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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: van Chuc Nguyen, ?.; Dandach, A.; Thi Thu Ha Vu, ?.; Fongarland, P.; +1 Authors

    Abstract Tungstated zirconia, ZrW, is reported as an efficient solid acid catalyst in the conversion of cellulose into lactic acid in hydrothermal conditions. The active phase of ZrW is generally ascribed to more or less polymerized WOx domains dispersed on zirconia. In this study, commercial uncalcined and calcined tungstated zirconia were used as catalysts for the conversion of cellulose under hydrothermal conditions at 190 °C. Their activities were also compared with uncalcined zirconium oxyhydroxide, ZrO2-x(OH)2x and calcined zirconia, ZrO2. Contrary to the expected results, it is disclosed that uncalcined ZrW exhibits higher catalytic activity and stability than calcined ZrW. Modifications in the products distribution were observed as glycolic acid formation at the expense of lactic acid formation upon ZrW calcination. Even more surprising, the catalytic activity of W free amorphous zirconium oxyhydroxide ZrO2-x(OH)2x is similar to uncalcined ZrW, with lactic acid as the main product while ZrO2 does not have any catalytic activity. These results suggest that the active phase of these catalysts might combine the couple Zr4+ and OH− species while the role of W species would be of secondary importance.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Molecular Catalysisarrow_drop_down
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Molecular Catalysis
    Article . 2019
    License: Elsevier TDM
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    Hal-Diderot
    Article . 2019
    License: CC BY NC
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Molecular Catalysisarrow_drop_down
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Molecular Catalysis
      Article . 2019
      License: Elsevier TDM
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      Hal-Diderot
      Article . 2019
      License: CC BY NC
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  • Authors: Boukhari, Amar;

    Knowledge of the nuclear magnetic moments is of great importance to get a clear understanding of nuclear structure. The magnetic moment is sensitive to the single-particle nature of the valence nucleons. The development of radioactive beam facilities allows nowadays studying nuclear spins and moments of exotic nuclei which are far from the stability line. However, the measurement of magnetic moments of exotic nuclei produced as radioactive beams requires the development of reliable methods. Successful development of such methods would open up the possibility to discover new nuclear structure phenomena. The study outlined in this thesis is formed by two experiments. The first experiment was performed at ALTO facility in Orsay, France. One of the main requirements in order to measure a nuclear magnetic moment is to produce a spin-oriented ensemble. The latter can be produced by suitable reaction mechanism and nuclear spin interaction with the surrounding environment. The degree of the orientation depends on the formation process and reaction mechanism. The aim of this first experiment was investigating the level of nuclear spin orientation in incomplete fusion reaction mechanism. Two reaction channels were studied, the isomeric states in ⁶⁵mNi (I = 9/2⁺, Eₓ = 1017 keV, T₁/₂ = 26 ns), and ⁶⁶mCu (I = 6⁻, Eₓ = 563 keV, T₁/₂= 600 ns) with Time-Dependent Perturbed Angular Distribution (TDPAD) method. The result of the experiment demonstrates the possibility of obtaining spin alignment in incomplete fusion reaction of an order of 20%. This reaction mechanism, with such an important amount of spin alignment has potential near radioactive beam facilities to study the neutron-rich region with inverse kinematics reactions. The second experiment, and the main part of the thesis was performed at HIE-ISOLDE at CERN. This experiment aimed to obtain high precision g-factor information on a short-lived picosecond state. A new Time Differential Recoil-In-Vacuum (TDRIV) method was applied for the first time using post-accelerated radioactive beams. The g-factor measurement was performed for the first-excited state in ²⁸Mg nucleus (Eₓ = 1474(1) keV, T₁/₂ = 1.2(1) ps). Since the lifetime of the state is of the order of picoseconds, its g-factor can be measured only via the spin precession of the nucleus in an extremely strong magnetic field (kT). Such fields can only be produced at the nucleus by hyperfine interactions. In order to obtain a high precision on a g-factor measurement, a TDRIV calibration experiment was performed with a stable ²²Ne beam. This run allowed testing the system under the same conditions as with radioactive²⁸Mg beam. In addition, using the known g-factor of the first-excited state in ²²Ne allows to determine the absolute target-to-degrader distance so that to decrease the uncertainty and obtain a high precision g-factor measurement. The obtained calibration parameters from the ²²Ne data will be used in the determination of g-factor of ²⁸Mg.; La mesure des moments magnétiques nucléaires est d'une grande importance pour bien comprendre la structure nucléaire. Le moment magnétique est sensible à la nature de la particule indépendante. Le développement des faisceaux radioactifs permet aujourd'hui d'étudier les spins nucléaires et les moments de noyaux exotiques éloignés de la ligne de stabilité. Cependant, la mesure des moments magnétiques des noyaux radioactifs nécessite le développement des nouvelles méthodes fiables. Le développement réussi de telles méthodes ouvrirait la possibilité de découvrir de nouveaux phénomènes de structure nucléaire. L'étude présentée dans cette thèse est formée de deux expériences. La première expérience a été réalisée à ALTO à Orsay, en France. L'une des principales exigences pour mesurer un moment magnétique nucléaire est de produire un ensemble avec des spins orientés. Ce dernier peut être produit par un mécanisme de réaction approprié et une interaction de spin nucléaire avec le milieu environnant. Le degré d'orientation dépend du processus de formation et du mécanisme de réaction. Le but de cette première expérience était d’étudier le niveau d’orientation du spin nucléaire dans un mécanisme de réaction de fusion incomplète. Le résultat de l'expérience démontre la possibilité d'obtenir un alignement du spin dans une réaction de fusion incomplète d'un ordre de 20%. Ce mécanisme de réaction, avec une telle quantité d’alignement de spin, a le potentiel d’étudier la région riche en neutrons avec des faisceaux radioactifs. La deuxième expérience, et l'essentiel de la thèse, a été réalisée à HIE-ISOLDE au CERN. Cette expérience visait à obtenir des informations de haute précision sur le facteur g d’un état de courte durée. Une nouvelle méthode TDRIV (Time-Differential Recoil In Vacuum) a été appliquée pour la première fois avec des faisceaux radioactifs post-accélérés. La mesure du facteur g était réalisée pour le premier état excité dans un noyau de ²⁸Mg (Eₓ = 1474 (1) keV, T₁/₂ = 1,2 (1) ps).

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    Hal-Diderot
    Doctoral thesis . 2018
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      Doctoral thesis . 2018
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  • Authors: Eychenne, Camille;

    Fonder un projet de territoire à la lumière d'une bonne connaissance de ses composantes paysagères permet d'instaurer une dynamique durable de développement. Le paysage devient support de projet de territoire et outil de développement local.

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    Other literature type . 2016
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      Other literature type . 2016
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Cécile Mons; Thomas Botzanowski; Anton Nikolaev; Petra Hellwig; +4 Authors

    International audience; Human mitoNEET (mNT) is the first identified Fe−S protein of the mammalian outer mitochondrial membrane. Recently, we demonstrated the involvement of mNT in a specific cytosolic pathway dedicated to the reactivation of oxidatively damaged cytosolic aconitase by cluster transfer. In vitro studies using apo-ferredoxin (FDX) reveal that mNT uses an Fe-based redox switch mechanism to regulate the transfer of its cluster. Using the "gold standard" cluster recipient protein, FDX, we show that this transfer is direct and that only one of the two mNT clusters is transferred when the second one is decomposed. Combining complementary biophysical and biochemical approaches, we show that pH affects both the sensitivity of the cluster to O 2 and dimer stability. Around physiological cytosolic pH, the ability of mNT to transfer its cluster is tightly regulated by the pH. Finally, mNT is extremely resistant to H 2 O 2 compared to ISCU and SufB, two other Fe−S cluster transfer proteins, which is consistent with its involvement in a repair pathway of stress-damaged Fe−S proteins. Taken together, our results suggest that the ability of mNT to transfer its cluster to recipient proteins is not only controlled by the redox state of its cluster but also tightly modulated by the pH of the cytosol. We propose that when pathophysiological conditions such as cancer and neurodegenerative diseases dysregulate cellular pH homeostasis, this pH-dependent regulation of mNT is lost, as is the regulation of cellular pathways under the control of mNT. I ron−sulfur (Fe−S) clusters are evolutionarily ancient and highly conserved prosthetic cofactors. Composed of only iron and sulfur, they are involved in many essential biological processes. 1,2 MitoNEET (mNT), also known as CISD1, is the first identified Fe−S protein of the mammalian outer mitochondrial membrane (OMM). 3,4 This is a small homodimeric protein (13 kDa for each monomer) anchored to the OMM by its 32-amino acid N-terminus with the major part of the protein, including the C-terminal Fe−S binding domain, located in the cytosol. 4 Each monomer accommodates one [2Fe-2S] cluster coordinated by three cysteines (C72, C74, and C83) and one histidine (H87) in a CDGSH domain 5−8 as other members of the NEET protein family, 9 which also includes Miner1 (or CISD2) and Miner2 (or CISD3) in mammals. 10 Although the biological activity of mNT is still debated, 11 studies have shown that it is involved in the regulation of iron/reactive oxygen species homeo-stasis, 12−14 in the regulation of lipid and glucose metabolism , 13,15 and in cell proliferation in breast cancer. 16 In vitro studies revealed that holo-mNT (the form of the protein with the cluster) is able to transfer its Fe−S cluster to very diverse apoprotein (an Fe−S protein, which has lost its cluster) recipients assembling either a [2Fe-2S] cluster as ferredoxin from various organisms, 17,18 human anamorsin 19 and CISD2, 20 or a [4Fe-4S] cluster as mammalian iron regulatory protein-1 (IRP-1)/cytosolic aconitase (c-aconi-tase). 