Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchi labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests for long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.Comment: 48 pages, 8 figures. To be submitte

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Prediction and experimental validation of weld dimensions in thin plates using superimposed laser sources technique

The objective of this research is to develop a method to evaluate important weld dimensions in thin plates by using laser generated ultrasounds and EMAT receiver. The superimposed laser sources (SLS) technique is developed to generate narrowband Lamb waves with fixed wavelengths in thin plates. The method permits the flexibility of selecting desired wavelength. The signal processing procedure that combines wavenumber-frequency (k-w) domain filtering and synthetic phase tuning (SPT) is used to further reduce the complexity of Lamb waves. The k-w domain filtering technique helps to filter out the unwanted wave components traveling at the direction that is not of interest to us and the SPT technique is applied to amplify and isolate a particular Lamb wave mode. The signal processing procedure facilitates the calculation of reflection coefficients of Lamb waves that result from the presence of weld joints. The SLS and signal processing procedure are then applied to measure reflection coefficients in butt welds and lap welds. Two methods, the direct method and indirect method, are used to develop models that use reflection coefficients as predictors to predict these weld dimensions. The models developed in this research are shown to accurately predict weld dimensions in thin plates.Ph.D.Committee Chair: Ume, I. Charles; Committee Member: Mayor, J. Rhett; Committee Member: Michaels, Jennifer; Committee Member: Ruzzene, Massimo; Committee Member: Sitaraman, Sures

Characterize the Mechanical Properties of Ge Nanowires and Polymers with Nano-indentation and Scratch Technologies

奈米科技為人類第四次工業革命，由於奈米時代的來臨，奈米尺寸的元件或材料一一被提出，對於材料的機械性質，例如楊氏模數或硬度的瞭解是絕對必要的工作。 本論文首先探討的主題為鍺奈米線的性質，所使用的測量工具為原子力顯微鏡，所根據的基礎理論為奈米壓痕量測理論。希望藉此量測出鍺奈米線的性質，以利未來的應用。 實驗的主要目的，在利用原子力顯微鏡探針壓印鍺奈米線，並計算出其楊氏模數。實驗的第一步是校正光感測器電壓信號值與Z軸壓電驅動器位移之間的轉換常數以及壓印接觸面積函數。實驗的第二步是利用AFM探針壓印HCPP高分子材料並與MTS Nano Indenter的數值做比較以驗證AFM壓印的有效性。實驗的最後一步便是將鍺奈米線撒佈在鍍上金薄膜的晶圓上，藉以利用金薄膜與鍺奈米線性質的不同來確定是否壓印到鍺奈米線，並計算出鍺奈米線的楊氏模數為155GPa。 本論文的第二部分是探討材料抗磨耗的特性。本實驗利用奈米壓痕試驗機（Nano Indenter）作刻劃的實驗並且利用雷射反射共軛聚焦顯微鏡（Confocal Microscope）來觀察材料的表面性質。並且探討材料硬度、楊氏模數、時變效應以及刻劃子外形與速度、負載之間的關係，以期能為未來發展刻劃理論數學模型建立一良好的基礎。It is said that nano technology is the forth industrial revolution. Along with the arrival of nano era, a lot of nano-scale components or materials have been proposed. Therefore, it is an absolutely necessary task to study the mechanical properties such as Young’s Modulus and hardness, etc. of the materials. The first objective of this thesis is to investigate the properties of Ge nanowires. The apparatus for investigating Ge nanowires is atomic force microscopy, AFM. And the experiment is based on nanoindentation theory. It is expected to measure the properties of Ge nanowires for the further application in the future. The main purpose of the experiment is to indent on the Ge nanowires and derive its Young’s Modulus. The first step of the experiment was to calibrate the optical signal to Z piezo actuator displacement constant and the contact area function. Secondly, HCPP, a polymer, was indented with AFM. And the material properties acquired was compared with the data acquired by MTS Nano Indenter to validate the effectiveness of AFM indentation. Finally, Ge nanowires were dispersed evenly onto the wafer which was coated with Au film. By means of different properties possessed by Au and Ge nanowires, whether or not the Ge nanowires had been indented was known. Then the Young’s Modulus of Ge nanowires were shown to be 155GPa. The second part of this thesis is to characterize the abilities of different polymers to resist abrasion or scratching. Nano Indenter was used to perform scratch tests and Confocal Microscope was used to observe surface conditions of samples. The correlations between different factors such as hardness, Young’s Modulus, Time-dependent effects, shape of scratch tip, velocity and load were studied. The results can be contributed for setting up a sound foundation for building up a math model of scratching.目錄 誌謝 中文摘要 i 英文摘要 ii 目錄 iv 圖例目錄 vii 表格目錄 xi 第一章 緒論 1 1.1 前言 1 1.2 研究動機與目標 4 第二章 文獻回顧 6 2.1 一維奈米材料的製備與性質測定 6 2.1.1 一維奈米材料的製備 6 2.1.2 以原子力顯微鏡做性質測定 7 2.2 奈米壓印技術理論基礎 11 2.3 影響壓印實驗誤差之因素 18 2.3.1 壓痕尺寸效應 18 2.3.2 基材效應 20 2.3.3 表面粗糙度效應 21 2.3.4 黏彈性質效應 21 2.3.5 熱漂移效應 23 2.3.6 側向運動效應 23 2.3.7 壓痕邊緣之堆積與下沉效應 24 第三章 實驗材料、設備與架構 27 3.1 實驗材料 27 3.1.1 鍺奈米線製備 27 3.1.2 實驗材料準備流程 28 3.2 實驗設備 31 3.2.1 Veeco AutoProbe M5 31 3.2.2 MTS Nano Indenter 32 3.2.3 Zeiss Confocal Microscope 34 3.3 實驗架構 35 3.3.1 實驗流程 35 3.3.2 AFM壓印圖形解釋 36 3.3.3 系統架設與數學模型 39 第四章 實驗參數校正 45 4.1 轉換常數校正 45 4.2 探針規格與面積函數校正 48 第五章 實驗結果與討論 53 5.1 HCPP壓印實驗結果 53 5.1.1 AFM實驗結果 53 5.1.2 MTS Nano Indenter實驗結果 57 5.1.3 實驗結果與比較 58 5.2 鍺奈米線壓印實驗結果 60 5.2.1 實驗前期準備 60 5.2.2 AFM掃描圖形分析 61 5.2.3 AFM鍺奈米線壓印分析 74 5.2.4 鍺奈米線壓印結果總整理 80 5.3 刻劃實驗結果 86 5.3.1 刻劃實驗目的 86 5.3.2 刻劃樣示與材料性質 87 5.3.3 刻劃實驗結果與討論 89 5.3.4 刻劃實驗結論 100 第六章 結論與未來展望 101 Reference 10

