Biomedical subjects

Qing Cao

Publications and source records attributed to Qing Cao.

At least 19 recordsLinked to original sources

PubMed2007

Structure-based maximal affinity model predicts small-molecule druggability.

Lead generation is a major hurdle in small-molecule drug discovery, with an estimated 60% of projects failing from lack of lead matter or difficulty in optimizing leads for drug-like properties. It would be valuable to identify these less-druggable targets before incurring substantial expenditure and effort. Here we show that a model-based approach using basic biophysical principles yields good prediction of druggability based solely on the crystal structure of the target binding site. We quantitatively estimate the maximal affinity achievable by a drug-like molecule, and we show that these calculated values correlate with drug discovery outcomes. We experimentally test two predictions using high-throughput screening of a diverse compound collection. The collective results highlight the utility of our approach as well as strategies for tackling difficult targets.

Algorithms↗

PubMed2006

Growth hormone locus expands and diverges after the separation of New and Old World Monkeys.

While most mammals including the prosimians have a single copy of the growth hormone (GH) gene, anthropoids possess a cluster of GH-related genes. Throughout the evolution of the main anthropoid groups [New World Monkeys (NWM), Old World Monkeys (OWM), and apes], two features stand out of the GH loci. The first is the appearance of chorionic somatommamotropin hormone (CSH) genes within the OWM lineage and the second is the expansion of the loci intergenic regions in the OWM and apes. In relation with this loci expansion, the NWM possess intergenic regions of homogeneous lengths (3.5 kb). In contrast, heterogeneous lengths (6 and 13 kb) have been reported for species of the OWM. At the present, none of the OWM genomic GH loci organizations have been described. Here, we report the genomic organization of the GH locus in the rhesus monkey, this locus has six GH-related genes separated by five intergenic regions. The 5' end gene (GH-1) encodes for the pituitary GH and is followed by CSH-1, GH-2, CSH-2, CSH-3 and CSH-4 genes. The five intergenic regions have heterogeneous lengths and also present more or less the same Alu distribution as the human GH locus. To analyze the events that contributed to the extension of the intergenic regions of the GH locus and the emergence of the regulatory elements, the five GH locus intergenic regions of the spider monkey (NWM) were sequenced. The results of comparing the loci from both species suggest that the long intergenic regions (13 kb) of the rhesus GH locus share a common ancestor with the 3.5 kb intergenic regions of the spider monkey. However, the observed increased length of the former is due to an insertion (approximately 8.7 kb) at their 3' end. Interestingly in this insert, we discovered a DNA element resembling the enhancer of the CSH genes of the human GH locus. On the other hand, we observed that the short intergenic regions (6 kb) increased by a different recombination event.

Alu Elements↗

PubMed2006

Apodized multilevel diffractive lenses that produce desired diffraction-limited focal spots.

An apodized, multilevel diffractive lens that can produce a desired diffraction-limited focal spot is proposed for many applications, such as focusing, imaging, optical storage, and optical trapping. The three key points for the design are the innovative idea of complex conjugate subzones, the use of Babinet's principle, and the equivalent-pupil (or aperture) function theory of diffractive focusing elements composed of concentric transparent rings. As a concrete example, we numerically design a mixed multilevel diffractive lens (the highest phase level is 8) to produce a diffraction-limited Gaussian focal spot. Some related problems, such as the validity range and the combination with high-numerical-aperture refractive lenses, are also discussed.

Journal Article↗

PubMed2005

Electronically selective chemical functionalization of carbon nanotubes: correlation between Raman spectral and electrical responses.

Single-walled carbon nanotubes (SWNTs) demonstrate remarkable electronic and mechanical properties useful in developing areas such as nanoelectromechanical systems and flexible electronics. However, the highly inhomogeneous electronic distribution arising from different diameters and chirality in any given as-synthesized SWNT samples imposes severe limitations. Recently demonstrated selective chemical functionalization methods may provide a simple scalable means of eliminating metallic tubes from SWNT transistors and electronic devices. Here, we report on combined electron transport and Raman studies on the reaction of 4-bromobenzene diazonium tetrafluoroborate directly with single and networks of SWNT transistors. First, Raman studies are carried out on isolated individual SWNTs grown on SiO2/Si substrates by chemical vapor deposition with and without metal contacts. Metallic tubes are found to have, on average, higher reactivity toward diazonium reagents. However, a considerable degradation of electrical properties of semiconducting tubes occurs if the reaction is carried out to the point where the conductivity of metallic tubes is significantly suppressed. Insights from single-tube studies are then applied to elucidate the electrical and the Raman responses of SWNT random network transistors of different channel lengths to chemical functionalization.

