Littérature scientifique sur le sujet « RSC complex, Rsc2 »

ABSTRACT Rsc1 and Rsc2 are alternative bromodomain-containing subunits of the ATP-dependent RSC chromatin remodeling complex in Saccharomyces cerevisiae. Smk1 is a sporulation-specific mitogen-activated protein kinase homolog that is required for the postmeiotic events of spore formation. In this study we show that RSC1 and RSC2 are haploinsufficient for spore formation in a smk1 hypomorph. Moreover, diploids lacking Rsc1 or Rsc2 show a subset of smk1-like phenotypes. High-copy-number RSC1 plasmids do not suppress rsc2-Δ/rsc2-Δ sporulation defects, and high-copy-number RSC2 plasmids do not suppress rsc1-Δ/rsc1-Δ sporulation defects. Mid-late sporulation-specific genes, which are normally expressed while key steps in spore assembly occur and which include genes that are required for spore wall formation, are not expressed in cells lacking Rsc1 or Rsc2. We speculate that the combined action of Rsc1 and Rsc2 at mid-late promoters is specifically required for the proper expression of this uniquely timed set of genes. Our data suggest that Smk1 and Rsc1/2 define parallel pathways that converge to provide signaling information and the expression of gene products, respectively, that are required for spore morphogenesis.

ABSTRACT The stable maintenance of the 2μm circle plasmid depends on its ability to overcome intrinsic maternal inheritance bias, which in yeast normally results in the failure to transmit DNA molecules efficiently to daughter cells. In addition to the plasmid proteins Rep1 and Rep2 acting on the plasmid DNA locus STB, it is likely that other chromosomally encoded yeast proteins are required. We have isolated mutants of yeast unable to maintain 2μm and found that RSC2 is essential for 2μm to overcome maternal inheritance bias. Rsc2 is part of a multisubunit RSC chromatin remodeling complex, and we show that in the absence of Rsc2 the chromatin structure of the STB region is significantly altered and the Rep1 protein loses its normal localization to subnuclear foci. Rsc1, a closely related homolog of Rsc2 present in an alternative form of the RSC complex, is not required for 2μm maintenance and does not replace the requirement for Rsc2 when overexpressed. This represents the first specific role for Rsc2 that has been related to a change in chromatin structure, as well as the first direct evidence linking chromatin structure to 2μm segregation.

ABSTRACT The budding yeast centromere-kinetochore complex ensures high-fidelity chromosome segregation in mitosis and meiosis by mediating the attachment and movement of chromosomes along spindle microtubules. To identify new genes and pathways whose function impinges on chromosome transmission, we developed a genomic haploinsufficiency modifier screen and used ctf13-30, encoding a mutant core kinetochore protein, as the reference point. We demonstrate through a series of secondary screens that the genomic modifier screen is a successful method for identifying genes that encode nonessential proteins required for the fidelity of chromosome segregation. One gene isolated in our screen was RSC2, a nonessential subunit of the RSC chromatin remodeling complex. rsc2 mutants have defects in both chromosome segregation and cohesion, but the localization of kinetochore proteins to centromeres is not affected. We determined that, in the absence of RSC2, cohesin could still associate with chromosomes but fails to achieve proper cohesion between sister chromatids, indicating that RSC has a role in the establishment of cohesion. In addition, numerous subunits of RSC were affinity purified and a new component of RSC, Rtt102, was identified. Our work indicates that only a subset of the nonessential RSC subunits function in maintaining chromosome transmission fidelity.

Upon prolonged activation of the spindle assembly checkpoint, cells escape from mitosis through a mechanism called adaptation or mitotic slippage, which is thought to underlie the resistance of cancer cells to antimitotic drugs. We show that, in budding yeast, this mechanism depends on known essential and nonessential regulators of mitotic exit, such as the Cdc14 early anaphase release (FEAR) pathway for the release of the Cdc14 phosphatase from the nucleolus in early anaphase. Moreover, the RSC (remodel the structure of chromatin) chromatin-remodeling complex bound to its accessory subunit Rsc2 is involved in this process as a novel component of the FEAR pathway. We show that Rsc2 interacts physically with the polo kinase Cdc5 and is required for timely phosphorylation of the Cdc14 inhibitor Net1, which is important to free Cdc14 in the active form. Our data suggest that fine-tuning regulators of mitotic exit have important functions during mitotic progression in cells treated with microtubule poisons and might be promising targets for cancer treatment.

DNA double-strand breaks (DSBs) are the most deleterious form of DNA damage and are repaired through non-homologous end-joining (NHEJ) or homologous recombination (HR). Repair initiation, regulation and communication with signaling pathways require several histone-modifying and chromatin-remodeling complexes. In budding yeast, this involves three primary complexes: INO80-C, which is primarily associated with HR, SWR1-C, which promotes NHEJ, and RSC-C, which is involved in both pathways as well as the general DNA damage response. Here we identify ARP6 as a factor involved in DSB repair through an RSC-C-related pathway. The loss of ARP6 significantly reduces the NHEJ repair efficiency of linearized plasmids with cohesive ends, impairs the repair of chromosomal breaks, and sensitizes cells to DNA-damaging agents. Genetic interaction analysis indicates that ARP6, MRE11 and RSC-C function within the same pathway, and the overexpression of ARP6 rescues rsc2∆ and mre11∆ sensitivity to DNA-damaging agents. Double mutants of ARP6, and members of the INO80 and SWR1 complexes, cause a significant reduction in repair efficiency, suggesting that ARP6 functions independently of SWR1-C and INO80-C. These findings support a novel role for ARP6 in DSB repair that is independent of the SWR1 chromatin remodeling complex, through an apparent RSC-C and MRE11-associated DNA repair pathway.

The assembly, distribution, and functional integrity of nuclear pore complexes (NPCs) in the nuclear envelope (NE) are key determinants in the nuclear periphery architecture. However, the mechanisms controlling proper NPC and NE structure are not fully defined. We used two different genetic screening approaches to identify Saccharomyces cerevisiae mutants with defects in NPC localization. The first approach examined green fluorescent protein (GFP)-Nic96 in 531 strains from the yeast Tet-promoters Hughes Collection with individual essential genes expressed from a doxycycline-regulated promoter (TetO7-orf). Under repressive conditions, depletion of the protein encoded by 44 TetO7-orf strains resulted in mislocalized GFP-Nic96. These included STH1, RSC4, RSC8, RSC9, RSC58, ARP7, and ARP9, each encoding components of the RSC chromatin remodeling complex. Second, a temperature-sensitive sth1-F793S (npa18-1) mutant was identified in an independent genetic screen for NPC assembly (npa) mutants. NPC mislocalization in the RSC mutants required new protein synthesis and ongoing transcription, confirming that lack of global transcription did not underlie the phenotypes. Electron microscopy studies showed significantly altered NEs and nuclear morphology, with coincident cytoplasmic membrane sheet accumulation. Strikingly, increasing membrane fluidity with benzyl alcohol treatment prevented the sth1-F793S NE structural defects and NPC mislocalization. We speculate that NE structure is functionally linked to proper chromatin architecture.

ABSTRACT Repair of chromosome double-strand breaks (DSBs) is central to cell survival and genome integrity. Nonhomologous end joining (NHEJ) is the major cellular repair pathway that eliminates chromosome DSBs. Here we report our genetic screen that identified Rsc8 and Rsc30, subunits of the Saccharomyces cerevisiae chromatin remodeling complex RSC, as novel NHEJ factors. Deletion of RSC30 gene or the C-terminal truncation of RSC8 impairs NHEJ of a chromosome DSB created by HO endonuclease in vivo. rsc30Δ maintains a robust level of homologous recombination and the damage-induced cell cycle checkpoints. By chromatin immunoprecipitation, we show recruitment of RSC to a chromosome DSB with kinetics congruent with its involvement in NHEJ. Recruitment of RSC to a DSB depends on Mre11, Rsc30, and yKu70 proteins. Rsc1p and Rsc2p, two other RSC subunits, physically interact with yKu80p and Mre11p. The interaction of Rsc1p with Mre11p appears to be vital for survival from genotoxic stress. These results suggest that chromatin remodeling by RSC is important for NHEJ.

