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EIGEN-6C4 and EGM2008 ultra-high Earth's gravity field models on their expanded order and degree are limited and exist certain omission errors. The RTM residual height anomalies is obtained from SRTM data and DTM2006.0 data via a prism integral forward-modelling method. The testing results show that (1) before fitting via RTM height anomalies the standard deviation of model height anomalies for EIGEN-6C4 and EGM2008 can be improved by 5.7 mm, the improvement rate respectively is 10 and 7%. (2) After fitting via RTM height anomalies their standard deviations can respectively be improved by 1.0 and 3.3 cm, the improvement rate respectively is 2 and 6%. (3) The RTM height anomalies change along with the increasing of the integral radius, and their values is tending towards stability, are converged to 2 cm, the height anomalies values of EIGEN-6C4 and EGM2008 models change respectively to be in order of cm in scope of 110 km and in scope of 105 km. (4) The RTM technique is an effective method of compensating the accuracy of ultra-high Earth's gravity field model to the benefit of raising the quasigeoid accuracy. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the safety and pharmacokinetics of edaravone administered by single or successive intravenous infusions in healthy Chinese volunteers. Methods: A total of 30 subjects (15 males and 15 females) were recruited and randomly assigned to three groups receiving edaravone doses of 20, 30, and 60 mg. All subjects received a single dose of edaravone during a 30-minute period, and only the 30mg dose group continued to receive the same dose successively by intravenous infusion twice daily for the next 5 days. Plasma concentrations of edaravone were monitored by high-performance liquid chromatography at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600, and 720 minutes after edaravone administration. Results: The area under the plasma concentration-time curve during a dosage interval (AUCτ) values of the single dose in the 20, 30, and 60 mg dose groups were 3.64 ± 1.37, 5.17 ± 0.93, and 11.25 ± 3.42 mg · h/L, respectively, while in the group receiving repeated dosing of 30mg, the mean AUCτ value was 5.06 ± 0.89mg · h/L. The corresponding maximum plasma drug concentration (Cmax) values were 1599.0 ± 382.6, 2378.7 ± 316.7, and 4540.1 ± 901.1 ng/mL, respectively, in the single-dose groups, and 2479.1 ± 477.9 ng/mL in the 30mg repeated-dose group. The mean AUCτ and Cmax ratios between the repeated-dose group and the single-dose groups were 0.98 and 1.04. All laboratory test abnormalities (including increased alanine transaminase and triacylglycerol levels, and decreased white blood cell counts and creatinine levels) were mild and tolerable. All abnormal blood biochemical indices returned to normal levels after 7 days. Conclusion: Edaravone was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUCτ values. [ABSTRACT FROM AUTHOR]

Background: Bencycloquidium bromide (BCQB) is a novel, potent and selective muscarinic M1/M3 receptor antagonist under development for the treatment of rhinorrhea in rhinitis. The pharmacokinetics and safety of BCQB in animals have been established in preclinical studies. However, no clinical pharmacokinetic data are available for BCQB in humans. Objective: The aim of this first-in-human study was to evaluate the pharmacokinetics, safety and tolerability of BCQB following single and multiple intranasal doses in healthy Chinese subjects. Methods: The clinical trial was comprised of the following four studies: (i) an open-label, single-dose escalation study to evaluate the safety and tolerability in healthy subjects after intranasal doses of BCQB ranging from 45 to 450 μg (total of six doses); (ii) an open-label, multiple-dose escalation study to assess the safety and tolerability in healthy subjects after intranasal administration with 120 and 150 μg doses of BCQB (360 and 450 μg/day) administered three times daily for 15 days; (iii) a randomized, open-label and parallel-group design to evaluate the single-dose pharmacokinetics of BCQB after intranasal dosing (45, 90, and 180 μg); and (iv) ten subjects received 120 μg of BCQB by intranasal administration, three times daily for 5 days with a final single dose on day 7 to assess its multiple-dose pharmacokinetics. Safety and tolerability of BCQB were evaluated by monitoring adverse events (AEs), ECG recordings, vital signs and clinical laboratory parameters. The pharmacokinetic parameters for BCQB were calculated by software using noncompartmental methods. Results: All AEs were mild, of limited duration and no more frequent at higher doses. There was no serious adverse event, death or withdrawal. No clinically significant change was noted in clinical laboratory parameters, cardiac parameters or vital signs. Following single intranasal dosing, BCQB was rapidly absorbed with a median time to maximum concentration (tmax) of 8 minutes for 45, 90, and 180 μg dose groups; the plasma concentration of BCQB decreased in a biphasic manner with the mean half-life (t½) of 8.5 hours; the maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) of BCQB increased linearly across the examined dose range of 45-180 μg. During the multiple dosing, the steady state was achieved within 3 days of 120 mg three times daily dosing of BCQB. A slightly greater AUC was observed after 5 days of multiple dosing, with the mean accumulation ratio of 1.26; however, the half-life was unchanged. Conclusion: BCQB was safe and well tolerated in healthy Chinese subjects when administered intranasally with single and multiple doses across the doses studied. The mean Cmax and AUC increased proportionally to the studied doses, and the steady state was achieved within 3 days after three times daily dosing. A slight accumulation of BCQB following multiple dosing was observed. The pharmacokinetics, safety and tolerability profiles of BCQB pose it as a good candidate for further development in the treatment of rhinorrhea in rhinitis. [ABSTRACT FROM AUTHOR]

