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Abstract Impedance-matched Marx generators (IMGs) are considered next generation pulsed-power drivers because of their long lifetime (> 10,000 shots), repetition rate (> 0.1-Hz), fast rise time (~ 100-ns), and high-energy-delivery efficiency (~ 90%). “TITAN” is a 14-stage IMG designed to deliver 1-TW to a 2-Ω matched load. In this paper, design, simulation, and experimental results for six stages of TITAN including its triggering system, air delivery system, and pulse shaping are presented. To achieve efficiency over 85% and maximize the capability of an IMG, synchronized triggering, reduced pre-fire rate, and pulse shaping ability are crucial. In this paper, novel engineering solutions are introduced, tested, and proven to overcome those challenges. 6-stage TITAN, powered by 102 identical bricks and 102 field-distortion-triggered gas switches, could generate ~ 600-kA and ~ 700-kV across a ~ 0.9-Ω matched load when fully charged to ± 100-kV. In these experiments, 6-stage TITAN is tested up to ± 70-kV charge voltage which delivers a peak power of 330-GW to a 1.2-Ω resistive load.

Background and purpose: In 2016 the National Cancer Institute (NCI) decided stopping to use NCI-60 cell lines for drug screening, suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research. The reason for NCI-60 cells 'retirement' was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials. Since the major cancer behaviors, such as proliferation and metastasis, are fundamentally altered with long-term culture, the tumor cell lines are not representative of the characteristics of cancer in patients. Currently, scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past. Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research. Methods: Breast cancer tissues were collected in the Department of Breast Surgery, Affiliated Hospital of Guizhou Medical University. The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (approval number: 2022 ethics No. 313), and the collection and use of tumor tissues complied with the Declaration of Helsinki. The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium. After the cells proliferated, the media were replaced with DEME medium. Cell line STR genotyping was done to determine cell-specific genetic markers and identification. Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors. Results: We created 6 primary breast cancer cell lines. The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features, clinical diagnosis, therapeutic regimens, clinical effectiveness and prognostic outcomes. The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines. Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines. Conclusion: We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

AbstractContext Ginsenoside metabolite compound K (CK) is an active metabolite produced by ginsenosides in vivo that has an anti-arthritic effect related to the glucocorticoid receptor (GR). However, the potential mechanisms of CK remain unclear.Objective This study explores the role and potential mechanisms of CK in vivo and in vitro.Materials and methods Adjuvant arthritis (AA) model was induced in Sprague-Dawley (SD) rats; the rats were randomly divided into four groups (n = 10): normal, AA, CK (80 mg/kg), and dexamethasone (Dex) group (1 mg/kg). From day 15, rats were treated with CK (once a day, i.g.) and Dex (once every 3 days, i.p.) for 18 days. To further verify the mechanism of CK, fibroblast-like synoviocytes (FLS) were stimulated by tumour necrosis factor α (TNF-α) to establish an inflammatory model in vitro.Results CK (80 mg/kg) reduced paw swelling (52%) and arthritis global assessment (31%) compared to that in AA rats. In addition, CK (80 mg/kg) suppressed GLUT1 (38%), HK2 (50%), and PKM2 (56%) levels compared with those in AA FLS. However, the effects of CK (30 μM) on these events were weakened or enhanced after GR knockdown or overexpression in FLS stimulated by TNF-α (30 ng/mL). CK (80 mg/kg) also downregulated the expression of P65 (61%), p-IκB (92%), and HIF-1α (59%).Discussion and conclusions The inhibition of CK on glycolysis and the NF-κB/HIF-1α pathway is potentially mediated through activating GR. These findings provide experimental evidence for elucidating the molecular mechanism of CK in treating rheumatoid arthritis (RA).

The significance of detecting faint and diminutive space targets cannot be overstated, as it underpins the preservation of Earth’s orbital environment’s safety and long-term sustainability. Founded by the different response characteristics between targets and backgrounds to aberrations, this paper proposes a novel aberration modulation correlation method (AMCM) for dim and small space target detection. By meticulously manipulating the light path using a wavefront corrector via a modulation signal, the target brightness will fluctuate periodically, while the background brightness remains essentially constant. Benefited by the strong correlation between targets’ characteristic changes and the modulation signal, dim and small targets can be effectively detected. Rigorous simulations and practical experiments have validated the remarkable efficacy of AMCM. Compared to conventional algorithms, AMCM boasts a substantial enhancement in the signal-to-noise ratio (SNR) detection limit from 5 to approximately 2, with an area under the precision–recall curve of 0.9396, underscoring its ability to accurately identify targets while minimizing false positives. In essence, AMCM offers an effective method for detecting dim and small space targets and is also conveniently integrated into other passive target detection systems.

Columnar jointed rock mass with unique joint network structure is a special type of jointed rock mass, which is a binary structure composed of high strength ‘basalt block’ and specific ‘dominant joint’. Relaxation, opening and slippage of columnar jointed surfaces and disintegration of columns occur easily during excavation under high ground stress, which eventually lead to disastrous collapses in columnar jointed rock mass. The construction safety of underground engineering under high stress is severed restricted by it. By combining acoustic wave, borehole camera and other integrated in-situ testing technology and numerical simulation, the mechanism of stress-structural collapse in columnar jointed rock mass under high stress is studied based on multiple columnar jointed rock mass collapses at left bank tailwater connection pipe of Baihetan hydropower station. The proposed controlling measures of excavation and support are also provided. The key of columnar joined rock mass collapse is the redistribution of stress in surrounding rock mass after the excavation and the strong unloading relaxation of columnar joined basalt, which causes the opening of its internal joint surfaces and structural deterioration, result in the disintegration of basalt columns. Thus, the chain catastrophic process of continuous unloading relaxation and progressive collapse of columnar jointed rock mass is induced. The research can provide reference for the prediction and control of deformation and failure of jointed rock masses in underground engineering under high geo-stress.

In astronomy, the images are sometimes undersampled. In the previous research works, image reconstructions have to be employed to recover the lost information from a set of undersampled images to achieve a high-resolution image using dithering or drizzle methods, which increase the complexity of alignment processes and make the real-time correction impossible. In this paper, the telescope is aligned by changing the positions of the secondary mirror using sharpness function method combined with the stochastic parallel gradient descent algorithm based on both well-sampled and undersampled images without image reconstructions. To improve the accuracy and robustness of the alignment, a new metric called relative root mean square error is proposed. Both numerical simulations and experiments are implemented, and the alignment precisions are measured by wavefront residual errors using Shack-Hartmann wavefront sensors. The results show that the correction processes can converge stably and quickly whether the images are well-sampled or undersampled. In experiments, the average wavefront error is 0.0595 λ for undersampled images and 0.0548 λ for well-sampled images after the telescope alignment, indicating that the misalignments are well compensated for both well-sampled and undersampled images.

As next-generation large-aperture telescopes, synthetic aperture is a promising method for realizing high resolution observations. Co-phasing the misaligned segmented aperture is an important procedure for high-resolution observations with segmented telescopes. In this paper, a piston error detection method is proposed based on two interference patterns. Two interference patterns are generated by using a lens placed across two adjacent pupils in the exit pupil plane at two wavelengths and a method based on phase retrieval technique is proposed to extract the piston error from the two interference patterns. The introduction of dual-wavelength in the scheme overcomes the 2π ambiguities problem and expands the piston error detection range. Meanwhile, the proposed piston error extraction method based on phase retrieval technique allows high precision measurement of the piston error and is robust to offset lens. Various simulations are demonstrated and the feasibility of the proposed piston error detection method is validated.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

To acquire images with higher accuracy of wide-field telescopes, deformable mirrors with more than 100 actuators are used, making the telescope alignment more complex and time-consuming. Furthermore, the position of the obscuration caused by the secondary mirror in the experiment system is changed with the difference of fields of view, making the response matrix of the deformable mirror different in various fields of view. To solve this problem, transfer functions corresponding to different fields of view are calculated according to the wavefront edge check and boundary conditions. In this paper, a model-based method combined with the stochastic parallel gradient descent (SPGD) algorithm is used. The experiment results show that our method can correct the aberrations with a high accuracy in both on-axis and off-axis fields, indicating that the effective actuators are well chosen corresponding to different fields of view.

The filtering fault detection problem for asynchronous switched discrete-time linear systems with mode-dependent average dwell time (MDADT) is investigated in this paper. A series of mode-dependent fault detection filters are designed with respect to each subsystem and are equipped with the switched system to obtain an augmented switched system. For the fact that the switching of the filter lags behind that of the subsystem frequently in actual situations, the resulting augmented switched system is consequently converted into an asynchronous augmented switched system. To guarantee the globally uniformly exponentially stability (GUES) and the H_/H∞ performance of the asynchronous filtering fault detection system, multiple Lyapunov functional and MDADT techniques are then used. The starting instants set of the subsystem is proposed to make it more convenient to apply the MDADT technique. The sufficient conditions for the existence of the designed filter and stability of asynchronous augmented switched systems are given in terms of linear matrix inequalities (LMIs). Finally, the effectiveness of the proposed methodology is demonstrated by two examples. [ABSTRACT FROM AUTHOR]