The purpose of this study was to measure and compare the voice onset times (VOTs) of healthy individuals using a normal and breathy voice in an effort to determine if VOT can be used as a noninvasive clinical indicator of laryngeal function. Recordings were made of 20 adults between the ages of 20-48 with normal laryngeal function, each using a normal (Group 1) and breathy voice (Group 2). The participants’ productions were designed and collected in such a manner to control for speaking rate, vowel context, pitch, and loudness; all of which have been shown to influence VOT. A mixed analyses of variance showed that hypofunctional productions demonstrated longer VOTs across all stop consonants when compared to normal productions. Within the stops, a significant difference between the voiced and voiceless stops was noted, although no gender differences were found. It was concluded that VOT can be used as an indirect clinical indicator of laryngeal function.

The purpose of this study was to measure and compare the voice onset times (VOTs) of healthy individuals using a normal and breathy voice in an effort to determine if VOT can be used as a noninvasive clinical indicator of laryngeal function. Recordings were made of 20 adults between the ages of 20-48 with normal laryngeal function, each using a normal (Group 1) and breathy voice (Group 2). The participants’ productions were designed and collected in such a manner to control for speaking rate, vowel context, pitch, and loudness; all of which have been shown to influence VOT. A mixed analyses of variance showed that hypofunctional productions demonstrated longer VOTs across all stop consonants when compared to normal productions. Within the stops, a significant difference between the voiced and voiceless stops was noted, although no gender differences were found. It was concluded that VOT can be used as an indirect clinical indicator of laryngeal function.

The N-methyl-D-aspartate receptor (NMDAR) hypofunctional hypothesis is believed to explain one of the contributing factors to schizophrenia. This hypothesis suggests the dysregulation of NMDAR, a protein responsible for receiving signals from the synapses between neurons, is the cause of some of the symptoms seen in schizophrenia. The post synaptic density protein 95 (PSD95) uses its PDZ-domains to help facilitate the received signal from NMDAR to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) which in turn transmits the signal through the neuron. One way to increase the function of NMDAR could be to increase its affinity towards PDZ-domains of PSD95 using a small molecule. Fragment based drug design (FBDD) is one way to screen for molecules that modulates the NMDAR-PDZ interaction. This work describes the development of differential scanning fluorimetry (DSF) and surface plasmon resonance (SPR) assays using a fusion protein to screen for molecules that potentiate the interaction between NMDAR and AMPAR as well as methods assisting in the prioritization of hits based on both affinity, selectivity, and mechanism. The developed assays were used to screen a library containing 768 compounds. Screen positives and other compounds of interest were triaged and evaluated based on affinity, selectivity, and ability to modulated peptide binding resulting in eight confirmed hits that interacts with the two PDZ-domains of PSD95 investigated. As part of this work, the dissociation constant (KD) was determined for a panel of peptides representing versions of the truncated NMDAR GluN2b-subunit C-terminal towards PDZ1 and 2 of PSD95.