An upper-crust lid over the Long Valley magma chamber.

Geophysical characterization of calderas is fundamental in assessing their potential for future catastrophic volcanic eruptions. The mechanism behind the unrest of Long Valley Caldera in California remains highly debated, with recent periods of uplift and seismicity driven either by the release of aqueous fluids from the magma chamber or by the intrusion of magma into the upper crust. We use distributed acoustic sensing data recorded along a 100-kilometer fiber-optic cable traversing the caldera to image its subsurface structure. Our images highlight a definite separation between the shallow hydrothermal system and the large magma chamber located at ~12-kilometer depth. The combination of the geological evidence with our results shows how fluids exsolved through second boiling provide the source of the observed uplift and seismicity

Efficient DNA walker guided by ordered cruciform-shaped DNA track for ultrasensitive and rapid electrochemical detection of lead ion

The rational design of DNA tracks is an effective pathway to guide the autonomous movement and high-efficiency recognition in DNA walkers, showing outstanding advantages for the cascade signal amplification of electrochemical biosensors. However, the uncontrolled distance between two adjacent tracks on the electrode could increase the risk of derailment and interruption of the reaction. Hence, a novel four-way balanced cruciform-shaped DNA track (C-DNT) was designed as a structured pathway to improve the effectiveness and stability of the reaction in DNA walkers. In this work, two kinds of cruciform-shaped DNA were interconnected as a robust structure that could avoid the invalid movement of the designed DNA walker on the electrode. When hairpin H2 was introduced onto the electrode, the strand displacement reaction (SDR) effectively triggered movements of the DNA walker along the cruciform-shaped track while leaving ferrocene (Fc) on the electrode, leading to a significant enhancement of the electrochemical signal. This design enabled the walker to move in an excellent organized and controllable manner, thus enhancing the reaction speed and walking efficiency. Compared to other walkers moving on random tracks, the reaction time of the C-DNT-based DNA walker could be reduced to 20 min. Lead ion (Pb2+) was used as a model target to evaluate the analytical performance of this biosensor, which exhibited a low detection limit of 0.033 pM along with a wide detection ranging from 0.1 pM to 500 nM. This strategy presented a novel concept for designing a high-performance DNA walker-based sensing platform for the detection of contaminants

Optimization study of CAR-T cell expansion targeting CD99

Background and purpose: Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable efficacy in treating hematological and lymphatic system tumors, but its effectiveness in solid tumors is relatively poor, which is partly attributed to target selection. For Ewing sarcoma (ES), CD99 can be a potential target for CAR-T cells. However, due to T cells’ endogenous expression of CD99 protein, CAR-T cells targeting CD99 face limitations in their expansion capacity in vitro. This study aimed to identify the optimal conditions for preparing CD99 CAR-T cells by incorporating CD99 knockdown short hairpin RNA (shRNA), optimizing the multiplicity of infection (MOI) for lentiviral transduction, and screening for the best culture medium and container for CAR-T cell expansion. Methods: shRNA sequences were screened to enhance the expansion capacity of CD99 CAR-T cells. Different MOI, culture media, and containers were used to assess CAR-T cell transduction efficiency, cell viability, proliferation capacity, specific killing ability, and interferon-γ (IFN-γ) release levels under various conditions, in order to identify the optimal cell preparation conditions. Results: The expansion level of KO-CD99 CAR-T cells obtained through shRNA knockdown was significantly higher than that of CD99 CAR-T cells [(16.40±0.40) vs (6.33±1.53), P<0.01]. The optimal expansion effect was observed when the transduction MOI was between 0.25 and 1.0, and OptiVitro was used as the culture medium. CAR-T cells cultured in ventilated flasks exhibited significantly higher expansion rates compared to cells cultured in bags [MOI=0.25: (50.23±3.32) vs (13.02±4.82); MOI=0.50: (49.96±0.83) vs (18.25±2.88); MOI=1.00: (48.27±5.08) vs (13.16±6.26); P<0.01], with better cell phenotype and higher specific killing ability. Conclusion: KO-CD99 CAR-T cells obtained through shRNA technology can achieve stable expansion. Based on the optimization of expansion conditions, KO-CD99 CAR-T cells exhibit superior expansion capacity and a higher proportion of memory T cells when the MOI is between 0.25 and 1.00, OptiVitro is used as the culture medium, and ventilated flasks are used as the culture container. These findings lay a solid foundation for further clinical trials of CD99 CAR-T cell therapy for ES

Association of polymicrobial interactions with dental caries development and prevention

Dental caries is a common oral disease. In many cases, disruption of the ecological balance of the oral cavity can result in the occurrence of dental caries. There are many cariogenic microbiota and factors, and their identification allows us to take corresponding prevention and control measures. With the development of microbiology, the caries-causing bacteria have evolved from the traditional single Streptococcus mutans to the discovery of oral symbiotic bacteria. Thus it is necessary to systematically organized the association of polymicrobial interactions with dental caries development. In terms of ecology, caries occurs due to an ecological imbalance of the microbiota, caused by the growth and reproduction of cariogenic microbiota due to external factors or the disruption of homeostasis by one’s own factors. To reduce the occurrence of dental caries effectively, and considering the latest scientific viewpoints, caries may be viewed from the perspective of ecology, and preventive measures can be taken; hence, this article systematically summarizes the prevention and treatment of dental caries from the aspects of ecological perspectives, in particular the ecological biofilm formation, bacterial quorum sensing, the main cariogenic microbiota, and preventive measures

Nemotron-4 15B Technical Report

We introduce Nemotron-4 15B, a 15-billion-parameter large multilingual language model trained on 8 trillion text tokens. Nemotron-4 15B demonstrates strong performance when assessed on English, multilingual, and coding tasks: it outperforms all existing similarly-sized open models on 4 out of 7 downstream evaluation areas and achieves competitive performance to the leading open models in the remaining ones. Specifically, Nemotron-4 15B exhibits the best multilingual capabilities of all similarly-sized models, even outperforming models over four times larger and those explicitly specialized for multilingual tasks

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure