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RÉSUMÉLe Service Prévision des Crues Vilaine et Côtiers Bretons (SPC VCB) est responsable de la vigilance crues sur les cours d’eau à enjeux de la région Bretagne depuis 2005. Depuis presque 20 ans, les attentes des gestionnaires de crise comme du grand public ont beaucoup évolué, et l’outillage du SPC VCB s’est étoffé. Afin d’observer l’impact du développement des modèles sur la qualité de la prévision, les modèles utilisés actuellement ou précédemment par le SPC VCB ont été classés en trois catégories : statistiques, hydrologiques et hydrauliques. Par la suite, la conformité des points de prévision par rapport aux données observées a été analysée pour chaque année hydrologique. Les données révèlent une diversification des modèles au fil du temps. En 2014, seuls les modèles statistiques étaient représentés. Aujourd’hui 59,7 % des sorties de modèles sont issues d’un modèle statistique, 34 % sont issues d’un modèle hydrologique et 6,3 % sont issues d’un modèle hydraulique. La moyenne de conformité annuelle a constamment augmenté au fil des années, passant de 52,6 % pour la période 2007–2011 à 74,5 % pour la période 2019–2023. Ces stratégies de modélisation ont participé à l’amélioration de la vigilance crues.

The NLRP3 inflammasome is a critical component of the innate immune response. NLRP3 activation is a tightly controlled process involving an initial priming to express NLRP3, pro-IL-1 β, and pro-IL-18, followed by an activation signal. The precise mechanism of activation is not fully understood due to the diverse range of activators, yet it effectively orchestrates the activation of caspase-1, which subsequently triggers the release of proinflammatory cytokines IL-1β and IL-18. NLRP3 dysregulation can lead to a variety of inflammatory diseases, highlighting its significant role in immune response and disease pathogenesis. NLRP3 is divided into three domains: the PYD, the NACHT, and the LRR domains. This review focuses on the LRR domain of NLRP3, detailing its structural characteristics, its function in pathogen sensing, its role in the degradation process, and its involvement in inflammasome auto-inhibition and activation. Additionally, we discuss the impact of mutations within the LRR domain found in atypical Cryopyrin-Associated Periodic Syndromes (CAPS), highlighting the clinical relevance of this domain.

The StarDICE experiment strives to establish an instrumental metrology chain with a targeted accuracy of 1 mmag in griz bandpasses to meet the calibration requirements of next-generation cosmological surveys. Atmospheric transmission is a significant source of systematic uncertainty. We propose a solution relying on an uncooled infrared thermal camera to evaluate gray extinction variations. However, achieving accurate measurements with thermal imaging systems necessitates prior calibration due to temperature-induced effects, compromising their spatial and temporal precision. Moreover, these systems cannot provide scene radiance in physical units by default. This study introduces a new calibration process utilizing a tailored forward modeling approach. The method incorporates sensor, housing, flat-field support, and ambient temperatures, along with raw digital response, as input data. Experimental measurements were conducted inside a climatic chamber, with a FLIR Tau2 camera imaging a thermoregulated blackbody source. The results demonstrate the calibration effectiveness, achieving precise radiance measurements with a temporal pixel dispersion of 0.09 W m−2 sr−1 and residual spatial noise of 0.03 W m−2 sr−1. We emphasize that the accuracy of scene radiance retrieval can be systematically affected by the camera’s close thermal environment, especially when the ambient temperature exceeds that of the scene.

Abstract Hydrogen sulfide (H2S) is a gaseous signaling molecule that participates in various signaling functions in health and diseases. The tetrameric cystathionine γ-lyase (CSE) contributes to H2S biogenesis and several investigations provide evidence on the pharmacological modulation of CSE as a potential target for the treatment of a multitude of conditions. D-penicillamine (D-pen) has recently been reported to selectively impede CSE-catalyzed H2S production but the molecular bases for such inhibitory effect have not been investigated. In this study, we report that D-pen follows a mixed-inhibition mechanism to inhibit both cystathionine (CST) cleavage and H2S biogenesis by human CSE. To decipher the molecular mechanisms underlying such a mixed inhibition, we performed docking and molecular dynamics (MD) simulations. Interestingly, MD analysis of CST binding reveals a likely active site configuration prior to gem-diamine intermediate formation, particularly H-bond formation between the amino group of the substrate and the O3′ of PLP. Similar analyses realized with both CST and D-pen identified three potent interfacial ligand-binding sites for D-pen and offered a rational for D-pen effect. Thus, inhibitor binding not only induces the creation of an entirely new interacting network at the vicinity of the interface between enzyme subunits, but it also exerts long range effects by propagating to the active site. Overall, our study paves the way for the design of new allosteric interfacial inhibitory compounds that will specifically modulate H2S biogenesis by cystathionine γ-lyase.

