The weak high-frequency character signal (HCS) cannot be detected substantially by the traditional vibrational resonance (VR) theory. In this paper, by introducing the scale transformation, the HCS ...in the original system can be transformed to the low-frequency character signal in the rescaled system. As we know, the two systems are equivalent and the VR can occur at low frequency in the rescaled system. Then, the VR can also occur at high frequency in the original system. We take the underdamped bistable system and the overdamped bistable system of the Duffing oscillator as examples. The method proposed in this paper is verified by both theoretical analysis and numerical simulations. The results obtained by the two ways are in good agreement. The results in this paper provide a tool to detect the weak character signal with arbitrary frequency in the engineering problems.
Summary
Dysregulation of plasma lipids is associated with age‐related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low‐density lipoprotein (LDL), ...induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg−1 day−1) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence‐associated β‐galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5‐treated but not L1‐treated mice. Similar to that, in Syrian hamsters with elevated serum L5 levels induced by a high‐fat diet, nuclear γH2AX deposition and senescence‐associated β‐galactosidase staining were increased in the aortic endothelium. This phenomenon was blocked in the presence of N‐acetyl‐cysteine (free‐radical scavenger) or caffeine (ATM blocker), as well as in lectin‐like oxidized LDL receptor‐1 (LOX‐1) knockout mice. In cultured human aortic endothelial cells, L5 augmented mitochondrial oxygen consumption and mitochondrial free‐radical production, which led to ATM activation, nuclear γH2AX deposition, Chk2 phosphorylation, and TP53 stabilization. L5 also decreased human telomerase reverse transcriptase (hTERT) protein levels and activity. Pharmacologic or genetic manipulation of the reactive oxygen species (ROS)/ATM/Chk2/TP53 pathway efficiently blocked L5‐induced endothelial senescence. In conclusion, L5 may promote mitochondrial free‐radical production and activate the DNA damage response to induce premature vascular endothelial senescence that leads to atherosclerosis. Novel therapeutic strategies that target L5‐induced endothelial senescence may be used to prevent and treat atherosclerotic vascular disease.
•Radiomics is quantitative image analysis that can predict immunotherapy response.•We found seven relevant studies, most of them focusing on non-small cell lung cancer.•Most reviewed studies had ...methodological shortcomings that limit their relevance.•Main issues were deficiencies in feature selection and lack of external validation.•Prospective studies that test the clinical utility of these models are needed.
Systemic therapy agents targeting immune checkpoint inhibitors have been approved for use since 2011. This type of therapy aims to trigger a patient’s immune response to attack tumor cells, rather than acting against the tumor directly. Radiomics is an automated method of medical image analysis that is now being actively investigated for predictive markers of treatment response in immunotherapy.
To conduct an early systematic review determining the current status of radiomic features as potential predictive markers of immunotherapy response. Provide a detailed critical appraisal of methodological quality of models, as this informs the degree of confidence about current reports of model performance. In addition, to offer some recommendations for future studies that could establish robust evidence for radiomic features as immunotherapy response markers.
A PubMed citation search was conducted for publications up to and including April 2020, followed by full-text screening. A total of seven articles meeting the eligibility criteria were examined in detail for study characteristics, model information and methodological quality. The review was conducted in the Cochrane style but has not been prospectively registered. Results are reported following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines.
A total of seven studies were examined in detail, comprising non-small cell lung cancer, metastatic melanoma and a diverse assortment of solid tumors. Methodological robustness of reviewed studies varied greatly. Principal shortcomings were lack of prospective registration, and deficiencies in feature selection and dimensionality reduction, model calibration, clinical utility and external validation. A few studies with overall moderate to good methodological quality were identified. These results suggest that current state-of-the-art performance of radiomics in regards to discrimination (area under the curve or concordance index) is in the vicinity of 0.7, but the very small number of studies to date prevents any conclusive remarks to be made. We recommended future improvements in regards to prospective study registration, clinical utility, methodological procedure and data sharing.
