30 research outputs found
3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries
Recent advances in electron microscopy have enabled the imaging of single
cells in 3D at nanometer length scale resolutions. An uncharted frontier for in
silico biology is the ability to simulate cellular processes using these
observed geometries. Enabling such simulations requires watertight meshing of
electron micrograph images into 3D volume meshes, which can then form the basis
of computer simulations of such processes using numerical techniques such as
the Finite Element Method. In this paper, we describe the use of our recently
rewritten mesh processing software, GAMer 2, to bridge the gap between poorly
conditioned meshes generated from segmented micrographs and boundary marked
tetrahedral meshes which are compatible with simulation. We demonstrate the
application of a workflow using GAMer 2 to a series of electron micrographs of
neuronal dendrite morphology explored at three different length scales and show
that the resulting meshes are suitable for finite element simulations. This
work is an important step towards making physical simulations of biological
processes in realistic geometries routine. Innovations in algorithms to
reconstruct and simulate cellular length scale phenomena based on emerging
structural data will enable realistic physical models and advance discovery at
the interface of geometry and cellular processes. We posit that a new frontier
at the intersection of computational technologies and single cell biology is
now open.Comment: 39 pages, 14 figures. High resolution figures and supplemental movies
available upon reques
An Open Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries
Advances in imaging methods such as electron microscopy, tomography and other
modalities are enabling high-resolution reconstructions of cellular and
organelle geometries. Such advances pave the way for using these geometries for
biophysical and mathematical modeling once these data can be represented as a
geometric mesh, which, when carefully conditioned, enables the discretization
and solution of partial differential equations. In this study, we outline the
steps for a na\"ive user to approach GAMer 2, a mesh generation code written in
C++ designed to convert structural datasets to realistic geometric meshes,
while preserving the underlying shapes. We present two example cases, 1) mesh
generation at the subcellular scale as informed by electron tomography, and 2)
meshing a protein with structure from x-ray crystallography. We further
demonstrate that the meshes generated by GAMer are suitable for use with
numerical methods. Together, this collection of libraries and tools simplifies
the process of constructing realistic geometric meshes from structural biology
data.Comment: 6 pages and 4 figures. Supplemental Movie available upon reques
SMART: Spatial Modeling Algorithms for Reaction and Transport
Recent advances in microscopy and 3D reconstruction methods have allowed for
characterization of cellular morphology in unprecedented detail, including the
irregular geometries of intracellular subcompartments such as membrane-bound
organelles. These geometries are now compatible with predictive modeling of
cellular function. Biological cells respond to stimuli through sequences of
chemical reactions generally referred to as cell signaling pathways. The
propagation and reaction of chemical substances in cell signaling pathways can
be represented by coupled nonlinear systems of reaction-transport equations.
These reaction pathways include numerous chemical species that react across
boundaries or interfaces (e.g., the cell membrane and membranes of organelles
within the cell) and domains (e.g., the bulk cell volume and the interior of
organelles). Such systems of multi-dimensional partial differential equations
(PDEs) are notoriously difficult to solve because of their high dimensionality,
non-linearities, strong coupling, stiffness, and potential instabilities. In
this work, we describe Spatial Modeling Algorithms for Reactions and Transport
(SMART), a high-performance finite-element-based simulation package for model
specification and numerical simulation of spatially-varying reaction-transport
processes. SMART is based on the FEniCS finite element library, provides a
symbolic representation framework for specifying reaction pathways, and
supports geometries in 2D and 3D including large and irregular cell geometries
obtained from modern ultrastructural characterization methods.Comment: 5 pages, 2 figures, submitted to the Journal of Open Source Software
(JOSS), code available at https://github.com/RangamaniLabUCSD/smar
Anomalous relaxation and self-organization in non-equilibrium processes
We study thermal relaxation in ordered arrays of coupled nonlinear elements
with external driving. We find, that our model exhibits dynamic
self-organization manifested in a universal stretched-exponential form of
relaxation. We identify two types of self-organization, cooperative and
anti-cooperative, which lead to fast and slow relaxation, respectively. We give
a qualitative explanation for the behavior of the stretched exponent in
different parameter ranges. We emphasize that this is a system exhibiting
stretched-exponential relaxation without explicit disorder or frustration.Comment: submitted to PR
Plasma Analogy and Non-Abelian Statistics for Ising-type Quantum Hall States
