MicroRNAs Modulate Hematopoietic Lineage Differentiation

MicroRNAs (miRNAs), an abundant class of ~22 nucleotide non-coding RNAs, are thought to play an important regulatory role in animal and plant development at the posttranscriptional level. Many miRNAs cloned from mouse bone marrow cells are differentially regulated in various hematopoietic lineages, suggesting that they might influence hematopoietic lineage differentiation. Some human miRNAs are linked to leukemias: the miR-15a/miR-16 locus is frequently deleted or down-regulated in patients with B-cell chronic lymphocytic leukemia and miR-142 is at a translocation site found in a case of aggressive B-cell leukemia. miR-181, a miRNA upregulated only in the B cell lineage of mouse bone marrow cells, promotes B cell differentiation and inhibits production of CD8⁺ T cells when expressed in hematopoietic stem/progenitor cells. In contrast miR-142s inhibits production of both CD4⁺ and CD8⁺ T cells and does not affect B cells. Collectively, these results indicate that microRNAs are components of the molecular circuitry controlling mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.

Dependency-Directed Localization of Software Bugs

Software bugs are violated specifications. Debugging is the process that culminates in repairing a program so that it satisfies its specification. An important part of debugging is localization, whereby the smallest region of the program that manifests the bug is found. The Debugging Assistant (DEBUSSI) localizes bugs by reasoning about logical dependencies. DEBUSSI manipulates the assumptions that underlie a bug manifestation, eventually localizing the bug to one particular assumption. At the same time, DEBUSSI acquires specification information, thereby extending its understanding of the buggy program. The techniques used for debugging fully implemented code are also appropriate for validating partial designs.

Planning and Teaching Compliant Motion Strategies

This thesis presents a new high level robot programming system. The programming system can be used to construct strategies consisting of compliant motions, in which a moving robot slides along obstacles in its environment. The programming system is referred to as high level because the user is spared of many robot-level details, such as the specification of conditional tests, motion termination conditions, and compliance parameters. Instead, the user specifies task-level information, including a geometric model of the robot and its environment. The user may also have to specify some suggested motions. There are two main system components. The first component is an interactive teaching system which accepts motion commands from a user and attempts to build a compliant motion strategy using the specified motions as building blocks. The second component is an autonomous compliant motion planner, which is intended to spare the user from dealing with "simple" problems. The planner simplifies the representation of the environment by decomposing the configuration space of the robot into a finite state space, whose states are vertices, edges, faces, and combinations thereof. States are inked to each other by arcs, which represent reliable compliant motions. Using best first search, states are expanded until a strategy is found from the start state to a global state. This component represents one of the first implemented compliant motion planners. The programming system has been implemented on a Symbolics 3600 computer, and tested on several examples. One of the resulting compliant motion strategies was successfully executed on an IBM 7565 robot manipulator.

Information Processing and Transmission in Cellular Automata

A cellular automaton is an iterative array of very simple identical information processing machines called cells. Each cell can communicate with neighboring cells. At discrete moments of time the cells can change from one state to another as a function of the states of the cell and its neighbors. Thus on a global basis, the collection of cells is characterized by some type of behavior. The goal of this investigation was to determine just how simple the individual cells could be while the global behavior achieved some specified criterion of complexity ??ually the ability to perform a computation or to reproduce some pattern. The chief result described in this thesis is that an array of identical square cells (in two dimensions), each cell of which communicates directly with only its four nearest edge neighbors and each of which can exist in only two states, can perform any computation. This computation proceeds in a straight forward way. A configuration is a specification of the states of all the cells in some area of the iterative array. Another result described in this thesis is the existence of a self-reproducing configuration in an array of four-state cells, a reduction of four states from the previously known eight-state case. The technique of information processing in cellular arrays involves the synthesis of some basic components. Then the desired behaviors are obtained by the interconnection of these components. A chapter on components describes some sets of basic components. Possible applications of the results of this investigation, descriptions of some interesting phenomena (for vanishingly small cells), and suggestions for further study are given later.

Motor Control and Learning by the State Space Model

A model is presented that deals with problems of motor control, motor learning, and sensorimotor integration. The equations of motion for a limb are parameterized and used in conjunction with a quantized, multi-dimensional memory organized by state variables. Descriptions of desired trajectories are translated into motor commands which will replicate the specified motions. The initial specification of a movement is free of information regarding the mechanics of the effector system. Learning occurs without the use of error correction when practice data are collected and analyzed.

On Motion Planning with Uncertainty

Robots must successfully plan and execute tasks in the presence of uncertainty. Uncertainty arises from errors in modeling, sensing, and control. Planning in the presence of uncertainty constitutes one facet of the general motion planning problem in robotics. This problem is concerned with the automatic synthesis of motion strategies from high level task specification and geometric models of environments. In order to develop successful motion strategies, it is necessary to understand the effect of uncertainty on the geometry of object interactions. Object interactions, both static and dynamic, may be represented in geometrical terms. This thesis investigates geometrical tools for modeling and overcoming uncertainty. The thesis describes an algorithm for computing backprojections o desired task configurations. Task goals and motion states are specified in terms of a moving object's configuration space. Backprojections specify regions in configuration space from which particular motions are guaranteed to accomplish a desired task. The backprojection algorithm considers surfaces in configuration space that facilitate sliding towards the goal, while avoiding surfaces on which motions may prematurely halt. In executing a motion for a backprojection region, a plan executor must be able to recognize that a desired task has been accomplished. Since sensors are subject to uncertainty, recognition of task success is not always possible. The thesis considers the structure of backprojection regions and of task goals that ensures goal recognizability. The thesis also develops a representation of friction in configuration space, in terms of a friction cone analogous to the real space friction cone. The friction cone provides the backprojection algorithm with a geometrical tool for determining points at which motions may halt.