Search results for: FRAGMENTATION PATHWAYS
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Photophysics of Ru(II) Dyads Derived from Pyrenyl-Substitued Imidazo[4,5-f][1,10]phenanthroline Ligands.
PublicationThe photophysics of a series of Ru(II) dyads based on the 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]-phenanthroline ligand was investigated. The ability of these metal complexes to intercalate DNA and induce cell death upon photoactivation makes them attractive photosensitizers for a range of photobiological applications, including photodynamic therapy. In the present study, time-resolved transient absorption and emission spectroscopy...
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Fecal indicators resistance to antimicrobial agents present in municipal wastewater
PublicationIn this study removal rate of six antimicrobial compounds (belonging to folate pathway inhibitors and macrolides class) was analyzed in processes of local wastewater treatment plant (WWTP) together with susceptibility patterns of erythromycin (E) resistant Enterococcus spp. and trimethoprim/sulfamethoxazole (SXT) resistant Escherichia coli. According to the obtained data, six of tested antimicrobial agents, namely erythromycin,...
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Modeling the global atmospheric transport and deposition of mercury to the Great Lakes
PublicationMercury contamination in the Great Lakes continues to have important public health and wildlife ecotoxicology impacts, and atmospheric deposition is a significant ongoing loading pathway. The objective of this study was to estimate the amount and source-attribution for atmospheric mercury deposition to each lake, information needed to prioritize amelioration efforts. A new global, Eulerian version of the HYSPLIT-Hg model was used...
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Nitrogen transformations and mass balances in anaerobic/anoxic/aerobic batch experiments with full-scale biomasses from BNR activated sludge systems.
PublicationThe aim of this study was to investigate nitrogen mass balances occurring inside full-scale BNR activated sludge systems, with special attention to colloidal and dissolved organic nitrogen (CON and DON) transformations. For this purpose, laboratory experiments were carried out using process biomass from two large BNR plants in northern Poland. Two parallel batch reactors were operated in a 3-phase (anaerobic/anoxic/aerobic) cycle....
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Nitrogen transformations and mass balances in anaerobic/anoxic/aerobic batch experiments with full-scale biomasses from BNR activated sludge systems.
PublicationThe aim of this study was to investigate nitrogen mass balances occurring inside full-scale BNR activated sludge systems, with special attention to colloidal and dissolved organic nitrogen (CON and DON) transformations. For this purpose, laboratory experiments were carried out using process biomass from two large BNR plants in northern Poland. Two parallel batch reactors were operated in a 3-phase (anaerobic/anoxic/aerobic) cycle....
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Importance of the combined effects of dissolved oxygen and pH on optimization of nitrogen removal in anammox-enriched granular sludge
PublicationThe combined effects of dissolved oxygen (DO) and pH on nitrogen removal were investigated in a laboratory-scale sequencing batch reactor (SBR) with anammox-enriched granular sludge obtained from a nitritation/anammox system. The highest specific nitrogen removal rate (SNRR) (1.1 gN gVSS−1 d−1) was observed under non-aerated conditions, resulting in the nitrogen removal efficiency of 81.6%. Although nitrogen removal was readily...
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Ti/TiO2 nanotubes sensitized PbS quantum dots as photoelectrodes applied for decomposition of anticancer drugs under simulated solar energy
PublicationOne of the challenges in research into photoelectrocatalytic (PEC) degradation of pollutants is finding the appropriate photoanode material, which has a significant impact on the process efficiency. Among all others, photoelectrodes based on an ordered TiO2 nanotube arrays are a promising material due to well-developed surface area and efficient charge separation. To increase the PEC activity of this material, the SILAR method was...
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Light‐Driven Multi‐Charge Separation in a Push‐Pull Ruthenium‐Based Photosensitizer – Assessed by RASSCF and TDDFT Simulations
PublicationThe performance of photosensitizers in the field of, for example, solar energy conversion, relies on their light-harvesting efficiency in the visible region, population of long-lived charge separated intermediates, as well as their charge-accumulation capacity amongst other properties. In this computational study, we investigate the photophysical properties of a bis(bipyridyl)ruthenium(II)-based black dye (Ru) incorporating a chromophoric...
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Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells
PublicationAndrogen receptor (AR) plays a crutial role in prostate cancer (PCa) development and metastasis. Here, we reported potent anti-PCa activity of a small molecule imidazoacridinone C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased AR binding to prostate-specific antigen (PSA)...
