GARNET – gene set analysis with exploration of annotation relations

<p>Abstract</p> <p>Background</p> <p>Gene set analysis is a powerful method of deducing biological meaning for an a priori defined set of genes. Numerous tools have been developed to test statistical enrichment or depletion in specific pathways or gene ontology (GO) terms. Major difficulties towards biological interpretation are integrating diverse types of annotation categories and exploring the relationships between annotation terms of similar information.</p> <p>Results</p> <p>GARNET (Gene Annotation Relationship NEtwork Tools) is an integrative platform for gene set analysis with many novel features. It includes tools for retrieval of genes from annotation database, statistical analysis & visualization of annotation relationships, and managing gene sets. In an effort to allow access to a full spectrum of amassed biological knowledge, we have integrated a variety of annotation data that include the GO, domain, disease, drug, chromosomal location, and custom-defined annotations. Diverse types of molecular networks (pathways, transcription and microRNA regulations, protein-protein interaction) are also included. The pair-wise relationship between annotation gene sets was calculated using kappa statistics. GARNET consists of three modules - <it>gene set manager</it>, <it>gene set analysis</it> and <it>gene set retrieval</it>, which are tightly integrated to provide virtually automatic analysis for gene sets. A dedicated viewer for annotation network has been developed to facilitate exploration of the related annotations.</p> <p>Conclusions</p> <p>GARNET (gene annotation relationship network tools) is an integrative platform for diverse types of gene set analysis, where complex relationships among gene annotations can be easily explored with an intuitive network visualization tool (<url>http://garnet.isysbio.org/</url> or <url>http://ercsb.ewha.ac.kr/garnet/</url>).</p

Magnetometry of individual polycrystalline ferromagnetic nanowires

Ferromagnetic nanowires are finding use as untethered sensors and actuators for probing micro- and nanoscale biophysical phenomena, such as for localized sensing and application of forces and torques on biological samples, for tissue heating through magnetic hyperthermia, and for micro-rheology. Quantifying the magnetic properties of individual isolated nanowires is crucial for such applications. We use dynamic cantilever magnetometry to measure the magnetic properties of individual sub-500nm diameter polycrystalline nanowires of Ni and Ni80Co20 fabricated by template-assisted electrochemical deposition. The values are compared with bulk, ensemble measurements when the nanowires are still embedded within their growth matrix. We find that single-particle and ensemble measurements of nanowires yield significantly different results that reflect inter-nanowire interactions and chemical modifications of the sample during the release process from the growth matrix. The results highlight the importance of performing single-particle characterization for objects that will be used as individual magnetic nanoactuators or nanosensors in biomedical applications

Tailored design of a water-based nanoreactor technology for producing processable Sub-40 Nm 3D COF nanoparticles at atmospheric conditions

Covalent organic frameworks (COFs) are crystalline materials with intrinsic porosity that offer a wide range of potential applications spanning diverse fields. Yet, the main goal in the COF research area is to achieve the most stable thermodynamic product while simultaneously targeting the desired size and structure crucial for enabling specific functions. While significant progress is made in the synthesis and processing of 2D COFs, the development of processable 3D COF nanocrystals remains challenging. Here, a water‐based nanoreactor technology for producing processable sub‐40 nm 3D COF nanoparticles at ambient conditions is presented. Significantly, this technology not only improves the processability of the synthesized 3D COF, but also unveils exciting possibilities for their utilization in previously unexplored domains, such as nano/microrobotics and biomedicine, which are limited by larger crystallites

Multiwavelength light-responsive Au/B-TiO2 Janus micromotors

Conventional photocatalytic micromotors are limited to the use of specific wavelengths of light due to their narrow light absorption spectrum, which limits their effectiveness for applications in biomedicine and environmental remediation. We present a multiwavelength light-responsive Janus micromotor consisting of a black TiO₂ microsphere asymmetrically coated with a thin Au layer. The black TiO₂ microspheres exhibit absorption ranges between 300 and 800 nm. The Janus micromotors are propelled by light, both in H₂O₂ solutions and in pure H₂O over a broad range of wavelengths including UV, blue, cyan, green, and red light. An analysis of the particles' motion shows that the motor speed decreases with increasing wavelength, which has not been previously realized. A significant increase in motor speed is observed when exploiting the entire visible light spectrum (>400 nm), suggesting a potential use of solar energy, which contains a great portion of visible light. Finally, stop-go motion is also demonstrated by controlling the visible light illumination, a necessary feature for the steerability of micro- and nanomachines

