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PurposeThe ability to generate natural killer (NK) cells from induced pluripotent stem cells (iPSCs) has given rise to new possibilities for the large-scale production of homogeneous immunotherapeutic cellular products and opened new avenues towards the creation of “off-the-shelf” cancer immunotherapies. However, the differentiation of NK cells from iPSCs remains poorly understood, particularly regarding the ontogenic landscape of iPSC-derived NK (iNK) cells produced in vitro and the influence that the differentiation strategy employed may have on the iNK profile. MethodsTo investigate this question, we conducted a comparative analysis of two sets of iNK cells generated from the same iPSC line using two different protocols: (i) a short-term, clinically compatible feeder-free protocol corresponding to primitive hematopoiesis, and (ii) a lymphoid-based protocol representing the definitive hematopoietic step. Results and discussionOur work demonstrated that both protocols are capable of producing functional iNK cells. However, the two sets of resulting iNKs exhibited distinct phenotypes and transcriptomic profiles. The lymphoid-based differentiation approach generated iNKs with a more mature and activated profile, which demonstrated higher cytotoxicity against cancer cell lines compared to iNK cells produced under short-term feeder-free conditions suggesting that the differentiation strategy must be considered when designing iNK cell–based adoptive immunotherapies.

Inelastic n-changing collisions play an important role in the evolution of Rydberg atoms into ultracold plasmas. However, for the initially intermediate n (n ∼ 40) Rydberg states, these collisions can hardly be observed due to the low electron temperature in ultracold plasmas. In this work, we designed an experimental scheme to facilitate collisions between free electrons at 1.5 eV and intermediate n Rydberg atoms. Using the field ionization technique, we measured the state distributions resulting from the evolution of initially cold rubidium atoms in the 45P3/2 Rydberg state. The experimentally obtained probability of inelastic collisions excitation agrees well with the Monte Carlo simulation results. In addition, our experimental results indicate that the n-changing population induced by hot electrons is significant for lower nP Rydberg states. Our work plays a significant role in calculating the rates of electron–ion three-body recombination in ultracold plasmas. [ABSTRACT FROM AUTHOR]

The failure mechanisms and mechanical properties of bollards present significant risks in port and maritime engineering thereby calling for a thorough investigation into these aspects. This study highlights the significance of elements like tensile strength shear stress and service loads while examining the difficulties related to metal bollard failures. This paper presents a case study on A60 steel bollards that combines numerical simulations with experimental testing using Catia and Mathcad software. The results reveal that even as the mechanical houses adjust with A60 steel standards, under accurate ambit and a hundred-ton load, compactness and shear stresses exceed the limit attrition of the bollard. The acceptable strain considerably surpasses the adaptable limit, advertence impending failure. The analysis recommends layout adjustments, presenting a higher array of the annular part of the demonstrated bollard and a safety factor of at least 1. 5 to boost the bollard attrition and forestall hurt under a hundred-ton load. This research contributes advantageous insights into bollard layout, acclamation real- global demanding situations, and promoting safety in maritime infrastructure.

The quadcopter persist as important roles across diverse applications, and the enhancement of their control efficacy has been the subject of extensive research. In this work, the authors proposed optimal Proportional Integral (PI) controller based Fuzzy Logic Control (FLC) for the roll, pitch, altitude, and yaw motions of the quadcopter system. The proposed technique uses the Particle Swarm Optimization (PSO) algorithm to tune the parameters of the FLC and enhance the quadcopter performance. The simulation results show that the proposed technique achieves smoothness of control and significant improvement over classical techniques, as the rise time and the settling time are reduced by 61 % and 66 %, respectively. These times are important for stabilizing the system's response speed and avoiding overshooting or oscillating. This indicates that the FLCPI-PSO can achieve the desired roll and altitude angles more rapidly and effectively.

