Developing high-strength welded joint of heavy-thick titanium alloy plates is in immediate need to unravel the strength-enhanced behaviors for high-pressure and low-temperature performance of ...deep-sea submersibles. Here, we synergistically employed transmission electron microscope (TEM) and electron back-scattered diffraction (EBSD) technologies to micro-crystallographically unravel the evolution behaviors of weld microstructure, grain orientation and grain boundaries for the welded joint of the heavy-thick Ti-6Al-4V plates with the thickness of up to 60 mm. Resulted, the strength-enhanced welded joint was evidently ascribed to the transformation of lath martensite into basketweave-martensite and the rigid-flexible mixture strategy of the enhanced conical-texture and the weakened basal-texture and cylindrical-texture. Furthermore, the remarkably lowered geometrically necessary dislocations (GNDs) density and the greatly decreased deformation-prone grains number due to the transformation of low-into-high angle grain boundaries indispensably strengthened the joint strength. Therefore, this work has made clear the strength-enhanced behaviors of Ti-6Al-4V welded joints for substantially improving high-strength welded structure of heavy-thick titanium alloy plates, and sufficiently promoting the service safety for deep-sea submersibles.
•Transformation of lath martensite into basketweave-martensite enhanced the welded joint strength.•Thermal cycling caused the rigid-flexible mixture of the enhanced conical-texture and the weakened basal-texture.•Transformation of low-into-high angle grain boundaries lowered GNDs density and decreased deformation-prone grains number.
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IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chinese Modular High-Temperature Gas-Cooled Reactor HTR-PM is a promising energy source for comprehensive utilization. The original coordinated control strategy of HTR-PM is a “turbine following ...reactor” strategy, which is not able to perform load following operation. To have more flexible operation capability, this paper presents a load following control strategy for HTR-PM. A balance of plant (BOP) model of HTR-PM is first developed for dynamic simulation, including the once through steam generator (OTSG), turbine generator, condenser, feed water heater, deaerator, feed water pump, valves and piping system. Then the original coordinated control strategy and the proposed load following control strategy are clarified, and model validation, simulation results are documented respectively. For turbine trip without reactor shutdown from 100%PFP transient, the steam dump strategy is improved to meet the safety requirements. Results demonstrate that the proposed load following strategy can meet the requirements of safety operation, which is desirable for participation in peak load regulating of power system.
•A load following control strategy for Chinese Modular High-Temperature Gas-Cooled Reactor HTR-PM is proposed.•HTR-PM balance of plant system is modeled and validated.•The proposed control strategy is verified by simulations of typical operation transients.•Steam dump system is improved to enhance system performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Highest mediastinal lymph node (HMLN) involvement is a category of uncertain resection, yet the prognostic significance of HMLN involvement remains controversial.
Methods
A total of 486 ...patients with pathological stage III-N2 disease who underwent radical resection were enrolled from January 2015 to December 2018. Patients were allocated into two groups—HMLN involvement (219 cases) and HMLN-negative (249 cases) groups. Kaplan–Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of HMLN involvement on 5-year recurrence-free survival (RFS) and overall survival (OS).
Results
The proportion of patients with multiple N2 diseases (72.1% vs. 23.7%;
p
< 0.001) and stage IIIA (87.2% vs. 77.5%;
p
< 0.009) were greater in the HMLN-involvement group than in the HMLN-negative group, and the survival rates of the HMLN-involvement group were significantly lower than those of the HMLN-negative group (RFS: 27.2% vs. 49.8%,
p
< 0.001; OS: 42.1% vs. 59.2%,
p
= 0.001). HMLN status was an independent factor for OS only (RFS: adjusted hazard ratio aHR 1.26, 95% confidence interval CI 0.94–1.68; OS: aHR 1.45, 95% CI 1.07–1.99) in the entire stage III cohort. After stratification of patients according to stage, the involvement of HMLN decreased both RFS and OS in the stage IIIA group (RFS: aHR 1.46, 95% CI 1.06–2.02; OS: aHR 1.70, 95% CI 1.19–2.42); however, no such difference was observed within the stage IIIB group.
