Institut Pascal

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

The Large Hadron Collider (LHC) at CERN will extend the frontiers of particle physics with its
\nunprecedented high energy and luminosity. Inside the LHC, bunches of up to 1011 protons (p)
\nwill collide 40 million times per second to provide 14 TeV proton-proton collisions at a design
\nluminosity of 1034 cm􀀀2s􀀀1. The LHC will also collide heavy ions (A), in particular lead nuclei, at
\n5.5 TeV per nucleon pair, at a design luminosity of 1027 cm􀀀2s􀀀1.
\nThe high interaction rates, radiation doses, particle multiplicities and energies, as well as the
\nrequirements for precision measurements have set new standards for the design of particle detectors.
\nTwo general purpose detectors, ATLAS (A Toroidal LHC ApparatuS) and CMS (Compact
\nMuon Solenoid) have been built for probing p-p and A-A collisions.
\nThis paper presents a comprehensive overview of the ATLAS detector prior to the first LHC
\ncollisions, written as the installation of the ATLAS detector is nearing completion. This detector
\nrepresents the work of a large collaboration of several thousand physicists, engineers, technicians,
\nand students over a period of fifteen years of dedicated design, development, fabrication, and installation.

An ordered draft sequence of the 17-gigabase hexaploid bread wheat ( Triticum aestivum ) genome has been produced by sequencing isolated chromosome arms. We have annotated 124,201 gene loci distributed nearly evenly across the homeologous chromosomes and subgenomes. Comparative gene analysis of wheat subgenomes and extant diploid and tetraploid wheat relatives showed that high sequence similarity and structural conservation are retained, with limited gene loss, after polyploidization. However, across the genomes there was evidence of dynamic gene gain, loss, and duplication since the divergence of the wheat lineages. A high degree of transcriptional autonomy and no global dominance was found for the subgenomes. These insights into the genome biology of a polyploid crop provide a springboard for faster gene isolation, rapid genetic marker development, and precise breeding to meet the needs of increasing food demand worldwide.

Alginate is a hydrocolloid from algae, specifically brown algae, which is a group that includes many of the seaweeds, like kelps and an extracellular polymer of some bacteria. Sodium alginate is one of the best-known members of the hydrogel group. The hydrogel is a water-swollen and cross-linked polymeric network produced by the simple reaction of one or more monomers. It has a linear (unbranched) structure based on d-mannuronic and l-guluronic acids. The placement of these monomers depending on the source of its production is alternating, sequential and random. The same arrangement of monomers can affect the physical and chemical properties of this polysaccharide. This polyuronide has a wide range of applications in various industries including the food industry, medicine, tissue engineering, wastewater treatment, the pharmaceutical industry and fuel. It is generally recognized as safe when used in accordance with good manufacturing or feeding practice. This review discusses its application in addition to its structural, physical, and chemical properties.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Layered materials can be assembled vertically to fabricate a new class of van der Waals heterostructures a few atomic layers thick, compatible with a wide range of substrates and optoelectronic device geometries, enabling new strategies for control of light-matter coupling. Here, we incorporate molybdenum diselenide/hexagonal boron nitride (MoSe2/hBN) quantum wells in a tunable optical microcavity. Part-light-part-matter polariton eigenstates are observed as a result of the strong coupling between MoSe2 excitons and cavity photons, evidenced from a clear anticrossing between the neutral exciton and the cavity modes with a splitting of 20 meV for a single MoSe2 monolayer, enhanced to 29 meV in MoSe2/hBN/MoSe2 double-quantum wells. The splitting at resonance provides an estimate of the exciton radiative lifetime of 0.4 ps. Our results pave the way for room-temperature polaritonic devices based on multiple-quantum-well van der Waals heterostructures, where polariton condensation and electrical polariton injection through the incorporation of graphene contacts may be realized.

