As Automated Driving Systems (ADS) technology gets assimilated into the market, the driver’s obligation will be changed to a supervisory role. A key point to consider is the driver’s engagement in the secondary task to maintain the driver/user in the control loop. The paper’s objective is to monitor driver engagement with a game and identify any impacts the task has on hazard recognition. We designed a driving simulation using Unity3D and incorporated three tasks: No-task, AR-Video, and AR-Game tasks. The driver engaged in an AR object interception game while monitoring the road for threatening road scenarios. From the results, there was less than 1 second difference between the means of gaming task (mean = 2.55s, std = 0.1002s) to no-task (mean = 2.55s, std = 0.1002s). Game scoring followed three profiles/phases: learning, saturation, and decline profile. From the profiles, it is possible to quantify/infer drivers’ engagement with the game task. The paper proposes alternative monitoring that has utility, i.e., entertaining the user. Further experiments AR-Game focusing on real-world car environment will be performed to confirm the performance following the recommendations derived from the current test.

The study presents a comparison of the common Child Restraint Systems (CRS) which reduces the value of dynamic loads affecting the child's body during car accidents. The analyzed systems were: child seats, Combi Booster Seats, and straps adjusting vehicle seat belts to children's sizes. The effectiveness of the analyzed devices was assessed on the basis of experimental tests carried out in the accredited laboratory approving the Child Restraint Systems. The tests were carried out accordingly to the new Regulation No. 129 UN / ECE. Whether the tested devices meet the guidelines of the new Regulations No. 129 despite approval in accordance with Regulation No. 44. Based on the research result, better safety parameters of some new solutions dedicated to children’s safety could be observed. The final results show that there is still space for improving the safety of young vehicle passengers.

The study presents a comparison of the common Child Restraint Systems (CRS) which reduces the value of dynamic loads affecting the child's body during car accidents. The analyzed systems were: child seats, Combi Booster Seats, and straps adjusting vehicle seat belts to children's sizes. The effectiveness of the analyzed devices was assessed on the basis of experimental tests carried out in the accredited laboratory approving the Child Restraint Systems. The tests were carried out accordingly to the new Regulation No. 129 UN / ECE. Whether the tested devices meet the guidelines of the new Regulations No. 129 despite approval in accordance with Regulation No. 44. Based on the research result, better safety parameters of some new solutions dedicated to children's safety could be observed. The final results show that there is still space for improving the safety of young vehicle passengers.

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.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

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.

Despite the use of commercial forest carbon protocols (CFCPs) for more than two decades, claiming ~566 MMtCO2e and a market value of ~USD $15.7 billion, comparative analysis of CFCP methodology and offset results is limited. In this study, five widely used biometric-based CFCPs were characterized, and common characteristics and differences were identified. CFCP claims of net forest carbon sequestration are compared with results of directly measured CO2 by eddy covariance, a meteorological method integrating gross vertical fluxes of forest and soil carbon, and the only alternative non-biometric source of net forest carbon sequestration data available. We show here that CFCPs share a structural feature delimiting forest carbon values by zero-threshold carbon accounting (gC m-2 ≤ 0), a pattern opposite to natural emissions of forest CO2 exchange based on direct measurement and a fundamental biological constraint on net forest carbon storage (i.e., soil efflux, ecosystem respiration). Exclusion of forest CO2 sources to the atmosphere precludes net carbon accounting, resulting in unavoidable over-crediting of CFCP offsets. CFCP carbon results are significantly different from global forest CO2 net ecosystem exchange population results (FluxNet2015 gC m-2) at the 95% to 99.99% confidence levels, inferring an annual median error of ~247% (gC m-2), also consistent with over-crediting. Direct CO2 measurement provides an alternative method for commercial forest carbon products, has the potential to harmonize global markets, and catalyze the role of forests in managing climate change through nature-based solutions.

(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.

In this paper we describe many important aspects connected with lubricants, namely: the most cheapest organic lubricant in the word, how effectively save lubricant between pairs of friction, what kind of rational shapes for the lubricant must be, what it will be connected with wear and tear using the new organic lubricant (for this purpose formulas and curves are shown in computer program MathCad with calculation). Moreover, there is one physical model which helps to catch car exhausted gases. In conclusion, some recommendations will be given to realize them into the practice during the operation for the different mechanisms including ecology.

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.

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

There are no studies that have investigated the characteristics of car use across THA patients, including those who do not drive. This study aimed to evaluate, in THA patients, (1) postoperative car usage, (2) comfort while entering and exiting a car, and (3) whether lower limb muscle strength affects action comfort. One hundred seventy-two post-THA patients completed the questionnaire in 2020, along with assessments of hip abductor and knee extensor muscle strength before surgery and at discharge. Patients whose overall comfort level was judged as “comfortable” were defined as the “comfort” group; others were placed in the “discomfort” group. Of the 172 patients, 161 reported car usage at a mean of 5.6 years after THA. Of these, 114 and 47 patients were placed in the "comfort" and "discomfort" groups, respectively. Patients in the "discomfort" group were three times more likely to experience discomfort using the contralateral side door than the surgical side door, and about twice as many patients experienced discomfort when entering as when exiting. Lower preoperative contralateral hip abductor muscle strength was the only independent predictor for discomfort. The take-home messages were that prevention of contralateral-side weakness may improve comfort during the action after THA.

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

Despite advances in the understanding of its molecular pathophysiology, prostate cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed in prostate cancer, which expression involves neovasculature of several tumor entities, thus envisaging an additional antiangiogenic effect. To optimize the CAR design, we compared two CARs with signaling domains containing one or two T cell costimulatory elements, in addition to CD3ζ. Conversely, what has been described for other CARs, a third-generation CAR (containing CD28 and 41BB co-signaling domains) induced a potent antitumor effect similar to a second-generation CAR (containing CD28 co-signaling domain), though we observed a detrimental effect of the additional costimulatory domain that was attributed to increased activation-induced cell death (AICD). This “super-stimulation” resulted in exhaustion of cells, higher frequencies of cell death and, more importantly, the impossibility of sufficiently expanding the CAR cells to obtain the minimum number of cells requested for in vivo therapies. While the superiority of 2nd and 3rd generation over 1st generation CAR T cells has been clearly shown in both preclinical and clinical studies, the optimal combination of costimulatory domains for 3rd generation CAR-T cells must still be defined and should be evaluated case-by-case in order to fine-tune immunotherapy approaches.

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.

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.

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.

Acceleration rates of vehicles are crucially important statistics needed in two main aspects: first, they are essential to incident reconstructor professionals as having a verified database on where basing the cinematic reconstructions is definitely difficult and moreover, they are useful in order to understand how to create the safest possible environment on the road. This key topic gives es-sential information for road design like intersection schemes, acceleration and deceleration lane length as well as traffic simulation modelling and furthermore, to educate vehicle drivers when entering the traffic flow and to provide limit acceleration values needed to develop autonomous vehicle’s software in order to guarantee a comfort drive. Literature reports tons of linear acceleration stats mainly referred to vehicle performances claimed by car manufacturers, but these data don’t recreate real drivers’ behaviour when entering the road by turning left or right or crossing an intersection. This work aims to integrate the most reliable data from literature with a hybrid and an electric vehicles statistic, adding also two contemporary thermal engine vehicles, extracted conducting probes that recreates real road environment. The entirety of these experiments reconstructs the scenario in which a car is entering the traffic of a two-lanes road, from a stationary position at a stop sign and the acceleration rates are collected using a M.E.M.S. (Microelectromechanical system). Finally, the space needed between the car that is about to enter or crossing the road and the car that is approaching the intersection is calculated, basing the computations on the acceleration values extracted from the probes. These spaces are pictured, as a way to give a concrete idea to readers.

