232 research outputs found

    Rippled area formed by surface plasmon polaritons upon femtosecond laser double-pulse irradiation of silicon: the role of carrier generation and relaxation processes

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    The formation of laser-induced periodic surface structures (LIPSS, ripples) upon irradiation of silicon with multiple irradiation sequences consisting of femtosecond laser pulse pairs (pulse duration 150 fs, central wavelength 800 nm) is studied numerically using a rate equation system along with a two-temperature model accounting for one- and two-photon absorption and subsequent carrier diffusion and Auger recombination processes. The temporal delay between the individual equal-energy fs-laser pulses was varied between 00 and ∌4\sim 4 ps for quantification of the transient carrier densities in the conduction band of the laser-excited silicon. The results of the numerical analysis reveal the importance of carrier generation and relaxation processes in fs-LIPSS formation on silicon and quantitatively explain the two time constants of the delay dependent decrease of the Low-Spatial-Frequency LIPSS (LSFL) area observed experimentally. The role of carrier generation, diffusion and recombination are quantified individually.Comment: 5 pages, 5 figures, Conference On Laser Ablation (COLA) 2013. The final publication is available at http://link.springer.com. Accepted for publication in Applied Physics

    Effet de la stimulation des TLR sur l'infection par le VIH-1 des lymphocytes T CD4+ et des cellules dendritiques primaires

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    Depuis sa dĂ©couverte en 1983, le virus du SIDA ne cesse de faire des ravages. MalgrĂ© l’apparition de la thĂ©rapie HAART, qui permet de prolonger l’espĂ©rance de vie des individus atteints, aucun traitement n’est actuellement disponible pour prĂ©venir ou Ă©radiquer complĂštement l’infection. Le virus mute beaucoup ce qui lui confĂšre rapidement une rĂ©sistance Ă  l’ensemble des traitements utilisĂ©s. L’objectif actuel du monde scientifique est donc de dĂ©velopper d’autres cibles qui pourraient restreindre les effets indĂ©sirables des mĂ©dicaments actuels tout en diminuant l’émergence de souches virales rĂ©sistantes. Afin de dĂ©velopper ces nouveaux traitements, il est essentiel de mieux comprendre le comportement du virus et ce, sous diverses conditions de l’organisme. Mon projet de doctorat s’inscrit dans cette thĂ©matique puisqu’il a permis d’étudier le comportement du virus suite Ă  la stimulation du TLR2, un rĂ©cepteur essentiel Ă  la reconnaissance, entre autre, de structures spĂ©cifiques des bactĂ©ries Gram positives. L’objectif global consistait Ă  dĂ©terminer si la stimulation de ce TLR, par un ligand synthĂ©tique, avait des effets sur l’état d’activation et le taux d’infection des lymphocytes T CD4+ naĂŻfs et mĂ©moires de mĂȘme que celui des cellules dendritiques. Les rĂ©sultats obtenus indiquent que la stimulation du TLR2 augmente l’infection de ces deux types cellulaires et favorise Ă©galement le transfert du virus des cellules dendritiques aux lymphocytes T CD4+. Sachant que l’activation des cellules favorise l’infection par le VIH 1 et que les produits bactĂ©riens prĂ©sents dans la circulation sanguine lors de la translocation microbienne activent les lymphocytes T CD4+ et les cellules dendritiques, toutes les conditions sont alors rĂ©unies pour mener Ă  une hyperactivation des cellules immunes. Ces rĂ©sultats dĂ©montrent que la reconnaissance des produits microbiens par les TLR participe Ă  la dissĂ©mination de l’infection en favorisant l’activation de cellules permissives Ă  l’infection.Since its discovery in 1983, HIV-1 continues to destroy many people lives and no treatment is actually available to treat or prevent infection. Despite the utilization of HAART therapy, the epidemy is still increasing and the worldwide really need new treatments. Due to his high capacity of mutations, HIV-1 rapidly develops resistance against all available treatments. The major aim of scientific community is to develop new therapeutics using different targets to try to avoid and control the resistance phenomenon. To develop these treatments, it is very important to acquire a better understanding of the HIV-1 biology. My doctorate project is tightly related to this because it permits to study the reaction of HIV-1 following TLR2 stimulation, a receptor very useful to sense pathogens. Since microbial translocation is a phenomenon frequently observed in HIV-1-patients, characterized by the presence of bacterial compounds into bloodstream, we evaluated if TLR2 stimulation, with a synthetic ligand, could modulated infection process. Our global objective was to determine if this stimulation could change the activation state and influence the infection in both CD4+ T lymphocytes and dendritic cells. Our results confirmed that TLR2 stimulation increases infection in both cell subtypes and also increases the transfer of viruses from dendritic cells to CD4+ T lymphocytes. Knowing that cell activation favors HIV-1 infection and that bacterial compounds present into bloodstream during microbial translocation stimulate TLR2 stimulation activates CD4+ T cells and dendritic cells, all conditions are put together to favors hyperactivation of the immune system. Our results demonstrate that TLR2 stimulation participates to HIV-1 dissemination by triggering activation of immune cells

    TLR2 and TLR4 triggering exerts contrasting effects with regard to HIV-1 infection of human dendritic cells and subsequent virus transfer to CD4+ T cells

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    <p>Abstract</p> <p>Background</p> <p>Recognition of microbial products through Toll-like receptors (TLRs) initiates inflammatory responses orchestrated by innate immune cells such as dendritic cells (DCs). As these cells are patrolling mucosal surfaces, a portal of entry for various pathogens including human immunodeficiency virus type-1 (HIV-1), we investigated the impact of TLR stimulation on productive HIV-1 infection of DCs and viral spreading to CD4<sup>+ </sup>T cells.</p> <p>Results</p> <p>We report here that engagement of TLR2 on DCs increases HIV-1 transmission toward CD4<sup>+ </sup>T cells by primarily affecting <it>de novo </it>virus production by DCs. No noticeable and consistent effect was observed following engagement of TLR5, 7 and 9. Additional studies indicated that both HIV-1 infection of DCs and DC-mediated virus transmission to CD4<sup>+ </sup>T cells were reduced upon TLR4 triggering due to secretion of type-I interferons.</p> <p>Conclusion</p> <p>It can thus be proposed that exposure of DCs to TLR2-binding bacterial constituents derived, for example, from pathogens causing sexually transmissible infections, might influence the process of DC-mediated viral dissemination, a phenomenon that might contribute to a more rapid disease progression.</p

    Rippled area formed by surface plasmon polaritons upon femtosecond laser double-pulse irradiation of silicon

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    International audienceThe formation of near-wavelength laser-induced periodic surface structures (LIPSS) on silicon upon irradiation with sequences of Ti:sapphire femtosecond laser pulse pairs (pulse duration 150 fs, central wavelength 800 nm) is studied theoretically. For this purpose, the nonlin-ear generation of conduction band electrons in silicon and their relaxation is numerically calculated using a two-temperature model approach including intrapulse changes of optical properties, transport, diffusion and recombina-tion effects. Following the idea that surface plasmon polaritons (SPP) can be excited when the material turns from semiconducting to metallic state, the "SPP active area" is calculated as function of fluence and double-pulse de-lay up to several picoseconds and compared to the experimentally observed rippled surface areas. Evidence is presented that multi-photon absorption explains the large increase of the rippled area for temporally overlapping pulses. For longer double-pulse delays, relevant relaxation processes are identified. The results demonstrate that femtosecond LIPSS on silicon are caused by the excitation of SPP and can be controlled by temporal pulse shaping. ©2013 Optical Society of America OCIS codes: (050.6624) Subwavelength structures; (140.3390) Laser materials processing; (160.6000) Semiconductor materials; (240.5420) Polaritons

    Acceptability in the Older Population: The Importance of an Appropriate Tablet Size

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))—a 3D-map juxtaposing two acceptability profiles—to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients ≄ 65 y in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia (n = 790), while not in those with swallowing disorders (n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets < 6.5 mm appeared to be accepted by patients with swallowing disorders. Among the 309 distinct tablets assessed in this study, ranging in size from 4.7 to 21.5 mm, 83% are ≄ 6.5 mm and consequently may be poorly accepted by institutionalized older people and older inpatients suffering from dysphagia. This underlines the need to develop and prescribe medicines with the best adapted characteristics to reach an optimal acceptability in targeted users.Peer reviewedFinal Published versio

    Poly-phased fluid flow in the giant fossil pockmark of Beauvoisin, SE basin of France

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    The giant Jurassic-aged pockmark field of Beauvoisin developed in a 800 m wide depression for over 3.4 Ma during the Oxfordian; it formed below about 600 m water depth. It is composed of sub-sites organized in clusters and forming vertically stacked carbonate lenses encased in marls . This fine-scale study is focused on a detailed analysis of petrographical organization and geochemical signatures of crystals that grew up in early to late fractures of carbonate lenses, surrounding nodules, and tubes that fed them. The isotopic signature (C, O and Sr) shows that at least three different episodes of fluid migration participated to the mineralization processes. Most of the carbonates precipitated when biogenic seepage was active in the shallow subsurface during the Oxfordian. The second phase occurred relatively soon after burial during early Cretaceous and thermogenic fluids came probably from underlying Pliensbachian, Late Toarcian or Bajocian levels. The third phase is a bitumen-rich fluid probably related to these levels reaching the oil window during Mio-Pliocene. The fluids migrated through faults induced by the emplacement of Triassic-salt diapir of Propiac during the Late Jurassic and that remained polyphased drain structures over time

    Imprinting: expanding the extra-pharmacological model of psychedelic drug action to incorporate delayed influences of sets and settings

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    BackgroundPsychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention.AimsTo investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment-resistant depression (TRD), and develop the concept of “imprinting” to account for such time-lagged effects across diverse hallucinogenic drugs.MethodsRecordings of treatment sessions and phenomenological interviews from 26 participants of a clinical trial investigating serial intravenous ketamine infusions for TRD, conducted from January 2021 to August 2022, were retrospectively reviewed. A broad literature search was undertaken to identify potentially underrecognized examples of imprinting with both serotonergic and atypical psychedelics, as well as analogous cognitive processes and neural mechanisms.ResultsIn naturalistic single-subject experiments of a 28-year-old female and a 34-year-old male, subjective ketamine experiences were significantly altered by varying exposures to particular forms of digital media in the days preceding treatments. Higher levels of media exposure reduced the mystical/emotional qualities of subsequent psychedelic ketamine experiences, overpowering standard intention-setting practices and altering therapeutic outcomes. Qualitative data from 24 additional patients yielded eight further spontaneous reports of past environmental exposures manifesting as visual hallucinations during ketamine experiences. We identified similar examples of imprinting with diverse psychoactive drugs in past publications, including in the first-ever report of ketamine in human subjects, as well as analogous processes known to underly dreaming.Conclusions/interpretationPast environmental exposures can significantly influence the phenomenology and therapeutic outcomes of psychedelic experiences, yet are underrecognized and understudied. To facilitate future research, we propose expanding the contextual model of psychedelic drug actions to incorporate imprinting, a novel concept that may aid clinicians, patients, and researchers to better understand psychedelic drug effects.Clinical trial registrationClinicalTrials.gov, identifier NCT04701866
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