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Pareto-optimal sets of multiobjective optimization problems with black-box and computationally expensive objective functions are generally hard to locate within a limited computational budget, and this situation gets even worse when more than three objectives are involved. To this end, we present a novel surrogate-assisted many-objective optimization algorithm RECAS. Unlike most prior studies, the proposed algorithm is a non–evolutionary-based method, and it iteratively determines new points for expensive evaluation via a series of independent reference vector assisted candidate searches. Furthermore, to make the number of surrogates to be maintained independent of the number of objectives, in each candidate search, RECAS constructs a surrogate model in an aggregated manner to approximate the quality assessment indicator of each point rather than a certain objective function. Under some mild assumptions, this study proves that RECAS converges almost surely to the Pareto-optimal front. In the numerical experiments, the effectiveness and reliability of RECAS are examined on both DTLZ and WFG test suites with the number of objectives varying from 2 to 10. Compared with six state-of-the-art many-objective optimization algorithms, RECAS generally performs better in maintaining convergent and well-spread approximation of the Pareto-optimal front. Finally, the good performance of RECAS on two watershed simulation model calibration problems indicates its great potential in handling real-world applications. History: Accepted by Antonio Frangioni, Area Editor for Design and Analysis of Algorithms–Continuous. Funding: This work was supported by the National University of Singapore start-up grant to C.A. Shoemaker [Grant R-266-000-109-133]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplementary Information [ https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.1260 ] or is available from the IJOC GitHub software repository ( https://github.com/INFORMSJoC ) at [ http://dx.doi.org/10.5281/zenodo.7243971 ].

The Ti/Cr clusters, from dimers to pentamers, on a single-layer h-BN are investigated using first-principles calculations. The relatively weak interaction with the h-BN monolayer makes it possible to build versatile and interesting 3D nanostructures.

Nanozymes with high catalytic stability and sustainability have emerged as powerful competitors to natural enzymes for diverse biocatalytic applications. However, constructing a nanozyme with high specificity is one of their biggest challenges. Herein, we develop a facile solid migration strategy to access a flower-like single copper site nanozyme (Cu SSN) via direct transformation of copper foam activated by 2-methylimidazole. With highly clustered CuN

The ice water path (IWP) is an important cloud parameter in atmospheric radiation, and there are still great difficulties in its retrieval. Artificial neural networks have become a popular method in atmospheric remote sensing in recent years. This study presents a global IWP retrieval based on deep neural networks using the measurements from the Microwave Humidity Sounder (MWHS) aboard the FengYun-3B (FY-3B) satellite. Since FY-3B/MWHS has quasi-polarization channels at 150 GHz, the effect of the polarimetric radiance difference (PD) was also studied. A retrieval database was established using collocations between MWHS and CloudSat 2C-ICE (CloudSat and CALIPSO Ice Cloud Property Product). Then, two types of networks were trained for cloud scene filtering and IWP retrieval. For the cloud filtering network, the microwave channels show a capacity with a false alarm ratio (FAR) of 0.31 and a probability of detection (POD) of 0.61. For the IWP retrieval network, different combination inputs of auxiliaries and channels were compared. The results show that the five MWHS channels combined with scan angle, latitude, and the ocean/land mask of inputs of auxiliary variables perform best. Applying the cloud filtering network and IWP retrieval network, the final root mean squared error (RMSE) is 916.76 g m−2, the mean absolute percentage error (MAPE) is 92 %, and the correlation coefficient (CC) is 0.65. Then, a tropical cyclone case measured simultaneously by MWHS and CloudSat was chosen to test the performance of the networks, and the result shows a good correlation (0.73) with 2C-ICE. Finally, the global annual mean IWP of MWHS is very close to that of 2C-ICE, and the 150 GHz channels give a significant improvement in the midlatitudes compared to using only 183 GHz channels.

A controlled chemical reaction on a specific bond in a single molecule is an inevitable step toward atomic engineering and fabrication. Here, we explored the debromination of a single 9,10-dibromoanthracene (DBA) molecule on a surface as stimulated by the voltage pulse through the tip of a scanning tunneling microscope (STM). A voltage threshold of about 2.2 V is obtained, and the nature of single-electron process is revealed. The spatially resolved debromination yield is obtained as a function of the pulse magnitude, which presents strong asymmetry for the two C-Br bonds. The optimal stimulation parameters including the pulse magnitude and the tip locations are suggested. The distinct dynamics in dissociation of the two bonds are illustrated by their energy diagrams and recoil paths, as derived by the first-principles density functional theory (DFT) calculation. The influence of the local electric field due to the STM tip on the dissociation of the C-Br bond has also been discussed. The study presents detailed practice for the controlled debromination in a single DBA molecule, which may lead to automated atomic engineering and fabrication of artificial nanostructures in the future.

