L’art et la nature

À propos de : Catherine et Raphaël Larrère, Penser et agir avec la nature : Une enquête philosophique, Paris, La Découverte, 2015. L’idée d’une nature sauvage à protéger des avancées techniques ne prend en compte ni la complexité des artefacts, ni ce qu’implique aujourd’hui la protection de la nature. En mettant l’accent sur la notion de biodiversité, C. et R. Larrère cherchent à donner un nouveau fondement à l’écologie politique

Identification of genes that contribute to the pathogenesis of invasive Pneumococcal Disease by In Vivo transcriptomic analysis

Streptococcus pneumoniae (the pneumococcus) continues to be responsible for a high level of global morbidity and mortality resulting from pneumonia, bacteremia, meningitis, and otitis media. Here we have used a novel technique involving niche-specific, genome-wide in vivo transcriptomic analyses to identify genes upregulated in distinct niches during pathogenesis after intranasal infection of mice with serotype 4 or 6A pneumococci. The analyses yielded 28 common, significantly upregulated genes in the lungs relative to those in the nasopharynx and 25 significantly upregulated genes in the blood relative to those in the lungs in both strains, some of which were previously unrecognized. The role of five upregulated genes from either the lungs or the blood in pneumococcal pathogenesis and virulence was then evaluated by targeted mutagenesis. One of the mutants (ΔmalX) was significantly attenuated for virulence in the lungs, two (ΔaliA and ΔilvH) were significantly attenuated for virulence in the blood relative to the wild type, and two others (ΔcbiO and ΔpiuA) were completely avirulent in a mouse intranasal challenge model. We also show that the products of aliA, malX, and piuA are promising candidates for incorporation into multicomponent protein-based pneumococcal vaccines currently under development. Importantly, we suggest that this new approach is a viable complement to existing strategies for the discovery of genes critical to the distinct stages of invasive pneumococcal disease and potentially has broad application for novel protein antigen discovery in other pathogens such as S. pyogenes, Haemophilus influenzae type b, and Neisseria meningitidis

Probing the quality control mechanism of theEscherichia colitwin-arginine translocase with folding variants of ade novo-designed heme protein

Protein transport across the cytoplasmic membrane of bacterial cells is mediated by either the general secretion (Sec) system or the twin arginine translocase (Tat). The Tat machinery exports folded and cofactor containing proteins from the cytoplasm to the periplasm by using the transmembrane proton motive force as a source of energy. The Tat apparatus apparently senses the folded state of its protein substrates, a quality control mechanism that prevents premature export of nascent unfolded or misfolded polypeptides, but its mechanistic basis has not yet been determined. Here, we investigated the innate ability of the model Escherichia coli Tat system to recognize and translocate de novo-designed protein substrates with experimentally determined differences in the extent of folding. Water-soluble, four-helix bundle maquette proteins were engineered to bind two, one or no heme b cofactors, resulting in a concomitant reduction in the extent of their folding, assessed with temperature-dependent CD spectroscopy and one-dimensional 1H NMR spectroscopy. Fusion of the archetypal N-terminal Tat signal peptide of the E. coli trimethylamine-N-oxide (TMAO) reductase (TorA) to the N-terminus of the protein maquettes was sufficient for the Tat system to recognize them as substrates. The clear correlation between the level of Tat-dependent export and the degree of heme b-induced folding of the maquette protein suggested that the membrane-bound Tat machinery can sense the extent of folding and conformational flexibility of its substrates. We propose that these artificial proteins are ideal substrates for future investigations of the Tat system’s quality control mechanism

Commissioning and operation of the readout system for the solid neutrino detector

The SoLid experiment aims to measure neutrino oscillation at a baseline of 6.4 m from the BR2 nuclear reactor in Belgium. Anti-neutrinos interact via inverse beta decay (IBD), resulting in a positron and neutron signal that are correlated in time and space. The detector operates in a surface building, with modest shielding, and relies on extremely efficient online rejection of backgrounds in order to identify these interactions. A novel detector design has been developed using 12800 5 cm cubes for high segmentation. Each cube is formed of a sandwich of two scintillators, PVT and 6LiF:ZnS(Ag), allowing the detection and identification of positrons and neutrons respectively. The active volume of the detector is an array of cubes measuring 80x80x250 cm (corresponding to a fiducial mass of 1.6 T), which is read out in layers using two dimensional arrays of wavelength shifting fibres and silicon photomultipliers, for a total of 3200 readout channels. Signals are recorded with 14 bit resolution, and at 40 MHz sampling frequency, for a total raw data rate of over 2 Tbit/s. In this paper, we describe a novel readout and trigger system built for the experiment, that satisfies requirements on: compactness, low power, high performance, and very low cost per channel. The system uses a combination of high price-performance FPGAs with a gigabit Ethernet based readout system, and its total power consumption is under 1 kW. The use of zero suppression techniques, combined with pulse shape discrimination trigger algorithms to detect neutrons, results in an online data reduction factor of around 10000. The neutron trigger is combined with a large per-channel history time buffer, allowing for unbiased positron detection. The system was commissioned in late 2017, with successful physics data taking established in early 2018

