Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias

<p>Abstract</p> <p>Background</p> <p>Gene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.</p> <p>Methods</p> <p>We searched for mutations in the <it>ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 </it>and <it>WT1 </it>genes in 65 myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without balanced translocation or complex karyotype.</p> <p>Results</p> <p>Mutations in <it>ASXL1 </it>and <it>CBL </it>were frequent in refractory anemia with excess of blasts. Mutations in <it>TET2 </it>occurred with similar frequency in MDSs and AMLs and associated equally with either <it>ASXL1 </it>or <it>NPM1 </it>mutations. Mutations of <it>RUNX1 </it>were mutually exclusive with <it>TET2 </it>and combined with <it>ASXL1 </it>but not with <it>NPM1</it>. Mutations in <it>FLT3 (</it>mutation and internal tandem duplication), <it>IDH1</it>, <it>IDH2</it>, <it>NPM1 </it>and <it>WT1 </it>occurred primarily in AMLs.</p> <p>Conclusion</p> <p>Only 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.</p

3D micro-macro fluid-structure model of pressure relief valve leak tightness

Controlling and assessing the leak tightness of a Pressure Relief Valve (PRV) has been a challenge since the original design of the product. With more stringent demands from the nu- clear power industry for leakproof PRV’s, closer to the set point, there has been a drive by both industry and academia for a better design method for many known metal-to-metal contacting seal/surface problems. This paper outlines a numerical modelling strategy drawn from industry experience and metrology measurements and investigates the effects of lapping and surface finish on leakage rate. Key influencing parameters of surface form, waviness and roughness are incorporated in the analysis. The numerical approach requires efficient coupling of a non-linear structural Finite Element Analysis (FEA) with a Computational Fluid Dynamic (CFD) solver. This allows the examination of the relationship between deformation of the contacting surfaces, based on the applied spring force, and the resulting micro-flow of gas through any available gaps and the overall leakage to be found. The API527 Seat Tightness methodology is followed to allow leakage rates to be measured and the computational model to be preliminarily validated. Using this model, engineers can adjust and optimise the design of pressure relief valves to find the minimal leakage condition for a given configuration. In addition, the numerical approach can potentially be applied to other metal-to-metal contacting surface components, such as flanges with metal gaskets, and help eliminate leakage

Convective Boiling in Metallic Foam: Experimental Analysis of the Pressure Loss

International audienceThe present work deals with the hydraulic characterization of twophase flow with phase change in a channel filled with metallic foam. We provide a general presentation of metallic foams including morphological characteristics, fabrication processes and industrial applications. The experimental facility, which consists of a hydrodynamic loop, the test section, measurement devices, and the data acquisition system, is presented. The Metallic foam sample tested in the present work is manufactured by SCPS (French manufacturer). N-pentane is used as a coolant fluid. The mass velocity values lie between 4 and 49 kg/ m 2 s, while the heating power in the test section ranges from 0 to 35 W/cm 2. The effect of fluid acceleration on the pressure profiles is demonstrated in the convective boiling regime. The measured pressure profiles are used to locate the thermodynamic zones inside the test channel. Then, the evolution of the pressure drop versus mass velocity is established and compared to results obtained from the application of the homogeneous model to two-phase flow

Impact de l'érosion sur l'envasement des barrages, la recharge des nappes phréatiques côtières et les intrusions marines dans la zone semi-aride méditerranéenne : cas du barrage de Boukourdane (Algérie)

