A novel model for one-dimensional morphoelasticity. Part II - Application to the contraction of fibroblast-populated collagen lattices

Fibroblast-populated collagen lattices are commonly used in experiments to study the interplay between fibroblasts and their pliable environment. Depending on the method by which\ud they are set, these lattices can contract significantly, in some cases contracting to as little as 10% of their initial lateral (or vertical) extent. When the reorganisation of such lattices by fibroblasts is interrupted, it has been observed that the gels re-expand slightly but do not return to their original size. In order to describe these phenomena, we apply our theory of one-dimensional morphoelasticity derived in Part I to obtain a system of coupled ordinary differential equations, which we use to describe the behaviour of a fibroblast-populated collagen lattice that is tethered by a spring of known stiffness. We obtain approximate solutions that describe the behaviour of the system at short times as well as those that are valid for long times. We also obtain an exact description of the behaviour of the system in the case where the lattice reorganisation is interrupted. In addition, we perform a perturbation analysis in the limit of large spring stiffness to obtain inner and outer asymptotic expansions for the solution, and examine the relation between force and traction stress in this limit. Finally, we compare predicted numerical values for the initial stiffness and viscosity of the gel with corresponding values for previously obtained sets of experimental data and also compare the qualitative behaviour with that of our model in each case. We find that our model captures many features of the observed behaviour of fibroblast-populated collagen lattices

A novel model for one-dimensional morphoelasticity. Part I - Theoretical foundations

While classical continuum theories of elasticity and viscoelasticity have long been used to describe the mechanical behaviour of solid biological tissues, they are of limited use for the description of biological tissues that undergo continuous remodelling. The structural changes to a soft tissue associated with growth and remodelling require a mathematical theory of ‘morphoelasticity’ that is more akin to plasticity than elasticity. However, previously-derived mathematical models for plasticity are difficult to apply and interpret in the context of growth and remodelling: many important concepts from the theory of plasticity do not have simple analogues in biomechanics.\ud \ud In this work, we describe a novel mathematical model that combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. While our focus here is on one-dimensional problems, our model builds on earlier work based on the multiplicative decomposition of the deformation gradient and can be adapted to develop a three-dimensional theory. The foundation of this work is the concept of ‘effective strain’, a measure of the difference between the current state and a hypothetical state where the tissue is mechanically relaxed. We develop one-dimensional equations for the evolution of effective strain, and discuss a number of potential applications of this theory. One significant application is the description of a contracting fibroblast-populated collagen lattice, which we further investigate in Part II

A two-compartment mechanochemical model of the roles of\ud transforming growth factor β and tissue tension in dermal wound healing

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor−β (TGFβ) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGFβ and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGFβ in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGFβ significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures

A fibrocontractive mechanochemical model of dermal wound\ud closure incorporating realistic growth factor kinetics

Fibroblasts and their activated phenotype, myofibroblasts, are the primary cell types involved in the contraction associated with dermal wound healing. Recent experimental evidence indicates that the transformation from fibroblasts to myofibroblasts involves two distinct processes: the cells are stimulated to change phenotype by the combined actions of transforming growth factor β (TGFβ) and mechanical tension. This observation indicates a need for a detailed exploration of the effect of the strong interactions between the mechanical changes and growth factors in dermal wound healing. We review the experimental findings in detail and develop a model of dermal wound healing that incorporates these phenomena. Our model includes the interactions between TGFβ and collagenase, providing a more biologically realistic form for the growth factor kinetics than those included in previous mechanochemical descriptions. A comparison is made between the model predictions and experimental data on human dermal wound healing and all the essential features are well matched

