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 415 records · Page 23Linked to original sources

arXiv2017

Explanation for Cancer in Rats, Mice and Humans due to Cell Phone Radiofrequency Radiation

Very recently, the National Toxicology Program reported a correlation between exposure to whole body 900 MHz radiofrequency radiation and cancer in the brains and hearts of Sprague Dawley male rats. This paper proposes the following explanation for these results. The neurons around the rat's brain and heart form closed electrical circuits and, following Faraday's Law, 900 MHz radiofrequency radiation induces 900 MHz electrical currents in these neural circuits. In turn, these 900 MHz currents in the neural circuits generate sufficient localized heat in the neural cell axons to shift the equilibrium concentration of carcinogenic radicals to higher levels and thus, to higher incidences of cancer. This model is then applied to mice and humans.

q-bio.TO↗

arXiv2017

Evaluation of a New Vasculature by High Resolution Light Microscopy: Primo Vessel and Node

The primo vascular system is composed of nodes and vessels. The bundle of sub-vessels of the promo vessel is laid into an external jacket composed of endothelial cells. The node is heterogeneous in nature, composed of twisted sub-vessel bundles that fill up nearly the entire node volume. The enlarged sub-vessel inside the node harbors microcells that express stem cells and stem cells niche markers. We conclude that these microcells are progenitors of multipotent stem cells and the nodes serve as the stem cell niches outside the bone marrow.

q-bio.TO↗

arXiv2016

Probing Three-dimensional Collective Cancer Invasion with DIGME

Multicellular migration and pattern formation play important roles in developmental biology, cancer metastasis and wound healing. To understand the collective cell dynamics in three dimensional extracellular matrix (ECM), we have developed a simple and mechanical-based strategy, Diskoid In Geometrically Micropatterned ECM (DIGME). DIGME allows easy engineering of the shape of 3-D tissue organoid, the mesoscale ECM heterogeneity, and the fiber alignment of collagen-based ECM all at the same time. We have employed DIGME to study the collective cancer invasion and find that DIGME provides a powerful tool to probe three dimensional dynamics of tumor organoid in patterned microenvironment.

q-bio.TO↗

arXiv2016

Growth and Scaling during Development and Regeneration

Life presents fascinating examples of self-organization and emergent phenomena. In multi-cellular organisms, a multitude of cells interact to form and maintain highly complex body plans of well-defined size. In this thesis, we investigate theoretical feedback mechanisms for both self-organized body plan patterning and size control. The thesis is inspired by the astonishing scaling and regeneration abilities of flatworms. These worms can perfectly regrow their entire body plan even from tiny amputation fragments like the tip of the tail. Moreover, they can grow and actively de-grow by more than a factor of 40 in length depending on feeding conditions. These capabilities prompt for remarkable physical mechanisms of self-organized pattern formation and scaling. First, we explore the basic principles and challenges of pattern scaling in mechanisms previously proposed to describe biological pattern formation. Next, we present a novel class of patterning mechanisms yielding entirely self-organized and self-scaling patterns. This framework captures essential features of body plan regeneration and scaling in flatworms. Further, we analyze shape and motility of flatworms. By applying principal component analysis, we characterize shape dynamics during different motility modes and also identify shape variations between different flatworm species. Finally, we investigate the metabolic control of cell turnover and growth. We identify three mechanisms of metabolic energy storage; theoretical descriptions thereof can explain the measured organism growth by rules on the cellular scale. In a close collaboration with experimental biologists, we combine minimal theoretical descriptions with state-of-the-art experiments and data analysis. This allows us to identify generic principles of scalable body plan patterning and growth control in flatworms.

physics.bio-ph↗

arXiv2016

Modelling the effect of curvature on the collective behaviour of cells growing new tissue

The growth of several biological tissues is known to be controlled in part by local geometrical features, such as the curvature of the tissue interface. This control leads to changes in tissue shape that in turn can affect the tissue's evolution. Understanding the cellular basis of this control is highly significant for bioscaffold tissue engineering, the evolution of bone microarchitecture, wound healing, and tumour growth. While previous models have proposed geometrical relationships between tissue growth and curvature, the role of cell density and cell vigor remains poorly understood. We propose a cell-based mathematical model of tissue growth to investigate the systematic influence of curvature on the collective crowding or spreading of tissue-synthesising cells induced by changes in local tissue surface area during the motion of the interface. Depending on the strength of diffusive damping, the model exhibits complex growth patterns such as undulating motion, efficient smoothing of irregularities, and the generation of cusps. We compare this model with in-vitro experiments of tissue deposition in bioscaffolds of different geometries. By accounting for the depletion of active cells, the model is able to capture both smoothing of initial substrate geometry and tissue deposition slowdown as observed experimentally.

