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Abstract As a kind of dependent random variables, the widely orthant dependent random variables, or WOD for short, have a very important place in dependence structures for the intricate properties. And so its behavior and properties in different statistical models will be a major part in our research interest. Based on WOD errors, the large deviation results of the least squares estimator in the nonlinear regression model are established, which extend the corresponding ones for independent errors and some dependent errors.

The WalKR signal transduction system is involved in extracellular signal recognition, but the details of this function are not well established. Here, the authors report the crystal structure of this two-component system alongside the characterisation of a small-molecule activator.

This systematic review and meta-analysis evaluated anti–programmed cell death (PD)-1 immunotherapy (nivolumab or pembrolizumab) for overall efficacy, safety, and effective dose relative to standard chemotherapy or other conventional drugs in the treatment of malignant tumors. We searched the following databases, PubMed, Medline, Embase, Cochrane, Wangfang Data, Weipu, and China National Knowledge Infrastructure, and the reference lists of the selected articles for randomized controlled trials (RCTs) of anti–PD-1 therapies in humans. The outcome measures were overall survival, treatment response, and adverse events. Only four randomized controlled trials met our inclusion criteria. Three of these evaluated responses to nivolumab, whereas one tested pembrolizumab. The result of our analysis suggested that nivolumab may improve the overall response rate in treating melanoma relative to chemotherapy and has few associated adverse events. Similarly, in metastatic melanoma patients, nivolumab had a significant advantage over dacarbazine in terms of 1-year survival, progression-free survival, and objective response rate. Regarding dose levels of nivolumab for patients with metastatic renal cell carcinoma, the outcomes in response to 2 and 10 mg/kg were similar, but both had significant advantages over 0.3 mg/kg. In addition, pembrolizumab showed similar outcomes in response to 2- and 10-mg/kg treatment. Anti–PD-1 immunotherapy appears to be safe and effective for patients with melanoma or metastatic renal cell carcinoma. Our meta-analysis is limited, but additional clinical trials are warranted to verify this preliminary evidence of positive outcomes and before anti–PD-1 therapy can be recommended for routine clinical use.

As the latest video coding standard, High Efficiency Video Coding (HEVC) tremendously improves the encoding efficiency compared with the preceding H.264/AVC standard, but at the cost of higher encoding complexity. This huge encoding complexity makes the implementation of HEVC intractable on live videos. For coping with this problem, two major challenges need to be solved: 1) How to accurately reduce the encoding complexity to achieve the target complexity? and 2) How to maintain the video quality after encoding complexity reduction? To solve these two challenges, we propose, in this paper, a hierarchical complexity control approach of HEVC. For the first goal, the complexity control is implemented in two levels to assure the control accuracy. In the largest coding unit (LCU) level, we adjust the maximum depths of LCUs in a frame to reduce the encoding complexity to the target. Since each frame has numerous LCUs, and each LCU can choose its maximum depth from one of the four maximum depths, the large degree of freedom contributes to the high control accuracy. However, there may be still some errors. These errors can be compensated in the frame level by a proposed frame level complexity control algorithm. For the second goal, one objective weight map and one subjective weight map are proposed to use in the process of complexity control to keep the objective and subjective video quality simultaneously. Finally, The experimental results show that our approach outperforms other state-of-the-art approaches, in terms of both control accuracy and video quality.

Regeneration of auditory hair cells in adult mammals is challenging. It is also difficult to track the sources of regenerated hair cells, especially in vivo. Previous paper found newly generated hair cells in deafened mouse by injecting a DNA methyltransferase inhibitor 5-azacytidine into the inner ear. This paper aims to investigate the cell sources of new hair cells. Transgenic mice with enhanced green fluorescent protein (EGFP) expression controlled by the Sox2 gene were used in the study. A combination of kanamycin and furosemide was applied to deafen adult mice, which received 4 mM 5-azacytidine injection into the inner ear three days later. Mice were followed for 3, 5, 7 and 14 days after surgery to track hair cell regeneration. Immunostaining of Myosin VIIa and EGFP signals were used to track the fate of Sox2-expressing supporting cells. The results show that (i) expression of EGFP in the transgenic mice colocalized the supporting cells in the organ of Corti, and (ii) the cell source of regenerated hair cells following 5-azacytidine treatment may be supporting cells during 5–7 days post 5-azacytidine injection. In conclusion, 5-azacytidine may promote the conversion of supporting cells to hair cells in chemically deafened adult mice.

At a time when COVID-19 is sweeping the world, farmland abandonment is obviously not conducive to solving food security problems. Since the formal institutions of local government in China have not been effective in the reduction of farmland abandonment, this study aims to explore whether informal institutions can help mitigate this problem. Based on big survey data from 8031 farmer households in 27 provinces in mainland China, this study uses an econometric model to investigate the quantitative impact of social capital on farmland abandonment, and to analyze the channels through which that impact manifests itself. The empirical results point to the following conclusions: (i) Social capital, as a key informal institution, can help reduce farmland abandonment. More specifically, after controlling for other variables, for every unit increase in social capital, the proportion of farmland abandonment can be predicted to drop by 7.17 percentage points. (ii) Both off-farm employment and farmland rent are channels for the impact of social capital on farmland abandonment. However, social capital’s effect on increasing farmland abandonment via the promotion of off-farm employment is small when compared with its effect on reducing farmland abandonment via the promotion of farmland rent. This study’s conclusions may help generate new ideas for reducing farmland abandonment. At the same time, the study may provide a sound, empirical basis for policies aimed at reducing the negative impact of COVID-19 on food security while also revitalizing rural areas.

Ecological or environmental compensation policies are usually designed with multiple policy objectives such as protecting the ecological environment and promoting farmers’ livelihoods, but in the enforcement process, there are often inconsistencies between realistic choices and policy objectives. Based on pooled cross-section data from the 2017–2019 public announcement of the selection of ecological forest rangers (EFRs, who mainly refers to manage and protect forests, grasslands, deserts and rivers, and report or prevent the situation or behavior of the forest area disasters, animal and plant resources, and infrastructure damage in time) among the poor in Sichuan Province in China, we used the Probit model to analyze the influencing factors of the re-employment behavior of EFRs among the poor, with the aim of assessing the differences between central government goal positioning and local government enforcement options. We find that (1) EFRs from poor households who have not yet escaped poverty and have a high per capita income level are given priority to be re-employed. This finding shows that the policy of ecological forest rangers for the poor (PEFRP, it mainly refers to an environmental protection policy that only hires the poor) pays close attention to poverty reduction goals, but it does not consider the poorest people because the EFRs with a higher income obtain higher re-employment opportunities. (2) Age, health, and education, which represent the human capital level, have no significant impact on renewal. This finding shows that the local government has not jointly achieved the goal of “poverty reduction and environmental protection” in the enforcement of the PEFRP and has deviated from the initial goal positioning of the central government. Therefore, in order to achieve the multiple policy objectives such as poverty reduction and environmental protection together, future policy enforcement needs to be adjusted in terms of local administrative assessment and the selection and recruitment of EFRs.

Labor force rural-urban migration will lead to changes to the land use patterns of farmers. Using the survey data on dynamic migration of the Chinese labor force in 2014, iv-probit and iv-tobit models were used to analyze the impact of labor migration on the land transfer of farmers. The results show that: (1) Off-farm employment would significantly impact land transfer of farmers and the results are robust. With every 10% increase in the proportion of off-farm employment of farmers, the average probability of rent-in land of farmers decreases by 1.55%, and the average transfer in land area of farmers decreased by 1.04%. Similarly, with every 10% increase in the proportion of off-farm employment of farmers, the average probability of rent-out land of farmers increases by 4.77%, and the average transfer out land area of farmers increases by 3.98%. (2) Part-time employment also has a significant impact on land transfer of farmers, but the impact of part-time employment on land transfer in is not robust. Specifically, with every 10% increase in part-farm employment, the average probability of rent-out land of farmers increases by 7.64%, and the average transfer out land area of farmers increases by 6.85%.

Land property security and advanced factor inputs play critical roles in agricultural modernization in developing countries. However, there are unclear relationships between land property security and advanced factor inputs. This study aims to clarify these relationships from the perspective of the differentiation of the realization process of land property security. From the perspective of property rights theory and endowment effects, data from 2934 farming households in rural China are used to determine the quantitative impacts of land registration and adjustment experience on the adoption of agricultural machinery. The results are as follows: (i) Land registration does not affect the adoption of agricultural machinery. (ii) Adjustment experience has a negative impact on the adoption of agricultural machinery. (iii) The interaction of land registration and adjustment experience has a positive impact on the adoption of agricultural machinery. This study provides some policy references with which developing countries can achieve agricultural modernization and revitalize the countryside by improving property rights security.

Rural households are micro-organizational systems that are composed of different family members. Against a background of fragmented land patterns and massive labor migration in China, it is of great significance for the sustainable development of regional economies to explore the optimal selection of livelihood strategies by rural households. Using a survey containing data from 8031 rural households from 27 provinces in China, this study analyzed the characteristics and spatial distribution trends of the land management scale, family life cycle, and livelihood strategy selection of rural households, and constructed Tobit econometric models to explore the correlations among these factors. The results show: (1) Rural households’ land management scale was primarily small-scale and, as it expanded, the proportion of the total cash income coming from agricultural activities increased. A relative majority of rural households were in the middle period of the family life cycle, and relatively few rural households were in the starting and empty nest periods. The proportion of the total cash income of rural households coming from agricultural pursuits while in the stable and the empty nest periods was relatively large, reaching 40.51% and 38.92%, respectively. In most provinces sampled, rural households’ livelihood strategies were non-agriculturally based, and the land management scale was mainly less than 0.67 ha. (2) Rural households’ land management scale positively correlated with their livelihood strategy selection. When other conditions remained unchanged, with every 1 ha increase in land management scale, the proportion of agricultural cash income in total family cash income increased, on average, by 3.7%. In comparison with rural households in the empty nest period, the proportions of agricultural cash income in the total family cash income of rural households in other family life cycles were relatively small. Specifically, for rural households in the starting, rearing, burden, stable, and maintenance periods, the proportion of agricultural cash income in the total family cash income decreased, on average, by 6.8%, 6.7%, 9.2%, 3.5%, and 16.3%, respectively.

With the feminization of agriculture, the role of women in the rural land transfer market is becoming increasingly important. However, at present, there is little research focusing on the relationship between the off-farm migration of female laborers and land transfer rates. Using data on 1652 agricultural land plots owned by 232 rural households in Sichuan Province in 2014, IV-Probit (The Probit model of tool variable method is added) and IV-Tobit (The Tobit model of tool variable method is added) models were constructed to explore the relationships between off-farm migration and rural household land transfer (whether the rural households have land transfer-in and the area of land transfer-in by rural households) with consideration of gender. The results show that: (1) Off-farm labor migration has a negative and significant impact on rural households’ land transfer-in rates. Under the same conditions, the off-farm migration rate increased by 10%, the probability of transfer-in land decreased by 2.6% on average, and the transfer-in area decreased by 2.7 mu on average. (2) The off-farm migration of female laborers inhibited land transfer-in rates. For every 10% increase in female labor migration, the probability of land transfer-in decreased by an average of 2.1%, and the land transfer-in area was reduced by an average of 3 mu (1 mu = 667 m2 or 0.067 ha). However, the impact of male labor migration on farmers’ land transfer-in is negative and not significant. This study provides a novel, gendered perspective to understand land transfer-in behaviors in hilly areas, which can provide further information on off-farm labor migration and the rational allocation of land resources.

