CLINICAL DEVELOPMENT OF FORMULATED THERAPEUTIC AND PROPHYLACTIC DNA-BASED VACCINES

Over the recent years, plasmid DNA vaccines have reached licensure against infectious hematopoietic necrosis virus in farmed salmon (Canada), West Nile virus in horses and metastatic melanoma in dogs (United States). A number of approaches are currently evaluated in clinical trials to enhance the potency of DNA vaccines in humans, including formulation of DNA with delivery systems and adjuvants as well as administration of DNA with devices. This presentation will report on the development of TransVaxTM, a poloxamer-formulated therapeutic DNA vaccine against human cytomegalovirus (CMV) in transplant patients. A vaccine that increases CMV-specific T-cell responses could reduce CMV reactivation after transplantation, thus decreasing the use of antiviral drugs and preventing CMV-associated disease. The interim analysis of a randomized, placebo-controlled Phase 2 trial in hematopoietic stem cell transplant (HCT) recipients will be presented. In a multicenter trial conducted in the United States, CMV-seropositive recipients undergoing allogeneic, matched HCT received either TransVaxTM (n=40) or placebo (n=34) at 3-5 days prior to and 3-6, 12 and 28 weeks after transplant. Viral load, antiviral use and immunogenicity endpoints will be discussed. In addition, the development of prophylactic DNA vaccine candidates against H5N1 and H1N1 pandemic influenza using the adjuvant Vaxfectin® will be described. In particular, the safety and immunogenicity of a Vaxfectin®-formulated DNA vaccine encoding the influenza virus H5 hemagglutinin in clinical trials will be reported. Two double-blind, placebo-controlled Phase 1 trials were conducted in approximately 100 healthy 18-45 year old adults at three sites in the United States using intramuscular injections with either needle or needle-free Biojector® 2000 device. Levels and kinetics of hemagglutination inhibition (HI) titers, neutralizing antibody titers and cross-clade HI titers will be reported. Interferon-ã-producing H5-specific T-cell responses will also be described

Similarities Between Proton and Neutron Induced Dark Current Distribution in CMOS Image Sensors

Several CMOS image sensors were exposed to neutron or proton beams (displacement damage dose range from 4 TeV/g to 1825 TeV/g) and their radiation-induced dark current distributions are compared. It appears that for a given displacement damage dose, the hot pixel tail distributions are very similar, if normalized properly. This behavior is observed on all the tested CIS designs (4 designs, 2 technologies) and all the tested particles (protons from 50 MeV to 500 MeV and neutrons from 14 MeV to 22 MeV). Thanks to this result, all the dark current distribution presented in this paper can be fitted by a simple model with a unique set of two factors (not varying from one experimental condition to another). The proposed normalization method of the dark current histogram can be used to compare any dark current distribution to the distributions observed in this work. This paper suggests that this model could be applied to other devices and/or irradiation conditions

Influence of displacement damage dose on dark current distributions of irradiated CMOS image sensors

Dark current increase distributions due to displacement damages are modeled using displacement damage dose concept. Several CMOS image sensors have been exposed to neutrons or protons and we have characterized their degradation in terms of dark current increase. We have been able to extract a set of two factors from the experimental dark current increase distributions. These factors are used to predict and build dark current increase distribution and leads to a better understanding of displacement damage effects on CMOS image sensors

Kinetic of biobased bitumen synthesis from microalgae biomass by hydrothermal liquefaction

The current worldwide consumption of bitumen is about 100 million tons. A remarkable combination of properties (adhesion, impermeability to water, specific thermo-rheological behavior) makes it a key material in road construction. Today’s bitumen is mostly obtained from petroleum refining, so bioabased alternatives have to be explored for the future. The ALGOROUTE project funded by the French National Agency for Research (ANR) focuses on the use of hydrothermal liquefaction (HTL) process for the production of bitumen mimicking binders from microalgae biomass. HTL applied to microalgae is inspired by the geological process of petroleum formation, but on a very short time scale: For conditions around 260 °C / 50 bar, bitumen like products have been obtained by our consortium for residence times of about 1 hour [1] [2]. Beside temperature and pressure, the key parameters are the reaction time, algae/water ratio and loading level of reactor. Please click Additional Files below to see the full abstract

