10 research outputs found

    Haemodynamic changes in both ROIs.

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    <p>Haemodynamic changes in the left ROI (blue bar) and right ROI (orange bar) for RDSs with 8 disparities for all participants (n = 11). Error bars represent the standard error of the mean across all participants. Statistical analysis indicates that there is a left lateralization of the activation pattern; furthermore, haemodynamic response to an RDS with 0.5° disparity is significantly stronger than to an RDS with 1.1°.</p

    The correlation between subjective assessments and fNIRS data at group level (n = 11).

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    <p>The correlation between subjective assessments and fNIRS data at group level (n = 11).</p

    Illustration of the data processing.

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    <p>(a): a bad trial sample with large background noise; (b): extracted brain activity from the raw data; (c): fitting the data by two normal distribution functions.</p

    Statistical results of subjective assessments.

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    <p>Correlations between subjective assessments and different binocular disparities (a, b, c, d). The evaluation of sustainability is correlated with the perception of stereopsis (e) and the degree of discomfort (f). Subsequent post-hoc pairwise comparisons (with FDR controlled) reveal that the differences of evaluations are all significant or marginally significant (P<sub>max</sub> = 0.052) among different disparities in (a), (b) and (d). The evaluation of RDS with 0.7° disparity is significantly larger than RDS with 1.1° in (c). *: Significance at the 0.05 level. **: Significance at the 0.01 level.</p

    Quantification of Hemoglobin and White Blood Cell DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9<i>H</i>‑pyrido[2,3‑<i>b</i>]indole and 4‑Aminobiphenyl Formed in Humans by Nanoflow Liquid Chromatography/Ion Trap Multistage Mass Spectrometry

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    Aromatic amines covalently bound to hemoglobin (Hb) as sulfinamide adducts at the cysteine 93 residue of the Hb β chain have served as biomarkers to assess exposure to this class of human carcinogens for the past 30 years. In this study, we report that 2-amino-9<i>H</i>-pyrido­[2,3-<i>b</i>]­indole (AαC), an abundant carcinogenic heterocyclic aromatic amine formed in tobacco smoke and charred cooked meats, also reacts with Hb to form a sulfinamide adduct. A novel nanoflow liquid chromatography/ion trap multistage mass spectrometry (nanoLC-IT/MS<sup>3</sup>) method was established to assess exposure to AαC and the tobacco-associated bladder carcinogen 4-aminobiphenyl (4-ABP) through their Hb sulfinamide adducts. Following mild acid hydrolysis of Hb <i>in vitro</i>, the liberated AαC and 4-ABP were derivatized with acetic anhydride to form the <i>N</i>-acetylated amines, which were measured by nanoLC-IT/MS<sup>3</sup>. The limits of quantification (LOQ) for AαC- and 4-ABP-Hb sulfinamide adducts were ≤7.1 pg/g Hb. In a pilot study, the mean level of Hb sulfinamide adducts of AαC and 4-ABP were, respectively, 3.4-fold and 4.8-fold higher in smokers (>20 cigarettes/day) than nonsmokers. In contrast, the major DNA adducts of 4-ABP, <i>N</i>-(2′-deoxyguanosin-8-yl)-4-aminobiphenyl, and AαC, <i>N</i>-(2′-deoxyguanosin-8-yl)-2-amino-9<i>H</i>-pyrido­[2,3-<i>b</i>]­indole, were below the LOQ (3 adducts per 10<sup>9</sup> bases) in white blood cell (WBC) DNA of smokers and nonsmokers. These findings reaffirm that tobacco smoke is a major source of exposure to AαC. Hb sulfinamide adducts are suitable biomarkers to biomonitor 4-ABP and AαC; however, neither carcinogen binds to DNA in WBC, even in heavy smokers, at levels sufficient for biomonitoring

    Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?

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    A database survey in this study revealed for the first time that there are 227 counterintuitive like-charge guanidinium pairings (Gdm<sup>+</sup>–Arg pairings) between ligands and receptors in the Protein Data Bank, implying the potential guanidinium–arginine binding between guanidine-containing drugs and their target proteins. Furthermore, there are 145 guanidine-containing molecules in the DrugBank, showing the prevalence of guanidinium groups in drugs. It has also been reported that the introduction of a guanidinium group forming Gdm<sup>+</sup>–Arg pairing improved the potency of the drug by more than 8-fold in a typical case. On the basis of the survey, six ligand–protein complexes with typical Gdm<sup>+</sup>–Arg pairings were chosen for QM/MM calculations. The calculations at the B97-D/6-311++g­(d,p) level revealed that the interaction could be as strong as −1.0 to −2.5 kcal/mol in DMSO and water, comparable to common intermolecular interactions. The calculations also unveiled that the Gdm<sup>+</sup>–Arg pairing interactions change from repulsive to attractive with the increase of dielectric constant, suggesting that the dielectric constant has a general stabilization effect on the Gdm<sup>+</sup>–Arg pairing. This study suggested that the like-charge guanidinium pairing interaction could be used not only for tuning the physical and chemical properties of drug leads but also for improving ligand binding affinity

    TiO<sub>2</sub> Nanolayer-Enhanced Fluorescence for Simultaneous Multiplex Mycotoxin Detection by Aptamer Microarrays on a Porous Silicon Surface

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    A new aptamer microarray method on the TiO<sub>2</sub>–porous silicon (PSi) surface was developed to simultaneously screen multiplex mycotoxins. The TiO<sub>2</sub> nanolayer on the surface of PSi can enhance the fluorescence intensity 14 times than that of the thermally oxidized PSi. The aptamer fluorescence signal recovery principle was performed on the TiO<sub>2</sub>–PSi surface by hybridization duplex strand DNA from the mycotoxin aptamer and antiaptamer, respectively, labeled with fluorescence dye and quencher. The aptamer microarray can simultaneously screen for multiplex mycotoxins with a dynamic linear detection range of 0.1–10 ng/mL for ochratoxin A (OTA), 0.01–10 ng/mL for aflatoxins B<sub>1</sub> (AFB<sub>1</sub>), and 0.001–10 ng/mL for fumonisin B<sub>1</sub> (FB<sub>1</sub>) and limits of detection of 15.4, 1.48, and 0.21 pg/mL for OTA, AFB<sub>1</sub>, and FB<sub>1</sub>, respectively. The newly developed method shows good specificity and recovery rates. This method can provide a simple, sensitive, and cost-efficient platform for simultaneous screening of multiplex mycotoxins and can be easily expanded to the other aptamer-based protocol
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