Analysis of Endogenous Particles in Exhaled Air

Exhaled air contains non-volatile particulate material from the respiratory tract. The precise location in which exhaled particles are formed is unknown, and details on their chemical content are scarce. The aim of this work was to chemically characterize and to study the mechanisms of formation of endogenous particles in exhaled air. A new instrument for counting and sampling particles in exhaled air by impaction was developed, as a part of this thesis, at the Department of Public Health and Community Medicine, Occupational and Environmental Medicine in collaboration with the Department of Chemistry, Atmospheric Science at the University of Gothenburg. In the first instance, exhaled particles were analyzed using time-of-flight secondary ion mass spectrometry (TOF-SIMS), which is a very sensitive technique for surface analysis. This method was also used to compare the composition of particles in exhaled air from subjects with asthma to that in healthy controls. Second, a method for the quantitative determination of glutathione was developed and applied in the analysis of exhaled particles and exhaled breath condensate. In parallel to chemical analysis, the hypothesis that particles are formed during the reopening of closed airways was tested by measuring particle number concentrations in the air exhaled by healthy volunteers performing different breathing maneuvers. This is the first study involving chemical analysis of particles in exhaled air. TOF-SIMS analysis revealed that exhaled particles contain several phospholipids (phosphatidylcholine, phosphatidylglycerol and phosphatidylinositol). These lipids are characteristic of the pulmonary surfactant which is present in the respiratory tract lining fluid (RTLF) that covers the epithelium in the alveoli and the airways. Using this method, it was found that the TOF-SIMS spectra of the particles exhaled by healthy subjects differed from those of the particles exhaled by subjects with asthma. These differences were attributed to differences in the abundance of phosphatidylcholine and phosphatidylglycerol between the two groups. By using the newly-developed method for glutathione analysis, it was possible to demonstrate the presence of glutathione in exhaled particles for the first time. The method was used to compare glutathione levels in exhaled particles to those in exhaled breath condensate; it was found that analysis of particles was more revealing in terms of the levels of glutathione in exhaled air. Studies of particle formation showed that deep exhalations to residual volume (RV) caused significantly higher concentrations of particles in the subsequent exhalation than did exhalations to functional residual capacity (FRC).This supports the theory that film rupture during airway reopening after airway closure is an important mechanism of particle formation. The results of these studies show that particles in exhaled air can be sampled by impaction, that surfactant phospholipids and glutathione are part of their chemical composition, and that they are largely formed in the peripheral airways, where airway closure takes place

Surface superconductivity in niobium for superconducting RF cavities

A systematic study is presented on the superconductivity (sc) parameters of the ultrapure niobium used for the fabrication of the nine-cell 1.3 GHz cavities for the linear collider project TESLA. Cylindrical Nb samples have been subjected to the same surface treatments that are applied to the TESLA cavities: buffered chemical polishing (BCP), electrolytic polishing (EP), low-temperature bakeout (LTB). The magnetization curves and the complex magnetic susceptibility have been measured over a wide range of temperatures and dc magnetic fields, and also for different frequencies of the applied ac magnetic field. The bulk superconductivity parameters such as the critical temperature T_c=9.26 K and the upper critical field B_c_2(0)=410 mT are found to be in good agreement with previous data. Evidence for surface superconductivity at fields above B_c_2 is found in all samples. The critical surface field exceeds the Ginzburg-Landau field B_c_3=1.695B_c_2 by about 10% in BCP-treated samples and increases even further if EP or LTB are applied. From the field dependence of the susceptibility and a power-law analysis of the complex ac conductivity and resistivity the existence of two different phases of surface superconductivity can be established which resemble the Meissner and Abrikosov phases in the bulk: (1) ''coherent surface superconductivity'', allowing sc shielding currents flowing around the entire cylindrical sample, for external fields B in the range B_c_2 < B < B_c_3"c"o"h, and (2) ''incoherent surface superconductivity'' with disconnected sc domains for B_c_3"c"o"h < B < B_c_3. The ''coherent'' critical surface field separating the two phases is found to be B_c_3"c"o"h=0.81 B_c_3 for all samples. The exponents in the power law analysis are different for BCP and EP samples, pointing to different surface topologies. (orig.)Available from TIB Hannover: RA 2999(04-027) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Direct, Interferon-Independent Activation of the CXCL10 Promoter by NF- B and Interferon Regulatory Factor 3 during Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection of hepatocytes leads to transcriptional induction of the chemokine CXCL10, which is considered an interferon (IFN)-stimulated gene. However, we have recently shown that IFNs are not required for CXCL10 induction in hepatocytes during acute HCV infection. Since the CXCL10 promoter contains binding sites for several proinflammatory transcription factors, we investigated the contribution of these factors to CXCL10 transcriptional induction during HCV infection in vitro. Wild-type and mutant CXCL10 promoter-luciferase reporter constructs were used to identify critical sites of transcriptional regulation. The proximal IFN-stimulated response element (ISRE) and NF-κB binding sites positively regulated CXCL10 transcription during HCV infection as well as following exposure to poly(I·C) (a Toll-like receptor 3 [TLR3] stimulus) and 5′ poly(U) HCV RNA (a retinoic acid-inducible gene I [RIG-I] stimulus) from two viral genotypes. Conversely, binding sites for AP-1 and CCAAT/enhancer-binding protein β (C/EBP-β) negatively regulated CXCL10 induction in response to TLR3 and RIG-I stimuli, while only C/EBP-β negatively regulated CXCL10 during HCV infection. We also demonstrated that interferon-regulatory factor 3 (IRF3) is transiently recruited to the proximal ISRE during HCV infection and localizes to the nucleus in HCV-infected primary human hepatocytes. Furthermore, IRF3 activated the CXCL10 promoter independently of type I or type III IFN signaling. The data indicate that sensing of HCV infection by RIG-I and TLR3 leads to direct recruitment of NF-κB and IRF3 to the CXCL10 promoter. Our study expands upon current knowledge regarding the mechanisms of CXCL10 induction in hepatocytes and lays the foundation for additional mechanistic studies that further elucidate the combinatorial and synergistic aspects of immune signaling pathways

Analyse rétrospective de la production de la Revue d'anthropologie des connaissances

L'article rappelle le projet scientifique et éditorial à l'origine de la Revue d'anthropologie des connaissances (RAC), lancée en 2007, en particulier la convergence pluridisciplinaire qui l'avait portée sur ses fondations. Il expose ensuite les pratiques et les choix de politique éditoriale qui l'ont façonnée et dont les procédures ne sont pas a priori moins importantes que les contenus et les orientations épistémiques. Elles concernent les procédures d'évaluation mais aussi les choix de support (l'accès électronique en ligne), de format d'articles notamment, de langue de publication, de diffusion (l'accès complet aux lecteurs) et de modèle économique