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Detailed information on the size of ice nucleating particles (INPs) may be useful in source identification, modeling their transport in the atmosphere to improve climate predictions, and determining how effectively or ineffectively instrumentation used for quantifying INPs in the atmosphere captures the full INP population. In this study we report immersion-mode INP number concentrations as a function of size at six ground sites in North America and one in Europe. The lowest INP number concentrations were observed at Arctic and alpine locations and the highest at suburban and agricultural locations, consistent with previous studies of INP concentrations in similar environments. We found that 91, 79, and 63% of INPs had an aerodynamic diameter > 1 μm at ice activation temperatures of -15, -20, and -25 °C, respectively, when averaging over all sampling locations. In addition, 62, 55, and 42% of INPs were in the coarse mode (> 2.5 μm) at ice activation temperatures of -15, -20, and -25°C, respectively, when averaging over all sampling locations. These results are consistent with six out of the seven studies in the literature that have focused on the size distribution of INPs in the atmosphere. Taken together, these findings strongly suggest that supermicron and coarse mode aerosol particles are a significant component of the ice nuclei population in many different ground-level environments. Further size-resolved studies of INPs as a function of altitude are required. [ABSTRACT FROM AUTHOR]

The effect of a post-industrial megacity on local and regional air quality was assessed via a month-long field measurement campaign in the Paris metropolitan area during winter 2010. Here we present source apportionment results from three aerosol mass spectrometers and two aethalometers deployed at three measurement stations within 5 the Paris region. Submicron aerosol composition is dominated by the organic fraction (30-36%) and nitrate (28-29%), with lower contributions from sulfate (14-16%), ammonium (12-14%) and black carbon (7-13%). Organic source apportionment was performed using positive matrix factorization, resulting in a set of organic factors corresponding both to primary emission sources and secondary production. The dominant primary sources are traffic (11-15% of organic mass), biomass burning (13-15%) and cooking (11-17% and up to 35% during meal hours). Secondary organic aerosol contributes more than 50% to the total organic mass and includes a highly oxidized factor from indeterminate and/or diverse sources and a less oxidized factor related to wood burning emissions. Black carbon was apportioned to traffic and wood burning sources using a model based on wavelength- dependent light absorption of these two combustion sources. The time series of organic and black carbon factors from related sources were strongly correlated. The similarities in aerosol composition, total mass and temporal variation between the three sites suggest that particulate pollution in Paris is dominated by regional factors, and that the emissions from Paris itself have a relatively low impact on its surroundings. [ABSTRACT FROM AUTHOR]

Examines the subpicosecond switch-off and -on of a semiconductor laser due to transient hot carrier effects. Basis for the laser relaxation oscillations; Importance of the energy transfer processes within the electronic system; Effects of carrier heating.

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience ( n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

Background: Ship engine emissions are important with regard to lung and cardiovascular diseases especially in coastal regions worldwide. Known cellular responses to combustion particles include oxidative stress and inflammatory signalling., Objectives: To provide a molecular link between the chemical and physical characteristics of ship emission particles and the cellular responses they elicit and to identify potentially harmful fractions in shipping emission aerosols., Methods: Through an air-liquid interface exposure system, we exposed human lung cells under realistic in vitro conditions to exhaust fumes from a ship engine running on either common heavy fuel oil (HFO) or cleaner-burning diesel fuel (DF). Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling including isotope labelling methods to characterise the lung cell responses., Results: The HFO emissions contained high concentrations of toxic compounds such as metals and polycyclic aromatic hydrocarbon, and were higher in particle mass. These compounds were lower in DF emissions, which in turn had higher concentrations of elemental carbon ("soot"). Common cellular reactions included cellular stress responses and endocytosis. Reactions to HFO emissions were dominated by oxidative stress and inflammatory responses, whereas DF emissions induced generally a broader biological response than HFO emissions and affected essential cellular pathways such as energy metabolism, protein synthesis, and chromatin modification., Conclusions: Despite a lower content of known toxic compounds, combustion particles from the clean shipping fuel DF influenced several essential pathways of lung cell metabolism more strongly than particles from the unrefined fuel HFO. This might be attributable to a higher soot content in DF. Thus the role of diesel soot, which is a known carcinogen in acute air pollution-induced health effects should be further investigated. For the use of HFO and DF we recommend a reduction of carbonaceous soot in the ship emissions by implementation of filtration devices.

