12 research outputs found
The Lantern Vol. 27, No. 2, Spring 1959
• The Case for a Stratified Society • Education Courses • Some Thoughts for God\u27s Thinking Creatures • Sawdust to the Oats? • To Change the Things I Can... • Vignette • I Meet Goliath • Reverie and Reminiscence • On Flight • In Defense of Jazz • A Description • Line of Retreat • Alan Lomax and the American Folk Song • Dawn Stillness • Seasons • Two Poems • Despair • Too Late • Education • For All Practical Purposes He Was Bald • Contrast • I Belong to the Sea • Waves • Love • The Glory and the Dreamhttps://digitalcommons.ursinus.edu/lantern/1077/thumbnail.jp
Towards a model of sporadic Alzheimer’s disease: aiding design of small molecule TrkA agonists
A Canadian Prospective Study of Linkage of Randomized Clinical Trial to Cancer and Mortality Registry Data
In a prospective study, we sought to determine acceptability of linkage of administrative and clinical trial data among Canadian patients and Research Ethics Boards (REBs). The goal is to develop a more harmonized approach to data, with potential to improve clinical trial conduct through enhanced data quality collected at reduced cost and inconvenience for patients. On completion of the original LY.12 randomized clinical trial in lymphoma (NCT00078949), participants were invited to enrol in the Long-term Innovative Follow-up Extension (LIFE) component. Those consenting to do so provided comprehensive identifying information to facilitate linkage with their administrative data. We prospectively designed a global assessment of this innovative approach to clinical trial follow-up including rates of REB approval and patient consent. The pre-specified benchmark for patient acceptability was 80%. Of 16 REBs who reviewed the research protocol, 14 (89%) provided approval; two in Quebec declined due to small patient numbers. Of 140 patients invited to participate, 115 (82%, 95% CI 76 to 88%) from across 9 Canadian provinces provided consent and their full name, date of birth, health insurance number and postal code to facilitate linkage with their administrative data for long-term follow-up. Linkage of clinical trial and administrative data is feasible and acceptable. Further collaborative work including many stakeholders is required to develop an optimized secure approach to research. A more coordinated national approach to health data could facilitate more rapid testing and identification of new effective treatments across multiple jurisdictions and diseases from diabetes to COVID-19
Use of paramagnetic shift reagents for simplification of nuclear magnetic resonance spectra of organic nitriles
Design and Nuclear Magnetic Resonance (NMR) Structure Determination of the Second Extracellular Immunoglobulin Tyrosine Kinase A (TrkAIg2) Domain Construct for Binding Site Elucidation in Drug Discovery
The tyrosine kinase A (TrkA) receptor
is a validated therapeutic
intervention point for a wide range of conditions. TrkA activation
by nerve growth factor (NGF) binding the second extracellular immunoglobulin
(TrkAIg2) domain triggers intracellular signaling cascades. In the
periphery, this promotes the pain phenotype and, in the brain, cell
survival or differentiation. Reproducible structural information and
detailed validation of protein–ligand interactions aid drug
discovery. However, the isolated TrkAIg2 domain crystallizes as a β-strand-swapped
dimer in the absence of NGF, occluding the binding surface. Here we
report the design and structural validation by nuclear magnetic resonance
spectroscopy of the first stable, biologically active construct of
the TrkAIg2 domain for binding site confirmation. Our structure closely
mimics the wild-type fold of TrkAIg2 in complex with NGF (1WWW.pdb), and the <sup>1</sup>H–<sup>15</sup>N correlation spectra confirm that both
NGF and a competing small molecule interact at the known binding interface
in solution