Force and deformation characteristics during the reconstruction and expansion of shallow single-tube tunnels into large-span multiarch tunnels

At present, there are an ever-increasing number of tunnel expansion projects in China. Studying the mechanical properties of the expanded tunnels is of great significance for guiding their safe construction. Through model testing and numerical simulation, the mechanical properties of a double-arch tunnel constructed through the expansion of the middle pilot heading from an existing single-tube tunnel were studied. The variation characteristics of the surface subsidence, surrounding rock stress, and stress and strain of the middle partition wall and lining during the tunnel reconstruction and expansion were investigated. The mechanism for transferring stress and strain between the left and right tunnel tubes was studied by a numerical simulation method. The results showed that the surface subsidence caused by the excavation of the left (i.e., the subsequent) tunnel tube was larger, and the maximum surface subsidence occurred at the right (i.e., the first) tunnel tube. The surrounding rock on the middle wall was the sensitive part of the tunnel excavation, the stress of the surrounding rock at the left spandrel of the right tunnel tube fluctuated and exhibited the most complex variation, and the stress of the surrounding rock at the right spandrel of the left tunnel tube exhibited the largest variation. The excavation of the left tunnel tube had a great influence on the forces of the middle partition wall and the lining structure of the right tunnel tube, the middle partition wall was subjected to eccentric compression towards the left tunnel tube, and the stress at the left spandrel under the initial support of the right tunnel tube exhibited complex variations. The excavation of the left and right tunnel tubes had a great influence on the stability of the surrounding rock, as well as on the force-induced deformation of the middle partition wall and the support structure, within the width of the single tunnel tube span behind the tunnel working face. Due to the different construction sequences, the stress and strain at the symmetric measurement points of the middle partition wall, as well as the left and right tunnel support structures, were very different

Patterns of MicroRNA Expression in Normal and Early Alzheimer\u27s Disease Human Temporal Cortex: White Matter versus Gray Matter

MicroRNA (miRNA) expression was assessed in human cerebral cortical gray matter (GM) and white matter (WM) in order to provide the first insights into the difference between GM and WM miRNA repertoires across a range of Alzheimer\u27s disease (AD) pathology. RNA was isolated separately from GM and WM portions of superior and middle temporal cerebral cortex (N = 10 elderly females, postmortem interval \u3c 4 h). miRNA profiling experiments were performed using state-of-the-art Exiqon© LNA-microarrays. A subset of miRNAs that appeared to be strongly expressed according to the microarrays did not appear to be conventional miRNAs according to Northern blot analyses. Some well-characterized miRNAs were substantially enriched in WM as expected. However, most of the miRNA expression variability that correlated with the presence of early AD-related pathology was seen in GM. We confirm that downregulation of a set of miRNAs in GM (including several miR-15/107 genes and miR-29 paralogs) correlated strongly with the density of diffuse amyloid plaques detected in adjacent tissue. A few miRNAs were differentially expressed in WM, including miR-212 that is downregulated in AD and miR-424 which is upregulated in AD. The expression of certain miRNAs correlates with other miRNAs across different cases, and particular subsets of miRNAs are coordinately expressed in relation to AD-related pathology. These data support the hypothesis that patterns of miRNA expression in cortical GM may contribute to AD pathogenetically, because the aggregate change in miRNA expression observed early in the disease would be predicted to cause profound changes in gene expression

Postoperative anatomical and functional outcomes of different stages of high myopia macular hole

Background Recently it was suggested that high myopia macular holes (HMMH) and macular holes accompanied by retinal detachment occur in the advanced stages of myopia traction maculopathy (MTM), while macular retinoschisis, shallow retinal detachment without holes, and lamellar macular holes occur in the early stages of MTM. Complete vitreous cortex removal associated with internal limiting membrane peeling is now widely used to treat HMMH. However, it remains uncertain at what HMMH stage patients would benefit most from surgical intervention. Our study was aimed to evaluate the postoperative anatomical changes and functional outcomes of high myopia macular holes (HMMH). Methods Patients were retrospectively collected between March 2009 and August 2011. Before and 1st, 3rd, and 9th month after 23G pars plana vitrectomy, all patients underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT) and MP-1. At each follow-up, best- corrected visual acuity (BCVA), photoreceptor inner and outer segments (IS/OS) defects, and retinal sensitivity (RS) were investigated. According to different preoperative macular hole morphologies, patients were divided into three groups: Group 1, macular hole with epiretinal membrane (ERM) traction and macular retinoschisis; Group 2, full-thickness macular hole (FTMH); Group 3, FTMH with subretinal fluid. Results 43 eyes from 43 patients met the inclusion criteria. The mean age was 60 years. BCVA and RS were significantly improved after vitrectomy; the mean IS/OS defect was significantly reduced. At 9 postoperative months, 11 of 43 (25.6 %) eyes achieved IS/OS junction integrity; 9 of these 11 (81.8 %) eyes belonged to Group 1, 2 (18.2 %) belonged to Group 2. Conclusions Pars plana vitrectomy combined with ILM peeling and gas tamponade results in limited functional outcomes in patients with HMMH. The appearance of subretinal fluid indicates a worse prognosis for surgical intervention

