γ-Globin Reactivation

β-thalassemia and sickle cell disease are major human genetic health problem in many parts of the world. Available treatments are not satisfactory as none of them exhibit the optimal combination of safety, efficiency and convenience of use that would make them applicable to most hemoglobinopathy patients, especially to those who lack access to modern medical facilities. The observation that induction of γ-globin gene expression ameliorates the disease phenotype led to the proposal to induce γ-globin gene expression for the treatment of these diseases. Screening of a small molecule libraries (186000 compounds) has been done but new reagents with a higher HbF inducing effect and reduced cytotoxicity than those already known (butyrates, HU) were not found. Despite all the attempts made during the last 30 years, it is still not known how the γ-globin genes are switched off after birth, e.g. whether it is absence of activating factors or presence of suppressing factors or combination of both that leads to the down regulation of the γ-globin genes in the adult. There is only very limited information about the factors that are bound to the γ-globin promoters in vivo, certainly in its repressed state. It is likely that factors other than those described in the literature (at the start of this work) are essential for the suppression process. We therefore wanted to develop new strategies that specifically target fetal gene activation without cytotoxicity, widespread epigenetic alterations or difficult to manage side effects through the identification of the relevant transcription factors acting at the promoter. To this end we designed a strategy to isolate and identify protein factors bound in vivo to the suppressed human γ-globin gene promoter and to study their effect on γ-globin regulation (chapter 3). This targeted, in vivo single gene promoter chromatin purification has been carried out for the first time and is a completely novel strategy. To optimize such a purification protocol, different parameters have been tested including the use of various purification tags, reagents, buffers, etcetera (presented in chapter2). An alternative approach would be to identify target molecules within pathways that are involved in γ-globin gene expression. These pathways can be studied in the context of high and low HbF expressing β-thalassemia and sickle cell disease patients (chapter 4). There are many reports describing the induction of different HbF levels in response to hydroxyurea treatments in patients. We therefore wanted to understand the mechanism by which HU induces γ-globin in patients using expression analysis between so-called ‘responder’ and ‘nonresponder’ patients, i.e. between those showing high γ-globin production versus low γ-globin production. The results of this study are presented in chapter4. Finally in chapter 5 we present a novel set of genetic markers that is associated with increased γ-gobin expression in β-thalassemia patients followed by a discussion of future prospects in Chapter 6

Coherent Doppler Lidar for Measuring Altitude, Ground Velocity, and Air Velocity of Aircraft and Spaceborne Vehicles

A Doppler lidar sensor system includes a laser generator that produces a highly pure single frequency laser beam, and a frequency modulator that modulates the laser beam with a highly linear frequency waveform. A first portion of the frequency modulated laser beam is amplified, and parts thereof are transmitted through at least three separate transmit/receive lenses. A second portion of the laser beam is used as a local oscillator beam for optical heterodyne detection. Radiation from the parts of the laser beam transmitted via the transmit/receive lenses is received by the respective transmit/receive lenses that transmitted the respective part of the laser beam. The received reflected radiation is compared with the local oscillator beam to calculate the frequency difference there between to determine various navigational data

High-Fidelity Flash Lidar Model Development

NASA's Autonomous Landing and Hazard Avoidance Technologies (ALHAT) project is currently developing the critical technologies to safely and precisely navigate and land crew, cargo and robotic spacecraft vehicles on and around planetary bodies. One key element of this project is a high-fidelity Flash Lidar sensor that can generate three-dimensional (3-D) images of the planetary surface. These images are processed with hazard detection and avoidance and hazard relative navigation algorithms, and then are subsequently used by the Guidance, Navigation and Control subsystem to generate an optimal navigation solution. A complex, high-fidelity model of the Flash Lidar was developed in order to evaluate the performance of the sensor and its interaction with the interfacing ALHAT components on vehicles with different configurations and under different flight trajectories. The model contains a parameterized, general approach to Flash Lidar detection and reflects physical attributes such as range and electronic noise sources, and laser pulse temporal and spatial profiles. It also provides the realistic interaction of the laser pulse with terrain features that include varying albedo, boulders, craters slopes and shadows. This paper gives a description of the Flash Lidar model and presents results from the Lidar operating under different scenarios

Navigation Doppler Lidar for Autonomous Ground, Aerial, and Space Vehicles

A Doppler lidar instrument has been developed and demonstrated for providing critical vector velocity and altitude/range data for autonomous precision navigation. Utilizing advanced component technologies, this lidar can be adapted to different types of vehicles

A Long Distance Laser Altimeter for Terrain Relative Navigation and Spacecraft Landing

