• Title/Summary/Keyword: Signal Strategy

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Inhibition of DNA-dependent Protein Kinase by Blocking Interaction between Ku Complex and Catalytic Subunit of DNA-dependent Protein Kinase

  • Kim, Chung-Hui;Cuong, Dang-Van;Kim, Jong-Su;Kim, Na-Ri;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.1
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    • pp.9-14
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    • 2003
  • Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

Biphasic Study to Characterize Agricultural Biogas Plants by High-Throughput 16S rRNA Gene Amplicon Sequencing and Microscopic Analysis

  • Maus, Irena;Kim, Yong Sung;Wibberg, Daniel;Stolze, Yvonne;Off, Sandra;Antonczyk, Sebastian;Puhler, Alfred;Scherer, Paul;Schluter, Andreas
    • Journal of Microbiology and Biotechnology
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    • v.27 no.2
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    • pp.321-334
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    • 2017
  • Process surveillance within agricultural biogas plants (BGPs) was concurrently studied by high-throughput 16S rRNA gene amplicon sequencing and an optimized quantitative microscopic fingerprinting (QMF) technique. In contrast to 16S rRNA gene amplicons, digitalized microscopy is a rapid and cost-effective method that facilitates enumeration and morphological differentiation of the most significant groups of methanogens regarding their shape and characteristic autofluorescent factor 420. Moreover, the fluorescence signal mirrors cell vitality. In this study, four different BGPs were investigated. The results indicated stable process performance in the mesophilic BGPs and in the thermophilic reactor. Bacterial subcommunity characterization revealed significant differences between the four BGPs. Most remarkably, the genera Defluviitoga and Halocella dominated the thermophilic bacterial subcommunity, whereas members of another taxon, Syntrophaceticus, were found to be abundant in the mesophilic BGP. The domain Archaea was dominated by the genus Methanoculleus in all four BGPs, followed by Methanosaeta in BGP1 and BGP3. In contrast, Methanothermobacter members were highly abundant in the thermophilic BGP4. Furthermore, a high consistency between the sequencing approach and the QMF method was shown, especially for the thermophilic BGP. The differences elucidated that using this biphasic approach for mesophilic BGPs provided novel insights regarding disaggregated single cells of Methanosarcina and Methanosaeta species. Both dominated the archaeal subcommunity and replaced coccoid Methanoculleus members belonging to the same group of Methanomicrobiales that have been frequently observed in similar BGPs. This work demonstrates that combining QMF and 16S rRNA gene amplicon sequencing is a complementary strategy to describe archaeal community structures within biogas processes.

Utilization of Rotational Beam Direction Patterns for Performance Enhancement of Cell Boundary UEs (셀 경계 단말의 성능 향상을 위한 회전성 빔 방향 패턴의 활용)

  • Lee, Donghyun;Sung, Wonjin
    • Journal of the Institute of Electronics and Information Engineers
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    • v.50 no.11
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    • pp.12-20
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    • 2013
  • Even though extensive research results have been applied to wireless cellular systems to improve their capacity and coverage, severe performance degradation experienced in cell boundary areas still remains as a major limiting factor to prohibit further improvement of user equipment (UE) throughput. In the Long Term Evolution-Advanced (LTE-A) standard of the Third Generation Partnership Project (3GPP), Some advanced techniques have been introduced to overcome this "cell-edge problem", including coordinated multipoint transmission and reception (CoMP) and inter-cell interference coordination (ICIC). In this paper, we propose yet another strategy to improve the performance of low-tier UEs by using the concept of multiple beam direction patterns (BDPs). Such multiple BDPs can be implemented using multi-layer antenna arrays stacked vertically at base station (BS) sites to transmit signals in different main beam directions. In comparison to conventional three-sector antennas with a fixed beam pattern, the proposed methods makes signal transmission in a rotational fashion to significantly enhance the reception quality of UEs located near sector (or cell) edge areas, preventing the situation where certain UEs are marginally covered by the BS for the whole transmission time. Performance evaluation results show that the proposed scheme outperforms the conventional three-sector transmission by 171% in low 5% UEs in terms of the UE throughput.

