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Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.
Compulsive behaviors in obsessive-compulsive disorder (OCD) have been related to impairment within the associative cortical-striatal system connecting the caudate and prefrontal cortex that underlies consciously-controlled goal-directed learning and behavior. However, little is known whether this impairment may serve as a biomarker for vulnerability to OCD.
Using resting-state functional magnetic resonance imaging (fMRI), we employed Granger causality analysis (GCA) to measure effective connectivity (EC) in previously validated striatal sub-regions, including the caudate, putamen, and the nucleus accumbens, in 35 OCD patients, 35 unaffected first-degree relatives and 35 matched healthy controls.
Both OCD patients and their first-degree relatives showed greater EC than controls between the left caudate and the orbital frontal cortex (OFC). Both OCD patients and their first-degree relatives showed lower EC than controls between the left caudate and lateral prefrontal cortex. These results are consistent with findings from task-related fMRI studies which found impairment in the goal-directed system in OCD patients.
The same changes in EC were present in both OCD patients and their unaffected first-degree relatives suggest that impairment in the goal-directed learning system may be a biomarker for OCD.
Deep learning methods have been applied to randomly generate images, such as in fashion, furniture design. To date, consideration of human aspects which play a vital role in a design process has not been given significant attention in deep learning approaches. In this paper, results are reported from a human- in-the-loop design method where brain EEG signals are used to capture preferable design features. In the framework developed, an encoder extracting EEG features from raw signals recorded from subjects when viewing images from ImageNet are learned. Secondly, a GAN model is trained conditioned on the encoded EEG features to generate design images. Thirdly, the trained model is used to generate design images from a person's EEG measured brain activity in the cognitive process of thinking about a design. To verify the proposed method, a case study is presented following the proposed approach. The results indicate that the method can generate preferred designs styles guided by the preference related brain signals. In addition, this method could also help improve communication between designers and clients where clients might not be able to express design requests clearly.
Alzheimer’s Disease (AD), characterized by deficits in memory and cognition and by behavioral impairment, is a progressive neurodegenerative disorder that influences more than 47 million people worldwide. Currently, no available drug is able to stop AD progression. Therefore, novel therapeutic strategies need to be investigated.
We analyzed the RNA sequencing data (RNA-seq) derived from the Gene Expression Omnibus (GEO) database to identify the differentially expressed mRNAs in AD. The AD mouse model Tg2576 was used to verify the effects of IGF-2. The Morris Water Maze was administered to test the role of IGF-2 in memory consolidation. In addition, we quantified cell apoptosis by the TUNEL assay. The levels of amyloid plaques and the levels of Aβ40 and Aβ42 in the hippocampus were also determined by immunohistochemistry and ELISA, respectively.
RNA-seq analysis revealed that IGF-2 was remarkably reduced in AD. The expression of the upstream genes PI3K and AKT and the downstream gene CREB in the PI3K signaling pathway was significantly increased in the hippocampus of Tg2576 mice cells treated with IGF-2. The Morris water maze test showed that IGF-2 improved memory consolidation in Tg2576 mice. The activity of caspase-3 was decreased in Tg2576 mice treated with IGF-2. Amyloid plaques in the hippocampus were reduced, and the levels of Aβ40 and Aβ42 were decreased. The above effects of IGF-2 on AD were blocked when the PI3K signaling pathway inhibitor wortmannin was added.
IGF-2 attenuates memory decline, oxidative stress, cell apoptosis and amyloid plaques in the AD mouse model Tg2576 by activating the PI3K/AKT/CREB signaling pathway.
At GE Research, we are combining “physics” with artificial intelligence and machine learning to advance manufacturing design, processing, and inspection, turning innovative technologies into real products and solutions across our industrial portfolio. This article provides a snapshot of how this physical plus digital transformation is evolving at GE.