Anti-Argonaute RIP-Chip Shows that miRNA Transfections Alter Global Patterns of mRNA Recruitment to Microribonucleoprotein Complexes

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the RIP-Chip assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify miRNA targets. As expected, the miRNA transfections altered the mRNA content of the miRNPs. Specific mRNA species recruited to miRNPs after miRNA transfections were moderately in agreement with computational target predictions. In addition to recruiting mRNA targets into miRNPs, miR-107 and to a lesser extent miR-128, but not miR-124 or miR-320, caused apparent exclusion of some mRNAs that are normally associated with miRNPs. MiR-107 and miR-128 transfections also result in decreased AGO mRNA and protein levels. However, AGO mRNAs were not recruited to miRNPs after either miR-107 or miR-128 transfection, confirming that miRNAs may alter gene expression without stable association between particular mRNAs and miRNPs. In summary, RIP-Chip assays constitute an optimized, validated, direct, and high-throughput biochemical assay that provides data about specific miRNA:mRNA interactions, as well as global patterns of regulation by miRNAs

Model-free adaptive iterative learning control of melt pool width in wire arc additive manufacturing

© 2020, Springer-Verlag London Ltd., part of Springer Nature. Wire arc additive manufacturing (WAAM) is a Direct Energy Deposition (DED) technology, which utilize electrical arc as heat source to deposit metal material bead by bead to make up the final component. However, issues like the lack of assurance in accuracy, repeatability and stability hinder the further application in industry. Therefore, a Model Free Adaptive Iterative Learning Control (MFAILC) algorithm was developed to be applied in WAAM process in this study. The dynamic process of WAAM is modelled by adaptive neuro fuzzy inference system (ANFIS). Based on this ANFIS model, simulations are performed to demonstrate the effectiveness of MFAILC algorithm. Furthermore, experiments are conducted to investigate the tracking performance and robustness of the MFAILC controller. This work will help to improve the forming accuracy and automatic level of WAAM

DUAL EFFECTS OF BILIRUBIN ON THE PROLIFERATION OF RAT RENAL NRK52E CELLS AND ITS ASSOCIATION WITH GAP JUNCTIONS

Objective: The effect of bilirubin on renal pathophysiology is controversial. This study aimed to observe the effects of bilirubin on the proliferation of normal rat renal tubular epithelial cell line (NRK52E) and its potential interplay with gap junction function. Methods: Cultured NRK52E cells, seeded respectively at high- or low- densities, were treated with varying concentrations of bilirubin for 24 hours. Cell injury was assessed by measuring cell viability and proliferation, and gap junction function was assessed by Parachute dye-coupling assay. Connexin 43 protein was assessed by Western blotting. Results: At doses from 17.1 to 513μmol/L, bilirubin dose-dependently enhanced cell viability and colony-formation rates when cells were seeded at either high- or low- densities (all p\u3c0.05 vs. solvent group) accompanied with enhanced intercellular fluorescence transmission and increased Cx43 protein expression in high-density cells. However, the above effects of BR were gradually reversed when its concentration increased from 684 to 1026μmol/L. In high-density cells, gap junction inhibitor 12-O-tetradecanoylphorbol 13- acetate attenuated bilirubin-induced enhancement of colony-formation and fluorescence transmission. However, in the presence of high concentration bilirubin (1026μmol/L), activation of gap junction with retinoid acid decreased colony-formation rates. Conclusion: Bilirubin can confer biphasic effects on renal NRK52E cell proliferation potentially by differentially affecting gap junction functions

