厌氧消化模型对生化反应抑制形式的模拟

对厌氧消化系统内的抑制动力学进行合理模拟是厌氧工艺顺利运行的前提,也是模型发展和应用的重要部分。ADM1系统分析了几种关键性抑制形式:pH抑制、氢抑制及弱酸和碱抑制。在综合考虑各种抑制动力学的基础上,给出了这些关键性抑制形式的表达公式,用于模拟各种抑制对厌氧反应器内生化反应的影响。

漂白过程H_2O_2分解及其抑制模拟

应用量气法对 H2 O2 在不同漂白条件下的分解动力学特征进行研究 .分析了影响 H2 O2

IMC based robust PID controller tuning for disturbance rejection

It is well-known that the IMC-PID controller tuning gives fast and improved set point response but slow disturbance rejection. A modification has been proposed in IMC-PID tuning rule for the improved disturbance rejection. For the modified IMC-PID tuning rule, a method has been developed to obtain the IMC-PID setting in closed-loop mode without acquiring detailed information of the process. The proposed method is based on the closed-loop step set point experiment using a proportional only controller with gain K_(c0). It is the direct approach to find the PID controller setting similar to classical Ziegler-Nichols closed-loop method. Based on simulations of a wide range of first-order with delay processes, a simple correlation has been derived to obtain the modified IMC-PID controller settings from closed-loop experiment. In this method, controller gain is a function of the overshoot obtained in the closed loop set point experiment. The integral and derivative time is mainly a function of the time to reach the first peak(overshoot). Simulation has been conducted for the broad class of processes and the controllers were tuned to have the same degree of robustness by measuring the maximum sensitivity, Ms, in order to obtain a reasonable comparison. The PID controller settings obtained in the proposed tuning method show better performance and robustness with other two-step tuning methods for the broad class of processes. It has also been applied to temperature control loop in distillation column model. The result has been compared to the open loop tuning method where it gives robust and fast response.

Biogenic isoprene emissions over China:sensitivity to the CO2 inhibition effect

Isoprene emissions emitted from vegetation are one of the most important precursors for tropospheric ozone and secondary organic aerosol formation. The authors estimate the biogenic isoprene emissions in China over 2006-2011 using a global chemical transport model （GEOS- Chem） driven by meteorological fields from the assimilated meteorological data from MERRA. The authors incorporate three different parameterizations of isoprene-CO2 interaction into the model, and perform three sensitivity simulations to investigate the effect of CO2 inhibition on isoprene emissions for the period 2006-2011 in China. The annual isoprene emissions rate across China is simulated to be 12.62 Tg C yr-1, averaged over 2006-2011, and decreases by about 2.7%-7.4% when the CO2 inhibition schemes are included. The CO2 inhibition effect might be significant in regions where the CO2 concentration and isoprene emissions are high. Estimates of isoprene emissions can differ depending on the scheme of CO2 inhibition. According to the results obtained from the sensitivity simulations, the authors find that the CO2 inhibition effect leads to 5.6% ±2.3% reductions in annual isoprene emissions over China. The authors also find that inclusion of CO2 inhibition can substantially alter the sensitivity of isoprene emissions to the changes in meteorological conditions during the study period.

Computational Analysis for Residue-Specific CDK2-Inhibitor Bindings

Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.

Selection of the Mimic Epitopes of Antigens from Schistosoma japonicum by Using Phage Display Techniques

To obtain short peptides simulating antigenic epitopes related to natural resistance against Schistosoma japonicum (S.j) in rats, and to explore their immune protection against S.j in mice, phage random peptide library of 12 amino acids were screened with purified IgG from normal rat sera. Positive clones that were obtained after three rounds of biopanning were detected by ELISA, and two of them were sequenced. Kunming mice were immunized with mixed phage clones. Each mouse was challenged with 40±1 S.j cercariae, and all mice were perfused 45 days post-challenge. The worms and the liver eggs were counted. The results were that the specific phages binding to IgG were enriched 300 folds after three rounds of biopanning. Twenty clones were detected by ELISA and 19 of them bound to the specific IgG of rat sera. The sequence of two clones revealed no homology with other sequences in the GenBank. Compared with the control groups, the reduction rates of the worm burden and liver egg were 33.6% and 59.8%, respectively. It was concluded that the specific peptides, which simulate antigenic molecules correlated with natural resistance to S.j in rats could be obtained by immunosceening phage random peptide library and a protective immunity against S.j can be detected by these epitopes in mice.

Molecular dynamics simulations investigate the long-range effects on TrpR(tryptophan repressor protein)

Molecular dynamics(MD)simulations and anisotropic thermal diffusion dynamics(ATD)simulations were performed on the wild TrpR and its 75 residue mutant(mTrpR)to investigate TrpR longrange effects.The ATD result shows that the mTrpR has higher fluctuation than the wild TrpR,and its helix chainⅡF has particular disorder.It is obvious that the 75 residue of wild TrpR and mTrpR affects the protein dynamics flexibilities by the long-range effects.The ATD and MD both confirm that the differences in the size of side-chain and three-dimensional structures of two different 75 residues in the wild TrpR and mTrpR will spread to the entire protein by way of the long-range effects.Long-range effect affects the protein side chain interaction,conformational changes,flexibilities and secondary structures.Further,the ATD result also shows that each 75 residue of the symmetric homodimer has the same effect,and the two 75 residues have a positive correlation in long-range regulating processes.The residues 48,50,71,79 in chainⅠof wild TrpR and residues 45,72,80 in chainⅡof mTrpR play important roles in long-range interaction processes.

Molecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides

Objective： To provide essential information for peptide inhibitor design, the interactions of Eps15 homology domain of Eps15 homology domain-containing protein 1 （EHD1 EH domain） with three peptides containing NPF （asparagine-proline-phenylalanine）, DPF （aspartic acid-proline-phenylalanine）, and GPF （glycine-proline-phenylalanine） motifs were deciphered at the atomic level. The binding affinities and the underlying structure basis were investigated. Methods： Molecular dynamics （MD） simulations were performed on EHD1 EH domain/peptide complexes for 60 ns using the GROMACS package. The binding free energies were calculated and decomposed by molecular mechanics/ generalized Born surface area （MM/GBSA） method using the AMBER package. The alanine scanning was performed to evaluate the binding hot spot residues using FoldX software. Results： The different binding affinities for the three peptides were affected dominantly by van der Waals interactions. Intermolecular hydrogen bonds provide the struc- tural basis of contributions of van der Waals interactions of the flanking residues to the binding. Conclusions： van der Waals interactions should be the main consideration when we design peptide inhibitors of EHD1 EH domain with high affinities. The ability to form intermolecular hydrogen bonds with protein residues can be used as the factor for choosing the flanking residues.

Simulation methodology development for rotating blade containment analysis

An experimental and numerical investigation on the aeroengine blade/case containment analysis is presented. Blade out containment capability analysis is an essential step in the new aeroengine design, but containment tests are time-consuming and incur significant costs; thus, developing a short-period and low-cost numerical method is warranted. Using explicit nonlinear dynamic finite element analysis software, the present study numerically investigated the high-speed impact process for simulated blade containment tests which were carried out on high-speed spin testing facility. A number of simulations were conducted using finite element models with different mesh sizes and different values of both the contact penalty factor and the friction coefficient. Detailed comparisons between the experimental and numerical results reveal that the mesh size and the friction coefficient have a considerable impact on the results produced. It is shown that a finer mesh will predict lower containment capability of the case, which is closer to the test data. A larger value of the friction coefficient also predicts lower containment capability. However, the contact penalty factor has little effect on the simulation results if it is large enough to avoid false penetration.

Containment of high-speed rotating disk fragments

Disk burst accidents sometimes happen in aeroengines.To avoid tragic consequences,aeroengine casings must have sufficient containment capability.Experiments and simulations need to be conducted to study the impact,distortion,and perforation caused by disk burst and which may give important clues to potential failure mechanisms.This paper presents some containment tests of high-speed rotating disk fragments,in which the original disks were burst into three equal fragments within a predetermined rotating speed range.The failure modes of the containment casing varied significantly with the thickness of the containment casing.Shearing,tearing,tensile fracture,and large plastic stretching deformation occurred in a thin-walled containment casing,while a thick-walled casing could contain disk fragments and withstand large plastic deformation.Numerical simulations were carried out to study the impact process and failure modes further.Good agreement was found between the results of the simulations and the tests.

Effects of combined drug therapy on HIV-1 infection dynamics

Infection of human immunodeficiency virus （HIV） is determined through the decay of healthy CD44- T-cells in a well-mixed compartment, such as a bloodstream. A mathe- matical model is considered to illustrate the effects of combined drug therapy, i.e. reverse transcription plus protease inhibitor, on viral growth and T-cell population dynamics. This model is used to explain the existence and stability of infected and uninfected steady states in HIV growth. An analytical technique, called variational iteration method （VIM）, is used to solve the mathematical model. This method is modified to obtain the rapidly convergent successive approximations of the exact solution. These approximations are obtained without any restrictions or the transformations that may change the physical behavior of the problem. Numerical simulations are computed and exhibited to illustrate the effects of proposed drug therapy on the growth or decay of infection.

Structure-based design and biological evaluation of novel mTOR inhibitors as potential anti-cervical agents

The mammalian target of rapamycin(mTOR) is a critical component of the PI3K-AKT signaling pathway. It is highly activated in cervical cancer, which continues to pose an important clinical challenge with an urgent need for new and improved therapeutic approaches. Herein, we describe the structure-based drug discovery and biological evaluation of a series of m TOR kinase inhibitors as potential anti-cervical cancer agents. The results of enzymatic activity assays supported C3 as a potential m TOR inhibitor, which exhibited high inhibitory activity with an IC50 of 1.57 μM. Molecular docking and dynamics simulation were conducted to predict the binding patterns, suggesting relationships between structure and activity. The anti-proliferative assay against diverse cancer cell lines was displayed subsequently, revealing that C3 exhibited significant proliferation inhibition against cervical cancer cell He La(IC50=0.38μM) compared with other cell lines. Moreover, C3 could effectively reduce the expression of phospho-ribosomal S6 protein(p-S6) in He La cells in a dose-dependent manner. Noteworthily, m TOR signaling and other cellular pathways might contribute to the significant effect of C3 against cervical cancer simultaneously. These data indicated that C3 represented a good lead molecule for further development as a therapeutic agent for cervical cancer treatment.