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Figure S1. Distribution map of linkage groups. x-axis, chromosome number; y-axis, genetic distance (in cM); and blue, bin marker. Figure S2. The genetic linkage map and physical map. The genetic map is shown in red, while the physical map is shown in blue, and the green line indicated the position of each marker on the genetic map and the physical map. Table S1. GBS-SNP markers and their BLAST hit information. Table S2. The phenotypic of the F2 individuals in HTS-1 Ă CM28TP. Table S3. Genes located in the intervals of hts. (DOCX 623 kb)

Quantitative Structure-Activity Relationship (QSAR) models of tyrosinase inhibitors were built using Random Forest (RF) algorithm and evaluated by the out-of-bag estimation (R2OOB) and 10-fold cross validation (Q2CV). We found that the performances of QSAR models were closely correlated with the systematic errors of inhibitory activities of tyrosinase inhibitors arising from the different measuring protocols. By defining ERRsys, outliers with larger errors can be efficiently identified and removed from heterogeneous activity data. A reasonable QSAR model (R2OOB of 0.74 and Q2CV of 0.80) was obtained by the exclusion of 13 outliers with larger systematic errors. It is a clear example of the challenge for QSAR model that can overwhelm heterogeneous data from different experimental protocols.

Weak machinery fault detection is a difficult task because of two main reasons (1) At the early stage of fault development, signature of fault related component performs incompletely and is quite different from that at the apparent failure stage. In most instances, it seems almost identical with the normal operating state. (2) The fault feature is always submerged and distorted by relatively strong background noise and macro-structural vibrations even if the fault component already performs completely, especially when the structure of fault components and interference are close. To solve these problems, we should penetrate into the underlying structure of the signal. Sparse representation provides a class of algorithms for finding succinct representations of signal that capture higher-level features in the data. With the purpose of extracting incomplete or seriously overwhelmed fault components, a sparse representation based latent components decomposition method is proposed in this paper. As a special case of sparse representation, shift-invariant sparse coding algorithm provides an effective basis functions learning scheme for capturing the underlying structure of machinery fault signal by iteratively solving two convex optimization problems: an L1-regularized least squares problem and an L2-constrained least squares problem. Among these basis functions, fault feature can be probably contained and extracted if optimal latent component is filtered. The proposed scheme is applied to analyze vibration signals of both rolling bearings and gears. Experiment of accelerated lifetime test of bearings validates the proposed method׳s ability of detecting early fault. Besides, experiments of fault bearings and gears with heavy noise and interference show the approach can effectively distinguish subtle differences between defect and interference. All the experimental data are analyzed by wavelet shrinkage and basis pursuit de-noising (BPDN) method for comparison.

A sub-class of distinct small molecule ROMK inhibitors were developed from the original lead 1. Medicinal chemistry endeavors led to novel ROMK inhibitors with good ROMK functional potency and improved hERG selectivity. Two of the described ROMK inhibitors were characterized for the first in vivo proof-of-concept biology studies, and results from an acute rat diuresis model confirmed the hypothesis that ROMK inhibitors represent new mechanism diuretic and natriuretic agents.

Although various methods have been presented in the literature for rotating machine fault detection, it still remains a huge challenge to accurately extract features from non-stationary vibration signals with a high noise level, typically in the case of rolling element bearings faults diagnosis. Due to its random and non-stationary nature, fault related features are difficult to extract by common techniques and are usually overwhelmed by noise and macro-structural vibrations. In this paper, a new time series decomposition method based on a dynamic linear model is proposed, which provides time domain decomposition of a non-stationary signal into collections of latent components. The signal of a damaged bearing consists of exponentially decaying ringing that occurs periodically at the bearing characteristic defect frequency. Dynamic linear models with time-varying cyclical components provide a more generalized and adaptive description on rolling element bearings’ vibration signal with time-varying cyclical behavior. This allows the precise isolation of latent, quasi-cyclical bearing fault components via inferences on the time-varying parameters which characterize these components. An accelerated whole lifetime test of bearing has been performed to collect vibration data, which is utilized to validate the effectiveness of the proposed method.

