Erwan Plougonven

SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma (MM)-associated osteolytic bone disease is a major cause of morbidity and mortality in MM patients and the development of new therapeutic strategies is of great interest. The proto-oncogene SRC is an attractive target for such a strategy. In the current study, we investigated the effect of treatment with the SRC inhibitor saracatinib (AZD0530) on osteoclast and osteoblast differentiation and function, and on the development of MM and its associated bone disease in the 5TGM.1 and 5T2MM murine MM models. In vitro data showed an inhibitory effect of saracatinib on osteoclast differentiation, polarization and resorptive function. In osteoblasts, collagen deposition and matrix mineralization were affected by saracatinib. MM cell proliferation and tumor burden remained unaltered following saracatinib treatment and we could not detect any synergistic effects with drugs that are part of standard care in MM. We observed a marked reduction of bone loss after treatment of MM-bearing mice with saracatinib as reflected by a restoration of trabecular bone parameters to levels observed in naive control mice. Histomorphometric analyses support that this occurs through an inhibition of bone resorption. In conclusion, these data further establish SRC inhibition as a promising therapeutic approach for the treatment of MM-associated osteolytic bone disease.

Convective drying behavior of sawdust-sludge mixtures in a fixed bed

ABSTRACT This work aims at comparing the temporal evolution of 3D characteristics of the sample bed as well as the drying mechanism of sewage sludge and sawdust-sludge mixtures during the drying process. The first step are characterizing the drying behavior of sawdust-sludge mixtures during the convective drying. The influences of the mixing step (no mixing against 30 s at 40 r/min) and of the mass fractions of sawdust (10%, 20%, 30%, and 40% on a dry basis) have been investigated. X-ray tomography, a non-invasive imaging technique, was used to assess changes in the volume and total exchange surface during the drying process. Drying experiment results show that sawdust addition has a positive impact on the drying process from a mass fraction of sawdust of 20%. The X-ray tomography experiment results show that the volume and total exchange surface of the sample bed both increase with increasing amounts of sawdust during the entire drying process. Moreover, a linear decrease of both the total exchange surface and volume with the decreased normalized moisture content is observed for sludges, while a plateau is reached after a linear phase for sawdust-sludge mixtures. As expected for sludges, the drying rate decreases nearly linearly with the decreased total exchange surface during the entire drying process. However, for the sawdust-sludge mixtures, at first the drying rate decreases nearly linearly with the decreased total exchange surface, and then the total exchange surface does not change but the drying rate still decreases until it reaches zero. These promising results open the way to new management ways, especially for very pasty sludge.

Quantitative analysis of the deformation of polypropylene foam under dynamic loading

A dynamic crash loading experiment is performed on a polypropylene foam. Several interrupted shocks are conducted, in between which microtomographic acquisitions are made, showing the evolution of the sample during its compression. This data can help construct and validate predictive models, although, because this material is multiscale (consitutive grains at the mesoscopic scale are made of microscopic closed cells), image processing is required to extract useful quantitative measures. Such processing is described here, so as to determine a representative volume for each grain of the sample, in order to associate to each grain and to each stage of the compression values such as grain density. This can help build a predictive model at the mesoscopic scale.

Influence of sawdust addition on drying of wastewater sludges: Comparison of structural characteristics

ABSTRACT This work aims to investigate the structural characteristics of wastewater sludges and sludge–wood mixtures, and how the addition of sawdust affects them in a positive way for the drying process. The study was performed for a fixed bed at the pilot scale, with sludges from three different wastewater treatment plants from the Liège province in Belgium, namely, Oupeye, Grosses Battes, and Embourg. X-ray tomography was chosen to evaluate variations in the structural characteristics before and after drying, which included volume, void fraction, and exchange surface of the bed. Results first confirm that the drying rate is raised after the sawdust addition operation for all three sludges, but the increase amount is smaller while the moisture of the sludge is high. With sawdust, the average drying rates increase by factors of 1.475 (Oupeye), 1.342 (Grosses Battes), and 1.162 (Embourg), respectively. It also increases initial volume as well as void fraction and surface exchange, however after drying this addition leads to less shrinkage and void fraction, and higher exchange surface. The initial void fraction increases by 7.25 (Oupeye), 8.30 (Grosses Battes), and 14.01% (Embourg), but the final void fraction decreases 1.56 (Oupeye), 10.83 (Grosses Battes), and 25.61% (Embourg). With high initial moisture content, we observed lower porosity and higher shrinkage.

