The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice

The two erythropoietin (EPO) receptor forms mediate different cellular responses to erythropoietin. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. In the skeletal system, EPO stimulates osteoclast precursors and induces bone loss. However, the underlying molecular mechanisms are still elusive. Here, we evaluated the role of the heteromeric complex in bone metabolism in vivo and in vitro by using Cibinetide (CIB), a non-erythropoietic EPO analogue that exclusively binds the heteromeric receptor. CIB is administered either alone or in combination with EPO. One month of CIB treatment significantly increased the cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Similarly, administration of CIB for five consecutive days to female mice that concurrently received EPO on days one and four, reduced the number of osteoclast progenitors, defined by flow cytometry as Lin⁻CD11b⁻Ly6C^hi CD115⁺, by 42.8% compared to treatment with EPO alone. In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment.     

Potentiometric and Thermodynamic Studies of (N-[-(4-Chlorophenyl) Methylene]Nicotinohydrazide) and Its Transition Metal Complexes

Abstract

Pharmacologically active organic ligands (N-[-(4-chlorophenyl) methylene] nicotinohydrazide) synthesized through the condensation of equimolar mixture of anti-mycobacterial agent (nicotinohydrazide) with aromatic aldehyde. The reaction progress and purity of organic ligands were verified by thin layer chromatography. Formation of organic ligands was confirmed with the help of MP, IR, ¹H NMR, 13C NMR and elemental analysis. Further formation of complexes of transition elements such as Mn(II), CO(II), Ni(II), Cu(II) and Zn(II) with organic ligand (Schiff base) N-[-(4-chlorophenyl)methylene] nicotinohydrazide were studied by the pH-metric technique at 25?°C, 35?°C and 45?°C in 70% (v/v)ethanol – water medium at 1?M (NaClO₄) ionic strength. The stability constants of these binary complexes were evaluated and order of stability constant found as Co (II) < Mn (II) < Ni (II) < Cu (II) < Zn (II). The thermodynamic parameters associated with the complexation reactions also were calculated. It is found that the change in enthalpy (ΔH) and change in Gibb’s free energy (ΔG) were negative for all of the systems which suggested that all of the reactions were exothermic. The change in entropy (ΔS) found positive for most of the complexes which indicate in metal-ligand binding process is entropy favorable.     

Mode‐matching analysis and design of substrate integrated waveguide T‐junction diplexer and corner filter

The mode‐matching technique is deployed in this paper in order to analyze and design a substrate integrated waveguide (SIW) T‐junction diplexer in Ku‐band. The diplexer has bandwidths of 4.12% and 3.79% at 14.55 and 15.85 GHz, respectively. Also in Ku‐band, an SIW corner filter is analyzed and designed with the same technique. Analytical results are compared with simulated data obtained from commercially available field solvers such as CST Microwave Studio and ANSYS HFSS. Excellent agreement between analytical and simulated data is achieved. Copyright © 2014 John Wiley & Sons, Ltd.     

The wear resistance of glass fibre reinforced epoxy composites

Polymers are usually characterized by low moduli and strength. Epoxy, as a thermoset material, has a low wear resistance. Additions of glass fibres improve the elastic modulus and tensile strength and can improve the wear resistance. The composites were prepared by pultrusion of the glass fibres after saturation of epoxy. The fibre volume fraction was varied up to 50%. Tensile and wear tests were carried out to examine the improvement in the composite properties. A small deviation of the tensile strength and the elastic modulus from the calculated values using the rule of mixture was observed due to the existence of porosities. The wear resistance increases with increasing the sliding velocity, with decreasing the applied contact pressure and with selecting the most favourable glass fibre volume fraction.     

Feasibility of PSO–ANFIS model to estimate rock fragmentation produced by mine blasting

Desired rock fragmentation is the main goal of the blasting operation in surface mines, civil and tunneling works. Therefore, precise prediction of rock fragmentation is very important to achieve an economically successful outcome. The primary objective of this article is to propose a new model for forecasting the rock fragmentation using adaptive neuro-fuzzy inference system (ANFIS) in combination with particle swarm optimization (PSO). The proposed PSO–ANFIS model has been compared with support vector machines (SVM), ANFIS and nonlinear multiple regression (MR) models. To construct the predictive models, 72 blasting events were investigated, and the values of rock fragmentation as well as five effective parameters on rock fragmentation, i.e., specific charge, stemming, spacing, burden and maximum charge used per delay were measured. Based on several statistical functions [e.g., coefficient of correlation (R ²) and root-mean-square error (RMSE)], it was found that the PSO–ANFIS (with R ² = 0.89 and RMSE = 1.31) performs better than the SVM (with R ² = 0.83 and RMSE = 1.66), ANFIS (with R ² = 0.81 and RMSE = 1.78) and nonlinear MR (with R ² = 0.57 and RMSE = 3.93) models. Finally, the sensitivity analysis shows that the burden and maximum charge used per delay have the least and the most effects on the rock fragmentation, respectively.