scholarly journals Quantification of spatial subclonal interactions enhancing the invasive phenotype of paediatric glioma

2021 ◽  
Author(s):  
Haider Tari ◽  
Ketty Kessler ◽  
Nicholas Trahearn ◽  
Benjamin Werner ◽  
Maria Vinci ◽  
...  

AbstractIntra-tumour heterogeneity is an intrinsic property of all cancers. In some cases, such variation can be maintained by interactions between tumour subclones with distinct molecular and phenotypic characteristics. In paediatric gliomas, interactions can take the form of enhanced invasive phenotype, a hallmark of these malignancies. However, subclonal interactions are hard to quantify and difficult to distinguish from spatial confounding factors and experimental bias. Here we combine spatial computational modelling of cellular interactions and invasion, with co-evolution experiments of clonally disassembled primary glioma lines derived at autopsy. We design a Bayesian inference framework to quantify spatial subclonal interactions between molecular and phenotypically distinct lineages with different patterns of invasion. We show how this approach could discriminate genuine subclonal interactions where one clone enhanced the invasive phenotype of another, from apparent interactions that were only due to the complex dynamics of subclones growing in space. This study provides a new approach for the identification and quantification of spatial subclonal interactions in cancer.

2020 ◽  
Vol 86 (5) ◽  
Author(s):  
Emanuele Papini ◽  
Antonio Cicone ◽  
Mirko Piersanti ◽  
Luca Franci ◽  
Petr Hellinger ◽  
...  

Turbulent space and astrophysical plasmas exhibit a complex dynamics, which involves nonlinear coupling across different temporal and spatial scales. There is growing evidence that impulsive events, such as magnetic reconnection instabilities, lead to a spatially localized enhancement of energy dissipation, thus speeding up the energy transfer at small scales. Capturing such a diverse dynamics is challenging. Here, we employ the Multidimensional Iterative Filtering (MIF) method, a novel technique for the analysis of non-stationary multidimensional signals. Unlike other traditional methods (e.g. based on Fourier or wavelet decomposition), MIF does not require any previous assumption on the functional form of the signal to be identified. Using MIF, we carry out a multiscale analysis of Hall-magnetohydrodynamic (HMHD) and hybrid particle-in-cell (HPIC) numerical simulations of decaying plasma turbulence. The results assess the ability of MIF to spatially identify and separate the different scales (the MHD inertial range, the sub-ion kinetic and the dissipation scales) of the plasma dynamics. Furthermore, MIF decomposition allows localized current structures to be detected and their contribution to the statistical and spectral properties of turbulence to be characterized. Overall, MIF arises as a very promising technique for the study of turbulent plasma environments.


2020 ◽  
Vol 6 (2) ◽  
pp. 319-328 ◽  
Author(s):  
Christina Kolaiti

This visual essay narrates three parallel bodies of photographic work, which negotiate the role of context, displacement and geocultural relocation as metaphors for self-definition. The conceptual framework of the work is underpinned by the psychoanalytic theories of Murray Bowen and Morgan Scott, which locate self-perception at the centre of the familial context and define the quest for self-definition as a symbolic process of map-making. This approach describes a psychological landscape where the fluid relationship between collective and personal identity is conveyed through the metaphor of ‘Mal de Débarquement’ (a diagnosable condition that means nausea of disembarkation). This kind of embedded fluidity in self-representation insinuates a new approach to the practice and possibilities of photographic portraiture, and challenges the traditional definition, which associates the portrait with the depiction of a fixed identity.


Author(s):  
Д.Д. Кульминский ◽  
В.И. Пономаренко ◽  
И.В. Сысоев ◽  
М.Д. Прохоров

A new approach is proposed that allows one to investigate experimentally complex dynamics in large ensembles of coupled radio engineering generators. The approach is used for the construction of an analog-to-digital experimental setup for studying ensembles of generators with time-delayed feedback. A possibility of specifying an arbitrary architecture of couplings and different types of couplings between generators is implemented in the setup. It is shown that the complex topology of couplings and parameters of all generators can be reconstructed from their experimental time series.


2021 ◽  
Vol 9 ◽  
Author(s):  
Sophie Chagnon-Lessard ◽  
Hubert Jean-Ruel ◽  
Michel Godin ◽  
Andrew E. Pelling

Our organs and tissues are in constant motion, exposing epithelial cells to mechanical stretch. How these external forces impact cellular morphology, organization and dynamics in healthy and diseased tissues is still being elucidated. Carcinoma, the most common type of cancer, develops in the sheets of cells forming the epithelium and lining our organs and cavities. It usually begins with the transformation of a single cell via the activation of oncogenes such as Ras. Here, we show in a model system how mechanical stretch in epithelial sheets results in a more invasive phenotype in transformed cells. Cyclic strain impedes the apical extrusion of RasV12 cells from the healthy monolayer and prevents the formation of strong circumferential belts of actin in RasV12 cells. Concurrently, strain also changes the metastatic phenotype of newly transformed cells by greatly promoting the formation of RasV12 protrusions, potentially making them harder to be eliminated from healthy tissues. We also show that RasV12 and wild type MDCK cells possess distinct sensitivity to strain. External forces remodel their actin cytoskeletons and adhesion complexes differently, resulting in a more invasive system dynamic. Our work demonstrates that the Rho-ROCK mechanotransduction pathway is involved in regulating a mechanically-induced switch to a more invasive phenotype. The insights gained in this study reveal that the complex dynamics at play in healthy and transformed epithelial cells is drastically different in a mechanically active microenvironment when compared to static conditions.


2019 ◽  
Vol 35 (1) ◽  
pp. 17-33
Author(s):  
Tobias Blanke ◽  
Michael Bryant ◽  
Mark Hedges

Abstract This article addresses an important challenge in artificial intelligence research in the humanities, which has impeded progress with supervised methods. It introduces a novel method to creating test collections from smaller subsets. This method is based on what we will introduce as distant supervision’ and will allow us to improve computational modelling in the digital humanities by including new methods of supervised learning. Using recurrent neural networks, we generated a training corpus and were able to train a highly accurate model that qualitatively and quantitatively improved a baseline model. To demonstrate our new approach experimentally, we employ a real-life research question based on existing humanities collections. We use neural network based sentiment analysis to decode Holocaust memories and present a methodology to combine supervised and unsupervised sentiment analysis to analyse the oral history interviews of the United States Holocaust Memorial Museum. Finally, we employed three advanced methods of computational semantics. These helped us decipher the decisions by the neural network and understand, for instance, the complex sentiments around family memories in the testimonies.


2020 ◽  
pp. 143-159
Author(s):  
Alessandra Terenzi ◽  
Matteo Colleoni

This study focuses on different groups of Palestinian citizens of Israel, representing more than 20% of the total Israeli population. Working on the link between urban space and social diversity, the authors will capture complex dynamics of segregation and social inequalities ex-isting among different Arab communities. This research aims to promote a new approach that, overcoming the stereotyped vision of two social monolithic blocks at war with each other - Jews and Arabs- shows a complex social mosaic of multiple cultural identities, characterizing the contemporary Israeli society.


1996 ◽  
Vol 263 (1370) ◽  
pp. 601-606 ◽  

Computational models of activity-dependent competitive neural plasticity typically impose competition in networks in which plasticity is accommodated by permitting changes in the efficacies of synapses in an anatomically fixed network. This is despite the fact that much evidence suggests that neurons compete for neurotrophins, during both target innervation and activity-dependent synaptic re-arrangement, which influence the sprouting and retraction of axonal processes. We therefore present a new approach to the computational modelling of competitive neural plasticity which permits neurons to compete explicitly for neurotrophins. This competition is associated with the sprouting and retraction of axonal processes. Because there is much uncertainty regarding the basic mechanisms, we adopt the powerful machinery of statistical mechanics to avoid the need to address these issues. We show that such an approach can readily account for a wide range of plasticity phenomena in a range of systems, including the results of various pharmacological manipulations.


2016 ◽  
Vol 13 (121) ◽  
pp. 20160218 ◽  
Author(s):  
Torsten Thalheim ◽  
Peter Buske ◽  
Jens Przybilla ◽  
Karen Rother ◽  
Markus Loeffler ◽  
...  

Three-dimensional (3D) computational tissue models can provide a comprehensive description of tissue dynamics at the molecular, cellular and tissue level. Moreover, they can support the development of hypotheses about cellular interactions and about synergies between major signalling pathways. We exemplify these capabilities by simulation of a 3D single-cell-based model of mouse small intestinal crypts. We analyse the impact of lineage specification, distribution and cellular lifespan on clonal competition and study effects of Notch- and Wnt activation on fixation of mutations within the tissue. Based on these results, we predict that experimentally observed synergistic effects between autonomous Notch- and Wnt signalling in triggering intestinal tumourigenesis originate in the suppression of Wnt-dependent secretory lineage specification by Notch, giving rise to an increased fixation probability of Wnt-activating mutations. Our study demonstrates that 3D computational tissue models can support a mechanistic understanding of long-term tissue dynamics under homeostasis and during transformation.


2012 ◽  
Vol 2012 ◽  
pp. 1-13
Author(s):  
V. S. Khoroshilov ◽  
A. E. Zakrzhevskii

In this paper, a new approach to the modelling of the deployment dynamics of a flexible multi-body system with the time dependent configurations is demonstrated in the frame of the study the dynamics of a spacecraft with the gyro-gravitational system of stabilization. Primarily the gravitational stabilizer that is made as a pantograph structure is in a compact form. The deployment of a flexible pantograph structure is performed after placing the spacecraft into orbit and completion of the preliminary damping by a special jet-propelled system, and after uncaging the gyros. After its deployment, the pantograph turns into an elongated structure that serves as a gravitational stabilizer and carrier of solar batteries. The objective of the study is the creation of the generalized mathematical model and the conducting of the computational modelling of the spacecraft dynamics. The equations of motion are derived with the use of the Eulerian-LaGrangian formalism and symbolic computing. Numerical simulations of the typical operational mode of the system are conducted taking into account various control profiles for the deployment. Numerical results indicate that the system used for attitude stabilization ensures the shape of the deployed design and prescribed accuracy of the orientation.


2021 ◽  
pp. jeb.237073
Author(s):  
Deepak K. Ravi ◽  
Marc Bartholet ◽  
Andreas Skiadopoulos ◽  
Jenny A. Kent ◽  
Jordan Wickstrom ◽  
...  

The capacity to recover after a perturbation is a well-known intrinsic property of physiological systems, including the locomotor system, and can be termed resilience. Despite an abundance of metrics proposed to measure the complex dynamics of bipedal locomotion, analytical tools for quantifying resilience are lacking. Here, we introduce a novel method to directly quantify resilience to perturbations during locomotion. We examine the extent to which synchronizing stepping with two different temporal structured auditory stimuli (periodic and 1/f structure) during walking modulates resilience to a large unexpected perturbation. Recovery time after perturbation was calculated from the horizontal velocity of body's center of mass. Our results indicate that synchronizing stepping with 1/f stimulus elicited greater resilience to mechanical perturbations during walking compared to the periodic stimulus (3.3 seconds faster). Our proposed method may help to gain a comprehensive understanding of movement recovery behavior of humans and other animals in their ecological contexts.


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