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An open path synthesis method for a spatial revolute-revolute-spherical-spherical (RRSS) mechanism is presented in this paper. The mathematical model for the trajectory curve is established. The characteristics of an RRSS mechanism in a standard installation position are revealed: the projection points of the coupler curve on the Oxy plane rotate by the corresponding input angles around the z-axis, and the generated points lie on an ellipse. Based on this finding, a 17-dimensional path generation problem can be translated into two lower-dimensional matching recognition problems and one actual size and installation position calculation problem. The path generation can be achieved by three steps. First, a database of four dimensional rotation angle parameters is established. By comparing the similarities between the mechanism feature curve of the prescribed open curve and its corresponding mechanism feature ellipse (MFE), the angles of installation, the initial angle of the input link, and the elliptic feature parameters of the desired RRSS mechanism can be approximately determined. Then, a 13-dimensional dynamic self-adapting numerical atlas database is established, which contains six basic dimensional types (BDTs) and seven wavelet feature parameters, and the BDTs of the desired RRSS mechanism are obtained. Finally, based on the relationship between the MFE of the prescribed curve and the BDTs of the desired RRSS mechanism, the calculation models for the actual link lengths and installation positions of the desired RRSS mechanism were established. Three examples are presented in this paper.

In this paper, a wavelet feature parameters method is proposed for non-periodic function generation of a spatial Revolute-Spherical-Spherical-Revolute (RSSR) mechanism. The mathematical model for the output function of an RSSR mechanism is established. The wavelet coefficients, including wavelet approximations and wavelet details, are extracted from the output function curve using a Daubechies wavelet. Based on the geometric significance of the wavelet coefficients, the wavelet details are used to describe the output function of an RSSR mechanism to eliminate the influence of translations of output function curve. The level of wavelet feature parameters is determined according to the relationship between the original output function curves and the reconstruction curves generated by wavelet coefficients. A numerical atlas database is established, which contains more than ten million groups of basic dimensional types. Based on a fuzzy reorganization method, the desired RSSR mechanism can be obtained. The non-periodic function synthesis of the RSSR mechanism is realized. An example is presented to demonstrate the efficacy and practicality of the proposed theory.

In this study, ultralow friction coefficient (COF, μ < 0.01) was obtained through polyalkylene glycol (PAG) aqueous solutions with different molecular weights (MWs) ranging from 270 to 3930 g·mol-1 under ambient conditions. With the increase in the MWs of PAG molecules, the threshold concentration to obtain this type of superlubric behavior gradually changed from 90 to 60 wt %. This phenomenon was closely related to the interaction between PAG chains and water molecules and the state of chemical binding. In the superlubricity system, superior load-bearing capacity was achieved at optimal threshold concentrations of all PAG aqueous solutions wherein multilayered adsorption layers that consisted of fully hydrated PAG molecules were formed on the sliding solid surfaces. With respect to the concentration below the threshold value, the existence of a shearing layer was indicated to play a significant role. Thus, the synergetic effect of sufficient adsorption of molecules and the unique shear rheology of the PAG aqueous solution were essential to achieve superlubricity.

As a convenient, effective and economical kidney replacement therapy for end-stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long-term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose-induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen-rich peritoneal dialysate. In addition, in vitro studies of high glucose-induced peritoneal fibrosis were performed using MeT-5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti-peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.

In recent years, the Chinese government has vigorously promoted the development of concentrating solar power (CSP) technology. For the commercialization of CSP technology, economically competitive costs of electricity generation is one of the major obstacles. However, studies of electricity generation cost analysis for CSP systems in China, particularly for the tower systems, are quite limited. This paper conducts an economic analysis by applying a levelized cost of electricity (LCOE) model for 100 MW tower CSP plants in five locations in China with four different molten-salts for thermal energy storage (TES). The results show that it is inappropriate to build a tower CSP plant nearby Shenzhen and Shanghai. The solar salt (NaNO3-KNO3, 60-40 wt.%) has lower LCOE than the other three new molten-salts. In order to calculate the time when the grid parity would be reached, four scenarios for CSP development roadmap proposed by International Energy Agency (IEA) were considered in this study. It was found that the LCOE of tower CSP would reach the grid parity in the years of 2038&ndash, 2041 in the case of no future penalties for the CO2 emissions. This study can provide support information for the Chinese government to formulate incentive policies for the CSP industry.

Temperature rising caused by global warming has imposed significant negative effects on crop qualities and yields. To get the well-known molecular mechanism upon the higher temperature, we carefully analyzed the RNA sequencing-based transcriptomic responses of two contrasting chieh-qua genotypes: A39 (heat-tolerant) and H5 (heat-sensitive). In this study, twelve cDNA libraries generated from A39 and H5 were performed with a transcriptome assay under normal and heat stress conditions, respectively. A total of 8705 differentially expressed genes (DEGs) were detected under normal conditions (3676 up-regulated and 5029 down-regulated) and 1505 genes under heat stress (914 up-regulated and 591 down-regulated), respectively. A significant positive correlation between RNA-Seq data and qRT-PCR results was identified. DEGs related to heat shock proteins (HSPs), ubiquitin-protein ligase, transcriptional factors, and pentatricopeptide repeat-containing proteins were significantly changed after heat stress. Several genes, which encoded HSPs (CL2311.Contig3 and CL6612.Contig2), cytochrome P450 (CL4517.Contig4 and CL683.Contig7), and bHLH TFs (CL914.Contig2 and CL8321.Contig1) were specifically induced after four days of heat stress. DEGs detected in our study between these two contrasting cultivars would provide a novel basis for isolating useful candidate genes of heat stress responses in chieh-qua.

Fusarium wilt results in undesirable effects on the quality and production of chieh-qua (Benincasa hispida Cogn. var. Chieh-qua How). Fusaric acid (FA), a secondary metabolite of biotin produced by pathogens of genus Fusarium, induced resistant responses in chieh-qua, however, the physiological and molecular mechanism(s) of FA resistance remains largely unknown. In our study, ‘A39’ (FA-resistant cultivar) exhibited decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) enzyme activity when exposed to FA compared with ‘H5’ (FA-susceptible cultivar). More apoptosis cells existed in ‘H5’ than ‘A39’ after 2 days of FA treatment. RNA-seq results revealed that a total of 2968 and 3931 differentially expressed genes (DEGs) were detected under normal conditions (1562 up-regulated and 1406 down-regulated) and FA treatment (2243 up-regulated and 1688 down-regulated), respectively. Interestingly, DEGs associated with pathogen-related protein and ethylene (ET) biosynthesis and signal pathways were most significantly changed during FA stress. Notably, several crucial genes encoding pathogenesis-related protein (CL4451.Contig2, CL2175.Contig4), peroxidase (Unigene49615 and CL11695.Contig2), and ET-responsive transcription factors (TFs) (CL9320.Contig1, CL9849.Contig3, CL6826.Contig2, CL919. Contig6, and CL518.Contig7) were specifically induced after FA treatment. Collectively, the study provides molecular data for isolating candidate genes involved in FA resistance, especially ET related genes in chieh-qua.

Pulmonary fungal disease is an emerging issue in immunocompetent patients, for whom the characteristics are only partially understood. We conducted a single-center retrospective study of histologically verified pulmonary fungal disease in Eastern China from 2006 to 2014 to understand the demographics, clinical manifestations, therapeutic approaches, and factors associated with prognosis in this population. All cases were diagnosed according to the 2008 European Organization for the Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infection Diseases Mycoses Study Group definition criteria. A total of 112 cases of pulmonary fungal diseases were enrolled (35 proven, 16 probable, 61 possible), and we analyzed the 35 patients with histologically proven pulmonary fungal diseases in this study. The main fungal species identified were Aspergillus (51.4 %), Cryptococcus (22.9 %), and Mucor (2.4 %). Treatment consisted of antifungal therapeutic agents (54.3 %), surgery and postsurgical agents (25.7 %), or surgery alone (14.3 %). The overall crude mortality rate was 14.3 %, and the mortality due to pulmonary fungal infections was 2.9 %. Significant predictors of mortality by univariate analysis were hypoalbuminemia (P = 0.005), cancer (P = 0.008), and positive culture (P = 0.044). Additionally, hypoalbuminemia was the only risk factor for mortality by multivariate analysis (RR = 7.56, 95 % CI 1.38–41.46). Pulmonary fungal disease in immunocompetent patients, with Aspergillus as the most common identified species, had a prognosis that was influenced by the level of serum albumin.

The abuse of opioids has become a serious problem in the world. In order to help control the use of opioids, this paper established a new spatial-time-based model based on Logistic model and SIR model to analyse the source and threshold of opioids, and then used factor vector association method to study the social factors of drug abuse in the data of NFLIS and the U.S. socio-economic census. Further we optimized the spatial-time-based model and make sensitivity analysis of parameters of model.

Heat stress is a major environmental factor limiting plant productivity and quality in agriculture. Cucumber, one of the most important vegetables among cucurbitaceae, prefers to grow in a warm environment. Until now the molecular knowledge of heat stress in cucumber remained unclear. In this study, we performed transcriptome analysis using two diverse genetic cucumber cultivars, L-9 and A-16 grown under normal and heat stress. L-9 displayed heat-tolerance phenotype with higher superoxide dismutase enzyme (SOD) enzyme activity and lower malondialdehyde (MDA) content than A-16 under heat stress. RNA-sequencing revealed that a total of 963 and 2778 genes are differentially expressed between L-9 and A-16 under normal and heat stress respectively. In addition, we found that differentially expressed genes (DEGs) associated with plant hormones signally pathway, transcription factors, and secondary metabolites showed significantly change in expression level after heat stress, which were confirmed by quantitative real-time PCR assay. Our results not only explored several crucial genes involved in cucumber heat resistance, but also provide a new insight into studying heat stress.

Hydrogen has a significant protective effect on calcium oxalate-induced renal injury, but its effect on metabolic profiles is unknown. This study showed the effects of hydrogen on serum and urine metabolites in a renal injury model. Ultra-HPLC quadrupole time-of-flight-MS-based metabolomics was used to characterise metabolic variations. Twenty-five serum metabolites and 14 urine metabolites showed differences in the the nitrogen and oxygen inhalation (NO), nitrogen and oxygen inhalation combined with calcium oxalate induction (CaOx), and hydrogen inhalation combined with calcium oxalate induction (HO+CaOx) groups. Nineteen serum metabolites and 7 urine metabolites showed significant restoration to normal levels after hydrogen gas (H2) treatment. These metabolites are primarily related to amino acid metabolism, fatty acid metabolism, and phospholipid metabolism. This study showed that a comprehensive metabolomics approach is an effective strategy to elucidate the mechanisms underlying the effects of hydrogen treatment on calcium oxalate-induced renal injury.

As an important fruit vegetable, fruit-related traits have become one of the breeding hotspots of wax gourd (Benincasa hispida). The fruit traits have an important role on the quality and yield of wax gourd, and QTL mapping of these traits will provide solid basis for fruit character improvement as well as high-yield breeding. In this study, the inheritance of four fruit-related traits, including fruit weight (FW), fruit length (FL), fruit diameter (FD) and flesh thickness (FT), was analyzed. All the frequency distribution of the four traits in an F2 population showed a single peak skewed distribution, which proved them to be quantitative. Subsequently, based on the high-density genetic map using 140 F2 individuals, nine QTLs associated with the four traits were detected on chromosome 3, 4, 5, 6, 9, 10 and 11. Four of the nine QTLs had major effect, which were responsible for more than 10.0% of phenotypic variance. Furthermore, the major QTLs of FW, FD and FT shared similar location intervals, which implied that this location might contain some pleiotropic genes. This is the first report on QTL mapping of quantitative trait in wax gourd, which plays an important role for fine mapping of these important fruit traits.

Drought stress is one of the most serious threats to cucumber quality and yield. To gain a good understanding of the molecular mechanism upon water deficiency, we compared and analyzed the RNA sequencing-based transcriptomic responses of two contrasting cucumber genotypes, L-9 (drought-tolerant) and A-16 (drought-sensitive). In our present study, combining the analysis of phenotype, twelve samples of cucumber were carried out a transcriptomic profile by RNA-Seq under normal and water-deficiency conditions, respectively. A total of 1008 transcripts were differentially expressed under normal conditions (466 up-regulated and 542 down-regulated) and 2265 transcripts under drought stress (979 up-regulated and 1286 down-regulated). The significant positive correlation between RNA sequencing data and a qRT-PCR analysis supported the results found. Differentially expressed genes (DEGs) involved in metabolic pathway and biosynthesis of secondary metabolism were significantly changed after drought stress. Several genes, which were related to sucrose biosynthesis (Csa3G784370 and Csa3G149890) and abscisic acid (ABA) signal transduction (Csa4M361820 and Csa6M382950), were specifically induced after 4 days of drought stress. DEGs between the two contrasting cultivars identified in our study provide a novel insight into isolating helpful candidate genes for drought tolerance in cucumber.

In this paper, the nonperiodic function synthesis of an RCCC mechanism is presented using a wavelet feature parameter (WFP) method. The output function and the sliding displacement of the RCCC mechanism are described by the wavelet approximate and wavelet details. Based on the relationship of wavelet details of the sliding displacement and its scaling, a normalization method for wavelet details of the sliding displacement is presented. The influence of proportional scaling of the linkage lengths is eliminated. An adaptive database is established. The problem of nonperiodic design requirements of RCCC mechanism function synthesis is solved. To demonstrate the feasibility of this method, two numerical examples are proposed. Based on the nonperiodic design requirements, the RCCC mechanisms are designed and simulated using matlab and catia software. The results show that the method proposed is effective for nonperiodic function generation of the RCCC mechanism with multiple positions.

In this study, a synthesis method for a non-integer periodic function generator of a four-bar mechanism using a Haar wavelet is presented. Using wavelet theory, the mathematical model for the output of a four-bar mechanism is established. Next, the characteristics of the four-bar mechanism output variable are described by the wavelet feature parameters; the relationship of the wavelet feature parameters between the output and its translation or dilation is also investigated. Based on this finding, three numerical atlas databases comprising of 203,500 groups of basic dimensional types of planar four-bar mechanisms, 148,995 groups of basic dimensional types of spherical four-bar mechanism and 11,175 groups of basic dimensional types of planar slider–crank mechanism are compiled. According to the internal relationship between the wavelet feature parameters, the sizes of the objective mechanism can be obtained using fuzzy recognition. Based on a genetic algorithm, optimization of the link parameters can be re...

Layered double hydroxides (LDHs) are a class of naturally occurring inorganic minerals that are composed of divalent and trivalent metal cations. In this study, three different sized NiAl-LDH nanoplatelets were synthesized by varying crystallization time during the microemulsification process. The layered structure and three-dimensional size of nanoplatelets were confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). As lubricant additives, their tribological properties in base oil were evaluated by use of a ball-on-disk reciprocating tribometer under three different loads: 50, 100, and 150 N (which created peak Hertz pressures of 1.74, 2.16, and 2.47 GPa). Under contact pressures of up 2.16 GPa, not only did the coefficient of friction (COF) decrease by about 10% after nano-LDHs were added but also the wear performance improved substantially. These improvements resulted from a protective tribolayer formation on the contact interface, as revealed by detailed surface and structure analytical studies. In particular, cross-sectional TEM images revealed that the larger size nanoplatelets (NiAl-24h), rather than the smaller ones (NiAl-6h) showed the best and most stable tribological performance. This was mainly because of their higher degree of crystallinity, which in turn resulted in the formation of a tribofilm with far superior mechanical properties during sliding. Owing to the simple synthetic method and superior tribological properties as oil-based additives, nano-LDHs hold great potential for use in demanding industrial applications in the future.

