1,258 research outputs found
L008 DĂ©faut de diffĂ©renciation veino-lymphatique embyonnaire par modulation de lâARN interfĂ©rence
LâARN interfĂ©rence, mĂ©canisme de rĂ©gulation de lâexpression des gĂšnes, est mĂ©diĂ©e par les siARNs et les microARNs, ARN non-codants de 20 Ă 22 nuclĂ©otides affectant la rĂ©gulation post-transcriptionnelle dâARNm cibles avec lesquels ils sâapparient.La RNase DICER est une enzyme centrale de la biosynthĂšse des siARNs et microARNs. Les souris dont le gĂšne dicer est invalidĂ© ont un phĂ©notype complexe, et meurent trĂšs tĂŽt pendant le dĂ©veloppement, notamment Ă cause dâun dĂ©faut dâangiogenĂšse.Afin dâĂ©tudier lâARN interfĂ©rence au cours de lâangiogenĂšse embryonnaire, des souris dont le gĂšne dicer est floxĂ© (mutant conditionnel) sont croisĂ©es avec des souris exprimant la recombinase Cre, de maniĂšre constitutive, sous le contrĂŽle du promoteur du gĂšne tie2, dirigeant ainsi son expression dans les cellules endothĂ©liales (CE) et les cellules hĂ©matopiĂ©tiques.Nos rĂ©sultats montrent que lâinvalidation de dicer sous le contrĂŽle du promoteur du gĂšne tie2 entraine une mortalitĂ© embryonnaire suite Ă un ĆdĂšme et des hĂ©morragies au treiziĂšme jour du dĂ©veloppement (E13,5). Lâanalyse histologique montre des vaisseaux lymphatiques remplis de sang, suggĂ©rant une mauvaise sĂ©paration du rĂ©seau sanguin et lymphatique. Cette hypothĂšse est Ă©tudiĂ©e par marquage des vaisseaux lymphatiques (LYVE-1) et des vaisseaux sanguins (PECAM) sur embryon entier et peaux isolĂ©es Ă diffĂ©rents stades prĂ©cĂ©dant la mort.Ces embryons prĂ©sentent Ă©galement un problĂšme de dĂ©veloppement du foie, probablement dĂ» Ă lâactivitĂ© du promoteur tie2 dans les lignĂ©es hĂ©matopoiĂ©tiques. La mise en culture de ces foies fĆtaux Ă E13,5 rĂ©vĂšle une atteinte des prĂ©curseurs hĂ©matopoĂ©tiques.LâĂ©tude de ces prĂ©curseurs Ă des stades plus prĂ©coces (E8,5) est en cours au laboratoire.Nos rĂ©sultats dĂ©montrent donc un rĂŽle important de lâARN interfĂ©rence dans le contrĂŽle Ă©pigĂ©nĂ©tique de lâangiogenĂšse et de la lymphangiogenĂšse embryonnaire mais Ă©galement dans le dĂ©veloppement de lâhĂ©matopoiĂšse, suggĂ©rant son implication dans la diffĂ©renciation veino-lymphangiogenĂšse, dont les mĂ©canismes molĂ©culaires seront discutĂ©s
Characterising The Atmospheric Dynamics Of HD209458b-like Hot Jupiters Using AI Driven Image Recognition/Categorisation
In-order to understand the results of recent observations of exoplanets,
models have become increasingly complex. Unfortunately this increases both the
computational cost and output size of said models. We intend to explore if
AI-image-recognition can alleviate this burden. We used DYNAMICO to run a
series of HD209458-like models with different orbital-radii. Training data for
a number of features of interest was selected from the initial outputs of these
models. This was used to train a pair of multi-categorisation
convolutional-neural-networks (CNN), which we applied to our
outer-atmosphere-equilibrated models. The features detected by our CNNs
revealed that our models fall into two regimes: models with a shorter
orbital-radii exhibit significant global mixing which shapes the entire
atmospheres dynamics. Whereas, models with longer orbital-radii exhibit
negligible mixing except at mid-pressures. Here, the initial non-detection of
any trained features revealed a surprise: a night-side hot-spot. Analysis
suggests that this occurs when rotational influence is sufficiently weak that
divergent flows from the day-side to the night-side dominate over
rotational-driven transport, such as the equatorial jet. We suggest that
image-classification may play an important role in future, computational,
atmospheric studies. However special care must be paid to the data feed into
the model, from the colourmap, to training the CNN on features with enough
breadth and complexity that the CNN can learn to detect them. However, by using
preliminary-studies and prior-models, this should be more than achievable for
future exascale calculations, allowing for a significant reduction in future
workloads and computational resources.Comment: Accepted for publication in Ap
Autoradiographic Characterization and Localization of Quisqualate Binding Sites in Rat Brain Using the Antagonist [ 3 H]6-Cyano-7-Nitroquinoxaline-2,3-Dione: Comparison with ( R,S )-[ 3 H]Î-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Binding Sites
