Direct catalytic macrolactonization and application of the phase separation strategy in complex molecule synthesis

Les macrolactones sont des squelettes structuraux importants dans de nombreuses sphères de l’industrie chimique, en particulier dans les marchés pharmaceutiques et cosmétiques. Toutefois, la stratégie traditionnelle pour la préparation de macrolactones demeure incommode en requérant notamment l’ajout (super)stœchiométrique d’agents activateurs. Conséquemment, des quantités stœchiométriques de sous-produits sont générées; ils sont souvent toxiques, dommageables pour l’environnement et nécessitent des méthodes de purification fastidieuses afin de les éliminer. La présente thèse décrit le développement d’une macrolactonisation efficace catalysée au hafnium directement à partir de précurseurs portant un acide carboxylique et un alcool primaire, ne générant que de l’eau comme sous-produit et ne nécessitant pas de techniques d’addition lente et/ou azéotropique. Le protocole a également été adapté à la synthèse directe de macrodiolides à partir de mélanges équimolaires de diols et de diacides carboxyliques et à la synthèse de dimères tête-à-queue de seco acides. Des muscs macrocycliques ainsi que des macrolactones pertinentes à la chimie médicinale ont pu être synthétisés avec l’approche développée. Un protocole pour l’estérification directe catalysée au hafnium entre des acides carboxyliques et des alcools primaires a aussi été développé. Différentes méthodes pour la macrolactonisation catalytique directe entre des alcools secondaires et des acides carboxyliques ont été étudiées. En outre, la stratégie de séparation de phase en macrocyclisation en débit continu a été appliquée lors de la synthèse totale formelle de la macrolactone ivorenolide A. Les étapes-clés de la synthèse incluent une macrocyclisation par le couplage d’alcynes de Glaser-Hay et une réaction de métathèse d’alcènes Z-sélective.

Institutional entrepreneurship and techniques of inclusiveness in the creation of the Intergovernmental Platform on Biodiversity and Ecosystem Services

This article contributes to understanding the conditions of social-ecological change by focusing on the agency of individuals in the pathways to institutionalization. Drawing on the case of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES), it addresses institutional entrepreneurship in an emerging environmental science-policy institution (ESPI) at a global scale. Drawing on ethnographic observations, semistructured interviews, and document analysis, we propose a detailed chronology of the genesis of the IPBES before focusing on the final phase of the negotiations toward the creation of the institution. We analyze the techniques and skills deployed by the chairman during the conference to handle the tensions at play both to prevent participants from deserting the negotiations arena and to prevent a lack of inclusiveness from discrediting the future institution. We stress that creating a new global environmental institution requires the situated exercise of an art of “having everybody on board” through techniques of inclusiveness that we characterize. Our results emphazise the major challenge of handling the fragmentation and plasticity of the groups of interest involved in the institutionalization process, thus adding to the theory of transformative agency of institutional entrepreneurs. Although inclusiveness might remain partly unattainable, such techniques of inclusiveness appear to be a major condition of the legitimacy and success of the institutionalization of a new global ESPI. Our results also add to the literature on boundary making within ESPIs by emphasizing the multiplicity and plasticity of the groups actually at stake.

Techniques for batch reinforcement learning in robotics

This thesis addresses the Batch Reinforcement Learning methods in Robotics. This sub-class of Reinforcement Learning has shown promising results and has been the focus of recent research. Three contributions are proposed that aim to extend the state-of-art methods allowing for a faster and more stable learning process, such as required for learning in Robotics. The Q-learning update-rule is widely applied, since it allows to learn without the presence of a model of the environment. However, this update-rule is transition-based and does not take advantage of the underlying episodic structure of collected batch of interactions. The Q-Batch update-rule is proposed in this thesis, to process experiencies along the trajectories collected in the interaction phase. This allows a faster propagation of obtained rewards and penalties, resulting in faster and more robust learning. Non-parametric function approximations are explored, such as Gaussian Processes. This type of approximators allows to encode prior knowledge about the latent function, in the form of kernels, providing a higher level of exibility and accuracy. The application of Gaussian Processes in Batch Reinforcement Learning presented a higher performance in learning tasks than other function approximations used in the literature. Lastly, in order to extract more information from the experiences collected by the agent, model-learning techniques are incorporated to learn the system dynamics. In this way, it is possible to augment the set of collected experiences with experiences generated through planning using the learned models. Experiments were carried out mainly in simulation, with some tests carried out in a physical robotic platform. The obtained results show that the proposed approaches are able to outperform the classical Fitted Q Iteration.

