990 resultados para 3-R-concept
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Sequential stages in the life cycle of the ionotropic 5-HT(3) receptor (5-HT(3)R) were resolved temporally and spatially in live cells by multicolor fluorescence confocal microscopy. The insertion of the enhanced cyan fluorescent protein into the large intracellular loop delivered a fluorescent 5-HT(3)R fully functional in terms of ligand binding specificity and channel activity, which allowed for the first time a complete real-time visualization and documentation of intracellular biogenesis, membrane targeting, and ligand-mediated internalization of a receptor belonging to the ligand-gated ion channel superfamily. Fluorescence signals of newly expressed receptors were detectable in the endoplasmic reticulum about 3 h after transfection onset. At this stage receptor subunits assembled to form active ligand binding sites as demonstrated in situ by binding of a fluorescent 5-HT(3)R-specific antagonist. After novel protein synthesis was chemically blocked, the 5-HT(3) R populations in the endoplasmic reticulum and Golgi cisternae moved virtually quantitatively to the cell surface, indicating efficient receptor folding and assembly. Intracellular 5-HT(3) receptors were trafficking in vesicle-like structures along microtubules to the cell surface at a velocity generally below 1 mum/s and were inserted into the plasma membrane in a characteristic cluster distribution overlapping with actin-rich domains. Internalization of cell surface 5-HT(3) receptors was observed within minutes after exposure to an extracellular agonist. Our orchestrated use of spectrally distinguishable fluorescent labels for the receptor, its cognate ligand, and specific organelle markers can be regarded as a general approach allowing subcellular insights into dynamic processes of membrane receptor trafficking.
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The dichloromethane extract prepared from the underground parts of Eleutherine bulbosa (Miller) Urban (Iridaceae) showed strong activity in the direct bioautography assay with the phytopathogenic fungus Cladosporium sphaerospermum. This assay was used to guide the fractionation of this extract and allowed the isolation of four compounds: the new naphthoquinone eleutherinone[8-methoxy-1-methyl-1,3-dihydro-naphtho(2,3-c)furan-4,9 -dione] and the known compounds, previously isolated from this species, eleutherin [9-methoxy-1(R),3(S)-dimethyl-3,4-dihydro-1H-benzo(g)isochromene-5,10-dione], isoeleutherin [9-methoxy-1(R),3(R)-dimethyl-3,4-dihydro-1H-benzo(g)isochromene-5,10-dione], and eleutherol [4-hydroxy-5-methoxy-3(R)-methyl-3H-naphtho(2,3-c)furan-1 -one]. All quinonoid compounds showed strong antifungal activity in the bioautography assay at 100 µg/spot, while eleutherol was inactive.
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Geographical information systems (GIS) are tools that have been recently tested for improving our understanding of the spatial distribution of disease. The objective of this paper was to further develop the GIS technology to model and control schistosomiasis using environmental, social, biological and remote-sensing variables. A final regression model (R² = 0.39) was established, after a variable selection phase, with a set of spatial variables including the presence or absence of Biomphalaria glabrata, winter enhanced vegetation index, summer minimum temperature and percentage of houses with water coming from a spring or well. A regional model was also developed by splitting the state of Minas Gerais (MG) into four regions and establishing a linear regression model for each of the four regions: 1 (R² = 0.97), 2 (R² = 0.60), 3 (R² = 0.63) and 4 (R² = 0.76). Based on these models, a schistosomiasis risk map was built for MG. In this paper, geostatistics was also used to make inferences about the presence of Biomphalaria spp. The result was a map of species and risk areas. The obtained risk map permits the association of uncertainties, which can be used to qualify the inferences and it can be thought of as an auxiliary tool for public health strategies.