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.

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.

Virtual reality (VR) can play a key role in automotive marketing research, lowering costs and shortening the time it takes to bring a new product to market. However, there are still few VR applications that support automotive customers' experiences during the early stages of product development. Through a systematic review of literature and patents, this study aims to identify the challenges and opportunities for the application of virtual reality in car clinics, and to categorize them into attributes. We searched through the knowledge databases of PatentScout, ScienceDirect, Springer, and IEEEXplore. We found 72 patents with a high concentration in a few inventors. The United States of America presented the greatest number of records and the most common applications related to the apparatus for automatically reading respondents' reactions in a virtual environment. In terms of articles, we found 19 research papers that discussed sixteen categories identified as challenges and opportunities for automotive marketing research: 1) cost, 2) location to customers, 3) flexibility in interactions, 4) model transportation, 5) depth perception, 6) haptic perception, 7) motion, 8) movement perception/ physical collision, 9) color and texture, 10) sound feedback, 11) product interaction/manipulation, 12) visual-spatial, 13) graphic quality, 14) intuitiveness, 15) cybersecurity and 16) cybersickness. We conclude that the automotive industry can employ virtual reality for marketing research, but relevant elements such as hardware and software definition, stimulus quality, and research objectives, among others, must be considered.

Keywords: Adrenergic signaling in cardiomyocytes; cardiac muscle contraction; Chagas disease; diabetic cardiomyopathy; dilated cardiomyopathy; glycerolipid metabolism; glycolisis/glucogenesis; hypertrophic cardiomyopathy; purine metabolism; steroid hormone biosynthesis.

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.

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.

Claudins are a family of 27 proteins that have an important role in the formation of tight junc-tions. They also have an important function in ions exchange, cell mobility, and in in the epitheli-al-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evi-dence shows improved outcomes when combining monoclonal antibodies against Claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently Chimeric anti-gen receptor T-cells targeting Claudin 18 are under investigation.

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.

Greenhouse gas (GHG) emissions from human activities have climbed significantly above pre-pandemic levels and reached record highs that unequivocally accelerate global warming. Industry has a significant impact on climate change, emitting at least 21 % of global GHGs and making little overall progress toward its reduction until now. Reducing industry’s emissions requires coordinated action along the value chains in order to promote mitigation options, such as energy and material efficiency, circular material flows, and transformative changes within production processes. The authors analyzed the GHG emissions generated during the manufacturing of three different products of automotive suppliers located in Austria. Despite previous efforts toward an environmentally compatible fabrication, additional and significant reduction potentials were identified. These measures for product carbon footprint (PCF) reduction included the sourcing of low-carbon materials (which are already available on the market), more extensive use of renewable energy, and changes towards more resource efficient manufacturing processes and machinery. Depending on the materials used, the PCF can be reduced by up to 80 %. The findings serve to prepare for future PCF reporting regulations and illustrate reduction potentials to achieve future market advantages, especially when PCFs become an awarding criterion.

This research paper examines the evolution of car purchasing behaviour among consumers in India from 2010 to the present. Through extensive literature review and questionnaire survey, it explores the reasons behind the changing preferences and decision-making processes of consumers in the Indian automobile market. The study draws upon various sources, including market research reports, industry publications, academic studies, and consumer surveys, to provide a comprehensive analysis of the factors influencing car purchasing behaviour in India over the last decade. The findings of this research paper can help automakers and marketers better understand consumer preferences and develop effective strategies to cater to the evolving needs of the Indian car market.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

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.

Prostate cancer (PCa) has become the most common tumor among males in Europe and the USA. Adoptive immunotherapy appears as a promising strategy to control the advanced stages of the disease by specific targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

In this paper, the physical station of space network was extended in time dimension by combining the train diagram information and station technical operation standard time. At the same time, the topology of railway space-time network which considered the secondary operation process of train was constructed and an improved A* algorithm based on car flow routing was proposed to generate feasible path sets. On this basis, a dynamic car flow organization optimization model was built to simulate the railway car flow organization process under abnormal conditions, and the results of solving the model could be used to obtain the real-time quantity of cars at each station.This paper can identify the dynamic bottleneck by comparing the real-time quantity of cars with the maximum quantity of cars at the station. Finally, the feasibility of this method was analyzed and verified by a case.

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.

Mesothelioma is a cancer arising from mesothelial cells lining the thoracic (pleura) or the abdominal (peritoneum) cavities, and more rarely from transformed mesothelial cells of pericardium or tunica vaginalis testis. The development of mesothelioma has been related to the exposure to carcinogenic mineral fibers, mainly asbestos. Malignant mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. We here review all these aspects to underline the progress being made in investigation and to emphasise how much work remains to be done to improve prognosis and treatment.

The key to ensuring the sustainability of transportation operations on the roads is to manage traffic flows homogeneously. By homogenizing the behavior of various drivers, traffic operation can be optimized, and traffic safety can be improved. However, the advent of autonomous vehicles is expected to have a major impact on the homogeneity of sustainable transportation operations. In this study, a method of driving in harmony with surrounding vehicles was studied to minimize the impact of autonomous vehicles on current traffic operation. In particular, in this study, a methodology was developed to optimize the driving behavior of autonomous vehicles by analyzing the driving behavior of following vehicles using spectrum analysis. Specifically, a method for calculating three indicators that can analyze the driving behavior of a following vehicle, such as reaction time, stimulus adaptation index, and collision risk avoidance index, was proposed. These indices produced consistent and robust results for all traffic conditions. If these indicators are used, it is expected that sustainable traffic management will be possible even when autonomous vehicles and human drivers are mixed on the road.

CAR-T therapy has achieved considerable treatment success in hematologic tumors by using patient derived autologous αβ T cells. There is an impetus to broaden the applicability of this approach by using a third-party donor derived CAR-T cell product which has a potent anti-tumor function but a constrained GVHD property. In this study, CAR-T cells were prepared from Vγ9Vδ2 T cells expanded by using a novel prodrug PTA and their anti-tumor functions were assessed in conjunction with persistency, localization, and phenotype. γδ T cells were successfully transduced with a CAR specific to CEA with signaling domains of CD3ζ and CD28 (CEA.CAR-γδ T cells), and exhibited potent tumor killing function in vitro. In a xenograft mouse model, CEA.CAR-γδ T cells suppressed CEA+ tumor growth though a limited time window. CEA.CAR-γδ T cells persisted and accumulated in the tumor even after tumor progression, however, ex vivo analysis revealed that those recovered at different time points from PBMC, spleen and tumors gradually lost tumor reactivity as assessed by IFN-γ production. Provision of GITR co-stimulation enhanced anti-tumor function of CEA.CAR-γδ T cells, the result of which imposes additional measurers to be adopted in CAR-γδ T cells for an allogeneic adoptive immunotherapy.

