanced air mobility (AAM) into the logistics of high-value electronic commodities can enhance efficiency and promote sustainability. The objective of this study is to optimize the logistics network for high-value electronics by integrating AAM solutions, specifically using heavy-lift cargo drones for middle-mile transport and using the mostly rural and small urban U.S. state of North Dakota as a case study. The analysis utilized geographic information system (GIS) and spatial optimization models to strategically assign underutilized airports as multimodal freight hubs to facilitate the shift from long-haul trucks to middle-mile air transport. Key findings demonstrate that electronics, because of their high value-to-weight ratio, are ideally suited for air transport. Comparative analysis shows that transport by drones can reduce the average cost per ton by up to 60% compared to traditional trucking. Optimization results indicate that a small number of strategically placed logistical hubs can reduce average travel distances by more than 13% for last-mile deliveries. Cost analyses demonstrate the viability of drones for middle-mile transport, especially on lower-volume rural routes, highlighting their efficiency and flexibility. The study emphasizes the importance of utilizing existing infrastructure to optimize the logistics network. By replacing truck traffic with drones, AAM can mitigate road congestion, reduce emissions, and extend infrastructure lifespan. These insights have critical implications for supply chain managers, shippers, urban planners, and policymakers, providing a decision support system and a roadmap for integrating AAM into logistics strategies.

Batch and transport experiments were used to investigate the remediation of a loamy sand soil contaminated with Cr(VI) using zero valent iron nanoparticles (nZVI) stabilized by the carboxy methyl cellulose (CMC-nZVI). The effect of pH, ionic strength (IS), and flow rate on the removal efficiency of Cr(VI) were investigated under equilibrium (uniform transport) and non-equilibrium (Two-site sorption) transport using the Hydrus-1D model. The overall removal efficiency ranged from 70 to over 90% based on the chemical characteristics of the CMC-nZVI suspension and the transport conditions. The concentration and pH of the CMC-nZVI suspension had the most significant effect on the removal efficiency and transport of Cr(VI) in the soil. The average removal efficiency of Cr(VI) was increased from 24.1 to 75.5% when the concentration of CMC-nZVI nanoparticles was increased from 10 to 250 mg L-1, mainly because of the increased total surface area at larger particle concentration. Batch experiments showed that removal efficiency of Cr(VI) was much larger under acidic conditions. The average removal efficiency of Cr(VI) reached 90.1 and 60.5 % at pH 5 and 7, respectively. The Two-site sorption model described quite well (r2 = 0.96-0.98) the transport of Cr(VI) in soil as compared to the uniform transport model (r2 = 0.81-0.98). The average retardation of Cr(VI) was 3.51 and 1.61 at pH 5 and 7, respectively, indicating earlier arrival for the breakthrough curves and shorter time to reach maximum relative concentration at lower pH. The Hydrus-1D model has proven to be an efficient tool for assessing the removal of Cr(VI) pollutants, offering innovative, cost-effective, and environmentally friendly remediation methodologies.

We report the electrical characterization and the field emission properties of CVD-grown MoS₂ bilayers deposited on SiO₂/Si substrate. Current-voltage characteristics are measured in the back-gate transistor configuration, with Ti contacts patterned by electron beam lithography. We confirm the n-type character of as-grown MoS₂ and we report normally-on field effect transistors. Local characterization of field emission is performed inside a scanning electron microscope chamber with piezo-controlled tungsten tips working as the anode and the cathode. We demonstrate that an electric field of ~200 V/μm is able to extract current from the flat part of MoS₂ bilayers, which therefore can be conveniently exploited for field emission applications even in low field-enhancement configurations. We show that a Fowler-Nordheim model, modified to account for electron confinement in 2D materials, fully describes the emission process.

