Solid-phase synthesis of lidocaine and procainamide analogues using backbone amide linker (BAL) anchoring

New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.     

Speech recognition in noise as a function of the number of spectral channels: comparison of acoustic hearing and cochlear implants

Speech recognition was measured as a function of spectral resolution (number of spectral channels) and speech-to-noise ratio in normal-hearing (NH) and cochlear-implant (CI) listeners. Vowel, consonant, word, and sentence recognition were measured in five normal-hearing listeners, ten listeners with the Nucleus-22 cochlear implant, and nine listeners with the Advanced Bionics Clarion cochlear implant. Recognition was measured as a function of the number of spectral channels (noise bands or electrodes) at signal-to-noise ratios of + 15, + 10, +5, 0 dB, and in quiet. Performance with three different speech processing strategies (SPEAK, CIS, and SAS) was similar across all conditions, and improved as the number of electrodes increased (up to seven or eight) for all conditions. For all noise levels, vowel and consonant recognition with the SPEAK speech processor did not improve with more than seven electrodes, while for normal-hearing listeners, performance continued to increase up to at least 20 channels. Speech recognition on more difficult speech materials (word and sentence recognition) showed a marginally significant increase in Nucleus-22 listeners from seven to ten electrodes. The average implant score on all processing strategies was poorer than scores of NH listeners with similar processing. However, the best CI scores were similar to the normal-hearing scores for that condition (up to seven channels). CI listeners with the highest performance level increased in performance as the number of electrodes increased up to seven, while CI listeners with low levels of speech recognition did not increase in performance as the number of electrodes was increased beyond four. These results quantify the effect of number of spectral channels on speech recognition in noise and demonstrate that most CI subjects are not able to fully utilize the spectral information provided by the number of electrodes used in their implant.     

Effect of stimulation rate on phoneme recognition by nucleus-22 cochlear implant listeners

This study investigated the effect of pulsatile stimulation rate on medial vowel and consonant recognition in cochlear implant listeners. Experiment 1 measured phoneme recognition as a function of stimulation rate in six Nucleus-22 cochlear implant listeners using an experimental four-channel continuous interleaved sampler (CIS) speech processing strategy. Results showed that all stimulation rates from 150 to 500 pulses/s/electrode produced equally good performance, while stimulation rates lower than 150 pulses/s/electrode produced significantly poorer performance. Experiment 2 measured phoneme recognition by implant listeners and normal-hearing listeners as a function of the low-pass cutoff frequency for envelope information. Results from both acoustic and electric hearing showed no significant difference in performance for all cutoff frequencies higher than 20 Hz. Both vowel and consonant scores dropped significantly when the cutoff frequency was reduced from 20 Hz to 2 Hz. The results of these two experiments suggest that temporal envelope information can be conveyed by relatively low stimulation rates. The pattern of results for both electrical and acoustic hearing is consistent with a simple model of temporal integration with an equivalent rectangular duration (ERD) of the temporal integrator of about 7 ms.     

Food Web Implications of δ13C and δ15N Variability over 370 km of the Regulated Colorado River USA

Abstract

Dual stable isotope analysis in the regulated Colorado River through Grand Canyon National Park, USA, revealed a food web that varied spatially through this arid biome. Down-river enrichment of δ¹³C data was detected across three trophic levels resulting in shifted food webs. Humpack chub δ¹³C and δ¹⁵N values from muscle plugs and fin clips did not differ significantly. Humpback chub and rainbow trout trophic position is positively correlated with standard length indicating an increase in piscivory by larger fishes. Recovery of the aquatic community from impoundment by Glen Canyon Dam and collecting refinements for stable isotope analysis within large rivers are discussed.     

Molecular mechanism of acid-triggered aryl-halide reductive elimination in well-defined aryl-Cu(III)-halide species

Well-defined aryl-Cu(III)-halide species undergo reductive elimination upon acid addition resulting in the formation of strong aryl-halide bonds. The computationally studied mechanism points towards ligand protonation as the rate-determining step, in agreement with previous experimental data.     

Low frequency narrow-band calls in bottlenose dolphins (Tursiops truncatus): signal properties, function, and conservation implications

Dolphins routinely use sound for social purposes, foraging and navigating. These sounds are most commonly classified as whistles (tonal, frequency modulated, typical frequencies 5-10 kHz) or clicks (impulsed and mostly ultrasonic). However, some low frequency sounds have been documented in several species of dolphins. Low frequency sounds produced by bottlenose dolphins (Tursiops truncatus) were recorded in three locations along the Gulf of Mexico. Sounds were characterized as being tonal with low peak frequencies (mean?=?990 Hz), short duration (mean?=?0.069 s), highly harmonic, and being produced in trains. Sound duration, peak frequency and number of sounds in trains were not significantly different between Mississippi and the two West Florida sites, however, the time interval between sounds within trains in West Florida was significantly shorter than in Mississippi (t?=?-3.001, p?=?0.011). The sounds were significantly correlated with groups engaging in social activity (F=8.323, p=0.005). The peak frequencies of these sounds were below what is normally thought of as the range of good hearing in bottlenose dolphins, and are likely subject to masking by boat noise.     

Conditional spin squeezing of a large ensemble via the vacuum Rabi splitting

We use the vacuum Rabi splitting to perform quantum nondemolition measurements that prepare a conditionally spin squeezed state of a collective atomic psuedospin. We infer a 3.4(6) dB improvement in quantum phase estimation relative to the standard quantum limit for a coherent spin state composed of uncorrelated atoms. The measured collective spin is composed of the two-level clock states of nearly 10(6) (87)Rb atoms confined inside a low finesse F=710 optical cavity. This technique may improve atomic sensor precision and/or bandwidth, and may lead to more precise tests of fundamental physics.     

Assessing views of coaching via a video-based tool

Mathematics coaches represent a unique group of didacticians, or individuals who work with practicing teachers. Twenty-eight mathematics coaches participated in this exploratory study, which used video viewing to examine the coach–teacher dynamic. To gather data about participants’ views of effective coaching practices, we developed the Video Assessment of Coaching instrument, which provided coaches with opportunities to express their views of effective practice and implementation. The participants expressed views of effective coaching that often did not align with those of coaching authors. The significance of this research lies in its efforts to document the views that mathematics coaches develop as practitioners, as an early step in the examination of the relationships between the views of coaches and coaches’ effectiveness in improving teacher practice, knowledge, and attitudes.