Anti-Inflammatory Effect and Mechanism of the Green Fruit Extract of Solanum integrifolium Poir.

The green fruit of Solanum integrifolium Poir. has been used traditionally as an anti-inflammatory and analgesic remedy in Taiwanese aboriginal medicine. The goal of this study is to evaluate the anti-inflammatory activity and mechanism of the green fruit extract of S. integrifolium. A bioactivity-guided fractionation procedure was developed to identify the active partition fraction. The methanol fraction (ME), with the highest phenolic content, exhibited the strongest inhibitory effect against LPS-mediated nitric oxide (NO) release and cytotoxicity in RAW264.7 macrophages. ME also significantly downregulated the expression of LPS-induced proinflammatory genes, such as iNOS, COX-2, IL-1β, IL-6, CCL2/MCP-1, and CCL3/MIP1α. Moreover, ME significantly upregulated HO-1 expression and stimulated the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with the HO-1 inhibitor zinc protoporphyrin and MEK/ERK inhibitor U0126 attenuated ME’s inhibitory activity against LPS-induced NO production. Taken together, this is the first study to demonstrate the anti-inflammatory activity of green fruit extract of S. integrifolium and its activity may be mediated by the upregulation of HO-1 expression and activation of ERK1/2 pathway

Diminished COX-2/PGE₂-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

<div><p>Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. In the current study, the role of G6PD on the inflammatory response was determined in both scramble control and G6PD-knockdown (G6PD-kd) A549 cells upon tumor necrosis factor-α (TNF-α) stimulation. A decreased expression pattern of induced COX-2 and reduced production of downstream PGE₂ occurred upon TNF-α stimulation in G6PD-kd A549 cells compared with scramble control A549 cells. TNF-α-induced antiviral activity revealed that decreased COX-2 expression enhanced the susceptibility to coronavirus 229E infection in G6PD-kd A549 cells and was a result of the decreased phosphorylation levels of MAPK (p38 and ERK1/2) and NF-κB. The impaired inflammatory response in G6PD-kd A549 cells was found to be mediated through NADPH oxidase (NOX) signaling as elucidated by cell pretreatment with a NOX2-siRNA or NOX inhibitor, diphenyleneiodonium chloride (DPI). In addition, NOX activity with TNF-α treatment in G6PD-kd A549 cells was not up-regulated and was coupled with a decrease in NOX subunit expression at the transcriptional level, implying that TNF-α-mediated NOX signaling requires the participation of G6PD. Together, these data suggest that G6PD deficiency affects the cellular inflammatory response and the decreased TNF-α-mediated antiviral response in G6PD-kd A549 cells is a result of dysregulated NOX/MAPK/NF-κB/COX-2 signaling.</p></div

The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed

G6PD deficiency increases the replication level of coronavirus via down-regulation of TNF-α-induced COX-2 expression and its downstream metabolite PGE₂ production in A549 cells.

<p>(A) Scramble control and G6PD-kd A549 were treated with 15 ng/ml TNF-α for the indicated time, and the expression of COX-2 mRNA was investigated by quantitative PCR. Data are reported as the means ±SD, n = 3. *p<0.05. (B) Scramble control and G6PD-kd A549 were treated with 15 ng/ml TNF-α for 24 h. COX-2 promoter activity was determined by the luciferase assay. Data are reported as the means ±SD, n = 3. *p<0.05. (C) The expression level of COX-2 protein upon 15 ng/ml TNF-α treatment at different time courses was shown, and β-actin was present as the loading control. Numbers represent relative fold differences of protein levels on the basis of densitometer quantitation. Data are means ±SD of three separate experiments, *p<0.05 and **p<0.01 represent levels of significant difference when comparing scramble control with TNF-α treatment at the corresponding time points. (D) PGE₂ secretion by 15 ng/ml TNF-α stimulation was detected by ELISA. Data are reported as the means ±SD, n = 3. *p<0.05. (E) Upper panel: Scramble control and G6PD-kd A549 cells were infected with coronavirus (0.1 MOI) for 8 h, and the infected cells were harvested for analyzing viral mRNA expression. Data are reported as the fold change normalized to infected scramble control cells. Data are reported as the means ±SD, n = 3. *p<0.05. Lower panel: Scramble control and G6PD-kd A549 cells were infected with HCoV-229E (0.1 MOI) for 24 h then viral particle was harvested and virus titer was determined using plaque assay. (F) Scramble control and G6PD-kd A549 cells were infected with coronavirus (0.1 MOI) for 8 h upon 15 ng/ml TNF-α with or without 10 μM celecoxib co-pretreatment, and the infected cells were harvested for analyzing viral mRNA expression. Data are reported as the fold normalized to infected control cells. Data are reported as the means ±SD, n = 3. *p<0.05.</p