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1.
Sun Yibin Pfahringer Bernhard Gomes Heitor Murilo Bifet Albert 《Data mining and knowledge discovery》2022,36(5):2006-2032
Data Mining and Knowledge Discovery - Most research in machine learning for data streams has focused on classification algorithms, whereas regression methods have received a lot less attention.... 相似文献
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Anne-Margarethe Enge Florian Kaltner Christoph Gottschalk Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(8)
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics. 相似文献
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Ilaria Patruno Dr. Dawn Thompson Dr. Sergio Dall'Angelo Prof. Albert D. Windhorst Dr. Danielle J. Vugts Dr. Alex J. Poot Dr. Nimesh Mody Prof. Matteo Zanda 《ChemMedChem》2020,15(16):1579-1590
Fenretinide (4-HPR) is a synthetic derivative of all-trans-retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4-HPR has been mostly investigated as an anti-cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4-HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4-HPR displays quite well-understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4-HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4-HPR analogues, followed by the biological evaluation of their anti-cancer and anti-obesity/diabetic properties. The click-type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3-L1 adipocytes during differentiation. Furthermore, it showed an IC50 of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF-7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [18F] 3b was successfully developed. Unfortunately, the stability of [18F] 3b turned out to be insufficient to pursue imaging studies. 相似文献
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Tatiana V. Rozhko Elena V. Nemtseva Maria V. Gardt Alexander V. Raikov Albert E. Lisitsa Gennadii A. Badun Nadezhda S. Kudryasheva 《International journal of molecular sciences》2020,21(22)
The present study considers a possible role of enzymatic reactions in the adaptive response of cells to the beta-emitting radionuclide tritium under conditions of low-dose exposures. Effects of tritiated water (HTO) on the reactions of bacterial luciferase and NAD(P)H:FMN-oxidoreductase, as well as a coupled system of these two reactions, were studied at radioactivity concentrations ≤ 200 MBq/L. Additionally, one of the simplest enzymatic reactions, photobiochemical proton transfer in Coelenteramide-containing Fluorescent Protein (CLM-FP), was also investigated. We found that HTO increased the activity of NAD(P)H:FMN-oxidoreductase at the initial stage of its reaction (by up to 230%); however, a rise of luciferase activity was moderate (<20%). The CLM-FP samples did not show any increase in the rate of the photobiochemical proton transfer under the exposure to HTO. The responses of the enzyme systems were compared to the ‘hormetic’ response of luminous marine bacterial cells studied earlier. We conclude that (1) the oxidoreductase reaction contributes significantly to the activation of the coupled enzyme system and bacterial cells by tritium, and (2) an increase in the organization level of biological systems promotes the hormesis phenomenon. 相似文献
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Dr. Mimouna Madaoui Dr. Olivier Vidal Albert Meyer Mathieu Noël Prof. Dr. Jean-Marie Lacroix Dr. Jean-Jacques Vasseur Prof. Dr. Alberto Marra Dr. François Morvan 《Chembiochem : a European journal of chemical biology》2020,21(23):3433-3448
Galacto- and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesised to target LecA and LecB lectins of Pseudomonas aeruginosa (PA) localised in the outer membrane and inside the bacterium. The resulting glycocluster–pseudosiderophore conjugates were evaluated as Trojan horses to cross the outer membrane of PA by iron transport. The data suggest that glycoclusters with catechol moieties are able to hijack the iron transport, whereas those with hydroxamates showed strong nonspecific interactions. Mono- and tricatechol galactoclusters ( G1C and G3C ) were evaluated as inhibitors of infection by PA in comparison with the free galactocluster ( G0 ). All of them exhibited an inhibitory effect between 46 to 75 % at 100 μM, with a higher potency than G0 . This result shows that LecA localised in the outer membrane of PA is involved in the infection mechanism. 相似文献
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During manufacturing of a component, cutting, turning, grinding, and milling operations are inevitable and these operations induce surface residual stresses. In this study, it is shown that, depending on the process employed for cutting, residual stresses generated at the cut surfaces can vary widely and they can, in turn, make the cut surfaces of austenitic stainless steel (SS) prone to stress corrosion cracking (SCC). An austenitic SS 304L plate was cut using three different procesess: bandsaw cutting, cutting using the cut-off wheel, and shearing. Surface residual stress measurement using the X-ray diffraction (XRD) technique is carried out close to the cutting edges and on the cross-section. SCC susceptibility studies were carried out as per ASTM G36 in 45% boiling magnesium chloride solution. Optical microscopic examination showed the presence of cracks, and confocal microscopy was used to measure the depth of cracks. The study confirmed that high tensile residual stresses present in the cut surfaces produced by cut-off wheel and shear cutting make the surfaces susceptible to SCC while the surfaces produced by bandsaw cutting are resistant to SCC. Hence, it is shown that there is a definite risk of SCC for product forms of austenitic SS with cut surfaces produced using cutting processes that generate high tensile residual stresses stored for a long period of time in a susceptible environment. 相似文献
10.
Gomes Heitor Murilo Read Jesse Bifet Albert Durrant Robert J. 《Knowledge and Information Systems》2021,63(7):1597-1625
Knowledge and Information Systems - Ensemble methods represent an effective way to solve supervised learning problems. Such methods are prevalent for learning from evolving data streams. One of the... 相似文献