global energy ( Gupta and Verma, 2015 ).
The process to obtain second-generation ethanol requires a pre- treatment i.e. delignification of the substrate, then hydrolysis of cellu- lose and hemicellulose (saccharification), sugar fermentation and pur- ification of ethanol to reach fuel specifications ( Mosier et al., 2005 ). However, one of the most challenging steps prior saccharification, is to increase the availability of polysaccharides for enzymes by delignifi- cation of plant fibres. Many types of physicochemical, chemical and biological pre-treatments have been developed to achieve this goal ( Alvira et al., 2010 ). Off all these strategies, biological pre-treatments using white-rot fungi involve no chemical hazard unlike other methods but they have never been used for second-generation bioethanol pro- duction. White-rot fungi are known to produce phenoloxidases ( Baldrian, 2006 ; Sinsabaugh, 2010 ): lignin peroxidases (LiP) ( Hammel
Due to the limited number of patients, no external val- idation was performed. Internal validation by leave-one- out already showed a reliable performance, suggesting that a voxel-wise machine learning approach, trained with the appropriate features and number of patients, may help identifying the location of radio-resistant re- gions within the pre-treatment GTV to guide dose escal- ation strategies. FDG PET has a poor resolution at the voxel level, which can complicate the analysis. However, the correlation between the maximal probability of be- longing to GTVfailure and the reliability of the predic- tion provided by the model would help to determine a sub-region of high risk of recurrence.
The lipid content was analysed in the mixture containing the NMMO solutions collected after the microalgae pre-treatment and after washing, as indicated in Fig. 1 . A sample of the mixture containing the NMMO was mixed with 10 ml of hexane; the hex- ane phase containing lipids was separated by centrifugation (3500 rpm, 10 min). This step was repeated three times. Hexane was dried under anhydrous sodium sulphate and evaporated in a rotary evaporator. For the lipid analysis in the pre-treated microal- gae, a sample of microalgae was re-suspended in deionised water and acidified until pH 2 prior to the hexane addition. The results were expressed as gram of extractable lipids per gram of volatile solids in the dry microalgae used for the experiments, g/gVS.
Combined effect of inoculum source and pre-treatments on microbial community
Fig. 1 shows a PCA performed from samples taken before inoculating the reactors and at the end of continuous opera- tion. Three main groups are observed, in which the change of the microbial community from the original sludge, after pre- treatment and after continuous operation is clearly evi- denced. In the first group ( Fig. 1 , on the right) the original sludge (AI and AnI) is associated with the sludge after heat pre-treatment (AI-HTi and AnI-HTi). In turn, this group is associated with the most important families of their microbial community, i.e., Rikenellaceae, Spirochaetaceae and WCHB1-69. The second group ( Fig. 1 , top) includes sludge after aeration pre-treatment (AI-ATi and AnI-ATi) and are related to families that increased their relative abundance in at least one of these samples such as Sphingomonadaceae, Flavobacteriaceae and Pseudomonadaceae. While the third group ( Fig. 1 , left down) is composed of all the samples taken at the end of the contin- uous operation and are related to the families that dominated the final microbial communities in each case, i.e. Porphyr- omonadaceae, Enterococcaceae, Clostridiaceae, Prevotellaceae and Enterobacteriaceae. In all cases, there is more similarity be- tween reactor communities inoculated with different sludge exposed to same pre-treatment, suggesting that the pre- treatment has more impact than the inoculum source on the total community structure. Despite the pre-treatments per- formed and the inoculum origin, the selection pressure imposed by biokinetic control appears to be crucial in deter- mining the dominant families of the H 2 -producing microbial community, particularly in the selection of Clostridiaceae family members. This is consistent with the literature, as members of this family are often selected during continuous H 2 production operated at low pH (values between 5.0 and 6.0) and short HRT ( <12 h) [ 4 , 27 , 64 , 65 ].
The performance characteristics of the fiberboard manufactured from the premixed raw material that was extrusion refined at an L/S ratio of 0.4 and with 40% of press cake, are presented in Table 4 . When comparing these results to the properties of the corresponding fiberboard from non-premixed material (L/S ratio 0.4, 40% press cake), it is clear that the extrusion mixing process led to lower board density, decreased mechanical properties and improved dimensional stability. In order to gain a better understanding of this outcome, it is important to note that the additional passage through the twin-screw extruder, aiming at its intimate mixing, further imposes a high pressure and shear treatment on the raw material, thus substantially increasing the overall pre-treatment severity. Such high severity treatments inevitably lead to a strong reduction in fiber length and the generation of fines. While these fines improve the contact between fibers, leading to fiberboards with enhanced bonding strength and water resistance, the reduction of long fibers, which play the role of reinforcement in the boards through their entanglement, results in materials with decreased mechanical properties [ 5 , 10 , 46 ]. This is consistent with the obtained results, which include a significant decrease in flexural strength and elastic modulus from 27.6 to 21.5 MPa and from 4.5 to 3.5 GPa, respectively, and a notable decrease in thickness swelling from 64 to 49%. The shortening of the fibers is also illustrated by the further reduction in impact strength of the panels, from 3.3 to 2.5 kJ/m 2 . The increased water resistance of the fiberboards may also be attributed to the extended hydrolysis of hemicellulose compounds. Here, the significant degradation of the fiber material under the severe processing conditions should also be taken into account. Partial hydrolysis of lignins and cellulose has been reported for high severity treatments of kenaf core [ 8 ] and residual softwood [ 28 ], which resulted in reduced mechanical properties. Moreover, excessive degradation and denaturation reactions may be detrimental to the binder properties of the lignins and protein fraction, thus reducing the bonding strength of the resulting fiberboards [ 10 , 50 ]. The reduced bonding ability of the raw materials could then constitute a hypothesis for the reduced fiberboard density (from 1330 to 1240 kg/m 3 ) observed after the inclusion of an extrusion premixing stage. Therefore, careful consideration and balancing of the fiber pre-treatment severity is often key to the production of boards with satisfactory performance.
The Oncology Unit of the Sant’Andrea Hospital of Rome adopted the pre-treatment 5-FUDR as a routine test giving a “toxicity warning” to plan careful monitoring of patients with a low 5-FUDR value. In general population, the 5-FUDR is a continuous parameter with a normal distribution (mean value 1.54 ± 0.41 ng 5-FU/ml/10 6 cells/min), whereas the mean 5-FUDR value in carriers of the DPYD *2 allele is 0.81±0.29 ng 5-FU/ml/10 6 cells/ min.  We have recently showed that a significant reduction of the individual 5-FUDR value is also found in subject carriers of a DPYD haplotype involving three polymorphisms apart from the *2.  Moreover, 5FU- DR value seems to be related to severe adverse events in colorectal cancer patients, with a higher toxicity rate when 5-FU degradation is slowed (5-FUDR ≤0.85 ng/ ml/10 6 cells/min) or accelerated ( 5-FUDR ≥ 2.2 ng/ml/10 6 cells/min), regardless of the DPYD status.  Since low 5-FUDR value was also found in subjects who were non carriers of defective DPYD alleles, we hypothesized that it could identify a further fraction of patients who will likely develop severe 5-FU toxicity.
Fig. 3. Effect of Pip6a-PMO pre-treatment on dystrophin rescue by low dose of AAV-U7ex23. (a)
Mdx TAs were injected with 1 nmole of Pip6a-PMO two weeks (-2w) before the injection of 1E+10 vg
of therapeutic AAV1-U7ex23 vector (day 0, d0). Control mdx TAs were injected with PPMO or AAV1- U7ex23 vector alone. Four TAs were injected per group. The mice were sacrificed 6 months later (6m). (b) Level of exon 23 skipping estimated by nested RT-PCR. The 901 bp PCR product corresponds to full-length dystrophin transcripts whereas the 688 bp product corresponds to transcripts lacking exon 23. (c) Quantification of exon 23 skipping performed by relative TaqMan qPCR and expressed as a percentage of total dystrophin transcripts. (d) Quantification of AAV genomes by absolute Taqman qPCR. AAV genome content is expressed as the AAV genome number relative to the value obtained for the non PPMO-treated mdx muscles. The data presented in (c) and (d) represent the mean values of the four TAs per group ± SEM. *p < 0.05, ***p < 0.001, Student’s t-test. (e) Dystrophin restoration evaluated by western blotting with NCL-DYS1 monoclonal antibodies (upper panel) on whole protein extracts from the treated muscles (lower panel: α-actinin). Dystrophin restoration was quantified by ImageJ software and expressed as the percentage of dystrophin expression in wt muscle.
3.4. Sintering optimization of doped powders
Doped samples prepared with either chloride or nitrate salts (300 ppm MgO, 200 ppm ZrO 2 , 200 ppm La 2 O 3 ) either thermally pre-treated or not were sintered by SPS. Final sintering temperature was optimised for each doping agent as densification was delayed by their presence ( fig. 4 ). RIT measurements were performed on these samples and the optimised results are given in Fig. 11 . The results are in good agreement with those of the conventional sintering presented above. The SPS efficiency is also sensitive to the powder preparation, as previously shown in Section 3.2 for natural sintering. The presence of large agglomerates in the thermally pre-treated powder is detrimental to full densification of the ceramic. The residual porosity is associated to the former large inter-agglomerate pores, reducing the RIT value. Moreover, doping with chloride salt has slightly increased the RIT, as previously shown in Section 3.3 , even though this effect was less pronounced than that of thermal pre-treatment. Finally, we were able to increase the RIT of doped-PCA up to 48.1% for La 2 O 3 -doped alumina.
3.4. Sintering optimization of doped powders
Doped samples prepared with either chloride or nitrate salts (300 ppm MgO, 200 ppm ZrO 2 , 200 ppm La 2 O 3 ) either
thermally pre-treated or not were sintered by SPS. Final sintering temperature was optimised for each doping agent as densification was delayed by their presence ( fig. 4 ). RIT measurements were performed on these samples and the optimised results are given in Fig. 11 . The results are in good agreement with those of the conventional sintering presented above. The SPS efficiency is also sensitive to the powder preparation, as previously shown in Section 3.2 for natural sintering. The presence of large agglomerates in the thermally pre-treated powder is detrimental to full densification of the ceramic. The residual porosity is associated to the former large inter-agglomerate pores, reducing the RIT value. Moreover, doping with chloride salt has slightly increased the RIT, as previously shown in Section 3.3 , even though this effect was less pronounced than that of thermal pre-treatment. Finally, we were able to increase the RIT of doped-PCA up to 48.1% for La 2 O 3 -doped alumina.
/ Laboratoire d’analyse et d’architecture des systèmes du CNRS
ADIPOSE STEM CELLS (ASCs) ISOLATION BY ON-CHIP PRE-TREATMENT OF BIOLOGICAL SAMPLES
M. Valette 1,2,3 , M. Bouguelmouna 1,3 , M. Mariotte 1,5 , R. Courson 1 , M.C. Blatché 1 , A. Girousse 4 , C. Sengenès 4 ,
Significant increase (80-90 lm) of the mean thickness was observed with the increase of laser energy density
from 1.0 to 2.2 J Æ cm 2 . Interestingly, the difference in
coating thickness of coatings deposited on untreated and on laser ablated (2.2 J Æ cm 2 , 37.5 Hz) substrate is around 50 lm. One can conclude that this difference corresponds well to the difference of average coating thickness as shown in Fig. 4 . The improved deposition efficiency with high fluence laser ablation is due essentially to the adhe- sion of a higher fraction of particles during the first pass as compared to other surface pre-treatment and laser abla- tion conditions. Nevertheless, it is clear that a large frac- tion of the impinging particles are not deposited during the first pass even at higher laser ablation fluence and so they should contribute to the surface modification as well.
The majority of platinum group metals (PGMs) are recovered from Ni-Cu smelter mattes produced from PGM bearing ores after concentration, and a small quantity is recovered from spent catalysts and copper anode slimes . A critical step in the process is a pressure oxidation leach (in either sulfuric acid or ammonia solution) to leach base metals from the matte, prior to a more aggressive chloride leach to leach the residual PGMs. This approach is not feasible for leaching lower grade and secondary materials. The aim of this study is to investigate the use of heap bioleaching, in a simulated environment, as a pre-treatment to PGM leaching from low grade materials to solubilise base metals and liberate PGM bearing minerals for recovery in a secondary leach step.
27. Steegen K, Carmona S, Bronze M, et al. Moderate Levels of Pre-Treatment HIV-1 Antiretroviral Drug Resistance Detected in the First South African National Survey. PLoS One 2016; 11(12): e0166305.
28. Gupta R, Gregson J, Parkin N, Haile-Selassie H, Tanuri A, Andrade Forero L, Kaleebu P, Watera C, Aghokeng A, Mutenda N, Dzangare J, Hone S, Hang ZZ, Garcia J, Garcia Z, Marchorro P, Beteta E, Giron A, Hamers R, Inzaule S, Frenkel LM, Chung MH, de Oliveira T, Pillay D, Naidoo K, Kharsany A, Kugathasan R, Cutino T, Hunt G, Avila Rios S, Doherty M, Jordan MR, Bertagnolio S. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect Dis 2018; 18(3): 346-55.
This study presents the development of an original 2- steps Lab-on-chip that aims at isolating Adipose Stem Cells (ASCs), cells of considerable interest for regenerative medicine, from complex biological samples. Based on hydrodynamic filtration, the device pre-isolates ASCs by removing cells with a diameter below 10µm such as red blood cells or lymphocytes.
responses using several strategies to promote their own survival [ 8 ]. One of these is to limit bacterial clearance by expanding T regulatory cells (Tregs) and myeloid de- rived suppressor cells [ 9 ]. The part played by Tregs in S. aureus arthritis is unclear. Tregs are defined by the ex- pression of CD4, CD25 and their essential transcription factor, Forkhead box protein 3 (FoxP3), and they have been implicated in the regulation of autoimmune dis- eases [ 10 – 14 ]. In autoimmune arthritis, Tregs suppress arthritis development and prevent osteoclast activation, thus reducing subsequent bone erosion [ 15 ]. Tregs con- stitutively express the IL2 receptor (IL2R) and although they do not produce IL2 themselves, they are dependent on IL2 for their peripheral homeostasis and maintenance [ 16 , 17 ]. Administration of low-dose IL2 tips the balance between Tregs and T effector cells (Teffs) towards Tregs [ 18 ] showing great promise for the treatment of auto- immune disorders [ 19 – 23 ]. Despite these successes, little is known of how the presence of low-dose IL2 and the consequent expansion of Tregs could affect beneficial ef- fector immune responses when patients receiving the treatment develop acute bacterial infections, such as S. aureus arthritis. We hypothesize that although the staphylococci themselves upregulate Tregs during the infection to evade the host immune response [ 8 , 24 ], a further expansion of Tregs could ameliorate the exces- sive inflammatory response that is responsible for joint damage and the subsequent detrimental sequelae of this disease. As these studies are very difficult to perform in humans, the aim of this study was to determine whether IL2 and its impact on Tregs influence the course of S. aureus arthritis with respect to survival, bacterial clear- ance and joint damage in our well-established mouse model of hematogenously spread S. aureus septic arth- ritis [ 25 ].
3.2.4 Pre-launch Review of the Geophysical Parameters
Bulk Structure Constraints Prior to good constraints on Mars radius and oblateness from Mariners 4 and 9, the earliest estimates of Mars interior structure varied from estimates with a small dense core (Jeffreys 1937 ) to a mostly undifferentiated body (Urey 1952 ). After the Mariner 4 flyby in 1965, and the Mariner 9 orbiter in 1971, improved estimates of the nor- malized polar moment of inertia (C/MR 2 , where C is rotational moment of inertia, and M and R are the mass and radius of Mars) to ∼ 0.377, assuming hydrostatic equilibrium, al- lowed for improved models with either small Fe-Ni cores (Binder 1969 ) or a range of larger core sizes with a mixture of Fe and FeS (Anderson 1972 ; Johnston et al. 1974 ). By the late 1970’s, the estimate of the moment of inertia had been further revised to 0.3654 after tak- ing into account isostatic compensation and the mass of Tharsis (Reasenberg 1977 ), which is closer to refined estimates after the Pathfinder mission in the 1990’s of 0.3662 (Folkner et al. 1997 ), although a broad range of values from 0.345 to 0.365 was still permitted by the data (e.g. Bills 1990 ). Improved models at this time matched this value and assumed sim- ple layered models (crust, mantle with a phase transition corresponding to the olivine-spinel transition, and core), with linear gradients of elastic and density structure within these layers scaled from Earth models by the lower pressure gradient, e.g. model AR (Anderson et al.