Feasibility of Optoelectronic Neural Stimulation Shown in Sciatic Nerve of Rats (흰쥐의 좌골 신경 자극을 통한 광전 자극의 가능성에 대한 연구)

  • Kim Eui tae;Oh Seung jae;Baac Hyoung won;Kim Sung june
    • Journal of Biomedical Engineering Research
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    • v.25 no.6
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    • pp.611-615
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    • 2004
  • A neural prostheses can be designed to permit stimulation of specific sites in the nervous system to restore their functions, lost due to disease or trauma. This study focuses on the feasibility of optoelecronic stimulation into nervous system. Optoelectronic stimulation supplies, power and signal into the implanted optical detector inside the body by optics. It can be effective strategy especially on the retinal prosthesis, because it enables the non-invasive connection between the external source and internal detector through natural optical window 'eye'. Therefore, we designed an effective neural stimulating setup by optically based stimulation. Stimulating on the sciatic nerve of a rat with proper depth probe through optical stimulation needs higher ratio of current spreading through the neural surface, because of high impedance of neural interface. To increase the insertion current spreading into the neuron, we used a parallel low resistance compared to load resistance organic interface and calculated the optimized outer parallel resistance for maximum insertion current with the assumption of limited current by photodiode. Optimized outer parallel resistance was at a range of 500Ω-700Ω and a current was at a level between 580uA and 650uA. Stimulating current efficiency from initial photodiode induced current was between 47.5 and 59.7%. Various amplitude and frequency of the optical stimulation on the sciatic nerve showed the reliable visual tremble, and the action potential was also recorded near the stimulating area. These result demonstrate that optoelectronic stimulation with no bias can be applied to the retinal prosthesis and other neuroprosthetic area.

Non-linear Relationship Between IP Proportion of Startup and Financing Performance: Moderating Role of Founder's Education Level (스타트업의 지식재산 비중과 자금조달의 비선형 관계: 창업자 지식수준의 조절효과)

  • Chung, Doohee
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.14 no.5
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    • pp.1-11
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    • 2019
  • Financing plays an important role in the survival and growth of startups. This study investigates key factors that improve startup financing performance. To this end, we analyze the relationship between the proportion of intellectual property and the financing performance. In addition, this study also examine the impact of the founder's education level on the financing of startups, and the moderating effect of the founder's education level on the relationship between intellectual property proportion and financing. Based on the survey data of 331 startups, this study found that the proportion of intellectual property and the financing performance have an inverted U-shaped nonlinear relationship. While the founder's education level has a positive impact on the financing performance, it negatively moderate the relationship between the intellectual property proportion and the financing performance. Through these findings, this study suggests that it is necessary to maintain an adequate proportion of intellectual property in order to maximize startup financing performance. The higher education level of founder enhances the startup financing. Since the founder's education level weaken the effect of intellectual proporty's effect on startup financing, however, startups need to control the proportion of intellectual property to improving financing according to the founder's education level. Based on signal theory, this study proposes a new strategy of intellectual property to enhance startup financing performance.

A Methodology of AI Learning Model Construction for Intelligent Coastal Surveillance (해안 경계 지능화를 위한 AI학습 모델 구축 방안)

  • Han, Changhee;Kim, Jong-Hwan;Cha, Jinho;Lee, Jongkwan;Jung, Yunyoung;Park, Jinseon;Kim, Youngtaek;Kim, Youngchan;Ha, Jeeseung;Lee, Kanguk;Kim, Yoonsung;Bang, Sungwan
    • Journal of Internet Computing and Services
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    • v.23 no.1
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    • pp.77-86
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    • 2022
  • The Republic of Korea is a country in which coastal surveillance is an imperative national task as it is surrounded by seas on three sides under the confrontation between South and North Korea. However, due to Defense Reform 2.0, the number of R/D (Radar) operating personnel has decreased, and the period of service has also been shortened. Moreover, there is always a possibility that a human error will occur. This paper presents specific guidelines for developing an AI learning model for the intelligent coastal surveillance system. We present a three-step strategy to realize the guidelines. The first stage is a typical stage of building an AI learning model, including data collection, storage, filtering, purification, and data transformation. In the second stage, R/D signal analysis is first performed. Subsequently, AI learning model development for classifying real and false images, coastal area analysis, and vulnerable area/time analysis are performed. In the final stage, validation, visualization, and demonstration of the AI learning model are performed. Through this research, the first achievement of making the existing weapon system intelligent by applying the application of AI technology was achieved.

3D Printing-Based Ultrafast Mixing and Injecting Systems for Time-Resolved Serial Femtosecond Crystallography (시간 분해 직렬 펨토초 결정학을 위한 3차원 프린팅 기반의 초고속 믹싱 및 인젝팅 시스템)

  • Ji, Inseo;Kang, Jeon-Woong;Kim, Taeyung;Kang, Min Seo;Kwon, Sun Beom;Hong, Jiwoo
    • Korean Chemical Engineering Research
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    • v.60 no.2
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    • pp.300-307
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    • 2022
  • Time-resolved serial femtosecond crystallography (TR-SFX) is a powerful technique for determining temporal variations in the structural properties of biomacromolecules on ultra-short time scales without causing structure damage by employing femtosecond X-ray laser pulses generated by an X-ray free electron laser (XFEL). The mixing rate of reactants and biomolecule samples, as well as the hit rate between crystal samples and x-ray pulses, are critical factors determining TR-SFX performance, such as accurate image acquisition and efficient sample consumption. We here develop two distinct sample delivery systems that enable ultra-fast mixing and on-demand droplet injecting via pneumatic application with a square pulse signal. The first strategy relies on inertial mixing, which is caused by the high-speed collision and subsequent coalescence of droplets ejected through a double nozzle, while the second relies on on-demand pneumatic jetting embedded with a 3D-printed micromixer. First, the colliding behaviors of the droplets ejected through the double nozzle, as well as the inertial mixing within the coalesced droplets, are investigated experimentally and numerically. The mixing performance of the pneumatic jetting system with an integrated micromixer is then evaluated by using similar approaches. The sample delivery system devised in this work is very valuable for three-dimensional biomolecular structure analysis, which is critical for elucidating the mechanisms by which certain proteins cause disease, as well as searching for antibody drugs and new drug candidates.

Notoginseng leaf triterpenes ameliorates mitochondrial oxidative injury via the NAMPT-SIRT1/2/3 signaling pathways in cerebral ischemic model rats

  • Weijie, Xie;Ting, Zhu;Ping, Zhou;Huibo, Xu;Xiangbao, Meng;Tao, Ding;Fengwei, Nan;Guibo, Sun;Xiaobo, Sun
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.199-209
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    • 2023
  • Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

miR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells

  • Ning Song;Jun Luo;Lian Huang;Xiaoying Chen;Huimin Niu;Lu Zhu
    • Animal Bioscience
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    • v.36 no.10
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    • pp.1488-1498
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    • 2023
  • Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3'-untranslated region (3'UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.

The Impact of Service Quality Signals on the Success of Online Food Delivery Services on O2O Platforms (O2O 플랫폼 내 서비스 품질 신호가 온라인 음식 배달 서비스 성공에 미치는 영향)

  • Mingi Song;Seunghun Lee;Gunwoong Lee
    • Information Systems Review
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    • v.24 no.3
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    • pp.43-68
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    • 2022
  • With the growing demand for online food delivery (OFD) services via Online to Offline (O2O) platforms, it is required for academic researchers to identify the success factors of OFD businesses. In line with this, this research examines the impact of the core service attributes of a restaurant (hygiene, interactivity, trust,and popularity) on business success in the OFD platform context from the perspective of information asymmetry. Furthermore, the moderating effects of hygiene factor between the core service attributes and the success of restaurants are evaluated. We utilize 1,146 restaurants registered on the largest OFD platform in Korea. The results of this study demonstrate that hygiene (certification), trust (franchise), popularity (favorite) factors have positive impacts on the success of OFD businesses. Moreover, we find that franchise restaurants with high response rates to customer reviews and inquiries achieve higher sales when they have hygiene certifications than those without the certification do. The key findings bear significant contributions to prior literature by empirically substantiating the pivotal role of service quality signals in fostering restaurant success on the OFD platforms. In addition, this study provides business implications for restaurants in O2O platform.