The goal of this lab is to look at how the characteristics of cementitious materials are affected by bending loads combined with dry and wet cycles of sulfate. In this paper, three sets of specimens with different water–cement ratios were designed. This study applied 20% and 40% of the ultimate bending load as a continuous bending load to the cementitious material specimens for a sulfate erosion test. It was discovered that the specimens' porosity, flexural strength, and compressive strength all tended to improve initially before declining as the cementitious material was degraded in the sulfate solution aged. The flexural strength of the cementitious materials declined as the bending load increased, and their internal sulfate ion concentration rose. A transport model of sulfate ions in cementitious materials under the coupling effect of bending load and sulfate erosion was created by combining the improved version of Fick’s second law and chemical reaction kinetics. The simulation results show that the ion transport properties of sulfate ions in cementitious materials are in accordance with the experimental laws. These research results formed the basis of the unified standards for the coupling of load dry and wet cycle systems, as well as evaluating the durability of cementitious materials under corrosive environments.

Water hyacinth (Eichhornia crassipes) is a potential accumulator of water pollutants in aquatic ecosystems, and its presence in water systems can affect water quality. This study used different field measurements and laboratory tests of Lake Water to determine the impact of water hyacinth phytoremediation capacity. A total of eight sampling stations used for the two lakes; Lake Koka and Lake Ziway. Sampling stations were selected from sites infested with water hyacinth (low, medium and high) and non-water hyacinth aquatic plants during wet and dry seasons to compare the effects of plants on water quality in the two lakes. All the sampled stations had various human interventions. The water samples were tested for the selected physico-chemical properties namely phosphate, nitrate, pH, electrical conductivity (EC), Biological oxygen demand (BOD5), temperature, and heavy metals (Chromium (Cr), Lead (Pb), Cadmium (Cd), Zinc (Zn), and Copper (Cu). These water quality variables were compared by means of ANOVA. Despite the COD of Lake Ziway, this study found no significant (p > 0.05) variation in the concentrations of Cu, EC, pH and temperature between wet and dry seasons in either lake. Variations in Zn concentration and other physico-chemical parameters (EC, BOD, COD, nitrate, phosphate) between low, medium and high levels of water hyacinth were significant in both lakes (p<0.05). Water hyacinth has shown significant phytoremediation nature during wet and dry seasons. The lowest average heavy metal, phosphate, and nitrate concentrations; and significant pH and temperature variations were observed in Lakes Koka and Lake Ziway, among water hyacinth and other grass-infested sites.

Nowadays, the European Union and the governments of the different countries have focused on the development of the Sustainable Development Goals (SDG) and the 2030 agenda, something that has been translated into education itself. Video Games, Gamification, and Game Based Learning have become different strategies and tools to enhance the learning process and some of the growing approaches used by teachers to develop sustainable education in the classrooms. This research aims to analyze the characteristics to promote sustainability in education using games and technology, specifically its learning benefits for Higher Education. A systematic review of the literature was conducted following the PRISMA methodology. At first, 2025 documents were found which, after the filtering phases, the number of articles has been reduced to nine, which subsequently were analyzed in depth. The results indicated that among the benefits of the use of games mediated by technologies are the following: it favors education for sustainability and it promotes the educational inclusion and the work of various social skills such as collaborative and cooperative work. Also, showed an increase of the number of publications between 2019 and 2023, reflecting the growing interest in the topic. However, there are some research gap in this field.

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96\% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

Nowadays, in low voltage (LV) electric distribution networks (EDNs), the Distribution Network Operators (DNOs) are encountering a high number of connected small-scale distributed generation units, mainly photovoltaic (PV) prosumers. The irregular behavior of the prosumers, together with the uncertainty degree of the requested and injected powers associated with all end-users from the LV EDN, can cause voltage variations with violations of the allowable limits. In this context, the paper developed an efficient and resilient expert system integrating the rule-based reasoning applied to the On-load Tap Changer (OLTC)-fitted transformer to improve the efficiency of the voltage control in the PV-rich LV EDNs. An in-depth analysis based on 75 scenarios, resulting from the combinations of three indicators: the penetration degree of the PV prosumers, consumption evolution associated with the consumers, and energy production of the PV systems, has been performed to demonstrate the efficiency of the proposed expert system in an LV EDN from a rural area belonging to a Romanian DNO. The success rate of the expert system has been 86.7% (65 out of 75 scenarios didn't have voltage issues, all values being between the allowable limits in 100% of the time slots associated with the analyzed period). For the other scenarios (representing 13.3%), the values have been inside the range [-10%, +10%] at least 95% of the time slots, according to the European Power Quality Standard, and for the rest of the time slots up to 100% being very close to the upper and lower limits of the range, with highly mitigating of the voltage variations.

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

The threat posed by climate change, the progressive erosion of natural resources, the polluting effects related to private motorization, energy waste, excessive consumption of agricultural and natural soils and their progressive waterproofing and reduction in vegetation cover, with the subsequent environmental degradation, have highlighted the need for a sustainable management of natural resources, in terms of an equitable and ethical development, to build inclusive communities able to adapt to the negative effects of emergency phenomena, through new capacities of economic, cultural and social resilience. This contribution presents the results of the activities conducted in the RivEr/Generation_LAB, a project organized by three CIVIS members (Sapienza University of Rome, Universitè libre de Bruxelles, Universidad Autonoma de Madrid) as a part of the CIVIS Project "RivEr/Generation_LAB. Linking resilience with inclusiveness in the urban built environment of Rome, Brussels, and Madrid", financed into the Hub4 Cities, Territories & Mobilities’ Call for proposals 2021. The project proposes a methodology of intervention in the Flaminio district, in particular on the 'Olympic Village' and its relationship with the Tiber River, in line with the Sustainable Development Goals, the Millennium Ecosystem Assessment and the New European Bauhaus, to establish new relationships between cities and the natural environment, favouring sustainable and inclusive public spaces.

This work considers the task of representation learning on the attributed relational graph (ARG). Both the nodes and edges in an ARG are associated with attributes/features allowing ARGs to encode rich structural information widely observed in real applications. Existing graph neural networks offer limited ability to capture complex interactions within local structural contexts, which hinders them from taking advantage of the expression power of ARGs. We propose Motif Convolution Module (MCM), a new motif-based graph representation learning technique to better utilize local structural information. The ability to handle continuous edge and node features is one of MCM’s advantages over existing motif-based models. MCM builds a motif vocabulary in an unsupervised way and deploys a novel motif convolution operation to extract the local structural context of individual nodes, which is then used to learn higher-level node representations via multilayer perceptron and/or message passing in graph neural networks. When compared with other graph learning approaches to classifying synthetic graphs, our approach is substantially better in capturing structural context. We also demonstrate the performance and explainability advantages of our approach by applying it to several molecular benchmarks.

Student attendance serves many other important purposes aside from monitoring. In certain universities, the attendance of students in a course is also used as one of the requirements for students to be allowed to sit for the final examination. Traditionally, among most Malaysian Institutions of Higher Learning (IHL), attendance recording is usually done using pen and paper, or uses simple web-based system that is time consuming and difficult for faculty periodic monitoring. To address the identified drawbacks, this research aims to develop a Smart Attendance for Faculty Monitoring System using the Bluetooth Low Energy (BLE) technology to assist faculty in recording, managing and monitoring students’ attendance and class schedules effectively. The system is developed for Android-based devices using an agile methodology consists of iteration and incremental approaches. Thus, to evaluate the effectiveness of the system, a survey was conducted on 140 respondents involving lecturers and students of Kolej Universiti Poly-Tech MARA (KUPTM). Respondents were selected using purposive sampling. The descriptive analysis showed that 87.9% of the respondents strongly agreed that the system is effective in assisting lecturers to record attendance, manage class schedules and student attendance as well as to assist faculty in monitoring students’ absenteeism.

Passive and forced drinking harm was prevalent but less recognized in Chinese adolescents. We educated adolescents on such harm to reduce their intention to drink. Students (n=1244) from 7 secondary schools in Hong Kong participated in a video-based health talk on passive and forced drinking harm. Paired t-test was used to assess their change in knowledge of passive and forced drinking, health and social harm of drinking after the health talk. McNemar's chi-squared test and adjusted multivariable logistic regression (AOR) were used to assess their change in intention to drink and intention to quit. Students were less likely to drink (OR 0.29, 95% CI 0.19-0.42) and more likely to quit drinking (OR 3.50, 1.10-14.6) after the health talk. Increased knowledge of passive drinking was associated with less intention to drink (AOR 0.93, 0.90-0.97), increased knowledge of health harm (adjusted b 0.06, 0.05-0.08), and social harm of drinking (adjusted b 0.12, 0.10-0.16). Similar associations were observed in forced drinking (intention to drink: AOR 0.87, 0.79-0.96; health harm: adjusted b 0.16, 0.12-0.19; social harm: adjusted b 0.36, 0.28-0.43). We showed preliminary evidence that the health talk on passive and forced drinking reduced the intention to drink in adolescents.

Coastal areas are highly vulnerable to climate change hazards (e.g., sea-level rise, flooding, coastal erosion), which can lead to significant impacts at the ecosystem and societal level. Interest in Ecosystem-based Adaptation (EbA) is gaining importance due to its potential multiple benefits, including social and environmental aspects, when compared to more traditional approaches such as hard engineering interventions. When assessing EbA strategies, further understanding of the nature-society functions, processes, values, and benefits is needed to increase its application. This study contributes to a better knowledge of EbA by developing a systematic literature review of studies performing socio-economic assessments of climate change adaptation in coastal areas. The analysis of 54 publications revealed that most of the studies assessed adaptation solutions through cost-benefit analysis, followed by multi-criteria analysis, and other techniques. Hybrid adaptation strategies based on different combinations of hard, soft and EbA interventions were considered as potential optimal solutions in a significant part of the assessments. This study suggests the potential co-benefits of EbA in the form of ecosystem services, livelihood diversification or biodiversity conservation, but also stresses the need for further research on this topic, as well as on evaluating how EbA perform in the long-term under climate changing conditions scenarios.

Grinding processes’ stochastic nature poses a challenge in predicting the quality of the resulting surfaces. Post-production measurements for form, surface roughness, and circumferential waviness are commonly performed due to infeasibility in measuring all quality parameters during the grinding operation. Therefore, it is challenging to diagnose the root cause of quality deviations in real-time resulting from variations in the machine’s operating condition. This paper introduces a novel approach to predicting the overall quality of the individual parts. The grinder is equipped with sensors to implement condition-based maintenance and is induced with five frequently occurring failure conditions for the experimental test runs. The crucial quality parameters are measured for the produced parts. Fuzzy c-means (FCM) and Hotelling’s T-squared (T2) have been evaluated to generate quality labels from the multi-variate quality data. Benchmarked random forest regression models are trained using fault diagnosis feature set and quality labels. Quality labels from the T2 statistic of quality parameters are preferred over FCM approach for their repeatability. The model, trained from T2 labels achieves more than 94% accuracy when compared to the measured ring disposition. The predicted overall quality using the sensors’ feature set is compared against the threshold to reach a trustworthy maintenance decision.

Quadrotor drones have rapidly gained interest recently. Numerous studies are underway for the commercial use of autonomous drones, and especially the distribution businesses are taking serious reviews on drone delivery services. However, there are still many concerns about urban drone operations. The risk of failures and accidents makes it difficult to provide drone-based services in the real world with ease. There have been many studies that introduced supplementary methods to handle drone failures and emergencies. However, we discovered the limitation of the existing methods. The majority of approaches were improving PID-based control algorithms which is the dominant drone control method. This type of low-level approach lacks situation awareness and the ability to handle unexpected situations. This study introduces an event-based control methodology that takes a high-level diagnosing approach that can implement situation awareness via time-window. While leaving the low-level controller to involve in operating the drone for most of the time in normal situations, our controller operates at a higher level and detects unexpected behaviors and abnormal situations of the drone. We tested our method with real-time 3D computer simulation environments with Unreal Engine[15] and AirSim[31]. We were able to verify that our approach can provide enhanced double safety and better ensure safe drone operations. We hope our discovery to possibly contribute to the advance of real-world drone services in the near future.

In the development of the safety-critical systems, it is important to perform Failure Modes and Effects Analysis (FMEA) process to identify potential failures. However, traditional FMEA activities tend to be considered difficult and time-consuming tasks. To compensate for the difficulty of the FMEA task, various types of tools are used to increase the quality and the effectiveness of the FMEA reports. This paper explains an Automatic FMEA tool which integrates the Model-based Design (MBD), FMEA, and Simulated Fault Injection techniques in a single environment. The Automatic FMEA tool has the following advantages compared to the existing FMEA analysis tool. First, the Automatic FMEA tool automatically generates FMEA reports compared to the traditional spreadsheet-based FMEA tools. Second, the Automatic FMEA tool analyzes the causality between the failure modes and the failure effects by performing model-based fault injection simulation. In order to demonstrate the applicability of the Automatic FMEA, we used the electronic fuel injection system (EFI) Simulink model. The results of the Automatic FMEA were compared to that of the legacy FMEA.

In this work, we have developed a non-ordinary state-based peridynamic model for multiple crack initiation and propagation due to compression-compression fatigue load. In each loading cycle, the fatigue loading is redistributed among the peridynamic solid body, leading to the progressive fatigue damage initiation and propagation in an autonomous fashion. The proposed fatigue model parameters are firstly validated by 3D numerical benchmark tests, and then it is applied to simulate widespread fatigue damage evolution of the aircraft wing corner box. The modified constitutive damage model has been implemented into the peridynamics framework at finite strain. Furthermore, the criterion algorithm from multiple initiation to propagation is discussed. It is shown that the numerical results obtained from peridynamics simulations are in general agreement with those from the experiment data. The comparison of experimental and numerical results indicates that the proposed non-ordinary state-based peridynamics fatigue model has the ability to capture the multiple crack initiation and propagation and other features of the aluminium alloy material.

The acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected. Antiretrovirals are only a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, new novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual-focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp3 atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available at https://figshare.com/s/ceb58d58e8f5585ce67e.

Telehealth is the delivery of many health care services and technologies to individuals at different geographical areas and is categorized as asynchronously or synchronously. The coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions in health care delivery to breast cancer (BCa) patients and there is increasing demand for telehealth services. Globally, telehealth has become an essential means of communication between patient and health care provider. The application of telehealth to the treatment of BCa patients is evolving and increasingly research has demonstrated its feasibility and effectiveness in improving clinical, psychological and social outcomes. Two areas of telehealth that have significantly grown in the past decade and particularly since the beginning of the COVID-19 pandemic are telerehabilitation and teleoncology. There two technological systems provides opportunities at every stage of the cancer care continuum for BCa patients. We conducted a systematic literature review that examined the use of telehealth services via its various modes of delivery among BCa patients particularly in areas of screening, diagnosis, treatment modalities, as well as satisfaction among patients and health care professionals. The advantages of telehealth models of service and delivery challenges in delivery to patients in remote arears are discussed.

During the COVID-19 outbreak, most university courses have been offered on online platforms. A sudden shift from face-to-face classroom learning to online formats could influence the learning effectiveness of classes. This study aims to investigate differences in the learning effectiveness of online and face-to-face lecture courses. It also explores factors that impact the effectiveness of online instruction. These factors include interactions among learners, interactions between learners and the instructor, the quality of online platforms, learners’ ability to use devices and follow instructions, and learners’ situational challenges. The study participants were 261 university students at King Mongkut’s University of Technology Thonburi in Bangkok, Thailand. All participants were enrolled in at least one lecture course, such as history, humans and the environment, the environment and development, or general philosophy, during the 2019 academic year. A questionnaire was distributed to participants after they completed these courses in May 2020. Paired simple t-test analyses were used to compare the effectiveness of online and face-to-face classes, and a multiple regression analysis was used to identify factors that impact the learning effectiveness of online classes. The results show that online classes are less effective than face-to-face courses. The multiple regression analysis also revealed that the effectiveness of online learning was significantly impacted by learners’ ability to interact with classmates during class, their ability to interact with instructors after the class, the quality of online platforms, and disturbances or distractions in learners’ environments.

In the last five years, European research and innovation programmes have prioritised the development of online catalogues and tools (handbooks, models, etc.) to facilitate the implementation and monitoring of Nature Based Solutions (NBS). However, only a few catalogues and toolkits within European programmes are directly related to mainstreaming of NBS for food production (i.e., edible NBS). Therefore, the main aim of this paper is to present existing NBS tools through the eyes of productive urban landscapes. We reviewed 32 projects related to NBS and 50 tools were identified and characterised. Then, the 6 tools already available, and providing indicators, were further analysed in terms of their format and knowledge domains. Our main conclusion demonstrates that there is a lack of tools capable of supporting users for planning and implementing edible NBS, calculating the food potential of the city and/or of individual edible NBS, including the needed resources for implementation and operation (water, nutrients, energy), and assessing their urban design value, environmental and socio-economic impacts. And when they do exist, there is a resistance to share the models and equations behind the tools to allow other projects to reuse or validate them, fact which is contrary to Open Science principles stood up by many research public agencies.

BODIPY dyes have recently raised attention as potential photosensitizers. In this work, commercial and novel photosensitizers (PSs) based on BODIPY chromophores (haloBODIPYs and orthogonal dimers strategically designed with intense bands in the blue, green or red region of the Visible spectra and high singlet oxygen production) were covalently linked to mesoporous silica nanoparticles (MSNs) further functionalized with PEG and folic acid (FA). MSNs of approximately 50 nm in size with different functional groups were synthesized to allow multiple alternatives of PS-PEG-FA decoration of their external surface. Different combinations varying the type of PS (commercial Rose Bengal, Thionine and Chlorine e6 or custom-made BODIPY-based), the linkage design and the length of PEG are detailed. All the nanosystems were physicochemically characterized (morphology, diameter, size distribution and PS loaded amount) and photophysically studied (absorption capacity, fluorescence efficiency, and singlet oxygen production) in suspension. For the most promising PS-PEG-FA silica nanoplatforms, the biocompatibility in dark conditions and the phototoxicity under suitable irradiation wavelengths (blue, green, or red) at regulated light doses (10-15 J/cm2) were compared with PSs free in solution in HeLa cells in vitro.

The evolution towards Industry 4.0 is driving the need for innovative solutions in the area of network management, considering the complex, dynamic and heterogeneous nature of ICT supply chains. To this end, Intent-Based networking (IBN) which is already proven to evolve how network management is driven today, can be implemented as a solution to facilitate the management of large ICT supply chains. In this paper, we first present a comparison of the main architectural components of typical IBN systems and, then, we study the key engineering requirements when integrating IBN with ICT supply chain network systems while considering AI methods. We also propose a general architecture design that enables intent translation of ICT supply chain specifications into lower level policies, to finally show an example of how the access control is performed in a modelled ICT supply chain system.

In 2019, Chinese government implemented the first round of National Centralized Drug Procurement (NCDP) pilot (so-called "4+7" policy) in mainland China, achieved a prominent price reduction of 52% on average for 25 bidding winning products. Under cross-price elasticity theory, the price behavior of pharmaceutical enterprises for policy-related drugs might change. This study used drug purchasing data from the Centralized Drug Procurement Survey in Shenzhen 2019, and applied single-group Interruption Time Series (ITS) design to examine the impact of "4+7" policy on the drug price index (DPI) of policy-related drugs. The ITS analysis showed that the DPI of winning (-0.183 per month, p<0.0001) and non-winning (-0.034 per month, p=0.046) products significantly decreased after the implementation of "4+7" policy. No significant difference was found for the immediate change of DPI for alternative drugs (p=0.537), while a significant decrease in change trend was detected in the post-"4+7" policy period (-0.003 per month, p=0.014). The DPI of the overall policy-related drugs significantly decreased (-0.261 per month, p<0.0001) after "4+7" policy. These findings indicate that the price behavior of pharmaceutical enterprises changed under NCDP policy, while the price linkage effect is still limited. It is necessary to further expand the scope of centralized purchased drugs and strengthen the monitoring of related drugs regarding price change and consumption structure.

Estimating the economic risks of climate shocks and climate stressors on spatially heterogeneous cities over time remain highly challenging. The purpose of this paper is to present a practical methodology to assess the economic risks of climate change in developing cities to inform spatially sensitive municipal climate response strategies. Building on a capital-based framework (CBF), spatially disaggregated baseline and future scenario scores for economic wealth and its exposure to climate change are developed for six different classes of capital and across 77 major suburbs in Cape Town, South Africa. Capital-at-risk was calculated by combining relative exposure and capital scores across different scenarios and with population impacted plotted against the major suburbs and the city’s 8 main planning districts. The economic risk assessment presented here provides a generic approach to assist investment planning and the implementation of adaptation options through an enhanced understanding of relative levels of capital endowment vis-à-vis relative levels of exposure to climate-related hazards over time. An informed climate response strategy in spatially heterogeneous cities need to include spatially sensitive estimates on capital-at-risk and populations disproportionally impacted by climate exposure over time. The economic risk assessment approach presented here helps in advancing to such a goal.

Bacterial cellulose (BC) is receiving great attention due to its unique properties such as high purity, water retention capacity, high mechanical strength, and biocompatibility. However, the production of BC has been limited because of high cost and low productivity. In this light, the isolation of new BC producing bacteria and selection of high productive strains became a promising issue. Kombucha tea is a fermented beverage in which the bacteria fraction of the microbial community is composed mostly by strains belonging to the genus Komagataeibacter. In this study Kombucha tea production trials were performed starting from a previous batch, and bacterial isolation was conducted along cultivation time. From the whole microbial pool, 46 isolates were tested for their ability in producing BC. The obtained BC yield ranged from 0.59 g/L, for the isolate K2G36, to 23 g/L for K2G30 used as the reference strain. The genetic intraspecific diversity of the 46 isolates was investigated using two repetitive-sequence-based PCR typing methods, which are the enterobacterial repetitive intergenic consensus (ERIC) elements and the (GTG)5 sequences, respectively. The results obtained using two different approaches revealed the suitability of the fingerprints techniques, showing a discrimination power, calculated as D index, of 0.94 for (GTG)5 rep-PCR and 0.95 for ERIC rep-PCR. In order to improve the sensitivity of the applied method, a combined model from the two genotyping experiments was performed, allowing to discriminate among strains.

Three kinds of Ni based alloy cladding coatings were prepared on 316L stainless steel at different power. The microstructure of the cladding layer was observed and analyzed by XRD, metallographic microscope and SEM. The hardness of the cladding layer was measured, and the wear resistance of the cladding layer was tested by friction instrument. The results show that the effect of laser cladding is good and the cladding layer has a good metallurgical bonding with the substrate. Different microstructures such as dendritic and equiaxed grains can be observed in the cladding layer. With the increase of laser power, more equiaxed and columnar dendrites can be observed. The phase composition of the cladding layer is mainly composed of γ - Ni solid solution and some intermetallic compounds such as Ni3B, Cr5B3 and Ni17Si3. The results of EDS show that there are some differences in the distribution of C and Si between dendrites. The hardness of the cladding layer is about 600 HV0.2, which is about three times of the substrate (~ 200 HV0.2). Through the analysis of the wear morphology, the substrate wear is serious, there are serious shedding, mainly adhesive wear and abrasive wear. However, the wear of cladding layer is slight, which is abrasive wear, and there are some grooves on the surface.

Nature Based Solutions (NBS) are becoming increasingly important in both the EU and individual countries' political agendas, as a sustainable means to reduce the risk posed by hydrometeorological hazards. However, as the use of NBS is increasing, a number of barriers regarding their practical implementation also becomes apparent. A number of review studies have summarized and classified barriers, mainly in urban settings. PHUSICOS is a H2020 Innovation Action to demonstrate the use of NBS in rural and mountain landscapes. Large scale demonstrator case sites with several sub-projects are established in Italy, Norway and in the French and Spanish Pyrenees. The present paper describes the project's NBS measures, and their experienced barriers, some of which have resulted in full cancellation of the planned interventions. Many of the barriers experienced in rural settings have the same root causes as the ones described from urban areas, and the main barrier-creating mechanisms are institutional factors, resistance among stakeholders and technical and economic issues. The key element, however, is lack of knowledge about the ability of NBS to deliver a series of co-benefits in addition to their risk-reducing effects, and that long-term thinking is required to see the effect of many of these co-benefits.

Several studies suggest that COVID-19 may be accompanied by symptoms such as a dry cough, muscle aches, sore throat, and mild to moderate respiratory illness. The symptoms of this disease indicate the fact that COVID-19 causes noticeable negative effects on the lungs. Therefore, considering the health status of the lungs using X-rays and CT scans of the chest can significantly help diagnose COVID-19 infection. Due to the fact that most of the methods that have been proposed to COVID-19 diagnose deal with the lengthy testing time and also might give more false positive and false negative results, this paper aims to review and implement artificial intelligence (AI) image-based diagnosis methods in order to detect coronavirus infection with zero or near to zero false positives and false negatives rates. Besides the already existing AI image-based medical diagnosis method for the other well-known disease, this study aims on finding the most accurate COVID-19 detection method among AI methods such as machine learning (ML) and artificial neural network (ANN), ensemble learning (EL) methods.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Battery/Supercapacitor(SC) current tracking control is a key issue for hybrid energy storage system (HESS) in electric vehicles. An innovative passivity-based L2-gain adaptive control (PBL2AC) based on port-controlled Hamiltonian model with dissipativity (PCHD) for reference current tracking and bus voltage stability in HESS is presented. The developed PCHD model has considered both parameter variations and external disturbances. By using L2-gain disturbance attenuation, the PBL2AC ensures robust reference current tracking and stable bus voltage. Moreover, adaptive mechanism is adopted to estimate the electrical parameters. To validate the proposed control scheme for HESS, simulations and experiments were done and compared with traditional PID and sliding mode control under several typical driving cycles, and results show that the effectiveness of the proposed controller can be confirmed.

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

Incorporating source-side linguistic knowledge into the neural machine translation (NMT) model has recently achieved impressive performance on machine translation tasks. One popular method is to generalize the word embedding layer of the encoder to encode each word and its linguistic features. The other method is to change the architecture of the encoder to encode syntactic information. However, the former cannot explicitly balance the contribution from the word and its linguistic features. The latter cannot flexibly utilize various types of linguistic information. Focusing on the above issues, this paper proposes a novel NMT approach that models the words in parallel to the linguistic knowledge by using two separate encoders. Compared with the single encoder based NMT model, the proposed approach additionally employs the knowledge-based encoder to specially encode linguistic features. Moreover, it shares parameters across encoders to enhance the model representation ability of the source-side language. Extensive experiments show that the approach achieves significant improvements of up to 2.4 and 1.1 BLEU points on Turkish→English and English→Turkish machine translation tasks, respectively, which indicates that it is capable of better utilizing the external linguistic knowledge and effective improving the machine translation quality.

Background: This retrospective study evaluates the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. The significant differences of survival between the two groups were only observed in patients with positive EGFR expression. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

Over the last few decades there has been an exponential growth in IT, motivating IT professionals and scientists to explore new dimensions resulting in the advancement of artificial intelligence and its subcategories like computer vision, deep learning and augmented reality. AR is comparatively a new area which was initially explored for gaming but recently a lot of work has been done in education using AR. Most of this focuses on improving students understanding and motivation. Like any other project, the performance of an AR based project is determined by the customer satisfaction which is usually affected by the theory of triple constraints; cost, time and scope. many studies have shown that most of the projects are under development because they are unable to overcome these constraints and meet project objectives. We were unable to find any notable work done regarding project management for augmented reality systems and application. Therefore, in this paper, we propose a system for management of AR applications which mainly focuses on catering triple constraints to meet desired objectives. Each variable is further divided into subprocesses and by following these processes successful completion of the project can be achieved.

The transition to reproduction is a crucial step in the life cycle of any organism. In Arabidopsis thaliana the establishment of reproductive growth can be divided into two phases: Firstly, cauline leaves with axillary meristems are formed and internode elongation begins. Secondly, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe a transposon insertion mutant in the Nossen accession with defects in floral development and growth. Most strikingly is the outgrowth of stems from the axillary bracts of the primary flower carrying secondary flowers. Therefore, we named this mutant flower-in-flower (fif). However, the transposon insertion in the annotated gene is not the cause for the fif phenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for the fif phenotype was found to be in the LEAFY gene. The mutation, a G-to-A exchange in the second exon of LEAFY, creates a novel lfy allele and results in a cysteine-to-tyrosine exchange in the α1-helix of LEAFY´s DNA-binding domain. This exchange abolishes target DNA-binding, whereas subcellular localization and homomerization are not affected. To explain the strong fif phenotype against this molecular findings, several hypotheses are discussed.

The Sustainable Development Goals, while complex at first sight, express a simple narrative about the relationships between people and nature. This paper illustrates this in the context of a coral reef land or seascape supporting coastal people. Coral reefs, their health described by measures of coral and fish diversity and abundance, provide key services and benefits to people. These services directly support 10s of millions of jobs in multiple economic sectors in coastal and distant states, protect and harbor communities and cities across tropical coastlines, sustain use of living and non-living resources, provide transport infrastructure and valuable natural products, and in future may provide energy solutions. Through these multiple benefits, coral reefs contribute to reducing hunger and poverty, thus improving health, and potentially strengthening gender and social equality. However, access and use result in pressures that may drive decline in coral reef health. Broader land and seascape factors also affect reef health and therefore delivery of benefits, including land-use change and altered freshwater flows, as well as climate change. Managing this complex system requires appropriate awareness and knowledge, governance mechanisms and investments by stakeholders. This ‘SDG narrative’ can be used from local to global levels, motivating actions and policy at and across these scales to sustain ecosystem function and use, for the oceans what is also increasingly called a blue economy.

As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables the explainable-AI eQTL analysis of SNP sets with over a million SNPs. Using this implementation we also present a new method, iRF Leave One Out Prediction (iRF-LOOP), for the creation of Predictive Expression Networks on the order of 40,000 genes or more. We compare the new implementation of iRF with the previous R version and analyze its time to completion on two of the world's fastest supercomputers Summit and Titan. We also show iRF-LOOP's ability to capture biologically significant results when creating Predictive Expression Networks. This new implementation of iRF will enable the analysis of biological data sets at scales that were previously not possible.

