Mechanism and nanosize products of the sol-gel reaction using diphenylsilanediol and 3-methacryloxypropyltrimethoxysilane as precursors

We use a first-principles calculation and small-angle neutron scattering (SANS) to investigate the mechanism and the nanosize products of the sol-gel reaction with diphenylsilanediol (DPD) and 3-methacryloxypropyltrimethoxysilane (MEMO) precursors in synthesizing a hybrid waveguide material. It is predicted that switching between a DPD hydroxyl and a MEMO methoxy with a reaction rate of 6.8 x 10(-6) s(-1) at 300 K is the fastest process for the first reaction step, thus generating diphenylmethoxysilanol (DPM) and 3-methacryloxypropyldimethoxysilanol (MEDO) as products. However, we determine that this reaction pathway could be modified by the presence of the H2O released from a catalyst such as Ba(OH)2.H2O. Next, switching between the DPM hydroxyl and the MEDO methoxy is followed to generate diphenyldimethoxysilane (DPDM) and 3-methacryloxypropylmethoxysilanediol (MEMDO). However, condensation between a MEMDO hydroxyl and a DPDM methoxy is found to be most favorable for the third reaction step, which generates the DPDM-MEMDO dimer and CH3OH molecule as products. In a similar fashion, a DPDM methoxy of the DPDM-MEMDO dimer can condense with a MEMDO hydroxyl of the second DPDM-MEMDO dimer to increase the chain, but its reaction rate of 2.8 x 10(-11) s(-1) is predicted to be about 5 times smaller than that between a DPDM methoxy and a MEMDO hydroxyl. This implies that the reaction rate for the larger nanostructures becomes smaller. Additionally, our SANS measurements determine that the final products from our sol-gel reaction are on the nanometer scale, at sizes from 1.76 to 2.36 nm.     

The effect of phenyl substituents on the release rates of esterase-sensitive coumarin-based prodrugs

A coumarin-based prodrug system has been recently developed in our laboratory for the preparation of esterase-sensitive prodrugs of amines, peptides, and peptidomimetics. The drug release rates from this prodrug system were found to be dependent on the structural features of the drug moiety. In certain cases, the release can be undesirably slow for drugs that are secondary amines with relatively high pKa's. Aimed at finding ways to manipulate the release rates to suit the need of different drugs, we have examined the effect of the phenyl ring substitutions on the release kinetics of such prodrugs and found that appropriately positioned alkyl substituents on the phenyl ring could help to facilitate the release by as much as 16-fold. Therefore, introduction of alkyl substituents on the phenyl ring should allow us to manipulate the release rates and, therefore, time profiles for different drugs.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Improved Compatibility of Styrene-Maleic Anhydride Copolymer/Polyethylene Blends Through Reactive Mixing

Abstract

To improve the compatibility of styrene-maleic anhydride copolymer/low density polyethylene (SMA/LDPE) blends, LDPE grafted with 2-hydroxyethyl methacrylate-isophorone diisocyanate (LDPE-g-HI) was prepared and blended with SMA of which anhydride was converted to carboxylic acid (SMAAc). The infrared spectra of LDPE-g-HI established the presence of isocyanate group. In the blend morphology, some adhesions between the two phases and much finer dispersions were observed in the SMAAc/LDPE-g-HI blends, indicating that chemical reactions took place during the melt blending. The lower heat capacity change at the glass transition temperature demonstrated that chemical bonds were produced in the SMAAc/LDPE-g-HI blends. From the results of the rheological test, it was found that strong positive deviation from the mixing rule occurred in viscosity for the SMAAc/LDPE-g-HI blends, concerning with good adhesion and finer dispersions. In the measurement of tensile property, the improved mechanical properties for the SMAAc/LDPE-g-HI blends were shown.     

Differential regulation of the histone chaperone HIRA during muscle cell differentiation by a phosphorylation switch

Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells. By generating a phosphospecific antibody, we found that a significant amount of HIRA was phosphorylated in myoblasts. The phosphorylation level of HIRA and the occupancy of phosphorylated protein on muscle genes gradually decreased during cellular differentiation. Remarkably, the forced expression of the phosphomimic form of HIRA resulted in reduced H3.3 deposition and suppressed the activation of muscle genes in myotubes. Our data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.     

Effects of structural properties of silicon carbide-derived carbons on their electrochemical double-layer capacitance in aqueous and organic electrolytes

High surface area silicon carbide-derived carbons (Si-CDCs) synthesized by chlorination of beta silicon carbide (βSiC) with two different particle sizes (6 μm and 50 nm) show different porosities with graphitic structure. Transmission electron microscopy, Raman spectroscopy and argon (Ar) and carbon dioxide (CO₂) sorption analyses are used to examine the textural properties of the Si-CDCs. The results show that the particle size of the precursor affects the surface area and porosity of carbons. Furthermore, an additional heat treatment of the Si-CDC with 50-nm particle size for 24 h at 1,000 °C results in a collapse of the pore structure and reduces the surface area. The capacitive behaviours are investigated in H₂SO₄ and in tetraethyl ammonium tetrafluoroborate (TEABF₄)/acetonitrile (AN). The electrochemical performance of the Si-CDCs is influenced by the particle size, surface area, pore volume and pore size distribution. The Si-CDCs exhibit capacitances in 1 M H₂SO₄ of up to 179 F g^?1 and very stable charge–discharge performance over 5,000 cycles. This study shows the crucial importance of ultramicropores less than 1 nm combined with nanosized particles for achieving high capacitance in aqueous electrolyte. Moreover, the graphitic degree at the surface of the Si-CDCs enhances considerably the rate capability and stability in both electrolytes.     

Configuration Design Sensitivity Analysis of Kinematic Responses of Mechanical Systems∗

Abstract

A continuum-based configuration design sensitivity analysis method is presented for kinematically driven mechanical systems. Configuration design variable for mechanical systems are defined. The 3-1-3 Euler angle is used as the orientation design variable. The reassembly process for a mechanical system after a configuration design change is eliminated by imposing kinematic admissibility conditions of the velocity field. The direct differentiation method is used to derive design sensitivity equations. Numerical examples are presented to demonstrate the validity and effectiveness of the proposed method.