14 On the basis of in cellulo experiments, we showed that mNT is able to repair the oxidatively damaged Fe−S cluster of human IRP-1/c-aconitase by transferring its cluster to the damaged protein. 14 Recently, we started to investigate in depth the in vitro cluster transfer reaction, focusing on the transfer from holo-mNT to [2Fe-2S] recipient protein. We unambiguously demonstrated that oxidized mNT ([2Fe-2S] 2+) triggers cluster transfer, whereas reduction of its cluster abrogates this transfer. Moreover, while O 2 significantly affects the lability of the oxidized mNT cluster, it does not interfere with the cluster

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    Biochemistry
    Article . 2018
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  • Authors: Payot, Claire;

    L'auteur de la thèse a souhaité limiter l'accès aux membres de l'Enseignement supérieur français.; L'arrivée sur le marché de nouvelles molécules d'immunothérapie (IT) révolutionne la prise en charge de certains cancers. Cependant leurs prix élevés et le peu de recul sur leurs effets à moyen et long termes, posent la question de la pertinence et de la place de ces molécules dans la stratégie thérapeutique des cancers. L'objectif de ce travail est d'obtenir des données en vie réelle de l'utilisation de nivolumab (N) et de pembrolizumab (P) au centre hospitalier de Metz Thionville (CHRMT). Ce travail décrit la cohorte de patients sous IT sur les deux premières années de son utilisation au CHRMT, puis les effets indésirables (EI) survenus chez ces patients ainsi, que la prise en charge de ces EI ; enfin, il décrit la survie globale et sans progression de ces patients et pour terminer le devenir des patients post IT. Cette étude observationnelle rétrospective s'étend sur les deux premières années de l'utilisation de l'IT au CHRMT, et concerne tous les patients ayant reçus N et P entre le premier juin 2016 et le 31 mai 2018. Les patients sont suivis 6 mois en post IT. Au total, sont étudiés 144 patients, 117 (81,3%) traités par N, et 27 (18,7%) par P. Le cancer bronchique (CB) est la principale indication de ces molécules. Les patients sous N et P ont présenté respectivement 2,7 et 2,9 EI durant leur traitement. La répartition des EI par système d'organe et le grade des EI ne sont pas statiquement différents d'une Dénomination Commune Internationale (DCI) à l'autre. Ils sont systémiques et non spécifiques d'organe. Les trois quarts des EI ne sont pas cotés graves d'après la classification CTCAE. Certains EI ont entrainé de longues pauses thérapeutiques, suite à la décroissance de corticoïdes, antidote de l'IT. On observe 55 patients qui ont progressé sous N soit 47% et 6 patients sous P soit 22%. Toutes indications confondues, le principal motif d'arrêt l'IT est la progression tumorale dans plus d'un cas sur deux (51%). Vient en seconde position, la survenue d'effets indésirables (26%). Cette étude a permis d'observer ce qui se passe en vie réelle, dans les conditions d'utilisations normales. Ce nombre conséquent d'EI, parfois grave, justifie une surveillance particulière et la mise en place de moyens appropriés pour leur prise en charge dans les meilleurs délais : sensibilisation du corps médical et des soignants, suivis biologiques, etc. Cependant rapporté au nombre de cures administrées dans cette cohorte, la fréquence d'effets indésirables reste relativement faible. Les grades et les cibles des EI de ces deux DCI sont comparables et appuie le lien avec leur mécanisme d'action immunologique. La bonne tolérance de ces traitements et les réponses à ces traitements parfois longues sont encourageantes. Une meilleure connaissance de ces EI par les équipes soignantes permettrait une détection précoce des EI et une prise en charge rapide afin d'éviter la suspension longue de l'immunothérapie, qui est une perte de chance pour ces patients.

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  • Authors: Arquillière, Philippe;

    Nowadays, microelectronic devices are omnipresent in our everyday life. To make them smaller and smaller as well as smarter and smarter, a new process which consists in stacking integrated circuits is being studied. In order to build this type of structures, the fabrication of microvias between layers is key. This work ultimately aims at developing an innovative process with reduced cost for the efficient metallization of these microvias. This can be achieved using perfectly calibrated metallic nanoparticles (NPs). In particular, bimetallic Mn-CuNPs could be interesting precursors to grow “self-formed” barriers and seed layers in microvias. Ionic liquids (ILs) are extremely well adapted media for the synthesis of such nano-objects, especially when organometallic precursors are used. It has been shown that theirspecific 3D structure provides a template to grow RuNPs of controlled size. The IL also acts as stabilizer, eliminating the need to use ligands that contaminate the metallic surface. In this work, this concept have been extended to the synthesis of other metallic NPs, such as Cu and Mn, as well as synthesis of NPs containing the two metals (bimetallic M-M’NPs). Remarkably, these M-M’NPs always exhibit a smaller size than the MNPs and M’NPs separately. These homogeneous and stable suspensions have been directly applied and sintered onto technological substrates in order to form uniform and adherent metallic layers.; De nos jours, nous sommes entourés de dispositifs microélectroniques de plus en plus petits et performants. Pour poursuivre cette évolution, une nouvelle technologie est en cours de développement qui consiste à empiler plusieurs circuits intégrés. L’une des clefs pour aboutir à ce type d’architecture est la formation de microvias entre les différentes couches. Ce travail s’inscrit dans un à objectif à long terme qui vise à la mise au point d'un procédé innovant à coût réduit pour la métallisation de ces microvias, à partir de nanoparticules (NPs) métalliques de taille parfaitement calibrée. En particulier, des NPs bimétalliques de Mn et Cu pourraient être des précurseurs intéressants pour l'élaboration de barrières dites auto-formées et de couches d’accroches dans les microvias. Les liquides ioniques sont des milieux intéressants pour la synthèse de telles NPs, notamment à partir de précurseurs organométalliques. Il a été démontré que leur structure tridimensionnelle spécifique « guide » la croissance de NPs de Ru et les stabilise tout en les laissant libres de toute contamination de surface. Dans ce travail, ce concept a été enrichi par la synthèse de NPs d’autres métaux tels que Cu et Mn, et étendu à la formation de NPs constituées de deux métaux (M-M’NPs bimétalliques). De façon remarquable, les M-M’NPs obtenues ont toujours une taille inférieure aux MNPs et M’NPs prises séparément. Ces suspensions homogènes, très stables dans le temps, ont été directement déposées et frittées sur des substrats technologiques dans le but de former des films métalliques uniformes et adhérents.

    Hal-Diderotarrow_drop_down
    Hal-Diderot
    Doctoral thesis . 2012
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      Doctoral thesis . 2012
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  • Authors: Taveau, Valentin;
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  • Authors: Augustin, J.-E.; Cosme, G.; Couchot, F.; Fulda, F.; +11 Authors
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  • Authors: Abellard, Patrick; Abellard, Alexandre; Ciulli, Axel;

    National audience

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    Authors: Sybous, A.; El, Kaaouachi; Ait Ben Ameur, N.; Capoen, Bruno; +5 Authors

    International audience; We present measurements of the electrical conductivity of barely metallic n-type GaAs that are driven to the metal-insulator transition (MIT) by magnetic field. The experiments were carried out at low temperature in the range (4.2-0.066 K) and in magnetic field up to 4 T. We have determined the magnetic field for which the conductivity changes from the metallic behavior to insulator regime. On the metallic side of the MIT, the electrical conductivity is found to obey σ=σ0+mT1/2 down to 66 mK. Physical explanation to the temperature dependence of the conductivity is given in metallic side of the MIT using a competition between different effects involved in the mechanisms of conduction, like electron-electron interaction effect, Zeeman spin-splitting effect, and weak localization effect.

