The Effect of Phonomyography Prototype for Intraoperative Neuromuscular Monitoring: A Preliminary Study.

Quantitative neuromuscular monitoring, as extolled by clinical guidelines, is advocated to circumvent the complications associated with neuromuscular blockers (NMBs), such as residual neuromuscular block (rNMB). Nonetheless, the worldwide utilization of such methods remains undesirable. Phonomyography (PMG) boasts the advantages of convenience, stability, and multi-muscle recording which may be a promising monitoring method. The purpose of this preliminary study is conducting a feasibility analysis and an effectiveness evaluation of a PMG prototype under general anesthesia. A prospective observational preliminary study was conducted. Twenty-five adults who had undergone none-cardiac elective surgery were enrolled. The PMG prototype and TOF-Watch SX simultaneously recorded the pharmacodynamic properties of single bolus rocuronium at the ipsilateral adductor pollicis for each patient. For the primary outcome, the time duration to 0.9 TOF ratio of the two devices reached no statistical significance (p > 0.05). For secondary outcomes, the multi-temporal neuromuscular-monitoring measurements between the two devices also reached no statistical significance (p > 0.05). What is more, both the Spearman's and Pearson's correlation tests revealed a strong correlation across all monitoring periods between the PMG prototype and TOF-Watch SX. Additionally, Bland-Altman plots demonstrated a good agreement between the two devices. Thus, the PMG prototype was a feasible, secure, and effective neuromuscular-monitoring technique during general anesthesia and was interchangeable with TOF-Watch SX.

Hand Grasp Pose Prediction Based on Motion Prior Field.

Shared control of bionic robot hands has recently attracted much research attention. However, few studies have performed predictive analysis for grasp pose, which is vital for the pre-shape planning of robotic wrists and hands. Aiming at shared control of dexterous hand grasp planning, this paper proposes a framework for grasp pose prediction based on the motion prior field. To map the hand-object pose to the final grasp pose, an object-centered motion prior field is established to learn the prediction model. The results of motion capture reconstruction show that, with the input of a 7-dimensional pose and cluster manifolds of dimension 100, the model performs best in terms of prediction accuracy (90.2%) and error distance (1.27 cm) in the sequence. The model makes correct predictions in the first 50% of the sequence during hand approach to the object. The outcomes of this study enable prediction of the grasp pose in advance as the hand approaches the object, which is very important for enabling the shared control of bionic and prosthetic hands.

Bolt-Loosening Detection Using 1D and 2D Input Data Based on Two-Stream Convolutional Neural Networks.

At present, the detection accuracy of bolt-loosening diagnoses is still not high. In order to improve the detection accuracy, this paper proposes a fault diagnosis model based on the TSCNN model, which can simultaneously extract fault features from vibration signals and time-frequency images and can precisely detect the bolt-loosening states. In this paper, the LeNet-5 network is improved by adjusting the size and number of the convolution kernels, introducing the dropout operation, and building a two-dimensional convolutional neural network (2DCNN) model. Combining the advantages of a one-dimensional convolutional neural network (1DCNN) with wide first-layer kernels to suppress high-frequency noise, a two-stream convolutional neural network (TSCNN) is proposed based on 1D and 2D input data. The proposed model uses raw vibration signals and time-frequency images as input and automatically extracts sensitive features and representative information. Finally, the effectiveness and superiority of the proposed approach are verified by practical experiments that are carried out on a machine tool guideway. The experimental results show that the proposed approach can effectively achieve end-to-end bolt-loosening fault diagnoses, with an average recognition accuracy of 99.58%. In addition, the method can easily achieve over 93% accuracy when the SNR is over 0 dB without any denoising preprocessing. The results show that the proposed approach not only achieves high classification accuracy but also has good noise immunity.

Geopolymer bricks prepared by MSWI fly ash and other solid wastes: Moulding pressure and curing method optimisation.

