• Title/Summary/Keyword: Genetic Responses

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Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

  • Md Tahsin Khan;Araf Mahmud;Md. Muzahidul Islam;Mst. Sayedatun Nessa Sumaia;Zeaur Rahim;Kamrul Islam;Asif Iqbal
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.42.1-42.23
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    • 2023
  • Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

  • Yang, Sungjae;Kim, Yong;Jeong, Deok;Kim, Jun Ho;Kim, Sunggyu;Son, Young-Jin;Yoo, Byong Chul;Jeong, Eun Jeong;Kim, Tae Woong;Han Lee, In-Sook;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.595-603
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    • 2016
  • (E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

Design of Fuzzy PI Controllers for the Temperature Control of Soldering Systems (솔더링 시스템의 온도 제어를 위한 퍼지 PI 제어기 설계)

  • Oh, Kabsuk;Kang, Geuntaek
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.2
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    • pp.325-333
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    • 2016
  • This paper proposes controller design algorithms for a ceramic soldering iron temperature control system, and reports their effectiveness in a control experiment. Because the responses of the ceramic soldering iron temperature to the control input are non-linear and very slow, precise modeling and controller design is difficult. In this study, the temperature characteristics of a ceramic soldering iron are represented by TSK fuzzy models consisting of TSK fuzzy rules. In the fuzzy rules, the premise variable is the control input and the consequences are the transfer functions. The transfer functions in the fuzzy model were obtained from the step input responses. As the responses of the ceramic soldering iron temperature are very slow, it is difficult to obtain the complete step input responses. This paper proposes a genetic algorithm to obtain the transfer functions from an incomplete step input responses, and showed its effectiveness in examples. This paper also reports a fuzzy controller design method from the TSK fuzzy model and examples. The proposed methods were applied to the temperature control experiments of ceramic iron. The TSK fuzzy model consisted of 7 TSK fuzzy rules, and the consequences were PI controllers. The experimental results of the proposed fuzzy PI controller were superior to the linear controller and were as good as in previous studies using a fuzzy PID controller.

Optimization of Satellite Structures by Simulated Annealing (시뮬레이티드 어닐링에 의한 인공위성 구조체 최적화)

  • Im Jongbin;Ji Sang-Hyun;Park Jungsun
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.29 no.2 s.233
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    • pp.262-269
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    • 2005
  • Optimization of a satellite structure under severe space launching environments is performed considering various design constraints. Simulate annealing, one of combinatorial optimization techniques, is used to optimize the satellite. The optimization results by the simulated annealing are compared to those by the method of modified feasible direction and genetic algorithm. Ten bar truss structure is optimized for feasibility study of the simulated annealing. Finally, the satellite structure is optimized by the simulated annealing algorithm under space environment. Weights of the satellite upper platform and propulsion module are minimized with consideration of several static and dynamic constraints. MSC/NASTRAN is used to find the static and dynamic responses. Simulated annealing has been programmed and integrated with the finite element analysis program for optimization. It is shown that the simulated annealing algorithm can be extended to the optimization of space structures.

Recent Status of Chicken Genome Researches (닭 유전체 연구의 최근 동향)

  • Seo, S.W.;Paek, W.K.;Lee, J.H.
    • Korean Journal of Poultry Science
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    • v.36 no.2
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    • pp.111-115
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    • 2009
  • Chicken has been being used as the protein sources for humans for long times. Since the release of chicken genome sequencing, large efforts have been carried out for identifying valuable genomic information in chicken including the genes affecting quantitative traits, development and immune responses. In this review, the recent progress of genomic researches has been discussed including the available world wide genetic materials in chicken.

A Highly Efficient Aeroelastic Optimization Method Based on a Surrogate Model

  • Zhiqiang, Wan;Xiaozhe, Wang;Chao, Yang
    • International Journal of Aeronautical and Space Sciences
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    • v.17 no.4
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    • pp.491-500
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    • 2016
  • This paper presents a highly efficient aeroelastic optimization method based on a surrogate model; the model is verified by considering the case of a high-aspect-ratio composite wing. Optimization frameworks using the Kriging model and genetic algorithm (GA), the Kriging model and improved particle swarm optimization (IPSO), and the back propagation neural network model (BP) and IPSO are presented. The feasibility of the method is verified, as the model can improve the optimization efficiency while also satisfying the engineering requirements. Moreover, the effects of the number of design variables and number of constraints on the optimization efficiency and objective function are analysed in detail. The accuracy of two surrogate models in aeroelastic optimization is also compared. The Kriging model is constructed more conveniently, and its predictive accuracy of the aeroelastic responses also satisfies the engineering requirements. According to the case of a high-aspect-ratio composite wing, the GA is better at global optimization.