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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Physica B Condensed Matter
    Article . 2011
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    Hal-Diderot
    Article . 2011
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Physica B Condensed ...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Physica B Condensed Matter
      Article . 2011
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      Article . 2011
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: van Chuc Nguyen, ?.; Dandach, A.; Thi Thu Ha Vu, ?.; Fongarland, P.; +1 Authors

    Abstract Tungstated zirconia, ZrW, is reported as an efficient solid acid catalyst in the conversion of cellulose into lactic acid in hydrothermal conditions. The active phase of ZrW is generally ascribed to more or less polymerized WOx domains dispersed on zirconia. In this study, commercial uncalcined and calcined tungstated zirconia were used as catalysts for the conversion of cellulose under hydrothermal conditions at 190 °C. Their activities were also compared with uncalcined zirconium oxyhydroxide, ZrO2-x(OH)2x and calcined zirconia, ZrO2. Contrary to the expected results, it is disclosed that uncalcined ZrW exhibits higher catalytic activity and stability than calcined ZrW. Modifications in the products distribution were observed as glycolic acid formation at the expense of lactic acid formation upon ZrW calcination. Even more surprising, the catalytic activity of W free amorphous zirconium oxyhydroxide ZrO2-x(OH)2x is similar to uncalcined ZrW, with lactic acid as the main product while ZrO2 does not have any catalytic activity. These results suggest that the active phase of these catalysts might combine the couple Zr4+ and OH− species while the role of W species would be of secondary importance.

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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Molecular Catalysis
    Article . 2019
    License: Elsevier TDM
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    Hal-Diderot
    Article . 2019
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      Molecular Catalysis
      Article . 2019
      License: Elsevier TDM
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      Hal-Diderot
      Article . 2019
      License: CC BY NC
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  • Authors: Boukhari, Amar;

