Single and dual fiber nano-tip optical tweezers: trapping and analysis

An original optical tweezers using one or two chemically etched fiber nano-tips is developed. We demonstrate optical trapping of 1 micrometer polystyrene spheres at optical powers down to 2 mW. Harmonic trap potentials were found in the case of dual fiber tweezers by analyzing the trapped particle position fluctuations. The trap stiffness was deduced using three different models. Consistent values of up to 1 fN/nm were found. The stiffness linearly decreases with decreasing light intensity and increasing fiber tip-to-tip distance

Berger Emmanuel, La Justice pénale sous la Révolution. Les enjeux d’un modèle judiciaire libéral

Cet ouvrage est le résultat de quatre années de recherches doctorales passées au sein du centre d’histoire du droit et de la justice (à l’université catholique de Louvain) et de l’institut d’histoire de la Révolution française (à l’université Paris 1-Panthéon-Sorbonne) et menées sous la direction des professeurs Xavier Rousseaux et Jean-Clément Martin. Emmanuel Berger a cherché à montrer qu’il existe sous la Révolution un modèle judiciaire libéral fondé sur les principes de préservation des l..

Développement et application d’une pince optique à fibres nano-structurées

Optical tweezers allow to trap and manipulate objects without any mechanical contact with light and with an extreme accuracy. This non-invasive and non-destructive technique is of large interest in many scientific domains such as biophysics and medicine. Conventional optical tweezers use a laser beam which is strongly focalised by a microscope objective.The use of optical fibers attracts increasing attention as highly flexible and compact tools for particle trapping. Fiber-based optical tweezers do not require bulky optics and require only little alignments.In this context, the objective of this thesis was to develop a dual fiber nano-tip optical tweezers in order to trap particles with micro and nano-meter sizes. Our tweezers consist of two chemically etched optical fiber tips placed in front of each other with typical gaps from 20~nm to 20~µm. This dual contra-propagative beams configuration allow to cancel light radiation pressure. Efficient trapping can thus be obtained at relative low light intensities. Moreover, strong focusing is not required. Our device present an high flexibility due to in situ optimization and control of the fibre positions and individual particle manipulation without any substrate.During our work, we experimentally demonstrated stable and reproducible trapping of one or several particles in suspension. Various dielectric particles were trapped, from one micrometer polystyrene beads to luminescent YAG:Ce particles with diameters down to 60~nm. During this thesis, the latter were specifically elaborated and optimized for the optical trapping. We also measured optical forces applied to trapped particles by analysing their residual Brownian motion. We showed the trapping potential is of harmonic shape, allowing to define its optical stiffness.vspace{10pt}Finally, by modifying the emitted optical beam shape, we were able to improve specific tweezers characteristics. On one hand, nondiffracting quasi-Bessel beams allow us to get a stable trapping at large fiber-to-fiber distances.On the other hand, the use of metallised fiber tips allows to improve the beam confinement and enhance optical forces while reducing light intensity. We proved the near-field coupling between two metallised tips which were especially elaborated in this work. Those last results open promising perspectives for the development of plasmonic tweezers working in the near-field, which are especially well adapted for nano-particles trapping.Les pinces optiques permettent de piéger et de manipuler des objets sans contact physique avec de la lumière et ce avec une extrême précision. Son caractère non-invasif et non-destructif en fait un outil idéal pour des applications dans des domaines tels que la biophysique et la médecine. La pince optique conventionnelle utilise un faisceau lumineux fortement focalisé par un objectif de microscope.La fibre optique est un composant très intéressant dans ce domaine puisqu'elle permet de guider la lumière et de piéger optiquement des objets sans l'utilisation de composants optiques encombrants et en limitant des étapes d'alignement. Elle donne ainsi une grande flexibilité et compacité aux pinces optiques.Dans ce contexte, l'objectif de cette thèse a été de développer une pince optique à deux fibres nano-structurées dans le but de piéger des particules de taille micro et nanométrique.Notre pince est constituée de deux fibres optiques gravées chimiquement en forme de pointe et positionnées en vis-à-vis à des distances typiques de 20 nm à 20 µm. Cette configuration à deux faisceaux contra-propagatifs permet d'annuler la pression de radiation de la lumière. Elle a l'avantage d'obtenir un piégeage efficace pour des intensités lumineuses relativement faibles. En outre, les faisceaux ne doivent pas nécessairement être fortement focalisés. Notre dispositif présente une grande souplesse grâce au contrôle in-situ de la position des fibres, l'injection de la lumière dans les fibres et la manipulation de particules individuelles sans aucun substrat.Au cours de ces travaux, nous avons démontré expérimentalement le piégeage stable et reproductible d'une ou plusieurs particules en suspension. Divers types de particules diélectriques ont été piégées, allant de la particule en polystyrène d'un micromètre à des particules luminescentes de YAG:Ce mesurant 60 nm de diamètre. Ces dernières ont été élaborées et optimisées spécifiquement pour le piégeage optique lors de ces travaux.Nous avons également mesuré les forces optiques appliquées aux particules piégées en analysant leur mouvement Brownien résiduel. Nous avons démontré que le potentiel de piégeage était harmonique, nous permettant de définir la constante de raideur optique.Enfin nous avons démontré qu'en modifiant la forme du faisceau optique d'émission, il était possible d'améliorer certaines caractéristiques de la pince. D'une part, les faisceaux quasi-Bessel qui sont très peu divergents nous ont permis de réaliser un piégeage stable et efficace à grande distance.D'autre part, l'utilisation de pointes métallisées permet de confiner le champ et d'améliorer les forces optiques tout en diminuant l'intensité lumineuse. Nous avons mis en évidence le couplage en champ proche entre deux pointes métallisées qui ont été spécialement élaborées pour la pince. Ces derniers résultats ouvrent des perspectives encourageantes pour le développement d'une pince plasmonique fonctionnant en champ proche qui est particulièrement bien adaptée pour le piégeage de nanoparticules