Cannabidiol and Other Cannabinoids in Demyelinating Diseases

A growing body of preclinical evidence indicates that certain cannabinoids, including cannabidiol (CBD) and synthetic derivatives, may play a role in the myelinating processes and are promising small molecules to be developed as drug candidates for management of demyelinating diseases such as multiple sclerosis (MS), stroke and traumatic brain injury (TBI), which are three of the most prevalent demyelinating disorders. Thanks to the properties described for CBD and its interesting profile in humans, both the phytocannabinoid and derivatives could be considered as potential candidates for clinical use. In this review we will summarize current advances in the use of CBD and other cannabinoids as future potential treatments. While new research is accelerating the process for the generation of novel drug candidates and identification of druggable targets, the collaboration of key players such as basic researchers, clinicians and pharmaceutical companies is required to bring novel therapies to the patients

North western Alps Holocene paleohydrology recorded by flooding activity in Lake Le Bourget, France and possible relations with Mont-Blanc glaciers fluctuations

International audienceA 14-m long piston core was retrieved from Lake Le Bourget, NWAlps (France), in order to provide a continuous record of flooding events of the Rhone River during the Holocene. The selection of the coring site was based on high resolution seismic profiling, in an area with limited mass wasting deposits and accumulated proximal Rhone River inter-and underflow deposits. The age-depth model of this core is based on (i) 14 AMS radiocarbon dates, (ii)radionuclide dating(137Cs) and (iii) the identification of historical data (flood events, eutrophication of the lake).The sedimentary record dates back to 9400 cal BP, and includes a thin mass wasting event deposited around 4500 cal BP. A multi-proxy approach was used to track the evolution and origin of clastic sedimentation during the Holocene, in order to identify periods of higher hydrologic al activity in the catchment area. Spectrophotometry was used to detect fluctuations in clastic supply and the study of clay minerals (especially the Illite crystallinity index) allowed locating the main source area of fine grained clastic particles settling at the lake after flood events. This dataset highlights up to 12 periods of more intense flooding events over the last 9400 years in Lake Le Bourget and shows that the main source area of clastic particles during this period is the upper part of the Arve River drainage basin. This part of the catchment area drains several large glaciers from the Mont-Blanc Massif, and fluctuations in Rhone River flood supply in Lake Le Bourget is interpreted as resulting essentially from Mont-Blanc Glacier activity during the Holocene.The comparison of clastic sedimentationin Lake Le Bourget with periods of increasing land use and periods of Alpine glacier and mid-European lake level fluctuations, suggest that the core LDB04 clastic record in Lake Le Bourget is a continuous proxy of the Holocene hydrologic al history of the NW Alps

Multijunction photovoltaics: integrating III–V semiconductor heterostructures on silicon

International audienceGallium arsenide phosphide nitride shows promise for developing highefficiency tandem solar cells on low-cost silicon substrate

Design of a lattice-matched III-V-N/Si photovoltaic tandem cell monolithically integrated on silicon substrate

International audienceIn this paper, we present a comprehensive study of high efficiencies tandem solar cells monolithically grown on a silicon substrate using GaAsPN absorber layer. InGaAs(N) quantum dots and GaAsPN quantum wells have been grown recently on GaP/Si susbstrate for applications related to light emission. For photovoltaic applications, we consider the GaAsPN diluted nitride alloy as the top junction material due to both its perfect lattice matching with Si and ideal bandgap energy for current generation in association with the Si bottom cell. Numerical simulation of the top cell is performed. The effect of layer thicknesses and doping on the cell efficiency are evidenced. In these structures a tunnel junction (TJ) is needed to interconnect both the top and bottom sub-cells. We compare the simulated performances of different TJ structures and show that the GaP(n+)/Si(p+) TJ is promising to improve performances of the current-voltage characteristic