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Background Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health. Methods We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW. Results Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models. Conclusions Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.

The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23–35 in 1990–1991) from the Coronary Artery Risk Development In Young Adults study, based on repeated measurements of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (ACR) from 1995 through 2015. Urinary sodium and potassium excretion (mg/day), calculated from three 24-hour urine collections in 1990–1991, were averaged to measure sodium and potassium intake. Serum creatinine was used to calculate eGFR using the CKD EPI equation; spot urine albumin and creatinine were used to calculate ACR, each at five visits from 1995–1996 through 2015–2016. CKD was defined as decreased eGFR (under 60 ml/min/1.73m(2)) or the development of albuminuria (ACR over 30 mg/g). We used log binomial regression models adjusted for socio-demographic, behavioral, and clinical factors to determine whether sodium and potassium intake were associated with incident CKD (decreased eGFR or developed albuminuria) among those free of CKD in 1995. Dietary sodium intake was not significantly associated with incident CKD. However, every 1,000 mg/day increment of potassium intake in 1990 was significantly associated with a 29% lower risk of incident albuminuria (relative risk 0.71, 95% confidence interval 0.53, 0.95), but not eGFR. Thus, higher dietary potassium intake may protect against the development of kidney damage, particularly albuminuria.

Background Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. Methods We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. Results ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. Conclusions The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.

We performed a meta-analysis of two large independent blood-based Alzheimer’s disease (AD) epigenome-wide association studies, the ADNI and AIBL studies, and identified 5 CpGs, mapped to the SPIDR, CDH6 genes, and intergenic regions, that were significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four additional methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. Our integrative analysis revealed expressions levels of 13 genes and 10 pathways were significantly associated with the AD-associated methylation differences in both brain and blood, many are involved in the immune responses in AD, such as the CD79A, LY86, SP100, CD163, CD200, and MS4A1 genes and the neutrophil degranulation, antigen processing and presentation, interferon signaling pathways. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model included age, sex, cell types and methylation risk score based on prioritized CpGs from cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 - 0.770, P-value = 2.78 × 10−5). Our study provides a valuable resource for future mechanistic and biomarker studies in AD.

Traditional linear active disturbance rejection control (LADRC) may have difficulty to achieve a rapid precise disturbance rejection for a permanent magnet synchronous linear motor (PMSLM). By making use of model information, a model predictive and compensated LADRC (MPLADRC) method is proposed in this paper. In this method, a model compensated extended state observer (MESO) is designed to transform the controlled object into an established mathematical model through total disturbance compensation. Meanwhile, considering the delay problem of MESO, a phase advance module is designed to improve the estimation speed of MESO for system disturbance and state, thus the MESO can rapidly compensate various uncertainty disturbances to the controlled object in real time. The model predictive controller (MPC) is then designed based on the mathematical model, and its optimal control law is then obtained through a quadratic objective function to further suppress the disturbance unobserved by the designed MESO. The proposed method can thus realize a dual-degree-of-freedom disturbance rejection through the MESO and MPC. The simulation and experimental results validate the effectiveness of the proposed MPLADRC in rapid anti-disturbance and fast positioning for the motion control of the PMSLM.

With the improvement of the manufacturing process and packaging technology of the precision electronic manufacturing industry, various precision circuits with large scale and fine features are widely used in high-end precision electronic products and instruments. At present, large-scale circuit substrates can reach very fine pitch and line width in only several micron-meter level. So the quality inspection equipment should have the inspection capabilities of large-scale and high-precision detection. Since a single view of image with high-resolution only have a small field of view, image stitching by registration and fusion is an effective method to inspect the whole large scale substrate. Hence, this paper proposes a micro vision image stitching method with high precision through coarse and fine registration. The real-time position information of the platform is used to calculate the approximate pixel offset between images to achieve coarse registration. Then, two convolutional neural regression networks connected by a spatial transformation network are used to achieve fine registration. A high-precision nano-positioning platform is used to establish image registration dataset, which is used for the training of convolutional neural regression networks. Experimental results show that under the condition of resolution of 0.5um//pixel and stitching overlap of 20%, our method can achieve less than 0.2 pixel registration error and less than 25ms registration time for a single image.

