The Old Dark House and the Space of Attraction

Writers have invoked the concept of the “cinema of attractions,” from early cinema studies, to claim that horror films sacrifice narrative integrity to deliver sudden frights and spectacular shocks. An examination of the history of the concept of the attraction, however, finds it heavily theorized by Sergei Eisenstein as something that can bind films together in powerful ways. In one horror film, The Old Dark House (1932), slamming doors, quaking thunder, shattering glass and a rampaging mute butler, while scary, also figure in James Whale’s scheme to criss-cross his film with motifs and other repetitions and produce a work that gains with every viewing. Even with its thin narrative, stock characters and, already in 1932, very familiar story about characters trapped in an old dark house, the film hangs together in intricate ways. Most elaborately, Whale embeds attractions in a grid that overlays the tiered spaces of the setting. Characters move up and down the creaky staircases and along the suspended hallways, chasing each other, scuffling, and withholding and disclosing secrets. Scenographic and narrative space mesh into a tight unity lit up by a constellation of “fun house” jolts. Props, including lamps and knives, circulate through these spaces as well, tracing patterns that startle viewers while simultaneously rendering the film rigorously and beautifully coherent.Certains auteurs ont utilisé le concept de « cinéma des attractions », issu des études sur le cinéma des premiers temps, pour affirmer que les films d’horreur sacrifient l’intégrité narrative au profit de chocs spectaculaires et d’éléments susceptibles de provoquer des peurs subites. Toutefois, en examinant l’histoire de ce concept, on constate que Sergei Eisenstein a souvent insisté sur la capacité de l’attraction à unifier un film de manière particulièrement efficace. Dans le film d’horreur The Old Dark House (1932), les claquements de porte, les roulements de tonnerre, les carreaux qui volent en éclats ainsi que le menaçant majordome muet, bien qu’effrayants, participent aussi de la stratégie de James Whale. Celui-ci sème son film de divers motifs et répétitions, afin de créer une oeuvre qui gagne en puissance à chaque visionnement. Malgré sa mince trame narrative, ses personnages typés et son histoire, déjà convenue en 1932, de personnages prisonniers d’une vieille et sinistre maison, le film parvient à garder sa cohésion grâce à un procédé complexe. De façon très calculée, Whale introduit les attractions au sein d’un réseau qui coïncide avec les différents niveaux du décor. Les personnages montent et descendent les escaliers grinçants, longent les corridors suspendus, se pourchassent et se chamaillent, révélant ou cachant certains secrets. Les espaces scénographique et narratif s’entremêlent ainsi en une unité serrée, où scintille une pléiade de chocs pareils à ceux des maisons hantées. Les accessoires, tels les lampes et les couteaux, circulent également dans ces espaces, traçant des motifs qui font sursauter le spectateur tout en donnant au film sa rigoureuse et élégante cohérence

Radiosynthesis and In Vivo Evaluation of Four Positron Emission Tomography Tracer Candidates for Imaging of Melatonin Receptors

Melatonin is a neurohormone that modulates several physiological functions in mammals through the activation of melatonin receptor type 1 and 2 (MT1 and MT2). The melatonergic system is an emerging therapeutic target for new pharmacological interventions in the treatment of sleep and mood disorders; thus, imaging tools to further investigate its role in the brain are highly sought-after. We aimed to develop selective radiotracers for in vivo imaging of both MT1 and MT2 by positron emission tomography (PET). We identified four previously reported MT ligands with picomolar affinities to the target based on different scaffolds which were also amenable for radiolabeling with either carbon-11 or fluorine-18. [11C]UCM765, [11C]UCM1014, [18F]3-fluoroagomelatine ([18F]3FAGM), and [18F]fluoroacetamidoagomelatine ([18F]FAAGM) have been synthesized in high radiochemical purity and evaluated in wild-type rats. All four tracers showed moderate to high brain permeability in rats with maximum standardized uptake values (SUVmax of 2.53, 1.75, 3.25, and 4.47, respectively) achieved 1-2 min after tracer administration, followed by a rapid washout from the brain. Several melatonin ligands failed to block the binding of any of the PET tracer candidates, while in some cases, homologous blocking surprisingly resulted in increased brain retention. Two 18F-labeled agomelatine derivatives were brought forward to PET scans in non-human primates and autoradiography on human brain tissues. No specific binding has been detected in blocking studies. To further investigate pharmacokinetic properties of the putative tracers, microsomal stability, plasma protein binding, log D, and membrane bidirectional permeability assays have been conducted. Based on the results, we conclude that the fast first pass metabolism by the enzymes in liver microsomes is the likely reason of the failure of our PET tracer candidates. Nevertheless, we showed that PET imaging can serve as a valuable tool to investigate the brain permeability of new therapeutic compounds targeting the melatonergic system