547 research outputs found
Analysis of azimuthal variation of rain attenuation
The attenuation due to rain is the main source of impairments in satellite links operating above 10 GHz. In the design of systems based on Low Earth Orbit (LEO) satellites, the analysis of the rain attenuation must take into account both azimuth and elevation variations. It requires a deep knowledge on the nature of this dependence. As measurements at several elevation and azimuth angles are not available, it is necessary to use prediction models that aim at reproducing the rain profiles of each link. This paper presents an analysis of the azimuth dependence of rain attenuation according to the size of the azimuthal window where this attenuation occurs. It is shown that the azimuthal rain attenuation windows smaller than 180° are few at higher elevation but their probability increases exponentially with the decreasing of the elevation
Determining the Surface-To-Bulk Progression in the Normal-State Electronic Structure of Sr2RuO4 by Angle-Resolved Photoemission and Density Functional Theory
In search of the potential realization of novel normal-state phases on the
surface of Sr2RuO4 - those stemming from either topological bulk properties or
the interplay between spin-orbit coupling (SO) and the broken symmetry of the
surface - we revisit the electronic structure of the top-most layers by ARPES
with improved data quality as well as ab-initio LDA slab calculations. We find
that the current model of a single surface layer (\surd2x\surd2)R45{\deg}
reconstruction does not explain all detected features. The observed
depth-dependent signal degradation, together with the close quantitative
agreement with LDA+SO slab calculations based on the LEED-determined surface
crystal structure, reveal that (at a minimum) the sub-surface layer also
undergoes a similar although weaker reconstruction. This points to a
surface-to-bulk progression of the electronic states driven by structural
instabilities, with no evidence for Dirac and Rashba-type states or surface
magnetism.Comment: 4 pages, 4 figures, 1 table. Further information and PDF available
at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/articles.htm
Selective Hybridization of a Terpyridine-Based Molecule with a Noble Metal
The electronic properties of metal-molecule interfaces can in principle be
controlled by molecular design and self-assembly, yielding great potential for
future nano- and optoelectronic technologies. However, the coupling between
molecular orbitals and the electronic states of the surface can significantly
influence molecular states. In particular, molecules designed to create
metal-organic self-assembled networks have functional groups that by necessity
are designed to interact strongly with metals. Here, we investigate the
adsorption interactions of a terpyridine (tpy)-based molecule on a noble metal,
Ag(111), by low-temperature scanning tunneling microscopy (STM) and
spectroscopy (STS) together with density functional theory (DFT) calculations.
By comparing the local density of states (DOS) information gained from STS for
the molecule on the bare Ag(111) surface with that of the molecule decoupled
from the underlying metal by a NaCl bilayer, we find that tpy-localized
orbitals hybridize strongly with the metal substrate. Meanwhile, those related
to the phenyl rings that link the two terminal tpy groups are less influenced
by the interaction with the surface. The selective hybridization of the tpy
groups provides an example of strong, orbital-specific electronic coupling
between a functional group and a noble-metal surface, which may alter the
intended balance of interactions and resulting electronic behavior of the
molecule-metal interface
Neutralization of nerve growth factor impairs proliferation and differentiation of adult neural progenitors in the subventricular zone
Adult neurogenesis is a multistep process regulated by several extrinsic factors, including neurotrophins. Among them, little is known about the role of nerve growth factor (NGF) in the neurogenic niches of the mouse. Here we analyzed the biology of adult neural stem cells (NSCs) from the subventricular zone (SVZ) of AD11 anti-NGF transgenic mice, in which the expression of the recombinant antibody aD11 leads to a chronic postnatal neutralization of endogenous NGF. We showed that AD11-NSCs proliferate 10-fold less, with respect to their control counterparts, and display a significant impairment in their ability to differentiate into \u3b2-tubulin positive neurons. We found a considerable reduction in the number of SVZ progenitors and neuroblasts also in vivo, which correlates with a lower number of newborn neurons in the olfactory bulbs of AD11 mice and a severe deficit in the ability of these mice to discriminate between different odors. We also demonstrated that, in AD11 mice, the morphology of both SVZ-resident and neurosphere-derived astrocytes is significantly altered. We were able to reproduce the AD11 phenotype in vitro, by acutely treating wild type NSCs with the anti-NGF antibody, further demonstrating that both the proliferation and the differentiation defects are due to the NGF deprivation. Consistently, the proliferative impairment of AD11 progenitors, as well as the atrophic morphology of AD11 astrocytes, can be partly rescued in vitro and in vivo by exogenous NGF addition. Altogether, our results demonstrate a causal link between NGF signaling and proper proliferation and differentiation of neural stem cells from the SVZ.Adult neurogenesis is a multistep process regulated by several extrinsic factors, including neurotrophins. Among them, little is known about the role of nerve growth factor (NGF) in the neurogenic niches of the mouse. Here we analyzed the biology of adult neural stem cells (NSCs) from