The preparation of geopolymer from alkaline solid waste instead of strong alkali presents the disadvantage of low early strength. However, improving the early mechanical properties of the geopolymer to meet the engineering requirements is challenging. In this paper, the effects of different moulding pressures and curing methods on the properties of red mud-ground granulated blast furnace slag activated by municipal solid waste incineration fly ash (MSWIFA)-carbide slag (CRMG) were studied and evaluated in terms of compressive strength and XRD, FTIR, SEM, and MIP techniques analysis. The results showed that the moulding pressure of 30 MPa could increase the compressive strength at 3 d by 182% and decrease the porosity from 30.28% to 27.38%. These results are attributable to the fact that the moulding pressure causes the particles to be tightly bound and promotes the geopolymerisation reaction. High-temperature (HT) curing could accelerate the hydration reaction and increase the compressive strength at 3 d by 133.7% and 141.6% compared with those obtained by water curing (WC) and room-temperature (RT) curing, respectively. Microscopic analyses showed that HT curing can promote the generation of C-(A)-S-H gel, geopolymer gel and hydrate calcium chloroaluminate (HCC), fill the pores, and increase the structure's compactness. Finally, the proposed method was verified by synthesising geopolymer pavement bricks (GPB), and the compressive strength at 3 d was found to reach 54 MPa under an optimal curing method (moulding pressure of 30 MPa, 90 °C for 12 h). Compared with concrete pavement bricks, GPB presents broad application prospects for saving economic costs and protecting the environment. The results provide a theoretical basis and technical support for the application of CRMG in rapid demoulding projects such as unfired bricks.

Exposures to temperature beyond threshold disproportionately reduce vegetation growth in the northern hemisphere.

In recent decades, terrestrial vegetation in the northern hemisphere (NH) has been exposed to warming and more extremely high temperatures. However, the consequences of these changes for terrestrial vegetation growth remain poorly quantified and understood. By examining a satellite-based vegetation index, tree-ring measurements and land-surface model simulations, we discovered a consistent convex pattern in the responses of vegetation growth to temperature exposure (TE) for forest, shrub and grass in both the temperate (30°-50° N) and boreal (50°-70° N) NH during the period of 1982-2012. The response of vegetation growth to TE for the three vegetation types in both the temperate and boreal NH increased convergently with increasing temperature, until vegetation type-dependent temperature thresholds were reached. A TE beyond these temperature thresholds resulted in disproportionately weak positive or even strong negative responses. Vegetation growth in the boreal NH was more vulnerable to extremely high-temperature events than vegetation growth in the temporal NH. The non-linear responses discovered here provide new insights into the dynamics of northern terrestrial ecosystems in a warmer world.

Uneven winter snow influence on tree growth across temperate China.

Winter snow is an important driver of tree growth in regions where growing-season precipitation is limited. However, observational evidence of this influence at larger spatial scales and across diverse bioclimatic regions is lacking. Here, we investigated the interannual effects of winter (here defined as previous October to current February) snow depth on tree growth across temperate China over the period of 1961-2015, using a regional network of tree ring records, in situ daily snow depth observations, and gridded climate data. We report uneven effects of winter snow depth on subsequent growing-season tree growth across temperate China. There shows little effect on tree growth in drier regions that we attribute mainly to limited snow accumulation during winter. By contrast, winter snow exerts important positive influence on tree growth in stands with high winter snow accumulation (e.g., in parts of cold arid regions). The magnitude of this effect depends on the proportion of winter snow to pre-growing-season (previous October to current April) precipitation. We further observed that tree growth in drier regions tends to be increasingly limited by warmer growing-season temperature and early growing-season water availability. No compensatory effect of winter snow on the intensifying drought limitation of tree growth was observed across temperate China. Our findings point toward an increase in drought vulnerability of temperate forests in a warming climate.

Prediction of finger kinematics from discharge timings of motor units: implications for intuitive control of myoelectric prostheses.

OBJECTIVE: The aim of the study was to characterize the accuracy in the identification of motor unit discharges during natural movements using high-density electromyography (EMG) signals and to investigate their correlation with finger kinematics. APPROACH: High-density EMG signals of forearm muscles and finger joint angles were recorded concurrently during hand movements of ten able-bodied subjects. EMG signals were decomposed into motor unit spike trains (MUSTs) with a blind-source separation method. The first principle component (FPC) of the low-pass filtered MUST was correlated with finger joint angles. MAIN RESULTS: On average, [Formula: see text] motor units were identified during each individual finger task with an estimated decomposition accuracy [Formula: see text]85%. The FPC extracted from discharge rates was strongly associated to the joint angles ([Formula: see text]), and preceded the joint angles on average by [Formula: see text] ms. Moreover, the FPC outperformed two time-domain features (the EMG envelop and the root mean square of EMG) in estimating joint angles. SIGNIFICANCE: These results indicated the possibility of identifying individual motor unit behavior in dynamic natural contractions. Moreover, the strong association between motor unit discharge behaviors and kinematics proves the potential of the approach for the simultaneous and proportional control of prostheses.

GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

BACKGROUND: Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. METHODS: Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi. RESULTS: Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ). CONCLUSIONS: Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

Differentiating drought legacy effects on vegetation growth over the temperate Northern Hemisphere.