With the aims of overcoming the limitations of the existing basic flow model derived from an axisymmetric generating body and extending the aerodynamic design method of the airframe/inlet integrated waverider vehicle, this study develops an upgraded basic flow model derived from an axisymmetric shock wave. It then upgrades the design method for airframe/inlet integration of an air-breathing hypersonic waverider vehicle, which is termed the ‘full-waverider vehicle’ in this study. In this paper, first, the design principle and method for the upgraded full-waverider vehicle derived from an axisymmetric basic shock wave are described in detail. Second, an upgraded basic flow model that accounts for both internal and external flows is derived from an axisymmetric basic shock wave by use of both the streamline tracing method and the method of characteristics (MOC). Third, the upgraded full-waverider vehicle is developed from the upgraded basic flow model by the streamline tracing method. Fourth, the design theories and methodologies of both the upgraded basic flow model and the upgraded full-waverider vehicle are validated by a numerical computation method. Finally, the aerodynamic performances and viscous effects of both the upgraded basic flow model and the upgraded full-waverider vehicle are analysed by numerical computation. The obtained results show that the upgraded basic flow model and aerodynamic design method are effective for the design of the airframe/inlet integration of an air-breathing hypersonic waverider vehicle.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
This paper presents a low insertion loss low-pass filter based on the spoof surface plasmon polariton (SSPP) with single comb-shape. Compared with traditional ones, the proposed filter provides lower insertion loss and return loss by optimizing the structural parameters of the mode conversion and SSPP parts. According to the measurement results, the average insertion loss of the fabricated filter is 0.41 dB and the return loss of which at the near-zero-hertz band is <−25.9 dB. The S parameter comparison result between the unoptimized and optimized filters demonstrates that the optimized filter provides lower insertion loss and return loss, smaller size, and better out-of-band rejection. The dispersion comparison result reveals the reasons behind the improved performances. The better performances of the optimized filter proves that breaking the regularity of traditional SSPP filters is beneficial to the filter's performances.
A dualband rejection filter and a triband rejection filter are proposed in this letter, both of which are implemented by cascading spoof surface plasmon polaritons (SSPPs) of the same structure but with diverse rejection bands. Compared with traditional ones, the proposed filters provide more compact structures, wider rejection bands, and better independent tunability. In the proposed filters, the rejection bandwidth, the center frequency of the rejection band and the filter's cutoff frequency can be adjusted independently. And the different rejection bands in the same filter also can be independently controlled. Agreements between the dispersion of SSPP units and the S21 of filters are also presented. Measurement results demonstrate that both filters load multiple rejection bands on the 27.7 GHz wide low-pass band and all the rejection bands locate in Ku and K bands. The average rejection bandwidth and the average rejection depth of the two filters are 1.49 GHz and 42.1 dB, respectively.
As a benchmark mortality model in forecasting future mortality rates and hedging longevity risk, the widely employed Lee–Carter model (Lee, R.D. and Carter, L.R. (1992) Modeling and forecasting U.S. mortality. Journal of the American Statistical Association, 87, 659–671.) suffers from a restrictive constraint on the unobserved mortality index for ensuring model’s identification and a possible inconsistent inference. Recently, a modified Lee–Carter model (Liu, Q., Ling, C. and Peng, L. (2018) Statistical inference for Lee–Carter mortality model and corresponding forecasts. North American Actuarial Journal, to appear.) removes this constraint and a simple least squares estimation is consistent with a normal limit when the mortality index follows from a unit root or near unit root AR(1) model with a nonzero intercept. This paper proposes a bias-corrected estimator for this modified Lee–Carter model, which is consistent and has a normal limit regardless of the mortality index being a stationary or near unit root or unit root AR(1) process with a nonzero intercept. Applications to the US mortality rates and a simulation study are provided as well.
Conventional underwater navigation and positioning methods for Autonomous Underwater Vehicles (AUVs) either require the installation of acoustic arrays, which make AUVs less independent, or result in cumulative errors. This paper proposes an Underwater Terrain Positioning Method (UTPM) using Maximum a Posteriori (MAP) estimation and a Pulse Coupled Neural Network (PCNN) model for highly accurate navigation by AUVs. The PCNN model is used as a secondary discriminant to effectively identify pseudo-anchor points in flat terrain feature areas and to find the true positioning point, which significantly improves the matching positioning accuracy in these areas. Simulation results show that the proposed method effectively corrects Inertial Navigation System (INS) cumulative errors and has high matching positioning accuracy, which satisfy the requirements of AUV underwater navigation and positioning.
Imaging studies have shown that the subcallosal region (SCR) volume was decreased in patients with major depressive disorder (MDD). However, whether the volumetric reductions in the SCR are due to thinning of the cortex or a loss of surface area (SA) remains unclear. In addition, the relationship between cortical measurements of the SCR and age through the adult life span in MDD remains unclear.
We used a cross-sectional design from 114 individuals with MDD and 112 matched healthy control (HC) individuals across the adult life span (range: 18–74 years). The mean cortical volume (CV), SA and cortical thickness (CT) of the SCR were computed using cortical parcellation based on FreeSurfer software. Multivariate analyses of covariance models were performed to compare differences between the MDD and HC groups on cortical measurements of the SCR. Multiple linear regression models were used to test age-by-group interaction effects on these cortical measurements of the SCR.
The MDD had significant reductions in the CV and SA of the left SCR compared with HC individuals after controlling of other variables. The left SCR CV and SA reductions compared with matched controls were observed only in early adulthood patients. We also found a significant age-related CT reduction in the SCR both in the MDD and HC participants.
The SCR volume reduction was mainly driven by SA in MDD. The different trajectories between the CT and SA of the SCR with age may provide valuable information to distinguish pathological processes and normal ageing in MDD.
Population-based colorectal cancer (CRC) screening programs that use a fecal immunochemical test (FIT) are often faced with a noncompliance issue and its subsequent waiting time (WT) for those FIT positives complying with confirmatory diagnosis. We aimed to identify factors associated with both of the correlated problems in the same model.
A total of 294,469 subjects, either with positive FIT test results or having a family history, collected from 2004 to 2013 were enrolled for analysis. We applied a hurdle Poisson regression model to accommodate the hurdle of compliance and also its related WT for undergoing colonoscopy while assessing factors responsible for the mixture of the two outcomes.
The effect on compliance and WT varied with contextual factors, such as geographic areas, type of screening units, and level of urbanization. The hurdle score, representing the risk score in association with noncompliance, and the WT score, reflecting the rate of taking colonoscopy, were used to classify subjects into each of three groups representing the degree of compliance and the level of health awareness.
Our model was not only successfully applied to evaluating factors associated with the compliance and the WT distribution, but also developed into a useful assessment model for stratifying the risk and predicting whether and when screenees comply with the procedure of receiving confirmatory diagnosis given contextual factors and individual characteristics.
A field study to optimize the nitrogen (N) top-dressing mode of panicle fertilization and improve rice yields was conducted in mid-eastern China. Japonica cultivar Yunongjing-6 was grown and panicle N fertilizer was applied at the beginning of the inverted fourth leaf stage using three different modes: manual broadcast application (BA) on the soil surface as a control treatment, deep application during ditching at a depth of 15 cm (DD) and manual BA on the soil surface during deep ditching (BAD). The activity of soil enzymes, including invertase, urease, phosphatase and catalase, was increased significantly at the jointing, booting and grain-filling stages with the DD and BAD treatments compared with the traditional BA mode. The DD and BAD treatments also increased basal internode and neck-panicle internode bleeding intensity. The DD treatment gave the highest crop yield, increasing the yield by 0.63 and 0.31 t/hm2 in 2011 and 2012, respectively, compared with BA. The results suggest that ditching during panicle N fertilizer application after sun-drying of the fields increases rice yields, most likely by improving the activity of soil enzymes and enhancing the physiological activity of roots and grain weight.
Hepatitis B constitutes a severe public health challenge in China. The Community-based Collaborative Innovation hepatitis B (CCI-HBV) project is a national epidemiological study of hepatitis B and has been conducting a comprehensive intervention in southern Zhejiang since 2009.
The comprehensive intervention in CCI-HBV areas includes the dynamic hepatitis B screening in local residents, the normalised treatment for hepatitis B infections and the upcoming full-aged hepatitis B vaccination. After two rounds of screening (each round taking for 4 years), the initial epidemiological baseline of hepatitis B in Qinggang was obtained, a coastal community in east China. By combining key data and system dynamics modelling, the regional hepatitis B epidemic in 20 years was predicted.
There were 1041 HBsAg positive cases out of 12 228 people in Round 1 indicating HBV prevalence of 8.5%. Of the 13 146 people tested in Round 2, 1171 people were HBsAg positive, with a prevalence of 8.9%. By comparing the two rounds of screening, the HBV incidence rate of 0.192 per 100 person-years was observed. By consulting electronic medical records, the HBV onset rate of 0.533 per 100 person-years was obtained. We generated a simulated model to replicate the real-world situation for the next two decades. To evaluate the effect of interventions on regional HBV prevalence, three comparative experiments were conducted.
In this study, the regional hepatitis B epidemic in 20 years was predicted and compared with HBV prevalence under different interventions. Owing to the existing challenges in research methodology, this study combined HBV field research and simulation to provide a system dynamics model with close-to-real key data to improve prediction accuracy. The simulation also provided a prompt guidance for the field implementation.
Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression.
A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE.
Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores.
This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.
The finite element simulations show that non-equibiaxial residual stresses (RS) can shift the load–depth curve from the unstressed curve and cause elliptical remnant indentation in spherical indentation. Thus the relative load change between stressed and unstressed samples and the asymmetry of elliptical remnant indentation were employed as characteristic parameters to evaluate the magnitude and directionality of RS. Through theoretical and numerical analysis, the effects of RS on indentation load and remnant impression as well as the affect mechanism were systematically discussed. Finally, two equations which could provide foundations for establishing spherical indentation method to evaluate non-equibiaxial RS were obtained.
Heavy metal contamination in the paddy soils of China is a serious concern because of its health risk through transfer in food chains. A field experiment was conducted in 2014–2015 to investigate the long-term effects of different biochar amendments on cadmium (Cd) and arsenic (As) immobilisation in a contaminated paddy field in southern China. Two types of biochar, a rice-straw-derived biochar (RB) and a coconut-by-product-derived biochar (CB), were amended separately to determine their impacts on rice yield and their efficacy in reducing Cd and As in rice. The two-year field experiment showed that biochar amendments significantly improved the rice yields and that CB is superior to RB, especially in the first growth season. Using a large amount of biochar amendment (22.5tha–1) significantly increased soil pH and total organic carbon, and concomitantly decreased the Cd content in rice grains over the four growth seasons, regardless of biochar type and application rate. Arsenic levels in rice were similar to the control, and results from this study suggest that there was a sustainable effect of biochar on Cd sequestration in soil and reduction of Cd accumulation in rice for at least two years. Biochar amendment in soil could be considered as a sustainable, reliable and cost-effective option to remediate heavy metal contamination in paddy fields for long periods.
The aim of this study was to investigate the in vivo degradation mechanism and the mechanical properties of poly(lactide-co-glycolide)/beta-tricalcium phosphate (PLGA/β-TCP) composite anchors. Anchors composed of PLGA and β-TCP were implanted in the dorsal subcutaneous tissue of beagle dogs for 6, 12, 16, and 26 weeks. The degradation of the materials was evaluated by measuring the changes in thermal behavior, crystallinity, and mechanical properties. Scanning electron microscope (SEM) was used to observe the surface and longitudinal section of the material. The evaluation of mechanical strength retention and degradation properties suggest that the addition of β-TCP particles efficiently enhances their mechanical properties and thermal characteristics and delays their degradation rate. By analyzing the results of SEM, X-ray diffraction, and differential scanning calorimetry, we can infer that after 12 weeks, the connection between β-TCP and PLGA becomes less compact, which accelerates the decline of mechanical strength.