Maximum relative height of one-dimensional interfaces : from Rayleigh to Airy distribution

We introduce an alternative definition of the relative height h^\kappa(x) of a one-dimensional fluctuating interface indexed by a continuously varying real paramater 0 \leq \kappa \leq 1. It interpolates between the height relative to the initial value (i.e. in x=0) when \kappa = 0 and the height relative to the spatially averaged height for \kappa = 1. We compute exactly the distribution P^\kappa(h_m,L) of the maximum h_m of these relative heights for systems of finite size L and periodic boundary conditions. One finds that it takes the scaling form P^\kappa(h_m,L) = L^{-1/2} f^\kappa (h_m L^{-1/2}) where the scaling function f^\kappa(x) interpolates between the Rayleigh distribution for \kappa=0 and the Airy distribution for \kappa=1, the latter being the probability distribution of the area under a Brownian excursion over the unit interval. For arbitrary \kappa, one finds that it is related to, albeit different from, the distribution of the area restricted to the interval [0, \kappa] under a Brownian excursion over the unit interval.Comment: 25 pages, 4 figure

Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Background Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. Scope and approach In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. Key findings and conclusions The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches

Record Statistics for Multiple Random Walks

We study the statistics of the number of records R_{n,N} for N identical and independent symmetric discrete-time random walks of n steps in one dimension, all starting at the origin at step 0. At each time step, each walker jumps by a random length drawn independently from a symmetric and continuous distribution. We consider two cases: (I) when the variance \sigma^2 of the jump distribution is finite and (II) when \sigma^2 is divergent as in the case of L\'evy flights with index 0 < \mu < 2. In both cases we find that the mean record number grows universally as \sim \alpha_N \sqrt{n} for large n, but with a very different behavior of the amplitude \alpha_N for N > 1 in the two cases. We find that for large N, \alpha_N \approx 2 \sqrt{\log N} independently of \sigma^2 in case I. In contrast, in case II, the amplitude approaches to an N-independent constant for large N, \alpha_N \approx 4/\sqrt{\pi}, independently of 0<\mu<2. For finite \sigma^2 we argue, and this is confirmed by our numerical simulations, that the full distribution of (R_{n,N}/\sqrt{n} - 2 \sqrt{\log N}) \sqrt{\log N} converges to a Gumbel law as n \to \infty and N \to \infty. In case II, our numerical simulations indicate that the distribution of R_{n,N}/\sqrt{n} converges, for n \to \infty and N \to \infty, to a universal nontrivial distribution, independently of \mu. We discuss the applications of our results to the study of the record statistics of 366 daily stock prices from the Standard & Poors 500 index.Comment: 25 pages, 8 figure

Extreme value statistics from the Real Space Renormalization Group: Brownian Motion, Bessel Processes and Continuous Time Random Walks

We use the Real Space Renormalization Group (RSRG) method to study extreme value statistics for a variety of Brownian motions, free or constrained such as the Brownian bridge, excursion, meander and reflected bridge, recovering some standard results, and extending others. We apply the same method to compute the distribution of extrema of Bessel processes. We briefly show how the continuous time random walk (CTRW) corresponds to a non standard fixed point of the RSRG transformation.Comment: 24 pages, 5 figure

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Pouvoir et impuissance poétiques : éléments de comparaison entre Pindare et Horace

Les séquences réflexives de contenu métapoétique dans lesquelles le poète parle de son inspiration, de sa façon de faire de la poésie et des objectifs qu'il attribue à son art, semblent gagner en profondeur critique ce qu'elles perdent en force illocutoire. L'enjeu de cet article consistera cependant à dépasser l'opposition apparente entre la thématisation du pouvoir de la poésie et son exercice effectif. Nous voudrions montrer que même lorsque la parole poétique se penche sur elle-même, elle est toujours, et peut-être plus que jamais, un acte de pouvoir ; loin que la réflexion suspende l'emprise illocutoire du poète sur son auditoire/lectorat, elle participe activement à sa force et à son originalité. Si les déclarations en première personne des poètes grecs archaïques n'entrent pas dans la catégorie moderne de la subjectivité telle que décrite par Hegel 1 , elles font toutefois souvent référence à l'intimité poïétique de l'oeuvre, à son modus operandi ou à sa vocation, mettant en lumière sur le devant de la scène les coulisses obscures de sa composition. Nous tenterons d'abord de cerner quelques caractéristiques textuelles de passages choisis sur les thèmes antithétiques du pouvoir et de l'impuissance poétiques chez deux auteurs lyriques qui en ont fait un usage particulièrement intéressant : Horace et Pindare. Mais nous défendrons surtout l'hypothèse qu'il est possible de mettre en scène l'impuissance de façon tout à fait éloquente

