When orthopaedic surgeons are considering using a new device clinically in their patients, it is important for them to consider how the new device was approved by the FDA. If the device was approved by the 510(k) pathway, then it may have been approved without additional clinical studies confirming efficacy or safety.
Genetic experiments with full length AraC and biophysical experiments with its dimerization domain plus linker suggest that arabinose binding to the dimerization domain changes the properties of the inter-domain linker which connects the dimerization domain to the DNA binding domain via interactions that do not depend on the DNA binding domain. Normal AraC function was found to tolerate considerable linker sequence alteration excepting proline substitutions. The proline substitutions partially activate transcription even in the absence of arabinose and hint that a structural shift between helix and coil may be involved. To permit fluorescence anisotropy measurements that could detect arabinose-dependent dynamic differences in the linkers, IAEDANS was conjugated to a cysteine residue substituted at the end of the linker of dimerization domain. Arabinose, but not other sugars, decreased the steady-state anisotropy, indicating either an increase in mobility and/or an increase in the fluorescence lifetime of the IAEDANS. Time-resolved fluorescence measurements showed that the arabinose-induced anisotropy decrease did not result from an increase in the excited-state lifetime. Hence arabinose-induced decreases in anisotropy appear to result from increased tumbling of the fluorophore. Arabinose did not decrease the anisotropy in mutants incapable of binding arabinose nor did it alter the anisotropy when IAEDANS was conjugated elsewhere in the dimerization domain. Experiments with heterodimers of the dimerization domain showed that the binding of arabinose to one subunit of the dimer decreases the fluorescence anisotropy of only a fluorophore on the linker of the other subunit.
Bibliometric analyses of the hand and wrist research have previously shown a significant increase in research productivity in Asia. We examined the key contributors to this change by performing bibliometric analyses regarding hand and wrist research in all Asian countries producing significant research. Original research articles from 1988 to 2007 were collected from seven English language journals based on the impact factor. Trends in research productivity were determined by country using linear regression analysis. Compared to the rest of the world, Asia produced fewer level I and basic studies, but more level IV studies. Significant increase in both research volume and productivity in Asia was observed, with Japan, Korea, and Taiwan having the highest aggregate productivity in hand and wrist research. From 1988 to 2007, the relative research production among Asian countries showed significant change, in contrary to that of Europe, Latin American, and the United States.
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