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 469 records · Page 26Linked to original sources

arXiv2017

Are Paralysed Chondrocytes Really Dying?

The aims of the current study were to establish a system of culture for induction of paralysed chondrocytes and to investigate if these cells are really dying. Chondrocytes were isolated from the growth cartilage of fetal equines, centrifuged and cultured as pellets in either 10% fetal calf serum or 10% horse serum for 28 days and processed for light and electron microscopy. Different cell types were counted and expressed as a percentage to the total cell number. Growth kinetics including the pellet weight and thickness and the cellular density were evaluated. After 7 days in culture, paralysed chondrocytes with similar morphology to those described in the rabbit growth cartilage could be identified in pellets in each serum type, however, the proportion of the cells was different. In pellet cultured with 10% fetal calf serum, more than 50% of the cells were paralysed chondrocytes but in 10% horse serum, less than 10% of cells were of paralysed type. At day 14, about 50% of the cells in pellets cultured in either serum type differentiated into hypertrophic dark chondrocytes and the proportion of paralysed cells was markedly decreased. After 21 days in each culture, more than 70% of the cells were hypertrophic dark chondrocytes and no paralysed chondrocytes could be observed. The paralysed chondrocytes may be not dying and they likely to be an immature form of hypertrophic dark chondrocytes. It is better to use the term immature dark chondrocytes instead of paralysed cells. This culture system will be useful for further molecular studies on paralysed chondrocytes and to explore the functions of these cells.

q-bio.TO↗

arXiv2017

On a diffuse interface model for tumour growth with non-local interactions and degenerate mobilities

We study a non-local variant of a diffuse interface model proposed by Hawkins--Darrud et al. (2012) for tumour growth in the presence of a chemical species acting as nutrient. The system consists of a Cahn--Hilliard equation coupled to a reaction-diffusion equation. For non-degenerate mobilities and smooth potentials, we derive well-posedness results, which are the non-local analogue of those obtained in Frigeri et al. (European J. Appl. Math. 2015). Furthermore, we establish existence of weak solutions for the case of degenerate mobilities and singular potentials, which serves to confine the order parameter to its physically relevant interval. Due to the non-local nature of the equations, under additional assumptions continuous dependence on initial data can also be shown.

math.AP↗

arXiv2017

The Case for Pyriproxyfen as a Potential Cause for Microcephaly; From Biology to Epidemiology

The Zika virus has been found in individual cases but has not been confirmed as the cause of in the large number of cases of microcephaly in Brazil in 2015-6. Indeed, disparities between the incidence of Zika and microcephaly across geographic locations has led to questions about the virus's role. Here we consider whether the insecticide pyriproxyfen used in Brazilian drinking water might be the primary cause or a cofactor. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog approved as an insecticide in the 1970s has been shown to cause developmental disorders in mammals. Isotretinoin is another retinoid causing microcephaly via activation of the retinoid X receptor in developing fetuses. We review tests of pyriproxyfen by the manufacturer Sumitomo, which actually found some evidence for this effect, including low brain mass and arhinencephaly in exposed rat pups. Pyriproxyfen use in Brazil is unprecedented, never having been applied to a water supply on a large scale. Claims that its geographical pattern of use rule it out as a cause have not been documented or confirmed. On the other hand, the very few microcephaly cases reported in Colombia and the wide discrepancies of incidence in different states across Brazil despite large numbers of Zika cases undermine the claim that Zika is the cause. Given this combination of potential molecular mechanism, toxicological and epidemiological evidence we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further.

q-bio.TO↗

arXiv2017

Structural Derivative Model for Tissue Radiation Response

By means of a recently-proposed metric or structural derivative, called scale-q-derivative approach, we formulate differential equation that models the cell death by a radiation exposure in tumor treatments. The considered independent variable here is the absorbed radiation dose D instead of usual time. The survival factor, Fs, for radiation damaged cell obtained here is in agreement with the literature on the maximum entropy principle, as it was recently shown and also exhibits an excellent agreement with the experimental data. Moreover, the well-known linear and quadratic models are obtained. With this approach, we give a step forward and suggest other expressions for survival factors that are dependent on the complex tumor structure.

physics.med-ph↗

arXiv2017

Angiogenesis regulators as a possible key to accelerated growth of secondary tumors following primary tumor resection

Resection of primary tumors is often followed by accelerated growth of metastases. Here we propose that this effect may be due to the fact that resection of primary tumor results in a decrease in the total systemic amount of angiogenesis stimulators, such as VEGF and bFGF. This in turn causes decrease in the systemic level of angiogenesis inhibitors, such as PF-4 and TSP-1, which at least temporarily relieves inhibition of secondary tumors, allowing them to grow. This construct is predicated on the notion that systemic level of angiogenesis inhibitors is regulated by the systemic level of angiogenesis stimulators, as the host is trying to maintain the homeostatic balance of stimulators to inhibitors in the body. We evaluate this hypothesis using a conceptual mathematical model and show that indeed, this mechanism can explain accelerated growth of secondary tumors following resection of a primary tumor. We also show that there exists a tradeoff between time of surgery and time to onset of metastatic growth. We conclude with a discussion of possible therapeutic approaches that may counteract this effect and reduce metastatic recurrences after surgery.

q-bio.TO↗

arXiv2017

Mechanical analysis of pimple growth and pain level characterization

Pimple is one of the most common skin diseases for humans. The mechanical modeling of pimple growth is very limited. A finite element model is developed to quantify the deformation field with the expansion of follicle, and then the mechanical stimulus is related to the sensation of pain during the development of pimple. Through these models, parametric studies show the dependence of mechanical stimulus and pain level on the pimple-surrounded structures, follicle depth and mechanical properties of the epidermis. The findings in this paper may provide useful insights on prevention or pain relief of pimples, as well as those related to cosmetics and other tissue growth.

physics.med-ph↗

arXiv2017

Detecting causality in Plant electrical signal by a hybrid causal analysis approach

At present, multi-electrode array (MEA) approach and optical recording allow us to acquire plant electrical activity with higher spatio-temporal resolution. To understand the dynamic information flow of the electrical signaling system and estimate the effective connectivity, we proposed a solution to combine the two casualty analysis approaches, i.e. Granger causality and transfer entropy, which they complement each other to measure dynamics effective connectivity of the complex system. Our findings in three qualitatively different levels of plant bioelectrical activities revealed direction of information flow and dynamic complex causal connectives by using the two causal analysis approaches, especially indicated that the direction of information flow is not only along the longitudinal section but also spreading in transection.

q-bio.NC↗

arXiv2017

Amoeboid-mesenchymal migration plasticity promotes invasion only in complex heterogeneous microenvironments

During tissue invasion individual tumor cells exhibit two interconvertible migration modes, namely mesenchymal and amoeboid migration. The cellular microenvironment triggers the switch between both modes, thereby allowing adaptation to dynamic conditions. It is, however, unclear if this amoeboid-mesenchymal migration plasticity contributes to a more effective tumor invasion. We address this question with a mathematical model, where the amoeboid-mesenchymal migration plasticity is regulated in response to local extracellular matrix resistance. Our numerical analysis reveals that extracellular matrix structure and presence of a chemotactic gradient are key determinants of the model behavior. Only in complex microenvironments, if the extracellular matrix is highly heterogeneous and a chemotactic gradient directs migration, the amoeboid-mesenchymal migration plasticity allows a more widespread invasion compared to the non-switching amoeboid and mesenchymal modes. Importantly, these specific conditions are characteristic for in vivo tumor invasion. Thus, our study suggests that \emph{in vitro} systems aiming at unraveling the underlying molecular mechanisms of tumor invasion should take into account the complexity of the microenvironment by considering the combined effects of structural heterogeneities and chemical gradients on cell migration.

q-bio.TO↗

arXiv2017

Use of a clinical PET/CT scanner for whole body biodistribution of intranasal nanoparticles

Whole body biodistribution of 100 nanometer sized polymer micellar nanoparticles (NPs) was determined following intranasal administration using PET/CT imaging on a clinical scanner. Nanoparticles labeled with Zirconium 89 were administered intranasally or intravenously to Sprague Dawley rats followed by serial ex vivo PET/CT imaging in a clinical scanner. At 30 minutes and 1 hour following intranasal delivery, the animals were sacrificed and placed in the PET/CT scanner. Images were acquired and transferred to a workstation for post-processing. 3D regions of interest were constructed. A different set of animals were used for ex vivo verification. These animals were also administered 100 nm polymer micellar NPs and sacrificed at 30 min and 1 hr following intranasal or intravenous delivery via intra-cardiac perfusion. Various organs, including brain, lungs, heart, liver, spleen, stomach and intestines, were procured following exsanguination. A gamma counter determined activity in each organ for comparison with corresponding PET/CT region of interest activity measurements. The ex vivo measurements of activity were consistent with the image-based value determinations. Use of a clinical PET/CT scanner is a feasible means to determine the temporal and spatial distribution of radiolabeled agents after intranasal and intravenous delivery. This work may allow for quantitative in vivo testing of new radionanotheranostic agents.

q-bio.TO↗

arXiv2017

Cardiac re-entry dynamics & self-termination in DT-MRI based model of Human Foetal Heart

The effect of heart geometry and anisotropy on cardiac re-entry dynamics and self-termination is studied here in anatomically realistic computer simulations of human foetal heart. 20 weeks of gestational age human foetal heart isotropic and anisotropic anatomy models from diffusion tensor MRI data sets are used in the computer simulations. The fibre orientation angles of the heart were obtained from the DT-MRI primary eigenvalues. In a spatially homogeneous electrophysiological mono domain model with the DT-MRI based heart geometries, we initiate simplified Fitz-Hugh-Nagumo kinetics cardiac re-entry at a prescribed location in a 2D slice, and in the full 3D anatomy model. In a slice of the heart, the MRI based fibre anisotropy changes the re-entry dynamics from pinned to anatomical re-entry. In the full 3D MRI based model, the foetal heart fibre anisotropy changes the re-entry dynamics from a persistent re-entry to the re-entry self-termination.

q-bio.TO↗

arXiv2017

Simulated Ablation for Detection of Cells Impacting Paracrine Signalling in Histology Analysis

Intra-tumour phenotypic heterogeneity limits accuracy of clinical diagnostics and hampers the efficiency of anti-cancer therapies. Dealing with this cellular heterogeneity requires adequate understanding of its sources, which is extremely difficult, as phenotypes of tumour cells integrate hardwired (epi)mutational differences with the dynamic responses to microenvironmental cues. The later come in form of both direct physical interactions, as well as inputs from gradients of secreted signalling molecules. Furthermore, tumour cells can not only receive microenvironmental cues, but also produce them. Despite high biological and clinical importance of understanding spatial aspects of paracrine signaling, adequate research tools are largely lacking. Here, a partial differential equation (PDE) based mathematical model is developed that mimics the process of cell ablation. This model suggests how each cell might contribute to the microenvironment by either absorbing or secreting diffusible factors, and quantifies the extent to which observed intensities can be explained via diffusion mediated signalling. The model allows for the separation of phenotypic responses to signalling gradients within tumour microenvironments from the combined influence of responses mediated by direct physical contact and hardwired (epi)genetic differences. The differential equation is solved around cell membrane outlines using a finite element method (FEM). The method is applied to a multi-channel immunofluorescence in situ hybridization (iFISH) stained breast cancer histological specimen and correlations are investigated between: HER2 gene amplification; HER2 protein expression; and cell interaction with the diffusible microenvironment. This approach allows partial deconvolution of the complex inputs...

q-bio.CB↗

arXiv2017

Quantifying Subtle Regions of Order and Disorder in Tumor Architecture by Calculating the Nearest-Neighbor Angular Profile

Pathologists routinely classify breast tumors according to recurring patterns of nuclear grades, cytoplasmic coloration, and large-scale morphological formations (i.e. streams of spindle cells, adenoid islands, etc.). The fact that there are large-scale morphological formations suggest that tumor cells still possess the genetic programming to arrange themselves in orderly patterns. However, small regions of order or subtle patterns of order are invisible to the human eye. The ability to detect subtle regions of order and correlate them with clinical outcome and resistance to treatment can enhance diagnostic efficacy. By measuring the acute angle that results when the line extending from the longest length within a nucleus intersects with the corresponding line of an adjacent nucleus, the degree of alignment between two adjacent nuclei can be measured. Through a series of systematic transformations, subtle regions of order and disorder within a tumor image can be quantified and visualized in the form of a heat map. This numerical transformation of spatial relationships between nuclei within tumors allows for the detection of subtly ordered regions.

q-bio.TO↗

arXiv2017

Quantifying Hidden Architectural Patterns in Metaplastic Tumors by Calculating the Quadrant-Slope Index (QSI)

The Quadrant-Slope Index (QSI) method was created in order to detect subtle patterns of organization in tumor images that have metaplastic elements, such as streams of spindle cells [1]. However, metaplastic tumors also have nuclei that may be aligned like a stream but are not obvious to the pathologist because the shape of the cytoplasm is unclear. The previous method that I developed, the Nearest-Neighbor Angular Profile (N-NAP) method [2], is good for detecting subtle patterns of order based on the assumption that breast tumor cells are attempting to arrange themselves side-by-side (like bricks), as in the luminal compartment of a normal mammary gland [3]. However, this assumption is not optimal for detecting cellular arrangements that are head-to-tail, such as in streams of spindle cells. Metaplastic carcinomas of the breast (i.e. basal-like breast cancers, triple-negative breast cancers) are believed to be derived from the stem or progenitor cells that reside in the basal/myoepithelial compartment of the normal mammary gland [Reviewed in 3]. Epithelial cells in the basal/myoepithelial compartment arrange themselves in an head-to-tail fashion, forming a net that surrounds the luminal compartment [3,4]. If cancer cells in a metaplastic tumor are trying to be normal, the optimal way to detect subtle regions of them attempting to be ordered normally should highlight the head-to-tail alignment of cells.

q-bio.TO↗

arXiv2017

Simulating Wear On Total Knee Replacements

Wear on total knee replacements (TKRs) is an important criterion for their performance characteristics. Numerical simulations of such wear has seen increasing attention over the last years. They have the potential to be much faster and less expensive than the in vitro tests in use today. While it is unlikely that in silico tests will replace actual physical tests in the foreseeable future, a judicious combination of both approaches can help making both implant design and pre-clinical testing quicker and more cost-effective. The challenge today for the design of simulation methods is to obtain results that convey quantitative information, and to do so quickly and reliably. This involves the choice of mathematical models as well as the numerical tools used to solve them. The correctness of the choice can only be validated by comparing with experimental results. In this paper we present finite element simulations of the wear in TKRs during the gait cycle standardized in the ISO 14243-1 document, used for compliance testing in several countries. As the ISO 14243-1 standard is precisely defined and publicly available, it can serve as an excellent benchmark for comparison of wear simulation methods. Our novel contact algorithm works without Lagrange multipliers and penalty methods, achieving unparalleled stability and efficiency. We compare our simulation results with the experimental data from physical tests using two different actual TKRs, each test being performed three times. We can closely predict the total mass loss due to wear after five million gait cycles. We also observe a good match between the wear patterns seen in experiments and our simulation results.

q-bio.TO↗

arXiv2017

Prefer Nested Segmentation to Compound Segmentation

Introduction: Intra-organ radiation dose sensitivity is becoming increasingly relevant in clinical radiotherapy. One method for assessment involves partitioning delineated regions of interest and comparing the relative contributions or importance to clinical outcomes. We show that an intuitive method for dividing organ contours, compound (sub-)segmentation, can unintentionally lead to sub-segments with inconsistent volumes, which will bias relative importance assessment. An improved technique, nested segmentation, is introduced and compared. Methods: Clinical radiotherapy planning parotid contours from 510 patients were segmented. Counts of radiotherapy dose matrix voxels interior to sub-segments were used to determine the equivalency of sub-segment volumes. The distribution of voxel counts within sub-segments were compared using Kolmogorov-Smirnov tests and characterized by their dispersion. Analytical solutions for 2D/3D analogues were derived and sub-segment area/volume were compared directly. Results: Both parotid and 2D/3D region of interest analogue segmentation confirmed compound segmentation intrinsically produces sub-segments with volumes that depend on the region of interest shape and selection location. Significant volume differences were observed when sub-segmenting parotid contours into 18ths, and vanishingly small sub-segments were observed when sub-segmenting into 96ths. Central sub-segments were considerably smaller than sub-segments on the periphery. Nested segmentation did not exhibit these shortcomings and produced sub-segments with equivalent volumes when dose grid and contour collinearity was addressed, even when dividing the parotid into 96ths. Nested segmentation was always faster or equivalent in runtime to compound segmentation. Conclusions: Nested segmentation is more suited than compound segmentation for analyses requiring equal weighting of sub-segments.

q-bio.QM↗

arXiv2017

A Nonconventional Analysis of CD$4^{+}$ and CD$8^{+}$ T Cell Responses During and After Acute Lymphocytic Choriomeningitis Virus Infection

A mathematical model from a previous work was re-fitted and analyzed for experimental data regarding the cellular immune response to the lymphocytic choriomeningitis virus. Specifically, the $CD8^{+}$ T cell response to six MHC class I-restricted epitopes (GP* and NP*) and $CD4^{+}$ T cell responses to two MHC class II-restricted epitopes\cite{de2003different}. In this work, we use calibration through log likelihood maximization to investigate if different parameters can produce a more accurate fit of the model presented previously in the paper titled \textit{Different Dynamics of CD$4^{+}$ and CD$8^{+}$ T Cell Responses During and After Acute Lymphocytic Choriomeningitis Virus Infection}\cite{de2003different}

q-bio.TO↗

arXiv2017

Layer dependent role of collagen recruitment during loading of the rat bladder wall

In this work, we reevaluated long standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas, these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy (MPM) was used to directly measure the layer dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves were evaluated in the context of the inner bladder wall (lamina propria) and outer detrusor smooth muscle layer. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For elastic bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria and detrusor smooth muscle layers was found. A second important finding is that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder capacitance.

q-bio.TO↗

arXiv2017

Parametric Imaging of FDG-PET Data Using Physiology and Iterative Regularization: Application to the Hepatic and Renal Systems

The present paper proposes a novel computational method for parametric imaging of nuclear medicine data. The mathematical procedure is general enough to work for compartmental models of diverse complexity and is effective in the determination of the parametric maps of all kinetic parameters governing tracer flow. We consider applications to [18F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) data and analyze the two-compartment catenary model describing the standard FDG metabolization by an homogeneous tissue, e.g. the liver, and the three-compartment non-catenary model representing the renal physiology. The proposed imaging method starts from the reconstructed FDG-PET images of tracer concentration and preliminarily applies image processing algorithms for noise reduction and image segmentation processes for selecting the region enclosing the organ of physiologic interest. The optimization scheme solves pixelwise the non-linear inverse problem of determining the kinetic parameters from dynamic concentration data through a Gauss-Newton iterative algorithm with a penalty term accounting for the ill-posedness of the problem. We tested our imaging approach on FDG-PET data of murine models obtained by means of a dedicated microPET system, and we analyzed different PET slices containing axial sections of the liver and axial sections of the kidneys. The reconstructed parametric images proved to be reliable and qualitatively effective in the description of the local FDG metabolism with respect to the different physiologies.

q-bio.TO↗