Exploration of the structure of protein complexes, especially the change in conformation and aggregation behavior of proteins upon ligand binding, is crucial to clarify their bioactivities at the molecular level. We applied solution small-angle X-ray scattering (SAXS) to study the complex structure of bovine serum albumin (BSA) and trypsin binding with tea polyphenols, that is, catechin and epigallocatechin gallate (EGCG). We found that tea polyphenols can steadily promote the aggregation of proteins and protein complexes through their bridging effect. The numbers of proteins in the complexes and in the aggregates of complexes are extracted from SAXS intensity profiles, and their dependences as a function of the molar ratio of polyphenol to protein are discussed. EGCG has stronger capability than catechin to promote complex formation and further aggregation, and the aggregates of complexes have a denser core with a relatively smooth surface. The aggregates induced by catechin are loosely packed with a rough surface. BSA shows higher stability than trypsin in the formation of complex with a well-folded conformation. The synergistic unfolding of trypsin results in larger aggregates in the mixtures with more tea polyphenols. The binding affinity and number of tea polyphenols bound to each protein are further determined using fluorescence spectroscopy. The structure of protein complexes explored in this work is referable in the preparation of protein complex-based particles and the understanding of polyphenol-induced formation and further aggregation of protein complexes.

To realize fast and universal 3D interactive media production for equipment exhibition, the internet 3D platform for equipment manufacturing and exhibition is designed based on WebGL graphics-engine. The main function of the plat-form includes sequential content creation, panoramic content creation, 3D animation creation. Meanwhile, fast cable simulation method based on rigid body link is proposed, cable simulation function is achieved on all kinds of platform. The internet authoring platform supports assistant 3D, the naked-eye 3D, helmet VR 3D, kinect, and other hardware peripheral equipment. Trials by multiple users, designers can create internet-based interactive panoramic content, sequence content, 3D animated content, cable simulation independently and rapidly without assistance of programmer. The 3D platform provides a simple design method and a new design mode for equipment manufacturing and exhibition. On the basis of the 3D authoring platform, the application of other 3D function can be upgraded. The 3D authoring platform is a platform foundation for the equipment manufacturing, maintenance, sales in the whole process of 3D content information.

With the popularization of large-complex machinery, the maintenance personnel demand of such equipment is growing as well. Traditional way of training equipment maintenance means large cost of space and funds. We design an equipment maintenance training system based on Web3D technology. Compared with the traditional way, the virtual maintenance teaching system based on virtual reality technology can greatly save the cost by hardware. By the characteristics of Web3D technology, the system can solve the problem of platform and expansibility, which make it much more efficient and convenient than other virtual maintenance teaching system without Web3D.

The renal outer medullary potassium (ROMK) channel, located at the apical surface of epithelial cells in the thick ascending loop of Henle and cortical collecting duct, contributes to salt reabsorption and potassium secretion, and represents a target for the development of new mechanism of action diuretics. This idea is supported by the phenotype of antenatal Bartter's syndrome type II associated with loss-of-function mutations in the human ROMK channel, as well as, by cardiovascular studies of heterozygous carriers of channel mutations associated with type II Bartter's syndrome. Although the pharmacology of ROMK channels is still being developed, channel inhibitors have been identified and shown to cause natriuresis and diuresis, in the absence of any significant kaliuresis, on acute oral dosing to rats or dogs. Improvements in potency and selectivity have led to the discovery of MK-7145 [5,5'-((1R,1'R)-piperazine-1,4-diylbis(1-hydroxyethane-2,1-diyl))bis(4-methylisobenzofuran-1(3H)-one)], a potential clinical development candidate. In spontaneously hypertensive rats, oral dosing of MK-7145 causes dose-dependent lowering of blood pressure that is maintained during the entire treatment period, and that displays additive/synergistic effects when administered in combination with hydrochlorothiazide or candesartan, respectively. Acute or chronic oral administration of MK-7145 to normotensive dogs led to dose-dependent diuresis and natriuresis, without any significant urinary potassium losses or changes in plasma electrolyte levels. Elevations in bicarbonate and aldosterone were found after 6 days of dosing. These data indicate that pharmacological inhibition of ROMK has potential as a new mechanism for the treatment of hypertension and/or congestive heart failure. In addition, Bartter's syndrome type II features are manifested on exposure to ROMK inhibitors.

Artificial microRNA (amiRNA) technology utilizes microRNA (miRNA) biogenesis pathway to produce artificially selected small RNAs using miRNA gene backbone. It provides a feasible strategy for inducing loss of gene function, and has been applied in functional genomics study, improvement of crop quality and plant virus disease resistance. A big challenge in amiRNA applications is the unpredictability of silencing efficacy of the designed amiRNAs and not all constructed amiRNA candidates would be expressed effectively in plant cells. We and others found that high efficiency and specificity in RNA silencing can be achieved by designing amiRNAs with perfect or almost perfect sequence complementarity to their targets. In addition, we recently demonstrated that Agrobacterium-mediated transient expression system can be used to validate amiRNA constructs, which provides a simple, rapid and effective method to select highly expressible amiRNA candidates for stable genetic transformation. Here, we describe the methods for design of amiRNA candidates with perfect or almost perfect base-pairing to the target gene or gene groups, incorporation of amiRNA candidates in miR168a gene backbone by one step inverse PCR amplification, construction of plant amiRNA expression vectors, and assay of transient expression of amiRNAs in Nicotiana benthamiana through agro-infiltration, small RNA extraction, and amiRNA Northern blot.

The renal outer medullary potassium (ROMK) channel is a member of the inwardly rectifying family of potassium (Kir) channels. ROMK (Kir1.1) is predominantly expressed in kidney where it plays a major role in the salt reabsorption process. Loss-of-function mutations in the human Kir1.1 channel are associated with antenatal Bartter's syndrome type II, a life-threatening salt and water balance disorder. Heterozygous carriers of Kir1.1 mutations associated with antenatal Bartter's syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. These data suggest that Kir1.1 inhibitors could represent novel diuretics for the treatment of hypertension. Because little is known about the molecular pharmacology of Kir1.1 channels, assays that provide a robust, reliable readout of channel activity-while operating in high-capacity mode-are needed. In the present study, we describe high-capacity, 384- and 1,536-well plate, functional thallium flux, and IonWorks electrophysiology assays for the Kir1.1 channel that fulfill these criteria. In addition, 96-well (86)Rb(+) flux assays were established that can operate in the presence of 100% serum, and can provide an indication of the effect of a serum shift on compound potencies. The ability to grow Madin-Darby canine kidney cells expressing Kir1.1 in Transwell supports provides a polarized cell system that can be used to study the mechanism of Kir1.1 inhibition by different agents. All these functional Kir1.1 assays together can play an important role in supporting different aspects of drug development efforts during lead identification and/or optimization.

Various techniques have been presented to detect rolling element bearing faults, however, it is still a huge challenge to accurately extract features under high noise level. In this paper, a new approach based on matching pursuit for analyzing the signals of rolling element bearings is proposed. Different from most of the matching pursuit related works focusing on the time-frequency plane, complexity spectrum and complexity spectrum entropy are proposed in this research to accurately extract the fault feature of a rolling element bearing signal under a low signal to noise ratio. Both simulation and experiment show that complexity spectrum works better than envelope spectrum in distinguishing characteristic frequencies of fault bearings submerged in noise. An accelerated whole lifetime test of bearing has been performed to collect vibration data, which is analyzed by complexity spectrum entropy and other normal approaches. Results show that complexity spectrum entropy has some unique characteristics.

