Development of a physiologically based kinetic model for 99m-Technetium-labelled carbon nanoparticles inhaled by humans

International audienceParticulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. Recent studies investigated whether and to which extent inhaled ultrafine particles are able to translocate into the bloodstream in humans. However, their conclusions were conflicting. We developed a physiologically based kinetic model for 99m-technetium-labelled carbon nanoparticles (Technegas). The model was designed to analyse imaging data. It includes different translocation rates and kinetics for free technetium, and small and large technetium-labelled particles. It was calibrated with data from an experiment designed to assess the fate of nanoparticles in humans after inhalation of Technegas. The data provided time courses of radioactivity in the liver, stomach, urine, and blood. Parameter estimation was performed in a Bayesian context with Markov chain Monte Carlo (MCMC) techniques. Our analysis points to a likely translocation of particle-bound technetium from lung to blood, at a rate about twofold lower than the transfer rate of free technetium. Notably, restricting the model so that only free technetium would have been able to reach blood circulation resulted in much poorer fits to the experimental data. The percentage of small particles able to translocate was estimated at 12.7% of total particles. The percentage of unbound technetium was estimated at 6.7% of total technetium. To our knowledge, our model is the first PBPK model able to use imaging data to describe the absorption and distribution of nanoparticles. We believe that our modeling approach using Bayesian and MCMC techniques provides a reasonable description on which to base further model refinement

Model-Free Control applied for position control of Quadrotor using ROS

In this paper, an intelligent PD (iPD) controller named Model-Free Controller is proposed. Herein, it is used to control the position of a Vertical Take-Off and Landing (VTOL) Unmanned Aerial Vehicle (UAV) Quadrotor. This strategy increases the control performance as well as its robustness level with respect to the classical PD. This is due to the estimation principle provided by the ultra-local model that estimate the unknown disturbances and uncertainties each iteration. The efficiency of the proposed strategy is shown through various numerical simulations where a thorough analysis is provided. Moreover, a comparison study is elaborated between the iPD and the classical PD

The GUINEVERE Project for Accelerator Driven System Physics

paper 9414International audienceThe GUINEVERE project is part of the EUROTRANS Integrated Project of the 6th EURATOM Framework Programme. It is mainly devoted to ADS on-line reactivity monitoring validation, sub-criticality determination and operational procedures (loading, start-up, shut-down, ...) as a follow-up of the MUSE experiments. The project consists in coupling a fast lead core, set-up in the VENUS reactor at SCK*CEN Mol (B), with a GENEPI neutron source under construction by CNRS. To accommodate the accelerator in a vertical coupling configuration, the VENUS building is being heightened. The fast core will be loaded with enriched Uranium and will be moderated and reflected with solid lead (zero power experiment). For the purpose of the experimental programme, the neutron source has to be operated not only in pulsed mode but also in continuous mode to investigate the current-to-flux reactivity indicator in representative conditions of a powerful ADS. In this latter mode it is also required to make short beam interruptions to have access to the neutron population decrease as a function of time: from this spectrum it will be possible to apply different analysis techniques such as "prompt decay" fitting techniques and "source jerk" techniques. Beam interruptions will be repeated at a programmable frequency to improve time spectra statistics. Different sub-criticality levels (keff=0.99, 0.97, 0.95, ...) will be investigated in order to obtain a full set of data points for the final overall validation of the methodology. This paper describes the status of the experimental facility assembling, and the foreseen experimental programme to be started

Chemerin and Adiponectin Contribute Reciprocally to Metabolic Syndrome

Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15±5.08 kg/m2. Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00–33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS

The GUINEVERE project at the VENUS facility

Proc. on CD Rom log315International audienceThe GUINEVERE project is an international project in the framework of IP-EUROTRANS, the FP6 program which aims at addressing the main issues for ADS development in the framework of partitioning and transmutation for nuclear waste volume and radiotoxicity reduction. The GUINEVERE project is carried out in the context of domain 2 of IP-EUROTRANS, ECATS, devoted to specific experiments for the coupling of an accelerator, a target and a subcritical core. These experiments should provide an answer to the questions of online reactivity monitoring, sub-criticality determination and operational procedures (loading, start-up, shutdown, …) in an ADS by 2009-2010. The project has the objective to couple a fast lead core, within the VENUS building operated by the SCK•CEN, with a neutron generator able to work in three different modes: pulsed, continuous and continuous with beam interruptions at the millisecond scale. In order to achieve this goal, the VENUS facility has to be adapted and a modified GENEPI-3C accelerator has to be designed and constructed. The paper describes the main modifications to the reactor core and facility and to the accelerator, which will be executed during the years 2008 and 2009, and the experimental programme which will start in 2009

Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis.</p> <p>Methods and Results</p> <p>We evaluated whether cigarette smoke (CS) triggers pulmonary and systemic PTX3 expression <it>in vivo </it>in a murine model of COPD. Using immunohistochemical (IHC) staining, we observed PTX3 expression in endothelial cells of lung venules and veins but not in lung arteries, airways and parenchyma. Moreover, ELISA on lung homogenates and semi-quantitative scoring of IHC-stained sections revealed a significant upregulation of PTX3 upon subacute and chronic CS exposure. Interestingly, PTX3 expression was not enhanced upon subacute CS exposure in IL-1RI KO mice, suggesting that the IL-1 pathway is implicated in CS-induced expression of vascular PTX3. Serum PTX3 levels increased rapidly but transiently after acute CS exposure.</p> <p>To elucidate the functional role of PTX3 in CS-induced responses, we examined pulmonary inflammation, protease/antiprotease balance, emphysema and body weight changes in WT and Ptx3 KO mice. CS-induced pulmonary inflammation, peribronchial lymphoid aggregates, increase in MMP-12/TIMP-1 mRNA ratio, emphysema and failure to gain weight were not significantly different in Ptx3 KO mice compared to WT mice. In addition, Ptx3 deficiency did not affect the CS-induced alterations in the pulmonary (mRNA and protein) expression of VEGF-A and FGF-2, which are crucial regulators of angiogenesis.</p> <p>Conclusions</p> <p>CS increases pulmonary PTX3 expression in an IL-1 dependent manner. However, our results suggest that either PTX3 is not critical in CS-induced pulmonary inflammation, emphysema and body weight changes, or that its role can be fulfilled by other mediators with overlapping activities.</p

HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer

Forty-five colorectal adenocarcinomas were examined for alterations in the HIT family genes FHIT and PKCI-1/HINT by a combination of reverse transcriptase polymerase chain reaction and DNA sequencing. In all cases a single transcript corresponding to the reported sequence was detected using primers specific for the PKCI-1/HINT gene. In contrast multiple transcripts were detected using primers specific for the FHIT gene transcript. 6% (3/45) of tumours evinced no detectable expression of any FHIT transcript and a further 12% (6/45) produced only the normal full length transcripts. Ninety-six aberrant transcripts were characterized from the remaining tumours. Deviations from the normal full length sequence characterized included deletions, insertions of novel sequences, a point mutation as well as the usage of a putative alternate splice site in exon 10. Message variants were detected with approximately equal frequency in all tumour stages with the exception that templates with insertions were found solely in Dukes’ stage B tumours (P < 0.001). With the exception of the putative alternate splice site, aberrant transcripts were not detected in matched normal mucosa. These results suggest that members of the HIT family of genes are only selectively involved in tumorigenesis and that perturbation of FHIT gene expression is an early event in colorectal tumorigenesis. © 1999 Cancer Research Campaig