95 research outputs found

    The effect of temperature and water on secondary organic aerosol formation from ozonolysis of limonene, ?³-carene and ?-pinene

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    International audienceThe effect of reaction temperature and how water vapour influences the formation of secondary organic aerosol (SOA) in ozonolysis of limonene, ?3-carene and ?-pinene, both regarding number and mass of particles, has been investigated by using a laminar flow reactor G-FROST. Experiments with cyclohexane and 2-butanol (~3.5×1014 molecules cm?3) as OH scavengers were compared to experiments without any scavenger. The reactions were conducted in the temperature range between 298 and 243 K, and at relative humidities between <10 and 80%. Results showed that there is still a scavenger effect on number and mass concentrations at low temperatures between experiments with and without OH scavenger. This shows that the OH chemistry is influencing the SOA formation also at these temperatures. The overall temperature dependence on SOA formation is not as strong as expected from the partitioning theory. In some cases there is even a positive temperature dependence that must be related to changes in the chemical mechanism and/or reduced rates of secondary chemistry at low temperatures. The water effect at low temperature could be explained by physical uptake and cluster stabilisation. At higher temperatures, only a physical explanation is not sufficient and the observations are in line with water changing the chemical mechanism or reaction rates. The data presented adds to the understanding of SOA contribution to atmospheric aerosol composition, new particle formation and atmospheric degradation mechanisms

    Functional loss of IKBE leads to NF-KB deregulation in aggressive chronic lymphocytic leukemia

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    NF-?B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-?B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I?B?, a negative regulator of NF-?B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I?B? protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I?B? loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-?B deregulation during lymphomagenesis. <br/

    Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia

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    NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis

    A comparative study of the immunohistological and serological response of intact and T cell-deprived mice to Trichinella spiralis.

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    Thymectomized, lethally irradiated CBA mice reconstituted with anti-theta-serum-treated bone-marrow cells (TxB) were infected with T. spiralis at the age of 11 weeks. Intact, age-matched T. spiralis infected and non-infected CBA mice served as controls. Sera were collected up to 26 days after infection and examined for the presence of total and class-specific antibodies by indirect immunoflourescence. Mesenteric lymph nodes, spleen and axillary lymph nodes were examined by conventional histopathology for the presence of pyroninophilic blast cells, plasma blasts and plasma cells. Immunoflourescence was applied to examine cells containing immunoglobulins of various classes. Antibodies against T. siralis were demonstrated both in intact and TxB mice from day 10 after infection onwards. The amount of antibodies was lower in the TxB than in the intact mice. This might indicate that besides thymus-dependent, also thymus-independent antibodies against Trichinella are formed. No difference was observed in the thymus-independent areas of the lymphoid tissues from both intact and TxB mice, with the exception of a lower increase in number of IgM-containing cells in T cell-deprived mice. A marked increase in pyroninophilic blast cells was found in the thymus-dependent areas of the intact mice after infection, whereas only a very limited increase was observed in the T cell-deprived mice. The data were interpreted as supporting the thymus dependency of host response against Trichinella

    The effect of temperature and water on secondary organic aerosol formation from ozonolysis of limonene, &Delta;<sup>3</sup>-carene and α-pinene

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    The effect of reaction temperature and how water vapour influences the formation of secondary organic aerosol (SOA) in ozonolysis of limonene, &Delta;3-carene and α-pinene, both regarding number and mass of particles, has been investigated by using a laminar flow reactor (G-FROST). Experiments with cyclohexane and 2-butanol as OH scavengers were compared to experiments without any scavenger. The reactions were conducted in the temperature range between 298 and 243 K, and at relative humidities between &lt;10 and 80%. Results showed that there is still a scavenger effect on number and mass concentrations at low temperatures between experiments with and without an addition of an OH scavenger. This shows that the OH chemistry is influencing the SOA formation also at these temperatures. The overall temperature dependence on SOA formation is not as strong as expected from partitioning theory. In some cases there is even a positive temperature dependence that must be related to changes in the chemical mechanism and/or reduced rates of secondary chemistry at low temperatures. The precursor's α-pinene and &Delta;3-carene exhibit a similar temperature dependence regarding both number and mass of particles formed, whereas limonene shows a different dependence. The water effect at low temperature could be explained by physical uptake and cluster stabilisation. At higher temperatures, only a physical explanation is not sufficient and the observations are in line with water changing the chemical mechanism or reaction rates. The data presented adds to the understanding of SOA contribution to new particle formation and atmospheric degradation mechanisms

    DRIFTS and Knudsen cell study of the heterogeneous reactivity of SO<sub>2</sub> and NO<sub>2</sub> on mineral dust

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    International audienceThe heterogeneous oxidation of SO2 by NO2 on mineral dust was studied using Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) and a Knudsen cell. This made it possible to characterise, kinetically, both the formation of sulfate and nitrate as surface products and the gas phase loss of the reactive species. The gas phase loss rate was determined to be first order in both SO2 and NO2. From the DRIFTS experiment the uptake coefficient, ?, for the formation of sulfate was determined to be of the order of 10?10 using the BET area as the reactive surface area. No significant formation of sulfate was seen in the absence of NO2. The Knudsen cell study gave uptake coefficients of the order of 10?6 and 10-7 for SO2 and NO2, respectively. There was no significant difference in uptake when SO2 or NO2 were introduced individually compared to experiments in which SO2 and NO2 were present at the same time
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