Artificial microRNA (amiRNA) technology utilizes microRNA (miRNA) biogenesis pathway to produce artificially selected small RNAs using miRNA gene backbone. It provides a feasible strategy for inducing loss of gene function, and has been applied in functional genomics study, improvement of crop quality and plant virus disease resistance. A big challenge in amiRNA applications is the unpredictability of silencing efficacy of the designed amiRNAs and not all constructed amiRNA candidates would be expressed effectively in plant cells. We and others found that high efficiency and specificity in RNA silencing can be achieved by designing amiRNAs with perfect or almost perfect sequence complementarity to their targets. In addition, we recently demonstrated that Agrobacterium-mediated transient expression system can be used to validate amiRNA constructs, which provides a simple, rapid and effective method to select highly expressible amiRNA candidates for stable genetic transformation. Here, we describe the methods for design of amiRNA candidates with perfect or almost perfect base-pairing to the target gene or gene groups, incorporation of amiRNA candidates in miR168a gene backbone by one step inverse PCR amplification, construction of plant amiRNA expression vectors, and assay of transient expression of amiRNAs in Nicotiana benthamiana through agro-infiltration, small RNA extraction, and amiRNA Northern blot.

Based on Xilinx's Virtex-II Pro series device XC2VP30 FPGA (Field Programmable Gate Array) chip, we have designed the system to implement remote high-precision time data acquisition, control and processing using TCP/IP communication protocol. This paper describes the design and implement of the FPGA-based hardware platform and software, and the design of ethernet human-computer interaction interface in detail. FPGA-based SOPC (system on programmable chip) technology is the core of the system. Making full use of the FPGA logic cells and related peripheral controller can implement a reconfigurable chip system on FPGA, which can conduct data transmission with a remote control interface.

Following the discovery of small molecule acyl piperazine ROMK inhibitors and their initial preclinical validation as a novel diuretic agent, our group set out to discover new ROMK inhibitors with reduced risk for QT effects, suitable for further pharmacological experiments in additional species. Several strategies for decreasing hERG affinity while maintaining ROMK inhibition were investigated and are described herein. The most promising candidate, derived from the newly discovered 4-N-heteroaryl acetyl series, improved functional hERG/ROMK ratio by >10× over the previous lead. In vivo evaluation demonstrated comparable diuretic effects in rat with no detectable QT effects at the doses evaluated in an in vivo dog model.

To investigate the effect of saponin 6 of Anemone Taipaiensis on the proliferation of human U87 MG glioma cells and the possible mechanism.U87 MG cells were treated with different concentrations of saponin 6 (0.0, 1.6, 3.2, 6.4, 12.8 μg/mL) for 24 hours or 48 hours. Cell viability was measured by MTT assay; the apoptosis rate was detected by flow cytometry combined with annexin V-FITC /PI staining; Western blotting was applied to determine the protein level of activated caspase-3.Compared with control groups, saponin 6 significantly inhibited U87 MG cell proliferation in a time- and dose-depended manner. Apoptosis rate of U87 MG cells and the expression of activated caspase-3 were raised with the increasing concentration of saponin 6.Saponin 6 of Anemone Taipaiensis could depress cell proliferation in a dose-depended manner, increase the expression of activated caspase-3 and promote apoptosis in U87 MG cells.

Ionogel electrolytes can be fabricated for electrochemical actuators with many desirable advantages, including direct low-voltage control in air, high electrochemical and thermal stability, and complete silence during actuation. However, the demands for active actuators with above features and load-driving ability remain a challenge; much work is necessary to enhance the mechanical strength of electrolyte materials. Herein, we describe a cross-linked supramolecular approach to prepare tough nanocomposite gel electrolytes from HEMA, BMIMBF4, and TiO2 via self-initiated UV polymerization. The tough and stable ionogels are emerging to fabricate electric double-layer capacitor-like soft actuators, which can be driven by electrically induced ion migration. The ionogel-based actuator shows a displacement response of 5.6 mm to the driving voltage of 3.5 V. After adding the additional mass weight of the same as the actuator, it still shows a large displacement response of 3.9 mm. Furthermore, the actuator can not only work in harsh temperature environments (100°C and −10°C) but also realize the goal of grabbing an object by adjusting the applied voltage.

The renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct, plays an important role in kidney physiology by regulating salt reabsorption. Loss-of-function mutations in the human ROMK channel are associated with antenatal type II Bartter's syndrome, an autosomal recessive life-threatening salt-wasting disorder with mild hypokalemia. Similar observations have been reported from studies with ROMK knockout mice and rats. It is noteworthy that heterozygous carriers of Kir1.1 mutations associated with antenatal Bartter's syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. Although selective ROMK inhibitors would be expected to represent a new class of diuretics, this hypothesis has not been pharmacologically tested. Compound A [5-(2-(4-(2-(4-(1H-tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one)], a potent ROMK inhibitor with appropriate selectivity and characteristics for in vivo testing, has been identified. Compound A accesses the channel through the cytoplasmic side and binds to residues lining the pore within the transmembrane region below the selectivity filter. In normotensive rats and dogs, short-term oral administration of compound A caused concentration-dependent diuresis and natriuresis that were comparable to hydrochlorothiazide. Unlike hydrochlorothiazide, however, compound A did not cause any significant urinary potassium losses or changes in plasma electrolyte levels. These data indicate that pharmacologic inhibition of ROMK has the potential for affording diuretic/natriuretic efficacy similar to that of clinically used diuretics but without the dose-limiting hypokalemia associated with the use of loop and thiazide-like diuretics.

Extracts of eleven traditional Chinese medicines (TCM) with a reputation of usefulness in treating diabetes mellitus were examined for alpha-glucosidase and alpha-amylase inhibitory activities in vitro. The extract with the highest activity was selected for further characterization. The extract of the root bark of Aralia taibaiensis (EAT) outperformed other extracts in the assays with IC50 values of 0.48 +/- 0.01 mg/mL (BSG), 0.41 +/- 0.02mg/mL (SCG), 0.61 +/- .03mg/mL (BLA) and 0.77 +/- 0.03mg/mL (PPA), respectively. To identify which constituents were responsible for the activities, thirteen triterpenoid saponins were isolated from EAT and examined for their inhibitory effects against alpha-glucosidase and alpha-amylase. The results revealed that saponins 2, 3, 4 (IC50: 0.83 +/- 0.05 microM for BSG and IC50: 0.72 +/- 0.03 microM for SCG), 5, 6, 7, 9, 10, 11 and 12 (IC50: 1.07 +/- 0.04 micro.M for BSG and IC50: 0.93 +/- 0.05 micro.M for SCG) showed alpha-glucosidase inhibitory activities, while 2, 3, 4 (IC50: 0.93 +/- 0.04 micro.M for PPA), 5, 6, 7, 9, 10, 11 and 12 (IC50: 1.02 +/- 0.03 micro.M for PPA) possessed significant alpha-amylase inhibitory activities. In addition, the structure-activity relationship of the thirteen saponins was discussed based on their structure features and diabetes mellitus related activities. It is suggested that the glucuronic acid unit at C-3 of the aglycone is the imperative functional group of the antidiabetic activities, and two characteristic structural features are responsible for the remarkable alpha-glucosidase and alpha-amylase inhibitory activities.

The utility of artificial microRNAs (amiRNAs) to induce loss of gene function has been reported for many plant species, but expression efficiency of the different amiRNA constructs in different transgenic plants was less predictable. In this study, expressions of amiRNAs through the gene backbone of Arabidopsis miR168a were examined by both Agrobacterium-mediated transient expression and stable plant genetic transformation. A corresponding trend in expression of amiRNAs by the same amiRNA constructs between the transient and the stable expression systems was observed in the experiments. Plant genetic transformation of the constructs that were highly expressible in amiRNAs in the transient agro-infiltration assays resulted in generation of transgenic lines with high level of amiRNAs. This provides a simple method for rapid and effective selection of amiRNA constructs used for a time-consuming genetic transformation in plants.

