Search Results (22)

Background/Objectives: The GO-TRYKE^® Kid (GTK^®) is an arm- and leg-powered tricycle which, in addition to promoting strength, endurance, and coordination, aims to reactivate the central pattern generators of the spine for locomotion through cyclical movements. The present study investigated the effects of GTK^® training on walking ability, GTK^® riding performance, and health-related quality of life in children with walking disabilities. Methods: Nine children trained with the device twice a week for nine weeks. Short- and long-term effects on walking ability were measured using the timed up and go test (TUG) and the two-minute walk test (2MWT). GTK^® riding performance and health-related quality of life were compared before and after the intervention period. Results: While no long-term effect on walking was found, a significant short-term effect on functional walking ability was observed (p = 0.009). GTK^® riding performance improved significantly over the training period (p = 0.004). There were no significant changes in health-related quality of life. Conclusions: GTK^® enables children with walking disabilities to participate in cycling as part of play and sport. Further research is required to investigate its functional and participatory effects, as there is significant potential to improve physical activity and overall well-being in this population. Full article

In this paper, we investigate the sustainability of docked bike-sharing in Nanjing in terms of environmental benefits and financial operations by comparing the data of March 2017 and March 2023 in Nanjing. We modify a community detection method, give and prove dynamic boundary conditions for the objective function of the heuristic algorithm, and realize the estimation of the rebalancing coefficients for this mega-system, thus obtaining more accurate emission factors. We find that there are significant differences in the results obtained from environmental benefit assessments over time. Further, there are also significant differences at the national level. This may signify that the assessment data of one country’s system cannot give a direct reference for another country’s system. Second, we considered the economic basis required for the environmental benefits of docked bike-sharing systems. We have calculated the sustainability of the system’s financial operations by considering its revenues over the next nine years, including the cost of facility inputs, facility upgrades, dispatching costs, labor costs, maintenance costs, and the time value of money. The results show a 4.6-fold difference in emission factors between 2017 and 2023; comparing 2017 to 2023 (when demand loss has been severe), the investment in 2017 will be recouped 2 years later than in 2023. Switching distribution vehicles from fuel vehicles to electric trikes would severely deteriorate the operator’s key financial metrics while only reducing the emission factor value by 8.64 gCO${}_2$ eq/km, leading to an unsustainable system. This signals the potential for the financial unsustainability, or even bankruptcy, of operators if the requirements for sustained emissions reductions from the bike-sharing system are divorced from the form of the economy on which it is sustainably operated. Finally, we consider the geographical patterns between environmental benefits and financial operations. We find that financial sustainability varies across geographic locations. Under financial sustainability, we gave emission factors under the mix distribution vehicle scenario. Full article

Chemotherapy-refractive multiple myeloma (MM) is serious and life-threatening, and better treatments are urgently needed. BCMA is a prominent marker on the cell surface of MM cells, rendering it an accepted target for antibody therapy. Considering that MM is a liquid tumor and immunotherapy has enjoyed success against leukemia, we devise an approach designed to enhance NK cell activity against MM. Ordinarily, NK cells function to naturally survey the body and eliminate malignant cells. Our platform approach is designed to enhance NK function. A tri-specific immune-engaging TriKE is manufactured, consisting of a camelid nanobody VHH antibody fragment recognizing CD16 expressed on NK cells and an scFv antibody fragment specifically recognizing BCMA. These two fragments are crosslinked by the human cytokine interleukin-15 (IL-15) known to have prominent activating effects on NK cells. The molecule, when tested by flow cytometry, shows activation of NK cells in their numbers and activity. Additionally, the molecule demonstrates anti-cancer effects in an in vivo xenograft model of human MM. We believe that the drug will have the capability of enhancing NK cells at the site of the immune synapse, i.e., the effector:target cell interface, and this will promote cancer remissions. Full article

The aim of this work is to verify the possibility of transport of 26 biologically active ultrashort peptides (USPs) into cells via LAT and PEPT family transporters. Molecular modeling and computer-assisted docking of peptide ligands revealed that the size and structure of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analysis of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters has been carried out. The 26 biologically active USPs systematically showed higher binding scores to LAT1, LAT2, and PEPT1, as compared with di- and tri-peptides, for which no biological activity has been established. This indicates an important possible role which LAT and PEPT family transporters may play in a variety of biological activities of the 26 biologically active peptides under investigation in this study. Most of the 26 studied USPs were found to bind to the LAT1, LAT2, and PEPT1 transporters more efficiently than the known substrates or inhibitors of these transporters. Peptides ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP, and KEDG, and peptoids DS7 and KE17 with negatively charged Asp⁻ or Glu⁻ amino acid residues at the N-terminus and neutral or positively charged residues at the C-terminus of the peptide are found to be the most effective ligands of the transporters under investigation. It can be assumed that the antitumor effect of the KE, EW, EDG, and AEDG peptides could be associated with their ability to inhibit the LAT1, LAT2, and PEPT1 amino acid transporters. The data obtained lead to new prospects for further study of the mechanisms of transport of USP-based drugs into the cell and design of new antitumor drugs. Full article

Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137–198 MeV and Linear Energy Transfer (LET) range 1–9 keV/μm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM). The induction rate Mbp⁻¹ Gy⁻¹ for each type of damage, single strand breaks (SSBs), double-strand breaks (DSBs), base lesions and non-DSB clusters was measured after irradiations in solutions with varying scavenging capacity containing 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris) and coumarin-3-carboxylic acid (C3CA) as scavengers. Our combined results reveal the determining role of LET and Reactive Oxygen Species (ROS) in DNA fragmentation. Furthermore, AFM used to measure apparent DNA lengths provided us with insights into the role of increasing LET in the induction of highly complex DNA damage. Full article

The electric tricycle, often known as an e-trike, is a three-wheeled electric vehicle designed to transport a small group of people over short distances on side streets. This study aims to develop a service quality model of sustainable e-trike operations in the city of Manila, Philippines using stepwise regression analysis. A total of 230 participants from three districts in the City of Manila: Binondo, Recto, and Intramuros, were selected using the stratified sampling method. The main contribution of this study emerges from the quantification of the influence of sustainability indicators on the perceived service quality of e-trike passengers. The study identified 10 indicators: PWD accessibility (β = 0.2128), smoothness of the ride (β = 0.1001), noise level (β = 0.0886), discount rate (β = 0.0886), land use (β = 0.0835), comfort load (β = 0.0723), fare acceptability (β = 0.0577), e-trike intensity (β = 0.0420), fare affordability (β = 0.0339), and ease of availability (β = 0.0317) have significant importance in the service quality of e-trike operations. These indicators revealed the areas where improvements are needed to ensure the long-term viability of e-trike operations. Therefore, it is concluded that these factors should be the focus and priority for the improvement of e-trike operators, drivers, and transport groups to attain sustainability of e-trike operation in the country. Moreover, this study can also be used for other public transportations to improve their current service quality and operations. Full article

Leukemia is a malignancy of the bone marrow and blood resulting from the abnormal differentiation of hematopoietic stem cells (HSCs). There are four main types of leukemia including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). While chemotherapy and radiation have been conventional forms of treatment for leukemia, these therapies increase infection susceptibility, adverse side effects and immune cell inactivation. Immunotherapies are becoming promising treatment options for leukemia, with natural killer (NK) cell-mediated therapy providing a specific direction of interest. The role of NK cells is critical for cancer cell elimination as these immune cells are the first line of defense against cancer proliferation and are involved in both recognition and cytolysis of rapidly dividing and abnormal cell populations. NK cells possess various activating and inhibitory receptors, which regulate NK cell function, signaling either inhibition and continued surveillance, or activation and subsequent cytotoxic activity. In this review, we describe NK cells and NK cell receptors, functional impairment of NK cells in leukemia, NK cell immunotherapies currently under investigation, including monoclonal antibodies (mAbs), adoptive transfer, chimeric antigen receptor-NKs (CAR-NKs), bi-specific/tri-specific killer engagers (BiKEs/TriKEs) and future potential targets of NK cell-based immunotherapy for leukemia. Full article

Natural killer (NK) cell is a powerful malignant cells killer, providing rapid immune responses via direct cytotoxicity without the need of antigen processing and presentation. It plays an essential role in preventing early tumor, metastasis and minimal residual disease. Although adoptive NK therapies achieved great success in clinical trials against hematologic malignancies, their accumulation, activation, cytotoxic and immunoregulatory functions are severely impaired in the immunosuppressive microenvironment of solid tumors. Now with better understandings of the tumor evasive mechanisms from NK-mediated immunosurveillance, immunotherapies targeting the key molecules for NK cell dysfunction and exhaustion have been developed and tested in both preclinical and clinical studies. In this review, we introduce the challenges that NK cells encountered in solid tumor microenvironment (TME) and the therapeutic approaches to overcome these limitations, followed by an outline of the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies, as well as promising strategies to optimize current NK-targeted immunotherapies for solid tumors. Full article

Increasing knowledge of cancer immunology has led to the design of therapies using immune cells directly or manipulating their activity, collectively termed immunotherapy. In the field of immuno-oncology, research on adaptive immune T cells has led to the development of CAR-T cells. Innate immune cells such as NK cells can also eliminate oncogenically transformed cells and regulate cells of the immune system. Considering NK cells as a live drug, numerous methods for the isolation and activation of NK cells have been shown to be clinically and therapeutically relevant. In such processes, various cytokines and antibodies present a source of stimulation of NK cells and enhance the efficacy of such treatments. The ex vivo expansion and activation of NK cells, along with genetic modification with CAR, enhance their antitumor activity. Recent preclinical studies have shown an antitumor effect through extracellular vesicles (EVs) derived from NK cells. Work with autologous NK cells has provided insights for clinical applications. In this review, we outline the recent advances of NK-cell-based immunotherapies, summarizing CAR-NK cells, BiKEs, and TriKEs as treatment options against cancer. This review also discusses the challenges of NK cell immunotherapy. Full article

Global participation at the Paralympic Games has been steadily growing in the past 60 years. However, inequities in relation to geographic representation of Paralympians, sex representation, access to assistive technology, and medal success remain. The objectives of this research are to describe and compare trends in Paralympians’ participation and achievements in the Summer Paralympic Games by income level and sex, including in events requiring assistive products (wheelchairs, hand cycles/trikes, and prostheses). A retrospective secondary analysis of publicly available data was conducted. Participation, sex, and medal tally data were extracted from data available on the International Paralympic Committee website and archives. Data regarding income and population were collected from publicly available data available from the World Bank website. Participation in the Summer Paralympic Games differs significantly by income level (p = 0.000) with high- income countries sending, on average, more Paralympians than low- and middle-income countries. There is a significant difference between male and female participation (p = 0.00), with approximately 29% of all Paralympians being female. High-income countries demonstrate significantly higher achievement than low- and middle-income countries (p = 0.000), including in events requiring assistive products (p = 0.007). Despite growth in overall participation, low- and middle-income countries remain severely underrepresented in both participation and achievement at the Paralympic Games, especially in the events that require high quality assistive products to succeed. More equitable participation and achievement in the Paralympics may be supported by addressing the barriers for females, for people from low- and low-middle income countries, and for those without access to high quality assistive products required. Full article

Sustainable product design uses methodologies focused on eco-effectiveness and eco-efficiency for the proposal of innovative technological solutions and for the control of environmental impacts during the product life cycle. One of the main drawbacks of such techniques is their qualitative nature, associated with a decision-making process that is sometimes arbitrary, or with unverifiable data; this means that several complementary tools are currently being used to reduce the error in the results obtained. This situation makes the unification of procedures necessary. In this context, this research develops a methodology for the sustainable design of industrial products that integrates life cycle assessment (in its environmental, economic and social application) and cradle-to-cradle techniques. For this purpose, a new assessment process is proposed, based on damage, developing LCA+C2C endpoint indicators. The methodology is subsequently verified in a case study of products for sustainable mobility (city trike electric). The results show that an integrated LCA+C2C assessment can help to propose more balanced sustainable strategies and would be a suitable method to measure tradeoffs between economic, social and environmental results, for practical purposes and future redesigns. The unified method provides a procedure to design a solution with a trade-off between eco-efficient and eco-effective criteria; it also simplifies the design phases, facilitates the interpretation of the results and provides a quantitative scope to the cradle-to-cradle framework. Full article

