This study aimed to identify radiomic features of primary tumor and develop a model for indicating extrahepatic metastasis of hepatocellular carcinoma (HCC). Contrast-enhanced computed tomographic ...(CT) images of 177 HCC cases, including 26 metastatic (MET) and 151 non-metastatic (non-MET), were retrospectively collected and analyzed. For each case, 851 radiomic features, which quantify shape, intensity, texture, and heterogeneity within the segmented volume of the largest HCC tumor in arterial phase, were extracted using Pyradiomics. The dataset was randomly split into training and test sets. Synthetic Minority Oversampling Technique (SMOTE) was performed to augment the training set to 145 MET and 145 non-MET cases. The test set consists of six MET and six non-MET cases. The external validation set is comprised of 20 MET and 25 non-MET cases collected from an independent clinical unit. Logistic regression and support vector machine (SVM) models were identified based on the features selected using the stepwise forward method while the deep convolution neural network, visual geometry group 16 (VGG16), was trained using CT images directly. Grey-level size zone matrix (GLSZM) features constitute four of eight selected predictors of metastasis due to their perceptiveness to the tumor heterogeneity. The radiomic logistic regression model yielded an area under receiver operating characteristic curve (AUROC) of 0.944 on the test set and an AUROC of 0.744 on the external validation set. Logistic regression revealed no significant difference with SVM in the performance and outperformed VGG16 significantly. As extrahepatic metastasis workups, such as chest CT and bone scintigraphy, are standard but exhaustive, radiomic model facilitates a cost-effective method for stratifying HCC patients into eligibility groups of these workups.
In this paper, the effects of fuel utilization, air-to-fuel ratio (A/F) and pre-reforming rate on the plant efficiency, including heat and electric efficiencies, of sequential-type and fully ...recuperative-type of solid oxide fuel cell (SOFC) power plant are studied with the GCTool software developed by American Argonne National Laboratory (ANL). Methane is chosen as fuel, air as oxidant, and the pressure drop due to stream transported in the duct and components is considered in both types of power plant systems. A full analysis of the state at each node of the system is conducted. The results reveal that the A/F factor is the most important factor on system efficiency, and the pre-reforming rate of fuel is insignificant to the efficiency, but it can be used as an auxiliary tuner for the operating temperature of the solid oxide fuel cells in addition to A/F value. Under the same settings, overall plant efficiency is higher in the sequential type than in the fully recuperative type of SOFC power plants. On the other hand, for electric efficiency, the opposite trend is observed.
In this paper, the influence of energy recuperation on the efficiency of a solid oxide fuel cell (SOFC) power system is studied with the GCTool software developed by the American Argonne National ...Laboratory (ANL). The recuperative energies include partial recycled air exhausted from cathode side, recirculated fuel and steam from the anode side of the SOFC, and combustion gases from anode exhaust, individually. The methane is chosen as fuel, air is oxidant, and the pressure drops due to streams transported through the duct and components are taken into account in the power system. Full analysis of the state at each node of the system is conducted. The results show that, under the same setting, with an A/F of 4, a pre-reforming rate of 30%, and fuel utilization of 80%, the overall system efficiency is elevated from 50 to 68% in the case of recirculating partial fuel and steam from the anode exhaust of the SOFC. And, the configuration of diluted fuel recycled entirely from the outlet of the anode side of the SOFC is going to cause the overall efficiency to become the lowest in all cases in spite of reaching the highest electric efficiency of 41%. Recirculating partial air released from the outlet of the cathode side could provide extra heat to preheat inflow air, and the overall efficiency will be raised, apparently, as well.
In this paper, the influence of energy recuperation on the efficiency of a solid oxide fuel cell (SOFC) power system is studied with the GCTool software developed by the American Argonne National ...Laboratory (ANL). The recuperative energies include partial recycled air exhausted from cathode side, recirculated fuel and steam from the anode side of the SOFC, and combustion gases from anode exhaust, individually. The methane is chosen as fuel, air is oxidant, and the pressure drops due to streams transported through the duct and components are taken into account in the power system. Full analysis of the state at each node of the system is conducted. The results show that, under the same setting, with an A/F of 4, a pre-reforming rate of 30%, and fuel utilization of 80%, the overall system efficiency is elevated from 50 to 68% in the case of recirculating partial fuel and steam from the anode exhaust of the SOFC. And, the configuration of diluted fuel recycled entirely from the outlet of the anode side of the SOFC is going to cause the overall efficiency to become the lowest in all cases in spite of reaching the highest electric efficiency of 41%. Recirculating partial air released from the outlet of the cathode side could provide extra heat to preheat inflow air, and the overall efficiency will be raised, apparently, as well.
