Sources of airborne microorganisms in the built environment

Each day people are exposed to millions of bioaerosols, including whole microorganisms, which can have both beneficial and detrimental effects. The next chapter in understanding the airborne microbiome of the built environment is characterizing the various sources of airborne microorganisms and the relative contribution of each. We have identified the following eight major categories of sources of airborne bacteria, viruses, and fungi in the built environment: humans; pets; plants; plumbing systems; heating, ventilation, and air-conditioning systems; mold; dust resuspension; and the outdoor environment. Certain species are associated with certain sources, but the full potential of source characterization and source apportionment has not yet been realized. Ideally, future studies will quantify detailed emission rates of microorganisms from each source and will identify the relative contribution of each source to the indoor air microbiome. This information could then be used to probe fundamental relationships between specific sources and human health, to design interventions to improve building health and human health, or even to provide evidence for forensic investigations

Regulation of Reactive Oxygen Species and the Antioxidant Protein DJ-1 in Mastocytosis

Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates with activating mutations in the receptor tyrosine kinase KIT. Constitutive activation of tyrosine kinase oncogenes has been linked to imbalances in oxidant/antioxidant mechanisms in other myeloproliferative disorders. However, the impact of KIT mutations on the redox status in SM and the potential therapeutic implications are not well understood. Here, we examined the regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1 (PARK-7), which increases with cancer progression and acts to lessen oxidative damage to malignant cells, in relationship with SM severity. ROS levels were increased in both indolent (ISM) and aggressive variants of the disease (ASM). However, while DJ-1 levels were reduced in ISM with lower mast cell burden, they rose in ISM with higher mast cell burden and were significantly elevated in patients with ASM. Studies on mast cell lines revealed that activating KIT mutations induced constant ROS production and consequent DJ-1 oxidation and degradation that could explain the reduced levels of DJ-1 in the ISM population, while IL-6, a cytokine that increases with disease severity, caused a counteracting transcriptional induction of DJ-1 which would protect malignant mast cells from oxidative damage. A mouse model of mastocytosis recapitulated the biphasic changes in DJ-1 and the escalating IL-6, ROS and DJ-1 levels as mast cells accumulate, findings which were reversed with anti-IL-6 receptor blocking antibody. Our findings provide evidence of increased ROS and a biphasic regulation of the antioxidant DJ-1 in variants of SM and implicate IL-6 in DJ-1 induction and expansion of mast cells with KIT mutations. We propose consideration of IL-6 blockade as a potential adjunctive therapy in the treatment of patients with advanced mastocytosis, as it would reduce DJ-1 levels making mutation-positive mast cells vulnerable to oxidative damage

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Computational modelling of full interaction between crystal plasticity and oxygen diffusion at a crack tip

Oxidation-promoted crack growth, one of the major concerns for nickel-based superalloys, is closely linked to the diffusion of oxygen into the crack tip. The phenomenon is still not well understood yet, especially the full interaction between oxygen diffusion and severe near-tip mechanical deformation. This work aimed at the development of a robust numerical strategy to model the full coupling of crystal plasticity and oxygen diffusion in a single crystal nickel-based superalloy. In order to accomplish this, finite element package ABAQUS is used as a platform to develop a series of user-defined subroutines to model the fully coupled process of deformation and diffusion. The formulation allowed easy incorporation of nonlinear material behaviour, various loading conditions and arbitrary model geometries. Using this method, finite element analyses of oxygen diffusion, coupled with crystal plastic deformation, were carried out to simulate oxygen penetration at a crack tip and associated change of near-tip stress field, which has significance in understanding crack growth acceleration in oxidation environment. Based on fully coupled diffusion-deformation analyses, a case study was carried out to predict crack growth rate in oxidation environment and under dwell-fatigue loading conditions, for which a two-parameter failure criterion, in terms of accumulated inelastic strain and oxygen concentration at the crack tip, has been utilized

Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders

<p>Abstract</p> <p>Background</p> <p>Anti-IgE therapy inhibits mast cell and basophil activation, blocks IgE binding to both FcεRI and CD23 and down regulates FcεRI expression by antigen (Ag) presenting cells (APCs). In addition to its classical role in immediate hypersensitivity, IgE has been shown <it>in vitro </it>to facilitate Ag presentation of allergens, whereby APC bound IgE preferentially takes up allergens for subsequent processing and presentation. The purpose of this study was to determine whether anti-IgE therapy, by blocking facilitated Ag presentation <it>in vivo</it>, attenuates allergen specific Th2 cell responses.</p> <p>Methods</p> <p>To test this hypothesis, food allergen specific T cell responses were examined during a 16-week clinical trial of omalizumab in nine subjects with eosinophilic gastroenteritis and food sensitization. Allergen specific T cell responses were measured using carboxyfluorescein succinimidyl ester dye dilution coupled with intracellular cytokine staining and polychromatic flow cytometry. Four independent indices of allergen specific T cell response (proliferation, Ag dose response, precursor frequency, and the ratio of Th2:Th1 cytokine expression) were determined.</p> <p>Results</p> <p>Eight of the 9 subjects had measurable food allergen specific responses, with a median proliferation index of 112-fold. Allergen specific T cell proliferation was limited to CD4 T cells, whereas CD8 T cell did not proliferate. Food allergen specific responses were Th2 skewed relative to tetanus specific responses in the same subjects. In contradistinction to the original hypothesis, anti-IgE treatment did not diminish any of the four measured indices of allergen specific T cell response.</p> <p>Conclusions</p> <p>In sum, using multiple indices of T cell function, this study failed to demonstrate that anti-IgE therapy broadly or potently inhibits allergen specific T cell responses. As such, these data do not support a major role for IgE facilitated Ag presentation augmenting allergen specific T cell responses <it>in vivo</it>.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT00084097">NCT00084097</a></p

Bipolar Ionization Did Not Reduce Airborne Bacteria in a Lecture Hall

Ionization treatment of indoor air has attracted attention for its potential to inactivate airborne pathogens and reduce disease transmission, yet its real-world effectiveness remains unverified. We evaluated the impact of an in-duct, bipolar ionization system on airborne particles, including culturable bacteria, in a lecture hall. The ionizer was off with variable fan speed for 1 week, on with variable fan speed for a second week, and on with high and constant fan speed for a third week. We measured ion concentrations and aerosol particle concentrations, and we collected bioaerosol samples for analysis of 16S rRNA gene copies representing total bacteria and colony forming units (CFUs) on Tryptic Soy Agar representing culturable bacteria. There were no significant differences in positive, in-room ion concentrations between any weeks; however, negative, in-room ion concentrations were significantly lower when the ionizer was on with constant fan speed. To account for day-to-day variability in total bacteria concentrations, related to occupancy and other factors, we examined the ratio of CFUs to 16S rRNA gene copies (CFU gc) and found no significant differences whether the ionizer was on or off. This result indicates that the ionizer was not effective at reducing levels of culturable airborne bacteria in this study

Spectra Observed Following Cargo Interrogation

The authors present calculations of photon spectra observed following irradiation of bare HEU, HEU embedded in steel and wood cargos, and steel and wood alone. These spectra might be useful starting points for statistical detection efforts aimed at determining whether fissile material is present in a cargo. Detailed comparisons between calculations and experiments are presented and overall quite good (small {chi}{sup 2}) agreement is found. they do not present a complete solution to the problem of determining whether a given spectrum contains contributions from post-fission photons. However, it is shown that a brute-force fitting of observed spectra in terms of a few calculated ''basis'' spectra gives meaningful predictions about the presence of {sup 235}U in cargo. Though this may not be the most powerful method, it does give well defined confidence limits and seems to have strong predictive power

Seasonal dynamics of the airborne bacterial community and selected viruses in a children's daycare center

Children's daycare centers appear to be hubs of respiratory infectious disease transmission, yet there is only limited information about the airborne microbial communities that are present in daycare centers. We have investigated the microbial community of the air in a daycare center, including seasonal dynamics in the bacterial community and the presence of specific viral pathogens. We collected filters from the heating, ventilation, and air conditioning (HVAC) system of a daycare center every two weeks over the course of a year. Amplifying and sequencing the 16S rRNA gene revealed that the air was dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes that are commonly associated with the human skin flora. Clear seasonal differences in the microbial community were not evident; however, the community structure differed when the daycare center was closed and unoccupied for a 13-day period. These results suggest that human occupancy, rather than the environment, is the major driver in shaping the microbial community structure in the air of the daycare center. Using PCR for targeted viruses, we detected a seasonal pattern in the presence of respiratory syncytial virus that included the period of typical occurrence of the disease related to the virus; however, we did not detect the presence of adenovirus or rotavirus at any time

Debris collection from implosion of microballoons

Recovery of krypton from implosion of glass microballoons has been studied in the development of a radiochemical diagnostic for determination of /sub fuel/. Collection onto metal surfaces following implosions performed on the OMEGA laser with 1-3 TW (1-2 kJ) of 0.35 ..mu..m light is consistent with an ion implantation mechanism. The dependence of the intrinsic collection efficiency on the energy fluence to the collector surface and its variation in implosions carried out under the same nominal conditions indicate ion energies extending to at least 0.1 MeV and energy distribution functions that are sensitive to the details of the implosion dynamics. Intrinsic sticking efficiencies approaching 0.5 can be obtained in the limit of low total energy fluence to the collector surface (less than or equal to 0.1 J cm/sup -2/)