2,364 research outputs found

    A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

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    Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

    Explanation of the Colour Change in Alexandrites.

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    Alexandrites are remarkable and rare gemstones. They display an extraordinary colour change according to the ambient lighting, from emerald green in daylight to ruby red in incandescent light from tungsten lamps or candles. While this colour change has been correctly attributed to chromium impurities and their absorption band in the yellow region of the visible light spectrum, no adequate explanation of the mechanism has been given. Here, the alexandrite effect is fully explained by considering the von Kries model of the human colour constancy mechanism. This implies that our colour constancy mechanism is real (objective) and primarily attuned to correct for the colour temperature of black-body illuminants

    Determination and Distribution Study of Pogostone in Rat Tissues by Ultra-Fast Liquid Chromatography

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    Purpose: To develop and validate a rapid, sensitive and reliable ultra-fast liquid chromatography (UFLC) method with photodiode array (PDA) detection for the determination of pogostone (PO) in rat tissues using honokiol as internal standard (IS).Methods: Rats were randomly divided into two groups (intravenous administration group and oral administration group) and given of a single dose of 10 mg/kg PO by intravenous administration and oral administration, respectively. After intravenous injection, the rats were sacrificed at 15, 60 and 360 min, while rats, after oral administration, were euthanasized at 30, 90 and 360 min, respectively. For the analysis of the preparation, optimal chromatographic conditions were determined using Acquity UPLC BEH C18 column with acetonitrile-water containing 0.1 % formic acid (55:45, v/v) as the mobile phase, at a flow rate of 400 μL/min. UV detection wavelength was set at 310 nm with temperature maintained at 30 °C.Results: Good linear relationship of calibration curve (r > 0.9984) was achieved over the range of 0.1 - 40 μg/mL for all the tissue samples. The limit of quantification (LOQ) and limit of detection (LOD) were 0.1 and 0.05 μg/mL, respectively. This method proved to have good precision, accuracy, stability, extraction recovery and matrix effect for tissue distribution studies of PO in rats.Conclusion: The developed method is suitable for tissue distribution studies in rats following intravenous and oral administration of PO at a dose of 10 mg/kg.Keywords: Ultra-fast liquid chromatography, Tissue distribution, Pogostone, Honokiol, Rat

    Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge

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    OBJECTIVE: The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS) in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV) IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. METHODS: The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT) examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [D(L)CO] < 80% of predicted value [pred]) received regular lung function tests and HRCT examinations in the follow-up phase in order to document the changes in their lung condition. Some patients who complained of joint pain were given magnetic resonance imaging (MRI) examinations of their femoral heads. FINDINGS: Of all the subjects, 81.2% (311 of 383 patients) tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients) were suffering from lung diffusion abnormities (D(L)CO < 80% pred) and 21.5% (67 of 311 patients) exhibited lung fibrotic changes. In the 12 month duration of this study, all of the 40 patients with lung diffusion abnormities who were examined exhibited some improvement of lung function and fibrosis detected by radiography. Of the individuals receiving MRI examinations, 23.1% (18 of 78 patients) showed signs of femoral head necrosis. INTERPRETATION: The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis

    Transparent dense sodium

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    Under pressure, metals exhibit increasingly shorter interatomic distances. Intuitively, this response is expected to be accompanied by an increase in the widths of the valence and conduction bands and hence a more pronounced free-electron-like behaviour. But at the densities that can now be achieved experimentally, compression can be so substantial that core electrons overlap. This effect dramatically alters electronic properties from those typically associated with simple free-electron metals such as lithium and sodium, leading in turn to structurally complex phases and superconductivity with a high critical temperature. But the most intriguing prediction - that the seemingly simple metals Li and Na will transform under pressure into insulating states, owing to pairing of alkali atoms - has yet to be experimentally confirmed. Here we report experimental observations of a pressure-induced transformation of Na into an optically transparent phase at 200 GPa (corresponding to 5.0-fold compression). Experimental and computational data identify the new phase as a wide bandgap dielectric with a six-coordinated, highly distorted double-hexagonal close-packed structure. We attribute the emergence of this dense insulating state not to atom pairing, but to p-d hybridizations of valence electrons and their repulsion by core electrons into the lattice interstices. We expect that such insulating states may also form in other elements and compounds when compression is sufficiently strong that atomic cores start to overlap strongly.Comment: Published in Nature 458, 182-185 (2009

    Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

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    The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

    Fiber guiding at the Dirac frequency beyond photonic bandgaps

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    Light trapping within waveguides is a key practice of modern optics, both scientifically and technologically. Photonic crystal fibers traditionally rely on total internal reflection (index-guiding fibers) or a photonic bandgap (photonic-bandgap fibers) to achieve field confinement. Here, we report the discovery of a new light trapping within fibers by the so-called Dirac point of photonic band structures. Our analysis reveals that the Dirac point can establish suppression of radiation losses and consequently a novel guided mode for propagation in photonic crystal fibers. What is known as the Dirac point is a conical singularity of a photonic band structure where wave motion obeys the famous Dirac equation. We find the unexpected phenomenon of wave localization at this point beyond photonic bandgaps. This guiding relies on the Dirac point rather than total internal reflection or photonic bandgaps, thus providing a sort of advancement in conceptual understanding over the traditional fiber guiding. The result presented here demonstrates the discovery of a new type of photonic crystal fibers, with unique characteristics that could lead to new applications in fiber sensors and lasers. The Dirac equation is a special symbol of relativistic quantum mechanics. Because of the similarity between band structures of a solid and a photonic crystal, the discovery of the Dirac-point-induced wave trapping in photonic crystals could provide novel insights into many relativistic quantum effects of the transport phenomena of photons, phonons, and electrons

    Investigation on two abnormal phenomena about thermal conductivity enhancement of BN/EG nanofluids

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    The thermal conductivity of boron nitride/ethylene glycol (BN/EG) nanofluids was investigated by transient hot-wire method and two abnormal phenomena was reported. One is the abnormal higher thermal conductivity enhancement for BN/EG nanofluids at very low-volume fraction of particles, and the other is the thermal conductivity enhancement of BN/EG nanofluids synthesized with large BN nanoparticles (140 nm) which is higher than that synthesized with small BN nanoparticles (70 nm). The chain-like loose aggregation of nanoparticles is responsible for the abnormal increment of thermal conductivity enhancement for the BN/EG nanofluids at very low particles volume fraction. And the difference in specific surface area and aspect ratio of BN nanoparticles may be the main reasons for the abnormal difference between thermal conductivity enhancements for BN/EG nanofluids prepared with 140- and 70-nm BN nanoparticles, respectively
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