Clinical studies validated antibodies directed against HER2, trastuzumab, and pertuzumab, as useful methodology to target breast cancer cases where HER2 is expressed. The hope was that HER2 targeting using these antibodies in ovarian cancer patients would prove useful as well, but clinical studies have shown lackluster results in this setting, indicating a need for a more comprehensive approach. Immunotherapy approaches stimulating the innate immune system show great promise, although enhancing natural killer (NK) function is not an established mainstream immunotherapy. This study focused on a new nanobody platform technology in which the bispecific antibody was altered to incorporate a cytokine. Herein we describe bioengineered CAM1615HER2 consisting of a camelid VHH antibody fragment recognizing CD16 and a single chain variable fragment (scFv) recognizing HER2 cross-linked by the human interleukin-15 (IL-15) cytokine. This tri-specific killer engager (TriKE^TM) showed in vitro prowess in its ability to kill ovarian cancer human cell lines. In addition, we demonstrated its efficacy in inducing potent anti-cancer effects in an in vivo xenograft model of human ovarian cancer engrafting both cancer cells and human NK cells. While previous approaches with trastuzumab and pertuzumab faltered in ovarian cancer, the hope is incorporating targeting and cytokine priming within the same molecule will enhance efficacy in this setting. Full article

In order to realize emission-free solutions and clean transportation alternatives, this paper presents a new DC converter with pulse frequency control for a battery charger in electric vehicles (EVs) or light electric vehicles (LEVs). The circuit configuration includes a resonant tank on the high-voltage side and two variable winding sets on the output side to achieve wide output voltage operation for a universal LEV battery charger. The input terminal of the presented converter is a from DC microgrid with voltage levels of 380, 760, or 1500 V for house, industry plant, or DC transportation vehicle demands, respectively. To reduce voltage stresses on active devices, a cascade circuit structure with less voltage rating on power semiconductors is used on the primary side. Two resonant capacitors were selected on the resonant tank, not only to achieve the two input voltage balance problem but also to realize the resonant operation to control load voltage. By using the variable switching frequency approach to regulate load voltage, active switches are turned on with soft switching operation to improve converter efficiency. In order to achieve wide output voltage capability for universal battery charger demands such as scooters, electric motorbikes, Li-ion e-trikes, golf carts, luxury golf cars, and quad applications, two variable winding sets were selected to have a wide voltage output (50~160 V). Finally, experiments with a 1 kW rated prototype were demonstrated to validate the performance and benefits of presented converter. Full article

The mass properties of a vehicle play a decisive role in its dynamics and characteristics and are fundamental for vehicle dynamics models and controllers. These values are not yet known for the vehicle class of the ultra-light velomobiles and similar multi-track bicycle vehicles. In the future, however, such vehicles could play a role in reducing the CO₂ emissions generated by individual transportation. As a basis for vehicle dynamics modeling, accident reconstruction, and controller development for this vehicle class, this paper investigated ranges of mass properties and their influence on vehicle stability considering driver influence. In total, 13 vehicles (10 velomobiles and 3 trikes) were examined using different experimental setups. It was shown that most vehicles exhibited understeering behavior based on the center of gravity position and calculations of the static stability factor showed significantly lower rollover stability compared with conventional vehicles. The measured moments of inertia were used to develop and examine different approximation approaches for the yaw moment of inertia using conventional approaches from the passenger car sector and stepwise regression. This created the basis for parameter estimation from easily measurable vehicle parameters and provided the possibility to generate realistic parameter sets for vehicle dynamic models. Existing tests do not consider the influence of driver movements, such as pedaling movements or possible inclination of the upper body. This offers the potential for further investigations of the dynamic influences on the investigated variables. Full article

Nearly four decades after their conceptualization, antibody-based therapies are slowly being added to the treatment landscape of acute myeloid leukemia (AML). While the antibody–drug conjugate gemtuzumab ozogamicin is the only antibody-based therapy that has been approved for AML treatment thus far, several bispecific antibodies have been developed and shown early encouraging results. Bispecific antibodies comprise a wide variety of constructs that share the common concept of simultaneous binding of a surface target on malignant cells and most commonly CD3 on T cells leading to an endogenous, HLA-independent, immune response against malignant cells. However, the use of bispecific antibodies in AML has been limited by the absence of highly specific leukemia-associated antigens leading to on-target, off-leukemia side effects as well as reduced efficacy due to antigen escape. Herein, we discuss the history and evolution of bispecific T cell engagers as well as various adaptations such as dual affinity retargeting antibodies, bi- and tri-specific killer engager antibodies. Common side effects including cytokine release syndrome and management thereof are highlighted. Lastly, we expound on the future direction and integration of such antibody-based therapies with other immunotherapies (programmed cell death-1 inhibitors and chimeric antigen receptor T cells). Full article