Histone deacetylase 6 (HDAC6) regulates many physiological processes that are involved in cancer development and progression such as cell proliferation, apoptosis, motility, epithelial to mesenchymal transition, by deacetylation of multiple substrates and association with interacting proteins. Due to its the ability to remove misfolded proteins, induce autophagy, and regulate unfolded protein response, HDAC6 plays a protective role in responses to stress and enables tumor cells survival. HDAC6 is often overexpressed in tumors, including colorectal cancer (CRC) and is correlated with poor disease prognosis. However, it has been shown in animal models that HDAC6 is not essential for normal mammalian development. Therefore, it represents a good target for the development of novel cancer therapeutics. Selective inhibition of HDAC6 impairs growth and progression of many tumors without inducing major adverse events in experimental animals. In CRC, HDAC6 inhibitors have shown potential to reduce tumor progression and to enhance the therapeutic effect of other drugs. As HDAC6 is involved in regulation of immune responses, HDAC6 inhibitors have shown potential to improve antitumor immunity by increasing immunogenicity of tumor cells, augmenting immune cell activity and alleviating immunosuppression in tumor microenvironment. Therefore, HDAC6 inhibitors may represent promising candidates to improve the effect and to overcome resistance to immunotherapy.

B-cell lymphoid malignancies is a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling. To bypass the C481S mutation, non-covalent BTK inhibitors, such as pirtobrutinib, were developed and are active against both wild-type and the C481S mutation. In this review, we discuss the molecular and genetic mechanisms which contribute to acquisition of resistance to covalent and non-covalent BTK inhibitors. In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTK inhibitors and the development of new therapeutic strategies highlight the ongoing advances, that are being made towards the pursue of cure of B-cell lymphoid malignancies.

The architecture, Engineering, and Construction (AEC) industry is dealing with serious challenges on a global scale, i.e., project delays, budget overruns, and insufficient stakeholder collaboration. In this context, Value Engineering (VE) and Building Information Modeling (BIM) have been used recently to address these challenges and cope with large-scale and complex construction projects. An extensive body of literature highlights significant advantages of integrated VE within BIM technology. Despite this, it is full practical potential has not yet been realized. For this reason, this paper aims to investigate the integration of Value Engineering (VE) and Building Information Modeling (BIM) within a Common Data Environment (CDE) for the Architecture, Engineering, and Construction (AEC) industry. In doing this research, a comprehensive framework was developed and systematically implemented into practice through the use of four interconnected modules: (M. 1); Creating CDE, (M. 2); Design BIM Model Development, (M. 3); Value Analysis / Engineering Model, and (M. 4); Value Engineering Study. Introducing a new term the ""VEIDEA"" databank based on the OmniClass classification system provides a structured database utilized to store, manage, and accumulate VE ideas. Moreover, the study incorporates the Analytical Hierarchy Process (AHP) to automate the evaluation phase. Such a framework seeks to assist designers and VE team members make informed decisions when choosing appropriate design alternatives. Lastly, a case study method was adopted to examine the proposed framework for an office building. Quantitative data showed a significant link between cost savings and VR integration with BIM technology. For instance, cost of the RC slabs dropped by 20%, while flooring materials cost dropped by a 39%. Empirically, evidence from the case study supports literature regarding t the potential for significant enhancements in both cost-effectiveness and overall project performance through this innovative integration. In the context of knowledge contribution, this study provides an innovative way to assist designers and VE team members in making well-informed decisions when choosing appropriate design alternatives.

Today, transit control systems go beyond simple controllers located at the intersections of our streets, involving large companies in the field, which with the implementation and use of sophisticated equipment encompass endless new and advanced technologies that manage to give control to the massive automotive park, thus ensuring fluidity and road safety. Many of these systems are used in the big world capitals, which is why the model used in Santiago, Chile is a system applied and brought directly by the SIEMENS Company of England (specifically the system used in the City of London). It is capable of transmitting the different control signals in a similar and digital way from the different interconnected devices in and out of the road infrastructure.

The acoustic startle response (ASR) is an explosive motor response leaded by a sudden and intense acoustic stimulus. ASR has several clinically relevant forms of plasticity, including habituation and sensorimotor gating. Although ASR and its plasticity have been intensively studied in different animal models, including zebrafish (Danio rerio) larvae, information in adult zebrafish is still very scarce. In this manuscript we present Zebra_K, a new automated high-content kinematic analysis platform for assessing ASR, its habituation and prepulse inhibition (PPI), a quantitative measure of sensorimotor gating, in adult zebrafish. The analysis of the kinematic parameters in 1,875 ASR in adult zebrafish has shown a single response wave consistent with the short-latency C-bend described in zebrafish larvae. Moreover, protocols have been designed and validated in Zebra_K for the analysis of sensitivity, habituation and PPI of this response. Then, this platform has been used to determine the effect of pharmacological and physiological modulators of ASR plasticity. As described in other animal models, the NMDA-receptor antagonist ketamine increased the responsiveness to the acoustic stimuli, decreasing habituation and leading to complete abolition of PPI. Moreover, the effect of the gender on zebrafish ASR plasticity has been analyzed for the first time. Females exhibited higher responsiveness and a lower habituation and PPI than males, a result consistent with the gender effect described in other animal models and in humans. These results enhance the interest of using adult zebrafish to assess the potential effect of chemicals or genetic manipulations on ASR plasticity.

