In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer

The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to our understanding of oncogenesis. Yet, these approaches remain labour-intensive and challenging. To tackle such a hurdle, an integrative, multidisciplinary effort is required. In this article, we highlight the use of logical computational models, combined with experimental validations, as an effective approach to identify cooperative mechanisms and therapeutic strategies in the context of cancer biology. In silico models overcome limitations of reductionist approaches by capturing tumour complexity and by generating powerful testable hypotheses. We review representative examples of logical models reported in the literature and their validation. We then provide further analyses of our logical model of Epithelium to Mesenchymal Transition (EMT), searching for additional cooperative interactions involving inputs from the tumour microenvironment and gain of function mutations in NOTCH.     

Assessing the capabilities of the zonal model to predict the isothermal airflow induced by a linear ceiling diffuser

The objective of this work is to evaluate the quality of the zonal airflow predictions compared to those provided by computational fluid dynamics (CFD) tools for an isothermal airflow induced in a room by a linear ceiling diffuser. This comparative analysis was conducted for a typical rectangular office designed for two people, considering two different arrangements of obstacles within the room volume. The ventilation was provided by a four-way ceiling diffuser type with large aspect ratio slots, the outlet integrated into it, operating in a three-way mode with slot Reynolds number of 2700. As a result, the airflow was transitional or weakly turbulent. The airflow patterns obtained with the zonal models were first compared qualitatively with the CFD computations. A quantitative comparison based on the mean velocities at the interface of the zonal grid was then carried out. The characteristic features of the zonal predictions are shown and the limitations of the zonal and CFD approaches are discussed.     

D.C. scanning thermal microscopy: Characterisation and interpretation of the measurement

The used Scanning Thermal Microscopy (SThM) probe is a thin Pt resistance wire acting as a heat source and as a detector simultaneously. Its energetic balance is investigated by the study of the temperature profile along the probe. A theoretical approach of the measurement, based on this investigation, is then proposed. Simulations with this modelling are shown to predict how the heat, electrically produced in the probe, is dissipated in the probe-sample system. In particular, it is shown that the steady-state of conduction losses to the thermal element support varies versus the thermal conductivity of the sample and can lead to bad interpretations of the measurement.     

A comparison of three turbulence models for the prediction of parallel lobed jets in perforated panel optimization

The general context of the present study is the design of high induction HVAC air diffusers by means of passive jet control. When the diffuser is a perforated panel with lobed orifices (Meslem et al. 2010), the optimization of jet induction consists in improving the orifice’s geometry, the spacing between orifices and their arrangement on the panel. In this study, the flow field of a turbulent twin cross-shaped jet is investigated numerically using the standard k-ε model, the Shear Stress Transport (SST) k-ω model and the Reynolds Stress Model (RSM). The results are compared with PIV measurements. The objective is to assess their capability and limitations to predict the significant features of twin jet flow when the flow is numerically resolved through a lobed diffuser. It is shown that the k-ε and RSM models are more appropriate for predicting potential jet core length, the change in jet centreline streamwise velocity, and flow expansion in the symmetry plane of the twin jet flow. However, these models overestimate the overall flow expansion and the jet volumetric flow rate. The SST k-ω model seems more appropriate for the prediction of such dynamic integral quantities. A high level of turbulent kinetic energy predicted by the k-ε and RSM models in the near field of jets is probably the reason for this overestimation of jet induction. The SST k-ω model would appear to be the most appropriate tool for optimizing orifice design, orifice to orifice spacing and relative orifice orientation on a perforated panel diffuser.     

Pore microgeometry analysis in low-resistivity sandstone reservoirs

The objective of this work is to analyse the pore microgeometry and its effect on petrophysical properties in six low-resistivity sandstone reservoirs by combining a 2D quantitative petrographic image analysis (PIA) and 3D petrophysical tools. The classic petrophysical tools enable the measurement of different classic reservoir properties such as specific surface area, average pore diameter, pore size distribution, macroporosity and microporosity, capillary pressure versus saturation, pore chamber–pore throat diameter ratio, electrical properties and permeability. The petrographic image analysis quantifies pore microgeometry in more than four orders of magnitude, from submicron to millimeter scale. Chloritic low-resistivity sandstones show dual porosity structure defined as chloritic texture. The pore microgeometrical parameters measured by petrographic image analysis allow one to model different reservoir properties such as capillary pressure, permeability and electrical behaviour. The results obtained in these models show that pore microgeometry plays an important role in the physical properties of low-resistivity sandstone reservoirs.     