ABSTRACT RSC is an essential chromatin remodeling complex in Saccharomyces cerevisiae that performs central roles in transcriptional regulation and cell cycle progression. Here we identify Htl1 as a novel factor that associates with the RSC complex both physically and functionally. We isolated HTL1 through a genetic screen for mutants that displayed additive growth defects with a conditional mutation in the protein kinase C gene (PKC1), which has been suggested through genetic connections to interact functionally with RSC. Several lines of evidence connect HTL1 to RSC function. First, an htl1Δ mutant displayed temperature-sensitive growth and a G2/M cell cycle arrest at restrictive temperatures, a phenotype similar to that of strains with conditional mutations in essential RSC components. Second, we isolated RSC3, which encodes a component of the RSC complex, as a dosage suppressor of the htl1Δ growth arrest. Third, an htl1Δ mutant displayed additive growth defects with conditional rsc3 alleles. Fourth, overexpression of HTL1 suppressed the growth defect of a strain with a conditional mutation in another RSC component, RSC8. Finally, we demonstrate that Htl1 is a nuclear protein that can associate in vivo with a fraction of the RSC complex. We propose that an RSC-Htl1 complex acts coordinately with protein kinase C to regulate the G2/M transition.

ABSTRACT RSC is an essential, multisubunit chromatin remodeling complex. We show here that the Rsc4 subunit of RSC interacted via its C terminus with Rpb5, a conserved subunit shared by all three nuclear RNA polymerases (Pol). Furthermore, the RSC complex coimmunoprecipitated with all three RNA polymerases. Mutations in the C terminus of Rsc4 conferred a thermosensitive phenotype and the loss of interaction with Rpb5. Certain thermosensitive rpb5 mutations were lethal in combination with an rsc4 mutation, supporting the physiological significance of the interaction. Pol II transcription of ca. 12% of the yeast genome was increased or decreased twofold or more in a rsc4 C-terminal mutant. The transcription of the Pol III-transcribed genes SNR6 and RPR1 was also reduced, in agreement with the observed localization of RSC near many class III genes. Rsc4 C-terminal mutations did not alter the stability or assembly of the RSC complex, suggesting an impact on Rsc4 function. Strikingly, a C-terminal mutation of Rsc4 did not impair RSC recruitment to the RSC-responsive genes DUT1 and SMX3 but rather changed the chromatin accessibility of DNases to their promoter regions, suggesting that the altered transcription of DUT1 and SMX3 was the consequence of altered chromatin remodeling.

Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. Biochemical analysis showed that CaRSC comprises 13 subunits and contains two novel non-essential members, which we named Nri1 and Nri2 (Novel RSC Interactors) that are exclusive to the CTG clade of Saccharomycotina. Genetic analysis showed distinct essentiality of C. albicans RSC subunits compared to model fungal species suggesting functional and structural divergence of RSC functions in this fungal pathogen. Transcriptomic and proteomic profiling of a conditional mutant of the essential catalytic subunit gene STH1 demonstrated global roles of RSC in C. albicans biology, with the majority of growth-related processes affected, as well as mis-regulation of genes involved in morphotype switching, host-pathogen interaction and adaptive fitness. We further assessed the functions of non-essential CaRSC subunits, showing that the novel subunit Nri1 and the bromodomain subunit Rsc4 play roles in filamentation and stress responses; and also interacted at the genetic level to regulate cell viability. Consistent with these roles, Rsc4 is required for full virulence of C. albicans in the murine model of systemic infection. Taken together, our data builds the first comprehensive study of the composition and roles of RSC in C. albicans, showing both conserved and distinct features compared to model fungal systems. The study illuminates how C. albicans uses RSC-dependent transcriptional regulation to respond to environmental signals and drive survival fitness and virulence in mammals.

Faithful chromosome segregation during mitosis is fundamental for cell viability and genome stability. For a correct division, all kinetochores must be attached to the mitotic spindle and cohesion must be timely removed. Anaphase is triggered by the Anaphase Promoting Complex bound to its regulatory subunit Cdc20 (APC-Cdc20) that polyubiquitylates securin (Pds1 in budding yeast), whose role is to maintain inactive the protease separase (Esp1 in budding yeast) until anaphase onset. Once active, separase cleaves cohesin, thus triggering sister chromatid separation. Separase also promotes cyclinB proteolysis and mitotic exit due to its involvement in the Cdc14-early anaphase release (FEAR) pathway that promotes a partial activation of the Cdc14 phophatase, which is in turn key for CDK inactivation and mitotic exit. Cdc14 is maintained inactive throughout most of the cell cycle bound to its inhibitor Net1/Cfi1 and trapped in the nucleolus. At the beginning of anaphase Cdc14 is released from the nucleolus into the nucleus by the FEAR pathway; subsequently, Cdc14 is released also in the cytoplasm by the MEN (Mitotic Exit Network) pathway. In this way Cdc14 is fully active and can trigger mitotic exit by cyclinB-CDK inactivation. The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism conserved in all eukaryotic organisms that ensures the correct segregation of the genetic material. In fact, it inhibits the metaphase to anaphase transition until all kinetochores are properly attached to the mitotic spindle by inactivating the APC-Cdc20 complex, thus providing the time for error correction. Cells do not arrest indefinitely upon SAC activation. After a variable period of time cells escape from the metaphase arrest also in the presence of a damaged mitotic spindle or faulty kinetochore attachments to spindle microtubules. This process is referred to as adaptation or mitotic slippage and is often involved in the resistance to chemotherapeutic compounds that target the mitotic spindle. In spite of its importance, the adaptation process is still little known. Within this context, the goals of my Ph.D. were: (1) to characterize the molecular mechanisms underlying SAC adaptation and (2) to search for factors involved in this process. For these purposes we used the yeast Saccharomyces cerevisiae as a model organism. (1) We characterized the adaptation process in either the presence or the absence of mitotic spindle perturbations. We depolymerized spindles by using two different drugs that alter microtubule dynamics, i.e. nocodazole and benomyl, whereas we induced SAC hyperactivation without spindle damage by overproducing Mad2 (GAL1-MAD2 cells), one of the key proteins for SAC signal generation and maintenance. We observed that in all the conditions cells are able to adapt, but with different kinetics. In particular, cells adapt faster in benomyl, while in nocodazole and with high levels of Mad2 cells need more time to slip out of mitosis. The few data available about SAC adaptation in higher eukaryotes indicate that SAC adaptation is accompanied by chromatid separation, a decrease in mitotic CDK activity and mitotic exit. Indeed, like in mammalian cells, yeast securin and cyclinB are degraded and sister chromatids are separated during adaptation. In addition, cyclinB stabilization, as well as Cdc20 and Cdc5 (polo kinase) inactivation, markedly delay adaptation, while the only yeast CKI (Sic1) is not involved in this process. Finally, when yeast cells adapt the SAC is likely to be turned off, as shown by the disassembly of the Mad1/Bub3 checkpoint complex. (2) To search for factors involved in SAC adaptation, we performed a genetic screen using GAL1-MAD2 cells. In particular, we screened for mutants that would remain arrested for prolonged times in mitosis upon MAD2 overexpression. We identified Rsc2, a non-essential component of the RSC chromatin remodelling complex, as a regulator of SAC adaptation in yeast. We demonstrated that RSCRsc2 is involved in fine tuning mitotic exit during the unperturbed cell cycle. Its activity becomes particularly important in conditions that would activate the SAC, as it contributes to cyclinB degradation. In the absence of Rsc2 Net1 phosphorylation and the early anaphase release of Cdc14 from the nucleolus are impaired, whereas expression of a dominant allele of CDC14 that loosens Net1 inhibition (CDC14TAB6-1) is sufficient to restore mitotic exit in conditions where Rsc2 becomes essential for this process. We further demonstrated that the ATPase activity of RSC is required for mitotic exit regulation, suggesting that its chromatin-remodelling activity is involved in this process. By studying possible genetic interactions between the RSC2 deletion and FEAR or MEN mutations, we found that RSC2 deletion confers synthetic lethality or sickness to MEN but not to FEAR mutants. Altogether, our data suggest that RSCRsc2 is a novel component of the FEAR pathway. Finally, we demonstrated that Rsc2 interacts in vivo and in vitro with the polo kinase Cdc5, which controls mitotic exit at different levels. Since RSC binds to acetylated histone tails, it is possible that histone transacetylases are also involved in SAC adaptation. We tested if the SAGA (Spt-Ada-Gcn5 Acetyltransferase) complex is involved in SAC adaptation by deleting ADA2 or GCN5 in yeast. Indeed, SAGA seems involved in adaptation, although the contribution of Ada2 and Gcn5 in the process differs depending on the conditions used to activate the SAC. Finally, since we found that upon treatment with benomyl (a microtubule destabilizer) cells adapt dividing nuclei, we wondered if SAC adaptation could be linked to the presence of cytoplasmic microtubules that are still partially detectable in these conditions. We therefore asked whether motor proteins and microtubule regulators are involved in mitotic slippage. Indeed, we found that in the absence of Kip2 and Bik1, which specifically bind to cytoplasmic microtubules, cells divide nuclei and exit mitosis slower than wild type cells, demonstrating that cytoplasmic microtubules and associated proteins could accelerate SAC adaptation. In conclusion, SAC adaptation is a very complex process whose timing probably depends on the interplay between different mechanisms. An important aim for a complete comprehension of this process, as well as for the development of new and more efficient cancer therapies, will be to identify novel factors implicated in adaptation and clarify how their function might be linked to one another.