Using quantitative autoradiography, we have investigated the binding sites for the potent competitive non- N -methyl-D-aspartate (non-NMDA) glutamate receptor antagonist [ 3 H]6-cyano-7-nitro-quinoxaline-2,3-dione ([ 3 H]-CNQX) in rat brain sections. [ 3 H]CNQX binding was regionally distributed, with the highest levels of binding present in hippocampus in the stratum radiatum of CA1, stratum lucidum of CA3, and molecular layer of dentate gyrus. Scatchard analysis of [ 3 H]CNQX binding in the cerebellar molecular layer revealed an apparent single binding site with a K D = 67 ± 9.0 n M and B max = 3.56 ± 0.34 pmol/mg protein. In displacement studies, quisqualate, L-glutamate, and kainate also appeared to bind to a single class of sites. However, ( R,S )- Π-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) displacement of [ 3 H]CNQX binding revealed two binding sites in the cerebellar molecular layer. Binding of [ 3 H]AMPA to quisqualate receptors in the presence of potassium thiocyanate produced curvilinear Scatchard plots. The curves could be resolved into two binding sites with K D1 = 9.0 ± 3.5 n M , B max = 0.15 ± 0.05 pmol/mg protein, K D2 = 278 ± 50 n M , and B max = 1.54 ± 0.20 pmol/mg protein. The heterogeneous anatomical distribution of [ 3 H]CNQX binding sites correlated to the binding of L-[ 3 H]glutamate to quisqualate receptors and to sites labeled with [ 3 H]AMPA. These results suggest that the non-NMDA glutamate receptor antagonist [ 3 H]CNQX binds with equal affinity to two states of quisqualate receptors which have different affinities for the agonist [ 3 H]AMPA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65634/1/j.1471-4159.1990.tb01925.x.pd
Partially linear censored quantile regression
Censored regression quantile (CRQ) methods provide a powerful and flexible approach to the analysis of censored survival data when standard linear models are felt to be appropriate. In many cases however, greater flexibility is desired to go beyond the usual multiple regression paradigm. One area of common interest is that of partially linear models: one (or more) of the explanatory covariates are assumed to act on the response through a non-linear function. Here the CRQ approach of Portnoy (J Am Stat Assoc 98:1001â1012, 2003) is extended to this partially linear setting. Basic consistency results are presented. A simulation experiment and unemployment example justify the value of the partially linear approach over methods based on the Cox proportional hazards model and on methods not permitting nonlinearity
Air quality in the mid-21st century for the city of Paris under two climate scenarios; from the regional to local scale
Ozone and PM<sub>2.5</sub> concentrations over the city of Paris are modeled with
the CHIMERE air-quality model at 4 km Ă 4 km horizontal resolution for two
future emission scenarios. A high-resolution (1 km Ă 1 km) emission projection
until 2020 for the greater Paris region is developed by local experts
(AIRPARIF) and is further extended to year 2050 based on regional-scale
emission projections developed by the Global Energy Assessment. Model
evaluation is performed based on a 10-year control simulation. Ozone is in
very good agreement with measurements while PM<sub>2.5</sub> is underestimated by
20% over the urban area mainly due to a large wet bias in wintertime
precipitation. A significant increase of maximum ozone relative to present-day levels over Paris is modeled under the "business-as-usual" scenario
(+7 ppb) while a more optimistic "mitigation" scenario leads to a moderate
ozone decrease (â3.5 ppb) in year 2050. These results are substantially
different to previous regional-scale projections where 2050 ozone is found
to decrease under both future scenarios. A sensitivity analysis showed that
this difference is due to the fact that ozone formation over Paris at the
current urban-scale study is driven by volatile organic compound (VOC)-limited chemistry, whereas at
the regional-scale ozone formation occurs under NO<sub>x</sub>-sensitive
conditions. This explains why the sharp NO<sub>x</sub> reductions implemented in
the future scenarios have a different effect on ozone projections at
different scales. In rural areas, projections at both scales yield similar
results showing that the longer timescale processes of emission transport
and ozone formation are less sensitive to model resolution. PM<sub>2.5</sub> concentrations decrease by 78% and 89% under business-as-usual
and mitigation scenarios, respectively, compared to the present-day period.
The reduction is much more prominent over the urban part of the domain due
to the effective reductions of road transport and residential emissions
resulting in the smoothing of the large urban increment modeled in the
control simulation
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