Accurate detection of dysmorphic nuclei using dynamic programming and supervised classification

A vast array of pathologies is typified by the presence of nuclei with an abnormal morphology. Dysmorphic nuclear phenotypes feature dramatic size changes or foldings, but also entail much subtler deviations such as nuclear protrusions called blebs. Due to their unpredictable size, shape and intensity, dysmorphic nuclei are often not accurately detected in standard image analysis routines. To enable accurate detection of dysmorphic nuclei in confocal and widefield fluorescence microscopy images, we have developed an automated segmentation algorithm, called Blebbed Nuclei Detector (BleND), which relies on two-pass thresholding for initial nuclear contour detection, and an optimal path finding algorithm, based on dynamic programming, for refining these contours. Using a robust error metric, we show that our method matches manual segmentation in terms of precision and outperforms state-of-the-art nuclear segmentation methods. Its high performance allowed for building and integrating a robust classifier that recognizes dysmorphic nuclei with an accuracy above 95%. The combined segmentation-classification routine is bound to facilitate nucleus-based diagnostics and enable real-time recognition of dysmorphic nuclei in intelligent microscopy workflows

Cellular Automata Models of Road Traffic

In this paper, we give an elaborate and understandable review of traffic cellular automata (TCA) models, which are a class of computationally efficient microscopic traffic flow models. TCA models arise from the physics discipline of statistical mechanics, having the goal of reproducing the correct macroscopic behaviour based on a minimal description of microscopic interactions. After giving an overview of cellular automata (CA) models, their background and physical setup, we introduce the mathematical notations, show how to perform measurements on a TCA model's lattice of cells, as well as how to convert these quantities into real-world units and vice versa. The majority of this paper then relays an extensive account of the behavioural aspects of several TCA models encountered in literature. Already, several reviews of TCA models exist, but none of them consider all the models exclusively from the behavioural point of view. In this respect, our overview fills this void, as it focusses on the behaviour of the TCA models, by means of time-space and phase-space diagrams, and histograms showing the distributions of vehicles' speeds, space, and time gaps. In the report, we subsequently give a concise overview of TCA models that are employed in a multi-lane setting, and some of the TCA models used to describe city traffic as a two-dimensional grid of cells, or as a road network with explicitly modelled intersections. The final part of the paper illustrates some of the more common analytical approximations to single-cell TCA models.Comment: Accepted for publication in "Physics Reports". A version of this paper with high-quality images can be found at: http://phdsven.dyns.cx (go to "Papers written"

Fast Multi-frame Stereo Scene Flow with Motion Segmentation

We propose a new multi-frame method for efficiently computing scene flow (dense depth and optical flow) and camera ego-motion for a dynamic scene observed from a moving stereo camera rig. Our technique also segments out moving objects from the rigid scene. In our method, we first estimate the disparity map and the 6-DOF camera motion using stereo matching and visual odometry. We then identify regions inconsistent with the estimated camera motion and compute per-pixel optical flow only at these regions. This flow proposal is fused with the camera motion-based flow proposal using fusion moves to obtain the final optical flow and motion segmentation. This unified framework benefits all four tasks - stereo, optical flow, visual odometry and motion segmentation leading to overall higher accuracy and efficiency. Our method is currently ranked third on the KITTI 2015 scene flow benchmark. Furthermore, our CPU implementation runs in 2-3 seconds per frame which is 1-3 orders of magnitude faster than the top six methods. We also report a thorough evaluation on challenging Sintel sequences with fast camera and object motion, where our method consistently outperforms OSF [Menze and Geiger, 2015], which is currently ranked second on the KITTI benchmark.Comment: 15 pages. To appear at IEEE Conference on Computer Vision and Pattern Recognition (CVPR 2017). Our results were submitted to KITTI 2015 Stereo Scene Flow Benchmark in November 201

The evolution of cell formation problem methodologies based on recent studies (1997-2008): review and directions for future research

This paper presents a literature review of the cell formation (CF) problem concentrating on formulations proposed in the last decade. It refers to a number of solution approaches that have been employed for CF such as mathematical programming, heuristic and metaheuristic methodologies and artificial intelligence strategies. A comparison and evaluation of all methodologies is attempted and some shortcomings are highlighted. Finally, suggestions for future research are proposed useful for CF researchers

Collapse Barriers and Halo Abundance: Testing the Excursion Set Ansatz

Our heuristic understanding of the abundance of dark matter halos centers around the concept of a density threshold, or "barrier", for gravitational collapse. If one adopts the ansatz that regions of the linearly evolved density field smoothed on mass scale M with an overdensity that exceeds the barrier will undergo gravitational collapse into halos of mass M, the corresponding abundance of such halos can be estimated simply as a fraction of the mass density satisfying the collapse criterion divided by the mass M. The key ingredient of this ansatz is therefore the functional form of the collapse barrier as a function of mass M or, equivalently, of the variance sigma^2(M). Several such barriers based on the spherical, Zel'dovich, and ellipsoidal collapse models have been extensively discussed. Using large scale cosmological simulations, we show that the relation between the linear overdensity and the mass variance for regions that collapse to form halos by the present epoch resembles expectations from dynamical models of ellipsoidal collapse. However, we also show that using such a collapse barrier with the excursion set ansatz predicts a halo mass function inconsistent with that measured directly in cosmological simulations. This inconsistency demonstrates a failure of the excursion set ansatz as a physical model for halo collapse. We discuss implications of our results for understanding the collapse epoch for halos as a function of mass, and avenues for improving consistency between analytical models for the collapse epoch and the results of cosmological simulations.Comment: Version accepted by ApJ, scheduled for May 2009, v696. High-res version available at http://kicp.uchicago.edu/~brant/astro-ph/excursion_set_ansatz/robertson_excursion_set_ansatz.pd

CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis

Retinoblastoma is a pediatric eye tumor in which bi-allelic inactivation of the Retinoblastoma 1 (RB1) gene is the initiating genetic lesion. Although recently curative rates of retinoblastoma have increased, there are at this time no molecular targeted therapies available. This is, in part, due to the lack of highly penetrant and rapid retinoblastoma animal models that facilitate rapid identification of targets that allow therapeutic intervention. Different mouse models are available, all based on genetic deactivation of both Rb1 and Retinoblastoma-like 1 (Rbl1), and each showing different kinetics of retinoblastoma development. Here, we show by CRISPR/Cas9 techniques that similar to the mouse, neither rb1 nor rbl1 single mosaic mutant Xenopus tropicalis develop tumors, whereas rb1/rbl1 double mosaic mutant tadpoles rapidly develop retinoblastoma. Moreover, occasionally presence of pinealoblastoma (trilateral retinoblastoma) was detected. We thus present the first CRISPR/Cas9 mediated cancer model in Xenopus tropicalis and the first genuine genetic non-mammalian retinoblastoma model. The rapid kinetics of our model paves the way for use as a pre-clinical model. Additionally, this retinoblastoma model provides unique possibilities for fast elucidation of novel drug targets by triple multiplex CRISPR/Cas9 gRNA injections (rb1 + rbl1 + modifier gene) in order to address the clinically unmet need of targeted retinoblastoma therapy

Characteristics of oligonucleotide frequencies across genomes: Conservation versus variation, strand symmetry, and evolutionary implications

One of the objectives of evolutionary genomics is to reveal the genetic information contained in the primordial genome (called the primary genetic information in this paper, with the primordial genome defined here as the most primitive nucleic acid genome for earth’s life) by searching for primitive traits or relics remained in modern genomes. As the shorter a sequence is, the less probable it would be modified during genome evolution. For that reason, some characteristics of very short nucleotide sequences would have considerable chances to persist during billions of years of evolution. Consequently, conservation of certain genomic features of mononucleotides, dinucleotides, and higher-order oligonucleotides across various genomes may exist; some, if not all, of these features would be relics of the primary genetic information. Based on this assumption, we analyzed the pattern of frequencies of mononucleotides, dinucleotides, and higher-order oligonucleotides of the whole-genome sequences from 458 species (including archaea, bacteria, and eukaryotes). Also, we studied the phenomenon of strand symmetry in these genomes. The results show that the conservation of frequencies of some dinucleotides and higher-order oligonucleotides across genomes does exist, and that strand symmetry is a ubiquitous and explicit phenomenon that may contribute to frequency conservation. We propose a new hypothesis for the origin of strand symmetry and frequency conservation as well as for the constitution of early genomes. We conclude that the phenomena of strand symmetry and the pattern of frequency conservation would be original features of the primary genetic information