Knowledge discovery in biomedical research and drug design : The development and application of biological databases

Ph.DDOCTOR OF PHILOSOPH

Structure Analysis for Tunnel Longitudinal Deformation Based on Segment Dislocation Mode

AbstractAccording to tunnel structure around joints, tunnel longitudinal deformation is analyzed and a three-dimensional finite element model is built based on segment dislocation mode. Tunnel structure stress analysis is conducted from two aspects of segment in the shear and bolt in the tension. The analysis results show: (1) Segment shear model. When segment dislocation reaches 0.03mm, the principal stressσ1 exceeds 3.0Mpa which is over concrete's tensile strength. Therefore, when convex tenon and concave tenon generate shear, there must be horizontal slipping and bolt is tensioned. (2) Bolt tension model. When joint opening value reaches 2mm, bolt stress exceeds 640Mpa, which is bolt's yield strength. When joint opening value reaches 6mm, which is the waterproof control standard for tunnel, bolt stress reaches 688.7Mpa, which is less than bolt's failure strength. The subway tunnel's structure safety should be controlled from the perspective of waterproof

Ultra-narrowband interference circuits enable low-noise and high-rate photon counting for InGaAs/InP avalanche photodiodes

Afterpulsing noise in InGaAs/InP single photon avalanche photodiodes (APDs) is caused by carrier trapping and can be suppressed successfully through limiting the avalanche charge via sub-nanosecond gating. Detection of faint avalanches requires an electronic circuit that is able to effectively remove the gate-induced capacitive response while keeping photon signals intact. Here we demonstrate a novel ultra-narrowband interference circuit (UNIC) that can reject the capacitive response by up to 80 dB per stage with little distortion to avalanche signals. Cascading two UNIC's in a readout circuit, we were able to enable high count rate of up to 700 MC/s and low afterpulsing of 0.5 % at a detection efficiency of 25.3 % for 1.25 GHz sinusoidally gated InGaAs/InP APDs. At -30 degree C, we measured 1 % afterpulsing at a detection efficiency of 21.2 %

Analysis on the influence of rotational speed to aerodynamic performance of vertical axis wind turbine

AbstractA two dimensional vertical axis wind turbine's model was established in this paper, and two dimensional unsteady incompressible N-S equations and Realizable kɛ− turbulence model were solved with software FLUENT. SIMPLC algorithm was applied, combined with the sliding grid technology; the influence of rotational speed to the flow structure of vertical axis wind turbine was discussed. The results showed that, the rotation of wind turbine had significant influence on wake, and higher the rotational speed, the greater reduction of the wake velocity. The wake velocity restored gradually away from the rotational part. There was much larger turbulent kinetic energy near the tail of the wind turbine's blade. The value of turbulent kinetic energy reduced gradually away from the rotational part, and the flow restored the stratospheric state gradually. With the increase of wind turbine's rotational speed, the value of turbulent kinetic energy in calculation domain increased too. The results showed that the flow structure of vertical axis wind turbine's rotational process could be revealed effectively by numerical simulation, provided theoretical reference for the engineering design of the vertical axis wind turbine

Bis[(2-pyrid­yl)(2-pyridyl­amino)­methano­lato]manganese(III) nitrate

The MnIII atom in the title complex, [Mn(C11H10N3O)2]NO3, is coordinated by the two tridentate (2-pyrid­yl)(2-pyridyl­amino)­methano­late ligands, forming a six-coordinate environment. The four pyridyl N atoms constitute the equatorial plane on which the manganese(III) ion lies; the coordination plane suffers a slight distortion as indicated by the average plane deviation of 0.058 Å. The methano­late O atoms occupy the axial positions. The coordination geometry is thus octa­hedral. In the title compound, the cations are linked by nitrate anions via N—H⋯O hydrogen bonds to form one-dimensional chains. Moreover, the one-dimensional structure is stabilized by inter­molecular edge-to-face aromatic π–π inter­actions with a center-of-inversion at a distance of ca 4.634 Å

