• 제목/요약/키워드: Multiple Target

검색결과 1,486건 처리시간 0.031초

주의력결핍 과잉행동장애 치료제 개발을 위한 카테콜아민계 표적화 (Targeting Catecholamines to Develop New Drugs for Attention Deficit Hyperactivity Disorder)

  • 정성철;조창환;김혜지;고은아;하민우;권오빈
    • Journal of Medicine and Life Science
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    • 제18권3호
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    • pp.41-48
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    • 2021
  • The prevalence of attention deficit hyperactivity disorder (ADHD), a developmental neuropsychiatric disorder, is high among children and adolescents. The pathogenesis of ADHD is mediated with genetic, biological, and environmental factors. Most therapeutic drugs for ADHD have so far targeted biological causes, primarily by regulating catecholaminergic neurotransmitters. However, ADHD drugs that are clinically treated have various problems in their addictiveness and drug stability; thus, it is recommended that efficacy and safety should be secured through simultaneous prescription of multiple drugs rather than a single drug treatment. Accordingly, it is necessary to develop drugs that newly target pathogenic mechanisms of ADHD. In this study, we attempt to confirm the possibility of developing new drugs by reviewing dopamine-related developmental mechanisms of neurons and their correlation with ADHD. Histone deacetylase inhibitors (HDACi) can regulate the concentration of intracellular dopamine in neurons by expressing vesicular monoamine transporter 2 and inducing the exocytosis of neurotransmitters to the synaptic cleft, thereby promoting the development of neurons and signal transmission. This cellular modulation of HDACi is expected to treat ADHD by regulating endogenous catecholamines such as dopamine. Although studies are still in the preclinical stage, HDAC inhibitors clearly have potential as a therapeutic agent with low addictiveness and high efficacy for ADHD treatment.

약물 정보 문서 임베딩을 이용한 딥러닝 기반 약물 간 상호작용 예측 (Prediction of Drug-Drug Interaction Based on Deep Learning Using Drug Information Document Embedding)

  • 정선우;유선용
    • 한국정보통신학회:학술대회논문집
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    • 한국정보통신학회 2022년도 춘계학술대회
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    • pp.276-278
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    • 2022
  • 모든 약물은 신체 내에서 특정한 작용을 하며, 많은 경우 합병증 또는 기존 약물치료 중 새롭게 발생하는 증상에 의해 약물이 혼용되는 경우가 발생한다. 이런 경우 신체 내에서 예상치 못한 상호작용이 발생할 수 있다. 따라서 약물 간 상호작용을 예측하는 것은 안전한 약물 사용을 위해 매우 중요한 과제이다. 본 연구에서는 다중 약물 사용 시 발생 가능한 약물 간 상호작용 예측을 위해 약물 정보 문서를 이용해 학습시키는 딥러닝 기반의 예측 모델을 제안한다. 약물 정보 문서는 DrugBank 데이터를 이용해 약물의 작용 기전, 독성, 표적 등 여러 속성을 결합해 생성되었으며, 두 약물 문서가 한 쌍으로 묶여 딥러닝 기반 예측 모델에 입력으로 사용되고 해당 모델은 두 약물 간 상호작용을 출력한다. 해당 연구는 임베딩 방법이나 데이터 전처리 방법 등 다양한 조건의 변화에 따른 실험 결과의 차이를 분석하여 차후 새로운 약물쌍 간 상호작용을 예측하는 데에 활용이 가능하다.

