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Lunar DRO pinpoint return is the final stage of manned deep space exploration via a lunar DRO station. A re-entry capsule suffers from complicated dynamic and thermal effects during an entire flight. The optimization of the lunar DRO return trajectory exhibits strong non-linearity. To obtain a global optimal return trajectory, an entire-flight lunar DRO pinpoint return model including a Moon–Earth transfer stage and an Earth atmosphere re-entry stage is constructed. A re-entry point on the atmosphere boundary is introduced to connect these two stages. Then, an entire-flight global optimization framework for lunar DRO pinpoint return is developed. The design of the entire-flight return trajectory is simplified as the optimization of the re-entry point. Moreover, to further improve the design efficiency, a rapid landing point prediction method for the Earth re-entry is developed based on a deep neural network. This predicting network maps the re-entry point in the atmosphere and the landing point on Earth with respect to optimal control re-entry trajectories. Numerical simulations validate the optimization accuracy and efficiency of the proposed methods. The entire-flight return trajectory achieves a high accuracy of the landing point and low fuel consumption.

The progress of communication technology and the Internet has made the dual-channel supply chain have great development. Supply chain members have to compete and cooperate with other enterprises on the chain in order to obtain greater self-benefit. In the competitive-cooperative relationship among enterprises, price discrimination and sales effort are common tools of operation, and Nash equilibrium theory is a common strategy in the process of supply chain game. Whether manufacturers can promote retailers to implement sales efforts through price discrimination and ensure that the overall revenue of the supply chain is improved at the Nash equilibrium is great significance to both the supply chain and individual enterprises. This paper constructs a decentralized dual-channel supply chain mathematical model composed of an independent manufacturer, an offline retailer, and an online retailer, taking into account the impact of the offline retailer’s sales efforts on his demand and its positive external for the other channel. The revenue matrix of retailers’ decisions about whether or not to pay their sales efforts is built under the condition that manufacturers charge different wholesale prices to different retailers and solves the condition of every decision combination becoming the Nash equilibrium using the Nash equilibrium game theory. Finally, the optimal pricing strategy of the manufacturers is analysed to get the constraints of this dual-channel supply chain achieving Pareto improvement when manufacturer uses wholesale price discrimination strategy.

The distribution and change of sea surface salinity (SSS) have an important influence on the sea dynamic environment, marine ecological environment, global water cycle, and global climate change. Satellite remote sensing is the only practical way to continuously observe SSS over a wide area and for a long period of time. The salinity retrieval model of flat sea surface, which primarily includes empirical model and iterative model, is the key to retrieving satellite SSS products. The empirical models have high computational efficiency but low inversion accuracy, while the iterative models have high inversion accuracy but low computational efficiency. In order to reconcile the contradiction between the computational efficiency and inversion accuracy of existing models, this paper proposes a universal deep neural network (DNN) model architecture and corresponding training scheme, and provides 3 DNN models with extremely high computational efficiency and high inversion accuracy. The inversion error range, the root mean square error (RMSE), and the mean absolute error (MAE) of the DNN models on 311,121 sets of data have decreased by more than 40 times, 150 times, and 150 times, respectively, compared to the empirical model. The computational efficiency of the DNN models on 420,903 sets of data has improved by more than 100,000 times compared to the iterative model. Therefore, the algorithm developed in this paper can effectively solve the contradiction between the computational efficiency and inversion accuracy of existing models, and provide a theoretical support for high-precision and high-efficiency salinity inversion research.

Abstract Late-onset Alzheimer disease (LOAD) is highly polygenic, with a heritability estimated between 40 and 80%, yet risk variants identified in genome-wide studies explain only ~8% of phenotypic variance. Due to its increased power and interpretability, genetically regulated expression (GReX) analysis is an emerging approach to investigate the genetic mechanisms of complex diseases. Here, we conducted GReX analysis within and across 51 tissues on 39 LOAD GWAS data sets comprising 58,713 cases and controls from the Alzheimer’s Disease Genetics Consortium (ADGC) and the International Genomics of Alzheimer’s Project (IGAP). Meta-analysis across studies identified 216 unique significant genes, including 72 with no previously reported LOAD GWAS associations. Cross-brain-tissue and cross-GTEx models revealed eight additional genes significantly associated with LOAD. Conditional analysis of previously reported loci using established LOAD-risk variants identified eight genes reaching genome-wide significance independent of known signals. Moreover, the proportion of SNP-based heritability is highly enriched in genes identified by GReX analysis. In summary, GReX-based meta-analysis in LOAD identifies 216 genes (including 72 novel genes), illuminating the role of gene regulatory models in LOAD.

