Frida Kahlo’s Self-Identity: An Analysis of Self-Portrait on the Borderline Between Mexico and the United States

Self-Portrait on the Borderline Between Mexico and the United States by the Mexican artist Frida Kahlo reveals a multitude of insights. This paper assesses how the nuances embodied in the painting serve as critical clues to comprehend Frida Kahlo’s personal experiences, Mexican culture, and the approach of discovering the contextual background through the work of art. Beginning with a detailed formal analysis of the portrait, this paper further explores it by making connections with contextual evidence. Through timely reference to Frida Kahlo’s political stance, cultural identity, and health, the paper demonstrates how the painting proffers insight into both the artist’s life and Aztec culture

Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation

Inhibiting BCR-ABL kinase activity with tyrosine kinase inhibitors (TKIs) has been the frontline therapy for CML. Resistance to TKIs frequently occurs, but the mechanisms remain elusive. First, to uncover survival pathways involved in TKI resistance in CML, I conducted a genome-wide RNAi screen in human CML cells to identify genes governing cellular sensitivity to the first generation TKI called IM (Gleevec). I identified genes converging on and activating the MEK/ERK pathway through transcriptional up-regulation of PRKCH. Combining IM with a MEK inhibitor synergistically kills TKI-resistant CML cells and CML stem cells. Next, I performed single cell RNA-seq to compare expression profiles of CML stem cells and hematopoietic stem cells isolated from the same patient. Among the genes that are preferentially expressed in CML stem cells is PIM2, which encodes a pro-survival serine-threonine kinase that phosphorylates and inhibits the pro-apoptotic protein BAD. Inhibiting PIM2 function sensitizes CML stem cells to IM-induced apoptosis and prevents disease relapse in a CML mouse model. Last, I devised a CRISPR-Cas9 based strategy to perform insertional mutagenesis at a defined genomic location in murine hematopoietic Ba/F3 cells. As proof of principle, we showed its capability to perform unbiased, saturated point mutagenesis in a 9 amino acid region of BCR-ABL encompassing the socalled “gatekeeper” residue, an important determinant of TKI binding. We found that the ranking order of mutations from the screen correlated well with their prevalence in IM-resistant CML patients. Overall, my findings reveal novel resistance mechanisms in CML and provide alternative therapeutic strategies

GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2

Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. Transformation of HSCs by the breakpoint cluster region-ABL tyrosine kinase (BCR-ABL) oncogene causes chronic myelogenous leukemia (CML). The E-twenty six (ets) transcription factor GA binding protein (GABP) is a tetrameric transcription factor complex that contains GABPalpha and GABPbeta proteins. Deletion in bone marrow of Gabpa, the gene that encodes the DNA-binding component, caused cell cycle arrest in HSCs and profound loss of hematopoietic progenitor cells. Loss of Gabpalpha prevented development of CML, although mice continued to generate BCR-ABL-expressing Gabpalpha-null cells for months that were serially transplantable and contributed to all lineages in secondary recipients. A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GABP in HSCs. Prkd2 expression was markedly reduced in Gabpalpha-null HSCs and progenitor cells. Reduced expression of PRKD2 or pharmacologic inhibition decreased cell cycling, and PRKD2 rescued growth of Gabpalpha-null BCR-ABL-expressing cells. Thus, GABP is required for HSC cell cycle entry and CML development through its control of PRKD2. This offers a potential therapeutic target in leukemia

A wall-climbing robot for indoor inspections

Regular inspection is indispensable during the operation period of existing buildings. The time-consuming and laborious nature of traditional inspection methods has triggered the research interest in using mobile robots to facilitate the inspection process. However, one critical issue that has been overlooked in the development of existing indoor inspection robot systems is that the developed robot prototypes can easily cause interference problems in occupied buildings. Wall-climbing robotic inspection systems shall overcome the intrusiveness issue owing to little intersections between their working spaces and people’s activity spaces. Therefore, an indoor wall-climbing robot system for inspection purposes is developed in this research

Exploration of using a wall-climbing robot system for indoor inspection in occupied buildings

Abstract Indoor inspection robots operating in occupied buildings need to minimize disturbance to occupants and access high areas of a room and cramped spaces obstructed by obstacles for higher inspection coverage. However, existing indoor inspection robots are still unable to meet these requirements. This paper aims to explore the feasibility of applying wall-climbing robots to address these requirements. To this end, we propose a small-sized wall-climbing robot prototype that can move on common indoor surfaces. We extend the proposed prototype to support thermographic inspection by integrating thermal imaging technology into it. Experiment results show that the proposed robot prototype can reach more wall and floor areas for inspection than previously developed indoor inspection robots. It has also been demonstrated that the reduced size and the wall-climbing ability allow the robot to largely avoid human activity areas, thereby reducing disturbance to occupants. This study represents the first attempt to introduce wall-climbing robots into the indoor inspection domain and provides the initial validation of their advantages over existing indoor inspection robots regarding improving inspection coverage and minimizing disturbance to occupants. The findings in this study can provide valuable insights for the future design, selection and application of robotic systems for indoor inspection tasks

A Proposed Ontology for Knowledge Representation in Designing Building Inspection Robot Systems

Robotic technology is now rapidly penetrating the building inspection field and has great potential in improving inspection efficiency and accuracy. However, existing building inspection robot systems are usually designed to adapt to limited application scenarios. Making use of building inspection domain knowledge especially knowledge about building inspection tasks and physical surroundings of building defects is essential to tackle the problems of existing building inspection robot systems. To support knowledge sharing between building inspection and robotics domains and collaborative design processes, a high-level shared ontology is developed in this study to formalize the knowledge that is relevant to the design of a building inspection robot system. It contains two main domain ontology models including a Robot System Model and a Building Inspection Model

BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription

The oncoprotein BCR-ABL transforms myeloid progenitor cells and is responsible for the development of chronic myeloid leukemia (CML). In transformed cells, BCR-ABL suppresses apoptosis as well as autophagy, a catabolic process in which cellular components are degraded by the lysosomal machinery. The mechanism by which BCR-ABL suppresses autophagy is not known. Here we report that in both mouse and human BCR-ABL-transformed cells, activating transcription factor 5 (ATF5), a pro-survival factor, suppresses autophagy but does not affect apoptosis. We find that BCR-ABL, through phosphoinositide-3-kinase (PI3K)/AKT/FOXO4 signaling, transcriptionally upregulates ATF5 expression and that ATF5, in turn, stimulates transcription of mammalian target of rapamycin (mTOR; also called mechanistic target of rapamycin), a well-established master negative-regulator of autophagy. Previous studies have shown that the BCR-ABL inhibitor imatinib mesylate induces both apoptosis and autophagy, and that the resultant autophagy modulates the efficiency by which imatinib kills BCR-ABL-transformed cells. We demonstrate that imatinib-induced autophagy is due to inhibition of the BCR-ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway that we have identified in this study