the subventricular zone (SVZ) of AD11 anti-NGF transgenic mice, in which the expression of the recombinant antibody aD11 leads to a chronic postnatal neutralization of endogenous NGF. We showed that AD11-NSCs proliferate 10-fold less, with respect to their control counterparts, and display a significant impairment in their ability to differentiate into \u3b2-tubulin positive neurons. We found a considerable reduction in the number of SVZ progenitors and neuroblasts also in vivo, which correlates with a lower number of newborn neurons in the olfactory bulbs of AD11 mice and a severe deficit in the ability of these mice to discriminate between different odors. We also demonstrated that, in AD11 mice, the morphology of both SVZ-resident and neurosphere-derived astrocytes is significantly altered. We were able to reproduce the AD11 phenotype in vitro, by acutely treating wild type NSCs with the anti-NGF antibody, further demonstrating that both the proliferation and the differentiation defects are due to the NGF deprivation. Consistently, the proliferative impairment of AD11 progenitors, as well as the atrophic morphology of AD11 astrocytes, can be partly rescued in vitro and in vivo by exogenous NGF addition. Altogether, our results demonstrate a causal link between NGF signaling and proper proliferation and differentiation of neural stem cells from the SVZ
NGF steers microglia toward a neuroprotective phenotype
Microglia are the sentinels of the brain but a clear understanding of the factors that modulate their activation in physiological and pathological conditions is still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on microglia by steering them toward a neuroprotective and anti-inflammatory phenotype. We show that microglial cells express functional NGF receptors in vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia, NGF treatment leads to a modulation of motility, phagocytosis and degradation pathways. At the functional level, NGF induces an increase in membrane dynamics and macropinocytosis and, in vivo, it activates an outward rectifying current that appears to modulate glutamatergic neurotransmission in nearby neurons. Since microglia are supposed to be a major player in Aβ peptide clearance in the brain, we tested the effects of NGF on its phagocytosis. NGF was shown to promote TrkA-mediated engulfment of Aβ by microglia, and to enhance its degradation. Additionally, the proinflammatory activation induced by Aβ treatment is counteracted by the concomitant administration of NGF. Moreover, by acting specifically on microglia, NGF protects neurons from the Aβ-induced loss of dendritic spines and inhibition of long term potentiation. Finally, in an ex-vivo setup of acute brain slices, we observed a similar increase in Aβ engulfment by microglial cells under the influence of NGF. Our work substantiates a role for NGF in the regulation of microglial homeostatic activities and points toward this neurotrophin as a neuroprotective agent in Aβ accumulation pathologies, via its anti-inflammatory activity on microglia
Effect of Efalizumab on neutrophil and monocyte functions in patients with psoriasis
We evaluated the effect of efalizumab on neutrophil and monocyte functions. The in vitro preincubation with efalizumab concentrations similar to those reached during in vivo therapy almost completely saturated CD11a binding sites without affecting the membrane expression of CD11b, CD128a or CD128b. There was a significant reduction in the chemotactic activity of the pre-treated cells toward three different chemo-attractants, whereas their phagocytic capacity and production of oxygen radicals remained unchanged. One month after the administration of efalizumab to five patients with psoriasis (T1) circulating neutrophil counts increased by 34% from pre-therapy (T0) with no change in the number of monocytes. In the same patients the CD11a binding sites on phagocytes were >90% saturated, and there was also a significant down-modulation on neutrophils (44% of T0) and monocytes (63% of T0). In line with in vitro results, efalizumab treatment caused a significant deficiency in the chemotactic properties of neutrophils and monocytes, but no changes in phagocytosis, oxidative burst, production of pro-inflammatory cytokines or the membrane expression of CD11b, CD128a and CD128b. Our findings suggest that neutrophils and monocytes may be among the targets of efalizumab activity in patients with psoriasis
Graphene promotes axon elongation through local stall of Nerve Growth Factor signaling endosomes
Several works reported increased differentiation of neuronal cells grown on
graphene; however, the molecular mechanism driving axon elongation on this
material has remained elusive. Here, we study the axonal transport of nerve
growth factor (NGF), the neurotrophin supporting development of peripheral
neurons, as a key player in the time course of axonal elongation of dorsal root
ganglion neurons on graphene. We find that graphene drastically reduces the
number of retrogradely transported NGF vesicles in favor of a stalled
population in the first two days of culture, in which the boost of axon
elongation is observed. This correlates with a mutual charge redistribution,
observed via Raman spectroscopy and electrophysiological recordings.
Furthermore, ultrastructural analysis indicates a reduced microtubule distance
and an elongated axonal topology. Thus, both electrophysiological and
structural effects can account for graphene action on neuron development.
Unraveling the molecular players underneath this interplay may open new avenues
for axon regeneration applications
Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice
Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases
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