Searcharxiv⌕ Search

SEARCH · Searcharxiv

Results for “q-bio.TO”

Search indexed arXiv papers on artificial intelligence, large language models, computer vision and robotics. Read source abstracts and follow links to arXiv.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
arXiv2014

Stochastic biophysical modeling of irradiated cells

The paper presents a computational stochastic model of virtual cells irradiation, based on Quasi-Markov Chain Monte Carlo method and using biophysical input. The model is based on a stochastic tree of probabilities for each cell of the entire colony. Biophysics of the cells is described by probabilities and probability distributions provided as the input. The adaptation of nucleation and catastrophe theories, well known in physics, yields sigmoidal relationships for carcinogenic risk as a function of the irradiation. Adaptive response and bystander effect, incorporated into the model, improves its application. The results show that behavior of virtual cells can be successfully modeled, e.g. cancer transformation, creation of mutations, radioadaptation or radiotherapy. The used methodology makes the model universal and practical for simulations of general processes. Potential biophysical curves and relationships are also widely discussed in the paper. However, the presented theoretical model does not describe the real cells and tissues. Also the exposure geometry (e.g., uniform or non-uniform exposure), type of radiation (e.g., X-rays, gamma rays, neutrons, heavy ions, etc.) as well as microdosimetry are not presently addressed. The model is focused mainly on creation of general and maximal wide mathematical description of irradiated hypothetical cells treated as complex physical systems.

physics.bio-ph↗
arXiv2014

Cancer Metastasis: Collective Invasion in Heterogeneous Multicellular Systems

Heterogeneity within tumour cell populations is associated with an increase in malignancy and appears to play an important role during cancer metastasis. Using in silico experiments, we study the interplay between collective behaviours and cell motility heterogeneities in a model system. Working with tumour spheroids that contain two non-proliferating cell populations of different motile properties, we explore the conditions required for maximal invasion into surrounding tissues. We show emerging spatial patterns of cellular organisation and invasion which are consistent with in vitro and in vivo observations. This demonstrates that mechanical interactions at the cellular level are sufficient to account for many of the observed morphologies of invasion and that heterogeneity in cell motility can be more important than average mechanical properties in controlling the fate of large cell populations.

q-bio.TO↗
arXiv2015

A Mathematical Model for Lymphangiogenesis in Normal and Diabetic Wounds

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis) very few have been proposed for the regeneration of the lymphatic network. Moreover, lymphangiogenesis is markedly distinct from angiogenesis, occurring at different times and in a different manner. Here a model of five ordinary differential equations is presented to describe the formation of lymphatic capillaries following a skin wound. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from experimental and clinical data. The system is then solved numerically and the results are compared with the available biological literature. Finally, a parameter sensitivity analysis of the model is taken as a starting point for suggesting new therapeutic approaches targeting the enhancement of lymphangiogenesis in diabetic wounds. The work provides a deeper understanding of the phenomenon in question, clarifying the main factors involved. In particular, the balance between TGF-$β$ and VEGF levels, rather than their absolute values, is identified as crucial to effective lymphangiogenesis. In addition, the results indicate lowering the macrophage-mediated activation of TGF-$β$ and increasing the basal lymphatic endothelial cell growth rate, \emph{inter alia}, as potential treatments. It is hoped the findings of this paper may be considered in the development of future experiments investigating novel lymphangiogenic therapies.

q-bio.TO↗
arXiv2014

Analysis of the nutrient uptake by roots in fixed volume of soil as predicted by fixed boundary, moving boundary and architectural models

This work examines the relevance of the one-dimensional models used to study the influx and the cumulative uptake of nutrient by roots. The physical models studied are the fixed boundary model (Barber and Cushman 1981) and an improved version of our moving boundary model (Reginato et al. 2000). A weight averaged expression to compute influx on root surface and a generalized formula to estimate the cumulative nutrient uptake are used. The moving boundary model problem is solved by the adaptive finite element method. For comparison of simulations of influx and cumulative uptake versus observed results six set of data extracted from literature are used. For ions without limitations of availability fixed and moving boundary models produces similar results with small errors. Instead, to low concentrations, the fixed boundary model over predicts while the moving boundary model always produces better results mainly for K. For the P uptake the moving boundary model produces better results only when the concentrations are very low and their predictions are comparable to the obtained by a 3D-architectural model. The obtained improvements would explain any failures of previous models for ions of low availability. Therefore, our model could be a simpler alternative due to its low computational burden.

q-bio.TO↗
arXiv2015

Statistical Problems in a Paper on Variation In Cancer Risk Among Tissues, and New Discoveries

Tomasetti and Vogelstein (2015) collected data on 31 different tissue types and found a correlation of 0.8 between the logarithms of the incidence of cancer (LCI), and the estimated number of stem cell divisions in those tissues (LSCD). Some of their conclusions however are statistically erroneous. Their excess risk score, "ERS" (log10 LCI x log10 LSCD), is non-monotonic under a change of time units for the rates, which renders meaningless the results derived from it, including a cluster of 22 "R-tumor" types for which they conclude, "primary prevention measures are not likely to be very effective". Further, r = 0.8 is consistent with the three orders of magnitude variation in other unmeasured factors, leaving room for the possibility of primary prevention if such factors can be intervened upon. Further exploration of the data reveals additional findings: (1) that LCI grows at approximately the square root of LSCD, which may provide a clue to the biology; (2) among different possible combinations of the primary data, the one maximizing the correlations with LCI is almost precisely the formula used by Tomasetti and Vogelstein to estimate LSCD, giving support to stem cell divisions as an independent factor in carcinogenesis, while not excluding other such factors.

q-bio.QM↗
arXiv2015

Strabismic syndromes and syndromic strabismus - a brief review

Strabismus can be found in association with congenital heart diseases, for examples, in velocardiofacial (DiGeorge) syndrome, Down syndrome, mild dysmorphic features, in CHARGE association, Turner syndrome, Ullrich-Turner syndrome, cardiofaciocutaneous syndrome.1-4 Some types of strabismus is heritable (e.g. infantile esotropia syndrome), particularly the ones associated with multisystem disorders, e.g. Moebius syndrome, Prader-Willi syndrome, craniofacial dysostoses, and mitochondrial myopathies.5 Due to the complexities that a case of strabismus may pertain to, it is worthwhile to get to know more about the strabismic syndromes and syndromic strabismus. This brief review -as its name implied- does not attempt to cover every angle of the syndromic conditions, but offers a refreshment on our knowledge about more prevalent strabismus-related syndromes.

q-bio.TO↗
arXiv2015

Ion mediated crosslink driven mucous swelling kinetics

We present an experimentally guided, multi-phasic, multi-species ionic gel model to compare and make qualitative predictions on the rheology of mucus of healthy individuals (Wild Type) versus those infected with Cystic Fibrosis. The mixture theory consists of the mucus (polymer phase) and water (solvent phase) as well as several different ions: H+, Na+ and Ca++. The model is linearized to study the hydration of spherically symmetric mucus gels and calibrated against the experimental data of mucus diffusivities. Near equilibrium, the linearized form of the equation describing the radial size of the gel, reduces to the well-known expression used in the kinetic theory of swelling hydrogels. Numerical studies reveal that the Donnan potential is the dominating mechanism driving the mucus swelling/deswelling transition. However, the altered swelling kinetics of the Cystic Fibrosis infected mucus is not merely governed by the hydroelectric composition of the swelling media, but also due to the altered movement of electrolytes as well as due to the defective properties of the mucin polymer network.

q-bio.TO↗
arXiv2015

Chapter 9 TISSUE ENGINEERING

Tissue Engineering (TE) is an interdisciplinary field dealing with the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ. Currently, TE is emerging as an invaluable field of study and is one of the most promising fields for the next century. The ultimate goal is to develop powerful new therapies for biological substitutes - that will successfully restore the structural and functional disorders of human and animal system.

q-bio.TO↗
arXiv2016

Musings on the theory that variation in cancer risk among tissues can be explained by the number of divisions of normal stem cells

This manuscript has been written to address questions related to our recent publication (Science 347:78-81, 2015). We appreciate the many reactions to this paper that have been communicated to us, either privately or publicly. The following addresses several of the most important statistical and technical issues related to our analysis and conclusions. Our responses to non-technical questions are available at http://www.hopkinsmedicine.org/news/media/releases/bad_luck_of_random_mutations_plays_predominant_role_in_cancer_study_shows

stat.AP↗
arXiv2015

Statistical interpretations and new findings on Variation in Cancer Risk Among Tissues