With the continuous improvement of technical indexes of precision electronic packaging equipment, its performance is primarily confirmed by the motion features of the multi-axis motion platform, which plays a key role for the precision packaging equipment. In recent years, the control technologies of multi-axis motion platforms have been rapidly developed to satisfy the demands of high precision and high acceleration. Nevertheless, under the condition of high-speed and large stroke motion, the motion platform usually has very limited positioning accuracy. The positioning accuracy of a multi-axis motion stage has become increasingly prominent for high-end electronic packaging equipment, and will determine their performance. In view of the motion planning, dynamic error compensation, and multi-axis cooperative control involved in the multi-axis motion platform, the research progress on this topic is investigated and described in this paper. The key issues related to the motion platform are summarized and the future development trend is prospected.

Phase-measuring profilometry (PMP) has become one of the most effective means of three-dimensional (3D) shape measurement. Owing to the low robustness of the phase-unwrapping algorithm and the large number of projection patterns, the off-the-shelf PMP methods have a limited speed and accuracy for the measurement of discontinuous objects. To improve the measurement speed and accuracy, a composite color-coding method is presented in this paper. The main idea of the coding is embedding sinusoidal stripes, phase-coding stripes, and Gray code into the red, blue, and green channels of a color pattern, respectively. The Gray code is used for identifying the order of the sub-stair phase, which is quantized into m levels with a stair height of 2 π /m. Each stair corresponds to the 2 π phase-changed period of the sinusoidal fringes. The complexity of the phase unwrapping is low, and the proposed method needs fewer patterns for measurement than conventional methods. The experimental results indicate that the proposed method can achieve more accurate and efficient 3D shape measurement than the traditional phase-coding methods and is suitable for measuring discontinuous objects with complex shapes.

Background and Purpose— It is unclear whether disparities in mortality among stroke survivors exist long term. Therefore, the purpose of the current study is to describe rates of longer term mortality among stroke survivors (ie, beyond 30 days) and to determine whether socioeconomic disparities exist. Methods— This analysis included 1329 black and white participants, aged ≥45 years, enrolled between 2003 and 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) who suffered a first stroke and survived at least 30 days after the event. Long-term mortality among stroke survivors was defined in person-years as time from 30 days after a first stroke to date of death or censoring. Mortality rate ratios (MRRs) were used to compare rates of poststroke mortality by demographic and socioeconomic characteristics. Results— Among adults who survived ≥30 days poststroke, the age-adjusted rate of mortality was 82.3 per 1000 person-years (95% CI, 75.4–89.2). Long-term mortality among stroke survivors was higher in older individuals (MRR for 75+ versus 50k, 1.4; 95% CI, 1.1–1.9), and lower neighborhood socioeconomic status (SES; MRR for low versus high neighborhood SES, 1.4; 95% CI, 1.1–1.7). There were no differences in age-adjusted rates of long-term poststroke mortality by race, rurality, or US region. Conclusions— Rates of long-term mortality among stroke survivors were higher among individuals with lower SES and among those residing in neighborhoods of lower SES. These results emphasize the need for improvements in long-term care poststroke, especially among individuals of lower SES.

Severe acute pancreatitis (SAP) is a condition characterized by highly fatal acute inflammation and is usually associated with multiple organ dysfunction syndrome. Acute lung injury (ALI) is the most common complications of SAP, which is the accelerator of other organ dysfunction caused by SAP and the primary cause of early death due to SAP. Acadesine, an adenosine analog and an AMPK activator, has been discovered to modulate glucose and lipid metabolism, and inhibit the production of pro-inflammatory cytokines and iNOS. However, its role in SAP-ALI and its mechanism remains unclear and need to be explored. Herein, we discovered that acadesine mitigated the generation of reactive oxygen species (ROS) in human pulmonary microvascular endothelial cells (HPMECs), alleviated apoptosis and recovered barrier integrity, thereby contributing to anti-inflammatory effects in vitro and in vivo. Moreover, Nrf2 deficiency partially eliminated the effects of acadesine-induced antioxidant effects and thus weakened the protective effects on cells and Nrf2-knockout (Nrf2

To better understand DNA methylation in Alzheimer's disease (AD) from both mechanistic and biomarker perspectives, we performed an epigenome-wide meta-analysis of blood DNA methylation in two large independent blood-based studies in AD, the ADNI and AIBL studies, and identified 5 CpGs, mapped to the SPIDR, CDH6 genes, and intergenic regions, that are significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four brain methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model includes age, sex, immune cell type proportions, and methylation risk score based on prioritized CpGs in cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 - 0.770, P-value = 2.78 × 10

Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer’s disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation differences in AD neuropathology, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort, we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such as TMEM39A and TNXB that are associated with the AD Braak stage in a sex-specific manner. TMEM39A is known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes. TNXB encodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated genes in AD neuropathology, such as MBP and AZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation differences were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Our study implicated multiple new loci and biological processes that affected AD neuropathology in a sex-specific manner.

Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer’s disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation changes in AD, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such as TMEM39A and TNXB that are associated with AD in a sex-specific manner. TMEM39A is known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes. TNXB encodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated AD genes, such as MBP and AZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation changes were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Importantly, a number of drugs commonly prescribed for AD patients also targeted these genes with sex-specific DNA methylation changes. Our study implicated multiple new loci and biological processes that affected AD in a sex-specific manner and highlighted the importance of sex-specific treatment regimens for AD patients.

Deep eutectic solvents (DESs) is a newly developed green solvent with low cost, easy preparation and regeneration. Because of its excellent solubility and swelling effect in lignocellulose, it has received widespread attention and recognition. In this study, choline-based deep eutectic solvents (DESs)—choline chloride-urea (CC-U), choline chloride-ethylene glycol (CC-EG), choline chloride-glycerol (CC-G), choline chloride-lactic acid (CC-LA), and choline chloride-oxalic acid (CC-OA)—were used to extract and separate bagasse. The effects of hydrogen bond donors on lignin separation and the fiber and lignin structure were investigated. All five DESs could dissolve lignin from bagasse, acidic DESs exhibited higher solubility than basic DESs. CC-OA effectively separated lignin and hemicellulose. CC-LA showed weaker lignin separation ability than CC-OA. CC-G, CC-EG, and CC-U were more inclined to selectively separate lignin than hemicellulose. The crystalline cellulose II structure was retained after DES pretreatment. Acidic DESs effectively improved the crystallinity of bagasse fiber, the crystallinities for CC-OA and CC-LA pretreatment were 62.26% and 61.65%, respectively. The lignin dissolved in DES was mainly syringyl lignin. The lignin dissolved in CC-U, CC-LA, and CC-OA contained a small amount of guaiacyl lignin.

Purpose Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health. Methods We pooled data from the Mexican Health and Aging Study (N = 17,771) and Mexican-born U.S. Health and Retirement Study (N = 898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration. Results Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count = 1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood. Conclusions In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.

Current binary defocus technology mainly focuses on fringe generation suitable for specific frequencies without considering fringe adaptability for defocus-degree variation, which decreases the measuring accuracy for this scenario. To achieve a high-quality measurement, we propose a robust binary fringe generation method to minimize the phase error caused by changes in defocus and the random error in measurement. In the method, we establish a complete phase error model and construct a novel objective function, to the best of our knowledge, to optimize the binarization threshold of each pixel. Through derivation of the threshold gradient calculation formula, we quickly obtain optimal binary fringes that can adapt to different fringe pitches and various degrees of defocus. The experimental results verify that the proposed method can generate robust binary fringes adaptive to different fringe pitches and defocus degree variation, and thus achieve high-quality 3D measurements.

Additional file 1: Supplementary Figures. Figure S1. Quantile-quantile (QQ) plots of observed and expected distributions of P-values in Gasparoni, London, Mount Sinai, and ROSMAP cohorts. Figure S2. Comparison of methylation-Braak stage associations in female samples and male samples. Figure S3. Enrichment of FDR-significant CpGs and CpGs located within FDR-significant DMRs with positive and negative effect estimates in various genomic features and chromatin states. Figure S4. Gene Set Enrichment of the TYROBP causal network with sex-specific Braak-associated DNA methylation differences. Figure S5. Forest plots for several top CpGs identified in sex-stratified analysis and sex-by-Braak stage interaction analysis.

Emerging evidence has demonstrated that several microvesicles (MVs) are secreted in bronchoalveolar lavage fluid (BALF) during the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the impact of alveolar macrophage (AM)-derived MVs on epithelial cells and their in vivo effects on ALI/ARDS require further exploration. In this study, MVs were isolated from BALF of mice or mouse alveolar macrophage (MHS) cells by sequential centrifugation and then delivered to epithelial cells or mice. Enzyme-linked immunosorbent assay revealed that BALF-derived MVs (BALF-MVs) and MHS-derived MVs (AM-MVs) were rich in tumor necrosis factor-α (TNF-α) at the early stage of lung injury. In vitro, both inflammatory BALF-MVs and AM-MVs decreased the expression of α subunit of epithelial sodium channel (α-ENaC), γ-ENaC, and Na+,K+-ATPase α1 and β1 in lung epithelial cells. However, antibodies against TNF-α inhibited the effects of inflammatory AM-MVs in epithelial cells. In vivo, the inflammatory AM-MVs, delivered intratracheally to mice, impaired lung tissues and increased the injury score. They also resulted in decreased alveolar fluid clearance and increased lung wet weight/dry weight ratio. Furthermore, inflammatory AM-MVs downregulated the α-ENaC, γ-ENaC, and Na+,K+-ATPase α1 and β1 levels in lung tissues. According to our results, inflammatory AM-derived MVs may potentially contribute to lung injury and pulmonary edema, thereby indicating a potential novel therapeutic approach against ALI/ARDS based on AM-MVs.

The internal model control (IMC) based PID controller for delayed processes often needs to compromise the set-point tracking response and disturbance response. For the complex second-order delayed unstable process with two unstable poles, there are no simple and effective PID controller tuning rules. In this paper, an IMC-PID control method based on extended state observer (ESO) is proposed. Firstly, in order to reduce the estimation burden of traditional ESO and improve the accuracy of disturbance estimation, a synchronous model ESO (SMESO) is designed. The SMESO considers the information of the nominal model, synchronizes the control input and the system response output in time, thus transforming the delayed process into a perfect model form. Then, through the first-order Taylor expansion and pole-zero cancellation, the parameter tuning rules of IMC-PID controller for the second-order delayed unstable process are derived. Finally, the effectiveness of the proposed method is illustrated by simulation examples.

In the field of microelectronics packaging, microled mass transferring technology has become the key for manufacturing of large-scale display panel, and the defect repair technology is particularly important for the quality control of the display panel. In general, this repair process requires the motion mechanism to reach and replace the defective chip target in a high-speed and high positioning precision for the entire panel. In order to meet the requirements of MicroLED panel repair, this paper introduces an XY parallel decoupling flexible micro-motion platform for the large-stroke macro-micro composite stage. The flexible platform is guided by two pairs of flexible double bridge amplifying mechanisms, which are distributed symmetrically around the moving platform. The mobile pair, which is spliced by S-type hinges, is connected to the moving platform to achieve the performance of decoupling input and output. Based on the micro stage structure, the flexibility and stiffness analysis are performed through static and dynamic modeling of the flexible platform. The particle swarm optimization method is used for size optimization and mechanism modeling. The performance of the micro-motion stage was verified by finite element simulation analysis. The simulation results show that the XY flexible platform proposed in this paper has good parallel decoupling and amplification ratio, and can be used to develop the macro-micro motion stage for defect repair of MicroLED panel.

Iterative closest point algorithms suffer from non-convergence and local minima when dealing with cloud points with a different sampling density. Alternative global or semi-global registration algorithms may suffer from efficiency problem. This paper proposes a new registration algorithm through the differential topological singularity points (DTSP) based on the Helmholtz-Hodge decomposition (HHD), which is called DTSP-ICP method. The DTSP-ICP method contains two algorithms. First, the curvature gradient fields on surfaces are decomposed by the HHD into three orthogonal parts: divergence-free vector field, curl-free vector field, and a harmonic vector field, and then the DTSP algorithm is used to extract the differential topological singularity points in the curl-free vector field. Second, the ICP algorithm is utilized to register the singularity points into one aligned model. The singularity points represent the feature of the whole model, and the DTSP algorithm is designed to capture the nature of the differential topological structure of a mesh model. Through the singularity alignment, the DTSP-ICP method, therefore, possesses better performance in triangular model registration. The experimental results show that independent of sampling schemes, the proposed DTSP-ICP method can maintain convergence and robustness in cases where other alignment algorithms including the ICP alone are unstable. Moreover, this DTSP-ICP method can avoid the local errors of model registration based on Euclidean distance and overcome the computation insufficiencies observed in other global or semi-global registration publications. Finally, we demonstrate the significance of the DTSP-ICP algorithm’s advantages on a variety of challenging models through result comparison with that of two other typical methods.

