Functional Optical Tomography of the Retina in Mouse Models with Neurodegenerative Diseases

The retina is a thin yet sophisticated ocular tissue that converts light into electrical signals for vision processing. There are six types of neurons, ten distinct layers, and three vascular plexuses. Retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), inherited retinal disorders (IRDs), and diabetic retinopathy (DR), are caused by dysfunction of different cell types. As part of the central nervous system (CNS), pathological hallmarks of cerebral neurodegenerative diseases, such as Alzheimer's disease (AD), are also reflected in the retina. Currently, there is no outright cure for retinal and cerebral neurodegenerative diseases. Early detection is thus essential for their prediction, diagnosis, and prognosis. A key strategy for early detection is to be vigilant for changes in early functional abnormality of retinal cells. Optical mapping of intrinsic signal changes in the retina promises a non-invasive technique for objective functional testing. Optical coherence tomography (OCT) has been widely used to conduct depth-resolved functional imaging of the retina. The research in this thesis aimed to scrutinize functional aspects of neural and vascular activities in the retina as well as their defects caused by neurodegenerative diseases. Our hypothesis is that both retinal- and cerebral-neurodegenerative diseases may directly impair functions of different retinal cells before showing morphological abnormalities, and cellular dysfunctions may be detected by optical tomographic techniques. As a functional extension of OCT, intrinsic signal optoretinography (ORG) study has been done with a retinal neurodegenerative mouse model. ORG is analogous to electroretinography (ERG). ORG generally refers to the non-invasive, optical imaging of functional activity in the retina. OCT-based ORG can provide objective assessment of retinal function with layer specificity. We developed a custom-built spectral domain OCT system for ORG measurement in mouse retinas. Different light conditions were applied to examine both light-evoked phototransduction response and dark-induced morphophysiological changes. We analyzed intrinsic optical signal (IOS) changes and alterations of hyper-reflective OCT bands. IOS data processing was refined, and imaging protocols were optimized in this study. As another functional extension of OCT, OCT angiography (OCTA) study has been done with a retinal neurodegenerative mouse model and a cerebral neurodegenerative mouse model. OCTA is a non-invasive imaging modality that generates volumetric data of vascular structure in the eye. We developed a custom-built OCTA system and advanced speckle-variance-based decorrelation algorithms for vessel map construction. In addition, a simple but robust artery-vein classification method was devised in this study. We investigated retinal vascular degeneration in both retinal- and cerebral neurodegenerative mouse models. We also observed the hyaloid vascular system in vivo and its degeneration in mouse pups. Quantitative vascular information was generated and compared between different strains in this study. In summary, the research in this thesis enhanced our understanding of the optophysiological response of the retina under different light conditions and established an experimental basis for future clinical applications. Abnormal signatures of OCTA features found in this study will also be beneficial in understanding pathophysiological mechanisms of the retinal and hyaloid vascular system. Above all, limitations of the present study and arising hypothesis rooted from intriguing observations in this study would provide valuable scientific questions to answer in future study

Wave-Tunable Lattice Equivalents toward Micro- and Nanomanipulation

The assembly of micro- and nanomaterials is a key issue in the development of potential bottom-up construction of building blocks, but creating periodic arrays of such materials in an efficient and scalable manner still remains challenging. Here, we show that a cymatic assembly approach in which micro- and nanomaterials in a liquid medium that resonate at low-frequency standing waves can be used for the assembly in a spatially periodic and temporally stationary fashion that emerges from the wave displacement antinodes of the standing wave. We also show that employing a two-dimensional liquid, rather than a droplet, with a coffee-ring effect yields a result that exhibits distinct lattice equivalents comprising the materials. The crystallographic parameters, such as the lattice parameters, can be adjusted, where the parameters along the <i>x</i>- and <i>y</i>-axes are controlled by the applied wave frequencies, and the one along <i>z</i>-axis is controlled by a transparent layer as a spacer to create three-dimensional crystal equivalents. This work represents an advancement in assembling micro- and nanomaterials into macroscale architectures on the centimeter-length scale, thus establishing that a standing wave can direct micro- and nanomaterial assembly to mimic plane and space lattices

