A Two-Point Modulation Spread-Spectrum Clock Generator With FIR-Embedded Binary Phase Detection and 1-Bit High-Order ΔΣ Modulation

Xu, Ni,Shen, Yiyu,Lv, Sitao,Liu, Han,Rhee, Woogeun,Wang, Zhihua The Institute of Electronics and Information Engin 2016 Journal of semiconductor technology and science Vol.16 No.4

This paper describes a spread-spectrum clock generation method by utilizing a ${\Delta}{\Sigma}$ digital PLL (DPLL) which is solely based on binary phase detection and does not require a linear time-to-digital converter (TDC) or other linear digital-to-time converter (DTC) circuitry. A 1-bit high-order ${\Delta}{\Sigma}$ modulator and a hybrid finite-impulse response (FIR) filter are employed to mitigate the phase-folding problem caused by the nonlinearity of the bang-bang phase detector (BBPD). The ${\Delta}{\Sigma}$ DPLL employs a two-point modulation technique to further enhance linearity at the turning point of a triangular modulation profile. We also show that the two-point modulation is useful for the BBPLL to improve the spread-spectrum performance by suppressing the frequency deviation at the input of the BBPD, thus reducing the peak phase deviation. Based on the proposed architecture, a 3.2 GHz spread-spectrum clock generator (SSCG) is implemented in 65 nm CMOS. Experimental results show that the proposed SSCG achieves peak power reductions of 18.5 dB and 11 dB with 10 kHz and 100 kHz resolution bandwidths respectively, consuming 6.34 mW from a 1 V supply.

Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells

Xu, Qian,Liu, Zhihua,Guo, Ling,Liu, Rui,Li, Rulei,Chu, Xiang,Yang, Jiajia,Luo, Jia,Chen, Faming,Deng, Manjing Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.11

Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of $HIF-1{\alpha}$, vascular endothelial growth factor (VEGF), and RUNX2 ex vivo and in situ. VEGF is a target gene of $HIF-1{\alpha}$, and the increased expression of VEGF and RUNX2 proteins was enhanced by cobalt chloride ($CoCl_2$, $100{\mu}mol/L$), an agonist of $HIF-1{\alpha}$, and suppressed by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, $10{\mu}mol/L$), an antagonist of $HIF-1{\alpha}$. In addition, VEGF could regulate the expression of RUNX2, as RUNX2 expression was enhanced by human VEGF ($hVEGF_{165}$) and suppressed by VEGF siRNA. In addition, knocking down VEGF could decrease the expression of osteogenesis-related genes, i.e., RUNX2, alkaline phosphatase (ALP), and type I collagen (COL1), and hypoxia could enhance the expression of ALP, COL1, and osteocalcin (OCN) in the early stage of osteogenesis of PDLSCs. Taken together, our results showed that hypoxia could mediate the expression of RUNX2 in PDLSCs via $HIF-1{\alpha}$-induced VEGF and play a positive role in the early stage of osteogenesis of PDLSCs.

Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18

Xu Xiaohui,Song Cheng,Chen Zhihua,Yu Chenxiao,Wang Yi,Tang Yiting,Luo Judong 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1

Purpose The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC). Materials and Methods In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3’-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used. Results In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay. Conclusion HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.

Effect of aberrantly methylated androgen receptor target gene PCDH7 on the development of androgen-independent prostate cancer cells

Siqi Xu,Xiaoyan Wu,Zhihua Tao,Hongsheng Li1,Chenliang Fan,Songjin Chen,Jianwei Guo,Yao Ning,Xuqi Hu 한국유전학회 2020 Genes & Genomics Vol.42 No.3

