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This paper proposes the use of sensor-integrated silicon cantilever arrays to measure drug-induced cardiac toxicity in real time. The proposed cantilever sensors, unlike the conventional electrophysiological methods, aim to evaluate cardiac toxicity by measuring the contraction force of the cardiomyocytes corresponding to the target drugs. The surface of the silicon cantilever consists of microgrooves to maximize the alignment and the contraction force of the cardiomyocytes. This type of surface pattern also helps in the maturation of the cardiomyocytes by increasing the sarcomere length. The preliminary characterization of the cantilever sensors was performed on the cantilever surface, with the cardiomyocytes seeded with a density of 1000 cells/mm2, and the cardiac contractility was measured as a function of the culture days. The change in the contraction force of the cardiomyocytes due to the drug concentration was successfully measured through the integrated strain sensor in the culture media. The reliability of the sensor-integrated cantilevers and the feasibility of their mass production ensure that they meet the practical requirements in the medical applications.

It is an important aspect of current cancer research to search for effective and low-toxicity anticancer drugs and adjuvants. Polysaccharides, as immunomodulators, can improve the immune function of the body, kill tumor cells directly and prevent tumor development by increasing the resistance of the body to carcinogenic factors. The aim of the present study was to identify natural polysaccharide compounds with novel structure and antitumor activity via the separation and analysis of polysaccharide components from Ramaria flaccida (Fr.) Quel. (RF-1). In the present study, high-performance gel permeation chromatography, gas chromatography-mass spectrometry and nuclear magnetic resonance were used to identify the structure of polysaccharides from RF-1. Subsequently, the antitumor activity and mechanism of RF-1 were studied by establishing an in vivo S180 tumor model, and by using Illumina sequencing technology and enzyme-linked immunosorbent assay (ELISA). The present results revealed that the average molecular weight of RF-1 was 17,093 Da and that RF-1 was composed of the monosaccharides glucose and galactose, with a 2:1 ratio. The main chain of RF-1 consisted of (1→6, 2)-α-D-galactopyranose and (1→6, 4)- α-D-glucopyranose. One of the branched chains was linked to 4-O of the main glucose chain by (1→6)-α-D-glucopyranose and next linked by one (→4)-β-D-glucopyranose. The other two branched chains were both linked to 2-O of the main glucose chain by one (→4)-β-D-glucopyranose. In addition, RF-1 inhibited the growth of S180 tumors in vivo. When the concentration of RF-1 was 20 mg/kg, the inhibition rate of S180 tumors in mice was 48.4%. Compared with the blank control group, 1,971 differentially expressed genes were identified, of which 818 were upregulated and 1,153 were downregulated in the RF-1 group. A Gene Ontology enrichment analysis generated 47,091 assignments to biological processes, 5,250 assignments to cellular components, and 6,466 assignments to molecular functions. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the Wnt and MAPK signaling pathways were significantly enriched. The number of differentially annotated genes in these two pathways was 19 and 33, respectively. Additionally, ELISA results revealed that the protein levels of interleukin (IL)-1β, IL-6, vascular endothelial growth factor (VEGF) and VEGF receptor in the RF-1 group were significantly downregulated compared with the S180 blank control group (P

Background: There is an urgent need for the detection of aggressive prostate cancer. Glycoproteins play essential roles in cancer development, while urine is a noninvasive and easily obtainable biological fluid that contains secretory glycoproteins from the urogenital system. Therefore, here we aimed to identify urinary glycoproteins that are capable of differentiating aggressive from non-aggressive prostate cancer. Methods: Quantitative mass spectrometry data of glycopeptides from a discovery cohort comprised of 74 aggressive (Gleason score ≥8) and 68 non-aggressive (Gleason score = 6) prostate cancer urine specimens were acquired via a data independent acquisition approach. The glycopeptides showing distinct expression profiles in aggressive relative to non-aggressive prostate cancer were further evaluated for their performance in distinguishing the two groups either individually or in combination with others using repeated 5-fold cross validation with logistic regression to build predictive models. Predictive models showing good performance from the discovery cohort were further evaluated using a validation cohort. Results: Among the 20 candidate glycoproteins, urinary ACPP outperformed the other candidates. Urinary ACPP can also serve as an adjunct to serum PSA to further improve the discrimination power for aggressive prostate cancer (AUC= 0.82, 95% confidence interval 0.75 to 0.89). A three-signature panel including urinary ACPP, urinary CLU, and serum PSA displayed the ability to distinguish aggressive prostate cancer from non-aggressive prostate cancer with an AUC of 0.86 (95% confidence interval 0.8 to 0.92). Another three-signature panel containing urinary ACPP, urinary LOX, and serum PSA also demonstrated its ability in recognizing aggressive prostate cancer (AUC=0.82, 95% confidence interval 0.75 to 0.9). Moreover, consistent performance was observed from each panel when evaluated using a validation cohort. Conclusion: We have identified glycopeptides of urinary glycoproteins associated with aggressive prostate cancer using a quantitative mass spectrometry-based glycoproteomic approach and demonstrated their potential to serve as noninvasive urinary glycoprotein biomarkers worthy of further validation by a multi-center study.