Design of an Adaptive Fuzzy Controller using Genetic Algorithm (유전알고리즘을 이용한 적응 퍼지 제어기의 설계)

  • Huh, Sung-Hoe;Seo, Ho-Joon;Park, Jang-Hyun;Yun, Pil-Sang;Park, Gwi-Tae
    • Proceedings of the KIEE Conference
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    • 1999.11c
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    • pp.530-532
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    • 1999
  • In adaptive fuzzy control, system designer develops an adaptive law for the output of the unknown plant to track a given signal. The adaptation gains of the adaptive law are critical elements in the overall system, however, they were used to be selected by the designer's experience or intuition. In this paper, genetic algorithm is used to search an optimal adaptation gain and simulation results will be presented to show the improved tracking responses.

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Design of an Optimal State Feedback Controller for Container Crane Systems with Constraints (제약조건을 가지는 컨테이너 크레인 시스템용 최적 상태궤환 제어기 설계)

  • 주상래;진강규
    • Journal of Advanced Marine Engineering and Technology
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    • v.24 no.2
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    • pp.50-56
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    • 2000
  • This paper presents the design of an optimal state feedback controller for container cranes under some design specifications. To do this, the nonlinear equation of a container crane system is linearized and then augmented to eliminate the steady-state error, and some constraints are derived from the design specifications. Designing the controller involves a constrained optimization problem which classical gradient-based methods have difficulties in handling. Therefore, a real-coding genetic algorithm incorporating the penalty strategy is used. The responses of the proposed control system are compared with those of the unconstrained optimal control system to illustrate the efficiency.

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Multiobjective size and topolgy optimization of dome structures

  • Tugrul, Talaslioglu
    • Structural Engineering and Mechanics
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    • v.43 no.6
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    • pp.795-821
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    • 2012
  • The size and topology of geometrically nonlinear dome structures are optimized thereby minimizing both its entire weight & joint (node) displacements and maximizing load-carrying capacity. Design constraints are implemented from provisions of American Petroleum Institute specification (API RP2A-LRFD). In accordance with the proposed design constraints, the member responses computed by use of arc-length technique as a nonlinear structural analysis method are checked at each load increment. Thus, a penalization process utilized for inclusion of unfeasible designations to genetic search is correspondingly neglected. In order to solve this complex design optimization problem with multiple objective functions, Non-dominated Sorting Genetic Algorithm II (NSGA II) approach is employed as a multi-objective optimization tool. Furthermore, the flexibility of proposed optimization is enhanced thereby integrating an automatic dome generating tool. Thus, it is possible to generate three distinct sphere-shaped dome configurations with varying topologies. It is demonstrated that the inclusion of brace (diagonal) members into the geometrical configuration of dome structure provides a weight-saving dome designation with higher load-carrying capacity. The proposed optimization approach is recommended for the design optimization of geometrically nonlinear dome structures.

Molecular Genetics of Anxiety Disorder (불안장애의 분자유전학적 이해)

  • Kim, Jung-Jin
    • Anxiety and mood
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    • v.3 no.1
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    • pp.3-7
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    • 2007
  • Anxiety disorder is likely caused by an interaction of multiple loci in brain, rather than a single locus. Hyperactive neurotransmitter circuits between the cortex, thalamus, amygdala, and hypothalamus are responsible for production of anxiety symptoms. Familial studies performed on anxiety disorder suggested that anxiety disorder should be caused by genetic etiology. Numerous linkage and association studies showed different genetic loci of anxiety disorder. Candidate genes have been focused on important neurotransmitters, neuropeptide, or genes affecting neuronal growth, development, protection or apoptosis. Anxiety disorder has various symptoms and comorbid diseases in family or proband. Therefore, further studies focused on symptomatic dimension of anxiety disorder or responses to drugs are required.

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