A Robust Structural PGN Model for Control of Cell-Cycle Progression Stabilized by Negative Feedbacks

The cell division cycle comprises a sequence of phenomena controlled by a stable and robust genetic network. We applied a probabilistic genetic network (PGN) to construct a hypothetical model with a dynamical behavior displaying the degree of robustness typical of the biological cell cycle. The structure of our PGN model was inspired in well-established biological facts such as the existence of integrator subsystems, negative and positive feedback loops, and redundant signaling pathways. Our model represents genes interactions as stochastic processes and presents strong robustness in the presence of moderate noise and parameters fluctuations. A recently published deterministic yeast cell-cycle model does not perform as well as our PGN model, even upon moderate noise conditions. In addition, self stimulatory mechanisms can give our PGN model the possibility of having a pacemaker activity similar to the observed in the oscillatory embryonic cell cycle.

Theoretical models to predict the mechanical behavior of thick composite tubes

This paper shows theoretical models (analytical formulations) to predict the mechanical behavior of thick composite tubes and how some parameters can influence this behavior. Thus, firstly, it was developed the analytical formulations for a pressurized tube made of composite material with a single thick ply and only one lamination angle. For this case, the stress distribution and the displacement fields are investigated as function of different lamination angles and reinforcement volume fractions. The results obtained by the theoretical model are physic consistent and coherent with the literature information. After that, the previous formulations are extended in order to predict the mechanical behavior of a thick laminated tube. Both analytical formulations are implemented as a computational tool via Matlab code. The results obtained by the computational tool are compared to the finite element analyses, and the stress distribution is considered coherent. Moreover, the engineering computational tool is used to perform failure analysis, using different types of failure criteria, which identifies the damaged ply and the mode of failure.

The 3C cooperation model applied to the classical requirement analysis

Aspects related to the users' cooperative work are not considered in the traditional approach of software engineering, since the user is viewed independently of his/her workplace environment or group, with the individual model generalized to the study of collective behavior of all users. This work proposes a process for software requirements to address issues involving cooperative work in information systems that provide distributed coordination in the users' actions and the communication among them occurs indirectly through the data entered while using the software. To achieve this goal, this research uses ergonomics, the 3C cooperation model, awareness and software engineering concepts. Action-research is used as a research methodology applied in three cycles during the development of a corporate workflow system in a technological research company. This article discusses the third cycle, which corresponds to the process that deals with the refinement of the cooperative work requirements with the software in actual use in the workplace, where the inclusion of a computer system changes the users' workplace, from the face to face interaction to the interaction mediated by the software. The results showed that the highest degree of users' awareness about their activities and other system users contribute to a decrease in their errors and in the inappropriate use of the system.

Steel fiber reinforced concrete pipes: part 1: technological analysis of the mechanical behavior

This paper is the first part of an extensive work focusing the technological development of steel fiber reinforced concrete pipes (FRCP). Here is presented and discussed the experimental campaign focusing the test procedure and the mechanical behavior obtained for each of the dosages of fiber used. In the second part ("Steel fiber reinforced concrete pipes. Part 2: Numerical model to simulate the crushing test"), the aspects of FRCP numerical modeling are presented and analyzed using the same experimental results in order to be validated. This study was carried out trying to reduce some uncertainties related to FRCP performance and provide a better condition to the use of these components. In this respect, an experimental study was carried out using sewage concrete pipes in full scale as specimens. The diameter of the specimens was 600 mm, and they had a length of 2500 mm. The pipes were reinforced with traditional bars and different contents of steel fibers in order to compare their performance through the crushing test. Two test procedures were used in that sense. In the 1st Series, the diameter displacement was monitored by the use of two LVDTs positioned at both extremities of the pipes. In the 2nd Series, just one LVDT is positioned at the spigot. The results shown a more rigidity response of the pipe during tests when the displacements were measured at the enlarged section of the socket. The fiber reinforcement was very effective, especially when low level of displacement was imposed to the FRCP. At this condition, the steel fibers showed an equivalent performance to superior class pipes made with traditional reinforced. The fiber content of 40 kg/m3 provided a hardening behavior for the FRCP, and could be considered as equivalent to the critical volume in this condition.

Steel fibre reinforced concrete pipes. Part 2: numerical model to simulate the crushing test

This paper is part of an extensive work about the technological development, experimental analysis and numerical modeling of steel fibre reinforced concrete pipes. The first part ("Steel fibre reinforced concrete pipes. Part 1: technological analysis of the mechanical behavior") dealt with the technological development of the experimental campaign, the test procedure and the discussion of the structural behavior obtained for each of the dosages of fibre used. This second part deals with the aspects of numerical modeling. In this respect, a numerical model called MAP, which simulates the behavior of fibre reinforced concrete pipes with medium-low range diameters, is introduced. The bases of the numerical model are also mentioned. Subsequently, the experimental results are contrasted with those produced by the numerical model, obtaining excellent correlations. It was possible to conclude that the numerical model is a useful tool for the design of this type of pipes, which represents an important step forward to establish the structural fibres as reinforcement for concrete pipes. Finally, the design for the optimal amount of fibres for a pipe with a diameter of 400 mm is presented as an illustrating example with strategic interest.

Irreversibility by competition on a Glauber-Ising model by means of the entropy production.

An out of equilibrium Ising model subjected to an irreversible dynamics is analyzed by means of a stochastic dynamics, on a effort that aims to understand the observed critical behavior as consequence of the intrinsic microscopic characteristics. The study focus on the kinetic phase transitions that take place by assuming a lattice model with inversion symmetry and under the influence of two competing Glauber dynamics, intended to describe the stationary states using the entropy production, which characterize the system behavior and clarifies its reversibility conditions. Thus, it is considered a square lattice formed by two sublattices interconnected, each one of which is in contact with a heat bath at different temperature from the other. Analytical and numerical treatments are faced, using mean-field approximations and Monte Carlo simulations. For the one dimensional model exact results for the entropy production were obtained, though in this case the phase transition that takes place in the two dimensional counterpart is not observed, fact which is in accordance with the behavior shared by lattice models presenting inversion symmetry. Results found for the stationary state show a critical behavior of the same class as the equilibrium Ising model with a phase transition of the second order, which is evidenced by a divergence with an exponent µ ¼ 0:003 of the entropy production derivative.

Mechanical Alterations in airway smooth muscle after interaction with indoor pollutant – A mathematical model.

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully understood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholine (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle ¯bers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, incorporates the phenomenology of both MCh and FA and reproduces experimental results observed with in vitro exposure of smooth muscle to FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells in a tissue level model. The model can also be used in different biological scales.

Model for the Dynamics of the Cytoskeleton.

Particle tracking of microbeads attached to the cytoskeleton (CSK) reveals an intermittent dynamic. The mean squared displacement (MSD) is subdiffusive for small Δt and superdiffusive for large Δt, which are associated with periods of traps and periods of jumps respectively. The analysis of the displacements has shown a non-Gaussian behavior, what is indicative of an active motion, classifying the cells as a far from equilibrium material. Using Langevin dynamics, we reconstruct the dynamic of the CSK. The model is based on the bundles of actin filaments that link themself with the bead RGD coating, trapping it in an harmonic potential. We consider a one- dimensional motion of a particle, neglecting inertial effects (over-damped Langevin dynamics). The resultant force is decomposed in friction force, elastic force and random force, which is used as white noise representing the effect due to molecular agitation. These description until now shows a static situation where the bead performed a random walk in an elastic potential. In order to modeling the active remodeling of the CSK, we vary the equilibrium position of the potential. Inserting a motion in the well center, we change the equilibrium position linearly with time with constant velocity. The result found exhibits a MSD versus time ’tau’ with three regimes. The first regime is when ‘tau’ < ‘tau IND 0’, where ‘tau IND 0’ is the relaxation time, representing the thermal motion. At this regime the particle can diffuse freely. The second regime is a plateau, ‘tau IND 0’ < ‘tau’ < ‘tau IND 1’, representing the particle caged in the potential. Here, ‘tau IND 1’ is a characteristic time that limit the confinement period. And the third regime, ‘tau’ > ‘tau IND 1’, is when the particles are in the superdiffusive behavior. This is where most of the experiments are performed, under 20 frames per second (FPS), thus there is no experimental evidence that support the first regime. We are currently performing experiments with high frequency, up to 100 FPS, attempting to visualize this diffusive behavior. Beside the first regime, our simple model can reproduce MSD curves similar to what has been found experimentally, which can be helpful to understanding CSK structure and properties.

Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.

Mechanical alterations in airway smooth muscle after interaction with indoor pollutant - A mathematical model

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully w1derstood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholinc (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle fibers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, ir1corporates the phenomenology of both MCh and FA and reproduces experirnental results observed with ir1 vitro exposure of smooth muscle to .FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells ir1 a tissue level model. The model can also be used in different biological scales.

Statistical models for experimental model membranes.

Biological membranes are constituted from lipid bilayers and proteins. Investigation of protein-membrane interaction, essential for biological function of cells, must rest upon solid knowledge of lipid bilayer behavior. Thus, extensive studies of an experimental model for membranes, lipid bilayers in water solution, have been undertaken in the last decades. These systems present structural, thermal and electrical properties which depend on temperature, ionic strength or concentration. In this talk, we shall discuss statistical models for lipid bilayers, as well as the relation between their properties and results for properties of lipid dispersions investigated by the laboratories supervised by Teresa Lamy (IF-USP) and Amando Ito (FFCL-USP).

Surface ecophysiological behavior across vegetation and moisture gradients in tropical South America

Surface ecophysiology at five sites in tropical South America across vegetation and moisture gradients is investigated. From the moist northwest (Manaus) to the relatively dry southeast (Pé de Gigante, state of São Paulo) simulated seasonal cycles of latent and sensible heat, and carbon flux produced with the Simple Biosphere Model (SiB3) are confronted with observational data. In the northwest, abundant moisture is available, suggesting that the ecosystem is light-limited. In these wettest regions, Bowen ratio is consistently low, with little or no annual cycle. Carbon flux shows little or no annual cycle as well; efflux and uptake are determined by high-frequency variability in light and moisture availability. Moving downgradient in annual precipitation amount, dry season length is more clearly defined. In these regions, a dry season sink of carbon is observed and simulated. This sink is the result of the combination of increased photosynthetic production due to higher light levels, and decreased respiratory efflux due to soil drying. The differential response time of photosynthetic and respiratory processes produce observed annual cycles of net carbon flux. In drier regions, moisture and carbon fluxes are in-phase; there is carbon uptake during seasonal rains and efflux during the dry season. At the driest site, there is also a large annual cycle in latent and sensible heat flux.

A holistic approach to model-based testing of Web service compositions

The behavior of composed Web services depends on the results of the invoked services; unexpected behavior of one of the invoked services can threat the correct execution of an entire composition. This paper proposes an event-based approach to black-box testing of Web service compositions based on event sequence graphs, which are extended by facilities to deal not only with service behavior under regular circumstances (i.e., where cooperating services are working as expected) but also with their behavior in undesirable situations (i.e., where cooperating services are not working as expected). Furthermore, the approach can be used independently of artifacts (e.g., Business Process Execution Language) or type of composition (orchestration/choreography). A large case study, based on a commercial Web application, demonstrates the feasibility of the approach and analyzes its characteristics. Test generation and execution are supported by dedicated tools. Especially, the use of an enterprise service bus for test execution is noteworthy and differs from other approaches. The results of the case study encourage to suggest that the new approach has the power to detect faults systematically, performing properly even with complex and large compositions. Copyright © 2012 John Wiley & Sons, Ltd.

Universal behavior of the Shannon mutual information of critical quantum chains

We consider the Shannon mutual information of subsystems of critical quantum chains in their ground states. Our results indicate a universal leading behavior for large subsystem sizes. Moreover, as happens with the entanglement entropy, its finite-size behavior yields the conformal anomaly c of the underlying conformal field theory governing the long-distance physics of the quantum chain. We study analytically a chain of coupled harmonic oscillators and numerically the Q-state Potts models (Q = 2, 3, and 4), the XXZ quantum chain, and the spin-1 Fateev-Zamolodchikov model. The Shannon mutual information is a quantity easily computed, and our results indicate that for relatively small lattice sizes, its finite-size behavior already detects the universality class of quantum critical behavior.

A new conceptual model of nitrification: A key factor in resolving the metabolic state of the ocean

Máster en Oceanografía