La cuadriculación efectuada sobre Rúan y sus alrededores permite la cartografía informática de datos sociodemográficos aplicada al conjunto de la ciudad. Se han aplicado dos métodos cartográficos ...sobre esta cuadriculación que permiten tener una buena interpretación cuadriculada y mejorar su representación. La nivelación simplifica la lectura del mapa al suprimir el "ruido" y la "3D" modifica por completo la cuadriculación al introducir el relieve.
The gridmap of Rouen and its suburbs makes computer mapping of sociodemographic data concerning the entire city possible. Two cartographical methods were used on this gridmap providing a new perception of the information and improved representation. The smoothing technique simplifies map reading by eliminating «noises» and the 3D function completely modifies the grid by adding relief.
Le carroyage effectué sur l’agglomération de Rouen permet la cartographie informatique de données sociodémographiques sur l’ensemble de la ville. Sur ce carroyage ont été appliquées deux méthodes cartographiques permettant d’avoir une nouvelle perception de l’information carroyée et d’améliorer sa représentation. Le lissage simplifie la lecture de la carte en supprimant le «bruit» et la «3D» modifie complètement le carroyage en introduisant le relief.
The gridmap of Rouen and its suburbs makes computer mapping of sociodemographic data concerning the entire city possible. Two cartographical methods were used on this gridmap providing a new ...perception of the information and improved representation. The smoothing technique simplifies map reading by eliminating «noises» and the 3D function completely modifies the grid by adding relief.
Le carroyage effectué sur l’agglomération de Rouen permet la cartographie informatique de données sociodémographiques sur l’ensemble de la ville. Sur ce carroyage ont été appliquées deux méthodes cartographiques permettant d’avoir une nouvelle perception de l’information carroyée et d’améliorer sa représentation. Le lissage simplifie la lecture de la carte en supprimant le «bruit» et la «3D» modifie complètement le carroyage en introduisant le relief.
La cuadriculación efectuada sobre Rúan y sus alrededores permite la cartografía informática de datos sociodemográficos aplicada al conjunto de la ciudad. Se han aplicado dos métodos cartográficos sobre esta cuadriculación que permiten tener una buena interpretación cuadriculada y mejorar su representación. La nivelación simplifica la lectura del mapa al suprimir el "ruido" y la "3D" modifica por completo la cuadriculación al introducir el relieve.
Bizet Frédéric. Carroyage et SIG urbain: les chômeurs à Rouen. In: Mappemonde, 1997/2. pp. 32-34.
Les jeux de plateau utilisent le plus souvent une carte «papier » comme support. Au-delà de l’aspect cartographique, ces jeux intègrent également des notions de territorialité et d’analyse spatiale.
...Boardgames often use a " paper" map as a prop. Beyond the cartographic aspect, those games also incorporate notions of territoriality and of space analysis.
Los juegos de planicie utilizan la mayoría de las veces un mapa de "papel" como soporte. Más allá del aspecto cartográfico, esos juegos integran nociones de territorialidad y de análisis espacial.
- This article shows a quantitative approach of some urban social facts from the census data, but with an original method (the square gridding) and the statistic treatment which is issued from remote ...sensing.
Résumé. - Cet article montre une approche quantitative de certains faits sociaux urbains à partir des données du recensement, mais sous un angle original de par les caractéristiques du carroyage et du traitement apporté.
Human cytochrome P450 reductase is a membrane protein located on the cytoplasmic side of the endoplasmic reticulum. It contains two binding domains for FAD and FMN, which are connected by a flexible ...region 1. CPR transfers electrons from NADPH to cytochromes P450 through flavins. Two crystallographic structures were obtained for Rattus norvegicus showing "closed" and "open" conformations 2 These two structures show different distances between the flavin cofactors. Indeed, for inter-flavin Electronic Transfer (ET), the two FAD and FMN domains must be nearby (a "closed" conformation), but inter-protein ET (FMN to CYPs) requires a more "open" conformation. The understanding and characterization of domain movement associated with ET is essential and will be studied by measuring distances between two paramagnetic centers via two approaches: 1) using endogenous probes by isolating the flavin radical, and 2) by Site-Directed Spin Labeling and EPR, based on the insertion of paramagnetic nitroxide probes. Classically, these are specific to cysteines 3. However, C566 is involved in the enzymatic activity and cannot be modified. The incorporation of non-natural amino acids and their labelling with specific nitroxides has been shown to be a powerful alternative 4 First experiments on human soluble CPR concerning the labelling of non-natural amino acids, as well as the trapping of flavin centers will be presented.
We present a two-photon microendoscope capable of in vivo label-free deep-tissue high-resolution fast imaging through a very long optical fiber. First, an advanced light-pulse spectro-temporal ...shaping device optimally precompensates for linear and nonlinear distortions occurring during propagation within the endoscopic fiber. This enables the delivery of sub-40-fs duration infrared excitation pulses at the output of 5 meters of fiber. Second, the endoscopic fiber is a custom-made double-clad polarization-maintaining photonic crystal fiber specifically designed to optimize the imaging resolution and the intrinsic luminescence backward collection. Third, a miniaturized fiber-scanner of 2.2 mm outer diameter allows simultaneous second harmonic generation (SHG) and two-photon excited autofluorescence (TPEF) imaging at 8 frames per second. This microendoscope's transverse and axial resolutions amount respectively to 0.8 μm and 12 μm, with a field-of-view as large as 450 μm. This microendoscope's unprecedented capabilities are validated during label-free imaging, ex vivo on various fixed human tissue samples, and in vivo on an anesthetized mouse kidney demonstrating an imaging penetration depth greater than 300 μm below the surface of the organ. The results reported in this manuscript confirm that nonlinear microendoscopy can become a valuable clinical tool for real-time in situ assessment of pathological states.
The flavoprotein Cytochrome P450 reductase (CPR) is the unique electron pathway from NADPH to Cytochrome P450 (CYPs). The conformational dynamics of human CPR in solution, which involves transitions ...from a "locked/closed" to an "unlocked/open" state, is crucial for electron transfer. To date, however, the factors guiding these changes remain unknown. By Site-Directed Spin Labelling coupled to Electron Paramagnetic Resonance spectroscopy, we have incorporated a non-canonical amino acid onto the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) domains of soluble human CPR, and labelled it with a specific nitroxide spin probe. Taking advantage of the endogenous FMN cofactor, we successfully measured for the first time, the distance distribution by DEER between the semiquinone state FMNH
and the nitroxide. The DEER data revealed a salt concentration-dependent distance distribution, evidence of an "open" CPR conformation at high salt concentrations exceeding previous reports. We also conducted molecular dynamics simulations which unveiled a diverse ensemble of conformations for the "open" semiquinone state of the CPR at high salt concentration. This study unravels the conformational landscape of the one electron reduced state of CPR, which had never been studied before.
A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader ...of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.
Amyloid diseases are degenerative pathologies, highly prevalent today because they are closely related to aging, that have in common the erroneous folding of intrinsically disordered proteins (IDPs) ...which aggregate and lead to cell death. Type 2 Diabetes involves a peptide called human islet amyloid polypeptide (hIAPP), which undergoes a conformational change, triggering the aggregation process leading to amyloid aggregates and fibers rich in β-sheets mainly found in the pancreas of all diabetic patients. Inhibiting the aggregation of amyloid proteins has emerged as a relevant therapeutic approach and we have recently developed the design of acyclic flexible hairpins based on peptidic recognition sequences of the amyloid β peptide (Aβ
1–42
) as a successful strategy to inhibit its aggregation involved in Alzheimer’s disease. The present work reports the extension of our strategy to hIAPP aggregation inhibitors. The design, synthesis, conformational analyses, and biophysical evaluations of dynamic β-hairpin like structures built on a piperidine-pyrrolidine β-turn inducer are described. By linking to this β-turn inducer three different arms (i) pentapeptide, (ii) tripeptide, and (iii) α/aza/aza/pseudotripeptide, we demonstrate that the careful selection of the peptide-based arms from the sequence of hIAPP allowed to selectively modulate its aggregation, while the peptide character can be decreased. Biophysical assays combining, Thioflavin-T fluorescence, transmission electronic microscopy, capillary electrophoresis, and mass spectrometry showed that the designed compounds inhibit both the oligomerization and the fibrillization of hIAPP. They are also capable to decrease the aggregation process in the presence of membrane models and to strongly delay the membrane-leakage induced by hIAPP. More generally, this work provides the proof of concept that our rational design is a versatile and relevant strategy for developing efficient and selective inhibitors of aggregation of amyloidogenic proteins.
Multiphoton microscopy (MPM) has the capacity to record second-harmonic generation (SHG) and endogenous two-photon excitation fluorescence (2PEF) signals emitted from biological tissues. The ...development of fiber-based miniaturized endomicroscopes delivering pulses in the femtosecond range will allow the transfer of MPM to clinical endoscopy. We present real-time SHG and 2PEF ex vivo images using an endomicroscope, which totally complies with clinical endoscopy regulations. This system is based on the proximal scanning of a commercial multicore image guide (IG). For understanding the inhomogeneities of the recorded images, we quantitatively characterize the IG at the single-core level during nonlinear excitation. The obtained results suggest that these inhomogeneities originate from the variable core geometries that, therefore, exhibit variable nonlinear and dispersive properties. Finally, we propose a method based on modulation of dispersion precompensation to address the image inhomogeneity issue and, as a proof of concept, we demonstrate its capability to improve the nonlinear image quality.
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