1,819 research outputs found
Study of long-term sustained operation of gaseous detectors for the high rate environment in CMS
No full textThe muon system of CMS aims to provide an efficient and fast identification of the muons produced in the proton-proton collisions. However, the forward region of the end-caps is only instrumented with Cathode Strip Chambers. This lack of redundancy will be problematic after the high-luminosity upgrade of the LHC (HL-LHC), for which the increase of the background rate would degrade the Level-1 trigger performance and thus the selection of interesting physics channels. The goal of the CMS muon upgrade is to maintain the L1 trigger rate with maximum selection efficiency in order to fully exploit the HL-LHC. The CMS GEM Collaboration has proposed to instrument the vacant high-eta region of the muon end-caps with Gas Electron Multiplier (GEM) detectors, called GE1/1 chambers. The Ph.D. subject proposed by the CMS GEM Collaboration aims to demonstrate that the GE1/1 technology is the most suitable choice for the upgrade of the muon end-caps. Three main research projects were conducted in this context. The first project included the precise measurement of the fundamental characteristics and the detection performance of the triple-GEM detectors produced with the single-mask technique. Those characteristics are essential to ensure that the detectors can operate in the forward region of CMS. The second project was focused on the long-term operation of GE1/1 detectors, in particular the study of the aging phenomenon, which includes all the processes that lead to a significant and permanent degradation of the performance of the detectors. Several aging tests were performed at the CERN irradiation facilities to prove that the GE1/1 chambers can operate during at least 10 years at HL-LHC without suffering from performance losses. The excellent properties measured during the R&D phase led to the approval of the GE1/1 project by the CMS Collaboration. The third project, conducted in the framework of the mass production, consisted of developing of the main steps of the Quality Control of the GE1/1 chambers
Study of long-term operation of triple-GEM detectors for the high rate environment in CMS
No full textThe CMS GEM collaboration is working on the possible instrumentation of the high-eta region of the CMS Endcap with Gas Electron Multiplier (GEM) detectors, a technology capable to sustain the hostile environment that will be encountered at the high-luminosity LHC. To ensure the long-term operation of large triple-GEM detectors in the CMS experiment, we are performing a set of studies in order to measure and understand the aging effect of triple-GEM Muon chambers. The aging includes all the processes that lead to a significant degradation of the performances of the detector gain drop, non-uniformity, dark current, discharges and resolution loss. The project is focused on monitoring continuously the response of the detector when irradiated by a source of Cs 137 at CERN in the Gamma Irradiation Facility (GIF). Moreover, the new technology employed for stretching the GEM foils, so called NS2, introduces new, carefully chosen materials and components in the detectors. Outgassing tests are performed in order to validate the use of these components. The entire experiment is designed so that all relevant parameters are understood and monitored. This allows isolating the effects of possible aging and therefore establishing a set of recommendations for assembly and operation of triple-GEM detectors at high eta in CMS
Reduction of high voltage discharge in GEM detectors for the ME0 station of the CMS forward muon system
No full textThe Phase 2 upgrade of the CMS muon spectrometer will include the installation of two new muon stations based on Gas Electron Multiplier (GEM) technology. While the GE1/1 station is already installed and the GE2/1 detectors are under construction, the ME0 station is expected to be inserted in CMS during the Long Shutdown 3 (LS3). The new ME0 system will increase the acceptance for muon detection in the region where there is a high radiation background. When triple-GEM detectors, including ME0, operate at high gain, there are occasional discharges within the transfer gaps that are likely followed by less-common secondary discharges and may cause irreversible damage to the detector. The ME0 detector has the advantage of using double-segmented GEM foils that help lower the probability of high voltage discharges, and in turn, this protects the detector and maintains the high detection efficiency. To optimize the ME0 design, we studied the impact of High Voltage (HV) filter resistors and segment orientation of ME0 GEM foils on discharge propagation probability within the detector