Depuis quelques années, Naval Group s'approprie la technologie de Focalisation en Tous Points (FTP plus connue sous son acronyme anglais TFM) en l'appliquant progressivement à ses cas industriels. Deux applications sont présentées dans cet article : – une utilisation de la TFM pour les mesures de profilométrie interne de composants, – une utilisation de la TFM pour le contrôle d'une soudure de forte épaisseur. Pour chaque cas, l'application est décrite et les comparaisons entre différentes techniques ultrasonores sont effectuées. Une analyse des gains potentiels est présentée. Des explications physiques utilisant la simulation CIVA sont proposées. Les éventuels inconvénients sont aussi discutés.

Depuis quelques années, Naval Group s’approprie la technologie Focalisation en Tous Points (FTP plus connue sous son acronyme anglais TFM) en l’appliquant progressivement sur des cas industriels concrets. Ce papier présente un premier retour d’expérience de la qualification formelle de la technologie TFM appliquée à l’inspection en service des chaufferies nucléaires embarquées de la propulsion navale. L’application présentée ici utilise la technologie TFM en mode émission/réception séparée sur des soudures de composant nucléaire en acier austénitique ou ferritique de forte épaisseur. Ces applications font l’objet d’une qualification conventionnelle au sens du référentiel interne actuellement en cours d’instruction. La configuration est brièvement présentée : elle utilise des traducteurs positionnés en mode Pitch Catch. La liste des paramètres influents est présentée et quelques résultats tirés des dossiers de justifications techniques utilisant assez largement la simulation mais aussi les expériences sont discutées. Certaines spécificités de la TFM en termes de qualifications sont soulignées. Les avantages/inconvénients de la technique sont évoquées et lorsque c’est possible, quantifiées.

We present the Multi-Object Spectroscopy of Transient (MOST) Hosts survey. The survey is planned to run throughout the 5 yr of operation of the Dark Energy Spectroscopic Instrument (DESI) and will generate a spectroscopic catalog of the hosts of most transients observed to date, in particular all the supernovae observed by most public, untargeted, wide-field, optical surveys (Palomar Transient Factory, PTF/intermediate PTF, Sloan Digital Sky Survey II, Zwicky Transient Facility, DECAT, DESIRT). Science cases for the MOST Hosts survey include Type Ia supernova cosmology, fundamental plane and peculiar velocity measurements, and the understanding of the correlations between transients and their host-galaxy properties. Here we present the first release of the MOST Hosts survey: 21,931 hosts of 20,235 transients. These numbers represent 36% of the final MOST Hosts sample, consisting of 60,212 potential host galaxies of 38,603 transients (a transient can be assigned multiple potential hosts). Of all the transients in the MOST Hosts list, only 26.7% have existing classifications, and so the survey will provide redshifts (and luminosities) for nearly 30,000 transients. A preliminary Hubble diagram and a transient luminosity–duration diagram are shown as examples of future potential uses of the MOST Hosts survey. The survey will also provide a training sample of spectroscopically observed transients for classifiers relying only on photometry, as we enter an era when most newly observed transients will lack spectroscopic classification. The MOST Hosts DESI survey data will be released on a rolling cadence and updated to match the DESI releases. Dates of future releases and updates are available through the https://mosthosts.desi.lbl.gov website.

The Dark Energy Spectroscopic Instrument (DESI) is currently measuring the spectra of 40 million galaxies and quasars, the largest such survey ever made to probe the nature of cosmological dark energy. The 4 m Mayall telescope at Kitt Peak National Observatory has been adapted for DESI, including the construction of a 3.°2 diameter prime focus corrector that focuses astronomical light onto a 0.8 m diameter focal surface with excellent image quality over the DESI bandpass of 360–980 nm. The wide-field corrector includes six lenses, as large as 1.1 m in diameter and as heavy as 237 kilograms, including two counterrotating wedged lenses that correct for atmospheric dispersion over zenith angles from 0° to 60°. The lenses, cells, and barrel assembly all meet precise alignment tolerances on the order of tens of microns. The barrel alignment is maintained throughout a range of observing angles and temperature excursions in the Mayall dome by use of a hexapod, which is itself supported by a new cage, ring, and truss structure. In this paper we describe the design, fabrication, and performance of the new corrector and associated structure, focusing on how they meet DESI requirements. In particular, we describe the prescription and specifications of the lenses, design choices and error budgeting of the barrel assembly, stray light mitigations, and integration and test at the Mayall telescope. We conclude with some validation highlights that demonstrate the successful corrector on-sky performance, and we list some lessons learned during the multiyear fabrication phase.