SoLid: A short baseline reactor neutrino experiment

The SoLid experiment, short for Search for Oscillations with a Lithium-6 detector, is a new generation neutrino experiment which tries to address the key challenges for high precision reactor neutrino measurements at very short distances from a reactor core and with little or no overburden. The primary goal of the SoLid experiment is to perform a precise measurement of the electron antineutrino energy spectrum and flux and to search for very short distance neutrino oscillations as a probe of eV-scale sterile neutrinos. This paper describes the SoLid detection principle, the mechanical design and the construction of the detector. It then reports on the installation and commissioning on site near the BR2 reactor, Belgium, and finally highlights its performance in terms of detector response and calibration

Development of a quality assurance process for the SoLid experiment

The SoLid experiment has been designed to search for an oscillation pattern induced by a light sterile neutrino state, utilising the BR2 reactor of SCK⋅CEN, in Belgium. The detector leverages a new hybrid technology, utilising two distinct scintillators in a cubic array, creating a highly segmented detector volume. A combination of 5 cm cubic polyvinyltoluene cells, with 6LiF:ZnS(Ag) sheets on two faces of each cube, facilitate reconstruction of the neutrino signals. Whilst the high granularity provides a powerful toolset to discriminate backgrounds; by itself the segmentation also represents a challenge in terms of homogeneity and calibration, for a consistent detector response. The search for this light sterile neutrino implies a sensitivity to distortions of around Script O(10)% in the energy spectrum of reactor bar nue. Hence, a very good neutron detection efficiency, light yield and homogeneous detector response are critical for data validation. The minimal requirements for the SoLid physics program are a light yield and a neutron detection efficiency larger than 40 PA/MeV/cube and 50% respectively. In order to guarantee these minimal requirements, the collaboration developed a rigorous quality assurance process for all 12800 cubic cells of the detector. To carry out the quality assurance process, an automated calibration system called CALIPSO was designed and constructed. CALIPSO provides precise, automatic placement of radioactive sources in front of each cube of a given detector plane (16×16 cubes). A combination of 22Na, 252Cf and AmBe gamma and neutron sources were used by CALIPSO during the quality assurance process. Initially, the scanning identified defective components allowing for repair during initial construction of the SoLid detector. Secondly, a full analysis of the calibration data revealed initial estimations for the light yield of over 60 PA/MeV and neutron reconstruction efficiency of 68%, validating the SoLid physics requirements

Performance of a full scale prototype detector at the BR2 reactor for the SoLid experiment

The SoLid collaboration has developed a new detector technology to detect electron anti-neutrinos at close proximity to the Belgian BR2 reactor at surface level. A 288 kg prototype detector was deployed in 2015 and collected data during the operational period of the reactor and during reactor shut-down. Dedicated calibration campaigns were also performed with gamma and neutron sources. This paper describes the construction of the prototype detector with a high control on its proton content and the stability of its operation over a period of several months after deployment at the BR2 reactor site. All detector cells provide sufficient light yields to achieve a target energy resolution of better than 20%/√E(MeV). The capability of the detector to track muons is exploited to equalize the light response of a large number of channels to a precision of 3% and to demonstrate the stability of the energy scale over time. Particle identification based on pulse-shape discrimination is demonstrated with calibration sources. Despite a lower neutron detection efficiency due to triggering constraints, the main backgrounds at the reactor site were determined and taken into account in the shielding strategy for the main experiment. The results obtained with this prototype proved essential in the design optimization of the final detector

Protéger l’environnement. De la science à l’action

Dans les années 1970, l’éthique de l’environnement émerge au sein des philosophies nord-américaines et européennes avec pour proposition de repenser les rapports « humains-nature » dans une optique qui va au delà des seuls intérêts et droits individuels humains. Ce projet de « nouvelle éthique » confronte l’idée alors largement admise par les éthiques occidentales classiques que les entités biologiques et écologiques, comme les animaux non humains, les organismes, les espèces, les communautés écologiques et les écosystèmes, n’ont de valeur morale qu’en vertu de l’usage que peuvent en faire les sociétés humaines. L’institutionnalisation de l’écologie comme science des interactions entre organismes et entre ces organismes et leur environnement naturel, et le recours aux travaux de naturalistes et écologues pour penser la protection des milieux naturels et celle des entités vivantes qui les composent, précèdent cependant de plusieurs décennies le développement d’une philosophie de l’environnement.Aujourd’hui, le lien entre éthique de l’environnement et écologie est d’autant plus important que l’écologie informe et marque fortement notre connaissance, conceptualisation, valorisation et relation au monde vivant. Face aux destructions toujours plus massives et dramatiques des milieux naturels, et face à l’évolution des enjeux éthiques et sociopolitiques qui les accompagnent, ce recueil propose, à travers neuf textes inédits de philosophes, écologues et géographe, de mettre à contribution la recherche menée en écologie, en philosophie de l’écologie et en éthique de l’environnement pour y répondre

Assessment of Health-Related Quality of Life in Robin Sequence: A Comparison of Mandibular Distraction Osteogenesis and Tongue-Lip Adhesion

BACKGROUND: Numerous studies have proven the efficacy of mandibular distraction osteogenesis or tongue-lip adhesion in Robin sequence infants with upper airway obstruction. However, none has compared health-related quality of life outcomes. METHODS: In the present retrospective study, Robin sequence infants younger than 1 year, who underwent mandibular distraction osteogenesis or tongue-lip adhesion, were included (2006 to 2016). The infants' caregivers were asked to complete a questionnaire based on the Glasgow Children's Benefit Inventory. RESULTS: The response rate was 71 percent (22 of the 31 questionnaires; mandibular distraction osteogenesis, 12 of 15; and tongue-lip adhesion, 10 of 16) and median age at surgery was 24 days (range, 5 to 131 days). Median total Glasgow Children's Benefit Inventory scores after mandibular distraction osteogenesis and after tongue-lip adhesion were 21.9 (interquartile range, 9.4) and 26.0 (interquartile range, 37.5), respectively (p = 0.716), indicating an overall benefit from both procedures. Positive changes were observed in all subgroups emotion, physical health, learning, and vitality. In syndromic Robin sequence, both procedures demonstrated a lower positive change in health-related quality of life compared with isolated Robin sequence (p = 0.303). CONCLUSIONS: Both surgical procedures demonstrated an overall benefit in health-related quality-of-life outcomes, with no significant differences. The authors' findings contribute to the debate regarding the use of mandibular distraction osteogenesis versus tongue-lip adhesion in the surgical treatment of Robin sequence; however, studies evaluating health-related quality of life in larger Robin sequence cohorts are necessary to identify which procedure is likely to be best in each individual Robin sequence infant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III

Long-term speech outcome in patients with Robin sequence after cleft palate repair and tongue-lip adhesion: A 21-year retrospective analysis

The purpose of this study was to assess the effect of tongue−lip adhesion (TLA) on the long-term speech and articulation outcomes of patients with Robin sequence (RS) after cleft palate repair. Outcomes were compared to those in patients with RS who required positioning alone and to patients with isolated cleft palate (ICP). All consecutive patients with RS (with or without TLA) versus isolated cleft palate (ICP) who underwent cleft palate repair were retrospectively reviewed. Speech and articulation included all assessments between the age of 3–6 years. Secondary speech operations, velopharyngeal insufficiency (VPI), hypernasality, and articulation errors by cleft-type characteristics (CTC), including 4 categories (passive), non-oral, anterior-oral, and posterior-oral. A total of 41 RS patients and 61 ICP patients underwent repair with sufficient follow-up. Of them, 23 patients underwent a TLA at median age of 12 days. Rates of hypernasality (p = 0.004), secondary speech operations (p = 0.004), and posterior oral CTC (p = 0.042) were higher in RS compared to ICP. Isolated RS had speech outcomes similar to those of ICP; however, syndromic RS patients needed more secondary speech operations compared to isolated RS (p = 0.043). TLA-RS patients did not demonstrate differences in speech outcomes or any CTCs (all p > 0.05) compared to non−TLA-RS patients, except for the anterior oral CTC (74% TLA-RS vs 28% non−TLA-RS, p = 0.005). Within the limitations of the study, it seem that TLA does not affect long-term velopharyngeal function in patients with RS. However, TLA-RS patients demonstrated higher rates of anterior-oral CTC, which might be related to a different positioning of the tongue after TLA. Every effort should be taken to treat patients with RS conservatively instead of with TLA because of this demonstrated a negative effect on one type of articulation error. However, if conservative therapy fails, a TLA is still a valuable adjunct in the treatment of RS, and cleft speech pathologists who treat such patients should be more aware of this phenomenon in order to improve long-term articulation outcomes