In microelectronics manufacturing, the macro-micro precision positioning system is often utilized to achieve a high-precision positioning motion with high-velocity and large-stroke. The working efficiency of the stage is affected by the inertial vibration of the macromotion which will cause more time to settle. This paper adopts an active vibration reduction method through a piezoelectric (PZT) device to quickly reduce the designed vibration amplitude of the macro-micro positioning stage. In the paper, we propose a dynamic adaptive vibration reduction strategy to work against the motion of the macro-stage through the PZT to settle the stage with much less time. The start-up condition and extension principle of the piezoelectric element used in the vibration reduction action are designed and finalized. The method can therefore dynamically start up the actuation of the PZT to act on the macromotion at right moment and determine the effect of the vibration reduction through the extension length of the PZT. A dynamic model, a force analysis, and an amplitude reduction analysis are performed to understand the vibration reduction action applied in the macro-micro stage and a dynamic simulation is conducted to examine the effect of the method. The experimental tests are carried out on the stage through the exploration of different extensions and waveform types of the piezoelectric device. The experimental results indicate that the settling time of the macromotion can be greatly reduced with the proposed method without decreasing its positioning accuracy for motion with high velocity and large stroke. This novel method is useful for applications of the electronic manufacturing equipment with high-velocity and high-accuracy requirements.

ObjectiveTo identify preferred neurofilament assays and clinically validate serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) as prognostic and potential pharmacodynamic biomarkers relevant to amyotrophic lateral sclerosis (ALS) therapy development.MethodsIn this prospective, multicenter, longitudinal observational study of patients with ALS (n = 229), primary lateral sclerosis (n = 20), and progressive muscular atrophy (n = 11), biological specimens were collected, processed, and stored according to strict standard operating procedures (SOPs). Neurofilament assays were performed in a blinded manner by independent contract research organizations.ResultsFor serum NfL and pNfH measured using the Simoa assay, there were no missing data (i.e., technical replicates below the lower limit of detection were not encountered). For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples, respectively. Mean coefficients of variation for NfL in serum and CSF were both ∼3%. Mean coefficients of variation for pNfH in serum and CSF were ∼4%–5% and ∼2%–3%, respectively, in all assays. Baseline serum NfL concentration, but not pNfH, predicted the future Revised ALS Functional Rating Scale (ALSFRS-R) slope and survival. Incorporation of baseline serum NfL into mixed effects models of ALSFRS-R slopes yields an estimated sample size saving of ∼8%. Depending on the method used to estimate effect size, use of serum NfL (and perhaps pNfH) as pharmacodynamic biomarkers, instead of the ALSFRS-R slope, yields significantly larger sample size savings.ConclusionsSerum NfL may be considered a clinically validated prognostic biomarker for ALS. Serum NfL (and perhaps pNfH), quantified using the Simoa assay, has potential utility as a pharmacodynamic biomarker of treatment effect.

This paper proposes a type of straight-beam three-quater round type (STR) flexure hinge for a micro-actuation motion stage in the field of precision micro-operation manufacturing. Based on the hinge, a three degree-of-freedom precision parallel micro-motion stage is designed. Firstly, the rigid and flexure structural design of the STR flexure hinge is presented, and theoretical analysis and simulation performance verification are carried out. Based on the elastic statics and calculus theory, the flexibility expression of the flexure hinge is derived under different stresses. The flexibility of the hinge is verified by ANSYS software. The results show that the designed flexure hinge can effectively achieve complaisant deflection and rigid support with high stress. Moreover, a XθYθZ micro-motion stage based on the STR hinge is established, and the dynamic performance of the stage is simulated and verified by Matlab/Simulink. Finally, the experimental stage is set up. The experimental results are compared with the simulation results, and the stage can achieve about 3.7 times micro-actuation amplification ratio and 68 μm displacement stroke.

ObjectiveIdentify preferred neurofilament assays, and clinically validate serum NfL and pNfH as prognostic and potential pharmacodynamic biomarkers relevant to ALS therapy development.MethodsProspective, multi-center, longitudinal observational study of patients with ALS (n=229), primary lateral sclerosis (PLS, n=20) and progressive muscular atrophy (PMA, n=11). Biological specimens were collected, processed and stored according to strict standard operating procedures (SOPs) 1. Neurofilament assays were performed in a blinded manner by independent contract research organizations (CROs).ResultsFor serum NfL and pNfH measured using the Simoa assay, missing data (i.e. both technical replicates below the lower limit of detection (LLD) was not encountered. For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples respectively. Mean coefficients of variation (CVs) for pNfH in serum and CSF were ∼4-5% and ∼2-3% respectively in all assays. Baseline NfL concentration, but not pNfH, predicted the future ALSFRS-R slope and survival.Incorporation of baseline serum NfL into mixed effects models of ALSFRS-R slopes yields an estimated sample size saving of ∼8%. Depending on the method used to estimate effect size, use of serum NfL (and perhaps pNfH) as pharmacodynamic biomarkers, instead of the ALSFRS-R slope, yields significantly larger sample size savings.ConclusionsSerum NfL may be considered a clinically validated prognostic biomarker for ALS. Serum NfL (and perhaps pNfH), quantified using the Simoa assay, have potential utility as pharmacodynamic biomarkers of treatment effect.

In the controller design of high-order nonlinear systems, it is beneficial to possess high-order differential information of input and output signals. In this paper, an N-order differentiator (NOD) method is proposed and designed to obtain the differential information of each order of the reference signal, which is based on the idea of a control loop and only needs to adjust one parameter. Then two high-order active disturbance rejection control (ADRC) structures are designed for the control of high-order nonlinear systems. One is ADRC with high-order observer (NOD-HOADRC) that directly designs the high-order extended state observer (HOESO), and the other is ADRC with cascade observes (NOD-SOADRC) that designs several extended state observers in series (SOESO). Numerical simulations verify the effectiveness of the two control structures. The simulation results show that the NOD-HOADRC can achieve no static difference control, and the dynamic performance is obviously stronger than the PID controller. The NOD-SOADRC has extremely strong tracking performance and anti-interference ability by widening the observer bandwidth.

BACKGROUND AND PURPOSE: It is unclear whether disparities in mortality among stroke survivors exist long-term. Therefore, the purpose of the current study is to describe rates of longer term mortality among stroke survivors (i.e. beyond 30 days) and to determine whether socioeconomic disparities exist. METHODS: This analysis included 1,329 black and white participants, ages 45 and older, enrolled between 2003–2007 in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who suffered a first stroke and survived at least 30 days following the event. Long-term mortality among stroke survivors was defined in person-years as time from 30 days after a first stroke to date of death or censoring. Mortality rate ratios (MRRs) were used to compare rates of post-stroke mortality by demographic and socioeconomic characteristics. RESULTS: Among adults who survived ≥ 30 days post stroke, the age-adjusted rate of mortality was 82.3 per 1,000 person-years (95% CI: 75.4, 89.2). Long-term mortality among stroke survivors was higher in older individuals (MRR for 75+ vs. < 65: 3.2, 95% CI: 2.6, 4.1) and among men than women (MRR: 1.3, 95% CI: 1.1, 1.6). It was also higher among those with less educational attainment (MRR for < high school vs. college graduate: 1.5, 95% CI: 1.1, 1.9), lower income (MRR for < $20k vs. > 50K: 1.4, 95% CI: 1.1, 1.9), and lower neighborhood SES (MRR for low vs. high neighborhood SES: 1.4, 95% CI: 1.1, 1.7). There were no differences in age-adjusted rates of long-term post-stroke mortality by race, rurality, or US region. CONCLUSIONS: Rates of long-term mortality among stroke survivors were higher among individuals with lower socioeconomic status (SES) and among those residing in neighborhoods of lower SES. These results emphasize the need for improvements in long term care post-stroke, especially among individuals of lower SES.

The measurement accuracy of high-speed binary defocusing fringe projection profilometry depends on the fringe pitch and defocus degree. During the measurement process, the degree of defocus changes with the measurement depth of the scenes. This makes it difficult to obtain a suitable defocus degree and achieve high-precision measurement owing to dynamic changes in the measurement object or environment. To address this problem, we propose a highly dynamic defocus response method to adaptively adjust fringe pitches for binary defocusing fringe projection profilometry. As the defocus degree changes significantly, the proposed method can respond quickly and adjust the fringe pitches adaptively to the scenes. Therefore, a high-precision dynamic measurement can be achieved for the current measuring scene. In this study, considering the effect of random error and nonlinear error, we established a complete phase-error model and used it as an optimization function. Based on this function, we obtained the optimal fringe pitch expression with the defocus degree and harmonic response parameters as variables. With the proposed method, we can obtain the defocus degree and harmonic response parameters during the measurement process and calculate the optimal fringe pitches for the current scenes. Thus, the proposed method can dynamically adapt to the measuring depth change and achieve an accurate measurement without modifying any hardware parameters.