Background Androgen-independent prostate cancer (AIPC) is an extremely malignant tumor developed from the androgen dependent (ADPC). However, the mechanism of transition process from ADPC to AIPC remains unknown. Objective Here we aimed to identify the androgen receptor (AR) target gene and its roles in AIPC. Methods Target genes of AR were identified by ChIP-seq in AIPC cells. AR target gene PCDH7 was detected by real time PCR and western blot. Methylation of PCDH7 was measured by bisulfite sequencing and bisulfite amplicon sequencing. Cell growth, invasion and apoptosis were measured by CCK-8, transwell and flow cytometry, respectively. Results AR was significantly enriched in the upstream of PCDH7 gene. The expression of PCDH7 was significantly decreased, while the methylation of PCDH7 was increased in the AIPC cells compared to the ADPC cells. DNA methyltransferase inhibitor significantly suppressed the methylation and increased the mRNA and protein level of PCDH7. Moreover, overexpression of DNMT1 remarkably reduced the mRNA and protein level of PCDH7. DNA methyltransferase inhibitor decreased the cell growth and invasion while promote the cell apoptosis in the AIPC cells. AR significantly target PCDH7, whose hypermethylation may repress cell growth and invasion, and promote apoptosis in AIPC. Conclusions This study might provide a novel potential target for the treatment of AIPC.

Obstacle-negotiation performance on challenging terrain for a parallel legwheeled robot

Kang Xu,Shou-Kun Wang,Binkai Yue,Jun-Zheng Wang,Fei Guo,Zhihua Chen 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.1

High obstacle-negotiation performance of quadruped robots for the challenging terrain is strongly demanded in some fields, including payload delivery and disaster relief. In this study, a parallel leg-wheeled robot with the high mobility performance on targeted types of rough terrain is proposed. In contrast to other obstacle-negotiating robots, the strength of this robot is that it has adequate over-obstacle capabilities with a horizontal body in terms of different obstacle shapes, which mainly derives from the multi-DOF (degree of freedom) flexible locomotion of legs and the independent actuated wheels as end effectors. Particularly for a steep terrain where a large inertia robot negotiates it with low efficiency and stability, the proposed step-over gait, combined with static gait and wheeled locomotion, improves the overobstacle efficiency and maintains pose stability. Finally, simulations and experiments verify the performance on negotiating the diverse obstacles with level body over challenging terrain.

A Two-Point Modulation Spread-Spectrum Clock Generator With FIR-Embedded Binary Phase Detection and 1-Bit High-Order Δ∑Modulation

Ni Xu,Yiyu Shen,Sitao Lv,Han Liu,Woogeun Rhee,Zhihua Wang 대한전자공학회 2016 Journal of semiconductor technology and science Vol.16 No.4

This paper describes a spread-spectrum clock generation method by utilizing a Δ∑ digital PLL (DPLL) which is solely based on binary phase detection and does not require a linear time-to-digital converter (TDC) or other linear digital-to-time converter (DTC) circuitry. A 1-bit high-order Δ∑ modulator and a hybrid finite-impulse response (FIR) filter are employed to mitigate the phase-folding problem caused by the nonlinearity of the bang-bang phase detector (BBPD). The Δ∑ DPLL employs a two-point modulation technique to further enhance linearity at the turning point of a triangular modulation profile. We also show that the two-point modulation is useful for the BBPLL to improve the spread-spectrum performance by suppressing the frequency deviation at the input of the BBPD, thus reducing the peak phase deviation. Based on the proposed architecture, a 3.2 ㎓ spread-spectrum clock generator (SSCG) is implemented in 65 ㎚ CMOS. Experimental results show that the proposed SSCG achieves peak power reductions of 18.5 ㏈ and 11 ㏈ with 10 ㎑ and 100 ㎑ resolution bandwidths respectively, consuming 6.34 ㎽ from a 1 V supply.

Improvement of Pristinamycin Production by Genome Shuffling and Medium Optimization for Streptomyces Pristinaespiralis

Bo Xu,Zhihua Jin,Qingchao Jin,Ninghui Li,Peilin Cen 한국생물공학회 2009 Biotechnology and Bioprocess Engineering Vol.14 No.2

