1,710 research outputs found
STUDIES ON THE CONFORMATIONAL STABILITY, DYNAMICS AND VISCOSITY OF IMMUNOGLOBULINS
Proteins, such as immunoglobulins, are inherently dynamic molecules with unique biological functions. The intra- and intermolecular interactions that govern the dynamic nature and function of immunoglobulins may also influence their stability. A molecular understanding of interrelationship between dynamics, function and conformational stability of immunoglobulins, both in solution and in presence of co-solutes, can be important for their pharmaceutical development. In addition, it is important to understand the differences in any such correlations between closely related immunoglobulins. Furthermore, molecular interactions in immunoglobulins can be unique at low and high concentrations, which necessitate newer complementary approaches to investigate such complex systems. Therefore, a better understanding of interactions that govern protein structure, dynamics and conformational stability at low and high concentrations and in presence of excipients should aid in designing, optimizing and developing rational formulation conditions for protein based therapeutics. A variety of experimental methods sensitive to structure, dynamics and conformational stability of proteins in solution were employed in these studies. External perturbations such a change in pH, ionic strength and temperature were used to probe the response of proteins, both at low and high concentrations. Different monoclonal antibodies within IgG1 isotype were used to investigate interrelationships between protein dynamics and conformational stability in absence and presence of co-solutes. In addition, an ultraviolet spectroscopy based approach was developed to understand interactions modulating solution viscosity in high concentration immunoglobulin solutions. These studies provide evidence that immunoglobulins belonging to the same IgG1 subtype can have notable differences in their conformational stability, dynamics, aggregation propensity, hydration properties and their response to co-solutes. In addition, alterations in protein dynamics (at a global protein level and in local regions with differences in solvent exposures) by stabilizing or destabilizing excipients were found to modulate the conformational stability of a monoclonal antibody. Furthermore, it was determined that potential interactions and factors modulating solution viscosity at high protein concentrations may also result in changes in their extinction coefficients. The work presented in this dissertation provides evidence that factors modulating protein dynamics and those governing intra- and intermolecular interactions can influence the conformational stability, aggregation and viscosity of proteins in solution
Paramagnetic magnetization signals and curious metastable behaviour in field-cooled magnetization of a single crystal of superconductor 2H-NbSe2
We present here some newer characteristics pertaining to paramagnetic
Meissner effect like response in a single crystal of the low Tc superconducting
compound 2H-NbSe2 via a detailed study of effects of perturbation on the
field-cooled magnetization response. In the temperature range, where an
anomalous paramagnetic magnetization occurs, the field-cooled magnetization
response is found to be highly metastable: it displays a curious tendency to
switch randomly from a given paramagnetic value to a diamagnetic or to a
different paramagnetic value, when the system is perturbed by an impulse of an
externally applied ac field. The new facets revealed in a single crystal of
2H-NbSe2 surprisingly bear a marked resemblance with the characteristics of
magnetization behaviour anticipated for the giant vortex states with multiple
flux quanta predicted to occur in mesoscopic-sized superconducting specimen and
possible transitions amongst such states.Comment: 12 pages, 9 figures, submitted to Journal of Physics: Condensed
Matte
Forensic Analysis of an Uncontrolled Fill
This paper outlines the forensic analysis done in relation to a filling done to raise the general ground level in an area where a large housing complex is under construction near New Delhi, India. After the structures had been completed, trenches were dug to lay sewage and other service lines and the soil at the bottom had been observed to be in a slushy condition. A meticulous and detailed forensic diagnosis and analysis indicated uncontrolled filling. Measures were evolved to contain the slushy zone and compact the upper layers so that the service lines as well as roads could be laid. The paper presents the investigations conducted, analysis performed, and evaluation of the successful and satisfactory performance of the recommended remedial measures
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