11,831 research outputs found

    Variable optical elements for fast focus control

    Full text link
    In this Review, we survey recent developments in the emerging field of high-speed variable-z-focus optical elements, which are driving important innovations in advanced imaging and materials processing applications. Three-dimensional biomedical imaging, high-throughput industrial inspection, advanced spectroscopies, and other optical characterization and materials modification methods have made great strides forward in recent years due to precise and rapid axial control of light. Three state-of-the-art key optical technologies that enable fast z-focus modulation are reviewed, along with a discussion of the implications of the new developments in variable optical elements and their impact on technologically relevant applications

    Interview with Wolfgang Knauss

    Get PDF
    An oral history in four sessions (September 2019–January 2020) with Wolfgang Knauss, von Kármán Professor of Aeronautics and Applied Mechanics, Emeritus. Born in Germany in 1933, he speaks about his early life and experiences under the Nazi regime, his teenage years in Siegen and Heidelberg during the Allied occupation, and his move to Pasadena, California, in 1954 under the sponsorship of a local minister and his family. He enrolled in Caltech as an undergraduate in 1957, commencing a more than half-century affiliation with the Institute and GALCIT (today the Graduate Aerospace Laboratories of Caltech). He recalls the roots of his interest in aeronautics, his PhD solid mechanics studies with his advisor, M. Williams, and the GALCIT environment in the late 1950s and 1960s at the dawn of the Space Age, including the impact of Sputnik and classes with NASA astronauts. He discusses his experimental and theoretical work on materials deformation, dynamic fracture, and crack propagation, including his solid-propellant fuels research for NASA and the US Army, wide-ranging programs with the US Navy, and his pioneering micromechanics investigations and work on the time-dependent fracture of polymers in the 1990s. He offers his perspective on GALCIT’s academic culture, its solid mechanics and fluid mechanics programs, and its evolving administrative directions over the course of five decades, as well as its impact and reputation both within and beyond Caltech. He describes his work with Caltech’s undergraduate admissions committee and his scientific collaborations with numerous graduate students and postdocs and shares his recollections of GALCIT and other Caltech colleagues, including C. Babcock, D. Coles, R.P. Feynman, Y.C. Fung, G. Neugebauer, G. Housner, D. Hudson, H. Liepmann, A. Klein, G. Ravichandran, A. Rosakis, A. Roshko, and E. Sechler. Six appendices contributed by Dr. Knauss, offering further insight into his life and career, also form part of this oral history and are cross-referenced in the main text

    Targeting Fusion Proteins of HIV-1 and SARS-CoV-2

    Get PDF
    Viruses are disease-causing pathogenic agents that require host cells to replicate. Fusion of host and viral membranes is critical for the lifecycle of enveloped viruses. Studying viral fusion proteins can allow us to better understand how they shape immune responses and inform the design of therapeutics such as drugs, monoclonal antibodies, and vaccines. This thesis discusses two approaches to targeting two fusion proteins: Env from HIV-1 and S from SARS-CoV-2. The first chapter of this thesis is an introduction to viruses with a specific focus on HIV-1 CD4 mimetic drugs and antibodies against SARS-CoV-2. It discusses the architecture of these viruses and fusion proteins and how small molecules, peptides, and antibodies can target these proteins successfully to treat and prevent disease. In addition, a brief overview is included of the techniques involved in structural biology and how it has informed the study of viruses. For the interested reader, chapter 2 contains a review article that serves as a more in-depth introduction for both viruses as well as how the use of structural biology has informed the study of viral surface proteins and neutralizing antibody responses to them. The subsequent chapters provide a body of work divided into two parts. The first part in chapter 3 involves a study on conformational changes induced in the HIV-1 Env protein by CD4-mimemtic drugs using single particle cryo-EM. The second part encompassing chapters 4 and 5 includes two studies on antibodies isolated from convalescent COVID-19 donors. The former involves classification of antibody responses to the SARS-CoV-2 S receptor-binding domain (RBD). The latter discusses an anti-RBD antibody class that binds to a conserved epitope on the RBD and shows cross-binding and cross-neutralization to other coronaviruses in the sarbecovirus subgenus.</p

    Application of advanced fluorescence microscopy and spectroscopy in live-cell imaging

    Get PDF
    Since its inception, fluorescence microscopy has been a key source of discoveries in cell biology. Advancements in fluorophores, labeling techniques and instrumentation have made fluorescence microscopy a versatile quantitative tool for studying dynamic processes and interactions both in vitro and in live-cells. In this thesis, I apply quantitative fluorescence microscopy techniques in live-cell environments to investigate several biological processes. To study Gag processing in HIV-1 particles, fluorescence lifetime imaging microscopy and single particle tracking are combined to follow nascent HIV-1 virus particles during assembly and release on the plasma membrane of living cells. Proteolytic release of eCFP embedded in the Gag lattice of immature HIV-1 virus particles results in a characteristic increase in its fluorescence lifetime. Gag processing and rearrangement can be detected in individual virus particles using this approach. In another project, a robust method for quantifying Förster resonance energy transfer in live-cells is developed to allow direct comparison of live-cell FRET experiments between laboratories. Finally, I apply image fluctuation spectroscopy to study protein behavior in a variety of cellular environments. Image cross-correlation spectroscopy is used to study the oligomerization of CXCR4, a G-protein coupled receptor on the plasma membrane. With raster image correlation spectroscopy, I measure the diffusion of histones in the nucleoplasm and heterochromatin domains of the nuclei of early mouse embryos. The lower diffusion coefficient of histones in the heterochromatin domain supports the conclusion that heterochromatin forms a liquid phase-separated domain. The wide range of topics covered in this thesis demonstrate that fluorescence microscopy is more than just an imaging tool but also a powerful instrument for the quantification and elucidation of dynamic cellular processes

    The Role of Transient Vibration of the Skull on Concussion

    Get PDF
    Concussion is a traumatic brain injury usually caused by a direct or indirect blow to the head that affects brain function. The maximum mechanical impedance of the brain tissue occurs at 450±50 Hz and may be affected by the skull resonant frequencies. After an impact to the head, vibration resonance of the skull damages the underlying cortex. The skull deforms and vibrates, like a bell for 3 to 5 milliseconds, bruising the cortex. Furthermore, the deceleration forces the frontal and temporal cortex against the skull, eliminating a layer of cerebrospinal fluid. When the skull vibrates, the force spreads directly to the cortex, with no layer of cerebrospinal fluid to reflect the wave or cushion its force. To date, there is few researches investigating the effect of transient vibration of the skull. Therefore, the overall goal of the proposed research is to gain better understanding of the role of transient vibration of the skull on concussion. This goal will be achieved by addressing three research objectives. First, a MRI skull and brain segmentation automatic technique is developed. Due to bones’ weak magnetic resonance signal, MRI scans struggle with differentiating bone tissue from other structures. One of the most important components for a successful segmentation is high-quality ground truth labels. Therefore, we introduce a deep learning framework for skull segmentation purpose where the ground truth labels are created from CT imaging using the standard tessellation language (STL). Furthermore, the brain region will be important for a future work, thus, we explore a new initialization concept of the convolutional neural network (CNN) by orthogonal moments to improve brain segmentation in MRI. Second, the creation of a novel 2D and 3D Automatic Method to Align the Facial Skeleton is introduced. An important aspect for further impact analysis is the ability to precisely simulate the same point of impact on multiple bone models. To perform this task, the skull must be precisely aligned in all anatomical planes. Therefore, we introduce a 2D/3D technique to align the facial skeleton that was initially developed for automatically calculating the craniofacial symmetry midline. In the 2D version, the entire concept of using cephalometric landmarks and manual image grid alignment to construct the training dataset was introduced. Then, this concept was extended to a 3D version where coronal and transverse planes are aligned using CNN approach. As the alignment in the sagittal plane is still undefined, a new alignment based on these techniques will be created to align the sagittal plane using Frankfort plane as a framework. Finally, the resonant frequencies of multiple skulls are assessed to determine how the skull resonant frequency vibrations propagate into the brain tissue. After applying material properties and mesh to the skull, modal analysis is performed to assess the skull natural frequencies. Finally, theories will be raised regarding the relation between the skull geometry, such as shape and thickness, and vibration with brain tissue injury, which may result in concussive injury

    Contribution of non-canonical DNA G-quadruplex structures to premature ageing

    Get PDF
    Previous studies have identified Cockayne Syndrome B (CSB) as a helicase that can resolve non-canonical DNA structures, called G-quadruplexes (G4s). The aim of this study is to investigate the properties of CSB as a G4-binder and -resolvase, and examine the correlation between the G4-helicase activity of CSB and premature ageing phenotype observed in CSB-deficient cells. Accordingly, the recombinant CSB full-length protein (FL) and its helicase- “like" domain (HD) were respectively expressed from insect and bacterial cells, and their resolvase and binding activities were tested over a large panel of DNA substrates. Native gel analysis and biophysical characterisations revealed that ribosomal DNA (rDNA) sequences, that typically act as CSB substrate, can form intermolecular G4s. We discovered that intermolecular G4s were strongly bound by CSB with picomolar affinity, whilst negligible binding to intramolecular G4s was observed. In vitro and cellular data demonstrated that G4-ligands can compete with CSB for binding to intermolecular rDNA G4, which results in CSB being displaced off the nucleoli of cells upon treatment with G4-ligands. Immunostaining with the selective G4-antibody BG4 revealed a lack of BG4-staining in the nucleoli of CSB-deficient cells after exogenous expression of recombinant CSB, further corroborating the hypothesis that CSB can bind intermolecular rDNA G4s in the nucleoli and compete with BG4 for the binding of such DNA-substrate. The work presented in this thesis allowed us to observe that (I) intermolecular G4s are likely to form from long-range distant rDNA sequences within the nucleoli of cells, and (II) CSB specifically binds and resolves these structures. Our results provide the first evidence of an endogenous protein that specifically interacts with intermolecular G4s, suggesting potential biological significance of these structures. The biological relevance of intermolecular rDNA G4s could be key in rare genetic disorders like Cockayne Syndrome, where senescence and premature ageing is observed when CSB is functionally mutated.Open Acces

    Analysis of spatial point patterns on surfaces

    Get PDF
    With the advent of improved data acquisition technologies more complex spatial datasets can be collected at scale meaning theoretical and methodological developments in spatial statistics are imperative in order to analyse and generate meaningful conclusions. Spatial statistics has seen a plethora of applications in life sciences with particular emphasis on ecology, epidemiology and cell microscopy. Applications of these techniques provides researchers with insight on how the locations of objects of interest can be influenced by their neighbours and the environment. Examples include understanding the spatial distribution of trees observed within some window, and understanding how neighbouring trees and potentially soil contents can influence this. Whilst the literature for spatial statistics is rich the common assumption is that point processes are usually restricted to some d-dimensional Euclidean space, for example cell locations in a rectangular window of 2-dimensional Euclidean space. As such current theory is not capable of handling patterns which lie on more complex spaces, for example cubes and ellipsoids. Recent efforts have successfully extended methodology from Euclidean space to spheres by using the chordal distance (the shortest distance between any two points on a sphere) in place of the Euclidean distance. In this thesis we build on this work by considering point processes lying on more complex surfaces. Our first significant contribution discusses the construction of functional summary statistics for Poisson processes which lie on compact subsets of Rd which are off lower dimension. We map the process from its original space to the sphere where it is possible to take advantage of rotational symmetries which allow for well-defined summary statistics. These in turn can be used to determine whether an observed point patterns exhibits clustered or regular behaviour. Partnering this work we also provide a hypothesis testing procedure based on these functional summary statistics to determine whether an observed point pattern is complete spatially random. Two test statistics are proposed, one based on the commonly used L-function for planar processes and the other a standardisation of the K-function. These test statistics are compared in an extensive simulation study across ellipsoids of varying dimensions and processes which display differing levels of aggregation or regularity. Estimates of first order properties of a point process are extremely important. They can provide a graphical illustration of inhomogeneity and are useful in second order analysis. We demonstrate how kernel estimation can be extended from a Euclidean space to a Riemannian manifold where the Euclidean metric is now substituted for a Riemannian one. Many of the desirable properties for Euclidean kernel estimates carry over to the Riemannian setting. The issue of edge correction is also discussed and two criteria for bandwidth selection are proposed. These two selection criteria are explored through a simulation study. Finally, an important area of research in spatial statistics is exploring the interaction between different processes, for example how different species of plant spatially interact within some window. Under the framework of marked point processes we show that functional summary statistics for multivariate point patterns can be constructed on the sphere. This is extended to more general convex shapes through an appropriate mapping from the original shape to the sphere. A number of examples highlight that these summary statistics can capture independence, aggregation and repulsion between components of a multivariate process on both the sphere and more general surfaces.Open Acces