Background: Plasminogen activator inhibitor (PAI)-1 levels and activity are known to increase during metabolic syndrome and obesity. In addition, previous studies have implicated PAI-1 in adipose tissue (AT) expansion while also contributing to insulin resistance. As inflammation is also known to occur in AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model PAI-1 contributes to macrophage-mediated inflammation and metabolic dysfunction.Methods: Four- to five-weeks-old male C57B6/6J mice were fed a HFD (45%) for 14 weeks, while age-matched control mice were fed a standard laboratory chow diet (10% fat). Additional studies were performed in PAI-1 knockout mice and wild type mice treated with an inhibitor (PAI-039) of PAI-1. Macrophage polarization were measured by real time PCR.Results: HFD mice showed increased expression of PAI-1 in visceral white AT (WAT) that also displayed increased macrophage numbers. PAI-1 deficient mice exhibited increased numbers of anti-inflammatory macrophages in WAT and were resistant to HFD-induced obesity. Similarly, pharmacological inhibition of PAI-1 using PAI-039 significantly decreased macrophage infiltration in WAT and improved metabolic status in HFD-induced wild-type mice. Importantly, the numbers of M1 macrophages appeared to be increased by the HFD and decreased by either genetic PAI-1 depletion or PAI-039 treatment.Conclusions: Collectively, our findings provide support for PAI-1 contributing to the development of inflammation in adipose tissue and explain the mechanism of inflammation modulated by PAI-1 in the disordered metabolism in HFD-induced obesity.

Successful generation of pentaploid wheat (genome, BBAAD) via interspecific hybridization between tetraploid wheat (BBAA) and hexaploid wheat (BBAADD) holds great promise to mutually exchange desirable traits between the two cultivated wheat species, as well as providing a novel facet for evolutionary studies of polyploid wheat. Taking advantage of the viable and fertile nature of an extracted tetraploid wheat (ETW) with a BBAA genome that is virtually identical with the BBAA component of a hexaploid common wheat, and a synthetic hexaploid wheat, we constructed four pentaploid wheats with several distinct yet complementary features, of which harboring homozygous BBAA subgenomes is a common feature. By using a combined FISH/GISH method that enables diagnosing all individual wheat chromosomes, we precisely karyotyped a larger number of cohorts from the immediate progenies of each of the four pentaploid wheats. We found that the BBAA component of hexaploid common wheat possesses a significantly stronger capacity to buffer and sustain imbalanced D genome chromosomes and appears to harbor more structural chromosome variations than the BBAA genome of tetraploid wheat. We also document that this stronger capacity of the hexaploid BBAA subgenomes behaves as a genetically controlled dominant trait. Our findings bear implications to the known greater than expected level of genetic diversity in, and the remarkable adaptability of, hexaploid common wheat as a staple crop of global significance, as well as in using pentaploidy as intermediates for reciprocal introgression of useful traits between tetraploid and hexaploid wheat cultivars.

A microstructure numerical model is an intensive computational problem, for which the simulation time is too long and the simulation scale is too small. To solve these two problems, in this article, we use MPI+CUDA hybrid particle heterogeneous parallel computing to implement the dendrite growth simulation of a PF-LBM phase-field 3D model. Message Passing Interface (MPI) can be used to conduct coarse granularity division, to break through the limitation of the simulate scale in a single machine. In each node, fine-grained division is implemented by the Compute Unified Device Architecture (CUDA) parallel way to realize the completely parallelism intra-node, and to improve overall computational efficiency. At the same time, in this article, the "pseudo three-dimensional array" programming method is brought up in CUDA programming, and also to improve the CUDA random number generation method, in order to simplify the CUDA array programming and reduce the CUDA random number generation time purposes. Experiments show that at the same simulation scale, the speed-up ratio with 21 nodes MPI+CUDA was 57, which was increased 54% over the 21 nodes MPI. Under the condition of computing efficiency close, the largest simulation scale with 21 nodes MPI+CUDA was 4203, which is 13 times to single GPU. Therefore, the MPI + CUDA hybrid granularity parallel method proposed in this paper also has the advantages of high computational efficiency of the GPU and MPI to expand the simulation scale.

Magnetic bearings have been used in flywheel energy storage systems to improve their performance because these kinds of bearings can provide non-contact supporting so that the friction between the rotor and the bearings is reduced significantly. However, the gyroscopic coupling, parameter coupling, and imbalance force affect the operating performance and stability of a magnetic suspended flywheel energy storage system with asymmetric rotor; therefore, the main purpose of this study is to propose a control method for achieving decoupling and stable operation of the aforementioned system. To this end, after deriving the mathematical model of a radial 4-degree-of-freedom rotor–bearing system, a novel cross-feedback-based modal decoupling controller is designed for vibration suppression caused by gyroscopic coupling, parameter coupling, and imbalance force. Better performance is obtained through comparing the decoupling performance, control performance, and disturbance rejection performance with a traditional decentralized proportional–integral–derivative controller and a cross-feedback controller via ADAMS–MATLAB co-simulation technology and experimental results.

Glioblastoma is the most common malignant tumor in central nervous system (CNS), and it is still insurmountable and has a poor prognosis. The proliferation and survival mechanism of glioma cells needs to be explored further for the development of glioma treatment. Hematopoietic-substrate-1 associated protein X-1 (HAX-1) has been reported as an anti-apoptosis protein that plays an important role in several malignant tumors. However, the effect and mechanism of HAX-1 in glioblastomas remains unknown. This study aimed to investigate the effect of HAX-1 in glioblastoma cells and explore the mechanism. The results of clone formation and Edu proliferation assay showed slower multiplication in HAX-1 knock-out cells. Flow cytometry showed cell cycle arrest mainly in G0/G1 phase. Apoptosis due to oxidative stress was increased after HAX-1 was knocked out. Western-blot assay exhibited that the levels of p21, Bax, and p53 proteins were significantly raised, and that the activation of the caspase cascade was enhanced in the absence of HAX-1. The degradation rate and ubiquitination of p53 declined because of the decrease in phosphorylation of proteins MDM2 and Akt1. Co-immunoprecipitation (Co-IP) and immunefluorescent co-localization assays were performed to test the influence of HAX-1 on the interaction between Akt1 and Hsp90, which is crucial for the activity of Akt1. In conclusion, this novel study suggested that HAX-1 could affect the Akt1 pathway through Hsp90. The knock-out of HAX-1 leads to the inactivity of the Ak1t/MDM2 axis, which leads to increased levels of p53, and finally generates cell cycle arrest and results in the apoptosis of glioblastoma cells.

To meet the requirements of riser safety monitoring in offshore oil fields, a new Fiber Bragg Grating (FBG)-based bundle-structure riser stress monitoring sensor has been developed. In cooperation with many departments, a 49-day marine test in water depths of 1365 m and 1252 m was completed on the “HYSY-981” ocean oil drilling platform. No welding and pasting were used when the sensor was installed on risers. Therefore, the installation is convenient, reliable and harmless to risers. The continuous, reasonable, time-consistent data obtained indicates that the sensor worked normally under water. In all detailed working conditions, the test results show that the sensor can do well in reflecting stresses and bending moments both in and in magnitude. The measured maximum stress is 132.7 MPa, which is below the allowable stress. In drilling and testing conditions, the average riser stress was 86.6 MPa, which is within the range of the China National Offshore Oil Corporation (CNOOC) mechanical simulation results.

Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.

In this study, the key technologies of a 6-m long bearing steel ingot produced by electroslag remelting withdrawing (ESRW) process, including bifilar mode supply, slag system development, and design of mold, were studied based on the laboratory research achievements. The 6-m long ingot of bearing steel GGr15 with a cross-section of 300 mm × 340 mm was produced using the ESRW process with a bifilar mode and a multi-taper T-mold in a plant. The testing results show that the melting rate using the ESRW bifilar mode technology is three times faster than traditional electroslag remelting (ESR), and the power consumption is only 1,320 kWh per ton steel. Through testing for the chemical composition, macrostructure and inclusions of remelted ingot, it can be concluded that the ESRW bifilar mode technology not only retains the characteristics of traditional ESR, but also improves the production efficiency and reduces the cost compared to traditional ESR.

BackgroundCoagulation factor V (FV) plays a key role in hemostasis, is present in plasma and platelets, and has both pro‐ and anticoagulant properties; however, the contribution of platelet‐derived FV to arterial thrombosis remains undetermined. Methods and ResultsUsing transgenic mice with various levels of FV gene expression that was restricted to the plasma or platelets, the roles of platelet FV were evaluated in the regulation of arterial thrombosis and platelet activation. Mice with higher levels of platelet FV exhibited faster thrombotic occlusion of the carotid artery after injury compared with mice with lower platelet FV levels. Infusion of platelets with higher levels of FV into transgenic mice with undetectable levels of platelet FV reduced the time to carotid artery occlusion. In contrast, infusion of purified recombinant plasma FV into mice with undetectable platelet FV levels failed to reduce the carotid occlusion times following injury. Evaluation of isolated platelets revealed that platelet‐derived FV was critical for the regulation of platelet activation. These effects were associated with an increased level of expression of P‐selectin and increased cGMP in platelets. ConclusionsWe established that platelet‐derived FV is a critical mediator of arterial thrombosis that involves platelet activation.

This study establishes a dynamic panel model for 12 Chinese-listed commercial banks and seven international commercial banks. More specifically, it examines the impact of green credit on the profitability of commercial banks and the differences between China and other countries while using the generalized method of moments. The research shows that the Equatorial Principles project-financing ratio of international banks positively affects bank profitability, while the ratio of green credit for Chinese commercial banks is inversely related to their profitability. Further, a comparative study of China and other countries highlights that the green credit business is at significantly different stages in China and the rest of the world. This study also finds that the profitability of China’s banking sector is positively affected by asset size, management expense ratio, cash ratio, and GDP growth rate, in addition to the common influencing factor of non-performing loan ratio, whereas asset size and capital adequacy ratio negatively affects the international banking sector. Drawing on these empirical conclusions, this study offers suggestions for the further development of green credit in Chinese commercial banks.

Green fluorescent protein (GFP) is widely used as a biomarker in living systems; however, GFP and its variants are prone to forming low-affinity dimers under physiological conditions. This undesirable tendency is exacerbated when fluorescent proteins (FP) are confined to membranes, fused to naturally-oligomeric proteins, or expressed at high levels in cells. Oligomerization of FPs introduces artifacts into the measurement of subunit stoichiometry, as well as interactions between proteins fused to FPs. Introduction of a single mutation, A206K, has been shown to disrupt hydrophobic interactions in the region responsible for GFP dimerization, thereby contributing to its monomerization. Nevertheless, a detailed understanding of how this single amino acid-dependent inhibition of dimerization in GFP occurs at the atomic level is still lacking. Single-molecule experiments combined with computational microscopy (atomistic molecular dynamics) revealed that the amino group of A206 contributes to GFP dimer formation via a multivalent electrostatic interaction. We further showed that myristoyl modification is an efficient mechanism to promote membrane attachment of GFP. Molecular dynamics-based site-directed mutagenesis has been used to identify the key functional residues in FPs. The data presented here have been utilized as a monomeric control in downstream single-molecule studies, facilitating more accurate stoichiometry quantification of functional protein complexes in living cells.

Airborne laser scanning (ALS) point cloud classification is a challenge due to factors including complex scene structure, various densities, surface morphology, and the number of ground objects. A point cloud classification method is presented in this paper, based on content-sensitive multilevel objects (point clusters) in consideration of the density distribution of ground objects. The space projection method is first used to convert the three-dimensional point cloud into a two-dimensional (2D) image. The image is then mapped to the 2D manifold space, and restricted centroidal Voronoi tessellation is built for initial segmentation of content-sensitive point clusters. Thus, the segmentation results take the entity content (density distribution) into account, and the initial classification unit is adapted to the density of ground objects. The normalized cut is then used to segment the initial point clusters to construct content-sensitive multilevel point clusters. Following this, the point-based hierarchical features of each point cluster are extracted, and the multilevel point-cluster feature is constructed by sparse coding and latent Dirichlet allocation models. Finally, the hierarchical classification framework is created based on multilevel point-cluster features, and the AdaBoost classifiers in each level are trained. The recognition results of different levels are combined to effectively improve the classification accuracy of the ALS point cloud in the test process. Two scenes are used to experimentally test the method, and it is compared with three other state-of-the-art techniques.

This paper calculates the influence and induction coefficient based on the input-output theory, in order to evaluate the current situation of Beijing’s service industry and its effects on regional development. With online comparison, the author concludes that the service sector is getting more and more important on economic development, while the second industry is still the pillar of growth. The author also finds that the impact of service sector’s influence coefficient on the growth rate of regional economy and the scope of industry is weaker than the induction coefficient. At last, this paper shows that the fundamental compelling power for Beijing’s service development is from the demand side of market, and this gives the benchmark point for policy making in service sector.

To provide a theoretical and practical foundation for ramie genetic analysis, simple sequence repeats (SSRs) were identified in the ramie genome and employed in this study. From the 115 369 sequences of a specific-locus amplified fragment library, a type of reduced representation library obtained by high-throughput sequencing, we identified 4774 sequences containing 5064 SSR motifs. SSRs of ramie included repeat motifs with lengths of 1 to 6 nucleotides, and the abundance of each motif type varied greatly. We found that mononucleotide, dinucleotide, and trinucleotide repeat motifs were the most prevalent (95.91%). A total of 98 distinct motif types were detected in the genomic-SSRs of ramie. Of them, The A/T mononucleotide motif was the most abundant, accounting for 41.45% of motifs, followed by AT/TA, accounting for 20.30%. The number of alleles per locus in 31 polymorphic microsatellite loci ranged from 2 to 7, and observed and expected heterozygosities ranged from 0.04 to 1.00 and 0.04 to 0.83, respectively. Furthermore, molecular identity cards (IDs) of the germplasms were constructed employing the ID Analysis 3.0 software. In the current study, the 26 germplasms of ramie can be distinguished by a combination of five SSR primers including Ibg5-5, Ibg3-210, Ibg1-11, Ibg6-468, and Ibg6-481. The allele polymorphisms produced by all SSR primers were used to analyze genetic relationships among the germplasms. The similarity coefficients ranged from 0.41 to 0.88. We found that these 26 germplasms were clustered into five categories using UPGMA, with poor correlation between germplasm and geographical distribution. Our study is the first large-scale SSR identification from ramie genomic sequences. We have further studied the SSR distribution pattern in the ramie genome, and proposed that it is possible to develop SSR loci from genomic data for population genetics studies, linkage mapping, quantitative trait locus mapping, cultivar fingerprinting, and as genetic diversity studies.

Although quorum-sensing (QS) systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS). Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR), and its C-terminal HTH (helix-turn-helix) domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator). Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

In the control of the rotary crane, it is important to consider the trade-off between the boom positioning characteristics and the sway of the load. However, it seems difficult to obtain good control performance in both of them using 1-degree-of-freedom control approach. Therefore, a robust 2-degree-of-freedom control approach is proposed in this article. First, a linear dynamic model of a rotary crane is derived using a disturbance observer. Next, a state feedback controller with integrator is designed based on the model, and controller gains are determined by using linear matrix inequality optimization for achieving robustness with respect to rope length variance. Then, a feedforward controller is designed by solving an optimal regulator problem based on the model of closed-loop system for improving the boom positioning characteristics of the crane. Finally, the experimental results confirm the effectiveness of the proposed method. Hence, the crane can be easily operated without sensor systems for measuring rope length, and consequently, the structure of the crane can be simplified and implementation cost can be reduced.

Carotenoid biosynthetic pathway produces not only pigments that protect photosynthetic system against photo-oxidative damage, but also precursors of abscisic acid, the major hormone regulates stress responses. To understand the response of carotenoid biosynthetic pathway to salt stress, the expression of the genes involved in carotenoid and ABA biosynthesis were compared in cultivated tomato Solanum lycopersicon cv. Moneymaker and its relative wild genotype S. pimpinellifolium (PI365967) together with the contents of carotenoids and ABA. The results showed that 11 of the 15 genes investigated were up-regulated and four unaltered in Moneymaker after 5 h of salt stress; whereas only four genes were up-regulated, four unaltered, and seven down-regulated in PI365967 after stress. Further comparison revealed that 11 salinity-induced genes were expressed significantly lower in Moneymaker than in PI365967 under normal condition, and 8 of them were induced to similar levels after salt stress. In consistence, ABA level was doubled in Moneymaker but kept consistent in PI365967 after salt stress, though the contents of neoxanthin, violaxanthin, β-carotene, lutein, and total carotenoids were kept unchanged in both species. Since it is known that PI365967 is more tolerant to salt stress than Moneymaker, we proposed that the constitutive high level of carotenoid and ABA biosynthetic pathway under normal growth condition could be benefit to PI365967 for establishing the early response to salt stress. In addition, CrtR-b1 and CrtR-b2 that encode β-carotenoid hydroxylases were the only genes in carotenoid biosynthetic pathway that were up-regulated by salt stress in both species. The CrtR-b2 gene was cloned from both species and no essential difference was found in the encoded amino acid sequences. Transformation of CrtR-b2 to tobacco improved the seed germination under salt stress condition, indicating that the hydrolysis of β-carotenoid is the target of transcriptional regulation of the carotenoid biosynthesis in both tomato cultivar and wild relative.

In this work, a rapid extraction method based on ultrasound-assisted extraction (UAE) of syringin from the bark of Ilex rotunda Thumb using response surface methodology (RSM) is described. The syringin was analyzed and quantified by high performance liquid chromatography coupled with UV detection (HPLC-UV). The extraction solvent, extraction temperature and extraction time, the three main factors for UAE, were optimized with Box-Behnken design (BBD) to obtain the highest extraction efficiency. The optimal conditions were the use of a sonication frequency of 40 kHz, 65% methanol as the solvent, an extraction time of 30 min and an extraction temperature of 40 °C. Using these optimal conditions, the experimental values agreed closely with the predicted values. The analysis of variance (ANOVA) indicated a high goodness of model fit and the success of the RSM method for optimizing syringin extraction from the bark of I. rotunda.

A new method based on accelerated solvent extraction (ASE) combined with response surface methodology (RSM) modeling and optimization has been developed for the extraction of four lignans in Fructus Schisandrae (the fruits of Schisandra chinensis Baill). The RSM method, based on a three level and three variable Box-Behnken design (BBD), was employed to obtain the optimal combination of extraction condition. In brief, the lignans schizandrin, schisandrol B, deoxyschizandrin and schisandrin B were optimally extracted with 87% ethanol as extraction solvent, extraction temperature of 160 °C, static extraction time of 10 min, extraction pressure of 1,500 psi, flush volume of 60% and one extraction cycle. The 3D response surface plot and the contour plot derived from the mathematical models were applied to determine the optimal conditions. Under the above conditions, the experimental value of four lignans was 14.72 mg/g, which is in close agreement with the value predicted by the model.

In this paper, ultrasound-assisted extraction (UAE) was applied to the extraction of anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) from Rheum palmatum L. The five anthraquinones were quantified and analyzed by high performance liquid chromatography coupled with UV detection (HPLC-UV). The extraction solvent, extraction temperature and extraction time parameters, the three main factors for UAE, were optimized with response surface methodology (RSM) to obtain the highest extraction efficiency. The optimal conditions were the use of 84% methanol as solvent, an extraction time of 33 min and an extraction temperature of 67 °C. Under these optimal conditions, the experimental values agreed closely with the predicted values. The analysis of variance indicated a high goodness of model fit and the success of RSM method for optimizing anthraquinones extraction in Rheum palmatum L.

The two-component system RhpRS was identified in Pseudomonas syringae as a regulator of the genes encoding the type III secretion system and type III effector proteins (together called the T3 genes). In the absence of the sensor kinase RhpS, the response regulator RhpR represses the induction of the T3 gene regulatory cascade consisting of hrpRS, hrpL, and the T3 genes in a phosphorylation-dependent manner. The repressor activity of RhpR is inhibited by RhpS, which presumably acts as a phosphatase under the T3 gene inducing conditions. Here, we show that RhpR binds and induces its own promoter in a phosphorylation-dependent manner. Deletion and mutagenesis analyses revealed an inverted repeat (IR) element, GTATC-N6-GATAC, in the rhpR promoter that confers the RhpR-dependent induction. Computational search of the P. syringae genomes for the putative IR elements and Northern blot analysis of the genes with a putative IR element in the promoter region uncovered five genes that were upregulated and two genes that were downregulated in an RhpR-dependent manner. Two genes that were strongly induced by RhpR were assayed for the IR element activity in gene regulation and, in both cases, the IR element mediated the RhpR-dependent gene induction. Chromatin immunoprecipitation assays indicated that RhpR binds the promoters containing a putative IR element but not the hrpR and hrpL promoters that do not have an IR element, suggesting that RhpR indirectly regulates the transcriptional cascade of hrpRS, hrpL, and the T3 genes.

Electroslag remelting cladding (ESRC) with a t-shape current carrying mold was adopted to make a compound roll including a working layer and mandrel. A comprehensive coupled transient model was established to reveal the basic phenomena of electromagnetic fields, flow fields, temperature fields, and multiphase flow. Meanwhile, the movement of the mandrel and working layer relative to the slag pool was simulated by dynamic mesh technology to reveal the interface bonding mechanism. The mechanism is as follows: The temperature of the mandrel increases and the mandrel melts slightly when the mandrel passes through the slag pool. The fusion layer is a mixture of molten steel of mandrel and working layer that is the connector between the mandrel and the working layer. Therefore, the interface bonding quality is dependent on a fusion layer that is affected by the voltage/power. The investigation indicates that the fusion layer thickness is between 2 and 4 mm in the condition of 40 V that benefits from obtaining a good interface bonding quality.

In the present study, a new electroslag cladding method by using of the advanced current supplying mold technology was used for manufacturing the high speed steel (HSS)/ductile cast iron (DCI) composite roll. The graphite morphology, matrix microstructure, elements distribution, carbides morphology, and carbides composition have been investigated by means of optical microscope (OM), scanning electron microscope (SEM), and energy dispersive spectroscopy (EDS). With increasing distance from the HSS side, a transition of graphite morphology from naught to existence and from small and dispersed to large and nonuniform was obtained at the interface. It was closely related to the fact that graphite in DCI participated in the phase change and the roll core surface and its nearby positions was heated to a high temperature by the liquid slag during the whole electroslag cladding process. Due to the combined effects of melting and elements diffusion, a significant migration of the alloying elements have occurred through the line scan analysis. Based on this, different types of carbides with the morphology and composition were found at the bonding interface. In addition, no obvious slag inclusions, porosity, shrinkage and other defects at the bonding interface were found. Results of the tensile test also illustrated that the bonding interface had a good quality and it could fully meet the requirements of the roll.

Pseudomonas syringae bacteria utilize the type III secretion system (T3SS) to deliver effector proteins into host cells. The T3SS and T3 effector genes (together called the T3 genes hereafter) are repressed in nutrient-rich medium but rapidly induced after the bacteria are transferred into minimal medium or infiltrated into plants. The induction of the T3 genes is mediated by HrpL, an alternative sigma factor that recognizes the conserved hrp box motif in the T3 gene promoters. The induction of hrpL is mediated by HrpR and HrpS, two homologous proteins that bind the hrpL promoter. To identify additional genes involved in regulation of the T3 genes, we screened for the P. syringae pv. phaseolicola NPS3121 transposon-tagged mutants with reduced induction of avrPto-luc and hrpL-luc, reporter genes for promoters of effector gene avrPto and hrpL, respectively. Determination of the transposon-insertion sites revealed genes with putative functions in signal transduction and transcriptional regulation, protein synthesis, and basic metabolism. A transcriptional regulator (AefRNPS3121) was identified in our screen that is homologous to AefR of P. syringae pv. syringae strain B728a, a regulator of the quorum-sensing signal and epiphytic traits, but was not known to regulate the T3 genes. AefRNPS3121 in P. syringae pv. phaseolicola NPS3121 and AefR in P. syringae pv. syringae B728a behave similarly in regulating the quorum-sensing signal in liquid medium but differ in regulating the epiphytic traits, including swarming motility, leaf entry, and epiphytic survival.

The bacterial Lon protease participates in a variety of biological processes. In Pseudomonas syringae, mutation of lon is known to activate hrpL and a few hrpL-regulated genes in rich medium. The elevated expression of hrpL and hrpL-regulated genes results from increased stability of HrpR, the transcriptional activator of hrpL, in the lon mutant. Here, we conducted a microarray analysis to identify genes that are differentially expressed in a lon¯ mutant of P. syringae pv. tomato DC3000 grown in the rich medium King's B (KB). Most genes induced in the lon¯ mutant belong to the HrpL regulon or are related to transcription, protein synthesis, and energy metabolism. A major group of genes reduced in the lon¯ mutant are related to cell wall biogenesis. The HrpL-regulated genes exhibit different induction patterns in the lon¯ mutant, suggesting that additional regulators other than HrpL are likely to be involved in regulation of these genes. Compared with the wild-type bacteria, lon¯ mutants of P. syringae pv. tomato DC3000 and P. syringae pv. phaseolicola NPS3121 strains exhibit elevated hrpL expression in KB medium, but reduced hrpL expression in minimal medium (MM). The reduced hrpL RNA is correlated with reduced hrpR and hrpS RNAs, suggesting that the Lon-mediated regulation of hrpL involves different mechanisms in KB and MM. The lon¯ mutation also reduced bacterial pathogenicity.

The Pseudomonas syringae type III secretion system (T3SS) is induced during interaction with the plant or culture in minimal medium (MM). How the bacterium senses these environments to activate the T3SS is poorly understood. Here, we report the identification of a novel two-component system (TCS), RhpRS, that regulates the induction of P. syringae T3SS genes. The rhpR and rhpS genes are organized in an operon with rhpR encoding a putative TCS response regulator and rhpS encoding a putative biphasic sensor kinase. Transposon insertion in rhpS severely reduced the induction of P. syringae T3SS genes in the plant as well as in MM and significantly compromised the pathogenicity on host plants and hypersensitive response-inducing activity on nonhost plants. However, deletion of the rhpRS locus allowed the induction of T3SS genes to the same level as in the wild-type strain and the recovery of pathogenicity upon infiltration into plants. Overexpression of RhpR in the ΔrhpRS deletion strain abolished the induction of T3SS genes. However, overexpression of RhpR in the wild-type strain or overexpression of RhpR(D70A), a mutant of the predicted phosphorylation site of RhpR, in the ΔrhpRS deletion strain only slightly reduced the induction of T3SS genes. Based on these results, we propose that the phosphorylated RhpR represses the induction of T3SS genes and that RhpS reverses phosphorylation of RhpR under the T3SS-inducing conditions. Epistasis analysis indicated that rhpS and rhpR act upstream of hrpR to regulate T3SS genes.

Aims. To explore the effects and mechanisms of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Methods. Subcutaneous injections of CCl4 were given to establish a rat model of liver cirrhosis and portal hypertension. Biomechanical technology was adopted to determine the dynamic changes of haemodynamic indices and fluid shear stress. Nitric oxide (NO), synthase (NOS), and endothelin-1 (ET-1) of the portal vein blood were measured. Changes in geometric structure and ultrastructure of the portal vein were observed using optical and electron microscopy. Results. After the CC14 injections, rat haemodynamics were notably altered. From week 4 onwards, PVP, PVF, and PVR gradually and significantly increased (P

Non-viral gene delivery system with many advantages has a great potential for the future of gene therapy. One inherent obstacle of such approach is the uptake by endocytosis into vesicular compartments. Receptor-mediated gene delivery method holds promise to overcome this obstacle. In this study, we developed a receptor-mediated gene delivery system based on a combination of the Pseudomonas exotoxin A (PE), which has a receptor binding and membrane translocation domain, and the hyperthermophilic archaeal histone (HPhA), which has the DNA binding ability. First, we constructed and expressed the rPE-HPhA fusion protein. We then examined the cytotoxicity and the DNA binding ability of rPE-HPhA. We further assessed the efficiency of transfection of the pEGF-C1 plasmid DNA to CHO cells by the rPE-HPhA system, in comparison to the cationic liposome method. The results showed that the transfection efficiency of rPE-HPhA was higher than that of cationic liposomes. In addition, the rPE-HPhA gene delivery system is non-specific to DNA sequence, topology or targeted cell type. Thus, the rPE-HPhA system can be used for delivering genes of interest into mammalian cells and has great potential to be applied for gene therapy.

Pseudomonas syringae pv. tomato DC3000 is a model pathogen infecting tomato and Arabidopsis plants. Genes encoding the type III secretion system and substrate proteins (collectively called TTSS genes) of this bacterium are induced in plants and in minimal medium (MM). The induction of TTSS genes is mediated by HrpL, an alternative sigma factor recognizing the hrp box in the promoter of TTSS genes. The transcription of hrpL is activated by HrpR and HrpS, two homologous DNA-binding proteins encoded by the hrpRS operon. Microarray analysis was conducted to evaluate the DC3000 genes regulated by hrpL and hrpRS in MM. The analysis identified a number of novel hrpL-activated genes with a putative TTSS-independent function. Genes regulated by hrpL were mostly regulated by hrpRS in the same manner, but a large number of genes regulated by hrpRS were hrpL-independent, indicating that hrpL represents one branch of the regulatory pathways downstream of hrpRS. The induction of the TTSS genes was associated with downregulation of the housekeeping genes, indicating that the activation of the TTSS has a cost on the basic cellular activities. The novel genes and pathways identified by the microarray provide new insight into the bacterial functions coordinating with the TTSS.

Nature Communications 7: Article number:11000 (2016); Published 18 March 2016: Updated 6 February 2017 In this Article, we presented a structural and functional characterization of the WalKR two-component system for signal transduction and a small molecule that can target WalKR, and reported the identification of amino acids that were proposed to be required for its signal transduction activity.

The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs.

As an attractive means of expanding mobile network capacity, heterogeneous network is regarded as an important direction of mobile network evolution. To increase the capacity of, for example, hot spots, a typical scenario in heterogeneous network is that the coverage areas of low power nodes (LPNs) are overlapped with macrocell. To increase the utilization of small cells generated by LPNs, cell range extension (CRE) is used to extend the coverage of the small cells by adding cell specific offset (CSO) to small cells during cell selection procedure. The value of CSO, however, needs to be set carefully. In this paper, the capacity of users in macrocells, users in small cells, and users in range extension areas is analyzed thoroughly in conditions with and without CRE. Based on the analysis, an adaptive CSO updating algorithm is proposed. The proposed algorithm updates the CSO value periodically by predicting the overall capacity and a new CSO value is selected which can give the optimal overall capacity. The proposed algorithm is evaluated by system-level simulations. Simulation results indicate that the proposed algorithm can ensure a nearly optimal performance in all tested traffic load situations.

Functional genomic elements, including transposable elements, small RNAs and non-coding RNAs, are involved in regulation of gene expression in response to plant stress. To identify genomic elements that regulate dehydration and alkaline tolerance in Boea hygrometrica, a resurrection plant that inhabits drought and alkaline Karst areas, a genomic DNA library from B. hygrometrica was constructed and subsequently transformed into Arabidopsis using binary bacterial artificial chromosome (BIBAC) vectors. Transgenic lines were screened under osmotic and alkaline conditions, leading to the identification of Clone L1-4 that conferred osmotic and alkaline tolerance. Sequence analyses revealed that L1-4 contained a 49-kb retroelement fragment from B. hygrometrica, of which only a truncated sequence was present in L1-4 transgenic Arabidopsis plants. Additional subcloning revealed that activity resided in a 2-kb sequence, designated Osmotic and Alkaline Resistance 1 (OAR1). In addition, transgenic Arabidopsis lines carrying an OAR1-homologue also showed similar stress tolerance phenotypes. Physiological and molecular analyses demonstrated that OAR1-transgenic plants exhibited improved photochemical efficiency and membrane integrity and biomarker gene expression under both osmotic and alkaline stresses. Short transcripts that originated from OAR1 were increased under stress conditions in both B. hygrometrica and Arabidopsis carrying OAR1. The relative copy number of OAR1 was stable in transgenic Arabidopsis under stress but increased in B. hygrometrica. Taken together, our results indicated a potential role of OAR1 element in plant tolerance to osmotic and alkaline stresses, and verified the feasibility of the BIBAC transformation technique to identify functional genomic elements from physiological model species.

Natural variation for primary root growth response to high Ca stress in Arabidopsis thaliana was studied by screening a series of accessions (ecotypes) under high Calcium (40 mM CaCl2) conditions. The genetic basis of this variation was further investigated by QTL analysis using recombinant inbred lines from Landsberg erecta (Ler) × Cape Verde Islands (Cvi) cross. Four QTLs were identified in chromosome 1, 2 and 5,and named response to high Calcium (RHCA) 1-4. The three QTLs (RHCA1, RHCA2 and RHCA4) were further confirmed by analysis of near isogenic lines harboring Cvi introgression fragments in Ler background. Real-time PCR analysis showed that several genes associated with high Ca response including SMT1 and XHT25 have changed expression pattern between Ler and near isogenic lines. These results were useful for detecting molecular mechanisms of plants for high Ca adaption.

Although Pseudomonas syringae uses the two-component system RhpRS to modulate the expression of type III secretion system (T3SS) genes and pathogenicity, the molecular mechanisms and the regulon of RhpRS have yet to be fully demonstrated. We have performed a genome-wide analysis of RhpR binding to DNA prepared from P. syringae pv. phaseolicola in order to identify candidate direct targets of RhpR-mediated transcriptional regulation, as described in our recent article [1]. The data are available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE58533. Here we describe the detailed methods and data analyses of our RhpR ChIP-seq dataset.