Essays in R&D competition

We examine R&D competition between a leader and a laggard in a model where consumers are horizontally differentiated. Each firms are endowed with different ‘ability to research.’ First, it is exogenously given to each firm by some predetermined ‘chance events.’ The technology level is improved gradually and cumulatively through R&D spending of each firms. The Result shows that the laggard with marginally better ‘ability to research’ will not be able to catch up to the leader. Only the laggard with significantly better ‘ability to research’ catches up to the leader and eventually becomes a new market leader. This result is consistent with the observation that a laggard possesses a drastic innovation. The interpretation of the observation is different by paying special attention to many unobserved laggards that fail to survive in spite of having better ‘ability to research.’ Rather than the laggard having more incentive to innovate, this paper concludes that, for a laggard to survive in the market, it must have a significantly better ‘ability to research.’ In addition, we analyze firms\u27 adoption behavior of a new ‘ability to research,’ or a new technology base, when it becomes publicly available. Again, we find that, unless a laggard initially has sufficiently better ability to research so that the value of the future market is significantly high, leader preemptively adopts the new technology

Essays in R&D competition

We examine R&D competition between a leader and a laggard in a model where consumers are horizontally differentiated. Each firms are endowed with different ‘ability to research.’ First, it is exogenously given to each firm by some predetermined ‘chance events.’ The technology level is improved gradually and cumulatively through R&D spending of each firms. The Result shows that the laggard with marginally better ‘ability to research’ will not be able to catch up to the leader. Only the laggard with significantly better ‘ability to research’ catches up to the leader and eventually becomes a new market leader. This result is consistent with the observation that a laggard possesses a drastic innovation. The interpretation of the observation is different by paying special attention to many unobserved laggards that fail to survive in spite of having better ‘ability to research.’ Rather than the laggard having more incentive to innovate, this paper concludes that, for a laggard to survive in the market, it must have a significantly better ‘ability to research.’ In addition, we analyze firms\u27 adoption behavior of a new ‘ability to research,’ or a new technology base, when it becomes publicly available. Again, we find that, unless a laggard initially has sufficiently better ability to research so that the value of the future market is significantly high, leader preemptively adopts the new technology

Nanobot Propulsion Methods: Theory and Experiments

Robots are mechanical systems that perform tasks through a series of perception, cognition, and manipulation steps. Robots with dimensions between 10-9 -10-4 m are classified as micro/nanobots. These are often called micro/nanoswimmers (or micro/nanomotors) since most micro/nanobots are used in liquid environments. These tiny robots can be precisely guided to locations where human access is restricted. Consequently, micro/nanobots are widely applicable in different fields, including environmental cleaning, medicine, exploration, and military applications. Micro/nanobots (or micro/nanoswimmers) are often designed differently from their macro-sized counterparts for two reasons. First, while macro-sized robots typically use onboard batteries, micro/nanobots generally use external energy sources, such as chemical, magnetic, electric, acoustic, and optical energy, due to the current technological restriction of battery miniaturization. Second, micro/nanobots must create a propulsive force differently than macro-sized robots. Unlike macro-sized robots, micro/nanobots swimming in a Newtonian liquid by reciprocal motion show zero net displacement since the drag force exerted on objects dominates over the inertial force at such small scales. Methods to create propulsive forces in micro/nanobots can be inspired by small-scale living entities. For example, microorganisms create propulsive forces by using non-reciprocal motion, such as spermatozoon and bacterial flagellum that use undulatory and cork-screw locomotion, respectively. The purpose of this dissertation is to design and fabricate micro/nanobots and study their propulsion mechanisms. Four micro/nanobots are newly designed by tuning properties of micro/nanobots, such as geometry, material, physical, and chemical properties. Furthermore, their propulsion mechanisms are understood for efficient and controlled propulsion by fully characterizing their resultant locomotion in Newtonian fluids. In the first chapter, general knowledge of micro/nanobots, including definition and theory of micro/nanobots, is introduced. In the following chapters (chapter 2-4), the state of the art of micro/nanobots actuated by different external energies is thoroughly reviewed, especially focusing on the effect of the design of micro/nanobots on their locomotion and propulsion mechanisms in fluids. Newly developed micro/nanobots are introduced in each chapter, consisting of subsections addressing motivation, experimental methods, results and discussion, and conclusion. Chapter 2 reports catalytically driven core−shell nanowires. The investigated catalytic locomotion in H2O2 solution shows that, unlike conventional bimetallic nanowires that are self-electroosmotically propelled, our core−shell nanowires show both a noticeable decrease in rotational diffusivity and increase in motor speed with increasing nanowire length. Numerical modeling based on self-electroosmosis attributes decreases in rotational diffusivity to the formation of toroidal vortices at the nanowire tail, but fails to explain the speed increase with length. To reconcile this inconsistency, we propose a combined mechanism of self-diffusiophoresis and electroosmosis based on the oxygen gradient produced by catalytic shells. The possible contribution of diffusiophoresis to an otherwise well-established electroosmotic mechanism sheds light on future designs of nanobots, at the same time highlighting the complex nature of nanoscale propulsion. Chapter 3 reports multi-wavelength light-responsive Janus microbots consisting of black TiO2 microspheres asymmetrically coated with a thin Au layer. Conventional photocatalytic micro/nanobots are limited to the use of specific wavelengths of light due to their narrow light absorption spectrum, which limits their effectiveness for applications in biomedicine and environmental remediation. Unlike conventional robots, our microbots are propelled by light, both in H2O2 solutions and in pure H2O over a broad range of wavelengths including UV, blue, cyan, green, and red light. An analysis of the motion of the robots shows that the robot speed decreases with increasing wavelength, which has not been previously realized. A significant increase in robot speed is observed when exploiting the entire visible light spectrum (>400 nm), suggesting a potential use of solar energy, which contains a great portion of visible light. Finally, stop−go motion is also demonstrated by controlling the visible light illumination, a necessary feature for the steerability of micro/ and nanomachines. Chapter 4 reports two types of newly developed nanobots that are magnetically actuated. First, nanowire-based magnetic surface walkers are reported. The nanowires are made of hard-magnetic CoPt alloy synthesized by means of template-assisted galvanostatic electrodeposition. The hard-magnetic behavior of the nanowires allows their alignment to be programmed with an applied magnetic field, as they can retain their magnetization direction after pre-magnetizing them. Their propulsion mechanism can be changed as a function of the applied rotating magnetic field frequency. By engineering the macroscopic magnetization, the locomotion mechanism of the nanowires is set to tumbling, precession, or rolling depending on the frequency of an applied rotating magnetic field. In addition, vortices were found by tracking polystyrene microbeads trapped around the CoPt nanowire when they were propelled by precession or rolling motion. Second, magnetically driven multilink nanowires are reported. The employed manufacturing process enables tuning the geometrical and material properties of nanowires and, therefore, allow resembling the shape and swimming strategies of spermatozoon. The resultant structure comprises an elastic eukaryote-like polypyrrole tail and rigid magnetic nickel links connected by flexible polymer bilayer hinges. Under a planar oscillatory magnetic field, the multilink nanowires display planar undulations. The multilink design exhibits an increase in swimming efficiency with increasing numbers of hinges in the structure. Annex 1 covers important yet overlooked aspects in the fabrication of nanowires observed during the fabrication process of nanobots. We examine the junction quality of electrochemically grown segmented nanowires. We particularly focus on the Au-Co system to illustrate this aspect. Annex 2 provides a strategy to fabricate supported anodic aluminum oxide (AAO) membranes, which served as templates to grow long nanowires with modulated diameters. This approach was also employed to fabricate core-shell nanobot reported in chapter 2

A universal method for planar lipid bilayer formation by freeze and thaw

A procedure based on freezing and thawing was developed to induce the rupture of adsorbed lipid vesicles on solid surfaces into supported lipid bilayers (SLBs). The SLB assembly exploits the phase transition of both lipids and water during freezing. It enables SLB formation independent of the type of substrates and lipids as long as the vesicles spontaneously adsorb onto the surface. The created SLB is a single bilayer, and has a diffusion coefficient of (0.6–4) × 10−8 cm2 s−1 on TiO2, which is in the same range as the SLBs formed by conventional techniques. The presented approach has the advantages of both the Langmuir–Blodgett method (the versatility in the selection of lipids and substrates) and vesicle fusion (self-assembly) at the same time