The design and simulation of an autonomous system for aircraft maintenance scheduling

International audienceOperational support is a key issue for aircraft maintenance, which aims to improve operational efficiency and reduce operating costs under the premise of ensuring flight safety. Although many works have emerged to achieve this aim, they mostly address the concept of maintenance systems, the relationship between stakeholders and the loop of maintenance information separately. Hence, the cooperation between stakeholders could be impeded especially when urgent decisions should be made, relying on historical data and real-time data. In this paper, we propose an innovative design of an autonomous system supporting the automatic decision-making for maintenance scheduling. The design starts from the proposition of the analysis framework, to concept formulation of the system, to information transitional level interface, and ends with an instance of system module interactions. The underlying architecture illustrates the high-level fusion of technical and business drives; optimizes strategies and plans with regard to maintenance costs, service level and reliability. An agent-based simulation system is developed as a proof to illustrate the feasibility of the system principle and algorithms. Furthermore, the simulation experiment analyzing the impact of maintenance sequence strategies on maintenance costs and service level has demonstrated the algorithm functionality and the feasibility of the proposed approach

Chromosomal DNA deletion confers phage resistance to Pseudomonas aeruginosa.

Bacteria develop a broad range of phage resistance mechanisms, such as prevention of phage adsorption and CRISPR/Cas system, to survive phage predation. In this study, Pseudomonas aeruginosa PA1 strain was infected with lytic phage PaP1, and phage-resistant mutants were selected. A high percentage (~30%) of these mutants displayed red pigmentation phenotype (Red mutant). Through comparative genomic analysis, one Red mutant PA1r was found to have a 219.6 kb genomic fragment deletion, which contains two key genes hmgA and galU related to the observed phenotypes. Deletion of hmgA resulted in the accumulation of a red compound homogentisic acid; while A galU mutant is devoid of O-antigen, which is required for phage adsorption. Intriguingly, while the loss of galU conferred phage resistance, it significantly attenuated PA1r in a mouse infection experiment. Our study revealed a novel phage resistance mechanism via chromosomal DNA deletion in P. aeruginosa

IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKKα, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikkα ablation (IkkαΔLu ) induces spontaneous ADCs and promotes KrasG12D-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKKα deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs KrasG12D-mediated ADC development in IkkαΔLu mice. Therefore, IKKα modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKKα functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism

Global characteristics and trends in research on Candida auris

IntroductionCandida auris, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients’ skin and transmit to others. Despite numerous reports of C. auris isolation in various countries, many studies have reported contradictory results.MethodA bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling C. auris infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva’s articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for ‘drug resistance,’ ‘antifungal susceptibility test,’ ‘infection,’ ‘Candida auris,’ and ‘identification.’ The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of C. auris.ConclusionThe bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling C. auris

IKKα negatively regulates ASC-dependent inflammasome activation.

The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IκB kinase α (IKKα) is a critical negative regulator of apoptosis-associated specklike protein containing a C-terminal caspase-activation-andrecruitment (CARD) domain (ASC)-dependent inflammasomes. IKKα controls the inflammasome at the level of the adaptor ASC, which interacts with IKKα in the nucleus of resting macrophages in an IKKα kinase-dependent manner. Loss of IKKα kinase activity results in inflammasome hyperactivation. Mechanistically, the downstream nuclear effector IKK-related kinase (IKKi) facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation. ASC remains under the control of IKKα in the perinuclear area following translocation of the ASC/IKKα complex. Signal 2 of NLRP3 activation leads to inhibition of IKKα kinase activity through the recruitment of PP2A, allowing ASC to participate in NLRP3 inflammasome assembly. Taken together, these findings reveal a IKKi-IKKα-ASC axis that serves as a common regulatory mechanism for ASC-dependent inflammasomes

Unlocking the mystery of the hard-to-sequence phage genome: PaP1 methylome and bacterial immunity

