79 research outputs found
Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells
In contrast to aspirin, salicylate, its active metabolite, possesses profound anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the transcription factor nuclear factor-κB (NF-κB) has been discussed to play a role in the anti-inflammatory profile of salicylate. However, NF-κB-independent effects of salicylate have been assumed but have up to now been poorly investigated. Therefore, the aim of the present study was to investigate NF-κB-independent anti-inflammatory mechanisms of salicylate in human umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-κB-independent proinflammatory stimulus and P-selectin as inflammatory read-out parameter. Using quantitative real-time reverse transcriptionpolymerase chain reaction, we found that salicylate decreases IL-4-induced P-selectin expression. As judged by Western blot analysis, salicylate increased endothelial heme oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II) protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c-Jun NH2-terminal kinase (JNK) was found to be activated by salicylate, and we could causally link this activation to the induction of HO-1 by using the JNK inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it was shown that the transcription factor AP-1 is crucially involved in the up-regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as novel NF-κB-independent anti-inflammatory target of salicylate in human endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for the induction of HO-1 by salicylate
Restricting consumer credit access: household survey evidence on effects around the Oregon rate cap
Many policymakers and some behavioral models hold that restricting access to expensive credit helps consumers by preventing overborrowing. The author examines some short-run effects of restricting access, using household panel survey data on payday loan users collected around the imposition of binding restrictions on payday loan terms in Oregon. The results suggest that borrowing fell in Oregon relative to Washington, with former payday loan users shifting partially into plausibly inferior substitutes. Additional evidence suggests that restricting access caused deterioration in the overall financial condition of the Oregon households. The results suggest that restricting access to expensive credit harms consumers on average.Consumer credit
The formation of mathematical notions of children of pre-school age in movement games
Darba tēma: Pirmsskolas vecuma bērnu matemātisko priekšstatu veidošanās kustību rotaļās Darba autors: Signe Tomsone Darba zinātniskais vadītājs: Dr. paed., Dagnija Vigule Darba mērķis: teorētiski un empīriski pētīt pirmskolas vecuma bērna matemātisko priekšstatu veidošanos kustību rotaļā. vai modificētu kustību rotaļu kopuma izveide bērnu matemātisko priekšstatu sekmēšanai pirmsskolā Darba apjoms: 49. lpp., 4 tabulas, 14 attēli, izmantoti 42 literatūras avoti. Pētījuma mērķis ir teorētiski un empīriski pētīt pirmskolas vecuma bērna matemātisko priekšstatu veidošanos kustību rotaļās. Dotā mērķa sasniegšanai teorētiski pētīti tādi jautājumi par pirmsskolas vecuma bērnu pedagoģiski, psiholoģiski un fizioloģiskajās likumsakarībām. Īpaša uzmanība pievērsta kustību rotaļu izmantošanai pirmsskolas pedagoģiskajā procesā matemātisko priekštatu veicināšanai. Papildus skatīta integrēta rotaļnodarbība. Par teorētisko bāzi kalpoja tādu autoru pētījumi kā D. Dzintare, I. Stangaine (2017), D. Lieģeniece (1999), D. Vigule (1998), A. Kalincenko (2006), I. Prudņikova (2004), A. Lopatina (2006), R. Jansone, A. Fernāte, I. Bula-Biteniece (2016), A. Flemmen (2005), I. Pontaga (2012), G. Domens, D. Domens, B. Heigijs (2015). Empīriskajā pētījumā veikta 6 - 7 gadus vecu bērnu vispārīgais raksturojums, izmantojot novērtējumu grupa. Apkopotas un īstenots modificēts kustību rotaļu kopums ar matemātisko priekšstatu veidošanā 4 nedēļu garumā. Veiktā pētījuma rezultātā konstatēts, ka ir uzlabojušies matemātisko priekštatu parametru rādītāji visiem pētījumā iesaistītajiem bērniem. Iegūtie rezultāti ļauj apstiprināt sākotnēji izvirzīto hipotēzi: pirmsskolas vecuma bērnu matemātisko priekšstatu veidošanos, būs sekmīgāka ja bērnam bez tradicionālās mācīšanās pieejas grupā: - tiks piedāvātas modificētas didaktiskās rotaļas kustību rotaļās; - tiks ļauts bērniem pašiem izvēlēties, kādu kustību rotaļu un ar kādiem noteikumiem vēlas spēlēt. Izmantojot dažādas matemātiskās kustību rotaļas, bērni mācās ne tikai zināt ciparus, bet arī tos skaitīt. Ir