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Biomedical subjects

Yuling Yan

Publications and source records attributed to Yuling Yan.

11 recordsLinked to original sources

Functional analysis of voice using simultaneous high-speed imaging and acoustic recordings.

We present a comprehensive, functional analysis of clinical voice data derived from both high-speed digital imaging (HSDI) of the larynx and simultaneously acquired acoustic recordings. The goals of this study are to: (1) correlate dynamic characteristics of the vocal folds derived from direct laryngeal imaging with indirectly acquired acoustic measurements; (2) define the advantages of using a combined imaging/acoustic approach for the analysis of voice condition; and (3) identify new quantitative measures to evaluate the regularity of the vocal fold vibration and the complexity of the vocal output -- these measures will be key to successful diagnosis of vocal abnormalities. Image- and acoustic-based analyses are performed using an analytic phase plot approach previously introduced by our group (referred to as 'Nyquist' plot). Fast Fourier Transform (FFT) spectral analyses are performed on the same data for a comparison. Clinical HSDI and acoustic recordings from subjects having normal and specific voice pathologies, including muscular tension dysphonia (MTD) and recurrent respiratory papillomatosis (RRP) were analyzed using the Nyquist plot approach. The results of these analyses show that a combined imaging/acoustic analysis approach provides better characterization of the vibratory behavior of the vocal folds as it correlates with vocal output and pathology.

Humans↗

Investigation of voice initiation and voice offset characteristics with high-speed digital imaging.

This study involves preliminary investigation of the characteristics of the voice initiation period (VIP) and voice offset period (VOP) using high-speed digital imaging. The goals of the study were to develop a methodology to objectively analyze these periods of phonation and to explore the feasibility of studying the effects of aging on these phonation segments. Results of the analysis of the data from two female subjects, one younger and one older, with the developed methodology, demonstrated that the older subject's VIP was characterized by a slow and irregular increase in glottal area waveform (GAW) until reaching 90% of the maximum opening of the glottis at 244 frames or 122 ms. The younger subject demonstrated a sharp increase in GAW during VIP, taking only 155 frames or 77.5 ms to reach the 90% mark. Also, the older subject took a greater number of frames for the vocal fold vibration to come to a complete stop than the younger subject during the VOP; 275 frames and 150 frames respectively.

Adult↗

Automatic tracing of vocal-fold motion from high-speed digital images.

Defining characteristics of the phonatory vocal fold vibration is essential for studies that aim to understand the mechanism of voice production and for clinical diagnosis of voice disorders. The application of high-speed digital imaging techniques to these studies makes it possible to capture sequences of images of the vibrating vocal folds at a frequency that can resolve the actual vocal fold vibrations of a patient. The objective of this study is to introduce a new approach for automatic tracing of vocal fold motion from image sequences acquired from high-speed digital imaging of the larynx. The approach involves three process steps. 1) Global thresholding--the threshold value is selected on the basis of the histogram of the image, which is assumed to follow Rayleigh distribution; 2) applying a morphology operator to remove the isolated object regions; 3) using region-growing to delineate the object, or the vocal fold opening region, and to obtain the area of the glottis; the segmented object obtained after global threshold and the morphological operation is used as a seed region for the final region-growing operation. The performance, effectiveness and validation of our approach is demonstrated using representative, high-speed imaging recordings of subjects having normal and pathological voices.

Computer Simulation↗

Family of site-selective molecular optical switches.

[reaction: see text] We describe the design, synthesis, and characterization of a family of thiol-reactive optical switches for labeling proteins and other biomolecules. Site-selective introduction of photochromic probes within biomolecules is being used as part of a new approach for optical control of biomolecular interactions and activities within cells. The thiol-reactive photochromic probes described in this report include a spironaphthoxazine and five spirobenzopyrans. The location of the thiol-reactive group on the spirobenzopyran is different for each probe; this feature can be used to control the geometry of the optical switch within a bioconjugate. The photochromes undergo rapid and reversible, optically driven transitions between a colorless spiro (SP) state and a brightly colored merocyanine (MC) state. The MC absorption of a spironaphthoxazine conjugate is red shifted by more than 100 nm compared to the equivalent spirobenzopyran, which may be exploited for the independent control of the MC to SP transition for up to two different spironaphthoxazine and spirobenzopyran conjugates within the same sample.

Binding Sites↗

Optical switching of dipolar interactions on proteins.

