EFFECTS OF GEOMETRY ON VORTEX SHEDDING FROM ELONGATED BLUFF BODIES

A 2-D, high-resolution, vortex particle method was implemented, and its validity and capabilities were demonstrated through comparisons with experimental and numerical data available in the literature for flows around bluff bodies. A series of simulations of the flow around flat plates with various nosings and elongation ratios were performed. The resultant Stc map (variation of chord-based Strouhal number, Stc, with elongation ratio, d t , and nosing angle, 6 ) reveals that there are an upper and a lower limit for Stc variations, and, by changing the separation angle at the leading edge, the transition between them appears to be continuous. For plates with a smaller separation angle at the leading edge, Stc increases almost linearly with dt after a jump, and eventually makes transition to a horizontal variation. From the analyses of mean flow characteristics, visualizations of the vorticity field, and quantitative analyses of identified vortices, the effects of geometry on a number of flow properties were identified, based on which a detailed description of the mechanics leading to various behaviors of Stc is given. It is the alternate predominance of the leading- and trailing-edge shedding in the overall shedding process that leads to the linear and horizontal variations, and abrupt jumps of Stc. When the trailing-edge shedding is in control, the shedding frequency jumps to a higher value and Stc tends to follow a linear variation. When the leading-edge shedding predominates, Stctends to follow a horizontal variation

Crystallographic, Molecular Dynamics, And Enzymatic Studies Of Multi-Drug Resistant Hiv-1 Protease And Implications For Structure Based Drug Design (project 1); Crystallographic Studies Of Human Myelin Protein Zero (project 2)

Under drug selection pressure, emerging mutations render HIV-1 protease drug resistance, leading to the therapy failure in anti-HIV treatment.Tthe multidrug-resistant 769 (MDR) HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, 90) is selected for the present study to understand drug resistance issue. Ten additional mutations are introduced to MDR769 HIV-1 protease to study the structural influences brought by these mutations. We get crystal structures of four variants (I10V, A82F, A82S and A82T) of MDR769 HIV-1 protease. All these mutations fail to further open the flaps and expand the active site cavity of MDR769 HIV-1 protease, which is characterized by wide open flaps and expanded active site cacity. The conserved flaps and active site cavity despite the introduction of additional mutations indicate that the MDR769 HIV-1 protease is the end stage form of HIV-1 protease. In addition, these crystal structures provide the first structure based evidence for the mutation induced conformational changes in the 80s loops of the HIV-1 protease apo-enzyme, although the flap and active site cavity are not changed dramatically. The alternate conformations of Pro81 (proline switch) in the I10V mutant and the side chain of Phe82 with flipped-out conformation in A82F mutant show distorted S1/S1\u27 binding pockets that causes loss of contacts and unstable binding of the inhibitors. Similarly, the mutants A82S and A82T show distortion in the S1/S1\u27 binding pockets due to local changes in the electrostatics caused by the mutation from non-polar to polar residues. Molecular mechanics studies performed to understand the wide-open nature of the MDR769 HIV-1 protease flaps show that the MDR protease exhibits a state of conformational rigidity with respect to the flap closure compared to that of the wild type protease. This suggests that the accumulation of mutations changes the structure of the MDR protease resulting in a cumulative steric hindrance during the flap closure. Our studies show that modeling a substrate (Gag - Capsid) into the active site cavity of the MDR protease does not solve the problem of flap closure. Since the flap closure is crucial in the protease inhibitor binding, based on our results, the conformational rigidity of MDR protease could be one of the novel mechanisms for the multidrug-resistance nature of the MDR protease. In addition, our molecular dynamics simulation reveals the realignment of the substrate peptide in the MDR769 HIV-1 protease, making it less accessible to the Asp25 and Asp 125 amino acid residues in the active site. This finding indirectly indicates the reduced catalytic activity of MDR769 HIV-1 protease in substrate cleavage compared to that of the WT HIV-1 protease. The IC50 values of the FDA approved HIV-1 protease inhibitors and the library of reduced CA/p2 peptide analogs are measured. The results indicate the reduced peptide analogs bind to MDR769 HIV-1 protease and WT HIV-1 protease with equal affinity, while the FDA approved inhibitors show reduced binding affinity to MDR769 HIV-1 protease compared to that of WT HIV-1 protease. This enzymatic study demonstrated that lopinavir was the least resisted HIV-1 protease inhibitor and that reduced peptide P1\u27F was comparable to FDA approved inhibitors in the inhibitory activity against HIV-1 protease. Based on the studies mentioned above, a library of potential drug candidates against HIV-1 protease is proposed to overcome the serious drug resistance issue. These drug candidates are synthesized in the lab and further evaluation of them will be performed. The extracellular domain of human myelin protein zero fused with maltose binding protein is crystallized to investigate the molecular mechanism of Charcot-Marie-Tooth disease subtype 1B. The based on the wild type structure of the extracellular domain of human myelin protein zero, five clinically important mutants are structurally investigated in details. The molecular pathology is proposed for these mutants individually. The relationship between amyloidosis disease and CMT1B will be expored further. In addition, this structure is another example of crystallographic studies facilited by the presence of maltose binding protei

Series Report 1: Establishment of Zhigang Liu\u27s Authentic Video Library

In foreign language education, a real text corpus plays a vital role. With years of Chinese language education experience, author Mr. Zhigang Liu continuously reflects and refines what and how he teaches. He has assembled a set of text corpus consisted of videos that are derived from film and television for use in practice, where the outcome has proven its effectiveness. This issue will feature Mr. Zhigang Liu’s vision behind his library of videos, including its initiative, progress, and method of use. This article serves as a general introduction of the database, covers the basis of its establishment, viability in Chinese language education, and several major features. Through this series of reports, it is hoped that it will be of help to the frontline of Chinese language education and, at the same time, provide encouragement for the professional development of educators who are inspired to achieve greatness in teaching Chinese language