svarīgi, lai matemātikas mācīšana būtu jautra un nozīmīgs bērnam, kas notiek dabiski. Pedagogu viens no svarīgākajiem uzdevumiem ir saprast bērnu, izprast vajadzības, radīt indivīda piemērotību katram bērnam izglītības situācijās un vidē. Bērnam ir svarīgi, lai mācīšanās laikā bērni apgūtu matemātiskos priekšstatus caur kustību rotaļām un tās būtu pēc iespējas interesantākas. Praktiskā pētījuma bāze: 14 bērni (6-7 gadi), 1 skolotāja.The theme of diplomas work: The formation of mathematical notions of children of pre-school age in movement games. The author: Signe Tomsone Scientific supervisor: Dr. paed., Dagnija Vigule Bachelor’s workload: theoretically and empirically study the formation of mathematical notions of a child of pre-school age in the game of movement or the creation of a modified set of movements to promote mathematical notions of children in preschool. Amount of work: 49 p., 4 tables, 14 figures, 42 literature sources used. The aim of the study is to study, in theory and empirically, the formationof mathematical notions of a child of pre-school age in motion games. In theory, issues relating to pedagogical, psychological and physiological legal relationships between children of pre- school age have been studied in order to achieve this objective. Particular attention shall be paid to the use of coupling games in the pre-school pedagogical process to promote mathematical forecast. In addition, an integral play lesson has been viewed. The theoretical basis was the study of authors such as D. Amber, I.Stangaine (2017), D. Liegeniece (1999), D. Vigule (1998), A. Kalincenko(2006), I. Prudnikova (2004), A. Lopatina (2006), R. Janson, A. Fernte, I. Bula-Bites (2016), A. Flemmen (2005), I. Pontaga (2012), G.Domens, B.Heigy (2015). The empirical study carried out a general profile of children aged 6-7, using the assessment group. A modified set of motion games has been compiled and implemented, with a mathematical impression of 4 weeks. A study carried out showed an improvement in mathematical pre-natal parameters for all children involved in the study. The result obtained allow you to confirm the hypothesis originally nominated: The development of mathematical notions of pre-school children will be more successful if a child without a traditional learning approach in the group: - be offered modified didactic games in motion games; - the children will be allowed to choose their own movement games andthe rules on which they want to play. Using different mathematical movement games, children learn not only to know digits, but to count them. It is important that teaching math is fun and important for a child that happens naturally. One of the most important tasks for educators is to understand a child, understand needs, create an individual’s suitability for each child in educational situations and the environment. It is important for a child that children learn mathematical notions through movement games and make themes interesting as possible when they are learning. Practical study base: 14 children (6-7 years), 1 teacher
The future of the "Homme-Trace" : a substantial societal challenge
Texte de référence pour le E-laboratoire international et interdisciplinaire "Human-Trace Complex Systems UNESCO" : https://en.wikiversity.org/wiki/Portal:Complex_Systems_Digital_Campus/E-Laboratory_on_human_traceHaving observed that the notion of trace is used in disciplines whose subjects and methods often stand far apart, the author has put forward some definitions from French anthroposemiotic research (signe-trace, signe-signal, "echoing of traces" etc.). The propositions result from her own findings in professional situations of communication. In this article, B. Galinon-Mélénec explains that confusing the sign and the trace is an anthropocentric view and that "if any sign is, in fact, a "signe-trace", a trace is not necessarily a sign". The latest scientific discoveries have led the author to propose a new anthropological definition spanning time: the Homme-Trace. Revealed by both anthropology and astrophysics, traces of the distant past make it possible to question the trace in terms of processes, interactions (human or nonhuman), systems and complexity. This paper serves as a basis for debate within the international and interdisciplinary e.laboratory "Human-Trace-Complex-Systems", with the aim of developing a collective intelligence of the notion of Trace. All disciplines are invited to respond to this substantial societal challenge
Phase diagram of methane and carbon dioxide hydrates computed by Monte Carlo simulations
