An All-in-One Debugging Approach: Java Debugging, Execution Visualization and Verification

We devise a widely applicable debugging approach to deal with the prevailing issue that bugs cannot be precisely reproduced in nondeterministic complex concurrent programs. A distinct efficient record-and-playback mechanism is designed to record all the internal states of execution including intermediate results by injecting our own bytecode, which does not affect the source code, and, through a two-step data processing mechanism, these data will be aggregated, structured and parallel processed for the purpose of replay in high fidelity while keeping the overhead at a satisfactory level. Docker and Git are employed to create a clean environment such that the execution will be undertaken repeatedly with a maximum precision of reproducing bugs. In our development, several other forefront technologies, such as MongoDB, Spark and Node.js are utilized and smoothly integrated for easy implementation. Altogether, we develop a system for Java Debugging Execution Visualization and Verification (JDevv), a debugging tool for Java although our debugging approach can apply to other languages as well. JDevv also offers an aggregated and interactive visualization for the ease of users’ code verification

Metadata Caching in Presto: Towards Fast Data Processing

Presto is an open-source distributed SQL query engine for OLAP, aiming for "SQL on everything". Since open-sourced in 2013, Presto has been consistently gaining popularity in large-scale data analytics and attracting adoption from a wide range of enterprises. From the development and operation of Presto, we witnessed a significant amount of CPU consumption on parsing column-oriented data files in Presto worker nodes. This blocks some companies, including Meta, from increasing analytical data volumes. In this paper, we present a metadata caching layer, built on top of the Alluxio SDK cache and incorporated in each Presto worker node, to cache the intermediate results in file parsing. The metadata cache provides two caching methods: caching the decompressed metadata bytes from raw data files and caching the deserialized metadata objects. Our evaluation of the TPC-DS benchmark on Presto demonstrates that when the cache is warm, the first method can reduce the query's CPU consumption by 10%-20%, whereas the second method can minimize the CPU usage by 20%-40%.Comment: 5 pages, 8 figure

I2P-Rec: Recognizing Images on Large-scale Point Cloud Maps through Bird's Eye View Projections

Place recognition is an important technique for autonomous cars to achieve full autonomy since it can provide an initial guess to online localization algorithms. Although current methods based on images or point clouds have achieved satisfactory performance, localizing the images on a large-scale point cloud map remains a fairly unexplored problem. This cross-modal matching task is challenging due to the difficulty in extracting consistent descriptors from images and point clouds. In this paper, we propose the I2P-Rec method to solve the problem by transforming the cross-modal data into the same modality. Specifically, we leverage on the recent success of depth estimation networks to recover point clouds from images. We then project the point clouds into Bird's Eye View (BEV) images. Using the BEV image as an intermediate representation, we extract global features with a Convolutional Neural Network followed by a NetVLAD layer to perform matching. The experimental results evaluated on the KITTI dataset show that, with only a small set of training data, I2P-Rec achieves recall rates at Top-1\% over 80\% and 90\%, when localizing monocular and stereo images on point cloud maps, respectively. We further evaluate I2P-Rec on a 1 km trajectory dataset collected by an autonomous logistics car and show that I2P-Rec can generalize well to previously unseen environments.Comment: Accepted by IROS 202

Investigating the role of a novel inhibitor of MOZ in B cell development and lymphoma