This paper proposes the recycling of plates from spent car batteries by the melt quenching method and the incorporation of NiO or Co3O4 contents in order to improve the electrochemical performance of new materials for applications as electrodes on batteries. The analysis of X - ray diffractograms indicates the gradual decrease of the sulfated crystalline phases, respectively 4PbO•PbSO4 and PbO•PbSO4 phases until their disappearance for higher dopant concentrations. IR data show a decreasing trend in the intensity of the bands assigned to sulfate ions and a conversion of [PbO3] pyramidal units into [PbO4] tetrahedral units by doping with high dopant levels yielding to the formation of the PbO2 crystalline phase. The EPR data indicate three resonance lines centered on the gyromagnetic factor, g ~ 2, 2.2 and 8, which are dependent on the NiO level. The first two resonance lines are assigned to nickel ions in higher oxidation states and the last signal centered at g ~ 8 corresponds to nickel metal nanoparticles. This compositional evolution can be explained by considering a process of drastic reduction of nickel ions in oxidation states superior to metallic nickel. The linewidth and the intensity of resonance lines situated at about g ~ 2, 2.17, 4.22 and 7.8 corresponding to the Co+2 ions from EPR spectra depend very strongly on the Co3O4 concentration. The best reversibility of the cyclic voltammograms was highlighted for the samples with x = 8 mol% NiO and 10 mol% Co3O4, which are recommended as suitable in applications as electrode for renewable batteries.

A widely discussed topic in the pathophysiology of thyroid nodules is the role of obesity that leads to increased systemic inflammatory markers. Leptin plays a vital role in forming thyroid nodules and cancer through several mechanisms. Together with chronic inflammation, there is an augmentation in the secretion of tumor necrosis factor (TNF) and cytokines interleukin 6 (IL-6), contributing to cancer development, progression and metastasis. In addition, leptin exerts a modulatory action in the growth, proliferation and invasion of thyroid carcinoma cell lines via activating various signal pathways, such as Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase (MAPK) and/or phosphoinositide 3-kinase (PI3K) /protein kinase B (Akt). Through several proposed mechanisms, aberrant endogenous estrogen levels have been suggested to play a vital role in the development of both benign and malignant nodules. Metabolic syndrome triggers the development of thyroid nodules by stimulating thyroid proliferation and angiogenesis due to hyperinsulinemia, hyperglycemia and dyslipidemia. Insulin resistance influences the distribution and structure of the thyroid blood vessels. Insulin growth factor -1 (IGF-1) and insulin affect the regulation of the expression of thyroid genes and the proliferation and differentiation of thyroid cells. TSH can promote the differentiation of pre-adipocytes to mature adipocytes, but also, in the presence of insulin, TSH possesses mitogenic properties. This review aims to summarize the underlying mechanisms explaining the role of obesity in the pathophysiology of thyroid nodules and discuss potential clinical implications.

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.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

The energy yield of the Vehicle-integrated photovoltaic (VIPV) differs from that of the standard photovoltaics (PV). It is mainly by the difference of the solar irradiance onto the car-roof and car-bodies as well as its curved-shape. Both meaningful and practical modeling and measurement of the solar irradiance for VIPV are needed to be newly established, not the extension of the current technologies. The solar irradiance was modeled by a random distribution of the shading objects and car-orientation with the correction of the curved surface of the PV modules. The measurement of the solar irradiance onto the car-roof and car-body was done using five pyranometers in five local axes on the car for one year. The measured dynamic solar irradiance onto the car-body and car-roof was used for validation of the solar irradiance model in the car.

A car-roof photovoltaic has an enormous potential to change our society. With this technology, 70% of the personal car can run by the solar energy collected by the solar panel on its car-roof. Unfortunately, it is not a simple extension of the conventional photovoltaic technology. This paper list what we need to do for realizing the future that majority of the personal cars run by renewable solar energy, after clarification of the difference from the conventional photovoltaic technology. In addition to the technological development, the standardization of this innovative technology will be important, and the list was made highlighting the standardization.

The importance of utilizing an optimal and efficient braking system is emphasized in this study. Braking system optimization and efficiency were practically determined through successive tests on the brake dynamometer, according to road safety regulations. Subsequently, the results were correlated with practical tests involving consecutive braking at different speeds, tracking both the time and distance of braking. The coefficient of friction (COF) was established for each braking instance by utilizing the braking force measured on the brake dynamometer. This paper aims to highlight the genuine impact of the braking system by measuring and establishing its braking efficiency depending on the car’s speed, time, and distance of braking.

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.

Background &amp; Aim: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. Methods: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between Dec 1st, 2017, and May 1st, 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid, surgical, and hospitalization-free treatment. Results: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p=0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p=0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p=0.593). Conclusion: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

The software design of autonomous vehicles (AVs) incorporates artificial intelligence (AI) characteristics to enhance their safety and overall driving performance. Central to vehicle’s operation is the ability to reason effectively in complex and uncertain environments. However, traditional logical systems, such as monotonic logic, often struggle to handle the inherent uncertainties and exceptions encountered in real-world scenarios. This paper proposes the utilization of non-monotonic logic in order to enhance the reasoning capabilities of autonomous vehicles. By incorporating non-monotonic reasoning, vehicles can navigate intricate traffic scenarios, make plausible inferences, and adapt their decisions when faced with conflicting information. This research aims to provide a comprehensive review of non-monotonic logic's application in autonomous vehicles, highlighting its advantages over traditional logical systems and its potential impact on safety and performance. Additionally, through this research, we seek to contribute to the advancement of autonomous driving technology by enhancing the reasoning capabilities of vehicles in various scenarios, such as car- following related to critical safety events. The personalized cognitive agent is proposed in driving behavior to consider particularly in their assumptions of homogeneous drivers. The personalized cognitive agent is incorporating heterogeneous driving behaviors, based on individual user preferences, characteristics, and needs. Driving behavior is a complex interplay of various factors, encompassing both human and external elements. Human factors, including age, experience, and gender, contribute significantly to how individuals navigate the roads. These factors influence decisions, reactions, and risk-taking tendencies on the part of drivers. Additionally, external factors such as weather conditions further compound this intricate dynamic, requiring drivers to adapt their behavior to the prevailing environment. The goal of a personalized cognitive agent is to provide tailored and customized experiences to cognitive vehicles, taking into account the unique requirements and individual preferences of occupants inside autonomous vehicles.

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.

Endothelial integrity plays a major role in homeostasis and is responsive to the numerous endogenous factors released. While its functional role in vascular tone is well described, its role in the pathophysiology of cardiovascular disease is of interest as a potential therapeutic target. We performed a systematic review to provide an overview of new therapeutic and diagnostic targets for the treatment of coronary artery disease related to endothelial dysfunction. Databases of PubMed, Ovid’s version of MEDLINE, and EMBASE were interrogated with appropriate search terms. 28 studies met inclusion criteria and were included in the final systematic review. We identified inflammation, pulmonary hypertension, diabetes mellitus and Fabry disease as pathophysiological mechanisms and explored the therapeutic options related to these conditions including medications such as Canakinumab. Endothelial dysfunction has a key role in several different pathophysiological processes which can be targeted for therapeutic options. Ongoing research should be targeted at making the transition to clinical practice. Further research is also needed on understanding the amelioration of endothelial dysfunction with the use of cardiovascular medications.

Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

Current article presents the study of psychological wellbeing of adolescents (n=168, age 15-17) gifted in math, humanities and sports and educated in advanced programs for gifted children. Theoretical framework of this study is eudemonic concept of psychological wellbeing by C. Ryff. Psychological wellbeing is measured with Ryff wellbeing scales in Russian adaptation by L.V. Zhukovskaya and E.G. Troshikhina. The study is aimed at understanding differences in psychological wellbeing of gifted teenagers connected to gender and type of giftedness. The results suggest that general wellbeing score did not differ for adolescents with different types of giftedness or of different genders. Separate components of psychological wellbeing, such as purpose in life and self-acceptance, are influenced by activity connected to the talent. Gender differences are subjected to age-specific trends of personal development in adolescence. Type of giftedness might reinforce these trends.

