Publications by authors named "Lesher G"

Significant progress has been made in the application of natural language processing (NLP) to augmentative and alternative communication (AAC), particularly in the areas of interface design and word prediction. This article will survey the current state-of-the-science of NLP in AAC and discuss its future applications for the development of next generation of AAC technology.

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A significant barrier to evidence-based practice in Augmentative and Alternative Communication (AAC) is the lack of validated performance measures that can be used by speech-language pathologists and rehabilitation engineers to evaluate the communication and device use of AAC consumers. Recently an effort has been made to develop automated data-logging techniques to facilitate the transcription and analysis of the AAC speaker's device use. A major source of error for the automated measurement of communication rate is the presence of excessive Inter-Selection Intervals (ISIs) (i.

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Background: Assessment of compliance with prescribed therapy is an important aspect of patient management that can be overlooked. Compliance with topical ophthalmic medications is frequently assessed without knowledge of doses obtained per bottle.

Method: Thirty-three normal subjects who agreed to participate were asked to instill one drop of Refresh Tears in each eye twice daily until a 3-ml bottle was empty.

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Many persons with disabilities lack the fine motor coordination necessary to operate traditional keyboards. For these individuals, ambiguous (or reduced) keyboards offer an alternative access method. By placing multiple characters on each key, the size and accessibility of the individual keys can be enhanced without requiring a larger keyboard.

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Psychophysical researchers often need to vary stimuli parametrically during experimental design. The X Portable Interface Package, a set of free software libraries for X-Windows, provides a suitable platform for quickly prototyping visual stimuli and administering simple experiments.

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Although illusory contours were first described nearly a century ago, researchers have only recently begun to approach a consensus on the processes underlying their formation. Neurophysiological and psychophysical evidence indicate that neural mechanisms of the early visual cortex subserve illusory contour generation, although cognitive factors play important roles in determining the final percept. I summarize experiments concerning the determinants of illusory contour strength and form, concentrating on findings particularly relevant to modeling.

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The transformation of 3-bromo-1,6-naphthyridin-2(1H)-ones 8 to thiazolo[4,5-b][1,6]naphthyridin-2(1H)-ones 12 resulted in a 2-9-fold increase in cAMP phosphodiesterase (PDE) III inhibitory potency. Unlike the secondary binding sites on the cAMP PDE III isozyme which interact with the methyl group of milrinone (2) and CI-930 (4), the site which interacts with the 5-substituents of 1,6-naphthyridin-2(1H)-ones and the 8-substituents of thiazolo[4,5-b][1,6]naphthyridin-2(1H)-ones 12 is able to accommodate a diverse group of substituents which have different steric and electronic requirements.

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We describe the biochemical and pharmacologic effects of two novel fused pyridinones derived from milrinone: WIN 58993 and WIN 62005. Both WIN 58993 and WIN 62005 competitively inhibit cyclic GMP-inhibitable low Km cyclic AMP phosphodiesterase (PDE III) from rat heart and canine aorta with Ki values of 25 +/- 3 and 26 +/- 5 nM, respectively, and are selective (at least 160-fold) for PDE III inhibition relative to other PDE isozymes. WIN 58993 and WIN 62005 were given to conscious, chronically instrumented rats and dogs intravenously (i.

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The objectives of this study were to determine the potency and selectivity of the structurally novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, WIN 58237 (1-cyclopentyl-3-methyl-6-(4- pyridyl)pyrazolo[3,4-d]pyrimidin-4-(5H)-one), and to determine if this compound possesses cyclic GMP (cGMP) PDE inhibitory activity in vitro and in vivo. WIN 58237 is a competitive inhibitor of cGMP PDE V from canine aorta, with a Ki value of 170 nM. It is a relatively less potent inhibitor of calmodulin-sensitive PDE I and cGMP-inhibitable cyclic AMP PDE III; but does inhibit cyclic AMP PDE IV with an IC50 value of approximately 300 nM.

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We describe the biochemical, pharmacologic, and in vivo pharmacodynamic profiles of two novel inhibitors of the cyclic GMP-inhibitable, low Km cyclic AMP phosphodiesterase (PDE) III; WIN 63291, a 6-quinolinyl analogue of the prototypic PDE III inhibitor milrinone and WIN 62582, an imidazopyridinone. Both WIN 62582 and WIN 63291 competitively inhibit PDE III from rat, dog, and human heart and from rat and canine aorta with IC50 values of 5-37 and 55-80 nM, respectively; the IC50 values for milrinone ranged from 300 to 520 nM. WIN 62582 and WIN 63291 are at least 1,000-fold selective for PDE III relative to inhibition of PDE isozymes I, II, IV, and V.

