Dendritic cell vaccination and immune monitoring

We exploited dendritic cells (DC) to vaccinate melanoma patients. We recently demonstrated a statistical significant correlation between favorable clinical outcome and the presence of vaccine-related tumor antigen-specific T cells in delayed type hypersensitivity (DTH) skin biopsies. However, favorable clinical outcome is only observed in a minority of the treated patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof of principle trials the fate, interactions and effectiveness of the injected DC

Self-antigen–specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response

A primary goal of cancer immunotherapy is to improve the naturally occurring, but weak, immune response to tumors. Ineffective responses to cancer vaccines may be caused, in part, by low numbers of self-reactive lymphocytes surviving negative selection. Here, we estimated the frequency of CD8+ T cells recognizing a self-antigen to be <0.0001% (∼1 in 1 million CD8+ T cells), which is so low as to preclude a strong immune response in some mice. Supplementing this repertoire with naive antigen-specific cells increased vaccine-elicited tumor immunity and autoimmunity, but a threshold was reached whereby the transfer of increased numbers of antigen-specific cells impaired functional benefit, most likely because of intraclonal competition in the irradiated host. We show that cells primed at precursor frequencies below this competitive threshold proliferate more, acquire polyfunctionality, and eradicate tumors more effectively. This work demonstrates the functional relevance of CD8+ T cell precursor frequency to tumor immunity and autoimmunity. Transferring optimized numbers of naive tumor-specific T cells, followed by in vivo activation, is a new approach that can be applied to human cancer immunotherapy. Further, precursor frequency as an isolated variable can be exploited to augment efficacy of clinical vaccine strategies designed to activate any antigen-specific CD8+ T cells

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Precision of satellite positioning: impact of satellite geometry

Precision of GNSS (Global Navigation Satellite System) is affected by a lot of different factors, such as satellite geometry. The quality of satellite geometry is evaluated by an indicator: DOP (Dilution Of Precision). Specific satellite geometry, such as conical satellite geometry, are able to strongly harm to the precision of positioning. These particular situations lead the normal matrix to a singular state and the DOP to high values.De nombreux facteurs sont susceptibles d’influencer la précision des systèmes globaux de positionnement et de navigation par satellites (GNSS, Global Navigation Satellite System), dont la géométrie de la constellation. La qualité de la géométrie de la constellation s’évalue au moyen d’un indicateur : le DOP (Dilution Of Precision). Certaines formes très particulières de la géométrie de la constellation nuisent de manière importante à la précision du positionnement par satellites. C’est le cas de la constellation de forme conique. Ces situations particulières se caractérisent par un état singulier de la matrice normale et de hautes valeurs du DOP

L’enfant et la publicité en ligne : le problème de la discrimination contenu publicitaire – contenu du site

De nombreux sites Internet consacrés aux enfants sont financés par la publicité. Cette étude s'intéresse au problème du distinguo par les enfants entre le contenu d'un site (la page web visitée) et le contenu publicitaire se trouvant sur cette même page (la bannière). Ce problème de la non-discrimination contenu du site - contenu publicitaire qui pourrait être particulièrement saillant par rapport à d’autres médias sera étudié expérimentalement chez des enfants de 7 ans et 11 an

An Efficient Dual and Triple Frequency Preprocessing Method for GALILEO and GPS Signals

Data preprocessing is a mandatory stage for most of GNSS applications. In the frame of space weather and precise point positioning applications, the Geomatics Unit of the University of Liège has purchased two Septentrio PolaRx3eG receivers which allow tracking GPS L1/L5 and Galileo E1/E5a signals. In order to fully exploit these new data, we developed a preprocessing method extending existing techniques. Our preprocessing method consists of three consecutive steps. The first step is devoted to the compensation of receiver clock slips affecting code pseudorange and carrier-phase measurements. The second step covers cycle slips detection and the third step assesses data quality in terms of noise essentially affecting code pseudorange measurements. This preprocessing method was initially developed for GPS L1/L5 and Galileo E1/E5a dual frequency data but finally enhanced to also preprocess triple frequency data from first operational Galileo satellites as soon as data are available. The developed method already showed promising results.Space Weather And Navigation Systems (SWANS

Galileo Single Frequency Ionospheric Correction: Performances in Terms of Position

For GPS single frequency users, the ionospheric contribution to the error budget is estimated by the well-known Klobuchar algorithm. For Galileo, it will be mitigated by a global algorithm based on the NeQuick model. This algorithm relies on the adaptation of the model to slant Total Electron Content (sTEC) measurements. Although the performance specifications of these algorithms are expressed in terms of delay and TEC, the users might be more interested in their impact on positioning. Therefore, we assessed the ability of the algorithms to improve the positioning accuracy using globally distributed permanent stations for the year 2002 marked by a high level of solar activity. We present uncorrected and corrected performances, interpret these and identify potential causes for Galileo correction discrepancies. We show vertical errors dropping by 56–64 % due to the analyzed ionospheric corrections, but horizontal errors decreasing by 27 % at most. By means of a fictitious symmetric satellite distribution, we highlight the role of TEC gradients in residual errors. We describe mechanisms permitted by the Galileo correction, which combine sTEC adaptation and topside mismodeling, and limit the horizontal accuracy. Hence, we support further investigation of potential alternative ionospheric corrections. We also provide an interesting insight into the ionospheric effects possibly experienced during the next solar maximum coinciding with Galileo Initial Operation Capability

Spatio-Temporal Analysis of Equatorial Ionospheric Scintillations in the Frame of Absolute GNSS Positioning Algorithms

The ionosphere has always been a major limitation for GNSS positioning applications. Free electrons in the ionosphere perturb the propagation of GNSS radio signals involving both refraction and diffraction effects. The ionospheric refraction mainly results in a modification of the propagation speed of the GNSS electromagnetic signals, inducing an error (propagation delay or phase advance depending on the observable) in GNSS measurements. In the frame of absolute positioning techniques, single-frequency algorithms usually exploit an ionospheric model to mitigate the ionospheric error while dual-frequency algorithms, such as the well-known Precise Point Positioning (PPP), take the benefit of the availability of two frequencies and the fact that the ionosphere is a dispersive medium to construct an ionosphere-free mathematical model. But these two strategies are not able to counteract the effect of the ionospheric diffraction which is due to small-scale irregularities in the free electron density. By scattering GNSS signals, these irregularities generate rapid fluctuations (scintillations) in the amplitude and phase of GNSS signals with critical consequences for GNSS applications: cycle slips, signal power fading, receiver loss of lock and poor resulting satellite geometry. The goal of our research is to develop a strategy to mitigate the effect of ionospheric scintillations on absolute GNSS positioning techniques, in particular the SPP (Standard Point Positioning) and the PPP (Precise Point Positioning). The strategy is based on the adjustment of the stochastic model. In order to construct the stochastic model (diagonal and non-diagonal elements) and study the correlation between observables, we adopted a “spatial” and an “empirical” approach. The spatial approach consists in a study of the spatial autocorrelation existing in scintillations effects on GNSS signals. The spatial autocorrelation is detected by using specific spatial analysis techniques applied on data from a network of ISMR (Ionospheric Scintillation Monitoring Receiver) stations located at equatorial and polar latitudes, where scintillations effects are most severe. The knowledge of how scintillation effects are spatially correlated is helpful for determining a coherent stochastic model. The empirical approach does not take into account the phenomenon spatiality and the locations of the measurements but only the observation data. Its objective is to determine the statistical correlation which exists between GNSS measurements during a scintillation event by using a moving filter applied on GNSS observation and scintillation data. The spatial approach exploits data and data locations while the empirical approach is based only the data itself