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Impact of soluble organic matter and particulate organic matter on anammox system: Performance, microbial community and N2O production
PublicationIn this study, the effects of soluble readily biodegradable COD (sCOD) and particulate slowly biodegradable COD (pCOD) on anammox process were investigated. The results of the longterm experiment indicated that a low sCOD/N ratio of 0.5 could accelerate the anammox and denitrification activity, to reach as high as 84.9% ±2.8% TN removal efficiency. Partial denitrification-anammox (PDN/anammox) and denitrification were proposed...
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Caffeine Inhibits Differentiation Of Lung Cancer Stem Cells By Modulating Their Respiratory Metabolism
PublicationIt is ell established that many tumor types contain a fraction of cells, with stem cell-like properties, called cancer stem cells (CSCs), that are resistant to apoptosis induced by therapeutic agents. The presence of CSCs may explain why a standard anticancer treatment, that eliminates only differentiated cancer cells, does not lead to cancer cure.We previously showed the existence of caffeine-sensitive mechanism that controls...
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Reactions of the Lithiated DiphosphinetBu2P-P(SiMe3)Li with [(η6-C6H6)RuCl2]2in the Presence of Tertiary Phosphines
PublicationtBu2P–P(SiMe3)Li reacted with [(η6-C6H6)RuCl2]2at–40 °C in the presence of PR3(PR3=PEt3,PEt2Ph, PEtPh2) by the nucleophilic addition of the tBu2P–P(SiMe3) moiety to the benzene ring to yield solely the complexes [(R3P)2Ru(Cl)-{η5-C6H6(Me3SiP–PtBu2)}] (1). These products decomposed slowly at ambient temperature to yield benzene, Ru clusters, and small amounts of the dinuclear ruthenium complexes [{(R3P)2Ru}2(μ,η2:2-P2)2Ru(PR3)2](Ru–Ru)(6)....
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Video Semantic Analysis Framework based on Run-time Production Rules - Towards Cognitive Vision
PublicationThis paper proposes a service-oriented architecture for video analysis which separates object detection from event recognition. Our aim is to introduce new tools to be considered in the pathway towards Cognitive Vision as a support for classical Computer Vision techniques that have been broadly used by the scientific community. In the article, we particularly focus in solving some of the reported scalability issues found in current...
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Consciousness Study of Subjects with Unresponsive Wakefulness Syndrome Employing Multimodal Interfaces
PublicationThe paper presents a novel multimodal-based methodology for consciousness study of individuals with unresponsive wakefulness syndrome. Two interfaces were employed in the experiments: eye gaze tracking system – CyberEye developed at the Multimedia Systems Department, and EEG device with electrode placement in the international 10-20 standard. It was a pilot study for checking if it is possible to determine objective methods based...
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Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity
PublicationColorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this study, we synthesized a series of novel tetrahydroquinolinones and assessed their ability to inhibit CRC growth and proliferation by evoking...
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Soft skills among academics: Five theoretically informed lessons for current times
PublicationRESEARCH OBJECTIVE: The aim of this article is to provide a comprehensive examination of the role of soft skills among academics in the context of the evolving higher-education landscape. THE RESEARCH PROBLEM AND METHODS: We use a scoping review of existing literature to discuss the importance of soft skills in academia. Through critical analysis and synthesis, we identify patterns and gaps in current knowledge and develop five...
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Distinct cellular uptake patterns of two anticancer unsymmetrical bisacridines and their metabolic transformation in tumor cells.
PublicationUnsymmetrical bisacridines (UAs) represent a novel class of anticancer agents. Their high cytotoxicity towards multiple human cancer cell lines and inhibition of human tumor xenograft growth in nude mice signal their potential for cancer treatment. Therefore, the mechanism of their strong biological activity is broadly investigated. Here, we explore the efflux and metabolism of UAs, as both strongly contribute to the development...
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A Review on Metal–Organic Framework as a Promising Catalyst for Biodiesel Production ENERGY & FUELS
PublicationThe rapid depletion of fossil-derived fuels along with rising environmental pollution have motivated academics and manufacturers to pursue more environmentally friendly and sustainable energy options in today’s globe. Biodiesel has developed as an ecologically favorable alternative. However, the mass manufacturing of biodiesel on an industrial scale confronts substantial cost and pricing challenges. To address this issue, high-efficiency...
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Pharmaceuticals wastewater treatment via different advanced oxidation processes: Reaction mechanism, operational factors, toxicities, and cost evaluation – A review
PublicationPharmaceuticals comprises different drugs used for treating different infections in human being and animals. The huge quantities of pharmaceuticals used are found to discharge into different water resources and cause different health and environmental problems. The continuous and large-scale discharge of pharmaceuticals increases their persistency which can consequently make them more toxic. The different advanced oxidation processes...
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Long-term performance and microbial characteristics of the anammox-enriched granular sludge cultivated in a bench-scale sequencing batch reactor
PublicationThe anammox-enriched granular sludge was successfully formed during the long-term biogranulation experiment lasting over 330 days. The cultivation was conducted at 30 ◦C in a 10-L sequencing batch reactor (SBR) fed with synthetic medium containing ammonia, nitrite and trace elements. The properties of the developed granules were investigated in terms of the biomass activity (including the growth rate of anammox bacteria), size...
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Assessment of cytotoxic and endocrine potential of selected xenobiotics commonly present in food products
PublicationMore and more increased intensity of anthropopressure processes can be observed, among other things, in the release of great quantities of synthetic substances into the environment, including the Endocrine Disrupting Compounds (EDC). A vast number of chemical substances is considered to belong to the this group, including substances which occur naturally in the environment, such as mycotoxins and phytoestrogens, and substances...
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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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sp2-rich dendrite-like carbon nanowalls as effective electrode for environmental monitoring of explosive nitroaromatic
PublicationNitroaromatic compounds are commonly used explosive materials that pose a risk to human health and ecosystems due to their acute toxicity and carcinogenicity. Nitroaromatics have numerous pathways into the environment via discarded munitions (e.g. into the Baltic Sea after World War II), after use in mining operations, and in industrial run-off from factories producing these compounds (which are produced across the world to date)....
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AGREEMIP: The Analytical Greenness Assessment Tool for Molecularly Imprinted Polymers Synthesis
PublicationMolecular imprinting technology is well established in areas where a high selectivity is required, such as catalysis, sensing, and separations/sample preparation. However, according to the Principles of Green Chemistry, it is evident that the various steps required to obtain molecularly imprinted polymers (MIPs) are far from ideal. In this regard, greener alternatives to the synthesis of MIPs have been proposed in recent years....
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Optimization of the Aeration Strategies in a Deammonification Sequencing Batch Reactor for Efficient Nitrogen Removal and Mitigation of N2O Production
PublicationIn deammonification systems, nitrite-oxidizing bacteria (NOB) suppression and nitrous oxide (N2O) mitigation are two important operational objectives. To carry out this multivariable analysis of response, a comprehensive model for the N cycle was developed and evaluated against experimental data from a laboratory-scale deammonification granular sludge sequencing batch reactor. Different aeration strategies were tested, and the manipulated...
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High-performance activation of ozone by sonocavitation for BTEX degradation in water
PublicationThis work presents a novel advanced oxidation process (AOP) for degradation of emerging organic pollutants – benzene, toluene, ethylbenzene and xylenes (BTEXs) in water. A comparative study was performed for sonocavitation assisted ozonation under 40–120 kHz and 80–200 kHz dual frequency ultrasounds (DFUS). Based on the obtained results, the combination of 40–120 kHz i.e., low-frequency US (LFDUS) with O3 exhibited excellent oxidation...
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Biomass in biogas production: Pretreatment and codigestion
PublicationGlobally, there is increasing awareness that the implementation of ‘waste to energy’ technology is one of the best means to achieve sustainable energy development. The most popular approach is the conversion of organic-rich compounds into clean and renewable products by anaerobic digestion (AD). Biogas can be produced from agricultural residues, municipal/industrial biowastes, and sustainable biomass, especially materials that...
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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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Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells
PublicationNanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry...
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Hybrid metal and non-metal activation of Oxone by magnetite nanostructures co-immobilized with nano-carbon black to degrade tetracycline: Fenton and electrochemical enhancement with bio-assay
PublicationElectrochemically synthesized magnetite nanostructures (ESMNPs) as a metal activator and nano-carbon black (NCB) as a non-metal activator were co-immobilized by alginate natural polymer to activate Oxone for the degradation of tetracycline (TC) antibiotic. The formation of sulfate radical was indirectly confirmed during the Oxone/ESMNPs/NCB/alginate process via the addition of scavenging compounds. This study revealed the high...
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Foliate-Targeting Quantum Dots-β-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells
PublicationTargeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and β-cyclodextrin (β-CD) with foliate-targeting properties for the delivery of anticancer compound...
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Enhanced susceptibility of SARS-CoV-2 spike RBD protein assay targeted by cellular receptors ACE2 and CD147: Multivariate data analysis of multisine impedimetric response
PublicationSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of spike protein to the host cell surface-expressing angiotensin-converting enzyme 2 (ACE2) or by endocytosis mediated by extracellular matrix metalloproteinase inducer (CD147). We present extended statistical studies of the multisine dynamic electrochemical impedance spectroscopy (DEIS) revealing interactions between Spike RBD and...
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Design of Resilient Vehicle-to-Infrastructure Systems
PublicationVehicular ad hoc networks (VANETs) have recently gained noticeable attention due to advantages in improving road traffic safety, shaping the road traffic and providing infotainment opportunities to travellers. However, transmission characteristics following from the IEEE 802.11p standard and the high mobility of VANET nodes remarkably reduce the lifetime, reach and capacity of wireless links, and often lead to simultaneous disruptions...
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Structure, Mechanical, Thermal and Fire Behavior Assessments of Environmentally Friendly Crude Glycerol-Based Rigid Polyisocyanurate Foams
PublicationIn this work, rigid polyisocyanurate foams were prepared at partial substitution (0–70 wt%) of commercially available petrochemical polyol, with previously synthesized biopolyol based on crude glycerol and castor oil. Influence of the biopolyol content on morphology, chemical structure, static and dynamic mechanical properties, thermal insulation properties, thermal stability and flammability was investigated. Incorporation of...
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Mathematical modelling of two-step nitrification-denitrification for treatment of sludge digester liquors: influence of nitrite (NO2-N) on the process kinetics
PublicationSeparate treatment of the sludge digester liquors is an alternative for expansion of the mainstream treatment line. In order to reduce the oxygen demand for nitrification and organic carbon demand for denitrification, a shortcut in the nitrogen conversion pathway has been promoted in recent years, i.e. nitrification-denitrification via NO2-N instead of NO3-N. Although NO2-N is a common intermediate product of nitrification and...
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Chitosan-based electrospun nanofibers for encapsulating food bioactive ingredients: A review
PublicationToday, society has been more aware of healthy food products and related items containing bioactive compounds, which potentially contribute to human health. Unfortunately, the long-term stability and bioactivity of biologically active compounds against environmental factors compromise their target and effective action. In this way, lab-designed vehicles, such as nanoparticles and nanofibers, provide enough properties for their preservation...
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The relationship between standard reduction potentials of catechins and biological activities involved in redox control
PublicationRedox homeostasis involves factors that ensure proper function of cells. The excess reactive oxygen species (ROS) leads to oxidative stress and increased risk of oxidative damage to cellular components. In contrast, upon reductive stress, insufficient ROS abundance may result in faulty cell signalling. It may be expected that dietary antioxidants, depending on their standard reduction potentials (E°), will affect both scenarios....
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Activated sodium percarbonate-ozone (SPC/O3) hybrid hydrodynamic cavitation system for advanced oxidation processes (AOPs) of 1,4-dioxane in water
PublicationHydrodynamic cavitation (HC) was employed to activate sodium percarbonate (SPC) and ozone (O3) to degrade recalcitrant 1,4-dioxane. The degradation efficiency > 99 % with a rate constant of 4.04 × 10−2 min−1 was achieved in 120 min under the optimal conditions of cavitation number (Cv) 0.27, pH 5, molar ratio of oxidant to pollutant (rox) 8, ozone dose of 0.86 g h−1 under 25 ± 2 °C with initial concentration of 1,4-dioxane 100...
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Identification of novel halogenated naturally occurring compounds in marine biota by high-resolution mass spectrometry and combined screening approaches
PublicationMarine animals, plants or bacteria are a source of bioactive naturally-occurring halogenated compounds (NHCs) such as bromophenols (BPs), bromoanisoles (BAs) and hydroxylated or methoxylated analogues of polybrominated diphenyl ethers (HO-PBDEs, MeO-PBDEs) and bromobiphenyls (HO-BBs, MeO-BBs). This study applied a comprehensive screening approach using liquid chromatography high-resolution mass spectrometry and combining target,...
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O07 Filaggrin insufficiency renders keratinocyte-derived small extracellular vesicles capable of affecting CD1a-mediated T-cell responses and promoting allergic inflammation
PublicationThe association between FLG loss-of-function mutations and the development of atopic dermatitis (AD) indicates that filaggrin is critical to skin barrier function; the mutations are also linked to additional allergic manifestations, but it is unknown how the skin may influence inflammation in distant tissues. Here we investigated the impact of filaggrin insufficiency on keratinocyte-derived exosome-enriched small extracellular...
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The compositional space of exhaled breath condensate and its link to the human breath volatilome
PublicationBreath analysis is commonly understood to target gaseous or volatile organic compounds (VOCs) for the characterization of different pathologies. Targeted analysis is most effective if a working hypothesis can be based on a plethora of data. The recently published volatilome builds an optimal basis for organizing powerful target sets. However, the origin and pathways of biosynthesis of many VOCs are not known, which complicates...