A high precision laser altimeter was developed under the Autonomous Landing and Hazard Avoidance (ALHAT) project at NASA Langley Research Center. The laser altimeter provides slant-path range measurements from operational ranges exceeding 30 km that will be used to support surface-relative state estimation and navigation during planetary descent and precision landing. The altimeter uses an advanced time-of-arrival receiver, which produces multiple signal-return range measurements from tens of kilometers with 5 cm precision. The transmitter is eye-safe, simplifying operations and testing on earth. The prototype is fully autonomous, and able to withstand the thermal and mechanical stresses experienced during test flights conducted aboard helicopters, fixed-wing aircraft, and Morpheus, a terrestrial rocket-powered vehicle developed by NASA Johnson Space Center. This paper provides an overview of the sensor and presents results obtained during recent field experiments including a helicopter flight test conducted in December 2012 and Morpheus flight tests conducted during March of 2014

Development of Lidar Sensor Systems for Autonomous Safe Landing on Planetary Bodies

Lidar has been identified by NASA as a key technology for enabling autonomous safe landing of future robotic and crewed lunar landing vehicles. NASA LaRC has been developing three laser/lidar sensor systems under the ALHAT project. The capabilities of these Lidar sensor systems were evaluated through a series of static tests using a calibrated target and through dynamic tests aboard helicopters and a fixed wing aircraft. The airborne tests were performed over Moon-like terrain in the California and Nevada deserts. These tests provided the necessary data for the development of signal processing software, and algorithms for hazard detection and navigation. The tests helped identify technology areas needing improvement and will also help guide future technology advancement activities

Phosphide-based optical emitters for monolithic integration with GaAs MESFETs

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 1995.Includes bibliographical references (p. 137-144).by Joseph F. Ahadian.M.S

Lidar Systems for Precision Navigation and Safe Landing on Planetary Bodies

The ability of lidar technology to provide three-dimensional elevation maps of the terrain, high precision distance to the ground, and approach velocity can enable safe landing of robotic and manned vehicles with a high degree of precision. Currently, NASA is developing novel lidar sensors aimed at needs of future planetary landing missions. These lidar sensors are a 3-Dimensional Imaging Flash Lidar, a Doppler Lidar, and a Laser Altimeter. The Flash Lidar is capable of generating elevation maps of the terrain that indicate hazardous features such as rocks, craters, and steep slopes. The elevation maps collected during the approach phase of a landing vehicle, at about 1 km above the ground, can be used to determine the most suitable safe landing site. The Doppler Lidar provides highly accurate ground relative velocity and distance data allowing for precision navigation to the landing site. Our Doppler lidar utilizes three laser beams pointed to different directions to measure line of sight velocities and ranges to the ground from altitudes of over 2 km. Throughout the landing trajectory starting at altitudes of about 20 km, the Laser Altimeter can provide very accurate ground relative altitude measurements that are used to improve the vehicle position knowledge obtained from the vehicle navigation system. At altitudes from approximately 15 km to 10 km, either the Laser Altimeter or the Flash Lidar can be used to generate contour maps of the terrain, identifying known surface features such as craters, to perform Terrain relative Navigation thus further reducing the vehicle s relative position error. This paper describes the operational capabilities of each lidar sensor and provides a status of their development. Keywords: Laser Remote Sensing, Laser Radar, Doppler Lidar, Flash Lidar, 3-D Imaging, Laser Altimeter, Precession Landing, Hazard Detectio

Imaging Flash Lidar for Autonomous Safe Landing and Spacecraft Proximity Operation

3-D Imaging flash lidar is recognized as a primary candidate sensor for safe precision landing on solar system bodies (Moon, Mars, Jupiter and Saturn moons, etc.), and autonomous rendezvous proximity operations and docking/capture necessary for asteroid sample return and redirect missions, spacecraft docking, satellite servicing, and space debris removal. During the final stages of landing, from about 1 km to 500 m above the ground, the flash lidar can generate 3-Dimensional images of the terrain to identify hazardous features such as craters, rocks, and steep slopes. The onboard fli1ght computer can then use the 3-D map of terrain to guide the vehicle to a safe location. As an automated rendezvous and docking sensor, the flash lidar can provide relative range, velocity, and bearing from an approaching spacecraft to another spacecraft or a space station from several kilometers distance. NASA Langley Research Center has developed and demonstrated a flash lidar sensor system capable of generating 16k pixels range images with 7 cm precision, at a 20 Hz frame rate, from a maximum slant range of 1800 m from the target area. This paper describes the lidar instrument design and capabilities as demonstrated by the closed-loop flight tests onboard a rocket-propelled free-flyer vehicle (Morpheus). Then a plan for continued advancement of the flash lidar technology will be explained. This proposed plan is aimed at the development of a common sensor that with a modest design adjustment can meet the needs of both landing and proximity operation and docking applications