Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization

ABSTRACTCombining genome-wide structural models with phenomenological data is at the forefront of efforts to understand the organizational principles regulating the human genome. Here, we use chromosome-chromosome contact data as knowledge- based constraints for large-scale three-dimensional models of the human diploid genome. The resulting models remain minimally entangled and acquire several functional features that are observed in vivo and that were never used as input for the model. We find, for instance, that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina-associated domains are pushed to the periphery. These and other properties persist upon adding local contact constraints, suggesting their compatibility with non-local constraints for the genome organization. The results show that suitable combinations of data analysis and physical modelling can expose the unexpectedly rich functionally-related properties implicit in chromosome-chromosome contact data. Specific directions are suggested for further developments based on combining experimental data analysis and genomic structural modelling.

Download Full-text

Protein Folding: Search for Basic Physical Models

The Scientific World JOURNAL ◽

10.1100/tsw.2003.50 ◽

2003 ◽

Vol 3 ◽

pp. 623-635 ◽

Cited By ~ 3

Author(s):

Ivan Y. Torshin ◽

Robert W. Harrison

Keyword(s):

Protein Folding ◽

Tertiary Structure ◽

Three Dimensional ◽

Physical Models ◽

Dimensional Structure ◽

Computational Techniques ◽

Linear Sequence ◽

Physical Forces

How a unique three-dimensional structure is rapidly formed from the linear sequence of a polypeptide is one of the important questions in contemporary science. Apart from biological context ofin vivoprotein folding (which has been studied only for a few proteins), the roles of the fundamental physical forces in thein vitrofolding remain largely unstudied. Despite a degree of success in using descriptions based on statistical and/or thermodynamic approaches, few of the current models explicitly include more basic physical forces (such as electrostatics and Van Der Waals forces). Moreover, the present-day models rarely take into account that the protein folding is, essentially, a rapid process that produces a highly specific architecture. This review considers several physical models that may provide more direct links between sequence and tertiary structure in terms of the physical forces. In particular, elaboration of such simple models is likely to produce extremely effective computational techniques with value for modern genomics.

Download Full-text

Inside the Decentralised Casino: A Longitudinal Study of Actual Cryptocurrency Gambling Transactions

10.31219/osf.io/xhfpw ◽

2020 ◽

Author(s):

Oliver James Scholten ◽

David Zendle ◽

James Alfred Walker

Keyword(s):

Data Analysis ◽

Longitudinal Study ◽

Large Scale ◽

Online Gambling ◽

Research Platform ◽

Player Behaviour ◽

Typical User

Decentralised gambling applications are a new way for individuals to engage in online gambling. Decentralised gambling applications are distinguished from traditional online casinos in that individuals use cryptocurrency as a stake. Furthermore, rather than being stored on a traditional server, decentralised gambling applications are stored on a cryptocurrency’s blockchain.Previous work in the player behaviour tracking literature has examined the spending profiles of gamblers on traditional online casinos. However, parallel work has not taken place in the decentralised gambling domain. The profile of gamblers on decentralised gambling applications are therefore not known.This paper explores 2,232,741 transactions from 24,234 unique addresses to three such applications operating atop the Ethereum cryptocurrency network over 583 days. We present spending profiles across these applications, providing the first detailed summary of spending behaviours in this technologically advanced domain. We find that the typical user spends approximately \$110 equivalent across a median of 6 bets in a single day, although heavily involved bettors spend approximately \$100,000 equivalent over a median of 644 bets across 35 days. Our findings suggest that the use of decentralised gambling applications typically involves lower and less frequent expenditures than other online casinos, but that the most heavily involved players in this new domain spend substantially more. Our findings also demonstrate the use of these applications as a research platform, specifically for large scale longitudinal in-vivo data analysis.

Download Full-text

Generation and Annihilation of Magnetic Helicity in Active Regions

Highlights of Astronomy ◽

10.1017/s1539299600015227 ◽

2005 ◽

Vol 13 ◽

pp. 113-116

Author(s):

K. Kusano

Keyword(s):

Numerical Simulations ◽

Solar Flares ◽

Large Scale ◽

Inversion Layer ◽

Three Dimensional ◽

Active Regions ◽

Nonlinear Process ◽

Magnetic Helicity ◽

Numerical Techniques ◽

Magnetogram Data

AbstractGeneration and annihilation processes of magnetic helicity in solar coronal active regions are investigated based on the observations and the simulations. We first examined the reliability of the numerical techniques, which enable to measure the magnetic helicity flux through the photosphere based on the magnetogram data. Secondly, in terms of the new technique, we found that magnetic helicities of the both signs are simultaneously injected into active regions. Motivated by this result, finally, we investigated the nonlinear process of the magnetic helicity annihilation, using the three-dimensional numerical simulations. The simulations clearly indicated that the helicity reversal can cause the eruption of large-scale plasmoid through the nonlinear process of the resistive instability growing on the helicity inversion layer. From these studies, we point out that the annihilation of magnetic helicity is a key process for the onset mechanism of solar flares.

Download Full-text

Developing Innovative Deep Water Pipeline Construction Techniques with Physical Models

Journal of Offshore Mechanics and Arctic Engineering ◽

10.1115/1.2426982 ◽

2004 ◽

Vol 129 (1) ◽

pp. 56-60 ◽

Cited By ~ 3

Author(s):

R. J. Brown ◽

Andrew Palmer

Keyword(s):

Deep Water ◽

Large Scale ◽

Three Dimensional ◽

Physical Models ◽

Governing Equations ◽

Pipeline Construction ◽

Construction Techniques ◽

Construction Risk ◽

Water Pipeline ◽

Model Technique

On the large scale of deep-water construction, marine pipelines are extremely flexible. Construction procedures can exploit that flexibility to connect pipelines and risers to floaters, manifolds, wellheads, buoys, and platforms. The paper describes a three-dimensional physical model technique. It helps the engineer to think imaginatively and rapidly to explore different options, with the objective of minimizing construction risk and creating procedures that can be accomplished by the equipment available. The relevant governing equations are derived, and from them come the conditions required for the model to obey the correct mechanical similarity conditions. The model is exact, and can be used to derive forces and stresses; it is much more than just a picture. The paper describes a series of applications to two- and three-dimensional pipeline construction problems, most recently an application to the current Thunder Horse project.

Download Full-text

Segmentation-less, automated vascular vectorization robustly extracts neurovascular network statistics from in vivo two-photon images

10.1101/2020.06.15.151076 ◽

2020 ◽

Cited By ~ 1

Author(s):

Samuel A. Mihelic ◽

William A. Sikora ◽

Ahmed M. Hassan ◽

Michael R. Williamson ◽

Theresa A. Jones ◽

...

Keyword(s):

Image Segmentation ◽

Statistical Power ◽

Large Scale ◽

Performance Metrics ◽

Three Dimensional ◽

Vascular Anatomy ◽

Input Image ◽

Network Graph ◽

Two Photon

AbstractRecent advances in two-photon microscopy (2PM) have allowed large scale imaging and analysis of cortical blood vessel networks in living mice. However, extracting a network graph and vector representations for vessels remain bottlenecks in many applications. Vascular vectorization is algorithmically difficult because blood vessels have many shapes and sizes, the samples are often unevenly illuminated, and large image volumes are required to achieve good statistical power. State-of-the-art, three-dimensional, vascular vectorization approaches require a segmented/binary image, relying on manual or supervised-machine annotation. Therefore, voxel-by-voxel image segmentation is biased by the human annotator/trainer. Furthermore, segmented images oftentimes require remedial morphological filtering before skeletonization/vectorization. To address these limitations, we propose a vectorization method to extract vascular objects directly from unsegmented images. The Segmentation-Less, Automated, Vascular Vectorization (SLAVV) source code in MATLAB is openly available on GitHub. This novel method uses simple models of vascular anatomy, efficient linear filtering, and low-complexity vector extraction algorithms to remove the image segmentation requirement, replacing it with manual or automated vector classification. SLAVV is demonstrated on three in vivo 2PM image volumes of microvascular networks (capillaries, arterioles and venules) in the mouse cortex. Vectorization performance is proven robust to the choice of plasma- or endothelial-labeled contrast, and processing costs are shown to scale with input image volume. Fully-automated SLAVV performance is evaluated on various, simulated 2PM images based on the large, [1.4, 0.9, 0.6] mm input image, and performance metrics show greater robustness to image quality than an intensity-based thresholding approach.

Download Full-text

Super-resolution emulator of cosmological simulations using deep physical models

Monthly Notices of the Royal Astronomical Society ◽

10.1093/mnras/staa1428 ◽

2020 ◽

Vol 495 (4) ◽

pp. 4227-4236 ◽

Cited By ~ 3

Author(s):

Doogesh Kodi Ramanah ◽

Tom Charnock ◽

Francisco Villaescusa-Navarro ◽

Benjamin D Wandelt

Keyword(s):

Large Scale ◽

Initial Conditions ◽

Computational Cost ◽

Physical Modelling ◽

Real Space ◽

Physical Models ◽

Small Scale ◽

Cosmological Simulations ◽

Scale Structures ◽

Small Scale Structures

ABSTRACT We present an extension of our recently developed Wasserstein optimized model to emulate accurate high-resolution (HR) features from computationally cheaper low-resolution (LR) cosmological simulations. Our deep physical modelling technique relies on restricted neural networks to perform a mapping of the distribution of the LR cosmic density field to the space of the HR small-scale structures. We constrain our network using a single triplet of HR initial conditions and the corresponding LR and HR evolved dark matter simulations from the quijote suite of simulations. We exploit the information content of the HR initial conditions as a well-constructed prior distribution from which the network emulates the small-scale structures. Once fitted, our physical model yields emulated HR simulations at low computational cost, while also providing some insights about how the large-scale modes affect the small-scale structure in real space.

Download Full-text

Atherosclerosis imaging

ESC CardioMed ◽

10.1093/med/9780198784906.003.0109 ◽

2018 ◽

pp. 524-528

Author(s):

Chun Yuan ◽

Zach Miller ◽

Jianming Cai

Keyword(s):

Atherosclerotic Plaque ◽

Large Scale ◽

Three Dimensional ◽

Plaque Imaging ◽

Fibrous Cap ◽

Intraplaque Haemorrhage ◽

Clinical Events ◽

Flexible Imaging ◽

Atherosclerosis Imaging

Atherosclerosis imaging goes beyond the simple identification of luminal stenosis. Besides stenosis measurement, there are two main motivations for atherosclerosis imaging: one is to identify the so-called vulnerable plaque, defined as atherosclerotic plaque that poses increased risk of rupture and clinical events, such as heart attack or stroke; the other is to identify ‘positively remodelled’ plaques—plaques that grow outward from the lumen but cause minimal or no stenosis. Cardiovascular magnetic resonance (CMR) has histologically validated capabilities to characterize carotid plaque features in vivo, including a lipid-rich necrotic core, fibrous cap, intraplaque haemorrhage (IPH), calcification, and inflammation. A multicontrast two-dimensional imaging approach has been used in many prospective studies relating baseline CMR characteristics of carotid atherosclerosis with plaque progression and clinical events. These studies have demonstrated the importance of detecting IPH, lipid-rich necrotic cores, and fibrous caps. Building on these findings, a number of three-dimensional CMR techniques have been recently developed that allow higher spatial resolution plaque imaging and easier application clinically with short scan times. Three-dimensional plaque imaging offers flexible imaging plane and view angle analysis, large coverage, multivascular beds capability, and is a fast and cost-effective screening for clinical use. Atherosclerosis imaging has also been applied to detect plaques in other vascular beds such as the coronary artery, intracranial artery, and peripheral artery, although each bed comes with unique imaging needs. Large-scale studies are needed to determine the impact of atherosclerotic plaque CMR on patient outcomes.

Download Full-text

A COMPARISON OF PHYSICAL MODEL WITH FIELD DATA OVER OLIVER FIELD, VULCAN GRABEN

The APPEA Journal ◽

10.1071/aj94002 ◽

1995 ◽

Vol 35 (1) ◽

pp. 26 ◽

Cited By ~ 1

Author(s):

B.J. Evans ◽

B.F. Oke ◽

M. Urosevic ◽

K. Chakraborty

Keyword(s):

Physical Model ◽

Seismic Data ◽

Field Data ◽

Joint Venture ◽

Survey Design ◽

Three Dimensional ◽

Physical Modelling ◽

Field Work ◽

Physical Models ◽

2D And 3D

Physical models representing the three dimensional geology of oil fields can be built from materials such as plastics and resins. Using ultrasound transmitters and receivers, 2D and 3D seismic surveys can be simulated to aid in the survey design of field work, provide insight into data processing, and can test interpretation concepts. Such modelling simulates most aspects of both land and marine seismic.In 1993 BHP Petroleum, on behalf of the AC/P6 Joint Venture, contracted Curtin University's Geophysics Group to build a 1:40,000 scale, 11-layer, 2.5D model of the Oliver Field so that 2D and 3D field data acquisition and processing could be simulated. A 2.5D model is invariant in the strike direction, but can answer most of the questions of a true 3D model at a fraction of the effort and cost. This was the first such model built in Australia, and one of the most complex physical models ever built.Of interest was the quality of imaging under the fault shadow near reservoir level, and whether the application of dip or strike 3D acquisition and processing approaches could improve the seismic data quality. Consequently, both dip (2D) and strike (2.5D) seismic data were acquired over the model using similar parameters to those used in conventional offshore acquisition. The data were processed to migration stage and compared with the field seismic data. Numerical model and field VSP data were also processed and compared with the field and physical model seismic data.The good agreement between processed physical model seismic and field seismic shows that physical modelling of geology has application in both two and three dimensional interpretation, acquisition planning, and processing testing and optimisation.This physical model experiment proved conclusively that shallow faults with a relatively large velocity contrast across them cause 'back' faults on the seismic data which do not exist in reality. Furthermore, this experiment proved for the first time using a physical model that strike 3D marine recording is preferable to dip 3D marine recording.

Download Full-text

Genome Compartmentalization with Nuclear Landmarks: Random yet Precise

10.1101/2021.11.12.468401 ◽

2021 ◽

Author(s):

Kartik Kamat ◽

Yifeng Qi ◽

Yuchuan Wang ◽

Jian Ma ◽

Bin Zhang

Keyword(s):

Phase Separation ◽

Genome Organization ◽

Large Scale ◽

Three Dimensional ◽

Nuclear Lamina ◽

Spatial Arrangement ◽

Nuclear Bodies ◽

Chromatin Interaction ◽

Nuclear Speckles ◽

Heterogeneous Distribution

The three-dimensional (3D) organization of eukaryotic genomes plays an important role in genome function. While significant progress has been made in deciphering the folding mechanisms of individual chromosomes, the principles of the dynamic large-scale spatial arrangement of all chromosomes inside the nucleus are poorly understood. We use polymer simulations to model the diploid human genome compartmentalization relative to nuclear bodies such as nuclear lamina, nucleoli, and speckles. We show that a self-organization process based on a co-phase separation between chromosomes and nuclear bodies can capture various features of genome organization, including the formation of chromosome territories, phase separation of A/B compartments, and the liquid property of nuclear bodies. The simulated 3D structures quantitatively reproduce both sequencing-based genomic mapping and imaging assays that probe chromatin interaction with nuclear bodies. Importantly, our model captures the heterogeneous distribution of chromosome positioning across cells, while simultaneously producing well-defined distances between active chromatin and nuclear speckles. Such heterogeneity and preciseness of genome organization can coexist due to the non-specificity of phase separation and the slow chromosome dynamics. Together, our work reveals that the co-phase separation provides a robust mechanism for encoding functionally important 3D contacts without requiring thermodynamic equilibration that can be difficult to achieve.

Download Full-text

Evaluation of Brachial Plexus Using Combined Stereological Techniques of Diffusion Tensor Imaging and Fiber Tracking

Journal of Brachial Plexus and Peripheral Nerve Injury ◽

10.1055/s-0039-1687913 ◽

2019 ◽

Vol 14 (01) ◽

pp. e16-e23

Author(s):

Niyazi Acer ◽

Mehmet Turgut

Keyword(s):

Diffusion Tensor Imaging ◽

Brachial Plexus ◽

Diffusion Tensor ◽

Three Dimensional ◽

Fiber Tracking ◽

Nerve Fibers ◽

Fiber Tractography ◽

Functional Features

Background Brachial plexus (BP) is composed of intercommunications among the ventral roots of the nerves C5, C6, C7, C8, and T1 in the neck. The in vivo and in vitro evaluation of axons of the peripheral nervous system is performed using different techniques. Recently, many studies describing the application of fiber tractography and stereological axon number estimation to peripheral nerves have been published. Methods Various quantitative parameters of nerve fibers, including axon number, density, axonal area, and myelin thickness, can be estimated using stereological techniques. In vivo three-dimensional reconstruction of axons of BP can be visualized using a combined technique of diffusion tensor imaging (DTI) and fiber tracking with the potential to evaluate nerve fiber content. Conclusion It is concluded that terminal branches of BP can be successfully visualized using DTI, which is a highly reproducible method for the evaluation of BP as it shows anatomical and functional features of neural structures. We believe that quantitative morphological findings obtained from BP will be useful for new experimental, developmental, and pathological studies in the future.

Download Full-text