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Search results for: microsomes
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Bacterial and Fungal Endophytic Microbiomes of Salicornia europaea
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Analysis of airborne metal containing particles with EDX/EDS detectorsin electron microscopes
PublicationIn years 2006-2010 particulate matter analysis was undertaken for dust samples collected from Gdansk and London area in orderto compare their morphology and composition. Part of those studies was devoted to analysis of particulate matter (PM) bearingmetals. Characterization of the morphology and size of the particles collected onto the filters was performed using a scanning electronmicroscope (SEM) and transmission electron microscope...
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How Does Salinity Shape Bacterial and Fungal Microbiomes of Alnus glutinosa Roots?
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Metabolic transformations of antitumor imidazoacridinone, C-1311, with microsomal fractions of rat and human liver
PublicationWykazano, że enzymatyczna aktywacja jest konieczna dla aktywności biologicznej pochodnej C-1311 (Symadex R), która znajduje się w II fazie badań klinicznych. Zbadano przemiany enzymatyczne tego związku w obecności frakcji enzymatycznych mikrosomalnych komórek wątroby szczura i ludzkiej. Badania te wykazały, że związek C-1311 jest bardziej podatny na przemiany w obecności frakcji mikrosomalnej niż S9 i cytozolowej. Inkubacja związku...
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Metabolic transformations of antitumor imidazoacridinone, C-1311, with microsomal fractions of rat and human liver
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Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes
PublicationThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase...
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Flavin monooxygenases, FMO1 and FMO3, not cytochrome p450 isoenzymes, contribute to metabolism of anti-tumour triazoloacridinone, C-1305, in liver microsomes and HepG2 cells.
PublicationCelem pracy było określenie roli wybranych enzymów frakcji mikrosomalnej komórek wątroby w metabolizmie pochodnej triazoloakrydonu, związku C-1305. Wykazano, że badana pochodna ulega transformacji wobec frakcji enzymów izolowanych z hepatocytów szczurzych i ludzkich oraz jest metabolizowana przez komórki linii HepG2. Badania wykazały ponadto, że enzymami odpowiedzialnymi za obserwowane przemiany były monooksygenazy flawinowe, FMO1...
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Enhancing chain-elongating microbiomes: Sequential fungi-bacteria cooperation for efficient food waste upgrading using endogenous electron donors
PublicationThe upgrading of organic waste such as food waste (FW) into medium-chain carboxylates (MCC) is within a bio-based circular economy concept. An efficient chain elongation (CE) microbiome is difficult to obtain, which normally requires long-term acclimatization and an exogenous supplement of electron donor (ED, especially ethanol). In this study, the CE microbiome was rapidly shaped within 18 days and an efficient endogenous ethanol-based...
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Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.
PublicationThe knowledge of the metabolic pathways and the biotransformation of new drugs is one of the major challenges in pharmaceutical research. It is crucial for elucidation of degradation routes of the new biologically active compounds, especially in the area of possible toxicity. Conventional in vitro drug metabolism studies are based on incubating drug candidate with e.g. hepatocytes or, most importantly, liver cell microsomes and...
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In vitro enzyme kinetics and NMR-based product elucidation for glutathione S-conjugation of the anticancer unsymmetrical bisacridine C-2028 in liver microsomes and cytosol: major role of glutathione S-transferase M1-1 isoenzyme
PublicationThis work is the next step in studying the interplay between C-2028 (anticancer-active unsymmetrical bisacridine developed in our group) and the glutathione S-transferase/glutathione (GST/GSH) system. Here, we analyzed the concentration- and pH-dependent GSH conjugation of C-2028 in rat liver microsomes and cytosol. We also applied three recombinant human GST isoenzymes, which altered expression was found in various tumors. The...
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Prediction of Overall In Vitro Microsomal Stability of Drug Candidates Based on Molecular Modeling and Support Vector Machines. Case Study of Novel Arylpiperazines Derivatives
PublicationOther than efficacy of interaction with the molecular target, metabolic stability is the primary factor responsible for the failure or success of a compound in the drug development pipeline. The ideal drug candidate should be stable enough to reach its therapeutic site of action. Despite many recent excellent achievements in the field of computational methods supporting drug metabolism studies, a well-recognized procedure to model...
