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Fluid-conveying pipes are widely used to transfer bulk fluids from one point to another in many engineering applications. They are subject to various excitations from the conveying fluids, the supporting structures, and the working environment, and thus are prone to vibrations such as flow-induced vibrations and acoustic-induced vibrations. Vibrations can generate variable dynamic stress and large deformation on fluid-conveying pipes, leading to vibration-induced fatigue and damage on the pipes, or even leading to failure of the entire piping system and catastrophic accidents. Therefore, the vibration control of fluid-conveying pipes is essential to ensure the integrity and safety of pipeline systems, and has attracted considerable attention from both researchers and engineers. The present paper aims to provide an extensive review of the state-of-the-art research on the vibration control of fluid-conveying pipes. The vibration analysis of fluid-conveying pipes is briefly discussed to show some key issues involved in the vibration analysis. Then, the research progress on the vibration control of fluid-conveying pipes is reviewed from four aspects in terms of passive control, active vibration control, semi-active vibration control, and structural optimization design for vibration reduction. Furthermore, the main results of existing research on the vibration control of fluid-conveying pipes are summarized, and future promising research directions are recommended to address the current research gaps. This paper contributes to the understanding of vibration control of fluid-conveying pipes, and will help the research work on the vibration control of fluid-conveying pipes attract more attention. [ABSTRACT FROM AUTHOR]

In order to improve the quality of welded joints and increase the service life of pipelines, ABAQUS finite element software was used to simulate the temperature field of 18,4 mm thick X80 pipeline steel in multi-layer and multi pass welding. The peak temperature of different passes was compared, and the change trend of temperature field in the welding process was obtained. The results show that the peak temperature of the weld and its adjacent areas is higher, and the peak temperature of the weld center is the highest. Due to the fast welding speed, the heat cannot be transferred to other areas in time, resulting in uneven heating of the entire test panel. [ABSTRACT FROM AUTHOR]

To obtain the exact mechanical properties of TC4 titanium alloy, the compression experiments on TC4 titanium alloy at different strain rates (10-2,10-3,10-4 s-1) were performed at room-temperature on the MTS-810 electrohydraulic servo material testing machine. The data of TC4 titanium alloy compression experiments at different rates were obtained. And furthermore Johnson-Cook constitutive model is established. Due to different conditions, the equation is simplified, the constitutive parameters are obtained by step-by-step estimation method, and the Johnson-Cook (JC) constitutive model of TC4 titanium alloy at room temperature is established. The prediction results of the model were compared with the experimental data, the prediction curve is in good agreement, which verifies the feasibility of the model. [ABSTRACT FROM AUTHOR]

We study an asymptotic property of weighted sequences of nonnegative functions which extends and unifies previous results concerned with precise asymptotics. As applications, we prove precise asymptotics for partial sums of independent identically distributed classical, noncommutative and free random variables. [ABSTRACT FROM AUTHOR]

Hot forging forming of railway wagon bogie adapter is a new railway wagon bogie adapter processing technology. In this paper, a hot forging die for railway wagon bogie adapter was designed, and the forming quality were analyzed by using DEFORM-3D software. Then, the feasibility of the process was verified by experiments. It was found that using this mold can eliminate the defects such as loose as-cast in metal smelting process, optimize the microstructure, forging products with good density, product quality and other characteristics of stability. [ABSTRACT FROM AUTHOR]

Using Gleeble-3800 thermal simulation testing machine, the TC4 titanium alloy was subjected to hot compression experiments under the conditions of deformation temperature of 810 – 950 °C, strain rate of 0.001 - 1s-1. The research shows that the flow stress of TC4 titanium alloy is more sensitive to the deformation temperature and strain rate during thermal deformation, and it increases with the decrease of the deformation temperature and the increase of the strain rate. Based on BP neural network, a constitutive model of TC4 titanium alloy α+β two-phase region is established. The correlation coefficient reaches 0,996, which proves that the model can predict the high temperature flow stress of TC4 titanium alloy. [ABSTRACT FROM AUTHOR]

The Gleeble – 3500 thermal simulation testing machine was used to perform isothermal tensile test on 7075 aluminum alloy at a deformation temperature of 300 – 450 °C and a strain rate of 0,01 – 1 s-1, and the true stress-strain curve of the alloy was obtained. Based on the true stress-strain data, the modified Zerilli-Armstrong (M-ZA) model was used to construct the constitutive model of the alloy, and the fitting accuracy of the model was analyzed. [ABSTRACT FROM AUTHOR]

Use Gleeble-3800 thermal simulation test machine to conduct thermal tensile test on 6005A aluminum alloy at 623~723 K and 0,01~1 s-1 strain rate. Using the obtained true stress-strain curve, the modified Zerilli-Armstrong (m- Z-A) model considering strain compensation was used to construct the constitutive model of the alloy. The results show that the correlation coefficient and average absolute error of the m-Z-A model are 0,97311 and 4,1779 %, respectively. The experimental data is in good agreement with the predicted curve obtained by calculating the model, which verifies the feasibility of the model. [ABSTRACT FROM AUTHOR]

The deformation behavior of 6005A aluminum alloy at a strain rate of 0,01-10s-1, a deformation temperature of 673- 773K and a total strain of 0,8 was studied. Using the stress-strain data of 6005A aluminum alloy with a strain of 0,05- 0,8, an Arrhenius-type constitutive model was established. And verified the accuracy of the model. The results show that: the flow stress of 6005A aluminum alloy increases with the increase of strain rate, and decreases with the increase of deformation temperature; Under different strains, the correlation coefficient (R) between the experimental value and the predicted value is as high as 98 %, and the average relative error (AARE) is less than 10 %, indicating that the established model has high predictability. [ABSTRACT FROM AUTHOR]