During the last two decades, the introduction of tyrosine kinase inhibitors (TKIs) to the therapy has changed the natural history of CML but progression into accelerated and blast phase (AP/BP) occurs in 3-5% of cases, especially in patients resistant to several lines of TKIs. In TKI-refractory patients in advanced phases, the only curative option is hematopoietic stem cell transplantation. We and others have shown the relevance of the expression of the Interleukin-2-Receptor α subunit (IL2RA/CD25) as a biomarker of CML progression, suggesting its potential use as a therapeutic target for CAR-based therapies. Here we show the development of a CAR-NK therapy model able to target efficiently a blast crisis cell line (K562). The design of the CAR was based on the scFv of the clinically approved anti-CD25 monoclonal antibody (Basiliximab). The CAR construct was integrated into NK92 cells resulting in the generation of CD25 CAR-NK92 cells. Target K562 cells were engineered by lentiviral gene transfer of CD25. In vitro functionality experiments and in vivo leukemogenicity experiments in NSG mice transplanted by K562-CD25 cells showed the efficacy and specificity of this strategy. These proof-of-concept studies could represent a first step for further development of this technology in refractory/relapsed (R/R) CML patients in BP as well as in R/R acute myeloblastic leukemias (AML).

Objective: Chronic myeloid leukemia (CML) is a disease caused by the acquisition of BCR-ABL1 fusion in hematopoietic stem cells. In this study, we focus on the oncofetal ENOX2 protein as a potential secretable biomarker in CML. Materials and Methods: We used cell culture, western blot, quantitative RT-PCR, ELISA, transcriptome analyses, and bioinformatics techniques to investigate ENOX2 mRNA and protein expression. Results: Western blot analyses of UT-7 and TET-inducible Ba/F3 cell lines demonstrated the upregulation of the ENOX2 protein. BCR-ABL1 was found to induce ENOX2 overexpression in a kinase-dependent manner. We confirmed increased ENOX2 mRNA expression in a cohort of CML patients at diagnosis. In a series of CML patients, ELISA assays showed a highly significant increase of ENOX2 protein levels in the plasma of patients with CML compared to controls. Reanalyzing the transcriptomic dataset confirmed ENOX2 mRNA overexpression in the chronic phase of the disease. Bioinformatic analyses identified several genes whose mRNA expressions were positively correlated with ENOX2 in the context of BCR-ABL1. Some of them encode proteins involved in cellular functions compatible with the growth deregulation observed in CML. Conclusion: Our results highlight the upregulation of a secreted redox protein in a BCR-ABL1-dependent manner in CML. The data presented here suggest that ENOX2, through its transcriptional mechanism, plays a significant role in BCR-ABL1 leukemogenesis.

The primary objective of this study was to assess the benefits of incorporating higher NMP content as a cement substitute in mortar and concrete mixtures. Our aim was to quantify and elucidate the impact of Natural Moroccan Pozzolanic material (NMP) on compressive strength, insulation performance, and corrosion resistance of reinforced concrete when exposed to chloride attack. Higher NMP dosages were considered for both economic and environmental reasons. Notably, this study is the first of its kind to focus on NMP as a cement substitute. In this study, we investigated the performance of reinforced concrete containing varying percentages of NMP as a partial substitution for Portland Cement (PC), ranging from 10% to 50% by weight. We evaluated the corrosion behavior of reinforced concrete in an aggressive medium (3% sodium chloride) after 3 and 90 days using electrochemical impedance spectroscopy (EIS). We also assessed chloride permeability by measuring the degree of chloride penetration. Additionally, we conducted microstructural characterization using Scanning Electron Microscopy (SEM) equipped with energy-dispersive X-ray spectroscopy (EDX) and Raman spectroscopy to analyse the impact of NMP incorporation into concrete. The study's findings revealed that a partial substitution of cement with up to 50% NMP in concrete can be achieved without compromising overall strength. The highest compressive and bending strengths were observed in mixes with a 30% replacement of cement with NMP. The increased silica, alumina, and calcium content of NMP led to the formation of new calcium silicate hydrates (CSH) and calcium alumino silicate hydrates (CASH) gels, including tobermorite and Al-tobermorite, due to a pozzolanic reaction. Furthermore, the use of NMP in concrete construction improved thermal properties, reducing heat transfer and enhancing thermal comfort. Electrochemical impedance spectroscopy (EIS) and Open Circuit Potential (OCP) results indicated that the addition of natural Moroccan pozzolan enhanced the corrosion resistance of reinforced concrete exposed to 3% NaCl medium. Additionally, the incorporation of NMP significantly reduced cement usage, aligning with sustainable development goals by lowering CO2 emissions.