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Purpose:Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors.Patients and Methods:INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan–Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry.Results:Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed.Conclusions:INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond.See related commentary by Slingluff Jr, p. 529

Histological diagnosis, age, number of cycles received and Overall Survival

Immunophenotyping of circulating CD4 and CD8 T cells

Number and percentage of patients reporting studytreatment-related AEs per cycle

Clinical features of patients with OS 1 year

Flow Chart

Kaplan-Meier representation of Overall Survival and Progression Free Survival

This file compiles all the results identified as "data not shown" in the manuscript

Best Overall Response

Flow Cytometry antibody references

Human telomerase reverse transcriptase (hTERT) is broadly expressed in many cancers. High hTERT expression have been described in chronic lymphocytic leukemia (CLL). Here we investigated the relationship between anti-hTERT immunity and disease progression in 49 CLL patients. Anti-hTERT T cell responses were evaluated by IFNγ-ELISpot. Complementary flow cytometry analyses were performed, and data were analyzed in regards of the treatment received by CLL patients afterward and disease progression. Anti-hTERT responses were more frequently observed in non-progressive watch and wait patients, and in progressive patients scheduled to receive ibrutinib, as compared to patients scheduled to receive other types of treatment. In vitro, addition of the anti-PD-1 antibody nivolumab increased anti-hTERT responses. Importantly, Kaplan Meier analyses showed significantly longer progression-free survival in patients with anti-hTERT immune responses at diagnosis as compared to non-responder patients. Our results show that anti-hTERT T cell responses represent a new potential biomarker predictive of CLL clinical outcome.

International audience; The database presented in this study has been acquired during the SOuth west FOGs 3D (SOFOG3D) experiment for processes study. This international campaign led by Météo-France during the winter 2019-2020 aimed at deploying a unique network of both in situ and remote sensing measurements in order to document spatial and temporal variabilities of fog events. To support this scientific objective but also to conduct first data assimilation experiments within the French convective scale model AROME, an unprecedented network of 8 ground-based microwave radiometers (MWR) has been deployed in 7 different locations known to be prone to fog occurrences. The database gives access to vertical profiles of temperature and humidity (both absolute and relative) from the surface up to 10 km altitude as well as integrated water vapor and liquid water path estimates. The retrieved profiles offer a very large database that can be exploited for several scientific purposes: fog process studies at specific location, documentation on the variability of fog properties at the regional scale, better understanding of the atmospheric boundary layer (ABL) height and dynamics during wintertime conditions, development of nowcasting products dedicated to fog alerts, data assimilation experiments to improve fog forecasts, development of synergetical advanced products, and evaluation of new model configurations with advanced parameterization or resolutions. Keywords Microwave radiometer • Brightness temperatures • Fog • Temperature • Humidity • Liquid water path • Integrated water vapor All the authors contributed to the instrumental deployment of microwave radiometers. Pauline Martinet and Vinciane Unger conducted the scientific evaluation, data preparation, and the data delivery on the AERIS portal.

Purpose: Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors. Patients and Methods: INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan–Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry. Results: Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed. Conclusions: INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond. See related commentary by Slingluff Jr, p. 529

Fog forecasts still remain quite inaccurate due to the complexity, non linearities and fine scale of the main physical processes driving the fog lifecycle. Additionally to the complex modelling of fog processes, current numerical weather prediction models are known to suffer from a lack of operational observations in the atmospheric boundary layer and more generally during cloudy-sky conditions. Continuous observations of both thermodynamics and microphysics during the fog lifecycle are thus essential to develop future operational networks with the aim of validating current physical parameterizations and improving the model initial state through data assimilation techniques. In this context, an international network of 8 ground-based microwave radiometers (MWRs) has been deployed at a regional-scale on a 300 x 300 km domain during the SOFOG3D (SOuth FOGs 3D experiment for fog processes study) that has been conducted from October 2019 to April 2020. The MWR network has been extended with ceilometers at all MWR sites and additional microphysical observations from the 95 GHz cloud radar BASTA at two major sites as well as wind measurements from a Doppler lidar deployed at the super-site. After an overview of the SOFOG3D objectives and experimental set-up, preliminary results exploiting mainly the MWR network and cloud radar observations will be presented. Firstly, the capability of MWRs to provide temperature and humidity retrievals within fog and stratus clouds will be evaluated and discussed against radiosoundings launched during intensive observation periods (IOPs). Secondly, first retrievals of liquid water content profiles within fog and stratus clouds derived from the synergy between MWRs and the BASTA cloud radar will be presented. To that end, a one dimensional variational approach (1D-Var) directly assimilating MWR brightness temperatures and cloud-radar reflectivities has been developed. 1D-Var retrievals will be validated through a dataset of simulated observations and real fog cases of the SOFOG3D experiment. The capability of MWR and cloud radar observations to improve the initial state of the AROME model during fog conditions will be discussed with a focus on selected case studies. Finally, the usefulness of ground-based remote sensing networks to improve our understanding of fog processes and to validate physical parameterizations will be illustrated using the operational AROME model and the AROME Ensemble Prediction System

Telomerase reverse transcriptase (TERT) is highly expressed in more than 90% of canine cancer cells and low to absent in normal cells. Given that immune tolerance to telomerase is easily broken both naturally and experimentally, telomerase is an attractive tumor associated antigen for cancer immunotherapy. Indeed, therapeutic trials using human telomerase peptides have been performed. We have developed an immunogenic yet catalytically inactive human telomerase DNA construct that is in clinical trials with patients presenting solid tumors. Paralleling this human construct, we have developed a canine telomerase DNA vaccine, called pDUV5. When administered intradermally to mice combined with electrogene transfer, pDUV5 induced canine TERT specific cytotoxic T-cells as measured by IFN-γ ELISpot assay. Intradermal vaccination of healthy dogs with 400 μg of pDUV5 generated strong, broad and long lasting TERT specific cellular immune responses. In vitro immunization with cTERT peptides revealed the maintenance of cTERT specific T-cells in PBMCs from tumor bearing dogs showing that this repertoire was not depleted. This study highlights the potential of pDUV5 as a cancer vaccine and supports its evaluation for the treatment of spontaneous canine tumors.

We report on a direct detection differential absorption lidar (DIAL), designed for remote detection of CH4 and CO2. The system is based on a single-frequency optical parametric oscillator/amplifier system, tunable in the 1.57-1.65 µm range. The DIAL system, called NAOMI GAZL, was tested on a controlled gas release facility in October 2018.

Background INVAC-1 is an optimized DNA plasmid encoding an inactive form of human Telomerase Reverse Transcriptase (hTERT), a universal tumor antigen expressed in most of human tumors with little or no expression in normal somatic cells. Primary pharmacodynamics, safety and toxicology studies showed that INVAC-1 was enzymatically inactive, immunogenically safe and well tolerated. In murine models, we demonstrated that INVAC-1 was able to induce hTERT specific cellular immune responses with CD4+ Th1 effector and memory CD8+ T-cells as well as slow tumor growth and increase survival rate by 50% in tumor-bearing mice. Methods We conducted a First-In-Human (FIH) study, 2-centre, Phase I, open label, 3+3 escalation design and multiple dose study examining the safety and tolerability of INVAC-1 administered at three dose levels (100, 400 and 800 µg) in 26 patients with relapsed or solid refractory tumors. INVAC-1 was administered either by intradermal (ID) injection followed by electroporation (EP) (n=20) or by Tropis® Needle Free Injection System (n=6). Results INVAC-1 vaccination was safe and well tolerated when administered ID (either with EP or by Tropis®) at the three tested doses. Only one treatment-related grade 3 SAE was reported. 58% of patients experienced disease stabilization up to 9.9 months. One-year survival was reached for 65% of patients. INVAC-1 elicited both hTERT specific Th1-dominant CD4 and cytotoxic CD8 T cell responses with no vaccine-induced peripheral immunosuppression. Anti-hTERT immune responses were enhanced by adding anti-PD-1 immune checkpoint inhibitor ex vivo. In addition, INVAC-1 vaccination was able to promote epitope spreading. Finally, correlation analysis between clinical and immunological data showed that patients with OS >1 year presented a significantly higher hTERT immune response after INVAC-1 vaccination compared to patients with OS Citation Format: Julie Garibal, Jacques Medioni, Luis Teixeira, Olivier Adotevi, Marie-Agnès Dragon-Durey, Caroline Laheurte, Claire Germain, Marie Escande, Maria Wehbe, Valérie Doppler, Thierry Huet, Pierre Langlade Demoyen. INVAC-1, an optimized telomerase DNA vaccine in patients with advanced solid tumors: Final results of first-in-human phase I study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT021.

International audience; Cancer immunotherapy is seeing an increasing focus on vaccination with tumor-associated antigens (TAAs). Human telomerase (hTERT) is a TAA expressed by most tumors to overcome telomere shortening. Tolerance to hTERT can be easily broken both naturally and experimentally and hTERT DNA vaccine candidates have been introduced in clinical trials. DNA prime/boost strategies have been widely developed to immunize efficiently against infectious diseases. We explored the use of a recombinant measles virus (MV) hTERT vector to boost DNA priming as recombinant live attenuated measles virus has an impressive safety and efficacy record. Here, we show that a MV-TERT vector can rapidly and strongly boost DNA hTERT priming in MV susceptible IFNAR/CD46 mouse models. The cellular immune responses were Th1 polarized. No humoral responses were elicited. The 4 kb hTERT transgene did not impact MV replication or induction of cell-mediated responses. These findings validate the MV-TERT vector to boost cell-mediated responses following DNA priming in humans.

DIfferential Absorption Lidars (DIAL) can be powerful tools for remote detection of various gaseous species. We report here on the instruments that we have recently developed, based on specific optical sources, for industrial safety applications, as well as for defense applications.

International audience; Ceilometers are widely spread instruments mainly used for cloud base height determination. However, recent models are more sensitive to aerosols; hence, nowadays there is an increasing interest in these instruments to retrieve aerosol optical and microphysical properties.The high number of them distributed around the globe compared to the robust lidar systems and the fact that ceilometers work under unattended conditions are the main reasons behind this interest. In this paper a new methodology is proposed to retrieve aerosol vertical extinction and backscatter profiles from a Vaisala ceilometer CL51. This methodology is based in two parts: first, a signal pre-processing with a suppression of the dark current and background noises, and a correction of the water vapor absorption using near-real time temperature and absolute humidity (AH) profiles from a co-located Microwave radiometer (MWR). Then an iterative Klett-based algorithm that uses AERONET (AErosol RObotic NETwork) AOD (Aerosol Optical Depth) as an input to retrieve the extinction and backscatter profiles. The error analysis of the aerosol retrievals has been performed between MWR measurements and modelled radiosondes from HYSPLIT. The absolute errors found in temperature and AH are leading to errors in the pre-processed RCS signals up to 9%, and then in particle backscatter and particle extinction coefficients up to 2:2% and 25%, respectively.; Les ceilomètres sont des instruments très répandus, principalement utilisés pour déterminer la hauteur de la base des nuages. Cependant, des modèles récents sont plus sensibles aux aérosols ; c'est pourquoi, de nos jours, on s'intéresse de plus en plus à ces instruments pour mesurer des données optiques des aérosols et leurs propriétés microphysiques. Le nombre élevé de ces derniers, répartis dans le monde entier, par rapport aux systèmes lidar robustes et le fait que les plafonds fonctionnent dans des conditions non surveillées sont les principales raisons de cet intérêt. Dans ce document, une nouvelle méthodologie est proposée pour déterminer par inversion les profils d'extinction verticale et de rétrodiffusion des aérosols à partir d'un modèle CL51 de ceilomètre de Vaisala. Cette méthodologie est basée sur deux parties : premièrement, un prétraitement du signal avec une suppression du courant d'obscurité et du fond et une correction de l'absorption de la vapeur d'eau en utilisant des profils de température et d'humidité absolue (AH) en temps quasi réel d'un radiomètre à micro-ondes (MWR) colocalisé. Ensuite, un algorithme itératif basé sur Klett qui utilise AERONET (AErosol RObotic NETwork) AOD (Aerosol Optical Depth) comme entrée est appliquée pour récupérer les profils d'extinction et de rétrodiffusion. Les erreurs absolues trouvées dans la température et l'AH entraînent des erreurs dans les signaux RCS prétraités jusqu'à 9 %, puis dans les coefficients de rétrodiffusion et d'extinction des particules jusqu'à 2,2 % et 25 %, respectivement.

2642 Background: INVAC-1 is an optimized DNA plasmid encoding an inactive form of human Telomerase Reverse Transcriptase (hTERT), a universal tumor antigen expressed in most of human tumors with little or no expression in somatic cells. We report here the final results of a First-In-Human Phase I study evaluating INVAC-1 as a single agent in patients (pts) with advanced solid tumors, ended in June 2018. Methods: A two center Phase I trial evaluated INVAC-1 given monthly for a minimum of 3 cycles and up to 9 cycles by intradermal injection followed by electroporation (n = 20) or using a needle-free injection system (n = 6). Primary objectives included safety, tolerability and dose limiting toxicities to identify the maximum tolerated dose and recommended phase 2 dose. Secondary objectives included immune response (assessed by IFN-γ Elispot) and anti-tumor activity. Immuno-monitoring included detection of autoantibodies, lymphocyte phenotyping and inflammatory cytokine levels in blood. Anti-tumor activity was evaluated through RECIST 1.1 adapted to immune response, and plasma circulating tumor DNA (ctDNA). Results: 26 pts with refractory/progressive tumors were enrolled and treated with 3 escalating doses of 100, 400 and 800 µg. 15 pts experienced stable disease according to RECIST. For 11 of them, the treatment was extended, up to 9 months. INVAC-1 was well tolerated with no dose-limiting toxicities. No significant biological signs of autoimmunity were observed. No significant modification in inflammatory plasma cytokines levels was observed after INVAC-1 administration. INVAC-1 triggered de novo or enhanced pre-existing CD4/CD8 specific anti-hTERT response in 63% of pts. This specific anti-hTERT immune response was enhanced ex vivo by adding the immune checkpoint inhibitor nivolumab. ctDNA was evaluated in 17 pts. We observed a ctDNA decrease in 6 cases, a stable level in 5 cases and an increase in 6 cases. Conclusions: Results indicate that INVAC-1 was well tolerated and immunogenic at the doses and schedule tested. Disease stabilization was obtained for the majority of pts (58%) according to RECIST criteria or ctDNA levels. Clinical trial information: NCT02301754.

