Digital Apprentice for Chatter Detection: An On-line Learning Approach to Regenerative Chatter Detection in Machining via Human-Machine Interaction

Regenerative chatter in machining, which is characterized by self-excited vibration, is a common process anomaly that limits productivity and part quality in machining operations. This thesis proposes an on-line approach for chatter detection via effective human-machine interaction, facilitating knowledge transfer from experienced machinists to the “digital apprentice” through the “learnable skill primitive” (LSP) method that establishes a chatter detection threshold. The research focus is to develop the methodology for chatter-specific knowledge acquisition and a human-machine interface inspired by computing techniques and frameworks such as learning from demonstration, reinforcement learning, and interactive agent shaping. In this work, the milling operation is selected as a case study for the proposed LSP method. Digital audio data is acquired from milling experiments through a studio-style condenser microphone mounted inside a milling machine. The data is pre-processed through various digital filters before Fast Fourier Transform (FFT) is performed to identify the chatter frequency contents. During the training phase, data for the human operator’s natural reaction to chatter is collected via a specially designed human-machine interface. The learned chatter detection thresholds are obtained through the “learnable skill primitive” method by temporally mapping the reaction data to the cutting signal. In addition, a variance mitigation strategy is developed to reduce the negative impact of the high variance in the operator’s reaction time to chatter. During the testing phase, experiments are conducted to evaluate the detection accuracy, detection speed, and robustness of the learned chatter detection thresholds. Experimental data support the claim that the learned thresholds can detect chatter with good detection accuracy and detection speed. Finally, the learned threshold is demonstrated to be robust to milling of different workpiece materials under different cutting conditions such as feeds, speeds, axial and radial immersions (depths of cut), and directions of cutting.M.S

Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D.

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 significantly increased the mobility and tube formation of the LECs, inhibited cisplatin-induced LEC apoptosis, but had no effect on cell proliferation and the cell cycle. Moreover, recombinant Sulf2 (rSulf2) combined with VEGF-D further promoted the proliferation, cell cycle, mobility and tube-like structure formation in the LECs, and at the same time inhibited cisplatin-induced apoptosis especially in the late stage. Sulf2 also significantly increased the density of lymphatic vessels in mouse ears and breast cancer xenografts in vivo. AKT1 was also shown to be upregulated and activated by Sulf2. Our results confirmed that Sulf2 facilitated lymphangiogenesis in breast cancer cells by regulating VEGF-D and that the AKT1‑related signaling pathway was involved

Activity Assay of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer Cells Using Peptide-Conjugated Magnetic Beads

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited treatment options. Epidermal growth factor receptor I (EGFR) has emerged as a promising target in TNBC. Limited success of the EGFR kinase inhibiting small molecules in clinical trials may be attributed in part to inaccuracy in identifying EGFR signatures in patient tumors. In light of the absence of a simple correlation between EGFR expression and its degree of activation, a simple and reliable tool that can quantify EGFR kinase activity in tumor samples may be of therapeutic value in predicting patient-specific EGFR targeted therapies. This study reports the development of an assay that can quantitatively profile EGFR kinase activities and inhibitor sensitivities in TNBC cell lysates by using peptide reporters covalently tethered to magnetic beads in a controlled orientation. The use of magnetic beads provides rapid sample handling and easy product isolation. The potential of this approach was demonstrated by screening a set of five clinically relevant EGFR tyrosine kinase inhibitors. Formatted for microwell plates, this magnetic bead-based kinase assay may be used as a complementary approach for direct high-throughput screening of small molecule inhibitors.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140099/1/adt.2012.454.pd

Nanodelivery Systems Delivering Hypoxia-Inducible Factor-1 Alpha Short Interfering RNA and Antisense Oligonucleotide for Cancer Treatment

Hypoxia-inducible factor (HIF), which plays a crucial role in oxygen homeostasis, contributes to immunosuppression, tumor angiogenesis, multidrug resistance, photodynamic therapy resistance, and metastasis. HIF as a therapeutic target has attracted scientists’ strong academic research interests. Short interfering RNA (siRNA) and antisense oligonucleotide (ASO) are the more promising and broadly utilized methods for oligonucleotide-based therapy. Their physicochemical characteristics such as hydrophilicity, negative charge, and high molecular weight make them impossible to cross the cell membrane. Moreover, siRNA and ASO are subjected to a rapid deterioration in circulation and cannot translocate into nuclear. Delivery of siRNA and ASO to specific gene targets should be realized without off-target gene silencing and affecting the healthy cells. Nanoparticles as vectors for delivery of siRNA and ASO possess great advantages and flourish in academic research. In this review, we summarized and analyzed regulation mechanisms of HIF under hypoxia, the significant role of HIF in promoting tumor progression, and recent academic research on nanoparticle-based delivery of HIF siRNA and ASO for cancer immunotherapy, antiangiogenesis, reversal of multidrug resistance and radioresistance, potentiating photodynamic therapy, inhibiting tumor metastasis and proliferation, and enhancing apoptosis are reviewed in this thesis. Furthermore, we hope to provide some rewarding suggestions and enlightenments for targeting HIF gene therapy

Global burden of colistin-resistant bacteria : mobilized colistin resistance genes study (1980-2018)

Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1-9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid

Unified Finite Horizon H

This paper addresses the H∞ fusion filtering problem for networked dynamical systems, where measurements may arrive at fusion center in four different scenes and the fusion center could receive none, one, or multiple measurements in a fusion period. A unified H∞ performance criterion function, which is suitable for different measurement arrival scenes, is designed for the filtering process of networked dynamical systems. Then, the H∞ performance criterion function is described as an indefinite quadratic inequality and solved by a novel noise projection method in Krein space. On this basis, a unified finite horizon H∞ filtering method is proposed for networked dynamical systems. Simulation results are provided to illustrate the correctness and the effectiveness of the theoretical analysis

Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury

Inflammatory response plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI. Wild-type Nrf2 (+/+) and Nrf2 (−/−)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Electrophoretic mobility shift assays (EMSAs) were performed to analyze the activation of nuclear factor kappa B (NF-κB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Immunohistochemistry staining experiments were performed to detect the expression of intercellular adhesion molecule-1 (ICAM-1). Nrf2 (−/−) mice were shown to have more NF-κB activation, inflammatory cytokines TNF-α, IL-1β and IL-6 production, and ICAM-1 expression in brain after TBI compared with their wild-type Nrf2 (+/+) counterparts. The results suggest that Nrf2 plays an important protective role in limiting the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI

Improving gold recovery from a refractory ore via Na₂SO₄ assisted roasting and alkaline Na₂S leaching

Gold recovery from refractory gold ores with controlled roasting remained well below 80%. Na2SO4 was added in an O-2-enriched single stage roasting of a refractory gold ore to improve its gold recovery. Changes in physicochemical properties of the calcines suggested that this reduced the sintering as well as facilitated the formation of pores and a water soluble phase within the calcine. Thermodynamic analysis and leaching results demonstrated that Na2S solutions could effectively remove Sb species from the calcine. An extraction process that includes Na2SO4 assisted roasting and alkaline Na2S leaching is shown to be able to achieve a gold recovery of over 95% from the refractory ore