Short-range order in disordered phases using neutron diffraction

Neutron diffraction is a powerful technique that allows to probe the structure of disordered phases across a variety of length scales. However, due to the inherent complexity of these disordered hases, the analysis of the information contained in the experimental data is not obvious. In this work, a few alternative methods are presented that allow to make the most of the neutron diffraction measurements as well as the molecular configurations obtained from molecular dynamics simulations or data modelling. They mainly consist in a Bayesian approach to fit the molecular structures measured with neutron diffraction, and a multidimensional analysis of the molecular structure probability distribution functions obtained from simulations or data modelling techniques, instead of the standard averaging over many variables. These methodologies are then applied to the structural investigation of several disordered systems in order to answer a series of open questions: the origin of the liquid-liquid transition in trans-1,2-dichloroethene (C2Cl2H2), the extreme fragility of 1,1,2,2-tetrachloro-1,2-difluoroethane's orientational glass (F-112, C2Cl4F2), the local density paradox in carbon tetrachloride (CCl4), and the roles of steric and electrostatic interactions in the short range order of the liquids of quasitetrahedral molecules, particularly trichlorobromomethane (CBrCl3) and dibromodichloromethane (CBr2Cl2). Additionally, a concise summary of the theoretical framework for neutron diffraction of disordered systems, as well as the practicalities of the experimental setup and the necessary data treatment, are also included to provide interested researchers with a self-contained overview on the topic.La difracció de neutrons és una tècnica molt potent que permet sondar l'estructura de fases desordenades en un ventall d'escales de longitud. Tanmateix, degut a la complexitat inherent d'aquestes fases desordenades, l'anàlisi de la informació que es desprèn de les dades experimentals no és evident. En aquest treball es presenten diversos mètodes alternatius que permeten treure el màxim profit de les mesures de difracció de neutrons, així com de les configuracions moleculars obtingudes en simulacions de dinàmica molecular o del modelatge de les dades. Aquests mètodes consisteixen principalment en un enfocament bayesià en l'ajust de les estructures moleculars mesurades amb difracció de neutrons, i en una anàlisi multidimensional de les funcions de distribució de probabilitat de l'estructura molecular obtingudes en simulacions o tècniques de modelatge de dades, en comptes del mitjanat de diverses variables estàndard. Aquestes metodologies s'apliquen a la investigació de diversos sistemes desordenats per tal de resoldre una sèrie de qüestions obertes: l'origen de la transició líquid-líquid en el trans-1,2-dicloroetà (C2Cl2H2), l'extrema fragilitat del vidre orientacional del 1,1,2,2-tetracloro-1,2-difluoroetà (F-112, C2Cl4F2), la paradoxa de la densitat local en el tetraclorur de carboni (CCl4), i els rols de les interaccions estèrica i electrostàtica en l'ordre de curt abast de líquids de molècules quasitetraèdriques, en particular el triclorobromometà (CBrCl3) i el dibromodiclorometà (CBr2Cl2). Addicionalment, també s'hi inclou un breu repàs del marc teòric de la difracció de neutrons en sistemes desordenats, així com dels aspectes pràctics de l'equip experimental i del tractament de dades necessari, per tal que els investigadors interessats disposin d'una visió general completa sobre tema

Multiphoton imaging of melanoma 3D models with plasmonic nanocapsules

We report the synthesis of plasmonic nanocapsules and the cellular responses they induce in 3D melanoma models for their perspective use as a photothermal therapeutic agent. The wall of the nanocapsules is composed of polyelectrolytes. The inner part is functionalized with discrete gold nanoislands. The cavity of the nanocapsules contains a fluorescent payload to show their ability for loading a cargo. The nanocapsules exhibit simultaneous two-photon luminescent, fluorescent properties and X-ray contrasting ability. The average fluorescence lifetime (τ) of the nanocapsules measured with FLIM (0.3 ns) is maintained regardless of the intracellular environment, thus proving their abilities for bioimaging of models such as 3D spheroids with a complex architecture. Their multimodal imaging properties are exploited for the first time to study tumorspheres cellular responses exposed to the nanocapsules. Specifically, we studied cellular uptake, toxicity, intracellular fate, generation of reactive oxygen species, and effect on the levels of hypoxia by using multi-photon and confocal laser scanning microscopy. Because of the high X-ray attenuation and atomic number of the gold nanostructure, we imaged the nanocapsule-cell interactions without processing the sample. We confirmed maintenance of the nanocapsules’ geometry in the intracellular milieu with no impairment of the cellular ultrastructure. Furthermore, we observed the lack of cellular toxicity and no alteration in oxygen or reactive oxygen species levels. These results in 3D melanoma models contribute to the development of these nanocapsules for their exploitation in future applications as agents for imaging-guided photothermal therapy. Statement of Significance: The novelty of the work is that our plasmonic nanocapsules are multimodal. They are responsive to X-ray and to multiphoton and single-photon excitation. This allowed us to study their interaction with 2D and 3D cellular structures and specifically to obtain information on tumor cell parameters such as hypoxia, reactive oxygen species, and toxicity. These nanocapsules will be further validated as imaging-guided photothermal probe

