Aerosol charging state at an urban site: new analytical approach and implications for ion-induced nucleation

The charging state of aerosol populations was determined using an Ion-DMPS in Helsinki, Finland between December 2008 and February 2010. We extrapolated the charging state and calculated the ion-induced nucleation fraction to be around 1.3 % ± 0.4 % at 2 nm and 1.3 % ± 0.5 % at 1.5 nm, on average. We present a new method to retrieve the average charging state for a new particle formation event, at a given size and polarity. We improve the uncertainty assessment and fitting technique used previously with an Ion-DMPS. We also use a new theoretical framework that allows for different concentrations of small ions for different polarities (polarity asymmetry). We extrapolate the ion-induced fraction using polarity symmetry and asymmetry. Finally, a method to calculate the growth rates from the behaviour of the charging state as a function of the particle diameter using polarity symmetry and asymmetry is presented and used on a selection of new particle formation events

Aerosol dynamics simulations on the connection of sulphuric acid and new particle formation

International audienceWe have performed a series of simulations with an aerosol dynamics box model to study the connection between new particle formation and sulphuric acid concentration. For nucleation either activation mechanism with a linear dependence on the sulphuric acid concentration or ternary H2O-H2SO4-NH3 nucleation was assumed. We investigated the factors that affect the sulphuric acid dependence during the early stages of particle growth, and tried to find conditions which would yield the linear dependence between the particle number concentration at 3?6 nm and sulphuric acid, as observed in field experiments. The simulations showed that the correlation with sulphuric acid may change during the growth from nucleation size to 3?6 nm size range, the main reason being the size dependent growth rate between 1 and 3 nm. In addition, the assumed size for the nucleated clusters had a crucial impact on the sulphuric acid dependence at 3 nm. The simulations yielded a linear dependence between the particle number concentration at 3 nm and sulphuric acid, when a low saturation vapour pressure for the condensable organic vapour was assumed, or when nucleation took place at ~2 nm instead of ~1 nm. Comparison of results with activation and ternary nucleation showed that ternary nucleation cannot explain the experimentally observed linear or square dependence on sulphuric acid

Using measurements of the aerosol charging state in determination of the particle growth rate and the proportion of ion-induced nucleation

The fraction of charged nucleation mode particles as a function of particle diameter depends on the particle growth rate and the proportion of particles formed via ion-induced nucleation. In this study we have tested the applicability of recent data analysis methods to determine the growth rate and the proportion of ion-induced nucleation from the measured charged fractions. For this purpose we have conducted a series of aerosol dynamic simulations covering a wide range of atmospheric conditions. The growth rate and initial fraction of charged particles were estimated from simulated data using these methods and compared with the values obtained directly from the simulations. We found that the data analysis methods used in this study should not be used when the nuclei growth rate is less than ~3 nm h<sup>−1</sup>, or when charged particles grow much more rapidly than neutral ones. Furthermore, we found that the difference in removal rates of neutral and charged particles should be taken into account when estimating the proportion of ion-induced nucleation. Neglecting the higher removal rate of charged particles compared with that of neutral ones could result in an underestimation of the proportion of ion-induced nucleation by up to a factor of 2. This underestimation is further increased if charged particles grow more rapidly than neutral ones. We also provided a simple way of assessing whether these methods are suitable for analyzing data measured under specific conditions. The assessment procedure was illustrated using a few examples of actual measurement sites with a more detailed examination of the typical conditions observed at the SMEAR II station in Hyytiälä, Finland

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved

Experimental investigation of ion-ion recombination under atmospheric conditions

We present the results of laboratory measurements of the ion–ion recombination coefficient at different temperatures, relative humidities and concentrations of ozone and sulfur dioxide. The experiments were carried out using the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at CERN, the walls of which are made of conductive material, making it possible to measure small ions. We produced ions in the chamber using a 3.5 GeV c−1 beam of positively charged pions (π+) generated by the CERN Proton Synchrotron (PS). When the PS was switched off, galactic cosmic rays were the only ionization source in the chamber. The range of the ion production rate varied from 2 to 100 cm−3 s−1, covering the typical range of ionization throughout the troposphere. The temperature ranged from −55 to 20 °C, the relative humidity (RH) from 0 to 70 %, the SO2 concentration from 0 to 40 ppb, and the ozone concentration from 200 to 700 ppb. The best agreement of the retrieved ion–ion recombination coefficient with the commonly used literature value of 1.6 × 10−6 cm3 s−1 was found at a temperature of 5 °C and a RH of 40 % (1.5 ± 0.6) × 10−6 cm3 s−1. At 20 °C and 40 % RH, the retrieved ion–ion recombination coefficient was instead (2.3 ± 0.7) × 10−6 cm3 s−1. We observed no dependency of the ion–ion recombination coefficient on ozone concentration and a weak variation with sulfur dioxide concentration. However, we observed a more than fourfold increase in the ion–ion recombination coefficient with decreasing temperature. We compared our results with three different models and found an overall agreement for temperatures above 0 °C, but a disagreement at lower temperatures. We observed a strong increase in the recombination coefficient for decreasing relative humidities, which has not been reported previously

Syndecan-1 expression has prognostic significance in head and neck carcinoma

The syndecans are a family of cell-surface heparan sulphate proteoglycans that regulate cell behaviour by binding extracellular matrix molecules such as growth factors. The syndecan family has four members, of which syndecan-1 is the most studied and best characterized. We have studied the prognostic significance of syndecan-1 expression in squamous cell carcinoma (SCC) of the head and neck treated with surgery and post-operative radiotherapy. Paraffin-embedded tissue samples taken from 175 patients with primary SCC, followed up from 2 to 15 years after surgery, were studied for expression of syndecan-1 by immunohistochemistry. A low number (≤50%, the median value) of syndecan-1-positive tumour cells was associated with low histological grade of differentiation (P < 0.0001), a large primary tumour size (T1–2 vs T3–4, P = 0.02), positive nodal status (N0 vs N1–3, P = 0.0006), and high clinical stage (stage I or II vs III or IV, P < 0.0001). Low syndecan-1 expression was also associated with unfavourable overall survival in a univariate analysis (P = 0.001). In a multivariate survival analysis, the clinical stage and syndecan-1 expression were the only independent prognostic factors. We conclude that syndecan-1 is a novel prognostic factor in SCC of the head and neck treated with surgery and post-operative radiotherapy. © 1999 Cancer Research Campaig

Atmospheric nucleation: highlights of the EUCAARI project and future directions

Within the project EUCAARI (European Integrated project on Aerosol Cloud Climate and Air Quality interactions), atmospheric nucleation was studied by (i) developing and testing new air ion and cluster spectrometers, (ii) conducting homogeneous nucleation experiments for sulphate and organic systems in the laboratory, (iii) investigating atmospheric nucleation mechanism under field conditions, and (iv) applying new theoretical and modelling tools for data interpretation and development of parameterisations. The current paper provides a synthesis of the obtained results and identifies the remaining major knowledge gaps related to atmospheric nucleation. The most important technical achievement of the project was the development of new instruments for measuring sub-3 nm particle populations, along with the extensive application of these instruments in both the laboratory and the field. All the results obtained during EUCAARI indicate that sulphuric acid plays a central role in atmospheric nucleation. However, also vapours other than sulphuric acid are needed to explain the nucleation and the subsequent growth processes, at least in continental boundary layers. Candidate vapours in this respect are some organic compounds, ammonia, and especially amines. Both our field and laboratory data demonstrate that the nucleation rate scales to the first or second power of the nucleating vapour concentration(s). This agrees with the few earlier field observations, but is in stark contrast with classical thermodynamic nucleation theories. The average formation rates of 2-nm particles were found to vary by almost two orders of magnitude between the different EUCAARI sites, whereas the formation rates of charged 2-nm particles varied very little between the sites. Overall, our observations are indicative of frequent, yet moderate, ion-induced nucleation usually outweighed by much stronger neutral nucleation events in the continental lower troposphere. The most concrete outcome of the EUCAARI nucleation studies are the new semi-empirical nucleation rate parameterizations based on field observations, along with updated aerosol formation parameterizations

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

C-Jun N-terminal kinase (JNK) isoforms play differing roles in otitis media

BACKGROUND: Innate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood. CJUN terminal kinase (JNK) is potentially involved in both processes. RESULTS: Genes involved in both innate immune and growth factor activation of JNK are upregulated during OM, while expression of both positive and negative JNK regulatory genes is altered. When compared to wildtypes (WTs), C57BL/6 mice deficient in JNK1 exhibit enhanced mucosal thickening, with delayed recovery, enhanced neutrophil recruitment early in OM, and delayed bacterial clearance. In contrast, JNK2(−/−) mice exhibit delayed mucosal hyperplasia that eventually exceeds that of WTs and is slow to recover, delayed recruitment of neutrophils, and failure of bacterial clearance. CONCLUSIONS: The results suggest that JNK1 and JNK2 play primarily opposing roles in mucosal hyperplasia and neutrophil recruitment early in OM. However, both isoforms are required for the normal resolution of middle ear infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0046-z) contains supplementary material, which is available to authorized users