Two-dimensional lattices of coupled micropillars etched in a planar semiconductor microcavity offer a workbench to engineer the band structure of polaritons. We report experimental studies of honeycomb lattices where the polariton low-energy dispersion is analogous to that of electrons in graphene. Using energy-resolved photoluminescence, we directly observe Dirac cones, around which the dynamics of polaritons is described by the Dirac equation for massless particles. At higher energies, we observe p orbital bands, one of them with the nondispersive character of a flatband. The realization of this structure which holds massless, massive, and infinitely massive particles opens the route towards studies of the interplay of dispersion, interactions, and frustration in a novel and controlled environment.

We present a survey of recent work on robot manipulation and sensing of deformable objects, a field with relevant applications in diverse industries such as medicine (e.g. surgical assistance), food handling, manufacturing, and domestic chores (e.g. folding clothes). We classify the reviewed approaches into four categories based on the type of object they manipulate. Furthermore, within this object classification, we divide the approaches based on the particular task they perform on the deformable object. Finally, we conclude this survey with a discussion of the current state-of-the-art approaches and propose future directions within the proposed classification.

Metasurfaces are ultrathin optical elements that are highly promising for constructing lightweight and compact optical systems. For their practical implementation, it is imperative to maximize the metasurface efficiency. Topology optimization provides a pathway for pushing the limits of metasurface efficiency; however, topology optimization methods have been limited to the design of microscale devices due to the extensive computational resources that are required. We introduce a new strategy for optimizing large-area metasurfaces in a computationally efficient manner. By stitching together individually optimized sections of the metasurface, we can reduce the computational complexity of the optimization from high-polynomial to linear. As a proof of concept, we design and experimentally demonstrate large-area, high-numerical-aperture silicon metasurface lenses with focusing efficiencies exceeding 90%. These concepts can be generalized to the design of multifunctional, broadband diffractive optical devices and will enable the implementation of large-area, high-performance metasurfaces in practical optical systems.

INTRODUCTION: Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients. METHODS: We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort (n=87) was used for validation. RESULTS: Fuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean=64.6 years) than C2 (mean=56.8 years; P=0.03) and C3 patients (mean=51.9 years; P=0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P<0.0001 for both comparisons). Significant event-free survival (P=0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 (P=0.01) and C2 (P=0.02). Event-free survival analysis results were confirmed when our cohort was pooled with the external cohort (n=194; P=0.01). Functional annotation showed that 22% of triple-negative patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response and low M2-like macrophages were a hallmark of C3, and that these patients had a better event-free survival than C2 patients, characterized by low immune response and high M2-like macrophages: P=0.02 for our cohort, and P=0.03 for pooled cohorts. CONCLUSIONS: We identified three subtypes of triple-negative patients: luminal androgen receptor (22%), basal-like with low immune response and high M2-like macrophages (45%), and basal-enriched with high immune response and low M2-like macrophages (33%). We noted out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in triple-negative basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype triple-negative patients.

Inflammation is the initial response of the immune system to potentially harmful stimuli (e.g., injury, stress, and infections). The process involves activation of macrophages and neutrophils, which produce mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory and anti-inflammatory cytokines. The pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) are considered as biomarkers of inflammation. Even though it occurs as a physiological defense mechanism, its involvement in the pathogenesis of various diseases is reported. Rheumatoid arthritis, inflammatory bowel disease, Alzheimer’s disease, and cardiovascular diseases are only a part of the diseases, in which pathogenesis the chronic inflammation is involved. Fucoidans are complex polysaccharides from brown seaweeds and some marine invertebrates, composed mainly of l-fucose and sulfate ester groups and minor amounts of neutral monosaccharides and uronic acids. Algae-derived fucoidans are studied intensively during the last years regarding their multiple biological activities and possible therapeutic potential. However, the source, species, molecular weight, composition, and structure of the polysaccharides, as well as the route of administration of fucoidans, could be crucial for their effects. Fucoidan is reported to act on different stages of the inflammatory process: (i) blocking of lymphocyte adhesion and invasion, (ii) inhibition of multiple enzymes, and (iii) induction of apoptosis. In this review, we focused on the immunemodulating and anti-inflammatory effects of fucoidans derived from macroalgae and the models used for their evaluation. Additional insights on the molecular structure of the compound are included.