Le complexe RSC est un des facteurs de remodelage de la chromatine capables de lever la barrière nucléosomale notamment lors de la transcription. Ce processus est effectué chez les eucaryotes par trois ARN polymérases (pol). Nous avons montré que le complexe RSC interagit avec les pol I et III. La protéine Rsc4 interagit par son domaine C-terminal avec la protéine ABC27, commune aux trois ARN polymérases. Nous avons isolé une mutation de la sous-unité Rsc4 qui abolit cette interaction. Les profils d'expression génomiques, établis par puces à ADN, ont permis de caractériser ses effets sur la transcription par la pol II. Curieusement, la majorité des gènes induits sont répartis sur le chromosome XII de manière non polaire. La présence de l'ADN ribosomique sur ce chromosome suggère un lien avec ce comportement particulier. Par ailleurs, la maturation de l'ARN 35S, transcrit par la pol I, est altérée, mais nous n'avons pas pu caractériser des défauts de transcription par les pol I et III<br>The RSC complex is one of the chromatin remodeling complexes that helps the transcripiton machinery to overcome the nucleosomal barrier. Eukaryotic transcription is carried out by three RNA polymerases. We have demonstrated that RSC complex interacts with pol I and III. The Rsc4 protein interacts by its C-teminal domain with the ABC27 protein, a subunit shared by the three eukaryotic RNA polymerases, We have isolated a mutation in the Rsc4 subunit that ablolish thi interaction. We performed genome profiling experiments using DNA microarrays to characterise pol II transcription defects. Surprisingly, the vast majority of the upregulated genes localised to the chromosome XII, spreading all along in a non-polar manner. We propose that the presence of the rDNA cluster on chromosome XII could be responsible for this peculiar transcriptional pattern. We have seen defects in the 35S RNA maturation but have been unable to clearly establish defects on pol I and pol III transcription

Regional Security Complex Theory (RSCT) innefattar analysenheter som är nära kopplade till försvarsmateriella handelavtal och har därför ett teoretiskt ramverk som kan hjälpa förstå och förklara avtalen i detalj. Det är dock oklart exakt hur detta ska göras eftersom det inte tas upp i Regions and Powers: The Structure of International Security. Syftet med denna uppsats är att med hjälp av RSCT förklara Mistralaären för att sedan undersöka om det finns en underliggande process gemensamt för liknande fall.

New corrole–BODIPY conjugates have been synthesized in high yield under mild conditions. Upon excitation at the absorption maximum of the BODIPY antenna chromophore, the fluorescence intensity of the free base corrole–BODIPY conjugate increases by ca. 300%, and significant phosphorescence intensity is observed for the iridium(III) complex of the conjugate, while almost no phosphorescence is observed for the parent iridium(III) corrole, due to through-bond energy transfer from the BODIPY antenna-chromophore to the corrole core.<br>Original publication is available at http://dx.doi.org/10.1039/c5ra07250f<br>Arbortext Advanced Print Publisher 9.1.510/W Unicode<br>Acrobat Distiller 8.1.0 (Windows); modified using iText� 5.3.3 �2000-2012 1T3XT BVBA (AGPL-version)

Cette thèse présente la reconstruction de l’histoire tectono-thermique du massif varisque des Jebilet (Maroc) à fort potentiel minier, depuis son évolution pré-orogénique au Dévonien supérieur-Carbonifère inférieur jusqu’à sa structuration pendant l’orogénèse varisque-alléghanienne au Carbonifère supérieur-Permien inférieur. Pour répondre à cette problématique, ce travail s’organise autour de deux approches : (1) l’une métrologique appliquée à la géothermométrie Raman sur la matière carbonée (RSCM) et (2) l’autre intégrant une étude structurale, géochronologique et une analyse de la thermicité.L’approche métrologique a permis de valider l’applicabilité du géothermomètre RSCM (1) dans un contexte de métamorphisme polyphasé, (2) pour des roches carbonatées et des skarns des Jebilet et (3) de proposer un nouveau paramètre Raman RSA permettant de mieux préciser les températures supérieures à 500°C et d’étendre l’applicabilité de la méthode jusqu’à des températures maximales qui atteignent les 700°C.A partir de l’approche intégrée, trois épisodes tectono-thermiques ont été mis en évidence. Le premier épisode D₀ correspond à une tectonique extensive permettant l’ouverture du bassin des Jebilet au Dévonien supérieur-Carbonifère inférieur. Cette tectonique extensive est accompagnée par une anomalie thermique supérieure à 500°C déduites des mesures de géothermométrie RSCM (TRSCM) et par une importante activité magmatique bimodale et granodioritique datée dans ce travail entre 358 ± 7 et 336 ± 4 Ma. Au Carbonifère supérieur débute la phase compressive structurant le massif des Jebilet avec la mise en place de nappes superficielles au Namuro-Westphalien (D₁), suivie par la phase varisque majeure (D₂). L’analyse structurale a permis de montrer une évolution progressive du régime de déformation de D2 depuis une compression coaxiale à une transpression dextre compatible avec un raccourcissement horizontal WNW-ESE à NW-SE. D₂₁ est associée à deux événements thermiques, le premier syn-tectonique de moyenne température (300°<br>This thesis presents the reconstruction of the tectono-thermal history of the Paleozoic Jebilet massif (Morocco), from its pre-orogenic evolution at the Upper Devonian-Lower Carboniferous to its structuration during the variscan-alleghanian orogeny at the Upper Carboniferous-Lower Permian. To address this issue, this work is organized around two approaches: (1) one metrological applied to the Raman Spectroscopy of Carbonaceous Matterial (RSCM) and (2) the other integrating a structural and geochronological study and a thermicity analysis.The metrological approach allowed to validate the applicability of the RSCM geothermometer (1) in a context of polyphase metamorphism, (2) for carbonate rocks and skarns of Jebilet and (3) to propose a new parameter Raman RSA allowing to better specify temperatures above 500°C and extend the applicability of the method to maximum temperatures of up to 700°C.From the integrated approach, three tectono-thermal episodes were highlighted. The first episode D₀, corresponds to an extensive tectonic allowing the opening of the Jebilet basin at the Upper Devonian-Lower Carboniferous. This opening is accompanied by a HT thermal anomaly as shown by the important bimodal and granodioritic magmatic activity dated between 358 ± 7 Ma and 336 ± 4 Ma and the TRSCM higher than 500°C recorded by the rocks. During Upper Carboniferous, the compressive phase structuring the Jebilet massif begins with the emplacement of superficial nappes (D₁), followed by the variscan major phase (D2). Structural analysis showed a gradual evolution of D₂ deformation regime from coaxial compression to dextral transpression consistent with WNW-ESE to NW-SE horizontal shortening. D₂ is associated with two thermal events, the first is syn-tectonic with TRSCM between 300 and 400°C, and the second is syn- to post-tectonic with TRSCM between 600 and 660°C.This tectono-thermal context would be the expression of geodynamic processes involving from the Upper Devonian a delamination of the Rheic lithosphere by "slab break-off" or "slab roll-back" which would induce (1) the rise of hot asthenospheric current, and (2) the clockwise rotation of Gondwana and its gradual amalgamation with Laurussia structuring the variscan-alleghanian belt during the Upper Carboniferous-Lower Permian

Les cordillères Bético-Rifaines sont situées en Méditerranée occidentale, où elles forment un arc étroit. Comparée à d’autres segments orogéniques, leur évolution géodynamique reste extrêmement discutée en raison d’une histoire tectono-métamorphique polyphasée depuis le rifting Mésozoïque, jusqu’à l’histoire alpine incluant subduction,collision et effondrement tardi-orogénique. Cette thèse s’est focalisée sur deux problématiques restant activement débattues et qui concernent le complexe Alpujárride, appartenant aux Zones Internes (ZI) des Cordillères Bétiques.Deux zones d’étude ont été ciblées, avec (i) les massifs péridotitiques affleurant à l’ouest et dont les modalités de mise en place restent énigmatiques et (ii) les unités tectoniques affleurant à l’est et dans lesquelles les paragenèses de haute pression-basse température (HP/BT) en lien avec l’épisode de subduction alpine, sont les mieux préservées mais dont les contraintes temporelles sont largement incertaines.Ce travail de recherche s’est attaché à utiliser une approche multi-échelles, depuis celle de l’affleurement jusqu’à celle de la région, et pluridisciplinaire, avec un travail de cartographie détaillée, des observations structurales et pétrographiques, de la thermométrie Raman et des datations 40Ar/39Ar. Nos résultats mettent en évidence(i) l’exhumation du massif péridotitique de Ronda dans un contexte d’hyper-amincissement de la croûte continentale résultant d’un épisode de rifting et (ii) la fin de l’épisode métamorphique de HP/BT vers 38 Ma avec l’initiation du retrait du panneau plongeant et l’ouverture d’un bassin d’arrière-arc, associée à un métamorphisme de haute température-basse pression (HT/BP). C’est dans ce contexte extensif que le complexe Alpujárride s’exhume après une phase majeure d’amincissement crustal. Cet épisode de métamorphisme de HT/BP prend fin avec la mise en place des ZI des Cordillères Bético-Rifaines sur les marges Ibérie et Afrique, vers 20 Ma<br>The Betic-Rif Cordillera, located in the western Mediterranean region, forms a narrow, arcuate orogenic belt. By comparison with other orogenic belts in the Mediterranean realm, its geodynamic evolution is higly controversial because of a long and complex tectono-metamorphic history, including the Mesozoic rifting and the Alpineorogenesis where subduction, collisional and post-orogenic extensional events are successively recorded. This Ph.D.thesis aims to address two major issues about the geodynamic evolution of the Alpujárride Complex, a group of metamorphic units that belong to the Internal Zones of the Betic Cordillera. Two study areas have been investigated with (i) the peridotitic massifs located in the western part of this complex whose mechanisms and timing of exhumation remain unclear and (ii) the tectonic units located further east that display well-preserved high pressure low temperature (HP/LT) mineral parageneses related to the Alpine subduction episode but with high uncertainties regarding the age of this metamorphic event.This work has been carried out by following a multi-scale and multi-disciplinary approach, from the outcrop- to the regional-scale, including detailed field mapping, structural measurements, petrographic observations, Ramanthermometry and 40Ar/39Ar dating. Our results evidence (i) the exhumation of the Ronda peridotite controlled by anhyper-extension event associated with a rifting stage and (ii) the end of the HP/LT peak conditions around 38 Ma,juste before the inception of the slab roll-back and back-arc opening associated with a high temperature-lowpressure (HT-LP) metamorphic overprint. The Alpujárride Complex is exhumed during this stage, while the crust ishigly stretched. This HT-LP metamorphic event ended with the thrusting of the Internal Zones of the Betic-RifCordillera onto the Iberian and African margins, around 20 Ma ago

碩士<br>國立陽明大學<br>遺傳學研究所<br>92<br>RSC complex, an essential chromatin-remodeling complex in Saccharomyces cerevisiae, performs central roles in transcriptional regulation and cell cycle progression. RSC complex has been found to interact with Htl1p. To study the relationship between Htl1p and RSC complex, a series of analysis, including ion exchange column chromatography, sucrose gradient assay, multiple copy suppressor and partial protease, were performed in this thesis. By ion exchange column chromatography and sucrose gradient assay, the eluted protein and the distribution of subunits of RSC complex with or without DNase treatment were different between htl1 mutant and wild type cells. According to the analysis of sucrose gradient distribution in wild type and htl1 deletion strains at 37℃, we found Htl1p may play a role in maintaining stability of RSC complex, especially in the interaction between Rsc8p and Sth1p. Therefore, the instability of RSC complexes might be the main reason that causes temperature sensitivity. To further characterize if the interaction of Sth1p and Rsc8p is crucial for the temperature sensitive phenotype. A fusion protein experiment was designed. We constructed STH1-LINKER-RSC8 (SLR) fusion gene and inserted it into the strain without HTL1. So far that Ura+ spore can grow at 30℃ and 37℃. Partial protease digestion demonstrated that Rsc8p exhibits endopeptidase Glu-C sensitivity in htl1 deletion mutant. In order to further characterize HTL1 gene, we screened suppressors of Benomyl sensitivity of htl1 deletion strain by multicopy suppressor scheme. However, no suppressor of htl1 deletion strain was obtained.

碩士<br>國立陽明大學<br>生命科學系暨基因體科學研究所<br>105<br>Eukaryotes evolved a specific strategy for DNA packaging. A repeating unit, nucleosome, consists of 147 base pairs of DNA segment wrapped histone core proteins. Nucleosome plays an important role in the regulation of DNA-dependent biosynthesis and gene expression by its structure. Chromatin structure remodeling complex (RSC, Remodel the Structure of Chromatin) is essential for the regulation of nucleosome structure in vivo. Previous researches indicated that RSC complex can hydrolyze ATP to perturb nucleosome structures resulting in nucleosome sliding and histone octamer ejection. However, the mechanisms and the transition state of RSC-mediated nucleosome remodeling are still unclear. Here we utilize tether particle motion (TPM) experiments to investigate the RSC-mediated nucleosome remodeling process in detail. RSC has been known to play an important role in DNA-dependent biosynthesis pathways. Therefore, we study the interplay between RSC and other factors, acceptor DNA and nucleosome assembly protein (Nap1). By using TPM experiments, the histone octamer ejection was observed during RSC-mediated nucleosome remodeling. Moreover, the high percentage of the RSC-mediated histone octamer ejection was observed under saturated ATP and in the presence of acceptor DNA. In contrast, the ratio of RSC-mediated histone octamer ejection decreased in the presence of Nap1. In this project, the whole reaction scheme of RSC-mediated nucleosome remodeling process, including nucleosome sliding and histone octamer ejection, can be depicted based on TPM results.

AbstractChromatin architecture has a profound effect on the gene expression in eukaryotes. It is constantly modulated in the cells in response to different stress condition and during the normal physiological process in the cell. The chromatin is also modulated during the cell growth and division, where several proteins involved during the cell cycle are synthesized, and hence the gene expression profile and chromatin state of an actively dividing cell differ from that of a resting cell in G0 state. Candida albicans, which is a harmless commensal in human host and an opportunistic fungal pathogen also show dynamic chromatin architecture, and this is facilitated by the several epigenetic determinants, which modulate the chromatin architecture. In this context, RSC (Remodel the structure of chromatin) complex in C. albicans is previously shown to be crucial for cell viability and to carry out several DNA templated events, like kinetochore function and cohesion enrichment. To correlate the role of RSC in kinetochore function with the chromatin architecture at centromeric and non-centromeric region, here we have shown that the chromatin at non-CEN7 regions shows lesser occupancy of nucleosomes in absence of Sth1 protein (catalytic component of RSC complex), which is due to the reduced binding but not due to the reduced expression of the histones.

The geopolitical importance of the Arctic is intensifying with the economic and strategic opportunities being unraveled in the wake of the impact of climate change. The chapter analyses the actors and the factors affecting the current security relations in the region and recommends the creation of a regional security architecture (RSA) to deal with the emerging conflict potential of the Arctic. Through the establishment of an effective RSA for the Arctic, the prime objective of building a security environment that protects the region and promotes sustainable economic growth will be achieved. The chapter has been conceptualized under the broad theme of security studies while drawing specifically from the constructivist-structuralist framework of the regional security complex theory (RSCT).

The purpose of the essay is to examine the aspects and procedures of the National Project for the Inclusion and Integration of Roma, Sinti and Caminanti Children carried out in Italy in the years 2013-2016 by the Ministry of Labor and Social Policies. Some previous laws and regulations aiming at curbing the significant school dropout of Gypsy pupils and at promoting their integration are also taken into consideration. Given the unique cultural and linguistic identity of RSC pupils, the complex implementation of inclusive education practices is here discussed, along with the main ethnic and linguistic peculiarities of RSC pupils in view of their difficult school and social integration within the gagé’s world.

Abstract The BECM are proposed to classify spatial four-link mechanisms according to groups such as crank-rocker, double-rocker and double-crank (drag link). The BECM can determine the feasible regions and number of the extreme values exactly and solve them simply without complex derivation and calcultion. The paper concerns itself mainly with the RSSR linkage but it can be applied also to other types such as RSSP, RSCP, RSCR etc. The method is very simple and the geometric concept is very clear. Although the graphical methods is mainly introduced in this paper, certainly, it can also be coded in computer to solve out their accurate values.

A cDNA encoding full length single chain urokinase-type plasminogen activator (scu-PA) was cloned and sequenced. The recombinant scu-PA (rscu-PA) cDNA as well as the cDNA of two mutants constructed by deoxyoligonucleotide directed mutagenesis of Lys158 in rscu-PA to Gly158 (rscu-PA-Gly158 ) or to Glu158 (rscu-PA-Glu158 ) were inserted into SV40 early promoter/enhancer based expression vectors, which were used to transfect Chinese Hamster Ovary (CHO) cells. The expression products were purified from serum-free conditioned media by immunoadsorption on an insolubilized monoclonal antibody raised against natural scu-PA (nscu-PA), followed by gel filtration.The amidolytic activity of the three rscu-PAs was low (&lt; 500 IU/mg). The mutant rscu-PAs, in contrast to the rscu-PA and nscu-PA, could not be converted into an amidolytically active two-chain form (tcu-PA) by plasmin. The mutant scu-PAs had a very low specific activity (&lt; 1,000 IU/mg) on fibrin plates, whereas wild type rscu-PA had a specific activity &lt; 1000 IU/mg. The mutant scu-PAs did not cause lysis of a I-fibrin labeled plasma clot immersed in citrated human plasma. Serum-free medium from a control transfected CHO cell line showed no significant plasminogen activating activity.In a purified system, both rscu-PA-Gly and rscu-PA-Glu activate plasminogen following Michaelis-Menten kinetics, with a much lower affinity (K = 60-80 yM) but with a higher catalytic rate constant (k2 = B.01 s-1) as compared to the wild type rscu-PA (K =1.0 yM, k = 0.002 s-1).It is concluded thaz conversion of scu-PA to tcu-PA is prerequisite for the activation of plasminogen. However, Lys158 seems to be important for the stability of the Michaelis complex between scu-PA and plasminogen.

Abstract Aerial application of dispersants are an effective means of responding to oil spills in coastal waters and the deeper waters of the Outer Continental Shelf or Gulf of Mexico. To ensure the safety of responders and nearby wildlife, a buffer area is put in place around the spilled oil to be treated, within which spraying operations are conducted. In 2015, a research project was initiated to develop a prototype Decision Support Tool (DST) designed specifically for estimating the spray drift during the aerial application of dispersants on an oil spill. In 2019, an initiative was undertaken to further develop the DST and address known data gaps in the modeling used in the prototype, expand on the aircraft included in the tool, and include a contour plot output of dispersant deposition. The DST has been designed specifically for estimating the spray drift during the aerial application of dispersants on an oil spill through the use of complex Computational Fluid Dynamics (CFD) modeling. The DST program operational space was developed based on direct input from Oil Spill Response Operators (OSROs) for ten airframes currently used in the United States for aerial response operations, including both turbo propeller and turbo fan engine types. The DST employs a database of results generated using the latest in CFD modeling technology to examine flow structures and drift effects created by various operating conditions, coupled with specific configurations of different oil spill response aircraft and their spray systems (boom and nozzle configurations). The DST uses a Response Surface Curve (RSC) for each airframe to predict the drift extent of dispersant particles and mass deposition concentration, the RSC for each airframe was derived from a database of results generated using the latest CFD modeling technology. The studies conducted to generate data for the DST RSCs provided considerable insight into the relationships between the particle dispersant behavior for different airframe types. Trends were identified in particle dispersion behavior when airframes were flown with a heavy payload (full weight) compared to lighter payload (empty weight). These trends change depending on the airframe used and, more specifically, the location and arrangement of the boom used to release the droplets relative to the location of the main wing. Change in Particle Size Distribution (PSD) was also investigated for flight operations of one airframe and the impact on the drift extent reported. The DST will provide oil spill responders with information related to the extent of any areas potentially impacted by dispersant drift. This will assist the operational control personnel in establishing setback distances, information which becomes increasingly important as a spill escalates beyond a Tier 1 response where the size of the spill, and the resources committed, become significant. In addition, the DST generates a contour plot of mass deposition at ground level based on the operational and environmental parameters input to the program, providing the user with a graphical display of where the majority of the aerial dispersant is predicted to land. While the analysis and tool development are complete, a formal peer review has not been completed at the time of the paper publication.

Abstract Aerial application of dispersants are an effective means of responding to oil spills in coastal waters and the deeper waters of the Outer Continental Shelf or Gulf of Mexico. To ensure the safety of responders and nearby wildlife, a buffer area is put in place around the spilled oil to be treated, within which spraying operations are conducted. In 2015, a research project was initiated to develop a prototype Decision Support Tool (DST) designed specifically for estimating the spray drift during the aerial application of dispersants on an oil spill. In 2019, an initiative was undertaken to further develop the DST and address known data gaps in the modeling used in the prototype, expand on the aircraft included in the tool, and include a contour plot output of dispersant deposition. The DST has been designed specifically for estimating the spray drift during the aerial application of dispersants on an oil spill through the use of complex Computational Fluid Dynamics (CFD) modeling. The DST program operational space was developed based on direct input from Oil Spill Response Operators (OSROs) for ten airframes currently used in the United States for aerial response operations, including both turbo propeller and turbo fan engine types. The DST employs a database of results generated using the latest in CFD modeling technology to examine flow structures and drift effects created by various operating conditions, coupled with specific configurations of different oil spill response aircraft and their spray systems (boom and nozzle configurations). The DST uses a Response Surface Curve (RSC) for each airframe to predict the drift extent of dispersant particles and mass deposition concentration, the RSC for each airframe was derived from a database of results generated using the latest CFD modeling technology. The studies conducted to generate data for the DST RSCs provided considerable insight into the relationships between the particle dispersant behavior for different airframe types. Trends were identified in particle dispersion behavior when airframes were flown with a heavy payload (full weight) compared to lighter payload (empty weight). These trends change depending on the airframe used and, more specifically, the location and arrangement of the boom used to release the droplets relative to the location of the main wing. Change in Particle Size Distribution (PSD) was also investigated for flight operations of one airframe and the impact on the drift extent reported. The DST will provide oil spill responders with information related to the extent of any areas potentially impacted by dispersant drift. This will assist the operational control personnel in establishing setback distances, information which becomes increasingly important as a spill escalates beyond a Tier 1 response where the size of the spill, and the resources committed, become significant. In addition, the DST generates a contour plot of mass deposition at ground level based on the operational and environmental parameters input to the program, providing the user with a graphical display of where the majority of the aerial dispersant is predicted to land. While the analysis and tool development are complete, a formal peer review has not been completed at the time of the paper publication.

The Russian Academy of Sciences together with the Electronic Library eLibrary.ru have developed an academic rating of scientific journals from the Special Collection (SC), which includes about 15% of the journals of the Russian Science Citation Index (RSCI). The academic rating is based on the methodology of calculating the thematic ratings of the RSCI. The basis of the academic rating formula is the impact factor of the journal, which takes into account the citations of articles only from the journals of the SC collection and journals included in the international bibliographic databases Web of Science and Scopus. The paper concludes that the methodology for calculating the academic rating has significant drawbacks, which did not allow the academic rating to give a complete and objective assessment of the authority of Russian scientific journals.

The maritime industry is transitioning toward zero emission. To ensure compliance with future emission reduction regulations, many different alternative fuels and technology options are being investigated and evaluated. However, as these are ongoing developments, this results in varying and changing data on the performance and requirements of options. On top of that, while regulatory ambitions are aiming for increasingly larger reductions of Green House Gases (GHG) and other harmful substances, the level and details of the future regulations are unknown and subject to ongoing scientific and societal discussions. The level of uncertainty regarding regulation and technology for the energy transition can be defined as being deeply uncertain, which means uncertainty cannot be ordered in terms of possibility or occurrence. Although uncertainty is not uncommon in ship design, ship owners and designers are faced with an unprecedented level of uncertainty and require new methods to deal with this. This paper therefore investigates and compares several methods that could be used to increase the feasibility of future energy carriers in the design process, while accounting for the uncertainty in regulation and technical details of alternative fuels. Three promising methods were identified in a literature research: Firstly, Dynamic Adaptive Policy Pathways (DAPP) evaluates alternative options and develops possible pathways to compliance. Secondly, Responsive Systems Comparison (RSC) determines performance of a design in established scenarios (epoch), also allowing evaluation including retrofit (changeability). Thirdly, Robust Decision making (RDM) explores the effect of uncertainties on a pre-specified design and analyses its vulnerability. Within this paper, a first comparison is carried out by applying each method to a general cargo ship case. The goal is to better understand the usability and potential of each method for the energy transition in shipping. Each of the researched methods was shown to allow for different insights in option performance in uncertain conditions during the early design stage. With DAPP providing a global, but clear overview of the possible future pathways toward emission reduction compliance of the design, RSC giving a more detailed insight of technology options in specific scenarios (including evaluation of changeability in a scenario) and RDM allowing a more in depth research of the alternative fuel’s parameters and the circumstances under which these might comply. With each method demonstrating its own strength, future research will develop more realistic and complex designs and processes to be applied to a combination of the beneficial aspects of two or more methods.

Abstract To accelerate the design automation process for the spatial mechanism design, this paper presents an efficient kinematic analysis method, called the joint displacement method. Based on this method, the kinematic analysis for a seven-link, two-loop spatial RSCC-SRR mechanism can be accomplished in 1.52 second on a PC/486-based computer for a complete 60-steps (6 degrees/step) crank-revolution. This method is applicable for both single-loop and multiloop spatial mechanisms with revolute, cylindrical, translational, spherical and universal joints, with the high computational efficiency which hasn’t been found in the literatures. The general purpose computer program coded in C language has been tested with a wide variety of mechanisms, which produces very satisfactory results.

За последние 30 лет произошла революция в психотерапии под влиянием методологии доказательного подхода. Во всем мире преимущество получили методы доказательной психотерапии. Скорость внедрения результатов исследований в практику предопределяется феноменом научной влиятельности. Для определения данного феномена автор предлагает использовать процентиль по ядру РИНЦ. Впервые был составлен рейтинг научной влиятельности психотерапевтов Санкт-Петербурга. Всего в рейтинге представлен 31 специалист (процентиль по ядру РИНЦ от 4 до 51) из 12 организаций, расположенных по средней величине процентиля по ядру РИНЦ следующим образом: 1) Научный медицинский исследовательский центр психиатрии и неврологии им. В. М. Бехтерева — 16,1; 2) Петербургская школа психотерапии и психологии отношений — 17,7; 3) Санкт-Петербургский государственный педиатрический медицинский университет — 31,0; 4) Северо-Западный государственный медицинский университет им. И. И. Мечникова — 39,5. Важно отметить, что в рейтинг попали негосударственные организации, которые в отличие от государственных не имеют доступа к прямому государственному финансированию научных исследований. Методы психотерапии в рейтинге представлены следующим образом: психоанализ — 8,7; позитивная динамическая психотерапия — 17,7; когнитивно-поведенческая психотерапия — 31,3 и личностно-ориентированная (реконструктивная) — 31,6. Полученные результаты могут учитываться руководителями коммерческих структур, учреждений здравоохранения и образования при составлении перспективных планов, а также врачами и психологами при выборе образовательных программ профессиональной переподготовки в области психотерапии. Over the past 30 years, there has been a revolution in psychotherapy under the influence of evidence-based methodology. The methods of evidence-based psychotherapy have gained preference all over the world. The rapidity of implementation of research results into practice is predetermined by the phenomenon of scientific influence. To determine this phenomenon, the author proposes to use the RSCI (Russian Science Citation Index) core percentile. The rating of the scientific influence of St. Petersburg psychotherapists was compiled for the first time ever. In total, the rating includes 31 specialists (with the 133 RSCI core percentile from 4 to 51) representing 12 organizations, ranked in accordance with the average RSCI core percentile as follows: 1) Scientific Medical Research Center for Psychiatry and Neurology named after V. M. Bekhterev — 16.1; 2) St. Petersburg School of Psychotherapy and Psychology of attitudes — 17.7; 3) St. Petersburg State Pediatric Medical University — 31.0; 4) North-Western State Medical University named after I. I. Mechnikov — 39.5. It is important to note that the rating includes non-governmental organizations, which, unlike state-run ones, do not have access to direct state funding for scientific research. Methods of psychotherapy are presented in the rating as follows: psychoanalysis — 8.7; positive dynamic psychotherapy — 17.7; cognitive-behavioral psychotherapy — 31.3, and personality-oriented (person-centered) psychotherapy — 31.6. The results obtained can be taken into account by the heads of commercial structures, health care and educational institutions when drawing up long-term plans, as well as by doctors and psychologists when choosing educational programs for professional retraining in the field of psychotherapy.

Cette étude porte sur une des innovations contemporaines liées à l’économie de la publication scientifique : les accords dits transformants, un objet relativement circonscrit au sein des relations entre consortiums de bibliothèques et éditeurs scientifiques, et temporellement situé entre 2015 et 2020. Ce type d’accords a pour objectif affiché d’organiser la transition du modèle traditionnel de l’abonnement à des revues (souvent proposées par regroupements thématiques ou collections) vers celui de l’accès ouvert en opérant une réaffectation des budgets qui y sont consacrés. Notre travail d’analyse sociologique constitue une première étude systématique de cet objet, fondée sur la recension de 197 accords. Le corpus ainsi constitué inclut des accords caractérisés par la coprésence d’une composante d’abonnement et d’une composante de publication en accès ouvert, même minimale (« jetons » de publication offerts, réduction sur les APC...). En conséquence, ont été exclus de l’analyse les accords portant uniquement sur du financement centralisé de publication en accès ouvert, que ce soit avec des éditeurs ne proposant que des revues avec paiement par l’auteur (PLOS, Frontiers, MDPI...) ou des éditeurs dont une partie du catalogue est constitué de revues en accès ouvert. L’accord le plus ancien de notre corpus a été signé en 2010, les plus récents en 2020 – les accords ne commençant qu’en 2021, même annoncés au cours de l’étude, n’ont pas été retenus. Plusieurs résultats se dégagent de notre analyse. Tout d’abord, on note une grande diversité des acteurs impliqués avec 22 pays et 39 éditeurs, même si certains consortiums (Pays-Bas, Suède, Autriche, Allemagne) et éditeurs (CUP, Elsevier, RSC, Springer) en ont signé beaucoup plus que d’autres. Ensuite, la durée des accords, comprise entre une et six années, révèle une distribution très inégalitaire, avec plus de la moitié des accords (103) signés pour 3 ans, ainsi qu’une faible proportion pour 4 ans ou plus (22 accords). Enfin, en dépit d’appels répétés à la transparence, moins de la moitié des accords (96) ont un texte accessible au moment de cette étude, sans qu’on puisse observer une tendance récente à une plus grande disponibilité. L’analyse montre également des degrés d’ouverture très variables, allant d’une simple information sur le répertoire ESAC en passant par la mise à disposition d’un format annotable jusqu’à l’attribution d’un DOI et d’une licence de réutilisation (CC-BY), en incluant le détail des sommes monétaires. Parmi les 96 accords disponibles, dont 47 signés en 2020, 62 ont fait l’objet d’une analyse en profondeur. C’est à notre connaissance la première analyse à cette échelle, sur un type de matériel non seulement inédit, mais qui était auparavant soumis à des clauses de confidentialité. Fondée sur une lecture minutieuse, l’étude décrit de manière fine leurs propriétés, depuis la matérialité du document jusqu’aux formules financières, en passant par leur morphologie et l’ensemble des droits et devoirs des parties. Les contenus des accords sont donc analysés comme une collection dont nous cherchons à déterminer les points communs et les variations, à travers des codages explicites sur certaines de leurs caractéristiques. L’étude pointe également des incertitudes, et notamment leur caractère « transitionnel », qui demeure fortement discuté. D’un point de vue morphologique, les accords montrent une grande diversité en matière de taille (de 7 à 488 pages) et de structure. Néanmoins, par définition, ils articulent tous deux objets essentiels : d’une part, les conditions de réalisation d’une lecture d’articles de revues, sous forme d’abonnement, mêlant des préoccupations d’accès et de sécurité ; d’autre part, les modalités de publication en accès ouvert, articulant la gestion d’un nouveau type de workflow à toute une série d’options possibles. Parmi ces options, mentionnons notamment le périmètre des revues considérées (hybrides et/ou accès ouvert), les licences disponibles, le degré d’obligation de cette publication, les auteurs éligibles ou le volume d’articles publiables. L’un des résultats les plus importants de cette analyse approfondie est la mise au jour d’un découplage presque complet, au sein même des accords, entre l’objet abonnement et l’objet publication. Bien entendu, l’abonnement est systématiquement configuré dans un monde fermé, soumis à paiement qui déclenche des séries d’identification des circulations légitimes tant du contenu informationnel que des usagers. Il insiste notamment sur les interdictions de réutilisation ou même de copie des articles scientifiques. À l’opposé, la publication en accès ouvert est attachée à un monde régi par l’accès gratuit au contenu, ce qui induit des préoccupations de gestion du workflow et des modalités d’accessibilité. De plus, les différents éléments constitutifs de ces objets contractuels ne sont pas couplés : d’un côté, les lecteurs sont constitués de l’ensemble des membres des institutions abonnées, de l’autre, seuls les auteurs correspondants (« corresponding authors ») sont concernés ; les listes de revues accessibles à la lecture et celles réservées à la publication en accès ouvert sont le plus souvent distinctes ; les workflows ont des objectifs et des organisations matérielles totalement différentes, etc. L’articulation entre les deux objets contractuels relève uniquement d’une formule de distribution financière qui, outre des combinaisons particulières entre l’un et l’autre, permet d’attribuer des étiquettes distinctes aux accords (offset agreement, publish &amp; read, read &amp; publish, read &amp; free articles, read &amp; discount). Au-delà de cette distribution, l’étude des arrangements financiers montre une gamme de dispositions allant d’une prévisibilité budgétaire totale, donc identique aux accords d’abonnement antérieurs, à une incertitude sur le volume de publication ou sur le montant définitif des sommes échangées. Les modalités concrètes de calcul des montants associés à la publication en accès ouvert sont relativement variées. S’il existe effectivement des formules récurrentes (volume d’articles multiplié par un prix individuel, reprise de la moyenne des sommes totales d’APC des années précédentes...), le calcul des sommes en jeu est toujours le résultat d’une négociation singulière entre un consortium et un éditeur scientifique, et aboutit parfois à des formules originales et complexes. À ce titre, l’espace des possibles en matière de formules financières n’est jamais totalement clos. Par ailleurs, la volonté des consortiums d’opérer une « transformation » de leurs accords vers la publication à coût constant renvoie à des définitions diversifiées du « coût » (inclusion ou non des dépenses d’APC préexistantes) et de la constance (admission ou pas d’une « inflation » à 2 ou 3%). De plus, nous n’avons observé aucune disposition contractuelle permettant d’anticiper les sommes en jeu au-delà de l’horizon temporel de l’accord courant. La grande diversité des accords provient d’une part des conditions initiales des relations entre consortiums et éditeurs scientifiques – les sommes dépensées en abonnement étant le point de départ des nouveaux accords –, d’autre part des objectifs de chaque partie. Même si cette étude excluait volontairement les négociations, les accords portent des traces de ces objectifs. Ainsi, de nombreux accords sont de nature explicitement expérimentale, quand certains visent un contrôle budgétaire strict, ou d’autres ambitionnent, dans la période plus récente, la publication du plus grand nombre possible d’articles en accès ouvert. C’est dans ce dernier cas qu’on touche à l’ambiguïté des attentes générales sur les accords transformants. En effet, pour les consortiums, la dimension « transformante » consiste essentiellement à transférer les sommes traditionnellement allouées à l’abonnement vers la publication en accès ouvert. Mais l’objectif n’est jamais de transformer le modèle économique des revues, c'est-à-dire de faire basculer des revues sous abonnement ou hybrides en revues entièrement en accès ouvert. D’ailleurs, aucune clause ne vise une telle fin – à l’exception du modèle d’accord proposé par l’éditeur ACM. Du côté des éditeurs, et notamment de Springer, le caractère cumulatif des accords nationaux passés vise à projeter un monde de la publication où l’accès ouvert devient de fait quantitativement très dominant, sans pour autant modifier de manière pérenne le modèle économique de leurs revues. Notre étude montre que les accords transformants actuels ne permettent pas d’assurer de manière durable une transition de l’économie de la publication vers l’accès ouvert, dans la mesure où ils n’offrent pas de garantie sur le contrôle des dépenses ni sur la pérennité de l’ouverture des contenus. L’avenir des relations entre consortium et éditeur demeure largement indéterminé.Cette