In this paper, we focus on the vehicle-to-vehicle dynamic channel in tactical communication environments, which shows time-varying and nonstationary characteristics due to the fast mobility, directional antennas, and harsh terrain. These situations present great challenges for the channel state information (CSI) acquisition. To obtain an accurate CSI and reduce pilot overhead, we propose a CSI predictor based on the long short-term memory (LSTM) network. As an improved recurrent neural network (RNN), LSTM units have an excellent learning result on both long- and short-term inputs by adding the gating mechanism. Using the outdated sampling CSI sequence as input data of LSTM units enables the predictor to extract complex data characteristics and capture the temporal law of the nonstationary channel. Simulation results are demonstrated to verify that the LSTM-based predictor has better performance than conventional algorithms in IEEE 802.11p standard. Additionally, the key factors that affect the performance of the proposed predictor are further analyzed.

The hydrological exchange process between Poyang Lake (PYL), the largest freshwater lake in China, and the Yangtze River leads to drastic changes in water area (WA) and water level (WL), as well as apparent fluctuations in lake nutrients, algal organisms, and trophic level index. This study investigated the current status of the PYL water environment and the influence of hydrological changes on the nutrient status of the floodplain of the lake. Based on monthly measured data from six hydrological stations from 2016 to 2019, it was hypothesized that WA and WL were the key regulators of the spatial and temporal distribution patterns of lake water quality and algal growth, including water temperature, water clarity (Secchi depth [SD]), and nutrient levels. The results revealed that (1) the spatial and temporal distribution characteristics of major nutrients in PYL were influenced by dynamic changes in hydrological characteristics (SD, total nitrogen [TN], and total phosphorus [TP]); (2) the eutrophication level in PYL has been in a steady state in recent years, while the central area has been more prone to the risk of eutrophication (e.g., the peak eutrophication index during Period 1 [January to April] in the water near the Duchang station reached 70); and (3) there were significant correlations among environmental variables, nutrients, and algal organisms, with different spatial and temporal distribution characteristics (p 0.05), while the changes in WA and WL considerably influenced the water environment in the PYL.

Embryonic tissues undergoing shape change draw mechanical input from extraembryonic substrates. In avian eggs, the early blastoderm disk is under the tension of the vitelline membrane (VM). Here we report that the chicken VM characteristically downregulates tension and stiffness to facilitate stage-specific embryo morphogenesis. Experimental relaxation of the VM early in development impairs blastoderm expansion, while maintaining VM tension in later stages resists the convergence of the posterior body causing stalled elongation, failure of neural tube closure, and axis rupture. Biochemical and structural analysis shows that VM weakening is associated with the reduction of outer-layer glycoprotein fibers, which is caused by an increasing albumen pH due to CO2 release from the egg. Our results identify a previously unrecognized potential cause of body axis defects through mis-regulation of extraembryonic tissue tension.

Heavy neutrinos are usually introduced to accommodate tiny neutrino masses via seesaw mechanism, or to alleviate the cosmology problem, and there may exist charged Higgs which couple to the leptons with different flavors. These two features can appear in the Twin Higgs models. What interests us is that such new particles and interactions may lead to new contributions to the lepton flavor violating processes [Formula: see text] and [Formula: see text]. We find that current experimental data can constrain the parameter spaces and certain lepton flavor violating processes can possibly be tested by the next generation experiments.

The curse of dimensionality has long been one of the biggest challenges in solving large-scale simulation ranking and selection (R&S) problems. As the number of systems grows, existing approaches to R&S relying on the Bonferroni correction become increasingly conservative, rendering them overachieving in error control and consuming more computational resources than necessary. In “Bonferroni-Free and Indifference-Zone-Flexible Sequential Elimination Procedures for Ranking and Selection,” Wang, Wan, and Chen develop Bonferroni-free and indifference-zone-optional ranking and selection procedures to deliver the prescribed probabilistic guarantee without overshooting. Their approach is to conduct always valid and fully sequential hypothesis tests that enable continuous monitoring of each candidate system and control the probability of correct selection. In addition, the indifference-zone parameter becomes dispensable in their procedures; however, when provided appropriately, it could improve the procedures’ computational and statistical efficiency.