Different materials prepared by appropriate synthesis methods and applying different post syn-thesis processes could be used as hole transport layer in perovskite solar cells. In the present work annealing was employed to enhance physical properties of copper oxide (CuO) thin films fabricated via spin coating technique and the effects of annealing on their optical, morphological, electrical and structural properties were investigated. The XRD findings revealed the polycrystalline structure with large crystallite size. Optical spectra showed larger transmission beyond the visible region, reduced absorption, and a decrease in bandgap energy from 1.93 eV to 1.81 eV. The Ag phonon modes at 299.22 and 304 cm-1 shown by the Raman shift confirmed the development of the CuO pure phase. FTIR spectra showed the Cu-O stretching band at 759, 764 and 446 cm−1. SEM revealed the agglomeration of nano crystallites with large grains on the surface. The carrier type conductivity of annealed CuO thin films was determined via two-point hot probe technique. Low resistivity values were determined via four-point probe method. These findings indicate that CuO thin films may be successfully used as a companion with an n-type layer in p-n junction solar cells, and a hole transport layer in perovskite solar cells.

Global dust events have become more frequent due to climate change and increased human activity, significantly impacting air quality and human health. Previous studies have often focused on simulating cross-regional dust transport based on atmospheric parameters; however, comprehensive monitoring of dust events remains challenging. Therefore, this study utilized Fengyun-4A (FY-4A) satellite Advanced Geostationary Radiation Imager (AGRI) imagery, Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) lidar, and other auxiliary data to conduct three-dimensional spatiotemporal monitoring and cross-regional transport analysis of two typical dust events in the Beijing–Tianjin–Hebei (BTH) region of China using four dust intensity indices (Icsd, Dust Detection Index (DDI), Dust value (DV), and Dust Strength Index (DSI)) and the HYSPLIT model. We found that among the four indices, DDI was the most suitable for studying dust in the BTH region, with a detection accuracy (POCD) of > 88% at all times and reaching a maximum of 96.14%. Both the 2021 and 2023 dust events originated from large-scale deforestation in southern Mongolia and the border area of Inner Mongolia, with dust plumes distributed between 2 and 12 km being transported across regions to the BTH area. Further, when dust aerosols are primarily concentrated below 4 km and PM10 concentrations consistently exceed 600 µg/m³, large dust storms are more likely to occur in the BTH region. The findings of this study provide valuable insights into the sources, transport pathways, and environmental impacts of dust aerosols.

Efficient fixed crane position analysis is critical in precast buildings construction to maximize lifting efficiency for precast elements. The primary objective is to minimize the travel distances of fixed cranes, thereby enhancing operational efficiency and cost control. This involves strategically reducing the distances between the transport truck parking, where elements are stored, the fixed crane, and the construction installation point. Despite its significance, existing studies often overlook the dynamic movement efficiency of transport trucks, particularly when dealing with multiple transport trucks and various models of fixed cranes, rendering the opti-mization of this scenario a challenging NP-hard problem susceptible to combinatorial explosion. This study presents a novel mathematical model leveraging the Genetic Algorithm (GA). The model aims to solve optimal model and position of fixed cranes, along with identifying ideal positions for transport truck parking. The study's methodology is validated and demonstrated through a project case study. Comparative analyses between the proposed model and the original planning underscore a noteworthy 6% reduction in both duration and costs when lifting elements directly from transport trucks, as opposed to establishing an on-site stock yard. Furthermore, the developed GA exhibits a substantial improvement in final solutions, achieving a remarkable 30% reduction in both operational duration and costs. This research contributes valuable insights into fixed crane position analysis of precast building construction, providing foundation for enhanced operational efficiency and cost-effectiveness in the industry.

