BOiLS: Bayesian Optimisation for Logic Synthesis

Optimising the quality-of-results (QoR) of circuits during logic synthesis is a formidable challenge necessitating the exploration of exponentially sized search spaces. While expert-designed operations aid in uncovering effective sequences, the increase in complexity of logic circuits favours automated procedures. To enable efficient and scalable solvers, we propose BOiLS, the first algorithm adapting Bayesian optimisation to navigate the space of synthesis operations. BOiLS requires no human intervention and trades-off exploration versus exploitation through novel Gaussian process kernels and trust-region constrained acquisitions. In a set of experiments on EPFL benchmarks, we demonstrate BOiLS's superior performance compared to state-of-the-art in terms of both sample efficiency and QoR values

Spectral fingerprinting of cellular lipid droplets using stimulated Raman scattering microscopy and chemometric analysis

Hyperspectral stimulated Raman scattering (SRS) microscopy is a powerful method for direct visualisation and compositional analysis of cellular lipid droplets. Here we report the application of spectral phasor analysis as a convenient method for the segmentation of lipid droplets using the hyperspectral SRS spectrum in the high wavenumber and fingerprint region of the spectrum. Spectral phasor analysis was shown to discriminate six fatty acids based on vibrational spectroscopic features in solution. The methodology was then applied to studying fatty acid metabolism and storage in a mammalian cancer cell model and during drug-induced steatosis in a hepatocellular carcinoma cell model. The accumulation of fatty acids into cellular lipid droplets was shown to vary as a function of the degree of unsaturation, whilst in a model of drug-induced steatosis, the detection of increased saturated fatty acid esters was observed. Taking advantage of the fingerprint and high wavenumber regions of the SRS spectrum has yielded a greater insight into lipid droplet composition in a cellular context. This approach will find application in the label-free profiling of intracellular lipids in complex disease models

Quelques contribtuions à l'optimisation globale

This work addresses the sequential optimization of an unknown and potentially nonconvex function over a continuous and bounded set. The setup we consider assumes that the function evaluations are noiseless and that the derivative information of the function is unavailable. These problems are of particular interest when the function values are typically expensive to compute, and its derivatives are not available either because the evaluations result from some physical measures, or, more commonly, because it is the result of a possible heavy computer simulation. This includes in particular the problem of tuning the hyperparameters of large neural nets. In the first part, we consider the problem of designing sequential strategies which lead to efficient optimization of an unknown function under the only assumption that it has finite Lipschitz constant. We introduce and analyze a first algorithm, called LIPO, which assumes the Lipschitz constant to be known. Consistency and minimax rates for LIPO are proved, as well as fast rates under an additional Hölder like condition. An adaptive version of LIPO is also introduced for the more realistic setup where the Lipschitz constant is unknown and has to be estimated along with the optimization, and similar theoretical guarantees are shown to hold for the adaptive version of the algorithm. In the second part, we propose to explore concepts from ranking theory based on overlaying level sets in order to develop optimization methods that do not rely on the smoothness of the function. We start by observing that the optimization of the function essentially relies on learning the bipartite rule it induces. Based on this idea, we relate global optimization to bipartite ranking which allows to address the case of functions with weak regularity properties. Novel meta-algorithms for global optimization which rely on the choice of any bipartite ranking method are introduced and theoretical properties are provided in terms of statistical consistency and finite-time convergence toward the optimum. Eventually, the algorithms developed in the thesis are compared to existing state-of-the-art methods over typical benchmark problems for global optimization.Ce travail de thèse s’intéresse au problème d’optimisation séquentielle d’une fonction inconnue définie sur un ensemble continu et borné. Ce type de problème apparaît notamment dans la conception de systèmes complexes, lorsque l’on cherche à optimiser le résultat de simulations numériques ou plus simplement lorsque la fonction que l’on souhaite optimiser ne présente aucune forme de régularité évidente comme la linéarité ou la convexité. Dans un premier temps, nous nous focalisons sur le cas particulier des fonctions lipschitziennes. Nous introduisons deux nouvelles stratégies ayant pour but d’optimiser n’importe quelle fonction de coefficient de Lipschitz connu puis inconnu. Ensuite, en introduisant différentes mesures de régularité, nous formulons et obtenons des résultats de consistance pour ces méthodes ainsi que des vitesses de convergence sur leurs erreurs d’approximation

SERS nanotags for folate receptor α detection at the single cell level : discrimination of overexpressing cells and potential for live cell applications

Folate receptor α (FRα) is a high affinity folate membrane receptor that is overexpressed in a wide variety of cancers. Detecting the overexpression of this receptor is important for cancer cells identification and to potentially guide the choice of treatment since several FRα-targeted drugs are currently in clinical trials. In this work, we built SERS nanotags based on core@shell Au@Ag nanoparticles labelled with resonant Raman-reporter and functionalised with a thiolated PEG linker bearing folic acid at the chain end. Using SERS mapping on single cells, we showed that the nanotags (FR-nanotags) could specifically target FRα on overexpressing HeLa cells and could measure the gradual blocking of FRα by free folic acid introduced in the media along the nanotags. With a control nanotag, we showed that the SERS response was 10-fold higher on HeLa cells when folic acid is present on the PEG linker compared to PEG chains without folic acid. Non-specific binding of the FR-nanotags was demonstrated to be low and mainly caused by the folic acid molecule at the PEG chain end. When comparing cancer cells with different expression levels of FRα, we obtained 4-fold higher SERS response on overexpressing HeLa cells compared to non-overexpressing A549 cells, allowing the discrimination of both cell lines with a high contrast. Owing to the biocompatibility of the developed nanotags, we demonstrated that measurements of FRα on live HeLa cells were also possible and gave similar results to measurements on fixed cells, indicating the versatility of the developed nanotags for detecting FRα under various experimental conditions