Molecular Monte Carlo simulations are used to compute the three-phase (hydrate-liquid water-gas) equilibrium lines of methane and carbon dioxide hydrates, using the Transferable Potentials for Phase Equilibria model for carbon dioxide, the united atom optimized potential for liquid simulations model for methane, and the TIP4P/Ice and TIP4P/2005 models for water. The three-phase equilibrium temperatures have been computed for pressures between 50 and 4000 bar via free-energy calculations. The computed results are as expected for methane hydrates but deviate from the direct-coexistence molecular dynamics (MD) studies for carbon dioxide hydrates. At pressures higher than 1000 bar, both the methane and carbon dioxide hydrates dissociate at lower temperatures than expected from experiments and MD studies. The dissociation enthalpy is found to be largely independent on water models, and its values are measured to be 7.6 and 6.0 kJ/mol of water for methane hydrates and carbon dioxide hydrates, respectively. We evaluate the effect of systematic errors on the determination of chemical potentials and show that systematic errors of 0.1 kJ/mol in the chemical potential of water correspond to deviations of 5 K in the three-phase equilibrium temperatures. (Graph Presented).Accepted Author ManuscriptEngineering Thermodynamic
Work Safety Measures in Nurse's Practice Facing Biological Risk Factors in x Health Facility
Bakalaura darba tēma ir ,,Darba drošības pasākumi māsu praksē saskaroties ar bioloģiskiem riska faktoriem x veselības aprūpes iestādē”. Mūsdienu sabiedrībā pieaug inficēto personu skaits, rodas jaunas, nezināmas infekcijas, ar kurām māsa var saskarties jebkurā dežūrā. Kā biežāk izplatītās un bīstamākās no tām ir HIV infekcija (2015.gadā pasaulē bija 36,7 miljoni HIV inficēto), B hepatīts ( 2015.gadā inficēto cilvēku skaits bija aptuveni 257 miljoni) un C hepatīts (2015.gadā inficēto cilvēku skaits bija sasniedzis 71 miljonu). Pēc darba autores domām šie skaitļi ir pietiekami lieli, lai medicīnas darbiniekiem būtu ļoti augsta iespējamība inficēties ar kādu no šīm saslimšanām, darot savu darbu, īpaši neatliekamās situācijās, kad nav iespējas, noskaidrot pacienta anamnēzi. Darba mērķis: noskaidrot kādus profilaktiskos pasākumus saskarē ar bioloģiskajiem aģentiem savā darbā pielieto māsas. Kvalifikācijas darbs sastāv no ievada, teorētiskās daļas, praktiskās daļas, secinājumiem un 3 pielikumiem. Teorētiskajā daļā apkopota pieejamā literatūra par bioloģiskiem riska faktoriem, darba drošības pasākumiem māsu praksē un saslimšanas, kuras izraisa saskare ar bioloģiskiem aģentiem māsu darba vietās. Pētnieciskais darbs tika veikts vienā no Latvijas slimnīcām, izmantojot kvantitatīvo pētniecības metodi, kurā, izmantotais instruments bija aptaujas anketa ar 15 jautājumiem. Anketas, kuru apstiprināja Rīgas Austrumu klīniskās universitātes slimnīcas atbalsta fonda Medicīnisko un biomedicīnisko pētījumu Ētikas komitejas, sastādītāja ir šī bakalaura darba autore. Sagatavotās aptaujas anketas izmantošanai saņemts pozitīvs slēdziens Nr. ZD/08-06/01-18/157. Anketas ir sastādītāja šī bakalaura darba autore. Pētnieciskā darba laikā tika aptaujātas 100 slimnīcā dažādās profila nodaļās strādājošas māsas par viņu darba drošību un epidemioloģiskā režīma pasākumiem saskarē ar bioloģiskajiem riska faktoriem. Veicot pētniecisko darbību, darba autore secina, ka izvirzītā hipotēze, ka māsas ievēro darba drošību un epidemioloģiskā režīma pasākumus saskarē ar bioloģiskajiem riska faktoriem, ir apstiprinājusies daļēji. Atslēgas vārdi: bioloģiskie riska faktori, darba drošības pasākumi.A qualification paper’s title is “Work safety measures in nurse’s practice facing biological risk factors in x health facility”. Nowadays in the society is increasing the number of infected persons and there are new unknown infections with which nurses can face daily. As the most prevalent and most dangerous of them are HIV (in 2015 there were 36.7 million people living with HIV in the world), hepatitis B (in 2015 there were about 257 million people) and hepatitis C (in 2015 the number of people infected had reached 71 million). In the author's opinion, these figures are large enough and can be shown that a medical staff is very high risk of being infected with one of these diseases, while doing their work, especially in emergency situations, when it is not possible to find out the patient's medical history. Aim: to find out which preventive measures in contact with biological agents nurses are using in their work. The qualification’s paper consists from introduction, theoretical part, practice part, conclusion and three annexes. Theoretical part contains sum-up of the available literature about biological risk factors, safety measures in the nurse’s practice and illnesses, which causes the result of the contact with biological agents at the nurse’s workplaces. The research work was hold out in one of the Latvian hospitals using quantitative research method, where used research instruments was a questionnaire with 15 questions. The questionnaire was preparing by the author. In order to use the questionnaires for the research a positive decision Nr. ZD/08-06/01-18/157 was received. During the research work, 100 hospital nurses working in the various profile departments were surveying regarded their work safety and epidemiological regime action while in contact with biological risk factors. Carrying out the research work, the author concludes that the set hypothesis, that the nurses comply with safety measures and epidemiological regime actions in contact with biological risks factors, is partially confirmed. Keywords: biological risks factors, work safety measures
ANP inhibits TNF-alpha-induced endothelial MCP-1 expression--involvement of p38 MAPK and MKP-1
Atrial natriuretic peptide (ANP) has been shown to reduce tumor necrosis factor-alpha (TNF-alpha)-induced activation of endothelial cells via inhibition of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB pathways. The aim of this study was to determine whether ANP is able to inhibit TNF-alpha-induced expression of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells and to elucidate the mechanisms involved. Pretreatment of human umbilical vein endothelial cells (HUVEC) with ANP significantly reduced TNF-alpha-induced expression of MCP-1 protein and mRNA. The effects of ANP were shown to be mediated via the guanylyl-cyclase (GC)-coupled A receptor. Activation of the other GC-coupled receptor (natriuretic peptide receptor-B) by the C-type natriuretic peptide as well as activation of soluble GC with S-nitroso-L-glutathione (GSNO) exerted similar effects as ANP, supporting a role for cyclic guanosine monophosphate (cGMP) in the signal transduction. Antisense experiments showed a requirement of MAPK phosphatase-1 (MKP-1) induction and therefore, inhibition of p38 MAPK in the ANP-mediated inhibition of TNF-alpha-induced expression of MCP-1. To investigate a potential interplay between TNF-alpha-induced activation of p38 MAPK and NF-kappaB, the p38 MAPK inhibitor SB203580 and a dominant-negative p38 MAPK mutant were used. The results indicated that the blockade of p38 MAPK activity leads to an increased activation of NF-kappaB and therefore, suggest a counter-regulatory action of p38 MAPK and NF-kappaB. As antisense experiments revealed a pivotal role for MKP-1 induction and therefore, p38 MAPK inhibition in ANP-mediated attenuation of MCP-1 expression, this action seems to be rather independent of NF-kappaB inhibitio
Light microscopy images taken onboard KAXIS V3 2015/2016
Progress Code: completedStatement: Samples were collected and imaged opportunistically around other primary duties and so there may be some gaps in the spatial coveraged intended.<b>Purpose</b><br/>The purpose of the dataset is to a) document phytoplankton biodiversity of the region b) increase taxonomic resolution by capturing taxonomic features that may be lost upon sample preservation.Samples were collected using a prototype basket sampler that concentrated phytoplankton from the underway water supply in the OG lab onboard Aurora Australis. The sampler filtered water during transit, and the distance travelled and the approximate volume of water sampled was recorded. A phytoplankton net tow was collected at each station. The majority of imaging was undertaken using a Leica DMLB2 microscope with phase contrastand Leica ICC50 digital in body camera. Samples were preserved with either glutaraldhyde or Lugols iodine for later examination as well. Details of sample collected are included in the Voyage sample log
Re-inventing Harmony in Electroacoustic Music: A commentary on my Recent Music
Re-inventing Harmony in Electroacoustic Music reflects on research regarding structuring pitch-based material in my music written between 1999 and 2010. The selected works illustrates the process leading up to my research based on psychoacoustic consonance and dissonance and my strategies to create a new kind of harmony – a harmony based on concrete sounds with inharmonic spectra.
The discussion will refer to pieces by composers who have worked with harmony based on the analysis of sound spectra; instrumental and mixed works by spectralist composers such as Grisey, Murail and Saariaho and electroacoustic works by Harvey and others.
I will address the importance of research in the psychoacoustic field, in particular, research by
William A. Sethares regarding inharmonic spectra and scales and how it has affected my works
Modélisation de la leucémie aiguë lymphoblastique B induite par la mutation PAX5 P80R
The team is interested in alterations in transcription factors involved in acute leukemia, including PAX5, which is essential for B-cell development. This is why the PAX5-ELN transgenic mouse model was generated, which expresses the oncogenic fusion protein during B-cell development, and recapitulates the multi-step process of B-ALL (Jamrog L et al., PNAS, 2018). I was involved in identifying the cells at the origin of-B-ALL and characterizing their functional and molecular properties. Our work indicates that at pre-leukemic stage, PAX5-ELN induces the emergence of an aberrant population of B-progenitors with an abnormal self-renewal property. This population is enriched in quiescent cells resistant to chemotherapeutic agents, activating a molecular stem cell program and supporting long-term leukemic initiation. This work is the subject of a recent publication signed by myself as second author (Fregona V, Bayet M et al., J Exp Med, in press). In parallel, my thesis focused on modeling the initiation and leukemic transformation induced by the PAX5P80R mutation, a frequent initiating alteration in patients. I used fetal liver cells derived from Pax5-/- mouse embryos to select lymphoid progenitors not committed to the B lineage. After transduction with CTL, PAX5 Wt or PAX5P80R retroviruses, I showed that PAX5P80R does not restore efficiently definitive commitment of cells to the B lineage. Transplantation experiments have shown that PAX5P80R induces aberrant engraftment potential followed by the development of B-ALL. This leukemic transformation is associated with the selection of clones carrying additional mutations affecting the JAK/STAT signaling pathway. Our analyses identified Hif2 as a potential candidate for leukemogenesis. Finally, pharmalogical screening of Hif inhibitors revealed Acriflavine as an interesting compound targeting leukemic cells. Thus, the modeling of B-ALL by the PAX5P80R mutation provides the team with a new tool to mimic the multi-step process of B-ALL, and to decipher the biological mechanisms by which the mutation leads to tumor transformation. This work is the subject of a manuscript in preparation which I have signed as first author (Bayet M, Fregona V, et al., in preparation). The PAX5-ELN and PAX5P80R models not only make it possible to study the various stages of B leukemogeneis, but also serve as a basis for the development of small molecule screening on primary cells. I therefore set up a miniaturized and robust protocol by FACS to screen chemical compounds targeting pre-leukemic cells. Our multiparametric approach enables us to simultaneously assess the effect of compounds on pre-leukeic cells and normal B subpopulations. I screened a bank of 1040 synthetic and natural compounds (essential chemical library) reflecting the chemical diversity of the French national chemical library. This screening, combined with dose-response counter-screening, enabled me to identify 5 molecules of interest. Overall, my work demonstrates the feasibility of small-molecule screening on a population enriched in leukemia-initiating cells, taking into account the intrinsic complexity of primary B-cells. Finally, I edited and published a review in the journal Cancers outlining the concepts of tumor heterogeneity in patients' leukemic cells, the utility of transgenic mouse models to explore the leukemia initiating cell compartment, and current efforts to discover new targeted therapies (Fregona V*, Bayet M* et al, Cancers (Basel), 2021), wich I