Critical Molecular Pathways in Cancer Stem Cells of Chronic Myeloid Leukemia: A Dissertation

Chronic myeloid leukemia (CML) is a disease characterized by the expansion of granulocytic cells. The BCR-ABL tyrosine kinase inhibitor imatinib, the frontline treatment for Ph+ leukemias, can induce complete hematologic and cytogenetic response in most chronic phase CML patients. Despite the remarkable initial clinic effects, it is now recognized that imatinib will unlikely cure patients because a small cell population containing leukemic stem cells (LSCs) with self-renewal capacity is insensitive to tyrosine kinase inhibitors. In Chapter I, I briefly review the BCR-ABL kinase and its related signaling pathways. BCR-ABL kinase activates several signaling pathways including MAPK, STAT, and JNK/SAPK. BCR-ABL also mediates kinase-independent pathways through SRC family kinases. I will also discuss pathways involving β-catenin, hedgehog, FoxO and Alox5 are critical to the regulation of self-renewal and differentiation in LSC of CML. As detailed in Chapter II, I describe our work evaluating the effects of omacetaxine, a novel CML drug inducing cell apoptosis by inhibition of protein synthesis, on self-renewal and differentiation of LSCs and BCR-ABL-induced CML and acute lymphoblastic leukemia (B-ALL) in mice. We found that treatment with omacetaxine decreased the number of LSCs and prolonged the survival of mice with CML or B-ALL. In chapter III, I describe that Alox5 is an essential gene in the function of LSCs and CML development. We show evidence that Alox5 affects differentiation, cell division, and survival of long-term LSCs. Treatment of CML mice with a 5-LO inhibitor also impaired the function of LSCs similarly and prolonged survival. In chapter IV, I present evidence of our work showing a further dissection the Alox5 pathway by comparing the gene expression profiles of wild type and Alox5-/- LSCs. We show that Msr1 deletion causes acceleration of CML development. We also show that Msr1 affects CML development by regulating the PI3K-AKT pathway and β-catenin. Taken together, these results demonstrate that some pathways including Alox5 and Msr1 play an important role in regulating the self-renewal and differentiation of LSC. More efforts should be put into developing the novel strategies that may effectively target LSCs and thus cure CML

VoxDet: Voxel Learning for Novel Instance Detection

Detecting unseen instances based on multi-view templates is a challenging problem due to its open-world nature. Traditional methodologies, which primarily rely on 2D representations and matching techniques, are often inadequate in handling pose variations and occlusions. To solve this, we introduce VoxDet, a pioneer 3D geometry-aware framework that fully utilizes the strong 3D voxel representation and reliable voxel matching mechanism. VoxDet first ingeniously proposes template voxel aggregation (TVA) module, effectively transforming multi-view 2D images into 3D voxel features. By leveraging associated camera poses, these features are aggregated into a compact 3D template voxel. In novel instance detection, this voxel representation demonstrates heightened resilience to occlusion and pose variations. We also discover that a 3D reconstruction objective helps to pre-train the 2D-3D mapping in TVA. Second, to quickly align with the template voxel, VoxDet incorporates a Query Voxel Matching (QVM) module. The 2D queries are first converted into their voxel representation with the learned 2D-3D mapping. We find that since the 3D voxel representations encode the geometry, we can first estimate the relative rotation and then compare the aligned voxels, leading to improved accuracy and efficiency. Exhaustive experiments are conducted on the demanding LineMod-Occlusion, YCB-video, and the newly built RoboTools benchmarks, where VoxDet outperforms various 2D baselines remarkably with 20% higher recall and faster speed. To the best of our knowledge, VoxDet is the first to incorporate implicit 3D knowledge for 2D tasks.Comment: 17 pages, 10 figure

Temperature- and field angular-dependent helical spin period characterized by magnetic dynamics in a chiral helimagnet MnNb3S6MnNb_3S_6

The chiral magnets with topological spin textures provide a rare platform to explore topology and magnetism for potential application implementation. Here, we study the magnetic dynamics of several spin configurations on the monoaxial chiral magnetic crystal $MnNb_3S_6$ via broadband ferromagnetic resonance (FMR) technique at cryogenic temperature. In the high-field forced ferromagnetic state (FFM) regime, the obtained frequency f vs. resonance field Hres dispersion curve follows the well-known Kittel formula for a single FFM, while in the low-field chiral magnetic soliton lattice (CSL) regime, the dependence of Hres on magnetic field angle can be well-described by our modified Kittel formula including the mixture of a helical spin segment and the FFM phase. Furthermore, compared to the sophisticated Lorentz micrograph technique, the observed magnetic dynamics corresponding to different spin configurations allow us to obtain temperature- and field-dependent proportion of helical spin texture and helical spin period ratio L(H)/L(0) via our modified Kittel formula. Our results demonstrated that field- and temperature-dependent nontrivial magnetic structures and corresponding distinct spin dynamics in chiral magnets can be an alternative and efficient approach to uncovering and controlling nontrivial topological magnetic dynamics.Comment: 29 pages (including Supporting Information), 7 figures, accepted by SCIENCE CHINA Physics, Mechanics & Astronom

YOLOv5s-gnConv: detecting personal protective equipment for workers at height

IntroductionFalls from height (FFH) accidents can devastate families and individuals. Currently, the best way to prevent falls from heights is to wear personal protective equipment (PPE). However, traditional manual checking methods for safety hazards are inefficient and difficult to detect and eliminate potential risks.MethodsTo better detect whether a person working at height is wearing PPE or not, this paper first applies field research and Python crawling techniques to create a dataset of people working at height, extends the dataset to 10,000 images through data enhancement (brightness, rotation, blurring, and Moica), and categorizes the dataset into a training set, a validation set, and a test set according to the ratio of 7:2:1. In this study, three improved YOLOv5s models are proposed for detecting PPE in construction sites with many open-air operations, complex construction scenarios, and frequent personnel changes. Among them, YOLOv5s-gnconv is wholly based on the convolutional structure, which achieves effective modeling of higher-order spatial interactions through gated convolution (gnConv) and cyclic design, improves the performance of the algorithm, and increases the expressiveness of the model while reducing the network parameters.ResultsExperimental results show that YOLOv5s-gnconv outperforms the official model YOLOv5s by 5.01%, 4.72%, and 4.26% in precision, recall, and mAP_0.5, respectively. It better ensures the safety of workers working at height.DiscussionTo deploy the YOLOv5s-gnConv model in a construction site environment and to effectively monitor and manage the safety of workers at height, we also discuss the impacts and potential limitations of lighting conditions, camera angles, and worker movement patterns

Optical and Electronic Properties of Femtosecond Laser-Induced Sulfur-Hyperdoped Silicon N+/P Photodiodes

Impurity-mediated near-infrared (NIR) photoresponse in silicon is of great interest for photovoltaics and photodetectors. In this paper, we have fabricated a series of n+/p photodetectors with hyperdoped silicon prepared by ion-implantation and femtosecond pulsed laser. These devices showed a remarkable enhancement on absorption and photoresponse at NIR wavelengths. The device fabricated with implantation dose of 1014 ions/cm2 has exhibited the best performance. The proposed method offers an approach to fabricate low-cost broadband silicon-based photodetectors

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