Direct determination of the NaF/AlF3 molar ratio by raman spectroscopy in NaF-AlF3-CaF2 melts at 1000° C

For the last 40 years, Raman spectroscopy has been very useful in investigating the structure of corrosive molten salts, such as the cryolite-based melts widely used as electrolyte in the Hall-Heroult process. Even if this process remains the most economically efficient for metallic aluminum electro-production, it suffers from a high energy loss, which is dependent on the melt composition. Therefore, controlling the chemical composition of the electrolyte is essential. The present paper proposes to apply Raman spectroscopy for the direct determination of the NaF-AlF3 molar ratio in NaF-AlF3-CaF2-based melts. Despite the experimental difficulties, a calibration curve based on equilibria taking place in the melt has been developed and the procedure has been successfully compared to industrial samples of known compositions. The possible exportation of the laboratory scale procedure to an industrial environment application for the control of the Hall-Heroult process is finally discussed

Determination of nucleoside triphosphatase activities from measurement of true inorganic phosphate in the presence of labile phosphate compounds

One of the most common assays for nucleoside triphosphatase (NTPase) activity entails the quantification of inorganic phosphate (Pi) as a colored phosphomolybdate complex at low pH. While this assay is very sensitive, it is not selective for Pi in the presence of labile organic phosphate compounds (OPCs). Since NTPase activity assays typically require a large excess of OPCs, such as nucleotides, selectivity for Pi in the presence of OPCs is often critical in evaluating enzyme activity. Here we present an improved method for the measurement of enzymatic nucleotide hydrolysis as Pi released, which achieves selectivity for Pi in the presence of OPCs while also avoiding the costs and hazards inherent in other methods for measuring nucleotide hydrolysis. We apply this method to the measurement of ATP hydrolysis by nitrogenase and GTP hydrolysis by elongation factor G (EF-G) in order to demonstrate the broad applicability of our method for the determination of nucleotide hydrolysis in the presence of interfering OPCs

Dataset for Surface Enhanced Raman Spectroscopy for quantitative analysis: results of a large-scale European multi-instrument interlaboratory study

This dataset contains all the spectra used in "Surface Enhanced Raman Spectroscopy for quantitative analysis: results of a large-scale European multi-instrument interlaboratory study". Data are available in 2 different formats: - a compressed archive with 1 folder ("Dataset”) cointaining all the 3516 TXT files (1 file = 1 spectrum) uploaded by all participants (all spectra of the Interlaboratory study); - 1 single CSV file (“ILSspectra.csv”) with all the 3516 spectra uploaded by all participants in the form of a table. The data are structured as follow, with each row being 1 spectrum, preceded by metadata: "labcode", "substrate", "laser", "method", "sample", "type", "conc", "batch", "replica". Note that for those spectra starting after 400 cm-1 and/or ending before 2000 cm-1 missing values were expressed as NAs

Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory Study

peer reviewedaudience: researcher, professional, studentSurface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint signals of molecules and for the investigation of a series of surface chemical reactions. Many studies introduced quantitative applications of SERS in various fields, and several SERS methods have been implemented for each specific application, ranging in performance characteristics, analytes used, instruments, and analytical matrices. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in highly regulated environments is still considered risky, and the perception of a poorly reproducible and insufficiently robust analytical technique has persistently retarded its routine implementation. Collaborative trials are a type of interlaboratory study (ILS) frequently performed to ascertain the quality of a single analytical method. The idea of an ILS of quantification with SERS arose within the framework of Working Group 1 (WG1) of the EU COST Action BM1401 Raman4Clinics in an effort to overcome the problematic perception of quantitative SERS methods. Here, we report the first interlaboratory SERS study ever conducted, involving 15 laboratories and 44 researchers. In this study, we tried to define a methodology to assess the reproducibility and trueness of a quantitative SERS method and to compare different methods. In our opinion, this is a first important step toward a "standardization" process of SERS protocols, not proposed by a single laboratory but by a larger community. Copyright © 2020 American Chemical Society

Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study

International audienceThe variable configuration of Raman spectroscopic platforms is one of the major obstacles in establishing Raman spectroscopy as a valuable physicochemical method within real-world scenarios such as clinical diagnostics. For such real world applications like diagnostic classification, the models should ideally be usable to predict data from different setups. Whether it is done by training a rugged model with data from many setups or by a primary-replica strategy where models are developed on a ‘primary’ setup and the test data are generated on ‘replicate’ setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable. However, Raman spectra can be highly sensitive to the measurement conditions, and they change from setup to setup even if the same samples are measured. Although increasingly recognized as an issue, the dependence of the Raman spectra on the instrumental configuration is far from being fully understood and great effort is needed to address the resulting spectral variations and to correct for them. To make the severity of the situation clear, we present a round robin experiment investigating the comparability of 35 Raman spectroscopic devices with different configurations in 15 institutes within seven European countries from the COST (European Cooperation in Science and Technology) action Raman4clinics. The experiment was developed in a fashion that allows various instrumental configurations ranging from highly confocal setups to fibre-optic based systems with different excitation wavelengths. We illustrate the spectral variations caused by the instrumental configurations from the perspectives of peak shifts, intensity variations, peak widths, and noise levels. We conclude this contribution with recommendations that may help to improve the inter-laboratory studies