Automatic Designs in Deep Neural Networks

To train a Deep Neural Network (DNN) that performs well for a task, many design steps are taken including data designs, model designs and loss designs. Despite that remarkable progress has been made in all these domains of designing DNNs, the unexplored design space of each component is still vast. That brings the research field of developing automated techniques to lift some heavy work from human researchers when exploring the design space. The automated designs can help human researchers to make massive or challenging design choices and reduce the expertise required from human researchers. Much effort has been made towards automated designs of DNNs, including synthetic data generation, automated data augmentation, neural architecture search and so on. Despite the huge effort, the automation of DNN designs is still far from complete. This thesis contributes in two ways: identifying new problems in the DNN design pipeline that can be solved automatically, and proposing new solutions to problems that have been explored by automated designs. The first part of this thesis presents two problems that were usually solved with manual designs but can benefit from automated designs. To tackle the problem of inefficient computation due to using a static DNN architecture for different inputs, some manual efforts have been made to use different networks for different inputs as needed, such as cascade models. We propose an automated dynamic inference framework that can cut this manual effort and automatically choose different architectures for different inputs during inference. To tackle the problem of designing differentiable loss functions for non-differentiable performance metrics, researchers usually design the loss manually for each individual task. We propose an unified loss framework that reduces the amount of manual design of losses in different tasks. The second part of this thesis discusses developing new techniques in domains where the automated design has been shown effective. In the synthetic data generation domain, we propose a novel method to automatically generate synthetic data for small-data object detection. The synthetic data generated can amend the limited annotated real data of the small-data object detection tasks, such as rare disease detection. In the architecture search domain, we propose an architecture search method customized for generative adversarial networks (GANs). GANs are commonly known unstable to train where we propose this new method that can stabilize the training of GANs in the architecture search process.PHDComputer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163208/1/llanlan_1.pd

Prediction of Proapoptotic Anticancer Therapeutic Response Based on Visualization of Death Ligand-Receptor Interaction and Specific Marker of Cellular Proliferation

Emerging targeted therapeutics hold great promise for the treatment of human cancer. However there are still challenges for selecting patients that most likely will benefit from targeted drugs. One of the major limitations of classical imaging methods is the significant delay to provide quantifiable and objective evidence of response to cancer therapy. Molecular imaging may be useful in targeted drug development by assessing the target expression and drug-target interaction, and predicting therapeutic response in both preclinical and clinical settings. The apoptosis pathway triggered by the Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) receptors is a potential target for therapeutic intervention. TRAIL and its proapoptotic receptor agonistic monoclonal antibodies are being developed as targeted therapeutics in the treatment of human cancer. It is our hypothesis that visualization of proapoptotic receptors and binding of their agonists to proapoptotic receptors can noninvasively predict proapoptotic response if the pathway is intact. Hence the objective of this work is to develop efficient multimodality molecular imaging methods to predict proapoptotic anticancer therapy response before or at the very early stage of treatment. Towards this goal, we have labeled proapoptotic receptor agonists (PARAs) with near-infrared (NIR) fluorescent dyes to image PARAs binding to their targets expressed on the cell surface in cultured cells and in human tumor xenografts grown subcutaneously in immunodeficient mice. Both in vitro and in vivo studies demonstrated that imaging PARAs binding to their targets was well correlated with proapoptotic anticancer therapeutic response when TRAIL signaling pathway was intact. To pursue a more general molecular imaging marker that can predict anticancer therapeutic response even when the signaling pathway is impaired, we explored a novel radiotracer for positron emission tomography (PET) imaging [(18)F]-3\u27-fluoro-3\u27-deoxy-L-thymidine ([(18)F]-FLT), an analogue of thymidine and a specific marker of DNA replication and cellular proliferation. Our results suggested that early changes in [(18)F]-PET may not only predict the tumor histological response to anticancer therapeutics but also determine superiority of one treatment regimen over another. In summary our proof-of-concept studies show that multimodality molecular imaging will greatly aid in accelerating anticancer drug approval process and improving survival and response rates in hard-to-treat cancer