Radiomics has a potentially significant role for predicting immunotherapy response. Additional multi-institutional studies with robust methodological underpinning and repeated external validations are required to establish the (added) value of radiomics within the pantheon of clinical tools for decision-making in immunotherapy.
The Asteroid Impact and Deflection Assessment (AIDA) mission will be the first space experiment to demonstrate asteroid impact hazard mitigation by using a kinetic impactor to deflect an asteroid. ...AIDA is an international cooperation entering Phase A study at NASA and ESA, consisting of two mission elements: the NASA Double Asteroid Redirection Test (DART) mission and the ESA Asteroid Impact Mission (AIM) rendezvous mission. The primary goals of AIDA are (i) to test our ability to perform a spacecraft impact on a potentially hazardous near-Earth asteroid and (ii) to measure and characterize the deflection caused by the impact. The AIDA target will be the binary asteroid (65803) Didymos, with the deflection experiment to occur in October, 2022. The DART impact on the secondary member of the binary at ~6km/s will alter the binary orbit period, which can be measured by Earth-based observatories. The AIM spacecraft will characterize the asteroid target and monitor results of the impact in situ at Didymos. AIDA will return fundamental new information on the mechanical response and impact cratering process at real asteroid scales, and consequently on the collisional evolution of asteroids with implications for planetary defense, human spaceflight, and near-Earth object science and resource utilization. AIDA will return unique information on an asteroid׳s strength, surface physical properties and internal structure. Supporting Earth-based optical and radar observations, numerical simulation studies and laboratory experiments will be an integral part of AIDA.
•AIDA will be the first space mission to demonstrate asteroid impact hazard mitigation.•AIDA will use a kinetic impactor to deflect an asteroid and measure the deflection.•AIDA is an international cooperation between ESA and NASA.•AIDA will study asteroid strength, surface physical properties and internal structure.
The medial sural artery perforator flap is a versatile option in reconstructive microsurgery. However, most reports of this flap have been limited by sample size. This study reviews the experience of ...a single large-volume center using the medial sural artery perforator flap and its variants for a variety of reconstructive purposes.
A retrospective review of all patients who received the medial sural artery perforator flap reconstruction between March of 2006 and July of 2014 was performed.
Two-hundred medial sural artery perforator flaps were used at three anatomical regions: head and neck (n = 129), upper extremity (n = 47), and lower extremity (n = 24). Flaps were transferred as free (n = 189) and pedicled (n = 11). Overall flap survival was 96 percent. Flap variants used included chimeric flap (n = 11) and dual skin paddle (n = 2). Plantaris tendon and saphenous/sural nerve graft were harvested in conjunction in 20 and seven patients, respectively. In 5 percent of the cases harvested in the conventional manner, a reliable perforator could not be found.
The medial sural artery perforator flap is a reliable, alternative workhorse flap for nearly any small- to medium-size defect. It can be harvested as free or pedicled and the option to include multiple tissue components further expands its versatility.
Therapeutic, IV.
Background: Gene silencing by abnormal methylation of promoter regions of regulatory genes is commonly associated with cancer. Silenced tumor suppressor genes are obvious targets for reactivation by ...methylation inhibitors such as 5-azacytidine (5-Aza-CR) and 5-aza-2′-deoxycytidine (5-Aza-CdR). However, both compounds are chemically unstable and toxic and neither can be given orally. We characterized a new demethylating agent, zebularine 1-(beta-d-ribofuranosyl)-1,2-dihydropyrimidin-2-one, which is a chemically stable cytidine analog. Methods: We tested the ability of zebularine to reactivate a silenced Neurospora crassa gene using a hygromycin gene reactivation assay. We then analyzed the ability of zebularine to inhibit DNA methylation in C3H 10T1/2 Cl8 (10T1/2) mouse embryo cells as assayed by induction of a myogenic phenotype and in T24 human bladder carcinoma cells, using the methylation-sensitive single nucleotide primer extension (Ms-SNuPE) assay. We also evaluated the effects of zebularine (administered orally or intraperitoneally) on growth of EJ6 human bladder carcinoma cells grown in BALB/c nu/nu mice (five mice per group) and the in vivo reactivation of a methylated p16 gene in these cells. All statistical tests were two-sided. Results: In N. crassa, zebularine inhibited DNA methylation and reactivated a gene previously silenced by methylation. Zebularine induced the myogenic phenotype in 10T1/2 cells, which is a phenomenon unique to DNA methylation inhibitors. Zebularine reactivated a silenced p16 gene and demethylated its promoter region in T24 bladder carcinoma cells in vitro and in tumors grown in mice. Zebularine was only slightly cytotoxic to T24 cells in vitro (1 mM zebularine for 48 hours decreased plating efficiency by 17% 95% confidence interval (CI) = 12.8% to 21.2%) and to tumor-bearing mice (average maximal weight change in mice treated with 1000 mg/kg zebularine = 11% 95% CI = 4% to 19%). Compared with those in control mice, tumor volumes were statistically significantly reduced in mice treated with high-dose zebularine administered by intraperitoneal injection (P<.001) or by oral gavage (P<.001). Conclusions: Zebularine is a stable DNA demethylating agent and the first drug in its class able to reactivate an epigenetically silenced gene by oral administration.