In view of future changes in climate, it is important to better understand how different plant functional groups (PFGs) respond to warmer and drier conditions, particularly in temperate regions where an increase in both the frequency and severity of drought is expected. The patterns and mechanisms of immediate and delayed impacts of extreme drought on vegetation growth remain poorly quantified. Using satellite measurements of vegetation greenness, in-situ tree-ring records, eddy-covariance CO2 and water flux measurements, and meta-analyses of source water of plant use among PFGs, we show that drought legacy effects on vegetation growth differ markedly between forests, shrubs and grass across diverse bioclimatic conditions over the temperate Northern Hemisphere. Deep-rooted forests exhibit a drought legacy response with reduced growth during up to 4 years after an extreme drought, whereas shrubs and grass have drought legacy effects of approximately 2 years and 1 year, respectively. Statistical analyses partly attribute the differences in drought legacy effects among PFGs to plant eco-hydrological properties (related to traits), including plant water use and hydraulic responses. These results can be used to improve the representation of drought response of different PFGs in land surface models, and assess their biogeochemical and biophysical feedbacks in response to a warmer and drier climate.

TGF-ß1 stimulates HDAC4 nucleus-to-cytoplasm translocation and NADPH oxidase 4-derived reactive oxygen species in normal human lung fibroblasts.

Myofibroblasts are important mediators of fibrogenesis; thus blocking fibroblast-to-myofibroblast differentiation (FMD) may be an effective strategy to treat pulmonary fibrosis (PF). Previously, we reported that histone deacetylase 4 (HDAC4) activity is necessary for transforming growth factor-ß1 (TGF-ß1)-induced human lung FMD. Here, we show that TGF-ß1 increases NADPH oxidase 4 (NOX4) mRNA and protein expression in normal human lung fibroblasts (NHLFs) and causes nuclear export of HDAC4. Application of the NOX family inhibitor diphenyleneiodonium chloride reduces TGF-ß1-induced HDAC4 nuclear export, expression of the myofibroblast marker α-smooth muscle actin (α-SMA), and α-SMA fiber formation. Inhibition of HDAC4 nucleus-to-cytoplasm translocation using leptomycin B (LMB) had little effect on α-SMA expression but blocked α-SMA fiber formation. A coimmunoprecipitation assay showed that HDAC4 associates with α-SMA. Moreover, LMB abolishes TGF-ß1-induced α-SMA fiber formation and cell contraction. Relevant to human pulmonary fibrosis, idiopathic PF specimens showed significantly higher NOX4 RNA expression and scant HDAC4 staining within nuclei of fibroblast foci myofibroblasts. Taken together, these results indicate that reactive oxygen species promote TGF-ß1-mediated myofibroblast differentiation and HDAC4 nuclear export. The physical association of HDAC4 with α-SMA suggests that HDAC4 has a role in regulating the α-SMA cytoskeleton arrangement.

A portable multi-channel wireless NIRS device for muscle activity real-time monitoring.

Near-infrared spectroscopy (NIRS) is a relative new technology in monitoring muscle oxygenation and hemo-dynamics. This paper presents a portable multi-channel wireless NIRS device for real-time monitoring of muscle activity. The NIRS sensor is designed miniaturized and modularized, to make multi-site monitoring convenient. Wireless communication is applied to data transmission avoiding of cumbersome wires and the whole system is highly integrated. Special care is taken to eliminate motion artifact when designing the NIRS sensor and attaching it to human skin. Besides, the system is designed with high sampling rate so as to monitor rapid oxygenation changes during muscle activities. Dark noise and long-term drift tests have been carried out, and the result indicates the device has a good performance of accuracy and stability. In vivo experiments including arterial occlusion and isometric voluntary forearm muscle contraction were performed, demonstrating the system has the ability to monitor muscle oxygenation parameters effectively even in exercise.

Identification of two forms of the Eso1 protein in Schizosaccharomyces pombe.

In Schizosaccharomyces pombe, Eso1p is a protein fusion. Two-thirds of its N-terminus is conserved to budding yeast Rad30, which functions in error-free replication of UV-damaged DNA. A third of the C-terminus is highly conserved to budding yeast Eco1, a lysine acetyltransferase, which is essential for the establishment of cohesion. Both Rad30p and Eco1p need to be finely tuned in budding yeast. Given the distinct function existed in Rad30p and Eco1p, it is enigmatic how the Eso1p, the protein fusion regulated in S. pombe, works. We have identified two forms of the Eso1 protein by Western blot, and detected the Eco1-homology fragment by M/S analysis following TAP purification of Eso1 protein. The result raises the possibility that Eso1 might be processed in vivo to release the Eco1-homology fragment, which allows the independent regulation of Rad30-homology and Eco1-homology fragments.

Amino-functionalized macroporous silica for efficient tryptic digestion in acidic solutions.

Amino-functionalized macroporous silica foam (NH2 -MOSF) has been developed as a host reactor to realize highly efficient proteolysis in acidic solutions where normal tryptic reactions cannot occur. The digestion protocol consists simply of adding the functionalized NH2 -MOSF into the protein and trypsin solutions without altering the bulk pH or preloading the enzymes on the materials. With this protocol, digestion of sample fractions from LC can be efficiently realized in the acidic solutions directly. Digestion of a protein fraction extracted from rat liver tissue after LC separation was performed to illustrate this principle, where 103 proteins were successfully identified at pH 3 after 1.5 h of tryptic digestion.

A genetic screen to discover pathways affecting cohesin function in Schizosaccharomyces pombe identifies chromatin effectors.

Cohesion, the force that holds sister chromatids together from the time of DNA replication until separation at the metaphase to anaphase transition, is mediated by the cohesin complex. This complex is also involved in DNA damage repair, chromosomes condensation, and gene regulation. To learn more about the cellular functions of cohesin, we conducted a genetic screen in Schizosaccharomyces pombe with two different cohesin mutants (eso1-G799D and mis4-242). We found synthetic negative interactions with deletions of genes involved in DNA replication and heterochromatin formation. We also found a few gene deletions that rescued the growth of eso1-G799D at the nonpermissive temperature, and these genes partially rescue the lagging chromosome phenotype. These genes are all chromatin effectors. Overall, our screen revealed an intimate association between cohesin and chromatin.

N-Acetyltransferase 2 genotype, exfoliated urothelial cells and benzidine exposure.

Most studies report an association of the slow N-acetyltransferase 2 (NAT2) status with elevated bladder cancer risk. In this study, NAT2 genotypes and the decades-long records of Papanicolaou's grading of exfoliated urothelial cells in a former benzidine-exposed cohort of the Shanghai dyestuff industry (29 bladder cancer patients; 307 non-cancer cohort members, some of them presenting different grades of pre-malignant alterations of exfoliated urothelial cells) were investigated. The cohort members had been enrolled in regular medical surveillance since mid-1980s. No overall increase of slow NAT2 genotypes in the former benzidine-exposed bladder cancer patients was found, compared with non-diseased members of the same cohort. A lower presentation of the homozygous wild genotype NAT2 4/4 was observed in bladder cancer patients, compared with non-diseased members with averaged Papanicolaou's grading (APG)3 II (OR=0.31, 95 percent CI 0.10-0.96, p=0.034) or with APG less than II (OR=0.36,95 percent CI 0.12-1.10, p=0.063). Nevertheless, neither a protective influence of rapid NAT2 genotypes on bladder cancer risk nor on pre-malignant cytological alterations could be confirmed by the present data.

Characterization of efficient proteolysis by trypsin loaded macroporous silica.

Tryptic digestion of proteins in trypsin loaded porous silica has been shown to be highly efficient. Enzymatic silica-reactors were prepared by immobilizing trypsin into macroporous ordered siliceous foam (MOSF) and into mesoporous SBA-15 silica which has a smaller pore size. The tryptic products from the silica reactors were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and a higher proteolysis efficiency was obtained with MOSF. These results can be well interpreted by a sequential digestion model taking into account the confinement and concentration enrichment of both the substrates and enzymes within the silica pores. Proteins at low concentrations and proteins in urea and surfactant solutions were also successfully digested with the MOSF-based reactor and identified by MS. Considering that the immobilized trypsin could retain its enzymatic activity for weeks, this MOSF reactor provides many advantages compared to free enzyme proteolysis. As a proof-of-concept, the digest of a real complex sample extracted from the cytoplasm of mouse liver tissue using trypsin loaded MOSF yielded better results than the typical in-solution protocol.

Post-transcriptional up-regulation of miR-21 by type I collagen.

Composition of extracellular matrix (ECM) is crucial to the establishment and maintenance of epithelial apical-basolateral polarity. Increased ECM rigidity caused by deposition of fibrillar collagen, for example, collagen type I (Col-1), promotes loss of epithelial polarity and tumor progression. microRNAs are small non-coding RNAs that regulate gene expression and fundamental cellular processes. The current study explored a link between microRNAs and Col-1 using organotypic three-dimensional culture in which epithelial cells are embedded within Matrigel, a mimic of basement membrane matrix (Matrigel 3-D). Matrigel 3-D culture of A549, MCF-7, and mK-ras-LE cells (lung and mammary epithelial cell lines) gave rise to acinus, an in vitro equivalent of apical-basolateral polarity that consists of a polarized monolayer of epithelial cells facing a central lumen. Supplementation of Col-1 disrupted acinus. Moreover, Col-1 up-regulated the expression of miR-21, a well-documented oncogenic microRNA, via a post-transcriptional mechanism. Similar post-transcriptional up-regulation of miR-21 correlated with deposition of Col-1 in a murine model of lung fibrogenesis. In summary, our findings link altered ECM composition/rigidity and the expression of oncogenic microRNAs. The current study also suggests a novel post-transcriptional mechanism for regulation of miR-21 expression at maturation from pre-miR-21 to mature miR-21.

Pharmacological inhibition of HDAC6 attenuates endothelial barrier dysfunction induced by thrombin.

BACKGROUND: Endothelial barrier dysfunction (EBD) involves microtubule disassembly and enhanced cell contractility. Histone deacetylase 6 (HDAC6) deacetylates α-tubulin, and thereby destabilizes microtubules. This study investigates a role for HDAC6 in EBD. METHODS: EBD was induced with thrombin±HDAC6 inhibitors (tubacin and MC1575), and assessed by transendothelial electrical resistance (TEER). Markers for microtubule disassembly (α-tubulin and acetylated α-tubulin) and contraction (phosphorylated myosin light chain 2, P-MLC2) were measured using immunoblots and immunofluorescence. RESULTS AND CONCLUSION: Thrombin induced a ∼50% decrease in TEER that was abrogated by the HDAC6 inhibitors. Moreover, inhibition of HDAC6 diminished edema in the lung injured by lipopolysaccharide. Lastly, inhibition of HDAC6 attenuated thrombin-induced microtubule disassembly and P-MLC2. Our results suggest that HDAC6 can be targeted to limit EBD.

Association of XPD/ERCC2 G23591A and A35931C polymorphisms with skin lesion prevalence in a multiethnic, arseniasis-hyperendemic village exposed to indoor combustion of high arsenic coal.

More than 2,000 arsenic-related skin lesions (as at 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high-arsenic coal. The skin lesion prevalence was significantly higher in ethnic Han villagers than in ethnic Hmong villagers. This study was focused on a possible involvement of XPD/ERCC2 G23591A and A35931C polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. G23591A and A35931C were genotyped by a PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analysed. A significant higher presentation of A/A35931 (homozygous wild) genotype in both clans was found in skin lesion patients, compared with their asymptomatic fellow villagers (67.1 vs. 46.3%, OR 2.36, 95% CI 1.35-4.14, P=0.002). Interestingly, the population frequencies of the A/A35931 genotype did not show significant differences between ethnic Han villagers and their Hmong neighbours (47.1 vs. 45.5%). Very low frequencies of homozygous and heterozygous variant genotypes of G23591A were recorded in the residents in target village. G/A23591 and A/A23591 were detected only in 3.2% (8/244) and 0.8% (2/244) of the villagers, respectively. The polymorphic status at the locus of A35931C might modulate the risk for arsenic-related skin lesions in the investigated groups.

Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no known effective pharmacological therapy. The fibroblastic foci of IPF contain activated myofibroblasts that are the major synthesizers of type I collagen. Transforming growth factor (TGF)-beta1 promotes differentiation of fibroblasts into myofibroblasts in vitro and in vivo. In the current study, we investigated the molecular link between TGF-beta1-mediated myofibroblast differentiation and histone deacetylase (HDAC) activity. Treatment of normal human lung fibroblasts (NHLFs) with the pan-HDAC inhibitor trichostatin A (TSA) inhibited TGF-beta1-mediated alpha-smooth muscle actin (alpha-SMA) and alpha1 type I collagen mRNA induction. TSA also blocked the TGF-beta1-driven contractile response in NHLFs. The inhibition of alpha-SMA expression by TSA was associated with reduced phosphorylation of Akt, and a pharmacological inhibitor of Akt blocked TGF-beta1-mediated alpha-SMA induction in a dose-dependent manner. HDAC4 knockdown was effective in inhibiting TGF-beta1-stimulated alpha-SMA expression as well as the phosphorylation of Akt. Moreover, the inhibitors of protein phosphatase 2A and 1 (PP2A and PP1) rescued the TGF-beta1-mediated alpha-SMA induction from the inhibitory effect of TSA. Together, these data demonstrate that the differentiation of NHLFs to myofibroblasts is HDAC4 dependent and requires phosphorylation of Akt.