Hyperfine excitation of N2_2H+^+ by H2_2: Toward a revision of N2_2H+^+ abundance in cold molecular clouds

The modelling of emission spectra of molecules seen in interstellar clouds requires the knowledge of collisional rate coefficients. Among the commonly observed species, N$_2$H$^+$ is of particular interest since it was shown to be a good probe of the physical conditions of cold molecular clouds. Thus, we have calculated hyperfine-structure resolved excitation rate coefficients of N$_2$H$^+$(X$^1\Sigma^+$) by H$_2(j=0)$, the most abundant collisional partner in the cold interstellar medium. The calculations are based on a new potential energy surface, obtained from highly correlated {\it ab initio} calculations. State-to-state rate coefficients between the first hyperfine levels were calculated, for temperatures ranging from 5 K to 70 K. By comparison with previously published N$_2$H$^+$-He rate coefficients, we found significant differences which cannot be reproduced by a simple scaling relationship. As a first application, we also performed radiative transfer calculations, for physical conditions typical of cold molecular clouds. We found that the simulated line intensities significantly increase when using the new H$_2$ rate coefficients, by comparison with the predictions based on the He rate coefficients. In particular, we revisited the modelling of the N$_2$H$^+$ emission in the LDN 183 core, using the new collisional data, and found that all three of the density, gas kinetic temperature and N$_2$H$^+$ abundance had to be revised

Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study

Treatment of rheumatoid arthritis (RA) with infliximab (Remicade(®)) has been associated with the induction of antinuclear autoantibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies. In the present study we investigated the humoral immune response induced by infliximab against organ-specific or non-organ-specific antigens not only in RA patients but also in patients with ankylosing spondylitis (AS) during a two-year followup. The association between the presence of autoantibodies and clinical manifestations was then examined. The occurrence of the various autoantibodies was analyzed in 24 RA and 15 AS patients all treated with infliximab and in 30 RA patients receiving methotrexate but not infliximab, using the appropriate methods of detection. Infliximab led to a significant induction of ANA and anti-dsDNA autoantibodies in 86.7% and 57% of RA patients and in 85% and 31% of AS patients, respectively. The incidence of antiphospholipid (aPL) autoantibodies was significantly higher in both RA patients (21%) and AS patients (27%) than in the control group. Most anti-dsDNA and aPL autoantibodies were of IgM isotype and were not associated with infusion side effects, lupus-like manifestations or infectious disease. No other autoantibodies were shown to be induced by the treatment. Our results confirmed the occurrence of ANA and anti-dsDNA autoantibodies and demonstrated that the induction of ANA, anti-dsDNA and aPL autoantibodies is related to infliximab treatment in both RA and AS, with no significant relationship to clinical manifestations

S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage.: S100B is absent in SVZ GFAP expressing cells

International audienceDuring the postnatal development, astrocytic cells in the neocortex progressively lose their neural stem cell (NSC) potential, whereas this peculiar attribute is preserved in the adult subventricular zone (SVZ). To understand this fundamental difference, many reports suggest that adult subventricular GFAP-expressing cells might be maintained in immature developmental stage. Here, we show that S100B, a marker of glial cells, is absent from GFAP-expressing cells of the SVZ and that its onset of expression characterizes a terminal maturation stage of cortical astrocytic cells. Nevertheless, when cultured in vitro, SVZ astrocytic cells developed as S100B expressing cells, as do cortical astrocytic cells, suggesting that SVZ microenvironment represses S100B expression. Using transgenic s100b-EGFP cells, we then demonstrated that S100B expression coincides with the loss of neurosphere forming abilities of GFAP expressing cells. By doing grafting experiments with cells derived from beta-actin-GFP mice, we next found that S100B expression in astrocytic cells is repressed in the SVZ, but not in the striatal parenchyma. Furthermore, we showed that treatment with epidermal growth factor represses S100B expression in GFAP-expressing cells in vitro as well as in vivo. Altogether, our results indicate that the S100B expression defines a late developmental stage after which GFAP-expressing cells lose their NSC potential and suggest that S100B expression is repressed by adult SVZ microenvironment

Alpine ibex ( Capra i: ibex ) is not a reservoir for chlamydial infections of domestic ruminants and humans