In South Korea, landslides are caused by localized heavy rainfall and typhoons, which often occur in the summer season at natural slopes in mountainous areas and artificial slopes in urban surroundings. Flow-type landslides frequently occur in mountainous areas. To evaluate flow-type landslides, it is essential to identify the physical characteristics of soil, giving focus to the soil on the top layers of various types of slope. This study conducts a survey and an analysis of the characteristics of landslides that occurred in the study area with different geological conditions of granite and gneiss. The characteristics of soil in the area and its surroundings that have or have not undergone landslides for every geological condition is also evaluated. Based on these characteristics and a statistics method, it extracts the triggering factors, permeability coefficients (k), and shearing strength with cohesion (c) and internal friction angel (φ) of soils that are highly related to landslides around weathered soil layers. As a result, the permeability coefficients show significant relevance with void ratio (e), the effective size of grains (D10), and uniformity coefficient (cu), while the shearing strength with the proportion of fine-grained soil (Fines), uniformity coefficient (cu), degree of saturation (S), dry weight density (rd), and void ratio (e). By obtaining this result, the study uses the regression analysis to suggest models to estimate the permeability coefficients and shearing strength. For the gneiss area, the statistics-based estimation model (SEM) is proposed as k_gn = (1.488 × 10^-02 × e) + (1.076 × D₁₀) + (-1.629 × 10^-04 × c_u) - (1.893 × 10^-02) for permeability coefficients; cgn = (-0.712 × Fines) + (-0.131 × c_u) + 15.335 for cohesion; and φgn = (27.01 × r_d) + (-12.594 × e) + 6.018 for internal frictional angle of soils. For the granite area, the statistics-based estimation model (SEM) is proposed as kgr = (8.281 × 10^-03 × e) + (0.639 × D₁₀) + (-2.766 × 10^-05 × c_u) - (9.907 × 10^-03) for permeability coefficients; c_gr = (-0.689 × Fines) + (-0.0744 × S) + 18.59 for cohesion; and φ_gr = (33.640 × r_d) + (-0.875 × e) - 9.685 for internal frictional angle of soils. The use of statistics-based estimation models (SEMs) for landslide-triggering factors that trigger landslides will support the simple calculation of permeability coefficient and shearing strength (cohesion and internal frictional angle), only requiring information about the physical properties of soil at the natural slopes that have different geological features such as gneiss and granite areas.

Background: This retrospective study evaluate the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. We also demonstrated that EGFR-knockout Caco2 cells are more sensitive to the inhibition effect of fluoropyrimidine than the control those. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression and treatment strategies, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

In this paper, we introduce a new class of Laguerre-based Hermite-Fubini numbers and polynomials and investigate some properties of these polynomials. We establish summation formulas of these polynomials by summation techniques series. Furthermore, we derive symmetric identities of Laguerre-based Hermite-Fubini numbers and polynomials by using generating functions.

This work presents some characteristics of MoNet, a computerized platform for the modeling and visualization of complex systems. Emphasis is on the ideas that allowed the successful progressive development of this modeling platform, which goes along with the implementation of applications to the modeling of several studied systems. The platform has the capacity to represent different aspects of systems modeled at different observation scales. This tool offers advantages in the sense of favoring the perception of the phenomenon of the emergence of information, associated with changes of scale. Some criteria used for the construction of this modeling platform are included. The power of current computers has made practical representing graphic resources such as shapes, line thickness, overlaying-text tags, colors and transparencies, in the graphical modeling of systems made up of many elements. By visualizing diagrams conveniently designed to highlight contrasts, these modeling platforms allow the recognition of patterns that drive our understanding of systems and their structure. Graphs that reflect the benefits of the tool regarding the visualization of systems at different scales of observation are presented to illustrate the application of the platform.

Mixing is considered as a critical process parameter (CPP) during process development due to its significant influence on reaction selectivity and process safety. Nevertheless, mixing issues are difficult to identify and solve owing to their complexity and dependence on knowledge of kinetics and hydrodynamics. In this paper, we proposed an optimization methodology using Computational Fluid Dynamics (CFD) based compartmental modelling to improve mixing and reaction selectivity. More importantly, we have demonstrated that through the implementation of surrogate-based optimization, the proposed methodology can be used as a computationally non-intensive way for rapid process development of reaction unit operations. For illustration purpose, reaction selectivity of a process with Bourne competitive reaction network is discussed. Results demonstrate that we can improve reaction selectivity by dynamically controlling rates and locations of feeding in the reactor. The proposed methodology incorporates mechanistic understanding of the reaction kinetics together with an efficient optimization algorithm to determine the optimal process operation and thus can serve as a tool for quality-by-design (QbD) during product development stage.

This paper deals with experimental study of the influence of conductive (Fe₃O₄) and insulating (Al₂O₃) nanostructured particles at various concentrations on the dielectric strength of transformer mineral oil. The method of preparation and characterization of these nanofluids (NFs) through the measurements of zeta potential, the real and imaginary parts of dielectric constant as well as the concentration and size of nanoparticles using Scanning Electron Microscope (SEM) images of nanoparticles powders and Dispersive x-ray Spectroscopy (EDS) analysis are presented. Experimental findings reveal that these two types of nanoparticles materials significantly improve AC breakdown voltage and the magnitude of this improvement depends on the concentration, size and nature (material) of nanoparticles. For a given type of nanoparticles, the effect is more marked with the smallest nanoparticles. The conductive nanoparticles offer higher enhancement of dielectric strength compared with insulating nanoparticles based nanofluids. With Fe₃O₄, the breakdown voltage (BDV) can exceed twice that of mineral oil and it increases by more than 76% with Al₂O₃. The physicochemical mechanisms implicated in this improvement are discussed.

Non-invasive, electroencephalography (EEG)-based brain-computer interfaces (BCIs) on motor imagery movements translate the subject’s motor intention into control signals through classifying the EEG patterns caused by different imagination tasks, e.g. hand movements. This type of BCI has been widely studied and used as an alternative mode of communication and environmental control for disabled patients, such as those suffering from a brainstem stroke or a spinal cord injury (SCI). Notwithstanding the success of traditional machine learning methods in classifying EEG signals, these methods still rely on hand-crafted features. The extraction of such features is a difficult task due to the high non-stationarity of EEG signals, which is a major cause for the stagnating progress in classification performance. Remarkable advances in deep learning methods allow end-to-end learning without any feature engineering, which could benefit BCI motor imagery applications. We developed three deep learning models: 1) a long short-term memory (LSTM); 2) a proposed spectrogram-based convolutional neural network model (pCNN); and 3) a recurrent convolutional neural network (RCNN), for decoding motor imagery movements directly from raw EEG signals without (manual) feature engineering. Results were evaluated on our own, publicly available, EEG data collected from 20 subjects and on an existing dataset known as 2b EEG dataset from "BCI Competition IV". Overall, better classification performance was achieved with deep learning models compared to state-of-the art machine learning techniques, which could chart a route ahead for developing new robust techniques for EEG signal decoding. We underpin this point by demonstrating the successful real-time control of a robotic arm using our CNN based BCI.

Initial water content significantly affects the efficiency of soil stabilization. In this study, the effects of initial water content on the compressibility, strength, microstructure and composition of a lean clay soil stabilized by compound calcium-based stabilizer were investigated by static compaction test, unconfined compression test, optical microscope observations, environment scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction spectroscopy. The results indicate that as the initial water content increases in the range studied, both the compaction energy and the maximum compaction force decrease linearly and there are less soil aggregates or agglomerations, and smaller proportion of large pores in the compacted mixture structure. In addition, for specimens cured with or without external water supply and under different compaction degrees, the variation law of the unconfined compressive strength with initial water content is different and the highest strength value is obtained at various initial water contents. With the increase of initial water content, the percentage of oxygen element tends to increase in the reaction products of the calcium-based stabilizer, whereas the crystalline mineral of the soil did not change obviously.

Metal hydrides are one of the types of functional materials that allow safe and compact storage of a large amount of hydrogen, which is increasingly used today as an alternate fuel or energy source. The possibility of obtaining the initial energy necessary for the production of hydrogen by electrolysis process from renewable energy sources, such as solar panels and wind generators, makes hydrogen energetic quite attractive and rapidly developing industry sector. Solid form of hydrogen storage with the possibility of reversible sorption, gives opportunity for creation autonomous energy storage systems. La-Ni based alloys allow hydrogen storing at ambient temperatures and pressure not higher than 15 bar, which makes the application of these alloys quite practical, interesting and prospects for analysis and modifications on the ways of stored hydrogen capacity increasing, alloys price reducing and application for renewable energy storage.

Decision tables have been used for many years in data processing and business applications to simulate complex rule sets. Several computer languages have been developed based on rule systems and they are easily programmed in several current languages. Land management and river-reservoir models simulate complex land management operations and reservoir management in highly regulated river systems. Decision tables are a precise yet compact way to model the rule sets and corresponding actions found in these models. In this study, we discuss the suitability of decision tables to simulate management in the river basin scale Soil and Water Assessment Tool (SWAT+) model. Decision tables are developed to simulate automated irrigation and reservoir releases. A simple auto irrigation application of decision tables was developed using plant water stress as a condition for irrigating corn in Texas. Sensitivity of the water stress trigger and irrigation application amounts were shown on soil moisture and corn yields. In addition, the Grapevine Reservoir near Dallas, Texas was used to illustrate the use of decision tables to simulate reservoir releases. The releases were conditioned on reservoir volumes and flood season. The release rules as implemented by the decision table realistically simulated flood releases as evidenced by a daily NSE (Nash-Sutcliffe Efficiency) of 0.52 and a percent bias of -1.1%. Using decision tables to simulate management in land, river and reservoir models was shown to have several advantages over current approaches including: 1) mature technology with considerable literature and applications, 2) ability to accurately represent complex, real world decision making, 3) code that is efficient, modular and easy to maintain, and 4) tables that are easy to maintain, support, and modify.

Antimony (Sb) Substitution less than 10 % is examined on a single crystal of a layered superconductor NdO_0.7F_0.3BiS₂. Superconducting transition temperature of the substituted samples decreases with increasing Sb concentration. A lattice constant along the c axis showed a large decrease compared with that along the a axis. Since in-plane chemical pressure monotonically decreases with increasing Sb concentration, the suppression of the superconductivity is well described in terms of the decrease in in-plane chemical pressure.

This paper attempts at applying adaptive network-based fuzzy inference system (ANFIS) for analysis of the resonant frequency of a microstrip rectangular patch antenna with two equal size slots which are placed on the patch vertically. The resonant frequency is calculated as the position of slots is shifted to the right and left sides on the patch. As a result , the antenna resonates at more than one frequency . Commonly, machine algorithms based on artificial neural networks are employed to recognize the whole resonant frequencies. However ,they fail to estimate the resonant frequencies correctly as in some cases variations are not very sensible and the resonant frequencies overlap each other . It can be concluded that artificial neural networks could be replaced in such designs by the adaptive network-based fuzzy Inference system due to its high approximation capability and much faster convergence rate.

