215 research outputs found
A novel AhR ligand, 2AI, protects the retina from environmental stress.
Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice
Galactomannan Does Not Precede Major Signs on a Pulmonary Computerized Tomographic Scan Suggestive of Invasive Aspergillosis in Patients with Hematological Malignancies
Background. Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. Methods. In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Results. We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. Conclusions. We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of G
Opening the way to molecular cycloaddition of large molecules on supported silicene
Within density functional theory, the adsorption of the H2Pc molecule on the (3 × 3) silicene/(4 × 4) Ag(111) surface has been investigated. We observe an electronic redistribution in the central macrocycle of the H2Pc molecule and the formation of two Si − N covalent bonds between the molecule and the silicene, in agreement with a cycloaddition reaction. However, while on SiC(0001)(3 × 3) or Si(111)(3√×3√)R30 °-boron, the H2Pc molecule remains planar, and the H2Pc molecule takes a butterfly conformation on the silicene/Ag substrate due to an electrostatic or a polarization repulsion between the molecule and the silicene. Our study opens a way to the experimental adsorption of large organic molecules on supported silicene
Hydrodynamics of topological defects in nematic liquid crystals
We show that back-flow, the coupling between the order parameter and the
velocity fields, has a significant effect on the motion of defects in nematic
liquid crystals. In particular the defect speed can depend strongly on the
topological strength in two dimensions and on the sense of rotation of the
director about the core in three dimensions.Comment: 4 pages including two figure
Energy Dissipation and Regularity for a Coupled Navier-Stokes and Q-Tensor System
We study a complex non-newtonian fluid that models the flow of nematic liquid
crystals. The fluid is described by a system that couples a forced
Navier-Stokes system with a parabolic-type system. We prove the existence of
global weak solutions in dimensions two and three. We show the existence of a
Lyapunov functional for the smooth solutions of the coupled system and use the
cancellations that allow its existence to prove higher global regularity, in
dimension two. We also show the weak-strong uniqueness in dimension two
Topological Defects in Nematic Droplets of Hard Spherocylinders
Using computer simulations we investigate the microscopic structure of the
singular director field within a nematic droplet. As a theoretical model for
nematic liquid crystals we take hard spherocylinders. To induce an overall
topological charge, the particles are either confined to a two-dimensional
circular cavity with homeotropic boundary or to the surface of a
three-dimensional sphere. Both systems exhibit half-integer topological point
defects. The isotropic defect core has a radius of the order of one particle
length and is surrounded by free-standing density oscillations. The effective
interaction between two defects is investigated. All results should be
experimentally observable in thin sheets of colloidal liquid crystals.Comment: 13 pages, 16 figures, Phys. Rev.
Defect structures in nematic liquid crystals around charged particles
We numerically study the orientation deformations in nematic liquid crystals
around charged particles. We set up a Ginzburg-Landau theory with inhomogeneous
electric field. If the dielectric anisotropy varepsilon_1 is positive, Saturn
ring defects are formed around the particles. For varepsilon_1<0, novel "ansa"
defects appear, which are disclination lines with their ends on the particle
surface. We find unique defect structures around two charged particles. To
lower the free energy, oppositely charged particle pairs tend to be aligned in
the parallel direction for varepsilon_1>0 and in the perpendicular plane for
varepsilon_1<0 with respect to the background director . For identically
charged pairs the preferred directions for varepsilon_1>0 and varepsilon_1<0
are exchanged. We also examie competition between the charge-induced anchoring
and the short-range anchoring. If the short-range anchoring is sufficiently
strong, it can be effective in the vicinity of the surface, while the director
orientation is governed by the long-range electrostatic interaction far from
the surface.Comment: 10 papes, 12 figures, to appear in European Physical Journal
On the calculation of effective electric field in In0.53Ga0.47As surface channel metal-oxide-semiconductor field-effect-transistors
The effective electron mobility of In0.53Ga0.47As metal-oxide-semiconductor field-effect-transistors with HfO2 gate oxide was measured over a wide range of channel doping concentration. The back bias dependence of effective electron mobility was used to correctly calculate the vertical effective electric field. The effective electron mobility at moderate to high vertical effective electric field shows universal behavior independent of substrate impurity concentration. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3588255
Defect structures and torque on an elongated colloidal particle immersed in a liquid crystal host
Combining molecular dynamics and Monte Carlo simulation we study defect
structures around an elongated colloidal particle embedded in a nematic liquid
crystal host. By studying nematic ordering near the particle and the
disclination core region we are able to examine the defect core structure and
the difference between two simulation techniques. In addition, we also study
the torque on a particle tilted with respect to the director, and modification
of this torque when the particle is close to the cell wall
Colloquium: Mechanical formalisms for tissue dynamics
The understanding of morphogenesis in living organisms has been renewed by
tremendous progressin experimental techniques that provide access to
cell-scale, quantitative information both on theshapes of cells within tissues
and on the genes being expressed. This information suggests that
ourunderstanding of the respective contributions of gene expression and
mechanics, and of their crucialentanglement, will soon leap forward.
Biomechanics increasingly benefits from models, which assistthe design and
interpretation of experiments, point out the main ingredients and assumptions,
andultimately lead to predictions. The newly accessible local information thus
calls for a reflectionon how to select suitable classes of mechanical models.
We review both mechanical ingredientssuggested by the current knowledge of
tissue behaviour, and modelling methods that can helpgenerate a rheological
diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and
tissue scale ("inter-cell") contributions. We recall the mathematical framework
developpedfor continuum materials and explain how to transform a constitutive
equation into a set of partialdifferential equations amenable to numerical
resolution. We show that when plastic behaviour isrelevant, the dissipation
function formalism appears appropriate to generate constitutive equations;its
variational nature facilitates numerical implementation, and we discuss
adaptations needed in thecase of large deformations. The present article
gathers theoretical methods that can readily enhancethe significance of the
data to be extracted from recent or future high throughput
biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few
corrections to the published version, all in Appendix D.2 devoted to large
deformation
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