Atomic imaging of complex molecular

One of the significant challenges of modern science is to track and image chemical reactions as they occur. The molecular movies, the precise spatiotemporal tracking of changes in their molecular dynamics, will provide a wealth of actionable insights into how nature works. Experimental techniques need to resolve the relevant molecular motions in atomic resolution, which includes (10^(-10) m) spatial dimensions and few- to hundreds of femtoseconds (10^(-15) s) temporal resolution. Laser-induced electron diffraction (LIED), a laser-based electron diffraction technique, images even singular molecular structures with combined sub-atomic picometre and femto-to attosecond spatiotemporal resolution. Here, a laser-driven attosecond electron wave packet scatters the parent’s ion after photoionization. The measured diffraction pattern of the electrons provides a unique fingerprint of molecular structure. Taking snapshots of molecular dynamics via the LIED technique is proved to be a potent tool to understand the intertwining of molecules and how they react, change, break, bend, etc. This thesis is especially interested in exploiting advanced LIED imaging techniques to retrieve large complex molecular structures. So far, LIED has successfully retrieved molecular information from small gas-phase molecules like oxygen (O2), nitrogen (N2), acetylene (C2H2), carbon disulfide (CS2), ammonia (NH3) and carbonyl sulfide (OCS). Nevertheless, most biology interesting organic molecules typically exist as liquid or solid at room temperature. In order to accomplish the final goal to extract these larger complex molecular structural information, we need to overcome two main challenges: delivering the liquid or solid samples as a gas-phase jet with sufficient gas density in the experiment and developing a new retrieval algorithm to extract the geometrical information from the diffraction pattern. We tested one of the most simple liquid molecules - water H2O in the reaction chamber as a primary step. We traced the variation of H2O+ cation structure under the different electric fields. To solve the problem of unsatisfactory gas density, we present a novel delivery system utilizing Tesla valves that generates more than an order-of-magnitude denser gaseous beam. Machine learning is well qualified to solve difficulties with manifold degrees of freedom. We use convolutional neural networks (CNNs) combined with LIED techniques to enable atomic-resolution imaging of the complex chiral molecule Fenchone (C10H16O).Uno de los desafíos importantes de la ciencia moderna es rastrear y obtener imágenes de las reacciones químicas a medida que ocurren. Las películas moleculares, el seguimiento espaciotemporal preciso de los cambios en su dinámica molecular, proporcionarán una gran cantidad de conocimientos prácticos sobre cómo funciona la naturaleza. Las técnicas experimentales necesitan resolver los movimientos moleculares relevantes en resolución atómica, que incluye ($10^{-10}$ m) dimensional espacial y resolución temporal de pocos a cientos de femtosegundos ($10^{-15}$ s). La difracción de electrones inducida por láser (LIED-Laser-induced electron diffraction), una técnica de difracción de electrones basada en láser, crea imágenes incluso de estructuras moleculares singulares con una resolución espaciotemporal subatómica combinada de picómetro y femto a attosegundo. Aquí, un paquete de ondas de electrones de attosegundos impulsado por láser dispersa el ion del padre después de la fotoionización. El patrón de difracción medido de los electrones proporciona una huella única de la estructura molecular. Se ha demostrado que tomar instantáneas de la dinámica molecular a través de la técnica LIED es una herramienta potente para comprender el entrelazamiento de las moléculas y cómo reaccionan, cambian, se rompen, se doblan, etc. Esta tesis está especialmente interesada en explotar técnicas avanzadas de imagen LIED para recuperar estructuras moleculares grandes y complejas. Hasta ahora, LIED ha recuperado con éxito información molecular de pequeñas moléculas en fase gaseosa como oxígeno (O2), nitrógeno (N2), acetileno (C2H2), disulfuro de carbono (CS2), amoníaco (NH3) y sulfuro de carbonilo (OCS). Sin embargo, la mayoría de las moléculas orgánicas interesantes para la biología suelen existir como líquidas o sólidas a temperatura ambiente. Para lograr el objetivo final de extraer esta información estructural molecular compleja más grande, debemos superar dos desafíos principales: entregar las muestras líquidas o sólidas como un chorro de fase gaseosa con suficiente densidad de gas en el experimento y desarrollar un nuevo algoritmo de recuperación para extraer la información geométrica del patrón de difracción. Probamos una de las moléculas líquidas más simples: agua H2O en la cámara de reacción como primer paso. Trazamos la variación de la estructura del catión H2O+ bajo los diferentes campos eléctricos. Para resolver el problema de la densidad de gas insatisfactoria, presentamos un novedoso sistema de suministro que utiliza válvulas Tesla que genera más de un haz gaseoso más denso en un orden de magnitud. El aprendizaje automático está bien calificado para resolver dificultades con múltiples grados de libertad. Utilizamos redes neuronales convolucionales (CNN-convolutional neural networks) combinadas con técnicas LIED para permitir imágenes de resolución atómica de la molécula quiral compleja Fenchone (C10H16OPostprint (published version

Axisymmetric contact problem for a flattened cell : contributions of substrate effect and cell thickness to the determination of viscoelastic properties by using AFM indentation

Nanoindentation technology has proven an effective method to investigate the viscoelastic properties of biological cells. The experimental data obtained by nanoindentation are frequently interpreted by Hertz contact model. However, in order to facilitate the application of Hertz contact model, a mass of studies assume cells have infinite thickness which does not necessarily represent the real situation. In this study, a rigorous contact model based upon linear elasticity is developed for the interpretation of indentation tests of flattened cells which represent a factual morphology. The cell, normally bonded to the petri dish, is initially treated as an elastic layer of finite thickness perfectly fixed to a rigid substrate, and the conic indenter is assumed to be frictionless. The theory of linear elasticity is utilized to solve this contact issue and then the solutions are extended to viscoelastic situation which is regarded as a good indicator for mechanical properties of biological cells. To test the present model, an AFM-based creep test has been conducted on living human hepatocellular carcinoma cell (SMMC-7721 cell) and its fullerenol-treated counterpart. The results indicate that the present model could not only describe very well the creep behavior of SMMC-7721 cells, but can also curb overestimation of the mechanical properties due to substrate effect. Moreover, the present model could identify the difference between the control and treated SMMC-7721 cells in terms of the extracted viscoelastic parameters, suggesting its potential in revealing the biomechanical effects of fullerenol-like drug treatment on cancerous cells

Investigation of effect of fullerenol on viscoelasticity properties of human hepatocellular carcinoma by AFM-Based creep tests

Cellular elasticity is frequently measured to investigate the biomechanical effects of drug treatment, diseases and aging. In light of cellular viscosity property exhibited by filament actin networks, this study investigates the viscoelasticity alterations of human hepatocellular carcinoma (SMMC-7721) cell subjected to fullerenol treatment by means of creep tests realized by AFM indentation. An SMMC-7721 cell was first modeled as a sphere and then a flattened layer with finite thickness. Both Sneddon’s solutions and Dimitriadis model have been modified to adapt for viscoelastic situation, which are used to fit the same indentation depth – time curves obtained by creep tests. We find that the SMMC-7721 cell’s creep behavior is well described by the two modified models, and the divergence of parameters determined by the two models is justified. By fullerenol treatment, the SMMC-7721 cell exhibits a significant decrease of elastic modulus and viscosity, which is presumably due to the disruption of actin filaments. This work represents a new attempt to understand the alternation of the viscoelastic properties of cancerous cells under the treatment of fullerenol, which has the significance of comprehensively elucidating the biomechanical effects of anticancer agents (such as fullerenol) on cancer cells

Art Museums at Home? A Content Analysis of Art Museums’ Websites During COVID-19.

This study explores the role of art museums’ websites in museum operations after the COVID-19 outbreak in the United States. It seeks to provide a landscape of the art museum reaction through a qualitative content analysis during the pandemic by sampling nine art museums’ websites in three states. The sampled websites showed a consistent increase in their elements and activities. Over a six-month period, the art museums' webpages changed in terms of content and structure to serve different types of audiences and to meet the constantly changing needs of the users. This study summarizes common and different strategies adopted by each museum and identifies functional changes in the art museum websites. The findings indicate the impact of COVID-19 on the art museum community and provide directions for the future virtualization and web-based activities of cultural heritage institutions experiencing unavoidable external factors affecting onsite visitation.Master of Science in Library Scienc

Determination of work of adhesion of biological cell under AFM bead indentation

Hertz contact theory has been widely used for the determination of cell elasticity based on AFM indentation experiments. In light of the adhesive contact between AFM tip and cell, this study applied Johnson–Kendall–Roberts (JKR) model to fit the indentation force–displacement (F–D) curves reported previously. A MIN6 cell has been modeled as first a sphere and then a flattened cell with different thicknesses. The results have shown that both basic JKR model and “generalized” JKR model can best describe the unloading force–displacement behaviors of the indentation curves. The Young׳s modulus of the cell and the work of adhesion of the cell–indenter interface are obtained. In comparison to the Hertzian contact model, the JKR model provides obviously better fitting to the experimental results, indicating that the adhesion is significant in the cell interaction

Investigation of work of adhesion of biological cell (human hepatocellular carcinoma) by AFM nanoindentation

In this study, we presented an investigation of mechanical properties by AFM nanoindentation on human hepatocellular carcinoma cells treated with fullerenol for 24, 48 and 72 hours. AFM nanoindentation was routinely applied to investigate the morphology and biomechanical properties of living carcinoma cells, and adhesion phenomena (negative force) were detected in the obtained force-displacement curves. Conventionally, Hertz contact model has been widely used for determination of cell elasticity, however this contact model cannot account for adhesion. Alternatively, JKR contact model, as expected for adhesion circumstance, has been applied to fit the obtained force-displacement curves. In this investigation, we have derived both the work of adhesion and the elastic modulus of biological cells (human hepatocellular carcinoma) under fullerenol treatment. The results show that the chosen JKR model can provide better fitting results than Hertz contact model. The results show that both Young’s modulus and work of adhesion exhibit significant variation as the treatment time increases. The calculated mechanical properties of elastic modulus and work of adhesion can be used as an effective bio-index to evaluate the effects of fullerenol or other anticancer agents on cancer cells and thus to provide insight into cancer progression in the treatment

Effects of Xinwei granule on expression levels of cyclin D1 and its upstream genes in gastric intraepithelial neoplasia tissues

Purpose: To explore the effects of Xinwei granule (XWG) on low-grade gastric intraepithelial neoplasia (LGIN) and the underlying mechanisms. Methods: To establish LGIN model, Wistar rats were treated with N-methyl-N'-nitrosoguanidine for 3 months. LGIN model rats were randomly grouped into five groups (n = 15), viz, negative control (NC), normal saline (NS) group, Xinwei granule (XWG) group, Weifuchun tablet (WFCT) group, and vatacoenayme tablet (VT) group. Normal rats (n = 17) served as negative control. Histological evaluation of gastric mucosa was undertaken using hematoxylin and eosin staining. Quantitative realtime polymerase chain reaction (qRT-PCR), western blot, and immunohistochemical assays were performed to determine mRNA expressions, protein expression, and the distribution of cyclin D1, kruppel-like factor 4 (KLF4), and p21-WAF1-CIP1, respectively. Results: Compared with LGIN group, the body weight of the rats increased in XWG, WFCT, and VT groups. The pathological characteristics of LGIN group were alleviated by XWG, WFCT and VT treatments. The positive expression of cyclin D1 was enhanced in LGIN group, but reduced in XWG, WFCT and VT groups. The expression levels of KLF4 and p21-WAF1-CIP1, upstream regulators of cyclin D1 reduced in LGIN groups. However, administration of XWG, WFCT and VT strengthened the expressions of KLF4 and p21-WAF1-CIP1. More importantly, the protective effects of XWG against LGIN were superior to those of WFCT and VT. Conclusion: Xinwei granules alleviate LGIN in vivo by inhibiting cyclin D1 expression and enhancing KLF4 and p21-WAF1-CIP1 expression

Effect of microarc oxidation time on electrochemical behaviors of coated bio-compatible magnesium alloy

Magnesium alloys are newly promising biomaterials with potential application of human bone replacement. However, there is a drawback due to their high corrosion rates. In this study, AZ31 magnesium alloys were coated using microarc oxidation (MAO) process. Two oxidation durations, 1 minute and 5 minutes, were used. The samples were immersed in the simulated body fluid (SBF) for up to seven days. Then the electrochemical behaviors of the two samples were comparatively investigated. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) experiments were used. The results show that the 5-minute MAO coated sample had a better corrosion resistance than the 1-minute MAO coated sample. The study shows processing parameters, e.g., oxidation time, can be used to design an optimized MAO-coated magnesium alloy with controlled corrosion rates

The dual effect of background music on creativity: perspectives of music preference and cognitive interference

Music, an influential environmental factor, significantly shapes cognitive processing and everyday experiences, thus rendering its effects on creativity a dynamic topic within the field of cognitive science. However, debates continue about whether music bolsters, obstructs, or exerts a dual influence on individual creativity. Among the points of contention is the impact of contrasting musical emotions–both positive and negative–on creative tasks. In this study, we focused on traditional Chinese music, drawn from a culture known for its ‘preference for sadness,’ as our selected emotional stimulus and background music. This choice, underrepresented in previous research, was based on its uniqueness. We examined the effects of differing music genres (including vocal and instrumental), each characterized by a distinct emotional valence (positive or negative), on performance in the Alternative Uses Task (AUT). To conduct this study, we utilized an affective arousal paradigm, with a quiet background serving as a neutral control setting. A total of 114 participants were randomly assigned to three distinct groups after completing a music preference questionnaire: instrumental, vocal, and silent. Our findings showed that when compared to a quiet environment, both instrumental and vocal music as background stimuli significantly affected AUT performance. Notably, music with a negative emotional charge bolstered individual originality in creative performance. These results lend support to the dual role of background music in creativity, with instrumental music appearing to enhance creativity through factors such as emotional arousal, cognitive interference, music preference, and psychological restoration. This study challenges conventional understanding that only positive background music boosts creativity and provides empirical validation for the two-path model (positive and negative) of emotional influence on creativity