Tomasetti and Vogelstein (2015a) find that the incidence of a set of cancer types is correlated with the total number of normal stem cell divisions. Here, we separate the effects of standing stem cell number (i.e., organ or tissue size) and per stem cell lifetime replication rate. We show that each has a statistically significant and independent effect on explaining variation in cancer incidence over the 31 cases considered by Tomasetti and Vogelstein. When considering the total number of stem cell divisions and when removing cases associated with disease or carcinogens, we find that cancer incidence attains a plateau of approximately 0.6% incidence for the cases considered by these authors. We further demonstrate that grouping by anatomical site explains most of the remaining variation in risk between cancer types. This new analysis suggests that cancer risk depends not only on the number of stem cell divisions but varies enormously ($\sim$10,000 times) depending on the stem cell's environment. Future research should investigate how tissue characteristics (anatomical site, type, size, stem cell divisions) explain cancer incidence over a wider range of cancers, to what extent different tissues express specific protective mechanisms, and whether any differential protection can be attributed to natural selection.

q-bio.PE↗
arXiv2015

Towards the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction

Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increases any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two adimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation.

physics.med-ph↗
arXiv2015

Robust and probabilistic optimization of dose schedules in radiotherapy

We consider the effects of parameter uncertainty on the optimal radiation schedule in the context of the linear-quadratic model. Our interest arises from the observation that if inter-patient variations in OAR and tumor sensitivities to radiation or sparing factor of the OAR are not accounted for during radiation scheduling, the performance of the therapy may be strongly degraded or the OAR may receive a substantially larger dose than the maximum threshold. This paper proposes two radiation scheduling concepts to incorporate inter-patient variability into the scheduling optimization problem. The first approach is a robust formulation that formulates the problem as a conservative model that optimizes the worst case dose scheduling that may occur. The second method is a probabilistic approach, where the model parameters are given by a set of random variables. This formulation insures that our constraints are satisfied with a given probability, and that our objective function achieves a desired level with a stated probability. We used a transformation to reduce the resulting optimization problem to two dimensions. We showed that the optimal solution lies on the boundary of the feasible region and we used a branch and bound algorithm to find the global optimal solution. We observed that if the number of fractions in the optimal conventional schedule is the same as the robust and stochastic solutions, it is preferable to administer equal or smaller total dose. In addition if there exist more (fewer) treatment sessions in the probabilistic or robust solution compared to the conventional schedule, a reduction in total dose squared (total dose) will be expected. Finally, we performed numerical experiments in the setting of head-and-neck tumors to reveal the effect of parameter uncertainty on optimal schedules and to evaluate the sensitivity of the model to the choice of key model parameters.

q-bio.TO↗
arXiv2015

Analysis of Transcranial Focused Ultrasound Beam Profile Sensitivity for Neuromodulation of the Human Brain

Objective. While ultrasound is largely established for use in diagnostic imaging and heating therapies, its application for neuromodulation is relatively new and not well understood. The objective of the present study was to investigate issues related to interactions between focused acoustic beams and brain tissues to better understand possible limitations of transcranial ultrasound for neuromodulation. Approach. A computational model of transcranial focused ultrasound was constructed and validated against bench top experimental data. The models were then incrementally extended to address and investigate a number of issues related to the use of ultrasound for neuromodulation. These included the effect of variations in skull geometry and gyral anatomy, as well as the effect of transmission across multiple tissue and media layers, such as scalp, skull, CSF, and gray/white matter on ultrasound insertion behavior. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. Main results. Depending on factors such as acoustic frequency, the insertion behavior of a transcranial focused ultrasound beam is only subtly influenced by the geometry and acoustic properties of the underlying tissues. Significance. These issues are critical for the refinement of device design and the overall advancement of ultrasound methods for noninvasive neuromodulation.

q-bio.TO↗
arXiv2015

Analysis of the unilateral contact problem for biphasic cartilage layers with an elliptic contact zone and accounting for the tangential displacements

A three-dimensional unilateral contact problem for articular cartilage layers attached to subchondral bones shaped as elliptic paraboloids is considered in the framework of the biphasic cartilage model. The main novelty of the study is in accounting not only for the normal (vertical), but also for tangential vertical (horisontal) displacements of the contacting surfaces. Exact general relationships have been established between the contact approach and some integral characteristics of the contact pressure, including the contact force. Asymptotic representations for the contact pressure integral characteristics are obtained in terms of the contact approach and some integral characteristics of the contact zone. The main result is represented by the first-order approximation problem.