In-silico Antigenicity Determination and Clustering of Dengue Virus Serotypes

Emerging or re-emerging dengue virus (DENV) causes dengue fever epidemics globally. Current DENV serotypes are defined based on genetic clustering, while discrepancies are frequently observed between the genetic clustering and the antigenicity experiments. Rapid antigenicity determination of DENV mutants in high-throughput way is critical for vaccine selection and epidemic prevention during early outbreaks, where accurate prediction methods are seldom reported for DENV. Here, a highly accurate and efficient in-silico model was set up for DENV based on possible antigenicity-dominant positions (ADPs) of envelope (E) protein. Independent testing showed a high performance of our model with AUC-value of 0.937 and accuracy of 0.896 through quantitative Linear Regression (LR) model. More importantly, our model can successfully detect those cross-reactions between inter-serotype strains, while current genetic clustering failed. Prediction cluster of 1,143 historical strains showed new DENV clusters, and we proposed DENV2 should be further classified into two subgroups. Thus, the DENV serotyping may be re-considered antigenetically rather than genetically. As the first algorithm tailor-made for DENV antigenicity measurement based on mutated sequences, our model may provide fast-responding opportunity for the antigenicity surveillance on DENV variants and potential vaccine study

Genome wide exploration of the origin and evolution of amino acids

Background: Even after years of exploration, the terrestrial origin of bio-molecules remains unsolved and controversial. Today, observation of amino acid composition in proteins has become an alternative way for a global understanding of the mystery encoded in whole genomes and seeking clues for the origin of amino acids. Results: In this study, we statistically monitored the frequencies of 20 alpha-amino acids in 549 taxa from three kingdoms of life: archaebacteria, eubacteria, and eukaryotes. We found that the amino acids evolved independently in these three kingdoms; but, conserved linkages were observed in two groups of amino acids, (A, G, H, L, P, Q, R, and W) and (F, I, K, N, S, and Y). Moreover, the amino acids encoded by GC-poor codons (F, Y, N, K, I, and M) were found to "lose" their usage in the development from single cell eukaryotic organisms like S. cerevisiae to H. sapiens, while the amino acids encoded by GC-rich codons (P, A, G, and W) were found to gain usage. These findings further support the co-evolution hypothesis of amino acids and genetic codes. Conclusion: We proposed a new chronological order of the appearance of amino acids (L, A, V/E/G, S, I, K, T, R/D, P, N, F, Q, Y, M, H, W, C). Two conserved evolutionary paths of amino acids were also suggested: A -> G -> R -> P and K -> Y.National Natural Science Foundation of China [20572061, 20732004]; Program for New Century Excellent Talents in University (NCET) of MO

Frequency and distribution of AP-1 sites in the human genome

The AP-1-binding sequences are promoter/enhancer elements that play an essential role in the induction of many genes in mammalian cells; however, the number of genes containing AP-1 sites remains unknown. In order to better address the overall effect of AP-1 on expression of genes encoded by the entire genome, a genome-wide analysis of the frequency and distribution of AP-1 sites would be useful; yet to date, no such analysis of AP-1 sites or any other promoter/enhancer elements has been performed. We present here our study of the consensus AP-1 site and two single-bp variants showing that the frequency of AP-1 sites in promoter regions is significantly lower than their average rate of occurrence in the whole genomic sequence, as well as the frequency of a random heptanucleotide suggesting that nature has selected for a decrease in the frequency of AP-1 sites in the regulatory regions of genes. In addition, genes containing multiple AP-1 sites are more prevalent than those containing only one copy of an AP-1 site, which again may have evolved to allow for greater signal amplification or integration in the regulation of AP-1 target genes. However, the number of AP-1-regulated genes identified in various studies is far smaller than the number of genes containing potential AP-1 sites, indicating that not all AP-1 sites are activated in a given cell under a given condition, and is consistent with the prediction by others that cellular context determines which AP-1 sites are targeted by AP-1

A novel BRDT inhibitor NHWD870 shows potential as a male contraceptive in mice

Small molecule inhibitors of the bromodomain and extraterminal domain (BET) family proteins have emerged as a promising option for not only the treatment of multiple cancers but also for disturbing the process of sperm maturation with potential for use as a viable contraceptive target. In this paper, we report a new generation of BET family inhibitor, NHWD870, that provide a complete and reversible contraceptive effect in mice which is stronger than that of JQ1 and its synthesized derivatives. This study is hoped to lead to the clinical trial eventually