q-bio.TO↗

arXiv2016

Toward a closed-loop subcutaneous delivery of L-DOPA

L-DOPA has been the gold standard treatment for Parkinson's disease since 50 years. Being the direct biochemical precursor of dopamine, L-DOPA is effectively converted in the brain, but two major phenomena reduce its therapeutic action: i) competition with amino acids in the gut wall and in the blood brain barrier and ii) its fast kinetics (absorption, distribution, metabolism, and elimination). Continuous administration of L-DOPA, such as jejunal pumps, have addressed the issue of fast absorption. Considering a subcutaneous delivery of L-DOPA allows to bypass the gastrointestinal tract and avoid competition with dietary amino acids. Remains the competition at the blood barrier between amino acids and L-DOPA, which we address by proposing a closed-loop controlled, continuous subcutaneous delivery pump. In the proof-of-concept format, the delivery strategy evaluated on comprehensive model of L-DOPA kinetics, holds the promise of improving the treatment of late-stage Parkinson's disease patients.

q-bio.TO↗

arXiv2016

TLR-exosomes exhibit distinct kinetics and effector function

The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. Here we show that exosomes from TLR stimulated cells (TLR-exosomes) can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function. We are the first to show that exosomes derived from poly(I:C) stimulated cells induce in vivo macrophage M1-like polarization within murine lymph nodes. These TLR-exosomes demonstrate enhanced trafficking to the node and preferentially recruit neutrophils as compared to control-exosomes. This work definitively establishes the differential effector function for TLR-exosomes in communicating the activation state of the cell of origin.

q-bio.CB↗

arXiv2016

Global weak solutions and asymptotic limits of a Cahn--Hilliard--Darcy system modelling tumour growth

We study the existence of weak solutions to a Cahn--Hilliard--Darcy system coupled with a convection-reaction-diffusion equation through the fluxes, through the source terms and in Darcy's law. The system of equations arises from a mixture model for tumour growth accounting for transport mechanisms such as chemotaxis and active transport. We prove, via a Galerkin approximation, the existence of global weak solutions in two and three dimensions, along with new regularity results for the velocity field and for the pressure. Due to the coupling with the Darcy system, the time derivatives have lower regularity compared to systems without Darcy flow, but in the two dimensional case we employ a new regularity result for the velocity to obtain better integrability and temporal regularity for the time derivatives. Then, we deduce the global existence of weak solutions for two variants of the model; one where the velocity is zero and another where the chemotaxis and active transport mechanisms are absent.

math.AP↗

arXiv2016

Personalized Mathematical Model Predicting Endotoxin-Induced Inflammatory Responses in Young Men

The initial reaction of the body to pathogenic microbial infection or severe tissue trauma is an acute inflammatory response. The magnitude of such a response is of critical importance, since an uncontrolled response can cause further tissue damage, sepsis, and ultimately death, while an insufficient response can result in inadequate clearance of pathogens. A normal inflammatory response helps to annihilate threats posed by microbial pathogenic ligands, such as endotoxins, and thus, restore the body to a healthy state. Using a personalized mathematical model, comprehension and a detailed description of the interactions between pro- and anti-inflammatory cytokines can provide important insight in the evaluation of a patient with sepsis or a susceptible patient in surgery. Our model is calibrated to experimental data obtained from experiments measuring pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF-), and chemokine ligand-8 (CXCL8)) and the anti-inflammatory cytokine interleukin-10 (IL-10) over 8 hours in 20 healthy young male subjects, given a low dose intravenous injection of lipopolysaccharide (LPS), resulting in endotoxin-stimulated inflammation. Through the calibration process, we created a personalized mathematical model that can accurately determine individual differences between subjects, as well as identify those who showed an abnormal response.

q-bio.QM↗

arXiv2016

Bulging brains

Brain swelling is a serious condition associated with an accumulation of fluid inside the brain that can be caused by trauma, stroke, infection, or tumors. It increases the pressure inside the skull and reduces blood and oxygen supply. To relieve the intracranial pressure, neurosurgeons remove part of the skull and allow the swollen brain to bulge outward, a procedure known as decompressive craniectomy. Decompressive craniectomy has been preformed for more than a century; yet, its effects on the swollen brain remain poorly understood. Here we characterize the deformation, strain, and stretch in bulging brains using the nonlinear field theories of mechanics. Our study shows that even small swelling volumes of 28 to 56 ml induce maximum principal strains in excess of 30%. For radially outward-pointing axons, we observe maximal normal stretches of 1.3 deep inside the bulge and maximal tangential stretches of 1.3 around the craniectomy edge. While the stretch magnitude varies with opening site and swelling region, our study suggests that the locations of maximum stretch are universally shared amongst all bulging brains. Our model can inform neurosurgeons and rationalize the shape and position of the skull opening, with the overall goal to reduce brain damage and improve the structural and functional outcomes of decompressive craniectomy in trauma patients.

q-bio.TO↗

arXiv2017

Druse-Induced Morphology Evolution in Retinal Pigment Epithelium

The retinal pigment epithelium (RPE) is a key site of pathogenesis for many retina diseases. The formation of drusen in the retina is characteristic of retinal degeneration. We investigate morphological changes in the RPE in the presence of soft drusen using an integrated experimental and modeling approach. We collect RPE flat mount images from donated human eyes and develop 1) statistical tools to quantify the images and 2) a cell-based model to simulate the morphology evolution. We compare three different mechanisms of RPE repair evolution, cell apoptosis, cell fusion, and expansion, and Simulations of our RPE morphogenesis model quantitatively reproduce deformations of human RPE morphology due to drusen, suggesting that a purse-string mechanism is sufficient to explain how RPE heals cell loss caused by drusen-damage. We found that drusen beneath tissue promote cell death in a number that far exceeds the cell numbers covering the drusen. Tissue deformations are studied using area distributions, Voronoi domains and a texture tensor.

q-bio.TO↗

arXiv2016

Uncertainty of current understanding regarding OBT formation in plants

Radiological impact models are important tools that support nuclear safety. For tritium, a special radionuclide that readily enters the life cycle, the processes involved in its transport into the environment are complex and inadequately understood. For example, tritiated water (HTO) enters plants by leaf and root uptake and is converted to organically bound tritium (OBT) in exchangeable and non-exchangeable forms; however, the observed OBT/HTO ratios in crops exhibit large variability and contradict the current models for routine releases. Non-routine or spike releases of tritium further complicate the prediction of OBT formation. The experimental data for a short and intense atmospheric contamination of wheat are presented together with various models predictions. The experimental data on wheat demonstrate that the OBT formation is a long process, it is dependent on receptor location and stack dynamics, there are differences between night and day releases, and the HTO dynamics in leaf and ear is a very important contributor to OBT formation.

physics.bio-ph↗

arXiv2016

Global Sensitivity Analysis in a Mathematical Model of the Renal Interstitium

The pressure in the renal interstitium is an important factor for normal kidney function. Here we develop a computational model of the rat kidney and use it to investigate the relationship between arterial blood pressure and interstitial fluid pressure. In addition, we investigate how tissue flexibility influences this relationship. Due to the complexity of the model, the large number of parameters, and the inherent uncertainty of the experimental data, we utilize Monte Carlo sampling to study the model's behavior under a wide range of parameter values and to compute first- and total-order sensitivity indices. Characteristically, at elevated arterial blood pressure, the model predicts cases with increased or reduced interstitial pressure. The transition between the two cases is controlled mostly by the compliance of the blood vessels located before the afferent arterioles.

q-bio.TO↗

arXiv2017

A high-throughput analysis of ovarian cycle disruption by mixtures of aromatase inhibitors

Background: Combining computational toxicology with ExpoCast exposure estimates and ToxCast assay data gives us access to predictions of human health risks stemming from exposures to chemical mixtures. Objectives: To explore, through mathematical modeling and simulations, the size of potential effects of random mixtures of aromatase inhibitors on the dynamics of women's menstrual cycles. Methods: We simulated random exposures to millions of potential mixtures of 86 aromatase inhibitors. A pharmacokinetic model of intake and disposition of the chemicals predicted their internal concentration as a function of time (up to two years). A ToxCast aromatase assay provided concentration-inhibition relationships for each chemical. The resulting total aromatase inhibition was input to a mathematical model of the hormonal hypothalamus-pituitary-ovarian control of ovulation in women. Results: Above 10% inhibition of estradiol synthesis by aromatase inhibitors, noticeable (eventually reversible) effects on ovulation were predicted. Exposures to individual chemicals never led to such effects. In our best estimate, about 10% of the combined exposures simulated had mild to catastrophic impacts on ovulation. A lower bound on that figure, obtained using an optimistic exposure scenario, was 0.3%. Conclusions: These results demonstrate the possibility to predict large-scale mixture effects for endocrine disrupters with a predictive toxicology approach, suitable for high-throughput ranking and risk assessment. The size of the effects predicted is consistent with an increased risk of infertility in women from everyday exposures to our chemical environment.

