GATE simulation for medical physics with genius Web portal

présenté par C. ThiamPCSV team of the LPC laboratory in Clermont-Ferrand is involved in the deployment of biomedical applications on the grid architecture. One of these applications deals with the deployment of GATE (Geant4 Application for Tomographic Emission) for medical physics application. The aim of the developments actually performed is to enable an application of the GATE platform in clinical routine. However, this perspective is only possible if the computing time and user time are highly reduced. The new grid architecture, developed within the framework of the European project Enabling Grid for E-sciencE (EGEE) is there to answer this requirement. The use of the grid resources must be transparent easy and rapid for the medical physicists. For this perpose, we adapted the GENIUS web portal in order to facilitate the GATE simulations planning on the grid. We will present a demonstration of the GENIUS portal which integrates all the functionalities of EGEE: to create, to submit and manage GATE jobs on the grid architecture. Our GATE activities for dosimetry application entered in to direct phase of evaluation by the cancer treatment center of Clermont Ferrand (Centre Jean perrin).A work station is currently available in this center to test the use of GATE application on the grid through GENIUS. This portal will allow in a long term to use GATE application in brachytherapy and radiotherapy treatment planning using medical data (medical images, DICOM, binary data dose calculation in the heterogeneous mediums) and to analyze the results obtained in visual form. Other functionalities are under development and will make possible to register medical data on grid storages elements and to manage them. However, these data must be anonymised before their recording on the grid. Their access via the GENIUS portal must be made safe and fast (compared simulation computing time). In order to be sure that the medical data are accessible for calculations, their replication on various storage element (SE) should be possible. The grid services give the possibility of managing this information in a free way and transparently. Operations of data handling and catalogues on the grid are ensured by the Replica Manager system which integrates all tools making it possible to manage data on the grid. The computing grid give promising results and meet a definite need: reach acceptable computing time for a future use of Monte Carlo simulations for treatment planning in brachytherapy and radiotherapy

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA mDial-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42 Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4 MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDial-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function

Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells

Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti- tumor immune activity via antigen presentation and induction of pro- inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation. Furthermore, sodium oleate potentiated nitric oxide (NO) production in MSC-2, thereby increasing their suppressive capacity. In primary polarized bone marrow cells, sodium oleate (C18:1) and linoleate (C18:2), but not stearate (C18:0) were identified as potent FFA to induce a regulatory phenotype. This effect was abrogated in MSC-2 as well as primary cells by specific inhibition of droplets formation while the inhibition of de novo FFA synthesis proved ineffective, suggesting a critical role for exogenous FFA in the functional induction of MSCs. Taken together our data introduce a new unsaturated fatty acid-dependent pathway shaping the functional phenotype of MSCs, facilitating the tumor escape from the immune system

“Even if You Know Everything You Can Forget”: Health Worker Perceptions of Mobile Phone Text-Messaging to Improve Malaria Case-Management in Kenya

This paper presents the results of a qualitative study to investigate the perceptions and experiences of health workers involved in a a cluster-randomized controlled trial of a novel intervention to improve health worker malaria case-management in 107 government health facilities in Kenya. The intervention involved sending text-messages about paediatric outpatient malaria case-management accompanied by “motivating” quotes to health workers’ mobile phones. Ten malaria messages were developed reflecting recommendations from the Kenyan national guidelines. Two messages were delivered per day for 5 working days and the process was repeated for 26 weeks (May to October 2009). The accompanying quotes were unique to each message. The intervention was delivered to 119 health workers and there were significant improvements in correct artemether-lumefantrine (AL) management both immediately after the intervention (November 2009) and 6 months later (May 2010). In-depth interviews with 24 health workers were undertaken to investigate the possible drivers of this change. The results suggest high acceptance of all components of the intervention, with the active delivery of information in an on the job setting, the ready availability of new and stored text messages and the perception of being kept ‘up to date’ as important factors influencing practice. Applying the construct of stages of change we infer that in this intervention the SMS messages were operating primarily at the action and maintenance stages of behaviour change achieving their effect by creating an enabling environment and providing a prompt to action for the implementation of case management practices that had already been accepted as the clinical norm by the health workers. Future trials testing the effectiveness of SMS reminders in creating an enabling environment for the establishment of new norms in clinical practice as well as in providing a prompt to action for the implementation of the new case-management guidelines are justified

Amphipathic helices target perilipins 1-3 to lipid droplets

Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on the surface of lipid droplets. Failure of this activity results in severe metabolic disease in humans. Unlike all other lipid droplet-associated proteins, PLINs localize almost exclusively to the phospholipid monolayer surrounding the droplet. To understand how they sense and associate with the unique topology of the droplet surface, we studied the localization of human PLINs inSaccharomyces cerevisiae,demonstrating that the targeting mechanism is highly conserved and that 11-mer repeat regions are sufficient for droplet targeting. Mutations designed to disrupt folding of this region into amphipathic helices (AHs) significantly decreased lipid droplet targetingin vivoandin vitro Finally, we demonstrated a substantial increase in the helicity of this region in the presence of detergent micelles, which was prevented by an AH-disrupting missense mutation. We conclude that highly conserved 11-mer repeat regions of PLINs target lipid droplets by folding into AHs on the droplet surface, thus enabling PLINs to regulate the interface between the hydrophobic lipid core and its surrounding hydrophilic environment.This work was supported by grants from The Wellcome Trust (091551 and 107064 to DBS), the U.K. NIHR Cambridge Biomedical Research Centre, the Medical Research Council (G0701446 to SS and a Doctoral training grant awarded to the University of Cambridge for ERR), core facilities at the MRC Metabolic Diseases Unit (MC_UU_12012/5) and by the Innovative Medicines Initiative Joint Undertaking, EMIF-Metabolism award.This is the final version of the article. It first appeared from ASBMB via https://doi.org/10.1074/jbc.M115.69104

KELT-22Ab: A Massive, Short-Period Hot Jupiter Transiting a Near-solar Twin

We present the discovery of KELT-22Ab, a hot Jupiter from the KELT-South survey. KELT-22Ab transits the moderately bright (V ∼ 11.1) Sun-like G2V star TYC 7518-468-1. The planet has an orbital period of days, a radius of , and a relatively large mass of . The star has , , K, (cgs), and [m/H] = ; thus other than its slightly super-solar metallicity, it appears to be a near-solar twin. Surprisingly, KELT-22A exhibits kinematics and a Galactic orbit that are somewhat atypical for thin-disk stars. Nevertheless, the star is rotating rapidly for its estimated age, and shows evidence of chromospheric activity. Imaging reveals a slightly fainter companion to KELT-22A that is likely bound, with a projected separation of 6″ (∼1400 au). In addition to the orbital motion caused by the transiting planet, we detect a possible linear trend in the radial velocity of KELT-22A, suggesting the presence of another relatively nearby body that is perhaps non-stellar. KELT-22Ab is highly irradiated (as a consequence of the small semimajor axis of ), and is mildly inflated. At such small separations, tidal forces become significant. The configuration of this system is optimal for measuring the rate of tidal dissipation within the host star. Our models predict that, due to tidal forces, the semimajor axis is decreasing rapidly, and KELT-22Ab is predicted to spiral into the star within the next Gyr

Validating AU Microscopii d with Transit Timing Variations

AU Mic is a young (22 Myr) nearby exoplanetary system that exhibits excess TTVs that cannot be accounted for by the two known transiting planets nor stellar activity. We present the statistical "validation" of the tentative planet AU Mic d (even though there are examples of "confirmed" planets with ambiguous orbital periods). We add 18 new transits and nine midpoint times in an updated TTV analysis to prior work. We perform the joint modeling of transit light curves using EXOFASTv2 and extract the transit midpoint times. Next, we construct an O-C diagram and use Exo-Striker to model the TTVs. We generate TTV log-likelihood periodograms to explore possible solutions for the period of planet d and then follow those up with detailed TTV and RV MCMC modeling and stability tests. We find several candidate periods for AU Mic d, all of which are near resonances with AU Mic b and c of varying order. Based on our model comparisons, the most-favored orbital period of AU Mic d is 12.73596+/-0.00793 days (T_{C,d}=2458340.55781+/-0.11641 BJD), which puts the three planets near a 4:6:9 mean-motion orbital resonance. The mass for d is 1.053+/-0.511 M_E, making this planet Earth-like in mass. If confirmed, AU Mic d would be the first known Earth-mass planet orbiting a young star and would provide a valuable opportunity in probing a young terrestrial planet's atmosphere. Additional TTV observation of the AU Mic system are needed to further constrain the planetary masses, search for possible transits of AU Mic d, and detect possible additional planets beyond AU Mic c.Comment: 89 pages, 35 figures, 34 tables. Redid EXOFASTv2 transit modeling to recover more reasonable stellar posteriors, so redid Exo-Striker TTV modeling for consistency. Despite these changes, the overall results remain unchanged: the 12-7-day case is still the most favored. Submitted to AAS Journals on 2023 Feb 9t