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Flow field distribution plays a vital role in electrochemical machining (ECM) because it can directly affect the machining stability and accuracy of ECM. In counter-rotating electrochemical machining (CRECM), the uniformity of the flow field is difficult to control due to the complicated and changeable flow channel shape. Through the simulation of the conventional lateral fluid flow pattern, it is found that the complexity of the flow channel with grid structures makes the flow field of machining area strongly disordered, which leads to the low velocity zones and dead zones. Based on the simulation results, a new electrolyte flow pattern with an auxiliary internal fluid is proposed, which can remarkably improve the uniformity of flow field by apply supplementary electrolyte to the machining area. Experimental results show that the new flow pattern effectively improves the machining stability of CRECM, and enhances the machining precision of grid structures, the sidewall taper angle is reduced from 29.3° to 7.7°.

Counter-rotating electrochemical machining (CRECM) is a novel electrochemical machining (ECM) method, which can be used to machine convex structures with complex shapes on the outer surface of casings. In this study, the evolution of the convex structure during CRECM is studied. The complex motion form of CRECM is replaced by an equivalent kinematic model, in which the movement of the cathode tool is realized by matrix equations. The trajectory of the cathode tool center satisfies the Archimedes spiral equation, and the feed depth in adjacent cycles is a constant. The simulation results show that the variations of five quality indexes for the convex structure: as machining time increases, the height increases linearly, and the width reduces linearly, the fillets at the top and root fit the rational function, and the inclination angle of the convex satisfies the exponential function. The current density distributions with different rotation angles is investigated. Owing to the differential distribution of current density on workpiece surface, the convex is manufactured with the cathode window transferring into and out of the processing area. Experimental results agree very well with the simulation, which indicates that the proposed model is effective for prediction the evolution of the convex structure in CRECM.

Counter-rotating electrochemical machining (CRECM) is an innovative ECM method that can be used to manufacture revolving parts, especially titanium alloy casings. Because titanium alloys are easily passivated metals, sufficient electrical quantity is required to achieve the transition from pitting to smoothing with a lower speed. However, a low rotational speed means more material is removed in a machining cycle, which is not conducive to wall thickness control. Therefore, achieving fast smoothing at a relatively high rotational speed for titanium alloys is focused. In this paper, the proposed methodology applies an auxiliary cathode to accelerate the transition from pitting corrosion to smoothness of titanium alloys at a relatively high rotational speed. Experimental results show that titanium alloy can be smoothed regardless of rotational speed with an auxiliary cathode. The auxiliary cathode can weaken the off-current density region and accelerate the breakdown of the oxide layer, and the layer-by-layer dissolution of micron-thick materials is achieved at a relatively high rotational speed. The grid-like convex structure is produced at a relatively high rotational speed with an auxiliary cathode, and the surface roughness is 1.808 μm. This fully demonstrates the reliability of the auxiliary cathode for achieving the smoothness of titanium alloys.

The role of Mo alloy element on the tribological behaviors of AT13/Mo coatings sliding against Si3N4 balls under boundary lubrication condition was investigated. The results revealed that the AT13 and AT13/Mo coatings were mainly composed of γ-Al2O3, α-Al2O3 and TixOy ceramic phases and both coatings underwent a transition from boundary lubrication to dry friction. Furthermore, the addition of Mo could greatly reduce friction. Moreover, the tribological properties of AT13/Mo coating under boundary lubrication condition were superior over those of pure AT13 coatings. According to XPS results, Mo has undergone a chemical reaction to generate a tribofilm covering the friction interface under boundary lubrication condition, and the film containing MoS2 and MoO2 can greatly enhance load-bearing capability and provide good boundary lubrication effect.

The effects of oxygen-enriched atmosphere on the morphological evolution of soot emitted from a methane co-flow laminar diffusion flame were studied using a 12-μm SiC fiber deposition sampling method combined with field emission scanning electron microscopy (FESEM) analysis. The temperature distribution and the soot morphological evolution along the flame radial and axial directions at different oxygen concentrations were systematically investigated. Results showed that the soot morphology was strongly dependent on its position and oxygen concentration in flames. At the same flame height, the soot morphology changed significantly when the oxygen concentration increased from 21% to 31%. The soot generation rate increased rapidly under the elevated oxidative condition, and the position of soot inception was closer to the burner nozzle. As the flame height and oxygen concentration increased, soot particles in the flame centerline were enlarged and evolved to fiber-like depositions. Furthermore, the large clusters of soot particles gradually evolved to even denser spongy and fibrous particles around the flame edges. In addition, unique sponge-like soot deposits were observed for the first time in methane flames.