DIRECT NUMERICAL SIMULATION OF INCOMPRESSIBLE MULTIPHASE FLOW WITH PHASE CHANGE

Phase change problems arise in many practical applications such as air-conditioning and refrigeration, thermal energy storage systems and thermal management of electronic devices. The physical phenomenon in such applications are complex and are often difficult to be studied in detail with the help of only experimental techniques. The efforts to improve computational techniques for analyzing two-phase flow problems with phase change are therefore gaining momentum. The development of numerical methods for multiphase flow has been motivated generally by the need to account more accurately for (a) large topological changes such as phase breakup and merging, (b) sharp representation of the interface and its discontinuous properties and (c) accurate and mass conserving motion of the interface. In addition to these considerations, numerical simulation of multiphase flow with phase change introduces additional challenges related to discontinuities in the velocity and the temperature fields. Moreover, the velocity field is no longer divergence free. For phase change problems, the focus of developmental efforts has thus been on numerically attaining a proper conservation of energy across the interface in addition to the accurate treatment of fluxes of mass and momentum conservation as well as the associated interface advection. Among the initial efforts related to the simulation of bubble growth in film boiling applications the work in \cite{Welch1995} was based on the interface tracking method using a moving unstructured mesh. That study considered moderate interfacial deformations. A similar problem was subsequently studied using moving, boundary fitted grids \cite{Son1997}, again for regimes of relatively small topological changes. A hybrid interface tracking method with a moving interface grid overlapping a static Eulerian grid was developed \cite{Juric1998} for the computation of a range of phase change problems including, three-dimensional film boiling \cite{esmaeeli2004computations}, multimode two-dimensional pool boiling \cite{Esmaeeli2004} and film boiling on horizontal cylinders \cite{Esmaeeli2004a}. The handling of interface merging and pinch off however remains a challenge with methods that explicitly track the interface. As large topological changes are crucial for phase change problems, attention has turned in recent years to front capturing methods utilizing implicit interfaces that are more effective in treating complex interface deformations. The VOF (Volume of Fluid) method was adopted in \cite{Welch2000} to simulate the one-dimensional Stefan problem and the two-dimensional film boiling problem. The approach employed a specific model for mass transfer across the interface involving a mass source term within cells containing the interface. This VOF based approach was further coupled with the level set method in \cite{Son1998}, employing a smeared-out Heaviside function to avoid the numerical instability related to the source term. The coupled level set, volume of fluid method and the diffused interface approach was used for film boiling with water and R134a at the near critical pressure condition \cite{Tomar2005}. The effect of superheat and saturation pressure on the frequency of bubble formation were analyzed with this approach. The work in \cite{Gibou2007} used the ghost fluid and the level set methods for phase change simulations. A similar approach was adopted in \cite{Son2008} to study various boiling problems including three-dimensional film boiling on a horizontal cylinder, nucleate boiling in microcavity \cite{lee2010numerical} and flow boiling in a finned microchannel \cite{lee2012direct}. The work in \cite{tanguy2007level} also used the ghost fluid method and proposed an improved algorithm based on enforcing continuity and divergence-free condition for the extended velocity field. The work in \cite{sato2013sharp} employed a multiphase model based on volume fraction with interface sharpening scheme and derived a phase change model based on local interface area and mass flux. Among the front capturing methods, sharp interface methods have been found to be particularly effective both for implementing sharp jumps and for resolving the interfacial velocity field. However, sharp velocity jumps render the solution susceptible to erroneous oscillations in pressure and also lead to spurious interface velocities. To implement phase change, the work in \cite{Hardt2008} employed point mass source terms derived from a physical basis for the evaporating mass flux. To avoid numerical instability, the authors smeared the mass source by solving a pseudo time-step diffusion equation. This measure however led to mass conservation issues due to non-symmetric integration over the distributed mass source region. The problem of spurious pressure oscillations related to point mass sources was also investigated by \cite{Schlottke2008}. Although their method is based on the VOF, the large pressure peaks associated with sharp mass source was observed to be similar to that for the interface tracking method. Such spurious fluctuation in pressure are essentially undesirable because the effect is globally transmitted in incompressible flow. Hence, the pressure field formation due to phase change need to be implemented with greater accuracy than is reported in current literature. The accuracy of interface advection in the presence of interfacial mass flux (mass flux conservation) has been discussed in \cite{tanguy2007level,tanguy2014benchmarks}. The authors found that the method of extending one phase velocity to entire domain suggested by Nguyen et al. in \cite{nguyen2001boundary} suffers from a lack of mass flux conservation when the density difference is high. To improve the solution, the authors impose a divergence-free condition for the extended velocity field by solving a constant coefficient Poisson equation. The approach has shown good results with enclosed bubble or droplet but is not general for more complex flow and requires additional solution of the linear system of equations. In current thesis, an improved approach that addresses both the numerical oscillation of pressure and the spurious interface velocity field is presented by featuring (i) continuous velocity and density fields within a thin interfacial region and (ii) temporal velocity correction steps to avoid unphysical pressure source term. Also I propose a general (iii) mass flux projection correction for improved mass flux conservation. The pressure and the temperature gradient jump condition are treated sharply. A series of one-dimensional and two-dimensional problems are solved to verify the performance of the new algorithm. Two-dimensional and cylindrical film boiling problems are also demonstrated and show good qualitative agreement with the experimental observations and heat transfer correlations. Finally, a study on Taylor bubble flow with heat transfer and phase change in a small vertical tube in axisymmetric coordinates is carried out using the new multiphase, phase change method.

Swath bathymetry using phase difference: Theoretical analysis of acoustical measurement precision

The phase difference principle is widely applied nowadays to sonar systems used for sea floor bathymetry, The apparent angle of a target point is obtained from the phase difference measured between two close receiving arrays. Here we study the influence of the phase difference estimation errors caused by the physical structure of the backscattered signals. It is shown that, under certain current conditions, beyond the commonly considered effects of additive external noise and baseline decorrelation, the processing may be affected by the shifting footprint effect: this is due to the fact that the two interferometer receivers get simultaneous echo contributions coming from slightly shifted seabed parts, which results in a degradation of the signal coherence and, hence, of the phase difference measurement. This geometrical effect is described analytically and checked with numerical simulations, both for square- and sine-shaped signal envelopes. Its relative influence depends on the geometrical configuration and receiver spacing; it may be prevalent in practical cases associated with bathymetric sonars. The cases of square and smooth signal envelopes are both considered. The measurements close to nadir, which are known to be especially difficult with interferometry systems, are addressed in particular.

The phase diagram of the mercury-indium alloy system

The mercury-indium phase diagram has been investigated over the whole composition range from -78°C to the melting point of indium, using thermal analysis, X-ray and superconductivity techniques. This is believed to be the first application of superconductivity measurements to phase diagram investigations. A compound, HgIn, of very limited range of composition, melts congruently at -19.3°C; and gives rise to eutectics at 61.5 at. % indium and -31°C, and at 34.7% indium and -37.2°C. The β phase extends from 2.5 to 19.1 % indium and has a maximum melting point of -14.2°C at 14.2% indium. It forms a peritectic or eutectic at a temperature indistinguishable from the melting point of pure mercury with a solid solution in mercury containing some, but less than 0.3%, indium. A transition from face-centred tetragonal to face-centred cubic in the indium-rich solid solutions at about 93% indium gives rise to a peritectic at 108°C. The solubility of mercury in this face-centred cubic phase falls from about 22% at-31°C to 13% at -78°C. © 1963.

Tile-Based Two-Dimensional Phase Unwrapping for Digital Holography Using a Modular Framework

A variety of physical and biomedical imaging techniques, such as digital holography, interferometric synthetic aperture radar (InSAR), or magnetic resonance imaging (MRI) enable measurement of the phase of a physical quantity additionally to its amplitude. However, the phase can commonly only be measured modulo 2π, as a so called wrapped phase map. Phase unwrapping is the process of obtaining the underlying physical phase map from the wrapped phase. Tile-based phase unwrapping algorithms operate by first tessellating the phase map, then unwrapping individual tiles, and finally merging them to a continuous phase map. They can be implemented computationally efficiently and are robust to noise. However, they are prone to failure in the presence of phase residues or erroneous unwraps of single tiles. We tried to overcome these shortcomings by creating novel tile unwrapping and merging algorithms as well as creating a framework that allows to combine them in modular fashion. To increase the robustness of the tile unwrapping step, we implemented a model-based algorithm that makes efficient use of linear algebra to unwrap individual tiles. Furthermore, we adapted an established pixel-based unwrapping algorithm to create a quality guided tile merger. These original algorithms as well as previously existing ones were implemented in a modular phase unwrapping C++ framework. By examining different combinations of unwrapping and merging algorithms we compared our method to existing approaches. We could show that the appropriate choice of unwrapping and merging algorithms can significantly improve the unwrapped result in the presence of phase residues and noise. Beyond that, our modular framework allows for efficient design and test of new tile-based phase unwrapping algorithms. The software developed in this study is freely available.

Description de la mise en place des techniques p?dagogiques de type collaboratif pour l?am?lioration de la comp?tence communicative orale en fran?ais, chez les ?l?ves de terminale d?un lyc?e priv? [recurso electr?nico]

R?SUM?: Ce m?moire a comme but la description de la mise en place de deux unit?s didactiques pour l?am?lioration de la comp?tence communicative orale en fran?ais d?un groupe d??l?ves de terminale d?un lyc?e de Cali. Ce travail s?inscrit dans la recherche action qui nous a permis de mener un processus de diagnostic, d?impl?mentation et d??valuation. Les techniques utilis?es ont ?t? les enqu?tes, entretiens aux ?l?ves et au professeur titulaire, observations de classes et enregistrements audio et vid?o. L?analyse de la phase d?impl?mentation s?est faite ? partir de trois grandes cat?gories qui rassemblent le sens de l?approche collaborative et la comp?tence communicative orale. Les r?sultats montrent que les ?l?ves ont am?lior? leur expression orale en fran?ais notamment l?enrichissement de vocabulaire et la fluidit?, ? travers des contenus proches de leur r?alit?. Nous montrons les b?n?fices de l?approche collaborative tels que le travail de groupe, le changement de r?les de l?enseignant et des ?l?ves et la possibilit? de co-?valuation du processus dans un cours de fran?ais langue ?trang?re.

Validation d’un procédé automatisé d’extraction sur phase solide de glandes digestives de moules pour l’identification et la quantification des dinophysistoxines en LC/ESI/SM2 par piégeage d’ions quadripolaire

This report presents a new extraction method of the dinophysistoxins (DTXs), confirmed by quantification using high-performance liquid chromatography coupled to mass spectrometry with an ion trap and electro spray interface (HPLC/ESI/MS2). The method originality consists on the adaptation of DTXs basic extraction procedure (liquid/ liquid) to a solid phase extraction (SPE) via a robotic station: ASPEC XLi The parameters of the automatization procedure were optimized to obtain the best DTXs recovery rate. These improvements were loaded with digestive gland mussel homogenat realized on a silica cartridge SPE, activated in hexane/chloroform (50:50), washed with hexane/chloroform (50:50) and extracted by an elution gradient (chloroform methanol (65:35) and methanol (100%)). This method was validated according to two normative referentials (linearity, detection quantification limits and accuracy…) : - The Guide of the Pharmacy industry: Analytical Validation, report of the commission SFSTP 1992 (French Corporation of the Sciences and Technical Pharmaceutical), - - The Procedure of validation of an alternative method in compare to a reference method. (AFNOR, 1998. NF V 03-110). Comparison with the classical liquid/liquid extraction and the automated method present clear advantages. In an analytical method the extraction is generally considered to be the most labor-intensive and error-prone step. This new procedure allowed us to increase throughput, to improve the reproducibility and to reduce the error risks due to the individual manual treatments.

Development of procedures for the triazole fungicides determination in fruits and liquid samples using microextraction techniques and chromatographic separation

Agricultural crops can be damaged by funguses, insects, worms and other organisms that cause diseases and decrease the yield of production. The effect of these damaging agents can be reduced using pesticides. Among them, triazole compounds are effective substances against fungus; for example, Oidium. Nevertheless, it has been detected that the residues of these fungicides in foods as well as in derivate products can affect the health of the consumers. Therefore, the European Union has established several regulations fixing the maximum residue of pesticide levels in a wide range of foods trying to assure the consumer safety. Hence, it is very important to develop adequate methods to determine these pesticide compounds. In most cases, gas or liquid chromatographic (GC, LC) separations are used in the analysis of the samples. But firstly, it is necessary to use proper sample treatments in order to preconcentrate and isolate the target analytes. To reach this aim, microextraction techniques are very effective tools; because allow to do both preconcentration and extraction of the analytes in one simple step that considerably reduces the source of errors. With these objectives, two remarkable techniques have been widely used during the last years: solid phase microextraction (SPME) and liquid phase microextraction (LPME) with its different options. Both techniques that avoid the use or reduce the amount of toxic solvents are convenient coupled to chromatographic equipments providing good quantitative results in a wide number of matrices and compounds. In this work simple and reliable methods have been developed using SPME and ultrasound assisted emulsification microextraction (USAEME) coupled to GC or LC for triazole fungicides determination. The proposed methods allow confidently determine triazole concentrations of μg L‐1 order in different fruit samples. Chemometric tools have been used to accomplish successful determinations. Firstly, in the selection and optimization of the variables involved in the microextraction processes; and secondly, to overcome the problems related to the overlapping peaks. Different fractional factorial designs have been used for the screening of the experimental variables; and central composite designs have been carried out to get the best experimental conditions. Trying to solve the overlapping peak problems multivariate calibration methods have been used. Parallel Factor Analysis 2 (PARAFAC2), Multivariate Curve Resolution (MCR) and Parallel Factor Analysis with Linear Dependencies (PARALIND) have been proposed, the adequate algorithms have been used according to data characteristics, and the results have been compared. Because its occurrence in Basque Country and its relevance in the production of cider and txakoli regional wines the grape and apple samples were selected. These crops are often treated with triazole compounds trying to solve the problems caused by the funguses. The peel and pulp from grape and apple, their juices and some commercial products such as musts, juice and cider have been analysed showing the adequacy of the developed methods for the triazole determination in this kind of fruit samples.

Direct catalytic macrolactonization and application of the phase separation strategy in complex molecule synthesis

Les macrolactones sont des squelettes structuraux importants dans de nombreuses sphères de l’industrie chimique, en particulier dans les marchés pharmaceutiques et cosmétiques. Toutefois, la stratégie traditionnelle pour la préparation de macrolactones demeure incommode en requérant notamment l’ajout (super)stœchiométrique d’agents activateurs. Conséquemment, des quantités stœchiométriques de sous-produits sont générées; ils sont souvent toxiques, dommageables pour l’environnement et nécessitent des méthodes de purification fastidieuses afin de les éliminer. La présente thèse décrit le développement d’une macrolactonisation efficace catalysée au hafnium directement à partir de précurseurs portant un acide carboxylique et un alcool primaire, ne générant que de l’eau comme sous-produit et ne nécessitant pas de techniques d’addition lente et/ou azéotropique. Le protocole a également été adapté à la synthèse directe de macrodiolides à partir de mélanges équimolaires de diols et de diacides carboxyliques et à la synthèse de dimères tête-à-queue de seco acides. Des muscs macrocycliques ainsi que des macrolactones pertinentes à la chimie médicinale ont pu être synthétisés avec l’approche développée. Un protocole pour l’estérification directe catalysée au hafnium entre des acides carboxyliques et des alcools primaires a aussi été développé. Différentes méthodes pour la macrolactonisation catalytique directe entre des alcools secondaires et des acides carboxyliques ont été étudiées. En outre, la stratégie de séparation de phase en macrocyclisation en débit continu a été appliquée lors de la synthèse totale formelle de la macrolactone ivorenolide A. Les étapes-clés de la synthèse incluent une macrocyclisation par le couplage d’alcynes de Glaser-Hay et une réaction de métathèse d’alcènes Z-sélective.