With Internet of Things (IoT) gaining presence throughout different industries a lot of new technologies have been introduced to support this undertaking. Implications on one such technology, wireless systems allowed for the use of different communication methods to achieve the goal of transferring data reliably, with more cost efficiency and over longer distances. Anywhere from a single house with only a few IoT devices such as a smart light bulb or a smart thermostat connected to the network, all the way to a complex system that can control power grids throughout countries, IoT has been becoming a necessity in everyday lives. This paper presents an overview of the devices, systems and wireless technologies used in different IoT architectures (Healthcare, Vehicular Networks, Mining, Learning, Energy, Smart Cities, Behaviors and Decision Making), their upbringings and challenges to this date and some foreseen in the future.

Tunnel-interchange connecting sections pose significant safety challenges on mountainous expressways due to their high incidence of accidents. Improving road safety necessitates a comprehensive understanding of driver behavior in such areas. This study explores the influences of road characteristics, signage information volume, and traffic conditions on drivers' car-following and lane-changing behavior in tunnel-interchange diverging areas. Utilizing driving data from 25 subjects of 72 simulated road models, driving performance is assessed using Friedman rank test and multivariate variance analysis. The results highlight the significant influence of both connection distance and signage information load on driving behavior. In tunnel-interchange scenarios, the reduction of velocity increased by 62.61%, and speed variability surged by 61.11%, indicating potential adverse effects on driving stability due to the environmental transitions. Decreased connection distances are associated with reduced lane-changing durations, larger steering angles, and increased failure rates. Furthermore, every two units increase in signage information leads to a 13.16% rise in maximum deceleration and a 5% increase in time headway. Notably, the signage information volume shows a significant interaction with connection distance (F=1.60, P=0.045) for most car-following indicators. Hence, the study recommends a maximum connection distance of 700 m and signage information not exceeding nine units for optimal safety and stability.

Keywords: Echocardiographic alterations; left ventricle; dog; Trypanosoma cruzi; flow patterns; dilated cardiomyopathy; Chagas disease

Addressing the pressing challenge of global warming, reducing greenhouse gas emissions in the transportation sector is a critical imperative. Battery and fuel-cell electric vehicles have emerged as promising solutions for curbing emissions in this sector. In this study, we conducted a comprehensive life cycle assessment (LCA) for typical passenger vehicles, heavy duty trucks and city buses using either proton-exchange membrane fuel cells or Li-ion batteries with different cell chemistries. To ensure accuracy, we supplemented existing studies with data from the literature, particularly for the recycling phase, as database limitations were encountered. Our results highlight that fuel cell and battery systems exhibit large emissions in the production phase. Recycling can significantly offset some of these emissions, but a comparison of the technologies examined revealed considerable differences. Overall, battery electric vehicles consistently outperform fuel cell electric vehicles regarding absolute greenhouse gas emissions. Hence, we recommend prioritizing battery electric over fuel cell vehicles. However, deploying fuel cell electric vehicles could become attractive in a hydrogen economy scenario where other factors, e. g. the conversion and storage of surplus renewable electricity via electrolysis, become important.

ADHD, one of the most prevalent diseases during childhood, we still do not know its precisely origin, although oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in these patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, and the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results show a treatment-related improvement in the redox profile, with the reduction of advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase of the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These result support by the first time the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

This article presents a state-of-the-art literature review to understand people’s perceptions and opinions of Autonomous Vehicles (AVs) and the factors that influence AV adoption. A strategic literature search was conducted to select articles for this review. Most of the articles were published within the last five years and they used a household questionnaire survey to collect data. Mostly, they used statistical and econometric methods to evaluate the factors that affect people’s intentions to adopt AVs. The results show that psychological factors often appear as the most important internal factors of people’s willingness to adopt AVs. Additionally, other internal factors such as the socioeconomic profile of individuals and their household, and knowledge and familiarity with AV technologies would affect AV adoption tendencies. User attributes also indirectly affect AV adoption by influencing the psychological factors of users. We identify several critical external factors such as opportunities (e.g., safety and security, low congestion, energy use) and challenges (e.g., system failure, privacy breach, and legal issues), while another influential group includes transportation factors (e.g., travel mode, distance, and time), urban form (e.g., urban/rural, density, land use diversity), affinity to new technology, and the institutional regulatory environment. We discuss some recommendations for policy makers, auto industries, and private stakeholders to formulate policies and strategies to increase market share of AVs. Finally, we identify some limitations of previous studies and provide a blueprint for future research on AV adoption.

Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial successes against B-cell malignancies, what has led to a growing scientific and clinical interest on extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immuno-suppressive tumour microenvironment, that is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, accounting for their immunosuppressive capabilities. Using the mathematical model, we show that the use of large numbers of CAR-T cells targeting the solid tumour antigens could overcome the cancer immunosuppressive potential. To achieve such high levels of CAR-T cells we propose and study computationaly, the manufacture and injection of CAR-T cells targeting two antigens: CD19 and a tumour-associated antigen. We study in-silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive generation of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its inmune suppression capabilities. That strategy could benefit from the combination with PD-1 inhibitors and of low tumour loads. Our computational results provide a theoretical support for the treatment of different types of solid tumours using T-cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD1 drugs after completion of classical cytoreductive treatments.

The numerous biological activities of phenothiazine and sulphonamide derivatives, especially their antibacterial qualities, have attracted so much interest. In this study, the synthesis and characterization of phenothiazine-3-sulphonamide derivatives and evaluation their antimicrobial activity against the following pathogenic microorganisms is reported. Two gram-positive bacteria; (Staphylococcus aureus, and Streptococcus pyogenes), two gram-negative bacteria; (Escherichia coli, and Salmonella typhi) as well as one fungus (Aspergillus fumigatus) were used while ciprofloxacin, gentamycin and ketoconazole served as standard drugs. The synthesis of the derivatives was achieved through a base catalyzed the reaction of 4-chloroaniline with 1-naphthylamine to form 1-(naphthalen-1-yl) benzene-1,4-diamine. This intermediate was then treated with sulphur and iodine to yield the phenothiazine derivative while subsequent treatment of the phenothiazine compound with sulphonyl chlorides gave the final products. The synthesized compounds were characterized via proton nuclear magnetic resonance (1HNMR), carbon-13 nuclear magnetic resonance (13C NMR) and Fourier-transform infrared (FTIR) spectroscopic techniques. The minimum inhibitory concentration (MIC) of each compound was then determined using the agar well diffusion method. To predict the binding energies and patterns of the synthesized compounds with target proteins of the above mentioned microorganisms, molecular docking simulations were run using Autodock Vina software (version 4.2). The spectra data of the compounds for FTIR, 1H NMR and 13C NMR (δ) spectral data were consistent with the assigned structures of the synthesized compounds. The binding energies (kcal/mol) for in silico antimicrobial studies were in the range -5.1 to -7.6 kcal/mol. The MIC values were in the range -3.5 to 1.0 mg/L. The results of the in vitro test revealed that the synthesized compounds exhibits promising antimicrobial activity, and showed excellent bactericidal and fungicidal activities. The results obtained showed that the synthesized compounds possess drug-like properties and are good starting materials for drug production.

Background: Redo mitral valve surgery is the standard of care for failed mitral bioprostheses or recurrence of mitral regurgitation after repair. Nonetheless, catheterbased valve-in-valve (ViV) or valve-in-ring (ViR)-procedures increasingly become viable alternatives in high risk subpopula-tions. Despite reported good initial results, only little is known about longer-term outcomes. The present series report long-term outcomes of transcatheter mitral ViV- and ViR-procedures. Methods: All consecutive patients (n=54) undergoing transcatheter mitral ViV- or ViR-procedures for failed bioprostheses or recurring regurgitation after mitral repair were retrospectively en-rolled in the time period between 2011 and 2021. The mean age was 76.5 ± 6.5 years, and 30 (55.6%) of the patients were male. The procedures were done using a commercially available balloon-expandable transcatheter heart valve. Clinical and echocardiographic follow-up data were obtained out of the hospital’s database and analyzed. Follow-up reached up to 9.9 years with a total of 164.3 patient-years. Results: A total 25 patients received a ViV- and 29 patients a ViR-procedure. Both groups were at high surgical risk with an STS-PROM of 5.9 ± 3.7 % in ViV- and 8.7 ± 9.0% in ViR-patients, respectively (p<0.01). The procedures itself were mainly unevent-ful with no intraoperative deaths and a low conversion rate (n=2/54; 3.7%). VARC-2 procedural success was low (ViV 20.0% and ViR 10.3%; p=0.45), which was either driven by high rates of transvalvular pressure gradients “>5mmHg” (ViV 92.0% and ViR 27.6%; p<0.01) or residual regurgitation “>trace” (ViV 28.0% and ViR 82.7%; p<0.01). ICU-stay was prolonged in both groups (ViV 3.8 ± 6.8 days and ViR 4.3 ± 6.3 days; p=0.96) with acceptable hospital stay (ViV 9.9 ± 5.9 days and ViR 13.5 ± 8.0 days; p=0.13). Despite 30-days mortality was acceptable (ViV 4.0% and ViR 6.9%; p=1.00), the mean posthospital survival time was disappointingly low (ViV 3.9 ± 2.6 years and ViR 2.3 ± 2.7 years; p<0.01). Overall survival I the entire group was 33.3%.Cardiac reasons for death were frequent in both groups (ViV 38.5% and ViR 52.2%). Cox-regression analysis identified ViR-procedures as a predictor of mortality (HR 2.36, CI 1.19 - 4.67, p=0.01). Conclusions: Despite acceptable immediate outcomes in this high-risk subpopulation, long-terms results are discouraging. Transvalvular pressure gradients as well as residual regurgitations remained drawbacks in this real-world population. The indication for catheterbased mitral ViV- or ViR-procedures thoughtfully must be made in consideration of conventional redo-surgery or conservative treatment.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC₅₀ value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile. The current study provides insight for further investigation of the antitumour potential of the molecule.

In this paper, we discuss major issues of mathematics teaching and learning in Nepal. The issues coming from theories such as social and radical constructivism suggest that teachers are not trained to use such approach in teaching mathematics, and there is a lack of teaching aids and materials and technological tools. The issues related to social aspects are gender issues, language issues, social justice issues, and issues related to the achievement gap. The cultural issues are related to the diversity of language and ethnicity. The issues related to political aspects are equity and access, economic status, pedagogical choice, and professional organizations and unions. The issues related to technology include the technological skills, use of technology, and affordance. Finally, we suggest that all the stakeholders should pay attention to resolving these issues by improving the curriculum, training teachers, resourcing the classroom with locally made and new technological tools.

Physics behind collimated highly directional nature of lasers, and factors that keep the seven coloured waves that form white light together during their journey from Sun to Earth, in the face of the natural disruptive forces, is not fully understood. Energy levels were measured, in terms of alterations in induced current and voltage, in beams from a red laser, white LED light and the Sunlight before and during their disruption by diffusers (frosted glass for the lasers) and diffractors (diffraction grating for the white light) using a photovoltaic solar cell panel attached to a digital multimeter. Results show that disruption of the beams results in release of extra energy named as ‘Latent Light Binding’ Energy’. It is hypothesized that the ‘binding’ energy keeps laser waves firmly bound together both end-on and side-on enabling laser beams to travel long distances in collimated manner. Likewise, the 7 coloured waves that constitute white light are kept together, probably side-on, in their journey from the Sun to the Earth. The observation that diffraction of sunbeam is associated with increased power generation provides a new lead to improve harnessing of solar energy, where, currently, the focus is mainly on improving efficiency of photovoltaic cell.

Piceatannol is a naturally occurring polyphenolic compound that is widely found in grapes, blueberries, mushrooms, passion fruit and other edible fruits and vegetables. It has a variety of biological activities and pharmacological effects, including anti-inflammatory, antioxidation, antiaging, antiviral, antitumor, anticancer, antiatherosclerosis, antiparasitic, immunoregulatory, and cardiovascular protection effects. The aim of this study was to investigate the antiherpesvirus effects of piceatannol. Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiherpesvirus effect of piceatannol. In this study, we evaluated the antiviral activity of piceatannol against PRV in vitro and in vivo. The results showed that piceatannol could reatrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, the IC50 was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. The addition of piceatannol at different stages of PRV infection inhibited the viral adsorption and intracellular replication phases of PRV. Piceatannol significantly reduced the expression levels of the IE180, EP0, UL29, UL44, US6 and UL27 genes of PRV within 48 h, significantly reduced the expression levels of the PRV gB and gD proteins, and reduced PRV-induced apoptosis. Molecular docking showed that piceatannol had good binding activity with the PRV gB and gD proteins. The results of animal experiments in vitro indicated that piceatannol could delay the onset of disease, improve the survival rate of the mice (14.3%), reduce the viral load in the brain and kidney of the mice, alleviate the pathological changes in the mouse tissues and organs, and increase the levels of TNF-α, IEN-γ and IL-4 in the serum of the mice. These data indicate that piceatannol has good anti-PRV activity in vitro and in vivo, indicating that it could be a novel antiherpesvirus infection agent in the future.

Diabetes mellitus is a global health issue that necessitates the development of novel therapeutic approaches. Today numerous experimental methods have been used and set up to evaluate novel drugs with antidiabetic effects. In addition, several research studies have been done to induce diabetes under in vitro and in vivo conditions, but only a small number of these efforts are currently in a usable stage. This review aims to provide useful guidance for researchers who seek to evaluate the antidiabetic potential of drugs, agents, or new medications using the standard methods published by authorities and academics worldwide organizations and research centers. In this review, we collected 132 relevant articles from prominent databases such as PubMed, ScienceDirect, Scopus and others to summarize in vitro and in vivo experimental validation of antidiabetic treatment from 1943 to present.

Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.

Sarcomas are a group of malignancies of mesenchymal origin with plethora of subtypes. Given the sheer heterogeneity of various subtypes and rarity of the disease, management of sarcomas has been challenging with poor patient outcomes. Surgery, radiation therapy and chemotherapy have remained the backbone of treatment in patients with sarcoma. The introduction of immunotherapy has rev-olutionized the treatment of various solid and hematological malignancies. In this review, we discuss basics of immunotherapy and immune microenvironment in sarcomas, various modalities of im-munotherapy such as immune checkpoint blockade, oncolytic viruses, cancer targeted antibodies, vaccine therapy and adoptive cell therapies like CAR T-cell therapy, T cell therapy, TCR therapy.