physics.bio-ph↗
arXiv2017

Aging as a process of accumulation of Misrepairs

We recently introduced Misrepair-accumulation theory as an interpretation on aging mechanism. For better understanding this theory, we discuss here in more details the new concept of Misrepair and the concept of accumulation of Misrepairs. I. Aging takes place uniquely on the systems that have a well-defined structure: an organization of its sub-structures. Aging of a non-living system is a result of accumulation of injuries (damage) of its structure. II. A generalized concept of Misrepair is important for reaching to a unified understanding of aging changes. In the situation of a severe injury, incorrect repair is a repair essential for maintaining structural integrity for increasing the surviving chance of an organism. With the same mechanism as that in "Misrepair of DNA" , the term of "Misrepair" can be used for describing all kinds of incorrect repairs on different types of living structures, including molecules, cells and tissues. A new concept of Misrepair is therefore proposed and defined as incorrect reconstruction of an injured living structure. Misrepair mechanism is beneficial for the survival of an organism, and it is essential for the survival of a species. III. Alteration of structure made by Misrepair is irreversible; therefore Misrepairs accumulate and disorganize gradually a structure, which appears as aging of it. Accumulation of Misrepairs takes place on molecular, cellular and tissue levels respectively: on tissue level, it appears as disorganization of cells and extracellular matrixes (ECMs); on cellular level, it appears as deformation of cytoskeleton and change of cell shape; and on DNA, it appears as accumulation of DNA mutations and alteration of DNA sequence. An essential change in aging of an organism is an irreversible change of the spatial relationship between cells/ECMs in a tissue. In conclusion, aging of an organism is a result of accumulation of Misrepairs on tissue level.

q-bio.TO↗
arXiv2015

Structural Changes of Active Skeletal Muscles: Modelling, Validation and Numerical Experiments

The purpose of this study was to report numerical validation of a 3D finite element model of contracting muscle. The model was based on continuum theory for fibre-reinforced composite materials. Here we simulated contractions for an idealized medial gastrocnemius muscle in man, using the model. Simulations were performed to test the force-length relation of the whole muscle, to evaluate the changes in internal fascicle geometry during contractions, and to assess the importance of material formulations for the aponeurosis and tendon. The simulation results were compared to previously published experimental values. The force-length profile for the whole muscle showed a realistic profile. As the muscle contracted the fascicles curved into S-shaped trajectories and curled around 3D paths, both of which matched previous experimental findings. As the fascicles shortened they increased in their cross-sectional area, but this increase was asymmetric with the smaller increase occurring within the fascicle-plane: the Poisson's ratio in this plane matched that previously shown from ultrasound imaging. The distribution of strains in the aponeurosis and tendon was shown to be a function of their material properties. This study demonstrated that the model could replicate realistic patterns of whole muscle-force, and changes to the internal muscle geometry, and so will be useful for testing mechanisms that affect the structural changes within contracting muscle.

q-bio.QM↗
arXiv2015

Slow Limb Movements Require Precise Control of Muscle Stiffness

Slow and accurate finger and limb movements are essential to daily activities, but their neural control and governing mechanics are relatively unexplored. We consider neuromechanical systems where slow movements are produced by neural commands that modulate muscle stiffness. This formulation based on strain-energy equilibria is in agreement with prior work on neural control of muscle and limb impedance. Slow limb movements are driftless in the sense that movement stops when neural commands stop. We demonstrate, in the context of two planar tendon-driven systems representing a finger and a leg, that the control of muscle stiffness suffices to produce stable and accurate limb postures and quasi-static (slow) transitions among them. We prove, however, that stable postures are achievable only when muscles are pre-tensioned, as is the case for natural muscle tone. Our results further indicate, in accordance with experimental findings, that slow movements are non-smooth. The non-smoothness arises because the precision with which individual muscle stiffnesses need to be controlled changes substantially throughout the limb's motion. These results underscore the fundamental roles of muscle tone and accurate neural control of muscle stiffness in producing stable limb postures and slow movements.

q-bio.TO↗