Plasmons in nanoparticles: atomistic Ab Initio theory for large systems

205 p.El trabajo realizado en esta tesis doctoral se centra en la implementación de nuevos algoritmos y de suaplicación en diferentes tipos de nanoestructuras. El programa científico en el que se han llevado a cabolas extensiones es una implementación eficiente de la teoría funcional de densidad dependiente deltiempo, conocida como MBPT-LCAO.Las principales extensiones realizadas son las siguientes: implementación de la espectroscopía de pérdidade energía de electrones en el espacio real, mejora del procedimiento iterativo para permitir cálculos degran tamaño sin precedentes, cálculo del campo eléctrico inducido e implementación de la espectroscopíade dispersión Raman.Estas implementaciones se han utilizado en agregados y agregados dímeros de sodio y plata, así como ennanotubos de carbono y nitruro de boro. Se han calculado tanto el espectro de absorción como los camposeléctricos inducidos para todos estos sistemas. De esta forma, este trabajo nos ha permitido entendermejor la respuesta de tales nanoestructuras bajo la influencia de una perturbación externa

DNA CODING FOR IMAGE STORAGE USING IMAGE COMPRESSION TECHNIQUES

International audienceLiving in the age of the digital media explosion the urge for finding new efficient methods of data storage increases significantly. Existing storage devices such as hard disks, flash, tape or even optical storage have limited durability in the range of 5 to 20 years. Recent studies have proven that the method of DNA data storage introduces a strong candidate to achieve data longevity. The DNA's biological properties permit the compression of a great amount of information into an extraordinary small volume while also promising efficient data storage for millions of years with no loss of information. This work proposes a new encoding scheme especially designed for the encoding of still images, extending the existing algorithms of DNA data storage by introducing image compression techniques

Plasmons in nanoparticles: atomistic Ab Initio theory for large systems

205 p.El trabajo realizado en esta tesis doctoral se centra en la implementación de nuevos algoritmos y de suaplicación en diferentes tipos de nanoestructuras. El programa científico en el que se han llevado a cabolas extensiones es una implementación eficiente de la teoría funcional de densidad dependiente deltiempo, conocida como MBPT-LCAO.Las principales extensiones realizadas son las siguientes: implementación de la espectroscopía de pérdidade energía de electrones en el espacio real, mejora del procedimiento iterativo para permitir cálculos degran tamaño sin precedentes, cálculo del campo eléctrico inducido e implementación de la espectroscopíade dispersión Raman.Estas implementaciones se han utilizado en agregados y agregados dímeros de sodio y plata, así como ennanotubos de carbono y nitruro de boro. Se han calculado tanto el espectro de absorción como los camposeléctricos inducidos para todos estos sistemas. De esta forma, este trabajo nos ha permitido entendermejor la respuesta de tales nanoestructuras bajo la influencia de una perturbación externa

Plasmonic response of metallic nanojunctions driven by single atom motion: Quantum transport revealed in optics

The correlation between transport properties across subnanometric metallic gaps and the optical response of the system is a complex effect that is determined by the fine atomic-scale details of the junction structure. As experimental advances are progressively accessing transport and optical characterization of smaller nanojunctions, a clear connection between the structural, electronic, and optical properties in these nanocavities is needed. Using ab initio calculations, we present here a study of the simultaneous evolution of the structure and the optical response of a plasmonic junction as the particles forming the cavity, two Na380 clusters, approach and retract. Atomic reorganizations are responsible for a large hysteresis of the plasmonic response of the system, which shows a jump-to-contact instability during the approach process and the formation of an atom-sized neck across the junction during retraction. Our calculations demonstrate that, due to the quantization of the conductance in metal nanocontacts, atomic-scale reconfigurations play a crucial role in determining the optical response of the whole system. We observe abrupt changes in the intensities and spectral positions of the dominating plasmon resonances and find a one-to-one correspondence between these jumps and those of the quantized transport as the neck cross-section diminishes. These results reveal an important connection between transport and optics at the atomic scale, which is at the frontier of current optoelectronics and can drive new options in optical engineering of signals driven by the motion and manipulation of single atoms.We acknowledge financial support from Projects FIS2013-41184-P and MAT2013-46593-C6-2-P from MINECO. M.B., P.K., F.M., and D.S.P. also acknowledge support from the ANR-ORGAVOLT project and the Euroregion Aquitaine-Euskadi program. M.B. acknowledges support from the Departamento de Educacion of the Basque Government through a Ph.D. grant. P.K. acknowledges financial support from the Fellows Gipuzkoa program of the Gipuzkoako Foru Aldundia through the FEDER funding scheme of the European Union. J.A. also acknowledges support from Grant 70NANB15H321, “PLASMOQUANTUM”, from the US Department of Commerce (NIST).Peer Reviewe

Atomistic near-field nanoplasmonics: Reaching atomic-scale resolution in nanooptics

Electromagnetic field localization in nanoantennas is one of the leitmotivs that drives the development of plasmonics. The near-fields in these plasmonic nanoantennas are commonly addressed theoretically within classical frameworks that neglect atomic-scale features. This approach is often appropriate since the irregularities produced at the atomic scale are typically hidden in far-field optical spectroscopies. However, a variety of physical and chemical processes rely on the fine distribution of the local fields at this ultraconfined scale. We use time-dependent density functional theory and perform atomistic quantum mechanical calculations of the optical response of plasmonic nanoparticles, and their dimers, characterized by the presence of crystallographic planes, facets, vertices, and steps. Using sodium clusters as an example, we show that the atomistic details of the nanoparticles morphologies determine the presence of subnanometric near-field hot spots that are further enhanced by the action of the underlying nanometric plasmonic fields. This situation is analogue to a self-similar nanoantenna cascade effect, scaled down to atomic dimensions, and it provides new insights into the limits of field enhancement and confinement, with important implications in the optical resolution of field-enhanced spectroscopies and microscopies.We acknowledge financial support from projects FIS2013-14481-P and MAT2013-46593-C6-2-P from MINECO. M.B., P.K., F.M., and D.S.P. also acknowledge support from the ANR-ORGAVOLT project and the Euroregion Aquitaine-Euskadi program. M.B. acknowledges support from the Departamento de Educacion of the Basque Government through a PhD grant, as well as from Euskampus and the DIPC at the initial stages of this work. R.E. and P.K. acknowledge financial support from the Fellows Gipuzkoa program of the Gipuzkoako Foru Aldundia through the FEDER funding scheme of the European Union, “Una manera de hacer Europa”.Peer Reviewe

miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1

As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases. © 2013 Lino Cardenas et al

Identification of Keratinocyte Growth Factor as a Target of microRNA-155 in Lung Fibroblasts: Implication in Epithelial-Mesenchymal Interactions

International audienceBACKGROUND: Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection

Plasmons in nanoparticles: atomistic Ab Initio theory for large systems

Thesis submitted to the University of the Basque Country for the degree of Doctor in Physics.La capacidad de entender la materia y su interacción con el medio determinan en gran parte el desarrollo de las nuevas tecnologías. Hoy en día, las nanotecnologías son un campo emergente de investigación debido al gran impacto que tienen en la sociedad. Las simulaciones computacionales de fenómenos físicos en la nanoescala han contribuido a la aceleración de su desarrollo. En esta tesis doctoral nos hemos basado en simulaciones ab initio atomísticas para explicar el comportamiento de nanopartículas sometidas a estímulos externos. Con “atomístico” nos referimos a que la geometría del sistema se descibe mediante posiciones realístas de los átomos, es decir, que se tienen en cuenta las posiciones atómicas y la atracción Coulombiana generada por cada núcleo, en vez de reemplazarlas por un potencial efectivo suave que confina los electrónes en objetos de forma simple, como una esfera. “ab initio” significa que nos hemos basado en las leyes de la mecánica cuántica para modelar los electrones del sistema. De esta forma, en este trabajo hemos podido simular la interacción de centenas de electrones confinados dentro de nanopartículas, tanto entre ellos como con el medio. Este problema se conoce como el problema de muchos cuerpos ( many body problem en inglés). Desafortunadamente, hay que recurrir a aproximaciones para resolver el problema de muchos cuerpos. Las aproximaciones adoptadas en esta tesis son las integradas en la teoriá del funcional de la densidad (DFT, en inglés density functional theory) implementadas en los paquetes de SIESTA (Spanish Initiative for Electronic Simulations with Thousands of Atoms), así como su extensión a fenómenos dependientes del tiempo (TDDFT, en inglés timedependent DFT) implementadas en los paquetes de MBPT-LCAO (Many Body Perturbation Theory - Linear Combination of Atomic Orbitals) y PySCFNAO (Python-Based Simulations of Chemistry Framework - Numerical Atomic Orbitals). Por otra parte, en esta tesis doctoral hemos conseguido implementar con éxito nuevas funcionalidades en los paquetes de MBPT-LCAO y PySCF-NAO. Ambos paquetes han sido utilizados para calcular las propiedades de estados excitados de sistemas finitos como agregados atómicos (clusters en inglés) metálicos, fragmentos de nanotubos y moléculas pequeñas.I have to acknowledge the financial support from the Departamento de Educación of the Basque Government through a PhD grant, as well as from Euskampus and the DIPC at the initial stage of my work. I gratefully acknowledge the support of NVIDIA Corporation with the donation of the Tesla K40 GPU used for this research.Peer reviewe