Maternal embryonic leucine zipper kinase inhibitor OTSSP167 has preclinical activity in multiple myeloma bone disease

Multiple myeloma bone disease is characterized by an uncoupling of bone remodeling in the multiple myeloma microenvironment, resulting in the development of lytic bone lesions. Most myeloma patients suffer from these bone lesions, which not only cause morbidity but also negatively impact survival. The development of novel therapies, ideally with a combined anti-resorptive and bone-anabolic effect, is of great interest because lesions persist with the current standard of care, even in patients in complete remission. We have previously shown that MELK plays a central role in proliferation-associated high-risk multiple myeloma and its inhibition with OTSSP167 resulted in decreased tumor load. MELK inhibition in bone cells has not yet been explored, although some reports suggest that factors downstream of MELK stimulate osteoclast activity and inhibit osteoblast activity, which makes MELK inhibition a promising therapeutic approach. Therefore, we assessed the effect of OTSSP167 on bone cell activity and the development of myeloma-induced bone disease. OTSSP167 inhibited osteoclast activity in vitro by decreasing progenitor viability as well as via a direct anti-resorptive effect on mature osteoclasts. In addition, OTSSP167 stimulated matrix deposition and mineralization by osteoblasts in vitro. This combined anti-resorptive and osteoblast-stimulating effect of OTSSP167 resulted in the complete prevention of lytic lesions and bone loss in myeloma-bearing mice. Immunohistomorphometric analyses corroborated our in vitro findings. In conclusion, we show that OTSSP167 has a direct effect on myeloma-induced bone disease in addition to its anti-multiple myeloma effect, which warrants further clinical development of MELK inhibition in multiple myeloma.

Can the pore scale geometry explain soil sample scale hydrodynamic properties

For decades, the development of new visualization techniques has brought incredible insights into our understanding of how soil structure affects soil function. X-ray microtomography is a technique often used by soil scientists but challenges remain with the implementation of the procedure, including how well the samples represent the uniqueness of the pore network and structure and the systemic compromise between sample size and resolution. We, therefore, chose to study soil samples from two perspectives: a macroscopic scale with hydrodynamic characterization and a microscopic scale with structural characterization through the use of X-ray microtomography (X-ray µCT) at a voxel size of 21.5³ µm³ (resampled at 43³ µm³). The objective of this paper is to unravel the relationships between macroscopic soil properties and microscopic soil structure. The twenty-four samples came from an agricultural field (Cutanic Luvisol) and the macroscopic hydrodynamic properties were determined using laboratory measurements of the saturated hydraulic conductivity (Ks), air permeability (ka), and retention curves (SWRC). The X-ray µCT images were segmented using a global method and multiple microscopic measurements were calculated. We used Bayesian statistics to report the credible correlation coefficients and linear regressions models between macro- and microscopic measurements. Due to the small voxel size, we observed unprecedented relationships, such as positive correlations between log(Ks) and a µCT global connectivity indicator, the fractal dimension of the µCT images or the µCT degree of anisotropy. The air permeability measured at a water matric potential of -70 kPa was correlated to the average coordination number and the X-ray µCT porosity, but was best explained by the average pore volume of the smallest pores. Continuous SWRC were better predicted near saturation when the pore-size distributions calculated on the X-ray µCT images were used as model input. We also showed a link between pores of different sizes. Identifying the key geometrical indicators that induce soil hydrodynamic behavior is of major interest for the generation of phenomenological pore network models. These models are useful to test physical equations of fluid transport that ultimately depend on a multitude of processes, and induce numerous biological processes.