q-bio.TO↗

arXiv2016

The Evolving Definition of Sepsis

Sepsis affects millions of people worldwide each year. It occurs when a normal human immune response to a bacterial, viral or fungal infection becomes dysfunctional and triggers widespread inflammation that results in severe tissue damage that leads to organ failure, shock, and death. Sepsis, requires immediate treatment and has a high readmission rate for survivors. It is also one of the most expensive conditions to treat. In 2013, there were more than 1.6 million cases of sepsis in the United States with a financial cost of more than $23 billion. Sepsis was first described in antiquity, and given its current name, by the ancient Greek physician Hippocrates. Despite its long medical history, severity, and financial burden, the causes of sepsis are not well understood, and there is no standard approach to diagnosis and treatment. The definition of sepsis, the characterization of its clinical stages, and sepsis monitoring tools have changed three times in the past 25 years, most recently in March 2016. The universal adoption of this latest definition, sepsis-3, and a screening tool, qSOFA, are currently under debate in the medical community. A means to rapidly identify and treat sepsis could reduce the five million deaths due to sepsis each year worldwide. This paper reviews the evolution of the definition of sepsis and the controversy surrounding the sepsis-3 definition and the sepsis screening tool, qSOFA.

q-bio.TO↗

arXiv2016

Non-invasive evaluation of skin tension lines with elastic waves

Background: Since their discovery by Karl Langer in the 19th Century, Skin Tension Lines (STLs) have been used by surgeons to decide the location and orientation of an incision. Although these lines are patient-specific, most surgeons rely on generic maps to determine their orientation. Beyond the imprecise pinch test, there remains no accepted method for determining STLs in vivo. Methods: (i) The speed of an elastic motion travelling radially on the skin of canine cadavers was measured with a commercial device called the Reviscometer. (ii) Similar to the original experiments conducted by Karl Langer, circular excisions were made on the skin and the geometric changes to the resulting wounds and excised samples were used to determine the orientation of STLs. Results: A marked anisotropy in the speed of the elastic wave travelling radially was observed. The orientation of the fastest wave was found to correlate with the orientation of the elongated wound (P<0.001, R^2 = 74%). Similarly, the orientation of fastest wave was the same for both in vivo and excised isolated samples, indicating that the STLs have a structural basis. Resulting wounds expanded by an average area of 9% (+16% along STL and -10% across) while excised skin shrunk by an average area of 33% (23% along STL and 10% across). Conclusion: Elastic surface wave propagation has been validated experimentally as a robust method for determining the orientation of STLs non-destructively and non-invasively. This study has implications for the identification of STLs and for the prediction of skin tension levels, both important factors in both human and veterinary reconstructive surgery.

physics.med-ph↗

arXiv2016

Bone fusion in normal and pathological development is constrained by the network architecture of the human skull

The premature fusion of cranial bones, craniosynostosis, affects the correct development of the skull producing morphological malformations in newborns. To assess the susceptibility of each craniofacial articulation to close prematurely, we used a network model of the skull to quantify the link reliability (an index based on stochastic block modeling and Bayesian inference) of each articulation. We show that, of the 93 human skull articulations at birth, the few articulations that are associated with nonsyndromic craniosynostosis conditions have statistically significant lower reliability scores than the others. In a similar way, articulations that close during the normal postnatal development of the skull have also lower reliability scores than those articulations that persist through adult live. These results indicate a relationship between the architecture of the skull network and the specific articulations that close during normal development and in pathological conditions. Our findings suggest that the topological arrangement of skull bones might act as an epigenetic factor, predisposing some articulations to closure, both in normal and pathological development, and also affecting the long-term evolution of the skull.

q-bio.TO↗

arXiv2016

Vertex stability and topological transitions in vertex models of foams and epithelia

In computer simulations of dry foams and of epithelial tissues, vertex models are often used to describe the shape and motion of individual cells. Although these models have been widely adopted, relatively little is known about their basic theoretical properties. For example, while fourfold vertices in real foams are always unstable, it remains unclear whether a simplified vertex model description has the same behavior. Here, we study vertex stability and the dynamics of T1 topological transitions in vertex models. We show that, when all edges have the same tension, stationary fourfold vertices in these models do indeed always break up. In contrast, when tensions are allowed to depend on edge orientation, fourfold vertices can become stable, as is observed in some biological systems. More generally, our formulation of vertex stability leads to an improved treatment of T1 transitions in simulations and paves the way for studies of more biologically realistic models that couple topological transitions to the dynamics of regulatory proteins.

q-bio.TO↗