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The Attenuation Mechanism and Live Vaccine Potential of a Low-Virulence Edwardsiella ictaluri Strain Obtained by Rifampicin Passaging Culture

  • Shuyi Wang;Jingwen Hao;Jicheng Yang;Qianqian Zhang;Aihua Li
    • Journal of Microbiology and Biotechnology
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    • 제33권2호
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    • pp.167-179
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    • 2023
  • The rifampicin-resistant strain E9-302 of Edwardsiella ictaluri strain 669 (WT) was generated by continuous passage on BHI agar plates containing increasing concentrations of rifampicin. E9-302 was attenuated significantly by 119 times to zebrafish Danio rerio compared to WT in terms of the 50% lethal dose (LD50). Zebrafish vaccinated with E9-302 via intraperitoneal (IP) injection at a dose of 1 × 103 CFU/fish had relative percentage survival (RPS) rates of 85.7% when challenged with wild-type E. ictaluri via IP 14 days post-vaccination (dpv). After 14 days of primary vaccination with E9-302 via immersion (IM) at a dose of 4 × 107 CFU/ml, a booster IM vaccination with E9-302 at a dose of 2 × 107 CFU/ml exhibited 65.2% RPS against challenge with wild-type E. ictaluri via IP 7 days later. These results indicated that the rifampicin-resistant attenuated strain E9-302 had potential as a live vaccine against E. ictaluri infection. A previously unreported amino acid site change at position 142 of the RNA polymerase (RNAP) β subunit encoded by the gene rpoB associated with rifampicin resistance was identified. Analysis of the whole-genome sequencing results revealed multiple missense mutations in the virulence-related genes esrB and sspH2 in E9-302 compared with WT, and a 189 bp mismatch in one gene, whose coding product was highly homologous to glycosyltransferase family 39 protein. This study preliminarily explored the molecular mechanism underlying the virulence attenuation of rifampicin-resistant strain E9-302 and provided a new target for the subsequent study of the pathogenic mechanism of E. ictaluri.

실시간 차선인식 알고리즘을 위한 최적의 멀티코어 아키텍처 디자인 공간 탐색 (Optimal Design Space Exploration of Multi-core Architecture for Real-time Lane Detection Algorithm)

  • 정인규;김종면
    • 예술인문사회 융합 멀티미디어 논문지
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    • 제7권3호
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    • pp.339-349
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    • 2017
  • 본 논문에서는 주행 중인 차량의 차선 인식을 위해 4단계로 구성된 알고리즘을 제안한다. 첫 번째 단계에서는 관심영역 추출한다. 두 번째 단계에서는 신호 잡음을 제기하기 위해 중간 값 필터를 이용한다. 세 번째 단계에서는 입력되는 이미지의 배경과 전경의 두 클래스로 구분하기 위한 이진화 알고리즘을 수행한다. 마지막 단계에서는 이진화 과정 후에 남아 있는 노이즈나 불완전한 에지 등을 제거하여 선명한 차선을 얻기 위해 이미지 침식 알고리즘을 이용한다. 하지만 이러한 차선 인식 앍고리즘은 높은 계산량을 요구하여 실시간 처리가 어려운 실정이다. 따라서 본 논문에서는 멀티코어 아키텍처를 이용하여 실시간 차선이탈 감지 알고리즘을 병렬구현 한다. 또한, 차선이탈 감지 알고리즘을 위한 최적의 멀티코어 아키텍처의 구조를 탐색하기 위해 총 8가지의 서로 다른 프로세싱 엘리먼트 구조를 이용하여 실험하였고, 모의실험 결과 40×40의 프로세싱 엘리먼트 구조에서 최적의 성능, 에너지 효율 및 면적 효율을 보였다.

Dengue Virus 2 NS2B Targets MAVS and IKKε to Evade the Antiviral Innate Immune Response