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Se han sintetizado nueve alcoholes que incorporan diversos isómeros de los grupos piridil o quinolil y metil-o-carborano u o-carborano, 1-[n′-Piridil(hidroxi)metil]-2-R-1,2-dicarba-closo-dodecaboranos (n′ = 2, R = H (2a); n′ = 3, R = Me (1c) y H (2c)), 1-[2′-6-metil-piridil(hidroxi)metil]-2-R-1,2-dicarba-closo-dodecaboranos (R = Me (1b) y H (2b)), 1-[n′-Quinolil(hidroxi)metil]-2-R-1,2-dicarba-closo-dodecaboranos (n′ = 2, R = Me (1e) y H (2e); n′ = 4, R = Me (1f) y H (2f), mediante la adición de la sal de litio del metil-o-carborano u o-carborano a los aldehídos correspondientes. Los compuestos se han obtenido con rendimientos altos en la mayoría de los casos y han sido caracterizados mediante Resonancia Magnética Nuclear, por Espectroscopía Infrarroja y análisis elemental. Las estructuras cristalinas de siete de los nueve compuestos (1c, 1f, 2a, 2b, 2c, 2e y 2f) se han determinado mediante Cristalografía por Rayos X. Se han analizado las estructuras cristalinas de los todos los compuestos y se han comparado con las estructuras de los compuestos relacionados 1a, 1b, y 2a, obtenidas previamente en el grupo de Síntesis Inorgánica y Catálisis del ICMAB. Todas las estructuras muestran interacciones por puentes de hidrógeno O–H···N moderadamente fuertes. Posteriormente se ha sintetizado el derivado mesilado 4 (derivado del o-carborano) mediante la reacción del alcohol 2a con cloruro de mesitilo a temperatura ambiente, con rendimiento alto. El nuevo mesilato 4 se ha caracterizado mediante Resonancia Magnética Nuclear. El nuevo mesilato resulta un compuesto de partida muy versátil para la síntesis de nuevos derivados mediante la substitución del grupo mesilo por nucleófilos apropiados, como por ejemplo las aminas. El grupo ha publicado recientemente la síntesis de diaminas mediante la reacción de substitución del mesilato relacionado 3 (derivado del metil-o-carborano) con aminas, entre ellas la bencilamina. Se ha realizado por tanto la reacción de substitución del grupo mesilato en 4 por la bencilamina para obtener la diamina correspondiente. Los resultados preliminares de esta reacción muestran que si bien el grupo mesilato en 4 ha sido substituido, el clúster se degrada casi en su totalidad a un derivado tipo nido. Esto contrasta claramente con la reactividad del mesilato análogo 3 frente a la bencilamina, ya que en este caso se obtiene la diamina deseada y el clúster no se degrada apreciablemente bajo las mismas condiciones de reacción. Se han realizado estudios preliminares por RMN que muestran que la bencilamina substituye al grupo mesilo en 4 y posteriormente el clúster closo se degrada a una especie nido que no ha sido posible caracterizar totalmente hasta el momento.
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Neste estudo avaliou-se a relação entre o teor de H + Al e o pH SMP, visando estabelecer uma equação para estimar a acidez potencial de solos do Semi-Árido do Nordeste Brasileiro. As análises dos teores de H + Al e dos valores de pH SMP foram realizadas em 81 amostras de solo, variando os teores de carbono de 1,8 a 35,6 g kg-1 e os de argila de 60 a 590 g kg-1. Os resultados demonstraram que a acidez potencial dessas amostras de solo, expressa em mmol c dm-3, pode ser estimada pelo valor do pH em solução tampão SMP, por meio da equação de regressão: H + Al = 31,521 (pH SMP)² - 451,61 pH SMP + 1625,3 (R² = 0,87**).
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Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP(3))-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in the absence of spontaneous oscillations. The interaction of IP(3)Rs with the anti-apoptotic protein Bcl-X(L) was previously described to prevent cell death by modulating intracellular Ca(2+) signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-X(L), fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca(2+) oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for ALS.
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Developed from human activities, mathematical knowledge is bound to the world and cultures that men and women experience. One can say that mathematics is rooted in humans’ everyday life, an environment where people reach agreement regarding certain “laws” and principles in mathematics. Through interaction with worldly phenomena and people, children will always gain experience that they can then in turn use to understand future situations. Consequently, the environment in which a child grows up plays an important role in what that child experiences and what possibilities for learning that child has. Variation theory, a branch of phenomenographical research, defines human learning as changes in understanding and acting towards a specific phenomenon. Variation theory implies a focus on that which it is possible to learn in a specific learning situation, since only a limited number of critical aspects of a phenomenon can be simultaneously discerned and focused on. The aim of this study is to discern how toddlers experience and learn mathematics in a daycare environment. The study focuses on what toddlers experience, how their learning experience is formed, and how toddlers use their understanding to master their environment. Twenty-three children were observed videographically during everyday activities. The videographic methodology aims to describe and interpret human actions in natural settings. The children are aged from 1 year, 1 month to 3 years, 9 months. Descriptions of the toddlers’ actions and communication with other children and adults are analyzed phenomenographically in order to discover how the children come to understand the different aspects of mathematics they encounter. The study’s analysis reveals that toddlers encounter various mathematical concepts, similarities and differences, and the relationship between parts and whole. Children form their understanding of such aspects in interaction with other children and adults in their everyday life. The results also show that for a certain type of learning to occur, some critical conditions must exist. Variation, simultaneity, reasonableness and fixed points are critical conditions of learning that appear to be important for toddlers’ learning. These four critical conditions are integral parts of the learning process. How children understand mathematics influences how they use mathematics as a tool to master their surrounding world. The results of the study’s analysis of how children use their understanding of mathematics shows that children use mathematics to uphold societal rules, to describe their surrounding world, and as a tool for problem solving. Accordingly, mathematics can be considered a very important phenomenon that children should come into contact with in different ways and which needs to be recognized as a necessary part of children’s everyday life. Adults working with young children play an important role in setting perimeters for children’s experiences and possibilities to explore mathematical concepts and phenomena. Therefore, this study is significant as regards understanding how children learn mathematics through everyday activities.
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Olika aspekter av psykisk hälsa och psykoterapi för personer med utvecklingsstörning undersöktes med hjälp av intervjuer. Syftet var att göra en kartläggning över erfarenheter och åsikter bland personer som arbetar med utvecklingsstörda i Svenskfinland. Totalt deltog 15 personer i undersökningen, 10 omsorgspsykologer, 4 socialkuratorer och en privatpraktiserande psykoterapeut. Deras erfarenhet av arbete med personer med utvecklingsstörning var i medeltal 17,3 år. Undersökningens resultat visar att psykisk ohälsa är ofta förekommande bland personer med utvecklingsstörning och att utvecklingsstörningen numera ofta särskiljs från psykiska störningar. Det är förändringar i beteendet som är signalen på psykisk ohälsa och oförmågan att uttrycka sitt mående som är det största hindret till att få lämplig vård. Andra hinder är bristen på ett fungerande samarbete mellan omsorg, sjukvård och mentalvård och okunskap beträffande många olika aspekter av psykisk ohälsa hos utvecklingsstörda. Inställningen till psykoterapi för utvecklingsstörda håller på att förändras till det positivare, och man börjar även uppmärksamma handikappmedvetenhet och identitetsutveckling samt dess betydelse för den psykiska hälsan. Denna undersökning betonar mötet mellan terapeut och klient som en betydelsefull faktor i samtal med personer med utvecklingsstörning. Resultaten stöder forskning på området, och fördjupar förståelsen av de olika aspekterna kring psykisk hälsa, stödsamtal och psykoterapi för personer med utvecklingsstörning.