The corrosion inhibition behavior of cetyl pyridinium chloride (CPC) on mild steel (MS) in 0.5 M H₂SO₄ solution was examined using the weight loss method and potentiodynamic polarization method. The experimented MS surface was characterized by Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), and Atomic Force Microscopy (AFM). Corrosion rate and corrosion efficiency was calsulated via weight loss and potentiodynamic polarization methods where the corrosion rate in 0.5 M H₂SO₄ , 0.000192 M, and 0.0077 M of CPC solution was 12.09×10^-3, 8.23×10^-3, 6.63×10^-5 (mm/Year), respectively and the inhibition efficiency of 94.42% and 98.54%. FESEM studies demonstrated the corrosion attack on MS surface. Also, the EDX showed the presence of nitrogen of CPC. Thus, CPC acts as an important corrosion inhibitor.

BUB1 is overexpressed in most human solid cancers including breast cancer. Higher BUB1 levels are associated with poor prognosis especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC. Our previous studies demonstrated that BUB1 kinase inhibitor (BAY1816032) reduced tumor cell proliferation and significantly enhanced radiotherapy efficacy in TNBC. In this study, we evaluated the effectiveness of BAY1816032 with a PARP inhibitor (olaparib), platinum agent (cisplatin), and microtubule poison (paclitaxel) alone or in combination with radiotherapy using cytotoxicity and clonogenic survival assays. BUB1 inhibitor sensitized BRCA1/2 wild-type SUM159 and MDA-MB-231 cells to olaparib, cisplatin and paclitaxel synergistically (combination index; CI

Background: Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here we report studies that address this question. Methods: 14 weeks on high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Results: Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and prevent cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Conclusions: Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.

This publication aims to create 4K UHD video sequences with a specific focus on smart cities and transport. The created database will be accessible to all experts in the field and can be further used for research purposes. All reference video sequences will be transcoded into different quality settings. The resolution, compression standard, and bitrate will be changed. The work will aim to find out the best combination of video parameters from the measured values. Thanks to the overall evaluation, we will ensure for each single video sequence the quality with the best experience for the providers that will offer the service. The database will also be available with its objective and subjective ratings, with dynamicity information characterized by spatial and temporal information. After, It will be possible to compare the results of the subjective evaluation of a selected sample of our respondents with the work of other researchers who can evaluate with a different sample of evaluators.

We study the deterministic dynamics of N point particles moving at constant speed in a 2D table made of two polygonal urns connected by an active rectangular channel, which applies a feedback-control on the particles, inverting the horizontal component of their velocities, when their number in the channel exceeds a fixed threshold. Such a bounce--back mechanism is non-dissipative: it preserves volumes in phase space. An additional passive channel closes the billiard table forming a circuit in which a stationary current may flow. Under specific constraints on the geometry and on the initial conditions, the large N limit allows nonequilibrium phase transitions between homogeneous and inhomogeneous phases. The role of ergodicity in making a probabilistic theory applicable is discussed both for rational and irrational urns. The theoretical predictions are compared with the numerical simulation results. Connections with the dynamics of feedback-controlled biological systems are highlighted.

Following a recent proof of Shannon's entropy power inequality (EPI), a comprehensive framework for deriving various EPIs for the Rényi entropy is presented that uses transport arguments from normal densities and a change of variable by rotation. Simple arguments are given to recover the previously known Rényi EPIs and derive new ones, by unifying a multiplicative form with constant c and a modification with exponent α of previous works. In particular, for log-concave densities, we obtain a simple transportation proof of a sharp varentropy bound.

The insulin-regulated aminopeptidase (IRAP; oxytocinase) is part of the M1 aminopeptidase family and is highly expressed in many tissues, including the neocortex and hippocampus of the brain. IRAP is involved in various physiological functions and has been identified as a receptor for the endogenous hexapeptide Angiotensin IV (Ang IV). Binding of Ang IV inhibits the enzymatic activity of IRAP and has proven to enhance learning and memory in animal models. The macrocyclic compound 9 (C9) is a potent synthetic IRAP inhibitor developed from the previously reported inhibitor HA08. In this study, we have examined compound C9 and its effects on cognitive markers drebrin, microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP) in primary hippocampal and cortical cultures. Cells from Sprague Dawley rats were cultured for 14 days before treatment with C9 for 4 consecutive days. The cells were analysed for protein expression of drebrin, MAP2, GFAP, glucose transporter type 4 (GLUT4), vesicular glutamate transporter 1 (vGluT1), and synapsin I using immunocytochemistry. The gene expression of related proteins was determined using qPCR, and viability assays were performed to evaluate toxicity. The results showed that protein expression of drebrin and MAP2 was increased, and the corresponding mRNA levels were decreased, after treatment with C9 in the hippocampal cultures. The ratio of MAP2 positive neurons and GFAP positive astrocytes was altered in both hippocampal and cortical cultures, and there were no toxic effects observed. In conclusion, IRAP inhibitor compound C9 enhance the expression of pro-cognitive markers drebrin and MAP2 which further confirms IRAP as a relevant pharmaceutical target and C9 as a promising candidate for further investigation.

Transportation systems through the ages have seen drastic evolutions in terms of transportation methods, speed of transport, infrastructure, technology, connectivity, influence on the environment, and accessibility. The massive transformation seen in the transportation sector has been fueled by the industrial revolutions which have continued expansion and progress into the fourth industrial revolution. However, the methodologies of data collection and processing used by the many drivers of this progress differ. The significance of standardized data and its mode of collection cannot be overstated as it has a major impact on the process outcomes. In order to achieve a better understanding of the impact of this, this study methodically reviewed the literature on the subject of the data collection and processing mechanism of 4IR technologies in the context of the transport industry with an emphasis on the areas of accomplishment of several studies and drawing attention to their limitations. Although the industry has advanced significantly as a result of the adoption and application of various research studies in this field, considerable focus needs to be placed in the areas of standardized data collection and computational approaches, which will ultimately assist in achieving various benefits in the transportation industry.

In the dynamic interplay between people and their physical environments, the Global South stands as a mosaic undergoing a multitude of transformative influences in architecture and urbanism where examining social sustainability becomes imperative. While prevailing attention remains on environmental and economic sustainability, this study addresses a persistent gap in the urban literature by focusing on the dynamic and manifold nature of social sustainability. Positioning itself within the context of sustainable development, the study links the pursuit of social aspects of sustainability with selected unique urban contexts from the Global South. Five cases that include Alexandria (Egypt), Tripoli (Libya), Basra (Iraq), Lilongwe (Malawi), and Accra (Ghana) are discussed through multi-layered investigations that involve attitude surveys, interviews, focus groups, participatory systematic observations, and behavioral mapping, engaging directly with inhabitants and stakeholders. Uncovering people-place narratives in the identified contexts, the cases are developed into five knowledge typologies that serve as practical tools for planning and design decision-making, policy formulation, and academic discourse. Discussions are conceived to demonstrate the transformative role people-place narratives play in fostering a more sustainable and equitable urban future. Conclusions are drawn to offer practical insights for stakeholders involved in various capacities in shaping the urban landscape of the Global South.

Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

Streptococcus pneumoniae causes invasive infections such as otitis media, pneumonia and meningitis. It produces pneumolysin (Ply) toxin, which forms a pore to host cell membrane and has multiple functions in S. pneumoniae pathogenesis. The Ply C-terminal domain 4 mediates binding to membrane cholesterol and induces the formation of pores composed of up to 40 Ply monomers. Ply has a key role in the establishment of nasal colonization, pneumococcal transmission from host to host and pathogenicity. Altogether, 27 hydrolyzable tannins were tested for Ply inhibition in hemolysis assay and tannin-protein precipitation assay. Pentagalloylglucose (PGG) and gemin A showed nanomolar inhibitory activity. Ply oligomerization on the erythrocyte surface was inhibited with PGG. PGG also inhibited Ply cytotoxicity to A549 human lung epithelial cells. Molecular modelling of Ply interaction with PGG suggested that it binds to the pocket formed by domains 2, 3 and 4. In this study, we reveal the structural features of hydrolyzable tannins that are required for interaction with Ply. Monomeric hydrolysable tannins containing a sufficient number of polyvalent and flexible galloyl groups have highest inhibitory power to Ply cytotoxicity, and are followed by oligomers. Of the oligomers, macrocyclic and C-glycosidic structures were weaker in their inhibition than the glucopyranose-based oligomers. Accordingly, PGG-type monomers and certain oligomers might have therapeutic value in the targeting of S. pneumoniae infections.

For many years marine algae has been subject of numerous researches and as a source of natural products with antiviral activity, such as terpenes, alkaloids and sulphated polysaccharides. However, the anti-Zika virus (ZIKV) potential of algae has not been studied. In this study we evaluated extracts seven species of the three major classes of seaweeds (Phaeophyceae, Chlorophyceae and Rhodophyceae) against ZIKV. All seaweeds tested are native of the Brazilian coast, except for Kappaphycus alvarezii that can be cultivated. ZIKV a mosquito-borne flavivirus, has become a public health problem. In recent years there has been an increase in the number of cases and a strong association between ZIKV outbreak and the spread of cases of Guillain-Barré Syndrome and microcephaly. All seaweed extracts tested in this work inhibits ZIKV replication in a dose-dependent manner. Caulerpa racemosa, Kappaphycus alvarezii and Osmundaria obtusiloba extracts were able to inhibit viral replication at low concentrations with EC₅₀ values ranging from 1.38 to 1.98 µg/mL. We observed that O. obtusiloba presented a significant virucidal effect. Our results suggest that extracts of C. racemosa, K. alvarezii and O. obtusiloba presented very promising results, being excellent candidates for further studies, demonstrating that marine algae are an interesting source for the development of novel anti-ZIKV agents.

In the smart city, information and communications technologies (ICTs) are proposed as solutions to urban challenges, including sustainability concerns. While sustainability commonly refers to economic and environmental dimensions, the concept also contains a social component. Our study asked how smartphone applications (apps) address social sustainability challenges in urban transport, if at all. We focused on transport disadvantages experienced due to low income, physical disability, and language barriers. A review of 60 apps showed that transport apps respond to these equity and inclusion issues in two ways: (a) by employing universal design in general-use apps; including cost-conscious features; and providing language options (b) by specifically developing smartphone apps for persons with disabilities. The article discusses the study by positioning it in the literature of smart cities as well as socially sustainable transport.

We have investigated the influence of the relative proportions of glass formers in a series of lithium alumino-borosilicate glasses with respect to electrical conductivity () and glass transition temperature (Tg) as functions of glass structure, as determined by Raman spectroscopy. The ternary lithium alumino-borate glass exhibits the highest  and lowest Tg among all the compositions of the glass series, 30Li2O•3Al2O3• (67-x) B2O3•xSiO2. However, as B2O3 is replaced by SiO2, a shallow minimum in  as well as a shallow maximum in Tg are observed near x = 27, where the Raman spectra indicate isolated diborate/tetraborate/orthoborate groups are being progressively replaced by danburite/reedmergnerite-like borosilicate network units. Overall, as the glasses become silica-rich,  is minimized, while Tg is maximized. In general, these findings show correlations among Tg, (sensitive to network polymerization),  (proportional to ionic mobility), and the different borate and silicate glass structural units as determined by Raman spectroscopy. X-ray diffraction analyses demonstrate the absence of appreciable crystallinity in the glasses investigated. However, scanning electron microscopy (SEM) images of HF-etched samples showed that glasses, and especially the borate-rich compositions comprise two distinct glassy phases. The isolated phase is 25-100 nm in diameter, dispersed evenly in a glassy matrix.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