Structure-Function Relationships in Bacterial Regulatory Proteins and an Enzyme Involved in Antibiotic Biosynthesis

The first part of my thesis is focused on a new family of two-component response regulator proteins: Aspartate-Less Regulators (ALR). They lack the catalytic aspartate residue required for the phosphorylation mechanism of typical two component response regulators. We are using biophysical tools to characterize two proteins with redox-sensitive ALR domains: repressor of iron transport regulator (RitR) from Streptococcus pneumonia R6 and diguanylate cyclase Q15Z91 from Pseudoalteromonas atalantica. The structure of inactive RitRC128S monomer showed that the ALR domain and the DNA-binding domain are linked by an α-helix that runs the length of the entire protein, with C128 near the C-terminal end. Bioinformatic analysis of all streptococcal RitR homologs showed that Cys128 is strictly conserved, suggesting that RitR may be a novel redox sensor. Hydrogen peroxide was used to oxidize the cysteine thiol group to determine the structure of the oxidized, dimeric form of RitR. Oxidation of C128 to the disulfide caused a conformational change that caused the DBD to release from the ALR domain. Surprisingly, the freed DBD was observed bound to the ALR domain of the other, disulfide-linked molecule of RitR, recapitulating almost exactly the structure of the inactive, monomeric protein. An extended dimeric conformation was found in the RitRL86A/V93A variant. It binds to the target DNA according to gel filtration and differential scanning fluorimetry. The crystal structure of the RitRL86A/V93A ALR domain showed an unprecedented conformational change for a response regulator protein, where helix α4 is disordered and the two protomers swap their α5 helices to form the dimer. Combined with the C128D mutant in vivo studies, it seems that oxidation of C128 is part of the activation mechanism, but there must be an additional factor that leads to dimerization of the ALR domains. The second ALR protein Q15Z91 has R61 replacing the phosphorylatable aspartate residue in the ALR domain. According to the structure of Q15Z91 with GTP and c-di-GMP, purified Q15Z91 is an activated but product-inhibited dimer. C142 is conserved in the same position as C128 in RitR, and substitution demonstrated that C142 residue is also a redox sensor that involved in Q15Z91 activity regulation. The second part is a mechanistic enzymology project aimed at understanding the structure and mechanism of the novel pyridoxal-5’-phosphate (PLP)-dependent L-arginine hydroxylase/deaminase, MppP, from Streptomyces wadayamensis (SwMppP). SwMppP is predicted to be a type I/II aminotransferase based on primary sequence identity. However, NMR and ESI-MS results showed that SwMppP is not an aminotransferase, but rather a hydroxylase. The enzyme catalyzes the oxygen-dependent hydroxylation of L-arginine, forming 4-hydroxy-2-ketoarginine and the abortive side-product 2-ketoargine in a ratio of 1.7:1. This is exciting because SwMppP is the first PLP-dependent enzyme to react with oxygen in any context other than oxidative decarboxylation. The discovery of this new activity is especially surprising given that the tertiary structure of SwMppP is very similar to that of the prototypical aminotransferase, the E. coli aspartate aminotransferase (PDB entry 1ARS; RMSD of aligned Cα atoms is 3.7 Å). The major differences between the two enzymes are the disordered N terminus of SwMppP, and changes of a limited number of amino acids near the PLP cofactor. The N-terminal helix transitions from a disordered, random-coil state to a helical conformation covering the active site only if/when the substrate is bound. Specific roles of the un-conserved residues in the active site are being studied by mutagenesis. So far, most of the SwMppP mutants have lost the hydroxylase activity and only produce abortive side product 2-ketoarginine. Our mechanistic studies have revealed that formation of the fully oxidized (hydroxylated) product requires 2 equivalents of dioxygen, while formation of 2-ketoarginine requires only one equivalent of dioxygen. Interestingly, the hydroxyl group of 4-hydroxy-2-ketoarginine comes from H2O, not dioxygen. Mutagenesis, structural and kinetic studies were used to understand how the residues in the active site stabilize the quinonoid form of the L-arginine-PLP complex to promote the reaction with dioxygen. Our structural and kinetic characterization of the wild-type and variant forms of SwMppP have allowed us to propose a model where the oxygen incorporated in the hydroxy-arginine product is derived from water rather than from dioxygen. In addition, SwMppP exhibits very high substrate specificity. Either change on the substrate length or guanidine group would result in no binding affinity or little activity

THE USE Of BLENDED LEARNING MODEL TO ENHANCE STUDENT'S LEARNING INTEREST IN ENGLISH

The goal of this study is to ascertain whether employing a blended learning paradigm has increased students' interest in learning. In this study, a descriptive method is combined with a qualitative approach. The population of this study consisted of 36 students in class II-A of the STKIP Yasika Mathematics Education Study Program, which used purposive sampling as its sample technique. Data reduction, data presentation, and conclusion drawing or verification are used in the analysis of data gathering procedures, which include surveys, interviews, and observations. The results showed that, on average, 86 percent of students in class II-A of the Mathematics Education Study Program in STKIP Yasika exhibited a greater interest in studying English when blended learning is used. These results include the following indicators: 1) feelings of enjoyment with the very strong category (89%); 2) attention with the very strong category (83%); 3) very high interest in learning (91%); and 3) actively involved with the very strong category (81%

Off-Axial Tensile Properties of Precontraint PVDF Coated Polyester Fabrics under Different Tensile Rates

Two types of Precontraint PVDF coated polyester are taken as the research objects. A series of uniaxial tensile tests were carried out to study the tensile performances of the specimens in eleven in-plane directions including 0°, 5°, 15°, 25°, 35°, 45°, 55°, 65°, 75°, 85°, and 90°, and six tensile rates (10 mm/min, 25 mm/min, 50 mm/min, 100 mm/min, 200 mm/min, and 500 mm/min) were also considered. The corresponding failure modes and fracture mechanisms were discussed, and the relationships between tensile strength and strain at break and tensile rate and off-axial angles were obtained. Results show that the Precontraint PVDF coated woven fabrics are typically anisotropic. With off-axial angle increasing, the tensile strength decreases while the strain at break increases. Three failure modes can be observed, including failure of yarns pulled out, yarns fracture, and mixture failure. With tensile rate increasing, the tensile strength increases slightly while the strain at break decreases. The tensile strength and strain at break show good linear relationship with tensile rate’s logarithm

The use of computerised accounting systems among accountants on small and micro businesses in Xi'an, Shaan Xi of China

The main purpose of this study is to examine the relationship between the perceived ease of use, perceived usefulness and usage of Computerized Accounting System (CAS) among accountants in small and micro businesses in Xi’an, Shaan Xi of China. This study uses the quantitative method for data analysis. Data were collected using a set of questionnaires distributed to a sample of 400 accountants, 221 of the questionnaire were returned and only 201 were used for further analysis. The results showed a positive relationship between perceived ease of use, perceived usefulness and the use of CAS. About the current usage state of CAS in China, there were about 73.6 % of businesses already implemented CAS in Xi’an Shaan Xi of China. U8 as the most popular type of accounting software, has about 32.8 % of the respondents. The recommendation for this research can be improved by conducting the other factors that have effect on the adoption of CAS. A larger sample should also be covered not just focus on the selected city of China. The data from this research is collected from the online survey. Another approach should also be considered for data collection. Through information provided in this research, accountants, business owners, government, software provider and other related parties could acquire a better understanding of the benefits of CAS. Most of the previous studies were undertaken outside of China such as United States, Kenya, Nigeria, and Malaysia. This study try to form the perspective of the small and micro businesses on the usage and the implementation of CAS especially in Xi’an, Shaan Xi of China to encourage them to use the accounting software