Conclusions
HMLN involvement is a prognostic factor of deteriorating survival in highly advanced N2 disease only in patients with stage IIIA.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
With complex process integration approach and severe fabrication limitations caused by introduction of new materials and diminishing process margins, there are mounting concerns with the increased ...failure rate at the early life cycle (e.g.<1year operation) of product application known as infant mortality failures. A paradigm change in reliability qualification methodology aim at understanding the impact of variation on reliability is required to ensure reliability robustness. Using Electromigration (EM) as an example, this paper described a methodology where the impact of process variation on reliability is studied. A model that predicts the impact of process variation on EM sigma is also proposed which enables variation and its impact on reliability to be quantified. Using this methodology, the critical process parameters impacting reliability could be identified and controlled to ensure reliability robustness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Adjuvant chemotherapy after radical resection of stage IIIA non-small-cell lung cancer (NSCLC) has quite poor outcomes. We aimed to investigate whether adjuvant erlotinib therapy improves 2-year ...disease-free survival compared with chemotherapy in epidermal growth factor receptor (EGFR) mutation-positive stage IIIA NSCLC.
In this randomised, open-label, phase 2 trial, eligible patients aged 18-75 years who had undergone complete (R0) resection of histologically or pathologically confirmed stage IIIA EGFR mutation-positive NSCLC and had not received any previous anticancer therapies were enrolled. Patients were randomly assigned (1:1) to receive either adjuvant erlotinib (150 mg once daily administered orally) or vinorelbine and cisplatin chemotherapy (four cycles of vinorelbine 25 mg/m
intravenously on days 1 and 8 of each 21-day cycle plus cisplatin 75 mg/m
intravenously on day 1 of each 21-day cycle). Randomisation was done by Simon's minimisation with a random element and was stratified by EGFR activating mutation type (exon 19 vs 21), histology (adenocarcinoma vs non-adenocarcinoma), and smoking status (smoker vs non-smoker). The primary endpoint in the unblinded intention-to-treat analysis was 2-year disease-free survival. This ongoing study is registered with ClinicalTrials.gov, number NCT01683175.
Between Sept 8, 2012, and May 21, 2015, 102 patients from 16 centres across China were enrolled and randomly assigned to receive erlotinib (n=51) or chemotherapy (n=51). Median follow-up was 33·0 months (IQR 17·8-43·1). 2-year disease-free survival was 81·4% (95% CI 69·6-93·1) in the erlotinib group and 44·6% (26·9-62·4) in the chemotherapy group (relative risk 1·823 95% CI 1·194-2·784; p=0·0054). The difference in 2-year disease-free survival between the groups was 36·7% (95% CI 15·5-58·0; p=0·0007). Adverse events of any grade occurred in 29 (58%) of 50 patients in the erlotinib group and 28 (65%) of 43 patients in the chemotherapy group. Grade 3 or worse adverse events occurred in six (12%) of 50 patients in the erlotinib group versus 11 (26%) of 43 in the chemotherapy group; the most common of these in the erlotinib group was rash (in two 4% of 50 patients) and in the chemotherapy group were decreased neutrophil count (in seven 16% of 43 patients) and myelosuppression (in four 9%). No treatment-related deaths were reported.
Adjuvant erlotinib improved 2-year disease-free survival in patients with EGFR mutation-positive stage IIIA NSCLC compared with chemotherapy, with a better tolerability profile. This study suggests that tyrosine kinase inhibitors could have a potentially important role as adjuvant therapy in EGFR mutation-positive stage IIIA NSCLC. However, this trial was a phase 2 study. Mature overall survival data are also needed. Ongoing studies will hopefully confirm the role of adjuvant EGFR tyrosine kinase inhibitor therapy in patients with NSCLC.
National Key Research and Development Program of China and Shanghai Roche Pharmaceuticals Ltd.
Coronary artery damage from Kawasaki disease (KD) is closely linked to the dysfunction of the endothelial progenitor cells (EPCs). The aim of the present study was to evaluate the modulatory effect ...of granulocyte colony-stimulating factor (G-CSF) on EPCs and elastin breakdown of coronary arteries in a KD mouse model.