Protein tyrosine phosphorylation (pTyr) plays a prominent role in signal transduction and regulation in all eukaryotic cells. In conventional immunoaffinity purification (IP) methods, phosphotyrosine peptides are isolated from the digest of cellular protein extracts with a phosphotyrosine-specific antibody and are identified by tandem mass spectrometry. However, low sensitivity, poor reproducibility, and high cost are universal concerns for IP approaches. In this study, we presented an antibody-free approach to identify phosphotyrosine peptides by using protein tyrosine phosphatase (PTP). It was found that most of the PTPs including PTP1B, TCPTP, and SHP1 can efficiently and selectively dephosphorylate phosphotyrosine peptides. We then designed a workflow by combining two Ti

Purpose: Cardiac myxoma (CM) is a rare but important cause of ischemic stroke, and typically involves the middle cerebral artery and rarely affects the brainstem only. The safety and efficacy of in...

The algorithms for online secondary path modeling, with the injection of auxiliary noise, have always been applied to active noise control (ANC) systems to deal with the problem of when the secondary path is time-varying. The applications of ANC in vehicles for active sound quality control may pose new challenges for the current online secondary path modeling algorithms due to the disturbance noise signal from unconcerned frequencies. Therefore, this paper presents a framework of online secondary path modeling for active sound quality control systems. On the basis of current algorithms, an adaptive step size least mean square (ASS-LMS) algorithm of the secondary path modeling with interference signals is proposed. The ASS-LMS algorithm improves the stability of iteration without reducing convergence speed. Furthermore, a modified strategy for scheduling the auxiliary noise power is also proposed. The proposed modification reduces the degradation of the sound quality control performance caused by auxiliary noise. Simulations results are provided to verify the effectiveness of the algorithms proposed in this paper.

Determination of site-specific glycoforms is the key to reveal the micro-heterogeneity of protein glycosylation at proteome level. Herein, we presented an integrated virtual multistage MS strategy to identify intact glycopeptides, which allowed the determination of site-specific glycoforms. In this strategy, the enzymatically de-glycosylated peptides and intact glycopeptides were mixed and analyzed in the same LC-MS/MS run. The acquired MS2 spectra of intact glycopeptides allowed determination of the glycans, and the MS2 spectra of the de-glycosylated peptides enabled the identification of peptide backbone sequences. Compared with the conventional multistage strategy, the peptide backbones could be directly identified by the MS2 of the de-glycopeptides with higher sensitivity. This strategy was first validated by analyzing the glycosites and site-specific glycoforms of mouse liver tissues. Then, it was applied to differential analysis of the glycoproteomes of hepatocellular carcinoma (HCC) and adjacent liver tissues. Compared with the identification scheme using only MS2 spectra of intact glycopeptides or glycosites, this approach enabled quantitative analysis on two levels, i.e. glycosites and site-specific glycoforms, simultaneously. Thus, it could be a powerful tool to characterize the subtle differences in the macro- and micro-heterogeneity of protein glycosylation for different samples.

© 2018 Elsevier Ltd Driven by the increasing requirement for road conditions in the field of the controllable suspension system, this paper presents a novel nonlinear road-excitation classification procedure for arbitrary suspension control strategy. The proposed procedure includes four steps: the definition of controller parameters, selection of insensitive frequency ranges, calculation of superior features, and generation of the classifier. To better illustrate the proposed procedure, the clipped optimal control strategy is taken as an example in the simulation part. Simulation results reveal that the proposed method can accurately estimate road excitation level for various controller parameters, vehicle speeds, and vehicle models. Three contributions have been made in this paper: (1) A road classification procedure that can be used for road adaptive suspension control with any control algorithm is developed; (2) In order to improve classification accuracy, the concept of insensitive index which is based on the time-frequency analysis is proposed; (3) Experimental validation with a quarter vehicle test rig is performed, which has verified the effectiveness of the proposed method for the adaptive controllable suspension system.

Many biotechniques including protein microarray, drug screening, biosensors rely on the immobilization of recombinant proteins on the solid supports. It is well known that random orientation of the immobilized proteins could impair their biologic functions. Thus, it is very important to develop new site-specific immobilization approach. In this study, we presented a chemoenzymatic approach for site-specific conjugation of recombinant proteins onto solid support. In this strategy, the affinity tag on recombinant protein was enzymatically cleaved to expose the N-terminal serine, which was oxidized to carry an aldehyde group and was then covalently coupled to hydrazide resin through hydrazone ligation. As this approach takes advantage of the most frequently used TEV protease, it requires no further sequence design on recombinant protein. This method was validated by site specific coupling of a synthetic peptide and a recombinant protein onto solid supports. It was found that the site specific immobilized SH2 domain is functional and could be used to enrich tyrosine phosphorylated peptides.

PtTe nanotubes (PtTe NTs) were firstly synthesized in ethylene glycol by using Te NTs as both sacrificial templates and reducing agents via a galvanic replacement reaction of Te with Pt. Then, the Cu-decorated PtTe NTs (Cu-PtTe NTs) were obtained by depositing copper atom clusters on the surface of PtTe NTs with copper chloride as the reactant and hydrazine hydrate as the reducing agent, respectively. Structural and morphological investigations reveal that Cu-PtTe NTs are 150–200 nm in length and about 20 nm in diameter with a wall thickness of ∼3 nm, which are composed of two crystalline phases: Pt and PtTe2 alloy. Compared with PtTe NTs and commercial Pt/C, Cu-PtTe NTs show remarkably enhanced electrocatalytic activity and durability toward oxygen reduction due to an electronic effect generated by the introduction of copper into the lattice of PtTe alloy NTs.

Recently, we have found that two urinary glycoproteins, prostatic acid phosphatase (ACPP) and clusterin (CLU), combined with serum prostate-specific antigen (PSA) can serve as a three-signature panel for detecting aggressive prostate cancer (PCa) based on a quantitative glycoproteomic study. To facilitate the translation of candidates into clinically applicable tests, robust and accurate targeted parallel reaction monitoring (PRM) assays that can be widely adopted in multiple labs were developed in this study. The developed PRM assays for the urinary glycopeptides, FLN*ESYK from ACPP and EDALN*ETR from CLU, demonstrated good repeatability and a sufficient working range covering three to four orders of magnitude, and their performance in differentiating aggressive PCa was assessed by the quantitative analysis of urine specimens collected from 69 nonaggressive (Gleason score = 6) and 73 aggressive (Gleason ≥ 8) PCa patients. When ACPP combined with CLU, the discrimination power was improved from an area under a curve (AUC) of 0.66 to 0.78. By combining ACPP, CLU, and serum PSA to form a three-signature panel, the AUC was further improved to 0.83 (sensitivity: 84.9%, specificity: 66.7%). Since the serum PSA test alone had an AUC of 0.68, our results demonstrated that the new urinary glycopeptide PRM assays can serve as an adjunct to the serum PSA test to achieve better predictive power toward aggressive PCa. In summary, our developed PRM assays for urinary glycopeptides were successfully applied to clinical PCa urine samples with a promising performance in aggressive PCa detection.

The fruit trichomes of Cucurbitaceae are widely desired in many Asian countries and have been a key determinant of cucumber (Cucumis sativus L.) cultivar selection for commercial production and breeding. However, our understanding of the initiation and development of cucumber trichomes is still limited. Here, we found that the cucumber TINY BRANCHED HAIR (TBH) gene is preferentially expressed in multicellular trichomes. Overexpression of CsTBH in tbh mutants restored the trichome phenotype and increased the percentage of female flowers, whereas silencing of CsTBH in wild-type plants resulted in stunted trichomes with a lower rate of female flowers. Furthermore, we provide evidence that CsTBH can directly bind to the promoters of cucumber 1-Aminocyclopropane-1-Carboxylate Synthase (CsACS) genes and regulate their expression, which affects multicellular trichome development, ethylene accumulation, and sex expression. Two cucumber acs mutants with different trichome morphology and sex morphs compared with their near-isogenic line further support our findings. Collectively, our study provides new information on the molecular mechanism of CsTBH in regulating multicellular trichome development and sex expression through an ethylene pathway.

Global dimming reduces incident global radiation but increases the fraction of diffuse radiation, and thus affects crop yields; however, the underlying mechanisms of such an effect have not been revealed. We hypothesized that crop source–sink imbalance of either carbon (C) or nitrogen (N) during grain filling is a key factor underlying the effect of global dimming on yields. We presented a practical framework to assess both C and N source–sink relationships, using data of biomass and N accumulation from periodical sampling conducted in field experiments for wheat and rice from 2013 to 2016. We found a fertilization effect of the increased diffuse radiation fraction under global dimming, which alleviated the negative impact of decreased global radiation on source supply and sink growth, but the source supply and sink growth were still decreased by dimming, for both C and N. In wheat, the C source supply decreased more than the C sink demand, and as a result, crops remobilized more pre-heading C reserves, in response to dimming. However, these responses were converse in rice, which presumably stemmed from the more increment in radiation use efficiency and the more limited sink size in rice than wheat. The global dimming affected source supply and sink growth of C more significantly than that of N. Therefore, yields in both crops were dependent more on the source–sink imbalance of C than that of N during grain filling. Our revealed source–sink relationships, and their differences and similarities between wheat and rice, provide a basis for designing strategies to alleviate the impact of global dimming on crop productivity.

Background Proteomic characterization of cancers is essential for a comprehensive understanding of key molecular aberrations. However, proteomic profiling of a large cohort of cancer tissues is often limited by the conventional approaches. Methods We present a proteomic landscape of 16 major types of human cancer, based on the analysis of 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent tissues, and 12 normal tissues, using mass spectrometry-based data-independent acquisition approach. Results In our study, a total of 8527 proteins were mapped to brain, head and neck, breast, lung (both small cell and non-small cell lung cancers), esophagus, stomach, pancreas, liver, colon, kidney, bladder, prostate, uterus and ovary cancers, including 2458 tissue-enriched proteins. Our DIA-based proteomic approach has characterized major human cancers and identified universally expressed proteins as well as tissue-type-specific and cancer-type-specific proteins. In addition, 1139 therapeutic targetable proteins and 21 cancer/testis (CT) antigens were observed. Conclusions Our discoveries not only advance our understanding of human cancers, but also have implications for the design of future large-scale cancer proteomic studies to assist the development of diagnostic and/or therapeutic targets in multiple cancers.

With the gradual improvement of network services, the explosive growth of concurrent business access and more complex Web transactions are a severe test for the ability of servers in the network. The multi-server cluster system is currently the main means to effectively solve the above problems. As the core of cluster system research, load balancing mainly solves the problem of reasonable allocation of a large number of concurrent requests in the cluster. Based on the actual situation of my company, this paper builds a server cluster system based on Nginx. The Nginx reverse proxy function module is configured to enable the server cluster system to have load balancing function, and the load distribution policy can be adjusted in real time according to the actual situation of the back-end server load, thereby realizing full utilization of the back-end server. A server cluster load balancing configuration strategy based on the characteristics of my company is proposed. This strategy has a good implementation. It effectively solves the surge in concurrent service access of enterprise service bus. It has good portability and has certain reference significance for the subsequent informationization construction.

CsGL2-LIKE, a HD-ZIP IV transcription factor, regulates male flowering time and fertility in cucumber and interacts with the jasmonate repressor CsJAZ1 to form a HD-ZIP IV–CsJAZ1 complex., Cucumber is dioecious by nature, having both male and female flowers, and is a model system for unisexual flower development. Knowledge related to male flowering is limited, but it is reported to be regulated by transcription factors and hormone signals. Here, we report functional characterization of the cucumber (Cucumis sativus) GL2-LIKE gene, which encodes a homeodomain leucine zipper (HD-ZIP) IV transcription factor that plays an important role in regulating male flower development. Spatial–temporal expression analyses revealed high-level expression of CsGL2-LIKE in the male flower buds and anthers. CsGL2-LIKE is closely related to AtGL2, which is known to play a key role in trichome development. However, ectopic expression of CsGL2-LIKE in Arabidopsis gl2-8 mutant was unable to rescue the gl2-8 phenotype. Interestingly, the silencing of CsGL2-LIKE delayed male flowering by inhibiting the expression of the florigen gene FT and reduced pollen vigor and seed viability. Protein–protein interaction assays showed that CsGL2-LIKE interacts with the jasmonate ZIM domain protein CsJAZ1 to form a HD-ZIP IV–CsJAZ1 complex. Collectively, our study indicates that CsGL2-LIKE regulates male flowering in cucumber, and reveals a novel function of a HD-ZIP IV transcription factor in regulating male flower development of cucumber.

Additional file 1. Supplementary methods, detailed information of protein extraction, trypsin digestion of tissue samples, and peptide desalting. Figure S1, sample quality control and reproducibility of the DIA data. Figure S2, characterization of housekeeping proteins. Figure S3, proteome analysis of tissue-enriched proteins. Figure S4, protein and mRNA expression from Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA). Figure S5, protein expression of MCM2, MCM4 and MCM6 in different cancer types tumor and normal tissues. Figure S6, protein expression of cancer/testis (CT) antigens according to the Human Protein Atlas (HPA).

In an 8-year study, the influence of integrated fertilization (combination of organic and inorganic fertilizers) on maize (Zea mays L.) yield and nutrition, with respect to nitrogen, phosphorus and potassium, at the different growth stages, was investigated in Quzhou County of the North China Plain. Three treatments were chosen for this study: inorganic fertilizers without organic fertilizers (IF), inorganic fertilizers plus low organic fertilizers (LOF) and inorganic fertilizers plus high organic fertilizers (HOF). The results showed that integrated fertilization significantly improved maize grain yield; the magnitude of increase in maize grain yield with HOF and LOF was 1.52 and 0.74 t ha−1, respectively, over the IF (9.20 t ha−1). The total plant biomass and uptake of nitrogen, phosphorus and potassium in maize plants across growing stages were significantly improved with integrated fertilization. The integrated supply of nutrients was also beneficial in improving soil organic carbon, total nitrogen, available phosphorus and exchangeable potassium over the years. The result suggests that nutrient management practices for maize cultivation in the North China Plain should preferably include the integrated use of organic and inorganic fertilizers (3.75 t ha−1 organic fertilizers supplemented with 125 kg N ha−1) to increase soil fertility and maize yield.