BRAF is one of the most frequently mutated oncogenes, with an overall frequency of about 50%. Targeting BRAF and its effector mitogen-activated protein kinase kinase 1/2 (MEK1/2) is now a key therapeutic strategy for BRAF-mutant tumors, and therapies based on dual BRAF/MEK inhibition showed significant efficacy in a broad spectrum of BRAF tumors. Nonetheless, BRAF/MEK inhibition therapy is not always effective for BRAF tumor suppression, and significant challenges remain to improve its clinical outcomes. First, certain BRAF tumors have an intrinsic ability to rapidly adapt to the presence of BRAF and MEK1/2 inhibitors by bypassing drug effects via rewired signaling, metabolic, and regulatory networks. Second, almost all tumors initially responsive to BRAF and MEK1/2 inhibitors eventually acquire therapy resistance via an additional genetic or epigenetic alteration(s). Overcoming these challenges requires identifying the molecular mechanism underlying tumor cell resistance to BRAF and MEK inhibitors and analyzing their specificity in different BRAF tumors. This review aims to update this information.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anticancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50kDa), medium (MMW, 50-100kDa) and high (HMW, >100kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had highest the levels of sugars, acids and sulphation among molecular weight fractions. There was a dose dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in sub G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress induced apoptosis-like cell death for F. vesiculosus fucoidan but features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Flavonoids are a biochemically diverse group of specialized metabolites in plants that are derived from phenylalanine. While the biosynthesis of the flavonoid aglycone is highly conserved across species and well characterized, numerous species-specific decoration steps and their relevance remained largely unexplored. The flavonoid biosynthesis takes place at the cytosolic site of the endoplasmatic reticulum (ER), but accumulation of various flavonoids was observed in the central vacuole. A universal explanation for the subcellular transport of flavonoids has eluded researchers for decades. Current knowledge suggests that a glutathione S-transferase-like protein (ligandin) protects anthocyanins and potentially proanthocyanidin precursors during the transport to the central vacuole. ABCC transporters and to a lower extend MATE transporters sequester anthocyanins into the vacuole. Glycosides of specific proanthocyanidin precursors are sequestered through MATE transporters. A P-ATPase in the tonoplast and potentially other proteins generate the proton gradient that is required for the MATE-mediated antiport. Vesicle-mediated transport of flavonoids from the ER to the vacuole is considered as an alternative or additional route.

The link between ICTs, freight transport, and CO₂ emissions has not received much explicit examination by researchers, despite freight transportation being an egregious contributor to environmental degradation. This paper investigates how ICTs can affect environmental quality when interacting with freight transport activities in 43 countries over the period 2002-2014, using carbon emissions as a proxy for environmental damages. ICTs are measured in terms of internet, telephone, and mobile phone technologies. Using GMM methodology, the results show that ICTs contribute to dampening environmental degradation when interacting with freight transport activities. Specifically, a 10% increase in the interaction between ICTs and freight transportation will decrease carbon emissions by between 1.27% and 3.02%. The results further suggest that fixed and smartphone technologies are the main contributors to reducing emissions when adopted in some specific transport sectors (i.e. road, rail, and inland), while the internet is the most efficient technology when interacting with air transport activity. In addition, the interaction between ICTs and multimodality accelerates environmental quality. The policy implications of these findings are discussed.

Microbe-plant interactions are linked with the core microbiota, and both the plant and the microbial partners depend on one other to thrive in nature. However, why and how the below-ground core microbiota become established aboveground is poorly understood. We tracked the movement of a probiotic Streptomyces endophyte throughout a managed strawberry ecosystem. Probiotics in the rhizosphere and anthosphere were genetically identical, yet these niches were segregated in space and time. The probiotic in the rhizosphere moved upward via the vascular bundle, relocated to aboveground plant parts, and protected against Botrytis cinerea. It also moved from flowers to roots, and among flowers via pollinators that were protected against pollinator pathogens. Our results reveal a solid evidence in tripartite interaction with Streptomyces exploiting plant and pollinator partners.

We report the electronic, magnetic and transport properties of a prototypical antiferromagnetic (AFM) spintronic device. We chose Cr as the active layer because it is the only room-temperature AFM elemental metal. We sandwiched Cr between two non-magnetic metals (Pt or Au) with large spin-orbit coupling. We also inserted a buffer layer of insulating MgO to mimic the structure and finite resistivity of a real device. We found that, while spin-orbit has a negligible effect on the current flowing through the device, the MgO layer plays a crucial role. Its effect is to decouple the Cr magnetic moment from Pt (or Au) and to develop an overall spin magnetization. We have also calculated the spin-polarized ballistic conductance of the device within the Büttiker-Landauer framework, and we have found that for small applied bias our Pt/Cr/MgO/Pt device presents a spin polarization of the current amounting to ~25%.