The deformation structure in terms of shear band patterns in bulk metallic glasses (BMGs) under static indentation, dynamic indentation, and dynamic scratch tests has been investigated. The evolved shear band patterns appear to be a strong function of loading rate, although the plastic regions beneath the loading surface have similarities in shape irrespective of loading type. Comparison of currently available modeling estimates with experimental measurements has revealed that these models predict the plastic zone size reasonably well at low loads but deviate considerably at higher loads. The variation in spacing of shear bands is rationalized on the basis of the shear displacement accommodated by the shear bands formed under different loading rates, which results from a proposed shear-band formation mechanism based on the momentum diffusion model. [ABSTRACT FROM AUTHOR]

We report on a Chinese girl with Frasier syndrome (FS). She presented with steroid-resistant focal segmental glomerulosclerosis (FSGS) and male pseudohermaphroditism. The WT1 IVS 9 + 5 G>A mutation was detected in one allele in the proband. The ratio of +KTS/−KTS was 0.67 in the proband’s cDNA. The expression of podocyte molecules (WT1, nephrin, podocin, α-actinin 4 and CD2AP) were also investigated in a renal specimen of this FS patient. WT1 expression showed diffuse nuclear staining, with less obvious speckles in the patient’s glomeruli than in those of controls. The distribution and intensity of podocyte molecules were altered both in normal- and abnormal-appearing glomeruli. In conclusion, the study presented a case of FS by clinical manifestation, renal pathology, karyotype analysis and genetic testing. A lower ratio of +KTS/−KTS and an abnormal distribution of WT1, as well as abnormal expressions of other podocyte molecules, were also revealed. The mechanisms of WT1 mutation causing FS still need to be investigated. [ABSTRACT FROM AUTHOR]

Well-defined polybutylacrylate (PBA) was prepared by atom transfer radical polymerization (ATRP). A novel end-functionalized PBA (macromolecular ligand) was synthesized via PBA bonded with thiocarbamide. Since thiocarbamide possesses strong chelating ability, end-functionalized PBA possesses some new properties such as coordination with metallic ions. After metallic ions were introduced into it, two kinds of end-functionalized PBA metal complexes were got. The structure and property of PBA, end-functionalized PBA and its metal complexes were characterized by 1H NMR, UV, GPC, Atomic Emission Spectrometry (AES), Cyclic Voltammogram (CV) and Dielectric Constant. The results indicate that the properties of end-functionalized PBA with well-defined structure were improved greatly by introducing a small quantity of transitional metallic ions into it. The novel end-functionalized PBA metal complexes exhibit stable electrochemical activity, dielectric property and have a good prospect in many fields as functional polymer. [ABSTRACT FROM AUTHOR]

Static and dynamic Vickers indentations were performed on ZrHf-based bulk amorphous alloys. A decrease in indentation hardness was observed at higher strain rates compared with static indentation hardness. For equivalent loads, dynamic indentations produced more severe deformation features on the loading surface than static indentations. Using bonded interface technique, the induced shear band patterns beneath the indentations were studied. In static indentations, the majority of the deformation was primarily accommodated by closely spaced semicircular shear bands surrounding the indentation. In dynamic indentations two sets of widely spaced semicircular shear bands with two different curvatures were observed. The observed shear band patterns and softening in hardness were rationalized based on the variations in the confinement pressure, strain rate, and temperature within the indentation region during dynamic indentations. It is also proposed that free volume migration and formation of nano-voids leading to cracking are favored due to adiabatic heating and consequently cause the observed softening at high strain rates. [ABSTRACT FROM AUTHOR]