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Työn tavoitteena ovat valtakunnalliset liikenneturvallisuustavoitteet vuoteen 2020 mennessä ja niiden saavuttaminen tienpitäjän toimenpitein.Tässä työssä tarkasteltiin maanteitä, joilla on kesäaikana voimassa 100 km/h nopeusrajoitus. Työssä vertailtiin nykyisten 100 km/h väylien tierekisteritietoja uusiin nopeus-rajoitusohjeisiin (LVM:n yleisohje 2009) sekä vertailtiin ko. tiejaksojen onnettomuustiheyksiä ja -asteita valtakunnallisiin lukuihin (Liikennevirasto, 2012). Lisäksi 100 km/h tieosuuksien ympäristön asukastiheyttä tarkasteltiin Rakennus- ja huoneistorekisteritietojen perusteella. Näiden tietojen perusteella muodostuivat mahdolliset nopeusrajoituksen alentamista vaativat tiejaksot. Nopeusrajoituksen alentamista liikenneturvallisuustilanteen parantamiseksi tarkasteltiin seuraavien priorisointiperiaatteiden mukaisesti: 1. 0-vision ja ihmisen kestokyvyn mukainen priorisointi: • Millä 100 km/h tiejaksoilla ei ole keskikaidetta? 2. Vastaavatko 100 km/h tiejaksot nykyisiä nopeusrajoitusohjeita? 3. Esiintyykö 100 km/h tiejaksoilla korkeita onnettomuustiheyksiä ja -asteita? Varsinais-Suomen ELY-keskuksen liikennevastuualueen johtotiimin päätöksen mukaisesti nopeusrajoitusta alennetaan 80 km/h:iin yhteensä 23 kilometrin matkalla. Lisäksi talvinopeusrajoitusta alennetaan yhteensä 9 kilometrin pituisella tiejaksolla. Nopeusrajoitustoimenpiteiden lisäksi yhden liittymän kohdalle päätettiin asettaa ohituskiellot ja yhdelle tiejaksolle esitettiin tehtäväksi puuston raivausta. Toimenpiteillä saavutetaan noin 0,78 vuosittainen vähenemä henkilövahinkoon johtaneissa onnettomuuksissa. Toimenpiteiden yhteiskuntataloudelliset kustannukset ovat yhteensä 600 000 euroa/vuosi.
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Rats fed a high-fructose diet represent an animal model for insulin resistance and hypertension. We recently showed that a high-fructose diet containing vegetable oil but a normal sodium/potassium ratio induced mild insulin resistance with decreased insulin receptor substrate-1 tyrosine phosphorylation in the liver and muscle of normal rats. In the present study, we examined the mean blood pressure, serum lipid levels and insulin sensitivity by estimating in vivo insulin activity using the 15-min intravenous insulin tolerance test (ITT, 0.5 ml of 6 µg insulin, iv) followed by calculation of the rate constant for plasma glucose disappearance (Kitt) in male Wistar-Hannover rats (110-130 g) randomly divided into four diet groups: control, 1:3 sodium/potassium ratio (R Na:K) diet (C 1:3 R Na:K); control, 1:1 sodium/potassium ratio diet (CNa 1:1 R Na:K); high-fructose, 1:3 sodium/potassium ratio diet (F 1:3 R Na:K), and high-fructose, 1:1 sodium/potassium ratio diet (FNa 1:1 R Na:K) for 28 days. The change in R Na:K for the control and high-fructose diets had no effect on insulin sensitivity measured by ITT. In contrast, the 1:1 R Na:K increased blood pressure in rats receiving the control and high-fructose diets from 117 ± 3 and 118 ± 3 mmHg to 141 ± 4 and 132 ± 4 mmHg (P<0.05), respectively. Triacylglycerol levels were higher in both groups treated with a high-fructose diet when compared to controls (C 1:3 R Na:K: 1.2 ± 0.1 mmol/l vs F 1:3 R Na:K: 2.3 ± 0.4 mmol/l and CNa 1:1 R Na:K: 1.2 ± 0.2 mmol/l vs FNa 1:1 R Na:K: 2.6 ± 0.4 mmol/l, P<0.05). These data suggest that fructose alone does not induce hyperinsulinemia or hypertension in rats fed a normal R Na:K diet, whereas an elevation of sodium in the diet may contribute to the elevated blood pressure in this animal model.
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Contient : Forme abrégée desdits statuts, précédée (fol. 107 v°) de « la declaracion des rubriques et chapitres des establissemens qui s'ensuivent », et (fol. 108 r°) d'une ordonnance de PIERRE D'AUBUSSON, relative à cette forme de statuts, datée de Rhodes, le 5 août 1493 ; Résumé pour les prieurs et châtelain d'Emposte desdits statuts
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Contient : 1 « Cy commence le blazon des armes de nostre Rédemption. Nous, Dieu d'amour, créateur, roy de gloire... Loyaulx amans, recongnoissez ces armes » ; 2 « Devota commemoratio de Cruce », piêce de vers latins ; 3 Traité sur le blason, par Clément PRINSAULT, avec figures, précédé (fol. 3 r°) d'une courte préface ; 4 Traité sur les animaux qui figurent le plus souvent dans les armoiries (les descriptions sont à comparer avec celles du XVIIIe livre du traité de Barthélemy L'Anglais sur les Propriétés des Choses) : « Si parle du lyon et de sa noble vertu : Item ou péril il appert pareillement noble... » [Autre exemplaire, ms. franç. 14357, fol. 30.] Ce traité est accompagné de blasons
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This thesis describes the synthesis, structural studies, and stoichiometric and catalytic reactivity of novel Mo(IV) imido silylamide (R'N)Mo(R2)(173_RIN-SiR32-H)(PMe3)n (1: Rl = tBu, Ar', Ar; R2 = Cl; R32 = Me2, MePh, MeCl, Ph2, HPh; n = 2; 2: R' = Ar, R2 = SiH2Ph, n = 1) and hydride complexes (ArN)Mo(H)(R)(PMe3)3 (R = Cl (3), SiH2Ph (4». Compounds of type 1 were generated from (R'N)Mo(PMe3)n(L) (5: R' = tBu, Ar', Ar; L = PMe3, r/- C2H4) and chlorohydrosilanes by the imido/silane coupling approach, recently discovered in our group. The mechanism of the reaction of 5 with HSiCh to give (ArN)MoClz(PMe3)3 (8) was studied by VT NMR, which revealed the intermediacy of (ArN)MCh(172 -ArN=SiHCl)(PMe3)z (9). The imido/silyl coupling methodology was transferred to the reactions of 5 with chlorine-free hydrosilanes. This approach allowed for the isolation of a novel ,B-agostic compound (ArN)Mo(SiHzPh)(173 -NAr-SiHPhH)(PMe3) (10). The latter was found to be active in a variety of hydrosilation processes, including the rare monoaddition of PhSiH3 to benzonitrile. Stoichiometric reactions of 11 with unsaturated compounds appear to proceed via the silanimine intermediate (ArN)M(17z-ArN=SiHPh)(PMe3) (12) and, in the case of olefins and nitriles, give products of Si-C coupling, such as (ArN)Mo(R)(173 -NAr-SiHPh-CH=CHR')(PMe3) (13: R = Et, R' = H; 14: R = H, R' = Ph) and (ArN)Mo(172-NAr-SiHPh-CHR=N)(PMe3) (15). Compound 13 was also subjected to catalysis showing much improved activity in the hydrosilation of carbonyls and alkenes. Hydride complexes 3 and 4 were prepared starting from (ArN)MoCh(PMe3)3 (8). Both hydride species catalyze a diversity of hydrosilation processes that proceed via initial substrate activation but not silane addition. The proposed mechanism is supported by stoichiometric reactions of 3 and 4, kinetic NMR studies, and DFf calculations for the hydrosilation of benzaldehyde and acetone mediated by 4.