The on-line analysis of single aerosol particles with mass spectrometrical methods is an important tool for the investigation of aerosols. Often, a single laser pulse is used for one-step laser desorption/ionisation of aerosol particles. Resulting ions are detected with time-of-flight mass spectrometry. With this method, the detection of inorganic compounds is possible. The detection of more fragile organic compounds and carbon clusters can be accomplished by separating the desorption and the ionisation in two steps, e.g. by using two laser pulses. A further method is, using a heated metal surface for thermal desorption of aerosol particles. If an ultraviolet laser is used for ionisation, a selective ionisation of polycyclic aromatic hydrocarbons (PAH) and alkylated PAH is possible via a resonance-enhanced multiphoton-ionisation process. Laser velocimetry allows individual laser triggering for single particles and additionally delivers information on aerodynamic particle diameters. It was shown that particles deriving from different combustion sources can be differentiated according to their PAH patterns. For example, retene, a C(4)-alkylated phenanthrene derivative, is a marker for the combustion of coniferous wood. In this paper, the first field application of a thermal desorption resonance-enhanced multiphoton-ionisation single particle time-of-flight mass spectrometer during a measurement campaign in Augsburg, Germany in winter 2010 is presented. Larger PAH-containing particles (i.e. with aerodynamic diameters larger than 1 μm), which are suspected to be originated by re-suspension processes of agglomerated material, were in the focus of the investigation. Due to the low concentration of these particles, an on-line virtual impactor enrichment system was used. The detection of particle-bound PAH in ambient particles in this larger size region was possible and in addition, retene could be detected on several particles, which allows to identify wood combustion as generic source of these particles. The observed diurnal distribution of these larger particles, however, support the origin by traffic induced re-suspension of sedimented/agglomerated material.

The stability and DNA-binding properties of activation-labile (act1) human glucocorticoid receptors (hGRs) from the glucocorticoid-resistant mutant 3R7.6TG.4 were investigated. These receptors are able to bind reversibly associating ligands with normal affinity and specificity, but become unstable during attempted activation to the DNA binding form [Harmon et al. (1984) J. Steroid Biochem. 21, 227-236]. Affinity labeling and immunochemical analysis demonstrated that act1 receptors are not preferentially proteolyzed during attempted activation. In addition, analysis of binding to calf thymus DNA showed that after loss of ligand, act1 receptors retain the ability to bind to DNA nonspecifically. A 370 bp MMTV promoter fragment containing multiple GREs and an upstream 342 bp fragment lacking GRE sequences were used to assess the binding of act1 hGR to specific DNA sequences. Immunoadsorption of hGR-DNA complexes after incubation with 32P-end-labeled fragments showed that both normal and act1 hGR bound selectively to the GRE-containing fragment in an activation-dependent manner. Binding of both normal and act1 hGRs could be blocked with a synthetic oligonucleotide containing a perfect palindromic GRE, but not with an oligonucleotide in which the GRE was replaced by an ERE. Analogous results were obtained for normal and act1 hGR activated in the absence of ligand, or after incubation with the glucocorticoid antagonist RU 38486. These results suggest that sequence-specific binding of the hGR does not require the presence of bound ligand and suggest a role for the ligand in trans-activation of hormonally responsive genes.

The possible role of posttranslational modification in glucocorticoid receptor regulation was investigated. Glucocorticoid receptor (GR), prepared from the human B-cell line IM-9 and affinity labeled with [3H]-dexamethasone 21-mesylate, was examined by a combination of one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-resolution two-dimensional gel electrophoresis. Two-dimensional electrophoresis of immunopurified [3H]dexamethasone 21-mesylate-labeled GR revealed the presence of two isoelectric species (apparent pI approximately to 5.7, and 6.0-6.5). Both forms were present in preparations of unactivated receptor. After GR activation, the pI of neither isoform was altered, indicating that activation does not involve covalent charge modification of the steroid-binding protein. However, only the pI 6.0-6.5 isoform bound to DNA, suggesting that covalent charge modification of the GR can alter its ability to bind to DNA. Two-dimensional electrophoresis of tryptic and chymotryptic fragments showed that the charge heterogeneity responsible for the two GR isoforms is located in a Mr 26,500 tryptic fragment derived from the steroid-binding domain of the protein. In addition, analysis of [3H]dexamethasone 21-mesylate-labeled tryptic fragments suggests that the Mr 26,500 fragment corresponds to residues 499-743 of the human GR. These results demonstrate that posttranslational modification of the steroid-binding domain may regulate the ability of the protein to bind to DNA.

Quantification of an induced chemiluminescent (CL) response in phagocytes is currently being evaluated as an indicator system for determining those environmental pollutants that may predispose fish to disease. A CL assay was developed using phagocytes from the pronephros of rainbow trout (Salmo gairdneri). The CL response of phagocytes to phorbol myristate acetate, a chemical inducer of CL, was shown to be dose-dependent. The response to five species of bacteria was also evaluated. Staphylococcus aureus and Aeromonas hydrophila produced the most intense CL responses and the longest duration of response (100 min.) Yersinia ruckeri induced an immediate strong CL response of short duration (20 min.) whereas Vibrio anguillarum and Aerococcus viridans failed to stimulate CL under the test conditions employed. The effect of sub-toxic levels of Cu, Al, and Cd on the CL response of phagocytes to S. aureus was examined using phagocytes exposed to the metals immediately before assay or after 1 hr or 24 hr exposure times. Copper caused a significant decrease in CL to the baseline level under all treatment conditions upon stimulation with S. aureus. Similar results were obtained with Al except that the decrease in CL, although significant, was not to the baseline level. In contrast, Cd caused a significant increase in CL when added 1 hr prior to or immediately before the assay; but, following a 24 hr exposure, the results were variable, in that either no change or a decrease was observed. The addition of Cu to phagocytes already exhibiting a strong CL response to S. aureus caused an immediate decrease in CL to that seen with the negative controls.

The relationship between glucocorticoid receptor subunit dissociation and activation was investigated by DEAE-cellulose and DNA-cellulose chromatography of monomeric and multimeric [3H]triamcinolone acetonide ([3H]TA)-labeled IM-9 cell glucocorticoid receptors. Multimeric (7-8 nm) and monomeric (5-6 nm) complexes were isolated by Sephacryl S-300 chromatography. Multimeric complexes did not bind to DNA-cellulose and eluted from DEAE-cellulose at a salt concentration (0.2 M KCl) characteristic of unactivated steroid-receptor complexes. Monomeric [3H]TA-receptor complexes eluted from DEAE-cellulose at a salt concentration (20 mM KCl) characteristic of activated steroid-receptor complexes. However, only half of these complexes bound to DNA-cellulose. This proportion could not be increased by heat treatment, addition of bovine serum albumin, or incubation with RNase A. Incubation of monomeric complexes with heat inactivated cytosol resulted in a 2-fold increase in DNA-cellulose binding. Unlike receptor dissociation, this increase was not inhibited by the presence of sodium molybdate. Fractionation of heat inactivated cytosol by Sephadex G-25 chromatography demonstrated that the activity responsible for the increased DNA binding of monomeric [3H]TA-receptor complexes was macromolecular. These results are consistent with a two-step model for glucocorticoid receptor activation, in which subunit dissociation is a necessary but insufficient condition for complete activation. They also indicate that conversion of the steroid-receptor complex to the low-salt eluting form is a reflection of receptor dissociation but not necessarily acquisition of DNA-binding activity.

The molecular basis for the loss of steroid binding activity in receptorless (r-) glucocorticoid-resistant (dexr) mutants isolated from the glucocorticoid-sensitive (dexs) cell line CEM-C7 was investigated. Although there was little binding of the reversibly associating ligand [3H]dexamethasone in r- mutants, labeling with the covalent affinity ligand [3H] dexamethasone 21-mesylate revealed significant amounts of a 92 kilodalton human glucocorticoid receptor (hGR) protein. Immunoblots of hGR protein in r- and normal cells showed that r- mutants expressed approximately half the amount of immunoreactive hGR protein seen in dexs cells. Comparison of the genomic organization of the hGR genes in normal and mutant cells revealed no discernable differences in the structure, or dosage, indicating that the r- phenotype was not the result of gross deletion or rearrangement of the hGR genes. In addition, r- cells expressed the same 7 kilobase mRNA as normal cells. More importantly, the amount of hGR mRNA expressed in r- cells was never significantly less, and in some cases was greater than, that seen in normal cells, indicating that the decrease in immunoreactive hGR protein seen in r- cells is not the result of loss of hGR mRNA expression. Taken together with the known mutation rate of the hGR gene(s) in these cells, these results suggest that the hGR genes in dexs CEM-C7 cells are allelic and that dexs cells express both a normal hGR protein and one with an altered steroid binding site. Furthermore, they suggest that the r- phenotype is acquired as the result of mutation within the coding region of the originally functional allele, leading to loss of ligand binding and expression of immunoreactive product.