High-throughput capillary electrophoresis analysis of biopharmaceuticals utilizing sequential injections

The complexity of biotherapeutic products implies an ever-increasing list of product quality attributes that need to be monitored and characterized. In addition, the growing interest in implementing process analytical technology in biopharmaceutical production has further increased the testing burden, together with the need for rapid testing that can facilitate real-time or near-real-time decision-making. Capillary electrophoresis (CE) has made a place in biopharmaceutical analysis but is regarded as a low-throughput method, with the instrument dead time constituting more than 80% of the total time of analysis. In this study, the dead time of CE was utilized to analyse 3 mAb samples in a single-CE run. This approach resulted in an up to 77% reduction in the total analysis time and increased the productivity by up to 300%, compared to traditional single CE-ultraviolet runs, without compromising resolution or relative peak areas. Additionally, good method reproducibility was observed. The compatibility of the method has been demonstrated with protein A eluate and cation exchange chromatography fractions. We, thus, propose that sequential injections can be applied for fast and robust CE analysis of biopharmaceuticals.     

Thermal conduction through loose and granular two-phase materials at normal pressure

The integrated theory derived for the lattice-type dispersions is modified and extended to estimate the effective thermal conductivity of loose and granular two-phase materials at normal pressure assuming an effective continuous media approximation. A comparison of calculated values ofλ _e with the reported experimental results over a wide range of loose and granular two-phase materials shows a good agreement.     

Mathematical modelling of flow control in a tundish using electro-magnetic forces

The control of flow in a tundish is important for improving the quality of the steel. Dams, Wiers and Pouring chamber are some of the devices used for controlling the flow in the tundish. The investigation about the role of electromagnetic forces as a replacement for these devices is an objective for the present work. Thus, 3-D MHD simulation was performed to study the effect of electromagnetic forces on flow behaviour in the tundish. The MHD model developed for carrying out the simulation was validated with the analytical solution of the Hartman problem. The results obtained shows improvement in the desired characteristics for inclusion flotataion with magnetic flow modifier of optimum strength of magnetic field.     

On a conjecture of Lynch

Abstract

We comment on a conjecture of Lynch on annihilators of local cohomology.

Communicated by Lawrence Ein     

Line broadening studies in low energy plasma focus

Optical emission spectroscopic studies were carried out to characterise the plasma leading to the estimation of two plasma parameters, electron density and temperature. These experiments were conducted on a 2 kJ plasma device which is equipped with squirrel cage electrode configuration enclosed in a glass vacuum chamber filled with hydrogen at a pressure of 5 mbar. Spectral emissions obtained from each flash were photographed in the region of 4000–6000 Å using one metre Czerny-Turner spectrograph cum monochromator. Detailed examination of the observed features showed that theH _β andH _λ lines of hydrogen showed significant broadening of the order of 35 Å FWHM which is due to Stark effect expected in high density plasmas. Further several atomic lines of Cu and Zn from the electrode material (brass) showed broadening which was due to quadratic Stark effect. A comparative study of the broadening of lines obtained in DC arc, hollow cathode and plasma focus was made. Electron density from Stark broadened hydrogen lines and quadratic Stark Coefficient C₄ for the CuI and ZnI lines were evaluated. The excitation temperature was determined from the line intensity ratio method using CuI lines.     

Superconductivity with transition temperature up to 80 K for TbSr2Cu2.7Mo0.3O7+δ

A Tb-123 phase with the composition, TbSr₂Cu_2.7Mo_0.3O_7+δ, has been synthesized in single-phase form by the solid-state reaction route. Its phase purity has been confirmed from neutron powder diffraction studies. The as-synthesized Tb-123 sample does not show superconductivity down to 5 K. On the other hand, an unusually high antiferromagnetic ordering temperature (T_N) of around 7 K is seen for the Tb moments. After 120-atm-O₂ post-annealing, bulk superconductivity is achieved in this compound with a superconducting transition temperature (T_c) of about 30 K, without any significant effect on T_N. To achieve higher oxygen content and higher T_c, the as-synthesized sample was subjected to high-pressure oxygenation, carried out in a closed cell, at 5 GPa and 400 °C in the presence of AgO as an excess-oxygen source. This sample exhibited superconductivity onset at around 80 K with a Meissner fraction larger than 10% at 5 K. Our observation of superconductivity at 80 K is the highest T_c to-date for the Tb-123 type compounds.     

Empirical force-field assessment: The interplay between backbone torsions and noncovalent term scaling

The kinetic and thermodynamic aspects of the helix-coil transition in polyalanine-based peptides have been studied at the ensemble level using a distributed computing network. This study builds on a previous report, which critically assessed the performance of several contemporary force fields in reproducing experimental measurements and elucidated the complex nature of helix-coil systems. Here we consider the effects of modifying backbone torsions and the scaling of noncovalent interactions. Although these elements determine the potential of mean force between atoms separated by three covalent bonds (and thus largely determine the local conformational distributions observed in simulation), we demonstrate that the interplay between these factors is both complex and force field dependent. We quantitatively assess the heliophilicity of several helix-stabilizing potentials as well as the changes in heliophilicity resulting from such modifications, which can "make or break" the accuracy of a given force field, and our findings suggests that future force field development may need to better consider effect that vary with peptide length. This report also serves as an example of the utility of distributed computing in analyzing and improving upon contemporary force fields at the level of absolute ensemble equilibrium, the next step in force field development.     

Determination of azo compounds with N-bromosuccinimide in acetic acid medium

The bromination reaction of azo compounds with N-bromosuccinimide in acetic acid medium has been studied. Some reaction products have been isolated and reaction mechanisms suggested. The reaction study has been applied for the determination of 2-10 mg of azo compounds. The maximum deviation of the results from the theoretical value is generally within +/- 1%.     

Foldamer dynamics expressed via Markov state models. II. State space decomposition

The structural landscape of poly-phenylacetylene (pPA), otherwise known as m-phenylene ethynylene oligomers, has been shown to consist of a very diverse set of conformations, including helices, turns, and knots. Defining a state space decomposition to classify these conformations into easily identifiable states is an important step in understanding the dynamics in relation to Markov state models. We define the state decomposition of pPA oligomers in terms of the sequence of discretized dihedral angles between adjacent phenyl rings along the oligomer backbone. Furthermore, we derive in mathematical detail an approach to further reduce the number of states by grouping symmetrically equivalent states into a single parent state. A more challenging problem requires a formal definition for knotted states in the structural landscape. Assuming that the oligomer chain can only cross the ideal helix path once, we propose a technique to define a knotted state derived from a helical state determined by the position along the helical nucleus where the chain crosses the ideal helix path. Several examples of helical states and knotted states from the pPA 12-mer illustrate the principles outlined in this article.