Yuriko Saito, Aesthetics of the Familiar

L’ouverture que propose Saito du discours esthétique à l’ensemble de la sphère des expériences humaines est un pas qu’il faut franchir pour se détacher de la longue tradition philosophique classique puis analytique occidentale. En se détachant des objets de l’art, l’auteure nous amène à questionner ce qui constitue une part majeure de notre vie quotidienne : ce qui touche à nos sens et le rapport complexe à notre environnement que représente la routine. Loin de chercher à fonder une nouvelle ..

Statuts épistémologique et axiologique de la « théorie » architecturale.

La théorie de l’architecture occupe un statut particulier et ambigu parmi les différentes disciplines pratiques. D’un côté, son écriture dans le temps et par des auteurs variés semble indiquer la construction d’une connaissance partagée et objective, analogue aux théories formulées dans le champ des sciences. D’un autre, son rôle normatif pour la pratique lui donne un caractère axiologiquement orienté, au sens où elle vise à formuler des valeurs. Si son impact dans la discipline architecturale est indéniable, son étude est encore difficile, voire évitée par les tenants d’approches doctrinales. À défaut de proposer l’étude d’une théorie architecturale particulière, nous proposons de tenter de clarifier le statut de la théorie architecturale et les formes qu’elle peut prendre sur les plans épistémologiques et axiologiques — c’est-à-dire au regard des connaissances qu’elle prétend formuler et des valeurs qu’elle produit.Architectural theory lies in a rather peculiar and ambigous status among various practical fields. On the one hand, its writing in time and by various authors seems to indicate the construction of a shared and objective knowledge, analogous to the theories formulated in the field of science. On the other hand, its normative part endorse an oriented axiological character, in the extend that it aims to formulate values. If its impact in architectural field is undoubted, architectural theory’s study of is still complicated, if not avoided by the tenets of doctrinals approaches. Instead of proposing a study of one particular architectural theory, we aim to clarify the architectural theory’s status and the various ways it could take on the epistemological and axiological grounds — i.e. regarding the knowledge and values it produces

Increase in Growth and Alteration of C:N Ratios of Avicennia marina and Rhizophora stylosa Subject to Elevated CO2 Concentrations and Longer Tidal Flooding Duration

We investigated the effects of elevated CO2 concentrations and longer tidal flooding duration on two-year-old Avicennia marina and Rhizophora stylosa seedlings for a full year. The seedlings were grown in greenhouses for ambient CO2 (400 ppm) and in enclosed CO2-controlled chambers, which were installed inside the greenhouses for elevated CO2 (800 ppm). The tidal flooding duration was set-up according to the species distribution in the intertidal zone in New Caledonia for the controlled treatment and was increased by 1 h 45 min for the experimental treatment. A total of 400 A. marina and 720 R. stylosa were monitored during this experiment. We measured heights and basal diameters of all seedlings every 90 days, and we determined the above and below ground biomass at the end of the experiment. Our results showed that elevated CO2 increased the growth rates of both A. marina and R. stylosa, for which the final biomass was, respectively, 46 and 32% higher than in the ambient CO2 treatment. We suggest that this increase was driven by a stimulation of photosynthesis under elevated CO2, as demonstrated in a previous study. Considering the tidal flooding duration treatment, we observed a contrasted effect between the species. Longer tidal flooding increased the growth of A. marina, whereas it reduced the growth of R. stylosa in comparison to the controlled treatment. This result may be related to the specific ecosystem zonation in this semi-arid climate, which limits water inputs into the Avicennia zone that increases the salt concentration in the soil, whereas Rhizophora is regularly submerged by tides due to its lower position in the intertidal zone. As a result, the combination of both treatments had a positive cumulative effect on the growth of A. marina. Although it was not the case for R. stylosa, the negative effect of longer tidal flooding on this species did not suppress the enhancement of growth resulting from elevated CO2 concentrations. At the end of the experiment, elevated CO2 increased the C:N ratios of the seedlings, thereby producing a more refractory organic matter, which will potentially result in lower decomposition rates and thus may increase carbon accumulation in mangrove soils. These results suggest that future climate changes may enhance the productivity of mangrove seedlings by increasing their growth, which may in turn increase the carbon storage potential of mangroves in their biomass

Visible spectrum extended-focus optical coherence microscopy for label-free sub-cellular tomography

We present a novel extended-focus optical coherence microscope (OCM) attaining 0.7 {\mu}m axial and 0.4 {\mu}m lateral resolution maintained over a depth of 40 {\mu}m, while preserving the advantages of Fourier domain OCM. Our method uses an ultra-broad spectrum from a super- continuum laser source. As the spectrum spans from near-infrared to visible wavelengths (240 nm in bandwidth), we call the method visOCM. The combination of such a broad spectrum with a high-NA objective creates an almost isotropic 3D submicron resolution. We analyze the imaging performance of visOCM on microbead samples and demonstrate its image quality on cell cultures and ex-vivo mouse brain tissue.Comment: 15 pages, 7 figure

Probing ligand and cation binding sites in G-quadruplex nucleic acids by mass spectrometry and electron photodetachment dissociation sequencing

International audienceMass spectrometry provides exquisite detail on ligand and cation binding stoichiometries with a DNA target. The next important step is to develop reliable methods to determine the cation and ligand binding sites in each complex separated by the mass spectrometer. To circumvent the caveat of ligand derivatization for cross-linking, which may alter the ligand binding mode, we explored a tandem mass spectrometry (MS/MS) method that does not require ligand derivatization, and is therefore also applicable to localize metal cations. By obtaining more negative charge states for the complexes using supercharging agents, and by creating radical ions by electron photodetachment, oligonucleotide bonds become weaker than the DNA-cation or DNA-ligand noncovalent bonds upon collision-induced dissociation of the radicals. This electron photodetachment (EPD) method allows to locate the binding regions of cations and ligands by top-down sequencing of the oligonucleotide target. The very potent G-quadruplex ligands 360A and PhenDC3 were found to replace a potassium cation and bind close to the central loop of 4-repeat human telomeric sequences

Comorbidities of COPD

International audienceBy 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately. Extrapulmonary comorbidities are common in COPD and influence prognosis; we propose an exhaustive comorbidities revie

Traité sur les bêtes-à-laine d'Espagne : leur éducation, leurs voyages, la tonte ...

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Sign.: a8, A-Y8, Z2La h. de grab. pleg. es calc.: Lasteyrie Delin y Van-Maëll

Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity

Mass spectrometry and ion mobility spectrometry of G-quadruplexes. A study of solvent effects on dimer formation and structural transitions in the telomeric DNA sequence d(TAGGGTTAGGGT).

We survey here state of the art mass spectrometry methodologies for investigating G-quadruplexes, and will illustrate them with a new study on a simple model system: the dimeric G-quadruplex of the 12-mer telomeric DNA sequence d(TAGGGTTAGGGT), which can adopt either a parallel or an antiparallel structure. We will discuss the solution conditions compatible with electrospray ionisation, the quantification of complexes using ESI-MS, the interpretation of ammonium ion preservation in the complexes in the gas phase, and the use of ion mobility spectrometry to resolve ambiguities regarding the strand stoichiometry, or separate and characterise different structural isomers. We also describe that adding electrospray-compatible organic co-solvents (methanol, ethanol, isopropanol or acetonitrile) to aqueous ammonium acetate increases the stability and rate of formation of dimeric G-quadruplexes, and causes structural transitions to parallel structures. Structural changes were probed by circular dichroism and ion mobility spectrometry, and the excellent correlation between the two techniques validates the use of ion mobility to investigate G-quadruplex folding. We also demonstrate that parallel G-quadruplex structures are easier to preserve in the gas phase than antiparallel structures

Etude de G-Quadruplexes par Spectrométrie de Masse : chemins de Repliement et Modes de Liaison de Ligands

Un G-quadruplex (G4) est une structure non-canonique d’acides nucléiques formée par des séquences riches en guanines. Certains G4s sont polymorphiques, une même séquence peut former desG4s de différentes topologies. Les G4s sont proposés comme régulateurs de processus biologiques car ils sont trouvés dans des régions génomiques clés telles que dans des promoteurs de gènes et au niveau des télomères. Stabiliser ces G4s par rapport à la forme duplexe est une stratégie proposée pour combattre le cancer. Pour ce faire, des ligands spécifiques et affins sont utilisés. Le design de ces ligands implique habituellement de larges plans aromatiques, optimisés pour se lier par des interactions π-π sur les Gquartets extérieurs. Cependant, si ce type d’interaction était le seul mode de liaison, tous les ligands auraient des affinités similaires pour tous les G4s.Afin de caractériser les structures ciblées et de quelle manière les ligands vont interagir avec celles-ci, nous avons utilisé la spectrométrie de masse de type native (MS). D’abord, nous avons développé une méthode de préparation d’échantillons en conditions KCl pour former les G4s dans des conditions biologiquement pertinentes. Ensuite, nous avons caractérisé les équilibres de liaison du K+ aux G4s et caractérisé leur mécanisme de repliement. Ce mécanisme implique la présence d’une impasse constituée de G4s antiparallèles à 1- et 2-K+ qui sont formés rapidement. Enfin, nos études de liaison de ligands ont montré que certains des ligands les plus affins pouvaient influencer la structure des G4s comme observé par le nombre d’ions potassium liés. Les ligands Phen-DC3, 360A et PDS sont capables de déplacer les équilibres vers la forme à 1-K+ antiparallèle. La structure antiparallèle à 2-K+ est favorisée par la liaison coopérative de deux ligands Cu-ttpy. Ces résultats démontrent l’importance de la caractérisation des stoechiométries de complexes ternaires (G4:ligand:K+), obtenue par la spectrométrie de masse native.A G-quadruplex (G4) is a non-canonical nucleic acids structure formed by guanine-rich sequences. Some G4s are polymorphic, a given sequence can form G4s of different topologies. G4s are proposed to be biological regulators because they are found in key regions of the genome, for example, ingene promoters or at the telomeres. Stabilizing G4s formed in those regions as compared to the duplex form is a strategy to fight cancer. To do so, specific and affine ligands are used. Ligand design usually implies the optimization of large aromatic planes to π-π stack on external G-quartets. However, if this was the only binding mode, all ligands would bind with similar affinities to all G4s.To characterize which structures should be targeted and how the ligands interact with these structures, we used native mass spectrometry (MS).First, we developed a MS-compatible sample preparation method in KCl conditions in which G4s are folded with similar topologies as compared to those obtained in biologically relevant conditions. Then, we characterized the K+ binding equilibria and G4s folding pathways. This folding pathway involves the presence of a dead-end constituted by antiparallel G4s with either 1- or 2-K+ cations that are folded first. Finally, our ligand binding studies showed that some of the most affine ligands can influence G4’sstructures, as probed by the number of K+ ions bound. Ligands Phen-DC3, 360A and PDS are able to shift the equilibria towards the 1-K+ antiparallel G4s. The formation of antiparallel with 2-K+ complexes is induced by the cooperative binding of two Cu-ttpy ligands. Our results demonstrate the importance to characterize ternary complex stoichiometries (G4:ligand:K+) as obtained from native mass spectrometry