Validation of a flow-structure-interaction computation model of phonation

Computational models of vocal fold (VF) vibration are becoming increasingly sophisticated, their utility currently transiting from exploratory research to predictive research. However, validation of such models has remained largely qualitative, raising questions over their applicability to interpret clinical situations. In this paper, a computational model with a segregated implementation is detailed. The model is used to predict the fluid–structure interaction(FSI) observed in a physical replica of the VFs when it is excited by airflow. Detailed quantitative comparisons are provided between the computational model and the corresponding experiment. First, the flow model is separately validated in the absence of VF motion. Then, in the presence of flow-induced VF motion, comparisons are made of the flow pressure on the VF walls and of the resulting VF displacements. Self-similarity of spatial distributions of flow pressure and VF displacements is highlighted. The self-similarity leads to normalized pressure and displacement profiles. It is shown that by using linear superposition of average and fluctuation components of normalized computed displacements, it is possible to determine displacements in the physical VF replica over a range of VF vibration conditions. Mechanical stresses in the VF interior are related to the VF displacements, thereby the computational model can also determine VF stresses over a range of phonation conditions

The role of glottal surface adhesion on vocal folds biomechanics

The airway surface liquid (ASL) is a very thin mucus layer and covers the vocal fold (VF) surface. Adhesion mediated by the ASL occurs during phonation as the VFs separate after collision. Such adhesion is hypothesized to determine voice quality and health. However, biomechanical insights into the adhesive processes during VF oscillation are lacking. Here, a computational study is reported on self-sustained VF vibration involving contact and adhesion. The VF structural model and the glottal airflow are considered fully three dimensional. The mechanical behavior of the ASL is described through a constitutive traction–separation law where mucosal cohesive strength, cohesive energy, and rupture length enter. Cohesive energy values considered are bound below by the cohesive energy of water at standard temperature and pressure. Cohesive strength values considered are bound above by prior reported data on the adhesive strength of mucosal surface of rat small intestine. This model introduces a mechanical length scale into the analysis. The sensitivity of various aspects of VF dynamics such as flow-declination rate, VF separation under adhesive condition, and formation of multiple local fluid bridges is determined in relation to specific ASL adhesive properties. It is found that for the ASL considered here, the characteristics of the VF separation process are of debond type. Instabilities lead to the breakup of the bond area into several smaller bond patches. Such finding is consistent with in vivo observations

A computational study of systemic hydration in vocal fold collision

Mechanical stresses develop within vocal fold (VF) soft tissues due to phonation-associated vibration and collision. These stresses in turn affect the hydration of VF tissue and thus influence voice health. In this paper, high-fidelity numerical computations are described, taking into account fully 3D geometry, realistic tissue and air properties, and high-amplitude vibration and collision. A segregated solver approach is employed, using sophisticated commercial solvers for both the VF tissue and glottal airflow domains. The tissue viscoelastic properties were derived from a biphasic formulation. Two cases were considered, whereby the tissue viscoelastic properties corresponded to two different volume fractions of the fluid phase of the VF tissue. For each case, hydrostatic stresses occurring as a result of vibration and collision were investigated. Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF tissue was estimated from the hydrostatic stress gradient. Computed measures of overall VF dynamics (peak airflow velocity, magnitude of VF deformation, frequency of vibration and contact pressure) were well within the range of experimentally observed values. The VF motion leading to mechanical stresses within the VFs and their effect on the interstitial fluid flux is detailed. It is found that average deformation and vibration of VFs tend to increase the state of hydration of the VF tissue, whereas VF collision works to reduce hydration

Using Bad Learners to find Good Configurations

Finding the optimally performing configuration of a software system for a given setting is often challenging. Recent approaches address this challenge by learning performance models based on a sample set of configurations. However, building an accurate performance model can be very expensive (and is often infeasible in practice). The central insight of this paper is that exact performance values (e.g. the response time of a software system) are not required to rank configurations and to identify the optimal one. As shown by our experiments, models that are cheap to learn but inaccurate (with respect to the difference between actual and predicted performance) can still be used rank configurations and hence find the optimal configuration. This novel \emph{rank-based approach} allows us to significantly reduce the cost (in terms of number of measurements of sample configuration) as well as the time required to build models. We evaluate our approach with 21 scenarios based on 9 software systems and demonstrate that our approach is beneficial in 16 scenarios; for the remaining 5 scenarios, an accurate model can be built by using very few samples anyway, without the need for a rank-based approach.Comment: 11 pages, 11 figure

New generation of cell‐penetrating peptides: Functionality and potential clinical application

Cell‐penetrating peptides (CPPs) can transport various cargoes through membranes of live cells. Since the first generations of CPPs suffered from insufficient cell and tissue selectivity, stability against proteases, and escape from endosomes, a new generation of peptides, with optimized properties, was developed. These are either derived from natural sources or created through the combination of multivalent structures. The second method allows achieving high internalization efficiency, high cell and tissue selectivity, and release from endosomes via hybrid structures, combining sequences for endosomal release, homing sequences, and sequences for activation at the target tissue and for local delivery of cargoes. CPPs with innate tumor selectivity include azurin, crotamine, maurocalcine, lycosin‐I, buffalo cathelicidin, and peptide CB5005. Some of them can penetrate the membranes of live cells and influence intracellular signaling pathways, thereby exerting cytotoxic effects against tumor cells. To obtain multilayer penetration and stabilization against proteolytic degradation, as well as for better handling, CPPs are often conjugated to nanoparticles. A special problem for tumor treatment is the efficiency of drug transport through three‐dimensional cell cultures. Therefore, the capability of CPPs to deliver the drug even to the innermost tissues is of crucial importance. Notably, the ability of certain CPPs to penetrate barriers such as skin, the blood‐brain barrier (BBB), and cornea or conjunctiva of eyes enabled the replacement of dangerous and painful injections with soothing sprays, creams, and drops. However, it is difficult to rank the efficacy of CPPs because transport efficiency and tissue selectivity depend not only on the CPP itself but also on the target tissue or organ, as well as on the cargo and method of CPP‐cargo coupling. Therefore, the present review describes some examples of new‐generation CPPs and aims to provide advice on how to find or create the right CPP for a given task

