809 research outputs found
Application of the Preisach-Mayergoyz space model to analyze moisture effects on the nonlinear elastic response of rock
Axonal transport defects are a common phenotype in Drosophila models of ALS
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons resulting in a catastrophic loss of
motor function. Current therapies are severely limited owing to a poor mechanistic understanding of the pathobiology.
Mutations in a large number of genes have now been linked to ALS, including SOD1, TARDBP (TDP-43), FUS and C9orf72.
Functional analyses of these genes and their pathogenic mutations have provided great insights into the underlying disease
mechanisms. Defective axonal transport is hypothesized to be a key factor in the selective vulnerability of motor nerves due
to their extraordinary length and evidence that ALS occurs as a distal axonopathy. Axonal transport is seen as an early
pathogenic event that precedes cell loss and clinical symptoms and so represents an upstream mechanism for therapeutic
targeting. Studies have begun to describe the impact of a few pathogenic mutations on axonal transport but a broad survey
across a range of models and cargos is warranted. Here, we assessed the axonal transport of different cargos in multiple
Drosophila models of ALS. We found that axonal transport defects are common across all models tested, although they often
showed a differential effect between mitochondria and vesicle cargos. Motor deficits were also common across the models
and generally worsened with age, though surprisingly there was not a clear correlation between the severity of axonal
transport defects and motor ability. These results further support defects in axonal transport as a common factor in models
of ALS that may contribute to the pathogenic process
Nonequilibrium and Nonlinear Dynamics in Geomaterials I : The Low Strain Regime
Members of a wide class of geomaterials are known to display complex and
fascinating nonlinear and nonequilibrium dynamical behaviors over a wide range
of bulk strains, down to surprisingly low values, e.g., 10^{-7}. In this paper
we investigate two sandstones, Berea and Fontainebleau, and characterize their
behavior under the influence of very small external forces via carefully
controlled resonant bar experiments. By reducing environmental effects due to
temperature and humidity variations, we are able to systematically and
reproducibly study dynamical behavior at strains as low as 10^{-9}. Our study
establishes the existence of two strain thresholds, the first, epsilon_L, below
which the material is essentially linear, and the second, epsilon_M, below
which the material is nonlinear but where quasiequilibrium thermodynamics still
applies as evidenced by the success of Landau theory and a simple macroscopic
description based on the Duffing oscillator. At strains above epsilon_M the
behavior becomes truly nonequilibrium -- as demonstrated by the existence of
material conditioning -- and Landau theory no longer applies. The main focus of
this paper is the study of the region below the second threshold, but we also
comment on how our work clarifies and resolves previous experimental conflicts,
as well as suggest new directions of research.Comment: 14 pages, 15 figure
Lower Cretaceous Rodby and Palaeocene Lista Shales: Characterisation and Comparison of Top-Seal Mudstones at Two Planned CCS Sites, Offshore UK
Funding: The work reported here was part of the Accelerating Carbon Technologies (ACT) Acorn Carbon Capture and Storage (CCS) Project, under the ERA–NET Horizon 2020 programme, project 271500, and was jointly funded by the Department for Business, Energy and Industrial Strategy, United Kingdom; the Research Council of Norway; the Netherlands Enterprise Agency. Juan Alcalde is funded by the Spanish MICINN (Juan de la Cierva fellowship-IJC2018-036074-I). Alan James, CEO of Pale Blue Dot Ltd. (Banchory, UK), is warmly thanked for skilfully leading the Acorn Project and offering advice throughout the project, including during the preparation of this manuscript. We express our warm appreciation to guest editor Jim Buckman (Heriot Watt University, UK) for encouraging us to write and submit this paper. We would like to thank four diligent anonymous reviewers for their thoughtful and constructive comments on the initial version of the manuscript, and academic lead for this thematic issue.Peer reviewedPublisher PD
Listeria monocytogenes induces an interferon-enhanced activation of the integrated stress response that is detrimental for resolution of infection in mice
Mouse Ten-m/Odz Is a New Family of Dimeric Type II Transmembrane Proteins Expressed in Many Tissues
The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700–2,800 amino acids. All four proteins (Ten-m1–4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300–400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains
Calibrating Lattice Boltzmann Flow Simulations and Estimating Uncertainty in the Permeability of Complex Porous Media:Lattice Boltzmann Flow Simulations and Estimating Uncertainty
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Measurement of nonlinear elastic response in rock by the resonant bar method
In this work we are studying the behavior of the fundamental (Young's) mode resonant peak as a function of drive amplitude in rock samples. Our goal from these studies is to obtain nonlinear moduli for many rock types, and to study the nonlinear moduli as a function of water saturation and other changes in physical properties. Measurements were made on seven different room dry rock samples. For one sample measurements were taken at 16 saturation levels between 1 and 98%. All samples display a softening'' nonlinearity, that is, the resonant frequency shifts downward with increasing drive amplitude. In extreme cases, the resonant frequency changes by as much as 25% over a strain interval of 10[sup [minus]7] to [approximately]4 [times] 10[sup [minus]5]. Measurements indicate that the nonlinear response is extremely sensitive to saturation. Estimates of a combined cubic and quartic nonlinear parameter [Gamma] range from approximately [minus]300 to [minus]10[sup 9] for the rock samples
Prediction of permeability and formation factor of sandstone with hybrid lattice Boltzmann/finite element simulation on microtomographic images
In Fontainebleau sandstone, the evolution of transport properties with porosity is related to changes in both the size and connectivity of the pore space. Microcomputed tomography can be used to characterize the relevant geometric attributes, with the resolution that is sufficiently refined for realistic simulation of transport properties based on the 3D image. In this study, we adopted a hybrid computation scheme that is based on a hierarchical multi-scale approach. The specimen was partitioned into cubic sub-volumes for pore-scale simulation of hydraulic permeability and formation factor using the lattice Boltzmann method. The pore-scale results were then linked with finite element simulation in a homogenized scheme to compute and upscale the transport properties to specimen scale. The simulated permeability and formation factor have magnitude and anisotropy that are in good agreement with experimental rock physics data. Together with simulated and measured values of connected porosity and specific surface area, they provide useful insights into how pore geometry controls the evolution of the transport properties
TRE-dependent transcription activation by JDP2–CHOP10 association
The c-Jun dimerization protein 2, JDP2, is a member of the activating protein 1 (AP-1) family of transcription factors. Overexpression of JDP2 has been shown to result in repression of AP-1-dependent transcription and inhibition of cellular transformation. Other studies suggested that JDP2 may function as an oncogene. Here we describe the identification of CHOP10, a member of the CCAAT enhancer binding proteins, as a protein associating with JDP2. In contrast to the inhibition of transcription by JDP2, JDP2–CHOP complex strongly enhances transcription from promoters containing TPA response elements (TRE), but not from those containing cyclic AMP response elements (CRE). The association between JDP2 and CHOP10 involves the leucine zipper motifs of both proteins, whereas, the basic domain of CHOP10 contributes to the association of the JDP2–CHOP10 complex with the DNA. DNA binding of JDP2–CHOP complex is observed both in vitro and in vivo. Finally, overexpression of JDP2 results in increased cell viability following ER stress and counteracts CHOP10 pro-apoptotic activity. JDP2 expression may determine the threshold for cell sensitivity to ER stress. This is the first report describing TRE-dependent activation of transcription by JDP2 and thus may provide an explanation for the as yet unexplored oncogenic properties of JDP2
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