    Response of saline reservoir to different phaseCOâ‚‚-brine: experimental tests and image-based modelling

    Get PDF
    Geological CO₂ storage in saline rocks is a promising method for meeting the target of net zero emission and minimizing the anthropogenic CO₂ emitted into the earth’s atmosphere. Storage of CO₂ in saline rocks triggers CO₂-brine-rock interaction that alters the properties of the rock. Properties of rocks are very crucial for the integrity and efficiency of the storage process. Changes in properties of the reservoir rocks due to CO₂-brine-rock interaction must be well predicted, as some changes can reduce the storage integrity of the reservoir. Considering the thermodynamics, phase behavior, solubility of CO₂ in brine, and the variable pressure-temperature conditions of the reservoir, there will be undissolved CO₂ in a CO₂ storage reservoir alongside the brine for a long time, and there is a potential for phase evolution of the undissolved CO₂. The phase of CO₂ influence the CO₂-brine-rock interaction, different phaseCO₂-brine have a unique effect on the properties of the reservoir rocks, Therefore, this study evaluates the effect of four different phaseCO₂-brine reservoir states on the properties of reservoir rocks using experimental and image-based approach. Samples were saturated with the different phaseCO₂-brine, then subjected to reservoir conditions in a triaxial compression test. The representative element volume (REV)/representative element area (REA) for the rock samples was determined from processed digital images, and rock properties were evaluated using digital rock physics and rock image analysis techniques. This research has evaluated the effect of different phaseCO₂-brine on deformation rate and deformation behavior, bulk modulus, compressibility, strength, and stiffness as well as porosity and permeability of sample reservoir rocks. Changes in pore geometry properties, porosity, and permeability of the rocks in CO₂ storage conditions with different phaseCO₂-brine have been evaluated using digital rock physics techniques. Microscopic rock image analysis has been applied to provide evidence of changes in micro-fabric, the topology of minerals, and elemental composition of minerals in saline rocks resulting from different phaseCO₂-br that can exist in a saline CO₂ storage reservoir. It was seen that the properties of the reservoir that are most affected by the scCO₂-br state of the reservoir include secondary fatigue rate, bulk modulus, shear strength, change in the topology of minerals after saturation as well as change in shape and flatness of pore surfaces. The properties of the reservoir that is most affected by the gCO₂-br state of the reservoir include primary fatigue rate, change in permeability due to stress, change in porosity due to stress, and change topology of minerals due to stress. For all samples, the roundness and smoothness of grains as well as smoothness of pores increased after compression while the roundness of pores decreased. Change in elemental composition in rock minerals in CO₂-brine-rock interaction was seen to depend on the reactivity of the mineral with CO₂ and/or brine and the presence of brine accelerates such change. Carbon, oxygen, and silicon can be used as index minerals for elemental changes in a CO₂-brine-rock system. The result of this work can be applied to predicting the effect the different possible phases of CO₂ will have on the deformation, geomechanics indices, and storage integrity of giant CO₂ storage fields such as Sleipner, In Salah, etc
    • …
    corecore