Molecular Modeling and Affinity Determination of scFv Antibody: Proper Linker Peptide Enhances Its Activity

One of existing strategies to engineer active antibody is to link VH and VL domains via a linker peptide. How the composition, length, and conformation of the linker affect antibody activity, however, remains poorly understood. In this study, a dual approach that coordinates molecule modeling, biological measurements, and affinity evaluation was developed to quantify the binding activity of a novel stable miniaturized anti-CD20 antibody or singlechain fragment variable (scFv) with a linker peptide. Upon computer-guided homology modeling, distance geometry analysis, and molecular superimposition and optimization, three new linker peptides PT1, PT2, and PT3 with respective 7, 10, and 15 residues were proposed and three engineered antibodies were then constructed by linking the cloned VH and VL domains and fusing to a derivative of human IgG1. The binding stability and activity of scFv-Fc chimera to CD20 antigen was quantified using a micropipette adhesion frequency assay and a Scatchard analysis. Our data indicated that the binding affinity was similar for the chimera with PT2 or PT3 and ~24-fold higher than that for the chimera with PT1, supporting theoretical predictions in molecular modeling. These results further the understanding in the impact of linker peptide on antibody structure and activity.

Physical Modeling And Parametric Study On Two-Degree-Of-Freedom Viv Of A Cylinder Near Rigid Wall

Unlike most previous studies on the transverse vortex-induced vibration(VIV) of a cylinder mainly under the wallfree condition (Williamson & Govardhan,2004),this paper experimentally investigates the vortex-induced vibration of a cylinder with two degrees of freedom near a rigid wall exposed to steady flow.The amplitude and frequency responses of the cylinder are discussed.The lee wake flow patterns of the cylinder undergoing VIV were visualized by employing the hydrogen bubble technique.The effects of the gap-to-diameter ratio (e0/D) and the mass ratio on the vibration amplitude and frequency are analyzed.Comparisons of VIV response of the cylinder are made between one degree (only transverse) and two degrees of freedom (streamwise and transverse) and those between the present study and previous ones.The experimental observation indicates that there are two types of streamwise vibration,i.e.the first streamwise vibration (FSV) with small amplitude and the second streamwise vibration (SSV) which coexists with transverse vibration.The vortex shedding pattem for the FSV is approximately symmetric and that for the SSV is alternate.The first streamwise vibration tends to disappear with the decrease of e0/D.For the case of large gap-to-diameter ratios (e.g.e0/D = 0.54～1.58),the maximum amplitudes of the second streamwise vibration and transverse one increase with the increasing gapto-diameter ratio.But for the case of small gap-to-diameter ratios (e.g.e0/D = 0.16,0.23),the vibration amplitude of the cylinder increases slowly at the initial stage (i.e.at small reduced velocity V,),and across the maximum amplitude it decreases quickly at the last stage (i.e.at large Vr).Within the range ofthe examined small mass ratio (m＜4),both streamwise and transverse vibration amplitude of the cylinder decrease with the increase of mass ratio for the fixed value of V,.The vibration range (in terms of Vr ) tends to widen with the decrease of the mass ratio.In the second streamwise vibration region,the vibration frequency of the cylinder with a small mass ratio (e.g.mx = 1.44) undergoes a jump at a certain Vr,.The maximum amplitudes of the transverse vibration for two-degree-of-freedom case is larger than that for one-degree-of-freedom case,but the transverse vibration frequency of the cylinder with two degrees of freedom is lower than that with one degree of freedom (transverse).

Modelling and simulation of the second-order Doppler error of a laser dual-frequency interferometer

Only the first- order Doppler frequency shift is considered in current laser dual- frequency interferometers; however; the second- order Doppler frequency shift should be considered when the measurement corner cube ( MCC) moves at high velocity or variable velocity because it can cause considerable error. The influence of the second- order Doppler frequency shift on interferometer error is studied in this paper, and a model of the second- order Doppler error is put forward. Moreover, the model has been simulated with both high velocity and variable velocity motion. The simulated results show that the second- order Doppler error is proportional to the velocity of the MCC when it moves with uniform motion and the measured displacement is certain. When the MCC moves with variable motion, the second- order Doppler error concerns not only velocity but also acceleration. When muzzle velocity is zero the second- order Doppler error caused by an acceleration of 0.6g can be up to 2.5 nm in 0.4 s, which is not negligible in nanometric measurement. Moreover, when the muzzle velocity is nonzero, the accelerated motion may result in a greater error and decelerated motion may result in a smaller error.

Cooperation of Mtmr8 with PI3K Regulates Actin Filament Modeling and Muscle Development in Zebrafish

Background: It has been shown that mutations in at least four myotubularin family genes (MTM1, MTMR1, 2 and 13) are causative for human neuromuscular disorders. However, the pathway and regulative mechanism remain unknown. Methodology/Principal Findings: Here, we reported a new role for Mtmr8 in neuromuscular development of zebrafish. Firstly, we cloned and characterized zebrafish Mtmr8, and revealed the expression pattern predominantly in the eye field and somites during early somitogenesis. Using morpholino knockdown, then, we observed that loss-of-function of Mtmr8 led to defects in somitogenesis. Subsequently, the possible underlying mechanism and signal pathway were examined. We first checked the Akt phosphorylation, and observed an increase of Akt phosphorylation in the morphant embryos. Furthermore, we studied the PH/G domain function within Mtmr8. Although the PH/G domain deletion by itself did not result in embryonic defect, addition of PI3K inhibitor LY294002 did give a defective phenotype in the PH/G deletion morphants, indicating that the PH/G domain was essential for Mtmr8's function. Moreover, we investigated the cooperation of Mtmr8 with PI3K in actin filament modeling and muscle development, and found that both Mtmr8-MO1 and Mtmr8-MO2+LY294002 led to the disorganization of the actin cytoskeleton. In addition, we revealed a possible participation of Mtmr8 in the Hedgehog pathway, and cell transplantation experiments showed that Mtmr8 worked in a non-cell autonomous manner in actin modeling. Conclusion/Significance: The above data indicate that a conserved functional cooperation of Mtmr8 with PI3K regulates actin filament modeling and muscle development in zebrafish, and reveal a possible participation of Mtmr8 in the Hedgehog pathway. Therefore, this work provides a new clue to study the physiological function of MTM family members.

Optical matching layer structures in evanescent coupling photodiodes at a wavelength of 1.55 mu m: physics, design and simulation

We have studied the optical matching layers (OMLs) and external quantum efficiency in the evanescent coupling photodiodes (ECPDs) integrating a diluted waveguide as a fibre-to-waveguide coupler, by using the semi-vectorial beam propagation method (BPM). The physical basis of OML has been identified, thereby a general designing rule of OML is developed in such a kind of photodiode. In addition, the external quantum efficiency and the polarization sensitivity versus the absorption and coupling length are analysed. With an optical matching layer, the absorption medium with a length of 30 mu m could absorb 90% of the incident light at 1.55 mu m wavelength, thus the total absorption increases more than 7 times over that of the photodiode without any optical matching layer.

Modeling and optimization of semiconductor manufacturing process with neural networks

A neural network-based process model is proposed to optimize the semiconductor manufacturing process. Being different from some works in several research groups which developed neural network-based models to predict process quality with a set of process variables of only single manufacturing step, we applied this model to wafer fabrication parameters control and wafer lot yield optimization. The original data are collected from a wafer fabrication line, including technological parameters and wafer test results. The wafer lot yield is taken as the optimization target. Learning from historical technological records and wafer test results, the model can predict the wafer yield. To eliminate the "bad" or noisy samples from the sample set, an experimental method was used to determine the number of hidden units so that both good learning ability and prediction capability can be obtained.

Design and path planning for a remote-brained service robot

This article introduced an effective design method of robot called remote-brain, which is made the brain and body separated. It leaves the brain in the mother environment, by which we mean the environment in which the brain's software is developed, and talks with its body by wireless links. It also presents a real robot TUT06-B based on this method which has human-machine interaction, vision systems, manipulator etc. Then it discussed the path planning method for the robot based on ant colony algorithm in details, especially the Ant-cycle model. And it also analyzed the parameter of the algorithm which can affect the convergence. Finally, it gives the program flow chat of this algorithm.

On the design and simulation of high speed electro-optic modulator based on SOI waveguide MOS dual capacitor structure

zhangdi于2010-03-29批量导入

An analysis and simulation about conditioned launch for very short reach (VSR-4)

VSR4 links use graded index multimode fibers (GIMMFs) as the transmission medium with operation wavelength 850nm. For cost reasons, VCSEL has been selected as the optical source to VSR4. The minimum bandwidth specification for 62.5um GIMMF in VSR4 is only 400 MHz(.)km for over-filled-launch (OFL) condition. The distance of 300 meters is limited over transmission rates of 1.25Gbit/s on the basis of this specification. In order to overcome the OFL bandwidth limit by selective excitation of a limited number of modes, conditioned launch technique is investigated. In this paper, based on a comprehensive dispersion theory of GIMMF, a model is built to simulate the transmission of optical signal in GIMMFs and a comparison between OFL and conditioned launch is analyzed. The result can be the guidelines for the best choice of techniques for various LAN and interconnect systems also.

Circuit design and simulation of a CMOS-based preamplifier for brain neural signals

A novel CMOS-based preamplifier for amplifying brain neural signal obtained by scalp electrodes in brain-computer interface (BCI) is presented in this paper. By means of constructing effective equivalent input circuit structure of the preamplifier, two capacitors of 5 pF are included to realize the DC suppression compared to conventional preamplifiers. Then this preamplifier is designed and simulated using the standard 0.6 mu m MOS process technology model parameters with a supply voltage of 5 volts. With differential input structures adopted, simulation results of the preamplifier show that the input impedance amounts to more than 2 Gohm with brain neural signal frequency of 0.5 Hz-100 Hz. The equivalent input noise voltage is 18 nV/Hz(1/2). The common mode rejection ratio (CMRR) of 112 dB and the open-loop differential gain of 90 dB are achieved.

Design and Simulation Analysis of Spot-Size Converter in Silicon-On-Insulator

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Modeling and optimizing of high-concentration erbium-doped fiber amplifiers with consideration of ion-clusters

Starting from the modeling of isolated ions and ion-clusters, a closed form rate and power evolution equations for high-concentration erbium-doped fiber amplifiers are constructed. Based on the equations, the effects of the fraction of ion-clusters in total ions and the number of ions per cluster on the performance of high-concentration erbium-doped fiber amplifiers are analyzed numerically. The results show that the presence of the ion-clusters deteriorates amplifier performance, such as the signal power, signal gain, the threshold pump power for zero gain, saturated signal gain, and the maximum gain efficiency, etc. The optimum fiber length or other parameters should be modified with the ion-clusters being taken into account for the amplifiers to achieve a better performance. (c) 2007 Elsevier B.V. All rights reserved.