We present strong constraints on the spacetime variation of the fine-structure constant α using the Dark Energy Spectroscopic Instrument (DESI). In this pilot work, we utilize ∼110,000 galaxies with strong and narrow [O iii ] λ λ 4959, 5007 emission lines to measure the relative variation Δ α / α in space and time. The [O iii ] doublet is arguably the best choice for this purpose owing to its wide wavelength separation between the two lines and its strong emission in many galaxies. Our galaxy sample spans a redshift range of 0 < z < 0.95, covering half of all cosmic time. We divide the sample into subsamples in 10 redshift bins (Δ z = 0.1), and calculate Δ α / α for the individual subsamples. The uncertainties of the measured Δ α / α are roughly between 2 × 10 ^−6 and 2 × 10 ^−5 . We find an apparent α variation with redshift at a level of Δ α / α = (2–3) × 10 ^−5 . This is highly likely to be caused by systematics associated with wavelength calibration, since such small systematics can be caused by a wavelength distortion of 0.002–0.003 Å, which is beyond the accuracy that the current DESI data can achieve. We refine the wavelength calibration using sky lines for a small fraction of the galaxies, but this does not change our main results. We further probe the spatial variation of α in small redshift ranges, and do not find obvious, large-scale structures in the spatial distribution of Δ α / α . As DESI is ongoing, we will include more galaxies, and by improving the wavelength calibration, we expect to obtain a better constraint that is comparable to the strongest current constraint.

Abstract Objectives The purpose of this systematic review and meta‐analysis was to compare implant‐supported removable partial dentures (ISRPDs) with distal extension removable partial dentures (DERPDs) in terms of patient‐reported outcome measures (PROMs: patients' quality of life and satisfaction) and to determine mechanical and biological complications associated with ISRPDs. Material and Methods An electronic search was performed on four databases to identify studies treating Kennedy class I or II edentulous patients and which compared ISRPDs with DERPDs in terms of PROMS and studies, which evaluated mechanical and biological complications associated ISRPDs. Two authors independently extracted data on quality of life, patient satisfaction, and biomechanical complications from these studies. The risk of bias was assessed for each study, and for PROMs, the authors performed a meta‐analysis by using a random‐effects model. Results Thirteen articles were included based on the selection criteria. The difference in mean scores for quality of life (30.5 ± 1.8; 95% confidence interval [CI], 24.9–36.1) and patient satisfaction (−20.8 ± 0.2; 95% CI, −23.7 to −17.8) between treatments with conventional and implant‐supported removable dentures was statistically significant (p

The p53 tumor suppressor is also a regulator of metabolism, but the mechanisms controlling p53-associated metabolic activities remain poorly understood. Here the authors report that the deletion of the multifunctional protein E4F1 is protective against diet-induced obesity in mice, and E4F1 regulates adipocyte lipid metabolism through p53.

Even before considering their introduction into the mouth, the choice of materials for the optimization of the prosthesis depends on specific parameters such as their biocompatibility, solidity, resistance, and longevity. In the first part of this two-part review, we approach the various mechanical characteristics that affect this choice, which are closely related to the manufacturing process. Among the materials currently available, it is mainly polymers that are suitable for this use in this field. Historically, the most widely used polymer has been polymethyl methacrylate (PMMA), but more recently, polyamides (nylon) and polyether ether ketone (PEEK) have provided interesting advantages. The incorporation of certain molecules into these polymers will lead to modifications aimed at improving the mechanical properties of the prosthetic bases. In the second part of the review, the safety aspects of prostheses in the oral ecosystem (fragility of the undercuts of soft/hard tissues, neutral pH of saliva, and stability of the microbiota) are addressed. The microbial colonization of the prosthesis, in relation to the composition of the material used and its surface conditions (roughness, hydrophilicity), is of primary importance. Whatever the material and manufacturing process chosen, the coating or finishes dependent on the surface condition remain essential (polishing, non-stick coating) for limiting microbial colonization. The objective of this narrative review is to compile an inventory of the mechanical and physical properties as well as the clinical conditions likely to guide the choice between polymers for the base of removable prostheses.

Abstract A low-cost, compact, and high gain Fabry–Perot cavity (FPC) antenna which operates at 300 GHz is presented. The antenna is fabricated using laser-cutting brass technology. The proposed antenna consists of seven metallic layers; a ground layer, an integrated stepped horn element (three-layers), a coupling layer, a cavity layer, and an aperture-frequency selective surface (FSS) layer. The proposed aperture-FSS function acts as a partially reflective surface, contributing to a directive beam radiation. For verification, the proposed sub-terahertz (THz) FPC antenna prototype was developed, fabricated, and measured. The proposed antenna has a measured reflection coefficient below − 10 dB from 282 to 304 GHz with a bandwidth of 22 GHz. The maximum measured gain observed is 17.7 dBi at 289 GHz, and the gain is higher than 14.4 dBi from 285 to 310 GHz. The measured radiation pattern shows a highly directive pattern with a cross-polarization level below − 25 dB over the whole band in all cut planes, which confirms with the simulation results. The proposed antenna has a compact size, low fabrication cost, high gain, and wide operating bandwidth. The total height of the antenna is 1.24 $${\lambda }_{0}$$ λ 0 ( $${\lambda }_{0}$$ λ 0 at the design frequency, 300 GHz) , with a size of 2.6 mm × 2.6 mm. The proposed sub-THz waveguide-fed FPC antenna is suitable for 6G wireless communication systems.