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Bioaccumulation of Metals in Tissues of Marine Animals, Part I: the Role and Impact of Heavy Metals on Organisms
PublicationHeavy metals contribute to the anthropogenic contamination of marine ecosystems. Some of them are essential to the life processes of organisms; others are toxic, even at low concentrations. They penetrate organisms via food, respiratory pathways or the skin. The extent to which metals penetrate organisms is measured by the bioconcentration and bioaccumulation factors and also by their transport between organisms at different trophic...
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Application of dynamic headspace and gas chromatography coupled to mass spectrometry (DHS-GC-MS) for the determination of oxygenated volatile organic compounds in refinery effluents
PublicationThe paper presents a new procedure for the determination of oxygenated volatile organic compounds (O-VOCs) in postoxidative effluents from the production of petroleum asphalt using dynamic headspace coupled to gas chromatography-mass spectrometry in the selected ion monitoring (SIM) mode (DHSGC-MS). Among the GC capillary columns tested, a polar SLB-IL111 column with the ionic liquid stationary phase was found to be superior due...
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3-MCPD: A worldwide problem of food chemistry
Publication3-MCPD is a heat-induced food contaminant which has been widely investigated for decades. This paper presents an overview of current knowledge about 3-MCPD including its formation routes, occurrence in various foodstuffs, analytical approach, toxicological aspects and future research perspectives. So far 3-MCPD was determined in its free and bound form in thermally-treated foods, edible oils and fats, and infant foods including...
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Hydroxyl and sulfate radical-based degradation of ciprofloxacin using UV-C and/or Fe2+-catalyzed peroxymonosulfate: Effects of process parameters and toxicity evaluation
PublicationCiprofloxacin (CIP) is a valuable antibiotic and discharged in huge quantities in aquatic environment. Different •OH and SO4•−-based advanced oxidation technologies (AOTs), e.g., Fe2+/PMS, UV-C/PMS, and UV-C/Fe2+/PMS are developed for treatment of CIP. The removal of CIP by Fe2+/PMS, UV-C/PMS and UV-C/Fe2+/PMS was 63, 77, and 87 %, respectively, under identical conditions which showed better performance of UV-C/Fe2+/PMS. The UV-C/Fe2+/PMS...
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Impact of Climate Change on Water Sources and River‐Floodplain Mixing in the Natural Wetland Floodplain of Biebrza River
PublicationThe origins of river and floodplain waters (groundwater, rainfall, and snowmelt) and their extent during overbank flow events strongly impact ecological processes such as denitrification and vegetation development. However, the long-term sensitivity of floodplain water signatures to climate change remains elusive. We examined how the integrated hydrological model HydroGeoSphere and the Hydraulic Mixing-Cell method could help us...
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Non-Isocyanate-Based Waterborne Polyurethanes
PublicationNon-isocyanate polyurethanes (NIPUs) are a greener alternative for the conventional polyurethanes synthesized using toxic and moisture-sensitive di- or polyisocyanates. The most often described method of NIPU synthesis involves the reaction of five-membered cyclic carbonates with amines, and resulting polymers containing primary and secondary hydroxyl groups (so they are also known as polyhydroxyurethanes), which can be further...
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The coexistence and competition of canonical and comammox nitrite oxidizing bacteria in a nitrifying activated sludge system – Experimental observations and simulation studies
PublicationThe second step of nitrification can be mediated by nitrite oxidizing bacteria (NOB), i.e. Nitrospira and Nitrobacter, with different characteristics in terms of the r/K theory. In this study, an activated sludge model was developed to account for competition between two groups of canonical NOB and comammox bacteria. Heterotrophic denitrification on soluble microbial products was also incorporated into the model. Four 5-week washout...
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Implementation of advanced micropollutants removal technologies in wastewater treatment plants (WWTPs) - Examples and challenges based on selected EU countries
PublicationThe accumulation of micropollutants (MPs) and their increasing concentration in the aquatic environment are an emerging issue for water quality in the world. The complex web of exposure pathways, as well as the variety in the chemical structure and potency of MPs, represents enormous challenges for researchers and policy initiatives. In order to manage MPs, it has to be decided which of them have to be reduced and to what extent,...
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Bortezomib induces methylation changes in neuroblastoma cells that appear to play a significant role in resistance development to this compound
PublicationThe anticancer activity of bortezomib (BTZ) has been increasingly studied in a number of indications and promising results for the use of this treatment have been shown in neuroblastoma. As BTZ treatment is usually administered in cycles, the development of resistance and side effects in patients undergoing therapy with BTZ remains a major challenge for the clinical usage of this compound. Common resistance development also means...