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The effect of uncertainty in Reynolds-averaged Navier–Stokes (RANS) simulations is determined through the application of uncertainty quantification (UQ). In this study, the sensitivity of aerodynamic coefficients to uncertainty in the freestream turbulence intensity (FSTI) and surface roughness is computed for an airfoil (SC1095) and a rotorcraft fuselage model (Rotor-Body-Interaction-Mod7). A laminar–turbulent transition model has been extended to consider roughness-induced transition by incorporating an existing roughness-induced transition model. The current UQ analysis is based on the Monte Carlo method with the Gaussian distributions of uncertain input parameters. A surrogate model allows for incorporating the results of intensive RANS simulations into the Monte Carlo method. The surrogate model is generated using a cubic interpolation for a single-uncertain parameter or a radial basis function for multiple-uncertain parameters. The stochastic standard deviation is measured using combined FSTI and roughness uncertainties. The standard deviation of each aerodynamic coefficient depends on flow conditions (angle of attack, mean FSTI, and mean roughness) and the transition type (natural or separation-induced). The main source of output uncertainty is identified between the unknown FSTI and roughness under various flow conditions.

A new design was applied for the facile synthesis of pure organic photoluminescent molecules with dual excited-state intramolecular proton transfer (ESIPT) sites. In this novel class of emitters, full-color panel emission from blue, green, and yellow to red, including white light, can be achieved in different solvents as modulated by the enol-keto(1st)-keto(2nd) tautomer emissions. A comprehensive transient photophysical study verifies that keto(1st) and keto(2nd) have a precursor (0.8 ps)-successor (∼20 ps)-relayed absorbance relationship, and then a fast equilibrium between the two is established, resulting in dual emissions in the nanosecond scale (∼1900 ps). Through the research on copper ions' selective PL response, the dual-ESIPT mechanism was further verified; in addition, the study of solid-state PL changes upon the stimulus of organic vapor manifests the potential application sensitivity of the molecules as dual-ESIPT sensors. Theoretical results including reaction potential energy surface analyses manifest the fact that dual-proton transfer goes along a sequential route with a smaller energy barrier, firmly supporting the experimental results. An intrinsic system that undergoes intramolecular double proton relayed transfer is thus established for the achievement of much broadened optical responses and full-color display, providing reference for the design and application of advanced dual-ESIPT optical materials.

Mechanical cracks produced by mechanical pressure cause significant initial capacity loss but little capacity decay in subsequent cycles in ASSB. In contrast, in LELIBs mechanical cracks do not induce initial capacity loss but produce long lasting capacity decay during cycling.

Experimental near-wake flow field measurements from two Penn State University water tunnel tests of a defeatured helicopter hub are compared with two unsteady computational fluid dynamics (CFD) analyses: CREATETM-AV Helios and the University of Maryland Mercury. Both CFD frameworks employ an unstructured/Cartesian multimesh paradigm and turbulent Spalart–Allmaras detached eddy simulation (SA-DES) modeling. Experimental velocimetry measurements of mean wake velocities, harmonic content, and Reynolds stresses provide valuable validation data for CFD. Overall, the two CFD solvers were in good agreement with each other and qualitatively captured the mean and harmonic content of the wake structures with accuracy. Flow feature dissimilarities between the advancing and retreating sides were differentiated and indicated dominant regions of harmonic flow disturbances biased towards the retreating side, in good agreement with experimental observations. Quantitatively, some variation in velocity deficits and downwash were noted, either in profile character, magnitude, and/or location. Encouragingly, there was little tendency of excessive dissipation in the CFD near wake, and the harmonic content actually tended towards a common overprediction. Reynolds number effects were minimal, and grid density effects were studied but inconclusive. These efforts were part of the Third PSU Rotor Hub Flow Workshop in 2020.

The wingtip-mounted propeller configuration is widely used in many aircraft, particularly owing to the emergence of urban air mobility. This paper focuses on analyzing the aeroacoustic properties of a wingtip-mounted tractor propeller by understanding the aerodynamic interaction between the two geometric components. Computational fluid dynamics based on Reynolds-averaged Navier–Stokes equations were used to calculate the flow field and aerodynamic loads on a wingtip-mounted propeller model, and the results were compared with experimental data for validation. The resulting surface pressure was fed as input data for the acoustic analysis performed using a Ffowcs Williams–Hawkings equationbased acoustic solver at multiple angles of attack. The presence of the wing significantly increased the propeller noise along the rotational axis. With increasing angle of attack, the propeller noise increased further. By contrast, the wing noise decreased with the angle of attack due to propeller wake dissipation, leading to only a small increase in the maximum total noise.

In this paper, we propose an approach to tune optimal parameters of a robust PID controller by means of computed torque control (CTC) strategy for trajectory tracking of a Delta parallel robot, using a hybrid optimization algorithm of Particle Swarm Optimization (PSO) and differential evolution (DE). It differs from previous works that they propose robust PID controller parameters tuning based on conventional gradient-based optimization algorithms and apply them to process control. First, we reduce the tuning problem of a robust PID controller with CTC strategy satisfying requirements including robustness and disturbance attenuation to an optimization problem with nonlinear constraints by considering the nonlinear dynamic model of a Delta parallel robot. Second, we set up the design characteristics for the trajectory tracking of a Delta parallel robot. Then, we propose a robust PID controller in a way of obtaining the global optimization solution of the nonlinear optimization problem by running a PSO-DE hybrid optimization algorithm of finding the global optimal solution by maintaining the diversity of swarm during evolution based on the evolution of cognitive experience. Simulation and experimental results demonstrate that the proposed controller outperforms previous works with respect to robust performance and active disturbance attenuation when it is applied to tracking control of a Delta parallel robot.

Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotics because of its health benefits and safety. Fucose is among the most abundant hexoses in the human intestine, and LGG consumes fucose to produce energy or proliferate. However, no study has elucidated the metabolism by which LGG metabolizes fucose to produce energy, biomass, and extracellular metabolites. We used metabolomics and flux balance analysis to elucidate these mechanisms and highlight how they might affect the host. We found three different metabolic flux modes by which LGG anaerobically metabolizes fucose to produce energy and biomass. These metabolic flux modes differ from homolactic or heterolactic fermentation and account for the production of lactic acid, 1,2-propanediol, acetic acid, formic acid, and carbon dioxide as a result of fucose metabolism in LGG. We also used gas chromatography/time-of-flight mass spectrometry to identify a variety of short-chain fatty acids and organic acids secreted during fucose metabolism by LGG. Our study is the first to elucidate the unique fucose metabolism of LGG in anaerobic condition.

The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.

Although physical exercise may improve memory in older adults, whether the Chinese traditional fitness exercise Wuqinxi improves working memory and delays cognitive deterioration in older adults with mild cognitive impairment (MCI) has not been assessed in randomized controlled experiments.Fifty older adults with MCI based on their Montreal Cognitive Assessment scores were randomized to either a Wuqinxi exercise group or a non-exercise control group. The exercise group engaged in Wuqinxi once a week for 60 min each session for 40 weeks. Participants in the control group received no intervention and maintained their regular living habits. The n-back paradigm was used to measure changes in working memory before and after Wuqinxi exercise.In the 0-back task, the response speed of older adults with MCI who participated in Wuqinxi was faster than that of older adults with MCI in the non-exercise control group (P = 0.031); there was no significant difference in accuracy between the two groups (P 0.05). In the 1-back and 2-back tasks, there was no significant difference in response times or in accuracy between the two groups (P 0.05).In this randomized controlled study, participation in long-term Wuqinxi delayed the deterioration of working memory in older adults with MCI, suggesting that this exercise may be an effective intervention to delay or prevent the progression of MCI to Alzheimer's disease.

Since the approval of sorafenib for systemic treatment of advanced hepatocellular carcinoma (HCC), many tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown efficacy and tolerability as first-line treatments. On the other hand, these first-line therapies are associated with low objective response and drug resistance. Many drugs have been successfully tested for second-line treatment of advanced HCC. While the rapid proliferation of second-line treatments for advanced HCC brings hope to patients, it also complicates clinical decision-making.This review aims to facilitate decisions by summarizing the latest guidelines for second-line treatment of HCC in various countries or regions. We then review existing second-line treatment options and discuss challenges that should be addressed in the future. A literature search was conducted in April 2022 of PubMed/Medline, Cochrane library, and abstracts of international cancer meetings.There is no standard second-line treatment, especially for the case of sequential treatment after atezolizumab plus bevacizumab (atezo+bev) and further studies focused on sequential treatment are warranted in this setting. The design of clinical trials, different etiologies, and complications or quality of life (QoL) are interesting issues in the second-line setting.

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

Selenium (Se), whose electronic conductivity is nearly 25 orders higher than that of sulfur (S) and whose theoretical volumetric capacity is 3254 mAh cm

Short-chain fatty acids (SCFA) can regulate appetite by stimulating the secretion of satiety hormones. However, the impact of short-chain fatty acid propionate on the release of gut satiety hormones and appetite regulation in pigs is not completely understood. In this study, 16 pigs were infused with saline or sodium propionate through a fistula in the caecum during a 28-day experimental period. We characterized the effects of propionate administration on peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) secretion from colonic tissue, and investigated the role of propionate infusion on the expression of appetite-related genes in the colon and hypothalamus. Further, the direct impact of propionate administration on the expression of orexigenic neuropeptide agouti-related protein (

Conditional distributivity (also called restricted distributivity) is a form of relaxed distributivity on the restricted domain. There are three options for conditional distributivity in literature. In this paper, we focus on type-III conditional distributivity equation involving nullnorms over uninorms. Firstly, we show that it can be transformed into the other two types of conditional distributivity equations involving t-norms/t-conorms over uninorms. Secondly, type-I and type-II conditional distributivity equations involving t-norms/t-conorms over uninorms that are related to our study and remain unknown are investigated. Finally, we show that this new perspective results in not only all known solutions, but new solutions as well.

Peritoneal dialysis (PD) is a widely accepted renal replacement therapy for patients with end-stage renal disease (ESRD). Morphological and functional changes occur in the peritoneal membranes (PMs) of patients undergoing long-term PD. Peritoneal fibrosis (PF) is a common PD-related complication that ultimately leads to PM injury and peritoneal ultrafiltration failure. Autophagy is a cellular process of “self-eating” wherein damaged organelles, protein aggregates, and pathogenic microbes are degraded to maintain intracellular environment homeostasis and cell survival. Growing evidence shows that autophagy is involved in fibrosis progression, including renal fibrosis and hepatic fibrosis, in various organs. Multiple risk factors, including high-glucose peritoneal dialysis solution (HGPDS), stimulate the activation of autophagy, which participates in PF progression, in human peritoneal mesothelial cells (HPMCs). Nevertheless, the underlying roles and mechanisms of autophagy in PF progression remain unclear. In this review, we discuss the key roles and potential mechanisms of autophagy in PF to offer novel perspectives on future therapy strategies for PF and their limitations.

Fluorinated organic compounds are of great importance to modern industries, while their release to the environment is inevitable, causing extreme environmental pollution and the subsequent hazardou...

Although data-driven models, especially deep learning, have achieved astonishing results on many prediction tasks for nonlinear sequences, challenges still remain in finding an appropriate way to embed prior knowledge of physical dynamics in these models. In this work, we introduce a convex relaxation approach for learning robust Koopman operators of nonlinear dynamical systems, which are intended to construct approximate space spanned by eigenfunctions of the Koopman operator. Different from the classical dynamic mode decomposition, we use the layer weights of neural networks as eigenfunctions of the Koopman operator, providing intrinsic coordinates that globally linearize the dynamics. We find that the approximation of space can be regarded as an orthogonal Procrustes problem on the Stiefel manifold, which is highly sensitive to noise. The key contribution of this paper is to demonstrate that strict orthogonal constraint can be replaced by its convex relaxation, and the performance of the model can be improved without increasing the complexity when dealing with both clean and noisy data. After that, the overall model can be optimized via backpropagation in an end-to-end manner. The comparisons of the proposed method against several state-of-the-art competitors are shown on nonlinear oscillators and the lid-driven cavity flow.