Machine learning copies as a means for black box model evaluation

Treballs finals del Màster de Fonaments de Ciència de Dades, Facultat de matemàtiques, Universitat de Barcelona. Curs: 2020-2021. Tutor: David Zeber i Oriol Pujol Vila[en] The use of propietary black-box machine learning models and APIs in the form of Machine Learning as a Service, makes it very difficult to control and mitigate their potential harmful effects (such as lack of transparency, privacy safeguards, robustness, reusability or fairness). The state-of-the-art technique of Machine Learning Classifier Copying allows us to build a new model that replicates the decision behaviour of an existing one without the need of knowing its architecture nor having access to the original training data. PRESC (Performance and Robustness Evaluation for Statistical Classifiers) is an existing free software tool for the evaluation of machine learning classifiers, which is maintained by Mozilla’s Data Science team. It aims to provide a toolkit to analyze model performance beyond the standard accuracy-based methods and into areas which tend to be underexplored in data science practice. Among the multiple applications of Machine Learning Classifier Copying, a systematic construction and examination of model copies has the potential to be an universally accessible and inexpensive approach to study and evaluate a rich variety of original models, and to help understand its behavior. In this work, an implementation of Machine Learning Classifier Copying has been contributed to the PRESC project, so that this tool becomes readily accessible to researchers and practitioners, and its applicability and performance in a synthetic problem has been explored to understand the copying process. The solution provides a model agnostic sampling strategy and an automated copy process for a number of fundamentally different hypothesis spaces, so that the set of achievable copy-model-fidelity measures can be used as a diagnostic measure of the original model characteristics

Role of steric and electrostatic effects in the short-range order of quasitetrahedral molecular liquids

The study of how both steric and electrostatic interactions affect the structure of liquids formed by quasitetrahedral molecules has been undertaken in this work. We have studied trichlorobromomethane (CBrCl3) and dibromodichloromethane (CBr2Cl2), both displaying a dipole along their C3v and C2v molecular symmetry axes, respectively. The short-range order of the liquid state has been determined using neutron diffraction experiments that were modeled through the reverse Monte Carlo (RMC) technique. To study changes in steric effects due to the distortion of the tetrahedral symmetry, we have compared our results with a previous RMC modeling of carbon tetrachloride (CCl4). The subtle effects of the dipole in the structure of the liquid have been determined using a set of molecular dynamics simulations with and without atomic partial charges, being the force field validated via comparison with the diffraction data. In a first approximation, neither steric nor electrostatic interactions are able to modify the molecular ordering of a fully tetrahedral liquid such as CCl4. A more detailed analysis indicates that, although the interaction between dipoles does not have appreciable effects when aligned along the C3v molecular axes, as for the CBrCl3, it enhances the antiparallel orientation of dipoles when it is oriented along the C2v axes, as in the case of CBr2Cl2

Role of steric and electrostatic effects in the short-range order of quasitetrahedral molecular liquids

