Optical measurements of vocal fold tensile properties: implications for phonatory mechanics

In voice research, in vitro tensile stretch experiments of vocal fold tissues are commonly employed to determine the tissue biomechanical properties. In the standard stretch-release protocol, tissue deformation is computed from displacements applied to sutures inserted through the thyroid and arytenoid cartilages, with the cartilages assumed to be rigid. Here, a non-contact optical method was employed to determine the actual tissue deformation of vocal fold lamina propria specimens from three excised human larynges in uniaxial tensile tests. Specimen deformation was found to consist not only of deformation of the tissue itself, but also deformation of the cartilages, as well as suture alignment and tightening. Stress-stretch curves of a representative load cycle were characterized by an incompressible Ogden model. The initial longitudinal elastic modulus was found to be considerably higher if determined based on optical displacement measurements than typical values reported in the literature. The present findings could change the understanding of the mechanics underlying vocal fold vibration. Given the high longitudinal elastic modulus the lamina propria appeared to demonstrate a substantial level of anisotropy. Consequently, transverse shear could play a significant role in vocal fold vibration, and fundamental frequencies of phonation should be predicted by beam theories accounting for such effects.     

Design of a mechanical larynx with agarose as a soft tissue substitute for vocal fold applications

Mechanical and computational models consisting of flow channels with convergent and oscillating constrictions have been applied to study the dynamics of human vocal fold vibration. To the best of our knowledge, no mechanical model has been studied using a material substitute with similar physical properties to the human vocal fold for surgical experimentation. In this study, we design and develop a mechanical larynx with agarose as a vocal fold substitute, and assess its suitability for surgical experimentation. Agarose is selected as a substitute for the vocal fold as it exhibits similar nonlinear hyperelastic characteristics to biological soft tissue. Through uniaxial compression and extension tests, we determined that agarose of 0.375% concentration most closely resembles the vocal fold mucosa and ligament of a 20-year old male for small tensile strain with an R(2) value of 0.9634 and root mean square error of 344.05±39.84?Pa. Incisions of 10 mm lengthwise and 3 mm in depth were created parallel to the medial edge on the superior surface of agar phantom. These were subjected to vibrations of 80, 130, and 180 Hz, at constant amplitude of 0.9 mm over a period of 10 min each in the mechanical larynx model. Lateral expansion of the incision was observed to be most significant for the lower frequency of 80 Hz. This model serves as a basis for future assessments of wound closure techniques during microsurgery to the vocal fold.     

Modeling mechanical stresses as a factor in the etiology of benign vocal fold lesions

Vocal fold tissue lesions such as nodules and polyps are thought to develop in response to mechanical stress that occurs during vocal fold collision. Two computational models of vocal fold collision during voice production are used to investigate this hypothesis. A one-dimensional lumped mass model, whose parameters are derived from vocal fold tissue dimensions and material properties, predicts stress perpendicular to the direction of impact (normal stress). A previously published three-dimensional finite element model that incorporates the same dimensions and properties predicts the entire stress tensor. The hypothesis is supported by predictions from the finite element model that three components of normal stress and one component of shear stress are increased during collision in the typical location of lesions (i.e. the center of the superior medial edge of the vocal fold in the middle of the vibrating and contact region). The lumped mass model predicts that mechanical stress is negatively correlated with mucosal thickness (increased by voice warm-up and hydration), is positively correlated with driving force (proportional to voice intensity), and is affected by voice production method. These relationships are consistent with clinical observations of vocal fold lesion risk factors and have implications for improving prevention and treatment of benign vocal fold lesions.     

Non-invasive in vivo measurement of the shear modulus of human vocal fold tissue

Voice is the essential part of singing and speech communication. Voice disorders significantly affect the quality of life. The viscoelastic mechanical properties of the vocal fold mucosa determine the characteristics of the vocal folds oscillations, and thereby voice quality. In the present study, a non-invasive method was developed to determine the shear modulus of human vocal fold tissue in vivo via measurements of the mucosal wave propagation speed during phonation. Images of four human subjects' vocal folds were captured using high speed digital imaging (HSDI) and magnetic resonance imaging (MRI) for different phonation pitches, specifically fundamental frequencies between 110 and 440 Hz. The MRI images were used to obtain the morphometric dimensions of each subject's vocal folds in order to determine the pixel size in the high-speed images. The mucosal wave propagation speed was determined for each subject and at each pitch value using an automated image processing algorithm. The transverse shear modulus of the vocal fold mucosa was then calculated from a surface (Rayleigh) wave propagation dispersion equation using the measured wave speeds. It was found that the mucosal wave propagation speed and therefore the shear modulus of the vocal fold tissue were generally greater at higher pitches. The results were in good agreement with those from other studies obtained via in vitro measurements, thereby supporting the validity of the proposed measurement method. This method offers the potential for in vivo clinical assessments of vocal folds viscoelasticity from HSDI.     

Motor mechanisms of a vocal mimic: implications for birdsong production

The diverse vocal performances of oscine songbirds are produced by the independent but coordinated patterns of activity in muscles controlling separate sound generators on the left and right sides of their duplex vocal organ, the syrinx. Species with different song styles use the two sides of their syrinx in different ways to produce their species-typical songs. Understanding how a vocal mimic copies another species' song may provide an insight into whether there are alternative motor mechanisms for generating the model's song and what parts of his song are most difficult to produce. We show here that when a vocal mimic, the northern mockingbird, accurately copies the song of another species it also uses the vocal motor pattern employed by the model species. Deviations from the model's production mechanism result in predictable differences in the mockingbird's song. Species-specific acoustic features of the model seem most difficult to copy, suggesting that they have been exposed to the strongest selective pressure to maximize their performance.     

Modeling of the metabolic energy dissipation for restricted tumor growth

Energy dissipation mostly represents unwanted outcome but in the biochemical processes it may alter the biochemical pathways. However, it is rarely considered in the literature although energy dissipation and its alteration due to the changes in cell microenvironment may improve methods for guiding chemical and biochemical processes in the desired directions. Deeper insight into the changes of metabolic activity of tumor cells exposed to osmotic stress or irradiation may offer the possibility of tumor growth reduction. In this work effects of the osmotic stress and irradiation on the thermodynamical affinity of tumor cells and their damping effects on metabolic energy dissipation were investigated and modeled. Although many various models were applied to consider the tumor restrictive growth they have not considered the metabolic energy dissipation. In this work a pseudo rheological model in the form of “the metabolic spring-pot element” is formulated to describe theoretically the metabolic susceptibility of tumor spheroid. This analog model relates the thermodynamical affinity of cell growth with the volume expansion of tumor spheroid under isotropic loading conditions. Spheroid relaxation induces anomalous nature of the metabolic energy dissipation which causes the damping effects on cell growth. The proposed model can be used for determining the metabolic energy “structure” in the context of restrictive cell growth as well as for predicting optimal doses for cancer curing in order to tailor the clinical treatment for each person and each type of cancer.     

Synchrotron x-ray diffraction studies of the cornea, with implications for stromal hydration.

The intermolecular and interfibrillar spacings of collagen in bovine corneal stroma have been measured as a function of tissue hydration. Data were recorded from low- and high-angle x-ray diffraction patterns obtained using a high intensity synchrotron source. The most frequently occurring interfibrillar spacing varied from 34 nm in dry corneas to 76 nm at H = 5 (the hydration, H, is defined as the ratio of the weight of water to the dry weight). The most frequently occurring intermolecular Bragg spacing increased from 1.15 nm (dry) to approximately 1.60 nm at normal hydration (H approximately 3.2) and continued to increase only slowly above normal hydration. Most of the increase in the intermolecular spacing occurred between H = O and H = 1. Over this hydration range the interfibrillar and intermolecular spacings moved in tandem, which suggests that the initial water goes equally within and between the fibrils. Above H = 1 water goes preferentially between the fibrils. The results suggest that, even at normal hydration, water does not fill the interfibrillar space uniformly, and a proportion is located in another space or compartment. In dried-then-rehydrated corneas, a larger proportion of the water goes into this other compartment. In both cases, it is possible to postulate a second set or population of fibrils that are more widely and irregularly separated and therefore do not contribute significantly to the diffraction pattern.     

Protein fold recognition and dynamics in the space of contact maps

We introduce an energy function for contact maps of proteins. In addition to the standard term, that takes into account pair-wise interactions between amino acids, our potential contains a new hydrophobic energy term. Parameters of the energy function were obtained from a statistical analysis of the contact maps of known structures. The quality of our energy function was tested extensively in a variety of ways. In particular, fold recognition experiments revealed that for a fixed sequence the native map is identified correctly in an overwhelming majority of the cases tested. We succeeded in identifying the structure of some proteins that are known to pose difficulties for such tests (BPTI, spectrin, and cro-protein). In addition, many known pairs of homologous structures were correctly identified, even when the two sequences had relatively low sequence homology. We also introduced a dynamic Monte Carlo procedure in the space of contact maps, taking topological and polymeric constraints into account by restrictive dynamic rules. Various aspects of protein dynamics, including high-temperature melting and refolding, were simulated. Perspectives of application of the energy function and the method for structure checking and fold prediction are discussed. Proteins 26:391–410 © 1996 Wiley-Liss, Inc.     

The influence of tissue section thickness on the study of collagen by the Picrosirius-polarization method

Summary The influence of tissue section thickness on the color and intensity of birefringence displayed by collagen in tissue sections studied by means of the Picrosirius-polarization method, is reported in this paper. When dermal collagen sections of different thicknesses (ranging from 0.25 to 11 m) were studied by this method, it became evident that not only did the intensity of birefringence increase proportionally to tissue section thickness, as was to be expected, but also a gradual shift in color from green through yellow to red could be observed as tissue section thickness increased. The limitations of the Picrosirius-polarization method for the localization of collagen types I, II, and III in routinely used histological slides is discussed, showing that this method is useful for the study of the distribution of the different types of interstitial collagen in normal adult vertebrate organs.     

Modeling the influence of local environmental factors on malaria transmission in Benin and its implications for cohort study

Malaria remains endemic in tropical areas, especially in Africa. For the evaluation of new tools and to further our understanding of host-parasite interactions, knowing the environmental risk of transmission--even at a very local scale--is essential. The aim of this study was to assess how malaria transmission is influenced and can be predicted by local climatic and environmental factors.As the entomological part of a cohort study of 650 newborn babies in nine villages in the Tori Bossito district of Southern Benin between June 2007 and February 2010, human landing catches were performed to assess the density of malaria vectors and transmission intensity. Climatic factors as well as household characteristics were recorded throughout the study. Statistical correlations between Anopheles density and environmental and climatic factors were tested using a three-level Poisson mixed regression model. The results showed both temporal variations in vector density (related to season and rainfall), and spatial variations at the level of both village and house. These spatial variations could be largely explained by factors associated with the house's immediate surroundings, namely soil type, vegetation index and the proximity of a watercourse. Based on these results, a predictive regression model was developed using a leave-one-out method, to predict the spatiotemporal variability of malaria transmission in the nine villages.This study points up the importance of local environmental factors in malaria transmission and describes a model to predict the transmission risk of individual children, based on environmental and behavioral characteristics.     

Influence of asymmetric stiffness on the structural and aerodynamic response of synthetic vocal fold models

The influence of asymmetric vocal fold stiffness on voice production was evaluated using life-sized, self-oscillating vocal fold models with an idealized geometry based on the human vocal folds. The models were fabricated using flexible, materially-linear silicone compounds with Young's modulus values comparable to that of vocal fold tissue. The models included a two-layer design to simulate the vocal fold layered structure. The respective Young's moduli of elasticity of the “left” and “right” vocal fold models were varied to create asymmetric conditions. High-speed videokymography was used to measure maximum vocal fold excursion, vibration frequency, and left–right phase shift, all of which were significantly influenced by asymmetry. Onset pressure, a measure of vocal effort, increased with asymmetry. Particle image velocimetry (PIV) analysis showed significantly greater skewing of the glottal jet in the direction of the stiffer vocal fold model. Potential applications to various clinical conditions are mentioned, and suggestions for future related studies are presented.     

Design and validation of a bioreactor for engineering vocal fold tissues under combined tensile and vibrational stresses

Criteria are outlined for the design of a bioreactor that can simulate the vibrational stresses in vocal fold movement during speech. Requirements are 0-1 mm amplitudes in the 20-200 Hz frequency range, a variable on-off stress regime, and maintenance of tissue viability over several days. The bioreactor uses dual drivers, one for low frequency (or static) strains, and another for high-frequencies vibrational strains. Response is linear at the driving end for an input of 0-5 V. The amplitude decreases linearly with frequency at constant input voltage, and the phase changes by nearly 180 degrees over the 20-200 Hz range. Human vocal fold fibroblasts were cultured in a polymer substrate and subjected to static and vibrational forces. The results indicate that vibratory strain alters the expression levels of many extracellular matrix-related genes, as well as the spatial distribution of cells and matrix.     

