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Search results for: UGT METABOLIC TRANSFORMATIONS
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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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The studies of imidazoacridinone antitumor agent, C-1311, in the field of metabolic transformations with cytochrome P450 isoenzymes
PublicationPraca zawiera wyniki badań metabolicznej transformacji przeciwnowotworowej pochodnej imidazoakrydonu C-1311 wobec rekombinantowych ludzkich izoenzymów P450. Związek nie ulegał transformacji w badanych warunkach, natomiast wykazano, że ma zdolność hamowania aktywności izoezymów CYP1A2 i CYP3A4.
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Chiral Pyrazolo[4,3-e][1,2,4]triazine Sulfonamides—Their Biological Activity, Lipophilicity, Protein Affinity, and Metabolic Transformations
PublicationReferring to our previous laboratory results related to the tyrosinase and urease inhibition by pyrazolo[4,3-e][1,2,4]triazine sulfonamides, we examined here in silico the mechanism of action at the molecular level of the investigated pyrazolotriazine sulfonamides by the molecular docking method. The studied compounds being evaluated for their cytotoxic effect against cancer cell lines (MCF-7, K-562) and for recombinant Abl and...
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Metabolic Profiles of New Unsymmetrical Bisacridine Antitumor Agents in Electrochemical and Enzymatic Noncellular Systems and in Tumor Cells
PublicationNew unsymmetrical bisacridines (UAs) demonstrated high activity not only against a set of tumor cell lines but also against human tumor xenografts in nude mice. Representative UA compounds, named C-2028, C-2045 and C-2053, were characterized in respect to their physicochemical properties and the following studies aimed to elucidate the role of metabolic transformations in UAs action. We demonstrated with phase I and phase II enzymes...
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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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Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.
PublicationThe acridinone derivates C-1305 and C-1311 are promising antitumor agents with high activity against several experimental cellular and tumor models and which are under evaluation in pre-clinical and early phase clinical trials. Recent evidence from our laboratories has indicated that both compounds were conjugated by several UGT isoforms with the most active being extrahepatic UGT1A10. The present studies were designed to test...
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Electrochemical simulation of metabolic reduction and conjugation reactions of unsymmetrical bisacridine antitumor agents, C-2028 and C-2053
PublicationElectrochemistry (EC) coupled with analysis techniques such as liquid chromatography (LC) and mass spectrometry (MS) has been developed as a powerful tool for drug metabolism simulation. The application of EC in metabolic studies is particularly favourable due to the low matrix contribution compared to in vitro or in vivo biological models. In this paper, the EC(/LC)/MS system was applied to simulate phase I metabolism of the representative...
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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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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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The impact of lipophilicity on environmental processes, drug delivery and bioavailability of food components
PublicationLipophilic properties of the compound allow to predict its fate in living organisms and to propose the models of chemicals transport and accumulation in the ecosystem. Lipophilicity is also useful as the characteristic of chemicals in respect to their optimal attributes for specific biological and non-biological tasks. The lipophilicity descriptors define the potency of endo- and xenobiotics to metabolic transformations and their...
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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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Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis
PublicationUnsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic...
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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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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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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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URBAN TRANSFORMATIONS
PublicationMentor&Student Research Lab is a common initiative of the members of Gdańsk University of Technology student research club, Urban Revolution Laboratory LEM-ur and International Society of City and Regional Planners ISOCARP. The aim of the event was to promote collaboration of professionals and the student in the area of research on the city and the region. During three months' Workshop five groups leaded by ISOCARP Mentors performed...
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On Kinetic Nature of Hysteresis Phenomena in Stress-Induced Phase Transformations
PublicationA simplest model is developed which demonstrates that hysteresis phenomena in stress-induced phase transformations may have a kinetic nature and follow from the discrepancy between strain rate and characteristic rate of the new phase growth.
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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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Mentor&Student Research Lab – Urban Transformations – Introduction
PublicationMentor&Student Research Lab - "Urban Transformations" is a common initiative of the members of Gdańsk University of Technology student research club, Urban Revolution Laboratory and the International Society of City and Regional Planners ISOCARP. The aim of the event was to promote collaboration of professionals and the students in the area of research on the city and the region. During three months’ Workshop five groups leaded...
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THE PANTOGRAPH AND ITS GEOMETRIC TRANSFORMATIONS - A FORMER POPULAR TOOL FOR COPYING AND SCALING
PublicationDevelopment of digital technology has resulted in significant transformations of designer workshops. Computer applications replaced the previously existing tools and methods for drawing up of projects. Professional, sophisticated drawing instruments and tools for manual plotting, as well as basic drawing aids, have gradually fallen into oblivion and become relicts of a bygone era - the objects of collectors' interest. Gdansk University...
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Influence of image transformations and quality degradations on SURF detector efficiency
PublicationA method for task-oriented examination of SURF keypoint detector accuracy is presented in the paper. It consists of generating test images, based on a given exemplar, processed by affine transformations: random rotation and scaling, and varying degree of degradations: darkening, blurring, noising, and compression. Details of applied degradation procedure are presented, followed by essentials of SURF-based images matching. A distance...
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Bisphenol A analogues and metabolic syndrome in women with polycystic ovary syndrome
PublicationBisphenols (BPs) have become a chemical group of special interest due to their ability to interfere with the endocrine system and their ubiquitous presence in the environment. As some of them possess mild estrogenic and anti-androgenic effects, they might be associated with the diagnosis of polycystic ovary syndrome (PCOS). Acting on multiple tissues, BPs exposure may lead to metabolic derangements characteristic for metabolic...
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IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection
PublicationCellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favors the envelopment of newly synthesized viral particles. As all cells are equipped with restriction factors (RFs) able to exert a protective effect against invading pathogens, we asked whether a similar defense mechanism would also be in place to preserve the metabolic compartment from HCMV...
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Pathogenesis of psoriasis in the “omic” era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis
PublicationPsoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and...
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MRI assessment of ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with the presence of central obesity and metabolic syndrome
PublicationPurpose: Obesity, defined as a body mass index (BMI) exceeding 30 kg/m2, is a serious health problem, which can be called an epidemic on a global scale and is one of the most important causes of preventable death. The aim of this study was to assess ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with metabolic syndrome (MetS). Patients and methods:...
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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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Document transformations for data processing in information systems
PublicationAtrykuł przedstawia podejście do automatyzacji transformacjidokumentów użytkownika bazujące na technologii XML. W artykuleprzedstawiony został system Endoscopy Recommender System.ERS wykorzystuje dedykowane transformacje XML Schema do Java, Java dodokumentów XML. Dzięki tym transformacjom procesy pobierania iprzechowywania danych zostały w pełni zautomatyzowane.Zaimplementowane podejście XML data binding umożliwia walidacjępodstawowych...
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Pseudopotentials via Moutard Transformations and Differential Geometry
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Metabolic syndrome: a psychiatric outlook
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Elementary, binary and schlesinger transformations in differential ring geometry
PublicationPrzedstawiono elementarne przekształcenia Darboux dla rozwiązania równań różniczkowych w pierścieniu. Przedstawiono nowe rozwiązania za pomocą przekształcenia Shlesingera jako granicy elementarnego pD.
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Reduction restrictions of Darboux and Laplace transformations for the Goursat equation
PublicationZredukowane przekształcenia Darboux i Laplace`a dla równania Goursata zastosowane do rozwiązywania problemów nieliniowych i geometrycznych. Podaje się nowe rozwiązania równań KdV-MKdV w przestrzeni 2+1.
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Health economy of the metabolic syndrome pandemic
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Comparison of Renewable Energy Sources in ‘New’ EU Member States in the Context of National Energy Transformations
PublicationThe European Union strives to create sustainable, low-carbon economies; therefore, energy policies of all member states should move towards renewable energy sources (RES). That concerns also the so-called new EU member states. These countries, on the one hand, are characterized by significant historical similarities in terms of post-communist legacy and adopted development strategies linked with the EU membership, and on the other...
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Metabolic activity of tree saps of different origin towards cultured human cells in the light of grade correspondence analysis and multiple regression modeling
PublicationTree saps are nourishing biological media commonly used for beverage and syrup production. Although the nutritional aspect of tree saps is widely acknowledged, the exact relationship between the sap composition, origin, and effect on the metabolic rate of human cells is still elusive. Thus, we collected saps from seven different tree species and conducted composition-activity analysis. Saps from trees of Betulaceae, but not from...
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Public art in the era of urban transformations. A case study of Eduardo Paolozzi’s artistic output in Edinburgh and in London
PublicationUrban space dedicated to cultural life, entertainment or business is currently exposed to dynamic urbanistic transformations. Monumental works of art within the boundaries of cities, for years embedded in the urban landscape and awareness of viewers, are moved to other places or even destroyed. Decisions about a change of their location and context, which are fundamental aspects for the impression made by a given work of art, cause...
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Searching for the primary metabolic alterations of polycystic ovary syndrome by application of the untargeted metabolomics approach
PublicationDespite a large number of studies, the pathogenesis of polycystic ovary syndrome (PCOS) still remains unexplained. In light of ambiguous observations reported in metabolomics, there is a need to carry out studies focusing on confirming the discriminating power of the proposed metabolomics biomarkers. Our research aimed to perform a validation study of metabolites detected in our previous study from serum samples, on the new set...
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Modeling the Structure, Dynamics, and Transformations of Proteins with the UNRES Force Field
PublicationThe physics-based united-residue (UNRES) model of proteins ( www.unres.pl ) has been designed to carry out large-scale simulations of protein folding. The force field has been derived and parameterized based on the principles of statistical-mechanics, which makes it independent of structural databases and applicable to treat nonstandard situations such as, proteins that contain D-amino-acid residues. Powered by Langevin dynamics...
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Anthropogenic transformations of the Bytom area relief in the period of 1883-1994
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Structural Transformations in Agriculture in Poland and Ukraine: Towards Economic Sustainability
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Socio-Economic Transformations in Ukraine towards the Sustainable Development of Agriculture
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Clinoptilolite as a natural, active zeolite catalyst for the chemical transformations of geraniol
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The landscape transformations of post-industrial areas based on selected examples
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BASICS OF THE MANAGEMENT SYSTEM FOR TRANSFORMATIONS OF PRODUCTION PLANNING AND CONTROL PROCESSES
PublicationIntensive development of technologies, in particular of the spinotronics, nanotechnology, robotics, and ICT, shapes the new generation production systems. Their distinctive feature is the flexi-bility associated with production intelligence. It is required from all processes, including the production planning and control processes (PPCP). The article is of conceptual character. It was prepared based on literature research. It encompasses...
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The metabolic activity of denitrifying microorganisms accumulating polyphosphate in response to addition of fusel oil
PublicationThe effect of distillery waste product (fusel oil) as an alternative external organic carbon source (EOCS) was investigated in terms of the metabolic properties of denitrifying polyphosphate accumulating organisms (DPAOs). Samples of the non-acclimated biomass were collected from a local full-scale wastewater treatment plant employing A2/O type bioreactors. The acclimated biomass was obtained after cultivation (with fusel oil added)...
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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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Applying ground penetrating radar to tracking of ancient architectural transformations: the case of the monastery St. Peter on the Island of Rab (Croatia)
PublicationThe ground-penetrating radar (GPR) method has been used for many years in archaeological research. However, thismethod is still not widely used in studies of past architecture. The biggest problem with the implementation of the GPRmethod at such sites is usually connected with extensive debris layers, plant cover and standing relics of walls and otherfeatures that restrict the available measurement area. Despite of these, properly...
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PANTOGRAPH AS AN EXAMPLE OF THE USE OF GEOMETRIC TRANSFORMATIONS IN CONSTRUCTING OF OLD DRAWING INSTRUMENTS = PANTOGRAF JAKO PRZYKŁAD ZASTOSOWANIA PRZEKSZTAŁCEŃ GEOMETRYCZNYCH W KONSTRUOWANIU DAWNYCH PRZYRZĄDÓW KREŚLARSKICH
PublicationThe article describes the pantograph, considered to be the ancestor of today's photocopier. This instrument draws the copies, enlarges or reduces any figure. The author presents its genesis, the scope of application in the past, explains the structure and geometrical transformations used during its action. Based on a specific example, the work illustrates practical application of geometry in the past inventions for designing.
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Influence of heat transformations on microstructure and properties of some wrought aluminium alloys.
PublicationOmówiono wpływ spawania na podatność do korozji naprężeniowej stopów Al-Mg i Al-Zn-Mg stwierdzając, że wzrost zawartości cynku wywołuje wzrost właściwości mechanicznych i spadek odporności na korozję naprężeniową. Wykazano, że obróbka cieplna złożona z retrogresji i powtórnego starzenia w przypadku stopów Al-Zn-Mg nie powoduje szczególnych zmian odporności na korozję naprężeniową, co pozostaje w związku z niewielką zmianą struktur...
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Reversible transformations from pure to mixed states and the unique measureof information.
PublicationWprowadzono protokół w którym kwantowe stany czyste są w sposób odwracalny przeprowadzane w stany mieszane. W oparciu o analizę protokołu wyprowadzono jednoznaczną miarę informacji. Dokonano porównania z innymi nieodwracalnymi protokółami przeprowadzającymi stany czyste w mieszane.