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The syntheses, catalytic reactivity and mechanistic investigations of novel Mo(IV) and Mo(VI) imido systems is presented. Attempts at preparing mixed bis(imido) Mo(IV) complexes of the type (RN)(R′N)Mo(PMe3)n (n = 2 or 3) derived from the mono(imido) complexes (RN)Mo(PMe3)3(X)2 (R = tBu (1) or Ar (2); X = Cl2 or HCl, Ar=2,6-iPr2C6H3) are also described. The addition of lithiated silylamides to 1 or 2 results in the unexpected formation of the C-H activated cyclometallated complexes (RN)Mo(PMe3)2(η2-CH2PMe2)(X) (R = Ar, X = H (3); R = tBu, X = Cl (4)). Complexes 3 and 4 were used in the activation of R′E-H bonds (E = Si, B, C, O, P; R′ = alkyl or aryl), which typically give products of addition across the M-C bond of the type (RN)Mo(PMe3)3(ER′)(X) (4). In the case of 2,6-dimethylphenol, subsequent heating of 4 (R = Ar, R′ = 2,6-Me2C6H3, E = O) to 50 °C results in C-H activation to give the cyclometallated complex (ArN)Mo(PMe3)3(κ2-O,C-OPh(Me)CH2) (5). An alternative approach was developed in synthesizing the mixed imido complex (ArN)(tBuN)Mo(PMe3)(η2-C2H4) (6) through EtMgBr reduction of (ArN)(tBuN)MoCl2(DME) in the presence of PMe3. Complex 6 reacts with various hydro- and chlorosilanes to give β-agostic silylamido complexes and in one case, when Me2SiHCl is the silane, leads to the silanimine complex (tBuN)Mo(η2-SiMe2-NAr)(Et)(η2-C2H4) (7). Mechanistic studies on the formation of the Mo(VI) tris(silyl) complex (tBuN)Mo(SiHPh)(H){(μ-NtBu)(SiHPh)}(PMe3)2 (8) were done from the addition of three equivalents of PhSiH3 to (tBuN)Mo(PMe3)(η2-C2H4), resulting in identification of β- and γ-agostic SiH…Mo intermediates. The reactivity of complex 8 towards ethylene and nitriles was studied. In both cases coupling of unsaturated substrates with the Mo-Si bond of the metalacycle was observed. In the case of nitriles, insertion into the 4-membered disilaazamolybdacycle results in complexes of the type (tBuN)Mo{(κ2-Si,C-SiHPh-NtBu-SiHPh-N=C(R)}(PMe3)2. Catalytic hydrosilylation of carbonyls mediated by the β-agostic silylamido complex (ArN)2Mo(η3-NtBu-SiMe2-H)(H) (9) was investigated. Stoichiometric reactions with organic substrates showed that catalysis with 9 does not proceed via the conventional insertion of substrate into the Mo-H bond.
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La Loi modifiant le Code civil et d'autres dispositions législatives relativement à la publicité des droits personnels et réels mobiliers et à la constitution d'hypothèques mobilières sans dépossession, L.Q. 1998, ch. 5 a assujetti à la publicité pour fins d'opposabilité aux tiers la fiducie à titre onéreux constituée pour garantir l'exécution d'une obligation, les droits du crédit-bailleur et, dans certains cas, les droits des vendeurs à tempérament et avec faculté de rachat et du locateur à long terme. L'interprétation de certaines de ces dispositions législatives a suscité une vive controverse jurisprudentielle portant sur la requalification des contrats et l'effet de la publicité dans le contexte où le vendeur à tempérament et le locateur à long terme ont fait défaut de publier leurs droits en temps utile et avant la faillite de leur débiteur. Le présent mémoire étudie cette problématique en procédant à l'analyse des jugements pertinents, et plus particulièrement des arrêts de la Cour suprême dans Lefebvre (Syndic de); Tremblay (Syndic de), [2004] 3 R.C.S. 326 et Ouellet (Syndic de), [2004] 3 R.C.S. 348. Également, ce mémoire traite de l'amendement apporté par le législateur à la définition de « créancier garanti» de la Loi sur la faillite et l'insolvabilité, qui a tenté, sans succès, d'harmoniser cette notion avec celle du Code civil. Ainsi, il sera démontré que la situation juridique des contrats conclus à des fins de garantie s'est complexifiée au fil des ans.