Testing the ‘free radical theory of aging’ hypothesis: physiological differences in long-lived and short-lived colubrid snakes

We test the ‘free radical theory of aging’ using six species of colubrid snakes (numerous, widely distributed, non-venomous snakes of the family Colubridae) that exhibit long (\u3e 15 years) or short (\u3c 10 years) lifespans. Because the ‘rate of living theory’ predicts metabolic rates to be correlated with rates of aging and oxidative damage results from normal metabolic processes we sought to answer whether physiological parameters and locomotor performance (which is a good predictor of survival in juvenile snakes) mirrored the evolution of lifespans in these colubrid snakes. We measured whole animal metabolic rate (oxygen consumption ), locomotor performance, cellular metabolic rate (mitochondrial oxygen consumption), and oxidative stress potential (hydrogen peroxide production by mitochondria). Longer-lived colubrid snakes have greater locomotor performance and reduced hydrogen peroxide production than short-lived species, while whole animal metabolic rates and mitochondrial efficiency did not differ with lifespan. We present the first measures testing the ‘free radical theory of aging’ using reptilian species as model organisms. Using reptiles with different lifespans as model organisms should provide greater insight into mechanisms of aging

A Biologically Based Dynamic Model for Predicting the Disposition of Methanol and Its Metabolites in Animals and Humans

A multicompartment biologically based dynamic model was developed to describe the time evolution of methanol and its metabolites in the whole body and in accessible biological matrices of rats, monkeys, and humans following different exposure scenarios. The dynamic of intercompartment exchanges was described mathematically by a mass balance differential equation system. The model's conceptual and functional representation was the same for rats, monkeys, and humans, but relevant published data specific to the species of interest served to determine the critical parameters of the kinetics. Simulations provided a close approximation to kinetic data available in the published literature. The average pulmonary absorption fraction of methanol was estimated to be 0.60 in rats, 0.69 in monkeys, and 0.58-0.82 in human volunteers. The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h. Saturation of methanol metabolism appeared to occur at a lower exposure in rats than in monkeys and humans. Also, the main species difference in the kinetics was attributed to a metabolism rate constant of whole body formaldehyde to formate estimated to be twice as high in rats as in monkeys. Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules or is taken up by the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of synthetic pathways. This model can be used to quantitatively relate methanol or its metabolites in biological matrices to the absorbed dose and tissue burden at any point in time in rats, monkeys, and humans for different exposures, thus reducing uncertainties in the dose-response relationship, and animal-to-human and exposure scenario comparisons. The model, adapted to kinetic data in human volunteers exposed acutely to methanol vapors, predicts that 8-h inhalation exposures ranging from 500 to 2000 ppm, without physical activities, are needed to increase concentrations of blood formate and urinary formic acid above mean background values reported by various authors (4.9-10.3 and 6.3-13 mg/liter, respectively). This leaves blood and urinary methanol concentrations as the most sensitive biomarkers of absorbed methano

Hybrid simulation-optimization based approach for the optimal design of single-product biotechnological processes

In this work, we present a systematic method for the optimal development of bioprocesses that relies on the combined use of simulation packages and optimization tools. One of the main advantages of our method is that it allows for the simultaneous optimization of all the individual components of a bioprocess, including the main upstream and downstream units. The design task is mathematically formulated as a mixed-integer dynamic optimization (MIDO) problem, which is solved by a decomposition method that iterates between primal and master sub-problems. The primal dynamic optimization problem optimizes the operating conditions, bioreactor kinetics and equipment sizes, whereas the master levels entails the solution of a tailored mixed-integer linear programming (MILP) model that decides on the values of the integer variables (i.e., number of equipments in parallel and topological decisions). The dynamic optimization primal sub-problems are solved via a sequential approach that integrates the process simulator SuperPro Designer® with an external NLP solver implemented in Matlab®. The capabilities of the proposed methodology are illustrated through its application to a typical fermentation process and to the production of the amino acid L-lysine.Support from the Spanish Ministry of Education and Science (projects DPI2008-04099 and CTQ2009-14420-C02) and the Spanish Ministry of External Affairs (projects A/023551/09, A/031707/10 and HS2007-0006)

Large time behavior and asymptotic stability of the two-dimensional Euler and linearized Euler equations

We study the asymptotic behavior and the asymptotic stability of the two-dimensional Euler equations and of the two-dimensional linearized Euler equations close to parallel flows. We focus on spectrally stable jet profiles $U(y)$ with stationary streamlines $y_{0}$ such that $U'(y_{0})=0$, a case that has not been studied previously. We describe a new dynamical phenomenon: the depletion of the vorticity at the stationary streamlines. An unexpected consequence, is that the velocity decays for large times with power laws, similarly to what happens in the case of the Orr mechanism for base flows without stationary streamlines. The asymptotic behaviors of velocity and the asymptotic profiles of vorticity are theoretically predicted and compared with direct numerical simulations. We argue on the asymptotic stability of these flow velocities even in the absence of any dissipative mechanisms.Comment: To be published in Physica D, nonlinear phenomena (accepted January 2010

Prenatal Maternal Stress Predicts Childhood Asthma in Girls: Project Ice Storm

Little is known about how prenatal maternal stress (PNMS) influences risks of asthma in humans. In this small study, we sought to determine whether disaster-related PNMS would predict asthma risk in children. In June 1998, we assessed severity of objective hardship and subjective distress in women pregnant during the January 1998 Quebec Ice Storm. Lifetime asthma symptoms, diagnoses, and corticosteroid utilization were assessed when the children were 12 years old (N = 68). No effects of objective hardship or timing of the exposure were found. However, we found that, in girls only, higher levels of prenatal maternal subjective distress predicted greater lifetime risk of wheezing (OR = 1.11; 90% CI = 1.01–1.23), doctor-diagnosed asthma (OR = 1.09; 90% CI = 1.00–1.19), and lifetime utilization of corticosteroids (OR = 1.12; 90% CI = 1.01–1.25). Other perinatal and current maternal life events were also associated with asthma outcomes. Findings suggest that stress during pregnancy opens a window for fetal programming of immune functioning. A sex-based approach may be useful to examine how prenatal and postnatal environments combine to program the immune system. This small study needs to be replicated with a larger, more representative sample

Le tutorat centré sur la personne

Également disponible en version papierTitre de l'écran-titre (visionné le 13 janv. 2010)Comprend des bibliogr.Vol. 1. Phase I -- v. 2. Phase II : une grille d'auto-observation : considérations théoriques -- v. 3. Phase III : une grille d'auto-observation : rapport concernant la validation des trois composantes d'une grille d'analyse des styles d'enseignement des professeurs -- v. 4. Phase IV : le PEC, ma grille d'auto-observatio