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International audience; In chlordecone (CLD)-contaminated soils of the French West Indies, if microbial remediation or a physicochemical remediation process, e.g., in situ chemical reduction, is implemented, concentrations of degradation byproducts, such as hydrochlordecones, are expected to increase in the ecosystems. To study their impact in mixtures with CLD, bioassays were carried out. They consisted in evaluating the regenerative capacity of hydra polyps, from a clone whose phylogenetic analysis confirmed that it belonged to the species Hydra vulgaris Pallas, 1766. Hydra gastric sections were exposed to CLD alone or CLD plus dechlorinated byproducts (CLD-BP) for 96 h to assess regeneration. Based on chromatographic analysis, the CLD-BP mix was composed of the 5-monohydrochlordecone isomer (CAS nomenclature), four dihydrochlordecone isomers, and one trihydrochlordecone isomer representing 50%, 47%, and 3% of the total chromatographic area, respectively. A total of 18 mixtures of CLD and CLD-BP were tested. Six environmental concentrations of CLD (2.10 −4 μM to 4.10 −2 μM) and a similar range of CLD-BP were used. Results from exposures to CLD alone showed the following: (i) a significant decrease in the regenerative capacity of hydra, except at the lowest concentration (2.10 −4 μM); (ii) a concentration-independent deleterious effect. The regeneration scores obtained after the exposure to the addition of CLD-BP were not significantly different from those obtained after exposure to CLD alone. Using an experimental design, a modeling of the regeneration scores of hydra exposed to mixtures is proposed. Interpreted carefully, since they are limited to only one type of bioassay, the present results suggest that the situation in the aquatic environments should not become worse in terms of toxicity, if soil remediation programs resulting in the formation of hydrochlordecones are put in place.; Dans les sols des Antilles françaises contaminés par la chlordécone (CLD), si une remédiation microbienne ou un processus de remédiation physico-chimique, par exemple une réduction chimique in situ, est mise en œuvre, on s'attend à ce que les concentrations de sous-produits de dégradation, tels que les hydrochlordécones, augmentent dans les écosystèmes. Pour étudier leur impact dans les mélanges avec la CLD, des bio-essais ont été réalisés. Ils ont consisté à évaluer la capacité de régénération de polypes d'hydre, à partir d'un clone dont l'analyse phylogénétique a confirmé l'appartenance à l'espèce Hydra vulgaris Pallas, 1766. Des sections gastriques d'hydres ont été exposées à la CLD seule ou à la CLD plus des sous-produits déchlorés (CLD-BP) pendant 96 h pour évaluer la régénération. D'après l'analyse chromatographique, le mélange CLD-BP était composé de l'isomère 5-monohydrochlordécone (nomenclature CAS), de quatre isomères dihydrochlordécone et d'un isomère trihydrochlordécone représentant respectivement 50 %, 47 % et 3 % de la surface chromatographique totale. Au total, 18 mélanges de CLD et de CLD-BP ont été testés. Six concentrations environnementales de CLD (2.10-4 μM à 4.10-2 μM) et une gamme similaire de CLD-BP ont été utilisées. Les résultats des expositions à la CLD seule ont montré ce qui suit : (i) une diminution significative de la capacité de régénération de l'hydre, sauf à la plus faible concentration (2.10-4 μM) ; (ii) un effet délétère indépendant de la concentration. Les scores de régénération obtenus après l'exposition à l'ajout de CLD-BP n'étaient pas significativement différents de ceux obtenus après l'exposition à la CLD seule. À l'aide d'un plan expérimental, une modélisation des scores de régénération des hydres exposés à des mélanges est proposée. Interprétés avec précaution, car limités à un seul type de bioessai, les présents résultats suggèrent que la situation des milieux aquatiques ne devrait pas s'aggraver en termes de toxicité, si des programmes de dépollution des sols entraînant la formation d'hydrochlordécones sont mis en place.

International audience; Prosthetic implants are widely used in dentistry and orthopedics and, as a result, infections can occur which cause their removal. Therefore, it is essential to propose methods of eradicating the bacteria that remain on the prosthesis during treatment. For this purpose, it is necessary to develop surfaces whose antibacterial activity can be controlled. Herein, we designed innovative and smart phosphonium self-assembled monolayer (SAM) interfaces that can be electrically activated on demand for controlling bacterial contaminations on solid surfaces. Upon electroactivation with a low potential (0.2 V for 60 min., conditions determined through a DOE), a successful stamping out of Gram-positive and Gram-negative bacterial strains was obtained with SAM-modified titanium surfaces, effectively killing 95% of Staphylococcus aureus and 90% Klebsiellapneumoniae. More importantly, no toxicity towards eukaryotic cells was observed which further enhances the biocompatible character of these novel surfaces for further implementation.

Chlordecone (CLD), an obsolete insecticide, used in the French West Indies between 1972 and 1993, is persistent in the environment but can be dechlorinated either chemically or under the action of microorganisms. Therefore, if soil remediation programs based on these processes are implemented in areas still contaminated today, those will see their concentrations of dechlorinated derivatives increase and these compounds will be also found in freshwater by streaming, leaching and erosion processes. The purpose of the present study was to evaluate, at environmental concentrations, the toxic effects of mixtures of chlordecone and a three-chlorine substituted byproduct. A hydra clone, which has been confirmed to be Hydra vulgaris Pallas, 1766 has been retained for bioassays where the toxicity has been evaluated by regeneration capacity during exposure. Exposure to mixtures is complex to investigate by classical methods, therefore, an experimental design associated to a mathematical model has been used to predict the effects of all the mixtures and to detect the toxic influence of each compound. The predictive model is discussed regarding the stochastic “endocrine disruptor effect” of CLD. At probable environmental concentrations of the compounds in the mixture, results show that impairment of regeneration capacity is explained mostly by the presence of CLD in the mixtures and support the implementation of remediation programs aimed at dechlorination of this persistent organochlorine pesticide.