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Role of Human UDP-Glucuronosyltransferases in the Biotransformation of the Triazoloacridinone and Imidazoacridinone Antitumor Agents C-1305 and C-1311 : Highly Selective Substrates for UGT1A10
Publication5-Diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311 (NSC-645809), is an antitumor agent shown to be effective against breast cancer in phase II clinical trials. A similar compound, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, shows high activity against experimental tumors and is expected to have even more beneficial pharmacological properties than C-1311. Previously published studies showed that these...
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Electrochemical simulation of enzymatic transformations studied for the selected antitumor acridine derivatives
PublicationThe elucidation of the metabolic pathways and the biotransformation mechanisms of potential drugs is a crucial point in drug development. It allows to know the activation routes of the new biologically active compounds, especially in respect to their possible toxicity. Generally, in vivo or in vitro experiments with liver microsomes or hepatocytes are performed. However, these testing schemes are tedious, time consuming and of...
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Phase I and phase II metabolism simulation of antitumor-active 2-hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.
PublicationHere, we report the metabolic profile and the results of associated metabolic studies of 2-hydroxyacridinone (2-OH-AC), the reference compound for antitumor-active imidazo- and triazoloacridinones. Electrochemistry coupled with mass spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC for the first time. The reactivity of 2-OH-AC products to biomolecules was also examined. The usefulness of the electrochemistry...
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Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7
PublicationBackground The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity. Methods UGT-mediated...
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Influence of Holes Manufacture Technology on Perforated Plate Aerodynamics
PublicationTranspiration flow is a very important and still open subject in many technical applications. Perforated walls are useful for the purpose of “flow control”, as well as for the cooling of walls and blades (effusive cooling) in gas turbines. We are still not able to include large numbers of holes in the numerical calculations and therefore we need physical models. Problems are related also to the quality of the holes in perforated...
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Comparison of the fracture toughness of pine wood determined on the basis of orthogonal linear cutting and frame sawing
PublicationIn this paper, the values of the fracture toughness of Scots pine determined by cutting tests are presented. The cutting tests were carried out using the samples of Scotch pine (Pinus sylvestris L.) from Pomeranian Region, Poland. These experiments were carried out on two research stands: orthogonal linear cutting tests were conducted using the microtome instrument and the frame saw PRW-15M was used for sawing tests. The values...
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Porous carbon derived from rice husks as sustainable bioresources: insights into the role of micro-/mesoporous hierarchy in hosting active species for lithium–sulphur batteries
PublicationThe exploration of natural resources as sustainable precursors affords a family of green materials. Exploring highly abundant and available biowaste precursors remaining from food processing throughout a scalable and cost-effective material synthesis path is highly important especially for new materials discovery in emerging energy storage technologies such as lithium–sulphur (Li–S) batteries. Herein, we have produced a series...
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Electrochemical and in silico approaches for liver metabolic oxidation of antitumor-active triazoloacridinone C -1305
Publication5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) is a promising antitumor compound developed in our laboratory. A better understanding of its metabolic transformations is still needed to explain the multidirectional mechanism of pharmacological action of triazoloacridinone derivatives at all. Thus, the aim of the current work was to predict oxidative pathways of C-1305 that would reflect its phase I metabolism. The...
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Synthesis, molecular structure, and metabolic stability of new series of N' -(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1 H -pyrazol-1-yl)amidine as potential anti-cancer agents
PublicationA series of new N'-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1H-pyrazol-1-yl)amidine derivatives have been synthesized and evaluated in vitro by MTT assays for their antiproliferative activity against cell lines of colon cancer HCT-116, cervical cancer HeLa and breast cancer MCF-7. The studied compounds display selective activity mainly against HCT-116 and HeLa cells. Thus, five compounds show selective cytotoxic...
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Synthesis, Molecular Structure, Metabolic Stability and QSAR Studies of a Novel Series of Anticancer N-Acylbenzenesulfonamides
PublicationA series of novel N-acyl-4-chloro-5-methyl-2-(R1-methylthio)benzenesulfonamides 18–47 have been synthesized by the reaction of N-[4-chloro-5-methyl-2-(R1-methylthio) benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids. Some of them showed anticancer activity toward the human cancer cell lines MCF-7, HCT-116 and HeLa, with the growth percentages (GPs) in the range from 7% to 46%. Quantitative structure-activity relationship...
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Influence of plasmon resonance on the luminescence of titanium dioxide thin films doped with rare earth ions
PublicationIn this work the study of the optical properties of europium doped titanium dioxide thin films (TiO2:Eu) enhanced by gold plasmonic nanostructures are presented. Plasmonic platforms were manufactured by thermal annealing of thin film of Au, deposited on a Corning glass substrate. As a result of thermal treatment, gold spherical nanostructures with average dimensions of 50 nm were obtained. Luminescent TiO2:Eu film was deposited...
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Leveraging spatio-temporal features for joint deblurring and segmentation of instruments in dental video microscopy
PublicationIn dentistry, microscopes have become indispensable optical devices for high-quality treatment and micro-invasive surgery, especially in the field of endodontics. Recent machine vision advances enable more advanced, real-time applications including but not limited to dental video deblurring and workflow analysis through relevant metadata obtained by instrument motion trajectories. To this end, the proposed work addresses dental...
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Atomic Force Microscope data post-processing algorithm for higher harmonics imaging
PublicationPrevious works have proved that higher harmonics topography imaging using atomic force microscope (AFM) can significantly enhanced its measurement capabilities. Integrated tools dedicated to most of microscopes allow to visualize the investigated surface only by one selected harmonic. Because of the different characteristics of a sample, scanning tip and the environment, appropriate harmonic selection is time consuming and requires...
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Nanotubular oxide layers and hydroxyapatite coatings on ‘Ti–13Zr–13Nb’ alloy
PublicationThe presented research was aimed to determine the mechanical properties of the nanotubular oxide layer covered with hydroxyapatite coating. The Ti–13Zr–13Nb alloy was oxidised in 1M phosphoric acid with an addition of 0?5% HF for HF solution at 20 V voltage. The electrochemically assisted deposition of hydroxyapatite was performed at cyclic polarisation in NH4H2PO4 and CaCl2 solution at 80uC. The mechanical properties were determined...
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CYP3A4-dependent cellular response does not relate to CYP3A4-catalysed metabolites of C-1748 and C-1305 acridine antitumor agents in HepG2 cells
PublicationHigh CYP3A4 expression sensitizes tumor cells to certain antitumor agents while for others it can lower their therapeutic ef fi cacy. We have elucidated the in fl uence of CYP3A4 overexpression on the cellular response induced by antitumor acridine derivatives, C-1305 and C-1748, in two hepatocellular carcinoma (HepG2) cell lines, Hep3A4 stably transfected with CYP3A4 isoenzyme, and HepC34 expressing empty vector. The compounds...
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Novel 2-alkythio-4-chloro-N-[imino(heteroaryl)methyl]benzenesulfonamide Derivatives: Synthesis, Molecular Structure, Anticancer Activity and Metabolic Stability
PublicationA series of novel 2-alkythio-4-chloro-N-[imino-(heteroaryl)methyl]benzenesulfonamide derivatives, 8–24, were synthesized in the reaction of the N-(benzenesulfonyl)cyanamide potassium salts 1–7 with the appropriate mercaptoheterocycles. All the synthesized compounds were evaluated for their anticancer activity in HeLa, HCT-116 and MCF-7 cell lines. The most promising compounds, 11–13, molecular hybrids containing benzenesulfonamide...
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Microporous N-Doped Carbon Obtained from Salt Melt Pyrolysis of Chitosan toward Supercapacitor and Oxygen Reduction Catalysts
PublicationThe direct carbonization of low-cost and abundant chitosan biopolymer in the presencesalt eutectics leads to highly microporous, N-doped nanostructures. The microporous structureeasily manufactured using eutectic mixture (ZnCl2 -KCl) and chitosan. Potassium ions here can act as an intercalating agent, leading to the formation of lamellar carbon sheets, whereas zinc chloride generates significant porosity. Here, we present an efficient...
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Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability
PublicationA series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27–60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 M. It was found that for the analogues 36–38...
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Degradation of implantable materials – in vivo and in vitro research
PublicationThe article concerns the biological and electrochemical degradation of metallic implants in vivo and in vitro studies. The in vivo research dealt with degradation of plates used to join bones, as well as endoprostheses. The most common damages were: metalosis, breaking in the microstructure changes, breaking in area of holes, as well as plastic deformation throughout the length of an implant. The material used for the research...
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Comparison of PM10 concentration in Gdansk and London using electron microscopy
PublicationParticulate matter (PM) has been considered as one of the most dangerous elements of air pollution. Multiply analytical methods are employed to identify the composition of particles present in the air. The theoretical part of this work is a description of different research centres all over the world where particulate matter is being analyzed using various techniques. The purpose of this project is to analyze and compare particles...
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Modulation of UDP-glucuronidation by acridinone antitumor agents C-1305 and C-1311 in HepG2 and HT29 cell lines, despite slight impact in noncellular systems.
PublicationBackground Among the studied antitumor acridinone derivatives developed in our laboratory, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) and 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) exhibited cytotoxic and antitumor properties against several cancer types and were selected to be evaluated in preclinical and early-phase clinical trials. In the present work, we investigated the impact of C-1305...
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Electrochemical simulation of metabolism for antitumor-active imidazoacridinone C-1311 and in silico prediction of drug metabolic reactions
PublicationThe metabolism of antitumor-active 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) has been investigated widely over the last decade but some aspects of molecular mechanisms of its metabolic transformation are still not explained. In the current work, we have reported a direct and rapid analytical tool for better prediction of C-1311 metabolism which is based on electrochemistry (EC) coupled on-line with electrospray...
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Novel insights into conjugation of antitumor-active unsymmetrical bisacridine C-2028 with glutathione: characteristics of non-enzymatic and glutathione S-transferase-mediated reactions
PublicationUnsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C 2028. GSH supplemented incubations of C-2028 with rat, but not with human, liver...
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Diminshed toxicity of C-1748, 4-methyl-9-hydroxyethylamino-1-nitroacridine, compared with its demethyl analog, C-857, corresponds to its resistance to metabolism in HepG2 cells
PublicationThe narrow "therapeutic window" of anti-tumour therapy may be the result of drug metabolism leading to the activation or detoxification of antitumour agents. The aim of this work is to examine (i) whether the diminished toxicity of a potent antitumour drug, C-1748, 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine, compared with its 4-demethyl analogue, C-857, results from the differences between the metabolic pathways for the...
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Effect of selective laser treatment on initiation of fatigue crack in the main part of an undercarriage drag strut
PublicationThis paper presents the results of material characterization and a fatigue test conducted for a laser-re-melted drag strut used in an aircraft landing gear. The drag strut was re-melted with a CO2 laser beam. Eight re-melted paths were made in the form of spiral lines along the axis of the drag strut. Next, the drag strut was subjected to variable loads on a testing machine simulating loads occurring when an aircraft lands. The...
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Pregnane X receptor dependent up-regulation of CYP2C9 and CYP3A4 in tumor cells by antitumor acridine agents, C-1748 and C-1305, selectively diminished under hypoxia
PublicationInduction of proteins involved in drug metabolism and in drug delivery has a significant impact on drug-drug interactions and on the final therapeutic effects. Two antitumor acridine derivatives selected for present studies, C-1748 (9-(2’-hydroxyethylamino)-4-methyl-1-nitroacridine) and C-1305 (5-dimethylaminopropylamino-8-hydroxy-triazoloacridinone), expressed high and low susceptibility to metabolic transformations with liver...
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Toxoplasma gondii Recombinant antigen AMA1: Diagnostic Utility of Protein Fragments for the Detection of IgG and IgM Antibodies
PublicationToxoplasma gondii is an important zoonotic protozoan that infects a wide variety of vertebrates as intermediate hosts. For this reason, the diagnosis of this disease is very important and requires continuous improvement. One possibility is to use recombinant antigens in serological tests. Apical membrane antigen 1 (AMA1), a protein located in specific secretory organelles (micronemes) of T. gondii, is very interesting in regard...
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Mechanism-based inactivation of human cytochrome P450 1A2 and 3A4 isoenzymes by antitumor triazoloacridinone C-1305.
Publication5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, is a promising antitumor therapeutic agent with high activity against several experimental tumors. It was determined to be a potent and selective inhibitor of liver microsomal and human recombinant cytochrome P450 (CYP) 1A2 and 3A4 isoenzymes. Therefore, C-1305 might modulate the effectiveness of other drugs used in multidrug therapy. The objective of this study was...
