(1) Background: The article gives us an insight into the key issues of the car-sharing and its impact on urban sustainability. (2) Methods: A selection of 314 articles published in peer-reviewed journals from the Scopus database were analysed using Leximancer 5.0 for Automated Content analysis. (3) Results: Seven themes were identified explaining the researched topic of the car-sharing situation in Europe, which are Sharing, Economy, Model, Systems, Electrical car-sharing, Policy and Travel. There are two ways of sharing owned cars in Europe, access to cars from the fleet of private organizations and P2P car-sharing. Sustainable environmental solutions in the context of the electrification of cars are used. Car-sharing usually takes place online and can be free or for a free as defined by The European Economic and Social Committee. (4) Conclusions: The article provides an overview of understanding the concept of urban car-sharing in Europe.

Free Floating Car Sharing (FFCS) services are a flexible alternative to car ownership. These transportation services show highly dynamic usage both over different hours of the day, and across different city areas. In this work, we study the problem of predicting FFCS demand patterns -- a problem of great importance to an adequate provisioning of the service. We tackle both the prediction of the demand i) over time and ii) over space. We rely on months of real FFCS rides in Vancouver, which constitute our ground truth. We enrich this data with detailed socio-demographic information obtained from large open-data repositories to predict usage patterns. Our aim is to offer a thorough comparison of several machine learning algorithms in terms of accuracy and easiness of training, and to assess the effectiveness of current state-of-art approaches to address the prediction problem. Our results show that it is possible to predict the future usage with relative errors down to 10%, and the spatial prediction can be estimated with relative errors of about 40%. Our study also uncovered the socio-demographic features that most strongly correlate with FFCS usage, providing interesting insights for providers opening service in new regions.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

The incidence of right-turning pedestrian accidents is increasing in South Korea. Most of the accidents occurred when the larger vehicle was turning right, and the main cause of the accidents was found to be the driver's limited field of vision. After these accidents, the government has implemented a series of institutional measures with the objective of preventing such accidents. However, despite the institutional arrangements in place, pedestrian accidents continue to occur. We focused on the many limitations that autonomous vehicles, like humans, can face in such situations. To address this issue, we propose a right-turn pedestrian collision avoidance system by installing a LiDAR sensor in the center of the intersection to facilitate pedestrian detection. Furthermore, the urban road environment is considered, as this provides the optimal conditions for the model to perform at its best. During this research, we collected data on right-turn accidents using the CARLA simulator and ROS interface and demonstrated the effectiveness of our approach in preventing such incidents. Our results suggest that the implementation of this method can effectively reduce the incidence of right-turn accidents in autonomous vehicles.

Evaluation ecosystem service value (ESV) is critical for “lucid waters and lush mountains are invaluable assets”. However, the ESV estimation and spatial-temporal analysis for mountainous soil erosion area is rare, e.g., Changting county, China. In this study, we developed a remote sensing driven mountainous equivalent factor (RS-MEF) method to estimate the ESV of soil erosion area in subtropical mountain. It is a hybrid of a conventional equivalent factor framework and the remote sensing techniques for mountains, and achieves several highlights of spatial adjustment using carbon sink with vegetation canopy, improvement spatial resolution, and removal topographic effect. Using the RS-MEF method, we estimated that the ESV of Changting county was about 15.80 billion CNY in 2010 and 34.83 billion CNY in 2022. Specifically, the ESV per unit area of major soil erosion area (MSEA) in the county was less than that of non-major soil erosion area (n-MSEA), however, the ESV growth rate of MSEA from 2010 to 2022 was faster than that of n-MSEA. Therefore, the ESV gap between two areas was shortened from 28.99% in 2010 to 15.83% in 2022. Topographic gradient effect analysis illustrates that the area with high elevation and small slope is one control focus in the next step. Our study indicates that the ecological restoration in the county has made great achievements in the ESV perspective, with low ESV area shrank evidently in MSEA; and the achieved knowledge of the ESV growth and inherent factors is valuable and instructive for the next soil and water conservation.

In 2012 the Open Geospatial Consortium published GeoSPARQL defining “an RDF/OWL ontology for [spatial] information”, “SPARQL extension functions” for performing spatial operations on RDF data and “RIF rules” defining entailments to be drawn from graph pattern matching. In the 8+ years since its publication, GeoSPARQL has become the most important spatial Semantic Web standard, as judged by references to it in other Semantic Web standards and its wide use for Semantic Web data. An update to GeoSPARQL was proposed in 2019 to deliver a version 1.1 with a charter to: handle outstanding change requests and source new ones from the user community and to “better present” the standard, that is to better link all the standard’s parts and better document & exemplify elements. Expected updates included new geometry representations, alignments to other ontologies, handling of new spatial referencing systems, and new artifact presentation. In this paper, we describe motivating change requests and actual resultant updates in the candidate version 1.1 of the standard alongside reference implementations and usage examples. We also describe the theory behind particular updates, initial implementations of many parts of the standard, and our expectations for GeoSPARQL 1.1’s use.

Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

In recent years, more and more health data are being generated. These data come not only from professional health systems, but also from wearable devices. All these data combined form ‘big data’ that can be utilized to optimize treatments for each unique patient (‘precision medicine’). To achieve this precision medicine, it is necessary that hospitals, academia and industry work together to bridge the ‘valley of death’ of translational medicine. However, hospitals and academia often have problems with sharing their data, even though the patient is actually the owner of his/her own health data, and the sharing of data is associated with increased citation rate. Academic hospitals usually invest a lot of time in setting up clinical trials and collecting data, and want to be the first ones to publish papers on this data. The idea that society benefits the most if the patient’s data are shared as soon as possible so that other researchers can work with it, has not taken root yet. There are some publicly available datasets, but these are usually only shared after studies are finished and/or publications have been written based on the data, which means a severe delay of months or even years before others can use the data for analysis. One solution is to incentivize the hospitals to share their data with (other) academic institutes and the industry. Here we discuss several aspects of data sharing in the medical domain: publisher requirements, data ownership, support for data sharing, data sharing initiatives and how the use of federated data might be a solution. We also discuss some potential future developments around data sharing.

Cybercrime Threat Intelligence (CTI) allows us to change our actions from reactive to proactive in the fight against threat actors, and to make more informed, data-driven security decisions. Thus this study proposes the practical implementation of CTI in the Arab world. This study focuses on strengthening CTI by integrating Indicators of Compromise (IoCs) and collecting realistic security alerts from honeypot systems and open source intelligence. The collected data is stored in the Malware Information Sharing Platform (MISP), an open source platform that allows users to create and share IoCs with other organizations while staying informed about new threats. It features an intuitive interface for data analysis and threat identification, facilitating sharing, storage, and correlation of IoCs. Therefore, we leveraged MISP to generate IoCs based on the collected data and analyzed the results to identify potential cyber threats. The implemented platform aims to provide organizations with actionable information to prevent, detect and respond to cybercrime. This study presents a practical approach to strengthening CTI in the Arab world and provides an opportunity to strengthen the region’s security posture.

Although the dockless bike-sharing system, which can be regarded as a typical example of the resource-sharing system, has been increasingly popular for years with people especially in China, the imbalanced distribution of shared bikes gradually becomes a major problem for both bike-sharing companies and their customers. To solve the imbalance problem, we aim to investigate the long-term performance of a system under the influence of some key factors (with an emphasis on the unequal demand between different nodes), which can guide us to discover the causes of the problem and offer several valuable suggestions to the operators. According to the fundamental principle of a dockless bike-sharing system, we propose a model reduction method to reduce the complexity of the theoretical network models, which are developed based on the Markovian queueing theory with the consideration of higher-demand nodes and lower-demand nodes. The theoretical network models provide us with steady-state probabilities of having a certain number of bikes at one node, which are used as an important part of the optimization model for solving the imbalance problem by carrying out an operator-based relocation strategy. The objective of the optimization model is to maximize the total profit and determine the optimal relocation frequency. It is found that most of the shared bikes are possible to gather at one low-demand node eventually in the long run under the influence of the different arrival rates at different nodes, but the decrease of the number of bikes at the high-demand nodes is more sensitive to the unequal demands and may cause a great loss for operators, which should be payed attention to especially when solving the relocation problems.

(1) Background: The study aimed to investigate compressive strength for three computer-aided design/computer-aided manufacturing (CAD/CAM) dental materials: glassceramic IPS Empress CAD (IvoclarVivadent), hybrid ceramic Cerasmart (GC) and polymer-reinforced graphene G-CAM (Graphenano Dental). (2) Methods: 45 samples consisted of the molar crowns fabricated by three CAD/CAM materials were cemented adhesively on 3D printed abutments (Asiga DentalResin). The samples were divided into 3 groups (n=15) according to the crowns thickness; group 1 under the cusps/cervical margins - 0.6 mm/0.4 mm, group 2 - 1 mm/0.7 mm respectively, and group 3 - 1.5 mm/1 mm. Additionally, 20 cylindrical specimens fabricated by the three crowns and abutments material (n=5) were prepared by CAD/CAM technique. All samples and specimens were subjected to an axial compressive load by using a universal testing machine (Instron 3366-10kN, USA) until fracture. (3) Results: The compressive strength were for Empress CAD 1258 MPa, Cerasmart 501.3 MPa, G-CAM 435 MPa and Asiga resin 360 MPa. G-CAM crowns exhibited a higher maximum compressive load (1701.5-2011.8N) than both Cerasmart (1295.4-1642.9N) and Empress CAD (494.3-597.5N). (4) Conclusions: The CAD/CAM crown materials presented different mechanical behavior; Empress CAD and Cerasmart presented a fragile behavior, with a high compressive strength when compared to G-CAM and Asiga resins.

Sharing confidential information is a critical concern in today’s world. Secret sharing schemes facilitate the sharing of secrets in a way that ensures only authorized participants (shareholders) can access the secret using their allocated shares. Hierarchical secret sharing schemes (HSSSs) build upon Shamir’s scheme by organizing participants into different levels based on priority. Within HSSS, participants at each level can reconstruct the secret if a specified number, denoted as the threshold value (t), or more of them are present. Each level has a predetermined threshold value. If the number of participants falls below the threshold at any level, higher-level participants must be involved in reconstructing the secret at lower levels. Our paper proposes schemes that implement hierarchical access structures and enable the sharing of multiple secrets. Additionally, our proposed scheme includes share verification. We have analyzed potential attacks and demonstrated the scheme’s resistance against them. Through security analysis and comparison with existing schemes, we highlight the novelty and superiority of our proposed approach, contributing to advancements in secure information sharing practices.

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

This research deals with the possibility for construction of the database on the braking friction coefficient for actual roads from the viewpoint of traffic safety especially for automated driving such as level 4 or higher. In an automated driving such levels, the controller needs to control the vehicle, but the road surface condition, especially the road friction coefficient on wet roads, snowy or icy roads, changes greatly, and in some cases, changes by almost one order. Therefore, it is necessary for the controller to constantly collect environment information such as the road friction coefficients and prepare for emergencies such as obstacle avoidance. However, at present, the measurement of the road friction coefficients is not systemically performed, and a method for accurately measuring has not been established. In order to improve this situation, this study examines a method for continuously measurement for the road friction characteristics such as μ-s characteristics.

The conversion of native habitats into anthropogenic ones compromises the original composition and configuration of the landscapes, influencing ecological dynamics and affecting biodiversity. Increasingly, landscape ecology has shown that these effects can only be understood if accessed at adequate spatial scales, as the scale which landscape structure is evaluated influences species responses. Here, we investigated how three variables of landscape composition (proportion of forest, coffee crop and pasture) and two of configuration (number of fragments and mean nearest neighbor distance) interfere in the richness and composition of medium and large-sized mammals considering a multiscale approach. We recorded medium and large-sized mammal species in 13 landscapes with predominantly matrices of coffee and pasture in Minas Gerais, Brazil. Then, we built distance-based linear models to identify the scale of effect of each landscape variable for both response variables considering eight scales (from 250 m to 2000 m). Finally, we verified the influence of the landscape on the richness and composition of mammals, considering the landscape variables in their respective scales of effect. We found 67% of the probable species occurring in the region. The scales of effect varied among landscape variables probably due to the different variables affect different aspects of organisms' ecological requirements. The proportion of pasture in the landscape explained the variation in species richness, while the proportion of forest explained the variation in species composition. In addition, the proportion of pasture in the landscape had a positive influence on species richness, indicating that this matrix may favor the presence of generalist species of habitat and/or this result is due to the higher concentration of species in the fragments immersed in this matrix. These results suggest that considering different responses to biodiversity is important to understand different aspects of the landscape's influence on biodiversity. In addition, the composition of the landscape is fundamental for the perpetuation of species and, therefore, both forest cover and types of matrices in the landscape must be considered to improve species conservation strategies. Finally, generalizing a spatial scale can lead to misinterpretations about the influence of the landscape on biodiversity.

In order to meet the needs of an increasingly complex research landscape, researchers engage in “collaborative prosumption” through open data sharing and reuse. Although significant gains have been achieved in this regards because of growing requirements from funding agencies, governments and journals, the question of how reuse of openly available data for new research contribute to sustainability is yet to be appropriately addressed in the literature. Therefore, relying on a three stage stratified clustered random sampling of the Journal of Applied Econometrics data archive (JAEDA), the present research provides a case study of the value of research data recycling for sustainable research and economic development. More specifically our analysis show that reformatting from wide to long format, openly shared equity price index data on eleven European countries’ extracted from JAEDA, and augmented with country level geospatial Meta data, provides a new basis for interesting descriptive analytics and spatio-temporal econometric modeling and inference. Given the ever-increasing volume of openly available research data, our study provides a first-hand insight on open data reuse, which should benefit all stakeholders in the research community, as they seek sustainable solutions for scientific productivity and progress.

This study aims to test a model linking destination image, perceived value, tourist satisfaction, and tourist loyalty. Based on a sample of 300 tourists travelling by car from the World Natural Heritage Site of Tianchi, China, a new model of destination image was explored and data were analysed using partial least squares structural equation modelling (PLS-SEM). The results show that perceived value and satisfaction are direct antecedents of destination loyalty. Above all, perceived value and tourist satisfaction mediate the relationship between destination image and loyalty. Finally, this study discusses the theoretical and management implications of the findings in order to boost the tourism industry in the context of car trips.

Ridesharing effectively tackles urban mobility challenges by providing a service comparable to private vehicles while minimising resource usage. Our research primarily concentrates on dynamic ridesharing, which conventionally involves connecting drivers with passengers in need of transportation. The process of one-to-one matching presents a complex challenge, particularly when addressing it on a large scale, as the substantial number of potential matches make the attainment of a global optimum a challenging endeavour. This paper aims to address the absence of an optimal approach for dynamic ridesharing by refraining from conventional heuristic-based methods, commonly used to achieve timely solutions in large-scale ride-matching. We propose a novel approach that provides snapshot optimal solutions for various forms of one-to-one matching, ensuring they are generated within an acceptable timeframe for service providers. Additionally, we introduce and solve a new variant where the system itself provides the vehicles. The efficacy of our methodology is substantiated through experiments carried out with real-world data extracted from the openly available New York City taxicab dataset.

We use the theory of coherent measures to look at the problem of surplus sharing in an insurance business. The surplus share of an insured is calculated by the surplus premium in the contract. The theory of coherent risk measures and the resulting capital allocation gives a way to divide the surplus between the insured and the capital providers, i.e. the shareholders.

The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (licensed) bands. Therefore, in this paper, we present a SDR based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe two use cases for the proposed framework.

It is important to consider both requirements and limitations for the generation and sharing of genomic data. For example, human genomic sequence data should typically not be deposited publicly without the appropriate "explicit consent" to do so. This includes genetic identifying data that may exist within raw reads for bulk RNA Sequencing (RNA-Seq) data and genomic data from cell lines that are available to purchase. At the same time, data sharing is important for re-analysis and reproducibility/replication in the scientific community. A review of known rules and guidelines for genomic data sharing is provided. This includes specific rules for NIH-funded data for controlled access deposit of HeLa cell line data, including bulk RNA-Seq data. The ability to create “partial” Gene Expression Omnibus (GEO) public deposits with only processed data is described, with search criteria that can identify many “partial” GEO deposits for a variety of data types where reads were not made public for patient privacy concerns. However, it is the opinion of the author that this should be considered a short-term solution, and additional considerations and action should be carried out for genomic data generated in future experiments. Information about how to learn more about what is known for consent for cell line samples is also briefly provided, along with search results for genomic data from widely available cell lines that is deposited in controlled access databases. Finally, it should be made clear that this article presents some amount of opinion. Additionally, open feedback for this preprint is encouraged to further enhance knowledge and communication.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Few prior works study self-driving cars by deep learning with IoT collaboration. SDC-Net, which is an end-to-end multitask self-driving car camera cocoon IoT-based system, is one of the research that tackles this direction. However, by design SDC-Net is not able to identify the accident locations, it only classifies if it is a crash scene or not. In this work, we introduce an enhanced design for the SDC-Net system by 1) replacing the classification network with a detection one, 2) adapting our benchmark dataset labels built on the CARLA simulator to include the vehicles bounding boxes while keeping the same training, validation, and testing samples, 3) modifying the shared information via IoT to include the accident location. We keep the same path planning and automatic emergency braking network, the digital automation platform, and the input representations to formulate the comparative study. SDC-Net++ system is proposed to 1) output the relevant control actions, especially in case of accidents: accelerate, decelerate, maneuver, and brake, and 2) share the most critical information to the connected vehicles via IoT, especially the accident locations. A comparative study is also conducted between SDC-Net and SDC-Net++ with the same input representations: front camera only, panorama and bird-eye views, and with single-task networks: crash avoidance only, and multitask networks. Multitask network with a BEV input representation outperforms the nearest representation in precision, recall, f1-score, and accuracy by more than 15.134%, 12.046%, 13.593%, and 5%, respectively. SDC-Net++ multitask network with BEV outperforms SDC-Net multitask with BEV in precision, recall, f1-score, accuracy, and average MSE by more than 2.201%, 2.8%, 2.505%, 2%, and 18.677% respectively.

Production planning managers need much information within the organization to create the best production plan. This information is scattered throughout the organization. The planning unit must gather data from sales orders and specified priorities, and use information from production capacity assessments, in-line inventory levels, and many other variables to develop a reliable production plan. This research aims to examine the production planning system at a car part manufacturing company, diagnose the current issues in this area, and endeavor to develop a hierarchical production planning model at the AP levels for the company through a mixed-integer linear programming model.

A major challenge for the dissemination, replication, and reuse of epidemiological forecasting studies during COVID-19 pandemics is the lack of clear guidelines and platforms to exchange models in a Findable, Accessible, Interoperable, and Reusable (FAIR) manner, facilitating reproducibility of research outcomes. During the beginning of pandemics, models were developed in diverse tools that were not interoperable, opaque without traceability and semantics, and scattered across various platforms - making them hard to locate, infer and reuse. In this work, we demonstrate that implementing the standards developed by the systems biology community to encode and share COVID-19 epidemiological models can serve as a roadmap to implement models as a tool in medical informatics, in general. As a proof-of-concept, we encoded and shared 24 epidemiological models using the standard format for model exchange in systems biology, annotated them with cross-references to data resources, packed up all associated files in COMBINE archives for easy sharing, and finally, disseminated the models through BioModels repository to significantly enhance their reproducibility and repurposing potential. We recommend the use of systems biology standards to encode and share models of epidemic and pandemic forecasts to improve their findability, accessibility, interoperability, reusability, and reproducibility.

