Lagrange Multipliers in Infinite-Dimensional Systems, Methods of

International audienceThis entry will describe Lagrange multipliers method using a formulation which is valid for infinite-dimensional dynamical systems. The method of Lagrange multipliers is employed to deal with systems subject to constraints. The theoretical foundations of this method are presented, and a proof of the main theorem is illustrated for the relevant case of constraints defined on a Banach vector space

IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human bronchial epithelial cells

The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease. © 2014 Adams et al

Long-lived stops in MSSM scenarios with a neutralino LSP

This work investigates the possibility of a long-lived stop squark in supersymmetric models with the neutralino as the lightest supersymmetric particle (LSP). We study the implications of meta-stable stops on the sparticle mass spectra and the dark matter density. We find that in order to obtain a sufficiently long stop lifetime so as to be observable as a stable R-hadron at an LHC experiment, we need to fine tune the mass degeneracy between the stop and the LSP considerably. This increases the stop-neutralino coanihilation cross section, leaving the neutralino relic density lower than what is expected from the WMAP results for stop masses ~1.5 TeV/c^2. However, if such scenarios are realised in nature we demonstrate that the long-lived stops will be produced at the LHC and that stop-based R-hadrons with masses up to 1 TeV/c^2 can be detected after one year of running at design luminosity

Comparative analysis of inhaled particles contained in human bronchoalveolar lavage fluids, lung parenchyma and lymph nodes.

Translocation of inhaled particles from the alveolar spaces to lung parenchyma and lymph nodes is one of the mechanisms that determine the biopersistence of particles. This study compares the nonfibrous particulate burden in bronchoalveolar lavage (BAL) fluids, lung parenchyma, and thoracic lymph nodes and attempts to detect the degree of differentiation, if any, based on particle size or type. This comparison can only be done on BAL, lung parenchyma, and lymph node samples collected from the same subject over a short time. Patients undergoing surgical lung resection are suitable for this purpose. Particles recovered by digestion-filtration were counted, sized, and analyzed by analytical transmission electron microscopy. Total particle load ranges grossly between 10(5) to 10(7) p/ml in BAL, 10(9) to 10(10) p/g dry tissue in parenchyma and 10(10) to 10(11) p/g dry tissue in lymph nodes. Diameters are log-normally distributed and mean diameters range between 0.5 to 0.9 micron. Nonlamellar silicate particles have a significantly larger diameter in lymph nodes. Differences in particle type between the three sampling sites are small and nonsystematic

The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis

Background: The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype. Methods: PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored. Results: Gene expression data were consistent with the downregulation of the PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose lanifibranor demonstrated significant protection from lung fibrosis after bleomycin and from right ventricular hypertrophy following induction of pulmonary hypertension by SU5416, despite no significant change in right ventricular systolic pressure. Conclusions: In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg lanifibranor reduces the development of lung fibrosis and right ventricular hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity may contribute to the exaggerated fibroproliferative response to tissue injury in this transgenic model of scleroderma and its pulmonary complications

Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis

Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E(2), due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE(2) production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE(2) production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4

Nanoquartz in Late Permian C1 coal and the high incidence of female lung cancer in the Pearl River Origin area: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The Pearl River Origin area, Qujing District of Yunnan Province, has one of the highest female lung cancer mortality rates in China. Smoking was excluded as a cause of the lung cancer excess because almost all women were non-smokers. Crystalline silica embedded in the soot emissions from coal combustion was found to be associated with the lung cancer risk in a geographical correlation study. Lung cancer rates tend to be higher in places where the Late Permian C1 coal is produced. Therefore, we have hypothesized the two processes: C1 coal combustion --> nanoquartz in ambient air --> lung cancer excess in non-smoking women.</p> <p>Methods/Design</p> <p>We propose to conduct a retrospective cohort study to test the hypothesis above. We will search historical records and compile an inventory of the coal mines in operation during 1930–2009. To estimate the study subjects' retrospective exposure, we will reconstruct the historical exposure scenario by burning the coal samples, collected from operating or deserted coal mines by coal geologists, in a traditional firepit of an old house. Indoor air particulate samples will be collected for nanoquartz and polycyclic aromatic hydrocarbons (PAHs) analyses. Bulk quartz content will be quantified by X-ray diffraction analysis. Size distribution of quartz will be examined by electron microscopes and by centrifugation techniques. Lifetime cumulative exposure to nanoquartz will be estimated for each subject. Using the epidemiology data, we will examine whether the use of C1 coal and the cumulative exposure to nanoquartz are associated with an elevated risk of lung cancer.</p> <p>Discussion</p> <p>The high incidence rate of lung cancer in Xuan Wei, one of the counties in the current study area, was once attributed to high indoor air concentrations of PAHs. The research results have been cited for qualitative and quantitative cancer risk assessment of PAHs by the World Health Organization and other agencies. If nanoquartz is found to be the main underlying cause of the lung cancer epidemic in the study area, cancer potency estimates for PAHs by the international agencies based on the lung cancer data in this study setting should then be updated.</p

Interface localization near criticality

The theory of interface localization in near-critical planar systems at phase coexistence is formulated from first principles. We show that mutual delocalization of two interfaces, amounting to interfacial wetting, occurs when the bulk correlation length crit- ical exponent \u3bd is larger than or equal to 1. Interaction with a boundary or defect line involves an additional scale and a dependence of the localization strength on the distance from criticality. The implications are particularly rich in the boundary case, where de- localization proceeds through different renormalization patterns sharing the feature that the boundary field becomes irrelevant in the delocalized regime. The boundary delocal- ization (wetting) transition is shown to be continuous, with surface specific heat and layer thickness exponents which can take values that we determine

Pain from a Bullet Lingers on: An Uncommon Case of Lead Toxicity

Lead toxicity from a retained bullet as a cause for abdominal pain is rarely considered. Given its unpredictable latent period and nonspecific clinical symptoms, such cases are difficult to diagnose but may be fatal if unrecognized. We present the case of a 48-year-old man who presented with complaints of abdominal pain, weight loss and constipation. His past history was significant for a gunshot wound to the left hip about 20 years before. Radiographic studies confirmed the same with the presence of numerous intra-articular bullet fragments and a calcified hemarthrosis surrounding the left femoral head. Blood lead levels were elevated following which the patient was started on chelation therapy with succimer which resulted in symptomatic improvement. The aim of this paper is to highlight the importance of considering lead toxicity from a retained bullet as a cause of abdominal pain and to review the relevant literature

Quantum Black Holes from Cosmic Rays

We investigate the possibility for cosmic ray experiments to discover non-thermal small black holes with masses in the TeV range. Such black holes would result due to the impact between ultra high energy cosmic rays or neutrinos with nuclei from the upper atmosphere and decay instantaneously. They could be produced copiously if the Planck scale is in the few TeV region. As their masses are close to the Planck scale, these holes would typically decay into two particles emitted back-to-back. Depending on the angles between the emitted particles with respect to the center of mass direction of motion, it is possible for the simultaneous showers to be measured by the detectors.Comment: 6 pages, 3 figure