co-authored.L'équipe s'intéresse aux altérations de facteurs de transcription impliquées dans les leucémies aiguës, dont PAX5 qui est essentiel pour le développement des cellules B. C'est pourquoi le modèle murin transgénique PAX5-ELN a été généré, qui exprime la protéine de fusion oncogénique durant le développement des lymphocytes B, et récapitule le processus multi-étapes des LAL-B (Jamrog L et al., PNAS, 2018). J'ai participé à l'identification des cellules à l'origine de la LAL-B et à la caractérisation de leur propriétés fonctionnelles et moléculaires. Nos travaux indiquent qu'au stade pré-leucémique, PAX5-ELN induit l'émergence d'une population aberrante de progéniteurs B avec une propriété anormale d'auto-renouvellement. Cette population est enrichie en cellules quiescentes résistantes aux agents de chimiothérapie, activent un programme moléculaire de cellule souche, et sont le support de l'initiation leucémique à long terme. Ce travail fait l'objet d'une publication récente que je signe en deuxième auteure (Fregona V, Bayet M et al., J Exp Med, in press). En parallèle, ma thèse s'est tournée vers la modélisation de l'initiation et de la transformation leucémique induite par la mutation PAX5P80R, une altération initiatrice fréquente chez les patients. J'ai donc utilisé des cellules de foie fœtal issus d'embryon de souris Pax5-/- pour sélectionner les progéniteurs lymphoïdes non engagés dans le lignage B. Après transduction avec des rétrovirus CTL, PAX5 Wt ou PAX5P80R, j'ai montré que PAX5P80R ne restaure pas efficacement l'engagement définitif des cellules vers le lignage B. Les études de transplantation ont permis de montrer que PAX5P80R induit un potentiel de prise de greffe aberrant suivi du développement de la LAL-B. Cette transformation leucémique est associée à la sélection de clones porteurs de mutations additionnelles affectant la voie JAK/STAT. Nos analyses ont permis d'identifier Hif2 comme un candidat potentiel dans la leucémogenèse. Enfin, un criblage pharmacologique d'inhibiteurs de Hif révèle l'Acriflavine comme un composé intéressant ciblant les cellules leucémiques. Ainsi, la modélisation de la LAL-B par la mutation PAX5P80R fournit à l'équipe un nouvel outil mimant le processus multi-étapes de la LAL-B, et permet de déchiffrer les mécanismes biologiques par lesquels la mutation mène à la transformation tumorale. Ce travail fait l'objet d'un manuscrit en préparation que je signe en première auteure (Bayet M, Fregona V, et al., in preparation). Les modèles PAX5-ELN et PAX5P80R permettent non seulement d'étudier les différentes étapes de la leucémogenèse B, mais servent aussi de support pour le développement de criblage de petites molécules sur cellules primaires. J'ai donc mis en place un protocole miniaturisé et robuste par FACS pour cribler des composés chimiques ciblant les cellules pré-leucémiques. Notre approche multiparamétrique permet d'évaluer simultanément l'effet des composés sur les cellules pré-leucémiques et les sous-populations B normales. J'ai donc criblé une banque de 1040 composés synthétiques et naturels (chimiothèque essentielle) reflétant la diversité chimique de la chimiothèque nationale française. Ce criblage, associé à des contre-criblages en dose-réponse, m'a permis d'identifier 5 molécules d'intérêt. Dans l'ensemble, mon travail montre la faisabilité d'un criblage de petites molécules sur une population enrichie en cellules initiatrice de la leucémie et prenant en compte la complexité intrinsèque des cellules primaires du lignage B. Enfin, j'ai procédé à la rédaction et la publication d'une revue dans le journal Cancers qui expose les concepts d'hétérogénéité tumorales des cellules leucémiques des patients, l'utilité des modèles de souris transgéniques pour explorer le compartiment des cellules initiatrices de la leucémie, et les efforts actuels visant à découvrir de nouvelles thérapies ciblées (Fregona V*, Bayet M* et al, Cancers (Basel), 2021), que je signe en co-première auteure
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