ABSTRACT
This paper, the fourth in a series concerned with the level of access afforded to students who use educational interpreters, focuses on the intelligibility of interpreters who use Signing Exact English (SEE). Eight expert receivers of SEE were employed to evaluate the intelligibility of transliterated messages that varied in accuracy and lag time. Results of intelligibility tests showed that, similar to Cued Speech transliterators, (a) accuracy had a large positive effect on transliterator intelligibility, (b) overall intelligibility (69%) was higher than average accuracy (58%), and (c) the likelihood that an utterance reached 70% intelligibility was somewhat sigmoidal in shape, with the likelihood of reaching 70% intelligibility dropping off fastest for accuracy values <65%. Accuracy alone accounted for 53% of the variance in transliterator intelligibility; mouthing was identified as a secondary factor that explained an additional 11%. Although lag time accounted for just .4% of the remaining variance, utterances produced with lag times between .6 and 1.2 s were most likely to exceed 70% intelligibility. With 36% of the variance still unexplained, other sources of transliterator variability (for example, facial expression, nonmanual markers, and mouth/sign synchronization) may also play a role in intelligibility and should be explored in future research.
Subject(s)
Cognition/physiology , Cues , Deafness/rehabilitation , Language , Speech Intelligibility/physiology , Deafness/physiopathology , Deafness/psychology , Humans , Speech Production MeasurementABSTRACT
Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11beta-HSD1 inhibitors. However, the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer. A methyl group was added to the C-5 position to eliminate epimerization, leading to the discovery of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). This compound decreased fed blood glucose and insulin levels and reduced body weight in diet-induced obesity mice.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , Drug Discovery/methods , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacology , Thiazoles/administration & dosage , Thiazoles/pharmacology , 11-beta-Hydroxysteroid Dehydrogenase Type 1/chemistry , Administration, Oral , Animals , Dogs , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacokinetics , Humans , Male , Mice , Models, Molecular , Protein Conformation , Rats , Thiazoles/chemistry , Thiazoles/pharmacokineticsABSTRACT
A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines were synthesized and tested against cathepsin K, cathepsin L and cathepsin B. These new non-covalent inhibitors exhibited single-digit nM inhibition of the cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and human osteoclast resorption assays.