We study the non-Abelian statistics of quasiparticles in the Ising-type
quantum Hall states which are likely candidates to explain the observed Hall
conductivity plateaus in the second Landau level, most notably the one at
filling fraction nu=5/2. We complete the program started in Nucl. Phys. B 506,
685 (1997) and show that the degenerate four-quasihole and six-quasihole
wavefunctions of the Moore-Read Pfaffian state are orthogonal with equal
constant norms in the basis given by conformal blocks in a c=1+1/2 conformal
field theory. As a consequence, this proves that the non-Abelian statistics of
the excitations in this state are given by the explicit analytic continuation
of these wavefunctions. Our proof is based on a plasma analogy derived from the
Coulomb gas construction of Ising model correlation functions involving both
order and (at most two) disorder operators. We show how this computation also
determines the non-Abelian statistics of collections of more than six
quasiholes and give an explicit expression for the corresponding conformal
block-derived wavefunctions for an arbitrary number of quasiholes. Our method
also applies to the anti-Pfaffian wavefunction and to Bonderson-Slingerland
hierarchy states constructed over the Moore-Read and anti-Pfaffian states.Comment: 68 pages, 3 figures; v2: substantial revisions and additions for
clarity, minor correction
Competing orders and quantum criticality in doped antiferromagnets
We use a number of large-N limits to explore the competition between ground
states of square lattice doped antiferromagnets which break electromagnetic
U(1), time-reversal, or square lattice space group symmetries. Among the states
we find are d-, (s+id)-, and (d+id)-wave superconductors, Wigner crystals,
Wigner crystals of hole pairs, orbital antiferromagnets (or staggered-flux
states), and states with spin-Peierls and bond-centered charge stripe order. In
the vicinity of second-order quantum phase transitions between the states, we
go beyond the large-N limit by identifying the universal quantum field theories
for the critical points, and computing the finite temperature, quantum-critical
damping of fermion spectral functions. We identify candidate critical points
for the recently observed quantum-critical behavior in photoemission
experiments on BSCCO by Valla et al. (Science 285, 2110 (1999)). These involve
onset of a charge density wave, or of broken time-reversal symmetry with (d+id)
or (s+id) pairing, in a d-wave superconductor. It is not required (although it
is allowed) that the stable state in the doped cuprates to be anything other
than the d-wave superconductor--the other states need only be stable nearby in
parameter space. At finite temperatures, fluctuations associated with these
nearby states lead to the observed fermion damping in the vicinity of the nodal
points in the Brillouin zone. The cases with broken time-reversal symmetry are
appealing because the order parameter is not required to satisfy any special
commensurability conditions. The observed absence of inelastic damping of
quasiparticles with momenta (pi,k), (k,pi) (with 0 < k < pi) also appears very
naturally for the case of a transition to (d+id) order.Comment: 26 pages, 13 figures; added references, clarifications, and a new
figur
Ultraviolet polarisation sensitivity in the stomatopod crustacean Odontodactylus scyllarus
The ommatidia of crustacean eyes typically contain two classes of photoreceptors with orthogonally oriented microvilli. These receptors provide the basis for two-channel polarisation vision in the blueâgreen spectrum. The retinae of gonodactyloid stomatopod crustaceans possess a great variety of structural specialisations for elaborate polarisation vision. One type of specialisation is found in the small, distally placed R8 cells within the two most ventral rows of the mid-band. These ultraviolet-sensitive photoreceptors produce parallel microvilli, a feature suggestive for polarisation-sensitive photoreceptors. Here, we show by means of intracellular recordings combined with dye-injections that in the gonodactyloid species Odontodactylus scyllarus, the R8 cells of mid-band rows 5 and 6 are sensitive to linear polarised ultraviolet light. We show that mid-band row 5 R8 cells respond maximally to light with an e-vector oriented parallel to the mid-band, whereas mid-band row 6 R8 cells respond maximally to light with an e-vector oriented perpendicular to the mid-band. This orthogonal arrangement of ultraviolet-sensitive receptor cells could support ultraviolet polarisation vision. R8 cells of rows 5 and 6 are known to act as quarter-wave retarders around 500Â nm and thus are the first photoreceptor type described with a potential dual role in polarisation vision
Basic science232.âCertolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia Âź; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-ÎșB localization and IÎșB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-ÎșB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-ÎșB and degradation of IÎșB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-ÎșB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
TRY plant trait database â enhanced coverage and open access
Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of traitâbased plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for âplant growth formâ. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and traitâenvironmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives