Using BIACORE SPR, we have examined the mechanism of temperature effects on the binding kinetics of two closely related antibody Fabs (H10 and H26) which recognize coincident epitopes on hen egg-white lysozyme (HEL), and whose association and dissociation kinetics are best described by the two-step conformational change model which we interpret as molecular encounter and docking. Time-course series data obtained at a series of six temperatures (6, 10, 15, 25, 30 and 37 degrees C) showed that temperature differentially affects the rate constants of the encounter and docking steps. Docking is more temperature-sensitive than the encounter step, and energetically less favorable at higher temperatures. At elevated temperatures, the time required for docking is longer and the apparent increase in off-rate reflects the greater proportion of the molecules failing to dock and remaining in the less stable encounter state. As a consequence, distribution of free energy change between the encounter and docking steps is altered. At physiological temperature (37 degrees C) the docking step of the H26 complex is energetically unfavorable and most complexes essentially do not dock. There is a significant decrease in total free energy change of the H26 complex at higher temperatures. Elevated temperature changes the rate-limiting step of H26--HEL association from the encounter to the docking step, but not that of H10--HEL. Our results indicate that the mechanism by which elevated temperature reduces the affinities of antigen--antibody complexes is to decrease the net docking rate, and/or stability of the docked complex; at higher temperatures, a smaller proportion of the complexes actually anneal to a more stable docked state. This mechanism may have broad applicability to other receptor--ligand complexes.
Melt size‐dependent physical property variation is examined in a multicomponent GeSe2‐As2Se3‐PbSe chalcogenide glass developed for gradient refractive index applications. The impact of melting conditions on small (40 g) prototype laboratory‐scale melts extended to commercially‐relevant melt sizes (1.325 kg) have been studied and the role of thermal history variation on physical and optical property evolution in parent glass, the glass’ crystallization behavior and postheat‐treated glass ceramics, is quantified. As‐melted glass morphology, optical homogeneity and heat treatment‐induced microstructure following a fixed, two‐step nucleation and growth protocol exhibit marked variation with melt size. These attributes are shown to impact crystallization behavior (growth rates, resulting crystalline phase formation) and induced effective refractive index change, neff, in the resulting optical nanocomposite. The magnitude of these changes is discussed based on thermal history related melt conditions.
Optical materials capable of advanced functionality in the infrared will enable optical designs that can offer lightweight or small footprint solutions in both planar and bulk optical systems. The University of Central Florida's Glass Processing and Characterization Laboratory, together with our collaborators, have been evaluating compositional design and processing protocols for both bulk and film strategies employing multicomponent chalcogenide glasses (ChGs). These materials can be processed with broad compositional flexibility that allows tailoring of their transmission window, physical and optical properties, which allows them to be engineered for compatibility with other homogeneous amorphous or crystalline optical components. We review progress in forming ChG-based gradient refractive index (GRIN) materials from diverse processing methodologies, including solution-derived ChG layers, poled ChGs with gradient compositional and surface reactivity behavior, nanocomposite bulk ChGs and glass ceramics, and metalens structures realized through multiphoton lithography. We discussed current design and metrology tools that lend critical information to material design efforts to realize next-generation IR GRIN media for bulk or film applications.
PurposeTo further the understanding of growing pains (GP), in particular, the nature of this pain disorder.MethodsThis study included 33 children aged 5–12 years who met criteria for GP (cases) and 29 children without GP of similar age and sex (controls). Nineteen controls were siblings of cases. GP was diagnosed by standard consensus questionnaires. A questionnaire addressed characteristics of the pain and family history of GP. Evidence for peripheral neuropathic disorder was tested by somatosensory testing and provocation tests of peripheral nerves. Somatosensory testing by a blinded researcher involved threshold determination and/or response magnitude to nonpainful stimuli including touch, dynamic brush, cold, vibration, and deep pressure applied to limb and abdominal sites.ResultsDistributional, temporal, and quality characteristics of the pain were in accordance with published descriptions. There was no indication of primary musculoskeletal disorder. No evidence was found that GP is a peripheral neuropathic pain syndrome. There were minor but statistically significantly increased responses to cutaneous cold, vibration, and to deep pressure stimuli in cases compared to controls, evident in a wider distribution than the symptomatic lower limbs.ConclusionGP is a regional pain syndrome with evidence in this study of mild widespread disorder of somatosensory processing.
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