Individual MicroRNAs (miRNAs) Display Distinct mRNA Targeting Rules

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3\u27UTR of mRNAs,guided by the 5\u27 seed portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using an assay we validated previously-a RIP-Chip experimental design. RIP-Chip data provided a list of mRNAs recruited into the AGO-miRNP in correlation to each miRNA. These experimentally identified miRNA targets were analyzed for complementary six nucleotide seed sequences within the transfected miRNAs. We found that miR-124 targets tended to have sequences in the 3\u27UTR that would be recognized by the 5\u27 seed of miR-124, as described in previous studies. By contrast, miR-107 targets tended to have \u27seed\u27 sequences in the mRNA open reading frame, but not the 3\u27 UTR. Further, mRNA targets of miR-128 and miR-320 are less enriched for 6-mer seed sequences in comparison to miR-107 and miR-124. In sum, our data support the importance of the 5\u27 seed in determining binding characteristics for some miRNAs; however, the binding rules are complex, and individual miRNAs can have distinct sequence determinants that lead to mRNA targeting

The atomization current and droplet size of ethanol in two different small-scale electro-spraying systems

An experimental study on electro-spraying from small-scale combustors is carried out using liquid ethanol as fuel. Two systems of electro-spraying are employed in the present study; one is a nozzle system (without a ring electrode) and the other is a nozzle-ring system (with a ring electrode). The photos of electro-spraying at the cone-jet mode are taken by a digital camera. The voltage drop across the resistance in the loop is measured by a data acquisition instrument, and the atomization current is calculated according to Ohm's Law. The size and velocity of electro-spraying droplets are measured by a Phase Doppler Anemometer. A non-dimensional analysis on atomization current is completed to explain the electro-spraying phenomena of liquid at the stable cone-jet mode. The results show that, the lower atomization current and droplet velocity corresponds to smaller size of droplet. Based on the results of non-dimensional analysis, it is found that the dimensionless atomization current in both the nozzle system and nozzle-ring system obeys the scaling law as square root of the dimensionless flow rate. The charge density is of a −1.5 power dependence on droplet diameter. Both of the nozzle and the nozzle-ring systems show a good agreement with Rayleigh instability

Nevirapine Plasma Concentrations Are Associated with Virologic Response and Hepatotoxicity in Chinese Patients with HIV Infection

BACKGROUND: Limited information is available on the relationship between nevirapine plasma concentrations and virologic response or liver toxicity in Chinese patients with HIV infection. The objective of this prospective study was to test this relationship and to determine the minimal therapeutic trough concentration of nevirapine for Chinese patients. METHODS: A total of 227 HIV-infected, treatment naïve patients were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) and C(2) (2 hr postdose) for measurement of nevirapine concentrations 6 months after treatment initiation. Therapeutic outcomes, viral load and CD4 cell count, were assessed at 3 and 6 months after starting therapy, while the evaluation of hepatotoxicity was undertaken 12 months after nevirapine treatment. RESULTS: A significant correlation between nevirapine trough concentrations and viral load was noticed after 6 months of treatment, particularly in patients with partial response and viral failure (p<0.01). The therapeutic C(trough) of nevirapine for Chinese patients was determined to be 3.9 µg/ml using the receiver operating characteristic curve. Virologic failure was observed in 21% (6/29) of patients with low nevirapine concentrations (<3.9 µg/ml) versus 5% (4/87) in patients with concentrations higher than 3.9 µg/ml (p = 0.015). Hepatotoxicity was significantly associated with the median nevirapine trough concentrations among male patients (8.20 vs. 5.48 µg/ml, p = 0.015) and hepatitis C virus co-infection (p = 0.039). CONCLUSIONS: Among Chinese patients with HIV infection, the therapeutic C(trough) of nevirapine was 3.9 µg/ml, higher than the recommended 3.0 µg/ml. The correlation between nevirapine concentrations, efficacy and hepatotoxicity suggests the benefit of dosage adjustment based on therapeutic drug monitoring among Chinese HIV-infected patients to optimize nevirapine containing antiretroviral therapy

Associations between social and intellectual activities with cognitive trajectories in Chinese middle-aged and older adults: A nationally representative cohort study

BACKGROUND: Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 years from 2011 to 2016. Cognitive aging trajectories over time were analyzed using group-based trajectory modeling, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were reported. RESULTS: Among 8204 participants aged 50-75 years at baseline, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: persistently low trajectory (n = 1550, 18.9%), persistently moderate trajectory (n = 3194, 38.9%), and persistently high trajectory (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms, and health conditions, more frequent intellectual activities (OR 0.54, 95% CI 0.38-0.77) and social activities (OR 0.79, 95% CI 0.65-0.95) were both associated with a lower likelihood of being in the persistently low trajectory for global cognitive function. CONCLUSIONS: These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories