879 research outputs found
Forecasting future Humphrey Visual Fields using deep learning
Purpose
To determine if deep learning networks could be trained to forecast future 24–2 Humphrey
Visual Fields (HVFs).
Methods
All data points from consecutive 24–2 HVFs from 1998 to 2018 were extracted from a university
database. Ten-fold cross validation with a held out test set was used to develop the
three main phases of model development: model architecture selection, dataset combination
selection, and time-interval model training with transfer learning, to train a deep learning
artificial neural network capable of generating a point-wise visual field prediction. The pointwise
mean absolute error (PMAE) and difference in Mean Deviation (MD) between predicted
and actual future HVF were calculated.
Results
More than 1.7 million perimetry points were extracted to the hundredth decibel from 32,443
24–2 HVFs. The best performing model with 20 million trainable parameters, CascadeNet-
5, was selected. The overall point-wise PMAE for the test set was 2.47 dB (95% CI: 2.45 dB
to 2.48 dB), and deep learning showed a statistically significant improvement over linear
models. The 100 fully trained models successfully predicted future HVFs in glaucomatous
eyes up to 5.5 years in the future with a correlation of 0.92 between the MD of predicted and
actual future HVF and an average difference of 0.41 dB.
Conclusions
Using unfiltered real-world datasets, deep learning networks show the ability to not only
learn spatio-temporal HVF changes but also to generate predictions for future HVFs up to
5.5 years, given only a single HVF
Topological orbital ladders
We unveil a topological phase of interacting fermions on a two-leg ladder of
unequal parity orbitals, derived from the experimentally realized double-well
lattices by dimension reduction. topological invariant originates simply
from the staggered phases of -orbital quantum tunneling, requiring none of
the previously known mechanisms such as spin-orbit coupling or artificial gauge
field. Another unique feature is that upon crossing over to two dimensions with
coupled ladders, the edge modes from each ladder form a parity-protected flat
band at zero energy, opening the route to strongly correlated states controlled
by interactions. Experimental signatures are found in density correlations and
phase transitions to trivial band and Mott insulators.Comment: 12 pages, 5 figures, Revised title, abstract, and the discussion on
Majorana numbe
Quantum magnetism and criticality
Magnetic insulators have proved to be fertile ground for studying new types
of quantum many body states, and I survey recent experimental and theoretical
examples. The insights and methods transfer also to novel superconducting and
metallic states. Of particular interest are critical quantum states, sometimes
found at quantum phase transitions, which have gapless excitations with no
particle- or wave-like interpretation, and control a significant portion of the
finite temperature phase diagram. Remarkably, their theory is connected to
holographic descriptions of Hawking radiation from black holes.Comment: 39 pages, 10 figures, review article for non-specialists; (v2) added
clarifications and references; (v3) minor corrections; (v4) added footnote on
hydrodynamic long-time tail
Anyonic interferometry and protected memories in atomic spin lattices
Strongly correlated quantum systems can exhibit exotic behavior called
topological order which is characterized by non-local correlations that depend
on the system topology. Such systems can exhibit remarkable phenomena such as
quasi-particles with anyonic statistics and have been proposed as candidates
for naturally fault-tolerant quantum computation. Despite these remarkable
properties, anyons have never been observed in nature directly. Here we
describe how to unambiguously detect and characterize such states in recently
proposed spin lattice realizations using ultra-cold atoms or molecules trapped
in an optical lattice. We propose an experimentally feasible technique to
access non-local degrees of freedom by performing global operations on trapped
spins mediated by an optical cavity mode. We show how to reliably read and
write topologically protected quantum memory using an atomic or photonic qubit.
Furthermore, our technique can be used to probe statistics and dynamics of
anyonic excitations.Comment: 14 pages, 6 figure
Identifying Topological Order by Entanglement Entropy
Topological phases are unique states of matter incorporating long-range
quantum entanglement, hosting exotic excitations with fractional quantum
statistics. We report a practical method to identify topological phases in
arbitrary realistic models by accurately calculating the Topological
Entanglement Entropy (TEE) using the Density Matrix Renormalization Group
(DMRG). We argue that the DMRG algorithm naturally produces a minimally
entangled state, from amongst the quasi-degenerate ground states in a
topological phase. This proposal both explains the success of this method, and
the absence of ground state degeneracy found in prior DMRG sightings of
topological phases. We demonstrate the effectiveness of the calculational
procedure by obtaining the TEE for several microscopic models, with an accuracy
of order when the circumference of the cylinder is around ten times
the correlation length. As an example, we definitively show the ground state of
the quantum antiferromagnet on the kagom\'e lattice is a topological
spin liquid, and strongly constrain the full identification of this phase of
matter.Comment: 20 pages, 6 figure
Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.
Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses
Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
Phosphorylation of the muscle-specific formin splice variant FHOD3 by CK2 regulates its stability, myofibril targeting, and myofibril integrity
The CPT1C 5′UTR Contains a Repressing Upstream Open Reading Frame That Is Regulated by Cellular Energy Availability and AMPK
BACKGROUND:
Translational control is utilized as a means of regulating gene expression in many species. In most cases, posttranscriptional regulatory mechanisms play an important role in stress response pathways and can lead to dysfunctional physiology if blocked by mutations. Carnitine Palmitoyltransferase 1 C (CPT1C), the brain-specific member of the CPT 1 family, has previously been shown to be involved in regulating metabolism in situations of energy surplus.
PRINCIPAL FINDINGS:
Sequence analysis of the CPT1C mRNA revealed that it contains an upstream open reading frame (uORF) in the 5' UTR of its mRNA. Using CPT1C 5' UTR/luciferase constructs, we investigated the role of the uORF in translational regulation. The results presented here show that translation from the CPT1C main open reading frame (mORF) is repressed by the presence of the uORF, that this repression is relieved in response to specific stress stimuli, namely glucose deprivation and palmitate-BSA treatment, and that AMPK inhibition can relieve this uORF-dependent repression.
SIGNIFICANCE:
The fact that the mORF regulation is relieved in response to a specific set of stress stimuli rather than general stress response, hints at an involvement of CPT1C in cellular energy-sensing pathways and provides further evidence for a role of CPT1C in hypothalamic regulation of energy homeostasis
CDK5 Is Essential for Soluble Amyloid β-Induced Degradation of GKAP and Remodeling of the Synaptic Actin Cytoskeleton
The early stages of Alzheimer's disease are marked by synaptic dysfunction and loss. This process results from the disassembly and degradation of synaptic components, in particular of scaffolding proteins that compose the post-synaptic density (PSD), namely PSD95, Homer and Shank. Here we investigated in rat frontal cortex dissociated culture the mechanisms involved in the downregulation of GKAP (SAPAP1), which links the PSD95 complex to the Shank complex and cytoskeletal structures within the PSD. We show that Aβ causes the rapid loss of GKAP from synapses through a pathway that critically requires cdk5 activity, and is set in motion by NMDAR activity and Ca2+ influx. We show that GKAP is a direct substrate of cdk5 and that its phosphorylation results in polyubiquitination and proteasomal degradation of GKAP and remodeling (collapse) of the synaptic actin cytoskeleton; the latter effect is abolished in neurons expressing GKAP mutants that are resistant to phosphorylation by cdk5. Given that cdk5 also regulates degradation of PSD95, these results underscore the central position of cdk5 in mediating Aβ-induced PSD disassembly and synapse loss
The Role of Actin Turnover in Retrograde Actin Network Flow in Neuronal Growth Cones
The balance of actin filament polymerization and depolymerization maintains a steady state network treadmill in neuronal growth cones essential for motility and guidance. Here we have investigated the connection between depolymerization and treadmilling dynamics. We show that polymerization-competent barbed ends are concentrated at the leading edge and depolymerization is distributed throughout the peripheral domain. We found a high-to-low G-actin gradient between peripheral and central domains. Inhibiting turnover with jasplakinolide collapsed this gradient and lowered leading edge barbed end density. Ultrastructural analysis showed dramatic reduction of leading edge actin filament density and filament accumulation in central regions. Live cell imaging revealed that the leading edge retracted even as retrograde actin flow rate decreased exponentially. Inhibition of myosin II activity before jasplakinolide treatment lowered baseline retrograde flow rates and prevented leading edge retraction. Myosin II activity preferentially affected filopodial bundle disassembly distinct from the global effects of jasplakinolide on network turnover. We propose that growth cone retraction following turnover inhibition resulted from the persistence of myosin II contractility even as leading edge assembly rates decreased. The buildup of actin filaments in central regions combined with monomer depletion and reduced polymerization from barbed ends suggests a mechanism for the observed exponential decay in actin retrograde flow. Our results show that growth cone motility is critically dependent on continuous disassembly of the peripheral actin network
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