•A coupled translational-rotational quasi-zero stiffness system is proposed.•Independent excitations in different degree-of-freedom are considered.•Dynamic characteristics with jump phenomenon are ...investigated.•The results demonstrate good isolation performance in both directions.
Quasi-zero stiffness (QZS) vibration isolators can provide better isolation performance in the low frequency range than linear vibration isolators. Currently, most of the designed QZS isolators perform vibration isolation only in one direction and few papers are focused on simultaneously isolating the vibrations in two directions. In this paper, an integrated translational-rotational QZS vibration isolator is designed by using the cam-roller mechanism. The proposed QZS system is able to provide the high-static-low-dynamic stiffness in two directions simultaneously. The excitations in both translational and rotational directions are considered independent but with mutual interaction to their induced vibration response. The workable ranges of the QZS system and its limitations are first numerically identified. Then the static characteristics and typical nonlinear dynamic response with jump phenomena are theoretically investigated. The jump-down frequencies for small amplitude oscillations are determined from their amplitude-frequency relationships. Furthermore, the force transmissibility and moment transmissibility of the proposed QZS system are compared with those of the corresponding linear system without the cam-roller mechanism, which clearly demonstrate better isolation performance in both translational and rotational directions.
Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative ...determination method is not accurate enough.
We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis.
The DLRN showed good discrimination of the number of LNM on all cohorts overall C-indexes (95% confidence interval): 0.821 (0.785–0.858) in the primary cohort, 0.797 (0.771–0.823) in the external validation cohorts, and 0.822 (0.756–0.887) in the international validation cohort. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271).
A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.
•Evaluation of the lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC).•Deep leaning radiomic nomogram (DLRN) based on CT images can preoperatively determine the number of LNM in LAGC.•DLRN is significantly superior to the routinely used clinical N stages, tumor size, and clinical model.•DLRN is significantly associated with the overall survival of LAGC.
Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection ...or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients.
A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients’ PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability.
RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 95% confidence interval (CI) 0.923–0.993, 0.941 (95% CI 0.904–0.977), 0.928 (95% CI 0.886–0.971), and 0.920 (95% CI 0.862–0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability.
CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.
Résumé
S'appuyant sur la thèse selon laquelle il existerait un volume fixe d'emplois dans l'économie, beaucoup de pays de l'OCDE ont cherché à lutter contre le chômage, en augmentation depuis les ...années 1970, par des dispositifs favorisant les cessations d'activité anticipées. Or les études à l'échelle de l'OCDE font apparaître en réalité une corrélation positive entre l'emploi des jeunes et celui des travailleurs âgés. Cependant, comme la plupart des auteurs estiment des effets moyens, on dispose de relativement peu d'informations sur l'hétérogénéité de ce lien. L'auteure tente de combler cette lacune en étudiant cette hétérogénéité dans vingt pays de l'OCDE.
Developing a stable and safe electrolyte that works at voltages as high as 5 V is a formidable challenge in present Li‐ion‐battery research because such high voltages are beyond the electrochemical ...stability of the conventional carbonate‐based solvents available. In the past few years, extensive efforts have been carried out by the research community toward the exploration of high‐voltage electrolytes. In this review, recent progress in the study of several promising high‐voltage electrolyte systems, as well as their recipes, electrochemical performance, electrode compatibility, and characterization methods, are summarized and reviewed. These new electrolyte systems include high‐voltage film‐forming additives and new solvents, such as sulfones, ionic liquids, nitriles, and fluorinated carbonates. It appears to be very difficult to find a good high‐voltage (∼5 V) electrolyte with a single‐component solvent at the present stage. Using mixed fluorinated–carbonate solvents and additives are two realistic solutions for practical applications in the near term, while sulfones, nitriles, ionic liquids and solid‐state electrolyte/polymer electrolytes are promising candidates for the next generation of high‐voltage electrolyte systems.
Safe and stable: Developing a stable and safe electrolyte that works at high voltages is a formidable challenge in present Li‐ion‐battery research. Recent progress in the development of several promising high‐voltage electrolyte systems is summarized and reviewed.
The directional distance function (DDF) with multiple bad outputs allows estimation of conditional marginal abatement cost (MAC) that would be more informative than the unconditional MAC estimated ...with a single pollutant. Applying a multi-pollutant parametric output DDF approach, we estimate the MACs of CO2, SO2, and NOx emissions for 105 Chinese cities in 2006–2014. It is found that the period medians of the MACs for the three emissions all increase over time, while the medians of the MACs for different cities tend to vary significantly. A goodness-of-fit criterion is developed and used to evaluate the fit of alternative models, which demonstrates the superiority of the multi-pollutant model. We have also shown that there exists a positive relationship between MAC and economic growth. Finally, several policy implications are suggested for reducing the overall emission abatement costs of China.
•The period medians of the MACs for CO2, SO2, and NOx all increase over time.•The medians of the MACs for different cities tend to vary significantly.•A goodness-of-fit tests demonstrate the superiority of the multi-pollutant model.•A positive relationship between MAC and economic growth is observed.
The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆
-tetrahydrocannabinol (∆
-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of ...the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆
-THC is known to bring about the 'high' associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆
-THC, ∆
-tetrahydrocannabinolic acid (∆
-THCa), ∆
-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.
Aims
This study aimed to assess all-cause and cause-specific standardized mortality ratios (SMRs) in patients with systemic lupus erythematosus (SLE).
Methods
We surveyed studies examining all-cause ...and/or cause-specific SMR in patients with SLE compared to the general population using PUBMED, EMBASE and Cochrane databases and manual searches. We performed a meta-analysis of all-cause, sex-specific, ethnicity-specific, and cause-specific SMRs in SLE patients.
Results
Fifteen reports including 26,101 patients with SLE with 4640 deaths met the inclusion criteria. Compared to the general population, all-cause SMR was significantly increased 2.6-fold in patients with SLE (SMR 2.663, 95% CI 2.090–3.393, p < 1.0 × 10−8). Stratification by ethnicity showed that all-cause SMR was 2.721 (95% CI 1.867–3.966, p = 1.9 × 10−6) in Caucasians and 2.587 (95% CI 1.475–4.535, p = 0.001) in Asians. Sex-specific meta-analysis revealed that all-cause SMR was 3.141 (95% CI 2.351–4.198, p < 1.0 × 10−8) for women and 3.516 (95% CI 2.928–4.221, p < 1.0 × 10−8) for men. The risk of mortality was significantly increased for mortality due to renal disease (SMR 4.689, 95% CI 2.357–9.330, p = 1.10 × 10−5), cardiovascular disease (CVD) (SMR 2.253, 95% CI 1.304–3.892, p = 0.004), and infection (SMR 4.980, 95% CI 3.876–6.398, p < 1.0 × 10−8), although there was no significant increase in SMR for mortality due to cancer (SMR 1.163, 95% CI 0.572–2.363, p = 0.676).
Conclusions
Patients with SLE had higher rates of death from all causes, regardless of sex, ethnicity, renal disease, CVD or infection. However, the risk of death due to malignancy was not increased.
The embryonic pyruvate kinase M2 (PKM2) isoform is highly expressed in human cancer. In contrast to the established role of PKM2 in aerobic glycolysis or the Warburg effect, its non-metabolic ...functions remain elusive. Here we demonstrate, in human cancer cells, that epidermal growth factor receptor (EGFR) activation induces translocation of PKM2, but not PKM1, into the nucleus, where K433 of PKM2 binds to c-Src-phosphorylated Y333 of β-catenin. This interaction is required for both proteins to be recruited to the CCND1 promoter, leading to HDAC3 removal from the promoter, histone H3 acetylation and cyclin D1 expression. PKM2-dependent β-catenin transactivation is instrumental in EGFR-promoted tumour cell proliferation and brain tumour development. In addition, positive correlations have been identified between c-Src activity, β-catenin Y333 phosphorylation and PKM2 nuclear accumulation in human glioblastoma specimens. Furthermore, levels of β-catenin phosphorylation and nuclear PKM2 have been correlated with grades of glioma malignancy and prognosis. These findings reveal that EGF induces β-catenin transactivation via a mechanism distinct from that induced by Wnt/Wingless and highlight the essential non-metabolic functions of PKM2 in EGFR-promoted β-catenin transactivation, cell proliferation and tumorigenesis.
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