International audience; La chlordécone (CLD) est un insecticide organochloré obsolète qui a été utilisé aux Antilles françaisesde 1972 à 1993. Elle est persistante dans l’environnement et se transforme très lentement pardéchloration. En conséquence, elle est encore présente dans les sols mais aussi dans les écosystèmesd’eau douce suite au lessivage, la lixiviation et l’érosion des sols sous l’action des pluies. Dans la mesureoù des programmes de remédiation des sols seraient mis en place dans des zones encore contaminéesaujourd’hui, la concentration des dérivés déchlorés augmenterait alors que celle en CLD diminuerait.L’objet du présent travail est d’évaluer la toxicité de mélanges de CLD et d’un dérivé déchloré, à desconcentrations susceptibles d’être retrouvées dans les eaux de surface, envers un invertébré d’eaudouce modèle. Le dérivé déchloré choisi ici correspond à une tri-hydrochlordécone (CLD-3Cl) qui seforme au cours du procédé de remédiation ISCR (In Situ Chemical Reduction) testé avec succès par leBRGM à l’échelle de la parcelle (Mouvet et al., 2020, https://doi.org/10.1007/s11356-020-07603-z).Pour les essais biologiques de toxicité, le cnidaire Hydra vulgaris a été choisi comme invertébrémodèle. Ces bioessais ont consisté à évaluer la capacité de régénération de cette hydre d’eau douceaprès 96 h d’exposition au mélange CLD + CLD-3Cl. L’impact des mélanges étant complexes à étudierpar les méthodes classiques, la méthode des plans d’expériences a été utilisée pour réduire le nombred’expériences à réaliser sur la plage de concentrations étudiées (0 à 20 μg/L équivalent CLD) sansperdre d’informations et de détecter d’éventuelles interactions entre les composés. Un modèleprédictif de la toxicité du mélange en fonction des différents niveaux de concentrations possibles estproposé ici. Celui-ci permet de conforter le fait que la molécule déchlorée est moins toxique que laCLD et que la présence de dérivés déchlorés en mélange avec cette dernière ne devrait pas engendrerune toxicité supérieure à la CLD seule. Nos résultats montrent que les plans d’expériences sont desoutils très utiles en écotoxicologie et toxicologie environnementale pour évaluer les effets de mélangescomplexes avec de faibles concentrations de xénobiotiques.

The global increase of multidrug resistant bacteria and the lack of new classes of antibiotic especially those targeting Gram-negative pathogens are leaving the clinicians disarmed to treat numerous bacterial infections. Recently, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising investigated solutions to circumvent this problem. In this context, we have recently identified a new polyamino-isoprenyl derivative NV716 able to potentiate, at a very low concentration the activity of doxycycline against resistant P. aeruginosa bacterial strains by increasing its intracellular concentration. In this study we will report an experimental protocol to optimize a dry powder for inhalation ensuring the simultaneous delivery of an antibiotic (doxycycline) and an adjuvant (the polyaminoisoprenyl derivative NV716 since aerosol therapy could allow a rapid drug administration and target the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects. Thus, an experimental design was carried out permitting to identify the influence of several factors on the aerosolization efficiency of our combination and allowing us to find the right composition and manufacture leading to the best optimization of the simultaneous delivery of the two compounds in the form of an inhalable powder. More precisely, the powders of the two active ingredients were prepared by freeze drying and their aerosolization was improved by the addition of carrier particles of lactose inhalation grade. Under these conditions, the best formulation was defined by combining the optimal factors leading to the best aerodynamic properties' values (the lowest MMAD (Mass Median Aerodynamic Diameter) and the highest FPF (Fraction of Fine Particles)) without even using sophisticated engineering techniques. Finally, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.

International audience; Although the PIG-A gene mutation frequency (MF) is considered a good proxy to evaluate the somatic MF in animals, evidence remains scarce in humans. In this study, a granulocyte PIG-A-mutant assay was evaluated in patients undergoing radiation therapy (RT) for breast cancer. Breast cancer patients undergoing adjuvant RT were prospectively enrolled. RT involved the whole breast, with (WBNRT) or without (WBRT) nodal area irradiation. Blood samples were obtained from participants before (T0) RT, and T1, T2, and T3 samples were collected 3 weeks after the initiation of RT, at the end of RT, and at least 10 weeks after RT discontinuation, respectively. The MF was assessed using a flow cytometry protocol identifying PIG-A-mutant granulocytes. Cytokinesis-blocked micronucleated lymphocyte (CBML) frequencies were also evaluated. Thirty patients were included, and five of them had received chemotherapy prior to RT. The mean (±SD) PIG-A MFs were 7.7 (±12.1) per million at T0, 5.2 (±8.6) at T1, 6.4 (±8.0) at T2 and 3.8 (±36.0) at T3. No statistically significant increases were observed between the PIG-A MF at T0 and the MFs at other times. RT significantly increased the CBML frequencies: 7.9 ‰ (±3.1‰) versus 33.6‰ (±17.2‰) (p < .0001). By multivariate analysis, the CBML frequency was correlated with age at RT initiation (p = .043) and irradiation volume at RT discontinuation (p = .0001) but not with chemotherapy. RT for breast cancer therapy failed to induce an increase in the PIG-A MF. The PIG-A assay in humans needs further evaluation, in various genotoxic exposures and including various circulating human cells.

Enterotoxigenic E. coli (ETEC) is a leading cause of moderate-to-severe diarrhoea. ETEC colonizes the intestine through fimbrial tip adhesin colonization factors and produces heat-stable and/or heat-labile (LT) toxins, stimulating fluid and electrolyte release leading to watery diarrhoea. We reported that a vaccine containing recombinant colonization factor antigen (CfaEB) targeting fimbrial tip adhesin of the colonization factor antigen I (CFA/I) and an attenuated LT toxoid (dmLT) elicited mucosal and systemic immune responses against both targets. Additionally, the toll-like receptor 4 ligand second-generation lipid adjuvant (TLR4-SLA) induced a potent mucosal response, dependent on adjuvant formulation. However, a combination of vaccine components at their respective individual optimal doses may not achieve the optimal immune profile. We studied a subunit ETEC vaccine prototype in mice using a response surface design of experiments (DoE), consisting of 64 vaccine dose-combinations of CfaEB, dmLT and SLA in four formulations (aqueous, aluminium oxyhydroxide, squalene-in-water stable nanoemulsion [SE] or liposomes containing the saponin Quillaja saponaria-21 [LSQ]). Nine readouts focusing on antibody functionality and plasma cell response were selected to profile the immune response of parenterally administered ETEC vaccine prototype. The data were integrated in a model to identify the optimal dosage of each vaccine component and best formulation. Compared to maximal doses used in mouse models (10 µg CfaEB, 1 µg dmLT and 5 µg SLA), a reduction in the vaccine components up to 37%, 60% and 88% for CfaEB, dmLT and SLA, respectively, maintained or even maximized immune responses, with SE and LSQ the best formulations. The DoE approach can help determine the best vaccine composition with a limited number of experiments and may accelerate development of multi-antigen/component ETEC vaccines.

International audience; The efficiency of a versatile in vivo cascade involving a promiscuous alcohol dehydrogenase, obtained from a biodiversity search, and a Baeyer–Villiger monooxygenase was enhanced by the independent control of the production level of each enzyme to produce ε‐caprolactone and 3,4‐dihydrocoumarin. This goal was achieved by adjusting the copy number per cell of Escherichia coli plasmids. We started from the observation that this number generally correlates with the amount of produced enzyme and demonstrated that an in vivo multi‐enzymatic system can be improved by the judicious choice of plasmid, the lower activity of the enzyme that drives the limiting step being counter‐balanced by a higher concentration. Using a preconception‐free approach to the choice of the plasmid type, we observed positive and negative synergetic effects, sometimes unexpected and depending on the enzyme and plasmid combinations. Experimental optimization of the culture conditions allowed us to obtain the complete conversion of cyclohexanol (16 mM) and 1‐indanol (7.5 mM) at a 0.5‐L scale. The yield for the conversion of cyclohexanol was 80% (0.7 g ε‐caprolactone, for the productivity of 244 mg·L −1·h −1) and that for 1‐indanol 60% (0.3 g 3,4‐dihydrocoumarin, for the productivity of 140 mg·L −1·h −1).

Selection methods are commonly used to retain only the least correlated variables when data are described by a large number of variables. However, most of the currently available variable selection methods do not take the intrinsic quality of the subset retained into account. In this paper, we propose a new approach based on a multicriteria selection of variables. The intrinsic quality of the selected subset was assessed based on both criteria calculated from the model matrix and the procrustes analysis. This verification guarantees a good estimation of the coefficients for the model and a good representativity. This approach was applied to two cases: a benchmark dataset known as Coffee data and a real dataset produced by a study of quantitative structure–activity relationship. In both cases, the solutions were representative of the initial set and displayed good intrinsic quality, these solutions will therefore be useable in the modeling step.

Quality by Design is a recent concept from quality control which has led to new requirements demanded by the authorities, particularly in the pharmaceutical industry. Among these, the guideline ICHQ8 explains that quality cannot be tested into products but should be built in by design. Designs of Experiments have been used to establish the relationship between input and output parameters of a process or formula while minimizing the risk in the final decision. More precisely, modelling studies are carried out to better understand the process and to predict the outputs in the whole domain of interest. When there are many input and output parameters, the experimenter looks for a compromise zone in which all the output parameters comply with the specifications. In this area, we can define a region where all the inputs can vary without altering the quality of the product with a fixed probability that the objectives will be reached. This zone is called Design Space and the determination of their boundaries is recommended by the Food and Drug Administration. In this publication, we propose different methods such as Monte-Carlo method, Bootstrap technique, numerical approach and reliability method to determine the Design Space. A comparison study is achieved using a case study.

In the field of formulation, the behaviour of phenomena studied are often complex, including non-linear or chaotic zones which make classical strategies based on polynomial models inappropriate. In these situations, uniform experimental designs and kriging models are recommended. Nonetheless, when researchers have to set up an experimental strategy, they must choice the class of designs to be constructed, the number of experiments to be performed and the modeling kriging parameters to be used. To help with these choices, we propose a catalogue combining various uniform designs characterized by several intrinsic quality criteria and to establish decision-making rules linking these criteria to the quality of the information obtained from the design.

International audience; Solid-state fermentation (SSF) is a cultural method that holds tremendous potentials for the production of numerous microbial value-added compounds in various industries. As for every other process, experimental designs can provide tools to improve the product yields, diminish the production time and thus eventually decreasing the cost of the whole process. However, SSF, because of its solid nature, implies some constraints which consequently require specific tools to efficiently overcome them. The aim of this study was the improvement of the production of antioxidant naphtho-gamma-pyrones produced by Aspergillus niger G131 cultivated using SSF. Two experimental designs were presented, a combined design, taking into account two different types of variables to determine a proper solid medium, and a screening design with mixed-level factors to find solutes with significant positive effects on the output.

International audience; Uniform experimental designs (Space Filling Designs) are now widely used with independent variables, particularly in numerical simulation. A lot of construction methods have been developed to uniformly cover the domain of variables, but they remain rarely applied for the study of mixtures. In this article, we propose methods to build space-filling designs for mixtures that can be used to modelize complex phenomena in formulation. Various algorithms like Kennard and Stone, WSP, Strauss and Dmax algorithms, to construct these designs are detailed and compared with respect to uniformity criteria.

International audience; For the first time, Polyporus brumalis BRFM985 was cultivated on wheat straw to investigate the simultaneous effects of pretreatment parameters on anaerobic digestion: these include initial substrate humidity, temperature, duration, and metal supplementation. Surface response methodology was applied to quantify the importance of each parameter, as well as the synergistic effects between them. Firstly, metal addition and secondly, pretreatment duration, both resulted in a positive impact. According to calculations, the highest methane production (182 dm3 of methane per kilogram of initial Total Solids) is associated to pretreatment with metal addition during 20 days. In comparison with the least optimal conditions (118 dm3.kg−1 without metal addition, during 15 days), this result implies a 52% increase.

International audience; Drug/lense combinations have proven significant in the field of ocular therapeutics. The development of innovative systems and elaboration processes is an upcoming issue for ocular drug delivery. One challenging issue is the elaboration of drug loaded intraocular lenses (IOLs) to combine cataract surgery and post-operative treatments in a single procedure. In this work, we are studying the elaboration of such systems while using a green process using supercritical fluids for impregnating ophthalmic drugs on commercial IOLs. More particularly, rigid commercial intraocular lenses made from Poly (Methyl MethAcrylate) (PMMA), used in cataract surgery, are loaded with dexamethasone 21- phosphate disodium salt (DXP, an anti-inflammatory drug) and ciprofloxacin (CIP, an antibiotic) in order to prevent short- and mid-term postoperative complications.Supercritical impregnations were carried out in a batch mode and impregnation yields were determined through drug release kinetic studies in a solution simulating the aqueous humor. Before performing an experimental design, preliminary impregnation assays were conducted in order to delimit the operating domain. Transparent IOLs presenting an effective impregnation were obtained. The highest impregnation yields for DXP and CIP in PMMA IOLs were 18.3 and 2.8 μgdrug/mgIOL respectively. Despite the low solubility of each drug in the fluid phase, homogeneous and in-depth impregnations were successfully obtained with a prolonged drug delivery (about 40 days) for most impregnation experiments.

