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Summary: Adaptor chimeric antigen receptor (CAR) T‐cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T‐cell therapy in myeloid malignancies. The adaptor CAR T‐cell platform 'UniCAR' is currently under early clinical investigation. Recently, the first proof of concept of a well‐tolerated, rapidly switchable, CD123‐directed UniCAR T‐cell product treating patients with acute myeloid leukaemia (AML) was reported. Relapsed and refractory AML is prone to high plasticity under therapy pressure targeting one single tumour antigen. Thus, targeting of multiple tumour antigens seems to be required to achieve durable anti‐tumour responses, underlining the need to further design alternative AML‐specific target modules (TM) for the UniCAR platform. We here present the preclinical development of a novel FMS‐like tyrosine kinase 3 (FLT3)‐directed UniCAR T‐cell therapy, which is highly effective for in vitro killing of both AML cell lines and primary AML samples. Furthermore, we show in vivo functionality in a murine xenograft model. PET analyses further demonstrate a short serum half‐life of FLT3 TMs, which will enable a rapid on/off switch of UniCAR T cells. Overall, the presented preclinical data encourage the further development and clinical translation of FLT3‐specific UniCAR T cells for the therapy of AML. [ABSTRACT FROM AUTHOR]

During the cutting process, it is crucial to replace cutting tools at the right time to meet machining accuracy requirements. However, determining tool life relies on the unsystematic tacit knowledge of skilled engineers. Moreover, the increasing variety of cutting tools needed to accommodate the trend towards small quantities of various products has made it even more challenging to determine tool life. This study aimed to address this issue by developing a system that could accurately determine when to replace ball end-mills without requiring the judgment of skilled engineers. The results of the study showed that anomaly detection methods can be applied to images of worn tools to determine tool life accurately. By converting current value data during cutting into images and using image classification methods, it is possible to classify tools according to their wear conditions, such as new, early wear, end stage of wear, and end of tool life. The study also showed that constructing a multimodal judgment system using both tool appearance image abnormality detection and current value data image classification resulted in a 98% judgment accuracy rate for tools that had reached the end of their service life, with a correct answer rate of over 90%.

Incorporation of Au° inside SiO2 was achieved by a solid-state method from the pyrolysis of the composites (Chitosan)•(AuCl3)n•(SiO2)m and (PS-co-4-PVP)•(AuCl3)n•(SiO2)m Similarly, the incorporation of Ag° inside SiO2 it was made from thermal treatment of the composites (Chitosan)•(AgNO3)n•(SiO2)m and (PS-co-4-PVP)•(AgNO3)n•(SiO2)m. The nature of the polymer controls the particle size for the Au/SiO2 composite, while that for the Ag/SiO2 both, polymer Chitosan and PS-co-4-PVP, produces similar particle size. In the case of the composite Ag/SiO2 the particle size as small as 5 nm were obtained. The 1:1 or 1:5 metal/polymer ratios, as well as the nature of the polymer in the macromolecular precursors (Chitosan)•(AuCl3)n•(SiO2)m and (PS-co-4-PVP)•(AuCl3)n•(SiO2)m influences the dispersion of the Au° nanostructures inside SiO2 matrix. The results are compared with those previously obtained for bimetallic composites Au/Ag//SiO2. A formation mechanism of the Au°/SiO2 and Ag°/SiO2 composites involving the combustion of the organic matter and the growth of the Au° and Ag° nanoparticles inside the holes, generated from the combustion process, is proposed. [ABSTRACT FROM AUTHOR]

