Structural Consequence of Non-Synonymous Single-Nucleotide Variants in the N-Terminal Domain of LIS1

Disruptive neuronal migration during early brain development causes severe brain malformation. Characterized by mislocalization of cortical neurons, this condition is a result of the loss of function of migration regulating genes. One known neuronal migration disorder is lissencephaly (LIS), which is caused by deletions or mutations of the LIS1 (PAFAH1B1) gene that has been implicated in regulating the microtubule motor protein cytoplasmic dynein. Although this class of diseases has recently received considerable attention, the roles of non-synonymous polymorphisms (nsSNPs) in LIS1 on lissencephaly progression remain elusive. Therefore, the present study employed combined bioinformatics and molecular modeling approach to identify potential damaging nsSNPs in the LIS1 gene and provide atomic insight into their roles in LIS1 loss of function. Using this approach, we identified three high-risk nsSNPs, including rs121434486 (F31S), rs587784254 (W55R), and rs757993270 (W55L) in the LIS1 gene, which are located on the N-terminal domain of LIS1. Molecular dynamics simulation highlighted that all variants decreased helical conformation, increased the intermonomeric distance, and thus disrupted intermonomeric contacts in the LIS1 dimer. Furthermore, the presence of variants also caused a loss of positive electrostatic potential and reduced dimer binding potential. Since self-dimerization is an essential aspect of LIS1 to recruit interacting partners, thus these variants are associated with the loss of LIS1 functions. As a corollary, these findings may further provide critical insights on the roles of LIS1 variants in brain malformation.     

Dissolution potential of alkali halides in N,N-dimethyl formamide

Phase potential, diffusion potential, observed and true dissolution potentials of alkali halides in N,N-dimethyl formamide have been determined. True dissolution potentials are found to be positive in DMF. The sign and magnitude of these potentials have been explained on the basis of difference between the ionic mobilities of cations and anions.     

Experimental and numerical investigation of cutting forces in micro-milling of polycarbonate glass

Abstract

Polycarbonates have found important applications in various types of industries including optical, automotive, aerospace, biomedical, and defense manufacturing industries. Conventional mechanical machining has the capability to create complex multi-scale parts and components for various materials including polymeric materials. This study investigates the cutting forces generated during the machining of polycarbonate glass using the micro-milling process. The goal of this research is to machine high quality micro-channels in polycarbonates for microfluidic applications. Both experimental investigation and numerical simulations using the Finite Element Method (FEM) have been carried out to assess the cutting forces generated in three directions during machining of polycarbonate. The effectiveness of tool coating on the reduction of cutting forces has been investigated. It was found that with the careful combination of depth of cut and feed rate, the ductile mode machining of polycarbonate can be achieved, which produces lower cutting forces, that could result in improved surface finish and low tool wear. Both lower and higher of depths of cut were found to generate higher cutting forces due to dragging action and higher tool-workpiece contact area respectively. The Finite Element Method (FEM) was found to be effective in simulating the cutting forces with acceptable range of errors, and thus, could be used to predict cutting forces at the parametric combinations beyond the capacity of the machine or without carrying out further expensive experimentation, for which the chances of tool failure are higher.     

Using a geotextile with flocculated filter backwash water and its impact on aluminium concentrations

The use of geotextiles (i.e. geotextile tubes) in wastewater treatment applications is ever increasing. This paper examines the potential of using a geotextile to improve upon the treatment of aluminium present in a filter backwash water that is generated from a water treatment plant in Halifax, Canada. A field investigation to ascertain the distribution of aluminium in the filter backwash water treatment process is provided and compared to regulatory guidelines at the environmental compliance point. It is shown that aluminium is undergoing incomplete treatment at various times throughout the year. To examine a potential corrective action, the results of bench scale studies are presented in which cationic additives (i.e. CaO, MgO, and Fe₃O₄) are combined with a polymer to remove aluminium from solution and flocculate particulate matter from the filter backwash water. A geotextile is utilized to retain particulate matter generated from this process. It is shown that the combined use of the cationic additive with polymer can successfully reduce aluminium concentrations in the filter backwash water and that filtration via a geotextile can retain the aluminium particulate in the filter backwash water to levels close to regulatory requirements. Further optimization with the flocculation process is recommended prior to pilot testing.     

Effect of Sequestering Intrinsic Iron on the Electron Paramagnetic Resonance Signals in Powdered Soy Proteins

This investigation examined iron in powdered soy protein products using electron paramagnetic resonance (EPR) spectroscopy, and the effect that selectively binding free iron in isolated soy protein (ISP) had on the occurrence of metastable radicals in powdered soy proteins. EPR analyses of soybean defatted flour, commercial ISP and laboratory ISP samples revealed a peak at g = 4.3 characteristic of high‐spin ferric iron in a rhombic‐coordinated environment. Commercial ISP samples examined contained higher levels of the rhombic ferric iron than laboratory‐prepared ISP samples. During the first 6 wk of storage the primary singlet EPR signal at g = 2.0049 in the commercial ISP samples approximately doubled, and the laboratory prepared samples increased by about 9‐fold. The EPR signal was initially about 4‐times higher in the freshly prepared commercial samples compared to the corresponding laboratory ISP. Laboratory ISP samples prepared with added deferoxamine to sequester endogenous iron exhibited a large increase in the high‐spin ferric iron EPR signal at g = 4.3. ISP treated with deferoxamine also exhibited a multiple‐line EPR signal at about g = 2.007, instead of the typical singlet signal at g = 2.0049. The power at which the signal amplitude was half‐saturated also changed from about 1 mW in the control ISP to about 20 mW in the deferoxamine treated ISP. The multiple‐line EPR spectrum from the ISP treated with deferoxamine increased during storage over a 6‐wk period by about 6‐fold. The observed changes in EPR line‐shape, g‐value, and power saturation with the deferoxamine treatment indicate that the primary free‐radical signal in powdered ISP samples may be from stabilized tyrosine radicals with spin densities distributed over the aromatic ring.