Supplemental Figure 1. KDM6B and KDM6A expression profiles in breast cancer subtypes. Supplemental Figure 2. KDM6A over-expression is not associated with poor clinical outcome. Supplemental Figure 3.KDM6B knockdown does not result in cell death in SKBR3, MDA-MB-415, BT20 and SUM159 cells. Supplemental Figure 4.IGFBP5 is a prognostic factor that predicts poor prognosis in luminal breast cancer patients. Supplemental Figure5.IGFBP5 regulated by KDM6B and its effect on cell survival.

Despite showing promise against PIK3CA-mutant breast cancers in preclinical studies, PI3K/AKT pathway inhibitors demonstrate limited clinical efficacy as monotherapy. Here, we found that histone H3K27me3 demethylase KDM6B-targeted IGFBP5 expression provides a protective mechanism for PI3K/AKT inhibitor-induced apoptosis in breast cancer cells. We found that overexpression of KDM6B and IGFBP5 in luminal breast cancer are positively associated with poorer disease outcomes. Mechanistically, KDM6B promotes IGFBP5 expression by antagonizing EZH2-mediated repression, and pharmacologic inhibition of KDM6B augments apoptotic response to PI3K/AKT inhibitor treatment. Moreover, the IGFBP5 expression is upregulated upon acquired resistance to the PI3K inhibitor GDC-0941, which is associated with an epigenetic switch from H3K27me3 to H3K27Ac at the IGFBP5 gene promoter. Intriguingly, GDC-0941–resistant breast cancer cells remained sensitive to KDM6B or IGFBP5 inhibition, indicating the dependency on the KDM6B–IGFBP5 axis to confer the survival advantage in GDC-0941–resistant cells. Our study reveals an epigenetic mechanism associated with resistance to targeted therapy and demonstrates that therapeutic targeting of KDM6B-mediated IGFBP5 expression may provide a useful approach to mitigate both intrinsic and acquired resistance to the PI3K inhibitor in breast cancer. Mol Cancer Ther; 17(9); 1973–83. ©2018 AACR.

In recent years, arginine deiminase (ADI, EC 3.5.3.6) has attracted much attention as a biocatalyst that produces the functional amino acid l-citrulline from l-arginine and also as an anticancer enzyme. Here, we identified and characterized a putative ADI from the thermophilic bacterium Halothermothrix orenii. The H. orenii ADI (H-ADI) protein was expressed in Escherichia coli BL21(DE3) with a specific activity of 91.8 U/mg protein at 55°C and pH 6.5. The enzyme remained at 74% relative activity after incubation at 45°C for 180 min, only 25% at 50°C. The melting temperature was 56°C. H-ADI is not a metal-requiring enzyme; Ni

This study is aimed to evaluate the effectiveness of a theory-driven exercise intervention for Chinese community-dwelling (pre)frail older adults, and to clarify the underlying mechanisms of the exercise intervention in this population.A stepped-wedge cluster-randomized trial.A stepped-wedge cluster-randomized trial will be conducted among (pre)frail older adults at six communities in a county of central China. A 12-week multicomponent exercise intervention based on the integration of the Health Belief Model (HBM) and the Theory of Planned Behaviour (TPB) will be implemented to all participants during the study period. The primary outcomes are frailty, muscle mass, muscle strength and physical performance. Secondary outcomes include beliefs in exercise, exercise behaviours and other physical, mental and social functioning. Assessments will be conducted at baseline and at week 12, 24 and 36. A multilevel regression model will be used to evaluate the effectiveness of exercise interventions. A multilevel mediation model will be used to clarify the underlying mechanisms of this exercise intervention.This study is expected to provide an effective and practical mode for exercise interventions among Chinese community-dwelling (pre)frail older adults, and contribute to the existing evidence in this field.Chinese Clinical Trial Registry ChiCTR2100041981.

To investigate whether and how social support influenced frailty progression through depressive symptoms and physical activity.Of 1235 community-dwelling older adults enrolled at baseline, 778 (63.0%) undergoing at least one yearly follow-up were included in the final analysis. Data were collected on frailty, social support, depressive symptoms, physical activity and covariates.Two frailty trajectory classes were identified and labeled as alleviated frailty and deteriorated frailty. Subjective support prevented the deterioration of frailty through decreased depressive symptoms, while objective support and support utilization prevented the deterioration of frailty through increased physical activity.The pathways through which social support ameliorates frailty vary by support types. Subjective support interventions should be included in the multifactorial interdisciplinary management of frailty to address social and psychological vulnerabilities, along with objective support and support utilization interventions addressing physical inactivity.

