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Povzetek: Background Omics approaches have significantly increased our understanding of biological systems. However, they have had limited success in explaining the dramatically increased productivity of commercially important natural products by industrial high-producing strains, such as the erythromycin-producing actinomycete Saccharopolyspora erythraea. Further yield increase is of great importance but requires a better understanding of the underlying physiological processes. Results To reveal the mechanisms related to erythromycin yield increase, we have undertaken an integrated study of the genomic, transcriptomic, and proteomic differences between the wild type strain NRRL2338 (WT) and the industrial high-producing strain ABE1441 (HP) of S. erythraea at multiple time points of a simulated industrial bioprocess. 165 observed mutations lead to differences in gene expression profiles and protein abundance between the two strains, which were most prominent in the initial stages of erythromycin production. Enzymes involved in erythromycin biosynthesis, metabolism of branched chain amino acids and proteolysis were most strongly upregulated in the HP strain. Interestingly, genes related to TCA cycle and DNA-repair were downregulated. Additionally, comprehensive data analysis uncovered significant correlations in expression profiles of the erythromycin-biosynthetic genes, other biosynthetic gene clusters and previously unidentified putative regulatory genes. Based on this information, we demonstrated that overexpression of several genes involved in amino acid metabolism can contribute to increased yield of erythromycin, confirming the validity of our systems biology approach. Conclusions Our comprehensive omics approach, carried out in industrially relevant conditions, enabled the identification of key pathways affecting erythromycin yield and suggests strategies for rapid increase in the production of secondary metabolites in industrial environment.
Ključne besede: aktinomicete, Saccharopolyspora erythraea, sekundarni metaboliti, antibiotiki, eritromicin, biosinteza, metabolno inženirstvo, proteomika
Objavljeno v DiRROS: 25.07.2024; Ogledov: 42; Prenosov: 13
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Povzetek: In this chapter, we present a framework for applying artificial intelligence (AI)/machine learning (ML) in reliability, in the context of the iRel40 project. Data-driven models are becoming an increasingly fruitful tool for detecting patterns in complex data and identifying the circumstances in which they occur. Using only data, gathered along the value chain, data-driven methods are now being used to detect indications of potential early failures, signs of wear out or degradation, and other unwanted events within the development, fabrication, or service phases of the electronic components and systems. We present general considerations that were found to be important during the iRel40 project, when designing pipelines that combine data processing with the AI/ML models for predicting or detecting reliability issues. This chapter serves as an introduction to the definitions and concepts used within the specific use cases that rely on the AI/ML methodology within the iRel40 project.
Ključne besede: machine learning, artificial intelligence, data-driven models
Objavljeno v DiRROS: 23.07.2024; Ogledov: 14; Prenosov: 4
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Povzetek: Since arsenic (As) exposure is largely due to geochemical contamination, this study focused on the remediated area of Santana do Morro, a district of Santa Bárbara, Minas Gerais, Brazil, which was previously contaminated with As due to gold mining. Total As concentrations in sediment, soil and plants were determined, next to As species, anionic arsenic compounds As(III), As(V), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), in plants samples. Total As concentrations in soil and sediments were slightly elevated (16-18 µg g-1) and most of the plants contained low levels of As (< 1 µg g-1). The exception was a native plant Eleocharis geniculata (L.) which contained elevated levels of As (4 µg g-1). The exposure of this plant to As under controlled conditions (hydroponics) indicated its possible tolerance to elevated As levels and suggesting its potential use in phytomonitoring of As-contaminated sites. This plant is able to metabolize arsenate to arsenite and contained MMA and DMA, both in its natural habitat and under controlled conditions.
Ključne besede: arsenic species, soil, sediments, plants, Cyperacea, Iron Quadrangle
Objavljeno v DiRROS: 22.07.2024; Ogledov: 30; Prenosov: 12
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Povzetek: Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients. In addition to their potent cytotoxicity, NK cells secrete IFN-γ, upregulate GSLC surface expression of CD54 and MHC class I and increase sensitivity of GSLCs to chemotherapeutic drugs. Moreover, NK cell localization in peri-vascular regions in glioblastoma tissues and their close contact with GSLCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSLCs. Due to GSLC heterogeneity and plasticity in regards to their stage of differentiation personalized immunotherapeutic strategies should be designed to effectively target glioblastomas.
Ključne besede: glioblastoma, natural killer cells, translational oncology
Objavljeno v DiRROS: 16.07.2024; Ogledov: 90; Prenosov: 45
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Povzetek: The increase of the dielectric permittivity with an electric field and enhanced energy storage properties make antiferroelectrics very attractive for high-power electronic applications needed in emerging green energy technologies and neuromorphic computing platforms. Their exceptional functional properties are closely related to the electric field-induced antiferroelectric↔ferroelectric phase transition, which can be driven toward a critical end point by manipulation with an external electric field. The critical fluctuation of physical properties at the critical end point in ferroelectrics is a promising approach to improve their functional properties. Here, we demonstrate the existence of two critical end points in antiferroelectric ceramics with a ferroelectric-antiferroelectric-paraelectric phase sequence, using the model system Pb 0.99 Nb 0.02 [ ( Zr 0.57 Sn 0.43 ) 0.92 Ti 0.08 ] 0.98 O 3 . The critical fluctuation of the dielectric permittivity in the proximity of the antiferroelectric-to-paraelectric critical end point is responsible for the strong enhancement of the dielectric tunability (by a factor of > 2 ) measured at ≈ 395 K. The enhancement of the energy storage density at ≈ 370 K is related to the proximity of the ferroelectric-to-antiferroelectric critical end point. These findings open possibilities for material design and pave the way for the next generation of high-energy storage materials.
Ključne besede: electronic applications, high-power electronic, green energy, electric field
Objavljeno v DiRROS: 10.07.2024; Ogledov: 98; Prenosov: 58
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