A low-profile high-gain fully-metallic circularly polarized (CP) Fabry–Perot cavity (FPC) antenna using laser cutting technology at 300 GHz is presented. The CP-FPC antenna consists of seven metallic layers arranged from the bottom to the top: a ground layer, an integrated stepped horn element (three layers), a coupling slots layer, a cavity layer, and an aperture-frequency selective surface (FSS) layer. The high gain and self-generation of circular polarization are made by using this FSS layer by introducing periodic hexagonal–shaped aperture in a thin metallic layer. The aperture–FSS layer is used to excite two orthogonal modes of equal in magnitude and in phase quadrature, thus obtaining the RHCP radiation. The proposed CP-FPC antenna structure achieves a measured peak RHCP gain of 16.5 dBic at 292 GHz. The antenna achieves a measured impedance bandwidth of 281– 305 GHz for the reflection coefficient less than −10 dB. The axial ratio (AR) bandwidth AR ≤3 dB is 5.12 GHz from 292.8 to 297.92 GHz. The fabricated CP-FPC antenna uses a low-cost laser cutting technique with a low-profile and an area of 2.6 mm $\times2.6$ mm $\times1.24$ mm. The experimental results confirm a good agreement between the simulation and the measurements.

Cutaneous melanoma is a highly invasive tumor and, despite the development of recent therapies, most patients with advanced metastatic melanoma have a poor clinical outcome. The most frequent mutations in melanoma affect the BRAF oncogene, a protein kinase of the MAPK signaling pathway. Therapies targeting both BRAF and MEK are effective for only 50% of patients and, almost systematically, generate drug resistance. Genetic and non-genetic mechanisms associated with the strong heterogeneity and plasticity of melanoma cells have been suggested to favor drug resistance but are still poorly understood. Recently, we have introduced a novel mathematical formalism allowing the representation of the relation between tumor heterogeneity and drug resistance and proposed several models for the development of resistance of melanoma treated with BRAF/MEK inhibitors. In this paper, we further investigate this relationship by using a new computational model that copes with multiple cell states identified by single cell mRNA sequencing data in melanoma treated with BRAF/MEK inhibitors. We use this model to predict the outcome of different therapeutic strategies. The reference therapy, referred to as “continuous” consists in applying one or several drugs without disruption. In “combination therapy”, several drugs are used sequentially. In “adaptive therapy” drug application is interrupted when the tumor size is below a lower threshold and resumed when the size goes over an upper threshold. We show that, counter-intuitively, the optimal protocol in combination therapy of BRAF/MEK inhibitors with a hypothetical drug targeting cell states that develop later during the tumor response to kinase inhibitors, is to treat first with this hypothetical drug. Also, even though there is little difference in the timing of emergence of the resistance between continuous and adaptive therapies, the spatial distribution of the different melanoma subpopulations is more zonated in the case of adaptive therapy.

Background: The TP53 gene is one of the most commonly inactivated tumor suppressors in human cancers. p53 functions during cancer progression have been linked to a variety of transcriptional and non-transcriptional activities that lead to the tight control of cell proliferation, senescence, DNA repair, and cell death. However, converging evidence indicates that p53 also plays a major role in metabolism in both normal and cancer cells. Scope of review: We provide an overview of the current knowledge on the metabolic activities of wild type (WT) p53 and highlight some of the mechanisms by which p53 contributes to whole body energy homeostasis. We will also pinpoint some evidences suggesting that deregulation of p53-associated metabolic activities leads to human pathologies beyond cancer, including obesity, diabetes, liver, and cardiovascular diseases. Major conclusions: p53 is activated when cells are metabolically challenged but the origin, duration, and intensity of these stresses will dictate the outcome of the p53 response. p53 plays pivotal roles both upstream and downstream of several key metabolic regulators and is involved in multiple feedback-loops that ensure proper cellular homeostasis. The physiological roles of p53 in metabolism involve complex mechanisms of regulation implicating both cell autonomous effects as well as autocrine loops. However, the mechanisms by which p53 coordinates metabolism at the organismal level remain poorly understood. Perturbations of p53-regulated metabolic activities contribute to various metabolic disorders and are pivotal during cancer progression. Keywords: p53, Metabolism, Normal tissue homeostasis, Cancer

A novel compact high-efficient circularly polarized conical horn antenna is realized with Wire Electrical Discharge Machining (EDM) technique operating at 300 GHz for 6G wireless communications is presented. The proposed antenna structure consists of three main components; a waveguide feed, a circular polarizer disk, and a conical horn. The waveguide feed is a standard WR-03 rectangular waveguide which feeds the whole structure. The circular polarizer disk is comprised of a crossed slot with unequal lengths which are perpendicular to each other. By adjusting the lengths of both slots, two orthogonal modes are excited in the antenna to produce circular polarization. The conical horn is mounted on the circular polarizer disk. The proposed antenna was designed and optimized using CST Microwave Studio and is validated experimentally by an inexpensive direct Wire-cutting EDM technique over the WM-860 frequency band. The fabricated circularly polarized horn antenna achieved a wide impedance bandwidth of 20 % from 270 GHz to 330 GHz with a reflection coefficient ≤ -15 dB. The measured results show that the 3 dB axial ratio of the fabricated antenna prototype has a bandwidth of 7 GHz from 309 GHz to 316 GHz with a minimum axial ratio of 1.15 dB at 312 GHz. The measured normalized radiation patterns show good agreement with simulated results for different frequencies in both the elevation and azimuth planes at broadside direction with good symmetry in both planes.

We report the first results of a high-redshift ( z ≳ 5) quasar survey using the Dark Energy Spectroscopic Instrument (DESI). As a DESI secondary target program, this survey is designed to carry out a systematic search and investigation of quasars at 4.8 < z < 6.8. The target selection is based on the DESI Legacy Imaging Surveys (the Legacy Surveys) DR9 photometry, combined with the Pan-STARRS1 data and J -band photometry from public surveys. A first quasar sample has been constructed from the DESI Survey Validation 3 (SV3) and first-year observations until 2022 May. This sample includes more than 400 new quasars at redshift 4.7 ≤ z < 6.6, down to 21.5 magnitude (AB) in the z band, discovered from 35% of the entire target sample. Remarkably, there are 220 new quasars identified at z ≥ 5, more than one-third of existing quasars previously published at this redshift. The observations so far result in an average success rate of 23% at z > 4.7. The current spectral data set has already allowed analysis of interesting individual objects (e.g., quasars with damped Ly α absorbers and broad absorption line features), and statistical analysis will follow the survey’s completion. A set of science projects will be carried out leveraging this program, including quasar luminosity function, quasar clustering, intergalactic medium, quasar spectral properties, intervening absorbers, and properties of early supermassive black holes. Additionally, a sample of 38 new quasars at z ∼ 3.8–5.7 discovered from a pilot survey in the DESI SV1 is also published in this paper.

Over the next 5 yr, the Dark Energy Spectroscopic Instrument (DESI) will use 10 spectrographs with 5000 fibers on the 4 m Mayall Telescope at Kitt Peak National Observatory to conduct the first Stage IV dark energy galaxy survey. At z < 0.6, the DESI Bright Galaxy Survey (BGS) will produce the most detailed map of the universe during the dark-energy-dominated epoch with redshifts of >10 million galaxies spanning 14,000 deg ^2 . In this work, we present and validate the final BGS target selection and survey design. From the Legacy Surveys, BGS will target an r < 19.5 mag limited sample (BGS Bright), a fainter 19.5 < r < 20.175 color-selected sample (BGS Faint), and a smaller low- z quasar sample. BGS will observe these targets using exposure times scaled to achieve homogeneous completeness and cover the footprint three times. We use observations from the Survey Validation programs conducted prior to the main survey along with simulations to show that BGS can complete its strategy and make optimal use of “bright” time. BGS targets have stellar contamination 80% fiber assignment efficiency. Finally, BGS Bright and BGS Faint will achieve >95% redshift success over any observing condition. BGS meets the requirements for an extensive range of scientific applications. BGS will yield the most precise baryon acoustic oscillation and redshift-space distortion measurements at z < 0.4. It presents opportunities for new methods that require highly complete and dense samples (e.g., N -point statistics, multitracers). BGS further provides a powerful tool to study galaxy populations and the relations between galaxies and dark matter.