Medical waste management is crucial issues for keeping our life safe and safety. Without effective measures for waste management, we cannot keep ourselves safe from different types of contagious diseases; viruses, bacteria. Knowledge sharing assists healthcare staff in identifying and mitigating hazards on appropriate handling, segregation and disposal medical waste. The aim of the study is to identify a multifaceted analysis of knowledge sharing, training, communication and attitudes for effective medical waste management. This study selected 153 medical workers randomly, including nurses, lab technologists, and cleaners, from hospitals, diagnostic centers, and clinics in the northern part of Bangladesh. The study design of this research is mixed-methods. This research adopts a survey and interview as a research strategy. The samples are collected randomly. SPSS software packages, MS Excel Office, and PLS-SEM are used to analyze data. Most of the respondents always share their knowledge face-to-face according to the findings. The result also shows that there are positive relationship between sources of knowledge (p: 0.046), awareness and knowledge (p: 0.049), attitudes of waste management (p: 0.025) and effective medical waste management. However, there are no relationships between communication and collaboration (p: 0.943), the practice of waste management (p: 0.155), supervision and staff monitoring (p: 0.527), training and education (p: 0.656) and effective medical waste management. Its focus on the northern part of Bangladesh introduces regional specificity, potentially limiting the applicability of results to other regions. The knowledge-sharing practices for waste management among medical staff are examined within this research, along with the relationship between attitude, awareness, and knowledge, staff supervision and monitoring, practice, training, and education and effective medical waste management that have not been studied before home and abroad. This analysis highlights the critical need for an integrated approach to medical waste management, emphasizing the importance of continuous education, open communication, and cultivating a culture that prioritizes environmental sustainability. The insights from this study offer practical recommendations for healthcare institutions to improve their medical waste management practices, ultimately leading to enhanced health outcomes and better environmental protection.

The work at hand focuses on an adaptive system aimed at improving the soundproof performance of car door seals at specific working regimes (cruise), without interfering with the conventional open-closure operations. The idea addresses the necessity of increasing the seal effectiveness, jeopardized by aerodynamic actions more and more important as the speed increase, generating a pressure difference between the internal and the external filed, in the direction of opening the door. To recover this effect, an expanding mechanism was integrated within the seal cavity, driven by an SMA actuator. The material was activated (heated) by Joule effect; its compactness, intrinsic of smart materials, contributed to arrive to a final system characterized by a high level of integrability (expanding cells). In this paper, the development process is described together with the verification activity, aimed at proving the functionality of the realized device. Starting from the industrial requirements, the most appropriate solution was identified highlighting the working principle and the main design parameters involved. Then, the envisaged system was designed and its executive digital mock up (CAD) was released. Prototyping and laboratory validation showed the reliability of the numerical models and the associated predictions. On this basis, the integration task within the actual reference car was faced. To demonstrate the isolation effect of the proposed system, an experimental campaign was finally organized in an anechoic room, achieving significant results on the concept value.

Background: Amidst escalating climate change concerns, sustainable practices in healthcare logistics are critical. This study evaluates the ecological impact and efficiency of medical sample transportation using drones, combustion cars, and electric cars across diverse terrains and weather in Liechtenstein and Switzerland. Methods: We conducted a comparative analysis of CO2 emissions, transport distances, and delivery times for each transportation modality. Data collection involved multiple runs under various conditions, with CO2 emissions measured using onboard systems, and transport efficiency assessed via GPS tracking and time monitoring. Results: Combustion cars exhibited the highest average CO2 emissions at 159.5 grams per kilometer (g/km). Electric cars emitted significantly less, averaging 3.43 g/km, which is 2.15% of combustion car emissions. Drones were the most environmentally friendly, with an average emission of 0.09 g/km, representing 0.07% of combustion car emissions and 2.6% of electric car emissions. Drones also showed substantial transport efficiency, covering 17% shorter distances on flat terrain and 24% shorter in mountainous areas, with time savings ranging from 13% to 80%. Conclusion: This study highlights the potential of drone technology to revolutionize healthcare logistics by reducing environmental impact and optimizing operational efficiency. Integrating drones can significantly lower the carbon footprint, improve sample integrity, and enhance patient care, promoting a greener, more resilient healthcare system.

In this paper, we consider the zero distributions of q-shift monomi-als and difference polynomials of meromorphic functions with zero order, that extends the classical Hayman results on the zeros of differential poly-nomials to q-shift difference polynomials. We also investigate problem of q-shift difference polynomials that share a common value.

Access and Benefit Sharing (ABS) is a framework which refers to a relatively recent type of legal requirements for access to and/or use of “genetic resources”. They are based on diverse national and regional laws and regulations, which mostly result from the implementation of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary agreement, the Nagoya Protocol. Their ambition is to achieve fair and equitable sharing of benefits arising out of the use of genetic resources as an incentive to conserve and sustainably use them. This paper describes the experiences, practical constraints and complexities encountered by users of genetic resources when dealing with ABS legislation, with a focus on users from the private sector. We provide insights on how ABS laws have fundamentally changed the way of working with genetic resources in the hope that it inspires re-thinking of the ABS framework, to better support the overall objectives of the CBD.

This paper details the evolution of access network sharing models from legacy DSL to the most recent fibre-based technology and the main challenges faced from a technical and business perspectives. We first give an overview of existing access sharing models, that span physical local loop unbundling and virtual unbundled local access. We then describe different types of optical access technologies and highlight how they support network sharing. Next, we examine how the concept of SDN and network virtualization has been pivotal in enabling the idea of “true multi-tenancy”, through the use of programmability, flexible architecture and resource isolation. We give examples of recent developments of cloud central office and OLT virtualization. Finally, we provide an insight into the role that novel business models, such as blockchain and smart contract technology, could play in 5G networks. We discuss how these might evolve, to provide flexibility and dynamic operations that are needed in the data and control planes.

Alzheimer’s disease is a debilitating neurodegenerative condition which is known to be the most common cause of dementia. Despite its rapidly growing prevalence, medicine still lacks a comprehensive definition of the disease. As a result, Alzheimer’s disease remains neither preventable nor curable. In recent years, broad interdisciplinary collaborations in Alzheimer’s disease research are becoming more common. Furthermore, such collaborations have already demonstrated their superiority in addressing the complexity of the disease in innovative ways. However, establishing effective communication and optimal knowledge distribution between researchers and specialists with different expertise and background is not a straightforward task. To address this challenge, we propose the Alzheimer’s disease Ontology for Diagnosis and Preclinical Classification (AD-DPC) as a tool for effective knowledge sharing in interdisciplinary/multidisciplinary teams working on Alzheimer’s disease. It covers six major conceptual groups, namely Alzheimer's disease pathology, Alzheimer's disease spectrum, Diagnostic process, Symptoms, Assessments, and Relevant clinical findings. All concepts were annotated with definitions or elucidations and in some cases enriched with synonyms and additional resources. The potential of AD-DPC to support non-medical experts is demonstrated through an evaluation of its usability, applicability and correctness. The results show that the participants in the evaluation process who lack prior medical knowledge can successfully answer Alzheimer’s disease-related questions by interacting with AD-DPC. Furthermore, their perceived level of knowledge in the field increased leading to effective communication with medical experts.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

IP Multimedia Subsystem (IMS) supports high-speed transmission of multi-media like data, audio, and video between mobiles and other wireless devices. IMS is the most suitable for multimedia communication across multiple networks using the Internet of Things (IoT) and cloud computing. IoT-IMS can efficiently manage the huge amount of data generated by smart devices for audio-video during live streaming applications. During these services, the main problem is that an intruder can launch a Session Initialization Protocol (SIP) messages flooding attack on IMS that does not have the functionality to prevent itself from these types of attacks. In this paper, an intrusion detecting and preventing system (IDPS) is proposed that effectively detects the register flooding and spoofing attacks using SIP messages. We proposed a watermark embedding algorithm on the user side and an extraction algorithm on receiving side. A test-bed is set up for IMS where we have considered four different scenarios to evaluate the IDPS approach as compared to counterparts. Results illustrate the dominance of our scheme in terms of response time, register flooding attack detection ratios, CPU load utilization, fault detection ratio, and memory utilization. The fault detection ratio averagely 98.18

Revenue-sharing (RS) contracts are a common approach to incentivize innovation of upstream suppliers by addressing the uneven profit distribution between upstream and downstream firms. Considering the possible overconfidence characterizing decision makers in the supply chain, we investigate the effect of the RS contract and the tendency of overconfidence of supply chain members on the investment in R&D of key components of products in the context of an upstream supplier that is the leader in the R&D and production of key components. We find that regardless of the bargaining power of either party, a RS contract can increase the R&D investment in key components. Regarding the effects of overconfidence of either downstream manufacturer or up-stream supplier, it can increase the R&D investment in key components. Supplier (manufacturer) overconfidence can harm their own profits but increase the profits of the manufacturer (supplier), and when the level of overconfidence is below a certain threshold, the damage to their own profits is less than the increase in each other's profits, thus benefiting the whole supply chain. In addition, we also find a joint effect of RS contracts and overconfidence: when the bargaining power of the supplier is low, the RS contract has a certain compensatory effect on the loss of their own profits caused by overconfidence.

Facing unprecedented global declines in the extent and integrity of ecosystems, the 15^th UN Biodiversity Conference (COP-15) in Kunming, China, presents an opportunity for transformative change. However, a lack of consensus on two key issues – resource mobilization and Access and Benefit Sharing (ABS) associated with Digital Sequence Information (DSI) – risks stalling negotiations for an ambitious ‘Post-2020 Global Biodiversity Framework’ as the next 10-year strategic plan under the Convention on Biological Diversity. We highlight systemic misconceptions concerning the financing of biodiversity and the burden this places on the ABS system. In the context of DSI, we caution that conflating ABS with resource mobilization risks disrupting modern science policy built on open access, with potentially severe ramifications for scientific research and innovation. To resolve these tensions, we call for a recalibration of discussions on ABS in order to maximize the value delivered by biodiversity for all of society, including indigenous peoples and local communities.

This paper describes some of the challenges that need to be addressed in order to develop collaborative spectrum sharing systems. The importance of these challenges stems from the assumption that rules for spectrum sharing can change after the deployment of radio networks and the whole system must be able to adapt to them. To address such a requirement, we used a policy-based approach in which transmissions are controlled by a policy interpreter system, and the policies can be modified during system operation. Our primary goal was to develop a prototype of such a system. In this paper, we outline the implementation of policy interpretation, automatic generation of transmission opportunities in case a request for transmission is denied by the policy reasoner, and the generation of rendezvous channels for the synchronization of otherwise asynchronously running software defined radios.

Sharing activity is getting higher attention due to increasing popularity in recent years. In the paper, the authors investigated the main elements affecting the sharing activity. (1) Literature review: The theoretical part starts from the revision of definitions of sharing activity; description of the links between sharing and sustainable development, policy recommendations and relevant regulation in the field; later on, the study emphasises the key elements important for sharing. Finally, the authors investigated how the Covid-19 pandemic affected sharing activity; (2) Methods: During empirical research, the authors revised the list of 37 variables. The study uses data for each of the 27 EU countries from 2011 to 2020. The authors investigated correlation between macroeconomics variables to determine key variables for the regression model; (3) Results: The authors constructed a dynamic regression model that can be applied to predict the number of participants visiting sharing platforms in the European Union (EU); (4) Conclusions: The study shows that seeking to forecast the number of visits to sharing platforms it is necessary to use values of main macroeconomic variables such as consumer price index, productivity index, total unemployment rate, the number of users and households connected to the Internet, etc.

We report the experiences of the bike sharing system in Ningbo, China. To analyze the impact of the system, system log data are collected for the whole month of May 2014 (with more than 1.7 million usage records), supplemented by questionnaire data from 1,856 respondents. Our results show that public bike usage follows the same pattern as road traffic, with morning and evening peaks on week days. In terms of mode substitution, 16% of public bike trips would have been made by private cars. In average, each public bike is used 3.7 times per day, with each trip lasting around 23 minutes and covering around 3.5 kilometre. This translates into a reduction of car travel by more than 11 million kilometre per year, a significant contribution to the sustainability of urban transport in Ningbo.

In recent years, there have been many new global companies investing and operating in Vietnam as a form of sharing economy (Uber, Grab, Foody, Agoda, Facebook, Google, etc). These kinds of economic models are popular in the world but very new in Vietnam. Sharing economy enterprises bring both benefit and challenges for Vietnam. Before time, there is no policy and law to govern the activities of these companies. So they make the challenges for the authority of Vietnam to manage. This paper will analyze the nature, characters, and impacts of the sharing economy in Vietnam. It also mentions the problems and recommends some solutions to manage the activities of sharing - economy companies.

Bike sharing systems are a key element of a smart city as they have the potential for reducing pollutant emissions and traffic congestion thus substantially improving citizens’ quality of life. In these systems, bicycles are made available for shared use to individuals on a very short-term basis. They are rented in a station and returned in any other station with free docks. However, to achieve a satisfactory user experience, all the stations in the system must be neither overloaded nor empty. The occupancy level of the stations can be constantly monitored through IoT-based services. The goal of this work is to analyze occupancy level data acquired from real systems to discover situations of dock overload in multiple stations which could lead to service disruption. The proposed methodology relies on a pattern mining approach. A new pattern type, called Occupancy Monitoring Pattern (OMPs), is proposed to characterize situations of dock overload in multiple stations. Since stations are geo-referenced and their occupancy levels are periodically monitored, OMPs can be filtered and evaluated by considering also the spatial and temporal correlation of the acquired measurements. The results achieved on real Smart City data highlight the potential of these techniques in supporting domain experts in maintenance activities, such as periodic re-balancing of the occupancy levels of the stations, as well as in improving the user experience, such as suggesting alternative stations in the neighborhood.

This paper reports a new control strategy to improve sharing of unbalanced currents in islanded LV microgrids. This technique provides fast and effective sharing of positive-, negative- and zero-sequence currents, and is the first example of zero-sequence current sharing in the literature. The controllers are designed in the stationary frame. The control structure consists of four loops; 1)~the current controller; 2)~the voltage controller; 3)~the droop controller and the 4)~negative and zero sequence current controllers. The output current is considered unknown for the controller and is added to the control system as a disturbance. The proposed controller features a high gain in fundamental and harmonic frequencies, hence a good voltage quality is obtained in the presence of unbalanced and nonlinear loads. To this aim, a proportional-resonant (PR) controller is adopted as the current controller. By using a multi-resonant controller as current controller, a unified control structure is obtained which is suitable for both grid-connected and islanded modes. The voltage controller is designed using a resonant controller so that the voltage can have low VUF and THD in the presence of unbalanced and nonlinear loads. Furthermore, in this paper droop method is applied to the control structure to share real and reactive powers. Simulation studies show that the conventional droop method cannot share the oscillatory part of the output power that is due to the presence of unbalanced loads in the microgrid. This paper relies on using zero and negative sequence virtual impedance controller to share the oscillatory part of output power. By using zero-sequence virtual impedance controller (ZSVIC) and negative-sequence virtual impedance controller (NSVIC), the zero and negative sequence currents in the microgrid are controlled and shared effectively. By compensating zero- and negative-sequence currents locally, the flow of these currents in the microgrid is minimized, and the overall power quality of the islanded LV microgrid is improved.

Here we explore the emerging role of NKG2D CAR-T cell therapy in the realm of solid tumor treatment. Unique capabilities of NKG2D CAR-T cells to recognize stress-induced ligands on cancer cells are discussed, highlighting the therapy's potential for targeted and precise antitumor responses. We also examine the challenges and opportunities associated with NKG2D CAR-T cell therapy, emphasizing the ongoing advancements and clinical trial progress shaping its future. Ultimately, the discussion underscores the transformative promise of NKG2D CAR-T cell therapy in revolutionizing the landscape of solid tumor treatment and enhancing the prospects for improved patient outcomes.

The motivations for the move to electrified vehicles are discussed with reference to their improved energy efficiency, their potential for lower CO2 emissions (if the electricity system is decarbonized), their lower (or zero) NOx/particulate matter (PM) tailpipe emissions, and the lower overall costs for owners. Some of the assumptions made in life-cycle CO2 emissions calculations are discussed and the effect of these assumptions on the CO2 benefits of electric vehicles are made clear. A number of new tribological challenges have emerged, particularly for hybrid vehicles that have both a conventional internal combustion engine and a battery, such as the need to protect against the much greater number of stop-starts that the engine will have during its lifetime. In addition, new lubricants are required for electric vehicle transmissions systems. Although full battery electric vehicles (BEVs) will not require engine oils (as there is no engine) they will require a system to cool the batteries – alternative cooling systems are discussed, and where these are fluid based, the specific fluid requirements are outlined.

Peer-to-peer (P2P) energy trading is a new data-driven business model currently being trialed within the energy sector. Introducing P2P transactions to an essential service such as energy could have far-reaching implications for individuals and the grid. This paper raises considerations and questions from social, economic/markets and regulatory points of view, that should be understood and addressed by societies and policymakers. It does this by considering under what circumstances it is reasonable to conceptualize P2P energy trading as part of the sharing economy, and drawing parallels to the sharing economy experience in other sectors. In order to reap the full societal benefits, while avoiding considerable risks to infrastructure and individuals, a policy approach promoting dialogue and innovation is necessary. We suggest the regulatory sandbox is the most appropriate tool to achieve this and would help avoid the breakdown of trust between policymakers and platform companies observed in other sectors.

Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies, but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy was particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity (not all tumor cells express the target antigen), the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising anti-tumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies.

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this therapy to other malignancies and broader patient populations. However, several limitations remain, including those associated with the time-consuming and highly personalized manufacturing of autologous CAR-Ts. Technologies to establish “off-the-shelf” allogeneic CAR-Ts with low alloreactivity are currently being developed, with a strong focus on gene editing technologies. Although these technologies have many advantages, they have also strong limitations including double-strand breaks in the DNA with associated multiple safety risks as well as the lack of modulation. As an alternative, non-gene editing technologies provide an interesting approach to support the development of allogeneic CAR-Ts in the future, with possibilities of fine-tuning gene expression and easy development. Here we will review the different ways allogeneic CAR-Ts can be manufactured and discuss which technologies are currently used. The biggest hurdles for successful therapy of allogeneic CAR-Ts will be summarized and finally an overview of the current clinical evidence for allogeneic CAR-Ts in comparison to its autologous counterpart will be given.

Systemic autoimmune diseases (SAIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis such as B cells, co-stimulatory molecules, cytokines or their receptors, and signalling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc.

As machine learning and computer vision techniques and methods continue to advance, the collection of naturalistic traffic data from video feeds is becoming more and more feasible. That is especially true for the case of bicycles, for which the collection of naturalistic data is not achievable in the traditional vehicle approach. This study describes a research effort that aims to extract naturalistic cycling data from a video dataset for use in safety and mobility applications. The used videos come from a dataset collected in a previous Virginia Tech Transportation Institute study in collaboration with SPIN in which continuous video data at a non-signalized intersection on the Virginia Tech campus was recorded. The research team applied computer vision and machine learning techniques to develop a comprehensive framework for the extraction of naturalistic cycling trajectories. In total, this study resulted in the collection and classification of 619 bicycle trajectories based on their type of interactions with other road users. The results confirm the success of the proposed methodology in relation to extracting the locations, speeds, and accelerations of the bicycles at a high level of precision. Furthermore, preliminary insights into the acceleration and speed behavior of bicyclists around motorists are determined.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

Access to travel information is crucial for blind and partially sighted (BPS) people in travel planning. However, finding relevant information can be complex and challenging due to the unavailability of appropriate information and accessible information sources. To investigate this issue, a mixed-method study consisting of semi-structured interviews and co-design workshops was conducted to identify the needs of BPS people and the barriers BPS people experience due to the lack of access to such information. The findings provide insights into the information-seeking process and highlight the role of experience-sharing in cultivating a sense of agency, contribution, and interdependence. We contribute an accessible tourism ecosystem based on our findings to motivate research on technologies to support inclusive leisure travel for BPS people and to inform the design of inclusive tourism services.

Science continues to become more interdisciplinary and to involve increasingly complex data sets. Many projects in the biomedical and health-related sciences follow or aim to follow the principles of FAIR data sharing, which has been demonstrated to foster collaboration, to lead to better research outcomes, and to help ensure reproducibility of results. Data generated in the course of biomedical and health research present specific challenges for FAIR sharing in the sense that they are heterogeneous and highly sensitive to context and the needs of protection and privacy. Data sharing must respect these features without impeding timely dissemination of results, so that they can contribute to time-critical advances in medical therapy and treatment. Modeling and simulation of biomedical processes have become established tools, and a global community has been developing algorithms, methodologies, and standards for applying biomedical simulation models in clinical research. However, it can be difficult for clinician scientists to follow the specific rules and recommendations for FAIR data sharing within this domain. We seek to clarify the standard workflow for sharing experimental and clinical data with the simulation modeling community. By following these recommendations, data sharing will be improved, collaborations will become more effective, and the FAIR publication and subsequent reuse of data will become possible at the level of quality necessary to support biomedical and health-related sciences.

Next-generation sequencing (NGS) has been a widely-used technology in biomedical research for understanding the role of molecular genetics of cells in health and disease. A variety of computational tools have been developed to analyse the vastly growing NGS data, which often require bioinformatics skills, tedious work and significant amount of time. To facilitate data processing steps minding the gap between biologists and bioinformaticians, we developed CSI NGS Portal, an online platform which gathers established bioinformatics pipelines to provide fully automated NGS data analysis and sharing in a user-friendly website. The portal currently provides 16 standard pipelines for analysing data from DNA, RNA, smallRNA, ChIP, RIP, 4C, SHAPE, circRNA, eCLIP, Bisulfite and scRNA sequencing, and is flexible to expand with new pipelines. The users can upload raw data in fastq format and submit jobs in a few clicks, and the results will be self-accessible via the portal to view/download/share in real-time. The output can be readily used as the final report or as input for other tools depending on the pipeline. Overall, CSI NGS Portal helps researchers rapidly analyse their NGS data and share results with colleagues without the aid of a bioinformatician. The portal is freely available at: https://csibioinfo.nus.edu.sg/csingsportal

This study investigates the impact of information sharing on supply chain resilience by exploring the experiences and insights of supply chain professionals through qualitative research. Information sharing has become increasingly recognized as a vital component in enhancing the ability of supply chains to anticipate, respond to, and recover from disruptions. Through semi-structured interviews with 22 supply chain professionals across various industries, the study delves into the mechanisms through which information sharing influences supply chain resilience, the challenges faced, and the role of enabling factors such as technology and organizational culture. The findings reveal that effective information sharing enhances supply chain visibility, coordination, and adaptability. Enhanced visibility allows supply chain partners to monitor real-time operational data, facilitating early detection of potential disruptions. Improved coordination enables better alignment of activities, reducing inefficiencies and mitigating the bullwhip effect. Adaptability is bolstered through the timely exchange of information, allowing for rapid adjustments to changing conditions. However, the study also identifies significant barriers to effective information sharing, including concerns about data security, competitive advantage, and trust among partners. Trust and strong relationships emerge as critical factors for successful information sharing, highlighting the need to build and maintain trust to facilitate open communication. The role of technology is emphasized, with digital platforms, blockchain, and the Internet of Things (IoT) identified as key enablers of efficient and secure information exchange. The study concludes that fostering a supportive organizational culture and leadership commitment to transparency and collaboration, along with tailoring information-sharing strategies to specific supply chain contexts, is essential for enhancing supply chain resilience. This research contributes to the understanding of the impact of information sharing on supply chain resilience and provides practical insights for organizations aiming to strengthen their resilience in an increasingly complex global business environment.

Substantial research is required to ensure that micro-mobility ride sharing provides a better fulfillment of user needs. This study proposes a novel crowdsourcing model for the ride-sharing system where light vehicles such as scooters and bikes are crowdsourced. The proposed model consists of three entities: suppliers, customers, and a management party responsible for receiving, renting, booking, and demand matching with offered resources. It can allow suppliers to define the location of their private e-scooters/e-bikes and the period of time they are available for rent. Using a dataset of over 9 million e-scooter trips in Austin, Texas, we ran an agent-based simulation six times using three maximum battery ranges (i.e., 35, 45, and 60 km) and different numbers of e-scooters (e.g., 50 and 100) at each origin. Computational results show that the proposed model is promising and might be advantageous to shift the charging and maintenance efforts to a crowd of suppliers.

The Sharing Economy (SE) has dawn great attention from several stakeholders in society in the last five years. While business actors are interested in financial opportunities to meet consumer needs, new business models, the academia and governmental organizations are concerned with potential unintended effects on the society and environment. In the process of making a clearer comprehension of the SE phenomenon, researchers have identified that, despite its notable global growth, there still persists a lack of a more solid ground in understanding its origins and respective mechanisms under which it has been evolving over time as a category. In this research, we address the problematics of the origins and ascendency of the SE by examining the process by which the SE is arising as a new category, searching for conceptual clarification and pinpointing the legitimacy granted by key stakeholders. Our guiding research questions are: (1) how the SE was formed and evolved as a market category; and (2), as a market category, is the SE legitimate? Additionally, we attempt to identify the nature of the SE as a category. To answer these questions, we conducted an historical analysis of the expression SE and its equivalents. This paper deepens the discussion about the nature of the SE by providing evidence that (i) the SE has predominantly been formed by emergence processes, comprising social movement, similarity clustering and truce components. It is the combination of all these aforementioned processes that renders the SE a special case of market category formation, which, in turn, has been allowing communication, entrepreneurship, regulation and research about what really is the SE, and despite the evident lack of agreements regarding both the label and its content; (ii) there is a generalized legitimacy granted to the SE by a vast number of stakeholders, even though still lacking on the consolidation of socio-political legitimation, and (iii) the nature of the SE seems to fall in a metaphorical approach, particularly, the notion of radial categories.

The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (e.g., licensed) bands. Therefore, in this paper, we present an open source SDR-based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe three use cases where the proposed framework can be employed along with intelligent algorithms to achieve improved spectrum utilization.

The COVID-19 pandemic has underscored the intricate interplay between viral infections and opportunistic bacterial pathogens such as Klebsiella pneumoniae. K. pneumoniae harbors various antibiotic resistance determinants like extended-spectrum and plasmid-mediated AmpC β-lactamases and carbapenemases. In the two years following the pandemic, carbapenemase producing K. pneumoniae isolates obtained routinely in outpatient and inpatient setting demonstrated similar resistance patterns which prompted research. The aim was to compare and subsequently analyze carbapenem-resistant hospital and outpatient’s K. pneumoniae isolates’ resistance mechanisms, traits and molecular epidemiology, following the COVID-19 pandemic. Disk diffusion and broth dilution method were the methods of choice to determine antibiotic susceptibility. β-lactamases were screened by phenotypic methods and confirmed with PCR. In total 113 isolates were analysed. Resistance to amoxicillin-clavulanate and ertapenem was confirmed in all strains. High resistance rates (over 90%) were observed for extended-spectrum cephalosporins, and ciprofloxacin. OKNV testing and PCR detected OXA-48 in 106, NDM in 7 and KPC in only one isolate. ESBLs accompanied carbapenemases in 103 isolates. Carbapenem resistance in K. pneumoniae is becoming a global problem, hence careful monitoring of its resistance traits is of utmost importance in order to combat the arising threat. OXA-48 seems to continue predominating in the turbulent period after pandemic.

To drive safely, the driver must be aware of the surroundings, pay attention to the road traffic, and be ready to adapt to new circumstances. Most studies on driving safety focus on detecting anomalies in driver behavior and monitoring the cognitive capabilities of drivers. In our study, we proposed a classifier for basic activities in driving a car, based on a similar approach that could be applied to the recognition of basic activities in daily life, that is, using electrooculographic (EOG) signals and a one-dimensional convolutional neural network (1D CNN). Our classifier achieved an accuracy of 80% for the 16 primary and secondary activities. The accuracy related to primary activities in driving, including crossroad, parking, roundabout was 97.9%, 96.8%, 97.4%, and 99.5%, respectively. The F1 score for secondary driving actions (0.99) was higher than for primary driving activities (0.93–0.94). Furthermore, using the same algorithm, it was possible to distinguish four secondary activities related to activities of daily life and secondary when driving a car.

This purpose of the study presented in this article is to comparing different service quality measurements between Kano and TRIZ that plays the critical roles in the catering industrial. Data collected from a DINESERV questionnaire comprises service-quality standards to increase customer satisfaction of mobile dining car. Finally, the TRIZ is standardized measure designed to improve the idealization of strategy for selecting the most appropriate service quality model. In addition, the preferences of more than one decision maker are internally aggregated into the TOPSIS procedure. All these things provide several important theoretical and practical implications for developing a successful mobile catering app.

Gesture recognition has always been a technique to decrease the distance between the physical and the digital world. In this work, we introduce an Arduino based vehicle system which no longer require manual controlling of the cars. The proposed work is achieved by utilizing the Arduino microcontroller, accelerometer, RF sender/receiver, and Bluetooth. Two main contributions are presented in this work. Firstly, we show that the car can be controlled with hand-gestures according to the movement and position of the hand. Secondly, the proposed car system is further extended to be controlled by an android based mobile application having different modes (e.g., touch buttons mode, voice recognition mode). In addition, an automatic obstacle detection system is introduced to improve the safety measurements to avoid any hazards. The proposed systems are designed at lab-scale prototype to experimentally validate the efficiency, accuracy, and affordability of the systems. We remark that the proposed systems can be implemented under real conditions at large-scale in the future that will be useful in automobiles and robotics applications.

