Oxy210, a Semi-Synthetic Oxysterol,Exerts Anti-Inflammatory Effects in Macrophages via Inhibition of Toll-like Receptor (TLR) 4 and TLR2 Signaling and Modulation of Macrophage Polarization

Inflammatory responses by the innate and adaptive immune systems protect against infections and are essential to health and survival. Many diseases including atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, and obesity involve persistent chronic inflammation. Currently available anti-inflammatory agents, including non-steroidal anti-inflammatory drugs, steroids, and biologics, are often unsafe for chronic use due to adverse effects. The development of effective non-toxic anti-inflammatory agents for chronic use remains an important research arena. We previously reported that oral administration of Oxy210, a semi-synthetic oxysterol, ameliorates non-alcoholic steatohepatitis (NASH) induced by a high-fat diet in APOE*3-Leiden.CETP humanized mouse model of NASH and inhibits expression of hepatic and circulating levels of inflammatory cytokines. Here, we show that Oxy210 also inhibits diet-induced white adipose tissue inflammation in APOE*3-Leiden.CETP mice, evidenced by the inhibition of adipose tissue expression of IL-6, MCP-1, and CD68 macrophage marker. Oxy210 and related analogs exhibit anti-inflammatory effects in macrophages treated with lipopolysaccharide in vitro, mediated through inhibition of toll-like receptor 4 (TLR4), TLR2, and AP-1 signaling, independent of cyclooxygenase enzymes or steroid receptors. The anti-inflammatory effects of Oxy210 are correlated with the inhibition of macrophage polarization. We propose that Oxy210 and its structural analogs may be attractive candidates for future therapeutic development for targeting inflammatory diseases.     

Enhancing the fluidization quality of nanoparticles using external fields

Fluidization quality of beds containing alumina and iron oxide nanoparticles in the Agglomerate Bubbling Fluidization (ABF) was improved by applying a combination of vibration and magnetic field. Pressure fluctuations were measured and analyzed by Fast Fourier Transform (FFT), Recurrence Plot (RP) and Recurrence Quantitative Analysis (RQA). Results of FFT showed that the wall vibration creates a periodic signal at 100?Hz which is not originated from the bed hydrodynamics. RP of pressure fluctuations before and after applying the assisting forces showed that the white areas in the plot decrease in size, which indicates an increase in the contribution of meso-structures such as agglomerates and small bubbles. The transition in the equilibrium bed hydrodynamics, between the condition in which assisting forces are not applied and condition in which they are applied, was tracked. It was shown by the determinism of pressure fluctuations that when the iron oxide nanoparticles exist alongside with alumina nanoparticles, this transition to the new equilibrium condition was reached in a shorter time. Determinism of pressure fluctuation of beds containing iron oxide decreased after applying the assisting forces. This trend confirms that large bubbles start to disappear and become substituted by smaller structures when magnetic field is applied to the bed. Under this condition, the interphase contact efficiency increases and the bed becomes closer to the Agglomerate Particle Fluidization (APF) regime.     

Open-ended rectangular waveguide for nondestructive thicknessmeasurement and variation detection of lossy dielectric slabs backed bya conducting plate

Solutions for fields inside a slab of a generally lossy dielectric medium backed by a conducting plate, placed outside a waveguide-fed rectangular aperture, are used for the microwave nondestructive thickness measurement of such dielectric slabs. Upon construction of the waveguide terminating admittance expression from its variational form, an inverse problem is solved to extract the slab thickness form the conductance and susceptance in a recursive manner. A comparison between the experimental and theoretical results showed that the significance of higher order modes is minimal; hence, the dominant mode assumption is, in general, valid for describing the aperture field distribution. The validity of this assumption has led to the construction of a simple integral solution which is fast converging for generally lossy dielectric slabs, and may easily be implemented for real-time applications. Good agreement was obtained between the theoretical and experimental results. Multiple thicknesses of two different dielectric samples were estimated in this way     

Mechanical properties of cord-rubber composites

Concepts concerning the mechanical properties of cord-rubber composites are examined. The rôle of boundary conditions in the calculation of the effective composite properties is discussed. It is shown that certain effective properties are significantly dependent on the applied boundary, conditions on the model and on the test specimen. Properties calculated from models, ranging from one dimensional analysis to the three dimensional finite element approach, are compared with some published experimental data.     

Bioleaching of copper from smelter dust in a series of airlift bioreactors

Bioleaching of copper from the flue dust of the Sarcheshmeh copper smelter has been investigated. A series of continuous tests were carried out in two-stages of airlift bioreactors inoculated with the acidophilic, iron and sulfur oxidizing bacteria, initially derived from acid mine drainage. The effects of different parameters such as pulp density, retention time and temperature on the mesophile bioleach performance of the copper sulfide rich dust were evaluated after pre-leaching with dilute acid. Pulp densities of 2% and 4% gave the same oxidation–reduction potential in both reactors. However, increasing the average pulp density to 7% generated an unstable oxidation–reduction potential in the first bioreactor at 34 °C. Overall copper extractions calculated for 2%, 4% and 7% pulp densities were 90%, 89% and 86% with mean retention times of 2.7, 4 and 5 days, respectively. The process is net acid consuming and has the potential for further development and feasibility studies.     