The Dark Energy Spectroscopic Instrument (DESI) survey will measure large-scale structures using quasars as direct tracers of dark matter in the redshift range 0.9 < z < 2.1 and using Ly α forests in quasar spectra at z > 2.1. We present several methods to select candidate quasars for DESI, using input photometric imaging in three optical bands ( g , r , z ) from the DESI Legacy Imaging Surveys and two infrared bands (W1, W2) from the Wide-field Infrared Survey Explorer. These methods were extensively tested during the Survey Validation of DESI. In this paper, we report on the results obtained with the different methods and present the selection we optimized for the DESI main survey. The final quasar target selection is based on a random forest algorithm and selects quasars in the magnitude range of 16.5 < r < 23. Visual selection of ultra-deep observations indicates that the main selection consists of 71% quasars, 16% galaxies, 6% stars, and 7% inconclusive spectra. Using the spectra based on this selection, we build an automated quasar catalog that achieves a fraction of true QSOs higher than 99% for a nominal effective exposure time of ∼1000 s. With a 310 deg ^−2 target density, the main selection allows DESI to select more than 200 deg ^−2 quasars (including 60 deg ^−2 quasars with z > 2.1), exceeding the project requirements by 20%. The redshift distribution of the selected quasars is in excellent agreement with quasar luminosity function predictions.

DJ-1 (also called PARK7) is a ubiquitously expressed protein involved in the etiology of Parkinson disease and cancers. At least one of its three cysteine residues is functionally essential, and its oxidation state determines the specific function of the enzyme. DJ-1 was recently reported to be persulfidated in mammalian cell lines, but the implications of this post-translational modification have not yet been analyzed. Here, we report that recombinant DJ-1 is reversibly persulfidated at cysteine 106 by reaction with various sulfane donors and subsequently inhibited. Strikingly, this reaction is orders of magnitude faster than C106 oxidation by H2O2, and persulfidated DJ-1 behaves differently than sulfinylated DJ-1. Both these PTMs most likely play a dedicated role in DJ-1 signaling or protective pathways.

Cytochrome P450 2U1 (CYP2U1) identified from the human genome remains poorly known since few data are presently available on its physiological function(s) and substrate(s) specificity. CYP2U1 mutations are associated with complicated forms of hereditary spastic paraplegia, alterations of mitochondrial architecture and bioenergetics. In order to better know the biological roles of CYP2U1, we used a bioinformatics approach. The analysis of the data invited us to focus on leukotriene B4 (LTB4), an important inflammatory mediator. Here, we show that CYP2U1 efficiently catalyzes the hydroxylation of LTB4 predominantly on its ω-position. We also report docking experiments of LTB4 in a 3D model of truncated CYP2U1 that are in agreement with this hydroxylation regioselectivity. The involvement of CYP2U1 in the metabolism of LTB4 could have strong physiological consequences in cerebral pathologies including ischemic stroke because CYP2U1 is predominantly expressed in the brain.

New inhibitors of the bacterial transferase MraY from Aquifex aeolicus (MraYAA), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the O-acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraYAA transferase activity. Although with poor antibacterial activity, nine out of the ten compounds revealed the inhibition of the MraYAA activity in the range of 0.8 µM to 27.5 µM.

E4F1 is essential for early embryonic mouse development and for controlling the balance between proliferation and survival of actively dividing cells. We previously reported that E4F1 is essential for the survival of murine p53-deficient cancer cells by controlling the expression of genes involved in mitochondria functions and metabolism, and in cell-cycle checkpoints, including CHEK1, a major component of the DNA damage and replication stress responses. Here, combining ChIP-Seq and RNA-Seq approaches, we identified the transcriptional program directly controlled by E4F1 in Human Triple-Negative Breast Cancer cells (TNBC). E4F1 binds and regulates a limited list of direct target genes (57 genes) in these cells, including the human CHEK1 gene and, surprisingly, also two other genes encoding post-transcriptional regulators of the ATM/ATR-CHK1 axis, namely, the TTT complex component TTI2 and the phosphatase PPP5C, that are essential for the folding and stability, and the signaling of ATM/ATR kinases, respectively. Importantly, E4F1 also binds the promoter of these genes in vivo in Primary Derived Xenograft (PDX) of human TNBC. Consequently, the protein levels and signaling of CHK1 but also of ATM/ATR kinases are strongly downregulated in E4F1-depleted TNBC cells resulting in a deficiency of the DNA damage and replicative stress response in these cells. The E4F1-depleted cells fail to arrest into S-phase upon treatment with the replication-stalling agent Gemcitabine, and are highly sensitized to this drug, as well as to other DNA-damaging agents, such as Cisplatin. Altogether, our data indicate that in breast cancer cells the ATM/ATR-CHK1 signaling pathway and DNA damage-stress response are tightly controlled at the transcriptional and post-transcriptional level by E4F1.

Denture-related Candida stomatitis, which has been described clinically in the literature, is either localized or generalized inflammation of the oral mucosa in connection with a removable prosthesis. During this inflammatory process, the mycobacterial biofilm and the host’s immune response play an essential role. Among microorganisms of this mixed biofilm, the Candida species proliferates easily and changes from a commensal to an opportunistic pathogen. In this situation, the relationship between the Candida spp. and the host is influenced by the presence of the denture and conditioned both by the immune response and the oral microbiota. Specifically, this fungus is able to hijack the innate immune system of its host to cause infection. Additionally, older edentulous wearers of dentures may experience an imbalanced and decreased oral microbiome diversity. Under these conditions, the immune deficiency of these aging patients often promotes the spread of commensals and pathogens. The present narrative review aimed to analyze the innate and adaptive immune responses of patients with denture stomatitis and more particularly the involvement of Candida albicans sp. associated with this pathology.

Starting from a polemic in the early 1950s between two linguists interested in the vocabulary of cinema, this article wishes to consider the re-semiotisation of any digital archive as much as it encourages the emergence of a history of cinematographic concepts, as it constitutes a difficulty for this history due to the gap between the epistemological principles of this history and certain uses of digital archives induced by the re-semiotisation. Relying on the case of the history of the concept of editing, this article comes to propose a form of historical semantics of cinematographic concepts, taking into account the relationships they have with the technical operations that have been able to determine them, in order to find the “connectedness between doing and saying” (R. Koselleck). However, this connectedness and its nature remain, globally, that which is inaccessible in digital archives. On the one hand, this is because these archives favour a certain type of documents and tend to neglect others that are fundamental to the understanding of this connectedness; on the other hand, this is because the re-semiotisation of these archives, via full text research procedures, involves a method that is not explicit, which in a sense is based on biases that are far removed from the principles of the history of concepts.

The correct identification of metabolic activity in tissues or cells under different conditions can be extremely elusive due to mechanisms such as post-transcriptional modification of enzymes or different rates in protein degradation, making difficult to perform predictions on the basis of gene expression alone. Context-specific metabolic network reconstruction can overcome some of these limitations by leveraging the integration of multi-omics data into genome-scale metabolic networks (GSMN). Using the experimental information, context-specific models are reconstructed by extracting from the generic GSMN the sub-network most consistent with the data, subject to biochemical constraints. One advantage is that these context-specific models have more predictive power since they are tailored to the specific tissue, cell or condition, containing only the reactions predicted to be active in such context. However, an important limitation is that there are usually many different sub-networks that optimally fit the experimental data. This set of optimal networks represent alternative explanations of the possible metabolic state. Ignoring the set of possible solutions reduces the ability to obtain relevant information about the metabolism and may bias the interpretation of the true metabolic states. In this work we formalize the problem of enumerating optimal metabolic networks and we introduce DEXOM, an unified approach for diversity-based enumeration of context-specific metabolic networks. We developed different strategies for this purpose and we performed an exhaustive analysis using simulated and real data. In order to analyze the extent to which these results are biologically meaningful, we used the alternative solutions obtained with the different methods to measure: 1) the improvement of in silico predictions of essential genes in Saccharomyces cerevisiae using ensembles of metabolic network; and 2) the detection of alternative enriched pathways in different human cancer cell lines. We also provide DEXOM as an open-source library compatible with COBRA Toolbox 3.0, available at https://github.com/MetExplore/dexom.

New inhibitors of the bacterial tranferase MraY are described. Their structure is based on an aminoribosyl uridine scaffold, which is known to be important for the biological activity of natural MraY inhibitors. A decyl alkyl chain was introduced onto this scaffold through various linkers. The synthesized compounds were tested against the MraYAA transferase activity, and the most active compound with an original (S,S)-tartaric diamide linker inhibits MraY activity with an IC50 equal to 0.37 µM. Their antibacterial activity was also evaluated on a panel of Gram-positive and Gram-negative strains; however, the compounds showed no antibacterial activity. Docking and molecular dynamics studies revealed that this new linker established two stabilizing key interactions with N190 and H325, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin.

Cet article propose d’interroger l’idée d’un fantasme français du montage à l’américaine dans les années 1920, en analysant les écarts possibles entre, d’une part, ce qu’était alors le montage aux États-Unis et la façon dont il était perçu en France, et d’autre part, plus largement, entre ce qu’était le montage à l’époque (en France, aux États-Unis) et ce que nous croyons aujourd’hui qu’il était. Partant de cette analyse, l’hypothèse que souhaiterait défendre cette contribution tient au fait qu’il n’y aurait pas eu en France au sens strict de fantasme d’un montage à l’américaine (en premier lieu parce que la notion même de montage n’est pas encore fixée) mais plutôt le fantasme de pouvoir atteindre un tel système de représentation, sans devoir pour autant recourir à toutes les caractéristiques du système de production. Si la différence repérée par nombre de commentateurs entre le cinéma américain et le cinéma français est essentiellement affaire de différence de rythme, cette étude montrera que ce rythme est loin de n’être qu’une question de montage : il est construit dès le scénario, puis le découpage, mais il est aussi affaire de jeu, et d’échelle de cadrages. Par conséquent, le rythme procède de la relation entre divers aspects du système de représentation et obtenir la même longueur moyenne des plans que dans le cinéma américain ne suffit donc pas à reproduire le rythme des films américains. Enfin ce système de représentation découle d’un système de production qu’un grand nombre de metteurs en scène français de cette époque ne rêve pas de voir se mettre en place en France. Si bien que le fantasme du cinéma français, c’est donc sans doute celui d’un rythme à l’américaine, obtenu avec un système de représentation quelque peu différent, construit à partir d’un système de production résolument distinct, mais pas au sens plein celui d’un montage à l’américaine.

A system of 5020 robotic fiber positioners was installed in 2019 on the Mayall Telescope, at Kitt Peak National Observatory. The robots automatically retarget their optical fibers every 10–20 minutes, each to a precision of several microns, with a reconfiguration time of fewer than 2 minutes. Over the next 5 yr, they will enable the newly constructed Dark Energy Spectroscopic Instrument (DESI) to measure the spectra of 35 million galaxies and quasars. DESI will produce the largest 3D map of the universe to date and measure the expansion history of the cosmos. In addition to the 5020 robotic positioners and optical fibers, DESI’s Focal Plane System includes six guide cameras, four wave front cameras, 123 fiducial point sources, and a metrology camera mounted at the primary mirror. The system also includes associated structural, thermal, and electrical systems. In all, it contains over 675,000 individual parts. We discuss the design, construction, quality control, and integration of all these components. We include a summary of the key requirements, the review and acceptance process, on-sky validations of requirements, and lessons learned for future multiobject, fiber-fed spectrographs.

The amidotransferase MurT/GatD complex catalyzes peptidoglycan precursor amidation in some Gram-positive bacteria. Here the authors present the crystal structure of the Streptococcus pneumoniae MurT/GatD complex and provide mechanistic insights, which are of interest for drug development.

This communication presents a low-profile fully metallic high gain circularly polarized resonant cavity antenna, with a novel single-layer metasurface as superstrate operating at 300 GHz. The unit cell of the metallic metasurface layer consists of perforated grids of hexagonal and octagonal-shaped radiating apertures. The metasurface superstrate layer acts as a polarization convertor from linear-to-circular, which provides left-handed circularly polarized (LHCP) radiation. For simplicity and less design difficulty, a low cost laser cutting brass technology is proposed to design the antenna at sub-terahertz. The proposed circularly polarized resonant cavity antenna prototype has a low-profile planar metallic structure of volume 2.6λ0×2.6λ0×1.24λ0. Experimental results validate the design concept. The antenna yields a measured LHCP gain of 16.2 dBic with a directivity of 16.7 dBic at 302 GHz. This proposed circularly polarized resonant cavity antenna finds potential application in 6G sub-terahertz wireless communications.

3D imaging in animal models, during development or in adults, facilitates the identification of structural morphological changes that cannot be achieved with traditional 2D histological staining. Through the reconstruction of whole embryos or a region-of-interest, specific changes are better delimited and can be easily quantified. We focused here on high-resolution episcopic microscopy (HREM), and its potential for visualizing and quantifying the organ systems of normal and genetically altered embryos and adult organisms. Although the technique is based on episcopic images, these are of high resolution and are close to histological quality. The images reflect the tissue structure and densities revealed by histology, albeit in a grayscale color map. HREM technology permits researchers to take advantage of serial 2D aligned stacks of images to perform 3D reconstructions. Three-dimensional visualization allows for an appreciation of topology and morphology that is difficult to achieve with classical histological studies. The nature of the data lends itself to novel forms of computational analysis that permit the accurate quantitation and comparison of individual embryos in a manner that is impossible with histology. Here, we have developed a new HREM prototype consisting of the assembly of a Leica Biosystems Nanocut rotary microtome with optics and a camera. We describe some examples of applications in the prenatal and adult lifestage of the mouse to show the added value of HREM for phenotyping experimental cohorts to compare and quantify structure volumes. At prenatal stages, segmentations and 3D reconstructions allowed the quantification of neural tissue and ventricular system volumes of normal brains at E14.5 and E16.5 stages. 3D representations of normal cranial and peripheric nerves at E15.5 and of the normal urogenital system from stages E11.5 to E14.5 were also performed. We also present a methodology to quantify the volume of the atherosclerotic plaques of ApoEtm1Unc/tm1Unc mutant mice and illustrate a 3D reconstruction of knee ligaments in adult mice.