Interleukin 4, interferon-gamma, and prostaglandin E impact the osteoclastic cell-forming potential of murine bone marrow macrophages

Interleukin 4 (IL-4) is an immune cytokine that inhibits bone resorption in mice and suppresses osteoclastic cell formation in vitro through an undefined mechanism. In this report, we have established the cellular identity of the IL-4 target cell using a variety of bone marrow/stromal cell coculture methods. Initially, we found that the majority of IL-4's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells, not stromal cells. Consequently, bone marrow macrophages were used as osteoclastic cell progenitors after they had been transiently exposed to IL-4 (48 h), before the addition of stromal cells, 1,25-dihydroxyvitamin D3, and dexamethasone. In this circumstance, IL-4 impaired subsequent osteoclastic cell formation, suggesting that the macrophage may be potentially targeted by many factors known to influence osteoclast formation. Consequently, we discovered that interferon-gamma (IFN gamma), prostaglandin E (PGE), and cell-permeant cAMP analogs also impacted osteoclastic cell formation when used to selectively treat bone marrow macrophages. IFN gamma suppressed osteoclastic cell formation, whereas PGE and cAMP analog treatment led to the formation of significantly enlarged osteoclastic cells. Importantly, PGE antagonized the inhibitory effects of both IL-4 and IFN gamma on the osteoclastic cell-forming potential of bone marrow macrophages. Collectively, these findings establish bone marrow macrophages as osteoclastic cell precursors with the degree of their commitment to the osteoclast pathway sensitive to the effects of soluble mediators, including IL-4, IFN gamma, and PGE.     

Peroxisome biogenesis: back to the endoplasmic reticulum?

Proteins are targeted to the membrane and matrix of peroxisomes by distinct pathways. Recent observations suggest a further route: a subset of peroxisomal membrane proteins might be targeted first to the endoplasmic reticulum, and from there to peroxisomes by vesicle-mediated transport.     

Ribonuclease P (RNase P) RNA is converted to a Cd(2+)-ribozyme by a single Rp-phosphorothioate modification in the precursor tRNA at the RNase P cleavage site

To study the cleavage mechanism of bacterial Nase P RNA, we have synthesized precursor tRNA substrates carrying a single Rp- or Sp-phosphorothioate modification at the RNase P cleavage site. Both the Sp- and the Rp-diastereomer reduced the rate of processing by Escherichia coli RNase P RNA at least 1000-fold under conditions where the chemical step is rate-limiting. The Rp-modification had no effect and the Sp-modification had a moderate effect on precursor tRNA ground state binding to RNase P RNA. Processing of the Rp-diastereomeric substrate was largely restored in the presence of the "thiophilic" Cd2+ as the only divalent metal ion, demonstrating direct metal ion coordination to the (pro)-Rp substituent at the cleavage site and arguing against a specific role for Mg(2+)-ions at the pro-Sp oxygen. For the Rp-diastereomeric substrate, Hill plot analysis revealed a cooperative dependence upon [Cd2+] of nH = 1.8, consistent with a two-metal ion mechanism. In the presence of the Sp-modification, neither Mn2+ nor Cd2+ was able to restore detectable cleavage at the canonical site. Instead, the ribozyme promotes cleavage at the neighboring unmodified phosphodiester with low efficiency. Dramatic inhibition of the chemical step by both the Rp- and Sp-phosphorothioate modification is unprecedented among known ribozymes and points to unique features of transition state geometry in the RNase P RNA-catalyzed reaction.     

Numerical investigation of cyclic variations in gasoline engines using a hybrid URANS/LES modeling approach

Cycle to cycle variations are an important aspect in the development and optimization process of internal combustion engines. In this study the feasibility of using a detached eddy simulation (DES) SST model, which is a hybrid URANS/LES model, to predict cycle to cycle variations is investigated. In the near wall region or in regions where the grid resolution is not sufficiently fine to resolve smaller structures, the two-equation RANS shear-stress transport (SST) model is used. In the other regions with higher grid resolution an LES model is applied. First, the numerical requirements associated with the hybrid URANS/LES and the employed solver are studied in detail. The numerical dissipation of the spatial scheme and the choice of the temporal scheme including the step size are evaluated. In addition, the accuracy of the solver for moving meshes, which are required for engine calculations, is assessed. The modeling constant linking the grid size to the DES filter length scale is determined by calculating a decaying homogeneous isotropic turbulence test case for different grid resolutions. The final applications of the model are two different engine cases with increasing complexity. The first case is the statistically stationary flow through an engine intake port. The time resolved flow structure predicted by the DES SST model is analyzed and the resulting time-averaged velocity fields are compared to experimental data at different locations. The second application is a motored multi-cycle simulation of a series production engine. The instantaneous flow development during the intake and compression stroke of one single cycle is studied and the ensemble-averaged and the instantaneous velocity fields as well as the resolved velocity fluctuations are compared to optical measurements. Special emphasis is placed on the cyclic differences of the velocity fluctuations at the time of ignition in the vicinity of the spark plug and the expected influence on the combustion process.     

Estimating body shape of dressed humans

The paper presents a method to estimate the detailed 3D body shape of a person even if heavy or loose clothing is worn. The approach is based on a space of human shapes, learned from a large database of registered body scans. Together with this database we use as input a 3D scan or model of the person wearing clothes and apply a fitting method, based on ICP (iterated closest point) registration and Laplacian mesh deformation. The statistical model of human body shapes enforces that the model stays within the space of human shapes. The method therefore allows us to compute the most likely shape and pose of the subject, even if it is heavily occluded or body parts are not visible. Several experiments demonstrate the applicability and accuracy of our approach to recover occluded or missing body parts from 3D laser scans.     

Review of ECSC research work in ironmaking

The Treaty of the European Coal and Steel Community (ECSC), which expired in 2002, states in its Article 55 to promote technical and economic research with respect to the production and growing application of coal and steel. The results of funded research projects shall be made available to all representatives and partners concerned. For the European steel industry Article 55 was the basis for building up a steel research programme covering topics from raw materials to steel application and instigated a European network of researchers from the steel industry, research institutes and universities. On the basis of these research and development activities carried out by the ECSC steel research, the iron and steel industry has shown important advances in technology and environmental compatibility. Furthermore, the ECSC steel research has contributed to nearly all important technological developments. The main objective of the ECSC steel Research and Technology Development (RTD) programme was to sustain and develop the Community steel industry's competitiveness. The following report describes fundamental developments and activities within the framework of ECSC research with particular respect to hot metal production in the last 15 years.