Electric moped scooter sharing services have recently experienced strong growth rates, particularly in Europe. Due to their compactness, environmental-friendliness and convenience, shared e-mopeds are suitable modes of transport in urban mobility to help reduce the environmental impact. However, its traffic-related, economic and environmental effects are merely represented in academic research. We used passenger car traffic data in Berlin generated by the multi-agent transport simulation framework MATSim to develop a python-based simulation, resembling an e-moped sharing system. Based on the results, a total cost of ownership and a life cycle assessment for fleet sizes of 2,500, 10,000 and 50,000 vehicles were conducted. The results indicate that a substantial part of all passenger car trips in Berlin can be substituted. The larger the fleet, the more and longer trips are replaced. Simultaneously, the efficiency in terms of fleet utilization decreases. The scenario with 10,000 e-mopeds offers the lowest total distance-based costs for sharing operators, whereas a fleet consisting of 2,500 vehicles exhibits the lowest environmental emissions per kilometer driven over the expected lifespan of a shared e-moped. Based on the renewable energy potential for 2050 forecasted by the German Federal Environment Agency, a significant overall decline in environmental impacts can be achieved.

Infrared sensors are applied more and more widely in industrial production applications. Based on the theory of thermal radiation, this paper discusses the system design principle, temperature calibration method and thermal image analysis method in detail. The system has passed the measurement unit certification, showing that the field of view is 180°, the number of scanning points is 2048, the linear velocity is 10-100Hz, the spatial resolution is 2.5mrad, and the precision is ±1℃. On-line monitoring test has been done in the steelmaking plant of Bao Steel. The results show that the system has strong anti-interference ability, stability and reliability, and meets the application requirements of online monitoring.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

This paper establishes a prognosis of the long term environmental impact of various car subsidy concepts. The CO2 emissions of the German car fleet impacted by the purchase subsidies are determined. A balance model of the CO2 emissions of the whole car life cycle is developed. Consideration of production-, use- and End-of-Life processes are taken into account. The implementation of different subsidy scenarios directly affects the forecasted composition of the vehicle population and therefore the resulting life cycle assessment. All scenarios compensate the additional emissions required by the production pull-in within the considered period and hence reduce the accumulated CO2 emissions until 2030. The exclusive funding of BEVs is most effective with a break-even in 2025.

In the absence of a treaty protocol or verification regime, the Biological and Toxin Weapons Convention (BWC) instituted Confidence-Building Measures (CBMs) as a mechanism to increase confidence in compliance, by enhancing transparency and mitigating ambiguities regarding states parties’ biological activities. While a promising tool to support treaty compliance, low participation, concerns regarding the completeness and accuracy of CBM submissions, a dearth of analysis, and restricted access to many submissions have limited CBMs’ value. Through interviews with 53 international experts—38 from BWC delegations and 15 independent experts—we identified concrete opportunities to increase CBMs’ value while mitigating the burden on states parties. This study supports states parties’ efforts in the BWC Working Group on the Strengthening of the Convention, as part of a series of research on BWC assurance that aims to characterize challenges around BWC verification and increase certainty in BWC compliance.

: A comprehensive analysis was performed, considering blockchain technology (BT) proprieties in digital health, addressing medico-legal, privacy, and regulatory considerations. Adherence to personal data protection and healthcare regulatory guidelines were analyzed and compared for GDPR (Europe), HIPAA (United States), CCPA (California), PIPEDA (Canada), Privacy Act of 1988 (Australia), APPI (Japan), and LGPD (Brazil). Issues such as Health Systems, Strengthening and aligning policy orientations and initiatives, and emphasizing the role of data analysis in shaping health policies were explored. The study addressed conflicts between the legal frameworks and blockchain, comparing and suggesting solutions like revision of laws and integration of com-pliance mechanisms. Additionally, it sought to enhance IT-health literacy by integrating healthcare and legal domains. Ongoing collaboration between legal, health, and IT experts is essential for designing systems that effectively balance privacy rights and data protection while maximizing the benefits of disruptive technologies like blockchain.

The purpose of this study is to analyse the drivers and outcomes of the brand love derived from consumption experiences in the automobile retail sector. We examine the effects of consumers’ perceptions of perceived service quality and the trust they feel towards a car dealership (cognition) on emotions and brand love (affection), and the effects of brand love on consumers´ behavioural intentions (conation). This research provides insights into customer brand love in the automobile industry.

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the PiggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45,1% (± 26,1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and γ-secretase inhibitors (GSI), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrate the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

Multimodal traveling is expected to enhance mobility for users, reduce inequalities of car ownership and reduce emissions. In the same context, ride-sharing aims to minimize negative impacts related to emissions, reduce travelling costs and congestion, and increase passenger vehicle occupancy, and public transit ridership when planned for first/last mile trips. The goal of this study is to present the planning of a multimodal pilot demonstration and the challenges that emerged during and after its implementation in Athens, Greece. The demo aims to enhance the connection of low-density Attica Region areas to public transport (PT) modes, and specifically to the metro, through the provision of demand responsive ride-sharing services. During the demo period two different applications were utilized: the “Travel Companion” app and the “Driver Companion” app, which refer to passengers and drivers of the ride-sharing service. Identification of demo participants is performed through a Stated Preference (SP) experiment. Results of the demo implementation, as well as challenges that were faced show that although participants are willing to try new mobility solutions, the readiness and reliability of the new service are essential attributes towards maintaining existing users and engaging new ones.

This study presents a detailed assessment on the impact of the Brazilian legal framework related to the access and benefit sharing provisions of the UN Convention on Biological Diversity. The research is based on a comprehensive dataset that was systematically collected over several years, directly from the official government bodies responsible for its implementation. The aim of the study is to contribute to a fact-based discussion on the effectiveness of national ABS laws, focusing on the Brazilian legal framework, first established in the year 2000 and revised in 2015, as a case example. This study balances the costs and benefits of the Brazilian ABS system and assesses the regulatory challenges it poses to individuals, companies, and institutions that perform research, share knowledge, develop, manufacture or market products derived from Brazilian biodiversity. The study indicates that, after over 22 years of operation, the regulatory challenges are still real and relevant, and that the significant volume of data collected from users on access, prior commercialization and shipment of genetic materials abroad was never systematically assessed by the agencies in charge. Besides, it shows that the costs incurred by the government in managing the policy itself have been higher than the economic benefits it has made possible, and that the institutional mechanisms in place since 2015 have not been able to allocate the monetary benefits contributed by users to the National Benefit Sharing Fund to any projects aimed at developing sustainable uses or preserving Brazilian biodiversity.

The reconstruction of traffic accidents has grown as an interdisciplinary field since the first accident occurred. Various methods have been developed over time, starting with primary data collected at the scene of the accident. In this work, I proposed a method by which the value of the force in the safety belt buckle can be determined when it is equipped with a pretensioning system with pyrotechnic trigger in the tube, PBP or PLP type. The anti-return system of the pretensioner mechanism, which prevents the passenger's body from moving forward, contains a set of balls that block the movement of the piston in the pretensioner tube after its activation. When limiting the movement, the force the human body exerts on the safety belt webbing is transformed into the deformation of the pretensioner tube by the balls of the anti-return system. Depending on the magnitude of the force, the marks left by the balls differ. I propose a relationship of dependence between the acting force and the deformation of the tube. An experimental test bench was created to perform shock traction tests on the pre-tensioning system, under similar conditions to those of the human body acting on the belt in case of a frontal collision. Following the tests, the force value of the seat belt buckle cable and the diameter of the spherical indentations that the balls left in the pretensioner tube were measured. A mathematical model was proposed to determine the normal force with which a ball from the anti-return system deforms the tube. The normal force was also determined by two other methods specific to contact mechanics and used in the specialized literature. By comparing the normal forces obtained by the three methods, a good correlation between the proposed mathematical model and the Komvopoulos-Ye method resulted, the "Hardness" method not being suitable for this study. The determined polynomial regression curve allows finding out the force in the cable of the closer depending on the size of the deformations produced by the balls in the tube. The forces in the belt webbing can be thus determined and biomechanics specialists can evaluate the injuries to the chest and abdomen of the occupants of a vehicle.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

Multiple Myeloma (MM) is one of the incurable types of cancer in plasma cells. While immense progress has been made in the treatment of this malignancy, a large percentage of patients were unable to adapt to such therapy. Additionally, these therapies might be associated with significant diseases and are not always tolerated well in all patients. Since cancer in plasma cells has no cure, patients develop resistance to treatments, resulting in R/R MM. BCMA is primarily produced on mature B cells. Its up-regulation and activation are associated with multiple myeloma in both murine and human models, indicating that this might be an effective therapeutic target for this type of malignancy. Additionally, BCMA's predictive value, association with effective clinical trials, and capacity to be utilized in previously difficult to observe patient populations, imply that it might be used as a biomarker for multiple myeloma. Numerous kinds of BCMA-targeting medicines have demonstrated antimyeloma efficacy in individuals with refractory/relapsed MM, including CAR T-cell treatments, ADCs, bispecific antibody constructs. Among these medications, CART cell-mediated BCMA therapy has shown significant outcomes in multiple myeloma clinical trials. This review article outlines CAR T cell mediated BCMA medicines have the efficiency to change the therapeutic pattern for multiple myeloma significantly.

This paper introduces a structured design for an effective power-sharing technique among converter-interfaced distributed generation (DG) units within a microgrid that operates without a synchronous generator. The proposed power-sharing technique leverages the battery energy storage system (BESS) to promptly respond to network changes. The real power output of each commercial distributed energy resources (CDER) unit is governed by a frequency-droop characteristic and a complementary frequency restoration strategy. Deloading techniques are employed by solar and wind power generators to enhance response during power supply or demand disturbances. To ensure microgrid stability, small-signal analysis is conducted for controller design, including the determination of stability margins. Initial tuning of the power-sharing technique parameters is achieved using the Ziegler-Nichols Method, followed by further optimization through a meta-heuristical algorithm to enhance the response time of energy sources. The proposed power-sharing technique's performance is evaluated on a benchmark medium voltage network using industry-standard commercial software. The test results demonstrate the precise and rapid power-sharing capabilities among DGs facilitated by the proposed technique, highlighting its effectiveness in dynamic microgrid environments.