BACKGROUND: Whole-genome sequencing is an important method to understand the genetic information, gene function, biological characteristics and survival mechanisms of organisms. Sequencing large genomes is very simple at present. However, we encountered a hard-to-sequence genome of Pseudomonas aeruginosa phage PaP1. Shotgun sequencing method failed to complete the sequence of this genome. RESULTS: After persevering for 10 years and going over three generations of sequencing techniques, we successfully completed the sequence of the PaP1 genome with a length of 91,715 bp. Single-molecule real-time sequencing results revealed that this genome contains 51 N-6-methyladenines and 152 N-4-methylcytosines. Three significant modified sequence motifs were predicted, but not all of the sites found in the genome were methylated in these motifs. Further investigations revealed a novel immune mechanism of bacteria, in which host bacteria can recognise and repel modified bases containing inserts in a large scale. This mechanism could be accounted for the failure of the shotgun method in PaP1 genome sequencing. This problem was resolved using the nfi(-) mutant of Escherichia coli DH5α as a host bacterium to construct a shotgun library. CONCLUSIONS: This work provided insights into the hard-to-sequence phage PaP1 genome and discovered a new mechanism of bacterial immunity. The methylome of phage PaP1 is responsible for the failure of shotgun sequencing and for bacterial immunity mediated by enzyme Endo V activity; this methylome also provides a valuable resource for future studies on PaP1 genome replication and modification, as well as on gene regulation and host interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-803) contains supplementary material, which is available to authorized users

Comparative genomics and DNA methylation analysis of Pseudomonas aeruginosa clinical isolate PA3 by single-molecule real-time sequencing reveals new targets for antimicrobials

IntroductionPseudomonas aeruginosa (P.aeruginosa) is an important opportunistic pathogen with broad environmental adaptability and complex drug resistance. Single-molecule real-time (SMRT) sequencing technique has longer read-length sequences, more accuracy, and the ability to identify epigenetic DNA alterations.MethodsThis study applied SMRT technology to sequence a clinical strain P. aeruginosa PA3 to obtain its genome sequence and methylation modification information. Genomic, comparative, pan-genomic, and epigenetic analyses of PA3 were conducted.ResultsGeneral genome annotations of PA3 were discovered, as well as information about virulence factors, regulatory proteins (RPs), secreted proteins, type II toxin-antitoxin (TA) pairs, and genomic islands. A genome-wide comparison revealed that PA3 was comparable to other P. aeruginosa strains in terms of identity, but varied in areas of horizontal gene transfer (HGT). Phylogenetic analysis showed that PA3 was closely related to P. aeruginosa 60503 and P. aeruginosa 8380. P. aeruginosa's pan-genome consists of a core genome of roughly 4,300 genes and an accessory genome of at least 5,500 genes. The results of the epigenetic analysis identified one main methylation sites, N6-methyladenosine (m6A) and 1 motif (CATNNNNNNNTCCT/AGGANNNNNNNATG). 16 meaningful methylated sites were picked. Among these, purH, phaZ, and lexA are of great significance playing an important role in the drug resistance and biological environment adaptability of PA3, and the targeting of these genes may benefit further antibacterial studies.DisucssionThis study provided a detailed visualization and DNA methylation information of the PA3 genome and set a foundation for subsequent research into the molecular mechanism of DNA methyltransferase-controlled P. aeruginosa pathogenicity

Microstructure, Mechanical Properties, In Vitro Biodegradability, and Biocompatibility of Mg-Zn/HA Composites for Biomedical Implant Applications

Recently, Mg-Zn/hydroxyapatite (HA) composites have attracted much attention as potential candidates for use in bone implants. In this paper, the MgZn/HA composites were prepared using powder metallurgy (PM) and the merging mechanism of MgZn and HA particles was investigated by adjusting the weight ratio of the HA powder. The evolution of the HA distribution in the matrix was examined using SEM and micro-CT images. Afterward, the mechanical properties and biocompatibility of the composites were discussed in detail. The results revealed that the mechanical properties and biocompatibility of the Mg-Zn/HA composites were significantly affected by the HA content. Composites with a low HA content showed increased porosity, improved mechanical strength, and enhanced corrosion resistance after ball milling and cold pressing. These results underscore the importance of optimizing the HA content in Mg-Zn/HA composites for bone implants. Based on our findings, PM Mg-Zn/HA composites with a moderate HA content demonstrate the most promising characteristics as bone implants. The insights gained from this work contribute to the advancement of bone implant materials and hold great potential for enhancing orthopedic surgery outcomes