This paper proposes a novel 2-step global sensitivity analysis algorithm to provide an in-depth sensitivity analysis of the vehicle parameters on the system responses. A 9 degree-of-freedom...

With the advance of mass spectrometry based proteomics techniques, thousands of phosphorylation sites can be identified from a single cell line or a single tissue sample by large scale global analysis. However, such large scale analysis is time consuming. And, due to the high complexity of the phosphoproteome sample, this approach is often unable to identify low abundance regulatory phosphorylation sites. Alternatively, the “divide and conquer” strategy by targeted analysis of a subset of phosphoproteome, i.e. subphosphoproteome, can improve the detection sensitivity of these phosphorylation sites. In this review, we summarized the analytical methods in this field. The enrichment approaches for the analysis of subphosphoproteomes generated by tyrosine kinases and basophilic kinases were introduced. The strategies for the analysis of the subphosphoproteomes composed by endogenous phosphopeptides, multiply phosphorylated peptides, etc., were also reviewed.

Summary The fruit epidermal features such as the size of tubercules are important fruit quality traits for cucumber production. But the mechanisms underlying tubercule formation remain elusive. Here, tubercule size locus CsTS1 was identified by map‐based cloning and was found to encode an oleosin protein. Allelic variation was identified in the promoter region of CsTS1, resulting in low expression of CsTS1 in all 22 different small‐warty or nonwarty cucumber lines. High CsTS1 expression levels were closely correlated with increased fruit tubercule size among 44 different cucumber lines. Transgenic complementation and RNAi‐mediated gene silencing of CsTS1 in transgenic cucumber plants demonstrated that CsTS1 positively regulates the development of tubercules. CsTS1 is highly expressed in the peel at fruit tubercule forming and enlargement stage. Auxin content and expression of three auxin signalling pathway genes were altered in the 35S:CsTS1 and CsTS1‐RNAi fruit tubercules, a result that was supported by comparing the cell size of the control and transgenic fruit tubercules. CsTu, a C2H2 zinc finger domain transcription factor that regulates tubercule initiation, binds directly to the CsTS1 promoter and promotes its expression. Taken together, our results reveal a novel mechanism in which the CsTu‐TS1 complex promotes fruit tubercule formation in cucumber.

Aerated irrigation can promote plant growth, increase yield and improve fruit quality, but the study on the effect of aeration irrigation on the absorption and metabolism of plant urea is relatively few. In this study, subsurface drip irrigation (SDI) with tanks technique and 15N tracer techniques were utilized to investigate the effect of the rhizosphere aeration treatment on plant growth and urea absorption, distribution and utilization of ‘Red Globe’ grape seedlings. The results indicated that the net photosynthetic rate, stomatal conductance and transpiration rate of the leaves increased with the aeration treatment in the same irrigation period. Soil urease and nitrate reductase of the aeration treatment were significantly higher than those from the no aeration treatment at the first, third, and fifth day after irrigation, but the difference was not significant between seedlings of the two treatments at the seventh and ninth day after irrigation. However, experiments that determined the absorption and utilization of the urea-15N in plants indicated that the Ndff values of the plant parts were significantly lower with aeration than those without aeration (CK).The distributions of 15N in these two treatments in the same parts were distinctly different except for the leaves, and the 15N utilization rate (3.46%) of plants with aeration was noticeably obviously lower than that of the CK plants (9.63%).The results showed that when urea was used as the nitrogen source, the rhizosphere aeration treatment performed by SDI with tanks reduced the ability of the organs to absorb nitrogen, and altered the distribution of nitrogen in the different parts of the grape plants. Therefore, we concluded that rhizosphere aeration could improve plant photosynthesis and soil urease and nitrate reductase activity, but it had negative effects on urea uptake, indicating that rhizosphere aeration and urea application did not have synergistic effects.These results suggest that it is not suitable for aeration irrigation when urea is used as nitrogen fertilizer.

Chain-like PtCu nanowires were successfully synthesized in the absence of any templates or surfactants by a facile chemical co-reaction approach. The resulting PtCu nanowires were characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, and electrochemical techniques. Utilized as electrocatalysts, the PtCu nanowires exhibit superior catalytic activity toward both the oxygen reduction reaction (ORR) and methanol oxidation reaction (MOR) compared to commercially carbon-supported platinum (Pt/C-JM) catalyst, indicating their potential applications in fuel cell. In addition, the effect of the relative distribution of PtCu and PtCu3 alloy phases coexisting in PtCu nanowires catalysts on the ORR activity was also investigated.

This paper presents a new approach for vibration mitigation based on a dynamic vibration absorbing structure (DVAS) for electric vehicles (EVs) that use in-wheel switched reluctance motors (SRMs). The proposed approach aims to alleviate the negative effects of vibration caused by the unbalanced electromagnetic force (UMEF) that arises from road excitations. The analytical model of SRMs is first formulated using Fourier series, and then a model of the coupled longitudinal-vertical dynamics is developed taking into consideration the external excitations consisting of the aerodynamic drag force and road unevenness. In addition, numerical simulations for a conventional SRM-suspension system and two novel DVASs are carried out for varying road levels specified by ISO standards and vehicle velocities. The results of the comparison reveal that a 35% improvement in ride comfort, 30% improvement of road handling, and 68% improvement in air gap between rotor and stator can be achieved by adopting the novel DVAS compared to the conventional SRM-suspension system. Finally, multi-body simulation (MBS) is performed using LMS Motion to validate the feasibility of the proposed DVAS. Analysis of the results shows that the proposed method can augment the effective application of SRMs in EVs.

As the possibility of faults in active suspension actuators are higher and more severe compared to other components, this study presents a fault-tolerant control approach based on the second-order sliding mode control method. The aim of the controller is to improve riding comfort, guarantee handling stability, and provide adequate suspension stroke in the presence of disturbances and actuator faults. A nonlinear full-vehicle suspension system and hydraulic actuator with nonlinear characteristics are adopted for accurate control. Firstly, a nonlinear sliding manifold based on a nonsingular fast terminal sliding mode controller is introduced to suppress the sprung mass heave, pitch, and roll motions arising from road disturbances. Secondly, a second-order sliding mode-based super twisting controller is utilized to track the desired forces generated by the nonsingular fast terminal sliding mode controller with actuator faults and uncertainties. The controllers are robust against disturbances, uncertainties, and faults. Moreover, the stability of the super twisting controller is proved by the strong Lyapunov functions. Finally, numerical simulations are performed to demonstrate the effectiveness of the controller. Four different conditions, random road profile, bump road excitation, single-wheel bump excitation, and partial faults are considered. The main contributions of this study are: (1) combination of the above algorithms to deal with actuator faults and improve active suspension performance; (2) the controller proposed in this study has a simple structure. Simulation results indicate that the nonsingular fast terminal sliding mode super twisting controller can guarantee the performance of the closed-loop system under both faulty and healthy conditions.

CsMYB6 interacts with CsTRY and they work cooperatively to suppress fruit trichome initiation in cucumber., Fruit epidermal features such as the number and size of trichomes or spines are important fruit quality traits in cucumber production. Little is known about the molecular mechanisms underlying fruit spine formation in cucumber. Here, we report functional characterization of the cucumber CsMYB6 gene, which encodes a MIXTA-like MYB transcription factor that plays an important role in regulating fruit trichome development. Spatial-temporal expression analyses revealed high-level expression of CsMYB6 in the epidermis of cucumber ovaries during fruit spine initiation, which was similar to the expression of CsTRY, a homolog of the Arabidopsis TRY gene that also plays a key role in trichome development. Overexpression of CsMYB6 and CsTRY in cucumber and Arabidopsis revealed that CsMYB6 and CsTRY act as negative regulators of trichome initiation in both species, and that CsMYB6 acted upstream of CsTRY in this process. CsMYB6 was found to bind to the three MYB binding sites inside the promoter region of CsTRY, and protein–protein interaction assays suggested that CsTRY also directly interacted with CsMYB6 protein. The results also revealed conserved and divergent roles of CsMYB6 and its Arabidopsis homolog AtMYB106 in trichome development. Collectively, our results reveal a novel mechanism in which the CsMYB6-CsTRY complex negatively regulates fruit trichome formation in cucumber.

This paper presents novel algorithms for vibration control of the in-wheel motor (IWM) driven electric vehicles to improve its ride comfort and reduce IWM vibration. A quarter vehicle model is first developed based on a dynamic vibration absorbing structure (DVAS) driven by a switched reluctance motor (SRM). This model considers the coupled longitudinal-vertical dynamics and the unknown road profile as well as the unbalanced electromagnetic force induced by the SRM are treated as the excitation. The dynamics and boundary models of two commercially available semi-active dampers are then presented, which are used as the actuators of both the suspension and the DVAS structure. Based on the developed model, a hybrid controller with a hybrid acceleration driven damping algorithms is proposed to reduce the vibration of the sprung mass and the SRM. The controller parameters are subsequently determined by solving the multi-objective optimization problem with a multi-objective evolutionary optimization method. Numerical simulation results for random road and bumpy excitations are analyzed, and multi-body simulation is finally performed to validate the feasibility of the proposed controllers. Results indicate that the proposed hybrid controllers can effectively improve ride comfort and reduce the SRM vibration compared with the traditional suspension system with IWM.

Excavator is one of the most important construction machineries. Its working environment is complex and changeable. There is no perfect suspension system for excavator as cars, and the covering parts are mostly thin-wall welded parts. Therefore, the covering parts are easy to be damaged in the working process, which brings poor using experience problems to users. According to the user feedback survey, toolboxes are most prone to cracking in the cover. The quality of the toolbox determines the company’s reputation and brand competitiveness in the market to a certain extent. Therefore, it is important to study the vibration response of the toolbox. Aiming at the problem of box body cracking in the road test of a medium-sized excavator toolbox, this paper carried out modal simulation and test verification on the excavator toolbox, laying the foundation for the follow-up research.

The structural and electronic properties of arsenene and monolayer transition-metal dichalcogenides (β-As/MX2) heterostructures have been systematically investigated by density functional theory. It is found that all β-As/MX2 heterostructures with little lattice mismatch possess considerable band gaps. Their electronic properties can be effectively tuned via (biaxial or uniaxial) strain and electric field, but the variation trends are different. The band gaps of the β-As/MX2 heterostructures decrease linearly as the strain arises, while there is a Stark effect of the band gap under suitable electric field due to the spontaneous electric polarization in the heterostructures. Meanwhile, a series change of the semiconductor types of the β-As/MX2 heterostructures could also be obtained by the strain and electric field. These diverse electronic properties may provide a potential application in nanodevices based on arsenene and transition-metal dichalcogenides.

In this study, we developed a centrifugation assisted solid phase extraction (SPE) method for the selective enrichment of phosphopeptides using a new Ti4+-IMAC material synthesized in-house. This new material has the feature of big size and large specific surface area which makes it more suitable to enrich phosphopeptides in a SPE way. The spin tips loaded with the Ti4+-IMAC material were applied to enrich phosphopeptides from the complex protein digests. It was found that phosphopeptides can be specifically enriched from tryptic digest of bovine serum albumin and β-casein at a molar ratio up to 1000:1. And about 4700 unique phosphorylated peptides can be identified with the specificity as high as 99% from the tryptic digest of HeLa cell proteins. This tip was demonstrated to have good column-to-column reproducibility. Furthermore, it is fitted to analyze minute amount of sample. Compared with the conventional solution method, the SPE method facilitated the rapid and complete separation of the material with solution, which making it a time-saving and convenient method for phosphopeptide enrichment. Compared with the commercial TiO2 material, this new materials yielded much more phosphopeptide identifications and much higher enrichment specificity.

Monoclonal antibodies (mAbs), are one of the most important protein drugs have attracted increasing attention. However, the pharmacokinetics of mAbs has not been fully investigated due to the complexity of protein drugs. Traditonal immuno-based approaches can not recognize the proteoforms of mAbs because of the long development cycles, prohibitive cost, and interactions between different proteins. Therefore, reliable qualitative and quantitative analysis of the proteoforms of mAbs in biological samples is of crucial importance. Herein, a novel method was developed for absolute quantitation of mAbs and their glycoforms in complex biological samples such as serum and tissues. With the combination of HILIC enrichment and parallel reaction monitoring by high resolution mass spectrometry, most of the glycoforms can be accurately quantified at the fmol level through the use of the model mAb of bevacizumab. More importantly, the structural confirmation can be achieved simultaneously without the need for additional experiments. This strategy can be readily applied to the pharmacokinetic study of glycosylation modification and biomarker discovery for clinical applications.

The aim of conventional active noise control (ANC) system is to attenuate the sound pressure level (SPL) of unwanted noise as much as possible. However, it is desirable to retain some of the sound with a specified spectrum to meet the requirements of human perception in various applications. This is particularly true in automotive vehicle applications in which some engine noise is to be retained. An active noise equalizer (ANE) is proposed to meet this requirement. This paper proposes an active broadband sound quality control algorithm, based on traditional broadband ANE. The algorithm can not only shape the spectrum of the residual noise according to the sound quality filter, but also control the SPL of the residual noise to satisfy a predefined target accurately, when the amplitude of the disturbance noise changes. This aim is accomplished by introducing a gain factor which is adaptively determined based on the power of the instantaneous disturbance noise and the predefined target. This algorithm has four control modes according to the value of the gain factor. Simulations are carried out to validate the performance of the proposed algorithm using both simulated noise and real vehicle cabin noise. Simulation results show that the SPL error of the proposed control algorithm is within ±2 dB of the predetermined target in the majority of cases simulated. The tracking capability of the proposed algorithm is shown to exhibit good performance in the presence of a time varying SPL target and time varying disturbance noise.

Vehicle performance is largely affected by the properties of the suspension system, where semi-active suspension has been widely used in mass production of vehicles owing to its characteristics such as internal stability and low energy consumption. To solve the contradiction between ride comfort and road handling, road estimation based semi-active suspension has received considerable attention in recent years. In order to provide accurate estimation for advanced control strategies applications, this paper aims to develop a new method that can provide precise road class estimation based on measurable suspension system response (i.e. sprung mass acceleration, unsprung mass acceleration and rattle space). The response signal is first decomposed using wavelet packet analysis, and features in both time and frequency domains are subsequently extracted. Then, minimum redundancy maximum relevance (mRMR) is utilized to select superior features. Finally, a probabilistic neural network (PNN) classifier is applied to determine road classification output. The most representative semi-active control strategy, i.e. skyhook control, is used to validate this method, and simulation results with varying conditions including different control parameters and sprung mass are compared. The results show that unsprung mass acceleration is most suitable for road classification, and more robust to varying conditions in comparison to other responses.