The primary aim of this paper was to identifying the geographical origin of tobacco leaves based on stable isotopic and mineral elemental fingerprint. We collected eighty-one tobacco leaf samples from Argentina, Brazil, Zimbabwe, the U.S., Zambia, and China. And nine mineral element contents and four strontium and lead isotope ratios of the tobacco leaves were determined by thermal ionization mass spectrometry (TIMS) and inductively coupled plasma mass spectrometry (ICP-MS). After variance and stepwise discriminant analysis, the discriminant functions of the tobacco leaf’s geographical origin were established. The results indicate that: (1) the contents of six mineral elements including Cu, Zn, Cr, Ni, Cd, and Pb, together with four strontium and lead isotope ratios containing 87Sr/86Sr, 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb, were significantly different among six countries. (2) Different countries presented some characteristic mineral elemental and isotopic fingerprint. The even contents of mineral elements from Zambian tobacco leaf were much lower than the other countries, among which four elements consisting of Zn, Cr, As, and Cd were not detected. The three average lead isotope ratios including 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb from Zimbabwe tobacco leaves were far higher than the other countries, and the range of which was unoverlapped. (3) The effective identification of the geographical origin of tobacco leaf was accomplished by Fisher stepwise discriminant analysis and the characteristic tracing elements consisted of Cu, Zn, Cr, Ni, Cd, Pb, 87Sr/86Sr, 207Pb/204Pb, and 206Pb/204Pb. Based on the established discriminant functions, the original and cross-validation accuracy towards different geographical origins of tobacco leaves were 98.8% and 95.1%, respectively. The study shows that the strontium and lead isotopic with mineral elemental fingerprints is a potential effective method to identify the geographical origin of tobacco leaves from different countries.

A tokamak relies on the axisymmetric magnetic fields to confine fusion plasmas and aims to deliver sustainable and clean energy. However, misalignments arise inevitably in the tokamak construction, leading to small asymmetries in the magnetic field known as error fields (EFs). The EFs have been a major concern in the tokamak approaches because a small level EFs, even less than 0.1 %, can drive a plasma disruption. Contrary to conventional wisdom, we report that the EFs in a tokamak can be favorably used for controlling plasma instabilities, such as edge-localized modes (ELMs), while maintaining a hot fusion plasma at a temperature of 100 million kelvin. A novel optimization tailors the EFs to maintain an edge 3D response for ELM control with a minimized core 3D response to avoid plasma disruption and unnecessary degradation. We design and demonstrate such an edge-localized 3D response at the Korean Superconducting Tokamak Advanced Research facility, benefiting from its unique flexibility to change many degrees of freedom in the 3D coil space for the various fusion plasma regimes. This favorable control of the tokamak EF represents a notable advance for designing intrinsically 3D tokamaks to optimize stability and confinement for the next-step fusion reactors.

Increasing evidence has shown that the NOD-like receptor protein 1 (NLRP1) inflammasome is associated with Aβ generation and deposition, which contributes to neuronal damage and neuronal-inflammation in Alzheimer's disease (AD). However, the specific mechanism of NLRP1 inflammasome in the pathogenesis of AD is still unclear. It has been reported that autophagy dysfunction can aggravate the pathological symptoms of AD and plays an important role in regulating Aβ generation and clearance. We hypothesized that NLRP1 inflammasome activation may induce autophagy dysfunction contributing to the progression of AD. In the present study, we observed the relationship between Aβ generation and NLRP1 inflammasome activation, as well as AMPK/mTOR mediated-autophagy dysfunction in WT 9-month-old (M) mice, APP/PS1 6 M and APP/PS1 9 M mice. Additionally, we further studied the effect of NLRP1 knockdown on cognitive function, Aβ generation, neuroinflammation and AMPK/mTOR mediated autophagy in APP/PS1 9 M mice. Our results indicated that NLRP1 inflammasome activation and AMPK/mTOR mediated-autophagy dysfunction are closely implicated in Aβ generation and deposition in APP/PS1 9 M mice, but not in APP/PS1 6 M mice. Meanwhile, we found that knockdown of NLRP1 significantly improved learning and memory impairments, decreased the expressions of NLRP1, ASC, caspase-1, p-NF-κB, IL-1β, APP, CTF-β, BACE1 and Aβ1-42, and decreased the level of p-AMPK, Beclin 1 and LC3 II, and increased the level of p-mTOR and P62 in APP/PS1 9 M mice. Our study suggested that inhibition of NLRP1 inflammasome activation improves AMPK/mTOR mediated-autophagy dysfunction, resulting in the decrease of Aβ generation, and NLRP1 and autophagy might be important targets to delay the progression of AD.