109 research outputs found
SPORT: A new sub-nanosecond time-resolved instrument to study swift heavy ion-beam induced luminescence - Application to luminescence degradation of a fast plastic scintillator
We developed a new sub-nanosecond time-resolved instrument to study the
dynamics of UV-visible luminescence under high stopping power heavy ion
irradiation. We applied our instrument, called SPORT, on a fast plastic
scintillator (BC-400) irradiated with 27-MeV Ar ions having high mean
electronic stopping power of 2.6 MeV/\mu m. As a consequence of increasing
permanent radiation damages with increasing ion fluence, our investigations
reveal a degradation of scintillation intensity together with, thanks to the
time-resolved measurement, a decrease in the decay constant of the
scintillator. This combination indicates that luminescence degradation
processes by both dynamic and static quenching, the latter mechanism being
predominant. Under such high density excitation, the scintillation
deterioration of BC-400 is significantly enhanced compared to that observed in
previous investigations, mainly performed using light ions. The observed
non-linear behaviour implies that the dose at which luminescence starts
deteriorating is not independent on particles' stopping power, thus
illustrating that the radiation hardness of plastic scintillators can be
strongly weakened under high excitation density in heavy ion environments.Comment: 5 figures, accepted in Nucl. Instrum. Methods
Targeting HCV Entry For Development of Therapeutics
Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV) entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication inhibitors now under development. The current model for the pathway of entry involves the initial docking of the virus onto the cell surface through interactions of virion envelope and associated low density lipoproteins (LDL) with cell surface glycosaminoglycans and lipoprotein receptors, followed by more specific utilization with other hepatocyte membrane proteins: Scavenger Receptor Class B type 1 (SR-BI), CD81, Claudin 1 (CLDN1) and Occludin (OCLN). The use of blockers of these interactions, e.g. specific antibodies, suggests that inhibition of any one step in the entry pathway can inhibit infection. Despite this knowledge base, the tools for compound screening, HCV pseudoparticles (HCVpp) and cell culture virus (HCVcc), and the ability to adapt them to industrial use are only recently available and as a result drug discovery initiatives are in their infancy. Several therapies aiming at modulating the virus envelope to prevent host cell binding are in early clinical testing. The first test case for blocking a cellular co-receptor is an SR-BI modulator. ITX 5061, an orally active small molecule, targets SR-BI and has shown potent antiviral activity against HCVpp and HCVcc. ITX 5061 has exhibited good safety in previous clinical studies, and is being evaluated in the clinic in chronic HCV patients and patients undergoing liver transplantation. Entry inhibitors promise to be valuable players in the future development of curative therapy against HCV
Production of multi-charged phosphorus ions with ecris 'SUPERSHyPIE' at GANIL
The Ganil's Ion Production Group tested the source SUPERSHyPIE123 for theproduction of phosphorus n+ ion beams. The SUPERSHyPIE ecris is used for many testsof multi-charged ion production and supply ion beams for LIMBE4 (low energie beamline). This ion source works with a 14.5ghz RF power injected by a circular waveguide inthe axis of the sourc
Ion sources at GANIL
International audienceThe GANIL produces since many years heavy ion beams with Electron Cyclotron Resonance ion sources. Different facilities have been constructed during the last years in order to allow experiments in a large range of energy (from some tens of kV to 100 MeV/nucleon). The list of available ions has been greatly extended with the construction of the SPIRAL1 facility that produces and accelerates radioactives ions . An overview of the different developments made at GANIL for stable and radioactive ion beam production including the sources for the SPIRAL2 project is given in this paper
HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy
The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed chronic hepatitis B (CHB) patients and its impact in defining the subsequent virological responses to Tenofovir (TDF)-based rescue-therapy. By analyzing HBV clones encompassing reverse transcriptase (RT) and surface (S) region from LMV-failed and treatment-naĂŻve CHB patients, we identified 5 classical and 12 novel substitutions in HBV/RT and 9 substitutions in immune-epitopes of HBV/S that were significantly associated with LMV failure. In silico analysis showed spatial proximity of some of the newly-identified, mutated RT residues to the RT catalytic centre while most S-substitutions caused alteration in epitope hydrophobicity. TDF administration resulted in virological response in 60% of LMV-failed patients at 24-week but non-response in 40% of patients even after 48-weeks. Significantly high frequencies of 6 S-substitutions and one novel RT-substitution, rtH124N with 6.5-fold-reduced susceptibility to TDF in vitro, were noted at baseline in TDF non-responders than responders. Follow-up studies depicted greater evolutionary drift of HBV quasispecies and significant decline in frequencies of 3 RT and 6 S-substitutions in responder-subgroup after 24-week TDF-therapy while most variants persisted in non-responders. Thus, we identified the HBV-RT/S variants that could potentially predict unfavorable response to LMV/TDF-therapy and impede immune-mediated viral clearance
Ultra-deep pyrosequencing analysis of the hepatitis B virus preCore region and main catalytic motif of the viral polymerase in the same viral genome
Hepatitis B virus (HBV) pregenomic RNA contains a hairpin structure (Ï”) located in the preCore region, essential for viral replication. Ï” stability is enhanced by the presence of preCore variants and Ï” is recognized by the HBV polymerase (Pol). Mutations in the retrotranscriptase domain (YMDD) of Pol are associated with treatment resistance. The aim of this study was to analyze the preCore region and YMDD motif by ultra-deep pyrosequencing (UDPS). To evaluate the UDPS error rate, an internal control sequence was inserted in the amplicon. A newly developed technique enabled simultaneous analysis of the preCore region and Pol in the same viral genome, as well as the conserved sequence of the internal control. Nucleotide errors in HindIII yielded a UDPS error rate <0.05%. UDPS study confirmed the possibility of simultaneous detection of preCore and YMDD mutations, and demonstrated the complexity of the HBV quasispecies and cooperation between viruses. Thermodynamic stability of the Ï” signal was found to be the main constraint for selecting main preCore mutations. Analysis of Ï”-signal variability suggested the essential nature of the Ï” structural motif and that certain nucleotides may be involved in Ï” signal functions
Tunnel diode oscillator-based measurement of quantum oscillations amplitude in pulsed high magnetic fields: a quantitative field-dependent study
The impact of currently licensed therapies on viral and immune responses in Chronic Hepatitis B: considerations for future novel therapeutics.
Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussedWellcome Trust Clinical Research Training Fellowship (107389/Z/15/Z)NIHR Academic Clinical LectureshipBarts Charity Project Grants (723/1795 and MGU/0406NIHR Research for patient benefit award (PBâPGâ0614â34087) to PTF
Réalisation d'un dispositif de test de cibles pour la production d'ions radioactifs par la méthode ISOL
In the ISOL (isotope separation on line) technique, a primary ion beam impinges on a thick target, the incident ions are stopped through fragmentation reactions that generate radioactive nuclei. As soon as they have collected enough electrons, the radioactive nuclei begin diffusing outside the target as radioactive atoms. In order to improve this diffusion the target is strongly heated. The radioactive atoms diffuse till a ion source that ionize them, they are then accelerated to form a secondary beam that is delivered to the experimental area. This work deals with the design of an equipment able to measure the diffusion capacities of various targets, it is made up of -) a high temperature (> 2300 K) oven that will contain the target, -) a ionization source for ionizing radioactive atoms and -) a target dispatcher able to introduce in the oven or remove from the oven any target of a set of 12 targets. This equipment has proved to be able to test during a single experiment several primary beams and target materials. Measurements will be performed in a sequential way for the different projectile-target couples which will assure very closed experimental conditions for each measuring campaign.Ce travail s'inscrit dans le cadre d'un programme europĂ©en visant Ă optimiser le temps de relĂąchement d'atomes des systĂšmes de production d'ions radioactifs de type ISOL (Isotope Separator On Line). Il a pour but Ă la fois le dĂ©veloppement de faisceaux d'Ă©lĂ©ments nouveaux et l'amĂ©lioration en intensitĂ© et puretĂ© des faisceaux dĂ©jĂ existants. Dans la mĂ©thode ISOL, un faisceau primaire d'ions entre en collision avec les noyaux d'une cible solide et Ă©paisse (les ions incidents sont arrĂȘtĂ©s dans la cible). Les noyaux incidents se fragmentent et donnent lieu Ă des noyaux radioactifs, Ă©galement stoppĂ©s dans la cible. Une fois leur cortĂšge Ă©lectronique reconstituĂ©, ils diffusent en dehors de la cible. Pour accĂ©lĂ©rer le processus de diffusion, la cible est fortement chauffĂ©e. Sortis de la cible, les atomes radioactifs effusent jusqu'Ă une source d'ions dans laquelle ils sont ionisĂ©s. En sortie de source, ils sont accĂ©lĂ©rĂ©s pour former un faisceaux et sont transportĂ©s jusqu'aux aires expĂ©rimentales. Compte tenu du nombre important de paramĂštres qui gouvernent les phases de diffusion et d'effusion dans cette technique, celles-ci font l'objet d'Ă©tudes particuliĂšres. Afin d'apporter les connaissances nĂ©cessaires Ă la conception et Ă l'optimisation des futurs dispositifs de production d'ions radioactifs en ligne, il est nĂ©cessaire de dĂ©velopper une base de donnĂ©es sur les caractĂ©ristiques de diffusion des atomes dans les matĂ©riaux cibles. Dans ce but, le GANIL a conçu et rĂ©alisĂ© un nouveau dispositif permettant de tester au cours d'une mĂȘme expĂ©rience plusieurs couples de faisceaux primaires et de cibles, et ainsi d'augmenter de façon significative la vitesse d'obtention de rĂ©sultats. Les mesures sont rĂ©alisĂ©es Ă la suite les unes des autres pour les diffĂ©rents couples projectile-cible, ce qui assure qu'elles sont effectuĂ©es dans des conditions expĂ©rimentales trĂšs proches. La comparaison des rĂ©sultats sera donc peu affectĂ©e par le doute liĂ© Ă la difficultĂ© de reproduire des conditions expĂ©rimentales identiques. L'ensemble est constituĂ© d'un systĂšme d'analyse (ioniseur basĂ© sur une source Ă RĂ©sonance Cyclotronique Electronique associĂ© Ă un spectromĂštre de masse), d'un four destinĂ© Ă fixer la tempĂ©rature de la cible Ă Ă©tudier, et d'un distributeur de cibles. L'ensemble a Ă©tĂ© testĂ© et caractĂ©risĂ© (hors faisceau primaire)
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