Background & AimWe have developed a label-free high throughput machine learning-driven cell sorter based on cells’ morphological information. The cytometer acquires cell-specific waveform signals ...containing morphologic information from a defined training set. After a supervised machine learning model is developed from the training set, the cell of interest can be classified and sorted based on the scores obtained by the machine learning model. We investigated that the label-free cell classification and sorting of CAR-T cells to improve manufacturing process.CAR-T therapy has shown innovative therapeutic effects in leukemia treatment. However, many clinical studies have been conducted and the clinical results indicated that quality control for the therapeutic cell production process is always an issue for any cell therapy manufacturing process. Also, an ideal CAR-T cell population or “High-Quality CAR-T” with regard to a T cell subset, phenotype, and CAR construct is under investigation. Detailed analysis of CAR-T cells administered to CLL patients have been conducted and the results revealed the important features of clinically active CAR-T such as its glycolysis status, early memory phenotype or exhaustion low profile.Methods, Results & ConclusionTo avoid CAR-T manufacturing failure and/or improve the CAR-T quality, it is necessary to collect enough healthy and functional T cells from the patient by leukapheresis in the manufacturing process. We investigated that our label-free cytometer can discriminate healthy T cells from samples after hemolysis process, wherein CD3 positive T cells and other cells were used as a training set to develop the T cell classifier model. The accuracy of the label-free discrimination of T cells was found to be very high. This label-free classification may allow us to perform the quality control of CAR-T manufacturing without the use of surface markers and at the minimal sample loss.
Plant morphogenesis relies on cell proliferation and differentiation strictly controlled in space and time. As in other eukaryotes, progression through the plant cell cycle is governed by ...cyclin-dependent kinases (CDKs) that associate with their activator proteins called cyclins (CYCs), and the activity of CYC-CDK is modulated at both transcriptional and post-translational levels. Compared with animals and yeasts, plants generally possess many more genes encoding core cell cycle regulators and it has been puzzling how their functions are specified or overlapped in development or in response to various environmental changes. Thanks to the recent advances in high-throughput, genome-wide transcriptome and proteomic technologies, we are finally beginning to see how core regulators are assembled during the cell cycle and how their activities are modified by developmental and environmental cues. In this review we will summarize the latest progress in plant cell cycle research and provide an overview of some of the emerging molecular interfaces that link upstream signaling cascades and cell cycle regulation.
In metals, orbital motions of conduction electrons on the Fermi surface are quantized in magnetic fields, which is manifested by quantum oscillations in electrical resistivity. This Landau ...quantization is generally absent in insulators. Here, we report a notable exception in an insulator-ytterbium dodecaboride (YbB
). The resistivity of YbB
, which is of a much larger magnitude than the resistivity in metals, exhibits distinct quantum oscillations. These unconventional oscillations arise from the insulating bulk, even though the temperature dependence of the oscillation amplitude follows the conventional Fermi liquid theory of metals with a large effective mass. Quantum oscillations in the magnetic torque are also observed, albeit with a lighter effective mass.
Summary
Background
Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 ...genotype.
Aim
To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype.
Methods
Twenty‐eight healthy Japanese volunteers 7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs) received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty‐four‐hour intragastric pH monitoring was performed on day 7 on each regimen.
Results
In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype‐dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily.
Conclusion
Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.
The performance of hydrogen embrittlement, fatigue properties and impact toughness of ultra high strength transformation induced plasticity aided steels with bainitic ferrite matrix (TBF steels) has ...been discussed. Some characteristics and deformation transformation mechanism of the retained austenite has also been discussed. It has been observed that mechanical stability and volume fraction of the interlath retained austenite phase in the TBF steels play an important role in increasing delayed fracture strength, fatigue limit and impact toughness.
