Abrasive flow finishing (AFF) is an advanced nano-finishing process using abrasive-laden self-deformable putty for finishing, deburring, radiusing, chamfering, stress-relieving, and mirror-like ...polishing of the complicated components and inaccessible areas which are difficult or impossible to finish by other processes. Since its inception during 1950s, continuous research and advances in AFF are being reported globally. This paper presents comprehensive and critical review of the past research and developments on process modeling, rheological characterization of the AFF medium, development of finishing medium, development of various hybrid, derived, and hybrid-derived processes of AFF, and some novel applications of AFF for complicated shapes and difficult-to-finish materials. Major findings and observations, details of the workpiece material, finishing medium, process parameters, and responses have been presented in a tabular format for quick reference. It also covers some novel applications of AFF in the field of avionics, automobiles, biomedical, gears, additive manufacturing, cutting tool inserts, die and mold manufacturing, and recast layer removal. Finishing results for various materials such as mild steel, brass, aluminum, and its alloys, tool steel, copper, metal matrix composite, and photopolymer resin are also included. It also identifies directions for future research and provides an invaluable list of literature on past research works on AFF process. This review article will be very useful for the researchers working in micro- and nano-finishing applications and the industries involved in manufacturing of the automobiles, aero-engines, avionics components, biomedical implants, gears, impellers, dies and molds, and defense equipment.
•Stress field evolution by photoelasticity as a function of time used for verifying phase field modelling.•Miehe's recommendation of minimum length scale to mesh size ratio verified.•Isochromatic ...fringes suggest use of a lower ratio for computational advantage.•Novel SIF evaluation from phase field using an alternative multiparameter approach.
The resurgence of Griffith's energy balance approach has propelled fracture studies through the numerical implementation of Phase Field Modelling (PFM). Although significant advancements have been made, there are issues which need attention. These include the computational complexity of solving an additional partial differential equation (PDE) and the requirement for an extremely fine mesh to resolve the crack topology accurately. While adaptive algorithms and open-source programs like FEniCS assist in alleviating some of these computational difficulties, the complexity of resolving crack topology continues to be a significant barrier. Experimental techniques like photoelasticity have been indispensable tool in the field of fracture mechanics and have also been instrumental in proposing key concepts in fracture literature. This study systematically validates the efficacy of the PFM in the context of brittle fracture by meticulously conducting stress field-based comparisons utilising photoelasticity. Insights gained from the study also provide nuanced perspectives on mesh refinement issues and the practical applicability of PFM within the domain of linear elastic fracture mechanics to predict crack initiation and propagation. The stress evolution in phase field (PF) models is studied using experimental isochromatic fringe features from a Single Edge-Notched (SEN) specimen. Through a meticulous analysis combining crack propagation path, crack initiation point, and isochromatic fringe features, some recommendations have been formulated and subsequently validated across different classes of problems, such as the four-point bend beam and asymmetrically loaded beam with holes, each marked by inherent complexities. With these recommendations, the computational demand in the PFM for resolving crack topology can be reduced without losing the accuracy of the solution.
Diabetic Retinopathy (DR) occurs due to Type-II diabetes. It causes damages to the retinal blood vessels and reason for visual impairment. The predicted center is around the probability of variation ...in the estimation of retinal veins, and the crisp enrolls vessel development inside the retina. To witness the changes segmentation of retinal blood vessels has to be made. A framework to upgrade the quality of the segmentation results over morbid retinal images is proposed. This framework utilizes Contrast Limited Adaptive Histogram Equalization (CLAHE) for eliminating the background from the source image and enhances the foreground blood vessel pixels, Tandem Pulse Coupled Neural Network (TPCNN) model is endorsed for automatic feature vectors generation, and Deep Learning Based Support Vector Machine (DLBSVM) is proposed for classification and extraction of blood vessels. The DLBSVM parameters are fine-tuned via Firefly algorithm. The STARE, DRIVE, HRF, REVIEW, and DRIONS fundus image datasets are deliberated to assess the recommended techniques. The results render that the proposed technologies improve the segmentation with 80.61% Sensitivity, 99.54% Specificity, and 99.49% Accuracy.
Motile cilia are essential components of the mucociliary escalator and are central to respiratory-tract host defenses. Abnormalities in these evolutionarily conserved organelles cause primary ciliary ...dyskinesia (PCD). Despite recent strides characterizing the ciliome and sensory ciliopathies through exploration of the phenotype-genotype associations in model organisms, the genetic bases of most cases of PCD remain elusive. We identified nine related subjects with PCD from geographically dispersed Amish communities and performed exome sequencing of two affected individuals and their unaffected parents. A single autosomal-recessive nonsynonymous missense mutation was identified in HEATR2, an uncharacterized gene that belongs to a family not previously associated with ciliary assembly or function. Airway epithelial cells isolated from PCD-affected individuals had markedly reduced HEATR2 levels, absent dynein arms, and loss of ciliary beating. MicroRNA-mediated silencing of the orthologous gene in Chlamydomonas reinhardtii resulted in absent outer dynein arms, reduced flagellar beat frequency, and decreased cell velocity. These findings were recapitulated by small hairpin RNA-mediated knockdown of HEATR2 in airway epithelial cells from unaffected donors. Moreover, immunohistochemistry studies in human airway epithelial cells showed that HEATR2 was localized to the cytoplasm and not in cilia, which suggests a role in either dynein arm transport or assembly. The identification of HEATR2 contributes to the growing number of genes associated with PCD identified in both individuals and model organisms and shows that exome sequencing in family studies facilitates the discovery of novel disease-causing gene mutations.
Viral infections and type 2 immune responses are thought to be critical for the development of chronic respiratory disease, but the link between these events needs to be better defined. Here, we ...study a mouse model in which infection with a mouse parainfluenza virus known as Sendai virus (SeV) leads to long-term activation of innate immune cells that drive IL-13-dependent lung disease. We find that chronic postviral disease (signified by formation of excess airway mucus and accumulation of M2-differentiating lung macrophages) requires macrophage expression of triggering receptor expressed on myeloid cells-2 (TREM-2). Analysis of mechanism shows that viral replication increases lung macrophage levels of intracellular and cell surface TREM-2, and this action prevents macrophage apoptosis that would otherwise occur during the acute illness (5-12 d after inoculation). However, the largest increases in TREM-2 levels are found as the soluble form (sTREM-2) long after clearance of infection (49 d after inoculation). At this time, IL-13 and the adapter protein DAP12 promote TREM-2 cleavage to sTREM-2 that is unexpectedly active in preventing macrophage apoptosis. The results thereby define an unprecedented mechanism for a feed-forward expansion of lung macrophages (with IL-13 production and consequent M2 differentiation) that further explains how acute infection leads to chronic inflammatory disease.
Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus ...infection in mice revealed an unexpected role for innate immune cells in IL-13-dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production.
Electronic cigarettes (e-cigarettes) were introduced in the United States in 2007 and by 2014 they were the most popular tobacco product amongst youth and had overtaken use of regular tobacco ...cigarettes. E-cigarettes are used to aerosolize a liquid (e-liquid) that the user inhales. Flavorings in e-liquids is a primary reason for youth to initiate use of e-cigarettes. Evidence is growing in the scientific literature that inhalation of some flavorings is not without risk of harm. In this review, 67 original articles (primarily cellular in vitro) on the toxicity of flavored e-liquids were identified in the PubMed and Scopus databases and evaluated critically. At least 65 individual flavoring ingredients in e-liquids or aerosols from e-cigarettes induced toxicity in the respiratory tract, cardiovascular and circulatory systems, skeletal system, and skin. Cinnamaldehyde was most frequently reported to be cytotoxic, followed by vanillin, menthol, ethyl maltol, ethyl vanillin, benzaldehyde and linalool. Additionally, modern e-cigarettes can be modified to aerosolize cannabis as dried plant material or a concentrated extract. The U.S. experienced an outbreak of lung injuries, termed e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in 2019; among 2,022 hospitalized patients who had data on substance use (as of January 14, 2020), 82% reported using a delta-9-tetrahydrocannabinol (main psychoactive component in cannabis) containing e-cigarette, or vaping, product. Our literature search identified 33 articles related to EVALI. Vitamin E acetate, a diluent and thickening agent in cannabis-based products, was strongly linked to the EVALI outbreak in epidemiologic and laboratory studies; however, e-liquid chemistry is highly complex, and more than one mechanism of lung injury, ingredient, or thermal breakdown product may be responsible for toxicity. More research is needed, particularly with regard to e-cigarettes (generation, power settings, etc.), e-liquids (composition, bulk or vaped form), modeled systems (cell type, culture type, and dosimetry metrics), biological monitoring, secondhand exposures and contact with residues that contain nicotine and flavorings, and causative agents and mechanisms of EVALI toxicity.
Objective
To perform a genome‐wide DNA methylation study to identify DNA methylation changes in osteoarthritic (OA) cartilage tissue.
Methods
The contribution of differentially methylated genes to OA ...pathogenesis was assessed by bioinformatic analysis, gene expression analysis, and histopathologic severity correlation. Genome‐wide DNA methylation profiling of >485,000 methylation sites was performed on eroded and intact cartilage from within the same joint of 24 patients undergoing hip arthroplasty for OA. Genes with differentially methylated CpG sites were analyzed to identify overrepresented gene ontologies, pathways, and upstream regulators. The messenger RNA expression of a subset of differentially methylated genes was analyzed by reverse transcription–polymerase chain reaction. Histopathology was graded by modified Mankin score and correlated with DNA methylation.
Results
We identified 550 differentially methylated sites in OA. Most (69%) were hypomethylated and enriched among gene enhancers. We found differential methylation in genes with prior links to OA, including RUNX1, RUNX2, DLX5, FURIN, HTRA1, FGFR2, NFATC1, SNCAIP, and COL11A2. Among these, RUNX1, HTRA1, FGFR2, and COL11A2 were also differentially expressed. Furthermore, we found differential methylation in approximately one‐third of known OA susceptibility genes. Among differentially methylated genes, upstream regulator analysis showed enrichment of TGFB1 (P = 4.40 × 10−5) and several microRNAs including miR‐128 (P = 4.48 × 10−13), miR‐27a (P = 4.15 × 10−12), and miR‐9 (P = 9.20 × 10−10). Finally, we identified strong correlations between 20 CpG sites and the histologic Mankin score in OA.
Conclusion
Our data implicate epigenetic dysregulation of a host of genes and pathways in OA, including a number of OA susceptibility genes. Furthermore, we identified correlations between CpG methylation and histologic severity in OA.
Enhancing the response to interferon could offer an immunological advantage to the host. In support of this concept, we used a modified form of the transcription factor STAT1 to achieve ...hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. We found that the improvement depended on expression of a PARP9-DTX3L complex with distinct domains for interaction with STAT1 and for activity as an E3 ubiquitin ligase that acted on host histone H2BJ to promote interferon-stimulated gene expression and on viral 3C proteases to degrade these proteases via the immunoproteasome. Thus, PARP9-DTX3L acted on host and pathogen to achieve a double layer of immunity within a safe reserve in the interferon signaling pathway.
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