Directional Assembly of α‑Helical Peptides Induced by Cyclization

Effective stabilization of short peptide chains into a helical structure has been a challenge in the fields of chemistry and biology. Here we report a novel method for α-helix stabilization of short peptides through their confinement in a cyclic architecture. We synthesized block peptides based on a short peptide and a flexible linker as linear precursors. Subsequent cyclization of the peptide precursors resulted in a conformational change of the peptide unit from a random coil to an α-helix. The incorporation of hydrophobic residues into the peptide unit led to a facially amphiphilic conformation of the molecular cycle. The resulting amphiphilic peptide self-assembled into undulated nanofibers through the directional assembly of small oblate micelles

CHARMM-GUI: A graphical user interface for the CHARMM users

<p>The CHARMM-GUI is a graphical user interface for molecular dynamics for biology scientists. Using this interface, a scientists can read and modify PDB from various sources and generates input files solvating in a explicit or implicit solvent and solving PB (Poisson-Boltzman) Equation to compute solvent accessible surface. The interface also provides an easy access to set up the periodic boundary condition and environment for molecular dynamics. The input and output files generated while using the interface are available for downloading.</p

Automate setup for molecular dynamics simulations of protein/membrane complexes

<p>The molecular dynamics simulations of membrane proteins have provided deeper insights into their functions and interactions with surrounding environments at the atomic level. However, compared to the solvation of globular proteins, building a protein/membrane complex is still challenging and requires considerable experience with simulation softwares, due to the complexity of lipid bilayers. The Membrane Builder in the CHARMM- GUI (http://charmm-gui.org) is a graphical user interface (GUI) that helps users to set up a protein/membrane complex semi-automatically. After the users determine the orientation of a membrane protein and the system size in a full GUI fashion using the web-browser, the lipid molecules are built around the protein by either "insertion" or "replacement" methods. Here, we illustrate the usage of the Membrane Builder with 13 membrane proteins, whose fully equilibrated systems are freely available from an archive in the CHARMM-GUI website.</p

Bioinspired, Highly Stretchable, and Conductive Dry Adhesives Based on 1D–2D Hybrid Carbon Nanocomposites for All-in-One ECG Electrodes

Here we propose a concept of conductive dry adhesives (CDA) combining a gecko-inspired hierarchical structure and an elastomeric carbon nanocomposite. To complement the poor electrical percolation of 1D carbon nanotube (CNT) networks in an elastomeric matrix at a low filler content (∼1 wt %), a higher dimensional carbon material (<i>i</i>.<i>e</i>., carbon black, nanographite, and graphene nanopowder) is added into the mixture as an aid filler. The co-doped graphene and CNT in the composite show the lowest volume resistance (∼100 ohm·cm) at an optimized filler ratio (1:9, total filler content: 1 wt %) through a synergetic effect in electrical percolation. With an optimized conductive elastomer, gecko-inspired high-aspect-ratio (>3) microstructures over a large area (∼4 in.²) are successfully replicated from intaglio-patterned molds without collapse. The resultant CDA pad shows a high normal adhesion force (∼1.3 N/cm²) even on rough human skin and an excellent cycling property for repeatable use over 30 times without degradation of adhesion force, which cannot be achieved by commercial wet adhesives. The body-attachable CDA can be used as a metal-free, all-in-one component for measuring biosignals under daily activity conditions (<i>i</i>.<i>e</i>., underwater, movements) because of its superior conformality and water-repellent characteristic

Bioinspired, Highly Stretchable, and Conductive Dry Adhesives Based on 1D–2D Hybrid Carbon Nanocomposites for All-in-One ECG Electrodes

Here we propose a concept of conductive dry adhesives (CDA) combining a gecko-inspired hierarchical structure and an elastomeric carbon nanocomposite. To complement the poor electrical percolation of 1D carbon nanotube (CNT) networks in an elastomeric matrix at a low filler content (∼1 wt %), a higher dimensional carbon material (<i>i</i>.<i>e</i>., carbon black, nanographite, and graphene nanopowder) is added into the mixture as an aid filler. The co-doped graphene and CNT in the composite show the lowest volume resistance (∼100 ohm·cm) at an optimized filler ratio (1:9, total filler content: 1 wt %) through a synergetic effect in electrical percolation. With an optimized conductive elastomer, gecko-inspired high-aspect-ratio (>3) microstructures over a large area (∼4 in.²) are successfully replicated from intaglio-patterned molds without collapse. The resultant CDA pad shows a high normal adhesion force (∼1.3 N/cm²) even on rough human skin and an excellent cycling property for repeatable use over 30 times without degradation of adhesion force, which cannot be achieved by commercial wet adhesives. The body-attachable CDA can be used as a metal-free, all-in-one component for measuring biosignals under daily activity conditions (<i>i</i>.<i>e</i>., underwater, movements) because of its superior conformality and water-repellent characteristic

Supramolecular Switching between Flat Sheets and Helical Tubules Triggered by Coordination Interaction

Here we report the spontaneous formation of switchable sheets in aqueous solution, which is based on bent-shaped aromatic amphiphiles containing <i>m</i>-pyridine units at the terminals and a hydrophilic dendron at the apex. The aromatic segments self-assemble into flat sheets consisting of a zigzag conformation through π–π stacking interactions. Notably, the sheets reversibly transform into helical tubules at higher concentration and into discrete dimeric macrocycles at a lower concentration in response to Ag­(I) ions through reversible coordination interactions between the pyridine units of the aromatic segments and the Ag­(I) ions. While maintaining the coordination bonding interactions, the helical tubules reversibly transform into the dimeric macrocycles in response to the variation in concentration

Multivalent Nanofibers of a Controlled Length: Regulation of Bacterial Cell Agglutination

Control of the size and shape of molecular assemblies on the nanometer scale in aqueous solutions is very important for the regulation of biological functions. Among the well-defined supramolecular structures of organic amphiphiles, one-dimensional nanofibers have attracted much attention because of their potential applications in biocompatible materials. Although much progress has been made in the field of self-assembled nanofibers, the ability to control the fiber length remains limited. The approach for control of the fiber length presented herein overcomes this limitation through the coassembly of amphiphilic rod–coil molecules in which the crystallinity of the aromatic segment can be regulated by π–π stacking interactions. The introduction of carbohydrate segments into the fiber exterior endows the nanofibers with the ability to adhere to bacterial cells. Notably, the fiber length systematically regulates the agglutination and proliferation of bacterial cells exposed to these fibers

Single-Walled Carbon Nanotube Polyelectrolytes with a Coherent Skin Effect for Electromagnetic Interference Shielding

Compartmental shielding, using methods such as the conductive encapsulation of flexible polymer fibers, provides electrical pathways that are effective for electromagnetic interference (EMI) shielding in textile-based EMI shields. However, controlling the skin depth with electrically insulating polymer constituents remains challenging, particularly by requiring the high electrical conductivity of the encapsulants on the surface. Here, we demonstrate that the highly conductive single-walled carbon nanotube (SWCNT) polyelectrolytes provide a certain level of electrical conductivity (∼106 S/m) with effective percolation that reduces the skin depth to approximately 3 μm. This experimental skin depth was well-matched with the theoretical value of the skin depth. Sufficient charge accumulation in the SWCNT encapsulants with a hierarchical structure indicates the remarkable conductive features of the SWCNT polyelectrolytes and successfully demonstrates absorption-dominant EMI shielding. The macroscopic square mesh consisted of core/shell aramid/SWCNT fibers, exhibiting an ordered structure across multiple length scales, a modified hierarchy, and a superior EMI shielding effectiveness (SE), particularly in absorption. In particular, an EMI SE (i.e., 32 dB) of approximately 99.9% was achieved using a square mesh with an aperture width of 3 mm. The square meshes demonstrated excellent flexibility, thermal stability (Td > 500 °C), and mechanical robustness (σ = 2.26 ± 0.16 GPa, E = 79.0 ± 1.8 GPa, and ε = 2.99 ± 0.09%)