The WRKY transcription factors play an important role in plant resistance for biotic and abiotic stresses. In the present study, we cloned 10 WRKY gene homologs (CqWRKY) in Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua) using the rapid-amplification of cDNA ends (RACE) or homology-based cloning methods. We characterized the structure of these CqWRKY genes. Phylogenetic analysis of these sequences with cucumber homologs suggested possible structural conservation of these genes among cucurbit crops. We examined the expression levels of these genes in response to fusaric acid (FA) treatment between resistant and susceptible Chieh-qua lines with quantitative real-time PCR. All genes could be upregulated upon FA treatment, but four CqWRKY genes exhibited differential expression between resistant and susceptible lines before and after FA application. CqWRKY31 seemed to be a positive regulator while CqWRKY1, CqWRKY23 and CqWRKY53 were negative regulators of fusaric resistance. This is the first report of characterization of WRKY family genes in Chieh-qua. The results may also be useful in breeding Chieh-qua for Fusarium wilt resistance.

Wax gourd (2n=2x=24) is an important vegetable species in Cucurbitaceae. Because it can be stored for a very long period of time, it plays an important role in ensuring the annual supply and regulating off-season supply of the vegetables. However, the availability of genetic information about wax gourd is limited. This study aimed to identify the useful genetic information for wax gourd. The conserved domains of reverse transcriptase (RT) genes of Ty1-copia retrotransposons were isolated from the genome of wax gourd using degenerate oligonucleotide primers. A total of twenty eight RT sequences were obtained, which showed high heterogeneity with the similarity ranging from 47.5% to 94.3%. Sixteen (57.1%) of them were found to be defective, being disrupted by stop codons and/or frameshift mutations. These 28 sequences were divided into five subfamilies. The comparative phylogenetic analysis with other Cucurbitaceae species from GenBank database showed that most retrotransposons derived from the same genus tended to cluster together, although there were a few exceptions. These results indicate that both vertical transmission and horizontal transmission are the sources of Ty1-copia retrotransposons in wax gourd. Fluorescent in situ hybridization (FISH) with Ty1-copia retrotransposon sequences as probes revealed that this kind of retrotransposons had a dispersed genomic organization, physically distributed among all the chromosomes of wax gourd, with clusters in the heterochromatin regions. This is the first report of Ty1-copia retrotransposons in wax gourd, which would be helpful for our understanding about the organization and evolutions of wax gourd genome and also provide valuable information for our utilization of wax gourd retrotransposons.

Manipulating charge generation in a broad spectral region has proved to be crucial for nonfullerene-electron-acceptor-based organic solar cells (OSCs). 16.64% high efficiency binary OSCs are achieved through the use of a novel electron acceptor AQx-2 with quinoxaline-containing fused core and PBDB-TF as donor. The significant increase in photovoltaic performance of AQx-2 based devices is obtained merely by a subtle tailoring in molecular structure of its analogue AQx-1. Combining the detailed morphology and transient absorption spectroscopy analyses, a good structure-morphology-property relationship is established. The stronger π-π interaction results in efficient electron hopping and balanced electron and hole mobilities attributed to good charge transport. Moreover, the reduced phase separation morphology of AQx-2-based bulk heterojunction blend boosts hole transfer and suppresses geminate recombination. Such success in molecule design and precise morphology optimization may lead to next-generation high-performance OSCs.

In recent years, Chinese government is vigorously developing concentrating solar power (CSP) technology. It is one of the most promising renewable-based electricity generation technologies to deal with the increasing demand of electricity consumption and environmental sustainability. For the commercialization of CSP technology, low cost is a precondition. However, studies of electricity generation cost analysis for CSP systems, particularly for the tower systems, in China are quite limited. This paper conducts an economic analysis by applying the levelized cost of electricity (LCOE) model for 100 MW tower CSP plants in various locations in China with four different molten salts for thermal energy storage (TES). The results show that it’s inappropriate to build a CSP plant nearby Shenzhen and Shanghai since their LCOEs are higher than 6 RMB kWh−1. There is an optimal capacity of TES resulting in the lowest LCOE for a certain tower CSP plant. And the solar salt has lower LCOE than the other three new molten salts. In order to calculate the time when the grid parity will be reached, four scenarios for CSP development roadmap proposed by International Energy Agency (IEA) are considered in this study. It can be found that the grid parity of tower CSP electricity would be reached in the years of 2038-2041 in the case of no future penalties for the CO2 emissions, and bring forward about 7-14 years when considering the penalties for the CO2 emissions. This research can provide support for government to formulate incentive policies for the CSP industry.

In the era of big data, the rapid development of mobile participatory sensing devices brings the explosive expansion of data, making information overload a serious problem. In this case, a personalized recommendation system on mobile social media appears. Collaborative filtering is the most widely used approach in a recommendation system. Nevertheless, there still exist many problems, such as the serious data sparsity problem and the cold start problem. Existing approaches cannot effectively solve these problems. Most of the existing recommendation approaches are based on single information source and cannot effectively solve the cold start and data sparsity problems. In addition, some approaches proposed to solve data sparsity fail to consider the effects of users’ influences and prediction order on recommendation accuracy. Accordingly, from the perspective of increasing the categories of information, the similarity propagation approach based on a heterogeneous network is proposed to ease the cold start problems by improving the similarity calculation method. In addition, to ease the data sparsity problems, we propose a hybrid collaborative filtering approach based on a score prediction graph to finish the user-item score matrix in order. Finally, we conduct validation experiments on the MovieLens dataset. Compared with five state-of-the-art approaches, our approach outperforms them in terms of the performances of mean absolute error, root-mean-square error, recall, and diversity.

2 Centre of Molecular Physiology of the Brain (CMPB) at University Medicine GDepartment of Neurology, GGermany Non-technical summary Optical imaging is widely used to map functional areas of the cerebral cortex. We present a method for fast fluorescence imaging of map-level cortical activity using a calciumindicatorprotein.Sensory-evokedneuronalactivitycanbeimagedrepeatedlyinthesame mouseover weeks, enablingnew opportunitiesforthe longitudinalstudyof corticalfunctionand dysfunction. We hope this method will be flexibly applied across different cortical areas and to a variety of newly developed genetically encoded calcium and voltage sensors. Abstract In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methodsforchronicrecordingarelimited.Herewepresentatechniqueforlong-terminvestigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals reportsensory-evokedactivityinanaesthetizedmousesomatosensorycortexwithhighsensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations.

Endotoxin triggers a reorganization of the energy metabolic pathway, including the promotion of fatty acid utilization to adapt to a high energy demand during endotoxemia. However, the factors responsible for the metabolic adaptation and characteristic pathologies resulting from defective utilization fatty acids during endotoxin response have not been fully clarified. The thioredoxin binding protein-2 (TBP-2) knockout (TBP-2) mouse is an animal model of fatty acid oxidation disorder. The aim of this study was to determine whether and how TBP-2 is involved in metabolic regulation in a lipopolysaccharide (LPS)-induced endotoxemia model in mice.Prospective animal trial.Research laboratory.TBP-2 and wild control mice.TBP-2 and wild control mice were intraperitoneally injected with LPS. Mortality, serum levels of markers of hepatorenal injuries, cytokines, insulin, glucose and lipid derivatives, and the hepatic signaling pathway regulating gluconeogenesis were investigated.Following the administration of LPS, TBP-2 mice showed a predisposition for death without any significant elevation of inflammatory cytokines, compared to the wild mice. LPS-challenged TBP-2 mice showed fat deposition in the liver and kidney, organ injuries, glycogen depletion, and elevation of serum lipid derivatives such as free fatty acids, triglyceride and cholesterol. Hyperinsulinemia and hypoglycemia were observed in TBP-2 mice after LPS injection. Death due to the LPS administration was prevented by supplementation of glucose. Phosphorylation of Akt and FoxO1, an inhibitory pathway of gluconeogenesis in the liver of LPS-challenged TBP-2 mice was demonstrated, suggesting the enhancement of insulin signaling.TBP-2 is involved in metabolic control during LPS-induced endotoxemia. After the LPS challenge, TBP-2 mice showed several characteristic aspects, such as hepatorenal injuries, and dysregulation of the lipid and glucose metabolisms. Furthermore, hypoglycemia promoted by hyperinsulinemia may be a critical risk factor for mortality in circumstances in which fatty acid utilization is impaired during endotoxemia.

Cardiomyocyte differentiation is a complex multistep process requiring the proper temporal and spatial integration of multiple signaling pathways. Previous embryological and genetic studies have identified a number of signaling pathways that are critical to mediate the initial formation of the mesoderm and its allocation to the cardiomyocyte lineage. It has become clear that some of these signaling networks work autonomously, in differentiating myocardial cells whereas others work non-autonomously, in neighboring tissues, to regulate cardiac differentiation indirectly. Here, we provide an overview of three signaling networks that mediate cardiomyocyte specification and review recent insights into their specific roles in heart development. In addition, we demonstrate how systems level, 'omic approaches' and other high-throughput techniques such as small molecules screens are beginning to impact our understanding of cardiomyocyte specification and, to identify novel signaling pathways involved in this process. In particular, it now seems clear that at least one chemokine receptor CXCR4 is an important marker for cardiomyocyte progenitors and may play a functional role in their differentiation. Finally, we discuss some gaps in our current understanding of early lineage selection that could be addressed by various types of omic analysis.

Fused-ring electron acceptors (FREAs) have recently received intensive attention. Besides the continuing development of new FREAs, the demand for FREAs featuring good compatibility to donor materials is becoming more and more urgent, which is highly desirable for screening donor materials and achieving new breakthroughs. In this work, a new FREA is developed, ZITI, featuring an octacyclic dithienocyclopentaindenoindene central core. The core is designed by linking 2,7-dithienyl substituents and indenoindene with small methylene groups, in which the indeno[1,2-b]thiophene-2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile part provides a large and unoccupied π-surface. Most notably, ZITI possesses an excellent compatibility with commercially available polymer donors, delivering very high power conversion efficiencies of over 13%.

The processing of any noisy stimuli requires extra means from the nervous system. Several electrophysiological studies have proved that the processing of noise starts approximately 150–200 milliseconds after stimulus onset. This is suggested by the fact that the amplitude of the face-selective N170 component has been reduced and its latency prolonged by adding Gaussian noise to a face stimulus while the earlier P100 component is not influenced by added noise. While previous studies tested the electrophysiological correlates of noisy face perception in humans, the nature of added noise has not been studied yet in relation to face processing. Our goal was to distinguish the effects of added phase-noise from that of another irrelevant, overlapping non-face object (a car) on the electrophysiological correlates of human face processing. Subjects performed a two-alternative gender discrimination task with seven levels of difficulty, equalised between the phase-noise and overlapping object conditions. W...

The feeding-fasting nutritional transition triggers a dynamic change in metabolic pathways and is a model for understanding how these pathways are mutually organized. The targeted disruption of the thioredoxin binding protein-2 (TBP-2)/thioredoxin-interacting protein (Txnip)/VDUP1 gene in mice results in lethality with hypertriglyceridemia and hypoglycemia during fasting. To investigate the molecular mechanism of the nutritional transition and the role of TBP-2, microarray analyses were performed using the liver of TBP-2−/− mice in the fed and fasted states. We found that the fasting-induced reduction in the expression of lipogenic genes targeted by insulin (SREBP-1), such as FASN and THRSP, was abolished in TBP-2−/− mice, and the expression of lipoprotein lipase is down-regulated, which was consistent with the lipoprotein profile. TBP-2−/− mice also exhibited enhanced glucose-induced insulin secretion and sensitivity. Another feature of the hepatic gene expression in fed TBP-2−/− mice was the augmented expression of peroxisome proliferator activated receptor (PPAR) target genes, such as CD36, FABP2, ACOT1, and FGF21, to regulate fatty acid consumption. In TBP-2−/− mice, PPARα expression was elevated in the fed state, whereas the fasting-induced up-regulation of PPARα was attenuated. We also detected an increased expression of PPARγ coactivator-1α protein in fed TBP-2−/− mice. TBP-2 overexpression significantly inhibited PPARα-mediated transcriptional activity induced by a specific PPARα ligand in vitro. These results suggest that TBP-2 is a key regulator of PPARα expression and signaling, and coordinated regulation of PPARα and insulin secretion by TBP-2 is crucial in the feeding-fasting nutritional transition.TBP-2/Txnip is a key regulator of PPARα expression and signaling, and coordinated regulation of PPARα and insulin secretion by TBP-2/Txnip is crucial in fasting response.

Thioredoxin-binding protein-2 (TBP-2), also known as vitamin D3-up-regulated protein 1 (VDUP1), was identified as an endogenous molecule interacting with thioredoxin (TRX). Here, we show that dendritic cells (DC) derived from TBP-2-deficient mice are defective in the function of T cell activation. To compare TBP-2(-/-) DC function with wild-type (WT) DC, we stimulated DC with lipopolysaccharide (LPS). Although TBP-2(-/-) DC and WT DC expressed comparable levels of MHC class II and costimulatory molecules such as CD40, CD80 and CD86, the IL-12p40, IL-12p70 and IL-6 productions of TBP-2(-/-) DC were attenuated. In a mixed leukocyte reaction (MLR), the concentrations of IL-2, IFN-gamma, IL-4 and IL-10 in the culture supernatant of MLR with TBP-2(-/-) DC were significantly lower than those in the cultures with WT DC. In MLR also, as with LPS stimulation, IL-12p40 and IL-12p70 production from TBP-2(-/-) DC was less than that from WT DC. Proliferation of T cells cultured with TBP-2(-/-) DC was poorer than that with WT DC. In vivo delayed-type hypersensitivity responses in TBP-2(-/-) mice immunized with ovalbumin were significantly reduced compared to WT mice. These results indicate that TBP-2 plays a crucial role in DC to induce T cell responses.

This paper presents a synthesis method for the open path generation of a four-bar mechanism using the Haar wavelet. The synthesis method utilizes the wavelet transform and normalization to extract the wavelet output feature parameters (WOFP) of the open path. Analysis of the WOFP reveals a particular characteristic: for the same four-bar mechanism, not only do variations of the mechanism origin and angles and the proportional scaling of the linkage lengths have no influence on the details of the WOFP but the same holds true for the position of the point that generates the coupler curve. Based on this finding, a numerical atlas database comprises 192,596 groups of basic dimensional types was established and a method of matching recognition was proposed as well. According to the internal relationship of the wavelet characteristic dimension parameters (WCDP), the actual mechanism parameter values and position parameters of an objective four-bar mechanism can be calculated. Four examples are presented to verify the accuracy and practicality of the proposed theory.

Lung cancer is the leading cause of cancer death, and it is widely accepted that chronic inflammation is an important risk for the development of lung cancer. Now, it is recognized that the nucleotide-binding and oligomerization domain (NOD) like receptors (NLRs)-containing inflammasomes are involved in cancer-related inflammation. This study was designed to investigate the effects of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome on the proliferation and migration of lung adenocarcinoma cell line A549. Using 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, scratch assay, and Transwell migration assay, we showed that activation of the NLRP3 inflammasome by LPS+ATP enhanced the proliferation and migration of A549 cells. Western blot analysis showed that activation of phosphorylation of Akt, ERK1/2, CREB and the expression of Snail increased, while the expression of E-cadherin decreased after the activation of NLRP3 inflammasome. Moreover, these effects were inhibited by the following treatments: i) downregulating the expression of NLRP3 by short hairpin RNA (shRNA) interference, ii) inhibiting the activation of NLRP3 inflammasome with a caspase-1 inhibitor, iii) blocking the interleukin-1β (IL-1β) and IL-18 signal transduction with IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP). Collectively, these results indicate that NLRP3 inflammasome plays a vital role in regulating the proliferation and migration of A549 cells and it might be a potential target for the treatment of lung cancer.

Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K ATP ) channels have been identified in ASMCs. Mount evidence has suggested that K ATP channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K + channels triggers K + efflux, which leading to membrane hyperpolarization, preventing Ca 2+ entry through closing voltage-operated Ca 2+ channels. Intracellular Ca 2+ is the most important regulator of muscle contraction, cell proliferation and migration. K + efflux decreases Ca 2+ influx, which consequently influences ASMCs proliferation and migration. As a K ATP channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca 2+ /calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K ATP channel antagonist. These findings provide a strong evidence to support that Ipt antagonize the proliferating and migrating effects of PDGF-BB on human ASMCs through opening K ATP channels. Altogether, our results highlighted a novel profile of Ipt as a potent option against the airway remodeling in chronic airway diseases.

Haplotype maps of the genetic map. (PDF 1005Â kb)

Heat maps of the genetic map. (PDF 363Â kb)

Background—Cardiac myosin–induced myocarditis is an experimental autoimmune myocarditis (EAM) model used to investigate autoimmunological mechanisms in inflammatory heart diseases and resembles fulminant myocarditis in humans. We investigated the therapeutic role of thioredoxin-1 (TRX-1), a redox-regulatory protein with antioxidant and antiinflammatory effects, in murine EAM.Methods and Results—EAM was generated in 5-week-old male BALB/c mice by immunization with porcine cardiac myosin at days 0 and 7. Recombinant human TRX-1 (rhTRX-1), C32S/C35S mutant rhTRX-1, or saline was administered intraperitoneally every second day from day 0 to 20. In addition, rabbit anti-mouse TRX-1 serum or normal rabbit serum was administered intraperitoneally on days −1, 2, and 6. Animals were euthanized on day 21. Histological analysis of the heart showed that TRX-1 significantly reduced the severity of EAM, whereas mutant TRX-1 failed to have such an effect, and anti–TRX-1 antibody enhanced the disease markedly. Immunohistochemical analysis showed that TRX-1 significantly suppressed cardiac macrophage inflammatory protein (MIP)-1α, MIP-2, and 8-hydroxydeoxyguanosine expression and macrophage infiltration into the heart in EAM. Although serum levels of MIP-1α were not suppressed by TRX-1 until day 21, both an in vitro chemotaxis chamber assay and an in vivo air pouch model showed that TRX-1 significantly suppressed MIP-1α– or MIP-2–induced leukocyte chemotaxis. However, real-time reverse transcription–polymerase chain reaction showed that TRX-1 failed to decrease chemokine receptor expression increased in the bone marrow cells of EAM mice.Conclusions—TRX-1 attenuates EAM by suppressing chemokine expressions and leukocyte chemotaxis in mice.

Heat transfer fluid is one critical component for transferring and storing heat energy in concentrating solar power systems. Molten-salt mixtures can be used as high temperature heat transfer fluids because of their thermophysical properties. This paper studied the thermophysical properties of Li2CO3-Na2CO3-K2CO3 eutectic salt and three eutectic chloride salts NaCl-KCl-ZnCl2 with different compositions in the range of 450-600°C and 250-800°C, respectively. Properties including specific heat capacity, thermal conductivity, density and viscosity were determined based on imperial correlations and compared at different operating temperatures. The heat transfer coefficients of using different eutectic salts as heat transfer fluids were also calculated and compared in their operating temperature range. It is concluded that all the four eutectic salts can satisfy the requirements of a high-temperature heat transfer fluid.

In the interconnection environment, people combine basic services into composite services to provide more complex function for sophisticated applications. Accordingly, service fault localization in composite services becomes a critical issue for guaranteeing the normal running of composite services. This paper proposes a novel Causal Inference based Service Dependency Graph (CISDG) for statistical service fault localization. Our approach first utilizes the dependencies between basic services in the composite services by transforming the service dependency graph into a causal graph. Then it intuitively applies the causal inference to service fault localization on the composite services. Our work mainly focuses on developing CISDG and the causal inference on CISDG. To develop CISDG, we characterize the dependency and causal relationships between basic services and the target causal graph. To perform the causal inference on CISDG, we apply the well-known causal inference techniques such as the Back-Door Criterion and enhance the algorithm of the network diagnostic algorithm based Causal Inference (CIND) to improve the efficiency of the statistical service fault localization. The case study illustrates that our approach has advantages over its rivals in the service fault localization of composite services.

Thioredoxin-1 (TRX) is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE (FcepsilonRI) was significantly suppressed in TRX transgenic (TRX-tg) mice compared to wild type (WT) mice. Intracellular reactive oxygen species (ROS) of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production of cytokines (IL-6 and TNF-alpha) from mast cells in response to 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper (Th) 2 dominant in primary immune response, although there was no difference in the population of dendritic cells (DCs) and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.

Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-γ, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and -independent cell growth and PPARγ ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPARγ ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARγ activation.

Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin and has multiple regulatory functions in cellular redox, growth, differentiation, apoptosis, and aging. To investigate the function of TBP-2 in vivo, we generated mice with targeted inactivation of TBP-2 (TBP-2-/- mice). Here, we show that TBP-2 expression is markedly up-regulated during fasting in wild-type mice, while TBP-2-/- mice were predisposed to death with bleeding tendency, as well as hepatic and renal dysfunction as a result of 48 h of fasting. The fasting-induced death was rescued by supplementation of glucose but not by that of oleic acid, suggesting that inability of fatty acid utilization plays an important role in the anomaly of TBP-2-/- mice. In these mice, plasma free fatty acids levels are higher, whereas glucose levels are lower than those of wild-type mice. Compared with wild-type mice, TBP-2-/- mice showed increased levels of plasma ketone bodies, pyruvate and lactate, indicating that Krebs cycle-mediated fatty acid utilization is impaired. Because the fatal impairment of fatty acid utilization is a characteristically metabolic feature of Reye (-like) syndrome, TBP-2-/- mouse may represent a novel model for investigating the pathophysiology of these disorders.

Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive oxygen species and regulating redox-sensitive transcription factors. TRX-1 is induced in various inflammatory conditions and shows cytoprotective action. We investigated the roles of TRX-1 in the host defense mechanism against Helicobacter felis (H. felis) infection. Transgenic (TG) mice overexpressing human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2 months, histology, oxidative damage, and gene expression of several cytokines, including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the effects of TRX-1 on oxidative stress and neutrophil migration were studied both in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT mice developed moderate-to-severe gastritis, whereas the development of gastritis was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers, 8-hydroxy-2'-deoxyguanosine and malondialdehyde, increased in the stomach of infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1beta and tumor necrosis factor-alpha gene expression in H. felis-infected TRX-1-TG mice was significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.

BACKGROUND: Wax gourd is a widely used vegetable of Cucuribtaceae, and also has important medicinal and health values. However, the genomic resources of wax gourd were scarcity, and only a few nucleotide sequences could be obtained in public databases. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined transcriptome in wax gourd. More than 44 million of high quality reads were generated from five different tissues of wax gourd using Illumina paired-end sequencing technology. Approximately 4 Gbp data were generated, and de novo assembled into 65,059 unigenes, with an N50 of 1,132 bp. Based on sequence similarity search with known protein database, 36,070 (55.4%) showed significant similarity to known proteins in Nr database, and 24,969 (38.4%) had BLAST hits in Swiss-Prot database. Among the annotated unigenes, 14,994 of wax gourd unigenes were assigned to GO term annotation, and 23,977 were found to have COG classifications. In addition, a total of 18,713 unigenes were assigned to 281 KEGG pathways. Furthermore, 6,242 microsatellites (simple sequence repeats) were detected as potential molecular markers in wax gourd. Two hundred primer pairs for SSRs were designed for validation of the amplification and polymorphism. The result showed that 170 of the 200 primer pairs were successfully amplified and 49 (28.8%) of them exhibited polymorphisms. CONCLUSION/SIGNIFICANCE: Our study enriches the genomic resources of wax gourd and provides powerful information for future studies. The availability of this ample amount of information about the transcriptome and SSRs in wax gourd could serve as valuable basis for studies on the physiology, biochemistry, molecular genetics and molecular breeding of this important vegetable crop.

Wax gourd (2n = 2x = 24) is an important vegetable species in the Cucurbitaceae family, yet little is known about its genome structure. As the largest component of most plant genomes, retrotransposons might play an important role in the genetic variation and genome evolution of wax gourd. In this study, the presence of Ty3-gypsy-like retrotransposons, their heterogeneity and chromosomal distribution in wax gourd have been investigated. The conserved domains of reverse transcriptase of Ty3-gypsy-like retrotransposons have been amplified, and this resulted in thirty-five unique sequences. Seventeen (49%) of the sequences were defective as they were disrupted by a premature stop codon and/or contained frameshift mutations. These 35 sequences were divided into four groups and showed low or even no homology with Ty3-gypsy-like sequences from other species, indicating lack of horizontal transfer. The Ty3-gypsy-like retrotransposons have a dispersed genomic organization, physically distributed on all chromosomes with clusters in the heterochromatin regions. These results suggest that retrotransposons of this kind are widely distributed in wax gourd with high copy numbers, and contributed to the formation of chromosomes with non-uniform insertion and amplification. This is the first report on the presence of reverse transcriptase sequences of Ty3-gypsy-like retrotransposons in wax gourd genome.