Mental nerve paresthesia is a serious postoperative complication of mandibular third molar extraction. It appears that no study has examined the relationship between the surface morphology of the ...mandibular third molar roots and the possibility of mental nerve paresthesia following tooth extraction. Therefore, the root morphology of the mandibular third molars was examined according to age using dental cone beam computed tomography (CBCT), and the possibility of mental nerve paresthesia following tooth extraction was evaluated. The study included 1216 patients who had undergone mandibular third molar extractions. The root morphology of 1534 teeth in 791 patients who had CBCT performed before surgery was studied. Factors evaluated were age, complete or incomplete formation of the mandibular third molar roots, periodontal ligament atrophy of the mandibular third molar roots, hypercementosis, and mandibular canal deformation. Mandibular third molar root formation was completed between the ages of 19 and 30 years. Complete formation of the mandibular third molar roots (P = 0.002) and deformation of the mandibular canal (P < 0.001) were identified as risk factors for mental nerve paresthesia. These findings suggest that the risk of mental nerve paresthesia could be reduced if the extraction of third molars is performed prior to complete root formation.
Abstract
Genebanks provide access to diverse materials for crop improvement. To utilize and evaluate them effectively, core collections, such as the World Rice Core Collection (WRC) in the Genebank ...at the National Agriculture and Food Research Organization, have been developed. Because the WRC consists of 69 accessions with a high degree of genetic diversity, it has been used for >300 projects. To allow deeper investigation of existing WRC data and to further promote research using Genebank rice accessions, we performed whole-genome resequencing of these 69 accessions, examining their sequence variation by mapping against the Oryza sativa ssp. japonica Nipponbare genome. We obtained a total of 2,805,329 single nucleotide polymorphisms (SNPs) and 357,639 insertion–deletions. Based on the principal component analysis and population structure analysis of these data, the WRC can be classified into three major groups. We applied TASUKE, a multiple genome browser to visualize the different WRC genome sequences, and classified haplotype groups of genes affecting seed characteristics and heading date. TASUKE thus provides access to WRC genotypes as a tool for reverse genetics. We examined the suitability of the compact WRC population for genome-wide association studies (GWASs). Heading date, affected by a large number of quantitative trait loci (QTLs), was not associated with known genes, but several seed-related phenotypes were associated with known genes. Thus, for QTLs of strong effect, the compact WRC performed well in GWAS. This information enables us to understand genetic diversity in 37,000 rice accessions maintained in the Genebank and to find genes associated with different phenotypes.
The sequence data have been deposited in DNA Data Bank of Japan Sequence Read Archive (DRA) (Supplementary Table S1).
The Atacama Large Millimeter/submillimeter Array (ALMA) radio telescope has commenced science observations of the Sun starting in late 2016. Since the Sun is much larger than the field of view of ...individual ALMA dishes, the ALMA interferometer is unable to measure the background level of solar emission when observing the solar disk. The absolute temperature scale is a critical measurement for much of ALMA solar science, including the understanding of energy transfer through the solar atmosphere, the properties of prominences, and the study of shock heating in the chromosphere. In order to provide an absolute temperature scale, ALMA solar observing will take advantage of the remarkable fast-scanning capabilities of the ALMA 12 m dishes to make single-dish maps of the full Sun. This article reports on the results of an extensive commissioning effort to optimize the mapping procedure, and it describes the nature of the resulting data. Amplitude calibration is discussed in detail: a path that uses the two loads in the ALMA calibration system as well as sky measurements is described and applied to commissioning data. Inspection of a large number of single-dish datasets shows significant variation in the resulting temperatures, and based on the temperature distributions, we derive quiet-Sun values at disk center of 7300 K at
λ
=
3
mm
and 5900 K at
λ
=
1.3
mm
. These values have statistical uncertainties of about 100 K, but systematic uncertainties in the temperature scale that may be significantly larger. Example images are presented from two periods with very different levels of solar activity. At a resolution of about
25
″
, the 1.3 mm wavelength images show temperatures on the disk that vary over about a 2000 K range. Active regions and plages are among the hotter features, while a large sunspot umbra shows up as a depression, and filament channels are relatively cool. Prominences above the solar limb are a common feature of the single-dish images.
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