ABSTRACT: Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neurooncology, and the survival status of patients after relapse usually means rapid deterioration, and also the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulate the body's immune system to recognize and attack cancer cells , which could be used as a in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma, This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and focus on the rGBM especially.

Among the explored solutions to reduce the environmental impact of the transport sector, Vehicle Integrated Photovoltaics. Thus, we developed a simulation tool of the distance covered by VIPV. It considers various usage patterns and vehicle types, several characteristics of the PV system and all the losses that may decrease energy yield. Focusing on passenger car, simulations indicate the order of influence of the parameters on the outputs of the model: geographic locality, shading, thresholds due to extra-consumption to charge the vehicle battery from PV and frequency of recharge with the grid. With projections of the technology in 2030, with 30 % shading, VIPV cover up to 1444 km yearly distance. This represents up to 12 % of the driven mileage. For the best month, it can get up to 14 km/day. For average Europe and worst-case conditions, VIPV cover only 293 km per year. Life Cycle Assessment (LCA) of solarized passenger car shows negative balance for low-carbon electricity mix and average solar irradiance. In favorable conditions, the carbon footprint is up to 489 kg CO₂-equivalent avoided emissions on 13 years lifespan. Beyond km and LCA focus, VIPV may provide useful functions in non-interconnected zones and for resilience in disaster zones.

This paper presents designing an attitude motion control strategy for a half-car model using an anti-jerk predictive controller. Anti-jerk predictive controller based on active aerodynamics surfaces is employed to deal with the anticipated future road maneuvers and improve vehicle ride performance by canceling out external jerks acting on the vehicle body. The body jerks are produced during vehicle traversing on a double lane-change maneuver, acceleration, or braking. The control strategy helps the vehicle to achieve a realistic operation of the active aerodynamic surface to improve the vehicle’s ride performance, i.e., ride comfort and road holding during cornering, acceleration, or braking. The anti-jerk predictive controller is developed based on the predictive control strategy, which predicts future road inputs and uses them to compensate for the vehicle’s attitude motion. The simulation results show that the proposed control strategy effectively reduces the effects of vehicle body jerks transmitted to the passengers, improving ride comfort without degrading vehicle handling. The anti-jerk predictive controller successfully tracks the desired attitude position by canceling the external body jerks.

Diffuse intrinsic pontine glioma (DIPG) is recognized as a pediatric brainstem cancer with a 0% survival rate. On a molecular basis, DIPG commonly results from mutations in histone H3, specifically a mutation in the H3K27M gene, that promotes tumorigenesis and results in presentation of this fatal brainstem tumor. DIPG is challenging to treat, as surgical intervention is inefficacious due to the location where the glioma resides. To date, traditional treatments such as radiation, chemotherapy, and immunotherapy have not increased survival rates and have only been successful at relieving symptoms. Future therapeutic approaches such as proton beam radiation, Chimeric Antigen Receptor T Cell (CAR-T) immunotherapy, and alternative epigenetic pharmaceuticals are under investigation for potential benefits. Various clinical trials have also explored these treatment procedures to discover potential increases in survival rates in both animal and human studies. In this review, we will evaluate the pathology and molecular characteristics of DIPG, the current and future approaches to DIPG treatment; and, lastly, we will discuss clinical trials that have been completed to develop successful treatment options.

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.

Cellular therapy has emerged as an attractive option for the treatment of cancer, and adoptive transfer of chimeric antigen receptor (CAR) expressing T cells has gained FDA approval in hematologic malignancy. However, limited efficacy has been observed utilizing CAR-T therapy in solid tumors. Natural killer (NK) cells are crucial for tumor surveillance and exhibit potent killing capacity of aberrant cells in an antigen-independent manner. Adoptive transfer of unmodified allogeneic or autologous NK cells has shown limited clinical benefit due to factors including low cell number, low cytotoxicity and failure to migrate to tumor sites. To address these problems, immortalized and autologous NK cells have been genetically engineered to express high affinity receptors (CD16), CARs directed against surface proteins (PD-L1, CD19, Her2, etc.) and endogenous cytokines (IL-2 and IL-15) that are crucial for NK cell survival and cytotoxicity, with positive outcomes reported by several groups both preclinically and clinically. With a multitude of NK cell-based therapies currently in clinic trials, it is likely they will play a crucial role in next-generation cell therapy-based treatment. In this review we will highlight the recent advances and limitations of allogeneic, autologous and genetically enhanced NK cells used in adoptive cell therapy.

This article explores the relationship between convex functions defined on integers ($\mathbb{Z}$) and their extension to real numbers ($\mathbb{R}$). We introduce key definitions and investigate the hypothesis that there exists a unique convex curve within this family of functions, leading to a proof by contradiction. Our findings highlight the preservation of convexity as functions transition from integers to real numbers.

Among the alternatives pointed out as able to make livestock a more efficient activity and reduce its environmental impact, the use of feeds with high digestibility and the use of non-conventional fodder species can be highlighted. Tithonia diversifolia (Hemsl.) A. Gray (TD) has already gained attention as a feed for ruminants. Nonetheless, there has been little discussion about the impacts of this plant on the rumen dynamics that lead to better animal performance. The aim of this study was to assess how increasing levels of TD could affect ruminal microbial biomass synthesis, degradability, and in vitro gas production (IVGP) of diets. Four diets were evaluated: a control diet (TD0: 400 g kg-1 soybean meal and corn grain, and 600 g kg-1 Tifton 85 hay (Cynodon spp)) and three increasing levels of TD (TD9: 90, TD27: 270, and TD45: 450 g kg-1 – dry matter basis) as a replacement for dietary roughage. A 96-hour IVGP assay was carried out and five incubation times (2, 4, 10, 24, and 96 hours) were used for degradability determination. Gas produced, methane (CH4), degradability of organic matter (IVDOM), short-chained fatty acid (SCFA) production, partitioning factor (PF), and microbial biomass (MB) were evaluated among treatments. There was no significant effect (P&gt;0.05) between TD inclusion and IVGP at most incubation times; only at 6 hours of incubation did gas production increase linearly with TD inclusion (R2=0.19; P&lt;0.05). TD inclusion had no effects on CH4. IVDOM increased linearly with TD inclusion at 6 and 10 hours, with TD45 being more degradable than the control diet at 6 hours only. There was a positive linear relationship (R2=0.20; P&lt;0.05) between TD inclusion and PF. TD45 had significantly higher PF values than the control. MB also increased linearly (R2=0.30; P&lt;0.05) with TD inclusion, and all diets with TD had significantly more MB than the control diet. The inclusion of TD at the levels used in this work was revealed to have a positive impact on microbial protein synthesis, which could be related to the higher microbial efficiency of increased substrate quality.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

The automotive industry is continuously seeking innovative solutions to improve the energy efficiency and sustainability of vehicles. Among the various energy-consuming systems in automobiles, air conditioning plays a crucial role. However, conventional vapour compression-based air conditioning systems are known for their high energy consumption and environmental impact. In recent years, adsorption technology has gained significant attention as a promising alternative due to its potential for higher energy efficiency and reduced greenhouse gas emissions. This review paper presents a comprehensive analysis of advancements in adsorption air conditioning technology specifically designed for automotive applications. The paper examines the recent research and development efforts in enhancing the performance and practicality of these systems, encompassing areas such as advanced materials selection, and system integration strategies. Furthermore, this review highlights the benefits and challenges associated with implementing adsorption air conditioning systems in vehicles. The environmental impact and potential for waste heat recovery are also discussed. Additionally, emerging trends, such as hybridization with conventional vapour compression systems, are explored to further optimize the energy efficiency and sustainability of automotive air conditioning. By critically evaluating the existing literature and research advancements, this review provides insights into the state-of-the-art thermally driven technologies for automotive applications.

Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.

Direct yaw moment control (DYC) is an effective way to alter the behaviour of electric cars with independent drives. Controlling the torque applied to each wheel can improve the handling performance of a vehicle making it safer andfaster on a race track. The state-of-the-art literature covers the comparison of various controllers (PID, LPV, LQR, SMC, etc.) using ISO manoeuvres. However, more advanced comparison on important characteristics of the controllers performance is missed, such as the robustness of the controllers under changes in the vehicle model, steering behaviour, use of the friction circle and, ultimately, lap time on a track. In this study, we have compared the controllers according to some of the aforementioned parameters on a modelled race car. Interestingly, best lap times are not provided by perfect neutral or close-to-neutral behaviour of the vehicle, but rather by allowing certain deviations from the target yaw rate. In addition, a modified PID controller showed that its performance is comparable to other more complex control techniques such as MPC.

In the present work, we provide an electronic structure based method for the “on-the-fly” deter- mination of vibrational sum frequency generation (v-SFG) spectra. The predictive power of this scheme is demonstrated at the air-water interface. While the instantaneous fluctuations in dipole moment are obtained using the maximally localized Wannier functions, the fluctuations in polar- izability are approximated to be proportional to the second moment of Wannier functions. The spectrum henceforth obtained captures the signatures of hydrogen bond stretching, bending, as well as low-frequency librational modes.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Knowledge about ecological conditions and processes in centers of endemism (CoEs) is still limited with respect to various systematic groups of organisms, ecosystem types, ecological conditions and ecosystem functions. Endemics and CoEs play a prominent role in nature conservation monitoring and management, and in the organization of zoos, aquaria and botanical gardens. We review the meaning of different groups of organisms and indicators for the characterization of endemic-rich regions, the importance of heterogeneity in space, continuity in time, isolation and ex-situ management for the survival of endemic and threatened species. Currently, conversion of land cover and land use change are the most important causes of biodiversity decline and extinction risk of endemic and endangered species concentrated in CoEs. These are followed by climate change, including severe weather, and then natural processes such as volcanism, landslides or tsunamis. For conservation purposes the management of zoos, aquaria, botanical gardens, of regional land use, and social aspects of the diversity of endemics and CoEs have to be taken into account as well. We need better answers to questions about the relationship between ecoregions, CoEs and regional awareness of biodiversity, which is linked with human culture including the management of zoos, aquaria and botanical gardens, aesthetics, wellbeing, health and trade.

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

During normal ageing, physical changes take place, namely in terms of the biomechanical, musculoskeletal, and psychomotor systems, that reduce strength, flexibility, motor coordination, balance, and precision of movements. This article analyses the motion behaviour of a sample of 49 senior and pre-senior subjects during the process of entry to (ingress) and exit from (egress) new car models not experienced before, obtained over five days at the Geneva International Motor Show. The methodological process is based on visual studies using photography and video to analyse motion behaviour. This investigation identifies five entry movement strategies and three exit movement strategies in three types of vehicle groups. The movements adopted in the egress of the vehicle were more complex and difficult, in general, than those observed for ingress, requiring greater flexibility, agility/dexterity, and physical strength of subjects, involving more contact or support with vehicle parts. The main factor that influences movement strategies is essentially related to subjects’ levels of physical capacity and previous experiences. In conclusion, there are no significant changes in the subjects’ somatic movement strategies based on vehicle types.

In the Formula Student Racing Car, the anti-deformation ability of the frame will affect the four-wheel positioning parameters of the racing car, and then affect the handling and stability performance of the racing car. The quality of the frame directly determines the power and economy of the racing car, so the performance of the frame is very important to the performance of the race. In order to improve the performance of the frame and reduce the total weight of the frame, the research on the lightweight design of the frame is particularly important. In this paper, based on the variable density method, the global topology optimization of the frame is carried out to obtain the distribution of the frame material, realize the efficient use of the material, and improve the torsional stiffness of the frame. Based on the adjoint variable method, the sensitivity analysis of the frame is carried out. According to the sensitivity analysis results, the size of the frame is optimized. The total mass of the frame is reduced by 12.8 %, and the performance of the maximum displacement and maximum stress is improved. The lightweight design of the frame is realized as a whole.

Targeted cancer therapy has grown exponentially in the last decade, representing the largest frontier in the modern concept of precision medicine. This renaissance is largely due to our rapidly evolving ability to biochemically harness our immune systems to target cancer-specific antigens. Combined with an increasing armamentarium of surgical and non-invasive techniques for cancer mitigation we have upgraded cancer therapy from a non-specific assault on cell-division to a multi-modal, targeted approach. This renaissance has resulted in an increase in the perioperative footprint of patients with advanced cancer. The scope of the perioperative clinician has evolved from one of passive/reactive management of complications to a proactive approach that starts in the preoperative optimization phase and continues into the postoperative period. The perioperative world should not exist in a silo, and thus involvement of the oncology team is paramount. To provide safe oncologic care, it is essential to be up to date in newer cancer therapies, lest we act on erroneous and/or outdated information. Oncologists should weigh in on immune status, recent chemotherapeutic exposures, and potentially evolving toxicities. These might involve critical changes to perioperative infectious prophylaxis, steroid administration, and coagulopathy management. First, patients living beyond the typical life-expectancy for their cancer will carry a high burden of cancer-related downstream effects. General metabolic issues will include malnutrition, cachexia, and gastric outlet obstruction. Severe protein-calorie malnutrition, as well as hepatic and renal dysfunction can impact the metabolism and clearance of drugs. The cardiovascular, endocrinologic, pulmonary, and central nervous system implications of new cancer therapies will be discussed extensively below. Second, we have to enhance our ability to manage a cancer population who may be experiencing increasing novel chemotherapeutic toxicities. Newer agents differ from historical agents, which were blunt-force tools aimed at nonspecific destruction of cell-division. These drugs are efficacious but physiologically costly. Newer immunogenic therapies have a slightly improved acute safety profile, and a more complex chronic toxicity profile that may be overt or insidious. Chronic toxicities can present overtly or as a smoldering undertone to other active medical conditions such as sepsis, pneumonia, failure to thrive, or renal failure. The new therapies discussed in this review occur in the context of an overall increasingly multi-faceted cancer care machine. An example is screening for esophageal cancer in patients with Barrett's esophagus, or periodic chest CTs for patients with a strong history of tobacco use. These interventions are more likely to detect disease while it is still resectable, and resections will commonly accompany neo-adjuvant therapy. These approaches commonly involve new immunotherapies whose efficacy is higher-yield with a lower disease burden. In a recent example, the immune-checkpoint inhibitors (ICIs) ipilimumab plus nivolumab have significantly increased survival rate for squamous cell esophageal cancer when combined with standard chemotherapy. Surgical resection has evolved to one that often accompanies neoadjuvant chemo and radiation. The increasing efficacy of this approach may de-necessitate many major resections, and increase the number of sub-anatomic resections and minimally invasive procedures. Improved techniques - notably for hepatectomy, whipple procedure, prostatectomy, nephrectomy - have increased the safety profile and decreased the perioperative physiologic burden. This has enabled a broader subset of patients (due to cancer burden or due to medical comorbidities) to qualify for the operation, and increased the involvement of anesthesia and their perioperative services. With an increase in surgical candidacy comes an increase in post-surgical complications, and post-surgical maintenance such as drains, embolizations, imaging studies, etc. In the non-OR anesthesia realm, there have been considerable advancements in cancer “micro-treatments” such as hepatic metastasis embolization, tumor ablation, and peri-tumor vascular embolization. There are an ever-increasing number of IR-guided embolizations for bleeding tumors, aspiration of malignant effusions, and drainage of abscesses. This review serves to provide insight into new categories of chemotherapy and their perioperative implications.

This comprehensive study delves into the implementation and effectiveness of the flipped classroom model in engineering EMI (English as a Medium of Instruction) courses in Taiwan. Situated within the strategic framework of Taiwan's Bilingual Nation 2023 policy, this research aims to enhance the global competitiveness of Taiwan's semiconducting manufacturing engineering sector. The study’s primary focus is on understanding the perceptions and learning outcomes of EFL (English as a Foreign Language) students in engineering courses. Through a methodical approach using descriptive statistics and chi-square tests, the study analyzes data from 33 junior engineering students specializing in mechanical and mechatronic fields. The findings highlight a significant positive influence of the flipped classroom model on various aspects of student learning, including increased engagement, heightened creativity, and enhanced problem-solving skills. Additionally, the study emphasizes the critical role of timely L1 support in facilitating effective learning in EMI settings. These outcomes not only demonstrate the flipped classroom's viability as a sustainable educational approach but also provide crucial insights for educators and policymakers. By aligning cutting-edge teaching methods with the evolving needs of engineering education, this study contributes to the discourse on educational innovation. It ultimately guides the development of future engineering programs that cater to diverse student needs and fosters the cultivation of skilled engineering professionals.

This study was to designed to develop sorafenib-loaded polymeric nanoparticles, surface-modified with pluronic F-127 for the effective treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly lactic coglycolic acid (PLGA) was used to encapsulate different concentrations of sorafenib by a simple modified solvent evaporation method applying pluronic F-127 as a surfactant and coating agent. The preformulation and characterization studies were conducted to evaluate the incompatibilities among sorafenib, PLGA and pluronic F-127, and physicochemical properties of the formulations, respectively. The sizes of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 120 ± 10.1 nm, respectively. It has been confirmed from the in vitro release studies that PLGA sustained the release of sorafenib, avoiding the initial burst release, while the in vivo studies demonstared that surface-modified nanoparticles have greater affinity in the target aorgans than plain PLGA nanoparticles and free drug keeping the dose constant (20 mg/kg body weight). The delivery of sorafenib-loaded polymeric PLGA nanoparticles into the target tissues and their pharmacokinetic parameters have been improved significantly compared to the reported formulations.

The pinning force density FpJc,B=Jc×B (where Jc is the critical current density and B is the applied magnetic field) is one of the main parameters that characterize the resilience of a superconductor to carry a dissipative-free transport current in an applied magnetic field. Kramer (1973 J. Appl. Phys. 44 1360), and Dew-Hughes (1974 Phil. Mag. 30 293) proposed a widely used scaling law for the pinning force density amplitude: FpB=Fp,max×p+qp+qppqq×BBc2p×1-BBc2q, where Fp,max, Bc2, p, and q are free-fitting parameters. Since the late 1970-s till now, several research groups have reported experimental data on the dependence of Fp,max on the average grain size, d, in Nb3Sn-based conductors. Godeke (2006 Supercond. Sci. Techn. 19 R68) proposed that the dependence obeys the law Fp,maxd=A×ln1d+B. However, this scaling law has several problems, for instance, the logarithm is taken from a non-dimensionless variable, and Fp,maxd&lt;0 for large grain sizes, and Fp,maxd→∞ for d→0. Here, we reanalysed the full inventory of publicly available Fp,maxd data for Nb3Sn conductors and found that the dependence can be described by Fp,maxd=Fp,max0×exp-dδ law, where the characteristic length, δ, varies within a remarkably narrow range, that is, δ=175±13 nm, for samples fabricated by different technologies. The interpretation of the result is based on the idea that the in-field supercurrent flows within a thin surface layer (thickness of δ) near the grain boundary surfaces (similar to London’s law, where the self-field supercurrent flows within a thin surface layer with a thickness of the London penetration depth, λ, and the surface is a superconductor-vacuum surface). An alternative interpretation is that δ represents the characteristic length of the exponential decay flux pinning potential from the dominant defects in Nb3Sn superconductors, which are grain boundaries.

The Oxford English Dictionary includes 17 definitions for the word “model” as a noun and other 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For in-stance, “model railways” refer to replicas of railways and trains at a smaller scale and a “model student” refers to an exemplar individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning of a model. Even if the context is narrowed, specifically to the research related to the tumour microenvironment, a “model” can be understood in a wide variety of ways, from an animal model, to a mathematical expression. This paper presents a review of the different “models” of the tumour microenvironment grouped by the different def-initions of the word into four categories: model organisms, in vitro models, mathematical models, and computational models. Then, the frequency of different meanings of the word “model” related to the tumour microenvironment is measured from the number of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequency of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, in particular xenografts and mouse models are the most common used “models”, the number of entries have been slowly de-creasing. Mathematical models, prognostic and risk models follow in frequency and these have been growing in use.

In this review we look at the developments in the field of artificial intelligence (A.I) and their current impact as well as future implications in the field of cardiology, we as physicians and cardiologists have tried to put our perspective on the rapidly evolving field, In light of the fact that many of the healthcare workers and professionals across the world still find the concept of A.I quite complicated, elusive and somewhat paradoxical, we have tried to simplify the concept of artificial intelligence and make it easy for everyone to understand from all walks of life. The Databases utilized for our review are PubMed, PubMed Central, Google Scholar. The Keywords used for our Data Search are “Artificial Intelligence”, “A.I Cardiology”, “A.I in Cardiovascular Medicine”, “Machine Learning in Cardiology”. We screened all relevant since inception till March 25th and included 44 relevant articles after careful consideration into our paper. We have discussed the implementation of and scope of artificial intelligence across a broad spectrum of applications including cardiovascular imaging and diagnostics like electrocardiograms, echocardiograms, cardiac CT/MRIs to novel cardiac monitoring devices, CRISPR gene editing in cardiology and implementation of artificial intelligence in the field of Cardiovascular Bioprinting. This is the initial review in a series of reviews regarding A.I in Cardiology.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

This paper presents a comprehensive simulation study of Automated Guided Vehicles (AGVs) in a fabricated production environment for toy car assembly. This paper uses Petri Nets for modeling and the General Petri Net Simulator (GPenSIM) for model implementation on MATLAB and simulation. The primary focus of this research is to analyze the operational efficiency of AGVs under varying conditions, particularly examining the impact of battery charge reduction rates and the strategic placement of charging stations within the production line. By employing Colored Petri Nets (CPN) within GPenSIM, we have developed a detailed and dynamic model that captures the intricate movements and interactions of AGVs in a simulated manufacturing setting. By presenting an approach to simulating AGVs in a production environment, this paper specifically focuses on two critical operational parameters: the battery charge reduction rate of AGVs and the number of charging stations available in the production line. Unlike previous studies that have primarily concentrated on general path planning or bottleneck detection in manufacturing systems, this paper delves into the intricate balance between AGV operational efficiency and the logistical constraints imposed by battery life and charging infrastructure.

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.

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.