© 2016 Beinan WangThis Masters study aimed to determine the effects of inhibition of the histone acetyltransferase MOZ (MYST3/KAT6A) on wild type and pre-leukaemic progenitor B cells that overexpress the cellular proto-oncogene MYC using small molecule inhibitors in vitro and in vivo. The study was intended to begin to explore whether chemical inhibition of MOZ might be beneficial in retarding or preventing relapse in B cell lymphoma. Progenitor B cells in bone marrow undergo restricted self-renewal and have the ability to differentiate into each subsequent stage of B cell development. In Eµ-Myc transgenic mice, the Myc gene is overexpressed in progenitor B cells (large pre-B cell stage), which induces self-renewing expansion facilitating the addition of "second hit" mutations and tumour formation. Eµ-Myc transgenic mice are widely used to investigate MYC-driven cancer and B-cell related lymphoma. The histone acetyltransferase MOZ (MYST3/KAT6A) is required to maintain pre-B cell numbers, even in mice bearing the Eµ-Myc trans gene. The Eµ-Myc transgenic mice develop an aggressive form of MYC-driven B cell lymphoma with a mean latency of 105 days. Remarkably heterozygous mutation of Moz dramatically reduces the number of pre-leukemia cells and extends the life expectancy of transgenic mice 4-fold. This has prompted A/Prof. Tim Thomas (Walter and Eliza Hall Institute) to initiate a collaboration with the Cancer and Therapeutics Cooperative Research Centre (CTx) and Prof. Jonathan Baell (Monash Institute for Pharmacy) to develop MYST family inhibitor compounds CTx-035-8014, CTx-039-0984 and CTx-039-1119. Of these, CTx-035-8014 was developed first. CTx-035-8014 is the first nM inhibitor of any histone acetyltrasferases. It has high affinity for MOZ (KAT6A), and MYST4 (KAT6B) and is 5-fold less active towards other MYST family members. Prof. Baell has also developed a negative control compound, CTx-039-2474. This compound has a core structure identical to CTx-035-8014 but has two modifications that prevent binding to the acetyl-CoA pocket completely and thus can be used to control for off-target effects that may be caused by the core structure. In this study, I determined the role of MOZ specifically in the B cell lineage by examining the effects of homozygous deletion of Moz using a pre-pro-B cell specific cre-recombinase driven by the Mb1 promoter. I discovered that MOZ plays a role in B cell development independent of its known role in haematopoietic stem cell and progenitor cells. Importantly, I investigated the effects of the small molecule MOZ/MYST4 inhibitors on B cell progenitors. I demonstrated that CTx-035-8014 inhibited the growth of both wild type and Eµ-Myc preleukemia pre-B cells in vitro. I identified the cellular mechanisms affected: CTx-035-8014 retarded the cell cycle progression of pre-B cells by stimulating the highly proliferative large pre-B cells to differentiate into the relatively quiescent small pre-B cells. CTx-035-8014 did not induce cell death. Transcriptome analysis showed that treatment with CTx-035-8014 resulted in the downregulation of B-cell leukaemia/lymphoma related genes with a concomitant reduction in acetylation of histone 3 on lysine 9, which is the proposed histone target residue of MOZ. Comparison of RNA sequencing data from pre-B cells treated with CTx-035-8014 with data from pre B cells carrying a heterozygous deletion of Moz suggested that CTx-035-8014 acts primarily via inhibiting MOZ function in pre B cells. Finally, treating mice using CTx-039-0984 and CTx-039-1119 in vivo reduced the number of progenitor B cells without affecting femur cellularity. My results suggest that targeting MOZ is a promising therapeutic strategy, which may be applied to retard or prevent relapse in leukaemia/lymphoma in a clinical setting in the future

Immunization with Multiple Virulence Factors Provides Maternal and Neonatal Protection against Group B Streptococcus Serotypes

Group B streptococcus (GBS) commonly colonizes the vaginal tract and is a leading cause of life-threatening neonatal infections and adverse pregnancy outcomes. No effective vaccine is clinically available. Conserved bacterial virulence factors, including those of GBS, have been employed as vaccine components. We investigated serotype-independent protection against GBS by intranasal immunization with six conserved GBS virulence factors (GBSV6). GBSV6 induced systemic and vaginal antibodies and T cell responses in mice. The immunity reduced mouse mortality and vaginal colonization by various GBS serotypes and protected newborn mice of immunized dams against GBS challenge. Intranasal GBSV6 immunization also provided long-lasting protective immunity and had advantages over intramuscular GBSV6 immunization regarding restricting vaginal GBS colonization. Our findings indicate that intranasal immunization targeting multiple conserved GBS virulence factors induces serotype-independent immunity, which protects against GBS infection systemically and vaginally in dams and prevents newborn death. The study presents valuable strategies for GBS vaccine development

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus.

Conserved protein antigens among serotypes of group A Streptococcus pyogenes (GAS) have been focused for vaccine development because of the diversity of GAS serotypes and risks of autoimmunity post-GAS infection. Precise delineation of protective immune response to each of GAS antigens is critical for vaccine efficacy and safety. We recently reported that immunization with SrtA of GAS provides Th17-dependent clearance of heterologous serotypes of GAS in NALT. SCPA is a surface virulence molecule of GAS and known to induce antibody-mediated protection against GAS. We hypothesized that co-immunization with SrtA and SCPA would provide more efficient protection by eliciting combined Th17 and antibody responses. The present study showed that mice that were intranasally co-immunized with SrtA/SCPA cleared GAS more efficiently than the mice that were immunized with either SrtA or SCPA individually, and as efficient as the mice that experienced repeated GAS infections. The co-immunization induced Th17 and robust SCPA antibody responses, accompanied by a rapid influx of neutrophils and high myeloperoxidase activity in NALT, suggesting that simultaneous induction of mucosal Th17 and neutralizing antibody responses offers more effective GAS elimination through rapid infiltration and activation of neutrophils. Moreover, Th17 response was strongly induced in mice that experienced repeated GAS-infection and maintained at a high level even after the bacteria were cleared; whereas, it was moderately induced and promptly returned to baseline following bacterial elimination in SrtA/SCPA co-immunized mice. Additional results showed that the survival rate of systemic challenge was significantly higher in infection experienced than in co-immunized mice, indicating that more immune elements are required for protection against systemic than mucosal GAS infection