A Phase I Double Blind, Placebo-Controlled, Randomized Study of a Multigenic HIV-1 Adenovirus Subtype 35 Vector Vaccine in Healthy Uninfected Adults

<div><h3>Background</h3><p>We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35) vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults.</p> <h3>Methods</h3><p>Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions) or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively) within one of four dosage groups: Ad35-GRIN/ENV 2×10⁹ (A), 2×10¹⁰ (B), 2×10¹¹ (C), or Ad35-GRIN 1×10¹⁰ (D) viral particles.</p> <h3>Results</h3><p>No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A–D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC) per 10⁶ PBMC to any antigen was 78–139 across Groups A–C and 158–174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A–C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination.</p> <h3>Conclusion/Significance</h3><p>Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second vaccination. T-cell responses were broad and polyfunctional.</p> <h3>Trial Registration</h3><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/results?term=NCT00851383">NCT00851383</a></p> </div

Comparative physical maps derived from BAC end sequences of tilapia (Oreochromis niloticus)

Background: The Nile tilapia is the second most important fish in aquaculture. It is an excellent laboratory model, and is closely related to the African lake cichlids famous for their rapid rates of speciation. A suite of genomic resources has been developed for this species, including genetic maps and ESTs. Here we analyze BAC endsequences to develop comparative physical maps, and estimate the number of genome rearrangements, between tilapia and other model fish species. Results: We obtained sequence from one or both ends of 106,259 tilapia BACs. BLAST analysis against the genome assemblies of stickleback, medaka and pufferfish allowed identification of homologies for approximately 25,000 BACs for each species. We calculate that rearrangement breakpoints between tilapia and these species occur about every 3 Mb across the genome. Analysis of 35,000 clones previously assembled into contigs by restriction fingerprints allowed identification of longer-range syntenies. Conclusions: Our data suggest that chromosomal evolution in recent teleosts is dominated by alternate loss of gene duplicates, and by intra-chromosomal rearrangements (~one per million years). These physical maps are a useful resource for comparative positional cloning of traits in cichlid fishes. The paired BAC end sequences from these clones will be an important resource for scaffolding forthcoming shotgun sequence assemblies of the tilapia genome. (Résumé d'auteur

DPO and POPOP carboxylate-analog sensors by sequential palladium-catalysed direct arylation of oxazole-4-carboxylates.

International audienceSequential palladium-catalysed direct (het)arylation of oxazole-4-carboxylates is achieved to give rapid access to DPO and POPOP (di)carboxylate-analogs. Three novel DPO- and POPOP-type sensors with unusual Stokes shifts and high quantum yields are discovered

La DDmarche Fidelio. Fondements Et Mise En Pratique (FIDELIO Method, Foundations and Applications)

This article describes an Action Learning resource teaching situational intelligence. It aims to help managers find appropriate responses to complex management situations that they encounter. After reviewing different schools of thought concerning leadership and best management practice, we define situational intelligence as the intelligence of situations, others and oneself, and the ability to reconcile as well as possible the interests of the different actors involved in a situation. We use the contradictions underlying conquest management and finesse management as a reference framework. The "FIDELIO" method, an extension of the "SOLFI" approach used at HEC since 1999, uses leadership theories and stresses recent or newly revived concepts such as emotional intelligence, role theory, contradictions and paradoxes, uncertainty and ambiguity in management, etc. The teaching resource consists of a questionnaire, workshops, individual interviews and post-workshop reports. It contributes to personal development, to the discovery of management concepts and the communication of skills to staff. Participants experiment with different ways to represent their situations and consequently their leadership behaviors evolve. They become aware that leadership is contextual and that it is necessary to used conceptual references. They also work on their own ability to manage contradictions

Analysis by scanning force microscopy of enzyme-containing Langmuir-Blodgett films elaborated by a horizontal lifting method

A mixed Langmuir-Blodgett film constituted of behenic acid and glucose oxidase transferred on HOPG has been studied by scanning force microscopy at microscopic and nanoscopic scales; the results concerning the structures observed at the atomic scale are discussed in reference with a model. At the molecular level, it was possible to observe the arrangement of enzyme molecules and their individual structure revealing their two subunits.Un film de Langmuir-Blodgett mixte constitué d'acide béhénique et de glucose oxydase, transféré sur graphite pyrolytique a été étudié par microscopie à force atomique aux échelles microscopique et nanoscopique. Les résultats obtenus sont discutés par rapport à un modèle de la structure. Au niveau moléculaire, il est possible d'observer l'arrangement des molécules d'enzyme et leur structure individuelle mettant en jeu deux sous-unités

A new series of rod-like conjugated molecules with a pyrazine or a bipyrazine core. Synthesis and light emitting properties

International audienceIn this paper, we describe the synthesis of a wide range of new rod-like conjugated molecules with a pyrazine or a bipyrazine core connected to electron acceptor (A) or donor (D) groups through π-conjugated bridges as transmitters for the internal charge transfer (ICT). The key steps of the synthesis involve metallation and subsequent transmetallation of 2-chloropyrazine derivatives followed by Sonogashira or Negishi cross-coupling reactions. The bipyrazine core was obtained with a Stille cross-coupling reaction between the 2-chloro-6-tributylstannylpyrazine and the 2-chloro-6-iodopyrazine. Functionalization of the 6,6′-dichloro-2,2′-bipyrazine was performed by metallation, transmetallation and cross-coupling reactions. The light emitting properties of the so obtained molecules are then investigated in terms of absorption and emission spectra

Séparation d’énantiomères à caractère acide par chromatographie en phase supercritique avec une phase mobile basique

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The effect of high concentration additive on chiral separations in supercritical fluid chromatography

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One Click to Access Push-Triazole-Pull Fluorophores Incorporating a Pyrimidine Moiety: Structure-Photophysical Properties Relationships

International audienceUsing copper‐catalysed Huisgen 1,3‐dipolar cycloaddition, we describe the synthesis of new A‐π‐D compounds containing a pyrimidine moiety as π‐acceptor (A) and various para‐substituted benzene rings as donors (D). Structure–photophysical properties relationships revealed the triazole ring to be a better π‐conjugated linker than the triple bond

Rod-like conjugated molecules with ethynylene linkage and pyridazines moities: synthesis and light emitting properties.

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