Identifying active catalysts for the conversion of alcohols into aldehydes or ketones and molecular hydrogen is highly desirable. Here the authors develop and validate against experiments a screening model based on DFT calculations and scaling relationships for identifying alcohol dehydrogenation catalysts.

In order to further explore the coupling mechanism of operation risk in the tunneling process, and accurately and efficiently evaluate the operation risk level, the JHA-FRMA method after fitting optimization is used to identify risks from the three aspects of the operation node’s own function, upstream and downstream changes, and the impact of parallel operations. Analytical hierarchy process(AHP) and set pair analysis(SPA) are used to quantify the risk and the importance of operation nodes, and the operation risk is evaluated based on the degree of convergence of the connection degree, and applied to the tunneling process of a coal mine in Shanxi. The results show that the “cutting” operation has the highest risk level during the tunneling process. There are 3 huge risk points, 5 major risk points, and 12 high-risk paths in the whole process. This method realizes the comprehensive evaluation of static risk factors and dynamic risk situation in the operation process. The results obtained not only provide a basis for the effective implementation of the management and control mechanism of coal mine enterprises, but also provide effective guidance for workers and supervisors in the operation process.

Abstract Amyotrophic lateral sclerosis (ALS) is a multi‐system disease characterized primarily by progressive muscle weakness. Cognitive dysfunction is commonly observed in patients; however, factors influencing risk for cognitive dysfunction remain elusive. Using sparse canonical correlation analysis (sCCA), an unsupervised machine‐learning technique, we observed that single nucleotide polymorphisms collectively associate with baseline cognitive performance in a large ALS patient cohort (N = 327) from the multicenter Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium. We demonstrate that a polygenic risk score derived using sCCA relates to longitudinal cognitive decline in the same cohort and also to in vivo cortical thinning in the orbital frontal cortex, anterior cingulate cortex, lateral temporal cortex, premotor cortex, and hippocampus (N = 90) as well as post‐mortem motor cortical neuronal loss (N = 87) in independent ALS cohorts from the University of Pennsylvania Integrated Neurodegenerative Disease Biobank. Our findings suggest that common genetic polymorphisms may exert a polygenic contribution to the risk of cortical disease vulnerability and cognitive dysfunction in ALS.

Demands to deploy deep neural network (DNN) models on mobile devices and embedded systems have drastically grown in recent years. When transplanting DNN models to such platforms, requirements pertaining to computation and memory use are bottlenecks. To overcome them, network pruning has been carefully studied as a method of network compression. The effectiveness of network pruning is significantly affected by incorrect pruning on important connections. In this paper, we propose a network pruning method based on the modified $L_{1/2}$ penalty that reduces incorrect pruning by increasing the sparsity of the pretrained models. The modified $L_{1/2}$ penalty yields better sparsity than the $L_{1}$ penalty at a similar computational cost. Compared with the past work that numerically defines the importance of connections and re-establishes important weights when incorrect pruning occurs, our method achieves faster convergence by using a simpler pruning strategy. The results of experiments show that our method can compress LeNet300-100, LeNet-5, ResNet, AlexNet, and VGG16 by factors of $66\times $ , $322\times $ , $26\times $ , $21\times $ , and $16\times $ , respectively, with negligible loss of accuracy.

The reasonable distribution of revenue determines not only the coordination but also the development of supply chain. A hybrid channel supply chain model composed of manufacturer and traditional and online retailers was identified as the object of study, decision models under different cooperation modes were built, different revenues of supply chain members and overall were analyzed, satisfaction of characteristic function required by the Shapley value was proved, and the Shapley values of revenue distribution were calculated. In view of the shortcoming of the Shapley value method which takes contribution margin as the only consideration and ignores the impact of other factors such as cost on revenue distribution, the cost correction model was built by using production and sales cost to modify the traditional Shapley value; the reasonable distribution of individual benefits under the premise of maximizing the overall revenue of hybrid channel supply chain was realized.

Butorphanol and dexmedetomidine (DXM) can produce analgesia in birds. Intranasal (IN) route of drug administration is easier, and free of risks such as pain and tissue damage compared with intravenous, intramuscular or subcutaneous routes in bird species, including wild birds. Although previous studies have demonstrated the use of IN route for producing sedation, no studies are available on the pharmacokinetics and pharmacodynamics of IN drugs in birds. This study analyzed the pharmacokinetics and sedative–analgesic efficacy of intranasal butorphanol (2 mg/kg), dexmedetomidine (80 µg/kg) and their combination (butorphanol, 2 mg/kg; DXM, 80 µg/kg) in healthy, male, Ross broiler chickens (n = 6/group) aged between 6 and 8 weeks. Maximum plasma concentration (Cmax, p = 0.01), area under the plasma concentration-time curve from time zero to 120 min (AUC0 to 120, p = 0.02) and apparent volume of distribution at steady state (Vss, p = 0.02) of DXM were significantly higher than that of DXM co-administered with butorphanol. The mechanical nociceptive thresholds and the sedation scores of DXM group were significantly higher than the baseline value. Dexmedetomidine (80 µg/kg, IN) was effective in chickens, and the drug absorption was more rapid than that of DXM with butorphanol. However, the duration of action of DXM was short. Lower value of Cmax and nociceptive thresholds showed the nonsignificant efficacy of butorphanol at a dose of 2 mg/kg after IN administration in broiler chickens.