Structure-function analysis of the nsp14 N7-guanine methyltransferase reveals an essential role in Betacoronavirus replication.

As coronaviruses (CoVs) replicate in the host cell cytoplasm, they rely on their own capping machinery to ensure the efficient translation of their messenger RNAs (mRNAs), protect them from degradation by cellular 5' exoribonucleases (ExoNs), and escape innate immune sensing. The CoV nonstructural protein 14 (nsp14) is a bifunctional replicase subunit harboring an N-terminal 3'-to-5' ExoN domain and a C-terminal (N7-guanine)-methyltransferase (N7-MTase) domain that is presumably involved in viral mRNA capping. Here, we aimed to integrate structural, biochemical, and virological data to assess the importance of conserved N7-MTase residues for nsp14's enzymatic activities and virus viability. We revisited the crystal structure of severe acute respiratory syndrome (SARS)-CoV nsp14 to perform an in silico comparative analysis between betacoronaviruses. We identified several residues likely involved in the formation of the N7-MTase catalytic pocket, which presents a fold distinct from the Rossmann fold observed in most known MTases. Next, for SARS-CoV and Middle East respiratory syndrome CoV, site-directed mutagenesis of selected residues was used to assess their importance for in vitro enzymatic activity. Most of the engineered mutations abolished N7-MTase activity, while not affecting nsp14-ExoN activity. Upon reverse engineering of these mutations into different betacoronavirus genomes, we identified two substitutions (R310A and F426A in SARS-CoV nsp14) abrogating virus viability and one mutation (H424A) yielding a crippled phenotype across all viruses tested. Our results identify the N7-MTase as a critical enzyme for betacoronavirus replication and define key residues of its catalytic pocket that can be targeted to design inhibitors with a potential pan-coronaviral activity spectrum

Preliminary evidence that fatigue contributes to anhedonia in stable individuals diagnosed with schizophrenia

ObjectivesAnhedonia and fatigue are trans-diagnostic symptoms commonly observed in schizophrenia. Anhedonia is a core negative symptom with a strong relationship with depression and is associated with diminished global functioning. Similarly, fatigue is also associated to depression and research across psychiatric illnesses indicate that fatigue may persist even when primary symptoms are treated. Although fatigue is common in people diagnosed with schizophrenia, it is under studied within this population. The objective of this exploratory study was to investigate the association of fatigue and anhedonia by controlling for depression in a sample of individuals diagnosed with schizophrenia.MethodFifty-one stable individuals diagnosed with schizophrenia from the University Department of Adult Psychiatry in Montpellier took part in this study. Participants completed questionnaires on fatigue impact and depression, and were assessed for symptom severity. Following data collection, statistical analyses were conducted in order to explore associations between clinical variables and fatigue impact. Based on the results obtained, a hierarchical linear regression was conducted in order to investigate whether fatigue impact contributed to the variance of negative symptoms.ResultsThe hierarchical linear regression indicated that when controlling for depression, fatigue impact contributes to ~20% of the variance of anhedonia. Together the social impact of fatigue and depression contribute to 24% of the variation of anhedonia.ConclusionTo the best of our knowledge, this exploratory study is the first to investigate and show that fatigue impact may contribute to anhedonia. We recommend further research to investigate fatigue, its impact on symptomatology, and better categorization of negative symptoms in hopes of developing targeted fatigue treatment interventions

La chaleur de Joule considérée comme chaleur de Siemens

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