This work shows that optical switching between the spiro (SP) and merocyanine (MC) states of different photochromes specifically labeled to G-actin can be used to rapidly and reversibly modulate specific dipolar interactions within the conjugate. Members of a common spirobenzopyran photochrome and a related spironaphthoxazine that differ only in the locations of their alkylating groups were selectively labeled to Cys-374 on G-actin. The nature of MC and SP interactions within G-actin was investigated by using optical spectroscopy. The average absorption energy of the highly polarized MC is sensitive to interactions with polar groups on solvents and G-actin; the average absorption energy of the corresponding SP state was found to be relatively constant, consistent with its lower dipole moment compared with MC (5 and 20 D, respectively). Alternate excitation of spirobenzopyran G-actin conjugates with 365 and 546 nm leads to rapid transitions from the SP to MC states and MC to SP states, respectively; optical switching within spirobenzopyran-G-actin occurs with high fidelity and the recovery of specific dipolar interactions between the protein and the MC and SP states. The difference in the free energy for specific dipolar interactions between different MC states within G-actin (6 kcal/mol) is similar to that found for complexes of G-actin and its regulatory proteins. We propose, therefore, that optical switching between SP and MC within an appropriately labeled conjugate could be used to inhibit a functional interaction with a ligand in the MC, but not the SP, state.

Actins↗

Analysis of vocal-fold vibrations from high-speed laryngeal images using a Hilbert transform-based methodology.

This paper presents a Hilbert transform-based approach to analyze vocal fold vibrations in human subjects exhibiting normal and abnormal voice productions. This new approach is applied to the analysis of glottal area waveform (GAW) and is capable of providing useful information on the vocal fold vibration. The GAW is extracted from high-speed laryngeal images by delineating the glottal edge for each image frame. An analytic signal is generated through the Hilbert transform of the GAW, which yields a recognizable pattern of the vocal fold vibration in the analytic phase plane. The vibratory pattern is comprehensive and can be correlated with specific voice conditions. Quantitative measures of the glottal perturbation are introduced using the analytic amplitude and instantaneous frequency obtained from the analysis. Examples of clinical voice recordings are used to evaluate and test the effectiveness of this approach in providing qualitative representation and quantitative characteristics of vocal fold vibratory behavior. The results demonstrate the potential of using this new analytical tool incorporated with the high-speed laryngeal imaging modality for clinical voice assessment.

Equipment Design↗

Quantitative functional analysis of protein complexes on surfaces.

A major challenge in cell and molecular physiology research is to understand the mechanisms of biological processes in terms of the interactions, activities and regulation of the underlying proteins. Functional and mechanistic analyses of the large number of proteins that participate in the regulation of cellular processes will require new approaches and techniques for high throughput and multiplexed functional analyses of protein interactions, protein conformational dynamics and protein activity. In this review we focus on the development and application of proteomics and associated technologies for quantitative functional analysis of proteins and their complexes that include: (1) the application of surface plasmon resonance (SPR) imaging for multiplexed, label-free analyses of protein interactions, binding constants for biomolecular interactions and protein activities; and (2) high content analysis of protein motions within functional multiprotein complexes.

Animals↗

Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides.

This study characterizes the interactions between kabiramide C (KabC) and related macrolides and actin and establishes the mechanisms that underlie their inhibition of actin filament dynamics and cytotoxicity. The G-actin-KabC complex is formed through a two-step binding reaction and is extremely stable and long-lived. Competition-binding studies show that KabC binds to the same site on G-actin as Gelsolin domain 1 and CapG. KabC also binds to protomers within F-actin and results in the severing and capping of the (+) end; these studies suggest that free KabC and related macrolides act as biomimetics of Gelsolin. The G-actin-KabC complex binds to the (+) end of a growing filament, where it functions as a novel, unregulated, (+)-end capper and is largely responsible for the inhibition of motility and cytokinesis in approximately 10 -100 nM KabC-treated cells. KabC and related macrolides are useful probes to study the regulation of the actin filament (+) end and may lead to new therapies to treat diseases of the actin cytoskeleton.

2-Naphthylamine↗

Analysis of protein interactions using fluorescence technologies.

Biophotonics techniques, especially those involving fluorescence, are widely used in proteomics to characterize the in vitro interactions between proteins in high-throughput mode. On the other hand, fluorescence-based imaging studies often show that protein activity is regulated through large protein complexes that transiently form at specific sites in the cell. One could therefore argue that a systematic functional analysis of the human proteome requires technologies that are capable of time and spatially resolved, multiplexed analysis of protein interactions within cells.

Fluorescence Resonance Energy Transfer↗

Fluorescent kabiramides: new probes to quantify actin in vitro and in vivo.

We present the design, synthesis, and biochemical and spectroscopic characterization of five functional fluorescent conjugates of kabiramide C (KabC), a small molecule biomimetic of gelsolin. The tetramethylrhodamine (TMR), rhodol green (RG), IC5, dapoxyl (DAP), and fluorescein diester (FDE) conjugates of KabC bind specifically to actin at the barbed end in a 1:1 complex. These probes are shown to function in an indistinguishable manner to the unmodified KabC. Various modalities of the fluorescence emission of these KabC probes, including fluorescence anisotropy and fluorescence resonance energy transfer, are used for the development of assays for the rapid determination of G-actin concentration in solution. The TMR-KabC and FDE-KabC probes are cell permeable and provide unique imaging information on the distribution and dynamics of actin filament within living cells.

3T3 Cells↗