La différentiation de la forme comme fonction du névrotisme chez l'étudiant universitaire.

Predicted that since the learning of complex responses is obstructed by anxiety, the degree of differentiation in the drawings of an adult should be inversely related to his neuroticism. This hypothesis was confirmed by a significant negative correlation between the scores obtained by 33 university students on the Eysenck Personality Inventory and their scores on a scale of differentiation in the drawing of a tree. Possible applications of these results to the field of creativity are discussed. (1 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Crystal structure determination and stability of copper (II) hydroxymethylphosphonate dihydrate

Copper(II) hydroxymethylphosphonate dihydrate HOCH₂PO₃Cu, 2 H₂O is triclinic : a = 10.870(3), b = 5.130(2), $\text{c}\text{= 5.628(2)}\text{A}\text{?}$, α = 96.6(1)β = 114.6(1), γ = 97.2(1)°, S.G. Pl?, Z = 2. The structure was solved by the heavy atom method and full matrix least-squares refinement to a final R value = 0.035. The two Cu atoms in the cell are structurally different : Cu(1) is octahedrally surrounded by four phosphonate oxygen atoms and two hydroxyl groups. Cu(1)O₆ octahedra chains extend along [010]. Cu(2) is coordinated to two phosphonate oxygen atoms and four water molecules. Cu(2)O₆ octahedra link the chains to form infinite layers parallel to [101]. These layers are held together by means of hydrogen bonds. The right formula must therefore be written [Cu(HOCH₂PO₃)₂] Cu, 4 H₂O. The greater stability of the octahedral configuration versus the t.b.p. one and the occurence of bonding between copper atoms and hydroxyl groups can explain the increase of stability observed from methylphosphonate to hydroxymethylphosphonate copper complexes.     

Effect of temperature and water availability during late maturation of the soybean seed on germ and cotyledon isoflavone content and composition

BACKGROUND: Isoflavone content in soybean seeds is strongly influenced by both environment and genotype. However, little is known about the effect of environment and genotype on isoflavones in germ versus cotyledons. To determine the effect of temperature and soil moisture status during soybean seed development on seed isoflavone concentration and composition, a set of two French and three US cultivars of similar maturity were grown in the greenhouse. At the R6 growth stage, plants were subjected to one of three night/day temperature regimes (13/23°, 18/28° or 23/33 °C) in either optimal or sub‐optimal soil water conditions. RESULTS: In cotyledons, a three‐ to six‐fold variation in total isoflavone content was observed between the high and low temperature treatments, whereas the germ contents had less than a two‐fold variation. Soil water supply had less effect than temperature on the isoflavone contents and compositions. In both seed parts, the isoflavone concentrations were highly dependent on the cultivar. CONCLUSION: These results show that isoflavone content and composition in cotyledon and germ are unrelated and it should be possible to independently manipulate these seed traits through plant breeding and crop management systems. Copyright © 2007 Society of Chemical Industry     

Quantitative Evaluation of Thermal Inactivation Kinetics of Free-Floating Versus Surface-Attached Listeria innocua Cells

Surface pasteurization is one of the decontamination treatments that can contribute to better preservation of meat products retaining most of their quality characteristics relatively intact if compared with the raw products. The current research compares the kinetics of free-floating and surface attached Listeria innocua cells by using integrated microbial and heat transfer modelling approaches. Surface pasteurization treatments are applied on a (abiotic) Teflon® model system in a novel steam surface decontamination rig. The experimental set-up prevented following four technological aspects to occur, (1) cold purge migration to the surface during the heating process, (2) inactivation kinetics of a cocktail of microbes, (3) protective effect of food components, and (4) physical distribution of bacteria throughout the depth of the product skin. Microbial load predictions are performed based on the inactivation parameters obtained during free-floating cell experiments. These predictions, when compared with the microbial data of the surface treatments, prove that the surface attached cells were much more heat resistant, despite the experimental set-up preventing the aforementioned (technological) events to occur. Indeed, surface attached cells can have different physiological/phenotypical/genetical characteristics, such as cell aggregations, colony formations, presence of flagella. In a final step, three techniques are implemented to evaluate mathematically the kinetics of the surface attached cells. Overall, this research’s significance is lying in the quantitative assessment of microbial heat resistance. The technological reasons underlying the increased microbial heat resistance on biotic and abiotic surfaces should be reevaluated, taking into account possible physiological/phenotypical/genetical characteristics.