Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo.

Based on its capacity to inhibit in vitro HIV-1 replication in T cells and the release of pro-inflammatory cytokines in monocytes, the prenylated heterodimeric phloroglucinyl α-pyrone arzanol was identified as the major anti-inflammatory and anti-viral constituent from Helichrysum italicum. We have now investigated the activity of arzanol on the biosynthesis of pro-inflammatory eicosanoids, evaluating its anti-inflammatory efficacy in vitro and in vivo. Arzanol inhibited 5-lipoxygenase (EC 7.13.11.34) activity and related leukotriene formation in neutrophils, as well as the activity of cyclooxygenase (COX)-1 (EC 1.14.99.1) and the formation of COX-2-derived prostaglandin (PG)E(2)in vitro (IC(50)=2.3-9μM). Detailed studies revealed that arzanol primarily inhibits microsomal PGE(2) synthase (mPGES)-1 (EC 5.3.99.3, IC(50)=0.4μM) rather than COX-2. In fact, arzanol could block COX-2/mPGES-1-mediated PGE(2) biosynthesis in lipopolysaccharide-stimulated human monocytes and human whole blood, but not the concomitant COX-2-derived biosynthesis of thromboxane B(2) or of 6-keto PGF(1α), and the expression of COX-2 or mPGES-1 protein was not affected. Arzanol potently suppressed the inflammatory response of the carrageenan-induced pleurisy in rats (3.6mg/kg, i.p.), with significantly reduced levels of PGE(2) in the pleural exudates. Taken together, our data show that arzanol potently inhibits the biosynthesis of pro-inflammatory lipid mediators like PGE(2)in vitro and in vivo, providing a mechanistic rationale for the anti-inflammatory activity of H. italicum, and a rationale for further pre-clinical evaluation of this novel anti-inflammatory lead

Transition in plastic deformation of nanolayered thin films: Role of interfaces and temperature

Insights into the parameters governing the plasticity of immiscible, nanocrystalline metals stacked in the form of layers are pivotal both from scientific and applications’ perspectives. An outstanding case consists of the contact metallurgy of pure copper used ubiquitously as metallic interconnects in electronic devices. Diffusion barrier layers such W or TiN are necessary to prevent undesirable diffusion of Cu into the Si-based device during synthesis and service. Also, supersaturated Cu-Cr alloys are desirable for improving the strength, while retaining optimal functional properties required for the application. The scientific curiosity lies in understanding the effects of reducing microstructural length scales on the mechanical properties of both of these materials at elevated temperatures. In addition, alternate layering with an immiscible element forms a viable solution to the difficultly in synthesis and application of pure nanocrystalline materials due to their poor microstructural stability. The mechanical behavior of several nanolayered thin films consisting of soft and relatively hard metals or brittle ceramics have been extensively studied at ambient conditions [1-3] by using various models predicting strength as function of grain size or layer thickness. But, few have investigated the elevated temperature mechanical response [4] of similar systems and have been restricted to a specific metal (Al) – ceramic (SiC) combination [5]. This presentation attempts to highlight the role of interfaces and diffusion in plastic flow and failure of mutually immiscible, nanolayered systems at elevated temperatures. The nanolayered thin films consist of mainly sub-100 nm thick layers of pure Cu sandwiched by layers of pure metals of Cr and W and a pure ceramic of TiN, which were grown on Si(100) substrates to thickness of 2-5 μm by using direct current magnetron sputtering. The mechanical response at elevated temperatures of the films was studied by compressing micropillars, which were fabricated using a focused Ga+ beam, in situ SEM using an AlemnisÒ indenter modified for high temperature testing. Lateral flow of Cu promoted by stress-assisted diffusion at homologous temperatures as low as 0.35 occurred in all three systems in contrast to interfacial shear-dominated flow at lower temperatures (Fig. 1). Predictions of discrete dislocation and continuum plasticity models were used to evaluate the change in the yield strengths of the films with respect to the layer thicknesses of Cu in the different systems

Kinetics and crystallization path of a Fe-based metallic glass alloy

The thermal stability and the quantification of the different transformation processes involved in the overall crystallization of the Fe50Cr15Mo14C15B6 amorphous alloy were investigated by several characterization techniques. Formation of various metastable and stable phases during the devitrification process in the sequence a-Fe, ¿-Cr6Fe18Mo5, M23(C,B)6, M7C3, ¿-Fe3Mo3C and FeMo2B2 (with M = Fe, Cr, Mo), was observed by in-situ synchrotron high energy X-ray diffraction and in-situ transmission electron microscopy. By combining these techniques with differential scanning calorimetry data, the crystallization states and their temperature range of stability under continuous heating were related with the evolution of the crystallized fraction and the phase sequence as a function of temperature, revealing structural and chemical details of the different transformation mechanisms.Postprint (published version

Small scale fracture of multi metal carbide coatings

The micromechanical behavior of sputtered multi metal carbide (Hf-Nb-Ta-Zr)C coatings was investigated. A equiatomic high entropy alloy (Hf-Nb-Ta-Zr) and high density graphite were used as targets to reactively sputter carbide coatings on Si (100) with a silicon nitride buffer layer at different substrate temperatures (RT, 300, 450, 600 and 750 0C). Energy and wavelength dispersive x-ray spectra confirmed that the metal compositions were equiatomic with a carbon content close to stoichiometric value. X-ray diffraction revealed that a single phase with a rocksalt structure was obtained for all deposition conditions. Furthermore, XRD measurements highlighted that crystallinity improved markedly with increasing deposition temperatures and the magnitude of compressive stresses reduced, concomitantly. For the highest temperature, tensile stresses of 500MPa was noted. Optical microscopy also revealed extensive mud cracking of the film deposited at 750°C, consistent with high tensile stresses. Microstructures characterized by transmission electron microscopy revealed columnar grains with nanocrystalline dimensions. Coatings deposited at 600°C showed the highest hardness and indentation modulus of 32 and 350 GPa, respectively, measured with the continuous stiffness mode. Focused ion beam machining is used fabricate micro cantilever which are tested in situ in a SEM to evaluate fracture properties of these complex carbide coatings. Nanoindentation based toughness measurements are underway to compare toughness estimates these two techniques

Multiscale characterization of damage tolerance in barium titanate thin films

Barium titanate is a brittle, lead free ferroelectric and piezoelectric ceramic used in patterned and thin film forms in micro- and nano-scale electronic devices. Both during deposition and eventually during service, this material system develops stresses due to different loads acting on the system, which can lead to its failure due to cracking in the films and/or interface delamination. In situ microcantilever bending based fracture experiments and tensile tests based on shear lag tests in combination with digital image correlation were used to understand the cracking behavior of barium titanate films when deposited on flexible substrates. For the first time, the fracture behavior of these nanocrystalline barium titanate films has been quantified in terms of fracture toughness, fracture strength, and interface shear stresses for different film thicknesses. Critical defect size is estimated using the above information as a function of film thickness. It is found that damage tolerance in terms of fracture strength depends on film thickness. Furthermore, compared to a bulk single crystal, barium titanate fracture resistance of the nanocrystalline thin films is reduced. Both effects need to be considered in engineering design of reliable devices employing micro- and nano-scale barium titanate thin film structures