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The transformation of milrinone to 1,3-dihydro-5-methyl-6-(4-pyridinyl)-2H-imidazo[4,5-b]pyridin-2-one (13a), 5-methyl-6-(4-pyridinyl)thiazolo[4,5-b]pyridin-2(3H)-one (51), and 7-methyl-6-(4-pyridinyl)-1,8-naphthyridin-2(1H)-one (22) resulted in very potent cAMP PDE III inhibitors with in vitro activity in the nanomolar range. 1,3-Dihydro-2H-imidazo[4,5-b]pyridin-2-ones 13 were prepared from 2-aminopyridine-3-carboxylic acids (7, 10) via Curtius rearrangement. 1,8-Naphthyridin-2(1H)-one 22 and the corresponding 3,4-dihydro derivative 28 were prepared from 5-bromo-2-methyl[3,4'-bipyridin]-6-amine (21) and 5-bromo-2-methyl[3,4-bipyridin]-6(1H)-one (24), respectively, via Heck reaction.

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This in vitro study examined the ability of the available disposable soft contact lenses to absorb various ocular therapeutic agents and release them. After a 2-h or 4-h presoaking time, we measured the amount of drug released into fresh saline baths for up to 3 h. Drug levels were determined spectrophotometrically at the peak ultraviolet (UV) absorption wavelength for each drug.

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Illusory contours can be induced along directions approximately colinear to edges or approximately perpendicular to the ends of lines. Using a rating scale procedure we explored the relation between the two types of inducers by systematically varying the thickness of inducing elements to result in varying amounts of "edge-like" or "line-like" induction. Inducers for our illusory figures consisted of concentric rings with arcs missing.

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1-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-4-ox o-3-quinolinecarboxylic acid (1), a previously reported potent inhibitor of bacterial DNA gyrase, was found to be interactive with mammalian topoisomerase II (topo II). In a DNA-cleavage assay using topo II isolated from HeLa cells, 1 exhibited an EC50 value of 7.6 microM (VP-16; EC50 = 0.

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Two series of medorinone (3) analogs were prepared by modifications at C(2) and C(5). The C(2)-series was prepared from 2-chloro-5-methyl-1,6-naphthyridine (4) by replacement of the chloro group with various nucleophiles. The C(5)-series was prepared from 5-acyl-6-[2-(dimethylamino)-ethenyl]-2(1H)-pyridinone (11), 5-bromo-1,6-naphthyridin-2(1H)-one (17), and 1,3-diketones 19 and 27.

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1. Extracellular single-cell recording techniques were employed to investigate the effects of ocular misalignment on the postnatal development of the spatial response properties of striate cortical neurons. The primary objective of the study was to gain insight into the neural basis of strabismic amblyopia.

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The antibacterial activity of a new 7-dimethylpyridinyl quinolone, WIN 57273, was assessed by using in vitro and in vivo models. Agar inclusion and broth dilution in vitro tests revealed broad-spectrum activity against gram-positive and selected gram-negative organisms, with the greatest potency observed against the staphylococci. The MIC for 90% of coagulase-positive strains tested (MIC90) was less than or equal to 0.

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l-alpha-Acetylmethadol (LAAM) was administered to lactating rat dams, and subsequent effects on hepatic drug-metabolizing enzymes of their offspring were assessed. Dams were given LAAM or a control solution in their drinking water following parturition and throughout lactation. Hepatic ethylmorphine-N-demethylase (EMDM) and aniline hydroxylase (AH) activities, as well as cytochrome P-450 content, were determined in the offspring at 21-23 days of age, or following sexual maturation (61-64 days).

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4-Chloro-2-(4-pyridinyl)pyrimidines were treated with alkylamines to afford the corresponding N-substituted amino derivatives. 4-Amino-2-(4-pyridinyl)pyrimidines and their N-substituted analogues were converted to amides, carbamates, aminomethylenemalonates, and ureas. Many of these compounds were found to have potential antiallergic activity as indicated by the rat passive cutaneous anaphylaxis screen.

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The cardiotonic activity of a new, noncatechol, nonglycoside agent, amrinone, was investigated in vitro and in anesthestized and unanesthetized dogs. Amrinone (3-100 microgram/ml) caused a dose-dependent increase in papillary muscle developed tension and df/dt without significant changes in duration of the contractile cycle or time-to-peak tension. Amrinone induced slight increases in right atrial rate with no changes in electrophysiological properties of the cat papillary muscle or dog Purkinje fibers.

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