Fitting phase type distribution to service process with sequential phases

The work of this thesis is concerned with fitting Hypo-exponential and Erlang phase type distributions for modeling real life processes with non-exponential service time. There exist situations where exponential distributions cannot explain the distribution of service time properly. This thesis presents the application of two traditional statistical estimation techniques to approximate the service distributions of processes with coefficient of variation less than one. It also presents an algorithm to fit Hypo-exponential distribution for complex situations which can’t be handled properly with traditional estimation techniques. The result shows the effect of variation of sample size and other parameters on the efficiency of the estimation techniques by comparing their respective outputs. Furthermore it checks how accurately the proposed algorithm approximates a given distribution.

Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy.

We apply wide-field interferometric microscopy techniques to acquire quantitative phase profiles of ventricular cardiomyocytes in vitro during their rapid contraction with high temporal and spatial resolution. The whole-cell phase profiles are analyzed to yield valuable quantitative parameters characterizing the cell dynamics, without the need to decouple thickness from refractive index differences. Our experimental results verify that these new parameters can be used with wide field interferometric microscopy to discriminate the modulation of cardiomyocyte contraction dynamics due to temperature variation. To demonstrate the necessity of the proposed numerical analysis for cardiomyocytes, we present confocal dual-fluorescence-channel microscopy results which show that the rapid motion of the cell organelles during contraction preclude assuming a homogenous refractive index over the entire cell contents, or using multiple-exposure or scanning microscopy.

Highly dispersed Ptδ+ on TixCe(1−x)O2 as an active phase in preferential oxidation of CO

Structure–activity relationships for 1 wt.% Pt catalysts were investigated for a series of TixCe(1−x)O2 (x = 1, 0.98, 0.9, 0.5, 0.2 and 0) supports prepared by the sol–gel method. The catalysts prepared by impregnation were characterized in detail by applying a wide range of techniques as N2-isotherms, XRF, XRD, Raman, XPS, H2-TPR, Drifts, UV–vis, etc. and tested in the preferential oxidation of CO in the presence of H2. Also several reaction conditions were deeply analyzed. A strong correlation between catalyst performance and the electronic properties let us to propose, based in all the experimental results, a plausible reaction mechanism where several redox cycles are involved.

Development of measurement and modeling techniques to quantify atmospheric deposition of persistent, bioaccumulative and toxic chemicals in the Great Lakes

Measurement and modeling techniques were developed to improve over-water gaseous air-water exchange measurements for persistent bioaccumulative and toxic chemicals (PBTs). Analytical methods were applied to atmospheric measurements of hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Additionally, the sampling and analytical methods are well suited to study semivolatile organic compounds (SOCs) in air with applications related to secondary organic aerosol formation, urban, and indoor air quality. A novel gas-phase cleanup method is described for use with thermal desorption methods for analysis of atmospheric SOCs using multicapillary denuders. The cleanup selectively removed hydrogen-bonding chemicals from samples, including much of the background matrix of oxidized organic compounds in ambient air, and thereby improved precision and method detection limits for nonpolar analytes. A model is presented that predicts gas collection efficiency and particle collection artifact for SOCs in multicapillary denuders using polydimethylsiloxane (PDMS) sorbent. An approach is presented to estimate the equilibrium PDMS-gas partition coefficient (Kpdms) from an Abraham solvation parameter model for any SOC. A high flow rate (300 L min-1) multicapillary denuder was designed for measurement of trace atmospheric SOCs. Overall method precision and detection limits were determined using field duplicates and compared to the conventional high-volume sampler method. The high-flow denuder is an alternative to high-volume or passive samplers when separation of gas and particle-associated SOCs upstream of a filter and short sample collection time are advantageous. A Lagrangian internal boundary layer transport exchange (IBLTE) Model is described. The model predicts the near-surface variation in several quantities with fetch in coastal, offshore flow: 1) modification in potential temperature and gas mixing ratio, 2) surface fluxes of sensible heat, water vapor, and trace gases using the NOAA COARE Bulk Algorithm and Gas Transfer Model, 3) vertical gradients in potential temperature and mixing ratio. The model was applied to interpret micrometeorological measurements of air-water exchange flux of HCB and several PCB congeners in Lake Superior. The IBLTE Model can be applied to any scalar, including water vapor, carbon dioxide, dimethyl sulfide, and other scalar quantities of interest with respect to hydrology, climate, and ecosystem science.