Electronic emission of an isolated pyrene molecule induced by 50 to 125 keV protons has been investigated. The corresponding absolute double differential cross-sections have been measured at an angle of 35° with respect to the incident proton beam axis. These measurements were compared to the simulations of emitted electrons' spectra using a semi-classical trajectory Monte-Carlo (SCTMC) approach. The simulated SCTMC cross-sections show reasonably good agreement with the measured ones. [ABSTRACT FROM AUTHOR]

This article takes the 21 - 4N engine valve as the research object and studies the effects of die forging temperature (1 000 - 1 180 °C), die forging speed (0,15 - 200 mm / s) and friction coefficient (0,1 - 0,5) on die forging results. First, a finite element model (FEM) of the valve blank and die is established using Creo; next, the valve forging process is simulated using Deform - 3D; then, the response surface analysis method is used to analyze and discuss the results of die forging, and to optimize the process parameters with valve product damage as the optimization goal, and determine the best process parameters for 21 - 4N engine valve forging; finally, the obtained parameters are verified through experiments, and the experimental results and prediction results have a good consistency. [ABSTRACT FROM AUTHOR]

This article takes the 21 - 4N engine valve as the research object and studies the effects of die forging temperature (1 000 - 1 180 °C), die forging speed (0,15 - 200 mm / s) and friction coefficient (0,1 - 0,5) on die forging results. First, a finite element model (FEM) of the valve blank and die is established using Creo; next, the valve forging process is simulated using Deform - 3D; then, the response surface analysis method is used to analyze and discuss the results of die forging, and to optimize the process parameters with valve product damage as the optimization goal, and determine the best process parameters for 21 - 4N engine valve forging; finally, the obtained parameters are verified through experiments, and the experimental results and prediction results have a good consistency. [ABSTRACT FROM AUTHOR]

The 3Cr23Ni8Mn3N heat-resistant steel was subjected to isothermal constant strain rate compression experiments using a Gleeble - 1 500D thermal simulator. The thermal deformation behavior in the range of deformation temperature 1 000 - 1 180 °C and strain rate 0,01 - 10 s-1 was studied. Based on experimental data, the stress-strain curves of 3Cr23Ni8Mn3N were established. And the constitutive relation of BP neural network (3 × 10 × 10 × 1) was constructed. The flow stress was predicted and compared by the ANN constitutive model. The correlation coefficient (R) is 0,999, and the average relative error (AARE) is 0,697%. The results show that the ANN constitutive model has high accuracy for predicting the thermal deformation behavior of 3Cr23Ni8Mn3N. The model can provide a good reference value for thermal processing. [ABSTRACT FROM AUTHOR]

The effect of grain growth on 21-4N heat resistant steel was studied by static grain growth test. The experimental results show that the temperature inhibits carbide grain growth is between 1 000 - 1 120 °C. When heat preservation time is over 40 min, the driving force of grain boundary is balanced with binding force of carbide nail, grain size will not grow up. There is no limit of grain size due to no pinning effect of carbides when the temperature is above 1 180 °C. Based on the theory of grain boundary migration, the grain growth model of 21-4N heat-resistant steel was established, and the relationship between the average grain size and the time of heat preservation at different temperatures was predicted. [ABSTRACT FROM AUTHOR]

There are many uncertain factors in the test process of electroplating zinc. The establishment of control standards in the research process can reduce the workload and shorten the test cycle. Based on the electrochemical module developed by COMSOL multi-physics software, this study uses the computer's powerful computing power and the existing perfect theoretical system to simulate the experiment. The results show that the potential at the anode plate is higher, the potential at the cathode plate is lower, and the potential distribution in the middle area of the two plates is relatively uniform. When the plating time is 10 min, the outer surface of the galvanized part is basically coated with a relatively uniform zinc coating, which is about 2μm. Due to the large local current density in each edge area of the sample, the plating layer is relatively thick, but the difference is not large. [ABSTRACT FROM AUTHOR]

Metabolite interferences represent a major risk of inaccurate quantification when using LC–MS/MS bioanalytical assays. During LC–MS/MS bioanalysis of BMS-919194, a phosphate ester prodrug, in plasma samples from rat and monkey GLP toxicology studies, an unknown peak was detected in the MRM channel of the prodrug. This peak was not observed in previous discovery toxicology studies, in which a fast gradient LC–MS/MS method was used. We found out that this unknown peak would co-elute with the prodrug peak when the discovery method was used, therefore, causing significant overestimation of the exposure of the prodrug in the discovery toxicology studies. To understand the nature of this interfering peak and its impact to bioanalytical assay, we further investigated its formation and identification. The interfering compound and the prodrug were found to be isobaric and to have the same major product ions in electrospray ionization positive mode, thus, could not be differentiated using a triple quadrupole mass spectrometer. By using high-resolution mass spectrometry (HRMS), the interfering metabolite was successfully identified to be an isobaric sulfate metabolite of BMS-919194. To the best of our knowledge, this is the first report that a phosphate prodrug was metabolized in vivo to an isobaric sulfate metabolite, and this metabolite caused significant interference to the analysis of the prodrug. This work demonstrated the presence of the interference risk from isobaric sulfate metabolites to the bioanalysis of phosphate prodrugs in real samples. It is critical to evaluate and mitigate potential metabolite interferences during method development, therefore, minimize the related bioanalytical risks and ensure assay quality. Our work also showed the unique advantages of HRMS in identifying potential metabolite interference during LC–MS/MS bioanalysis. [ABSTRACT FROM AUTHOR]

Abstract: In this study, a new formulation for the thermo‐osmotic permeability of natural pore solutions containing monovalent and divalent cations is proposed. The mathematical formulation proposed here is based on the theoretical framework supporting thermo‐osmosis which relies on water structure alteration in the pore space of surface‐charged materials caused by solid‐fluid electrochemical interactions. The ionic content balancing the surface charge of clay minerals causes a disruption in the hydrogen bond network when more structured water is present at the clay surface. Analytical expressions based on our heuristic model are proposed and compared to the available data for NaCl solutions. It is shown that the introduction of divalent cations reduces the thermo‐osmotic permeability by one third compared to the monovalent case. The analytical expressions provided here can be used to advantage for safety calculations in deep underground nuclear waste repositories. [ABSTRACT FROM AUTHOR]

A time-delayed quadratic nonlinear mechanical system can exhibit two coexisting stable bifurcating solutions ( SBSs) after two-to-one resonant Hopf bifurcations occur in the corresponding autonomous time-delayed system. One SBS is of small-amplitude and has the Hopf bifurcation frequencies ( HBFs), while the other is of large-amplitude and contains the shifted Hopf bifurcation frequencies (the shifted HBFs). When the forcing frequency is tuned to be the sum of two HBFs or the sum of two shifted HBFs, two families of additive resonances can be induced in the forced response. The forced response under the additive resonance related to the HBFs can demonstrate periodic, quasi-periodic and chaotic motion. On the contrary, the forced response under the additive resonance associated with the shifted HBFs may exhibit period-three periodic motion and quasi-periodic motion. Bifurcation diagrams, time trajectories, frequency spectra, phase portraits and Poincaré sections are presented to show periodic, quasi-periodic, and chaotic motion of the time-delayed nonlinear system under the two families of additive resonances. [ABSTRACT FROM AUTHOR]

BMS-823778 is a potent 11-β-hydroxysteroid-dehydrogenase 1 (11βHSD-1) inhibitor and a potential therapeutic agent for type 2 diabetes mellitus (T2DM). A high performance liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay was developed and validated to enable reliable separation and quantification of both enantiomers of a chiral hydroxy metabolite (BMT-094817) in human plasma. Following liquid–liquid extraction in a 96-well plate format, chromatographic separation of the metabolite enantiomers was achieved by isocratic elution on a Chiralpak IA-3 column. Chromatographic conditions were optimized to ensure separation of both metabolite enantiomers. Metabolite enantiomers and stable isotope-labeled (SIL) internal standards were detected by positive ion electrospray tandem mass spectrometry. The LC–MS/MS assay was validated over a concentration range of 0.200–200 ng/mL. Intra- and inter-assay precision values for replicate quality control samples were less than 9.9% for both enantiomers during the assay validation. Mean quality control accuracy values were within ±7.3%. Assay recoveries were high (>75%) and consistent across the assay range. The metabolite enantiomers were stable in human blood for 2 h on ice. The analytes were also stable in human plasma for 25 h at room temperature, 34 days at −20 °C and −70 °C, and following five freeze-thaw cycles. No interconversion of the metabolite enantiomers was detected under any bioanalytical stress conditions, from blood collection/processing through extracted sample storage. The validated assay was successfully applied to the quantification of both metabolite enantiomers in human plasma in support of a human pharmacokinetic study. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration is a common orthopedic disease that has been recognized as the major cause of low back pain. About 80% of the population is affected by this disease. We explored molecular mechanisms of disc degeneration and identified the genes associated with the disease. The transcription profile of GSE34095 was downloaded from Gene Expression Omnibus database with three degenerative disc samples and three healthy disc samples. Gene ontology and pathway enrichment analysis were performed. We constructed a protein-protein interaction (PPI) network and a transcription factor (TF) target network. Differentially expressed genes (DEGs) in normal and disc degeneration samples were identified including 243 up-regulated genes and 351 down-regulated genes. Meanwhile, seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained by mapping the 594 DEGs to the KEGG and we found that the calcium signaling pathway was the most significant for developing disc degeneration. The pathways interaction network analysis showed that the adherens junction pathway interacted with other six pathways. In addition, the top five genes, FYN, PRKCD, YWHAB, YWHAZ and AR, with a high degree of interaction of 7, 4, 4, 4 and 4, respectively, were related to the disc degeneration in the PPI network. Furthermore, transcription factors including TFAP2A, E2F4, SP3 and AR had the potential to regulate disc degeneration through the mitogen-activated protein kinase, vascular endothelial growth factor and p53 pathways. The genes and pathways that we identified may be involved in disc degeneration. [ABSTRACT FROM AUTHOR]

Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus. Here we report a liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical assay of dapagliflozin in human plasma. A lower limit of quantitation (LLOQ) at 0.2 ng/mL with 50 μL of plasma was obtained, which reflects a 5-fold improvement of the overall assay sensitivity in comparison to the previous most sensitive assay using the same mass spectrometry instrumentation. In this new assay, acetate adduct ions in negative electrospray ionization mode were used as the precursor ions for selective reaction monitoring (SRM) detection. Sample preparation procedures and LC conditions were further developed to enhance the column life span and achieve the separation of dapagliflozin from potential interferences, especially its epimers. The assay also quantifies dapagliflozin's major systemic circulating glucuronide metabolite, BMS-801576, concentrations in human plasma. The assay was successfully transferred to contract research organizations (CROs), validated, and implemented for the sample analysis of pediatric and other critical clinical studies. This assay can be widely used for bioanalytical support of future clinical studies for the newly approved drug Farxiga or any combination therapy containing dapagliflozin. [ABSTRACT FROM AUTHOR]

Rationale: The in‐sample calibration curve (ISCC) approach of quantification utilizes the response of isotopologue ions from spiked‐in stable isotope labeled internal standard (SIL‐IS) to build a standard curve. The quantitative analysis of the study sample is achieved based on the response of selected monoisotopic analyte ion against the calibration curve. Although this methodology has been demonstrated to be feasible by unit and high‐resolution mass spectrometers, quantitation on high‐resolution mass spectrometer with product ions has not been tested. We tested the feasibility of this approach using product ions on an high‐resolution mass spectrometer equipped with an Orbitrap detector. Methods: Using a proteomics workflow for sample preparation, two surrogate peptides were quantified from a complex matrix of protein digest from human peripheral blood mononuclear cells (hPBMCs). SIL‐IS was spiked in at different levels to construct calibration curves in a traditional manner. ISCCs were prepared using extracted ion chromatograms from isotopically resolved mass spectra and compared with traditional calibration curves. Results: A linear response was observed with ISCC approach for at least two to three orders of magnitude in MS1 as well as targeted MS2 (tMS2). From protein digests, isobaric interferences were observed for endogenous peptides on the MS1 level; this was circumvented with product‐ion‐based quantitation where for one peptide, %CV for endogenous levels was more than 20% with ISCC but higher with the traditional calibration curve approach. For the second peptide, endogenous levels could not be determined in the traditional approach as calibrant levels did not bracket the lower end, and with the ISCC approach, isotopologues at abundances lower than the endogenous level allowed for quantitative assessments. Conclusions: ISCC demonstrated improved precision across surrogate peptides from endogenous protein digests. In samples where endogenous analyte concentrations were low in abundance, ISCC rescued what would have been a non‐reportable result in a traditional bioanalytical assay as calibrant levels were not prepared at adequately low levels to bracket unknowns. ISCC using high‐resolution mass spectrometer is feasible and ideal compared to unit resolution mass spectrometers. High‐resolution mass spectrometer allows for isotopic resolution for analytes with > + 2 charge state and provides flexibility in quantification using multiple product ions. ISCC using high‐resolution mass spectrometer allows for simultaneous assaying of low abundance isotopologues, the signal acquisition of which is not constrained by limits in data acquisition or calibrant preparation as with other approaches but rather limited by platform sensitivity. In contrast to unit resolution mass spectrometers, these features offered by high‐resolution mass spectrometer could be especially useful for the drug discovery assay support where there is less lead time for assay development than for the assays to support the drug development studies. [ABSTRACT FROM AUTHOR]

In the process of hoisting the memorial archway, because the balance beam directly lifts the memorial archway, it is easy to deform during the hoisting process, and the deformation will affect the follow-up work, resulting in the delay of the project progress. In order to avoid this situation, the existing conditions are used to calculate the load that the balance beam can bear. Using 3D modeling and numerical simulation software, conduct force analysis on the balanced beam, and compare the simulation results with the calculated values to determine whether the stress and deformation of the balanced beam meet the requirements. The simulation results show that the stress on the balance beam during the lifting process does not exceed the maximum yield stress of its own material, which meets the requirements of the working conditions. [ABSTRACT FROM AUTHOR]

In the process of carrying out the installation of large flue, because the thickness of the flue is thin, it is easy to deform when hoisting with wire rope, and too much deformation will affect the subsequent use of the flue, resulting in waste, so in order to reduce the deformation of the flue, the existing conditions are utilized, and the bracket is added inside the flue to play the role of support, and the deformation of the flue is reduced. Using 3D modeling and numerical simulation software, the flue structure before and after adding supports was modeled and numerically analyzed, and the two simulation results were compared, and the deformation of the flue after adding supports was analyzed to be relatively obvious under the action of hoisting. [ABSTRACT FROM AUTHOR]

Abstract: In recent years, there has been increasing interest in using LC–MS/MS to measure protein drugs (biotherapeutics) in plasma/serum to support pharmacokinetic/toxicokinetic (PK/TK) studies. A number of strategies have been proposed to quantify different types of protein drug candidates in biological matrices. However, the application of LC–MS/MS in biotherapeutics is still very limited in regulated bioanalysis due to practical challenges. In this manuscript, we propose a “data-dependent” approach for the LC–MS/MS support of protein drug candidates, focusing on operational aspects. We have developed and validated a fast, simple and reliable LC–MS/MS method to quantify a protein drug candidate in mouse serum. This method can fit into our current workflow for routine small molecule LC–MS/MS assays with an overall sample preparation time of less than two hours. The method has been demonstrated to be accurate, precise and rugged, and it has been successfully applied to analyze samples from toxicology studies. The results were verified using a ligand binding assay and tested by standard-addition sample reanalysis. In addition, general recommendations for developing and validating an LC–MS/MS assay based on surrogate peptide(s) of protein drug candidates are also proposed for regulated bioanalysis. [Copyright &y& Elsevier]

The trivial equilibrium of a weakly nonlinear oscillator having quadratic nonlinearities under a delayed feedback control can change its stability via a single Hopf bifurcation as the time delay increases. Double Hopf bifurcation occurs when the characteristic equation has two pairs of purely imaginary solutions. An interaction of resonant Hopf-Hopf bifurcations may be possible when the two critical time delays corresponding to the two Hopf bifurcations have the same value. With the aid of normal form theory and centre manifold theorem as well as the method of multiple scales, the present paper studies the dynamics of a quadratically nonlinear oscillator involving time delay in the vicinity of the point of two-to-one resonances of Hopf-Hopf bifurcations. The ratio of the frequencies of two Hopf bifurcations is numerically found to be nearly equal to two. The two resonant Hopf bifurcations can generate two respective periodic solutions. Consequently, the centre manifold corresponding to these two solutions is determined by a set of four first-order differential equations under two-to-one internal resonances. It is shown that the amplitudes of the two bifurcating periodic solutions admit the trivial solution and two-mode solutions for the averaged equations on the centre manifolds. Correspondingly, the cumulative behavior of the original nonlinear oscillator exhibits the initial equilibrium and a quasi-periodic motion having two frequencies. Illustrative examples are given to show the unstable zero solution, stable zero solution, and stable two-mode solution of the nonlinear oscillator under the two-to-one resonant Hopf-Hopf interactions. [ABSTRACT FROM AUTHOR]

Unstable drug candidates often lead to complexity for both sample collection and bioanalysis. Dried blood spot (DBS) technology is believed to be a viable solution to address this problem. However, it is currently a challenge to evaluate compound stability on DBS due to its solid format. The observed compound loss on a DBS card could be degradation and/or incomplete recovery. Therefore, a reliable bioanalytical method which can differentiate recovery loss from degradation is necessary for such stability evaluation. In this paper, the stability of an unstable drug candidate (KAI-9803) in human blood was evaluated using DBS. A reliable approach to evaluating analyte stability on DBS was developed with an appropriate time-zero sample, a consistent DBS sample processing method, and a suitable positive control. Commercially available DBS cards were evaluated, and it was found that KAI-9803 degraded during the drying process. An in-house modified DBS card was developed and demonstrated to be able to stabilize KAI-9803 during the drying process by rapidly lowering the pH of the spotted blood sample. The storage stability of KAI-9803 in human blood on this new card has been established for at least 48 days at room temperature. This in-house modified DBS card could provide a generic approach for other compounds which require stabilization at a low pH. [ABSTRACT FROM AUTHOR]

Currently, mass spectrometry-based protein bioanalysis is primarily achieved through monitoring the representative peptide(s) resulting from analyte protein digestion. However, this approach is often incapable of differentiating the measurement of protein analyte from its post-translational modifications (PTMs) and/or potential biotransformation (BTX) products. This disadvantage can be overcome by direct measurement of the intact protein analytes. Selected reaction monitoring (SRM) on triple quadrupole mass spectrometers has been used for the direct measurement of intact protein. However, the fragmentation efficiency though the SRM process could be limited in many cases, especially for high molecular weight proteins. In this study, we present a new strategy of intact protein bioanalysis by high-resolution (HR) full scan mass spectrometry using human lysozyme as a model protein. An HR linear ion-trap/Orbitrap mass spectrometer was used for detection. A composite of isotopic peaks from one or multiple charge states can be isolated from the background and used to improve the signal-to-noise ratio. The acquired data were processed by summing extracted ion chromatograms (EIC) of the 10 most intense isotopic ions of octuply protonated lysozyme. Quantitation of the plasma lysozyme was conducted by utilizing high resolving power and an EIC window fitting to the protein molecular weight. An assay with a linear dynamic range from 0.5 to 500 μg/mL was developed with good accuracy and precision. The assay was successfully employed for monitoring the level of endogenous lysozyme and a potential PTM in human plasma. The current instrumentation limitations and potential advantages of this approach for the bioanalysis of large proteins are discussed. [ABSTRACT FROM AUTHOR]

In a single degree-of-freedom weakly non-linear oscillator subjected to a periodic external excitation, a small-amplitude excitation may produce relatively large-amplitude vibrations under primary resonance conditions, when the forcing frequency is in the neighbourhood of the linearised natural frequency of the non-linear oscillator. Jump and hysteresis phenomena that result from saddle-node bifurcations may occur in the steady-state forced response. A non-linear vibration absorber is thus used to suppress the primary resonance vibrations. The two linearised natural frequencies of the resultant system formed by the non-linear primary system and nonlinear absorber are not under any internal resonance conditions. The method of multiple scales is used to obtain the averaged equations that determine the amplitudes and phases of the first-order approximate solutions. Illustrative examples are given to show the effectiveness of the non-linear vibration absorber for suppressing non-linear vibrations of the forced oscillator under primary resonance conditions. [ABSTRACT FROM AUTHOR]

We first systematically study the multivortex states in mesoscopic superconductors via self-consistent Bogoliubov-de Gennes equations. Our work focuses on how the geometrical symmetry affects the penetration and arrangement of vortices in mesoscopic superconductors and find that the key parameter determining the entrance of the vortex is the current density at the hot spots on the edge of sample. Through determining the spatial distribution of hot spots, the geometrical symmetry of the superconducting sample influences the nucleation and entrance of vortices. Our results propose one possible experimental approach to control and manipulate the quantum states of mesoscopic superconductors with their topological geometries, and they can be easily generalized to the confined superfluids and Bose-Einstein condensates. [ABSTRACT FROM AUTHOR]

Tumour-associated lymphatics contribute to a key component of metastatic spread, however, the biological interaction of tumour cells with intratumoural and peritumoural lymphatics (ITLs and PTLs) has remained unclear. To address this important issue, we have focused on the morphological and molecular aspects of newly formed lymphatics (lymphangiogenesis) and pre-existing lymphatics in the intratumoural and peritumoural tissues by using a hybridoma-induced tumour model. In the present study, ITLs with very high vessel density within the tumour mass showed small and flattened contours that varied from non-solid-to-solid tumours, whereas PTLs were relatively disorganized and tortuous, and packed with a cluster of tumour cells at the tumour periphery. Lymphatic endothelial cells (LECs) both in ITLs and PTLs were expressed with LYVE-1 and podoplanin in various tumour tissues, in which initial lymphatics were extremely extended and dilated. The tumour cells were frequently detected adhering to or penetrating lymphatic walls, especially near the open junctions. In the metastatic tissues, lymphangiogenic vasculatures occurred within the tumour matrix, and collecting PTLs represented abnormal twisty valve leaflets. The Western blot and RT-PCR analysis showed local variations of LEC proliferating potentials and lymphatic involvement in metastasis by a distinct profile of the protein and mRNA expression by LYVE-1, podoplanin, Prox-1 and vascular endothelial growth factor-3 (VEGFR-3). These findings indicated that both ITLs and PTLs, including enlarged pre-existing and newly formed lymphatics, may play a crucial role in metastasis with an active tumour cell adhesion, invasion, migration and implantation. [ABSTRACT FROM AUTHOR]

Abstract: The determination of protein concentrations in plasma samples often provides essential information in biomedical research, clinical diagnostics, and pharmaceutical discovery and development. Binding assays such as ELISA determine meaningful free analyte concentrations by using specific antigen or antibody reagents. Concurrently, mass spectrometric technology is becoming a promising complementary method to traditional binding assays. Mass spectrometric assays generally provide measurements of the total protein analyte concentration. However, it was found that antibodies may bind strongly with the protein analyte such that total concentrations cannot be determined. Thus, a sample preparation process was developed which included a novel “denaturing” step to dissociate binding between antibodies and the protein analyte prior to solid phase extraction of plasma samples and LC–MS/MS analysis. In so doing, the total protein analyte concentrations can be obtained. This sample preparation process was further studied by LC–MS analysis with a full mass range scan. It was found that the protein of interest and other plasma peptides were pre-concentrated, while plasma albumin was depleted in the extracts. This capability of the sample preparation process could provide additional advantages in proteomic research for biomarker discovery and validation. The performance of the assay with the novel denaturing step was further evaluated. The linear dynamic range was between 100.9ng/mL and 53920.0ng/mL with a coefficient of determination (r 2) ranging from 0.9979 and 0.9997. For LLOQ and ULOQ samples, the inter-assay CV was 12.6% and 2.7% and inter-assay mean accuracies were 103.7% and 99.5% of theoretical concentrations, respectively. For QC samples, the inter-assay CV was between 2.1% and 4.9%, and inter-assay mean accuracies were between 104.1% and 110.0% of theoretical concentrations. [Copyright &y& Elsevier]

Biotherapeutics such as protein and peptide drugs have attracted significant attention in the medical community and pharmaceutical industry in recent years. Immunogenicity is one of the major concerns in the development and application of biotherapeutics. Although great efforts have been put forth in reducing immunogenicity, monitoring the free ("active") drug concentration and the antibody formation is critical for preclinical and clinical studies. Currently, it is still a challenging task to have a standardized test method monitoring immunogenicity when bio-therapeutic compounds such as proteins and peptides are administrated. Combined with liquid chromatography/tandem mass spectrometry detection, the equilibrium dialysis technique that is conventionally used for measuring the free and bound concentration of small organic molecules was extended to the application of measuring the free and bound concentrations of a protein drug with a relative molecular mass over 10000 from plasma samples containing antibody. This novel approach could also be used for accurately measuring the antibody concentration when a reference standard of the antibody is available. [ABSTRACT FROM AUTHOR]

We report here a quantitative method for the analysis of ABT-578 in human whole blood samples. Sample preparation was achieved by a semi-automated 96-well format liquid–liquid extraction (LLE) method. Aluminum/polypropylene heat seal foil was used to enclose each well of the 96-well plate for the liquid–liquid extraction. A liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method with pre-column regeneration was developed for the analysis of sample extracts. Selective reaction monitoring (SRM) of the mass transitions m/z 983–935 and m/z 931–883 was employed for the detection of ABT-578 and internal standard, respectively. The ammonium adduct ions [M + NH4]+ generated from electrospray ionization were monitored as the precursor ions. The assay was validated for a linear dynamic range of 0.20–200.75 ng/ml. The correlation coefficient (r) was between 0.9959 and 0.9971. The intra-assay CV (%) was between 1.9 and 13.5% and the inter-assay CV (%) was between 4.7 and 11.3%. The inter-assay mean accuracy was between 86.4 and 102.5% of the theoretical concentrations. [Copyright &y& Elsevier]

Immunoassays are used extensively in the quantitative analysis of proteins in plasma, urine, and other biological matrixes to support preclinical and clinical studies. Although immunoassays are both sensitive and rapid, difficulties during development of these assays are compounded by the need to have a specific antibody or antigen to the protein of interest. Furthermore, calibration curves of immunoassays are inherently nonlinear, and the technique often detects many structurally related components in addition to the analyte of interest. We have developed a novel strategy of analyzing protein concentrations in plasma by utilizing 96-well solid-phase extraction and LC-MS/MS detection of the intact protein. This strategy has been successfully applied in method development and assay validation of quantitatively analyzing protein rK5 concentrations in monkey plasma samples. Additional techniques such as precolumn regeneration and column heating were also incorporated into the assay. Total run time for each sample was ∼15 min. An LLOQ of 99.2 ng/ mL from a sample volume of 50 gaL, corresponding to only 380 fmol (3.97 ng) of the rK5 analyte being injected onto the analytical column (assuming 100% extraction recovery), was obtained. The validated linear dynamic range was between 99.2 and 52 920.0 ng/mL, with a correlalion coefficient (r[SUP]2) ranging from 0.9972 and 0.9994. The intraassay CV for this assay was between 0.6 and 3.8%, and the interassay CV was between 1.7 and 3.2%. Inter-assay mean accuracies were between 101.5 and 104.7%. The assay has proven rugged and specific and has been employed to generate data in support of preclinical studies. This strategy for rK5 assay could be used for the development of bioanalytical assays to provide preclinical and clinical support for other protein drug candidates and, furthermore, for the validation of biomarkers discovered from proteomic research. [ABSTRACT FROM AUTHOR]

China's coal-dominated energy pattern has resulted in large amount of SO[sub2] emissions. Estimate of the sulfur-related health damage cost is necessary to help perform systematic cost-benefit analysis and set national energy and emission control priorities. Current researches were confined to gaseous SO[sub2] in urban areas: however, secondary sulfate (SO[sub2-][sup4] particles can exert serous impact in a wider region. Based on the concept of "intake fraction" , CALPUFF long-range dispersion model and 180 sample emission sources, multiple regression equation was obtained with good correlation (r = 0.85). which illustrates that populations were key parameters to determine intake fraction but source characteristics were insignificant. Based on the formula and the population were key parameters to determine intake fraction were mapped for Hunan Province(range: 1.1 × 10[sub-6] - 3.2 × 10[sub-6]) of China. A combination of county-level SO[sub2] emissions with the intake fractions yields a total 1.98 tons of sulfate(SO[sub4][2-] inhalation, and resulting total health damage cost to be 0.76(willingness to pay aproach, WTP) or 0.16 (human capital approach, HC) billion USD in 1997, about 2.1% or 0.445% of GDP in Hunan in 1997. Average health damage cost per ton of SO[sub2] emission is 930(WTP) or 200 USD(HC). The results demonstrated that more stringent regulation should be forced. [ABSTRACT FROM AUTHOR]

Linear-plus-nonlinear feedback control is used to stabilize Hopf bifurcation in a rotor-magnetic bearing system, for which the linearized system possesses a double zero eigenvalues. The addition of nonlinear (quadratic) terms to the original linear feedback control formulation is used to modify the coefficients of the nonlinear terms in the reduced normal forms. It is found that feedback control incorporating certain quadratic terms renders the Hopf bifurcation supercritical. Finally, illustrative examples are given to verify the analytical results. [ABSTRACT FROM AUTHOR]

The effect of time delays occurring in the feedback control loop on the linear stability of a simple magnetic bearing system is investigated by analyzing the associated characteristic transcendental equation. It is found that a Hopf bifurcation can take place when time delays pass certain values. The direction and stability of the Hopf bifurcation are determined by constructing a center manifold and by applying the normal form method. It is also found that a codimension two bifurcation can occur through a Hopf and a steady state bifurcation interaction. Finally, numerical simulations are performed to verify the analytical predictions. [Copyright &y& Elsevier]

The primary, superharmonic, and subharmonic resonances of a harmonically excited non-linear s.d.o.f. system with two distinct time-delays in the linear state feeback are studied. The two different time-delays are presented in the proportional feedback and the derivative feedback respectively. The method of multiple scales is utilized to obtain the first order approximation of response. The effect of the feedback gains and time-delays on the steady state responses of three types of resonances is investigated. It is found that a proper selection of the feedback gains and time-delays can enhance the control performance. [Copyright &y& Elsevier]

In the process of contemporary industrial pipeline installation, most pipelines must be cleaned before being put into use due to production and operation process requirements. This paper takes the offline trough cleaning of pipelines as the research object, and explores the evolution process of the metal microstructure under this cleaning method and the best cleaning conditions under the influence of the three factors of concentration, temperature and time. [ABSTRACT FROM AUTHOR]

The downhole expansion process of the expansion tube is the dynamic deformation process of the expansion tube metal material at different temperatures. In this paper, the dynamic tensile test is used to measure the dynamic tensile stress-strain curve of low-carbon alloy steel in the temperature range of 25 - 300 °C. upon analyzed the dynamic tensile test results, with the strain rate factor Z and McCormick physical model, the paper set up low carbon alloy steel constitutive equation of underground temperature field. The calculation results of the Sellars creep equation are compared with the residual stress value after expansion in the finite element analysis of the solid steel pipe expansion to verify the actual application reliability of the steel for the expansion pipe with high expansion rate. [ABSTRACT FROM AUTHOR]

Lifting is to use lifting equipment to lift components and install them to the designated position. On the main structure, lifting equipment is used to transport the flue and transport the sectional flue to the designated position. Certain deformation will occur during the lifting operation of the flue due to its force condition, but it is not known whether it is elastic deformation or plastic deformation. Therefore, this paper analyzes the stress and strain of the flue during operation by finite element method, and observes and analyzes the influence of plastic deformation on the whole flue. [ABSTRACT FROM AUTHOR]

In the practical environment, it is very common for the simultaneous occurrence of base excitation and crosswind. Scavenging the combined energy of vibration and wind with a single energy harvesting structure is fascinating. For this purpose, the effects of the wind speed and random excitation level are investigated with the stochastic averaging method (SAM) based on the energy envelope. The results of the analytical prediction are verified with the Monte-Carlo method (MCM). The numerical simulation shows that the introduction of wind can reduce the critical excitation level for triggering an inter-well jump and make a bi-stable energy harvester (BEH) realize the performance enhancement for a weak base excitation. However, as the strength of the wind increases to a particular level, the influence of the random base excitation on the dynamic responses is weakened, and the system exhibits a periodic galloping response. A comparison between a BEH and a linear energy harvester (LEH) indicates that the BEH demonstrates inferior performance for high-speed wind. Relevant experiments are conducted to investigate the validity of the theoretical prediction and numerical simulation. The experimental findings also show that strong random excitation is favorable for the BEH in the range of low wind speeds. However, as the speed of the incoming wind is up to a particular level, the disadvantage of the BEH becomes clear and evident. [ABSTRACT FROM AUTHOR]

Use Gleeble-1500D thermal simulation test machine to conduct thermal tensile test on AISI 1035 in the deformation temperature range of 1 173,15~1 373,15 K and strain rate range of 0,2 ~ 20 s-1. Using the obtained true stress-strain curves, an intrinsic model of the material was constructed using a model considering strain compensation. The results showed that the correlation coefficient of the Arrhenius model of AISI 1035 considering strain compensation was 0,984 with an average absolute error of 3,550 %, which can accurately predict the flow profitability. The experimental data matched well with the prediction curves obtained from the model calculation, which verified the feasibility of the model [ABSTRACT FROM AUTHOR]

In this work, with the completely asymmetric terahertz (THz) irradiation, electron transport through a two-level InAs quantum dot is theoretically discussed. The Coulomb interaction in this system is compared with the energy difference between the two energy levels and is finite contrasted with the Microwave Field system. We investigate the average current trend with the change of Coulomb interaction and the THz irradiation strength. Our results reveal that there exists the photon-electron pump effect at the Coulomb interaction related energy level, and demonstrate Fano-like resonance in the low THz field strength due to the presence of the photon induced excited state resonance. We also find that the Fano-like resonance can be suppressed with increasing the temperature. [ABSTRACT FROM AUTHOR]

This paper addresses the region-reaching control problem for a flexible-joint robotic manipulator which is formulated by Lagrangian dynamics. An adaptive control scheme is proposed for the manipulator system having two constrained regions which are constructed by selecting appropriate objective functions. The two joints of the flexible-joint manipulator can be, respectively, confined in different regions, and this gives more flexibility than the traditional fixed-point tracking control. By performing a straightforward Lyapunov stability analysis, a simple control algorithm is established to provide a solution for the region-reaching control problem. Finally, numerical simulations are given to validate the theoretical results. [ABSTRACT FROM AUTHOR]

Thermal compression test temperature ranged from 800 to 1 200 °C, the strain rate ranged from 0,01 to 10 s-l, and the deformation degree was 60% of engineering strain, the deformation behavior of 42CrMo gear steel was studied. As the deformation temperature increases and the strain rate decreases, the stress decreases significantly. By polynomial fitting the relationship between strain(0,05 - 0,9, at intervals of 0,05) and material constants, the straincompensationed Arrhenius constitutive equation for 42CrMo gear steel is established. The correlation coefficient between the experimental data and the predicted data reached 0,9925. This shows that the Arhenius constitutive equation has high accuracy in predicting steel 42CrMo for gear. [ABSTRACT FROM AUTHOR]

According to the practical engineering application, three-dimensional modeling of electric hoist and I-beam track is carried out, and the model is simplified to determine the electric hoist load, roller acceleration and speed, and the Abaqus software is used to simulate, analyze the simulation results, observe the actual maximum load under the track stress and strain to meet the requirements, calculate the allowable stress, Observe whether it exceeds the allowable stress and whether plastic deformation occurs. If the numerical simulation results of stress and strain are within the safety requirements, the project can be implemented. [ABSTRACT FROM AUTHOR]

Q235 steel components have poor corrosion resistance and are susceptible to erosion by corrosive media, so they are generally passivated before being put into service. This paper investigates the corrosion behaviour and corrosion mechanism of passivated Q235 steel in atmospheric environments through macro and micro morphological characterisation and electrochemical simulation analysis. [ABSTRACT FROM AUTHOR]

For the fatigue failure of 42CrMo, the tensile test was performed on the CT specimen at different load ratios using a fatigue tensile tester. Data on the fatigue crack growth rate of the material and the crack tip factor were obtained. Scanning electron microscopy (SEM) was used to observe the microstructure and crack initiation and propagation of fractures. The crack initiation and propagation path law during fatigue crack propagation were obtained. The fatigue crack life was calculated by Paris formula, and the fatigue crack growth test and microscopic observation were compared. The propagation law and fatigue crack life of different stages of crack propagation were analyzed. The results show that the stable propagation stage of fatigue crack propagation is the key stage to determine fatigue fracture, the rate of growth is related to the stress ratio. [ABSTRACT FROM AUTHOR]