Relaxation folding and the principle of the minimum rate of energy dissipation for conformational motions in a viscous medium

A numerical simulation of the folding of a model polymer chain of 50 units with valence bonds of a fixed length and fixed valence angle values has been performed using the strong friction approximation. The rate of energy dissipation in the system has been analyzed for conformational motions along a trajectory determined by the equations of mechanics and the trajectories characterized by random and variable deviations from the mechanical path. The validity of the principle of the minimum average rate of the energy dissipation for the conformational relaxation of a macromolecule in a viscous medium has been demonstrated. A profile of the relaxation energy funnel for the folding of a macromolecular chain has been constructed. Slow and rapid stages of folding could be distinguished in the energy funnel profile; the final state was separated from the nearest conformations of the folded chain by an energy gap.     

Dialect change in resident killer whales: implications for vocal learning and cultural transmission

Variation in vocal signals among populations and social groups of animals provides opportunities for the study of the mechanisms of behavioural change and their importance in generating and maintaining behavioural variation. We analysed two call types made by two matrilineal social groups of resident killer whales, Orcinus orca, over 12-13 years. We used a neural network-based index of acoustic similarity to identify mechanisms of call differentiation. A test for structural modification of the calls detected significant changes in one call type in both groups, but not in the other. For the modified call type, the rate of divergence between the two groups was significantly lower than the rate of modification within either group showing that calls were modified in a similar fashion in the two groups. An analysis of structural parameters detected no strong directionality in the change. The pattern of call modification could have been caused by maturational changes to the calls or, if killer whale dialects are learned behavioural traits, cultural drift in the structure of the calls together with horizontal transmission of modifications between the two groups. Such vocal matching between members of different matrilines would suggest that vocal learning is not limited to vertical transmission from mother to offspring, which has important implications for models of gene-culture coevolution. Copyright 2000 The Association for the Study of Animal Behaviour.     

Noninvasive fluid dynamic power loss assessments for total cavopulmonary connections using the viscous dissipation function: a feasibility study

The total cavopulmonary connection (TCPC) has shown great promise as an effective palliation for single-ventricle congenital heart defects. However, because the procedure results in complete bypass of the right-heart, fluid dynamic power losses may play a vital role in postoperative patient success. Past research has focused on determining power losses using control volume methods. Such methods are not directly applicable clinically without highly invasive pressure measurements. This work proposes the use of the viscous dissipation function as a tool for velocity gradient based estimation of fluid dynamic power loss. To validate this technique, numerical simulations were conducted in a model of the TCPC incorporating a 13.34 mm (one caval diameter) caval offset and a steady cardiac output of 2 L x min(-1). Inlet flow through the superior vena cava was 40 percent of the cardiac output, while outflow through the right pulmonary artery (RPA) was varied between 30 and 70 percent, simulating different blood flow distributions to the lungs. Power losses were determined using control volume and dissipation function techniques applied to the numerical data. Differences between losses computed using these techniques ranged between 3.2 and 9.9 percent over the range of RPA outflows studied. These losses were also compared with experimental measurements front a previous study. Computed power losses slightly exceeded experimental results due to different inlet flow conditions. Although additional experimental study is necessary to establish the clinical applicability of the dissipation function, it is believed that this method, in conjunction with velocity gradient information derived from imaging modalities such as magnetic resonance imaging, can provide a noninvasive means of assessing power losses within the TCPC in vivo.     

Distribution of the energy dissipation rates among degrees of freedom during conformational movements and folding of a macromolecular chain in a viscous medium

The principle of the minimum rate of energy dissipation for conformational movements in a viscous medium formulated in an earlier study (K.V. Shaitan, Biophysics, 2015, Vol. 60, p. 692) has been applied for a theoretical estimation of the distribution functions of the energy dissipation rates for selected elements of a macromolecule. Equipartition of energy dissipation rates among the nodes of the chain upon conformational movements in the statistical limit of the process is obtained. The uniform distribution of energy dissipation rates along the chain does affect on the formation of the collective conformational degrees of freedom and the folding dynamics.     

The role of vocal self-stimulation in female responses to males: implications for state-reading

As research neurobiologists, we pursue specific questions, and the answers rendered are also correspondingly specific. Our goal, however, is to understand an entire system or the whole organism. To that end, it is not only useful, but sometimes also necessary, that we periodically reappraise a body of specific data in light of current knowledge of the field at large. In this spirit, the present paper reviews my work on the neural and hormonal mechanisms underlying the reproductive system of ring doves and others' studies of songbirds. By integrating these fields I then advance the concept that inherent in the avian breeding system is the mechanism of "state-reading" (a term fashioned after "mindreading", which was coined by cognitive neuroscientists). State-reading helps to coordinate a sequence of endocrine and behavioral events to realize a desired objective, in this case, successful reproduction.     

Examining the influence of hydration status on physiological responses and running speed during trail running in the heat with controlled exercise intensity

The purpose of this study was to determine the effects of dehydration at a controlled relative intensity on physiological responses and trail running speed. Using a randomized, controlled crossover design in a field setting, 14 male and female competitive, endurance runners aged 30 ± 10.4 years completed 2 (hydrated [HY] and dehydrated [DHY]) submaximal trail runs in a warm environment. For each trial, the subjects ran 3 laps (4 km per lap) on trails with 4-minute rests between laps. The DHY were fluid restricted 22 hours before the trial and during the run. The HY arrived euhydrated and were given water during rest breaks. The subjects ran at a moderate pace matched between trials by providing pacing feedback via heart rate (HR) throughout the second trial. Gastrointestinal temperature (T(GI)), HR, running time, and ratings of perceived exertion (RPE) were monitored. Percent body mass (BM) losses were significantly greater for DHY pretrial (-1.65 ± 1.34%) than for HY (-0.03 ± 1.28%; p < 0.001). Posttrial, DHY BM losses (-3.64 ± 1.33%) were higher than those for HY (-1.38 ± 1.43%; p < 0.001). A significant main effect of T(GI) (p = 0.009) was found with DHY having higher T(GI) postrun (DHY: 39.09 ± 0.45°C, HY: 38.71 ± 0.45°C; p = 0.030), 10 minutes post (DHY: 38.85 ± 0.48°C, HY: 38.46 ± 0.46°C; p = 0.009) and 30 minutes post (DHY: 38.18 ± 0.41°C, HY: 37.60 ± 0.25°C; p = 0.000). The DHY had slower run times after lap 2 (p = 0.019) and lap 3 (p = 0.025). The DHY subjects completed the 12-km run 99 seconds slower than the HY (p = 0.027) subjects did. The RPE in DHY was slightly higher than that in HY immediately postrun (p = 0.055). Controlling relative intensity in hypohydrated runners resulted in slower run times, greater perceived effort, and elevated T(GI), which is clinically meaningful for athletes using HR as a gauge for exercise effort and performance.     

Experimental evidence for limited vocal recognition in a wild primate: implications for the social complexity hypothesis

Although monitoring social information is a key aspect of the social complexity hypothesis, surprisingly little work has compared social knowledge across different species of wild animals. In the present study, I use playback experiments to test for individual recognition in wild male geladas (Theropithecus gelada) to compare with published accounts of social knowledge in chacma baboons (Papio ursinus). Geladas and baboons are closely related primates living in socially complex groups that differ dramatically in group size—geladas routinely associate with more than 10 times the number of conspecifics than do baboons. Using grunts from non-rival males to simulate approaches, I examined the strength of a subject male''s response when the ‘approach’ was from the direction of (i) non-rival males (control), or (ii) rival males (a more salient stimulus if playback grunts are not recognized by the subject). I compared responses separately based on the degree of social overlap between the caller and the subject. Responses indicate that male geladas, unlike baboons, do not use vocalizations to recognize all of the individuals they regularly encounter. This represents, to my knowledge, the first documented evidence of ‘missing’ social knowledge in a natural primate population. The sharp distinction between baboons and geladas suggests that geladas are either unable or unmotivated to keep track of the individual identity of other males in their multi-level society—even males with whom they have a large degree of social overlap. Thus, these results are consistent with the central assumption of the social complexity hypothesis that social cognition is costly.