Natural Voltage-Gated Sodium Channel Ligands: Biosynthesis and Biology

Natural product biosynthetic pathways are composed of enzymes that use powerful chemistry to assemble complex molecules. Small molecule neurotoxins are examples of natural products with intricate scaffolds which often have high affinities for their biological targets. The focus of this Minireview is small molecule neurotoxins targeting voltage-gated sodium channels (VGSCs) and the state of knowledge on their associated biosynthetic pathways. There are three small molecule neurotoxin receptor sites on VGSCs associated with three different classes of molecules: guanidinium toxins, alkaloid toxins, and ladder polyethers. Each of these types of toxins have unique structural features which are assembled by biosynthetic enzymes and the extent of information known about these enzymes varies among each class. The biosynthetic enzymes involved in the formation of these toxins have the potential to become useful tools in the efficient synthesis of VGSC probes.     

Casting/mold thermal contact heat transfer during solidification of Al-Cu-Si alloy (LM 21) plates in thick and thin molds

Heat flow at the casting/mold interface was assessed and studied during solidification of Al-Cu-Si (LM 21) alloy in preheated cast iron molds of two different thicknesses, coated with graphite and alumina based dressings. The casting and the mold were instrumented with thermocouples connected to a computer controlled temperature data acquisition system. The thermal history at nodal locations in the mold and casting obtained during experimentation was used to estimate the heat flux by solving the one-dimensional inverse heat conduction problem. The cooling rate and solidification time were measured using the computer-aided cooling curve analysis data. The estimated heat flux transients showed a peak due to the formation of a stable solid shell, which has a higher thermal conductivity compared with the liquid metal in contact with the mold wall prior to the occurrence of the peak. The high values of heat flux transients obtained with thin molds were attributed to mold distortion due to thermal stresses. For thin molds, assumption of Newtonian heating yielded reliable interfacial heat transfer coefficients as compared with one-dimensional inverse modeling. The time of occurrence of peak heat flux increased with a decrease in the mold wall thickness and increase in the casting thickness.     

Ultrananocrystalline Diamond-Coated Microporous Silicon Nitride Membranes for Medical Implant Applications

Ultrananocrystalline diamond (UNCD) exhibits excellent biological and mechanical properties, which make it an appropriate choice for promoting epidermal cell migration on the surfaces of percutaneous implants. We deposited a ~150 nm thick UNCD film on a microporous silicon nitride membrane using microwave plasma chemical vapor deposition. Scanning electron microscopy and Raman spectroscopy were used to examine the pore structure and chemical bonding of this material, respectively. Growth of human epidermal keratinocytes on UNCD-coated microporous silicon nitride membranes and uncoated microporous silicon nitride membranes was compared using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The results show that the UNCD coating did not significantly alter the viability of human epidermal keratinocytes, indicating potential use of this material for improving skin sealing around percutaneous implants.     

Induced doping by sodium ion in poly(m-aminophenol) through the functional groups

Poly(m-aminophenol) (PmAP) was synthesized by the oxidative polymerization of m-aminophenol in sodium hydroxide medium using ammonium persulfate oxidant at room temperature. The synthesized polymer showed very good solution processability as it was well soluble in aqueous sodium hydroxide, dimethylsulfoxide (DMSO), dymethylformamide (DMF), etc. A free-standing film was cast from thermal evaporation of DMSO solution of the synthesized PmAP. The film was then doped with aqueous sodium hydroxide and methanol mixture by solution doping technique at room temperature. The doping conditions were standardized in terms of the DC-conductivity of the doped film. The doped PmAP was characterized by ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, Electron dispersion spectroscopy, X-ray diffraction spectroscopy, elemental analysis by atomic absorption spectroscopy, thermogravimetric analysis and DC-electrical conductivity. The DC-electrical conductivity of PmAP film was increased to 2.34 × 10^?5 S/cm from <10^?12 S/cm due to sodium ion doping. From all the above characterizations it was confirmed that the sodium ions were not the reason for the conduction. The incorporated sodium cation in the polymer through free –OH groups of the polymer chain was induced the electron cloud of the polymer and so the polymer became conducting.     

Free convection heat transfer over a horizontal plate at low prandtl number

Boundary layer equations for free convection heat transfer along a semi-infinite horizontal plate are derived by giving more importance to the energy equation. The equations are obtained for low Prandtl number and two separate polynomials are used to approximate the temperature and velocity profiles in these regions. The rate of heat transfer is compared with the available analytical and numerical results based on conventional boundary layer equations.     