The effect of oxygen concentrations on the formation and evolution of soot particles was investigated by analyzing soot morphology using SiC fiber deposition technique and thermophoretic sampling method in a co-flow diffusion ethylene flame. Soot particles were examined via transmission electron microscopy at different heights along the flame centerline. Results show that the flame temperature exhibits a bimodal distribution. As the flame height increases, the flame distribution gradually changes from bimodal to unimodal, and the increase in oxygen concentration not only causes the flame height to decrease, but also causes the bimodal distribution of the flame more pronounced. The morphological evolution of soot deposits are strongly dependent on the oxygen concentration, radial and axial position, and flame temperature. Soot deposits along the flame centerline begin to be oxidized into dense flocculent and fibrous mesh structures with the flame temperature increases. In front of the flame, the oxidation is enhanced with temperature rise at the same height, resulting in more dense morphology of the soot deposits and the decrease in primary particle size. The results of thermophoretic sampling show that soot growth undergoes various stages of nucleation, growth, coagulation, agglomeration and oxidation, and the average particle size distributions of soot increase first and then decrease. The increase in oxygen concentration leads to advances in all stages of soot formation, including surface growth, agglomeration and oxidation. Additionally, the flame temperatures increase sharply as the increase of flame heights, leading to the soot aggregates to be oxidized to loose chain-like agglomerates.

ARID1A is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that ARID1A deficiency induces global changes in the epigenetic landscape of enhancers and promoters. These broad and complex effects make it challenging to identify the driving mechanisms of ARID1A deficiency in promoting cancer progression. Here, we identified the anti-senescence effect of Arid1a deficiency in the progression of pancreatic intraepithelial neoplasia (PanIN) by profiling the transcriptome of individual PanINs in a mouse model. In a human cell line model, we found that ARID1A deficiency upregulates the expression of aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which plays an essential role in attenuating the senescence induced by oncogenic KRAS through scavenging reactive oxygen species. As a subunit of the SWI/SNF chromatin remodeling complex, our ATAC sequencing data showed that ARID1A deficiency increases the accessibility of the enhancer region of ALDH1A1. This study provides the first evidence that ARID1A deficiency promotes pancreatic tumorigenesis by attenuating KRAS-induced senescence through the upregulation of ALDH1A1 expression.

The characteristics of soot in the diffusion flames of methane and ethylene under different oxygen concentrations and the influence of mixing methane in ethylene on soot generation were investigated using thermophoretic sampling and subsequent transmission electron microscopy image analysis. The process of soot particle nucleation, surface growth, coagulation, agglomeration and oxidation along the flame axis was analyzed. The variation of soot particle size distribution and aggregate characteristics at different heights along the centerline of the flame at different oxygen concentrations and methane doping ratios were obtained. Results show that the various stages of soot generation in methane flame obviously lags behind the ethylene flame at different oxygen concentrations, and increasing the oxygen concentration makes the various stages of soot formation in the flame advance. A 10% methane doping can promote soot generation at low flame locations. Increasing the doping amount to 30%, the generation of soot can be promoted at high flame locations. The synergistic effect of soot formation in fuel combustion occurs in the above two cases. However, the synergistic effect of the fuel will disappear under high blending ratio conditions. The effect of methane-ethylene at high blend ratios is more like a neutralization effect.

To solve the problem of insufficient protective performance of the existing body armor, an impact-resistant shear stiffening gel (SSG) with excellent flexibility and formability was innovatively used as buffer plate for body armor, and then combined with ultra-high molecular weight polyethylene (UHMWPE) ballistic panel to form a UHMWPE/SSG composite body armor. Based on the ballistic impact experiment and numerical simulation, the effect of buffer plate on the protective performance, and the dynamic behavior and protective mechanism of UHMWPE/SSG were analyzed systematically. The results indicated that the flexible SSG buffer plate could quickly stiffen under ballistic impact, thereby producing the strong “Jamming” effect to resist impact deformation and absorb impact energy. Moreover, the “Jamming” effect enhanced with the increase of impact load, and showed a distribution mode that weakened from the ballistic impact area to the periphery. Compared with traditional buffer materials, more impact energy was dispersed and absorbed by SSG, but less impact energy was transmitted to the human body. Therefore, the impact strength of UHMWPE/SSG on the human body and backface signature of human body were also significantly reduced (up to 50%), which showed that the composite body armor with SSG buffer material exhibited superior protective performance.

ARID1A is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that ARID1A deficiency induces global changes in the epigenetic landscape of enhancers and promoters. These broad and complex effects make it challenging to identify the driving mechanisms of ARID1A deficiency in promoting cancer progression. Here we identified the anti-senescence effect of ARID1A deficiency in the progression of pancreatic intraepithelial neoplasia (PanIN) by profiling the transcriptome of individual PanINs in the mouse model. Interestingly, we found that ARID1A deficiency upregulates the expression of Aldehyde dehydrogenase ALDH1A1, which plays an essential role in attenuating the senescence induced by oncogenic KRAS. Despite that ALDH proteins have been commonly used as cancer stem cell markers, their effect in promoting attenuation of senescence is not known before. Therefore, ALDH proteins could be considered a potential adjuvant drug target in treating pancreatic cancer.

ARID1A is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that ARID1A deficiency induces global changes in the epigenetic landscape of enhancers and promoters. These broad and complex effects make it challenging to identify the driving mechanisms of ARID1A deficiency in promoting cancer progression. Here, we identified the anti-senescence effect of Arid1a deficiency in the progression of pancreatic intraepithelial neoplasia (PanIN) by profiling the transcriptome of individual PanINs in a mouse model. In a human cell line model, we found that ARID1A deficiency upregulates the expression of aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which plays an essential role in attenuating the senescence induced by oncogenic KRAS through scavenging reactive oxygen species. As a subunit of the SWI/SNF chromatin remodeling complex, our ATAC sequencing data showed that ARID1A deficiency increases the accessibility of the enhancer region of ALDH1A1. This study provides the first evidence that ARID1A deficiency promotes pancreatic tumorigenesis by attenuating KRAS-induced senescence through the upregulation of ALDH1A1 expression.

Droplet‐based single cell sequencing technologies, such as inDrop, Drop‐seq, and 10X Genomics, are catalyzing a revolution in the understanding of biology. Barcoding beads are key components for these technologies. What is limiting today are barcoding beads that are easy to fabricate, can efficiently deliver primers into drops, and thus achieve high detection efficiency. Here, this work reports an approach to fabricate dissolvable polyacrylamide beads, by crosslinking acrylamide with disulfide bridges that can be cleaved with dithiothreitol. The beads can be rapidly dissolved in drops and release DNA barcode primers. The dissolvable beads are easy to synthesize, and the primer cost for the beads is significantly lower than that for the previous barcoding beads. Furthermore, the dissolvable beads can be loaded into drops with >95% loading efficiency of a single bead per drop and the dissolution of beads does not influence reverse transcription or the polymerase chain reaction (PCR) in drops. Based on this approach, the dissolvable beads are used for single cell RNA and protein analysis., This work reports an approach to fabricate dissolvable polyacrylamide beads, by crosslinking acrylamide with disulfide bridges that can be cleaved with dithiothreitol. The beads can be rapidly dissolved in drops and release DNA barcode primers for droplet DNA barcoding, which demonstrate great potential for high‐throughput single cell sequencing.

ARID1A (AT-rich interacting domain-containing protein 1A) is one of the frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that ARID1A deficiency induces global changes in the epigenetic landscape of enhancers and gene regulations. These complex changes make it challenging to identify the driving mechanisms of ARID1A deficiency in promoting cancer progression. Using a mouse model, we identified the anti-senescence effect of ARID1A deficiency, which promotes the progression of pancreatic intraepithelial neoplasia (PanIN). To identify the underlying mechanism and the players, we profiled the transcriptomes of individual PanIN lesions. As a result, we observed not only the anti-senescence effect but also the complex trans-differentiation of neoplastic cells. Furthermore, we discovered that significantly upregulated aldehyde dehydrogenase (ALDH) help to inhibit Kras-induced reactive oxygen species (ROS) production and lead to the reduction of the cellular senescence, which results in the accelerated PanIN progression.

Cancer cells function as primary architects of the tumor microenvironment. Yet, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblasts (CAFs) are distinguishable on the basis of gene expression signatures they acquire in co-culture with epithelial- or mesenchymal-like lung adenocarcinoma (LUAD) cells. High expression of the EMT activator ZEB1 endows LUAD cells with the capacity to activate a soluble factor exchange that leads to CAF reprogramming, to generate CAF-led invasive projections in multicellular aggregates, and to respond to pro-metastatic signals from CAFs in mice. Thus, ZEB1-expressing LUAD cells are positioned at the apex of a signaling hierarchy in the tumor microenvironment.

SUMMARY Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. The EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis., In brief Bota-Rabassedas et al. show that EMT in lung adenocarcinoma cells activates a secretory process that governs CAF heterogeneity and, in turn, sensitizes lung adenocarcinoma cells to pro-metastatic signals from CAFs. Thus, EMT positions lung adenocarcinoma cells at the apex of a signaling hierarchy in the tumor microenvironment., Graphical Abstract

Counter-rotating electrochemical machining (CRECM) holds the unique advantages to machine thin-walled revolving parts, especially for thin-walled engine cases. The electric field intensity distribution on the revolving anode surface is non-uniform, which is difficult to calculate accurately. In this work, a novel equivalent model for analytic solution of the electric field in CRECM is proposed based on complex variable function, and anode material dissolution model is established for CRECM. The variations of the material removal rate (MRR) and interelectrode gap (IEG) at different machining parameters have been fully investigated. The results indicate the MRR can reach a relative equilibrium state after a transition stage. The relative equilibrium MRR is higher than the feed rate, leading to a linear increase in the IEG. Moreover, machining parameters are optimized numerically to shorten the time reaching the relative equilibrium state. Experiments are conducted to verify the theoretical results. The experimental results fit well with the theoretical values. It means that the proposed model is effective for the prediction of the material dissolution process in CRECM.

The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss.

The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.

The quantification of transcriptional variation in single cells, particularly within the same cell population, is currently limited by the low sensitivity and high technical noise of single-cell RNA-seq assays. We report multiple annealing and dC-tailing-based quantitative single-cell RNA-seq (MATQ-seq), a highly sensitive and quantitative method for single-cell sequencing of total RNA. By systematically determining technical noise, we show that MATQ-seq captures genuine biological variation between whole transcriptomes of single cells.

Background Point mutations or genomic deletions of FOXF1 result in a lethal developmental lung disease Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins. However, the clinical consequences of the constitutively increased dosage of FOXF1 are unknown. Methods Copy-number variations and their parental origin were identified using a combination of array CGH, long-range PCR, DNA sequencing, and microsatellite analyses. Minisatellite sequences across different species were compared using a gready clustering algorithm and genome-wide analysis of the distribution of minisatellite sequences was performed using R statistical software. Results We report four unrelated families with 16q24.1 duplications encompassing entire FOXF1. In a 4-year-old boy with speech delay and a café-au-lait macule, we identified an ~15 kb 16q24.1 duplication inherited from the reportedly healthy father, in addition to a de novo ~1.09 Mb mosaic 17q11.2 NF1 deletion. In a 13-year-old patient with autism and mood disorder, we found an ~0.3 Mb duplication harboring FOXF1 and an ~0.5 Mb 16q23.3 duplication, both inherited from the father with bipolar disorder. In a 47-year old patient with pyloric stenosis, mesenterium commune, and aplasia of the appendix, we identified an ~0.4 Mb duplication in 16q24.1 encompassing 16 genes including FOXF1. The patient transmitted the duplication to her daughter, who presented with similar symptoms. In a fourth patient with speech and motor delay, and borderline intellectual disability, we identified an ~1.7 Mb FOXF1 duplication adjacent to a large minisatellite. This duplication has a complex structure and arose de novo on the maternal chromosome, likely as a result of a DNA replication error initiated by the adjacent large tandem repeat. Using bioinformatic and array CGH analyses of the minisatellite, we found a large variation of its size in several different species and individuals, demonstrating both its evolutionarily instability and population polymorphism. Conclusions Our data indicate that constitutional duplication of FOXF1 in humans is not associated with any pediatric lung abnormalities. We propose that patients with gut malrotation, pyloric or duodenal stenosis, and gall bladder agenesis should be tested for FOXF1 alterations. We suggest that instability of minisatellites greater than 1 kb can lead to structural variation due to DNA replication errors. Electronic supplementary material The online version of this article (doi:10.1186/s12881-014-0128-z) contains supplementary material, which is available to authorized users.