The fusion protein AML1-ETO is generated from the translocation t(8;21)(q22;q22) and is identified in over 12% of normal acute myeloid leukemia cases. While AML1-ETO does not induce acute myeloid leukemia in the murine retroviral transduction model, a spliced isoform, AML1- ETO9a, is able to induce acute myeloid leukemia. One difference between AML1-ETO and AML1-ETO9a is the ability of AML1-ETO to induce an interferon response to a greater degree than AML1-ETO9a. Here I verify that interferons and interferon stimulated genes are transcribed to a greater degree in the presence of AE than AE9a in the U937T cell lines. I also show that AE expression and universal interferon treatment inhibit proliferation in the U937T cell line. Next I verify in mouse bone marrow cells that AE induces interferon stimulated genes more effectively than AE9a. In addition, the induction of interferon stimulated genes is greater in bone marrow cells of C57BL/ 6 wild type mice than interferon receptor knockout mice. I also show that both global interferon treatment and loss of interferon receptor lead to decreases in proliferation and self-renewal ability. Finally I show that lethally irradiated mice treated with AE9a transduced fetal liver cells from mice without interferon receptor experience enhanced acute myeloid leukemia development compared to mice receiving AE9a transduced fetal liver cells from wild type mice. I also show that similar spleen and liver mass, and leukocyte composition is observed in leukemic mice regardless of the genotype of the donor fetal liver cells

This dissertation addresses the problem of precisely determining the geodetic position (geoposition) and orientation of multiple ground-level video cameras. Each video camera is calibrated and equipped with a Global Positioning System (GPS) receiver and compass- magnetometer. The GPS receiver measures the latitude, longitude, and height above mean sea level of the video camera and the orientation of the video camera is derived from data acquired by a compass-magnetometer, which measures the pitch, roll, and yaw of the camera. Additionally, features are tracked throughout the video acquired by the calibrated camera in order to measure the relative camera motion between successive video frames. Each of the measurements from this disparate set of sensors is first mapped such that they are all relative to a common Earth-centered, Earth-fixed Cartesian coordinate frame. The uncertainty of each measurement is also propagated through this mapping. The geoposition and orientation of each camera is independently estimated from all of its associated sensor measurements. The measurements and their associated uncertainties are input at different frequencies and are sometimes incomplete due to GPS dropouts, corrupt video frames, etc., yet the recursive estimation process uses these multiple measurements to reliably calculate the most probable geoposition and orientation with quantified uncertainty at each video frame. Further, if multiple cameras are imaging the same region of a scene, cross-camera feature correspondences are established using a combination of guided matching and robust feature comparison. The resulting independent observations of corresponding features contained in the scene are used to jointly estimate the maximum likelihood of the geoposition and orientation of all cameras imaging the same region of a scene for which feature correspondences have been established. This yields decreased relative errors between the cameras, resulting in more precise estimates of the geoposition and orientation of the cameras. This approach scales well and allows the video cameras to be located anywhere in the proximity of the Earth

During knee movement, cartilage surfaces, which are lubricated with synovial fluid (SF), contact, compress, and slide relative to each other to facilitate joint motion. However, the mechanical behavior of cartilage during joint loading remains unclear. Surface degeneration, altered SF function, and focal articular defects are common following joint injury and may markedly alter the mechanical deformation of cartilage during joint motion. Changes in cartilage mechanics due to such factors may make cartilage more susceptible to further degeneration and wear, predisposing the joint to osteoarthritis. Thus, the goal of this dissertation was to further the understanding of cartilage mechanics under normal and pathologic conditions during joint loading, by elucidating the cartilage deformation during cartilage-on-cartilage articulation as well as the effects of degeneration, lubrication, and focal defects. An experimental approach was developed that allowed the in vitro compression and relative sliding of apposing cartilage surfaces while resultant tissue deformation was imaged at a microscopic level. During cartilage-on-cartilage articulation, cartilage shear deformation varied with tissue depth, elevated with tissue degeneration, and was relatively lower with normal SF lubrication than saline. Shear kinematic studies indicated SF reduced peak shear by allowing surfaces to slide sooner. During tibio-femoral cartilage articulation, axial and shear strains were markedly higher in tibial cartilage than femoral cartilage, being reflective of their respective moduli. Also during tibio-femoral cartilage articulation, acute injury impairs SF function as indicated by elevated shear deformation, while hyaluronan (HA) supplementation partially restores SF function as indicated by reducing resultant shear strains towards normal magnitudes. Finally, tests of patello-femoral cartilage articulation with and without a focal defect showed cartilage strains were drastically elevated in cartilage adjacent to, and lowered in cartilage in direct apposition of, a focal defect following lateral motion. Collectively, this work has further elucidated the contact mechanics of cartilage during joint movement in normal health and following acute injury or trauma. Such characterization may be beneficial to tissue engineering applications, such as engineering implantable cartilage constructs, as well as the development of treatments that address mechanically induced cartilage degeneration and wear.

Many qualitative social scientists conduct single-session interviews with large numbers of individuals so as to maximize the sample size and obtain a wide range of study participants. Yet in some circumstances, one-shot interviews cannot produce information of adequate quality, quantity, and validity. This article explains the several conditions that call for an alternative approach, serial interviewing, that entails interviewing participants on multiple occasions. This method is appropriate when studying complex or ill-defined issues, when interviews are subject to time constraints, when exploring change or variation over time, when participants are reluctant to share valid information, and when working with critical informants. A further benefit is the opportunity it provides for verifying and cross-checking information. This article delineates the general features of this technique. Through a series of encounters, the researcher builds familiarity and trust, probes a range of key topics from multiple angles, explores different facets of participants’ experiences, and learns from events that happen to take place during the interviews. This helps overcome biases associated with one-off interviews, including a tendency toward safe, simple answers in which participants flatten complexity, downplay sociopolitical conflict, and put themselves in a flattering light. This article illustrates the utility of this approach through examples drawn from published work and through a running illustration based on the author’s research on elected neighborhood leaders in Taipei. Serial interviewing helped produce relatively accurate and nuanced data concerning the power these leaders wield and their multiple roles as intermediaries between state and society.

Sickness behavior is broadly represented in vertebrates, usually in association with the fever response in response to acute infections. The reactions to sickness behavior in a group member or potential group member in humans is quite variable, depending upon circumstances. In animals, the reactions to sickness behavior in a group member or potential group member evoke a specific response that reflects the species-specific lifestyle. Groups of animals can employ varied strategies to reduce or address exposure to sickness. Most of these have scarcely been studied in nature from a disease perspective: (1) adjusting exposure to sick conspecifics or contaminated areas; (2) caring for a sick group member; (3) peripheralization and agonistic behaviors to strange non-group conspecifics; and (4) using special strategies at parturition when newborn are healthy but vulnerable. Unexplored in this regard is infanticide, where newborn that are born with very little immunity until they receive antibody-rich colostrum, could be a target of maternal infanticide if they manifest signs of sickness and could be infectious to littermates. The strategies used by different species are highly specific and dependent upon the particular circumstances. What is needed is a more general awareness and consideration of the possibilities that avoiding or adapting to sickness behavior may be driving some social behaviors of animals in nature.

Mammals live and thrive in environments presenting ongoing threats from parasites in the form of biting flies, ticks and intestinal worms and from pathogens as wound contaminants and agents of infectious disease. Several strategies have evolved that enable animals to deal with parasites and pathogens, including eliminating away from the sleeping-resting areas, use of an array of grooming techniques, use of saliva in licking, and consuming medicinal plant-based compounds. These strategies all are species-specific and reflect the particular environment that the animal inhabits.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.