The purpose of this work was to optimize the pretreatment process of wheat straw by Polyporus brumalis_BRFM985 in order to improve carbohydrate accessibility for more efficient bioconversion. Indeed, there is growing demands to develop sustainable routes for lignocellulosic feedstocks valorization into value‐added products in energy, chemicals, materials, and animal feed fields. To be achieved, implementation of cheap and ecofriendly biomass pretreatment processes is necessary. In this frame, white rot basidiomycetes, well known for their ability to degrade lignin efficiently and selectively, are of great interest. The pretreatment of wheat straw by Polyporus brumalis_BRFM985 was performed in packed bed bioreactor and optimized using response surface methodology. The four pretreatment parameters optimized were metals addition (Cu, Mn, and Fe), time of culture, initial water content, and temperature. Multicriteria optimization highlighted that wheat straw pretreatment by Polyporus brumalis_ BRFM985 in the presence of metals with high initial water content of 3.6 g H2O/g at 27°C for 15–16 days led to an improvement of carbohydrate accessibility with minimal matter loss.

A high quality activated carbon has been obtained, by physical activation with steam, from a Moroccan agricultural by-product (Argan shells) and their characteristics were investigated. In order to optimize experimental conditions of the preparation, a combination of a fractional factorial design and a Doehlert design was applied. In the first step of this work, a two-level fractional factorial design 2 (5–1) was used to study effects and first order interactions of various factors such as atmosphere in carbonization step, carbonization time at 400 °C, activation temperature, activation time and steam flow. The results reveal that the most influential factors on the yield and the methylene blue adsorption are activation temperature, activation time, steam flow and the presence of a significant interaction between activation temperature and activation time in both cases. In the second step, activation temperature and activation time were optimized using Response Surface Methodology with a Doehlert design, and Desirability function. The optimal conditions for the preparation of activated carbon have been identified to be an activation temperature of 880 °C, an activation time of 96 min and steam flow fixed at this positive level of 0.2 cm 3 min − 1 . The characteristics of prepared activated carbon obtained at the optimal conditions were determined using adsorption capacity of methylene blue, iodine and phenol, BET surface area, pHpzc, and surface functions based on Boehm method. Those characteristics (MB adsorption: 608.9 mg g − 1 , iodine adsorption: 1026.4 mg g − 1 , phenol adsorption: 633.3 mg g − 1 , BET surface area: 1292 m 2 g − 1 ) were shown greater than those of a commercial activated carbon used in water treatment and those reported by other researchers studying activated carbon preparation from various solid wastes by steam activation method. On the other hand, this work showed that Argan shells are a good precursor for the production of activated carbon, by steam physical activation, with high performance to be used in water treatment applications.

Construction of Space Filling Designs in high dimensional space remains difficult since powerful algorithms at low dimensions become difficult to use at higher dimensions that leads to non-uniform distribution in the factor space. We propose in this paper two approaches in order to repair designs: Curvilinear Component Analysis (CCA) and the Wootton, Sergent, Phan-Tan-Luu's algorithm called WSP in order to detect clusters and to fill gaps. Thus, CCA allows visualization of two or more very closely-spaced points in D dimensions by projecting them in a 2 dimensions space. Then identified clusters can be eliminated using the WSP algorithm. Moreover, the presence of gaps in input space could be very problematic since no information on the phenomenon is available and the WSP algorithm will be used in order to fill gaps by adding points in the “empty” zones. A new quality criterion has been proposed in order to follow the reparation steps. Examples in different dimensions are presented to illustrate these methods.

Not all phenomena can be studied using standard experimental designs. Indeed, non-linear phenomena require experimental designs to cover the whole variable space in a reasonable number of experiments. Space-filling designs (SFD) propose a uniform distribution of points and are well adapted to numerical simulations. However, not all SFDs are equivalent in terms of uniformity of point distribution throughout the variable space, as assessed by quality criteria (such as MinDist, Coverage, etc.) and many algorithms which are powerful in low dimensional spaces (D

International audience; We propose a new method to treat supersaturated designs which relies on the multivariate CCSWA (Common Components and Specific Weights Analysis), or ComDim, method. This method can be applied through two approaches. The first considers this method as a novel procedure to analyse supersaturated designs. This can reveal influential factors, and correctly identify the active factors even when the results do not fully comply with the standard hypotheses (sparsity). The second approach extracts the information common to the results obtained using a wide range of methods to analyse the designs. This could make it possible to overcome the errors specific to each of these methods.

In the computer experiments setting, if the relationship between the response and the inputs is unknown, then the purpose is to use designs that spread the points at which the response is observed evenly throughout the region. These designs are called space-filling designs (SFD) and the most known are Latin Hypercubes (random, orthogonal, optimized) and low discrepancy sequences. But, simulation codes becoming more and more complex, high dimensional optimal designs are needed to study a high number of parameters (more than 20 parameters) and the construction proves difficult. The aim of this study is to explore a construction method of new space-filling designs for high dimensional spaces. After a short presentation of the criteria considered to quantify the intrinsic quality of the designs, the generation of these designs using WSP algorithm is presented. As the first step consists in generating candidate points, the influence of the initial set of points is investigated in dimension 20 and the final designs are compared with others space-filling designs. Then, designs are proposed in dimension 20, 30, 40 and 50 and the study of the intrinsic quality of these new space-filling designs highlights the robustness of this generation method in high dimensional spaces.

This paper presents a new sensitivity analysis method called ISTHME based on the principles of Morris's method without the construction of randomized one-at-time (OAT) design. The presented method can be applied on any experimental design and more particularly on space filling designs. This specificity is very interesting in terms of time and calculation economy. Indeed, we can use a universal design, which is adapted to sensitivity analysis as well as optimization without any supplementary simulation.

Mixed-level supersaturated designs are designs in which the number of coefficients to estimate is greater than the number of experiments. This type of design is useful in the rapid preliminary investigation of a process with a large number of potentially relevant factors but with only a few of them having important effects. The purpose of this project was to determine the active parameters on a chemical process. A mixed-level supersaturated design of 12 experiments was carried out, allowing us to screen 17 two-level factors and 5 three-level factors. χ²-optimality of the design was confirmed. In order to verify the results, a 40-run matrix was built. One parameter was identified as very active in both analyses, and several others were suspected to have an effect on the process. Some differences were observed in the results, regarding the detection of the least influent factors. These are likely due to the loss of information generated by the reduction of runs in the supersaturated design, as this kind of design allows an important reduction of the number of experiments. Further studies should be considered to confirm the activity of some factors.

