Optimal Design of Validation Experiments for the Prediction of Quantities of Interest

Numerical predictions of quantities of interest measured within physical systems rely on the use of mathematical models that should be validated, or at best, not invalidated. Model validation usually involves the comparison of experimental data (outputs from the system of interest) and model predictions, both obtained at a specific validation scenario. The design of this validation experiment should be directly relevant to the objective of the model, that of predicting a quantity of interest at a prediction scenario. In this paper, we address two specific issues arising when designing validation experiments. The first issue consists in determining an appropriate validation scenario in cases where the prediction scenario cannot be carried out in a controlled environment. The second issue concerns the selection of observations when the quantity of interest cannot be readily observed. The proposed methodology involves the computation of influence matrices that characterize the response surface of given model functionals. Minimization of the distance between influence matrices allow one for selecting a validation experiment most representative of the prediction scenario. We illustrate our approach on two numerical examples. The first example considers the validation of a simple model based on an ordinary differential equation governing an object in free fall to put in evidence the importance of the choice of the validation experiment. The second numerical experiment focuses on the transport of a pollutant and demonstrates the impact that the choice of the quantity of interest has on the validation experiment to be performed.Comment: 31 pages, 10 figure

Multi-level Neural Networks for Accurate Solutions of Boundary-Value Problems

The solution to partial differential equations using deep learning approaches has shown promising results for several classes of initial and boundary-value problems. However, their ability to surpass, particularly in terms of accuracy, classical discretization methods such as the finite element methods, remains a significant challenge. Deep learning methods usually struggle to reliably decrease the error in their approximate solution. A new methodology to better control the error for deep learning methods is presented here. The main idea consists in computing an initial approximation to the problem using a simple neural network and in estimating, in an iterative manner, a correction by solving the problem for the residual error with a new network of increasing complexity. This sequential reduction of the residual of the partial differential equation allows one to decrease the solution error, which, in some cases, can be reduced to machine precision. The underlying explanation is that the method is able to capture at each level smaller scales of the solution using a new network. Numerical examples in 1D and 2D are presented to demonstrate the effectiveness of the proposed approach. This approach applies not only to physics informed neural networks but to other neural network solvers based on weak or strong formulations of the residual.Comment: 34 pages, 20 figure

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Stroke: Working Toward a Prioritized World Agenda

The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke

Stroke: Working Toward a Prioritized World Agenda

The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Caracterisation du gene HexB et etude du role des proteines HexA et HexB dans la reparation des mesappariements de l'ADN chez les bacteries Streptococcus pneumoniae

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 81951 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

No School Left Undemocratic: Experiencing Self-Government In A Free School

While schools have been assigned the role of introducing students to our current democratic systems, many have highlighted the paradox of teaching democracy in an undemocratic context (e.g. Biesta, 2007). Alternative models of schools that operate democratically such as free schools (democratic schools in which students and teachers largely have similar rights and obligations) can offer a great deal in terms of democratic education. In this paper, I will talk about the ethnographic study that I conducted about the experiences of Canadian free school students during school meetings (democratic activity during which students with teachers decide on the activities, operations and rules of the school). During this project, I attended 4 school meetings, spent a period of five weeks making observations in a free school and completed 17 interviews about these experiences. Based on this, I maintain that these meetings arose in a school that operated according to a consensus-based model and that students, while attending these meetings, experienced a combination of feelings that mostly included appreciation and concerns while being involved in decision-making processes. As well, I will contend that students, after having taken part in several school meetings, developed skills and attitudes associated to citizenship such as critical thinking and self-confidence. For conventional schools, this means that providing students with opportunities to take decisions democratically could help to foster such skills and attitudes

A mathematical framework for the analysis and comparison of contact detection methods for ellipses and ellipsoids

The purpose of this research is to provide a framework for the analysis and comparison of contact detection algorithms for pairs of ellipses and ellipsoids. This work focuses primarily on the category of algorithms that are the most computationally efficient and can produce estimates of the separation and the penetration distance between ellipses and ellipsoids. Specifically, only analytic representations of the ellipses and ellipsoids are considered and contact detection for moving pairs of ellipsoids is not treated. The first contribution is a mathematical framework for the study of these algorithms, most notably with existence and uniqueness proofs for classes of contact detection algorithms, formal descriptions of the asymptotics of pairs of ellipses in close contact (or overlap), and a global analysis of constraints on the normals. The framework highlights the key role played by the different definitions of contact found in the literature, independent of the numerical strategies deployed to estimate the separation/penetration distance. Specifically, it is shown that all the studied algorithms can be expressed as minimization problems, with or without non-binding constraints on the normal(s) at the contact point(s), and that the constraints can be used to identify the global minima among the critical points in the minimization problem. Another contribution of this research, based on the mathematical framework introduced, is a better classification of the known algorithms. These algorithms are compared on established test problems, and their strengths and weaknesses are highlighted and explained in terms of their classification. Furthermore, this research provides comparisons in speed and stability between the most efficient algorithms in each category over a large sample size of test problems. Among the other contributions, this research describes inexpensive but effective initial estimates of the contact to be used in iterative algorithms. Finally, the usefulness of the new framework is illustrated with the introduction of a fast algorithm combining some new and old ideas