A Lactobacillus casei cell wall extract (LCWE)-induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G-CSF (rhG-CSF). Nω-nitro-L-arginine methyl ester (L-NAME) was administrated for the negative intervention. Evaluations included coronary artery lesions, EPC number and functions, and the plasma concentration of nitric oxide (NO).
Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE. The number of circulating EPCs, plasma concentration of NO, and functions of bone marrow EPCs, including proliferation, adhesion, and migration abilities, were all lower in the KD model group compared with those in the control group. After administration of rhG-CSF, the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group. There were also increases in the functional indexes of EPCs. Furthermore, rhG-CSF administration improved the elastin breakdown effectively. However, these protective effects of rhG-CSF on coronary arteries were attenuated by L-NAME.
The present study indicated that the administration of G-CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system, and then accelerates the repair of coronary artery lesions in the KD.
Herein, a dual signal amplification strategy was employed in fabricating ultrasensitive electrochemical immunosensor for alpha fetoprotein (AFP) detection, which was realized by utilizing of ZnO ...nanorods/Au nanopaticles hybridized reduced graphene nanosheet (Au/ZnO/RGO) and horseradish-peroxidase (HRP) bioconjugated detection antibody (Ab2) functionalized Au@ZnO (Ab2/HRP-Au@ZnO). During the fabrication of the immunosensor, a new kind of multiple-head surfactants CxN3 with different alkyl chain length played important roles such as acting as the surfactants of Au/ZnO/RGO and the reductant agents of Au@ZnO composite. Due to the good adsorption property and large surface area of Au/ZnO/RGO, plenty of the capture antibodies (Ab1) were immobilized on the electrode surface, and trace AFP was sensitively monitored. Furthermore, Ab2/HRP-Au@ZnO exhibited high affinity interaction with AFP through “sandwich” immunoreactions, along with the peroxidase-like catalytic activity of Au@ZnO, leading to a further enhancement in the sensitivity of the proposed immunosensor. The successful synthesis of the nanomaterials was characterized through a serious of techniques including Raman, XRD, FT-IR, SEM and UV–vis. Under the optimal conditions, two linear ranges of 0.02–10,000 and 10,000–100,000pgmL-1 AFP with a lower detection limit of 0.01pg mL-1 (S/N=3) was obtained. Especially, the proposed AFP immunosensor can be applied to detect human serum samples with satisfactory results, indicating a potential application in clinical monitoring of tumor biomarkers.
•A dual-amplified electrochemical immunosensor based on Au/ZnO was fabricated.•C12N3 acted as the surfactants of Au/ZnO/RGO.•C18N3 acted as the reductant agents of Au@ZnO composite.•XRD, Raman, FT-IR, UV-Vis, SEM have been used for characterization.•Fabricated immunosensor showed excellent sensitivity and specificity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Lung cancer (LC) is one of the major malignant diseases threatening human health. The study aimed to identify the effect of citrulline on the malignant phenotype of LC cells and to further disclose ...the potential molecular mechanism of citrulline in regulating the development of LC, providing a novel molecular biological basis for the clinical treatment of LC. The effects of citrulline on the viability, proliferation, migration, and invasion of LC cells (A549, H1299) were validated by CCK-8, colony formation, EdU, and transwell assays. The cell glycolysis was assessed via determining the glucose uptake, lactate production, ATP levels, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). RNA-seq and molecular docking were performed to screen for citrulline-binding target proteins. Western blotting experiments were conducted to examine the expression of related signaling pathway molecules. In addition, the impacts of citrulline on LC growth in vivo were investigated by constructing mouse models. Citrulline augmented the viability of LC cells in a concentration and time-dependent manner. The proliferation, migration, invasion, glycolysis, and EMT processes of LC cells were substantially enhanced after citrulline treatment. Bioinformatics analysis indicated that citrulline could bind to RAB3C protein. Western blotting results indicated that citrulline activated the IL-6/STAT3 pathway by binding to RAB3C. In addition, animal experiments disclosed that citrulline promoted tumor growth in mice. Citrulline accelerated the glycolysis and activated the IL6/STAT3 pathway through the RAB3C protein, consequently facilitating the development of LC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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