Remediation of PAH-Contaminated Soils: Experimental Analysis and Modeling of Hydrodynamics and Mass Transfer in a Soil-Slurry Bioreactor

Extended Abstract Polycyclic Aromatic Hydrocarbon (PAHs)-contaminated soils are a great environmental and public health concern nowadays. Their remediation is an important field of research as several remediation techniques have been developed with the purpose of removing PAHs from soil. However, further researches are necessary to develop environmental friendly biotechnologies that allows public and private sectors to implement efficient and adaptable treatments for contaminated soils. Aerobic soil-slurry bioreactor technology has emerged as one of these technologies with high potential as an effective and feasible treatment technic for PAH-contaminated soils. For this treatment, soil is excavated, conditioned and loaded into an aerated aqueous bioreactor. Then, mechanical and/or pneumatic mixing maintains aerobic conditions and homogeneity. Furthermore, air supply and mixing represent the most energy intensive units Although, extensive research has been done on this topic, mechanisms involved in the removal of PAHs from soil are still not completely understood. In addition to the biological processes involved, important mass transfer mechanisms need to be considered (oxygen gas-liquid mass transfer, adsorption-desorption, volatilization of PAH, etc.). In general, even for volatile PAHs, volatilization is not considered in the studies whereas, in some conditions (high aeration rate), it can be a major mechanism of "PAH removal". The soil composition and concentration in the reactor should influence strongly the fluid viscosity, which is a key parameter governing the hydrodynamics and thus the mass transfer phenomena. Therefore, the aeration and mixing optimization requires a fine understanding of how different operational parameters influence the mixing and mass transfer mechanisms involved in the removal of PAHs from soil In this study, the influence of soil content (composition and concentrations) and operating conditions (air superficial velocity, stirring rate, etc.) on the mixing (rheology, etc.) and mass transfer phenomena (gas-liquid, adsorption-desorption) is addressed. Experiments are performed in a glass standard bioreactor designed to control hydrodynamic conditions and temperature. Air is injected from the bottom through a porous glass sparger. Mechanical agitation is performed by a marine propeller connected to a motor. Hydrodynamic parameters are monitored in order to study their influence on the process and, particularly on the oxygen and PAH transfer phenomena. Rheological behavior of soil/water matrix has been measured with a capillary rheometer The oxygen transfer tests showed that for a given air superficial velocity and stirring rate, the oxygen transfer coefficient in soil/water matrix is reduced in comparison with clean water results. This decrease depends on the soil composition and was more pronounced with an increase in the soil content. Moreover, the soil/water matrix could be assimilated to a non-Newtonian fluid with shear-thinning behavior (mainly pronounced for high soil content). The impact

Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with amyotrophic lateral sclerosis. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for 5 days every 28 days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-regulatory T-cell-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient regulatory T-cell-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis

Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial crypt cells: selective engagement and roles of PI3-K isoform complexes

In human intestinal epithelial crypt (HIEC) cells, the PI3-K/Akt-1 pathway is crucial for the promotion of cell survival and suppression of anoikis. Class I PI3-K consists of a complex formed by a catalytic (C) and regulatory (R) subunit. Three R (p85α, β, and p55γ) and four C (p110α, β, γ and δ) isoforms are known. Herein, we analyzed the expression of PI3-K isoforms in HIEC cells and determined their roles in cell survival, as well as in the β1 integrin/Fak/Src-mediated suppression of anoikis. We report that: (1) the predominant PI3-K complexes expressed by HIEC cells are p110α/p85β and p110α/p55γ; (2) the inhibition and/or siRNA-mediated expression silencing of p110α, but not that of p110β, γ or δ, results in Akt-1 down-activation and consequent apoptosis; (3) the expression silencing of p85β or p55γ, but not that of p85α, likewise induces Akt-1 down-activation and apoptosis; however, the impact of a loss of p55γ on both Akt-1 activation and cell survival is significantly greater than that from the loss of p85β; and (4) both the p110α/p85β and p110α/p55γ complexes are engaged by β1 integrin/Fak/Src signaling; however, the engagement of p110α/p85β is primarily Src-dependent, whereas that of p110α/p55γ is primarily Fak-dependent (but Src-independent). Hence, HIEC cells selectively express PI3-K isoform complexes, translating into distinct roles in Akt-1 activation and cell survival, as well as in a selective engagement by Fak and/or Src within the context of β1 integrin/Fak/Src-mediated suppression of anoikis

Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with ALS. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis (IMODALS) was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for five days every twenty-eight days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-Treg-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient Treg-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

Lithospheric imaging from teleseismic data by frequency-domain elastic full-waveform tomography

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A parametric analysis of two-dimensional elastic full waveform inversion of teleseismic data for lithospheric imaging

