Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis

Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity922124132FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2011/17965-3; 2011/13191-3; 2012/08303-

An Analysis of Fundamental Waffle Mode in Early AEOS Adaptive Optics Images

Adaptive optics (AO) systems have significantly improved astronomical imaging capabilities over the last decade, and are revolutionizing the kinds of science possible with 4-5m class ground-based telescopes. A thorough understanding of AO system performance at the telescope can enable new frontiers of science as observations push AO systems to their performance limits. We look at recent advances with wave front reconstruction (WFR) on the Advanced Electro-Optical System (AEOS) 3.6 m telescope to show how progress made in improving WFR can be measured directly in improved science images. We describe how a "waffle mode" wave front error (which is not sensed by a Fried geometry Shack-Hartmann wave front sensor) affects the AO point-spread function (PSF). We model details of AEOS AO to simulate a PSF which matches the actual AO PSF in the I-band, and show that while the older observed AEOS PSF contained several times more waffle error than expected, improved WFR techniques noticeably improve AEOS AO performance. We estimate the impact of these improved WFRs on H-band imaging at AEOS, chosen based on the optimization of the Lyot Project near-infrared coronagraph at this bandpass.Comment: 15 pages, 11 figures, 1 table; to appear in PASP, August 200

Low-level Laser Therapy to the Mouse Femur Enhances the Fungicidal Response of Neutrophils against Paracoccidioides brasiliensis

Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. the goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. the aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. the number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. the highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. the kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)National Institute of Health (US NIH)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fed Univ Alfenas UNIFAL MG, Inst Biomed Sci, Dept Microbiol & Immunol, Alfenas, MG, BrazilFed Univ Alfenas UNIFAL MG, Inst Biomed Sci, Dept Biochem, Alfenas, MG, BrazilState Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, São Paulo, SP, BrazilMassachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USAHarvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USAMIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USAFed Univ Alfenas UNIFAL MG, Inst Biomed Sci, Dept Pathol & Parasitol, Alfenas, MG, BrazilFed Univ São Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, São Paulo, SP, BrazilCNPq: 486135/2012-8CNPq: 304827/2012-6FAPEMIG: CBB-PPM-00119-14National Institute of Health (US NIH): R01AI050875CAPES: AEX-9765-14-0Web of Scienc

Toward on-sky adaptive optics control using reinforcement learning Model-based policy optimization for adaptive optics

Context. The direct imaging of potentially habitable exoplanets is one prime science case for the next generation of high contrast imaging instruments on ground-based, extremely large telescopes. To reach this demanding science goal, the instruments are equipped with eXtreme Adaptive Optics (XAO) systems which will control thousands of actuators at a framerate of kilohertz to several kilohertz. Most of the habitable exoplanets are located at small angular separations from their host stars, where the current control laws of XAO systems leave strong residuals. Aims. Current AO control strategies such as static matrix-based wavefront reconstruction and integrator control suffer from a temporal delay error and are sensitive to mis-registration, that is, to dynamic variations of the control system geometry. We aim to produce control methods that cope with these limitations, provide a significantly improved AO correction, and, therefore, reduce the residual flux in the coronagraphic point spread function (PSF). Methods. We extend previous work in reinforcement learning for AO. The improved method, called the Policy Optimization for Adaptive Optics (PO4AO), learns a dynamics model and optimizes a control neural network, called a policy. We introduce the method and study it through numerical simulations of XAO with Pyramid wavefront sensor (PWFS) for the 8-m and 40-m telescope aperture cases. We further implemented PO4AO and carried out experiments in a laboratory environment using Magellan Adaptive Optics eXtreme system (MagAO-X) at the Steward laboratory. Results. PO4AO provides the desired performance by improving the coronagraphic contrast in numerical simulations by factors of 3-5 within the control region of deformable mirror and PWFS, both in simulation and in the laboratory. The presented method is also quick to train, that is, on timescales of typically 5-10 s, and the inference time is sufficiently small (Peer reviewe

Toward on-sky adaptive optics control using reinforcement learning Model-based policy optimization for adaptive optics

Context. The direct imaging of potentially habitable exoplanets is one prime science case for the next generation of high contrast imaging instruments on ground-based, extremely large telescopes. To reach this demanding science goal, the instruments are equipped with eXtreme Adaptive Optics (XAO) systems which will control thousands of actuators at a framerate of kilohertz to several kilohertz. Most of the habitable exoplanets are located at small angular separations from their host stars, where the current control laws of XAO systems leave strong residuals. Aims. Current AO control strategies such as static matrix-based wavefront reconstruction and integrator control suffer from a temporal delay error and are sensitive to mis-registration, that is, to dynamic variations of the control system geometry. We aim to produce control methods that cope with these limitations, provide a significantly improved AO correction, and, therefore, reduce the residual flux in the coronagraphic point spread function (PSF). Methods. We extend previous work in reinforcement learning for AO. The improved method, called the Policy Optimization for Adaptive Optics (PO4AO), learns a dynamics model and optimizes a control neural network, called a policy. We introduce the method and study it through numerical simulations of XAO with Pyramid wavefront sensor (PWFS) for the 8-m and 40-m telescope aperture cases. We further implemented PO4AO and carried out experiments in a laboratory environment using Magellan Adaptive Optics eXtreme system (MagAO-X) at the Steward laboratory. Results. PO4AO provides the desired performance by improving the coronagraphic contrast in numerical simulations by factors of 3-5 within the control region of deformable mirror and PWFS, both in simulation and in the laboratory. The presented method is also quick to train, that is, on timescales of typically 5-10 s, and the inference time is sufficiently small (Peer reviewe

Data processing on simulated data for SHARK-NIR

A robust post processing technique is mandatory to analyse the coronagraphic high contrast imaging data. Angular Differential Imaging (ADI) and Principal Component Analysis (PCA) are the most used approaches to suppress the quasi-static structure in the Point Spread Function (PSF) in order to revealing planets at different separations from the host star. The focus of this work is to apply these two data reduction techniques to obtain the best limit detection for each coronagraphic setting that has been simulated for the SHARK-NIR, a coronagraphic camera that will be implemented at the Large Binocular Telescope (LBT). We investigated different seeing conditions ($0.4"-1"$) for stellar magnitude ranging from R=6 to R=14, with particular care in finding the best compromise between quasi-static speckle subtraction and planet detection.Comment: 9 pages, 8 figures, proceeding for the fifth Adaptive Optics for Extremely Large Telescopes (AO4ELT5) meeting in 201