International audience; n this article, we apply supersaturated strategies to identify active factors in the field of numerical simulation. As the number of simulations is inferior to the number of studied factors, new resolution techniques are proposed and provide excellent results. Indeed, classical supersaturated treatments could not be applied to the high dimensional problem. We show that these designs are well adapted to the high dimensional problem while maintaining the number of simulations at reasonable levels. Very small-sized supersaturated designs show low reliability. Keywords: Hadamard matrix; Supersaturated designs; Screening; Computer experiments; Genetic algorithm; Sensitivity analysis

New chiral aminophosphinite ligands are readily prepared and their behaviour as homogeneous catalysts was investigated in the linear dimerization of butadiene and isoprene. This latter reaction has been optimised using experimental research methodology, leading to a conversion rate above 50%.

We present the advantages of experimental design in the sensitivity analysis of optical coatings with a high number of layers by limited numbers of runs of the code. This methodology is effective in studying the uncertainties propagation, and to qualify the interactions between the layers. The results are illustrated by various types of filters and by the influence of two monitoring techniques on filter quality. The sensitivity analysis by experimental design of optical coatings is useful to assess the potential robustness of filters and give clues to study complex optronic systems. OCIS codes: 310.0310, 220.0220, 120.0120. doi: 10.3788/COL201008S1.0021. The study of complex optronic systems entails sensitivity analysis with a large number of parameters. Very often the response depends on synergies or interactions between these parameters. Due to interference characteristics of multilayer filters, optical coatings make possible the evaluation of methods that can explore highdimensional space parameters and the presence of interactions between parts of these parameters. For coatings production with a high number of layers, sensitivity analysis is an efficient way to determine the most critical layers of an optical coating [1] . Refractive index errors or thickness errors during the manufacturing of these layers can induce dramatic consequences on the desired optical properties [2] . We present the advantages of using the method of experimental design [3] , which is used for metamodel constructions and high-dimensional code explorations with limited numbers of runs of the code, particularly in the case of coatings with a high number of layers. This methodology is more effective in studying uncertainties propagation (refractive index or thickness values) to determine the influence of errors on the optical properties, and to quantify the interactions between the errors of each layer. The results are illustrated by various types of filters, particularly bandpass filters and multiple halfwave filters. Different designs such as factorial, fractional factorial, and space-filling designs are used to present the results. Furthermore, we study the influence of two monitoring techniques, and show the most critical coating layers and the dependency of these layers with future manufacturing. The results show that the study of thin-film filters is very useful in examining the interactions of highdimensional systems due to the filter’s adjustable number of layers, and the existence of interactions between these layers. Finally, we demonstrate that sensitivity analysis of optical coatings by experimental design is useful in assessing the potential robustness of filters, and gives clues to study complex optronic systems. The codes to study complex phenomena become more and more realistic with a larger input data set. However, due to the complexity of the mathematical system underlying the computer simulation tools, there are often no explicit input-output formulas. Although computer power has significantly increased in the past years, the evaluation of a particular setting of the design parameters may still be very time-consuming. The simulator is often replaced by a metamodel to approximate the relationship between the code and the design parameters. These metamodels are built using numerical designs of experiments that can indicate interactions between the parameters. The choice of an underlying empirical model (depending on accuracy and interactions level) can be written as Y = Cste + ∑ i biXi + ∑ i

In a previous paper, we showed that the preparation of sulfated diethanolamide of fatty acids is easy to carry out without organic solvents when using olive pomace oil as starting material; the reaction yield was, however, highly variable as a function of factor levels. The purpose of this research is to look for the optimal experimental conditions. We started by applying a supersaturated experimental design to screen for important factors among a list of 31 potentially influential factors in 18 experiments. Thus, we constructed a two-level supersaturated design as a half fraction of a 36-experiment Hadamard matrix and used it for this screening purpose. Multiple regression methods namely stepwise selection procedure, ridge regression and all-subset regressions were used to analyze the supersaturated design results according to a four step procedure. Results indicated that six factors, namely, molar ratio SO 3 /ester, amidation time, amide addition rate, alkali reagent, alkali concentration, and amidation temperature, were very influential factors. Three other factors were moderately influential: neutralization temperature, sodium methanoate amount, and methanol amount. In future research, these factors will be further studied in order to perform robustness tests of the process.

New cosmetic emulsion with biomimetic molecules have been investigated using experimental designs. For this purpose, six variables have been studied: the nature of surfactant (three mixture variables), the percentages of surfactant, co-surfactant and squalene, and five properties have been measured: stability, centrifugation, viscosity, pH, microscope analysis. Because of the complexity of the study, the optimization of these five responses has been carried out in two steps. First, a simple additive model has been postulated, in order to define a smaller domain of interest. A Doehlert, a grid and a simplex centriod designs have been built in order to generate candidate points. Exchange algorithm has allowed to extract a design with only 28 experiments. Results have shown that the percentage of squalene exhibits the greatest influence on the stability and on the viscosity of the emulsions. Secondly, a multiplicative model has been postulated using composite and simplex centroid design to generate candidate points. A set of 36 experiments has been selected. Conditions for the percentage of surfactant and co-surfactant, and for mixture variables have been determined in order to obtain a good compromise between the five responses. Finally, these studies have allowed to determine in the whole domain of interest an optimal formula composed only with biomimetic products and presenting good physico-chemical characteristics and stability.

The use of experimental designs in the field of numerical simulation improves global sensitivity analysis compared to Monte Carlo based method by decreasing the number of simulations. More particularly, supersaturated designs can be applied to decrease the number of calculations, because the number of simulations is inferior to the number of studied factors but its use is risky and depends on “parsimony principle”. This paper shows new supersaturated designs that use the a priori knowledge and thus overcome this difficulty.

This paper describes the application of subcritical wet oxidation to the disposal of sheep animal by-products originating from slaughterhouse. Animal by-products (ABPs) from categories 1 and 3 (gall, head, tail, spinal cord, offal, ileum and blood) were oxidized at high pressure and moderate temperature (P = 12.5–20 MPa, T = 200–320 °C). The oxidation experiments were performed on individual samples or on a reconstituted mixture representing the ABPs of a slaughtered sheep. The oxidation kinetics of a representative sample was studied and the apparent activation energy was found to be 42.9 kJ mol−1. The chemical by-products were also identified and quantified in the final oxidized solution: acetic acid and ammonia were identified in all samples as the major by-products representing around 31% and 69%, respectively, of residual TOC and initial nitrogen after the oxidation of a representative sample of ABPs containing initially 5 g L−1 of total organic carbon (TOC). The contribution of the experimental factors temperature, reaction time and concentration of the feed solution to remove the organic matter was assessed and optimized using an experimental design based on the response surface methodology. Fitting of the experimental data showed that the 2nd order polynomial model represented the data best. A multicriteria optimization, using the desirability function, allowed the determination of the best region of the experimental domain to optimise the TOC removal and the energy consumption.

International audience; The drug delivery through intraocular lenses (IOLs) allows the combination of cataract surgery act and postoperative treatment in a single procedure. In order to prepare such systems, “clean” supercritical CO2 processes are studied for loading commercial IOLs with ophthalmic drugs. Ciprofloxacin (CIP, an antibiotic) and dexamethasone 21-phosphate disodium (DXP, an anti-inflammatory drug) were impregnated into foldable IOLs made from poly-2-hydroxyethyl methacrylate (P-HEMA). A first pre-treatment step was conducted in order to remove absorbed conditioning physiological solution. Supercritical impregnations were then performed by varying the experimental conditions. In order to obtain transparent IOLs and avoid the appearance of undesirable foaming, it was necessary to couple slow pressurization and depressurization phases during supercritical treatments. The impregnation yields were determined through drug release studies. For both drugs, release studies showdeep and reproducible impregnation for different diopters.For the system P-HEMA/CIP, a series of impregnations was performed to delimit the experimental range at two pressures (80 and 200 bar) in the presence or absence of ethanol as a co-solvent for two diopters (+5.0 D and +21.0 D). Increase in pressure in the absence of a co-solvent resulted in improved CIP impregnation. The addition of ethanol (5 mol%) produced impregnation yields comparable to those obtained at 200 bar without co-solvent. A response surface methodology based on experimental designs was used to study the influence of operating conditions on impregnation of IOLs (+21.0 D) in the absence of co-solvent. Two input variables with 5 levels each were considered; the pressure (80–200 bar) and the impregnation duration (30–240 min). CIP impregnation yields ranging between 0.92 and 3.83 μgCIP/mgIOL were obtained from these experiments and response surface indicated the pressure as a key factor in the process.The DXP impregnation in P-HEMA was higher than CIP at all the tested conditions (8.50–14.53 μgDXP/mgIOL). Furthermore, unlike CIP, highest DXP impregnation yields were obtained in the presence of ethanol as a co-solvent (5 mol%). NMR spectroscopy was performed to confirm complete removal of ethanol in the co-solvent-treated IOLs

We report a numerical study on sunscreen design and optimization. Thanks to the combined use of electromagnetic modeling and design of experiments, we are able to screen the most relevant parameters of mineral filters and to optimize sunscreens. Several electromagnetic modeling methods are used depending on the type of particles, density of particles, etc. Both the sun protection factor (SPF) and the UVB/UVA ratio are considered. We show that the design of experiments' model should include interactions between materials and other parameters. We conclude that the material of the particles is a key parameter for the SPF and the UVB/UVA ratio. Among the materials considered, none is optimal for both. The SPF is also highly dependent on the size of the particles.

International audience; The water framework directives (WFD 2000/60/EC and 2013/39/EU) force European countries to monitor the quality of their aquatic environment. Among the priority hazardous substances targeted by the WFD, short chain chlorinated paraffins C-10-C-13 (SCCPs), still represent an analytical challenge, because few laboratories are nowadays able to analyze them. Moreover, an annual average quality standards as low as 0.4 mu g L-1 was set for SCCPs in surface water. Therefore, to test for compliance, the implementation of sensitive and reliable analysis method of SCCPs in water are required. The aim of this work was to address this issue by evaluating automated solid phase micro-extraction (SPME) combined on line with gas chromatography-electron capture negative ionization mass spectrometry (GC/ECNI-MS). Fiber polymer, extraction mode, ionic strength, extraction temperature and time were the most significant thermodynamic and kinetic parameters studied. To determine the suitable factors working ranges, the study of the extraction conditions was first carried out by using a classical one factor-at-a-time approach. Then a mixed level factorial 3 x 2(3) design was performed, in order to give rise to the most influent parameters and to estimate potential interactions effects between them. The most influent factors, i.e. extraction temperature and duration, were optimized by using a second experimental design, in order to maximize the chromatographic response. At the close of the study, a method involving headspace SPME (HS-SPME) coupled to GC/ECNI-MS is proposed. The optimum extraction conditions were sample temperature 90 degrees C, extraction time 80 min, with the PDMS 100 mu m fiber and desorption at 250 degrees C during 2 min. Linear response from 0.2 ng mL(-1) to 10 ng mL(-1) with r(2) = 0.99 and limits of detection and quantification, respectively of 4 pg mL(-1) and 120 pg mL(-1) in MilliQ water, were achieved. The method proved to be applicable in different types of waters and show key advantages, such as simplicity, automation and sensitivity, required for the monitoring programs linked to the WFD. (C) 2015 Elsevier B.V. All rights reserved.

International audience; In the field of keratoconus treatment, a lipid-based liquid crystal nanoparticles system has been developed to improve the preocular retention and ocular bioavailability of riboflavin, a water-soluble drug. The formulation of this ophthalmic drug delivery system was optimized by a simplex lattice experimental design. The delivery system is composed of three main components that are mono acyl glycerol (monoolein), poloxamer 407 and water and two secondary components that are riboflavin and glycerol (added to adjust the osmotic pressure). The amounts of these three main components were selected as the factors to systematically optimize the dependent variables that are the encapsulation efficiency and the particle size. In this way, 12 formulas describing experimental domain of interest were prepared. Results obtained using small angle X-rays scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) evidenced the presence of nano-objects with either sponge or hexagonal inverted structure. In the zone of interest, the percentage of each component was determined to obtain both high encapsulation efficiency and small size of particles. Two optimized formulations were found: F7 and F1. They are very close in the ternary phase diagram as they contain 6.83% of poloxamer 407; 44.18% and 42.03% of monoolein; 46.29% and 48.44% of water for F7 and F11, respectively. These formulations displayed a good compromise between inputs and outputs investigated.