Stripe phases, in which the rotational symmetry of charge density is spontaneously broken, occur in many strongly correlated systems with competing interactions1–11. However, identifying and studying ...such stripe phases remains challenging. Here we uncover stripe phases in WSe2/WS2 moiré superlattices by combining optical anisotropy and electronic compressibility measurements. We find strong electronic anisotropy over a large doping range peaked at 1/2 filling of the moiré superlattice. The 1/2 state is incompressible and assigned to an insulating stripe crystal phase. Wide-field imaging reveals domain configurations with a preferential alignment along the high-symmetry axes of the moiré superlattice. Away from 1/2 filling, we observe additional stripe crystals at commensurate filling 1/4, 2/5 and 3/5, and compressible electronic liquid crystal states at incommensurate fillings. Our results demonstrate that two-dimensional semiconductor moiré superlattices are a highly tunable platform from which to study the stripe phases and their interplay with other symmetry breaking ground states.Optical anisotropy and electronic compressibility measurements are used to uncover stripe phases, where the rotational symmetry of charge density is spontaneously broken, in a two-dimensional semiconductor moiré superlattice.
Abstract
SMAD4 is mutated in human lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generate a ...highly aggressive lung cancer mouse model bearing conditional
Kras
G12D
,
p53
fl/fl
LOF and
Smad4
fl/fl
LOF mutations (SPK), showing a much higher incidence of tumor metastases than the
Kras
G12D
,
p53
fl/fl
(PK) mice. Molecularly, PAK3 is identified as a downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice is achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3′UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components is observed in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.
Solution casting is a common processing method in industrial production. The phase-structure transitions driven by solvent evaporation directly impact the quality of the final film. However, due to ...the presence of solvents and other additives in the solution, it is difficult to detect the condensed matter structure during the drying process. This work studies structural transitions and heterogeneity of a poly(vinyl alcohol) (PVA) film during water evaporation using glycerol as a plasticizer. Aggregation-induced emission (AIE) molecules are utilized to indicate the change in PVA chain dynamics during evaporation. The gelation, crystallization, and glass transition can be clearly detected via emission intensity change of the AIE molecules during water evaporation. It is found that the critical concentrations triggering structural transitions increase with the glycerol content, attributed to the release of PVA segmental mobility by the plasticizer. Furthermore, structural uniformity in the thickness direction is realized while the PVA film was loaded with 20% glycerol. It is revealed that glycerol diminishing the heterogeneity is due to the dual effect of hydrophilic glycerol reducing the evaporation rate and enhancing diffusion. Finally, the mechanism of the plasticizer in delaying structural transitions and ameliorating the heterogeneity in PVA films is discussed, which could provide theoretical guidance for preparation of polymer films via solution casting.
Concentration-dependent phase transitions in concentrated solutions have remained speculation due to the serious impediment of macromolecule dynamics by intensive topological entanglement or ...intermolecular interaction as well as the absence of powerful tool for detecting changes in chain or segment movement. Herein, taking a general polymer, namely, poly(vinyl alcohol) (PVA), as an example, a water-soluble fluorescent molecule with aggregation-induced emission (AIE) is introduced into the PVA solutions as a chain dynamics indicator to investigate phase transitions at high concentrations through in situ monitoring of the solvent evaporation process. Two turning points of fluorescent intensity are observed for the first time at mean concentrations of ∼25% and ∼45%, corresponding to the gelation and amorphous-to-crystalline transitions, respectively. Our work offers a fundamental insight into the physical nature of concentrate-dependent nonequilibrium transitions and develops a reliable and sensitive approach based on the AIE phenomenon for following high-concentration-triggered property changes of a polymer solution.
Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1-7.5% of ...human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy.
Multiple mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been identified in EGFR-mutant non-small cell lung cancer (NSCLC); however, ...recurrent resistance to EGFR TKIs due to the heterogeneous mechanisms underlying resistance within a single patient remains a major challenge in the clinic. Here, we report a role of nuclear protein kinase Cδ (PKCδ) as a common axis across multiple known TKI-resistance mechanisms. Specifically, we demonstrate that TKI-inactivated EGFR dimerizes with other membrane receptors implicated in TKI resistance to promote PKCδ nuclear translocation. Moreover, the level of nuclear PKCδ is associated with TKI response in patients. The combined inhibition of PKCδ and EGFR induces marked regression of resistant NSCLC tumors with EGFR mutations.
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•PKCδ is a common mediator shared by multiple TKI-resistant pathways•TKI-induced EGFR heterodimers promote nuclear PKCδ and TKI resistance•Nuclear PKCδ associates with worse TKI response in EGFR-mutant NSCLC patients•Inhibition of PKCδ sensitizes resistant EGFR-mutant NSCLC to EGFR TKI
Lee et al. find nuclear PKCδ as a mediator of resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs). TKI-induced EGFR heterodimerization promotes PKCδ nuclear translocation, which is associated with TKI resistance in patients. Combined TKI and PKCδ inhibition induces regression of resistant NSCLC tumors.
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