Single‐walled carbon nanotube/poly(methyl methacrylate) composites for electromagnetic interference shielding

Single‐walled carbon nanotube (SWNT)/poly(methyl methacrylate) (PMMA) composites were prepared using coagulation method. The electrical conductivity and the electromagnetic interference (EMI) shielding of SWNT/PMMA composites over the X‐band (8–12 GHz) and the microwave (200–2000 MHz) frequency range have been investigated. The electrical conductivity of composites increases with SWNT loading by 13 orders of magnitude, from 10^?15 to 10^?2 Ω^?1 cm^?1 with a percolation threshold of about 3 wt% SWNTs. The effect of the sample thickness on the shielding effectiveness has been studied, and correlated to the electrical conductivity of composites. The data suggest that SWNT/PMMA composites containing higher SWNT loading (above 10 wt%) be useful for EMI shielding and those with lower SWNT loading be useful for electrostatic charge dissipation. The dominant shielding mechanism of SWNT/PMMA composites was also discussed. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers     

Role of V2O5 on the formation of chemical mullite from aluminosilicate precursor

Aluminosilicate precursor for the processing of mulite ceramics was synthesized chemically from inorganic salts following colloidal route. V₂O₅ was used as a sintering additive in different ratios with the precursor powder. The powder mixes were compacted and sintered at different elevated temperatures. The sintered masses were characterized by measuring the bulk density, porosity, flexural strength and fracture toughness. The extent of mullitization and final microstructure of the sintered masses were investigated by scanning electron microscopy and XRD analysis. It was observed that V₂O₅ exhibited favourable effect on the formation of properly crystallized mullite and in the improvement of different mechanical properties.     

Recent Advances in Reactive Extrusion Processing of Biodegradable Polymer‐Based Compositions

This review reports on recent advances in the design of biodegradable polymers built from petroleum and renewable resources using reactive extrusion processing. Reactive extrusion represents a unique tool to manufacture biodegradable polymers upon different types of reactive modification in a cost‐effective way. Partially based on our ongoing research, ring‐opening polymerization of biodegradable polyesters will be approached as well as the chemical modification of biodegradable polymers, particularly natural polymers. The development of environmentally friendly polymer blends as well as (nano)composites from natural polymers, including natural fibers and nanoclays, through reactive extrusion, as an efficient way to improve the interfacial adhesion between these components, will be also discussed.

     

Dissimilarity in the oxidative folding of onconase and ribonuclease A, two structural homologues

The oxidative folding of frog onconase (ONC), a member of theribonuclease A family, was examined and shows markedly differentbehavior compared to its structural homologue bovine pancreaticribonuclease A (RNase A) under similar conditions. Applicationof a reduction pulse (using a small amount of reduced dithiothreitol)during the oxidative regeneration of ONC indicated the survivalof the native protein along with three other (structured) species,I₁, I₂ and I₃, with the rest of the unstructured species beingconverted to fully reduced protein. Mass spectrometry indicatesthat I₁ has two disulfide bonds, whereas I₂ and I₃ have threedisulfide bonds each. A disulfide mapping method, based on cyanylation,was used to identify I₂ and I₃ as des-[30–75] and des-[19–68],respectively. On enzymatic digestion using trypsin, I₁ was identifiedas des-[19–68, 30–75]. Differences in the intermediatesthat are generated during the oxidative folding of the two structuralhomologues, RNase A and ONC, demonstrate that regenerative pathwaysare not necessarily influenced by tertiary structure. This indicatesthat the lack of a disulfide bond in ONC, analogous to the (65–72)disulfide bond in RNase A which plays an important role in itsoxidative regeneration, does not adversely affect the oxidativefolding of ONC.     

功能梯度类金刚石薄膜的脉冲激光制备

长期以来 ,高质量的纯类金刚石薄膜的成功制备一直受其巨大内部压应力的阻碍 ,因为这种压应力导致严重的附着问题。厚度大于 50 0nm的类金刚石薄膜中的压应力常使薄膜与基体剥离。作者采用功能梯度的设计概念 ,应用准分子脉冲激光沉积方法 ,成功制备了厚度超过 1 0 μm的高质量类金刚石薄膜。薄膜中的SP3碳原子含量超过 6 0 %。纳米硬度测试表明 ,薄膜的弹性模量高达 50 0GPa ,纳米硬度高达 6 0GPa ,薄膜与基体间附着良好。证明功能梯度的设计概念可以用于制备较厚的超硬类金刚石薄膜。