Accurate knowledge of the charge and Zemach radii of the proton is essential, not only for understanding its structure but also as input for tests of bound-state quantum electrodynamics and its ...predictions for the energy levels of hydrogen. These radii may be extracted from the laser spectroscopy of muonic hydrogen (μp, that is, a proton orbited by a muon). We measured the $2{\mathrm{S}}_{1/2}^{\mathrm{F}=0}-2{\mathrm{P}}_{3/2}^{\mathrm{F}=1}$ transition frequency in μp to be 54611.16(1.05) gigahertz (numbers in parentheses indicate one standard deviation of uncertainty) and reevaluated the $2{\mathrm{S}}_{1/2}^{\mathrm{F}=1}-2{\mathrm{P}}_{3/2}^{\mathrm{F}=1}$ transition frequency, yielding 49881.35(65) gigahertz. From the measurements, we determined the Zemach radius, r Z = 1.082(37) femtometers, and the magnetic radius, r M = 0.87(6) femtometer, of the proton. We also extracted the charge radius, r E = 0.84087(39) femtometer, with an order of magnitude more precision than the 2010-CODATA value and at 7σ variance with respect to it, thus reinforcing the proton radius puzzle.
We studied the long-term (20-year) cumulative effects of exclusion of livestock grazing on above- and belowground community properties compared with that before exclusion of livestock grazing in a ...typical steppe of the Loess Plateau, NW China. Our results show that twenty-year exclusion of livestock grazing significantly increased above- and belowground biomass, species richness, cover and height for five different communities. Most of belowground biomass was in the 0-20 cm horizon and grazing exclusion increased biomass especially at the depth of 0-10 cm. Our study suggests that long-term exclusion of livestock grazing can greatly improve community properties of typical steppe in the Loess Plateau.
Metal clusters adsorbed on graphene can give rise to interesting physical properties. Using functional theory we investigate Au sub(n) and Fe sub(n) (n = 1-5) clusters adsorbed on perfect and ...defected graphene with a single vacancy. With the exception of Fe clusters on defected graphene, clusters are bonded to graphene through an anchor atom. Geometries of clusters on graphene are similar to their free-standing structures except for the Fe sub(5) cluster on perfect graphene. Compared to Au, Fe clusters are more strongly bonded to graphene. We find that it is important to include long-range van der Waals interactions for Au clusters adsorbed on perfect graphene. An Au sub(5) cluster becomes parallel to the graphene only when the van der Waals interactions are taken into account. Charge transfer between clusters and graphene shows strong size dependency, and the amount is larger in the presence of the single vacancy on the graphene than a pristine sheet. Perfect graphene is found to be doped for Au clusters with an odd number of atoms and undoped with an even number of atoms. Magnetic moments are also calculated as a function of cluster size and an odd-even oscillation is observed in Au sub(n) -perfect as well as defected graphene system. While Fe sub(n) clusters remain to be magnetic for all n, the spin of a single Fe atom on a defect site is very small due to a covalent bonding to C atoms.
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