Chlamydophila (C.) abortus is the most common infectious abortigenic agent in small domestic ruminants in Switzerland. In contrast, the knowledge about chlamydiae in wild ruminants is scarce. As interactions between livestock and Alpine ibex (Capra i. ibex) occur on alpine pastures, the question raises if wild ruminants could play a role as carriers of chlamydiae. Thus, we investigated the prevalence of chlamydiae in Alpine ibex in Switzerland. In total, 624 sera, 676 eye swabs, 84 organ samples and 51 faecal samples from 664 ibex were investigated. Serum samples were tested by two commercial ELISA kits specific for C. abortus. Eye swabs, organs and faecal samples were examined by a Chlamydiaceae-specific real-time polymerase chain reaction (PCR). Positive cases were further investigated by the ArrayTube (AT) microarray method for chlamydial species determination. Of 624 serum samples investigated, 612 animals were negative, whereas nine sera (1.5%) reacted positively in one of the two tests and three sera showed an inconclusive result. Eye swabs of seven out of 412 ibex (1.7%) were tested positive for Chlamydiaceae by real-time PCR. By AT microarray, Chlamydophila (C.) pecorum was identified in two animals, Chlamydophila (C.) pneumoniae was detected in one animal and a mixed infection with C. abortus and C. pecorum was found in four animals. Organs and faecal samples were all negative by real-time PCR analysis. In summary, we conclude that C. abortus is not a common infectious agent in the Swiss ibex population. To our knowledge, this is the first description of C. pneumoniae in ibex. Further studies are necessary to elucidate the situation in other species of wild ruminants as chamois (Rupicapra r. rupicapra), red deer (Cervus elaphus) and roe deer (Capreolus c. capreolus) in Switzerlan

A stepwise breakdown of B-cell tolerance occurs within renal allografts during chronic rejection

Autoantibodies detected after kidney transplantation may contribute to chronic rejection. We and others have previously described the organization of immune effectors into functional intragraft tertiary lymphoid tissue, a site where breakdown of B-cell tolerance may occur. To test this, we performed a comprehensive analysis of 26 chronically rejected kidney grafts. Antibodies were screened by indirect immunofluorescence on HEp2 cells, a procedure that detects antibodies to intracellular antigens, and monkey kidney sections, which detects kidney tissue autoantigens. The incidence of anti-HEp2 autoantibodies was significantly higher in graft explant culture supernatants than in patient sera. Reactivity against monkey kidney sections was detected in almost half of culture supernatants with anti-HEp2 autoantibodies. A local enrichment in T helper 17 and B-cell-activating factor (CD257) correlated with intragraft production of anti-HEp2 antibodies. A decrease in Tregs and a symmetric increase of activated OX40 (CD134)-expressing CD4+ T cells were found in grafts in which anti-kidney autoantibodies were produced. Thus, a stepwise breakdown of B-cell tolerance occurs within the graft during chronic rejection. Hence, the intragraft microenvironment interferes with peripheral deletion of autoreactive immature B cells that, in turn, produce antibodies against intracellular autoantigens. When intragraft immune regulation is insufficient, spreading of the local response against kidney autoantigens is favored

Inhibition of the Proprotein Convertases Represses the Invasiveness of Human Primary Melanoma Cells with Altered p53, CDKN2A and N-Ras Genes

Altered tumor suppressor p53 and/or CDKN2A as well as Ras genes are frequently found in primary and metastatic melanomas. These alterations were found to be responsible for acquisition of invasive and metastatic potential through their defective regulatory control of metalloproteinases and urokinase genes.Using primary human melanoma M10 cells with altered p53, CDKN2A and N-Ras genes, we found that inhibition of the proprotein convertases (PCs), enzymes involved in the proteolytic activation of various cancer-related protein precursors resulted in significantly reduced invasiveness. Analysis of M10 cells and their gastric and lymph node derived metastatic cells revealed the presence of all the PCs found in the secretory pathway. Expression of the general PCs inhibitor alpha1-PDX in these cells in a stable manner (M10/PDX) had no effect on the mRNA expression levels of these PCs. Whereas, in vitro digestion assays and cell transfection experiments, revealed that M10/PDX cells display reduced PCs activity and are unable to process the PCs substrates proIGF-1R and proPDGF-A. These cells showed reduced migration and invasion that paralleled decreased gelatinase MMP-2 activity and increased expression and secretion of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, these cells showed decreased levels of urokinase-type plasminogen activator receptor (uPAR) and increased levels of plasminogen activator inhibitor-1 (PAI-1).Taken together, these data suggest that inhibition of PCs activity results in decreased invasiveness of primary human melanoma cells despite their altered p53, CDKN2A and N-Ras genes, suggesting that PCs may serve as novel therapeutic targets in melanoma

Agglomeration of stoichiometric hydroxyapatite: Impact on particle size distribution and purity in the precipitation and maturation steps

Stoichiometric hydroxyapatite (HAP) is a prominent biomaterial, notably used as coating on metal bone prostheses. High chemical purity and a specific particle size distribution are the main properties for such an application. Based on industrial practice, a reference synthesis was first performed in a lab-scale stirred reactor. Improvements were then suggested by varying the physicochemical and hydrodynamic conditions. The shear rate within the reactor, characterized by the mean Kolmogorov micro-scale, has a strong impact on the final agglomerate size distribution. By maintaining a rather high mixing rate and a high temperature, the duration of the synthesis can be reduced considerably without affecting the HAP purity provided the pH is properly regulated. This consists of imposing acidic conditions during a short period just after the initial formation of large aggregates and then setting the pH at above 7.5 to ensure the production of pure stoichiometric HAP

Orientações para a avaliação das intervenções visando a prevenção dos Problemas Músculo-Esqueléticos ligados ao trabalho

A melhoria das práticas de intervenção constitui hoje um desafio no campo da prevenção dos Problemas Músculo-Esqueléticos (PME) ligados ao trabalho. O desenvolvimento de conhecimentos respeitantes à intervenção em contexto de trabalho constitui dessa forma um desafio em termos de investigação, que convoca a temática da avaliação das intervenções. A pesquisa internacional no campo dos PME concentra grandemente os seus esforços e recomendações na avaliação dos efeitos das intervenções considerando o estado dos sintomas dos trabalhadores afectados e/ou a evolução das exposições.Neste texto, mostramos logo de início que esta orientação supõe a reunião de um certo número de condições importantes, frequentemente difíceis de reunir e geralmente subestimadas. Propomos que sejam levados em conta factores relativos à actividade de trabalho e às margens de manobra dos salariados ─ como critérios complementares da avaliação ─ sublinhando sempre a necessidade de esforços para torná-los operacionais. Num segundo momento, recordamos que a avaliação dos efeitos de uma intervenção é insuficiente para o desenvolvimento de conhecimentos sobre a intervenção em si : este supõe necessariamente a descrição precisa do processo de intervenção e a consideração do contexto do seu desenvolvimento. Enfim, a discussão sublinha o facto de que, na nossa perspectiva, a avaliação das intervenções constitui um projecto em si, que contribui directamente para a transformação do trabalho.Mejorar las prácticas de intervención constituye hoy en día un desafío en el campo de la prevención de lesiones músculo esqueléticas (LMS) relacionadas con el trabajo. El desarrollo de conocimientos sobre la intervención en las empresas es un desafío para la intervención dirigida a su evaluación. La investigación internacional en el campo de las LMS concentra sus trabajo y recomendaciones sobre la evaluación de los efectos de las intervenciones mediante la evaluación de los síntomas de salud o de las exposiciones. En este texto mostramos en primer lugar, que esta orientación supone que se reúnan un cierto número de condiciones importantes, generalmente subestimadas y a menudo difíciles de reunir. Proponemos que se tomen en cuenta, en tanto criterios complementarios de la evaluación, los indicadores relacionados a la actividad de trabajo y a los márgenes de maniobra, aunque señalamos que estos indicadores necesitan ser trabajados para volverlos operacionales. En segundo lugar, sostenemos que para desarrollar conocimientos sobre la intervención se necesita describir precisamente el proceso de intervención y tomar en cuenta el contexto en el que se desarrolla, por ello, la evaluación de sus efectos es insuficiente para desarrollar conocimientos sobre la intervención. Por último, la discusión señala que, desde nuestra perspectiva, la evaluación de las intervenciones constituye un proyecto en sí y que este contribuye directamente a la transformación del trabajo.L'amélioration des pratiques d'intervention constitue aujourd'hui un enjeu certain dans le champ de la prévention des Troubles Musculo-Squelettiques (TMS) liés au travail. Le développement des connaissances concernant l'intervention en milieu de travail est donc un enjeu de recherche, qui convoque la thématique de l'évaluation des interventions. La recherche internationale dans le champ des TMS concentre largement ses travaux et recommandations sur l'évaluation des effets des interventions par l'évolution de l'état des symptômes des travailleurs concernés et/ou l'évolution des expositions. Dans ce texte, nous montrons tout d'abord que cette orientation suppose de réunir un certain nombre de conditions importantes, souvent difficiles à réunir et généralement sous-estimées. Nous proposons la prise en compte d'indicateurs relatifs à l'activité de travail et aux marges de manoeuvre des salariés, comme critères complémentaires de l'évaluation, tout en soulignant la nécessité d'un travail à réaliser pour les rendre opérationnels. Dans un deuxième temps, nous rappelons que l'évaluation des effets de l'intervention est insuffisante au développement de connaissances sur l'intervention : celui-ci suppose nécessairement la description précise du processus de l'intervention et la prise en compte du contexte de son déroulement. Enfin, la discussion souligne le fait que, dans notre perspective, l'évaluation des interventions constitue un projet en soi, qui contribue directement à la transformation du travail.The improvement of intervention practices is today an undeniable issue in the field of work-related musculoskeletal disorder (MSD) prevention. The development of knowledge about workplace interventions is therefore a research issue, which deals with the theme of intervention evaluation. International research in the MSD field focuses its work and recommendations mainly on the evaluation of the effects of interventions through the evolution in the state of the symptoms of the workers involved and/or the evolution in the exposures. In this article, we show first that this orientation assumes that a certain number of important conditions are associated, which are often difficult to associate and generally underestimated. We suggest that indicators relating to the work activity be considered, as well as employees’ margins of maneuver, as additional criteria in the evaluation, while emphasizing the necessity that work be carried out to make them operational. Second, we reiterate that the evaluation of the intervention’s effects is insufficient for developing knowledge about the intervention: this necessarily assumes the precise description of the intervention process and the consideration of its execution context. Finally, the discussion underlines the fact that, from our perspective, intervention evaluation is a project in itself, contributing directly to the transformation of the work