Journal Article↗

PubMed2005

Performance analysis of very-small-aperture lasers.

The fabrication of very-small-aperture lasers is demonstrated, and their performance is analyzed. Because of strong optical feedback caused by a gold film on the front facet of the laser, its behavior changes: The threshold current decreases, the density of light inside the laser diode and the redshift effect of the spectra are enhanced, and the laser diode's lifetime is shorter than that of common laser diodes with large driving current.

Journal Article↗

PubMed2005

Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system.

Phosphodiesterases (PDEs) modulate signaling by cyclic nucleotides in diverse processes such as cardiac contractility, platelet aggregation, lipolysis, glycogenolysis, and smooth muscle contraction. Cyclic guanosine monophosphate (cGMP) stimulated human phosphodiesterase 2 (PDE2) is expressed mainly in brain and heart tissues. PDE2A is involved in the regulation of blood pressure and fluid homeostasis by the atrial natriuretic peptide (ANP), making PDE2-type enzymes important targets for drug discovery. The design of more potent and selective inhibitors of PDE2A for the treatment of heart disease would be greatly aided by the identification of active site residues in PDE2A that determine substrate and inhibitor selectivity. The identification of active site residues through traditional mutational studies involves the time-consuming and tedious purification of a large number of mutant proteins from overexpressing cells. Here we report an alternative approach to rapidly produce active site mutants of human PDE2A and identify their enzymatic properties using a wheat germ in vitro translation (IVT, also known as cell-free translation) system. We also present the crystal structure of the catalytic domain of human PDE2A determined at 1.7 A resolution, which provided a framework for the rational design of active site mutants. Using a rapid IVT approach for expression of human PDE2A mutants, we identified the roles of active site residues Asp811, Gln812, Ile826, and Tyr827 in inhibitor and substrate selectivity for PDE2A.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Process effects on activated carbon with large specific surface area from corn cob.

The main factors that affect the large specific surface area (SSA) of the activated carbon from agricultural waste corn cobs were studied by chemically activated method with solution of KOH and soap which acted as surfactant. The experiment showed that not only the activation temperature, activation time and the mass ratio of KOH to the carbonized material, but also the activated methods using activator obviously influenced the SSA of activated carbon. The experimental operating conditions were as follows: the carbonized temperature being 450 degrees C and keeping time being 4 h using N2 as protective gas; the activation temperature being 850 degrees C and holding time being 1.2 h; the mass ratio of KOH to carbonized material being 4.0; the time of soaking carbonized material in the solution of KOH and soap being 30 min. Under the optimal conditions, the SSA of activated carbon from corn cobs reached 2700 m2/g. And the addition of the soap as surfactant may shorten the soaking time. The structure of the activated carbon prepared had narrow distribution of pore size and the micro-pores accounted for 78%. The advantages of the method described were easy and feasible.

Carbon↗

PubMed2004

Density functional theory study on the bridge structure in dimeric aluminum (III) water complexes.

Density-functional theory methods were used to investigate the structure of dimeric aluminum (III) water complexes as a function of bridging group. The possibilities of oxygen, water, and hydroxyl bridge ligands and a variety of structural arrangements, such as cis/trans, with respect to the relative position of hydroxyl ligands, were considered. Within the limit of our computational level, we found that electrostatic repulsion between hydroxyls is important in deciding the polyaluminum structure. Although the structures of aluminum-hexaaquo predominate, species with small number of charges or a large number of hydroxyl ligands have a tendency toward a five-coordinate trigonal bipyramidal configuration. Because water is electronically neutral, it cannot provide enough negative charges as a bridge ligand to stabilize two Al(III) molecules. The energy differences among many configurational isomers of hydroxyl Al are so small that they may coexist and convert into each other easily at room temperature.

Journal Article↗

PubMed2004

Generalized confocal imaging systems for free-space optical interconnections.

A generalized confocal imaging system, which is composed of two confocal lenses and one field lens, is proposed for free-space optical interconnections. Unlike in a conventional 4-f system, both the object distance and the image distance can be almost arbitrarily chosen. This advantage is especially important for practical setups in which the object distance and the image distance cannot be designed to be the same. As a concrete example, we have designed and experimentally tested a planar-integrated micro-optical imaging system. The result is in good agreement with the theoretical prediction. Similarly to the conventional 4-f imaging system and the light-pipe imaging system, the system proposed here can also be used as one important part of a hybrid imaging setup.

Journal Article↗

PubMed2004

Pyrolytic behavior of waste corn cob.

The powder of the agricultural waste corn cob was pyrolyzed in a tube-typed stainless steel reactor of 200 ml volume under N2 atmosphere. The compositions of the gases and liquid obtained at different pyrolytic temperatures below 600 degrees C at the heating rate of 30 K/min were analyzed. With the increment of the pyrolytic temperature, the yields of the solid and the liquid products were decreased, but the yield of gas products was increased. The liquid products were approximately 34-40.96% (wt%), the gas products were 27-40.96% (wt%) and the solid products 23.6-31.6% (wt%). There were less changes for the yields of these products above 600 degrees C. The gas products were analyzed by gas chromatography (GC) as CO2, CO, H2, CH4, C2H4, C3H6, C3H8, etc. When the temperature was 350-400 degrees C, the gases had CO2 and CO 80-95% (v/v). When the temperature increased continuously, yields of H2, CH4, C2H4, C3H6 and C3H8 gradually increased. The liquid products were identified by GC-MS as phenols, 2-furanmethanol, 2-cyclopentanedione, etc. The Fourier transform infra-red spectrophotometer (FT-IR) analysis of the liquid product showed a strong -OH group absorption peak. Differential thermogravimetric analysis (DTG) showed that thermal decomposition process involves two steps. The heating rate affects not only the activation energy of the decomposition reaction, but also the path of the reaction. With the increment of the heating rate, the maximum rate temperature of the decomposition reaction was shifted to a higher temperature, and the order and activation energy of the total decomposition reaction were decreasing.

China↗

PubMed2004

BAC resources for the rat genome project.

Two 11-fold redundant bacterial artificial chromosome (BAC) libraries (RPCI-32 and CHORI-230) have been constructed to support the rat genome project. The first library was constructed using a male Brown Norway (BN/SsNHsd) rat as a DNA source long before plans for rat genome sequencing had been launched. The second library was prepared from a highly inbred female (BN/SsNHsd/MCW) rat in support of the rat genome sequencing project. The use of an inbred rat strain is essential to avoid problems with genome assembly resulting from the difficulty of distinguishing haplotype variation from variation among duplicons. We have demonstrated the suitability of the library by using a detailed quality assessment of large insert sizes, narrow size distribution, consistent redundancy for many markers, and long-range continuity of BAC contig maps. The widespread use of the two libraries as an integral part of the rat genome project has led to the database annotations for many clones, providing rat researchers with a rich resource of BAC clones that can be screened in silico for genes of interest.

Animals↗

PubMed2004

Comprehensive focusing analysis of various Fresnel zone plates.

A series-form expression for the individual diffracted field of a general annular ring is derived from the Rayleigh-Sommerfeld diffraction integral. It can be used for the accurate and fast simulation of any diffractive focusing element composed of concentric transparent rings. We present a comprehensive analysis, based on the leading term and the linear superposition principle, of the focusing performances of various Fresnel zone plates. Many problems, such as the equivalent aperture function, the diffraction efficiency, the focal spot pattern, the suppression of higher orders and the appearance of "fractional orders," and the explanation for the appearance of Fraunhofer diffraction patterns, are analytically investigated in detail. Because of the great similarity between Fresnel zone plates and multilevel diffractive lenses, most of the obtained results are also applicable to multilevel diffractive lenses.

Journal Article↗

PubMed2003

THY1 expression is associated with tumor suppression of human ovarian cancer.