Caractérisation structurale et fonctionnelle du complexe formé entre la chaîne Alpha soluble du Récepteur de l'Interleukine 15 Humaine et l'Interleukine-15 (implication en immuno-cancérologie)

L'Interleukine-15 (IL-15) est une cytokine qui présente des activités semblables à celles de l'IL-2 in vitro du fait de l'utilisation commune des chaînes réceptrices IL-2Rb et gc, la spécificité d'action étant conférée par une chaîne réceptrice a. L'IL-15Ra existe sous forme soluble après clivage protéolytique de la forme membranaire. Dans cette étude, nous avons caractérisé les mécanismes moléculaires régulant les activités agonistes et antagonistes des formes solubles de la chaîne IL-15Ra. Nous avons mis en évidence que le domaine du sIL-15Ra codée par l exon 3 et, située à l'extrémité C-terminale du domaine sushi liant la cytokine, participe à la forte affinité du complexe IL-15/sIL-15Ra et est indispensable à la fonction antagoniste du récepteur soluble. Nous avons également montré le rôle primordial du complexe IL-15/sIL-15Ra dans des pathologies cancéreuses et inflammatoires grâces au pouvoir pro-inflammatoire induit par le sIL-15Ra dans les cancers de la tête et du cou et son implication dans la réponse thérapeutique à l'infliximab (anti-TNF) dans la maladie de Crohn. Ce travail montre que le sIL-15Ra est une composante importante dans la régulation des activités de l'IL-15 et pourrait conduire à différentes applications thérapeutiques.The Interleukin-15 (IL-15) is a cytokine which outlines similar activities as those of IL-2 in vitro because of the common use of IL-2Rb and gc chains. The specificity of action is conferred by a private a chain (IL-15Ra). The a chain exists in soluble form after proteolytic cleavage of the membrane anchored IL-15Ra. In this study, we characterized the molecular mechanisms regulating the agonistic and antagonistic activities of the soluble forms of IL-15Ra (sIL-15Ra). We highlighted that the exon 3 encoded domain of the sIL-15Ra, located at the C-terminal end of the IL-15 binding domain (sushi) which participates to the high affinity of the IL-15/sIL-15Ra complex and is necessary for the antagonistic function of the soluble receptor. We also showed the vital role of this complex in cancer and inflammatory diseases through the capacity to escape to immunity of tumor with sIL-15Ra in head and neck cancers and it involvement in the therapeutic response to infliximab in Crohn disease. This work shows that the sIL-15Ra is an important component in the regulation of IL-15 and could lead to different therapeutic applications.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Role of chemokine receptors in allergic diseases

Immune cell trafficking is orchestrated by a family of small proteins named chemokines and leucocytes express chemokine receptors on their surface. Once chemokines are attached to these receptors, they trigger transendothelial migration. During basal conditions as well in various diseases, leukocyte migration is a crucial step for the immune system. Excessive or inappropriate expression of chemokine receptors in allergy is thus one of the key factors, which trigger the allergic response. Consequently, many studies have been made on the importance of chemokines and their receptors in allergic diseases such as asthma, food allergy and atopic dermatitis. Moreover, as these receptors can easily be blocked by an antagonist, this has led to the development of new therapeutic approaches aimed at suppressing the recruitment of immune cells during an allergic reaction. In this review, we will detail which chemokines and which chemokine receptors are important in the three main allergic diseases mentioned above and describe the chemokine receptor antagonists, which have been developed to date