Mammalian spermatozoa are unique cells in many ways, and the acquisition of their main function, i.e. fertilization capacity, is a multistep process starting in the male gonad and ending near the female egg for the few cells reaching this point. Owing to the unique character of this cell, the molecular pathways necessary to achieve its maturation also show some specific characteristics. One of the most striking specificities of the spermatozoon is that its DNA is highly compacted after the replacement of histones by protamines, making the classical processes of transcription and translation impossible. The sperm cells are thus totally dependent on their extracellular environment for their protection against oxidative stress, for example, or for the molecular changes occurring during the transit of the epididymis; the first organ in which post-testicular maturation takes place. The molecular mechanisms underlying sperm maturation are still largely unknown, but it has been shown in the past three decades that extracellular vesicles secreted by the male reproductive tract are involved in this process. This review will examine the roles played by two types of naturally occurring extracellular vesicles, epididymosomes and prostasomes, secreted by the epididymis and the prostate respectively. We will also describe how the use of artificial vesicles, liposomes, contributed to the study of male reproductive physiology.

The ALICE measurement of ${K}_{S}^{0}$ and $\ensuremath{\Lambda}$ production at midrapidity in Pb-Pb collisions at $\sqrt{{s}_{NN}}=2.76\text{ }\text{ }\mathrm{TeV}$ is presented. The transverse momentum (${p}_{T}$) spectra are shown for several collision centrality intervals and in the ${p}_{T}$ range from $0.4\text{ }\text{ }\mathrm{GeV}/c$ ($0.6\text{ }\text{ }\mathrm{GeV}/c$ for $\ensuremath{\Lambda}$) to $12\text{ }\text{ }\mathrm{GeV}/c$. The ${p}_{T}$ dependence of the $\ensuremath{\Lambda}/{K}_{S}^{0}$ ratios exhibits maxima in the vicinity of $3\text{ }\text{ }\mathrm{GeV}/c$, and the positions of the maxima shift towards higher ${p}_{T}$ with increasing collision centrality. The magnitude of these maxima increases by almost a factor of three between most peripheral and most central Pb-Pb collisions. This baryon excess at intermediate ${p}_{T}$ is not observed in $pp$ interactions at $\sqrt{s}=0.9\text{ }\text{ }\mathrm{TeV}$ and at $\sqrt{s}=7\text{ }\text{ }\mathrm{TeV}$. Qualitatively, the baryon enhancement in heavy-ion collisions is expected from radial flow. However, the measured ${p}_{T}$ spectra above $2\text{ }\text{ }\mathrm{GeV}/c$ progressively decouple from hydrodynamical-model calculations. For higher values of ${p}_{T}$, models that incorporate the influence of the medium on the fragmentation and hadronization processes describe qualitatively the ${p}_{T}$ dependence of the $\ensuremath{\Lambda}/{K}_{S}^{0}$ ratio.

The use of polysaccharide-based materials presents an eco-friendly technological solution, by reducing dependence on fossil resources while reducing a product's carbon footprint, when compared to conventional plastic packaging materials. This review discusses the potential of polysaccharides as a raw material to produce multifunctional materials for food packaging applications. The covered areas include the recent innovations and properties of the polysaccharide-based materials. Emphasis is given to hemicelluloses, marine polysaccharides, and bacterial exopolysaccharides and their potential application in the latest trends of food packaging materials, including edible coatings, intelligent films, and thermo-insulated aerogel packaging.

Abstract Both rich fundamental physics of microcavities and their intriguing potential applications are addressed in this book, oriented to undergraduate and postgraduate students as well as to physicists and engineers. We describe the essential steps of development of the physics of microcavities in their chronological order. We show how different types of structures combining optical and electronic confinement have come into play and were used to realize first weak and later strong light–matter coupling regimes. We discuss photonic crystals, microspheres, pillars and other types of artificial optical cavities with embedded semiconductor quantum wells, wires and dots. We present the most striking experimental findings of the recent two decades in the optics of semiconductor quantum structures. We address the fundamental physics and applications of superposition light-matter quasiparticles: exciton-polaritons and describe the most essential phenomena of modern Polaritonics: Physics of the Liquid Light. The book is intended as a working manual for advanced or graduate students and new researchers in the field.

We demonstrate that honeycomb arrays of microcavity pillars behave as an optical-frequency two-dimensional photonic topological insulator. We show that the interplay between the photonic spin-orbit coupling natively present in this system and the Zeeman splitting of exciton polaritons in external magnetic fields leads to the opening of a nontrivial gap characterized by a C=±2 set of band Chern numbers and to the formation of topologically protected one-way edge states.

We present measurements of the ratio of the proton elastic electromagnetic form factors, ${\ensuremath{\mu}}_{p}{G}_{\mathrm{Ep}}{/G}_{\mathrm{Mp}}.$ The Jefferson Lab Hall A Focal Plane Polarimeter was used to determine the longitudinal and transverse components of the recoil proton polarization in $\mathrm{ep}$ elastic scattering; the ratio of these polarization components is proportional to the ratio of the two form factors. These data reproduce the observation of Jones et al. [Phys. Rev. Lett. 84, 1398 (2000)], that the form factor ratio decreases significantly from unity above ${Q}^{2}=1 {\mathrm{GeV}}^{2}.$

Previously published and as vet unpublished QCD results obtained with the ALEPH detector at LEP1 are presented. The unprecedented statistics allows detailed studies of both perturbative and non-perturbative aspects of strong interactions to be carried out using hadronic Z and tau decays. The studies presented include precise determinations of the strong coupling constant. tests of its flavour independence, tests of the SU(3) gauge structure of QCD, study of coherence effects, and measurements of single-particle inclusive distributions and two-particle correlations for many identified baryons and mesons. (C) 1998 Elsevier Science B.V.

BACKGROUND: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. METHODS: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. RESULTS: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. CONCLUSIONS: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

Abstract Obesity is one of the most important risk factors of knee osteoarthritis (KOA), but its impact on clinical and functional consequences is less clear. The main objective of this cross-sectional study was to describe the relation between body mass index (BMI) and clinical expression of KOA. Participants with BMI ≥ 25 kg/m 2 and KOA completed anonymous self-administered questionnaires. They were classified according to BMI in three groups: overweight (BMI 25–30 kg/m 2 ), stage I obesity (BMI 30–35 kg/m 2 ) and stage II/III obesity (BMI ≥ 35 kg/m 2 ). The groups were compared in terms of pain, physical disability, level of physical activity (PA) and fears and beliefs concerning KOA. Among the 391 individuals included, 57.0% were overweight, 28.4% had stage I obesity and 14.6% had stage II/III obesity. Mean pain score on a 10-point visual analog scale was 4.3 (SD 2.4), 5.0 (SD 2.6) and 5.2 (SD 2.3) with overweight, stage I and stage II/III obesity, respectively (p = 0.0367). The mean WOMAC function score (out of 100) was 36.2 (SD 20.1), 39.5 (SD 21.4) and 45.6 (SD 18.4), respectively (p = 0.0409). The Knee Osteoarthritis Fears and Beliefs Questionnaire total score (KOFBEQ), daily activity score and physician score significantly differed among BMI groups (p = 0.0204, p = 0.0389 and p = 0.0413, respectively), and the PA level significantly differed (p = 0.0219). We found a dose–response relation between BMI and the clinical consequences of KOA. Strategies to treat KOA should differ by obesity severity. High PA level was associated with low BMI and contributes to preventing the clinical consequences of KOA.