Experimental analysis of interface contact behavior using a novel image processing method

The spatial and temporal evolution of real contact area of contact interface with loads is a challenge. It is generally believed that there is a positive linear correlation between real contact area and normal load. However, with the development of measuring instruments and methods, some scholars have found that the growth rate of real contact area will slow down with the increase of normal load under certain conditions, such as large-scale interface contact with small roughness surface,which is called the nonlinear phenomenon of real contact area. At present, there is no unified conclusion on the explanation of this phenomenon. We set up an experimental apparatus based on the total reflection principle to verify this phenomenon and analyze its mechanism. An image processing method is proposed, which can be used to quantitative analysis micro contact behaviors on macro contact phenomenon. The weighted superposition method is used to identify micro contact spots, to calculate the real contact area, and the color superimposed image is used to identify micro contact behaviors.Based on this method, the spatiotemporal evolution mechanism of real contact area nonlinear phenomena is quantitatively analyzed. Furthermore, the influence of nonlinear phenomenon of real contact area on the whole loading and unloading process is analyzed experimentally. It is found that the effects of fluid between contact interface, normal load amplitude and initial contact state on contact behavior cannot be ignored in large-scale interface contact with small roughness surface.     

Development of LC‐MS/MS method for the determination of dapiprazole on dried blood spots and urine: application to pharmacokinetics

A rapid and highly sensitive liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method for determination of dapiprazole on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse‐phase C₁₈ column (250 × 4.6 mm i.d., 5 µm), using 20 mm ammonium acetate (pH adjusted to 4.0 with acetic acid) and acetonitrile (80:20, v/v) as a mobile phase at 25 °C. LC‐MS detection was performed with selective ion monitoring using target ions at m/z 326 and m/z 306 for dapiprazole and mepiprazole used as internal standard, respectively. The calibration curve showed a good linearity in the concentration range of 1–3000 ng/mL. The effect of hematocrit on extraction of dapiprazole from DBS was evaluated. The mean recoveries of dapiprazole from DBS and urine were 93.88 and 90.29% respectively. The intra‐ and inter‐day precisions were <4.19% in DBS as well as urine. The limits of detection and quantification were 0.30 and 1.10 ng/mL in DBS and 0.45 and 1.50 ng/mL in urine samples, respectively. The method was validated as per US Food and Drug Administration guidelines and successfully applied to a pharmacokinetic study of dapiprazole in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

3D aluminum/silver hierarchical nanostructure with large areas of dense hot spots for surface‐enhanced raman scattering

Plasmonic nanomaterials possessing large‐volume, high‐density hot spots with high field enhancement are highly desirable for ultrasensitive surface‐enhanced Raman scattering (SERS) sensing. However, many as‐prepared plasmonic nanomaterials are limited in available dense hot spots and in sample size, which greatly hinder their wide applications in SERS devices. Here, we develop a two‐step physical deposition protocol and successfully fabricate 3D hierarchical nanostructures with highly dense hot spots across a large scale (6 × 6 cm²). The nanopatterned aluminum film was first prepared by thermal evaporation process, which can provide 3D quasi‐periodic cloud‐like nanostructure arrays suitable for noble metal deposition; then a large number of silver nanoparticles with controllable shape and size were decorated onto the alumina layer surfaces by laser molecular beam epitaxy, which can realize large‐area accessible dense hot spots. The optimized 3D‐structured SERS substrate exhibits high‐quality detection performance with excellent reproducibility (13.1 and 17.1%), whose LOD of rhodamine 6G molecules was 10^?9 M. Furthermore, the as‐prepared 3D aluminum/silver SERS substrate was applied in detection of melamine with the concentration down to 10^?7 M and direct detection of melamine in infant formula solution with the concentration as low 10 mg/L. Such method to realize large‐area hierarchical nanostructures can greatly simplify the fabrication procedure for 3D SERS platforms, and should be of technological significance in mass production of SERS‐based sensors.     

Calculation of hot spots for protein–protein interaction in p53/PMI-MDM2/MDMX complexes

The recently developed MM/GBSA_IE method is applied to computing hot and warm spots in p53/PMI-MDM2/MDMX protein–protein interaction systems. Comparison of the calculated hot (>2 kcal/mol) and warm spots (>1 kcal/mol) in P53 and PMI proteins interacting with MDM2 and MDMX shows a good quantitative agreement with the available experimental data. Further, our calculation predicted hot spots in MDM2 and MDMX proteins in their interactions with P53 and PMI and they help elucidate the interaction mechanism underlying this important PPI system. In agreement with the experimental result, the present calculation shows that PMI has more hot and warm spots and binds stronger to MDM2/MDMX. The analysis of these hot and warm spots helps elucidate the fundamental difference in binding between P53 and PMI to the MDM2/MDMX systems. Specifically, for p53/PMI-MDM2 systems, p53 and PMI use essentially the same residues (L54, I61, Y67, Q72, V93, H96, and I99) of MDM2 for binding. However, PMI enhanced interactions with residues L54, Y67, and Q72 of MDM2. For the p53/PMI-MDMX system, p53 and PMI use similar residues (M53, I60, Y66, Q71, V92, and Y99) of MDMX for binding. However, PMI exploited three extra residues (M61, K93, and L98) of MDMX for enhanced binding. In addition, PMI enhanced interaction with four residues (M53, Y66, Q71, and Y99) of MDMX. These results gave quantitative explanation on why the binding affinities of PMI-MDM2/MDMX interactions are stronger than that of p53-MDM2/MDMX although their binding modes are similar. © 2018 Wiley Periodicals, Inc.     

Simultaneous determination of amodiaquine and pioglitazone on dried blood spots (DBS) by HPLC–DAD and its usefulness in pharmacokinetic studies

A simple and rapid method for simultaneous determination of amodiaquine and pioglitazone in dried blood spots (DBS) was developed and validated. Blood samples were spotted on protein saver cards and dried and a 4-mm punch was extracted with methanol first and later with 1% acetic acid and dichloromethane. The separation was achieved on a C8 Zorbax Eclipse XDB analytical column (4?µm, 150?×?4.6?mm² i.d.) at 27°C with a mobile phase of methanol/0.2% acetic acid (60:40) at a flow rate of 0.8?mL/min and detected at 230?nm. The method was linear over the range 2–80?ng/mL for amodiaquine and 10–1500?ng/mL for pioglitazone with correlation coefficients greater than 0.9995. The limits of detection were 1.12 and 10.93?µg/L and the limits of quantification were 3.39 and 33.11?µg/L for amodiaquine and pioglitazone, respectively. The inter- and intra-day precision were <6.7 and <7% for amodiaquine and <6.3 and <3% for pioglitazone. The method was applied to estimate the pharmacokinetic (PK) parameters in four healthy volunteers and it was found to yield identical PK profiles with other earlier methods supporting the use of DBS as an alternative for PK study.     

A numerical study of weak shock wave propagation in a reactive bubbly liquid

A numerical study is presented on the response of a weakly shock compressed liquid column that contains reactive gas bubbles. Both the liquid and gas are considered compressible. Compressibility of the liquid allows calculation of shock and rarefaction waves in the pure liquid as well as in the gas/liquid mixture. A microscopic model for local bubble collapse is coupled with a macroscopic model of wave propagation through the gas/liquid mixture. In the particular cases presented here, the characteristic times of propagation of the shock wave and bubble collapse are of the same order of magnitude. Consequently, the coupling between various phenomena is very strong. The present model based on fundamental principles of two-phase fluid mechanics takes into account the coupling of localized bubble oscillations. This model is composed of a microscopic one in the scale of a bubble size, and a macroscopic one which is based on the mixture theory. The liquid under study is water, and the gas is a reactive mixture of argon, hydrogen and oxygen. Received 18 December 1995 / Accepted 2 June 1996     

N-glycosylation analysis of mouse immunoglobulin G isolated from dried blood spots

The association of immunoglobulin G (IgG) glycosylation changes with various human diseases and physiological conditions is well established. Since the mechanistical explanation of the regulation of IgG glycosylation and its functional role in these various states is still missing, the eyes of the biomedical community are now turned towards animal models, which enable intervention studies necessary for conclusions on causality. Mice are recognized and used as a good experimental model for human IgG glycosylation. However, smaller blood volumes, low IgG concentrations at young ages (which are most often used in mice experiments) and multiple sampling protocols during the course of longitudinal studies would profit from a robust workflow for mouse IgG glycome analysis from minute amounts of starting material, collected through a simple sampling procedure. For this purpose, we have developed a protocol for analysis of total N-glycans of IgG isolated from mouse dried blood spots (DBS), which we report here. We show that mouse DBS are a good source of material for IgG N-glycan analysis by multiplexed capillary gel electrophoresis with laser-induced fluorescence (xCGE-LIF).     

Suitability of methylmalonic acid and total homocysteine analysis in dried bloodspots

Methylmalonic acid (MMA) and total homocysteine (tHCYS) concentrations are used to detect acquired and inborn errors of cobalamin (vitamin B12, Cbl) metabolism and to evaluate the effect of therapeutic interventions. Dried blood spot sampling offers a patient-friendly and easy alternative to plasma sampling. However, dried blood spot concentrations are not necessarily equal to plasma concentrations. Therefore, the objective of this work was to establish the relationship between MMA and tHYS dried blood spot and plasma concentrations to facilitate clinical implementation of dried blood spot sampling. MMA and tHCYS in both plasma and DBS were validated on ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). While position of the punch (in DBS) did affect tHCYS concentration, no influence of hematocrit (Ht) and blood volume on both MMA and tHCYS concentrations was observed. The plasma assay performed better than the DBS assay by most criteria. However, the DBS matrix was superior for tHCYS stability. Paired plasma and DBS samples were obtained from patients suspected for Cbl deficiency and from patients with a known inborn error of metabolism affecting MMA or tHCYS concentration. Based on the strong correlation of tHCYS in both matrices (y = 0.46 ± 1.12 (r² = 0.91)), determination of tHCYS in plasma can be replaced by tHCYS in DBS. However, for MMA, a correlation in the higher (pathological) range of MMA exist, but no correlation was observed in the lower ranges. Therefore the added value of MMA concentrations in DBS is currently unknown and should be further investigated.     

Probing single molecules and molecular aggregates: Raman spectroscopic advances

Development of Raman spectroscopy, profiting from surface‐enhanced Raman scattering and tip‐enhanced Raman scattering techniques, has inspired extensive research interest for trace analysis and dynamic measurements up to single‐molecule level. For another, Raman spectroscopy has also been recognized of significance in solving some important issues relating to molecule aggregates in chemistry and biology, owing to the capability of non‐destructive detection and high‐resolution fingerprints by which molecules and their aggregates can be identified. Herein, we summarize the recent progress of Raman spectroscopy in probing single molecules and molecular aggregates and block out a future prospective of Raman spectroscopy applied in cluster science. Copyright © 2015 John Wiley & Sons, Ltd.     

多程放大器输出焦斑相对于靶的漂移

 对激光光路中光学元件矩阵分别施加“随机微扰”,用光线追踪程序计算光学元件几何参数失调对放大器漂的移影响。并给出漂移量的统计计算结果。