Background: Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. Methods: We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). Findings: OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ = 92.7 (14.7), PIQ = 108.9 (13.1), FIQ = 100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ = 100.1 (13.2), PIQ = 113.7 (10.8), FIQ = 107.4 (11.5)). The prevalence of low IQ (

With the strengthening of external supervision and the management requirements of internal quality and efficiency improvement of power grid, it is particularly important to improve the lean level of power grid investment. However, the accuracy and scientificity of the current grid infrastructure project investment plan adjustment need to be further improved, and the basis for the completion of investment submission is the on-site construction progress. Therefore, this topic carries out the analysis of the factors affecting the construction progress, including the types of the factors affecting the construction, the depth and breadth of the impact, and the impact of the milestone stage, and takes the analysis results of the shutdown factors as the reference basis for the adjustment of the investment plan, so as to improve the investment management level of the company.

The remelting method is introduced to improve the properties of the as-sprayed NiCrBSi coatings. In this work, tungsten carbide (WC) was selected as reinforcement and the as-sprayed and remelted NiCrBSi/WC composite coatings were investigated by X-ray diffraction, scanning electron microscopy, hardness test and tribology test. After spraying, WC particles are evenly distributed in the coating. The remelting process induced the decarburizing reaction of WC, resulting in the formation of dispersed W2C. The dispersed W2C particles play an important role in the dispersion strengthening. Meanwhile, the pores and lamellar structures are eliminated in the remelted NiCrBSi/WC composite coating. Due to these two advantages, the hardness and the high-temperature wear resistance of the remelted NiCrBSi/WC composite coating are significantly improved compared with those with an as-sprayed NiCrBSi coating; the as-sprayed NiCrBSi coating, as-sprayed NiCrBSi/WC composite coating and remelted NiCrBSi/WC composite coating have average hardness of 673.82, 785.14, 1061.23 HV, and their friction coefficients are 0.3418, 0.3261, 0.2431, respectively. The wear volume of the remelted NiCrBSi/WC composite coating is only one-third of that of the as-sprayed NiCrBSi coating.

Skull morphology is fundamental to evolution and the biological adaptation of species to their environments. With aquaculture fish species, head size is also important for economic reasons because it has a direct impact on fillet yield. However, little is known about the underlying genetic basis of head size. Catfish is the primary aquaculture species in the United States. In this study, we performed a genome-wide association study using the catfish 250K SNP array with backcross hybrid catfish to map the QTL for head size (head length, head width, and head depth). One significantly associated region on linkage group (LG) 7 was identified for head length. In addition, LGs 7, 9, and 16 contain suggestively associated regions for head length. For head width, significantly associated regions were found on LG9, and additional suggestively associated regions were identified on LGs 5 and 7. No region was found associated with head depth. Head size genetic loci were mapped in catfish to genomic regions with candidate genes involved in bone development. Comparative analysis indicated that homologs of several candidate genes are also involved in skull morphology in various other species ranging from amphibian to mammalian species, suggesting possible evolutionary conservation of those genes in the control of skull morphologies.

In order to deal with the severe external supervision and challenges, and improve the scientific rationality of internal investment structure decision-making, this study explored the idea of voltage level investment structure decision-making considering the power grid development and operation benefits. Firstly, based on the study of the relationship between historical investment scale and power grid indicators, the investment demand of power grid is determined; secondly, the influence path of investment on business efficiency is sorted out, and the differences of investment, capital transfer and depreciation of different voltage levels are studied and determined, and the operation benefit level of the company under different investment schemes is calculated. Finally, the index system of investment structure optimization is constructed to quantify the power grid and benefit status of the company under different investment structures, so as to optimize the company’s investment scheme and promote the high-quality development of the company and power grid.

This paper studies the effects of the covering layers on the performance of a cross-like Hall plate. Three different structures of a cross-like Hall plate in various sizes are designed and analyzed. The Hall plate sensitivity and offset are characterized using a self-built measurement system. The effect of the P-type region over the active area on the current-related sensitivity is studied for different Hall plate designs. In addition, the correlation between the P-type covering layer and offset is analyzed. The best structure out of three designs is determined. Besides, a modified eight-resistor circuit model for the Hall plate is presented with improved accuracy by taking the offset into account.

Lipoprotein subfractions help discriminate cardiometabolic disease risk. Genetic loci validated as associating with lipoprotein measures do not account for a large proportion of the individual variation in lipoprotein measures. We hypothesized that DNA methylation levels across the genome contribute to interindividual variation in lipoprotein measures. Using data from participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 663 for discovery and n = 331 for replication stages, respectively), we conducted the first systematic screen of the genome to determine associations between methylation status at ∼470,000 cytosine-guanine dinucleotide (CpG) sites in CD4+ T cells and 14 lipoprotein subfraction measures. We modeled associations between methylation at each CpG site and each lipoprotein measure separately using linear mixed models, adjusted for age, sex, study site, cell purity, and family structure. We identified two CpGs, both in the carnitine palmitoyltransferase-1A (CPT1A) gene, which reached significant levels of association with VLDL and LDL subfraction parameters in both discovery and replication phases (P < 1.1 × 10−7 in the discovery phase, P < .004 in the replication phase, and P < 1.1 × 10−12 in the full sample). CPT1A is regulated by PPARα, a ligand for drugs used to reduce CVD. Our associations between methylation in CPT1A and lipoprotein measures highlight the epigenetic role of this gene in metabolic dysfunction.

Advertising is a crucial tool for demand creation and market expansion; enterprises in supply chain use it widely to increase sales and improve profits. But the homogeneity of products sold in hybrid channel supply chain magnifies the positive externalities of advertising and leads to serious free-riding problem. To coordinate the supply chain effectively, firstly, this paper classifies hybrid channel supply chain based on the relationship between members and selects horizontally integrated, vertically integrated, and decentralized hybrid channel supply chains as research objects. Then, a demand function considering the common effect of price and advertising is proposed and coordination schemes for different types of supply chains are designed. Finally, a sensitivity analysis is performed to assess the impact of parameters on coordination using orthogonal experiment.

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10(-7) was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10(-14) and P for cg17058475 = 1.2x10(-9)). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

This work studies the effects of an aluminum covering on the performance of cross-like Hall devices. Four different Hall sensor structures of various sizes were designed and fabricated. The sensitivity and offset of the Hall sensors, two key points impacting their performance, were characterized using a self-built measurement system. The work analyzes the influences of the aluminum covering on those two aspects of the performance. The aluminum layer covering mainly leads to an eddy-current effect in an unstable magnetic field and an additional depletion region above the active region. Those two points have influences on the sensitivity and the offset voltage, respectively. The analysis guides the designer whether to choose covering with an aluminum layer the active region of the Hall sensor as a method to reduce the flicker noise and to improve the stability of the Hall sensor. Because Hall devices, as a reference element, always suffer from a large dispersion, improving their stability is a crucial issue.

Gastrodin, an anti‐inflammatory herbal agent, is known to suppress microglia activation. Here, we investigated whether it would exert a similar effect in reactive astrocytes and whether it might act through the renin‐angiotensin system (RAS) and sirtuin 3 (SIRT3). Angiotensinogen (ATO), angiotensin‐converting enzyme (ACE), angiotensin II type 1 (AT1) and type 2 (AT2) receptor and SIRT3 expression was detected in TNC‐1 astrocytes treated with BV‐2 microglia conditioned medium (CM) with or without gastrodin and lipopolysaccharide (LPS) pre‐treatment by RT‐PCR, immunofluorescence and western blotting analysis. Expression of C3 (A1 astrocyte marker), S100A10 (A2 astrocyte marker), proinflammatory cytokines and neurotrophic factors was then evaluated. The results showed a significant increase of ATO, ACE, AT1, SIRT3, C3, proinflammatory cytokines and neurotrophic factors expression in TNC‐1 astrocytes incubated in CM + LPS when compared with cells incubated in the CM, but AT2 and S100A10 expression was reduced. TNC‐1 astrocytes responded vigorously to BV‐2 CM treated with gastrodin + LPS as compared with the control. This was evident by the decreased expression of the abovementioned protein markers, except for AT2 and S100A10. Interestingly, SIRT3, IGF‐1 and BDNF expression was enhanced, suggesting that gastrodin inhibited the expression of RAS and proinflammatory mediators but promoted the expression of neurotrophic factors. And gastrodin regulated the phenotypic changes of astrocytes through AT1. Additionally, azilsartan (a specific inhibitor of AT1) inhibited the expression of C3 and S100A10, which remained unaffected in gastrodin and azilsartan combination treatment. These findings provide evidence that gastrodin may have a therapeutic effect via regulating RAS–SIRT3. [ABSTRACT FROM AUTHOR]