    Knowledge of the nuclear magnetic moments is of great importance to get a clear understanding of nuclear structure. The magnetic moment is sensitive to the single-particle nature of the valence nucleons. The development of radioactive beam facilities allows nowadays studying nuclear spins and moments of exotic nuclei which are far from the stability line. However, the measurement of magnetic moments of exotic nuclei produced as radioactive beams requires the development of reliable methods. Successful development of such methods would open up the possibility to discover new nuclear structure phenomena. The study outlined in this thesis is formed by two experiments. The first experiment was performed at ALTO facility in Orsay, France. One of the main requirements in order to measure a nuclear magnetic moment is to produce a spin-oriented ensemble. The latter can be produced by suitable reaction mechanism and nuclear spin interaction with the surrounding environment. The degree of the orientation depends on the formation process and reaction mechanism. The aim of this first experiment was investigating the level of nuclear spin orientation in incomplete fusion reaction mechanism. Two reaction channels were studied, the isomeric states in ⁶⁵mNi (I = 9/2⁺, Eₓ = 1017 keV, T₁/₂ = 26 ns), and ⁶⁶mCu (I = 6⁻, Eₓ = 563 keV, T₁/₂= 600 ns) with Time-Dependent Perturbed Angular Distribution (TDPAD) method. The result of the experiment demonstrates the possibility of obtaining spin alignment in incomplete fusion reaction of an order of 20%. This reaction mechanism, with such an important amount of spin alignment has potential near radioactive beam facilities to study the neutron-rich region with inverse kinematics reactions. The second experiment, and the main part of the thesis was performed at HIE-ISOLDE at CERN. This experiment aimed to obtain high precision g-factor information on a short-lived picosecond state. A new Time Differential Recoil-In-Vacuum (TDRIV) method was applied for the first time using post-accelerated radioactive beams. The g-factor measurement was performed for the first-excited state in ²⁸Mg nucleus (Eₓ = 1474(1) keV, T₁/₂ = 1.2(1) ps). Since the lifetime of the state is of the order of picoseconds, its g-factor can be measured only via the spin precession of the nucleus in an extremely strong magnetic field (kT). Such fields can only be produced at the nucleus by hyperfine interactions. In order to obtain a high precision on a g-factor measurement, a TDRIV calibration experiment was performed with a stable ²²Ne beam. This run allowed testing the system under the same conditions as with radioactive²⁸Mg beam. In addition, using the known g-factor of the first-excited state in ²²Ne allows to determine the absolute target-to-degrader distance so that to decrease the uncertainty and obtain a high precision g-factor measurement. The obtained calibration parameters from the ²²Ne data will be used in the determination of g-factor of ²⁸Mg.; La mesure des moments magnétiques nucléaires est d'une grande importance pour bien comprendre la structure nucléaire. Le moment magnétique est sensible à la nature de la particule indépendante. Le développement des faisceaux radioactifs permet aujourd'hui d'étudier les spins nucléaires et les moments de noyaux exotiques éloignés de la ligne de stabilité. Cependant, la mesure des moments magnétiques des noyaux radioactifs nécessite le développement des nouvelles méthodes fiables. Le développement réussi de telles méthodes ouvrirait la possibilité de découvrir de nouveaux phénomènes de structure nucléaire. L'étude présentée dans cette thèse est formée de deux expériences. La première expérience a été réalisée à ALTO à Orsay, en France. L'une des principales exigences pour mesurer un moment magnétique nucléaire est de produire un ensemble avec des spins orientés. Ce dernier peut être produit par un mécanisme de réaction approprié et une interaction de spin nucléaire avec le milieu environnant. Le degré d'orientation dépend du processus de formation et du mécanisme de réaction. Le but de cette première expérience était d’étudier le niveau d’orientation du spin nucléaire dans un mécanisme de réaction de fusion incomplète. Le résultat de l'expérience démontre la possibilité d'obtenir un alignement du spin dans une réaction de fusion incomplète d'un ordre de 20%. Ce mécanisme de réaction, avec une telle quantité d’alignement de spin, a le potentiel d’étudier la région riche en neutrons avec des faisceaux radioactifs. La deuxième expérience, et l'essentiel de la thèse, a été réalisée à HIE-ISOLDE au CERN. Cette expérience visait à obtenir des informations de haute précision sur le facteur g d’un état de courte durée. Une nouvelle méthode TDRIV (Time-Differential Recoil In Vacuum) a été appliquée pour la première fois avec des faisceaux radioactifs post-accélérés. La mesure du facteur g était réalisée pour le premier état excité dans un noyau de ²⁸Mg (Eₓ = 1474 (1) keV, T₁/₂ = 1,2 (1) ps).

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  • Authors: Eychenne, Camille;

    Fonder un projet de territoire à la lumière d'une bonne connaissance de ses composantes paysagères permet d'instaurer une dynamique durable de développement. Le paysage devient support de projet de territoire et outil de développement local.

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    Other literature type . 2016
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    Authors: Cécile Mons; Thomas Botzanowski; Anton Nikolaev; Petra Hellwig; +4 Authors

    International audience; Human mitoNEET (mNT) is the first identified Fe−S protein of the mammalian outer mitochondrial membrane. Recently, we demonstrated the involvement of mNT in a specific cytosolic pathway dedicated to the reactivation of oxidatively damaged cytosolic aconitase by cluster transfer. In vitro studies using apo-ferredoxin (FDX) reveal that mNT uses an Fe-based redox switch mechanism to regulate the transfer of its cluster. Using the "gold standard" cluster recipient protein, FDX, we show that this transfer is direct and that only one of the two mNT clusters is transferred when the second one is decomposed. Combining complementary biophysical and biochemical approaches, we show that pH affects both the sensitivity of the cluster to O 2 and dimer stability. Around physiological cytosolic pH, the ability of mNT to transfer its cluster is tightly regulated by the pH. Finally, mNT is extremely resistant to H 2 O 2 compared to ISCU and SufB, two other Fe−S cluster transfer proteins, which is consistent with its involvement in a repair pathway of stress-damaged Fe−S proteins. Taken together, our results suggest that the ability of mNT to transfer its cluster to recipient proteins is not only controlled by the redox state of its cluster but also tightly modulated by the pH of the cytosol. We propose that when pathophysiological conditions such as cancer and neurodegenerative diseases dysregulate cellular pH homeostasis, this pH-dependent regulation of mNT is lost, as is the regulation of cellular pathways under the control of mNT. I ron−sulfur (Fe−S) clusters are evolutionarily ancient and highly conserved prosthetic cofactors. Composed of only iron and sulfur, they are involved in many essential biological processes. 1,2 MitoNEET (mNT), also known as CISD1, is the first identified Fe−S protein of the mammalian outer mitochondrial membrane (OMM). 3,4 This is a small homodimeric protein (13 kDa for each monomer) anchored to the OMM by its 32-amino acid N-terminus with the major part of the protein, including the C-terminal Fe−S binding domain, located in the cytosol. 4 Each monomer accommodates one [2Fe-2S] cluster coordinated by three cysteines (C72, C74, and C83) and one histidine (H87) in a CDGSH domain 5−8 as other members of the NEET protein family, 9 which also includes Miner1 (or CISD2) and Miner2 (or CISD3) in mammals. 10 Although the biological activity of mNT is still debated, 11 studies have shown that it is involved in the regulation of iron/reactive oxygen species homeo-stasis, 12−14 in the regulation of lipid and glucose metabolism , 13,15 and in cell proliferation in breast cancer. 16 In vitro studies revealed that holo-mNT (the form of the protein with the cluster) is able to transfer its Fe−S cluster to very diverse apoprotein (an Fe−S protein, which has lost its cluster) recipients assembling either a [2Fe-2S] cluster as ferredoxin from various organisms, 17,18 human anamorsin 19 and CISD2, 20 or a [4Fe-4S] cluster as mammalian iron regulatory protein-1 (IRP-1)/cytosolic aconitase (c-aconi-tase). 14 On the basis of in cellulo experiments, we showed that mNT is able to repair the oxidatively damaged Fe−S cluster of human IRP-1/c-aconitase by transferring its cluster to the damaged protein. 14 Recently, we started to investigate in depth the in vitro cluster transfer reaction, focusing on the transfer from holo-mNT to [2Fe-2S] recipient protein. We unambiguously demonstrated that oxidized mNT ([2Fe-2S] 2+) triggers cluster transfer, whereas reduction of its cluster abrogates this transfer. Moreover, while O 2 significantly affects the lability of the oxidized mNT cluster, it does not interfere with the cluster

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    Biochemistry
    Article . 2018
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  • Authors: Payot, Claire;

    L'auteur de la thèse a souhaité limiter l'accès aux membres de l'Enseignement supérieur français.; L'arrivée sur le marché de nouvelles molécules d'immunothérapie (IT) révolutionne la prise en charge de certains cancers. Cependant leurs prix élevés et le peu de recul sur leurs effets à moyen et long termes, posent la question de la pertinence et de la place de ces molécules dans la stratégie thérapeutique des cancers. L'objectif de ce travail est d'obtenir des données en vie réelle de l'utilisation de nivolumab (N) et de pembrolizumab (P) au centre hospitalier de Metz Thionville (CHRMT). Ce travail décrit la cohorte de patients sous IT sur les deux premières années de son utilisation au CHRMT, puis les effets indésirables (EI) survenus chez ces patients ainsi, que la prise en charge de ces EI ; enfin, il décrit la survie globale et sans progression de ces patients et pour terminer le devenir des patients post IT. Cette étude observationnelle rétrospective s'étend sur les deux premières années de l'utilisation de l'IT au CHRMT, et concerne tous les patients ayant reçus N et P entre le premier juin 2016 et le 31 mai 2018. Les patients sont suivis 6 mois en post IT. Au total, sont étudiés 144 patients, 117 (81,3%) traités par N, et 27 (18,7%) par P. Le cancer bronchique (CB) est la principale indication de ces molécules. Les patients sous N et P ont présenté respectivement 2,7 et 2,9 EI durant leur traitement. La répartition des EI par système d'organe et le grade des EI ne sont pas statiquement différents d'une Dénomination Commune Internationale (DCI) à l'autre. Ils sont systémiques et non spécifiques d'organe. Les trois quarts des EI ne sont pas cotés graves d'après la classification CTCAE. Certains EI ont entrainé de longues pauses thérapeutiques, suite à la décroissance de corticoïdes, antidote de l'IT. On observe 55 patients qui ont progressé sous N soit 47% et 6 patients sous P soit 22%. Toutes indications confondues, le principal motif d'arrêt l'IT est la progression tumorale dans plus d'un cas sur deux (51%). Vient en seconde position, la survenue d'effets indésirables (26%). Cette étude a permis d'observer ce qui se passe en vie réelle, dans les conditions d'utilisations normales. Ce nombre conséquent d'EI, parfois grave, justifie une surveillance particulière et la mise en place de moyens appropriés pour leur prise en charge dans les meilleurs délais : sensibilisation du corps médical et des soignants, suivis biologiques, etc. Cependant rapporté au nombre de cures administrées dans cette cohorte, la fréquence d'effets indésirables reste relativement faible. Les grades et les cibles des EI de ces deux DCI sont comparables et appuie le lien avec leur mécanisme d'action immunologique. La bonne tolérance de ces traitements et les réponses à ces traitements parfois longues sont encourageantes. Une meilleure connaissance de ces EI par les équipes soignantes permettrait une détection précoce des EI et une prise en charge rapide afin d'éviter la suspension longue de l'immunothérapie, qui est une perte de chance pour ces patients.

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  • Authors: Arquillière, Philippe;

    Nowadays, microelectronic devices are omnipresent in our everyday life. To make them smaller and smaller as well as smarter and smarter, a new process which consists in stacking integrated circuits is being studied. In order to build this type of structures, the fabrication of microvias between layers is key. This work ultimately aims at developing an innovative process with reduced cost for the efficient metallization of these microvias. This can be achieved using perfectly calibrated metallic nanoparticles (NPs). In particular, bimetallic Mn-CuNPs could be interesting precursors to grow “self-formed” barriers and seed layers in microvias. Ionic liquids (ILs) are extremely well adapted media for the synthesis of such nano-objects, especially when organometallic precursors are used. It has been shown that theirspecific 3D structure provides a template to grow RuNPs of controlled size. The IL also acts as stabilizer, eliminating the need to use ligands that contaminate the metallic surface. In this work, this concept have been extended to the synthesis of other metallic NPs, such as Cu and Mn, as well as synthesis of NPs containing the two metals (bimetallic M-M’NPs). Remarkably, these M-M’NPs always exhibit a smaller size than the MNPs and M’NPs separately. These homogeneous and stable suspensions have been directly applied and sintered onto technological substrates in order to form uniform and adherent metallic layers.; De nos jours, nous sommes entourés de dispositifs microélectroniques de plus en plus petits et performants. Pour poursuivre cette évolution, une nouvelle technologie est en cours de développement qui consiste à empiler plusieurs circuits intégrés. L’une des clefs pour aboutir à ce type d’architecture est la formation de microvias entre les différentes couches. Ce travail s’inscrit dans un à objectif à long terme qui vise à la mise au point d'un procédé innovant à coût réduit pour la métallisation de ces microvias, à partir de nanoparticules (NPs) métalliques de taille parfaitement calibrée. En particulier, des NPs bimétalliques de Mn et Cu pourraient être des précurseurs intéressants pour l'élaboration de barrières dites auto-formées et de couches d’accroches dans les microvias. Les liquides ioniques sont des milieux intéressants pour la synthèse de telles NPs, notamment à partir de précurseurs organométalliques. Il a été démontré que leur structure tridimensionnelle spécifique « guide » la croissance de NPs de Ru et les stabilise tout en les laissant libres de toute contamination de surface. Dans ce travail, ce concept a été enrichi par la synthèse de NPs d’autres métaux tels que Cu et Mn, et étendu à la formation de NPs constituées de deux métaux (M-M’NPs bimétalliques). De façon remarquable, les M-M’NPs obtenues ont toujours une taille inférieure aux MNPs et M’NPs prises séparément. Ces suspensions homogènes, très stables dans le temps, ont été directement déposées et frittées sur des substrats technologiques dans le but de former des films métalliques uniformes et adhérents.

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  • Authors: Taveau, Valentin;
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  • Authors: Augustin, J.-E.; Cosme, G.; Couchot, F.; Fulda, F.; +11 Authors