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Mass spectrometry based identification of geometric isomers during metabolic stability study of a new cytotoxic sulfonamide derivatives supported by quantitative structure-retention relationships
PublicationA set of 15 new sulphonamide derivatives, presenting antitumor activity have been subjected to a metabolic stability study. The results showed that besides products of biotransformation, some additional peaks occurred in chromatograms. Tandem mass spectrometry revealed the same mass and fragmentation pathway, suggesting that geometric isomerization occurred. Thus, to support this hypothesis, quantitative structure-retention relationships...
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Metabolism of antitumour agent 1-nitroacridine derivative, C-1748 in pancreatic cancer cell lines
PublicationPancreatic cancer has the highest mortality rate of all major cancers because of limited treatment options. Surgical removal of the tumour is possible only in its early stage, nevertheless the asymptomatic development very often makes unable an accurate diagnose. In the case of metastatic pancreatic cancer only chemotherapy, mainly with gemcitabine, can be offered to patients. However, common resistance towards gemcitabine imposes...
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Analysis of metals in air particles from Gdańsk and London with EDX/EDS detectors in electron microscope
PublicationElectron microscopy with energy dispersive X-ray spectrometry (EDX/EDS) is the example of non-destructive analytical method for surface elemental analysis, with a potential detection limit of 0.1-0.5 wt.% for most elements. A spatial resolution <10 nm can be achieved using this technique, which provides a basis for the generation of quantitative and qualitative elemental data for individual particles. In order to obtain quantitative...
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Exploring synergistic effects in physical-chemical activation of Acorus calamus for water treatment solutions
PublicationThe research proposed a novel method of obtaining sorption material from readily available Acorus calamus bio- mass through a combination of physical and chemical activation processes. The material with the highest specific surface area (1652 m2 g−1) was obtained by physical activation with CO2, followed by chemical activation with KOH. Reversing the order of activation methods resulted in a lower specific surface area (1014 m2...
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Genotoxic properties of glucosinolates and isothiocyanates present in Brassica vegetables
PublicationThe bioactive phytochemicals found in Brassica vegetables, in this number glucosinolates (GLS), as well as products of their degradation such as isothiocyanates (ITC) and indoles, are regarded as the most promising chemopreventive compounds. These secondary metabolites display stron antibiological activity and constitute defence system preventing the development of agrophages attacking Brassica plants. Such properties suggest...
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The II phase metabolism of endogenous and exogenous compounds, including antitumor chemotherapeutics
PublicationThe II phase metabolism, it is a set of metabolism and excretion pathways of endogenous as well as exogenous compounds including xenobiotics. UDP-glucuronyltransferases (UGTs; EC 2.4.1.17) are the most crucial representatives of II phase enzymes, which are responsible for the transformation of bilirubine and bile acids, steroids and thyroid hormones and lipids. Exogenous compounds, including drugs, carcinogens, environmental pollutants...
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Novel Resveratrol-Based Substrates for Human Hepatic, Renal, and Intestinal UDP-Glucuronosyltransferases
PublicationTrans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anti-carcinogenic, and anti-aging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-Glucuronosyltransferases (UGTs). The aim of the current study was to test the hypothesis that the limited bioavailability of tRes can be improved by modifying its structure to create analogs...
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Method for prediction of the frost resistance ability of air‐entrained concrete based on the 3D air void characteristics by x‐ray micro‐CT
PublicationIn modern construction, one of the most important factors in the execution of contracts is time. Standard procedures for assessing the frost resistance or concrete are usually very time-consuming and can take up to 40 days. The current paper is experimentally and practically oriented. It presents an alternative testing method, based on air void network, that allows to assess the frost resistance of concrete within just a few days...
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Wire Arc Additive Manufactured Mild Steel and Austenitic Stainless Steel Components: Microstructure, Mechanical Properties and Residual Stresses
PublicationWire arc additive manufacturing (WAAM) is an additive manufacturing process based on the arc welding process in which wire is melted by an electric arc and deposited layer by layer. Due to the cost and rate benefits over powder-based additive manufacturing technologies and other alternative heat sources such as laser and electron beams, the process is currently receiving much attention in the industrial production sector. The gas...
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Ensembling noisy segmentation masks of blurred sperm images
PublicationBackground: Sperm tail morphology and motility have been demonstrated to be important factors in determining sperm quality for in vitro fertilization. However, many existing computer-aided sperm analysis systems leave the sperm tail out of the analysis, as detecting a few tail pixels is challenging. Moreover, some publicly available datasets for classifying morphological defects contain images limited only to the sperm head. This...