China is currently in a complex period of “three-phase superposition”. Under the new normal of the economy Financial deleveraging has achieved certain results. However, the non-performing loan ratio of commercial banks has shown a continuous upward trend since 2015. The empirical results show that the degree of internalization of commercial banks, credit balances, and gross domestic product have a negative impact on the NPL ratio, and the cost-to-income ratio and leverage ratio have a positive impact on the NPL ratio. Therefore, commercial banks should vigorously develop digital technology, expand the scale of credit, use technological advantages to reduce costs, establish an appropriate level of leverage, and effectively reduce the non-performing loan ratio to improve the asset quality of commercial banks.

A macro–micro composite precision positioning stage is mainly used in microelectronics manufacturing to achieve high velocity, high precision, and large-stroke positioning. The positioning accuracy and working efficiency of the stage are influenced by the inertial vibration caused by motion with high acceleration. This paper proposes an active vibration reduction (AVR) method employing a piezoelectric device for a designed macro–micro motion stage. The design model of the stage is established and its dynamic models are explored. The feasibility of the piezoelectric device as a vibration damper for the designed positioning stage is demonstrated through theoretical analyses, including natural frequency analysis and inertial vibration energy analysis. Furthermore, an optimal design of the stage with the AVR mechanism is established and then verified experimentally. The performance of the AVR method is examined and characterized through investigation of the differences in inertial vibration energy with and without the AVR, and the performance of the proposed method in terms of the vibration amplitude and positioning time is measured at different accelerations, velocities, and strokes. The theoretical and experimental analyses indicate the effectiveness of the proposed vibration reduction method, and this method could be employed in several applications that require vibration reduction.

Phase-shifting profilometry (PSP) is an efficient three-dimensional (3D) measurement technique. The accuracy of the PSP based 3D measurement system is generally affected by the nonlinear intensity response of the projector. In general, nonlinear errors can be reduced by projecting more fringe patterns, but this approach significantly increases the measuring time. To improve the measurement accuracy and speed, a new composite sine-trapezoidal phase-shifting profilometry technique that suppresses nonlinear error is proposed in this study. The main idea of the proposed method is projecting a set of sinusoidal fringe patterns and two sets of composite sine-trapezoidal fringe patterns with different intensity ranges in sequence. Among these patterns, the sinusoidal fringe is used to encode the pixel position, and the order of the wrapping phase is determined by the region code of the composite fringe. The flat intensity parts of the composite fringe are used to encode the nonlinear intensity response of the measurement system. Through system identification, the response parameters of the pixels can be obtained, and the gray value of the pixels can be corrected to gain a better phase distribution. Compared to the straight edges of the trapezoidal fringe, the sinusoidal edges of the composite fringe are more robust to the projector defocus, which improves the accuracy of the identification of the system intensity response model. Simulation results show that the proposed method can achieve a higher phase retrieval accuracy than the trapezoidal PSP and the sine PSP. The experiment results indicate that the proposed method has a better measurement accuracy than those of the standard 3-step and 4-step sine PSP methods.

In recent years, we have seen more and more interest in the field of medical images and shape comparison motivated by the latest advances in microcomputed tomography (μCT) acquisition, modelling, and visualization technologies. Usually, biologists need to evaluate the effect of different root canal preparation systems. Current root canal preparation evaluation methods are based on the volume difference, area difference, and transportation of two root canals before and after treatment. The purpose of root canal preparation is to minimize the volume difference and ensure the complete removal of the smear layer. Previous methods can reflect some general geometric differences, but they are not enough to evaluate the quality of root canal shape. To solve this problem, we proposed a novel root canal evaluation method based on spectrum and eigenfunctions of Steklov operators, which can be served as a better alternative to current methods in root canal preparation evaluation. Firstly, the ideal root canal model was simulated according to the root canal model before and after preparation. Secondly, the Steklov spectrum of the two models was calculated. Thirdly, based on the spectrum and the histogram of the Gaussian curvature on the surface, the weight of each eigenvalue was computed. Therefore, the Steklov spectrum distance (SSD), which measures shape difference between the root canals, was defined. Finally, the calculation method that quantifies the root canal preparation effect of root canals was obtained. Through experiments, our method manifested high robustness and accuracy compared with existing state-of-the-art approaches. It also demonstrates the significance of our algorithm’s advantages on a variety of challenging root canals through result comparison with counterpart methods.

