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The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple physiological processes and is involved in diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo-form and in complexed forms bound to either the conjugated sex hormones ß-estradiol 17-(ß-D-glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the hydrophilic patches in two transmembrane domains. Structural analysis combined with site-directed mutagenesis and ATPase activity assays revealed that ABCC3 possesses an amphiphilic substrate-binding pocket able to hold either conjugated hormone in an asymmetric pattern. These data build on consensus features of the substrate-binding pocket of MRPs and provide a structural platform for the rational design of inhibitors.
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Transportadoras de Casetes de Unión a ATP , Estradiol , Humanos , Transportadoras de Casetes de Unión a ATP/genética , Estradiol/farmacología , Estradiol/metabolismo , Mutagénesis Sitio-DirigidaRESUMEN
The desorption mechanism of heavy metals (HMs) in soil around the mining region are complex and affected by multiple pollution sources, including sewage discharge and atmospheric deposition. Meanwhile, pollution sources would change soil physical and chemical properties (mineralogy and organic matter), thus affecting the bioavailability of HMs. This study aimed to investigate the pollution source of HMs (Cd, Co, Cu, Cr, Mn, Ni, Pb, and Zn) in soil near mining, and further evaluate influence mechanism of dust fall on HMs pollution in soil by desorption dynamics processes and pH-dependence leaching test. Result presented that dust fall is the primary pollution source to HMs accumulation in soil. Additionally, the result of mineralogical analysis in dust fall revealed that quartz, kaolinite, calcite, chalcopyrite, and magnetite are the major mineralogical phases by XRD and SEM-EDS. Meanwhile, the abundance of kaolinite and calcite in dust fall is higher than in soil, which is the primary reason of higher acid-base buffer capacity of dust fall. Correspondingly, the weakened or disappeared of hydroxyl after the adding acid extraction (0-0.4 mmol· g-1) demonstrated that hydroxyl is the main participants of HMs absorption in soil and dust fall. These combined findings suggested that atmospheric deposition not only increases the pollution loading of HMs in soil, but also changes the mineral phase composition of soil, which would increase the adsorption capacity and bioavailability of HMs in soil. This is very remarkable that heavy metals in soil influenced by dust fall pollution could be released preferentially when soil pH is changed. The present results of this study would provide efficient and scientific targeted strategies for pollution control of HMs in soil near mining areas.
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Monitoreo del Ambiente , Metales Pesados , Contaminantes del Suelo , Humanos , China , Cobre/análisis , Polvo/análisis , Monitoreo del Ambiente/métodos , Caolín , Metales Pesados/análisis , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisisRESUMEN
Despite the decrease in anthropogenic emissions, haze episodes were still frequent in the Fenwei Plain, which was identified as one of the three key areas for air pollution control. Herein, PM2.5 samples were collected to investigate the influence of festival effect during the Chinese Spring Festival from February 2rd to 13th, 2019, in Linfen on the Fenwei Plain. The characteristics of element pollution, enrichment factor, source apportionment, regional transport of PM2.5, and health risk assessment were discussed. Meanwhile, the simulated lung fluid method (SLF) was carried out to accurately assess the inhalation risks of heavy metals (HMs). Results indicated that the average concentration of PM2.5 was 195.6 µg·m-3 during the studying period. Road fugitive dust (15.6%), firework burning source (25.6%), industrial emission (30.5%), and coal combustion (28.3%) were identified by positive matrix factorization (PMF) modeling. Using the HYSPLIT trajectory model, air masses from the central Shaanxi, southern Hebei, and northern Henan were the dominant transport paths during the Spring Festival, which contributed 21.9 and 41.2% of total trajectories, respectively. The findings that high PSCF and CWT levels were found in central Shaanxi, southern Hebei, and northern Henan were confirmed. The SLF mean bioaccessibility (%) of the solubility of particulate metals was in order of Mn > Ni > Sb > Ba > Zn > Pb > Cr. However, the carcinogenic risk value of Cr was the highest, exceeding the maximum acceptable risk. The present study provided important information for further analyzing the air pollution cause of Fenwei Plain.
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Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Carbón Mineral/análisis , Disponibilidad Biológica , Monitoreo del Ambiente/métodos , China , Estaciones del Año , Emisiones de Vehículos/análisisRESUMEN
Stringent pollution control measures are generally applied to improve air quality, especially in the Spring Festival in China. Meanwhile, human activities are reduced significantly due to nationwide lockdown measures to curtail the COVID-19 spreading in 2020. Herein, to better understand the influence of control measures and meteorology on air pollution, this study compared the variation of pollution source and their health risk during the 2019 and 2020 Spring Festival in Linfen, China. Results revealed that the average concentration of PM2.5 in 2020 decreased by 39.0% when compared to the 2019 Spring Festival. Organic carbon (OC) and SO42- were the primary contributor to PM2.5 with the value of 19.5% (21.1%) and 23.5% (25.5%) in 2019 (2020) Spring Festival, respectively. Based on the positive matrix factorization (PMF) model, six pollution sources of PM2.5 were indicated. Vehicle emissions (VE) had the maximum reduction in pollution source concentration (28.39 µg· m-3), followed by dust fall (DF) (11.47 µg· m-3), firework burning (FB) (10.39 µg· m-3), coal combustion (CC) (8.54 µg· m-3), and secondary inorganic aerosol (SIA) (3.95 µg· m-3). However, the apportionment concentration of biomass burning (BB) increased by 78.7%, indicating a significant increase in biomass combustion under control measures. PAHs-lifetime lung cancer risk (ILCR) of VE, CC, FB, BB, and DF, decreased by 44.6%, 43.2%, 34.1%, 21.3%, and 2.0%, respectively. Additionally, the average contribution of meteorological conditions on PM2.5 in 2020 increased by 20.21% compared to 2019 Spring Festival, demonstrating that meteorological conditions played a crucial role in located air pollution. This study revealed that the existing control measures in Linfen were efficient to reduce air pollution and health risk, whereas more BB emissions were worthy of further attention. Furthermore, the result was conducive to developing more effective control measures and putting more attention into unfavorable meteorological conditions in Linfen.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/análisis , COVID-19/epidemiología , China/epidemiología , Carbón Mineral/análisis , Control de Enfermedades Transmisibles , Polvo/análisis , Monitoreo del Ambiente , Humanos , Pandemias , Material Particulado/análisis , Material Particulado/toxicidad , Aerosoles y Gotitas Respiratorias , Estaciones del Año , Emisiones de Vehículos/análisisRESUMEN
In this paper, a robust control based on disturbance observer is proposed to improve the tracking accuracy of the Risley prism system (RPS). Applying the flexible thin-wall ring mechanism in the RPS causes a series of tracking and pointing challenges. Disturbances such as friction, shaft deformation, and model perturbation significantly deteriorate the tracking and pointing accuracy of the RPS. Two different observer-based control methods are proposed to guarantee the tracking precision of the RPS. Moreover, the disturbance observation and compensation (DOC) performance of the proposed methods is analyzed and compared. Finally, simulation and experiment results indicate that the proposed control methods, especially the DOC-expanded state observer control mode, obtain the best performance for disturbance rejection in the RPS.
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BACKGROUND: Interleukin-17A (IL17A) is a proinflammatory cytokine critically involved in autoimmune diseases, and monoclonal antibodies of IL17A have been approved for clinical treatment of psoriasis. However, a usable psoriatic animal model has been always required for preclinical evaluation of IL17A antagonists. Imiquimod (IMQ)-induced psoriasis model is widely used in fundamental research, but it's not able to accurately show anti-psoriatic effect of IL17A antagonists with conventional modelling condition. RESULTS: On female C57BL/6 mice, with optimization on the usage of IMQ, positive control reagent and anti-mIL17A antibody, a 7-day model with proper testing window, acceptable disease severity as well as high repeatability was developed, and the efficacy of IL17A antagonist can be objectively evaluated by several qualitative and quantitative indices. Meanwhile, we validated the detailed involvement of IL17A signaling in disease progression, confirmed that the expression levels of IL17A and its related cytokines were induced by IMQ application, and its downstream cytokines can be inhibited by IL17A antagonist treatment. In further study, we revealed that IL17A was transient induced by IMQ and directly caused downstream signaling activation. This finding on the kinetical change of IL17A signaling will manifest the pharmacokinetics-pharmacodynamics investigation of IL17A antagonists. CONCLUSIONS: Our work presents the application of a convenient psoriatic animal model in the research and development of IL17A antagonists, meanwhile providing extra evidence for understanding IL17A's role in the progression of IMQ-induced psoriasis model, which manifest the research and development of IL17A antagonists.
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Modelos Animales de Enfermedad , Interleucina-17/antagonistas & inhibidores , Psoriasis/tratamiento farmacológico , Animales , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Femenino , Imiquimod/efectos adversos , Ratones , Ratones Endogámicos C57BL , Psoriasis/inducido químicamente , Psoriasis/inmunología , Transducción de Señal/efectos de los fármacosRESUMEN
In this paper, a cascade double-loop control (DLC) combined with modeling compensation methods is proposed to improve the tracking precision of the multiaperture imaging system (MAIS). The application of the flexible thin-wall ring mechanism in the coupling rotating prism (CRP) system causes a series of tracking and pointing challenges. Disturbances such as friction, shaft deformation, and model perturbation significantly deteriorate the tracking and pointing accuracy of the CRP. Two different modeling compensation methods that are interfaced with classical DLC are proposed to guarantee the tracking precision of the MAIS. Moreover, the disturbance observation and compensation performance of two different modeling compensation methods are analyzed and compared. Finally, simulation and experiment results indicate that the proposed control methods, especially model compensation based on speed close-loop control, obtain the best performance for disturbance rejection in the MAIS.
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In high-speed free-space optical communication systems, the received laser beam must be coupled into a single-mode fiber at the input of the receiver module. However, propagation through atmospheric turbulence degrades the spatial coherence of a laser beam and poses challenges for fiber coupling. In this paper, we propose a novel method, called as adaptive stochastic parallel gradient descent (ASPGD), to achieve efficient fiber coupling. To be specific, we formulate the fiber coupling problem as a model-free optimization problem and solve it using ASPGD in parallel. To avoid converging to the extremum points and accelerate its convergence speed, we integrate the momentum and the adaptive gain coefficient estimation to the original stochastic parallel gradient descent (SPGD) method. Simulation and experimental results demonstrate that the proposed method reduces 50% of iterations, while keeping the stability by comparing it with the original SPGD method.
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Historical residual of persistent organic pollutants (POPs) in flood sediment from a karst cave were investigated. Fifteen vertical sediment samples were collected from a 6 m-deep flood sediment profile in the Longwang Cave, and the concentrations of organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs) and particle size distribution in the sediments were analysed. The concentrations of OCPs and PAHs varied from 0.85 ng g-1 to 63.1 ng g-1 (mean 8.11 ng g-1) and 5.05 ng g-1 to 82.6 ng g-1 (mean 13.9 ng g-1), respectively; major PAHs in the profile were 2- and 3-ringed PAHs and a few were 5- or 6- ringed PAHs, which indicated less influence from industry but a high impact from the local combustion of coal and biomass; HCHs and DDTs in the profile were historically residual in this region, and HCHs mainly originated from the application of Lindane, while DDTs originated from the application of dicofol and technical DDTs; no significant correlation between the concentrations of OCPs and PAHs and the sedimental particle size in the sediments was found.
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Hidrocarburos Clorados/historia , Residuos de Plaguicidas/historia , Hidrocarburos Policíclicos Aromáticos/historia , Contaminantes Químicos del Agua/historia , Cuevas , China , Inundaciones , Sedimentos Geológicos/química , Historia del Siglo XX , Hidrocarburos Clorados/análisis , Residuos de Plaguicidas/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Characterization and source identification of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) are conducted in urban Wuhan (WH), suburban Pingdingshan (PDS), and rural Suizhou (SZ) in China during summer harvest. This study analyzes 16 priority PAHs with 38 PM.2.5 samples in June. PAHs had similar physical-chemical properties like polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), which had been listed as Priority Pollutants. The concentration and detection frequency of OCPs and PCBs were considerably lower than those of PAHs in PM2.5. Results indicate that PDS adjoining the highway has the highest PM2.5-bound PAHs. SZ possesses the lowest concentration of PAHs. Principal component analysis and multivariate linear regression model and molecular diagnostic ratio distinguish the sources. Vehicle emissions and coal combustion are extracted in three sites, while the source of PDS also includes gas combustion. SZ was affected by gas combustion and petroleum. The potential source contribution function and the concentration-weighted trajectory track the potential pollution area. The sampling places might be affected by the local sources and short distance transmission cannot be neglected. The incremental lifetime cancer risks (ILCRs) model evaluates the exposure risk of PAHs. According to the ILCR model, WH and PDS are exposed to harmful PAHs. By contrast, SZ is a substantially safe place.
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Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Atmosféricos/química , China , Carbón Mineral/análisis , Monitoreo del Ambiente , Material Particulado/química , Plaguicidas/análisis , Hidrocarburos Policíclicos Aromáticos/química , Estaciones del Año , Emisiones de Vehículos/análisisRESUMEN
Variations of levels, possible source and air mass transmission were investigated for 16 USEPA priority-controlled PAHs in PM2.5 during 2018 Chinese Spring Festival (CSF) in Xiangyang City, central China which is the North-South pollutant airmass transport channel of China. Totally 37 samples were collected. Mass concentrations of Σ16PAHs for the Pre-CSF day (Pre-CSFD), during the CSF day (CSFD) and after the CSF day (Af-CSFD) are 33.78 ± 17.68 ng/m3, 22.98 ± 6.49 ng/m3, and 8.99 ± 4.44 ng/m3, respectively. High resolution samples showed that Σ16PAHs are higher in the morning (06:00-11:00) or afternoon (11:30-16:30), than those in the evening (17:00-22:00) and at night (22:30-05:30), whereas the result is reversed during the CSFD. Fireworks burning can obviously increase the mass concentration of PAHs. Air mass trajectory indicated that Xiangyang is a sink area of pollutants for northwest and southeast, and the sources of the northeast and southwest. The air mass only can be transmitted out through northeast and southwest. It is effective for improvement of air quality in Wuhan and Hunan to control fireworks emission in Henan and local areas. Fireworks burning was an important source for PAHs during CSFD, biomass, coal combustion, and traffic emission were the main sources of PAHs for Pre-CSFD and Af-CSFD periods. The health risk on the CSFD was higher than the acceptable levels, especially during the intensive fireworks burning, the risk value far exceed 1.0 × 10-4, controlling burning fireworks is required.
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Contaminantes Atmosféricos/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , China , Ciudades , Monitoreo del Ambiente , Vacaciones y Feriados , Material Particulado/análisis , Estaciones del AñoRESUMEN
An essential issue for the low-noise system application of the fiber optic gyroscope (FOG) is to reduce its noise level. The relative intensity noise (RIN) of the light source is the dominant noise of the FOG when the light power on the detector reaches a certain level. The noise subtraction method is effective for RIN reduction and easy to implement in a FOG. This paper theoretically analyzes the factors that influence the result of the method and deduces the function to calculate the noise suppression ratio that can be achieved. A method that uses an optimum filter design based on the Wiener filter in the reference detector signal is proposed to improve the subtraction result. A FOG system is set up to test the feasibility of the method. The experiment results meet with the theoretical analysis, and by using the Wiener filter, the achieved noise subtraction factor reaches the limitation that restrains the optical system and detection circuit.
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Micro-electro-mechanical system (MEMS) gyro is one of the extensively used inertia sensors in the field of optical target tracking (OTT). However, velocity closed-loop bandwidth of the OTT system is limited due to the resonance and measurement range issues of MEMS gyro. In this paper, the generalized sensor fusion framework, named the closed-loop fusion (CLF), is analyzed, and the optimal design principle of filter is proposed in detail in order to improve measurement of the bandwidth of MEMS gyro by integrating information of MEMS accelerometers. The fusion error optimization problem, which is the core issue of fusion design, can be solved better through the feedback compensation law of CLF framework and fusion filter optimal design. Differently from conventional methods, the fusion filter of CLF can be simply and accurately designed, and the determination of superposition of fusion information can also be effectively avoided. To show the validity of the proposed method, both sensor fusion simulations and closed-loop experiments of optical target tracking system have yielded excellent results.
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The stable alignment and transmission of free space optical communication (FSO) is susceptible to internal dynamics and external disturbances. In this paper, a virtual dual-loop feedback control (VDFC) with model-construction linear extended state observer (MCLESO), which is applied to the fast tip-tilt mirror platform to enhance the disturbance suppression ability (DSA) for FSO. MCLESO, which is modified on a classical linear extended state observer by introducing the available model information, is shown to use the input and output signal data of the system to observe total disturbances, including internal dynamics and external disturbance. Since the position and velocity signals are both observed only with the optoelectronic target detector and MCLESO, the controllers of the dual-loop feedback control (DFC) system are employed directly. This method has a more accurate control performance after model construction, which enhances the DSA of the tip-tilt mirror control system in low and medium frequency. It is also beneficial to miniaturization and cost saving by not using velocity sensors. Both simulations and experiments validate the effectiveness of the proposed method in the tip-tilt mirror control system under the condition of disturbance.
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In the charge-coupled device (CCD) and micro-electro-mechanical system (MEMS) accelerometer based low-cost multi-loop optoelectronic control system (OCS), due to accelerometers’ drift and noise in low frequency, the disturbance suppression (DS) is insufficient. Previously, based on the acceleration and position dual-loop control (ADLC), researchers combined a disturbance observer (DOB) with a virtual velocity loop to make some medium-frequency DS exchange for low-frequency performance. However, it is not optimal because the classic DOB based on accelerometers’ inaccurate signals cannot observe accurate disturbance in low frequency and the velocity based on a CCD and accelerometer time-domain fusion carried the CCD’s delay, resulting in the drop of medium-frequency DS. In this paper, considering the CCD’s advantage in low frequency and the accelerometer’s strength in high frequency, we propose to fuse their signals twice with a modified complementary filter method to respectively acquire an acceleration and velocity. The new acceleration with no drift and less noise but lower bandwidth creates a new acceleration model and is only used in fusion DOB (FDOB), while the velocity with little delay is to build an additional velocity loop. Compared with the traditional DOB enhanced by the time-domain fusion velocity loop, experiments verify that the proposed multiple fusion would apparently enhance the system’s DS, especially in low and medium frequency.
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In the CCD-based fine tracking optical system (FTOS), the whole disturbance suppression ability (DSA) is the product of the inner loop and outer position loop. Traditionally, high sampling fiber-optic gyroscopes (FOGs) are added to the platform to stabilize the line-of-sight (LOS). However, because of the FOGs' high cost and relatively big volume relative to the back narrow space of small rotating mirrors, we attempt in this work to utilize a cheaper and smaller micro-electro-mechanical system (MEMS) accelerometer to build the inner loop, replacing the FOG. Unfortunately, since accelerometers are susceptible to the low-frequency noise, according to the classical way of using accelerometers, the crucial low-frequency DSA of the system is insufficient. To solve this problem, in this paper, we propose an approach based on MEMS accelerometers combining disturbance observer (DOB) with triple-loop control (TLC) in which the composite velocity loop is built by acceleration integration and corrected by CCD. The DOB is firstly used to reform the platform, greatly improving the medium-frequency DSA. Then the composite velocity loop exchanges a part of medium-frequency performance for the low-frequency DSA. A detailed analysis and experiments verify the proposed method has a better DSA than the traditional way and could totally substitute FOG in the LOS stabilization.
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The effectiveness of standard triple therapy (STT) for the eradication of Helicobacter pylori has decreased recently. Sequential therapy (SQT) is a new regimen proposed to address this problem. The aim of this study was to compare the efficacy of SQT versus STT for H. pylori eradication. We searched The Cochrane Library, MEDLINE, Web of Science, and EMBASE databases up to July 2014. The risk ratios (RRs) of eradication rate were pooled, with a 95% confidence interval (CI). Thirty-six randomized clinical trials including a total of 10,316 patients met the inclusion criteria. The RR for eradication of H. pylori with SQT compared with STT was 1.14 (95% CI: 1.09-1.17), the eradication rates were 84.1% and 75.1%, respectively. There was significant heterogeneity between trial results (I = 73%; P < 0.00001). Subgroup analyses showed that SQT was superior to both 7- and 10-day STT, but not significantly better than 14-day STT. This superiority existed when patients were treated with either metronidazole or tinidazole. Patients with single clarithromycin-resistant strain showed a greater benefit of SQT over STT (eradication rates 80.9% vs. 40.7%), RR = 1.98 (95% CI: 1.33-2.94). There was no significant difference between groups in terms of the risk of adverse effects. In conclusion, SQT is more efficacious than STT (7 days and 10 days) in the eradication of HP, but the pooled rate seemed suboptimal. Further research is needed to develop more effective therapeutic approaches. Surveillance of resistance rates should be performed to guide treatment.
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Inhibidores de la Bomba de Protones/uso terapéutico , Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Claritromicina/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Helicobacter pylori/efectos de los fármacos , Humanos , Inhibidores de la Bomba de Protones/administración & dosificaciónRESUMEN
In this paper, an approach to improve the disturbance suppression performance of a fast steering mirror (FSM) tracking control system based on a charge-coupled device (CCD) and micro-electro-mechanical system (MEMS) inertial sensors is proposed. The disturbance observation and compensation (DOC) control method is recommended to enhance the classical multi-loop feedback control (MFC) for line-of-sight (LOS) stabilization in the FSM system. MEMS accelerometers and gyroscopes have been used in the FSM system tentatively to implement MFC instead of fiber-optic gyroscopes (FOG) because of its smaller, lighter, cheaper features and gradually improved performance. However, the stabilization performance of FSM is still suffering a large number of mechanical resonances and time delay induced by a low CCD sampling rate, which causes insufficient error attenuation when suffering uncertain disturbances. Thus, in order to make further improvements on the stabilization performance, a cascaded MFC enhanced by DOC method is proposed. The sensitivity of this method shows the significant improvement of the conventional MFC system. Simultaneously, the analysis of stabilization accuracy is also presented. A series of comparative experimental results demonstrate the disturbance suppression performance of the FSM control system based on the MEMS inertial sensors can be effectively improved by the proposed approach.
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OBJECTIVE: To investigate the clinical features of Wilson's disease (WD) for the purpose of avoiding misdiagnosis and therefore improving the prognosis of this rare disease. METHODS: This study enrolled all the patients diagnosed as WD who were admitted to West China Hospital, Sichuan University from Jan 2008 to Dec 2014. Their clinical manifestations, head and abdominal images data were extracted and analyzed. RESULTS: There were a total of 126 patients of WD, male female ratio was 75 : 51, median age was 21-years old. 10.3% (13/126) of them had family history, 87.3% (109/126) patients presented with neuropsychiatric symptoms, 14.3% (18/126) patients manifested as chronic liver disease. All patients had decreased serum ceruloplasmin level < 200 mg/L, 121 (96.9%) patients had serum ceruloplasmin level < 100 mg/L. Magnetic resonance imaging and abdominal ultrasound detected structural abnormalities in 92.7% (102/110) and 88.9% (97/109) patients respectively. Kayser-Fleischer rings on slit-lamp ophthalmologic examination was found in 98.3% (115/117) patients. One patient underwent liver biopsy and the result of rhodanine stain was positive. The time from onset to diagnosis varied from 3 d to 19 years [(1.59 ± 2.66) years]. 20 (15.9%) patients were initially misdiagnosed. CONCLUSION: The patients presenting with neurological signs or unexplained liver disease should be assessed carefully for WD. Serum ceruloplasmin, 24-h urinary copper, Kayser-Fleischer rings and sometimes even liver biopsy could be helpful for the diagnosis.
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Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/patología , Biopsia , Ceruloplasmina/análisis , China , Cobre/orina , Femenino , Humanos , Hepatopatías/patología , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Lámpara de Hendidura , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effect of hypoxia on the visfatin and the expression of smooth muscle-actin (alpha-SMA) and hypoxia-inducible factor-1alpha (HIF-1alpha) in rat hepatic stellate cells (HSCs). METHODS: Rat primary HSCs were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. Completely activated primary HSCs were exposed to hypoxic conditions (37 degrees C, 5% CO2, 1% O2, 94% N2), or normoxic conditions (37 degrees C, 5% CO2, 21% O2, 74% N2), for 3, 6, 12 or 24 h respectively. The expression of alpha-SMA, the marker of HSC activation, and visfatin were assessed by Real time-PCR and Western blot. The Expression of HIF-1alpha was detected by Real time-PCR. RESULTS: HIF-1alpha mRNA in rat HSCs was induced after exposed to hypoxia for 3 h, and maintained elevated status up to 24 h. HSCs exposed to 1% O2 hypoxic conditions for 6 h increased alpha-SMA mRNA and protein expression. Visfatin mRNA expression was up-regulated after subjected to hypoxia for 12 h, and protein level was elevated after 6 h hypoxia. A positive linear correlation existed between alpha-SMA and visfatin expression in responsible to hypoxia (r = 0.991 (genes) and r = 0.968 (proteins), P < 0.05). CONCLUSION: Microcirculation impairment could significantly induce alpha-SMA and visfatin expression in rat HSCs, which might potentate the activation process of HSCs.