Impact of erosion on the silting of dams, on the recharging groundwater and on coastal marine intrusion in the Mediterranean semi-arid area: Case of Boukourdane dam (Algeria). Description of the subject. Water erosion is a particularly important issue, especially in the Mediterranean and semi-arid zone. This zone is characterized by irregular rainfall patterns, which have a considerable influence on soil loss. In mountainous areas, water erosion phenomena are accentuated by steep slopes and low ground cover. The dams draining these areas undergo siltation linked to significant erosion. The silting of the dams drastically limits their capacity and thus their operating life. When used for recharging aquifers, the resuspension of fine particles may accumulate in the recharge areas and reduce infiltration capacity by clogging soil porosity. This leads to a significant reduction of groundwater levels. Additionally, groundwater situated in the coastal zone is submitted to intensive pumping. These two phenomena make groundwater particularly sensitive to marine intrusions. Objectives. This article aims, on the one hand to quantify the rate of siltation in the case of the Boukourdane dam (northern Algeria), which is used to recharge groundwater. On the other hand, the article also shows the reduction in permeability in the capturing field with the current management of releases. Method. Solid rates were set in relation to the liquid flow and sediment concentration occasionally taken from the wadi. The relation established made it possible to evaluate the solid contributions to the dam of Boukourdane. The impact of the releases on recharging the well field was evaluated by grouping wells and the well field mushrooms using heuristic k-means. Regressions were applied to the piezometric variations of each group. Results. This dam is fed by a catchment area of 156 km². Sediment transport was estimated from empirical formulas. The specific degradation rate was estimated at 366 t·km-2·year-1 during the 1993 to 2005 period. The increase in the frequency of extreme rainfall resulted in an increase in the soil erosion rate to 446 t·km-2·year-1 during the 1993 to 2013 period. The volume of sediments accumulated in the dam reached 8·104 m³·year-1 and 11·104 m³·year-1 respectively during these two periods. Conclusions. A change in the management of current releases has a positive impact on the partial restoration of the hydraulic conductivity and de facto, on the fight against marine intrusion

An overview of heat transfer enhancement methods and new perspectives: Focus on active methods using electroactive materials

International audienceThe main techniques for the enhancement of heat transfer between a solid wall and a fluid are reviewed for both single phase (liquid and gas) and two-phase (boiling and condensation) systems. First, a brief description of the commonly used passive techniques is given. For each of them, we report the values of the enhancement factor given in the literature. The principal active methods, i.e. methods involving the supply of external energy, are then detailed. The physical mechanisms leading to heat transfer enhancement are identified from the analyses published to date. The paper then focuses on the techniques that use periodic deformation of a wall over time. Such a wall deformation enhances heat transfer by disrupting the boundary layer and simultaneously setting the fluid in motion. The piezoelectric materials that can be implemented to generate the channel wall dynamic deformation are reviewed. As deformation of a wall is generally of low amplitude, the technique is well suited to micro channel systems: (i) in single-phase configuration, imposing a deformation traveling wave to a micro channel wall is found to simultaneously enhance heat transfer and set in motion the fluid; (ii) boiling in a narrow space is found to involve both boiling and cavitation phenomena in the nucleation process. (C) 2013 Elsevier Ltd. All rights reserved

Analysis of the contrast between natural occurrence of toxigenic Aspergilli of the Flavi section and aflatoxin B1 in cassava

International audienceAflatoxin B1 (AFB1) is a carcinogenic mycotoxin produced by Aspergilli of the section Flavi that may contaminate food, in the field or during storage. Cassava represents an important staple food in sub-Saharan Africa. The analysis of aflatoxigenic fungi in 36 cassava samples obtained from producers in Benin indicated that 40% were contaminated by Aspergilli of the section Flavi. Upon morphological and molecular characterization of the 20 isolates, 16 belonged to Aspergillus flavus, 2 to Aspergillus parvisclerotigenus and 2 to Aspergillus novoparasiticus. This is the first time that this latter species is isolated from food. Although most of these isolates were toxigenic on synthetic media, no AFB1 contamination was observed in these cassava samples. In order to determine the action of cassava on AFB1 synthesis, a highly toxigenic strain of A. flavus, was inoculated onto fresh cassava and despite a rapid development, no AFB1 was produced. The anti-aflatoxin property was observed with cassava from different geographical origins and on other aflatoxigenic strains of the section Flavi, but it was lost after heating, sun drying and freezing. Our data suggest that fresh cassava is safe regarding AFB1 contamination, however, processing may alter its ability to block toxinogenesis leading to secondary contamination. (C) 2013 Elsevier Ltd. All rights reserved