Neuroinflammation induced by protruded nucleus pulposus (NP) has been shown to play a significant role in facilitation of radicular pain. Resolvin D2 (RvD2), a novel member of resolvin family, exhibits potent anti-inflammatory, pro-resolving and antinociceptive effects. But the effect of RvD2 in radicular pain remains unknown. The radicular pain rat models were induced by application of NP to L5 dorsal root ganglion. Each animal received intrathecal injections of vehicle or RvD2 (10 ng µl−1 or 100 ng µl−1). Mechanical thresholds were determined by measuring the paw withdrawal threshold for 7 days. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) in ipsilateral lumbar segment of rat spinal dorsal horns were measured by using ELISA and real time-PCR. Western blot was used to measure the expressions of phosphorylated Akt (p-Akt) and phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β). The expressions and distributions of RvD2 receptor, G-protein-coupled receptor 18 (GPR18), were also explored in the spinal cord of rats by using double-label immunofluorescence. RvD2 treatment caused significant reductions in the intensity of mechanical hypersensitivity and spinal expressions of TNF-α and IL-6. Meanwhile, RvD2 increased the expressions of TGF-β1 and regulated Akt/GSK-3β signaling. Furthermore, immunofluorescence showed that GPR18 colocalized with neurons and astrocytes in spinal cord. The results suggested that RvD2 might attenuate mechanical allodynia via regulating the expressions of inflammatory mediators and activation of Akt/GSK-3β signal pathway. RvD2 might offer a hopeful method for radicular pain therapy.

White-light scanning interferometry (WLSI) is an important measurement technique that has been widely used in three-dimensional profile reconstruction. Because of the effects of environmental noise and phase changes caused by surface reflection, existing WLSI algorithms have problems in measurement accuracy and measurement speed. Addressing these problems, this paper proposes a fast template matching method to determine precisely the zero optical path difference (ZOPD) position in the WLSI. Due to the uniform shape of the interference signals, a template interference signal can be obtained in advance by performing a least-square fitting or Fourier interpolation on an interference signal of one pixel. In the method, the ZOPD position is initially obtained by the centroid method. Then, the ZOPD position is determined by a precise matching process through moving the template interference signal on the measured interference signal. Through the two-step processes, the ZOPD position can be obtained precisely with much less time. The method was simulated and verified through the measurement of a spherical surface, a 1.8-µm-height standard step and a flip-chip substrate. The experimental results show that the proposed algorithm can achieve both high precision and fast measurement.

This paper is a thorough study into the design and construction of office automation and its application in Android system, and it also puts forward a solution for the system challenges that exist in the market currently, in an effort to improve the existing OA system, to enable it to function better and to provide better service for modernization construction. Preface By OA system it means to fulfil automated and paperless office work through advanced technology. Its birth has brought about a brand new way of working for enterprises and public institutions and soon become an indispensible part of these organizations. Although the OA technology is well developed now, there are still quite a lot of defects in it. The traditional OA system has many restrictions on the facilities and locations of the office, which to a great extent restricts the freedom of those people that work out of the office, and the system development and upgrade are a great burden for small and medium sized firms. However, with the fast growth of cloud computing technology and smart phone, cloud OA and mobile OA come into shape which bring about sound solutions to the abovementioned problems. Focusing on these problems, this paper integrates the above 2 features and designs a mobile computing OA system.

Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidencein vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

Arterial coordinate control plays a major role in urban traffic, the actual influencing factors determine the design and application of coordinated control. This paper studies the various factors that affect the design of the signal timing for arterial coordinated control system. The paper summarizes and theoretically analyzes these influencing factors , and uses the existing rules of the traffic delay to analyze the delay, then constructs the simulation platform by TransModeler software to perform a lot of experiment in various scenarios to study the main factors. Finally the study of analysis and compare demonstrates the simulation result is more valuable than theories in the practical application of arterial coordinate control, and draws the conclusions which could help to design the signal timing arterial coordinated control system and estimate the quality of urban arterial road.