Computational analysis of cancer cell adhesion in curved vessels affected by wall shear stress for prediction of metastatic spreading

Introduction: The dynamics of circulating tumor cells (CTCs) within blood vessels play a pivotal role in predicting metastatic spreading of cancer within the body. However, the limited understanding and method to quantitatively investigate the influence of vascular architecture on CTC dynamics hinders our ability to predict metastatic process effectively. To address this limitation, the present study was conducted to investigate the influence of blood vessel tortuosity on the behaviour of CTCs, focusing specifically on establishing methods and examining the role of shear stress in CTC-vessel wall interactions and its subsequent impact on metastasis.Methods: We computationally simulated CTC behaviour under various shear stress conditions induced by vessel tortuosity. Our computational model, based on the lattice Boltzmann method (LBM) and a coarse-grained spectrin-link membrane model, efficiently simulates blood plasma dynamics and CTC deformability. The model incorporates fluid-structure interactions and receptor-ligand interactions crucial for CTC adhesion using the immersed boundary method (IBM).Results: Our findings reveal that uniform shear stress in straight vessels leads to predictable CTC-vessel interactions, whereas in curved vessels, asymmetrical flow patterns and altered shear stress create distinct adhesion dynamics, potentially influencing CTC extravasation. Quantitative analysis shows a 25% decrease in the wall shear stress in low-shear regions and a 58.5% increase in the high-shear region. We observed high-shear regions in curved vessels to be potential sites for increased CTC adhesion and extravasation, facilitated by elevated endothelial expression of adhesion molecules. This phenomenon correlates with the increased number of adhesion bonds, which rises to approximately 40 in high-shear regions, compared to around 12 for straight vessels and approximately 5–6 in low-shear regions. The findings also indicate an optimal cellular stiffness necessary for successful CTC extravasation in curved vessels.Discussion: By the quantitative assessment of the risk of CTC extravasation as a function of vessel tortuosity, our study offers a novel tool for the prediction of metastasis risk to support the development of personalized therapeutic interventions based on individual vascular characteristics and tumor cell properties

Experimental and modelling study of gerbil middle ear

This thesis presents in vivo experimental measurements of vibrations on the surgically exposed tympanic membrane (TM) in the gerbil and a finite-element model of the gerbil middle ear. The TM is composed of the pars tensa and pars flaccida and is connected to the middle-ear bones via the manubrium of the malleus. Measurements were done on the pars flaccida and at several points along the manubrium and on the pars tensa using a laser Doppler vibrometer. Measurements were first done with a closed middle-ear cavity. The manubrial points show an increasing displacement magnitude from the lateral process toward the umbo, with the apparent axis of rotation shifting at high frequencies. Above 5 kHz, phase differences between points along the manubrium may indicate flexing in the manubrium. The simple low-frequency vibration pattern of the pars tensa breaks up at between 1.8 and 2.8 kHz.The effects of progressive opening of the middle-ear cavity were then explored. In all responses, opening the cavity causes an increase in the low-frequency magnitude and a shift of the main middle-ear resonance to lower frequencies, and introduces an antiresonance. However, opening the cavity has little or no effect on either the mode of vibration of the manubrium or the breakup frequency of the pars tensa. An identification method was developed for eliminating the effect of the antiresonance. It was validated and then applied to manubrial and pars-tensa responses. The finite-element model developed in this study uses a set of baseline parameters based primarily on a priori estimates from the literature. Responses from the model were validated against our measurements and against measurements from other groups. The responses of the model are mostly within the range of variability seen in the experimental data. A sensitivity analysis ranked the parameters of the model based on their effects on the model results.Cette thèse présente des mesures expérimentales in vivo des vibrations du tympan chirurgicalement exposé de la gerbille et un modèle aux éléments finis de l’oreille moyenne de la gerbille. Le tympan est composé du pars tensa et du pars flaccida et est relié aux osselets de l’oreille moyenne par le manubrium du malleus. Des mesures ont été effectuées sur le pars flaccida, et sur plusieurs points le long du manubrium et sur le pars tensa, utilisant un vibromètre laser Doppler. Les mesures ont été d’abord effectuées avec la cavité de l’oreille moyenne fermée. Les points sur le manubrium montrent une amplitude de déplacement augmentant du processus latéral à l’umbo, avec un axe apparent de rotation qui se déplaçait à des fréquences élevées. Au-dessus de 5 kHz, les différences de phase entre les points le long du manubrium indiquent possiblement la flexion du manubrium. Le type simple de vibration de basse fréquence du pars tensa commence à devenir plus complexe (‘breaks up’) entre 1.8 et 2.8 kHz. Les effets de l’ouverture progressive de la cavité de l’oreille moyenne ont été ensuite explorés. Dans toutes les réponses, l’ouverture de la cavité provoque une augmentation de l’amplitude à basse fréquence et un décalage de la résonance principale de l’oreille moyenne aux fréquences plus basses, et aussi introduit une antirésonance. Toutefois, l’ouverture de la cavité a un effet minimal sur le mode de vibration du manubrium et sur la fréquence ‘break-up’ du pars tensa. Une méthode d’identification a été développée pour éliminer l’effet de l’antirésonance. Elle a été validée et ensuite a été appliquée aux mesures sur le manubrium et le pars tensa. Le modèle aux éléments finis développé dans cette étude utilise un ensemble de paramètres de référence basés principalement sur des estimations a priori de la littérature. Les réponses du modèle ont été validées contre nos mesures expérimentales et celles d’autres groupes. Les réponses du modèle sont pour la plupart à l’intérieur de la gamme de variabilité observée dans les données expérimentales. Une analyse de sensibilité a classé les paramètres du modèle selon leurs effets sur les résultats du modèle

BRAIN Journal - On the Relationship between Brain Laterality and Language Proficiency in L2: A Replication Study

ABSTRACT The present paper attempted to investigate whether there is any significant relationship between participants' brain laterality and L2 proficiency level. To carry out the experiment, 30 participants administered in the present study. Fifteen of them did not have any English language learning experience and were at the start of language learning, while the rest had attended L2 learning classes for about 2 years in a popular English language center, located in Bandar-e Anzali, Iran. Finally, the researchers concluded that the activity of the right hemisphere went up by the increase in language proficiency among bilinguals. Thereupon, the result of the paper was at variance with Albert and Obler's (1978) early work on hemispheric differentiation, which indicated that bilinguals were less hemispheric dominant than monolinguals

On Situating the Stance of Practice in SLA

The study of skill acquisition, as DeKeyser (1997) declares, is an important area within cognitive psychology. What is undeniable in skill acquisition is the fact that through extensive practice, the degree of attention on a task decreases and the task is performed without stopping; furthermore, the rate of error considerably decreases. The paper, in an attempt to work on situating the concept of practice in skill acquisition, goes on to hold that since each context has its own specific encoding cues, and that the skill achieved in that specific context is too specific to be transferred to other contexts, the degree of automaticity in employing the skill in that context is plausibly more than the other contexts. 

Impact of TAVR on coronary artery hemodynamics using clinical measurements and image‐based patient‐specific in silico modeling

Abstract In recent years, transcatheter aortic valve replacement (TAVR) has become the leading method for treating aortic stenosis. While the procedure has improved dramatically in the past decade, there are still uncertainties about the impact of TAVR on coronary blood flow. Recent research has indicated that negative coronary events after TAVR may be partially driven by impaired coronary blood flow dynamics. Furthermore, the current technologies to rapidly obtain non-invasive coronary blood flow data are relatively limited. Herein, we present a lumped parameter computational model to simulate coronary blood flow in the main arteries as well as a series of cardiovascular hemodynamic metrics. The model was designed to only use a few inputs parameters from echocardiography, computed tomography and a sphygmomanometer. The novel computational model was then validated and applied to 19 patients undergoing TAVR to examine the impact of the procedure on coronary blood flow in the left anterior descending (LAD) artery, left circumflex (LCX) artery and right coronary artery (RCA) and various global hemodynamics metrics. Based on our findings, the changes in coronary blood flow after TAVR varied and were subject specific (37% had increased flow in all three coronary arteries, 32% had decreased flow in all coronary arteries, and 31% had both increased and decreased flow in different coronary arteries). Additionally, valvular pressure gradient, left ventricle (LV) workload and maximum LV pressure decreased by 61.5%, 4.5% and 13.0% respectively, while mean arterial pressure and cardiac output increased by 6.9% and 9.9% after TAVR. By applying this proof-of-concept computational model, a series of hemodynamic metrics were generated non-invasively which can help to better understand the individual relationships between TAVR and mean and peak coronary flow rates. In the future, tools such as these may play a vital role by providing clinicians with rapid insight into various cardiac and coronary metrics, rendering the planning for TAVR and other cardiovascular procedures more personalized