With the rapid development of satellite remote sensing technology, the volume of image datasets in many application areas is growing exponentially and the demand for Land-Cover and Land-Use change remote sensing data is growing rapidly. It is thus becoming hard to efficiently and intelligently retrieve the change information that users need from massive image databases. In this paper, content-based image retrieval is successfully applied to change detection and a content-based remote sensing image change information retrieval model is introduced. First, the construction of a new model framework for change information retrieval in a remote sensing database is described. Then, as the target content cannot be expressed by one kind of feature alone, a multiple-feature integrated retrieval model is proposed. Thirdly, an experimental prototype system that was set up to demonstrate the validity and practicability of the model is described. The proposed model is a new method of acquiring change detection information from remote sensing imagery and so can reduce the need for image pre-processing, deal with problems related toseasonal changes as well as other problems encountered in the field of change detection. Meanwhile, the new model has important implications for improving remote sensing image management and autonomous information retrieval.

Indoor positioning based on the received signal strength (RSS) of the WiFi signal has become the most popular solution for indoor localization. In order to realize the rapid deployment of indoor localization systems, solutions based on crowdsourcing have been proposed. However, compared to conventional methods, crowdsourced RSS values are more erroneous and can result in large localization errors. To mitigate the negative effect of the erroneous measurements, a graph-based semi-supervised learning (G-SSL) method is used to exploit the correlation between the RSS values at nearby locations to estimate an optimal RSS value at each location. Before using the G-SSL method, the Linear Regression (LR) algorithm is proposed to solve the device diversity problem in crowdsourcing system. Since the spatial distribution of the APs is sparse, the Compressed Sensing (CS) method is applied to precisely estimate the location of the APs. Based on the location of the APs and a simple signal propagation model, the RSS difference between different locations is calculated and used as an additional constraint to improve the performance of G-SSL. Furthermore, to exploit the sparsity of the weights used in the G-SSL, we use the CS method to reconstruct these weights more accurately and make a further improvement on the performance of the G-SSL. Experimental results show improved results in terms of the smoothness of the radio map and the localization accuracy.

With the proliferation of locating devices, more and more raw spatial trajectories are formed, and many works enrich these raw trajectories with semantics, and mine patterns from both raw and semantic trajectories, but access control of spatial trajectories is not considered yet. We present a multi-policy secure model for semantic spatial trajectories. In our model, Mandatory Access Control, Role Based Access Control and Discretionary Access control are all enforced, separately and combined, and we represent the model semi-formally in Ontology Web Language.

Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectant, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic, and transcriptomic changes caused by disinfectant exposure in gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from exposure of gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of gram-negative bacteria in increasingly higher subMICs of NaOCl disinfectant was sufficient to increase the MIC to >2,500 µg/ml NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (P<0.01). Investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1,250 µg/ml NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to increased expression of the resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.

Excessive oxidative stress and exercise-induced fatigue reduce physical performance and can lead to dysfunction in antioxidant systems within muscular and hepatic tissues. Integrating natural substances with exercise may mitigate fatigue via anti-oxidant effects. This study aims to compare and evaluate the effects of exercise and supplementation with Sundarbans honey vs energy drinks on the strength, anxiety physiological profiles, and hepatic antioxidant capacity in mice undergoing extraneous exercise and fatigue. Forty-eight four-week-old Swiss albino mice were randomly assigned to one of eight groups: (1) Control, (2) Speed™ (Sp), (3) Royal Tiger™ (RT), (4) Sundarbans Honey (SH), (5) Exercise (Ex), (6) Exercise + Sundarbans Honey (Ex+SH), (7) Exercise + Speed™ (Ex+Sp), and (8) Exercise + Royal Tiger™ (Ex+RT). Supplements were administered via oral gavage: Sp (2.5 ml/kg BW), RT (2.5 ml/kg BW), and SH (1 g/kg BW), four times a week for 60 days. Mice in the Ex, Ex+SH, Ex+Sp, and Ex+RT groups underwent daily swimming and running. The strength, fatigue, anxiety levels, lipid profiles, and antioxidant biomarkers were evaluated post-treatment. The SH, Ex, and Ex+SH groups exhibited significantly enhanced physical performance (p

Kawasaki disease is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as disease progresses with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated to KD, but also evaluates the possibility of using circulating endothelial injury biomarkers such as, circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tool of KD: a “liquid biopsy” approach. The challenges of translating liquid biopsies to use in KD, and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostics is promising and we hope this will be translated to clinical applications in the near future.

As precision medicine such as targeted therapy and immunotherapy often have limited accessibility, low response rate and evolved resistance, it is urgent to develop simple, low-cost, and quick-turnaround personalized diagnostic technologies for drug response prediction with high sensitivity, speed, and accuracy. Major challenges of drug response prediction strategies employing digital database modeling are the scarcity of labeled clinical data, applicable only to a few classes of drugs, and losing the resolution at the individual patient level. Although these challenges have been partially addressed by large-scale cancer cell line datasets and more patient-relevant cell-based systems, the integration of different data types and data translation from pre-clinical to clinical utilities are still far-fetched. To overcome current limitations of precision medicine with a clinically proven drug response prediction assay, we have developed an innovative and proprietary technology based on in vitro patient testing and in silico data analytics. First, a patient-derived gene expression signature was established via transcriptomic profiling of cell-free mRNA (cfmRNA) from the patient’s blood. Second, a gene-to-drug data fusion and overlaying mechanism to transfer data was performed. Finally, a semi-supervised method was used for database searching, matching, annotation and ranking of drug efficacies from a pool of ~700 approved, investigational or clinical trial drug candidates. A personalized drug response report can be delivered to inform clinical decision within a week. The PGA (Patient-derived Gene expression-informed Anticancer drug efficacy) test has significantly improved patient outcomes when compared to the treatment plans without PGA support. Implementation of PGA, which combines patient-unique cfmRNA fingerprints with drug mapping power, has the potential to identify treatment options when patients are no longer responding to therapy and when standard-of-care is exhausted.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor stability and low bioavailability. This study investigated solid particle-in-oil-in-water (S/O/W) emulsions stabilized by whey protein isolate (WPI) and sodium caseinate (NaCas) as carriers to enhance the bioavailability and intestinal absorption of EGCG. Molecular docking revealed binding interactions between EGCG and these macromolecules. The emulsions exhibited high encapsulation efficiencies and augmented EGCG bioaccessibility by 64% compared to free EGCG in a simulated gastrointestinal digestion model. EGCG-loaded emulsions demonstrated minimal cytotoxicity towards Caco-2 cells and facilitated EGCG transport across the intestinal epithelial layer without compromising tight junction integrity. Notably, EGCG-loaded emulsions protected Caco-2 cells against oxidative stress by suppressing intracellular reactive oxygen species generation. The results demonstrate the potential of WPI- and NaCas-stabilized S/O/W emulsions to enhance the bioavailability, intestinal absorption, and bioactivity of EGCG, expanding its applications in functional foods and nutraceuticals.

Progress in laser-driven proton acceleration requires increasing the proton maximum energy and laser-to-proton conversion efficiency, while reducing the divergence of the proton beam. However, achieving all these qualities simultaneously has proven challenging experimentally, the increase in beam energy often coming at the cost of beam quality. Numerical simulations suggest that coupling multi-PW laser pulses with ultrathin foils could offer a route for such simultaneous improvement. Yet experimental investigations have been limited by the scarcity of such lasers and the need for very stringent temporal contrast conditions to prevent premature target expansion before the pulse maximum. Here, combining the newly commissioned Apollon laser facility that delivers high-power ultrashort (∼24fs) pulses, with a double plasma mirror scheme to enhance its temporal contrast, we demonstrate the generation of up to 35 MeV protons with only 5 J of laser energy. This approach also achieves improved laser-to-proton energy conversion efficiency, reduced beam divergence, and optimized spatial beam profile. Therefore, despite the laser energy losses induced by the plasma mirror, the proton beams produced by this method are enhanced on all accounts compared to those obtained under standard conditions. Particle-in-cell simulations reveal that this improvement results from the intensified electrostatic field caused by a more compact hot-electron distribution.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Background: Capmatinib and savolitinib, selective MET inhibitors, are widely used to treat various MET-positive cancers. In this study, we aimed to determine the effects of these inhibitors on MET-amplified gastric cancer (GC) cells. Methods: After screening 37 GC cell lines, the following cell lines were found to be MET-positive with copy number variation > 10: SNU-620, ESO51, MKN-45, SNU-5, and OE33 cell lines. Nest, we assessed the cytotoxic response of these cell lines to capmatinib or savolitinib alone using cell counting kit-8 and clonogenic cell survival assays. Western blotting was performed to assess the effects of capmatinib and savolitinib on the MET signaling pathway. Xenograft studies were performed to evaluate the in vivo therapeutic efficacy of savolitinib in MKN-45 cells. Results: Savolitinib and capmatinib exerted anti-proliferative effects on MET-amplified GC cell lines in a dose-dependent manner. Savolitinib inhibited the phosphorylation of MET and downstream signaling pathways, such as the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways, in MET-amplified GC cells. Additionally, savolitinib significantly decreased the number of colonies formed on the soft agar and exerted dose-dependent anti-tumor effects in a MKN-45 GC cell xenograft model. Furthermore, combination of trastuzumab and capmatinib exhibited enhanced inhibition of AKT and ERK activation in human epidermal growth factor receptor-2 (HER2)- and MET-positive OE-33 cells. Conclusions: Therefore, targeting MET with savolitinib and capmatinib efficiently suppressed the growth of MET-amplified GC cells. Moreover, these MET inhibitors exerted synergistic effects with trastuzumab on HER2- and MET-amplified GC cells.

For the first time, the effect of a significant change in the resistance of the aquatic environment of a population of protozoan microorganisms under the influence of radiofrequency electromagnetic radiation from cell phones has been experimentally studied. The results of the experiment demonstrate the biological nature of the changes occurring in the “water population of protozoa” system, which indicates that the impact of radiation directly affects the cell. This conclusion is confirmed by the same order of magnitude time of information exchange between individual individuals of the population in the calculation and in the experiment. An extremely low concentration of protozoa in the experiment was established, equal to 1000 pcs./liter, at which the indicated effect is observed.An unambiguous dependence of the biological effect in the “water – amoeba population” system on the average power of electromagnetic radiation of cell phones, both in standby mode and in talk mode, has been established. It is concluded that the presented method of changing the physical properties of the aquatic environment of a population of protozoa under the influence of electromagnetic fields can be a model experiment in identifying the mechanisms of interaction of biological systems with electromagnetic radiation, determining the response time of biological systems to external electromagnetic influence, and establishing the degree of influence of radiation in the 4G, 5G ranges.

This paper investigates an innovative photovoltaic cell configuration, denoted as “Au/CuSCN/RbGeI3/CdTe/ZnO/TiO2/FTO", using SCAPS-1D simulation. The research focuses on optimizing device performance by analyzing key components, including ZnO as the electron transport layer (ETL), RbGeI3 as the perovskite absorber layer, CuSCN as the hole transport layer (HTL), and CdTe as the active buffer layer. A comparison is made with the standard “Au/CuSCN/CH3NH3SnI3/CdTe/ZnO/TiO2/FTO" configuration under dark and illuminated conditions. Through an in-depth investigation involving temperature effects, generation rate analysis, RbGeI3 absorber layer thickness, Nd level, and interface defect levels, an optimized design for a unit area is achieved. The proposed solar cell demonstrates outstanding performance metrics, including an open circuit voltage (Voc) of 0.94V, a short circuit current density (Jsc) of 34.52mA/cm2, a fill factor (FF) of 77.77%, and an energy conversion efficiency (η) of 25.40%. These values significantly outperform the reference models with energy conversion efficiencies of 10.11% and 21.09%. Real-world applicability is validated by implementing these optimized characteristics in a photovoltaic system for Pakistan’s geographical location using PVSyst software. The suggested solar cell achieves a remarkable performance ratio (PR) of 85.6%, surpassing the PR of the reference basic solar cell model at 83%. The findings of this research offer a promising and superior solar cell design, incorporating innovative materials and optimization techniques to achieve exceptional energy conversion efficiency and overall performance. This study’s outcomes have the potential to advance photovoltaic technology and contribute to sustainable energy solutions worldwide.

The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

As marine traffic is contributing to pollution and mostly have predictable route with repetitive load profiles, to reduce their impact on environment, hybrid system with proton exchange membrane fuel cells (PEMFC-s) and battery pack, is promising replacement. For this purpose, the numerical model of repowered existing vessel that have two diesel engines with 300 kWe is developed. The goal of this paper is to develop numerical model which analyzes and determine equivalent hybrid ship propulsion system for known traveling route. The developed numerical model consists of an interconnected system with PEMFC stack and battery pack as power sources. Numerical model is developed and optimized to meet minimal required power demand for successful route demand, which has variable loads and daily sails six-time same voyage- in total 54 nautical miles. The results have shown that equivalent hybrid power system consists of 300 kWe PEMFC stack and battery pack with 424 kWh battery and state of charge varying between 20 and 87%. To power this new hybrid power system, hydrogen tank of 7200 l holding 284.7 kg at pressure of 700 bar is needed, compared to previous system that spend 1524 kg of diesel and generate 4886 kg of CO2.

Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine’s anticancer activity together with that of three other bisindoles - conophylline, leucophyllidine and bipleiophylline against human-derived carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (as observed in MDA-MB-468 breast cancer cells) or senescence (as detected in HT-29 colorectal carcinoma cells). Annexin V-FITC/PI, caspase activation and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Evident cell cycle perturbations were observed comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed induction of aberrant mitotic phenotypes - multi-nucleation, membrane blebbing and DNA-fragmentation. The DNA integrity assessment of HCT-116 and MDA-MB-468 showed irreparable damage identified by increased fluorescent γ-H2AX during the G1 cell cycle phase. Furthermore, γ-H2AX foci were visually validated in HCT-116 and MDA-MB-468 cells using confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by NQO1 expression. Collectively, we present conofolidine as a potential anticancer candidate capable of inducing heterogeneous modes of cancer cell death in vitro, encouraging further preclinical evaluation of this natural product.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

Chromosome segregation in female germ cells and early embryonic blastomeres is known to be highly prone to errors. The resulting aneuploidy is therefore the most frequent reason for termination of early development and embryo loss in mammals. And when compatible with embryonic and foetal development, aneuploidy leads into severe developmental disorders. The main surveillance mechanism, essential for protection of cells against aneuploidy, is the Spindle Assembly Checkpoint (SAC). And although all eukaryotic cells are perhaps able to mount SAC response, it is not clear, whether this pathway is active in all cell types, including blastomeres of early embryos. In this review, we will summarize and discuss the published literature with regards to mechanisms controlling chromosome segregation in early embryos. Our conclusion is that early embryos show limited capabilities to react to chromosome segregation defects, which might, at least partially, explain the widespread problem of aneuploidy during early development.

The principal barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses despite antiretroviral therapy (ART). HIV-1 transcriptional suppression, referred to as viral latency, is foremost among persistence determinants, as it allows infected cells to evade the cytopathic effects of virion production and killing by cytotoxic T lymphocytes (CTL) and other immune factors. HIV-1 persistence is also governed by cellular proliferation, an innate and essential capacity of CD4+ T cells that both sustains cell populations over time and enables a robust directed response to immunological threats. Yet when HIV-1 infects CD4+ T cells, this capacity for proliferation can counterproductively enable surreptitious HIV-1 propagation without the deleterious effects of viral gene expression in latently infected cells. Over time on ART, the HIV1 reservoir is shaped by both persistence determinants, with selective forces most often favoring clonally expanded infected cell populations harboring transcriptionally quiescent proviruses. Moreover, if HIV latency is incomplete or sporadically reversed in clonal infected cell populations that are replenished faster than they are depleted, such populations could both persist indefinitely and contribute to low-level persistent viremia during ART and viremic rebound if treatment is withdrawn. In this review, select genetic, epigenetic, cellular, and immunological determinants of viral transcriptional suppression and clonal expansion of HIV-1 reservoir T cells, interdependencies among these determinants, and implications for HIV-1 persistence will be presented and discussed.

A typical solid-state quantum sensor can be developed based on negatively charged nitrogen-vacancy (NV-) centers in diamond. The electron spin state of NV- can be controlled and read at room temperature. Through optical detection magnetic resonance (ODMR) technology, temperature measurement inside living cells can be achieved at the nanoscale. The key to ODMR technology is to apply microwave resonance to manipulate the electron spin state of NV-. Therefore, the microwave field characteristics formed near the NV- have a crucial impact on the sensitivity of ODMR measurement. This article mainly focuses on the temperature situation in cellular applications, and simulates the influence of structural parameters of double open loop resonant (DOLR) microwave antennas and broadband large-area (BLA) microwave antennas on the microwave field’s resonance frequency, quality factor Q, magnetic field strength, uniformity, etc. The parameters are optimized to have sufficient bandwidth, high signal-to-noise ratio, low power loss, and high magnetic field strength in the temperature range of 36 ℃ to 42.5 ℃. Finally, the ODMR spectra are used for effect comparison, and the signal-to-noise ratio and Q values of the ODMR spectra are compared when using different antennas. We have provided an optimization method for the design of microwave antennas and it is concluded that the DOLR microwave antenna is more suitable for living cell temperature measurement in our study.

The genus Euonymus (L.) consists of shrubs or woody plants, distributed mainly in the Northern Hemisphere. To date, from Euonymus spp. several hundreds of different secondary metabolites have been isolated and identified. In addition, fatty oil was found in the fruits of some species of these plants, which accumulates not only in the seeds, but also in the arils. This study presents the research of unique long-term (ten-year-old) suspension cell cultures of Euonymus maximoviczianus Prokh. which were obtained from arils of unripe capsules. Suspension cells retain the ability to form oil droplets containing neutral lipids, both in the dark and in the light, the cells are able to synthesize very-long-chain fatty acids (VLCFAs), and can synthesize delphinidin-3-O-hexoside, cyanidin-3-O-hexoside, and peonidin-3-O-hexoside. Here, we research of the fatty acid, VLCFA, and anthocyanin biosynthesis dynamics in the subcultivation, as well as the influence of methyl jasmonate (MeJa) on these processes in the dark- and under-light-grown cell cultures. In the darkness, the formation of VLCFAs is more intense, and the biosynthesis of anthocyanins is significantly activated in the light. MeJA substantially enhances the biosynthesis of anthocyanins in the light and, surprisingly, the formation of VLCFAs in the darknss. In connection with the commonality of the cytosolic pool of malonyl-CoA, which is necessary both for the biosynthesis of VLCFAs and dihydroflavonols (and, ultimately, anthocyanins), the competition of these biosynthetic pathways is discussed.

Background: PD1 and its ligand PD-L1 are related to the prognosis in many solid tumors, whether its role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: Retrospective monocentric study including all patients with OSCC diagnosed and treated between 01/2020 and 05/2022. PD-L1 expression was assessed by combined positive score (CPS), considering CPS > or equal to 1 as positive (1-20 “low expression”, and ≥20 “high”). Descriptive analysis of patient cohort and tumors was performed, including tumor size, stage, lymph node involvement, recur-rence and survival. Results: 65 patients (65 tumors) were analyzed. 66.15% of tumors were ad-vanced stages (III-IV), of them, 97.67% PD-L1+ versus 71.42% within early stages (I-II). T4 tumors expressed PD-L1 in 100% of cases, compared with 54’54% in T1 tumors. 50.79 % of tumors showed lymph node involvement (pN+), 100% of them showing PD-L1+. Prevalence of pN+ was 59.38% for PD-L1 high expression versus 40.63% for low expression. Patients' follow-up ranged from 2 to 34.5 months. No significant difference was seen between overall survival (OS) and PD-L1 +/- (CPS ≥1 vs CPS <1) neither PD-L1 high (CPS ≥20) vs low CPS <20) (p 0.97 and 0.64, re-spectively). Conclusions: The method used to measure (laboratory test with Dako 22C3 an-ti-PD-L1 primary antibody) PD-L1 was reliable and accurate, with a correlation coefficient be-tween the PD-L1 expression in the biopsy and surgical piece of 0.83 (p 0.0001). CPS≥1 was ob-served in large tumors (p<0.001), and was correlated with of lymph node metastases (p<0.004). Further analysis of PD-L1 expression and its relevance in tumor biology and prognosis is needed.

Exosomes, a subset of extracellular vesicles, have emerged as pivotal mediators of intercellular communication, revolutionizing our comprehension of cellular interactions. Their diverse cargo, comprising proteins, nucleic acids, and bioactive molecules, plays a crucial role in various physiological and pathological processes. In the intricate landscape of adult neurogenesis, exosomes wield significant influence, actively participating in the generation of new neurons within the adult mammalian brain. Originating predominantly from non-niche cells, these vesicles contribute substantially to the regulation of neuroinflammation, thereby impacting neurogenesis and offering therapeutic promise for neurological disorders. In the specific context of Parkinson's disease (PD), exosomes assume a multifaceted role, prominently implicated in the propagation of α-synuclein oligomers and the orchestration of neuroinflammation. Stem cell-derived exosomes present themselves as promising therapeutic agents, capable of reshaping the microenvironment, repairing neuronal damage, and mitigating apoptosis. The ongoing exploration of exosomes continues to unravel intricate biological processes, paving the way for innovative medical interventions and treatments, particularly within the challenging landscape of neurodegenerative diseases such as PD. The comprehensive understanding of exosomal functions holds the potential to advance our therapeutic approaches, offering new avenues for intervention and treatment strategies in the realm of neurodegenerative disorders.

