Interleukin-12p40 Modulates Human Metapneumovirus-Induced Pulmonary Disease in an Acute Mouse Model of Infection

The mechanisms that regulate the host immune response induced by human metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family, are largely unknown. Cytokines play an important role in modulating inflammatory responses during viral infections. IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV. In this work, we demonstrated that in mice deficient in IL-12p40, hMPV infection induced an exacerbated pulmonary inflammatory response and mucus production, altered cytokine response, and decreased lung function. However, hMPV infection in these mice does not have an effect on viral replication. These results identify an important regulatory role of IL-12p40 in hMPV infection

Intelligent Retrofitting Paradigm for Conventional Machines towards the Digital Triplet Hierarchy

Industry 4.0 is evolving through technological advancements, leveraging information technology to enhance industry with digitalisation and intelligent activities. Whereas Industry 5.0 is the Age of Augmentation, striving to concentrate on human-centricity, sustainability, and resilience of the intelligent factories and synergetic industry. The crucial enhancer for the improvements accomplished by digital transformation is the notion of ‘digital triplet D3’, which is an augmentation of the digital twin with artificial intelligence, human ingenuity, and experience. digital triplet D3 encompasses intelligent activities based on human awareness and the convergence among cyberspace, physical space, and humans, in which Implementing useful reference hierarchy is a crucial part of instigating Industry 5.0 into a reality. This paper depicts a digital triplet which discloses the potency of retrofitting a conventional drilling machine. This hierarchy included the perceptive level for complex decision-making by deploying machine learning based on human ingenuity and creativity, the concatenated level for controlling the physical system’s behaviour predictions and emulation, the observing level is the iterative observation of the actual behaviour of the physical system using real-time data, and the duplicating level visualises and emulates virtual features through physical tasks. The accomplishment demonstrated the viability of the hierarchy in imitating the real-time functionality of the physical system in cyberspace, an immaculate performance of this paradigm. The digital triplet’s complexity was diminished through the interaction among facile digital twins, intelligent activities, and human awareness. The performance parameters of the digital triplet D3 paradigm for retrofitting were eventually confirmed through appraising, anomaly analysis, and real-time monitoring

ANN & ANFIS Models for Prediction of Abrasive Wear of 3105 Aluminium Alloy with Polyurethane Coating

The quest for safety and reliability has increased significantly after Industrial revolution, so is the case for coating industries. In this paper 3105 Aluminium alloy sheet is coated with organic polyurethane coating. After the implementation of coating, various processes are undergone to check its reliability under elevated conditions. ANN & ANFIS model were developed and trained with an objective to find abrasive wear during the process. ANN & ANFIS model were compared with the experimental results. It is observed that the abrasive wear of a coated specimen can be predicted accurately and precisely using ANN and ANFIS models

Patients with triple-negative, JAK2V617F- A nd CALR-mutated essential thrombocythemia share a unique gene expression signature

Approximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called "triple-negative"(TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed. Using this platform, 10 (22%) of 46 patients had detectable mutations (MPL, n 5 6; JAK2V617F, n 5 4) with 3 of 10 cases harboring germline MPL mutations. RNA-sequencing and DNA methylation analysis were also performed by using peripheral blood mononuclear cells. Pathway analysis comparing healthy volunteers and ET patients (regardless of mutational status) identified significant enrichment for genes in the tumor necrosis factor, NFkB, and MAPK pathways and upregulation of platelet proliferative drivers such as ITGA2B and ITGB3. Correlation with DNA methylation showed a consistent pattern of hypomethylation at upregulated gene promoters. Interrogation of these promoter regions highlighted enrichment of transcriptional regulators, which were significantly upregulated in patients with ET regardless of mutation status, including CEBPb and NFkB. For "true"TN ET, patterns of gene expression and DNA methylation were similar to those in ET patients with known driver mutations. These observations suggest that the resultant ET phenotype may, at least in part and regardless of mutation type, be driven by transcriptional misregulation and may propagate downstream via the MAPK, tumor necrosis factor, and NFkB pathways with resultant JAK-STAT activation. These findings identify potential novel mechanisms of disease initiation that require further evaluation