Evaluation of detailed aromatic mechanisms (MCMv3 and MCMv3.1) against environmental chamber data

International audienceA high quality dataset on the photo-oxidation of benzene, toluene, p-xylene and 1,3,5-trimethylbenzene has been obtained from experiments in the European Photoreactor (EUPHORE), a large outdoor environmental reaction chamber. The experiments were designed to test sensitive features of detailed aromatic mechanisms, and the dataset has been used to evaluate the performance of the Master Chemical Mechanism Version 3 (MCMv3). An updated version (MCMv3.1) was constructed based on recent experimental data, and details of its development are described in a companion paper. The MCMv3.1 aromatic mechanisms have also been evaluated using the EUPHORE dataset. Significant deficiencies have been identified in the mechanisms, in particular: 1) an over-estimation of the ozone concentration, 2) an under-estimation of the NO oxidation rate, 3) an under-estimation of OH. The use of MCMv3.1 improves the model-measurement agreement in some areas but significant discrepancies remain

Measurements of photo-oxidation products from the reaction of a series of alkyl-benzenes with hydroxyl radicals during EXACT using comprehensive gas chromatography

Photo-oxidation products from the reaction of a series of alkyl-benzenes, (benzene, toluene, <i>p</i>-xylene and 1,3,5-trimethyl-benzene) with hydroxyl radicals in the presence of NO_x have been investigated using comprehensive gas chromatography (GCxGC). A GCxGC system has been developed which utilises valve modulation and independent separations as a function of both volatility and polarity. A number of carbonyl-type compounds were identified during a series of reactions carried out at the European Photoreactor (EUPHORE), a large volume outdoor reaction chamber in Valencia, Spain. Experiments were carried as part of the EXACT project (<b>E</b>ffects of the o<b>X</b>idation of <b>A</b>romatic <b>C</b>ompounds in the <b>T</b>roposphere). Two litre chamber air samples were cryo-focused, with a sampling frequency of 30 minutes, allowing the evolution of species to be followed over oxidation periods of 3-6 hours. To facilitate product identification, several carbonyl compounds, which were possible products of the photo-oxidation, were synthesised and used as reference standards.<br> <br> For toluene reactions, observed oxygenated intermediates found included the co-eluting pair <font face='Symbol'>a</font>-angelicalactone/4-oxo-2-pentenal, maleic anhydride, citraconic anhydride, benzaldehyde and <i>p</i>-methyl benzoquinone. In the <i>p</i>-xylene experiment, the products identified were E/Z-hex-3-en-2,5-dione and citraconic anhydride. For 1,3,5-TMB reactions, the products identified were 3,5-dimethylbenzaldehyde, 3,5-dimethyl-3H-furan-2-one and 3-methyl-5-methylene-5H-furan-2-one. Preliminary quantification was carried out on identified compounds using liquid standards. Comparison of FTIR and GCxGC for the measurement of the parent aromatics generally showed good agreement. Comparison of the concentrations observed by GCxGC to concentration-time profiles simulated using the Master Chemical Mechanism, MCMv3, demonstrates that this mechanism significantly over-predicts the concentrations of many product compounds and highlights the uncertainties which exist in our understanding of the atmospheric oxidation of aromatics

CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non- tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy

Extreme sensitivity of the spin-splitting and 0.7 anomaly to confining potential in one-dimensional nanoelectronic devices

Quantum point contacts (QPCs) have shown promise as nanoscale spin-selective components for spintronic applications and are of fundamental interest in the study of electron many-body effects such as the 0.7 x 2e^2/h anomaly. We report on the dependence of the 1D Lande g-factor g* and 0.7 anomaly on electron density and confinement in QPCs with two different top-gate architectures. We obtain g* values up to 2.8 for the lowest 1D subband, significantly exceeding previous in-plane g-factor values in AlGaAs/GaAs QPCs, and approaching that in InGaAs/InP QPCs. We show that g* is highly sensitive to confinement potential, particularly for the lowest 1D subband. This suggests careful management of the QPC's confinement potential may enable the high g* desirable for spintronic applications without resorting to narrow-gap materials such as InAs or InSb. The 0.7 anomaly and zero-bias peak are also highly sensitive to confining potential, explaining the conflicting density dependencies of the 0.7 anomaly in the literature.Comment: 23 pages, 7 figure

Dynamics of multiple insecticide resistance in the malaria vector Anopheles gambiae in a rice growing area in South-Western Burkina Faso

<p>Abstract</p> <p>Background</p> <p>Insecticide resistance of the main malaria vector, <it>Anopheles gambiae</it>, has been reported in south-western Burkina Faso, West Africa. Cross-resistance to DDT and pyrethroids was conferred by alterations at site of action in the sodium channel, the Leu-Phe <it>kdr </it>mutation; resistance to organophosphates and carbamates resulted from a single point mutation in the oxyanion hole of the acetylcholinesterase enzyme designed as <it>ace-1</it>^<it>R</it>.</p> <p>Methods</p> <p>An entomological survey was carried out during the rainy season of 2005 at Vallée du Kou, a rice growing area in south-western Burkina Faso. At the Vallée du Kou, both insecticide resistance mechanisms have been previously described in the M and S molecular forms of <it>An. gambiae</it>. This survey aimed i) to update the temporal dynamics and the circumsporozoite infection rate of the two molecular forms M and S of <it>An. gambiae </it>ii) to update the frequency of the Leu-Phe <it>kdr </it>mutation within these forms and finally iii) to investigate the occurrence of the <it>ace-1</it>^{<it>R </it>}mutation.</p> <p>Mosquitoes collected by indoor residual collection and by human landing catches were counted and morphologically identified. Species and molecular forms of <it>An. gambiae</it>, <it>ace-1</it>^{<it>R </it>}and Leu-Phe <it>kdr </it>mutations were determined using PCR techniques. The presence of the circumsporozoite protein of <it>Plasmodium falciparum </it>was determined using ELISA.</p> <p>Results</p> <p><it>Anopheles gambiae </it>populations were dominated by the M form. However the S form occurred in relative important proportion towards the end of the rainy season with a maximum peak in October at 51%. Sporozoite rates were similar in both forms. The frequency of the Leu-Phe <it>kdr </it>mutation in the S form reached a fixation level while it is still spreading in the M form. Furthermore, the <it>ace</it>-<it>1</it>^{<it>R </it>}mutation prevailed predominately in the S form and has just started spreading in the M form. The two mutations occurred concomitantly both in M and S populations.</p> <p>Conclusion</p> <p>These results showed that the Vallée du Kou, a rice growing area formerly occupied mainly by M susceptible populations, is progressively colonized by S resistant populations living in sympatry with the former. As a result, the distribution pattern of insecticide resistance mutations shows the occurrence of both resistance mechanisms concomitantly in the same populations. The impact of multiple resistance mechanisms in M and S populations of <it>An. gambiae </it>on vector control measures against malaria transmission, such as insecticide-treated nets (ITNs) and indoor residual spraying (IRS), in this area is discussed.</p

Malaria in Kakuma refugee camp, Turkana, Kenya: facilitation of Anopheles arabiensis vector populations by installed water distribution and catchment systems

<p>Abstract</p> <p>Background</p> <p>Malaria is a major health concern for displaced persons occupying refugee camps in sub-Saharan Africa, yet there is little information on the incidence of infection and nature of transmission in these settings. Kakuma Refugee Camp, located in a dry area of north-western Kenya, has hosted ca. 60,000 to 90,000 refugees since 1992, primarily from Sudan and Somalia. The purpose of this study was to investigate malaria prevalence and attack rate and sources of <it>Anopheles </it>vectors in Kakuma refugee camp, in 2005-2006, after a malaria epidemic was observed by staff at camp clinics.</p> <p>Methods</p> <p>Malaria prevalence and attack rate was estimated from cases of fever presenting to camp clinics and the hospital in August 2005, using rapid diagnostic tests and microscopy of blood smears. Larval habitats of vectors were sampled and mapped. Houses were sampled for adult vectors using the pyrethrum knockdown spray method, and mapped. Vectors were identified to species level and their infection with <it>Plasmodium falciparum </it>determined.</p> <p>Results</p> <p>Prevalence of febrile illness with <it>P. falciparum </it>was highest among the 5 to 17 year olds (62.4%) while malaria attack rate was highest among the two to 4 year olds (5.2/1,000/day). Infected individuals were spatially concentrated in three of the 11 residential zones of the camp. The indoor densities of <it>Anopheles arabiensis</it>, the sole malaria vector, were similar during the wet and dry seasons, but were distributed in an aggregated fashion and predominantly in the same zones where malaria attack rates were high. Larval habitats and larval populations were also concentrated in these zones. Larval habitats were man-made pits of water associated with tap-stands installed as the water delivery system to residents with year round availability in the camp. Three percent of <it>A. arabiensis </it>adult females were infected with <it>P. falciparum </it>sporozoites in the rainy season.</p> <p>Conclusions</p> <p>Malaria in Kakuma refugee camp was due mainly to infection with <it>P. falciparum </it>and showed a hyperendemic age-prevalence profile, in an area with otherwise low risk of malaria given prevailing climate. Transmission was sustained by <it>A. arabiensis</it>, whose populations were facilitated by installation of man-made water distribution and catchment systems.</p

Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model

<p>Abstract</p> <p>Background</p> <p>Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury.</p> <p>Methods</p> <p>Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (V_T) (20 ml/kg) and low V_T(6 ml/kg). Histological evaluation, TLR2, TLR4, <it>IRAK3 </it>gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (IκBα), tumor necrosis factor-alpha (<it>TNF-α</it>) and interleukin-6 (<it>IL6</it>) gene expression in the lungs and TNF-α and IL-6 protein serum concentrations were analyzed.</p> <p>Results</p> <p>High V_Tmechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of <it>IRAK3 </it>lung gene expression and protein levels, a significant decrease of IκBα, and a higher lung expression and serum concentrations of pro-inflammatory cytokines.</p> <p>Conclusions</p> <p>The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections.</p