Microwave diagnosis of rubber compounds

The results of a study investigating the dielectric properties of rubber compounds and their constituents in the frequency range of 5 to 24 GHz are presented. A completely filled short circuited waveguide technique was used to conduct these dielectric measurements. The influence of carbon black content in rubber was investigated for carefully prepared rubber samples. The results showed that for all frequencies, the dielectric constant increases as a function of increasing carbon black content. The variation of dielectric constant values decreases as frequency increases. The presence of curatives in uncured rubber samples was also detected, which indicates the sensitivity of microwaves to the chemical reaction triggered by curatives     

Nanoscale conjugated-polymer light-emitting diodes

We use e-beam lithography to pattern an indium tin oxide (ITO) electrode to create arrays of conjugated-polymer LEDs, each of which has a hole-injecting contact limited to 100 nm in diameter. Using optical microscopy, we estimate that the electroluminescence from a 100 nm diameter LED comes from a region characterized by a diameter of approximately 170 nm. This apparent broadening occurs due to current spreading within a PEDOT:PSS layer which was included to aid hole injection.     

Pantographing self adaptive gap elements

This paper develops a so-called pantographing self adative gap element type contact strategy. Due to the manner of formulation, the scheme has the capability to handle; large deformations in the contact zone; contact initiation in structure exhibiting either positive or indefinite stiffness characteristics; kinematic and material nonlinearity as well as; self adaptively adjusts load/time stepping. In this context, contact in pre and postbuckling structure can be treated. To illustrate the scheme, several benchmark problems are presented. These include contacting structure involving large deformation kinematics, inelastic behavior as well as pre and postbuckling stiffness characteristics.     

Study of crystal structure of (polyvinylidene fluoride/clay) nanocomposite films: Effect of process conditions and clay type

Three Polyvinylidene fluoride (PVDF) different in molecular structure were used to produce nanocomposities films by cast extrusion with a particular emphasis on maximizing the β crystal phase content. The PVDF/clay compounding followed by cast film production was carried out through melt extrusion using a twin screw extruder equipped with a slit die. X‐ray diffraction (XRD) results showed that clay melt intercalation is almost similar for all three PVDFs. The XRD results also revealed that nanocomposite films from PVDF with branched chain structure (PVDFB) generated the greatest amount of β phase. FTIR spectroscopy measurements confirmed the XRD results but also revealed that significant stretching of the melt films at the die or rapid cooling would adversely affect the formation of β phase. The amount of β phase obtained based on nanoclay compounding was compared with that obtained from conventional method: stretching of molded PVDF film with initial α phase. Stretching of PVDF film at 60°C yielded pure β phase that means complete transformation of α to β. From mechanical properties, tensile tests were carried out on PVDF nanocomposite films to evaluate mechanical strength. PVDF with low molecular weight exhibited a very low strain at break while branched PVDF and high molecular weight PVDF could sustain more strain. POLYM. ENG. SCI., 2009. © 2008 Society of Plastics Engineers     

A theoretical study of the tautomerism kinetics of 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one in the gas phase: NBO population and NICS analysis

The tautomerization reactions of the 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one studied by means of M06-2x and CBS-QB3 theoretical methods. The measured energy profiles are complemented with kinetic rate coefficients calculations using transition state theory (TST). In line with the optimized tautomers geometries using the CBS-QB3 method, the natural bond orbital (NBO) analysis reveals that the stabilization energies of non-bonding LP(e)_S8 to the σ*_N2–C3 antibonding orbitals increase from tautomers 1 to 2. Furthermore, the delocalization energies of LP(e)_S8→σ*_N2–C3 could explain the increase of LP(e)_S8 non-bonding orbitals occupancies in the tautomers 1 and 2 (2?>?1). The increase of LP(e)_S8→σ*_N2–C3 delocalizations could fairly explicate the kinetics of tautomeric pathways 1 and 2 (k_2?>?k₁). Moreover, the HOMO–LUMO energy gap is increased parallel with the decreasing of activation energy barriers. NBO results also show that the kinetics of these processes controlled using LP→σ* resonance energies. Furthermore, nucleus-independent chemical shift (NICS) indices show the calculated reaction and energy barriers are involved by changes in aromaticity characters as well as electron transfer from LP(e)_S8 to σ*_N2–C3 orbitals, thus these reactions are controlled from both thermodynamic and kinetic viewpoints by the changes aromaticity characters.