Role of gradients in vocal fold elastic modulus on phonation

New studies show that the elastic properties of the vocal folds (VFs) vary locally. In particular strong gradients exist in the distribution of elastic modulus along the length of the VF ligament, which is an important load-bearing constituent of the VF tissue. There is further evidence that changes in VF health are associated with alterations in modulus gradients. The role of VF modulus gradation on VF vibration and phonation remains unexplored. In this study the magnitude of the gradient in VF elastic modulus is varied, and sophisticated computational simulations are performed of the self-oscillation of three-dimensional VFs with realistic modeling of airflow physical properties. Results highlight that phonation frequency, characteristic modes of deformation and phase differences, glottal airflow rate, spectral-width of vocal output, and glottal jet dynamics are dependent on the magnitude of VF elastic modulus gradation. The results advance the understanding of how VF functional gradation can lead to perceptible changes in speech quality

Stratospheric age of air computed with trajectories based on various 3D-Var and 4D-Var data sets

International audienceThe age of stratospheric air is computed with a trajectory model, using ECMWF ERA-40 3D-Var and operational 4D-Var winds. Analysis as well as forecast data are used. In the latter case successive forecast segments are put together to get a time series of the wind fields. This is done for different forecast segment lengths. The sensitivity of the computed age to the forecast segment length and assimilation method are studied, and the results are compared with observations and with results from a chemistry transport model that uses the same data sets. A large number of backward trajectories are started in the stratosphere, and from the fraction of these trajectories that has passed the tropopause the age of air is computed. First, for ten different data sets 50-day backward trajectories starting in the tropical lower stratosphere are computed. The results show that in this region the computed cross-tropopause transport decreases with increasing forecast segment length. Next, for three selected data sets (3D-Var 24-h and 4D-Var 72-h forecast segments, and 4D-Var analyses) 5-year backward trajectories are computed that start all over the globe at an altitude of 20km. For all data sets the computed ages of air in the extratropics are smaller than the observation-based age. For 4D-Var forecast series they are closest to the observation-based values, but still 0.5-1.5 year too small. Compared to the difference in age between the results for the different data sets, the difference in age between the trajectory and the chemistry transport model results is small

Galaxias maculatus (Galaxiidae, Salmoniformes) infectados com Acanthostomoides apophalliformis (Digenea, Platyhelminthes) no Sul da Argentina: Histopatologia e ausência de mortalidade induzida

Este estudo foi conduzido para analisar ao nível histopatológico, lesões produzidas por Acanthostomoides apophalliformis no peixe nativo Galaxias maculatus, e relacioná-las com os resultados do mortalidade induzida por parasitas na população dessa espécie, no lago Moreno, Parque Nacional Nahuel Huapi, Argentina. A ausência de inflamação na maioria das lesões, o fígado sem alterações em uma distância curta do foco das lesões e a aparência viável dos parasitas, sugerem uma boa relação parasita-hospedeiro. Esta hipótese é reforçada pelos dados que mostram a ausência de mortalidade induzida por A. apophalliformis na população dos peixes.This study was conducted to analyze at histopathological level, lesions produced by Acanthostomoides apophalliformis in the native fish Galaxias maculatus, and relate them to quantitative results on parasite- induced fish mortality, in Lake Moreno, Southern, Argentina. Absence in most lesions of inflammatory reaction, unaltered hepatic parenchyma at a short distance from the foci of the lesions and viable appearance of parasites, all suggest a good reciprocal adaptation.. This hypothesis is reinforced by data showing the absence of A. apophalliformis-induced mortality in the fish population

The ARGUS Vertex Trigger

A fast second level trigger has been developed for the ARGUS experiment which recognizes tracks originating from the interaction region. The processor compares the hits in the ARGUS Micro Vertex Drift Chamber to 245760 masks stored in random access memories. The masks which are fully defined in three dimensions are able to reject tracks originating in the wall of the narrow beampipe of 10.5\,mm radius.Comment: gzipped Postscript, 27 page

Fiber-diffraction Interferometer using Coherent Fiber Optic Taper

We present a fiber-diffraction interferometer using a coherent fiber optic taper for optical testing in an uncontrolled environment. We use a coherent fiber optic taper and a single-mode fiber having thermally-expanded core. Part of the measurement wave coming from a test target is condensed through a fiber optic taper and spatially filtered from a single-mode fiber to be reference wave. Vibration of the cavity between the target and the interferometer probe is common to both reference and measurement waves, thus the interference fringe is stabilized in an optical way. Generation of the reference wave is stable even with the target movement. Focus shift of the input measurement wave is desensitized by a coherent fiber optic taper