The digital era offers many opportunities to the wind energy industry and research community. Digitalisation is one of the key drivers for reducing costs and risks over the whole wind energy project life cycle. One of the largest challenges in successfully implementing digitalisation is the lack of data sharing and collaboration between organisations in the sector. In order to overcome this challenge, a new collaboration method called WeDoWind was developed in recent work. The main innovation of this method is the way it creates tangible incentives to motivate and empower different types of people from all over the world to actually share data and knowledge in practice. In this present paper, the challenges related to comparing and evaluating different SCADA data based wind turbine fault detection models are investigated by carrying out a new case study, the "WinJi Gearbox Fault Detection Challenge", based on the WeDoWind Method. Six new solutions were submitted to the challenge, and a comparison and evaluation of the results show that, in general, some of the approaches (Particle Swarm Optimisation algorithm for constructing health indicators, performance monitoring using Deep Neural Networks, Combined Ward Hierarchical Clustering and Novelty Detection with Local Outlier Factor and Time-to-failure prediction using Random Forest Regression) appear to have a high potential to reach the goals of the Challenge. However, there are a number of concrete things that would have to have been done by the Challenge providers and the Challenge moderators in order to ensure success. This includes enabling access to more details of the different failure types, access to multiple data sets from more wind turbines experiencing gearbox failure, provision of a model or rule relating fault detection times or a remaining useful lifetime to the estimated costs for repairs, replacements and inspections, provision of a clear strategy for training and test periods in advance, as well as provision of a pre-defined template or requirements for the results. These learning outcomes are used directly to define a set of best practice data sharing guidelines for wind turbine fault detection model evaluation. They can be used by the sector in order to improve model evaluation and data sharing in the future.

Peer-to-peer (P2P) content distribution or file sharing system aims to facilitate the dissemination of large files over unreliable networks. Network coding is a new transmission technique that has captured the interest of researchers because of its ability to increase throughput and robustness of the network, and decrease the download time. In this survey paper, we extensively summarize, assess, compare, and classify the most recently used techniques to improve P2P content distribution systems performance using network coding. To the best of our knowledge, this survey is the first comprehensive survey that specifically focuses on the performance of network coding based P2P file sharing systems.

The use of chimeric antigen receptors (CAR-T cells) for the treatment of patients with malignant haematological diseases has become a well-established application, for conditions such as refractory or relapsed B cell acute lymphoblastic leukaemia (B-ALL), B cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR-T cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR-T cells with approval by different regulatory agencies around the globe. In the USA the Food and Drug Administration (FDA) has approved 6 commercial CAR-T cells that are widely distributed worldwide. At the time of this writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR-T cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all the current areas of treatments with CAR-T cells, we offer a brief summary of some of the most relevant aspects of the use of CAR-T cells for some of these conditions.

The purpose of this study is to investigate the failure mechanism and preventive strengthening methods of prefabricated full length small box girder (PSBG) under car explosion. After damage analysis during blast loads using the commercial software Autodyn, three strengthening methods are presented to improve the blast mitigation performance. The results show that the failure modes and bearing capacity are significantly different with various strengthening measures. Adhering U-shaped steel plate can effectively enhance the shear performance of PSBG under blast loads. Strengthening the bottom of the upper flange of box girder with steel plate can effectively mitigate the local bending failure, and enhance the overall flexural capacity during car explosion.

Chimeric antigen receptor (CAR) T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We will examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Malta produces approximately 15,000 tons of bluefin tuna every year, by-products are estimated to count for 55% of the harvest. Maltese tuna farmers established a company that processes these by-products into fish meal and oil that are sold to the pet food industry. In this study the logistic of tuna farming and management in Malta was analysed and the environmental impact of the activity was estimated. The biomass quality and the preservation state of tuna head and liver was assessed. The head had the highest ash content (1.68±0.02%) while the liver had the highest protein content (16.18±0.02%) and the highest crude fat, (34.87±0.76%). The highest concentration of oil was found in the head’s skin (50.07±0.84%). The predominant saturated fatty acids (SFAs) were c14:0, c16:0 and c18:0. Monounsaturated FAs (MUFAs) were the major fatty acids present in all samples, with the highest values in the tuna head. The oxidation levels found in the by-products upon arrival at the processing plant doesn’t compromise their quality. No histamine formation was predicted. Some oxidation was observed in the oil after extraction. The Life Cycle Assessment estimated that the environmental score of the activity is 105pts per ton of fishmeal and 25kg of oil produced (2.82 tCO2 eq). It is concluded that the processing of tuna by-products in Malta is a sustainable alternative to traditional disposal methods and their quality is high enough to be used as a source of proteins and lipids in farmed-animals feed.

The article presents the issues related to load sharing in direct current grid and a novel control method which has advantages over known solutions. Unlikely of many similar sounding papers this article shows attempt of creation fully controllable non-isolated system which allows load sharing between permanent magnet alternator equipped with machine side converter (MSC) and dual active bridge (DAB) tied to batteries or supercapacitor. The power sharing is essential feature of parallel connected direct current generators and all types of voltage sources in this way are contributing power to the system. Such system should have possibility of the rapid voltage build up in the case of sudden electrical load changes. To keep the optimal efficiency of the alternator the rotational speed changes according to proper mapping of driving combustion engine. When rotational speed is too low then sudden electrical load can cause significant voltage drop and time needed for voltage build up will vary according to RPM increase. In such situations the undervoltage system can trip the breaker and finally there may be a blackout. To avoid such problem the DC systems which consist of batteries and supercapacitor were introduced. System components include a self-excited synchronous generator (SESG) operating at variable shaft speed as well as batteries and supercapacitors that provide electricity for sudden electrical load changes on the distribution grid. The core of presented system is in power distribution method which consists of programmed controllers structure allowing precise currents distribution. A novelty in the proposed method is the use of a cascaded system of current and DC voltage regulators which allows power distribution precise control. In contrary to previously presented solutions, the proposed system allows fast and accurate control of currents loading parallel connected DC voltage sources for wide range generator speed changes. In presented solution both converters have been equipped with Schottky diodes preventing flow of equalizing currents between closed transistors in the parallel mode of operation. An experimental test-stand of the described system is presented with its theoretical basis and experimental results.

Home care centers face both an increase in demand and many variations during the execution of routes, compromising the routes initially planned: robust solutions are not effective enough, it is necessary to move on to resilient approaches. We create a close to reality use case supported by interviews of staff at home health care centers, where caregivers are faced with unexpected events that compromise their initial route. We model, analyze and compare three resilient approaches to deal with these disruptions: a baseline approach without any collaboration, a distributed collaborative approach, and a centralized collaborative approach, where we propose a centralization and sharing of information to improve local decision-making. The latter reduces the number of late arrivals by 11% and the total time of late arrival by 21%, and also halves the number of routes exceeding the end of work time (contrary to the distributed collaborative approach, due to the time wasted reaching colleagues). The use of a device, such as a smartphone application, to centralize and share information thus allows better mutual assistance between caregivers. Moreover, we highlight several possible openings like the coupling of simulation and optimization to propose a more resilient approach.

Network effects, economies of scale, and lock-in-effects increasingly lead to a concentration of digital resources and capabilities, hindering the free and equitable development of digital entrepreneurship (SDG9), new skills, and jobs (SDG8), especially in small communities (SDG11) and their small and medium-sized enterprises (“SMEs”). To ensure the affordability and accessibility of technologies, promote digital entrepreneurship and community well-being (SDG3), and protect digital rights, we propose data cooperatives [1,2] as a vehicle for secure, trusted, and sovereign data exchange [3,4]. In post-pandemic times, community/SME-led cooperatives can play a vital role by ensuring that supply chains to support digital commons are uninterrupted, resilient, and decentralized [5]. Digital commons and data sovereignty provide communities with affordable and easy access to information and the ability to collectively negotiate data-related decisions. Moreover, cooperative commons (a) provide access to the infrastructure that underpins the modern economy, (b) preserve property rights, and (c) ensure that privatization and monopolization do not further erode self-determination, especially in a world increasingly mediated by AI. Thus, governance plays a significant role in accelerating communities’/SMEs’ digital transformation and addressing their challenges. Cooperatives thrive on digital governance and standards such as open trusted Application Programming Interfaces (APIs) that increase the efficiency, technological capabilities, and capacities of participants and, most importantly, integrate, enable, and accelerate the digital transformation of SMEs in the overall process. This policy paper presents and discusses several transformative use cases for cooperative data governance. The use cases demonstrate how platform/data-cooperatives, and their novel value creation can be leveraged to take digital commons and value chains to a new level of collaboration while addressing the most pressing community issues. The proposed framework for a digital federated and sovereign reference architecture will create a blueprint for sustainable development both in the Global South and North.

The paper presents the open source tool climdex-kit which includes utilities to compute, analyze and visualize climate indices based on the input data, target domain and temporal extent defined by the user. It is intended to support researchers as well as practitioners and decision makers to derive, handle and interpret meaningful information for climate change studies and sectoral applications. It currently includes the computation of 30 indices based on temperature and precipitation, describing both mean and extreme climate conditions, and it is designed to work with climate model projections. The tool is written in Python and integrates utilities from the well-established Climate Data Operators (CDO) and NetCDF Operators (NCO) libraries. The specific utilities for selecting, aggregating and visualizing data are thought to help users to produce tailored results improving understanding and communication of future climate change. In order to show the functionalities of the package as well as its potential integration in regional climate services, climdex-kit was applied to an ensemble of downscaled climate model projections up to 2100 for the region Trentino – South Tyrol (north-eastern Italian Alps). The projections for a selection of indices accounting for extreme temperature and precipitation conditions were derived and different visualization choices discussed. The package climdex-kit is developed in a way that allows users to implement additional routines for calculating other indices as well as for easily adapting the routines to handle with different data types and spatio-temporal targets defined by the specific application. Effective climate services can in fact be developed only if flexible tools and customizable climate information are integrated with a clear understanding of data features and limitations.

The concept of distributed generation has made photovoltaic an integral source of energy in smart grid systems, especially in peer-to-peer energy trading frameworks that exploit excess power to fulfill the energy requirements of consumers in cost-efficient and eco-friendly manner. It is believed that P2P energy trading will dominate a significant portion of research in forthcoming power generation systems due to the excessive rise of energy demands across the globe. Despite a plethora of studies on energy optimization solutions in P2P trading, minimizing nanogrid energy trading cost and efficient energy sharing between consumers and prosumers are deemed among the challenging problems. This study overcomes essential issues overlooked by the contemporary P2P energy trading models by introducing a predictive optimization-oriented nanogrid energy trading model. The proposed study encompasses two stages: (1) predictive optimization model which harnesses BD-LSTM-based forecasted energy parameters (energy load, energy consumption, and PV generation) that are later incorporated in PSO-enabled objective function to reduce nanogrid trading cost, (2) optimal energy sharing plan is devised to decide the role of nanogrids as prosumers or consumers by emphasizing the use of PV-produced energy. The proposed model is validated on the case study containing nanogrid houses data. The simulation provides detailed experiments by comparing the energy demand and response using the proposed energy sharing model. The outcomes yield that the energy sharing plan holds a significant potential to fulfill maximum energy requirements of nanogrid house in P2P cluster and significantly reduces the energy cost compared to grid.

Aim: The aim of this study was to estimate the number of nurses who independently care for pa-tients with severe respiratory failure receiving mechanical ventilation (MV) or veno-venous ex-tracorporeal membrane oxygenation (VV-ECMO). Additionally, the study analyzed the actual role of nurses in the treatment of patients with MV and VV-ECMO. Methods: We conducted a cross-sectional study using postal surveys. The study included 725 Japanese intensive care units (ICUs). Descriptive statistics were conducted. Results: Among the 725 ICUs, we obtained 302 re-sponses (41.7%) and analyzed 282 responses. The median number of nurses per bed was 3.25. The median proportion of nurses who independently cared for patients with MV was 60% [IQR: 42.3-77.3]. The median proportion of nurses who independently cared for patients with VV-ECMO was 46.9 (35.7-63.3%) in the ICU experiencing VV-ECMO use. Concerning task-sharing, 33.8% of ICUs and nurses did not facilitate weaning from MV. Nurses always ti-trated sedatives in 44.5% of ICUs. Conclusion: Nurse staffing might be inadequate in all ICUs, es-pecially for severe respiratory failure. The proportion of competent nurses for caring for severe respiratory failure in ICUs should be considered when determining the work force of nurses.

While cycling presents environmental benefits and promotes a healthy lifestyle, the risks associated with overtaking maneuvers by motorized vehicles pose significant hindrances for many potential cyclists. Large-scale analysis of overtaking maneuvers could inform traffic researches and city planners on how to reduce these risks by better understanding these maneuvers. Drawing from the fields of sensor-based cycling research and of LiDAR-based traffic data sets, this paper provides a step towards addressing these safety concerns by introducing the Salzburg Bicycle 3d (SaBi3d) data set, consisting of LiDAR point clouds capturing car-to-bicycle overtaking maneuvers. The data set, collected using a LiDAR-equipped bicycle, facilitates detailed analysis of a large quantity of overtaking maneuvers without the need for manual annotation through enabling automatic labeling by a neural network. Additionally, a benchmark result for 3d object detection using a competitive neural network is provided as a baseline for future research. The SaBi3d data set is structured identically to the nuScenes data set, and therefore offers compatibility with numerous existing object detection systems. This work provides valuable resources for future researchers to better understand cycling infrastructure and mitigate risks, thus promoting cycling as a viable mode of transportation.

This study explored drivers’ emotion-based impressions of car-borne central control platforms (CBCCPs) personal-use vehicles. Thus, this preference-based study examined experts’ and drivers’ opinions regarding CBCCPs’ appeal from the perspective of Miryoku engineering. To this end, this study analyzed data via the EGM (evaluation grid method (EGM) and quantification theory type I. Results: Drivers’ preferences for specific CBCCP design characteristics were categorized into the factors “legible,” convenient,” and “tasteful,” which comprised the core of the EGM semantic hierarchical diagram. In addition, the importance of CBCCPs’ appeal factors and characteristics was assessed through quantification theory type I.The findings of this study provide valuable insights for designers, manufacturers, and researchers interested in the design of CBCCPs. Additionally, the results of this study can contribute to research on applied psychology, human-computer interactions, and car interface design.

The used car market has a high global economic importance, with more than 35 million cars sold yearly. Accurately predicting prices is a crucial task for both buyers and sellers to facilitate informed decisions in terms of opportunities or potential problems. Although various Machine Learning techniques have been applied to create robust prediction models, a comprehensive approach has yet to be studied. This research introduces two datasets from different markets, one with over 300,000 entries from Germany to serve as a training base for deep prediction models and a second dataset from Romania containing more than 15,000 car quotes used mainly to observe local traits. As such, we include extensive cross-market analyses by comparing the emerging Romanian market versus one of the world’s largest and most developed car markets, Germany. Our study uses several neural network architectures that capture complex relationships between car model features, individual add-ons, and visual features to predict used car prices accurately. Our models achieved a high R2 score exceeding 0.95 on both datasets, indicating their effectiveness in estimating used car prices. Moreover, we experimented with advanced convolutional architectures to predict car prices based solely on visual features extracted from car images. This approach exhibited transfer-learning capabilities, leading to improved prediction accuracy, especially since the Romanian training dataset is limited. Our experiments highlight the most important factors influencing the price, while our findings have practical implications for buyers and sellers in assessing the value of vehicles. At the same time, the insights gained from this study enable informed decision-making and provide valuable guidance in the used car market.

Multipartite entanglement is a resource for application in disparate protocols, of computing, communication and cryptography. In this paper, generation, characterisation and application of a genuine genuinely entangled seven-qubit resource state is studied. Theoretical schemes for quantum teleportation of arbitrary one, two and three qubits states, bidirectional teleportation of arbitrary two qubit states and probabilistic circular controlled teleportation as well as three schemes for undertaking tripartite quantum state sharing are presented.

Background/Objectives Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥3 thrombocytopenia occurs in around one third of patients, many of whom become platelet transfusion-dependent. Without pharmacological support, platelet recovery may last for months. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP.) Its role to manage thrombocytopenia, and other cytopenias, in CAR-T cell-treated patients has been scarcely addressed in the real-world setting. Our aim was to report the Feasibility of this approach and the outcome of patients included in the GETH-TC registry. Methods This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion-dependence subsequently to CAR-T cell treatment were recruited in 10 Spanish hospitals and followed-up for at least 30 days after the first dose of eltrombopag was administered. Results Thirty-eight patients were enroled and followed-up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At eltrombopag start, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units used correlated with the time needed to restore platelet counts to levels ³20x10⁹/L (Rho = 0.639, p <0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of 23 (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of 35 (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only 2 transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions Eltrombopag can be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.

In-wheel motor vehicles are gaining attention as a new type of electric vehicle due to their efficient power units located inside each wheel hub. However, they are more susceptible to wheel resonance due to the increase in unsprung mass caused by the motor's weight. This can result in decreased both the ride comfort and driving stability. To resolve this issue, this study aims to apply an optimal switching controller with a semi-active n actuator; magnetorheological (MR) damper. For the implementation of the optimal switching controller, a road type classification is also carried out. An acceleration sensor is used for road type classification, and control logics include a ride comfort controller; the linear quadratic regulator (LQR _Paved Road) and a wheel motion controller (LQR_Off Road) for improved driving stability. For paved roads, the LQR_Paved Road control input is applied to the MR damper. However, if a road type prone to wheel resonance is detected, the control logic switches to the LQR_Off Road. During the transition, a weighted average of both LQR_ Paved Road and LQR_Off Road control input is applied to the actuator. Computer simulations are undertaken to evaluate vibration control performance, including the ride comfort and driving stability at various road profiles.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

In this paper, we address the problem of car detection from aerial images using Convolutional Neural Networks (CNN). This problem presents additional challenges as compared to car (or any object) detection from ground images because features of vehicles from aerial images are more difficult to discern. To investigate this issue, we assess the performance of two state-of-the-art CNN algorithms, namely Faster R-CNN, which is the most popular region-based algorithm, and YOLOv3, which is known to be the fastest detection algorithm. We analyze two datasets with different characteristics to check the impact of various factors, such as UAV's altitude, camera resolution, and object size. The objective of this work is to conduct a robust comparison between these two cutting-edge algorithms. By using a variety of metrics, we show that YOLOv3 yields better performance in most configurations, except that it exhibits a lower recall and less confident detections when object sizes and scales in the testing dataset differ largely from those in the training dataset.

In this paper, we address the problem of car detection from aerial images using Convolutional Neural Networks (CNN). This problem presents additional challenges as compared to car (or any object) detection from ground images because features of vehicles from aerial images are more difficult to discern. To investigate this issue, we assess the performance of two state-of-the-art CNN algorithms, namely Faster R-CNN, which is the most popular region-based algorithm, and YOLOv3, which is known to be the fastest detection algorithm. We analyze two datasets with different characteristics to check the impact of various factors, such as UAV’s altitude, camera resolution, and object size. The objective of this work is to conduct a robust comparison between these two cutting-edge algorithms. By using a variety of metrics, we show that none of the two algorithms outperforms the other in all cases.

Based on the Organizational Support Theory, this study examines the relationship between human resource management practices and service performance of sharing workers by demonstrating the mediation role of work engagement. We tested this theoretical model using an in-person interview questionnaire survey of 318 downwind drivers. Results showed that: (1) the main effect of human resource management practices of sharing workers on service performance was significant; (2) work engagement played a prominent mediation role between human resource management practices and service performance of sharing workers; (3) the mediation role of employee vigor between the platform incentives and the performance of employee services was significant; (4) employee dedication had an obvious and indirectly positive mediating effect between sharing workers' dimensions of human resource management practice and their service performance; (5) employee absorption on the mediation role between the various dimensions of the sharing human resources management practices (platform support, platform incentives and platform constraints) and employee service performance was significant. This study has important value for the study on human resource management practices in the context of sharing economy, and provides practical enlightenment for employee management of the sharing economy platform.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.