étude porte sur une des innovations contemporaines liées à l’économie de la publication scientifique : les accords dits transformants, un objet relativement circonscrit au sein des relations entre consortiums de bibliothèques et éditeurs scientifiques, et temporellement situé entre 2015 et 2020. Ce type d’accords a pour objectif affiché d’organiser la transition du modèle traditionnel de l’abonnement à des revues (souvent proposées par regroupements thématiques ou collections) vers celui de l’accès ouvert en opérant une réaffectation des budgets qui y sont consacrés. Notre travail d’analyse sociologique constitue une première étude systématique de cet objet, fondée sur la recension de 197 accords. Le corpus ainsi constitué inclut des accords caractérisés par la coprésence d’une composante d’abonnement et d’une composante de publication en accès ouvert, même minimale (« jetons » de publication offerts, réduction sur les APC...). En conséquence, ont été exclus de l’analyse les accords portant uniquement sur du financement centralisé de publication en accès ouvert, que ce soit avec des éditeurs ne proposant que des revues avec paiement par l’auteur (PLOS, Frontiers, MDPI...) ou des éditeurs dont une partie du catalogue est constitué de revues en accès ouvert. L’accord le plus ancien de notre corpus a été signé en 2010, les plus récents en 2020 – les accords ne commençant qu’en 2021, même annoncés au cours de l’étude, n’ont pas été retenus. Plusieurs résultats se dégagent de notre analyse. Tout d’abord, on note une grande diversité des acteurs impliqués avec 22 pays et 39 éditeurs, même si certains consortiums (Pays-Bas, Suède, Autriche, Allemagne) et éditeurs (CUP, Elsevier, RSC, Springer) en ont signé beaucoup plus que d’autres. Ensuite, la durée des accords, comprise entre une et six années, révèle une distribution très inégalitaire, avec plus de la moitié des accords (103) signés pour 3 ans, ainsi qu’une faible proportion pour 4 ans ou plus (22 accords). Enfin, en dépit d’appels répétés à la transparence, moins de la moitié des accords (96) ont un texte accessible au moment de cette étude, sans qu’on puisse observer une tendance récente à une plus grande disponibilité. L’analyse montre également des degrés d’ouverture très variables, allant d’une simple information sur le répertoire ESAC en passant par la mise à disposition d’un format annotable jusqu’à l’attribution d’un DOI et d’une licence de réutilisation (CC-BY), en incluant le détail des sommes monétaires. Parmi les 96 accords disponibles, dont 47 signés en 2020, 62 ont fait l’objet d’une analyse en profondeur. C’est à notre connaissance la première analyse à cette échelle, sur un type de matériel non seulement inédit, mais qui était auparavant soumis à des clauses de confidentialité. Fondée sur une lecture minutieuse, l’étude décrit de manière fine leurs propriétés, depuis la matérialité du document jusqu’aux formules financières, en passant par leur morphologie et l’ensemble des droits et devoirs des parties. Les contenus des accords sont donc analysés comme une collection dont nous cherchons à déterminer les points communs et les variations, à travers des codages explicites sur certaines de leurs caractéristiques. L’étude pointe également des incertitudes, et notamment leur caractère « transitionnel », qui demeure fortement discuté. D’un point de vue morphologique, les accords montrent une grande diversité en matière de taille (de 7 à 488 pages) et de structure. Néanmoins, par définition, ils articulent tous deux objets essentiels : d’une part, les conditions de réalisation d’une lecture d’articles de revues, sous forme d’abonnement, mêlant des préoccupations d’accès et de sécurité ; d’autre part, les modalités de publication en accès ouvert, articulant la gestion d’un nouveau type de workflow à toute une série d’options possibles. Parmi ces options, mentionnons notamment le périmètre des revues considérées (hybrides et/ou accès ouvert), les licences disponibles, le degré d’obligation de cette publication, les auteurs éligibles ou le volume d’articles publiables. L’un des résultats les plus importants de cette analyse approfondie est la mise au jour d’un découplage presque complet, au sein même des accords, entre l’objet abonnement et l’objet publication. Bien entendu, l’abonnement est systématiquement configuré dans un monde fermé, soumis à paiement qui déclenche des séries d’identification des circulations légitimes tant du contenu informationnel que des usagers. Il insiste notamment sur les interdictions de réutilisation ou même de copie des articles scientifiques. À l’opposé, la publication en accès ouvert est attachée à un monde régi par l’accès gratuit au contenu, ce qui induit des préoccupations de gestion du workflow et des modalités d’accessibilité. De plus, les différents éléments constitutifs de ces objets contractuels ne sont pas couplés : d’un côté, les lecteurs sont constitués de l’ensemble des membres des institutions abonnées, de l’autre, seuls les auteurs correspondants (« corresponding authors ») sont concernés ; les listes de revues accessibles à la lecture et celles réservées à la publication en accès ouvert sont le plus souvent distinctes ; les workflows ont des objectifs et des organisations matérielles totalement différentes, etc. L’articulation entre les deux objets contractuels relève uniquement d’une formule de distribution financière qui, outre des combinaisons particulières entre l’un et l’autre, permet d’attribuer des étiquettes distinctes aux accords (offset agreement, publish &amp; read, read &amp; publish, read &amp; free articles, read &amp; discount). Au-delà de cette distribution, l’étude des arrangements financiers montre une gamme de dispositions allant d’une prévisibilité budgétaire totale, donc identique aux accords d’abonnement antérieurs, à une incertitude sur le volume de publication ou sur le montant définitif des sommes échangées. Les modalités concrètes de calcul des montants associés à la publication en accès ouvert sont relativement variées. S’il existe effectivement des formules récurrentes (volume d’articles multiplié par un prix individuel, reprise de la moyenne des sommes totales d’APC des années précédentes...), le calcul des sommes en jeu est toujours le résultat d’une négociation singulière entre un consortium et un éditeur scientifique, et aboutit parfois à des formules originales et complexes. À ce titre, l’espace des possibles en matière de formules financières n’est jamais totalement clos. Par ailleurs, la volonté des consortiums d’opérer une « transformation » de leurs accords vers la publication à coût constant renvoie à des définitions diversifiées du « coût » (inclusion ou non des dépenses d’APC préexistantes) et de la constance (admission ou pas d’une « inflation » à 2 ou 3%). De plus, nous n’avons observé aucune disposition contractuelle permettant d’anticiper les sommes en jeu au-delà de l’horizon temporel de l’accord courant. La grande diversité des accords provient d’une part des conditions initiales des relations entre consortiums et éditeurs scientifiques – les sommes dépensées en abonnement étant le point de départ des nouveaux accords –, d’autre part des objectifs de chaque partie. Même si cette étude excluait volontairement les négociations, les accords portent des traces de ces objectifs. Ainsi, de nombreux accords sont de nature explicitement expérimentale, quand certains visent un contrôle budgétaire strict, ou d’autres ambitionnent, dans la période plus récente, la publication du plus grand nombre possible d’articles en accès ouvert. C’est dans ce dernier cas qu’on touche à l’ambiguïté des attentes générales sur les accords transformants. En effet, pour les consortiums, la dimension « transformante » consiste essentiellement à transférer les sommes traditionnellement allouées à l’abonnement vers la publication en accès ouvert. Mais l’objectif n’est jamais de transformer le modèle économique des revues, c'est-à-dire de faire basculer des revues sous abonnement ou hybrides en revues entièrement en accès ouvert. D’ailleurs, aucune clause ne vise une telle fin – à l’exception du modèle d’accord proposé par l’éditeur ACM. Du côté des éditeurs, et notamment de Springer, le caractère cumulatif des accords nationaux passés vise à projeter un monde de la publication où l’accès ouvert devient de fait quantitativement très dominant, sans pour autant modifier de manière pérenne le modèle économique de leurs revues. Notre étude montre que les accords transformants actuels ne permettent pas d’assurer de manière durable une transition de l’économie de la publication vers l’accès ouvert, dans la mesure où ils n’offrent pas de garantie sur le contrôle des dépenses ni sur la pérennité de l’ouverture des contenus. L’avenir des relations entre consortium et éditeur demeure largement indéterminé.