To isolate an improved pristinamycin producing strain of Streptomyces pristinaespiralis, the technique of Genome shuffling was used which resulted in a high-yield recombinant G 3-56 strain. Strain G 3-56 yielded 322 ± 17 mg/L of pristinamycin which was 11.4-fold higher than that of the initial strain and 3.7-fold higher than strain UN-78 which previously had the highest yield of pristinamycin. The genetic characteristics of the recombinant G 3-56 strain was stable as revealed by our subculture experiments. The optimal production medium was determined using the orthogonal matrix method. Under the optimal medium conditions, the maximum yield of pristinamycin was 412 mg/L with about 1.24-fold higher than the original medium. To isolate an improved pristinamycin producing strain of Streptomyces pristinaespiralis, the technique of Genome shuffling was used which resulted in a high-yield recombinant G 3-56 strain. Strain G 3-56 yielded 322 ± 17 mg/L of pristinamycin which was 11.4-fold higher than that of the initial strain and 3.7-fold higher than strain UN-78 which previously had the highest yield of pristinamycin. The genetic characteristics of the recombinant G 3-56 strain was stable as revealed by our subculture experiments. The optimal production medium was determined using the orthogonal matrix method. Under the optimal medium conditions, the maximum yield of pristinamycin was 412 mg/L with about 1.24-fold higher than the original medium.

Structural behavior of aluminum reticulated shell structures considering semi-rigid and skin effect

Hongbo Liu,Zhihua Chen,Shuai Xu,Yidu Bu 국제구조공학회 2015 Structural Engineering and Mechanics, An Int'l Jou Vol.54 No.1

The aluminum dome has been widely used in natatorium, oil storage tank, power plant, coal, as well as other industrial buildings and structures. However, few research has focused on the structural behavior and design method of this dome. At present, most designs of aluminum alloy domes have referred to theories and methods of steel spatial structures. However, aluminum domes and steel domes have many differences, such as elasticity moduli, roof structures, and joint rigidities, which make the design and analysis method of steel spatial structures not fully suitable for aluminum alloy dome structures. In this study, a stability analysis method, which can consider structural imperfection, member initial curvature, semi-rigid joint, and skin effect, was presented and used to study the stability behavior of aluminum dome structures. In addition, some meaningful conclusions were obtained, which could be used in future designs and analyses of aluminum domes.

Fractional-N Frequency Synthesis: Overview and Practical Aspects with FIR-Embedded Design

Rhee, Woogeun,Xu, Ni,Zhou, Bo,Wang, Zhihua The Institute of Electronics and Information Engin 2013 Journal of semiconductor technology and science Vol.13 No.2

This paper gives an overview of fractional-N phase-locked loops (PLLs) with practical design perspectives focusing on a ${\Delta}{\Sigma}$ modulation technique and a finite-impulse response (FIR) filtering method. Spur generation and nonlinearity issues in the ${\Delta}{\Sigma}$ fractional-N PLLs are discussed with simulation and hardware results. High-order ${\Delta}{\Sigma}$ modulation with FIR-embedded filtering is considered for low noise frequency generation. Also, various architectures of finite-modulo fractional-N PLLs are reviewed for alternative low cost design, and the FIR filtering technique is shown to be useful for spur reduction in the finite-modulo fractional-N PLL design.

Experimental study on seismic behavior of two-storey modular structure

Yang Liu,Zhihua Chen,Jiadi Liu,Xu Zhong 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.37 No.3

Due to the unique construction method of modular steel buildings (MSBs) with units prefabricated fully off the site and assembled quickly on the site, the inter-module connection for easy operation and overall performance of the system were key issues. However, it was a lack of relevant research on the system-level performance of MSBs. This study investigated the seismic performance of two-storey modular steel structure with a proposed vertical rotary inter-module connection. Three full-scale quasi-static tests, with and without corrugated steel plate and its combination, were carried out to evaluate and compare their seismic behaviour. The hysteretic performance, skeleton curves, ductile performance, stiffness degradation, energy dissipation capacity, and deformation pattern were clarified. The results showed that good ductility and plastic deformation ability of such modular steel structures. Two lateral-force resistance mechanisms with different layout combinations were also discussed in detail. The corrugated steel plate could significantly improve the lateral stiffness and bearing capacity of the modular steel structure. The cooperative working mechanism of modules and inter-module connections was further analyzed. When the lateral stiffness of upper and lower modular structures was close, limited bending moment transfer may be considered for the inter-module connection. While a large lateral stiffness difference existed initially between the upper and lower structures, an obvious gap occurred at the inter-module connection, and this gap may significantly influence the bending moments transferred by the inter-module connections. Meanwhile, several design recommendations of inter-module connections were also given for the application of MSBs.