The renal outer medullary potassium channel (ROMK or Kir1.1) is a putative drug target for a novel class of diuretics that could be used for the treatment of hypertension and edematous states such as heart failure. An internal high-throughput screening campaign identified 1,4-bis(4-nitrophenethyl)piperazine (5) as a potent ROMK inhibitor. It is worth noting that this compound was identified as a minor impurity in a screening hit that was responsible for all of the initially observed ROMK activity. Structure–activity studies resulted in analogues with improved rat pharmacokinetic properties and selectivity over the hERG channel, providing tool compounds that can be used for in vivo pharmacological assessment. The featured ROMK inhibitors were also selective against other members of the inward rectifier family of potassium channels.

Mashup is a new data aggregation on web. The user who using spreadsheet would like to build their own mashups. To meet this need, we propose a spreadsheet-based Web mashups development framework, which enables users to develop mashups in the popular spreadsheet environment. Finally, we have developed and tested a proof-of-concept prototype to demonstrate the utility of the proposed framework.

The complete carbocyclic skeleton of ingenol is assembled via a route that employs ring-closing metathesis (RCM) to close the strained “inside-outside” BC ring system (i.e., 24 → 25).

To review the recent anatomy and biomechanical research progress of knee posteromedial corner, to analyze deficient aspect, and to predict future research directions.Domestic and international literature about the anatomy and function of knee posteromedial corner in recent years was reviewed extensively, at the same time, the biomechanics of corresponding structure was summarized and analyzed.The anatomical structures of knee posteromedial corner included the static stability structures and the dynamic stability structures. The dynamic stability structures were more important, including posterior root of medial meniscus, posterior oblique ligament, semimembranosus extensions, meniscotibial ligament and oblique popliteal ligament. The posterior oblique ligament was most important structure to contribute to stabilization of valgus, anterior internal rotation of knee and posterior movement of tibia.Anatomical reconstruction of knee posteromedial corner especially the posterior oblique ligament is the key to the reconstruction of knee posteromedial function stability.

To screen effective constituents of Discocleidion rufescens against bacteria.Compounds were isolated by bioassay-guided fractionation method with various chromatographic methods and their structures were determined by spectral analysis and chemical evidence.Seven compounds were isolated from the Et2O and n-BuOH extracts and identified as 5,7-dihydroxy-4'-methoxy flavone (1), quercetin (2), apigenin-7-O-beta-D-glucopyranoside (3), apigenin-7-O-neohesperidoside (4), luteolin-7-O-neohesperidoside (5), gallic acid (6) and beta-daucosteol (7).Compounds 1-6 were isolated from genus Discocleidion for the first time and exhibited certain inhibitory activity against Escherichia coli. Compound 6 also showed antibacterial activity against Staphylococus aureus.

The empirical analysis on the relationship among money supply, economic growth, and inflation in china from 1998 to 2007 with co-integration and Granger Causality test approaches shows: there is no co-integration relationship among money supply, inflation, and economic growth, but there is co-integration relationship between money supply and inflation while there is no co-integration relationship between money supply and economic growth. There is contradiction between the goal of economic growth and of price stability in China. We may be able to implement a loose monetary policy in the short run,but we should seek a new source to stimulate economic growth other than monetary policy in the long run.

A total synthesis of the biologically important diterpene ingenol has been completed. Ring-closing olefin metathesis was used to construct the strained "inside-outside" tetracyclic skeleton, and a series of diastereoselective reactions were employed to complete the synthesis. Another naturally occurring ingenane, 20-deoxyingenol, has also been prepared.

[reaction: see text] The complete carbocyclic skeleton of ingenol is assembled via a route that employs ring-closing metathesis (RCM) to close the strained "inside-outside" BC ring system (i.e., 24 --25).