Temporal tyrosine phosphorylation (pTyr) plays a crucial role in numerous cellular functions. The characterization of the tyrosine phosphorylation states of cells is of great interest for understanding the underlying mechanisms. In this study, we developed sensitive and cost-effective methods for the assay of the global protein tyrosine phosphorylation in complex samples by using a novel engineered pTyr binding protein, Src SH2 domain triple-point mutant (Trm-SH2). Taking the advantage of the pan-specific interaction of Trm-SH2 to pTyr, a high throughput approach was developed to determine the total protein tyrosine phosphorylation level in a sample. This method allowed the detection of 0.025 ng of tyrosine phosphorylated proteins. The Trm-SH2 was further exploited to develop a method to profile the global tyrosine phosphorylation state. When this approach was applied to analyze the tyrosine phosphoproteome upon stimulation, distinct patterns were observed. This approach is readily used in many research and clinical fields for the analysis of tyrosine phosphorylated proteins in complex samples, including classifying aberrant phosphotyrosine-dependent signaling in cancer.

The diversity of O-linked glycan structures has drawn increasing attention due to its vital biological roles. However, intact O-glycopeptides with different glycans are typically not well elucidated using the current methods. In this work, an integrated strategy was developed for comprehensive analysis of O-GalNAc glycosylation by combining hydrophilic interaction chromatography (HILIC) tip enrichment, beam-type collision induced decomposition (beam-CID) detection, and in silico deglycosylation method for spectra interpretation. In this strategy, the intact O-GalNAc glycopeptides were selectively enriched and the original spectra obtained by time-of-flight (TOF)-CID were preprocessed using an in silico deglycosylation method, enabling direct searching without setting multiple glycosylation modifications, which could significantly decrease the search space. This strategy was applied to analyze the O-GalNAc glycoproteome of human serum, leading to identification of 407 intact O-GalNAc glycopeptides from 93 glycoproteins. About 81% of the glycopeptides contained at least one sialic acid, which could reveal the microheterogeneity of O-GalNAc glycosylation. Up until now, this is the largest data set of intact O-GalNAc glycoforms from complex biological samples at the proteome level. Furthermore, this method is readily applicable to study O-glycoform heterogeneity in other complex biological systems.

Mass spectrometry (MS) based quantitative analyses of proteome and proteome post-translational modifications (PTMs) play more and more important roles in biological, pharmaceutical and clinical studies. However, it is still a big challenge to accurately quantify the proteins or proteins PTM sites with extreme relative abundances in comparative protein samples, such as the significantly dysregulated ones. Herein, a novel quantification strategy, Mixing at Specific Ratio (MaSR) before isotope labeling, had been developed to improve the quantification accuracy and coverage of extreme proteins and protein phosphorylation sites. Briefly, the comparative protein samples were firstly mixed together at specific ratios of 9:1 and 1:9 (w/w), followed with mass differentiate light and heavy isotope labeling, respectively. The extreme proteins and protein phosphorylation sites, even if the newly expressed or disappeared ones, could be accurately quantified due to all of the proteins' relative abundances had been adjusted to 2 orders of magnitude (1/9-9) by this strategy. The number of quantified phosphorylation sites with more than 20 folds changes was improved about 10 times in comparative quantification of pervanadate stimulated phosphoproteome of HeLa cells, and 134 newly generated and 21 disappeared phosphorylation sites were solely quantified by the MaSR strategy. The significantly up-regulated phosphorylation sites were mainly involved in the key phosphoproteins regulating the insulin-related pathways, such as PI3K-AKT and RAS-MAPK pathways. Therefore, the MaSR strategy exhibits as a promising way in elucidating the biological processes with significant dysregulations.

This paper presents a new method to address issues associated with vehicle system state estimation using an unscented Kalman filter (UKF) with considering full-car system and nonlinear tire force under various international standards organization (ISO) road conditions. Due to the fact that practical road information is complex and noise covariance cannot be treated as a constant, the influence of varying vehicle system process noise variance and measurement noise covariance on the estimation accuracy of the UKF is first discussed. To precisely estimate road information, a novel road classification method using measured signals (vertical acceleration of sprung mass and unsprung mass) of vehicle system is proposed. According to road excitation levels, different road process variances are defined to tune the vehicle system’s variance for application of UKF. Then, road classification and UKF are combined to form an adaptive UKF (AUKF) that takes into account the relationship of different road process noise variances and measurement noise covariances under varying road conditions. Simulation results reveal that the proposed AUKF algorithm has higher accuracy for state estimation of a vehicle system under various ISO road excitation condition.