Lasing from active optomechanical resonators
Get PDFThis study was funded by the Deutsche Forschungsgemeinschaft (project BA 1549/14-1), the State of Bavaria and the Ukrainian State Fund for Fundamental Researches (programme SFFR-DFG). A.V.A. also acknowledges financial support by the Alexander von Humboldt Foundation. M.B. acknowledges partial financial support from the Russian Ministry of Science and Education (contract No.14.Z50.31.0021).Planar microcavities with distributed Bragg reflectors (DBRs) host, besides confined optical modes, also mechanical resonances due to stop bands in the phonon dispersion relation of the DBRs. These resonances have frequencies in the 10- to 100-GHz range, depending on the resonatorâ optical wavelength, with quality factors exceeding 1,000. The interaction of photons and phonons in such optomechanical systems can be drastically enhanced, opening a new route towards the manipulation of light. Here we implemented active semiconducting layers into the microcavity to obtain a vertical-cavity surface-emitting laser (VCSEL). Thereby, three resonant excitations - photons, phonons and electrons - can interact strongly with each other providing modulation of the VCSEL laser emission: a picosecond strain pulse injected into the VCSEL excites long-living mechanical resonances therein. As a result, modulation of the lasing intensity at frequencies up to 40â €‰GHz is observed. From these findings, prospective applications of active optomechanical resonators integrated into nanophotonic circuits may emerge.Peer reviewe
Test Beam Study of Gas Electron Multiplier (GEM) Detectors for the Upgrade of CMS Endcap Muon System
No full textDynamiques de transfictionnalité et d’intercyclicité dans quelques sommes arthuriennes en moyen français. Un nouvel essai de stemmatologie arthurienne
Get PDFIl Duecento letterario francese è percorso dalla moda dei romanzi arturiani in prosa: inanzitutto, dopo i romanzi in versi di Chrétien, vi è il “petit cycle” del Graal, prima in versi, poi in prosa, attribuito a Robert de Boron; questo sarà presto seguito dal ciclo di Lancelot e di quello di Tristan en prose e del Guiron le Courtois; infine, trent’anni dopo, sarà scritto da un Veneziano sotto lo pseudonimo di Richard d’Irlande, le Prophéties de Merlin, un romanzo dalla straordinaria creatività. Fa seguito un periodo di relativa “calma” prima della diffusione, alla fine del Quattrocento, degli ultimi cicli arturiani in prosa francese: Ysaÿe le Triste e Perceforest.
La produzione ridotta di materiale arturiano tra la fine del Duecento e del Quattrocento, benché tradisca uno stallo creativo, non si accompagna alla mancanza di interesse suscitata dalla materia arturiana: anzi, un’ampia produzione manoscritta, a volte di lusso, a volte più umile, assiemme al passaggio alla stampa dei grandi cicli arturiani tra Quattro- e Cinquecento, tradiscono la presenza di un pubblico ancora ben nutrito. Quest’epoca vide anche la costituzione delle « versioni vulgate » sia del Tristan che del Guiron, la composizione di suites e di riscritture, e l’elaborazione di compilazione arturiane, tra cui l’ormai famosissima compilazione arturiana (assieme alla sorella minore, la compilazione guironiana) di Rustichello da Pisa. Infine, la moda dei romanzi arturiani si manifesta anche in alcune rappresentazioni teatrali, in particolare nei pas d’armes dell’aristocrazia borgognona e fiamminga. Si tratta anche di una delle epoche più importanti per l’enciclopedismo medioevale, di cui si scorge un riflesso nei tentativi di costituire delle summae arturiane in cui confluisce tutta la materia pre-esistente. Un esempio è costituito dall’eccezionale ms. Paris, BnF, fr. 112.
Lo sviluppo dei cicli arturiani, dalla fine del secolo XII all’alba del Rinascimento francese, è stato oggetto di numerosissimi lavori, dai primi tentativi degli studenti di Gaston Paris fino alle ricerche più recenti, come quelle di Patrick Moran o Noémie Chardonnens, passando per le notevoli ricostruzioni di Fanni Bogdanow o di Cedric Pickford. Ma tutti questi commenti sulla genesi e lo sviluppo della materia arturiana in prosa francese s’imbattono in un ostacolo maggiore: la mancanza di un dato fondamentale, ossia una conoscenza precisa della genealogia dei manoscritti, senza la quale è solo possibile fornire un commento basandosi sulle edizioni critiche o sull’esame di ciascun testimone in quanto oggetto semiotico isolato.
La nostra tesi, erede dell’esperienza del Gruppo Guiron, propone quindi un tentativo di andare oltre i limiti di questi approcci, provando ad affrontare il caso della fortuna interciclica di Alexandre l’Orphelin e del Tournoi de Sorelois, due piccole serie di episodi tratti dalle Prophéties de Merlin ed inserite nella quarta versione del Tristan en prose, nelle continuazioni di due testimoni di Guiron le Courtois e nel ms. Paris, BnF, fr. 112, che proveremo a confrontare con altri due casi di interpolazione interciclica dello stesso tipo: l’interpolazione di estratti dell’Agravain nelle terza e quarta versioni del Tristan en prose, da un lato, e, dall’altro, l’interpolazione dell’Erec en prose borgognone nel ms. Paris, BnF, fr. 358-363. Per raggiungere quest’obiettivo, abbiamo fatto ricorso innanzitutto ad un approccio strettamente filologico, i cui risultati ci hanno consentito di proporre qualche ipotesi relativa alla costituzione ed alla diffusione dei cicli e delle loro suites, da un punto di vista più narratologico e poetico.
Questa tesi è strutturata come segue. Dopo un primo capitolo, introduttivo, dedicato allo status quæstionis delle nostre conoscenze sulla diffusione dei cicli arturiani, con un focus sulle sue forze e sui suoi limiti, abbiamo proposto un ulteriore stato dell’arte relativo ai cicli arturiani che abbiamo scelto come oggetto di studio: le Prophéties de Merlin, Guiron le Courtois e le terza e quarta versioni del Tristan en prose. Dopodiché, abbiamo tentato di stabilire uno stemma codicum, prima per i testi al centro del nostro studio (Alexandre l’Orphelin e Tournoi de Sorelois), poi, basandosi su alcuni loci critici selezionati secondo criteri esplicitati, per le versioni tardive del Tristan en prose e delle Prophéties de Merlin. I risultati di questi studi, per forza parziali, ci hanno consentito poi di studiare, benché con conoscenze parziali, la diffusione interciclica di Alexandre l’Orphelin e del Tournoi de Sorelois in un modo che permetta di prendere in considerazione gli interventi della tradizione testuale di fronte all’inserzione di un racconto esterno, allogeno. Li abbiamo poi confrontati ad alcune considerazioni che lo stato delle nostre conoscenze ci consente di formulare sull’interpolazione di estratti dell’Agravain nelle terza e quarta versioni del Tristan en prose. Concluderemo quindi il nostro lavoro con qualche considerazione sul potenziale che contiene un approccio più stemmatologico della ciclicità arturiana, nella speranza che altri studi possano completare il nostro.
Infatti, il nostro lavoro è soprattutto un esperimento: si trattava inanzitutto di provare a tenere finalmente insieme due metodi troppo spesso tenuti distinti, ossia lo studio narratologico e l’approccio filologico, e di riflettere sulle osservazioni che potrebbero risultarne. Il nostro lavoro non pretende di rinnovare del tutto l’approccio della transfinzionalità e dell’interciclicità arturiane, senza parlare della costituzione dei cicli arturiani, ma, semplicemente, di vedere in che modo una conoscenza precisa dello sviluppo della tradizione testuale potrebbe aiutare a considerarla.In the XIIIth Century, one of the most successful literary genres was that of Arthurian prose romances: a “petit cycle” of the Holy Grail, first in verse, then in prose, attributed to Robert de Boron; soon to be followed by the Lancelot and the Tristan cycles, then, by Guiron le Courtois; last, but not least, thirty years later, a Venetian author who calls himself Richard d’Irlande penned the Prophéties de Merlin, a novel in which he shows an exceptionnal creativity. Follow two centuries of relative stillness before the diffusion, at the end of the XVth Century, of the last major arthurian cycles: Ysaÿe le Triste and Perceforest.
The lack of production of new arthurian texts between the end of the XIIIth and that of the XVth Century does not equal to its lack of success. On the contrary, an abundant production of manuscripts, sometimes de luxe, sometimes not quite, together with the printing of most arthurian romances at the end of the XVth Century and at the beginning of the XVIth, demonstrate the presence of numerous potential readers. In the same period, we see the creation of “vulgate versions” of both Tristan and Guiron, as well as the setting up of anthologies like Rustichello da Pisa’s Arthurian compilation (and its little sister, the Aventures des Bruns, or guironian compilation). Finally, the success of Arthurian romances can also be observed in some of the dramaturgic representations that fancied the aristocracy, especially in Flemish and Burgundian knights’ pas d’armes. Those centuries are also a time of medieval encyclopedism, of which we could find echoes in the various attempts to set up Arthurian summae that could embrace the essence of all preexistant materials: for instance, the exceptionnal ms. Bibliothèque nationale de France, fr. 112.
The development of Arthurian cycles, from the end of the XIIth Century to the beginning of the Renaissance, has been thoroughly studied, from the first trials of Gaston Paris’ students to the most recent research of Patrick Moran or Noémie Chardonnens, through the fascinating reconstructions of Fanni Bogdanow or Cedric Pickford. But all of those comments on the genesis and development of Arthurian French prose romances still face a major issue: we’re lacking a thorough knowledge of the genealogy of the manuscript tradition, and this lack of documentation means it is only possible to study those texts either by using a critical edition, or by studying each manuscript as a single semiotic object.
The present thesis proposes an attempt to overstep the limits of those approaches with a case study, that of the intercyclical transmission of Alexandre l’Orphelin and of the Tournoi de Sorelois, two little sets of episodes originally part of the Prophéties de Merlin, that were included in the fourth version of the Prose Tristan, in the continuations written in two mss of Guiron le Courtois, and in the ms. Paris, BnF, fr. 112. We then aim to compare it with another cases of intercyclical interpolation: on the one hand, the interpolation of Agravain parts into the third and fourth versions of the Prose Tristan. To do so, we will resort to a strictly philological approach, whose results will then allow us to draw a few hypothesis about the creation and the diffusion of cycles and their continuations, from a narratological point of view.
The present thesis will be structurated as follows. After a first, introductive, chapter dedicated to the status quaestionis of our knowledge about the diffusion of Arthurian cycles, with a focus on its strenghts as well as its limits, we will offer another status quaestionis for each of the three Arthurian romances we have chosen to study: Les Prophéties de Merlin, Guiron le Courtois, and the third and fourth versions of the Prose Tristan. We will then attempt to outline a stemma codicum, first for Alexandre l’Orphelin and the Tournoi de Sorelois, which are at the center of our preoccupations, then, relying on a few loci critici carefully selected, for the late versions of the Prose Tristan and for the Prophéties de Merlin. The results of those studies, although fragmentary, will then allow us to study the intercyclical diffusion of Alexandre l’Orphelin and the Tournoi de Sorelois in a way that could also take into account the potential interventions of the textual tradition when facing the insertion of an external, foreign, narrative. We will thereafter compare them to some other considerations that the status of our knowledge will allow us to put forward on the interpolation of excerpts from Prose Erec in the Flemish Continuation of Guiron le Courtois from ms. Paris, BnF, fr. 358-363, and also on the interpolation of parts of the Agravain into the third and fourth versions of the Prose Tristan. We will then conclude our work with a few reflexions about the potentialities of a stemmatical approach of Arthurian cycles, hoping that other studies will complete ours.
Because our thesis is about experimentation: we wanted to try to reconcile two approaches that are too often distinct, i. e. the narratological study and the filological reconstruction of the same text, to see what kind of information could result of such a research in a field that was until a few years ago particularly closed to lachmannism. We do not claim to renew the whole approach of transfictionnality and intercyclicity, or that of the formation of Arthurian cycles, but, simply, to see how a deeper knowledge of the ways the textual tradition did grow could help us understand it better.Le XIIIe siècle littéraire français est notamment celui d’une mode, celle des romans arthuriens en prose : d’abord, le « petit cycle » du Graal en vers, puis en prose, attribué à Robert de Boron ; ensuite, le cycle de Lancelot, rapidement suivi du Tristan en prose et du cycle de Guiron le Courtois ; enfin, près de trente ans plus tard, un Vénitien ayant adopté le pseudonyme de Richard d’Irlande diffusera ses Prophéties de Merlin, un roman d’une exceptionnelle créativité. S’ensuivra une période de calme relatif avant la diffusion, à la fin du XVe siècle, des derniers grands romans arthuriens en prose que sont Ysaÿe le Triste et le Perceforest.
La production réduite de matériaux arthuriens entre la fin du XIIIe et celle du XVe siècle, signe d’un certain épuisement créatif, ne signifie pas pour autant une absence de succès de la matière arthurienne, au contraire : en témoignent une ample production manuscrite, parfois fort luxueuse, parfois bien plus humble, ainsi que le passage à l’imprimé de tous les grands cycles arthuriens à la fin du XVe et au début du XVIe siècle, signe de la présence d’un lectorat potentiel vaste. Cette époque voit également la constitution des « versions vulgates » du Tristan comme du Guiron, la composition de suites ou de réécritures, ainsi que l’élaboration d’anthologies arthuriennes, dont la très célèbre compilation arthurienne (et sa petite sœur, la compilation guironienne) de Rusticien de Pise. Enfin, la mode des romans arthuriens se manifeste également dans certaines des mises en scène de la noblesse du temps, en particulier dans les pas d’armes des chevaliers bourguignons et flamands. C’est également l’une des grandes périodes de l’encyclopédisme médiéval, dont l’on pourrait trouver un reflet dans les tentatives de constituer des sommes arthuriennes englobant l’essence de toute la matière préexistante : en témoigne, par exemple, l’exceptionnel ms. BnF, français 112.
Le développement des cycles arthuriens, de la fin du XIIe siècle à l’aube de la Renaissance, a fait l’objet de nombreux travaux, des premiers tâtonnements des élèves de Gaston Paris aux recherches les plus récentes, telles celles de Patrick Moran ou de Noémie Chardonnens, en passant par les remarquables reconstructions de Fanni Bogdanow ou de Cedric Pickford. Mais tous ces commentaires sur la genèse et le développement de la matière arthurienne en prose française se heurtent à l’absence d’une donnée fondamentale : la généalogie des manuscrits, sans laquelle il n’est possible de fournir un commentaire qu’à partir des éditions critiques, de regroupements de manuscrits ou de l’examen de chaque témoin en tant qu’objet sémiotique isolé.
Notre thèse, forte de l’expérience du Groupe Guiron, propose ainsi une tentative de dépasser les limites de ces approches en s’attaquant au cas de la fortune intercyclique d’Alexandre l’Orphelin et du Tournoi de Sorelois, deux petites séries d’épisodes issues des Prophéties de Merlin insérées dans la quatrième version du Tristan en prose, dans les continuations de deux témoins de Guiron le Courtois et dans le ms. Paris, BnF, fr. 112, que nous mettrons en regard avec deux autres cas d’interpolation intercyclique comparables : l’interpolation d’extraits de l’Agravain dans les troisième et quatrième versions du Tristan en prose, d’une part, et, d’autre part, l’interpolation de l’Érec en prose bourguignon dans le ms. Paris, BnF, fr. 358-363. Pour ce faire, nous recourrons dans un premier temps à une approche strictement philologique, dont les résultats nous permettront ensuite d’émettre quelques hypothèses relatives à la constitution et à la diffusion des cycles et de leurs suites, d’un point de vue plus narratologique et poétique.
La présente thèse sera structurée comme suit. Après un premier chapitre, introductif, dédié à l’état de la question de nos connaissances sur la diffusion des cycles arthuriens, avec une mise en évidence de ses forces comme de ses limites, nous présenterons un état de l’art relatif aux trois ensembles arthuriens dont nous avons fait notre objet d’étude : les Prophéties de Merlin, Guiron le Courtois et les troisième et quatrième versions du Tristan en prose. Nous tenterons ensuite d’établir un stemma codicum, d’abord pour les textes au coeur de notre étude (Alexandre l’Orphelin et le Tournoi de Sorelois), puis, à partir de quelques lieux critiques sélectionnés, les versions tardives du Tristan en prose et les Prophéties de Merlin. Les résultats de ces études, forcément partielles, nous permettront ensuite d’étudier la diffusion intercyclique d’Alexandre l’Orphelin et du Tournoi de Sorelois d’une façon qui prenne aussi en compte le potentiel d’intervention de la tradition textuelle face à l’insertion d’un récit externe, allogène. Nous les comparerons à quelques considérations que l’état de nos connaissances nous permettront d’émettre à propos de l’interpolation d’extraits de l’Agravain dans les troisième et quatrième versions du Tristan en prose. Nous conclurons notre travail par quelques considérations sur le potentiel que recèle une approche plus stemmatologique de la cyclicité arthurienne, dans l’espoir que d’autres études pourront compléter la nôtre.
Car notre travail relève avant tout de l’expérimentation : il s’agissait de tenter de concilier deux méthodes trop souvent distinctes, à savoir l’étude narratologique et l’approche philologique, afin de voir quelles sortes d’observations pourraient en résulter, dans un domaine particulièrement réfractaire au lachmannisme. Notre recherche ne prétend en aucun cas renouveler entièrement l’approche de la transfictionnalité et de l’intercyclicité, sans parler de la constitution des cycles arthuriens, mais, tout simplement, de voir de quelle façon une connaissance approfondie du développement de la tradition textuelle peut aider à l’appréhender
Layout and Assembly Technique of the GEM Chambers for the Upgrade of the CMS First Muon Endcap Station
No full textTriple-GEM detector technology was recently selected by CMS for a part of the upgrade of its forward muon detector system as GEM detectors provide a stable operation in the high radiation environment expected during the future High-Luminosity phase of the Large Hadron Collider (HL-LHC). In a first step, GEM chambers (detectors) will be installed in the innermost muon endcap station in the 1.6 \textless \textbar \textbar \textless 2.2 pseudo-rapidity region, mainly to control level-1 muon trigger rates after the second LHC Long Shutdown. These new chambers will add redundancy to the muon system in the -region where the background rates are high, and the bending of the muon trajectories due to the CMS magnetic field is small. A novel construction technique for such chambers has been developed in such a way where foils are mounted onto a single stack and then uniformly stretched mechanically, avoiding the use of spacers and glue inside the active gas volume. We describe the layout, the stretching mechanism and the overall assembly technique of such GEM chambers
Erratum to: Measurement of the top quark mass with lepton+jets final states using pp collisions at
No full textIn this article the author name Luigi Calligaris was incorrectly written as A. Calligaris. The original article has been corrected
Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial
No full textBackground Up to now, immunisation regimens that have been assessed for development of HIV vaccines have included purified envelope (Env) protein among the boosting components of the regimen. We postulated that co-administration of Env protein with either a DNA or NYVAC vector during priming would result in early generation of antibody responses to the Env V1/V2 region, which are important markers for effective protection against infection. We aimed to assess the safety and immunogenicity of a multivalent HIV vaccine including either DNA or NYVAC vectors alone or in combination with Env glycoprotein (gp120) followed by a co-delivered NYVAC and Env protein boost. Methods We did a single-centre, double-blind, placebo-controlled phase 1b trial at the Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland). We included healthy volunteers aged 18-50 years who were at low risk of HIV infection. We randomly allocated participants using computer-generated random numbers to one of four vaccination schedules or placebo (4:1), and within these schedules participants were allocated either active treatment (T1, T2, T3, and T4) or placebo (C1, C2, C3, and C4). T1 consisted of two doses of NYVAC vector followed by two doses of NYVAC vector and gp120 Env protein; T2 comprised four doses of NYVAC vector and gp120 Env protein; T3 was two doses of DNA vector followed by two doses of NYVAC vector and gp120 Env protein; and T4 was two doses of DNA vector and gp120 Env protein followed by two doses of NYVAC vector and gp120 Env protein. Placebo injections were matched to the corresponding active treatment group. Doses were administered by injection at months 0, 1, 3, and 6. Primary outcomes were safety and immunogenicity of the vaccine schedules. Immune response measures included cross-clade and epitope-specific binding antibodies, neutralising antibodies, and antibody-dependent cell-mediated cytotoxicity measured 2 weeks after the month 1, 3, and 6 vaccinations. This trial is registered with ClinicalTrials.gov, NCT01799954. Findings Between Aug 23, 2012, and April 18, 2013, 148 healthy adult volunteers were screened for the trial, of whom 96 participants were enrolled. 20 individuals were allocated to each active treatment group (groups T1-4; n=80) and four were assigned to each placebo group (groups C1-4; n=16). Vaccines containing the NYVAC vector (groups T1 and T2) were associated with more frequent severe reactogenicity and more adverse events than were vaccines containing the DNA vector (groups T3 and T4). The most frequent adverse events judged related to study product were lymphadenopathy (n=9) and hypoaesthesia (n=2). Two participants, one in the placebo group and one in the DNA-primed T3 group, had serious adverse events that were judged unrelated to study product. One participant in the T3 group died from cranial trauma after a motor vehicle accident. Across the active treatment groups, IgG responses 2 weeks after the 6-month dose of vaccine were 74-95%. Early administration of gp120 Env protein (groups T2 and T4) was associated with a substantially earlier and higher area under the curve for gp120 Env binding, production of anti-V1/V2 and neutralising antibodies, and better antibody-response coverage over a period of 18 months, compared with vaccination regimens that delayed administration of gp120 Env protein until the 3-month vaccination (groups T1 and T3). Interpretation Co-administration of gp120 Env protein components with DNA or NYVAC vectors during priming led to early and potent induction of Env V1/V2 IgG binding antibody responses. This immunisation approach should be considered for induction of preventive antibodies in future HIV vaccine efficacy trials. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd
Whole-brain annotation and multi-connectome cell typing of Drosophila
Get PDFThe fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome1 with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome2, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and wevalidate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics. © The Author(s) 2024.TRUEsciescopu
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