Enhanced geothermal systems (EGS) is currently the most efficient method to mine heat from hot dry rock (HDR) reservoirs. The coupled thermo-hydro-mechanical (THM) effect therein is of critical ...importance to predict the long-term performance of EGS. A novel 3D THM coupling model integrating displacement discontinuity method (DDM), finite volume method (FVM) and finite element method (FEM) is developed in this study to aid such prediction. The present model is first validated against analytical solutions, and then applied to a penny shape EGS to simulate a 30-year prolonged injection. The simulation results reveal that EGS maintains high productivity during the early injection stage but once thermal drawdown takes place, the EGS productivity degrades rapidly. The fracture aperture model employed in the present study is capable of simulating hydraulic fractures in which the fluid pressure is large enough to overcome the normal stress exerted to the fracture faces and thus jack the fracture open. In contrast, most early studies adopted a compressive aperture model, where a substantial part of the normal stress is borne by fracture gouge/roughness. The strength of DDM + FVM + FEM scheme lies in the efficiency and versatility of simulating fractures. Our study indicates that the DDM + FVM + FEM scheme has high potential to serve as a competent alternative to performing the THM coupling simulation in EGS.
All-for-one tourism is a new planning concept proposed by Chinese tourism scholars and practitioners, which has been formally regarded as a new tourism model to develop the country’s tourism ...industries since 2016. It aims to stimulate the growth of the tourism industries across the entire region, encompassing all tourism and tourism-related resources at a destination. Hengdian Town is a tourism destination in China that has implemented the model of all-for-one tourism to develop and manage its film-related tourism. Based on the data collected from ethnographic methods (participant observations and individual interviews) in Hengdian Town, this paper examines the ways that the destination manages its film-related tourism, as well as the outcomes of such approaches, by applying the model of all-for-one tourism. The findings reveal that Hengdian Town has leveraged the model to manage its tourism resources and provided tourists with a comprehensive travel experience. This paper also explores the benefits and drawbacks of managing film-related tourism in the all-for-one tourism model. By focusing on film-related tourism, this study provides a unique perspective on the all-for-one tourism model.
Isorhapontigenin (ISO) is one of the main bioactive components of
Gnetum cleistostachyum
and was shown to possess antioxidant and antitumor functions. Herein, we hope to examine the neuroprotection ...impacts of ISO in rats subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R, 2/24 h) injuries. ISO was injected intraperitoneally into the rats immediately after cerebral ischemia. After 24 h of the reperfusion, infarct volume, brain water contents, neurological deficit, and cerebral blood flow were assessed. Hippocampus histopathology change was detected by H&E and TUNEL staining. The expressions of cleaved caspase-3, Bax and Bcl-2, and phospho-Akt (
p
-Akt) were investigated by real-time RT-PCR or western blot analysis. We found that ISO significantly suppressed the infarct volumes, brain water contents, and neurological deficit, increased CBF, and relieved histopathologic change in a dose-dependent manner. Reduced malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD) and GSH and glutathione peroxidase (GSH-PX) were observed in ISO group. ISO remarkably decreased caspase-3 and Bax and increased levels of Bcl-2. Additionally, ISO upregulated
p
-Akt expression. Blocking of PI3K activities by wortmannin can abolish the ISO-caused decrease in infarct volumes and neurologic deficit scores and abrogate the promotion of p-Akt. The data indicated that ISO played neuroprotective impacts against focal I/R injuries, possibly related to the activating of PI3K/Akt signaling.
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Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence ...is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA) as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: −0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
Radical cyclization represents a powerful strategy for construction of ring structures. Traditional radical cyclization, which is based on radical addition as the key step, necessitates the use of ...unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C−H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)−H bonds. It allows for efficient construction of chiral pyrrolidines and other valuable 5-membered cyclic compounds. This alternative strategy of radical cyclization provides a new retrosynthetic paradigm to prepare five-membered cyclic molecules from readily available open-chain aldehydes through the union of C−H and C=O elements for C−C bond formation.
Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of ...complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval CI: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%;
= .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%;
= .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license.
See also the editorial by Bae in this issue.
This study investigates the impact of firms' heterogeneous exposure to economic policy uncertainty (EPU exposure) on corporate innovation investment. The results show that, first, a significant ...negative relationship exists between EPU exposure and corporate innovation investment, and this result continues to hold after controlling for endogeneity and conducting a series of robustness tests. Second, operational risk and financial distress are the main channels through which EPU exposure affects innovation investment. Third, firm-specific factors, such as government ownership, government subsidies, profitability, R&D personnel level, and sufficiency of net working capital, shape the relationship between EPU exposure and innovation investment. This study contributes new evidence on the impact of EPU exposure on firm behavior in China, where ongoing economic and financial reforms introduce sources of significant uncertainty.
•This study explores the impact of EPU exposure on corporate innovation investment.•EPU exposure has a significantly negative effect on corporate innovation investment.•Operational risk and financial distress are the economic channels.•Firm characteristics shape the relationship between EPU exposure and innovation investment.
Long‐period (LP), hybrid, and volcano‐tectonic (VT) seismicity are important indicators for tracking the evolution of volcanic processes. Here, we propose an unsupervised learning method to classify ...5,949 seismic events in Kilauea volcano, Hawai'i, during a 4‐month period before the collapse of Pu'u’ O'o on April 30, 2018. The LPs and hybrids exhibit three major episodes, which progressively intensified and had increasing shallow events toward the eruption. The most intense episode starting 3 weeks before eruption coincides with changes in near‐caldera deformation and lava lake elevation in Halema'uma'u, serving as possible immediate precursors. However, the first two episodes imply magma migration was already active months prior to the eruption. The spatiotemporal patterns of abundant hybrids reveal that they are associated with magma movement but mixed with shear‐failure or near‐surface resonance. Our results provide useful constraints on the magmatic processes in the preparation phase of the Kilauea eruption in 2018.
Plain Language Summary
Many volcanoes around the world have been known to produce different types of seismic events, which can be used to infer volcanic processes underneath. However, classification of these events remains a challenging task. We propose a new classification method and apply it to numerous seismic events in Kilauea volcano, Hawai'i, before the collapse of Pu'u’ O'o in 2018. We successfully separate different types of events and observe interesting spatiotemporal patterns. The results show that, before the eruption, the long‐period and hybrid events have three episodes. Together with surface observations, the latest episode in April 9–27 shows an unusually high rate and more shallow origins, indicative of the impending eruption. In addition, the spatiotemporal patterns of hybrid events shed light on their physical mechanisms. These results provide useful constraints on the magma migration processes in the preparation phase of the Kilauea eruption in 2018.
Key Points
We classify long‐period, volcano‐tectonic, and hybrid events by spectral dissimilarity and hierarchical clustering
The unusual high seismicity rate and more shallow origins in the last episode in April 9–27 may be indicative of the impending eruption
The spatiotemporal patterns of hybrid events shed light on their physical mechanisms
The intrinsic limits of conventional ultrasound microbubble contrast agent greatly promoted the development and application of various nanomaterials for more efficient cancer ultrasound theranostics. ...Considerable successes have been achieved in the field of ultrasound molecular imaging and targeted therapy for tumor based on nanoparticulate theranostic agents. This review summarizes and discusses the emerging development on exploring organic and inorganic nanomaterials for ultrasound-based tumor diagnositic applications, and as synergistic agents for ultrasound targeted therapy in fighting cancer. The relationship between structure/composition and functionality of nanomaterials for ultrasound theranostic is discussed and revealed in detail. Finally, the further development and challenges facing clinical implementation of ultrasound nanomedicine are discussed. As a highly promising and valuable tumor-specific theranostic methodology, it is believed that ultrasound nanomedicine would pave a novel but efficient way for combating cancer.
The intrinsic limits of conventional ultrasound microbubble contrast agent greatly promoted the development and application of various nanomaterials for more efficient cancer ultrasound theranostics. Considerable successes have been achieved in the field of ultrasound molecular imaging and targeted therapy for tumor based on nanoparticulate theranostic agents. This review summarizes and discusses the emerging development on exploring organic and inorganic nanomaterials for ultrasound-based tumor diagnositic applications, and as synergistic agents for ultrasound targeted therapy in fighting cancer. The relationship between structure/composition and functionality of nanomaterials for ultrasound theranostic is discussed and revealed in detail. Finally, the further development and challenges facing clinical implementation of ultrasound nanomedicine are discussed. As a highly promising and valuable tumor-specific theranostic methodology, it is believed that ultrasound nanomedicine would pave a novel but efficient way for combating cancer. Display omitted
•Overviewing the most representative nanoplatforms for specific ultrasound-responsive theranostic applications on fighting cancer.•Revealing the relationship between structure/composition and functionality of versatile nanoplatforms for ultrasound theranostic of cancer.•Discussing of the development and challenges facing clinical implementation of ultrasound-responsive nanomedicine in combating cancers.