Despite great strides in diagnosis and treatment, cardiac diseases remain the number one cause of mortality in the developed world, with rates catching up at an alarming rate in the developing world. Targeted delivery of therapeutics, specifically to cardiomyocytes, would open up new frontiers. Our prior work using a combinatorial in vitro and in vivo phage display methodology identified a 12-amino acid long peptide that targets cardiomyocytes selectively after an intravenous injection in as little as 5 mins, and hence was termed cardiac targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension for development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed on the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10µM of Cyanine-5.5 labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by more extensive studies performed by Eurofins in stably transfected cell lines for an extensive list of GPCR-coupled receptors. Positive data for GPCR-coupled receptors was interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting 60, 6-week-old, wild-type CD1, male/female mice (1:1) injected with CTP (150 µg/Kg) intravenously. Mice were weighed immediately before injections and daily thereafter. Cohorts of mice were euthanized on day 0, 1, 2, 7 and 14 with inhalational CO2, followed by opening of the chest cavity, collection of blood via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after injections of CTP (150 µg/Kg) to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. In the Eurofins Cardiac Profiler Qube, no significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed by RT-qPCR. There was no change in blood pressures before and after injections with CTP at 10 mg/Kg. Blood counts and chemistries showed no evidence of significant hematological, hepatic or renal toxicities. Lastly, there was no significant difference in cardiac function, size or mass before and after CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies, in good laboratory practices fashion, are needed with more prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

. Background: regular exercise elicits adaptive changes from several organs and physiological processes, including erythrocyte properties. Methods: in a group of 79 subjects (62 men and 17 women; mean age 31.37 +/- 10.19 years) who trained several times a week as they practiced amateur sports, we evaluated the elongation index, marker of erythrocyte deformability, the red blood cell distribution width (RDW), indicator of erythrocyte anisocytosis, hematocrit, hemoglobin and the main erythrocyte indices (MCV, MCH, MCHC) in basal conditions. Results: in comparison with a group of healthy not trained volunteers, the values of the elongation index, and not the RDW, are increased and this datum is accompanied by an increase of MCV and MCHC, likely related to an increased presence of circulating young erythrocytes in trained subjects. We also divided the same group according to the median of the VO2max, observing that the subgroup above the median shows both an increase in the elongation index values and a decrease in MCH and MCHC. Conclusions: in trained subjects there is no correlation between the values of elongation index and the RDW, while of particular interest and of a certain complexity seem the interrelations among elongation index, RDW and the main erythrocyte indices.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell penetrating peptides (CPP) are 5-30 amino acid long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood-brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell or tissue specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for myriad different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outlining its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.

Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease characterized by mature B-cell neoplasms. The standard immunochemotherapy for DLBCL is R-CHOP, which includes rituximab, cyclophosphamide, doxoru-bicin, vincristine, and prednisone. Up to 30-40% of patients with DLBCL either exhibit primary refractory disease to standard treatment or experience relapse after the initial response. A 72-year-old man diagnosed with DLBCL involving chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) showed primary refractory disease after the fourth cycle of R-CHOP. The patient ultimately experienced cardiac involvement by the lymphoma and received salvage chemotherapy. He passed away about 15 months away after the diagnosis of DLBCL. We conducted fluorescence in situ hybridization (FISH) for further analysis of the chromosomal translocations. The breakpoint of chromosome 1q21 was located at a distance of around 151 Mb from the telomeric end of chromosome 1p. The breakpoint in chromosome 22q11 contains the immunoglobulin lambda locus. Furthermore, the breakpoint of chromosome 6p was in the telomeric region of chromosome 6p21. The breakpoint of chromosome 18q21 contains BCL2. This case report presents the first documented co-occurrence of chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) in a patient with DLBCL. These chromosomal translocations may indicate a worse clinical outcome.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for viral hepatitis, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777–0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

Aim: Glioblastoma multiform (GBM) is a prevalent brain cancer which accounts for 80% of cases globally with a noticeably short life expectancy subsequent diagnosis. There are several factors associated with GBM including alterations and over expressions of oncoproteins. Analysis of SEC61G expression in GBM patient’s favor tumour progression, which promotes an environment of oxidative stress, while preventing apoptosis. Methods: In this article using in silico tools including GEPIA2, ULCAN, LinkedOmics, Gene MANIA and mirTEd, we observed the role of SEC61G gene in GBM progression by analyzing the expression, positive correlation associated with metabolic, mitochondrial gene, immune cell infiltration level, gene interaction networks, miRNA association as well as survival analysis. Results: The expression of the mitochondrial, metabolic genes PGLS, PGK1, EIF6, and EIF3K which are involved in redox metabolism and CD63 immunoregulation, as well as other genes that promote tumour progression and invasion, including EGFR, LANCL2, BCL2L12, SEC61G-DT, KDELR1, CDKN2A, IFNA16, IFNA10, and BCL7C were positively correlated with the increased/high expression of SEC61G.We also found hsa-mir-380-5p to be unregulated in glioblastoma phenotypes. Conclusion: Our findings suggest that SEC61G associated redox metabolism, complement system and immunoregulation, as well as miRNA expression can be targeted to develop a potential therapeutic approach for GBM patients.

The utilization of fuel cells (FC) in automotive technology has experienced significant growth in recent years. Fuel cell hybrid electric vehicles (FCHEVs) are powered by a combination of fuel cells, batteries, or/and ultracapacitors (UCs). By integrating power converters with these power sources, the FCHEV system can overcome the limitations of using them separately. The performance of an FCHEV is influenced by the efficiency of the power electronics converter controller, as well as the technical efficiency of the power sources. FCHEVs need intricate energy management systems (EMSs) to function effectively. Poor EMS can lead to low efficiency and accelerated fuel cell and battery degradation. The literature discussed various types of EMSs, such as equivalent consumption minimization strategy, classical PI controller, fuzzy logic controller, and Mutative Fuzzy Logic Controller (MFLC). However, comparing different EMSs can be challenging due to the varying vehicle and system parameters, which might lead to false claims being made regarding system performance. This research aims to categorize and discuss the various topologies of FCHEVs, highlighting their pros and cons, and comparing several EMSs based on performance metrics such as State of Charge (SOC) and FC deterioration.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

There are compelling evidences that the immune system is to confer protection not only against foreign pathogens but also against cancer. But if the immune system can’t detect every malignant cell, and at the same time a suitable tumor microenvironment (TME) is formed by inflammatory processes, a carcinogenesis is not longer to be blocked. Once the tumor cells have found their niche, the tumor cells are trained by immune cells turned inside out in how to deal with the immune system "out there". The TME is a training camp and protected space for tumor cells. The Corona crisis has revived a therapeutic approach that was thought to be almost dead: RNA vaccines. Despite decades of research and many clinical studies, no registered RNA cancer vaccine exists today. But the SARS-CoV-2 RNA vaccines against COVID-19 disease have demonstrated their dangerous weaknesses. RNA vaccines manipulate the innate immunity and make the body susceptible to any viral infection. There is also the possibility of integration into the genome. The few approved therapeutic cancer vaccines show little effect. Despite some successes, immunotherapies remain ineffective for most patients with cancer. Powerful therapeutic cancer vaccines remain an unfulfilled dream, a misconception.

It has been more than three decades since the discovery of multifunctional factors, Non-POU Domain-Containing Octamer-Binding Protein, NonO and Splicing Factor, Proline-and Glutamine-Rich, SFPQ. Some of their functions, including their participations in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization have been well-documented. In this review, we focus on the roles of NonO and SFPQ in cell cycle with particular attention to their participation in nonhomologous end joining (NHEJ) and homologous recombination (HR) of DNA damage responses induced by irradiation. In these contexts, absence or malfunction of either or both lead to genome instability and ultimately to apoptosis, cellular senescence, and tumor development. This review also will shed light on NonO and SFPQ function in DNA/RNA/protein binding and their association with Ku heterodimer of the NHEJ pathway required for repair of DNA double-strand breaks (DSBs).

Cell sheet (CS) engineering using human MSC is of significant interest for regenerative medicine and this rapidly growing field translates to clinical use in a number of indications. Nevertheless, little is known of factors that define the timing of CS assembly from primary cultures which is important for planning treatments in both – autologous and allogeneic modes of use. We used a comparative in vitro approach with primary donors’ (n=14) adipose-derived MSC and evaluated the impact of healthy subject’s characteristics (age and sex), MSC culture features (population doubling time and lag-phase) and extracellular matrix (ECM) composition along with factors related to connective tissue formations (-SMA and FAP-) on CS assembly duration.

Determination of the fetal gender in the first trimester is important in twin pregnancy cases of familial X-linked genetic syndromes and helps determine chorionicity. We assessed and compared the accuracy of first-trimester ultrasound scans, and circulating cell-free fetal DNA (cffDNA) performed by non-invasive prenatal screening (NIPS) in determining fetal gender in the first trimester of twin pregnancies. For this purpose, we enrolled prospectively pregnant women with twin during the first trimester, gestational week (GA) 11-13. The fetal gender was determined using both ultrasound scans and cffDNA screening. Both results were compared to the newborn gender at delivery. A total of 113 women with twin pregnancies were enrolled. There was 100% sensitivity and specificity in Y chromosome detection using cffDNA. The accuracy of gender assignment using ultrasound in any first-trimester scans was 79.7%. Accuracy level increased from 54.2% in CRL 45-54 mm to 87.7% in CRL 55-67 mm and 91.5% in CRL 67-87 mm. Male fetuses had significantly higher chances of a gender assignment error compared to female fetuses, odds ratio = 23.57 (CI 7.356 - 75.66). This is the first study that compared the accuracy of gender determination in the first trimester by cffDNA and by ultrasound scanning in twin pregnancy. It was concluded that the cffDNA is highly sensitive and specific in determining the presence of the Y chromosome in twin pregnancies in the first trimester. Between CRL 67-87 mm, ultrasound scanning offers a highly accurate determination of fetal gender in twin pregnancies. Larger cohorts of multi-center studies are warranted.