Study of the Drying Behavior of Resorcinol Formaldehyde Hydrogels : Experimental Investigation and Numerical Framework

In this paper, we present the method used to investigate the drying behavior of the Resorcinol (R) formaldehyde (F) hydrogels and the tools needed for its numerical modeling. First, the studied material is introduced. Then the experiments are briefly presented and some preliminary results are given. Drying tests have been first carried out to characterize the drying kinetics of RF hydrogels. The experiments are used to calibrate the transfer parameters of a convective drying law based on the boundary layer model [Gerard et al. (2010)]. Ultimately, the goal is to model the Hydromechanical behavior of the RF gels during drying and predict crack genesis. To do so, a thermohydro-mechanical coupled model including a tensile failure criterion is suggested. The tensile failure criterion is based on the existence of a tension cut-off expressed in terms of a minimum mean effective stress. INTRODUCTION Production of carbon aerogels by CO2 supercritical drying of resorcinol (R) formaldehyde (F) hydrogels followed by pyrolysis has been studied since their introduction by Pekala [Pekala (1989)]. Their large mesopore volumes and high specific surface areas make them interesting for many potential applications such as adsorbents for gas separation, catalysts supports, etc [Job (2006)]. Supercritical drying is not applicable at an industrial scale because of technical and safety reasons. Some other methods to produce an aerogel-like mesoporous texture have been tested and it has been shown that it is possible to produce porous resorcinolformaldehyde xerogels by using atmospheric convective drying [Job et al. (2006)]. Since crack-free monoliths are required, the hydraulic and mechanical properties of the RF hydrogels and their evolution with water content are essential to model their thermo-hydro-mechanical behavior during convective drying and avoid cracking. This paper aims at presenting the methods used to investigate the drying behavior of the RF hydrogels and at introducing the hydromechanical model which will be use to simulate it. MATERIALS AND METHODS Samples Preparation Hydrogels are prepared by polycondensation of resorcinol, solubilized in water, with formaldehyde, in the presence of Na2CO3. The pH of the precursors solution is achieved by changing the resorcinol/sodium carbonate molar ratio, R/C. The resorcinolformaldehyde molar ratio, R/F, and the dilution ratio, the solvent on resorcinol plus formaldehyde molar ratio, are fixed at 0.5 (stochiometric ratio), and 5.7, respectively. Cylindrical samples were obtained by casting solution into glass molds and putting them back in the water bath for gelation and aging during 24 h at 70◦C. A second cylindrical mold, slightly smaller in diameter, was slipped into the first one and put in touch with the solution so that the contact between air and liquid was avoided. Evaporation was prevented by a paraffin film covering both cylinders. This procedure aims at avoiding thermal inertia and temperature gradients during the gelation phase. Moreover, the size of the samples was adapted to both the convective dryer chamber and the microtomograph used to follow shrinkage and cracking during drying. Convective Drying Test After gelation and aging, the samples are dried in a classical convective dryer under controlled air relative humidity, temperature and velocity designed for small samples [Léonard (2003)]. The sample is allowed to dry on its whole external surface. The sample is weighed every 10 s during the drying test. The drying kinetics can be analyzed based on the weight measurements, which are used to plot Krischer’s curve (Fig. 1a). It expresses the variation of the drying rate with water content. Krischer’s curve is studied in parallel with the evolution of temperature with time (Fig. 1b). This is the behavior observed in the case where the drying air temperature is significantly higher than the sample initial temperature [Musielak et Jacek (2007)]. On Krischer’s curve, three periods can be observed : 1. The preheating period (I) is very short and corresponds to an increase in drying rate. The temperature at the surface of the sample also increases from its initial value to the temperature of the wet bulb [Gerard et al. (2010)]. 2. The Constant Rate Period (CRP) (II) appears at the beginning of the drying process. It is characterized by a constant drying rate. The heat supply is completely used for the evaporation of the liquid water at the surface of the sample and thus, the temperature remains constant and equal to the temperature of the wet bulb. The evaporation occurs in a saturated boundary layer. The vapor and the heat transfers are only influenced by the external conditions, i.e. the drying air temperature, relative humidity or velocity [Nadeau et Puiggali (1995)]. This period will last until the sample is no longer saturated and internal transfers start to influence the drying rate. 3. The Falling Rate Period (FRP)(III) is characterized by an increase in the dried body temperature from the wet bulb temperature to the drying fluid temperature. The drying rate decreases because of the decrease in permeability with the desaturation of the medium. D ry in g ra te [k g/ m 2s ] Water content [kg/kg] 0 1 3 6 0 0.5 2