61 research outputs found
Food allergy skin sensitization: A comparative study with three different gluten products in Brown Norway rats
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 60â109 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:
âTypicalâ 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 (â€â18 years: 69, 48, 23; 85%), older adults (â„â70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each Pâ<â0.001). 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 sĂ©quences rĂ©flexives de contenu mĂ©tapoĂ©tique dans lesquelles le poĂšte parle de son inspiration, de sa façon de faire de la poĂ©sie et des objectifs qu'il attribue Ă son art, semblent gagner en profondeur critique ce qu'elles perdent en force illocutoire. L'enjeu de cet article consistera cependant Ă dĂ©passer l'opposition apparente entre la thĂ©matisation du pouvoir de la poĂ©sie et son exercice effectif. Nous voudrions montrer que mĂȘme lorsque la parole poĂ©tique se penche sur elle-mĂȘme, elle est toujours, et peut-ĂȘtre plus que jamais, un acte de pouvoir ; loin que la rĂ©flexion suspende l'emprise illocutoire du poĂšte sur son auditoire/lectorat, elle participe activement Ă sa force et Ă son originalitĂ©. Si les dĂ©clarations en premiĂšre personne des poĂštes grecs archaĂŻques n'entrent pas dans la catĂ©gorie moderne de la subjectivitĂ© telle que dĂ©crite par Hegel 1 , elles font toutefois souvent rĂ©fĂ©rence Ă l'intimitĂ© poĂŻĂ©tique de l'oeuvre, Ă son modus operandi ou Ă sa vocation, mettant en lumiĂšre sur le devant de la scĂšne les coulisses obscures de sa composition. Nous tenterons d'abord de cerner quelques caractĂ©ristiques textuelles de passages choisis sur les thĂšmes antithĂ©tiques du pouvoir et de l'impuissance poĂ©tiques chez deux auteurs lyriques qui en ont fait un usage particuliĂšrement intĂ©ressant : Horace et Pindare. Mais nous dĂ©fendrons surtout l'hypothĂšse qu'il est possible de mettre en scĂšne l'impuissance de façon tout Ă fait Ă©loquente
Caractérisation structurale et fonctionnelle du complexe formé entre la chaßne 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 prĂ©sente des activitĂ©s semblables Ă celles de l'IL-2 in vitro du fait de l'utilisation commune des chaĂźnes rĂ©ceptrices IL-2Rb et gc, la spĂ©cificitĂ© d'action Ă©tant confĂ©rĂ©e par une chaĂźne rĂ©ceptrice a. L'IL-15Ra existe sous forme soluble aprĂšs clivage protĂ©olytique de la forme membranaire. Dans cette Ă©tude, nous avons caractĂ©risĂ© les mĂ©canismes molĂ©culaires rĂ©gulant les activitĂ©s agonistes et antagonistes des formes solubles de la chaĂźne IL-15Ra. Nous avons mis en Ă©vidence que le domaine du sIL-15Ra codĂ©e par l exon 3 et, situĂ©e Ă l'extrĂ©mitĂ© C-terminale du domaine sushi liant la cytokine, participe Ă la forte affinitĂ© du complexe IL-15/sIL-15Ra et est indispensable Ă la fonction antagoniste du rĂ©cepteur soluble. Nous avons Ă©galement montrĂ© le rĂŽle primordial du complexe IL-15/sIL-15Ra dans des pathologies cancĂ©reuses et inflammatoires grĂąces au pouvoir pro-inflammatoire induit par le sIL-15Ra dans les cancers de la tĂȘte et du cou et son implication dans la rĂ©ponse thĂ©rapeutique Ă l'infliximab (anti-TNF) dans la maladie de Crohn. Ce travail montre que le sIL-15Ra est une composante importante dans la rĂ©gulation des activitĂ©s de l'IL-15 et pourrait conduire Ă diffĂ©rentes applications thĂ©rapeutiques.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 MĂ©decine 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
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