The development of dense networks of broad-band seismographs makes teleseismic data amenable to full-waveform inversion (FWI) methods for high-resolution lithospheric imaging. Compared to scattered-field migration, FWI seeks to involve the full seismic wavefield in the inversion. We present a parametric analysis of 2-D frequency-domain FWI in the framework of lithospheric imaging from teleseismic data to identify the main factors that impact on the quality of the reconstructed compressional (P)-wave and shear (5)-wave speed models. Compared to controlled-source seismology, the main adaptation of FWI to teleseismic configuration consists of the implementation with a scattered-filed formulation of plane-wave sources that impinge on the base of the lithospheric target located below the receiver network at an arbitrary incidence angle. Seismic modelling is performed with a hp-adaptive discontinuous Galerkin method on unstructured triangular mesh. A quasi-Newton inversion algorithm provides an approximate accounting for the Hessian operator, which contributes to reduce the footprint of the coarse acquisition geometry in the imaging. A versatile algorithm to compute the gradient of the misfit function with the adjoint-state method allows for abstraction between the forward-problem operators and the meshes that are during seismic modelling and inversion, respectively. An approximate correction for obliquity is derived for future application to real teleseismic data under the two-dimension approximation. Comparisons between the characteristic scales involved in exploration geophysics and in teleseismic seismology suggest that the resolution gain provided by full waveform technologies should be of the same order of magnitude for both applications. We first show the importance of the surface-reflected wavefield to dramatically improve the resolving power of FWI by combining tomography-like and migration-like imaging through the incorporation of the forward-scattered and the backscattered wavefields in the inversion. The resolution of FWI is assessed through checkerboard tests and confirms a resolution of the order of the wavelength for both the P and S speeds, when the full wavefield is incorporated in the inversion. Secondly, we show that computationally efficient strategies, which consist of decimating the number of frequency components involved in the inversion, do not apply to teleseismic acquisitions, because the scattering-angle bandwidth sampled by plane-wave sources can be narrow and coarsely sampled, compared to that provided by dense profiles of point sources in exploration seismology. The waveform inversion is less sensitive to the band of incidence angles spanned by the plane-wave sources and to the sampling of this band. However, the deficit of vertically propagating plane waves hampers the vertical resolution of planar layers. Aliasing artefacts created by coarse arrays of receivers are illustrated. We show how taking into account the Hessian in the inversion and the suitable management of frequencies in the inversion help to mitigate these artefacts. Acceptable reconstructions are shown for both the P- and S-wave speeds for a receiver spacing of up to 20 km in the 0.1-0.4 Hz frequency range. Building a reliable initial model for FWI is a highly non-linear problem in exploration seismology. We show how the low-frequency content of the teleseismic sources allow us to build accurate P- and S-wave speed models starting from simple vertical-gradient velocity models. All of these results are derived using a 2-D realistic synthetic experiment that was performed with noise-free data. Most of conclusions of this parametric study should apply in three dimensions. The impact of noise and the footprint of other experimental parameters such as the estimation of the temporal plane-wave signature and the estimation of the incidence angle of the impinging plane waves, need however to be assessed in the future

N2O emission assessment and mitigation in full-scale biofilm reactors

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N2O emission assessment and mitigation in full-scale biofilm reactors

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Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis

International audienceBackground and purpose: The prognostic value of serum neurofilament light chain (sNfL), a biomarker of neurodegeneration, compared to other prognos-tic factors of amyotrophic lateral sclerosis (ALS) at the time of diagnosis, remains unclear. Methods: Sera from ALS patients were prospectively collected at the first diagnostic visit in our centre. sNfL levels were determined by single molecule array in 207 ALS patients and in 21 healthy controls. The prognostic value of sNfL was compared with that of other known clinical prognostic factors using a Cox regression model and multivariate analysis. Results: Serum neurofilament light chain levels were higher in ALS patients than in controls (P < 0.0001). Seven parameters were predictive of death in ALS: older age, bulbar onset, higher ALS Functional Rating Scale revised (ALSFRS-R) score, greater weight loss, lower maximal inspiratory pressure, forced vital capacity and higher sNfL levels. A Cox regression model showed that sNfL (P < 0.0001), weight loss (P = 0.040) and site at onset (P = 0.048) were independent predictive factors of death. In a sub-cohort restricted to 139 patients with complete spirometry data, sNfL level (P < 0.005) and forced vital capacity (P = 0.022) were independent factors predictive of death. In a subgroup of 142 patients in whom ALSFRS-R score was available at several time points, sNfL levels positively correlated with ALSFRS-R rate of decline (r = 0.571, P < 10 À12). Conclusions: Higher sNfL concentration is a strong and independent prognos-tic factor of death in ALS as early as the time of diagnosis