With the realization of the Grand Canal's full water supply and the strong pursuit of green and low-carbon transportation in contemporary society, the value of the Grand Canal's water transport has been further affirmed, and its coordinated development with other transportation modes has become inevitable and important. This paper analyzes and combs through the characteristics, development status and existing problems of Grand Canal water transport and other transport modes in depth, and takes Jiangsu as an example. A collaboration model of Grand Canal water transport and other transport modes was built and their collaboration degree has been calculated. It is believed that the coordinated development of Grand Canal water transport and other transport modes can be greatly promoted via four aspects: optimizing the construction and governance of Grand Canal water transport, building an integrated management platform of transport modes, improving the integrated transport network structure, and promoting the deep integration of integrated shipping and tourism.

Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatment options for psoriasis, phosphodiesterase-4 (PDE4) inhibi-tors are emerging with expanding options. PDE4 inhibitors play a pivotal role in the inflamma-tory cascade by degrading cyclic adenosine monophosphate (cAMP), contributing to pro-inflammatory mediator production. Apremilast, an oral PDE4 inhibitor, is an approved class for psoriasis. While effective, its adverse effects can limit its utility. Roflumilast, a topical PDE4 inhibitor, was recently also approved for psoriasis and shows promise in clinical trials. Crisaborole, approved for atopic dermatitis, has also been studied in psoriasis. This updated re-view summarizes evidence from randomized clinical trials regarding the efficacy and safety of PDE4 inhibitors in psoriasis treatment. By highlighting their potential benefits and limitations, this review provides valuable insights for clinicians and researchers aiming to optimize psoriasis therapy.

This study investigated the effects of silibinin, derived from milk thistle (Silybum marianum), on lipopolysaccharide (LPS)-induced morphological changes in mouse macrophages. Silibinin was treated at various doses and time points to assess its effects on macrophage activation including morphological changes and phagocytosis. Silibinin effectively inhibited LPS-induced pseudopodia formation and size increase, while unstimulated cells remained round. Silibinin's impact on phagocytosis was dose- and time-dependent, showing a decrease. We explored its mechanism of action on kinases using a MAPK array. Among the three MAPK family members tested, silibinin had a limited effect on JNK and p38 but significantly inhibited ERK1/2 and related RSK1/2. Silibinin also inhibited MKK6, AKT3, MSK2, p70S6K, and GSK-3β. These findings highlight silibinin's potent inhibitory effects on phagocytosis and morphological changes in macrophages. We suggest its potential as an anti-inflammatory agent due to its ability to target key inflammatory pathways involving ERK1/2 and related kinases. Overall, this study demonstrates the promising therapeutic properties of silibinin in modulating macrophage function and inflammation.

Aims: Adolescence is a critical period because the brain is involved in the process of maturation that entails cognitive functions. On the way of maturation, an individual’s inhibitory control undergoes many changes and becomes vulnerable to different thrill-seeking like smoking, drinking, and so on. Smoking is highly prevalent among teenagers that are trying to take control of their behaviors in order to join society. They experience antisocial behavior too which is a trait that can lead adolescents to addiction. This trait is an inevitable part of psychopathy. Inhibitory deficits and psychopathy have been widely reported in addiction studies. The current study tried to investigate the relationship between psychopathic traits and behavioral inhibition between male smokers and non-smoker teenage students.Materials & Methods: Statistical sample of this research is 62 teenage students aged 17 years that are divided into smoker and non-smoker groups. The participants have been chosen through random sampling from the population of 10 high schools. The data have been gathered in Kordkoy and Gorgan in Golestan province. Behavioral bias has been measured by Go/NoGo task and psychopathic traits through youth psychopathic traits inventory. Also, the short form of Wechsler Adult Intelligence Scale test has been executed and used as a control variable.Findings: A meaningful difference has been found between the performance of smoker and non-smoker groups in Go/No Go task and psychopathic traits that are smokers performed weaker in comparison with non-smokers and psychopathic traits of smokers were meaningfully higher than non-smokers. On the other hand, there was no significant difference between these two groups in their Wechsler Adult Intelligence Scale scores.Conclusion: The results have shown that smokers have higher psychopathic traits and lower behavioral inhibition when compared with their non-smoker peers. According to the results of current research, smoking can decline the cognitive functions.