Cancer researchers are fascinated by the chemistry of diverse natural products which show exciting potential as anticancer agents. In this study, we aimed to investigate the anticancer properties of watermelon rind extract (WRE) by examining its effects on cell proliferation, apoptosis, senescence, and global gene expression in human renal cell adenocarcinoma cells (HRAC-769-P) in vitro. Our metabolome data analysis of WRE exhibited untargeted phyto-constituents and targeted citrulline (22.29 µg/mg). HRAC-769-P cells were cultured in RPMI-1640 media and treated with 22.4, 44.8, 67.2, 88.6, 112, 134.4, and 156.8 mg mL-1 for 24, 48, and 72 hrs. At 24 hrs after treatment, (88.6 mg ml-1 of WRE) cell proliferation significantly reduced, more than 34% compared to the control. Cell viability decreased 48 and 72 hours after treatment to 45% and 37%, respectively. We also examined poly caspase, SA-beta-galactosidase (SA-beta-gal), and wound healing activities using WRE. All treatments induced an early poly caspase response and a significant reduction in cell migration. Further, we analyzed the transcript profile of the cells grown at 44.8 mg ml-1 of WRE after 6 hours using RNA sequencing (RNAseq) analysis. We identified 186 differentially expressed genes (DEGs), including 149 upregulated genes and 37 downregulated genes, in cells treated with WRE compared to the control. The differentially expressed genes were associated with NF-Kappa B signaling and TNF pathways. Crucial apoptosis-related genes such as BMF, NPTX1, NFKBIA, NFKBIE, and NFKBID might induce intrinsic and extrinsic apoptosis. Another possible mechanism is a high quantity of citrulline may lead to induction of apoptosis by the production of increased nitric oxide. Hence, our study suggests the potential anticancer properties of WRE and provides insights into its effects on cellular processes and gene expression in HRAC-769-P cells.

A teratoma is a neoplasm composed of cell populations or tissues that remind, in their appearance, normal elements derived from at least two embryonic layers. Fetal mature teratomas are normally benign, cystic, and typically occur along the midline, while they are rare in the posterior mediastinum. Teratomas are frequently solitary, however they may sometimes be associated with other congenital anomalies and/or with chromosomal abnormalities. Clinically, they are often asymptomatic but can occasionally cause compression symptoms. Prenatal diagnoses are uncommon and made with ultrasonography; differential diagnosis with other congenital conditions is mandatory. We report the case of a 21 weeks of gestational age-old fetus with a Mature Triphyllic Fetal Cystic Teratoma, grade 0, located in the right posterior mediastinum.

Elevation of the intermediate amino acid metabolite Homocysteine (Hcy) causes Hyperhomocysteinemia (HHcy), a metabolic disorder frequently associated with mutations in the methionine-cysteine metabolic cycle as well as with nutritional deficiency and aging. Previous literature suggest that HHcy is a strong risk factor for cardiovascular diseases. Severe HHcy is well established to correlate with vascular pathologies primarily via endothelial cell death. Though moderate HHcy is more prevalent and associated with an increased risk of cardiovascular abnormalities in later part of life, its precise role in endothelial physiology is largely unknown. In this study, we report that moderate elevation of Hcy causes endothelial dysfunction through impairment of their migration and proliferation. We established that unlike severe elevation of Hcy, moderate HHcy is not associated with suppressed endothelial VEGF/VEGFR signaling and oxidative stress induction. We further showed that moderate HHcy induces a sub-lethal ER stress that causes defective endothelial migration through abnormal actin cytoskeletal remodeling. We also found that sub-lethal increase of Hcy causes endothelial proliferation defect by suppressing mitochondrial respiration and concomitantly increases glycolysis to compensate the consequential ATP loss and maintain overall energy homeostasis. Finally, analyzing an available microarray dataset, we confirmed that these hallmarks of moderate HHcy are conserved in adult endothelial cells as well. Thus, we identified adaptive UPR and metabolic rewiring as two key mechanistic signatures in moderate HHcy-associated endothelial dysfunction. As HHcy is clinically associated with enhanced vascular inflammation and hypercoagulability, identifying these mechanistic pathways may serve as future targets to regulate endothelial function and health.

Advanced genomics, transcriptomics and epigenomics techniques are providing unprecedented insights into the understanding of the molecular underpinnings of the central nervous system, including the neuro-sensory cochlea of the inner ear. Here, we report for the first time a comprehensive and updated overview of the most advanced omics techniques for the study of nucleic acids, and their applications in cochlear research. We describe the available in vitro and in vivo models for hearing research, the principles of genomics, transcriptomics and epigenomics, alongside their most advanced technologies (like single cell omics and spatial omics), which allows to investigate the molecular events that occur at single cell resolution retaining the spatial information.

The objective of this research was to evaluate the physicochemical and sanitary parameters of raw cow's milk intended for consumption in the Amazonas region, Peru. We sampled 31 collection centers and dairy processors. We evaluated physicochemical parameters (fat, protein, solids not fat, lactose, ash, pH, and density), somatic cell count, and microbiology (mesophilic aerobic bacteria and total coliforms) of raw milk. We applied an analysis of variance (α=0.05) and the comparison of means between the collection centers and livestock basins (p&lt;0.05). In addition, we performed a cluster analysis, principal components and correlation. Depending on the collection center, we found differences in all the physicochemical parameters, somatic cell count and milk microbiology. In the livestock basin analysis, we found differences for somatic cells, fat, protein, solids, pH, coliforms and bacteria. The Jumbilla basin presented less somatic cells, less fat was found in the Levanto basin and higher protein in the Yambrasbamba basin. Lactose, ash, density, total coliforms and mesophilic aerobic bacteria did not vary according to basin. The cluster analysis yielded four groups, Group 1 is higher in ash and density, Group 2 and 3 are higher in fat, Group 3 with higher protein, but higher in total coliforms and mesophilic aerobic bacteria. Group 4 registered the highest pH and the lowest protein concentration. There was a positive correlation of fat with protein and solids not fat, lactose with solids not fat, ash with density. Negative correlations of somatic cells with fat and, protein and solids not fat with pH.

The blended perfluorinated sulfonic acid ionomers are prepared to have equivalent weight (EW) ~1000, 980, and 830. The catalyst layers (CLs) using blended PFSA ionomers with different side chain lengths and EWs are investigated, compared to the CLs utilizing single ionomers. The IEC results indicate that the blended ionomers have the targeted EWs. As a result, it is found that the blended ionomers exhibit higher ion conductivity than the single ionomers at all temperatures due to higher water uptake of the blended ionomers. Even though they have a similar EW, it implies that the blended ionomers have bulk structure to form competent free volume. The blended ionomers with short side chain (SSC) and low EW can help reduce the activation energy due to the enhanced hydrophobic and hydrophilic segregation. In addition, it is observed that the catalyst layers using the blended ionomer form more porous microstructure to help reduce the resistance of oxygen transport and attributes to lower mass transfer loss. This effect is significantly revealed in the fuel cell operation at not the lower temperature (70 °C) and full humidification (100%) but the elevated temperature (80 °C) and lower relative humidity (50 and 75%). The blended ionomer-based catalyst layers with higher water uptake and porous CL structure result in higher fuel cell performance and better mass transport than the single ionomer-based catalyst layers.

Industrial hemp (Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained an increasing interest in different fields, including medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicolog-ical effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31, on three cell lines se-lected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of pro-inflammatory cytokines compared to Etoposide used as positive control, and the basal level of inflammatory cytokines was not altered, suggest-ing a safety profile of hemp EOs and their NEs to support their use for medical applications.

To increase the efficiency of fuel processor and HT-PEMFC (High Temperature-Proton Exchange Membrane Fuel Cell) combined system, it is essential to improve the efficiency of a fuel processor. In this research, the fuel processor was simulated by Aspen Hysys® simulator, and effect of the various operating conditions on the total efficiency was investigated. Thermal efficiency of the fuel processor increased as the temperature and S/C (Steam to carbon) ratio increased, and the efficiency was higher at the S/C ratio of 3 than at the S/C of 4 at the reformer temperature of 700 ℃ and higher. Under the selected operating conditions of the fuel processor, recycling of unreacted hydrogen from the anode off gas (AOG) of the HT-PEMFC improve the overall efficiency of the combined fuel processer and HT-PEMFC by a factor of 1.28. Operating conditions where the AOG supplied excessive heat than required for fuel processor operation were excluded. The high-efficiency operating conditions of the fuel cell system were proposed with the target of 5 kW of output as the capacity of the household HT-PEMFC.

Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc and by a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading risk factor for glaucoma development. However, glaucoma can also develop at normal pressure levels. An increased susceptibility of retinal ganglion cells to IOP, systemic vascular dysregulation, endothelial dysfunction and autoimmune imbalances have been suggested to play a role in the pathophysiology of normal tension glaucoma. Since inflammation and oxidative stress play a role in all forms of glaucoma, the goal of this review article is to resent an overview on the inflammatory and prooxidant mechanisms in the pathophysiology of glaucoma and to discuss immunomodulatory and antioxidant treatment approaches.

Bromodomain (BRD)-containing proteins are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD protein dysfunction has been linked to many diseases, including tumorigenesis. However, the role of BRD proteins in the pathogenesis of uterine fibroids (UFs) is entirely unknown. The present study aimed to determine the expression pattern of BRD9 protein in UFs and matching myometrium and further assess the impact of BRD9 inhibitors on UF phenotype and epigenetic/epitranscriptomic changes. Our studies demonstrated that the levels of BRD9 were significantly upregulated in UFs compared to matched myometrium, suggesting that the aberrant BRD protein expression may contribute to the pathogenesis of UFs. We then evaluated the potential roles of BRD9 using its specific inhibitor I-BRD9. Targeted inhibition of BRD9 suppressed the UF tumorigenesis with increased apoptosis and cell cycle arrest, decreased cell proliferation, and extracellular matrix deposition in UF cells. The latter is the key hallmark of UFs. Unbiased transcriptomic profiling coupled with downstream bioinformatics analysis further and extensively demonstrated that targeted inhibition of BRD9 impacted the cell cycle- and ECM-related biological pathways, reprogrammed the UF cell epigenome and epitranscriptome, and altered miRNA-mediated gene regulation in UFs. Taken together, our data support the critical role of BRD9 in UF cells and the strong interconnection between BRD9 and other pathways controlling the UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment option for this most common benign tumor in women of reproductive age.

Abstract Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the β-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerizes and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes lead to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research, However, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia