Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120

AIM: To investigate the interaction between human CCR5 receptors (CCR5) and HIV-1 envelope glycoprotein gp120 (HIV-1 gp120) and HIV-1 receptor CD4 antigens (CD4). METHODS: The structurally con served regions (SCR) of human CCR5 was built by the SYBYL/Biopolymer module using the corresponding transmembrane (TM) domain of bacteriorhodopsin (bR) as the template. The coordinates for amino-ter minal residue sequence, and carboxyl-terminal residue sequence, extracellular and cytoplasmic loops were generated using LOOP SEARCH algorithm. Subsequently the structural model was merged into the complex with HIV-1 gp120 and CD4. RESULTS: Human CCR5 interacted with both an HIV-1 gp120 and CD4. The N-terminal residues (especially Met1 and Gln4) of human CCR5, contacted with CD4 residues, mainly 7Nith one span (56 - 59) of CD4 in electrostatic interaction and hydrogen-bonds. The binding sites of human CCR5 were buried in a hydrophobic center surrounded by a highly basic periphery. On the other hand, direct interatomic contacts were made between ? CCR5 residues and 6 gp120 amino-acid residues, which included van der Waals contacts, hydrophobic interaction, and hydrogen bonds. CONCLUSION: The interaction model should be helpful for rational design of novel anti-HIV drugs.

Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies

The entry of human immunodeficiency virus (HIV) into cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors CD4 and members of the chemokine receptor family. The CC chemokine receptor CCR5 is such a receptor for several chemokines and a major coreceptor for the entry of R5 HIV type-1 (HIV-1) into cells. Although many studies focus on the interaction of CCR5 with HIV-1, the corresponding interaction sites in CCR5 and gp120 have not been matched. Here we used an approach combining protein structure modeling, docking and molecular dynamics simulation to build a series of structural models of the CCR5 in complexes with gp120 and CD4. Interactions such as hydrogen bonds, salt bridges and van der Waals contacts between CCR5 and gp120 were investigated. Three snapshots of CCR5-gp120-CD4 models revealed that the initial interactions of CCR5 with gp120 are involved in the negatively charged N-terminus (Nt) region of CCR5 and positively charged bridging sheet region of gp120. Further interactions occurred between extracellular loop2 (ECL2) of CCR5 and the base of V3 loop regions of gp120. These interactions may induce the conformational changes in gp120 and lead to the final entry of HIV into the cell. These results not only strongly support the two-step gp120-CCR5 binding mechanism, but also rationalize extensive biological data about the role of CCR5 in HIV-1 gp120 binding and entry, and may guide efforts to design novel inhibitors.

Characterize dynamic conformational space of human CCR5 extracellular domain by molecular modeling and molecular dynamics simulation

The chemokine receptor CCR5 is the receptor for several chemokines and major coreceptor for R5 human immunodeficiency virus type-1 strains entry into cell. Three-dimensional models of CCR5 were built by using homology modeling approach and 1 ns molecular dynamics (MD) simulation, because studies of site-directed mutagenesis and chimeric receptors have indicated that the N-terminus (Nt) and extracellular loops (ECLs) of CCR5 are important for ligands binding and viral fusion and entry, special attention was focused on disulfide bond function, conformational flexibility, hydrogen bonding, electrostatic interactions, and solvent-accessible surface area of Nt and ECLs of this protein part. We found that the extracellular segments of CCR5 formed a well-packet globular domain with complex interactions occurred between them in a majority of time of MID simulation, but Nt region could protrude from this domain sometimes. The disulfide bond Cys20-Cys269 is essential in controlling specific orientation of Nt region and maintaining conformational integrity of extracellular domain. RMS comparison analysis between conformers revealed the ECL1 of CCR5 stays relative rigid, whereas the ECL2 and Nt are rather flexible. Solvent-accessible surface area calculations indicated that the charged residues within Nt and ECL2 are often exposed to solvent. Integrating these results with available experimental data, a two-step gp120-CCR5 binding mechanism was proposed. The dynamic interaction of CCR5 extracellular domain with gp120 was emphasized. (C) 2004 Elsevier B.V. All rights reserved.

Population growth and physiological characteristics of microalgae in a miniaturized bioreactor during space flight

A strain of microalgae (Anabaena siamensis) had been cultured in a miniaturized bioreactor during a retrievable satellite flight for 15 days. By means of remote sensing equipment installed in the satellite, we gained the growth curve of microalgae population in space every day in real time. The curve indicated that the growth of microalgae in space was slower than the control on ground. Inoculation of the retrieved microalgae culture showed that the growth rate was distinctively higher than ground control. But after several generations, both cultures indicated similar growth rates. Those data showed that algae, can adapt to space environment easily which may be valuable for designing more complex bioreactor and controlled ecological life support system in future experiment. (C) 2006 Elsevier Ltd. All rights reserved.

Control of the lasing wavelength by a sampled grating in a complex-coupled DFB laser

The lasing wavelength of a complex-coupled DFB laser is controlled by a sampled grating. The key concepts of the approach are to utilize the -1st order (negative first order) reflection of a sampled grating for laser single mode operation, and use conventional holographic exposure combined with the usual photolithography to fabricate the sampled grating. The typical threshold current of the sampled grating based DFB laser is 32 mA, and the optical output is about 10 mW at an injected current of 100 mA. The lasing wavelength of the device is 1.5356 mu m, which is the -1st order wavelength of the sampled grating.

The design algorithm of an associative memory neural network

A design algorithm of an associative memory neural network is proposed. The benefit of this design algorithm is to make the designed associative memory model can implement the hoped situation. On the one hand, the designed model has realized the nonlinear association of infinite value pattern from n dimension space to m dimension space. The result has improved the ones of some old associative memory neural network. On the other hand, the memory samples are in the centers of the fault-tolerant. In average significance the radius of the memory sample fault-tolerant field is maximum.

The develop of 622Mbits/s free space laser communication system

622Mbits/s free space laser communication system is developed. IT's communication rate is 622Mbits/s. The whole system include three parts which are signal in and out circuit laser driver and receive circuit and optical antenna The communication principle is introduced The experiment result shows that the transmission of data and image are satisfied with demands of design. It have a definite market value.

Design and operation of integrated pilot-scale dimethyl ether synthesis system via pyrolysis/gasification of corncob

The integrated pilot-scale dimethyl ether (DME) synthesis system from corncob was demonstrated for modernizing utilization of biomass residues. The raw bio-syngas was obtained by the pyrolyzer/gasifier at the yield rate of 40-45 Nm(3)/h. The content of tar in the raw bio-syngas was decreased to less than 20 mg/Nm(3) by high temperature gasification of the pyrolysates under O-2-rich air. More than 70% CO2 in the raw bio-syngas was removed by pressure-swing adsorption unit (PSA). The bio-syngas (H-2/CO approximate to 1) was catalytically converted to DME in the fixed-bed tubular reactor directly over Cu/Zn/Al/HZSM-5 catalysts. CO conversion and space-time yield of DME were in the range of 82.0-73.6% and 124.3-203.8 kg/m(cat)(3)/h, respectively, with a similar DME selectivity when gas hourly space velocity (GHSV, volumetric flow rate of syngas at STP divided by the volume of catalyst) increased from 650 h(-1) to 1500 h(-1) at 260 degrees C and 4.3 MPa. And the selectivity to methanol and C-2(+) products was less than 0.65% under typical synthesis condition. The thermal energy conversion efficiency was ca. 32.0% and about 16.4% carbon in dried corncob was essentially converted to DME with the production cost of ca. (sic) 3737/ton DME. Cu (111) was assumed to be the active phase for DME synthesis, confirmed by X-ray diffraction (XRD) characterization.

Radar interferometer measurements of space debris using the Evpatoria RT-70 transmitter

The ability of the Evpatoria RT-70 radar complex to perform research on space debris was investigated in four trial experiments during 2001-2003. The echo-signals of 25 objects at geostationary, highly elliptical and medium-altitude orbits were recorded on magnetic tapes at radio telescopes in Russia, Italy, China and Poland. The multi-antenna system configuration gives potential to supplement the classic radar data with precise angular observations using the technique of Very Long Baseline Interferometry. The first stage of such processing was fulfilled by the correlator in N. Novgorod, Russia. The cross-correlation of transmitted and received signals was obtained for the 11 objects on the Evpatoria-Bear Lakes, Evpatoria-Urumqi and Evpatoria-Noto baselines. This activity also promoted developing the optical observations of geostationary objects, conducted for the improvement of the radar target ephemerides. (C) 2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Physical design of the new extraction system for SFC

The HIRFL (Heavy Ion Research Facility at Lanzhou) is a cyclotron complex. Its injector is a cector focusing cyclotron with K=69. Since the HIRFL started the operation in 1989, two bigger items of improvements have been finished, the species and intensity of the accelerated particles are increased obviously. But due to the lower extraction efficiency of the SFC, on one hand, a lot of beam lost, and on other hand, outgas from the surface of the electrostatic deflector is serious because of beam hitting. Even sometimes the vacuum press is destroyed. In the paper a new physical design is made to get an extraction system of the SFC with a higher efficiency.

The Compact Pulsed Hadron Source: A Design Perspective

During the past. decades, large-scale national neutron sources have been developed in Asia, Europe, and North America. Complementing such efforts, compact hadron beam complexes and neutron sources intended to serve primarily universities and industrial institutes have been proposed, and some have recently been established. Responding to the demand in China for pulsed neutron/proton-beam platforms that are dedicated to fundamental and applied research for users in multiple disciplines from materials characterization to hadron therapy and radiography to accelerator-driven sub-critical reactor systems (ADS) for nuclear waste transmutation, we have initiated the construction of a compact, yet expandable, accelerator complex-the Compact Pulsed Hadron Source (CPHS). It consists of an accelerator front-end (a high-intensity ion source, a 3-MeV radio-frequency quadrupole linac (RFQ), and a 13-MeV drift-tube linac (DTL)), a neutron target station (a beryllium target with solid methane and room-temperature water moderators/reflector), and experimental stations for neutron imaging/radiography, small-angle scattering, and proton irradiation. In the future, the CPHS may also serve as an injector to a ring for proton therapy and radiography or as the front end to an ADS test facility. In this paper, we describe the design of the CPHS technical systems and its intended operation.

Loss of p15/Ink4b accompanies tumorigenesis triggered by complex DNA double-strand breaks

DNA double-strand breaks (DSBs) are the most deleterious lesion inflicted by ionizing radiation. Although DSBs are potentially carcinogenic, it is not clear whether complex DSBs that are refractory to repair are more potently tumorigenic compared with simple breaks that can be rapidly repaired, correctly or incorrectly, by mammalian cells. We previously demonstrated that complex DSBs induced by high-linear energy transfer (LET) Fe ions are repaired slowly and incompletely, whereas those induced by low-LET gamma rays are repaired efficiently by mammalian cells. To determine whether Fe-induced DSBs are more potently tumorigenic than gamma ray-induced breaks, we irradiated 'sensitized' murine astrocytes that were deficient in Ink4a and Arf tumor suppressors and injected the surviving cells subcutaneously into nude mice. Using this model system, we find that Fe ions are potently tumorigenic, generating tumors with significantly higher frequency and shorter latency compared with tumors generated by gamma rays. Tumor formation by Fe-irradiated cells is accompanied by rampant genomic instability and multiple genomic changes, the most interesting of which is loss of the p15/Ink4b tumor suppressor due to deletion of a chromosomal region harboring the CDKN2A and CDKN2B loci. The additional loss of p15/Ink4b in tumors derived from cells that are already deficient in p16/Ink4a bolsters the hypothesis that p15 plays an important role in tumor suppression, especially in the absence of p16. Indeed, we find that reexpression of p15 in tumor-derived cells significantly attenuates the tumorigenic potential of these cells, indicating that p15 loss may be a critical event in tumorigenesis triggered by complex DSBs.

Design and synthesis of near-IR luminescent mesoporous materials covalently linked with tris(8-hydroxyquinolinate) lanthanide(III) complexes

By using the bifunctional ligand, 8-hydroxyquinoline-functionalized organosilane (Q-Si), the new mesoporous material Q-MCM-41 covalently bonded with 8-hydroxyquinoline was synthesized. Through the ligand exchange reaction, the new near-infrared (NIR) luminescent mesoporous LnQ(3)-MCM-41 (Ln = Er, Nd, Yb) materials were prepared by linking the lanthanide quinolinate complexes to the ordered mesoporous Q-MCM-41 material. The LnQ(3)-MCM-41 materials were characterized by powder X-ray diffraction and N-2 adsorption/desorption, and they all show the characteristic mesoporous structure of MCM-41 with highly uniform pore size distributions.

Supramolecular architectures, photophysics, and electroluminescence of 1,3,4-oxadiazole-based iridium(III) complexes: From mu-dichloro bridged dimer to mononuclear complexes

One mu-dichloro bridged diiridium complex and three mononuclear iridium(III) complexes based on the 1,3,4-oxadiazole derivatives as cyclometalated ligands and acetylacetonate (acac) or dithiolates O,O'-diethyldithiophosphate (Et(2)dtp) or N,N'-diethyldithiocarbamate (Et(2)dtc) as ancillary ligands have been synthesized and systematically studied by X-ray diffraction analysis. The results reveal that three mononuclear complexes all adopt distorted octahedral coordination geometry around the iridium center by two chelating ligands with cis-C-C and trans-N-N dispositions, which have the same coordination mode as the diiridium dimer. The dinuclear complex crystallizes in the monoclinic system and space group C2/c, whereas three mononuclear iridium complexes are all triclinic system and space group P(1) over bar. In the stacking structure of the dimer, one-dimensional tape-like chains along the b-axis are formed by hydrogen bondings, which are strengthened by pi stacking interactions between phenyl rings of 1,3,4-oxadiazole ligands. Then these chains assemble a three-dimensional alternating peak and valley fused wave-shape structure. In each stacking structure of three mononuclear complexes, two molecules form a dimer by the C-H center dot center dot center dot O hydrogen bondings, and these dimers are connected by pi stacking interactions along the b-axis, constructing a zigzag chain.

Self-assembly of a water chain with tetrameric and decameric clusters in the channel of a mixed-valence (CuCuII)-Cu-I complex

The reaction of Cu(BF4)(2) with pyridine-2,6-dicarboxylic acid (H(2)pydc) and trans-1,2-bis(4-pyridyl)ethylene (bpe) under hydrothermal conditions afforded a porous mixed-valence (CuCuII)-Cu-I coordination polymer. Coexistence of tetrameric and decameric water clusters within the channels of the complex leads to a novel water chain. The metal-organic framework provides both hydrophilic and hydrophobic environments for stabilizing the clusters and retains its integrity upon dehydration and rehydration.