3 resultados para ZINC-FINGER NUCLEASES

em CaltechTHESIS


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Pattern formation during animal development involves at least three processes: establishment of the competence of precursor cells to respond to intercellular signals, formation of a pattern of different cell fates adopted by precursor cells, and execution of the cell fate by generating a pattern of distinct descendants from precursor cells. I have analyzed the fundamental mechanisms of pattern formation by studying the development of Caenorhabditis elegans vulva.

In C. elegans, six multipotential vulval precursor cells (VPCs) are competent to respond to an inductive signal LIN-3 (EGF) mediated by LET- 23 (RTK) and a lateral signal via LIN-12 (Notch) to form a fixed pattern of 3°-3°-2°-1°-2°-3°. Results from expressing LIN-3 as a function of time in animals lacking endogenous LIN-3 indicate that both VPCs and VPC daughters are competent to respond to LIN-3. Although the daughters of VPCs specified to be 2° or 3° can be redirected to adopt the 1°fate, the decision to adopt the 1° fate is irreversible. Coupling of VPC competence to cell cycle progression reveals that VPC competence may be periodic during each cell cycle and involve LIN-39 (HOM-C). These mechanisms are essential to ensure a bias towards the 1° fate, while preventing an excessive response.

After adopting the 1° fate, the VPC executes its fate by dividing three rounds to form a fixed pattern of four inner vulF and four outer vulE descendants. These two types of descendants can be distinguished by a molecular marker zmp-1::GFP. A short-range signal from the anchor cell (AC), along with signaling between the inner and outer 1° VPC descendants and intrinsic polarity of 1° VPC daughters, patterns the 1° lineage. The Ras and the Wnt signaling pathways may be involved in these mechanisms.

The temporal expression pattern of egl-17::GFP, another marker ofthe 1° fate, correlates with three different steps of 1° fate execution: the commitment to the 1° fate, as well as later steps before and after establishment of the uterine-vulval connection. Six transcription factors, including LIN-1(ETS), LIN-39 (HOM-C), LIN-11(LIM), LIN-29 (zinc finger), COG-1 (homeobox) and EGL-38 (PAX2/5/8), are involved in different steps during 1° fate execution.

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The prospect of terawatt-scale electricity generation using a photovoltaic (PV) device places strict requirements on the active semiconductor optoelectronic properties and elemental abundance. After reviewing the constraints placed on an "earth-abundant" solar absorber, we find zinc phosphide (α-Zn3P2) to be an ideal candidate. In addition to its near-optimal direct band gap of 1.5 eV, high visible-light absorption coefficient (>104 cm-1), and long minority-carrier diffusion length (>5 μm), Zn3P2 is composed of abundant Zn and P elements and has excellent physical properties for scalable thin-film deposition. However, to date, a Zn3P2 device of sufficient efficiency for commercial applications has not been demonstrated. Record efficiencies of 6.0% for multicrystalline and 4.3% for thin-film cells have been reported, respectively. Performance has been limited by the intrinsic p-type conductivity of Zn3P2 which restricts us to Schottky and heterojunction device designs. Due to our poor understanding of Zn3P2 interfaces, an ideal heterojunction partner has not yet been found.

The goal of this thesis is to explore the upper limit of solar conversion efficiency achievable with a Zn3P2 absorber through the design of an optimal heterojunction PV device. To do so, we investigate three key aspects of material growth, interface energetics, and device design. First, the growth of Zn3P2 on GaAs(001) is studied using compound-source molecular-beam epitaxy (MBE). We successfully demonstrate the pseudomorphic growth of Zn3P2 epilayers of controlled orientation and optoelectronic properties. Next, the energy-band alignments of epitaxial Zn3P2 and II-VI and III-V semiconductor interfaces are measured via high-resolution x-ray photoelectron spectroscopy in order to determine the most appropriate heterojunction partner. From this work, we identify ZnSe as a nearly ideal n-type emitter for a Zn3P2 PV device. Finally, various II-VI/Zn3P2 heterojunction solar cells designs are fabricated, including substrate and superstrate architectures, and evaluated based on their solar conversion efficiency.

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Multi-finger caging offers a rigorous and robust approach to robot grasping. This thesis provides several novel algorithms for caging polygons and polyhedra in two and three dimensions. Caging refers to a robotic grasp that does not necessarily immobilize an object, but prevents it from escaping to infinity. The first algorithm considers caging a polygon in two dimensions using two point fingers. The second algorithm extends the first to three dimensions. The third algorithm considers caging a convex polygon in two dimensions using three point fingers, and considers robustness of this cage to variations in the relative positions of the fingers.

This thesis describes an algorithm for finding all two-finger cage formations of planar polygonal objects based on a contact-space formulation. It shows that two-finger cages have several useful properties in contact space. First, the critical points of the cage representation in the hand’s configuration space appear as critical points of the inter-finger distance function in contact space. Second, these critical points can be graphically characterized directly on the object’s boundary. Third, contact space admits a natural rectangular decomposition such that all critical points lie on the rectangle boundaries, and the sublevel sets of contact space and free space are topologically equivalent. These properties lead to a caging graph that can be readily constructed in contact space. Starting from a desired immobilizing grasp of a polygonal object, the caging graph is searched for the minimal, intermediate, and maximal caging regions surrounding the immobilizing grasp. An example constructed from real-world data illustrates and validates the method.

A second algorithm is developed for finding caging formations of a 3D polyhedron for two point fingers using a lower dimensional contact-space formulation. Results from the two-dimensional algorithm are extended to three dimension. Critical points of the inter-finger distance function are shown to be identical to the critical points of the cage. A decomposition of contact space into 4D regions having useful properties is demonstrated. A geometric analysis of the critical points of the inter-finger distance function results in a catalog of grasps in which the cages change topology, leading to a simple test to classify critical points. With these properties established, the search algorithm from the two-dimensional case may be applied to the three-dimensional problem. An implemented example demonstrates the method.

This thesis also presents a study of cages of convex polygonal objects using three point fingers. It considers a three-parameter model of the relative position of the fingers, which gives complete generality for three point fingers in the plane. It analyzes robustness of caging grasps to variations in the relative position of the fingers without breaking the cage. Using a simple decomposition of free space around the polygon, we present an algorithm which gives all caging placements of the fingers and a characterization of the robustness of these cages.