  • Ying Nie;Dongqing Deng;Lumin Mou;Qizhou Long;Jinzhi Chen;Jiahong Wu
    • Journal of Microbiology and Biotechnology
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    • 제33권5호
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    • pp.600-606
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    • 2023
  • Dengue virus (DENV) is a widespread arbovirus. To efficiently establish infection, DENV evolves multiple strategies to hijack the host innate immune response. Herein, we examined the inhibitory effects of DENV serotype 2 (DENV2) nonstructural proteins on RIG-I-directed antiviral immune response. We found that DENV2 NS2A, NS2B, NS4A, and NS4B significantly inhibited RIG-I-mediated IFN-β promoter activation. The roles of NS2B in RIG-I-directed antiviral immune response are unknown. Our study further showed that NS2B could dose-dependently suppress RIG-I/MAVS-induced activation of IFN-β promoter. Consistently, NS2B significantly decreased RIG-I- and MAVS-induced transcription of IFNB1, ISG15, and ISG56. Mechanistically, NS2B was found to interact with MAVS and IKKε to impair RIG-I-directed antiviral response. Our findings demonstrated a previously uncharacterized function of NS2B in RIG-I-mediated antiviral response, making it a promising drug target for anti-DENV treatments.

In Search of Corporate Growth and Scaleup: What Strategies Drive Unicorns and Hyper-Growing Companies?

  • Lee, Young-Dall;Oh, Soyoung
    • 한국벤처창업학회:학술대회논문집
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    • 한국벤처창업학회 2021년도 춘계학술대회
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    • pp.33-42
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    • 2021
  • Based on the findings of Lee et al.(2020) and Lee & Oh(2021), this paper aims to fill the gap in our knowledge regarding the relationship between strategic choices and corporate growth by utilizing a novel dataset of 'Unicorn' and 'Hyper-growing' companies. Two previous studies provide coherent findings that the relationship between firms' strategies and their performance should be explored under a more comprehensive framework with consideration of both internal and external factors. Therefore, in this study, we apply a single conceptual framework to two different datasets, which considers the strategy factors as independent variables, and the industry(market) and the firm age as moderating variables. For our dependent variables, valuations for unicorn companies and revenue CAGR for hyper-growing companies are used after categorizing them into three uniform groups. The strategy variables include 'Generic (Cost-leadership, Differentiation, focus) strategies', 'Growth(Organic, M&A) strategies', 'Leading(Pioneer, Fast-follower) strategies', 'Target market(B2B, B2C, B2G, C2C) strategies', 'Global(Global, Local) strategies', 'Digital(Online, Offline) strategies.' For industry(market) factors, it consists of historical growth rate for industries and economic, demographic, and regulatory aspects of states and countries. To overcome the differences in their units, they are also uniformly categorized into multiple groups. Before we conduct a regression analysis, we analyze the industry distribution of the 'Unicorn' and the 'Hyper-growing' companies with descriptive statistics at the integrated and individual levels. Next, we employ hierarchical regression models on Study A('Unicorn' companies in 2019) and Study B('Hyper-growing' companies in 2019) under the same comprehensive framework. We then analyze the relationship between the 'strategy' and the 'performance' factors with two different approaches: 1) an integrated regression model with both the sample of Study A and B and 2) respective regression models on Study A and B. This empirical study aims to provide a complete understanding and a reference to which strategy factors should be considered to promote firms' scale-up and growth.

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Ka-대역 GaN 저잡음 증폭기의 강건성 평가 (Robustness Evaluation of GaN Low-Noise Amplifier in Ka-band)

  • 이동주;안세환;주지한;권준범;김영훈;이상훈;서미희;김소수
    • 한국인터넷방송통신학회논문지
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    • 제22권6호
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    • pp.149-154
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    • 2022
  • GaN 소자는 고출력 및 고선형성 특성을 가지므로 레이더 수신기에서 저잡음 증폭기로 활용되어 리미터 없이 구현될 수 있으며, 이로 인해 잡음지수를 개선하고 면적을 줄일 수 있다. 본 논문에서는 Ka-대역 레이더용 수신기에 적용하기 위한 GaN 저잡음 증폭기를 기술하였다. 설계된 저잡음 증폭기는 150-nm GaN HEMT 공정으로 제작되었으며, 목표주파수 내에서 패키징 손실을 포함하여 >23 dB 이득, <6.5 dB의 잡음지수 특성을 보였다. 고입력 부하시험시 이득 및 잡음 저하가 있었으나, 반복시험시 추가적인 성능저하는 나타나지 않았다. 부하시험 후 잡음지수 및 S-파라미터 측정을 통해 GaN 저잡음 증폭기에서 ~40 dBm 펄스 입력 전력을 견딜 수 있음을 확인하였다.

Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation

  • Janghyun Kim;Bora Lee;Young Kim;Byeong C. Kim;Joon-Tae Kim;Hyong-Ho Cho
    • Genomics & Informatics
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    • 제21권1호
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    • pp.2.1-2.14
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    • 2023
  • Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.

Insight from sirtuins interactome: topological prominence and multifaceted roles of SIRT1 in modulating immunity, aging, and cancer

  • Nur Diyana Zulkifli;Nurulisa Zulkifle
    • Genomics & Informatics
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    • 제21권2호
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    • pp.23.1-23.9
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    • 2023
  • The mammalian sirtuin family, consisting of SIRT1-SIRT7, plays a vital role in various biological processes, including cancer, diabetes, neurodegeneration, cardiovascular disease, cellular metabolism, and cellular homeostasis maintenance. Due to their involvement in these biological processes, modulating sirtuin activity seems promising to impact immuneand aging-related diseases, as well as cancer pathways. However, more understanding is required regarding the safety and efficacy of sirtuin-targeted therapies due to the complex regulatory mechanisms that govern their activity, particularly in the context of multiple targets. In this study, the interaction landscape of the sirtuin family was analyzed using a systems biology approach. A sirtuin protein-protein interaction network was built using the Cytoscape platform and analyzed using the NetworkAnalyzer and stringApp plugins. The result revealed the sirtuin family's association with numerous proteins that play diverse roles, suggesting a complex interplay between sirtuins and other proteins. Based on network topological and functional analysis, SIRT1 was identified as the most prominent among sirtuin family members, demonstrating that 25 of its protein partners are involved in cancer, 22 in innate immune response, and 29 in aging, with some being linked to a combination of two or more pathways. This study lays the foundation for the development of novel therapies that can target sirtuins with precision and efficacy. By illustrating the various interactions among the proteins in the sirtuin family, we have revealed the multifaceted roles of SIRT1 and provided a framework for their possible roles to be precisely understood, manipulated, and translated into therapeutics in the future.

Analysis of common and characteristic actions of Panax ginseng and Panax notoginseng in wound healing based on network pharmacology and meta-analysis

  • Zhen Wang ;Xueheng Xie ;Mengchen Wang ;Meng Ding ;Shengliang Gu ;Xiaoyan Xing;Xiaobo Sun
    • Journal of Ginseng Research
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    • 제47권4호
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    • pp.493-505
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    • 2023
  • In recent years, an increasing number of reports have explored the wound healing mechanism of these two traditional Chinese herbal medicines- Panax ginseng and Panax notoginseng, but there is no systematic research on the related core functions and different mechanisms in the treatment of wound healing up to now. Based on network pharmacology and meta-analysis, the present work aimed to comprehensively review the commonality and diversity of P. ginseng and P. notoginseng in wound healing. In this study, a wound healing-related "ingredients-targets" network of two herbs was constructed. Thereafter, meta-analysis of the multiple target lists by Metascape showed that these two medicines significantly regulated blood vessel development, responses to cytokines and growth factors and oxygen levels, cell death, cell proliferation and differentiation, and cell adhesion. To better understand the discrepancy between these two herbs, it was found that common signaling pathways including Rap1, PI3K/AKT, MAPK, HIF-1 and Focal adhesion regulated the functions listed above. In parallel, the different pathways including renin-angiotensin system, RNA transport and circadian rhythm, autophagy, and the different metabolic pathways may also explained the discrepancies in the regulation of the above-mentioned functions, consistent with the Traditional Chinese Medicine theory about the effects of P. ginseng and P. notoginseng.