Microcell-mediated transfer of chromosome 11 into the human ovarian cancer cell line SKOV-3 results in suppression of tumorigenicity in severe combined immunodeficiency (SCID) mice. To identify the differentially expressed transcripts associated with suppression of tumorigenicity, cDNA populations from the slow-growing tumorigenic clone 11(H)8-3, tumorigenic clone 11(H)8-4, and parental SKOV-3 cells were subtracted from the nontumorigenic clones, 11(H)7-2 and 11(C)9-8. The subtracted cDNA populations were either cloned, sequenced and searched in GenBank, or analyzed by gene discovery array screening. A cDNA transcript corresponding to the THY1 gene located at chromosome 11q23 approximately q24 was found to be exclusively expressed in the two nontumorigenic cell clones. In contrast, THY1 expression was not detected in SKOV-3, the tumorigenic hybrid clones, or six other tumorigenic ovarian cancer cell lines. Further analysis using immunocytochemistry and quantitative flow cytometry with a Thy-1-specific antibody confirmed the exclusive expression of THY1 at the protein level in the two nontumorigenic clones. Several cell growth and differentiation-related genes, including thrombospondin 1 (THBS1), SPARC [secreted protein, acidic, cysteine-rich (osteonectin)], and fibronectin (FN1) were also found to be upregulated in the nontumorigenic clones; however, these were expressed in the slow-growing tumorigenic clones as well. Expression of these genes was not observed in the parental SKOV-3 cell line and therefore must be regulated by a gene or genes on chromosome 11. Our results suggest that THY1 is a putative tumor suppressor gene for ovarian cancer and that THBS1, SPARC, and FN1 are genes associated with the regulation of in vivo tumor growth rate.

Cell Division↗

PubMed2003

Generalized Jinc functions and their application to focusing and diffraction of circular apertures.

A family of generalized Jinc functions is defined and analyzed. The zero-order one is just the traditional Jinc function. In terms of these functions, series-form expressions are presented for the Fresnel diffraction of a circular aperture illuminated by converging spherical waves or plane waves. The leading term is nothing but the Airy formula for the Fraunhofer diffraction of circular apertures, and those high-order terms are directly related to those high-order Jinc functions. The truncation error of the retained terms is also analytically investigated. We show that, for the illumination of a converging spherical wave, the first 19 terms are sufficient for describing the three-dimensional field distribution in the whole focal region.

Journal Article↗

PubMed2003

Nonparaxial model for the focusing of high-numerical-aperture photon sieves.

Recently, a paraxially individual far-field model was presented for the focusing and imaging analysis of pinhole photon sieves. By use of a local Taylor expansion of the integrated function of the Rayleigh-Sommerfeld diffraction formula, the small-size property of the individual pinholes, and the linear superposition principle, we extend this model to the nonparaxial case of high-numerical-aperture photon sieves. Some related problems, such as the validity range of this nonparaxial model and the selection conditions for the individual pinholes, are also discussed in detail.

Journal Article↗

PubMed2003

Modified Fresnel zone plates that produce sharp Gaussian focal spots.

A modified Fresnel zone plate that can produce an approximate Gaussian focal spot is proposed for the focusing and imaging of soft x rays and extreme ultraviolet radiation. The selection conditions for the positions and the widths of the concentric open rings are analytically presented. The focal spot size can be much smaller than the width of the narrowest open ring, and the sidelobes and the higher orders can be effectively suppressed. Through numerical experiments, we confirm that a Gaussian focal spot with a beam width of 7.7 nm can be produced by a modified Fresnel zone plate with a minimum structure size of 30 nm.

Journal Article↗

PubMed2002

Negative role of surface plasmons in the transmission of metallic gratings with very narrow slits.

It is generally admitted that the extraordinary transmission of metallic grating with very narrow slits is mainly due to the excitation of surface plasmons on the upper and lower interfaces of the grating. We show that the surface plasmon contribution is not the prime effect and that waveguide mode resonance and diffraction are responsible for the extraordinary transmission. Additionally and surprisingly, we reveal that the transmittance of subwavelength metallic gratings is always nearly zero for frequencies corresponding to surface plasmon excitation. This finding implies that surface plasmons play a negative role in the transmission.

Journal Article↗

PubMed2002

Stable and efficient bloch-mode computational method for one-dimensional grating waveguides.

We present a stable and efficient method for the Bloch-mode computation of one-dimensional grating waveguides. The approach uses the Fourier modal method and the S-matrix algorithm to remove numerical instabilities. The use of perfectly matched layers provide a high accuracy. Numerical results obtained for different lamellar grating waveguides and for both TE and TM polarizations illustrate the performance of the approach.

Journal Article↗