Time-Space Tradeoff in Deep Learning Models for Crop Classification on Satellite Multi-Spectral Image Time Series

International audienceIn this article, we investigate several structured deep learning models for crop type classification on multi-spectral time series. In particular, our aim is to assess the respective importance of spatial and temporal structures in such data. With this objective, we consider several designs of convolutional, recurrent, and hybrid neural networks, and assess their performance on a large dataset of freely available Sentinel-2 imagery. We find that the best-performing approaches are hybrid configurations for which most of the parameters (up to 90%) are allocated to modeling the temporal structure of the data. Our results thus constitute a set of guidelines for the design of bespoke deep learning models for crop type classification

PIECEWISE-PLANAR APPROXIMATION OF LARGE 3D DATA AS GRAPH-STRUCTURED OPTIMIZATION

We introduce a new method for the piecewise-planar approximation of 3D data, including point clouds and meshes. Our method is designed to operate on large datasets (e.g. millions of vertices) containing planar structures, which are very frequent in anthropic scenes. Our approach is also adaptive to the local geometric complexity of the input data. Our main contribution is the formulation of the piecewise-planar approximation problem as a non-convex optimization problem. In turn, this problem can be efficiently solved with a graph-structured working set approach. We compare our results with a state-of-the-art region-growing-based segmentation method and show a significant improvement both in terms of approximation error and computation efficiency

Motor Outcomes After Neonatal Arterial Ischemic Stroke Related to Early MRI Data in a Prospective Study

OBJECTIVE: We aimed to correlate early imaging data with motor outcomes in a large, homogeneous, cohort of infants with neonatal (diagnosed before 29 days of life) arterial ischemic stroke (AIS).METHODS: From a prospective cohort of 100 children with neonatal AIS, we analyzed the MRI studies performed within the 28 first days of life for 80 infants evaluated at 2 years of age. The relationships between infarction location and corticospinal tract (CST) involvement and motor outcomes were studied RESULTS: Seventy-three infarctions involved the middle cerebral artery (MCA) territory. Of those, 50 were superficial infarctions, 5 deep infarctions, and 18 mixed infarctions. The CST was involved in 24 cases. Nineteen patients with MCA infarctions (26% [95% confidence interval: 16%–34%]) developed hemiplegia. Mixed infarctions (P < .0001) and CST involvement (P < .0001) were highly predictive of hemiplegia. In contrast, 88% of children with isolated superficial MCA infarctions did not exhibit impairment. CONCLUSIONS: Accurate prediction of motor outcomes can be obtained from early MRI scans after neonatal AIS. The absence of involvement of the CST resulted in normal motor development in 94% of cases. CST involvement resulted in congenital hemiplegia in 66% of cases

Selectivity via Cooperativity: Preferential Stabilization of the p65/14-3-3 Interaction with Semisynthetic Natural Products

Natural compounds are an important class of potent drug molecules including some retrospectively found to act as stabilizers of protein–protein interactions (PPIs). However, the design of synthetic PPI stabilizers remains an understudied approach. To date, there are limited examples where cooperativity has been utilized to guide the optimization of a PPI stabilizer. The 14-3-3 scaffold proteins provide an excellent platform to explore PPI stabilization because these proteins mediate several hundred PPIs, and a class of natural compounds, the fusicoccanes, are known to stabilize a subset of 14-3-3 protein interactions. 14-3-3 has been reported to negatively regulate the p65 subunit of the NF-κB transcription factor, which qualifies this protein complex as a potential target for drug discovery to control cell proliferation. Here, we report the high-resolution crystal structures of two 14-3-3 binding motifs of p65 in complex with 14-3-3. A semisynthetic natural product derivative, DP-005, binds to an interface pocket of the p65/14-3-3 complex and concomitantly stabilizes it. Cooperativity analyses of this interaction, and other disease relevant 14-3-3-PPIs, demonstrated selectivity of DP-005 for the p65/14-3-3 complex. The adaptation of a cooperative binding model provided a general approach to characterize stabilization and to assay for selectivity of PPI stabilizers

Molecular Implication of PP2A and Pin1 in the Alzheimer's Disease Specific Hyperphosphorylation of Tau

Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD) related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α)) is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D)) or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau.Our results show that phosphorylation of T231 (AT180) can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α)-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α) may contribute to the hyperphosphorylation of Tau observed in AD neurons

DEB025 (Alisporivir) Inhibits Hepatitis C Virus Replication by Preventing a Cyclophilin A Induced Cis-Trans Isomerisation in Domain II of NS5A

DEB025/Debio 025 (Alisporivir) is a cyclophilin (Cyp)-binding molecule with potent anti-hepatitis C virus (HCV) activity both in vitro and in vivo. It is currently being evaluated in phase II clinical trials. DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication. Here we report that it was very difficult to select resistant replicons (genotype 1b) to DEB025, requiring an average of 20 weeks (four independent experiments), compared to the typically <2 weeks with protease or polymerase inhibitors. This indicates a high genetic barrier to resistance for DEB025. Mutation D320E in NS5A was the only mutation consistently selected in the replicon genome. This mutation alone conferred a low-level (3.9-fold) resistance. Replacing the NS5A gene (but not the NS5B gene) from the wild type (WT) genome with the corresponding sequence from the DEB025res replicon resulted in transfer of resistance. Cross-resistance with cyclosporine A (CsA) was observed, whereas NS3 protease and NS5B polymerase inhibitors retained WT-activity against DEB025res replicons. Unlike WT, DEB025res replicon replicated efficiently in CypA knock down cells. However, DEB025 disrupted the interaction between CypA and NS5A regardless of whether the NS5A protein was derived from WT or DEB025res replicon. NMR titration experiments with peptides derived from the WT or the DEB025res domain II of NS5A corroborated this observation in a quantitative manner. Interestingly, comparative NMR studies on two 20-mer NS5A peptides that contain D320 or E320 revealed a shift in population between the major and minor conformers. These data suggest that D320E conferred low-level resistance to DEB025 probably by reducing the need for CypA-dependent isomerisation of NS5A. Prolonged DEB025 treatment and multiple genotypic changes may be necessary to generate significant resistance to DEB025, underlying the high barrier to resistance

A metodologia de Lamarck

Neste artigo, o método científico de Jean-Baptiste Lamarck é estudado sob o ponto de vista de seu discurso metodológico, bem como sob o ponto de vista de sua prática científica. Essa metodologia é comparada à preconizada por Condillac, assim como à dos "ideólogos" (idéologues) grupo no qual se costuma incluir o próprio Lamarck. Mostra-se que o discurso metodológico de Lamarck assemelha-se ao dos ideólogos; no entanto, sua prática científica não se coaduna com esse enfoque. Em vez de seguir uma abordagem empirista, a obra de Lamarck se fundamenta em princípios metafísicos gerais sobre a natureza. Sob o ponto de vista dos ideólogos, seu trabalho deveria ser rejeitado - o que de fato ocorreu - como um mero sistema (système) metafísico - no sentido pejorativo utilizado pelos seguidores de Condillac. No entanto, o presente artigo argumenta que esse é justamente um importante e inovador aspecto da obra de Lamarck, que permitiu a eclosão do evolucionismo moderno