Macrophage Fusion into Multinucleated Giant Cells In Vitro

Multinucleated giant cells (MGC) have been observed in a variety of granulomatous conditions, including microbial infections (e.g., tuberculosis), foreign body reactions to implants (e.g., medical devices), foreign body reactions to inhaled particles (e.g., engineered nanomaterials), and disorders of unknown etiology (e.g., sarcoidosis). Generally, MGC are morphologically classified based on the number and arrangement of nuclei. The two major types of MGC are foreign body giant cells and Langhans giant cells. These MGC are formed by the fusion of macrophages, often in response to persistent, foreign microorganisms or materials. Although MGC are known to be associated with granulomas, their involvement in the development of these conditions has not been well described. This is in part due to a lack of well-characterized models of MGC populations. The objective of this study is to develop an in vitro model of macrophage fusion in order to study MGC function. Previous reports have shown that MGC formation is induced by interleukin-4 (IL-4). Therefore, we investigated a model of IL-4-induced fusion in murine bone marrow-derived macrophages (BMdM). As expected, IL-4 treatment resulted in increased percent fusion of BMdM. The formation of MGC was optimized by modification of culture conditions, including alteration of the growth surface and treatment with either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Ongoing studies involve identification of molecules that regulate MGC formation. An increased understanding of this mechanism will provide additional targets to control fusion. Further development of this controlled in vitro model will facilitate future investigation of MGC inflammatory activity and contribution to pathogenesis of granulomas

A reduced model for shock and detonation waves. II. The reactive case

We present a mesoscopic model for reactive shock waves, which extends a previous model proposed in [G. Stoltz, Europhys. Lett. 76 (2006), 849]. A complex molecule (or a group of molecules) is replaced by a single mesoparticle, evolving according to some Dissipative Particle Dynamics. Chemical reactions can be handled in a mean way by considering an additional variable per particle describing a rate of reaction. The evolution of this rate is governed by the kinetics of a reversible exothermic reaction. Numerical results give profiles in qualitative agreement with all-atom studies

Local Government Fiscal Burden in Nonmetropolitan America

Rising fiscal pressure on local governments in rural areas of the United States is documented in this study. The level of fiscal burden on taxpayers to support local governments in nonmetropolitan areas is found to be higher than that in metropolitan areas between 1977 and 1987. Using a model from the urban fiscal literature, the level of fiscal burden in nonmetropolitan areas is found to be influenced by a combination of demographic, socioeconomic, intergovernmental, and historical factors. Intergovernmental revenue transfers from the state and federal government play a critical role in determining the level of fiscal burden rural taxpayers bear. These findings have implications for rural economic development and for understanding how rural areas are influenced by the larger society

Toxicity of Lunar and Martian Dust Simulants to Alveolar Macrophages Isolated from Human Volunteers

NASA is planning to build a habitat on the Moon and use the Moon as a stepping stone to Mars. JSC-1, an Arizona volcanic ash that has mineral properties similar to lunar soil, is used to produce lunar environments for instrument and equipment testing. NASA is concerned about potential health risks to workers exposed to these fine dusts in test facilities. The potential toxicity of JSC-1 and a Martian soil simulant (JSC-Mars-1, a Hawaiian volcanic ash) was evaluated using human alveolar macrophages (HAM) isolated from volunteers; titanium dioxide and quartz were used as reference dusts. This investigation is a prerequisite to studies of actual lunar dust. HAM were treated in vitro with these test dusts for 24 h; assays of cell viability and apoptosis showed that JSC-1 and TiO2 were comparable, and more toxic than saline control, but less toxic than quartz. HAM treated with JSC-1 or JSC-Mars 1 showed a dose-dependent increase in cytotoxicity. To elucidate the mechanism by which these dusts induce apoptosis, we investigated the involvement of the scavenger receptor (SR). Pretreatment of cells with polyinosinic acid, an SR blocker, significantly inhibited both apoptosis and necrosis. These results suggest HAM cytotoxicity may be initiated by interaction of the dust particles with SR. Besides being cytotoxic, silica is known to induce shifting of HAM phenotypes to an immune active status. The immunomodulatory effect of the simulants was investigated. Treatment of HAM with either simulant caused preferential damage to the suppressor macrophage subpopulation, leading to a net increase in the ratio of activator (RFD1+) to suppressor (RFD1+7+) macrophages, a result similar to treatment with silica. It is recommended that appropriate precautions be used to minimize exposure to these fine dusts in large-scale engineering applications

Dynamics of Spreading of Chainlike Molecules with Asymmetric Surface Interactions

In this work we study the spreading dynamics of tiny liquid droplets on solid surfaces in the case where the ends of the molecules feel different interactions with respect to the surface. We consider a simple model of dimers and short chainlike molecules that cannot form chemical bonds with the surface. We use constant temperature Molecular Dynamics techniques to examine in detail the microscopic structure of the time dependent precursor film. We find that in some cases it can exhibit a high degree of local order that can persist even for flexible chains. Our model also reproduces the experimentally observed early and late-time spreading regimes where the radius of the film grows proportional to the square root of time. The ratios of the associated transport coefficients are in good overall agreement with experiments. Our density profiles are also in good agreement with measurements on the spreading of molecules on hydrophobic surfaces.Comment: 12 pages, LaTeX with APS macros, 21 figures available by contacting [email protected], to appear in Phys. Rev.

Simulation of thermal conductivity and heat transport in solids

Using molecular dynamics (MD) with classical interaction potentials we present calculations of thermal conductivity and heat transport in crystals and glasses. Inducing shock waves and heat pulses into the systems we study the spreading of energy and temperature over the configurations. Phonon decay is investigated by exciting single modes in the structures and monitoring the time evolution of the amplitude using MD in a microcanonical ensemble. As examples, crystalline and amorphous modifications of Selenium and $\rm{SiO_2}$ are considered.Comment: Revtex, 8 pages, 11 postscript figures, accepted for publication in PR

Data Linkage: A powerful research tool with potential problems

Background: Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes