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Martin Poot
The highly complex structural genome variations chromothripsis, chromoanasynthesis, and chromoplexy are subsumed under the term chromoanagenesis, which means chromosome rebirth. Precipitated by numerous DNA double-strand breaks, they differ in number of and distances between breakpoints, associated copy number variations, order and orientation of segments, and flanking sequences at joining points. Results from patients with the autosomal dominant cancer susceptibility disorder Li-Fraumeni syndrome implicated somatic TP53 mutations in chromothripsis...
2018: Methods in Molecular Biology
Annekathrin Reinhardt, Damian Stichel, Daniel Schrimpf, Felix Sahm, Andrey Korshunov, David E Reuss, Christian Koelsche, Kristin Huang, Annika K Wefers, Volker Hovestadt, Martin Sill, Dorothee Gramatzki, Joerg Felsberg, Guido Reifenberger, Arend Koch, Ulrich-W Thomale, Albert Becker, Volkmar H Hans, Marco Prinz, Ori Staszewski, Till Acker, Hildegard Dohmen, Christian Hartmann, Wolf Mueller, Muin S A Tuffaha, Werner Paulus, Katharina Heß, Benjamin Brokinkel, Jens Schittenhelm, Camelia-Maria Monoranu, Almuth Friederike Kessler, Mario Loehr, Rolf Buslei, Martina Deckert, Christian Mawrin, Patricia Kohlhof, Ekkehard Hewer, Adriana Olar, Fausto J Rodriguez, Caterina Giannini, Amulya A NageswaraRao, Uri Tabori, Nuno Miguel Nunes, Michael Weller, Ute Pohl, Zane Jaunmuktane, Sebastian Brandner, Andreas Unterberg, Daniel Hänggi, Michael Platten, Stefan M Pfister, Wolfgang Wick, Christel Herold-Mende, David T W Jones, Andreas von Deimling, David Capper
Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas...
March 21, 2018: Acta Neuropathologica
Colin J Carlson, Eric Dougherty, Mike Boots, Wayne Getz, Sadie J Ryan
Ecologists are increasingly involved in the pandemic prediction process. In the course of the Zika outbreak in the Americas, several ecological models were developed to forecast the potential global distribution of the disease. Conflicting results produced by alternative methods are unresolved, hindering the development of appropriate public health forecasts. We compare ecological niche models and experimentally-driven mechanistic forecasts for Zika transmission in the continental United States. We use generic and uninformed stochastic county-level simulations to demonstrate the downstream epidemiological consequences of conflict among ecological models, and show how assumptions and parameterization in the ecological and epidemiological models propagate uncertainty and produce downstream model conflict...
March 21, 2018: Scientific Reports
Simon Maccracken Stump, Evan Curtis Johnson, Christopher A Klausmeier
Mutualisms are ubiquitous, but models predict they should be susceptible to cheating. Resolving this paradox has become relevant to synthetic ecology: cooperative cross-feeding, a nutrient-exchange mutualism, has been proposed to stabilize microbial consortia. Previous attempts to understand how cross-feeders remain robust to non-producing cheaters have relied on complex behaviour (e.g. cheater punishment) or group selection. Using a stochastic spatial model, we demonstrate two novel mechanisms that can allow cross-feeders to outcompete cheaters, rather than just escape from them...
March 2018: Journal of the Royal Society, Interface
Emma S T Aller, Lea M Jagd, Daniel J Kliebenstein, Meike Burow
The theoretical ability of epigenetic variation to influence the heritable variation of complex traits is gaining traction in the study of adaptation. This theory posits that epigenetic marks can control adaptive phenotypes but the relative potential of epigenetic variation in comparison to genetic variation in these traits is not presently understood. To compare the potential of epigenetic and genetic variation in adaptive traits, we analyzed the influence of DNA methylation variation on the accumulation of chemical defense compounds glucosinolates from the order Brassicales...
March 21, 2018: G3: Genes—Genomes—Genetics
György Abrusán, Joseph A Marsh
It has been suggested that the evolution of protein complexes is significantly influenced by stochastic, non-adaptive processes. Using ligand binding as a proxy of function, we show that the structure of ligand-binding sites significantly influences the evolution of protein complexes. We show that homomers with multi-chain binding sites (MBSs) evolve new functions slower than monomers or other homomers, and those binding cofactors and metals have more conserved quaternary structure than other homomers. Moreover, the ligands and ligand-binding pockets of homologous MBS homomers are more similar than monomers and other homomers...
March 20, 2018: Cell Reports
Caterina Monini, Micaela Cunha, Etienne Testa, Michaёl Beuve
NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and diffusion of reactive chemical species. In order to further characterize the new framework, we discuss the meaning and relevance of most of the NanOx parameters by evaluating their influence on the linear-quadratic coefficient α and on the dose deposited to achieve 10% or 1% of cell survival, D 10 % or D 1 % , as a function of LET...
March 21, 2018: Cancers
Markus Selmke, Utsab Khadka, Andreas P Bregulla, Frank Cichos, Haw Yang
Photon nudging is a new experimental method which enables the force-free manipulation and localization of individual self-propelled artificial micro-swimmers in fluidic environments. It uses a weak laser to stochastically and adaptively turn on and off the swimmer's propulsion when the swimmer, through rotational diffusion, points towards or away from its target, respectively. This contribution presents a theoretical framework for the statistics of both 2D and 3D controls. The main results are: the on- and off-time distributions for the controlling laser, the arrival time statistics for the swimmer to reach a remote target, and how the experimentally accessible control parameters influence the control, e...
March 21, 2018: Physical Chemistry Chemical Physics: PCCP
Mohit Kumar Jolly, Prakash Kulkarni, Keith Weninger, John Orban, Herbert Levine
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease...
2018: Frontiers in Oncology
K P Jayachandran, J M Guedes, H C Rodrigues
Electrical control of magnetization offers an extra degree of freedom in materials possessing both electric and magnetic dipole moments. A stochastic optimization combined with homogenization is applied for the solution for maximum magnetoelectric (ME) coupling coefficient α of a laminar ME composite with the thickness and orientation of ferroelectric phase as design variables. Simulated annealing with a generalized Monte Carlo scheme is used for optimization problem. Optimal microstructure with single and poly-crystalline configurations that enhances the overall α is identified...
March 20, 2018: Scientific Reports
Calvin K Lee, Jaime de Anda, Amy E Baker, Rachel R Bennett, Yun Luo, Ernest Y Lee, Joshua A Keefe, Joshua S Helali, Jie Ma, Kun Zhao, Ramin Golestanian, George A O'Toole, Gerard C L Wong
Using multigenerational, single-cell tracking we explore the earliest events of biofilm formation by Pseudomonas aeruginosa During initial stages of surface engagement (≤20 h), the surface cell population of this microbe comprises overwhelmingly cells that attach poorly (∼95% stay <30 s, well below the ∼1-h division time) with little increase in surface population. If we harvest cells previously exposed to a surface and direct them to a virgin surface, we find that these surface-exposed cells and their descendants attach strongly and then rapidly increase the surface cell population...
March 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sy-Miin Chow, Lu Ou, Arridhana Ciptadi, Emily B Prince, Dongjun You, Michael D Hunter, James M Rehg, Agata Rozga, Daniel S Messinger
A growing number of social scientists have turned to differential equations as a tool for capturing the dynamic interdependence among a system of variables. Current tools for fitting differential equation models do not provide a straightforward mechanism for diagnosing evidence for qualitative shifts in dynamics, nor do they provide ways of identifying the timing and possible determinants of such shifts. In this paper, we discuss regime-switching differential equation models, a novel modeling framework for representing abrupt changes in a system of differential equation models...
March 19, 2018: Psychometrika
Ivan Tyukin, Alexander N Gorban, Carlos Calvo, Julia Makarova, Valeri A Makarov
Codifying memories is one of the fundamental problems of modern Neuroscience. The functional mechanisms behind this phenomenon remain largely unknown. Experimental evidence suggests that some of the memory functions are performed by stratified brain structures such as the hippocampus. In this particular case, single neurons in the CA1 region receive a highly multidimensional input from the CA3 area, which is a hub for information processing. We thus assess the implication of the abundance of neuronal signalling routes converging onto single cells on the information processing...
March 19, 2018: Bulletin of Mathematical Biology
D J Huels, L Bruens, M C Hodder, P Cammareri, A D Campbell, R A Ridgway, D M Gay, M Solar-Abboud, W J Faller, C Nixon, L B Zeiger, M E McLaughlin, E Morrissey, D J Winton, H J Snippert, J van Rheenen, O J Sansom
Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell...
March 19, 2018: Nature Communications
Juan V Escobar, Isaac Pérez Castillo
When complex systems are driven to depletion by some external factor, their non-stationary dynamics can present an intermittent behaviour between relative tranquility and burst of activity whose consequences are often catastrophic. To understand and ultimately be able to predict such dynamics, we propose an underlying mechanism based on sharp thresholds of a local generalized energy density that naturally leads to negative feedback. We find a transition from a continuous regime to an intermittent one, in which avalanches can be predicted despite the stochastic nature of the process...
March 19, 2018: Scientific Reports
A N Gorban, I Y Tyukin
The concentrations of measure phenomena were discovered as the mathematical background to statistical mechanics at the end of the nineteenth/beginning of the twentieth century and have been explored in mathematics ever since. At the beginning of the twenty-first century, it became clear that the proper utilization of these phenomena in machine learning might transform the curse of dimensionality into the blessing of dimensionality This paper summarizes recently discovered phenomena of measure concentration which drastically simplify some machine learning problems in high dimension, and allow us to correct legacy artificial intelligence systems...
April 28, 2018: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Robin Hudson
This is a personal survey of aspects of quantum probability related to the Heisenberg commutation relation for canonical pairs. Using the failure, in general, of non-negativity of the Wigner distribution for canonical pairs to motivate a more satisfactory quantum notion of joint distribution, we visit a central limit theorem for such pairs and a resulting family of quantum planar Brownian motions which deform the classical planar Brownian motion, together with a corresponding family of quantum stochastic areas...
April 28, 2018: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Huei-Mien Ke, Dang Liu, Yoshitoshi Ogura, Tetsuya Hayashi, Henryk Urbanczyk, Isheng J Tsai
The mechanism of bacterial speciation remains a topic of tremendous interest. To understand the ecological and evolutionary mechanisms of speciation in Vibrio bacteria, we analyzed the genomic dissimilarities between three closely related species in the so-called Harveyi clade of the genus Vibrio : V. campbellii , V. jasicida and V. hyugaensis The analysis focused on strains isolated from diverse geographic locations, over a long period of time. Results of phylogenetic analyses and calculations of average nucleotide identities (ANI) supported classification of V...
March 19, 2018: Journal of Bacteriology
Absalom E Ezugwu, Francis Akutsah, Micheal O Olusanya, Aderemi O Adewumi
The intelligent water drop algorithm is a swarm-based metaheuristic algorithm, inspired by the characteristics of water drops in the river and the environmental changes resulting from the action of the flowing river. Since its appearance as an alternative stochastic optimization method, the algorithm has found applications in solving a wide range of combinatorial and functional optimization problems. This paper presents an improved intelligent water drop algorithm for solving multi-depot vehicle routing problems...
2018: PloS One
Diego F Munoz, Cong Xu, Sylvia K Plevritis
We present a Monte Carlo simulation model that reproduces US invasive breast cancer incidence and mortality trends from 1975 to 2010 as a function of screening and adjuvant treatment. This model was developed for multiple purposes, including to quantify the impact of screening and adjuvant therapy on past and current trends, predict future trends, and evaluate potential outcomes under hypothetical screening and treatment interventions. The model first generates the life histories of individual breast cancer patients by determining the patient's age, tumor size, estrogen receptor (ER) status, human epidermal growth factor 2 (HER2) status, SEER (Surveillance, Epidemiology, and End Results) historic stage, detection mode at time of detection, preclinical tumor course, and death age and cause of death (breast cancer v...
April 2018: Medical Decision Making: An International Journal of the Society for Medical Decision Making
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