International audience; This paper addresses the problem of critical operations in Degraded Visual Environment (DVE). DVE usually refer when the perception of a pilot is degraded by environmental factors, including the presence of obscurants from bad weather (e.g. fog, rain, snow) or accidental events (e.g. brownout, whiteout, smoke). Critical operations in DVE are a growing field of research as it is a cause of numerous fatal accidents for operational forces. Due to the lack of efficient sources and sensors in the Terahertz (THz) region, this domain has remained an unexplored part of the electromagnetic spectrum. Recently, the potential use of sub-Terahertz waves has been proposed to see through dense clouds of obscurants (e.g. sand, smoke) in DVE conditions. In order to conduct a performance evaluation of sub-Terahertz systems, several sub-terahertz systems (e.g. bolometer- array cameras, liquid helium cooled bolometers) were operated in artificial controlled DVE conditions at ONERA facilities. The purpose of this paper is to report field experiments results in controlled DVE conditions: attenuation measurements from 400 GHz to 700 GHz with a performance evaluation of different sub-Terahertz systems are presented.

MATISSE V3 will be a major release with new radiative transfer core. To accelerate the k-distributions generation step, a new code was developed and allows this generation three order of magnitude faster than before.

Enfuvirtide (also known as Fuzeon, T-20, or DP-178) is an antiretroviral fusion inhibitor which prevents human immunodeficiency virus type 1 (HIV-1) from entering host cells. This linear 36-mer synthetic peptide is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1-infected individuals and AIDS patients with multidrug-resistant HIV infections. Although enfuvirtide is an efficient anti-HIV-1 drug, its clinical use is limited by a short plasma half-life, i.e., approximately 2 h, which requires twice-daily subcutaneous injections, often resulting in skin sensitivity reaction side effects at the injection sites. Ultimately, 80% of patients stop enfuvirtide treatment within 6 months because of these side effects. We report on the development of long-lasting enfuvirtide conjugates by the use of the site-specific conjugation of enfuvirtide to an antithrombin-binding carrier pentasaccharide (CP) through polyethylene glycol (PEG) linkers of various lengths. These conjugates showed consistent and broad anti-HIV-1 activity in the nanomolar range. The coupling of the CP to enfuvirtide only moderately affected the in vitro anti-HIV-1 activity in the presence of antithrombin. Most importantly, one of these conjugates, enfuvirtide-PEG12-CP (EP40111), exhibited a prolonged elimination half-life of more than 10 h in rat plasma compared to the half-life of native enfuvirtide, which was 2.8 h. On the basis of the pharmacokinetic properties of antithrombin-binding pentasaccharides, the anticipated half-life of EP40111 in humans would putatively be about 120 h, which would allow subcutaneous injection once a week instead of twice daily. In conclusion, EP40111 is a promising compound with strong potency as a novel long-lasting anti-HIV-1 drug.

3087 Background: INVAC-1 is an optimized plasmid encoding an inactive form of human telomerase reverse transcriptase (hTERT). hTERT is a prototype of shared tumor antigen expressed in more than 85% of human tumors. Telomerase activation is associated with maintenance of telomere length and accounts for the unlimited proliferative capacity of cancer cells. In preclinical models, INVAC-1 triggered Th1-polarized hTERT-specific CD8+ and CD4+T-cell immune responses and anti-tumor effects. Here, we report clinical and pharmacodynamics results of the first clinical study with INVAC-1 as a single agent in solid tumors. Methods: A 3+3 design phase 1 First in Human study evaluating INVAC-1 given monthly for 3 cycles using electroporation-based intra-dermal (ID) injection was conducted. Primary objectives included safety, tolerability and dose limiting toxicities to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary objectives included immune response and anti-tumor activity. Results: 20 patients (pts) with refractory/progressive solid tumors were enrolled in two centers. 3 escalating doses were studied: 100 µg (3 pts), 400 µg (3 pts) and 800 µg (14 pts). At 3-month data cut-off, no dose limiting toxicities or treatment related SAEs have been reported; no MTD was defined. The most common treatment-related adverse events were grade 1 or 2: asthenia and local reaction at injection site. 12 pts experienced stable disease and clinical benefit. For 10 pts, the treatment was extended beyond the per-protocol 3-month duration, up to nine months for 2 pts. IFN-g polarized anti-hTERT immune responses were detected in 55% of pts, in response to INVAC-1 treatment. Conclusions: Results from this study indicate that INVAC-1 ID was safe, well tolerated and strongly immunogenic at the doses and schedule tested. Early anti-tumor activity has been observed. The RP2D of INVAC-1 is therefore a monthly ID injection of 800 µg. These results encourage a future evaluation of INVAC-1 is solid tumors, as well as in hematologic malignancies, either as monotherapy or in combination with various immunotherapeutic drugs. Clinical trial information: NCT02301754.

DNA vaccination consists in administering an antigen-encoding plasmid in order to trigger a specific immune response. This specific vaccine strategy is of particular interest to fight against various infectious diseases and cancer. Gene electrotransfer is the most efficient and safest non-viral gene transfer procedure and specific electrical parameters have been developed for several target tissues. Here, a gene electrotransfer protocol into the skin has been optimized in mice for efficient intradermal immunization against the well-known telomerase tumor antigen. First, the luciferase reporter gene was used to evaluate gene electrotransfer efficiency into the skin as a function of the electrical parameters and electrodes, either non-invasive or invasive. In a second time, these parameters were tested for their potency to generate specific cellular CD8 immune responses against telomerase epitopes. These CD8 T-cells were fully functional as they secreted IFNγ and were endowed with specific cytotoxic activity towards target cells. This simple and optimized procedure for efficient gene electrotransfer into the skin using the telomerase antigen is to be used in cancer patients for the phase 1 clinical evaluation of a therapeutic cancer DNA vaccine called INVAC-1.

Recently, a new p53 derivative has been designed, namely chimeric tumor suppressor 1 (CTS1), in which the p53 domains that are known to mediate p53 inactivation have been replaced. In this study, the antitumoral activity of CTS1 mediated by adenovirus vector has been evaluated in comparison with a p53 adenovirus vector in various human tumor cell lines. In vitro, in terms of cell growth inhibition, the CTS1 vector was significantly (P < .01) more efficient (2- to 7-fold) than the p53 vector in tumor models overexpressing an inhibitor of p53, murine double minute-2. This result was confirmed in vivo in a pre-established tumor developed in nude mice. In an osteosarcoma model overexpressing murine double minute-2, we have shown a significantly (P < .05) higher tumor growth delay with the CTS1 vector compared with the p53 vector (25.6 days compared with 12.4 days). Furthermore, both in vitro and in vivo, we have shown that this higher inhibition of tumor growth with the CTS1 vector was correlated with a higher induction of apoptosis. Therefore, CTS1 is a potentially improved tumor suppressor gene for the treatment of human tumors resistant to wild-type p53 gene therapy.

Using laser imaging systems to represent 3-D scene becomes a referent prospective technology in the areas of guidance and navigation. Measurements with high spatial resolution for significant range can be achieved, even in degraded visibility conditions such as the Brown-White Out, rain, fog, sandstorms... Moreover, this technology is well suited for assisted perception tasks (access to 3D information) and obstacle detection (telemetry of small objects). For airborne applications, it is very complementary to conventional enhanced vision systems such as Forward Looking Infrared (FLIR) and millimeter wave radar to provide images of land in environments with limited visibility. It also offers a 3D mapping of land or a single location in relation to the environment, which means alone or coupled with others, can realign and secure real-time database of information used such in a synthetic vision system (SVS). The objective of the work is to assess the impact of degraded visibility conditions on the laser radiometric propagation of a 3D laser scanner as they directly influence the performance of the ladar system [1].

The SE-WORKBENCH workshop, also called CHORALE (French acceptation for "simulated Optronic Acoustic Radar battlefield") is used by the French DGA (MoD) and several other Defense organizations and companies all around the World to perform multi-sensors simulations. CHORALE enables the user to create virtual and realistic multi spectral 3D scenes that may contain several types of target, and then generate the physical signal received by a sensor, typically an IR sensor. The SE-WORKBENCH can be used either as a collection of software modules through dedicated GUIs or as an API made of a large number of specialized toolkits. The SE-WORKBENCH is made of several functional block: one for geometrically and physically modeling the terrain and the targets, one for building the simulation scenario and one for rendering the synthetic environment, both in real and non real time. Among the modules that the modeling block is composed of, SE-ATMOSPHERE is used to simulate the atmospheric conditions of a Synthetic Environment and then to integrate the impact of these conditions on a scene. This software product generates an exploitable physical atmosphere by the SE WORKBENCH tools generating spectral images. It relies on several external radiative transfer models such as MODTRAN V4.2 in the current version. MATISSE [4,5] is a background scene generator developed for the computation of natural background spectral radiance images and useful atmospheric radiative quantities (radiance and transmission along a line of sight, local illumination, solar irradiance ...). Backgrounds include atmosphere, low and high altitude clouds, sea and land. A particular characteristic of the code is its ability to take into account atmospheric spatial variability (temperatures, mixing ratio, etc) along each line of sight. An Application Programming Interface (API) is included to facilitate its use in conjunction with external codes. MATISSE is currently considered as a new external radiative transfer model to be integrated in SE-ATMOSPHERE as a complement to MODTRAN. Compared to the latter which is used as a whole MATISSE can be used step by step and modularly as an API: this can avoid to pre compute large atmospheric parameters tables as it is done currently with MODTRAN. The use of MATISSE will also enable a real coupling between the ray tracing process of the SEWORKBENCH and the radiative transfer model of MATISSE. This will lead to the improvement of the link between a general atmospheric model and a specific 3D terrain. The paper will demonstrate the advantages for the SE WORKEBNCH of using MATISSE as a new atmospheric code, but also for computing the radiative properties of the sea surface.

MATISSE is a background scene generator developed for the computation of natural background spectral radiance images and useful atmospheric radiatives quantities (radiance and transmission along a line of sight, local illumination, solar irradiance ...). The spectral bandwidth ranges from 0.4 to 14 μm. Natural backgrounds include atmosphere (taking into account spatial variability), low and high altitude clouds, sea and land. The current version MATISSE-v1.5 can be run on SUN and IBM workstations as well as on PC under Windows and Linux environment. An IHM developed under Java environment is also implemented. MATISSE-v2.0 recovers all the MATISSE-v1.5 functionalities, and includes a new sea surface radiance model depending on wind speed, wind direction and the fetch value. The release of this new version in planned for April 2009. This paper gives a description of MATISSE-v1.5 and MATISSE-v2.0 and shows preliminary comparison results between generated images and measured images during the MIRAMER campaign, which hold in May 2008 in the Mediterranean Sea.

International audience; The background scene generator MATISSE, whose main functionality is to generate natural background radiance images, makes use of the so-called Correlated K (CK) model. It necessitates either to load or to compute thousands of CK coefficients for each atmospheric profile. When the CK coefficients cannot be loaded, the computation time becomes prohibitive. The idea developed in this paper is to substitute fast approximate models to the exact CK generator: using the latter, a representative set of numerical examples is built and used to train linear or nonlinear regression models. The resulting models enable an accurate CK coefficient computation for all the profiles of an image in a reasonable time.

Human telomerase reverse transcriptase (hTERT) is overexpressed in more than 85% of human cancers regardless of their cellular origin. As immunological tolerance to hTERT can be overcome not only spontaneously but also by vaccination, it represents a relevant universal tumor associated antigen (TAA). Indeed, hTERT specific cytotoxic T lymphocyte (CTL) precursors are present within the peripheral T-cell repertoire. Consequently, hTERT vaccine represents an attractive candidate for antitumor immunotherapy. Here, an optimized DNA plasmid encoding an inactivated form of hTERT, named INVAC-1, was designed in order to trigger cellular immunity against tumors. Intradermal injection of INVAC-1 followed by electrogene transfer (EGT) in a variety of mouse models elicited broad hTERT specific cellular immune responses including high CD4+ Th1 effector and memory CD8+ T‑cells. Furthermore, therapeutic INVAC‑1 immunization in a HLA-A2 spontaneous and aggressive mouse sarcoma model slows tumor growth and increases survival rate of 50% of tumor-bearing mice. These results emphasize that INVAC-1 based immunotherapy represents a relevant cancer vaccine candidate.

This paper concerns the presentation of the MATISSE-v1.4 code whose main func tionality is computation of spectral or integrated natural background radiance images. The spectral bandwidth ranges from 765 to 3300 cm -1 (3 to 13 µm) with a 5 cm -1 resolution. Natural backgrounds include the atmosphere, low and high altitude clouds, sea and land. The most particular functionality of the code is to take into account atmospheric spatial variability quantities (temperatures, mixing ratio, etc) along each line of sight of the image. In addition to image generation capacity, the code computes atmospheric radiance and transmission along a line of sight with the same spectral characteristics as in imaging mode. In this case, atmospheric refraction effects and radiation from high or low altitude clouds can be taken into account. A high spectral resolution mode is also available to propagate radiation from a high temperature medium in the same atmospheric state as that used for the image generation. Moreover, an Application Programming Interface (API) is included to facilitate its use in conjunction with external codes. In comparison with the previous version, the main improvement of MATISSE-v1.4 concerns the line of sight mode, the possibility to use a user atmospheric profile and computations in the Maritime Boundary Layer. This paper describes the range of functionalities of MATISSE-v1.4 as well as future developments.

In this paper we present MATISSE 1.1 a new background scene generator, whose goal is to compute spectral or integrated radiance images of natural background, as well as the transmission of a hot gas signature. The spectral bandwidth for this version of the code is from 750 to 3300 cm-1 (3 to 13 μm) with a 5 cm-1 resolution. Gaseous absorption is computed by a Correlated K model. The spatial variability of atmospheric quantities (temperatures and mixing ratios, among others) is taken into account, using variable profiles along the line of sight. Natural backgrounds include the atmospheric background, low altitude clouds and the Earth ground. The radiation models used are designed for observation at low spatial resolution of clouds and soils, so a texture model was developed to increase the high spatial resolution rendering in the metric range. Intermediate outputs of the code deliver radiance and transmission restricted to a single line of sight, in which case atmospheric refraction effects are taken into account. Along this line of sight the transmission can also be computed using a line-by-line model, which is useful to propagate the radiation emitted by a hot gas source (fires, aircraft or missile plume). MATISSE 1.1 was released in June 2002, so this paper is devoted to a presentation of the first results obtained with the code and some validation tests.

We have shown previously that the transduction of a number of human tumor cell lines with an adenovirus (AV1Y28) expressing a single-chain antibody fragment (scFv) directed against Ras proteins results in radiosensitization. Because Ras is involved in the regulation of a number of transcription factors, we have determined the effects of this adenovirus on the activation of nuclear factor-kappaB (NF-kappaB), a radiation-responsive transcription factor associated with cell survival. In U251 human glioma cells, radiation-induced NF-kappaB was significantly attenuated by prior transduction of the anti-Ras scFv adenovirus. This effect appeared to involve an inhibition of IkappaB kinase activity and IkappaBalpha phosphorylation. Inhibitors to the Ras effectors mitogen-activated protein kinase kinase, phosphatidylinositol 3-kinase, and p38, however, did not reduce radiation-induced NF-kappaB. Whereas AV1Y28 inhibited NF-kappaB activation by hydrogen peroxide and ferricyanide, it had no effect of tumor necrosis factor-alpha-induced NF-kappaB activation. These results are consistent with a novel Ras-dependent, oxidant-specific signaling pathway mediating the activation of NF-kappaB. In additional cell lines radiosensitized by AV1Y28, radiation-induced NF-kappaB activation was also inhibited by the anti-Ras scFv, whereas in cell lines not radiosensitized, radiation did not activate NF-kappaB. This correlation suggested that AV1Y28-mediated radiosensitization involved the inhibition of radiation-induced NF-kappaB activation. However, inhibition of NF-kappaB activation via the expression of a dominant-negative form of IkappaBalpha in U251 cells had no effect on radiation-induced cell killing and did not influence AV1Y28-mediated radiosensitization. Therefore, whereas AV1Y28 inhibits radiation-induced NF-kappaB activation, this process does not appear to play a direct role in its radiosensitizing actions.

MATISSE is a new atmospheric radiative transfer code currently under development at Onera. Its purpose is to compute background radiance images by taking into account atmospheric, cloud and ground radiation and the variability of atmospheric properties. Propagation is calculated using a Correlated K model (CK) developed at Onera. The spectral range is between 3 to 13 micrometers with a resolution of 5 cm -1 . Weather forecast outputs and aerosol climatology are used as inputs to account for spatial variability of atmospheric properties in radiance computations. Partial stratocumulus cloud cover can be generated and the radiation computations use Independent Pixel Approximation (IPA) and Bidirectional Reflectivity Distribution Functions (BRDF). Ground emission and reflectance are computed from spectral emissivities, BRDF and a simple thermal model for the local ground temperature. Databases include a Digital Terrain Elevation (DTED) and a land use database with 30' spatial resolution. Texture models are used to add realistic ground and cloud clutter down to 10 meter resolution. A line-by-line model is included to compute the spectral intensity propagated from high temperature exhaust plumes. Refraction effects are computed, but only along one single line of sight.

The objective of SIGMIP project is to undertake a technical and economical feasibility study for a regional geographical database. An operational prototype has been built up for demonstration. Applications dealing with industrial environment management, water resource management, natural environment, urban development and infrastructure projects have been developed., Le projet SIGMIP étudie la faisabilité technique et économique d’une base de données géographiques régionale. Une maquette opérationnelle a été mise en place à des fins de démonstration. Des applications concernant la gestion de l’environnement industriel, de l’eau, du milieu naturel, de l’urbanisme et des projets d’infrastructures ont été développées., El proyecto SIGMIP estudia la factibilidad técnica y económica de una base de datos geográficos regional. Se ha realizado un prototipo operacional con fines demostrativos. Se han desarrollado aplicaciones relativas a la gestión del entorno industrial, del agua, del medio ambiente, del urbanismo y de los proyectos de infraestructuras., Crépeau Christian, Huet Thierry. Le projet SIGMIP: vers un serveur régional d’information géographique en Midi-Pyrénées. In: Mappemonde, 1993/4. Facettes de SIG. pp. 30-31.

Simian immunodeficiency viruses have been isolated from four species of monkey, the 'captive' macaque and mangabey and the 'feral' African green monkey and mandrill. While none of these viruses is a replica of HIV-1, the macaque and mangabey viruses represent correct genetic models for HIV-2, possessing exactly the same complement of genes. Recently a lentivirus has been identified in two wild chimpanzees (Pan troglodytes troglodytes) in Gabon, west equatorial Africa, and isolated from one of them. This virus is referred to as SIVCPZ. Sera from these animals cross reacted with all the HIV-1 proteins including the envelope glycoproteins. Here, we describe the molecular cloning and sequencing of an infectious proviral clone of SIVCPZ. The overall genetic organization was the same as that of HIV-1, but phylogenetic analysis revealed that the sequence was more divergent than any HIV-1 sequence reported so far. The vpu gene product, found only in the type 1 viruses, was particularly different (64% divergent to HIV-1BRU) suggesting that the SIVCPZ represents a distinct subtype. These findings indicate that there is a larger pool of simian lentiviruses than previously suspected and revives debate as to the origins of HIV-1.

Line mixing effects have been investigated in the Q branch of CO 2 near 720 cm −1 , by means of a tunable diode laser. Spectra were obtained at room temperature, in the 100–1000 torr pressure range. In the high-frequency wing of the Q branch, below the Q (2) line, the observed absorption is nearly 50% less than that calculated on the assumption of purely additive Lorentz lines, whereas the Q branch itself is nearly insensitive to line coupling in the pressure range investigated. From the line broadening coefficients alone, a simple scaling law allows an estimate of the state-to-state rotationally inelastic transfer rates. Calculation of line mixing coefficients using these rates yields corrected absorption coefficients, in very good agreement with the observed ones, all over the analyzed spectral range. The results appear to be of importance for modeling outgoing radiances in temperature sounding channels near 14 μm.

In central equatorial Africa the frequency of uninterpretable or atypical Western blots (WB)--ie. antibodies to gag proteins only--can represent up to 50% of enzyme-linked immunosorbent assay (ELISA)-positive samples. To date the significance of such serology remains unknown. Nevertheless, an unusual HIV-1 strain has been isolated from the blood of a healthy Gabonese individual who presented an atypical WB. This virus, identified as isolated HIV-1OYl, grew to low titres of reverse transcriptase activity (less than 50,000 cpm/ml) and was not obviously cytopathic. Radioimmunoprecipitation and peptide ELISA studies indicated that the lack of env-specific reactivity was probably due to the absence of antibodies to the viral glycoproteins, rather than the virus encoding a highly divergent envelope protein. Molecular cloning and sequencing of the provirus proved it to be a string of HIV-1 which was genetically closer to European and North American than to African strains. Furthermore the envelope protein sequence contained all the features of a typical HIV-1 env gene. However, the tat gene derived from the proviral clone was functionally defective. Site-directed mutagenesis of this gene showed that this was due to the substitution of an essential cysteine residue for a serine. Polymerase chain reaction amplification of the tat gene, as well as parts of the gag and env gene sequences of HIV-1OYl, showed that essentially all of the proviruses were defective. These data emphasize the need to view HIV isolates as populations of distinct genomes capable of complementing each other.

Two cases of wild-born chimpanzees which were positive for HIV-1 antibodies were observed in Gabon. These animals were never experimentally exposed to HIV-1 and had no history of inoculation with human blood products. A retrovirus was isolated from one of these chimpanzees. Several of the viral proteins from this virus, designated SIVcpz-GAB-1 (simian immunodeficiency virus from chimpanzee), differed in molecular weight from the known corresponding HIV/SIV proteins. The major gag protein of SIVcpz migrated on SDS-PAGE with a relative molecular mass of 25.5 and the outer membrane proteins were 110, 155 and 185 kD, respectively. SIVcpz did not induce severe cytopathic effects in human and chimpanzee lymphocytes. Antigenically, SIVcpz seems to be closer to HIV-1 than to HIV-2 and the other SIVs. Nucleic acid hybridization experiments appear to indicate that the virus is different from HIV-1 and HIV-2.