The study of how both steric and electrostatic interactions affect the structure of liquids formed by quasitetrahedral molecules has been undertaken in this work. We have studied trichlorobromomethane (CBrCl3) and dibromodichloromethane (CBr2Cl2), both displaying a dipole along their C3v and C2v molecular symmetry axes, respectively. The short-range order of the liquid state has been determined using neutron diffraction experiments that were modeled through the reverse Monte Carlo (RMC) technique. To study changes in steric effects due to the distortion of the tetrahedral symmetry, we have compared our results with a previous RMC modeling of carbon tetrachloride (CCl4). The subtle effects of the dipole in the structure of the liquid have been determined using a set of molecular dynamics simulations with and without atomic partial charges, being the force field validated via comparison with the diffraction data. In a first approximation, neither steric nor electrostatic interactions are able to modify the molecular ordering of a fully tetrahedral liquid such as CCl4. A more detailed analysis indicates that, although the interaction between dipoles does not have appreciable effects when aligned along the C3v molecular axes, as for the CBrCl3, it enhances the antiparallel orientation of dipoles when it is oriented along the C2v axes, as in the case of CBr2Cl2

Microscopic dynamics of glycerol: a QENS study

We report on a quasielastic incoherent neutron scattering (QENS) experiment onliquid glycerol. QENS data were collected at thetemperature T=380 K and witharesolution(FWHM)R=55µeV.The analysis of the quasielastic signal enables us to draw a consistentpicture of the diffusive mechanism on a picosecond time scale and to compare with most recentmodels for glycerol dynamics. Model selection, performed with the fitting algorithm FABADA, givesus a preliminary description about the motions of the glycerol molecules in its liquid stat

Multiphoton imaging of melanoma 3D models with plasmonic nanocapsules

Data de publicació electrònica: 31-01-2022We report the synthesis of plasmonic nanocapsules and the cellular responses they induce in 3D melanoma models for their perspective use as a photothermal therapeutic agent. The wall of the nanocapsules is composed of polyelectrolytes. The inner part is functionalized with discrete gold nanoislands. The cavity of the nanocapsules contains a fluorescent payload to show their ability for loading a cargo. The nanocapsules exhibit simultaneous two-photon luminescent, fluorescent properties and X-ray contrasting ability. The average fluorescence lifetime (τ) of the nanocapsules measured with FLIM (0.3 ns) is maintained regardless of the intracellular environment, thus proving their abilities for bioimaging of models such as 3D spheroids with a complex architecture. Their multimodal imaging properties are exploited for the first time to study tumorspheres cellular responses exposed to the nanocapsules. Specifically, we studied cellular uptake, toxicity, intracellular fate, generation of reactive oxygen species, and effect on the levels of hypoxia by using multi-photon and confocal laser scanning microscopy. Because of the high X-ray attenuation and atomic number of the gold nanostructure, we imaged the nanocapsule-cell interactions without processing the sample. We confirmed maintenance of the nanocapsules' geometry in the intracellular milieu with no impairment of the cellular ultrastructure. Furthermore, we observed the lack of cellular toxicity and no alteration in oxygen or reactive oxygen species levels. These results in 3D melanoma models contribute to the development of these nanocapsules for their exploitation in future applications as agents for imaging-guided photothermal therapy. STATEMENT OF SIGNIFICANCE: The novelty of the work is that our plasmonic nanocapsules are multimodal. They are responsive to X-ray and to multiphoton and single-photon excitation. This allowed us to study their interaction with 2D and 3D cellular structures and specifically to obtain information on tumor cell parameters such as hypoxia, reactive oxygen species, and toxicity. These nanocapsules will be further validated as imaging-guided photothermal probes.Pilar Rivera Gil acknowledges the Ministry of Science, Innovation and Universities (MICINN); the AEI (AEI-PID2019–106755RB-I00, RYC-2012–10059, MDM-2014–0370–04/ BES-2015–075020, CTQ2013–45433-P[FEDER], MAT2016–75362-C3–2-R, AEI-SAF2015–73052-EXP, CEX2018–000792-M); and the AGAUR (2017 SGR 1054) for financial support. We thank the UPF/CRG Advanced Microscopy Unit (PRBB, Barcelona) for assistance in the setup of multiphoton microscopy. Work also supported by the Ministerio de Ciencia e Innovación de España (project PID2019-106211RB-I00), by the Comunidad Autónoma de Madrid (B2017/BMD-3867 RENIM-CM), and co-financed by the European Structural and Investment fund. Additional funding was provided by the European Union's Horizon 2020 FET Open program (Grant Agreement No. 801305, NanoTBTech), and also by COST action CA17140

Disorder effects on heat transport properties of orientationally disordered crystals

Postprint (published version