Effect of opening middle-ear cavity on vibrations of gerbil tympanic membrane

This paper presents in vivo experimental measurements of vibrations on the pars flaccida, along the manubrium and at several points on the pars tensa in the gerbil with open middle-ear cavity. The effects of progressive opening of the middle-ear cavity are presented, with up to five different extents of opening. In all manubrial, pars-tensa and pars-flaccida responses, opening the cavity causes an increase in the low-frequency magnitude and a shift of the main middle-ear resonance to lower frequencies and introduces an antiresonance. However, opening the cavity has little or no effect on either the mode of vibration of the manubrium or the breakup frequency of the pars tensa. When the opening is gradually widened, the antiresonance frequency moves to higher frequencies. When the opening is made as wide as anatomically possible, the antiresonance moves to almost 10 kHz. The main increase in the low-frequency response magnitude happens upon making the smallest hole in the cavity wall, and further progressive enlarging of the opening has little or no effect on the low-frequency magnitude. The antiresonance interferes with the response shapes. An identification method is suggested for eliminating the effect of the antiresonance in order to estimate the ideal open-cavity response. The method is validated and then applied to manubrial and pars-tensa responses. Estimating the ideal open-cavity responses will simplify comparison of the data with numerical models which do not include the air cavity. The data collected at intermediate stages of opening will be useful in validating models that do include the cavity

Experimental study of vibrations of gerbil tympanic membrane with closed middle ear cavity

The purpose of the present work is to investigate the spatial vibration pattern of the gerbil tympanic membrane (TM) as a function of frequency. In vivo vibration measurements were done at several locations on the pars flaccida and pars tensa, and along the manubrium, on surgically exposed gerbil TMs with closed middle ear cavities. A laser Doppler vibrometer was used to measure motions in response to audio frequency sine sweeps in the ear canal. Data are presented for two different pars flaccida conditions: naturally flat and retracted into the middle ear cavity. Resonance of the flat pars flaccida causes a minimum and a shallow maximum in the displacement magnitude of the manubrium and pars tensa at low frequencies. Compared with a flat pars flaccida, a retracted pars flaccida has much lower displacement magnitudes at low frequencies and does not affect the responses of the other points. All manubrial and pars tensa points show a broad resonance in the range of 1.6 to 2 kHz. Above this resonance, the displacement magnitudes of manubrial points, including the umbo, roll off with substantial irregularities. The manubrial points show an increasing displacement magnitude from the lateral process toward the umbo. Above 5 kHz, phase differences between points along the manubrium start to become more evident, which may indicate flexing of the tip of the manubrium or a change in the vibration mode of the malleus. At low frequencies, points on the posterior side of the pars tensa tend to show larger displacements than those on the anterior side. The simple low-frequency vibration pattern of the pars tensa becomes more complex at higher frequencies, with the breakup occurring at between 1.8 and 2.8 kHz. These observations will be important for the development and validation of middle ear finite-element models for the gerbil

Finite-element modelling of the response of the gerbil middle ear to sound

We present a finite-element model of the gerbil middle ear that, using a set of baseline parameters based primarily on a priori estimates from the literature, generates responses that are comparable with responses we measured in vivo using multi-point vibrometry and with those measured by other groups. We investigated the similarity of numerous features (umbo, pars-flaccida and pars-tensa displacement magnitudes, the resonance frequency and break-up frequency, etc.) in the experimental responses with corresponding ones in the model responses, as opposed to simply computing frequency-by-frequency differences between experimental and model responses. The umbo response of the model is within the range of variability seen in the experimental data in terms of the low-frequency (i.e., well below the middle-ear resonance) magnitude and phase, the main resonance frequency and magnitude, and the roll-off slope and irregularities in the response above the resonance frequency, but is somewhat high for frequencies above the resonance frequency. At low frequencies, the ossicular axis of rotation of the model appears to correspond to the anatomical axis but the behaviour is more complex at high frequencies (i.e., above the pars-tensa break-up). The behaviour of the pars tensa in the model is similar to what is observed experimentally in terms of magnitudes, phases, the break-up frequency of the spatial vibration pattern, and the bandwidths of the high-frequency response features. A sensitivity analysis showed that the parameters that have the strongest effects on the model results are the Young’s modulus, thickness and density of the pars tensa; the Young’s modulus of the stapedial annular ligament; and the Young’s modulus and density of the malleus. Displacements of the tympanic membrane and manubrium and the low-frequency displacement of the stapes did not show large changes when the material properties of the incus, stapes, incudomallear joint, incudostapedial joint, and posterior incudal ligament were changed by ±10 % from their values in the baseline parameter set