Tear film thickness variations and the role of the tear meniscus

A mathematical model is developed to investigate the two-dimensional variations in the thickness of tear fluid deposited on the eye surface during a blink. Such variations can become greatly enhanced as the tears evaporate during the interblink period.\ud The four mechanisms considered are: i) the deposition of the tear film from the upper eyelid meniscus, ii) the flow of tear fluid from under the eyelid as it is retracted and from the lacrimal gland, iii) the flow of tear fluid around the eye within the meniscus and iv) the drainage of tear fluid into the canaliculi through the inferior and superior puncta.\ud There are two main insights from the modelling. First is that the amount of fluid within the tear meniscus is much greater than previously employed in models and this significantly changes the predicted distribution of tears. Secondly the uniformity of the tear film for a single blink is: i) primarily dictated by the storage in the meniscus, ii) quite sensitive to the speed of the blink and the ratio of the viscosity to the surface tension iii) less sensitive to the precise puncta behaviour, the flow under the eyelids or the specific distribution of fluid along the meniscus at the start of the blink. The modelling briefly examines the flow into the puncta which interact strongly with the meniscus and acts to control the meniscus volume. In addition it considers flow from the lacrimal glands which appears to occurs continue even during the interblink period when the eyelids are stationary

Wound healing angiogenesis the clinical implications of a simple mathematical model

Nonhealing wounds are a major burden for health care systems worldwide. In addition, a patient who suffers from this type of wound usually has a reduced quality of life. While the wound healing process is undoubtedly complex, in this paper we develop a deterministic mathematical model, formulated as a system of partial differential equations, that focusses on an important aspect of successful healing: oxygen supply to the wound bed by a combination of diffusion from the surrounding unwounded tissue and delivery from newly-formed blood vessels. While the model equations can be solved numerically, the emphasis here is on the use of asymptotic methods to establish conditions under which new blood vessel growth can be initiated and wound-bed angiogenesis can progress. These conditions are given in terms of key model parameters including the rate of oxygen supply and its rate of consumption in the wound. We use our model to discuss the clinical use of treatments such as hyperbaric oxygen therapy, wound bed debridement, and revascularisation therapy that have the potential to initiate healing in chronic, stalled wounds

A New Brown Dwarf Desert? A Scarcity of Wide Ultracool Binaries

We present the results of a deep-imaging search for wide companions to low-mass stars and brown dwarfs using NSFCam on IRTF. We searched a sample of 132 M7-L8 dwarfs to magnitude limits of $J \sim 20.5$ and $K \sim 18.5$, corresponding to secondary-primary mass ratios of $\sim 0.5$. No companions were found with separations between 2{\arcsec} to 31{\arcsec} ($\sim$40 AU to $\sim$1000 AU). This null result implies a wide companion frequency below 2.3% at the 95% confidence level within the sensitivity limits of the survey. Preliminary modeling efforts indicate that we could have detected 85% of companions more massive than $0.05 M_{\odot}$ and 50% above $0.03 M_{\odot}$.Comment: 27 pages, 8 figures, 3 tables: accepted to the Astronomical Journa

Sensitivity analysis of a model for direct reduction in swelling coal char-hematite composite pellets

This paper describes a study of the optimisation of the modelling of the direct reduction process in swelling coal char-hematite composite pellets. Approximations of important physical parameters such as heats of reaction, specific heat and thermal conductivity of the reducing mixture have been developed. Without introducing significant errors, the computation time can be halved. The effect of the determination of pellet size and of the activation energies of the reducing reactions on the modelling results has also been investigated

Towards Robust Family-Infant Audio Analysis Based on Unsupervised Pretraining of Wav2vec 2.0 on Large-Scale Unlabeled Family Audio

To perform automatic family audio analysis, past studies have collected recordings using phone, video, or audio-only recording devices like LENA, investigated supervised learning methods, and used or fine-tuned general-purpose embeddings learned from large pretrained models. In this study, we advance the audio component of a new infant wearable multi-modal device called LittleBeats (LB) by learning family audio representation via wav2vec 2.0 (W2V2) pertaining. We show given a limited number of labeled LB home recordings, W2V2 pretrained using 1k-hour of unlabeled home recordings outperforms oracle W2V2 pretrained on 52k-hour unlabeled audio in terms of parent/infant speaker diarization (SD) and vocalization classifications (VC) at home. Extra relevant external unlabeled and labeled data further benefit W2V2 pretraining and fine-tuning. With SpecAug and environmental speech corruptions, we obtain 12% relative gain on SD and moderate boost on VC. Code and model weights are available.Comment: Accepted to Interspeech 202