International audience; Various industrial processes and anthropogenic activities in urban areas induce a release of metals, metalloids and organic pollutants. Phytoremediation of co-contaminated waters in constructed wetlands is a promising solution for reducing the impact on natural environments. In order to improve the design and management of constructed wetlands, more knowledge is needed concerning the effect of organic pollutants on plant metal and metalloid uptake. In this study, the effects of a mixture of organic pollutants commonly found in industrial effluents (hydrocarbons, polycyclic aromatic hydrocarbons, anionic detergent) on the uptake of ten metals and metalloids (MM), i.e. Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn, by five helophytes having a wide European distribution were studied. Main effects of plant species and pollutant conditions on metal uptake and interactions between factors were determined by a statistical treatment of a microcosm experiment. Overall, the order of element uptake in plants was Fe > Al > Mn > Cr, Ni, Zn, > Cu > As, Cd, Pb, which was consistent with relative concentrations in the rhizosphere environment of microcosms. Larger amounts of metals were retained in belowground biomass of plants than in aboveground parts. Statistical analysis showed that organic pollutants enhanced the accumulation of Mn in whole plants and the retention of Fe in belowground parts, while they reduced the accumulation of Cd, Ni, and Zn in whole plants and the retention of Cu in belowground parts. For the other MM (Al, As, Cr, Pb), effects were variable, depending on the plant species. Among the five plants tested, Carex cuprina generally removed the highest quantities of MM, which was the result of both a high metal accumulation capacity and high biomass production. Nevertheless, no significant proportion of the MM total loading could be removed in plants aboveground parts. (C) 2014 Elsevier Ltd. All rights reserved.

International audience; To develop self-assembled liquid crystalline nanoparticles as a drug delivery system for keratoconus treatment, a formulation containing riboflavin a water-soluble drug, two surfactants (poloxamer 407 and mono acyl glycerol -monoolein-) and water was optimized and prepared by emulsification and a homogenization process. A fractional factorial design was applied to estimate the main effects and interaction effects of five parameters on two responses, namely particle size and encapsulation efficiency. The five parameters are the temperature of the two phases, the duration of emulsification, the presence of heating during homogenization, the number of passes and pressure. The most influent parameters are the presence of heating during the homogenization and the pressure that led to the production of nanoparticles with an average size of 145 nm and an average encapsulation efficiency of 46%.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play an important role in the prevention of a lot of human diseases, and the supplementation in the alimentation of such fatty acids is thus recommended in certain diets. EPA and DHA were obtained by extraction and fractionation of fish industries waste, such as fish heads, produced for fish canning. Supercritical fluid extraction (SFE) of sardine oil was performed to optimize various parameters, such as pressure, temperature, CO 2 rate and time in order to obtain the highest yield of extracted oil with the highest amount of EPA and DHA in the extraction product. An experimental design was planned and the experiments were performed with a supercritical pilot (Hewlett-Packard), while the composition of each extract was determined by GLC. In the first approach, the oil yield was determined. Then, a quadratic model with three variables was studied to maximize the EPA and the DHA concentrations. A multicriteria optimization, using the desirability function, was performed to determine the best level for each parameter. Pressure, temperature and CO 2 rate were, respectively, set at 300 bars, 75 °C and 2.5 ml/min during 45 min extraction. A yield of 10.36% of extracted oil (compared with the dry material) was achieved with an amount of 10.95% of EPA and 13.01% of DHA (compared with all fatty acids of the extract). This result was compared with a traditional solvent extraction and the solvent extraction yield seemed to be better. In fact, the advantages of SFE were a shorter extraction time, a prevention of heating and a better organoleptic aspect by excluding the use of legally not allowed organic solvents.

The present research studies the optimization of the preparation of a hydrotrope (mixture of sodium toluenesulfonate and sodium xylenesulfonates) for liquid detergents using experimental designs. The preparation is carried out by selective sulfonation of toluene and xylene present in the BTX fraction of a natural gas. The optimization of five responses has been carried out in two steps. First, we carry out an asymmetrical screening design 2 1 3 6 //18 to select from seven factors, those factors which have significant influence on the amount of residual sodium sulfate in the product and on the total conversion of toluene and xylenes. Secondly, we carry out a Box–Behnken design to optimize three retained factors (temperature, molar ratio of acid to toluene plus xylenes, and the amount of desulfation agent), using response surface methodology. In addition, and in order to reach near-optimal sulfonation conditions, we use the desirability functions to optimize the five responses simultaneously. This allows us to determine for the whole process, sulfonation conditions leading to a high yield of toluene and xylene conversion and acceptable amounts of residual sodium sulfates and sodium benzenesulfonate.

Using derivatization by chloroethylnitrosourea (CENU) a new strategy was used for raising antibodies directed against hapten (

To develop biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles prepared by an original emulsion-extraction process, with glycofurol, a nontoxic excipient, as polymer solvent.The preparation of microparticles consisted in dissolving polymer in glycofurol. This solution was emulsified in a vegetable oil, and then amphiphilic agent was added into the emulsion to extract glycofurol and lead to microparticle formation. Physicochemical studies were carried out, and an experimental design was prepared in order to elucidate the impact of the formulation composition on the microparticle characteristics. Finally, encapsulation tests were made with a model protein.In a ternary diagram, a small feasibility area allowing particle formation was located. The resulting microparticles were spherical with a homogeneous, polymeric matrix structure. They exhibited a variable size from 3 to 15 microm, which was controlled by the different formulation parameters. Differential scanning calorimetry (DSC) analysis made it possible to detect their composition. Preliminary results showed that these particles were able to encapsulate a protein model, lysozyme.This simple and convenient technique enabled us to obtain spherical, biodegradable microparticles from acceptable excipients. Moreover, the process conditions made possible the encapsulation of drugs, including proteins.

The present research studies the formulation and optimization of a self-leveling composition for floor toppings. This formulation is, in particular, based on a fluoroanhydrite which is a by-product of a Tunisian plant for fluorhydric acid preparation; it also contains aggregates, a neutralizing agent, a hydration accelerator and, especially, a plasticizer prepared by sulfonation of the lignin extracted from the black liquor of a Tunisian esparto grass soda pulping process. The optimization of four responses (plasticity, compressive strength, initial and final setting times) has been carried out in two steps. First, we obtain a coarse composition with a relatively acceptable rheological properties. Second, we carry out a mixture design in the surroundings of the retained composition aimed at obtaining a product with the required characteristics formulated by the users of this kind of materials. To this end, the evolution of the plasticity and the setting times of the fresh mortar and the compressive strength of the hardened mortar in a four-component system with constraints were analyzed using a mathematically independent variable approach. Finally, and in order to reach a near-optimal composition, we use the desirability functions to optimize the four responses simultaneously. This allows us to determine the coordinates of a composition which is characterized by high plasticity, acceptable compressive strength and relatively rapid setting times.

Glial cell line-derived neurotrophic factor (GDNF) is a protein with potent trophic actions on dopaminergic neurons, which is under investigation as a therapeutic agent for the treatment of neurodegenerative disorders, including Parkinson's disease. The aim of this work was to develop GDNF-loaded microspheres, which could be implanted by stereotaxy in the brain and could offer an alternative strategy in the treatment of Parkinson's disease. A w/o/w extraction-evaporation technique was chosen to prepare protein-loaded microspheres. An in vitro release study of the protein was required to assess the retention of integrity and the performance of the microsphere formulation with regard to sustained release. In order to assess the in vitro release profile of the GDNF-loaded microspheres, a preliminary study was performed to select an appropriate buffer for GDNF stabilization, using experimental designs. GDNF was measured by both enzyme-linked immunosorbant assay (ELISA) and radioactivity using (125)I-GDNF. The GDNF-loaded microsphere release profile was assessed in a low continuous flow system, and showed a sustained release over 56 days of biologically active GDNF at clinically relevant doses.

A critical discussion about the possibility of improving the method validation process by means of experimental design is presented. The reported multivariate strategies concern the evaluation of the performance parameters robustness and intermediate precision, and the optimisation of bias and repeatability. In particular, accuracy and precision improvement constitutes a special subset of experimental design in which the bias and the relative standard deviation of the assay are optimised. D-optimal design was used in order to plan experiments for this aim. The analytical methods considered were capillary electrophoresis, HPLC, adsorptive stripping voltammetry and differential pulse polarography. All methods were applied to real pharmaceutical analysis problems.

In a previous study, we presented a new method for preparing a mixture of sodium toluenesulfonates (STS), sodium xylenesulfonates (SXS), sodium benzenesulfonate (SBS) and Na 2 SO 4 by sulfonating the BTX fraction of a Tunisian natural gas. Such mixtures can be used as a hydrotrope agent for concentrated liquid detergents. In the present work, we performed a mixture design in order to study the effect of each of these four components on the clear point and the viscosity of a liquid detergent, and therefore, to determine the conditions allowing to improve the effectiveness of the hydrotrope. Twenty-eight combinations of the 4 components out of 51 candidate points are selected by the Nemrod-W software according to the D-optimal criterion to fit two polynomial models. The statistical study shows that the fitted models were adequate to describe the clear point and the viscosity responses. Optimal conditions allowing to lower the two responses are then looking for by examining the response surface both as a contour plot, and as three-dimensional surface plot and the response trace. We prove that Na 2 SO 4 exhibits a harmful negative effect, while SXS and STS exhibit, respectively, a strong and moderate positive effect on both clear point and viscosity responses. As expected, SBS has a harmful effect on the two responses but the magnitude of this effect is lesser than that predicted by the preliminary experiments carried out with SBS alone. This phenomenon is explained by the formation of heteroassociation between SBS, STS and SXS similar to what is found in surfactants. The effectiveness of the hydrotrope, obtained by sulfonation of the BTX fraction of the Tunisian natural gas, is really improved by removing sulfates either by adding lime to precipitate gypsum, or isopropanol to reduce the solubility of Na 2 SO 4 .

International audience; The challenges in reducing the world's dependence on crude oil and the greenhouse gas accumulation in the atmosphere, while simultaneously improving engine performance through better fuel efficiency and reduced exhaust emissions, have led to the emergence of new fuels, with formulations blending petrodiesel, biodiesel, bioethanol and water in various proportions. In parallel, the sustainability of the new biofuel industries also requires to maintain a high level of biodiversity while playing on techno-diversity, using a variety of resources that do not compete with edible crops (nor by using arable land for energy crops or food crops for energy production) and flexible conversion technologies satisfying the eco-design, eco-energy and eco-materials criteria. In addition, it would be relevant to consider blending ethyl biodiesel, instead of methyl biodiesel, with petrodiesel, particularly if the fuel formulation is completed with bioethanol (or even water). The supercritical ethanolysis of lipid resources to produce ethyl biodiesel is a simple but efficient route that should have the potential to satisfy the sustainability criteria if analyzed holistically. Therefore, this review focuses specifically on the production of ethyl biodiesel via triglyceride supercritical ethanolysis within a global analysis "feedstocks-conversion-engine". The scientific and technical bottlenecks requiring further development are highlighted by emphasizing (i) the kinetic and thermodynamic aspects (experiments and modeling) required for the process simulation, the results of which aim at securing the life cycle assessment, first at the process level and then at the fuel level; (ii) the proposals to improve the supercritical process performance in terms of eco-material and eco-energy; (iii) the impacts of ethyl vs. methyl biodiesel fuels and of biodiesel ethanol petrodiesel blends (with or without water) on the diesel engine emissions and performance; (iv) the technological flexibility of the supercritical process allowing its conversion toward production of other key products. Finally, built on the state-of-the art review, a new R&D direction combining supercritical ethanolysis of lipids with the addition of CO2, glycerol recovery, and cogeneration, according to the biorefinery concept, is proposed and discussed.

Unsupervised variable reduction methods are intended for reducing the presence of redundancy and multicollinearity in the data. These are common issues when dealing with multivariate analysis associated to large number of variables. With respect to supervised selection, unsupervised reduction aims at selecting subsets of variables able to preserve information, but eliminating redundancy, noise and linearly or near-linearly dependent variables, without considering any dependent response. In this study, we propose the V-WSP algorithm for unsupervised variable reduction, which is a modification of the recently proposed WSP algorithm for design of experiments (DOE). Convergence, performances and comparison with several benchmark algorithms, as well as with other DOE strategies adapted to variable reduction, were evaluated on both simulated, benchmark and real QSAR datasets. The proposed algorithm demonstrated to converge to similar solutions with respect to other reduction strategies, with the advantage to be faster and simpler. © 2014 Elsevier B.V.

Many preliminary studies contain a large number of potentially relevant factors, but often only a few are believed to have actual effects. To isolate influential factors ( screening ) in an efficient way, special experimental strategies are needed, such as the supersaturated designs or the techniques of group screenin. For investigating k factors, these supersatured designs are composed of n observations where n ≪ k + 1. They are useful in situations in which the number of active factors is very small compared to the total number of factors being considered; more specifically, in practice experiments with simulated systems.