To identify patterns of intrinsic capacity (IC) and determine the association between these patterns with incident one-year outcomes.A total of 756 older adults aged ≥ 60 years were followed up after 1 year. IC was assessed using the revised integrated care for older people screening tool, and its patterns were examined by the latent class analysis. Logistic regression models were conducted to compare the risk of adverse outcomes.Three IC patterns were identified. Both "sharp declines in sensory domain" (Class 2) and "sharp declines in locomotion, psychological, cognition and vitality domains" (Class 3) were at greater risk of disabilities and poor physical quality of life than "relatively healthy" (Class 1). The Class 3 was twice as likely to be hospitalized as Class 1.Assessment of IC could provide valuable information on stratifying older adults into heterogeneous groups, promoting targeted interventions to delay the adverse outcomes.

This paper aims to present the current problems, solutions, and prospects of SPACs in the United States. First, the report introduces how SPACs function and merge with private companies. Then, it examines the advantages and disadvantages of the SPAC process, especially when contrasted with traditional IPOs. Finally, moving to more current events, it establishes the decline of SPACs in the past year before concluding with the new rules proposed by the SEC. We will also predict the future of SPACs and how the SEC's reforms will impact the market. The paper provides a bird's-eye view of the current status of SPACs in the United States, serving as a foundation for any expectations regarding SPACs.

Background Macrophage-like cells (MLCs) located at the ILM were observed in live human retinas using adaptive optics optical coherence tomography (OCT) as well as clinically-used OCT. The study aimed to quantitatively analyzing MLCs at the vitreoretinal interface (VRI) in diabetic retinopathy (DR) using en face OCT and swept-source optical coherence tomography angiography (SS-OCTA). Methods 190 DR eyes were included in the study, with 70 proliferative diabetic retinopathy (PDR) eyes and 120 non- proliferative diabetic retinopathy (NPDR) eyes. Sixty-three eyes from normal subjects were included as controls. MLCs were visualized in a 5 μm en face OCT slab above the VRI centered on the fovea. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the OCTA parameters and the MLC parameters among groups. We evaluated the MLC density among groups on binarized images after image processing. We also investigated the relationship between MLC density and other OCT parameters including retina thickness and vessel density (VD). Results The MLC density significantly increased in PDR eyes (PDR vs. NPDR, 8.97 (8.40) cells/mm2 vs.6.14 (8.78) cells/mm2, P = 0.013; PDR vs. normal, 8.97 (8.40) cells/mm2vs. 6.48 (6.71) cells/mm2, P = 0.027) and diabetic macular edema (DME) eyes (DME vs. without DME, 8.94 (8.26) vs.6.09 (9.00), P = 0.005). After adjusting for age and gender, MLC density in NPDR eyes negatively correlated to VD of deep capillary plexus (DCP) (P = 0.01). Conclusions SS-OCTA is a non-invasive and simple method for the characterization of MLCs at the VRI. PDR and DME are two factors that increase MLC density. MLC density also correlated with VD.

Nitric oxide (NO) has aroused wide interest in the treating infected wounds due to its characteristic functionalities. However, its utilization is limited due to its volatile properties, high reactivity, direct potential toxicity, and byproducts of NO donors limited its application. Herein, endogenously NO donor S-nitrosoglutathione (GSNO) was connected covalently to polydopamine nanoparticles (PDA-GSNO NPs) to minimize the loss of NO in aqueous medium. Meanwhile, near-infrared (NIR)-controlled NO release and photothermal therapy (PTT) was obtained through the photothermal conversion by PDA. Then chitosan (CS)/gelatin (GE) biocomposite hydrogel films with preferable biocompatibility, surface hydrophilicity, hydroabsorptivity, and mechanical adhesive properties were constructed. By embedding PDA-GSNO NPs into the films, a multifunctional wound dressing was fabricated. Under NIR light irradiation, the combination of PTT, NO-releasing, and CS antibacterial agents can strengthen the in vitro antimicrobial efficacy and in vivo wound healing activities. Meanwhile, the obtained wound dressing presented good biocompatibility. This work outlines an approach for combating bacterial infections and demonstrating the possibility for synergistic NO-releasing wound healing.