Context. This paper presents the results obtained with the Multi Unit Spectroscopic Explorer (MUSE) for the core of the lensing cluster Abell 1689, as part of MUSE's commissioning at the ESO Very Large Telescope. Aims. Integral-field observations with MUSE provide a unique view of the central 1 × 1 arcmin2 region at intermediate spectral resolution in the visible domain, allowing us to conduct a complete census of both cluster galaxies and lensed background sources. Methods. We performed a spectroscopic analysis of all sources found in the MUSE data cube. Two hundred and eighty-two objects were systematically extracted from the cube based on a guided-and-manual approach. We also tested three different tools for the automated detection and extraction of line emitters. Cluster galaxies and lensed sources were identified based on their spectral features. We investigated the multiple-image configuration for all known sources in the field. Results. Previous to our survey, 28 di erent lensed galaxies displaying 46 multiple images were known in the MUSE field of view, most of them were detected through photometric redshifts and lensing considerations. Of these, we spectroscopically confirm 12 images based on their emission lines, corresponding to 7 different lensed galaxies between z = 0.95 and 5.0. In addition, 14 new galaxies have been spectroscopically identified in this area thanks to MUSE data, with redshifts ranging between 0.8 and 6.2. All background sources detected within the MUSE field of view correspond to multiple-imaged systems lensed by A1689. Seventeen sources in total are found at z ≥ 3 based on their Lyman-α emission, with Lyman-α luminosities ranging between 40:5 ≲ log(Lyα) ≲ 42:5 after correction for magnification. This sample is particularly sensitive to the slope of the luminosity function toward the faintest end. The density of sources obtained in this survey is consistent with a steep value of α ≤-1.5, although this result still needs further investigation. Conclusions. These results illustrate the effciency of MUSE in characterizing lensing clusters on one hand and in studying faint and distant populations of galaxies on the other hand. In particular, our current survey of lensing clusters is expected to provide a unique census of sources responsible for the reionization in a representative volume at z ~ 4-7. [ABSTRACT FROM AUTHOR]

Recent experimental findings in animals and humans indicate adverse respiratory effects from short-term exposures to particulate air pollutants, especially in sensitive subpopulations such as asthmatics. The relationship between air pollution and asthma has mainly been determined using particulate matter (PM) measurements from central sites. Validated tools are needed to assess exposures most relevant to health effects. Recently; a personal passive particulate sampler (personal Data-RAM, pDR, MIE Inc., Bedford, MA) has become available for studying personal exposures to PM with time resolution at 1 min. The pDR measures light scatter from PM in the 0.1-10 μM range, the significant range for health effects. In order to assess the ability of the pDR in predicting gravimetric mass, pDRs were collocated with PM[SUB2.5] and PM[SUB10] Harvard Impactors (HI) inside and outside nine homes of asthmatic children and at an outdoor central Air Pollution Control District site. Results are presented of comparisons between the HI samplers and the pDR in various modes of operation: passive, active, and active with a heated inlet. When used outdoors at fixed sites the pDR readings exhibit interference from high relative humidity (RH) unless operated with a method for drying inlet air such as a heater, or if readings at times of high RH are adjusted. The pDR correlates more highly with the HI PM[SUB2.5] than with the HI PM[SUB10] (r[SUP2]=0.66 vs. 0.13 for outdoors, r[SUP2] = 0.42 vs. 0.20 for indoors). The pDR appears to be a useful tool for an epidemiologic study that aims to examine the relationship between health outcomes and personal exposure to peaks in PM. [ABSTRACT FROM AUTHOR]

The stability of Interleukin 2 (IL-2) is an essential characteristic for the development of a stable formulation. Thus, this function should be preserved during purification, formulation and long-term storage. For IL-2 the major degradation routes are oxidation and aggregation, so formulations avoiding this kind of modifications must be carefully design. In this work we developed two formulations of IL-2 which efficiently retained the stability of this cytokine. IL-2 was obtained from the Center for Genetic Engineering and Biotechnology (Havana, Cuba). All reagents used to prepared each formulation were of analytical grade and purchased by different commercial sources. IL-2 was prepared in different formulations by adding the additives (aminoacids, polymers and quelators) diluted into the formulation buffer to a convenient concentration. Formulations were filtered, and 1.0 mL volumes were aliquoted into 3 c.c. type 1 glass vials. Afterward vials were sealed with bromobutyl stoppers and aluminum seals. When lyophilization took place vials were sealed after the process. All steps were under laminar flow conditions. Samples were analyzed through the Quality Control System of CIGB. Results obtained by different techniques pointed to that additives used here (dextrane/glycine for the freeze-dried formulation, and EDTA/glycine for liquid formulation) efficiently preserved IL-2 stability. Although this is not an unexpected result because of the preferential exclusion mechanism by which solutes stabilized proteins, this is an essential verification to develop a stable formulation. As judged by different assays, the use of aminoacids and polymers may decrease IL-2 degradation in formulations developed in this work. [ABSTRACT FROM AUTHOR]