• Title/Summary/Keyword: Immune simulation

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Strategic construction of mRNA vaccine derived from conserved and experimentally validated epitopes of avian influenza type A virus: a reverse vaccinology approach

  • Leana Rich Herrera-Ong
    • Clinical and Experimental Vaccine Research
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    • v.12 no.2
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    • pp.156-171
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    • 2023
  • Purpose: The development of vaccines that confer protection against multiple avian influenza A (AIA) virus strains is necessary to prevent the emergence of highly infectious strains that may result in more severe outbreaks. Thus, this study applied reverse vaccinology approach in strategically constructing messenger RNA (mRNA) vaccine construct against avian influenza A (mVAIA) to induce cross-protection while targeting diverse AIA virulence factors. Materials and Methods: Immunoinformatics tools and databases were utilized to identify conserved experimentally validated AIA epitopes. CD8+ epitopes were docked with dominant chicken major histocompatibility complexes (MHCs) to evaluate complex formation. Conserved epitopes were adjoined in the optimized mVAIA sequence for efficient expression in Gallus gallus. Signal sequence for targeted secretory expression was included. Physicochemical properties, antigenicity, toxicity, and potential cross-reactivity were assessed. The tertiary structure of its protein sequence was modeled and validated in silico to investigate the accessibility of adjoined B-cell epitope. Potential immune responses were also simulated in C-ImmSim. Results: Eighteen experimentally validated epitopes were found conserved (Shannon index <2.0) in the study. These include one B-cell (SLLTEVETPIRNEWGCR) and 17 CD8+ epitopes, adjoined in a single mRNA construct. The CD8+ epitopes docked favorably with MHC peptidebinding groove, which were further supported by the acceptable ∆Gbind (-28.45 to -40.59 kJ/mol) and Kd (<1.00) values. The incorporated Sec/SPI (secretory/signal peptidase I) cleavage site was also recognized with a high probability (0.964814). Adjoined B-cell epitope was found within the disordered and accessible regions of the vaccine. Immune simulation results projected cytokine production, lymphocyte activation, and memory cell generation after the 1st dose of mVAIA. Conclusion: Results suggest that mVAIA possesses stability, safety, and immunogenicity. In vitro and in vivo confirmation in subsequent studies are anticipated.

The Within-Host Population Dynamics of Normal Flora in the Presence of an Invading Pathogen and Antibiotic Treatments

  • Kim, Jung-Mo;Lee, Dong-Hwan;Song, Yoon-Seok;Kang, Seong-Woo;Kim, Seung-Wook
    • Journal of Microbiology and Biotechnology
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    • v.17 no.1
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    • pp.146-153
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    • 2007
  • A mathematical competition model between normal flora and an invading pathogen was devised to allow analysis of bacterial infections in a host. The normal flora includes the various microorganisms that live on or within the host and act as a primary human immune system. Despite the important role of the normal flora, no mathematical study has been undertaken on models of the interaction between it and invading pathogens against a background of antibiotic treatment. To quantify key elements of bacterial behavior in a host, pairs of nonlinear differential equations were used to describe three categories of human health conditions, namely, healthy, latent infection, and active infection. In addition, a cutoff value was proposed to represent the minimum population level required for survival. The recovery of normal flora after antibiotic treatment was also included in the simulation because of its relation to human health recovery. The significance of each simulation parameter for the bacterial growth model was investigated. The devised simulation showed that bacterial proliferation rate, carrying capacity, initial population levels, and competition intensity have a significant effect on bacterial behavior. Consequently, a model was established to describe competition between normal flora and an infiltrating pathogen. Unlike other population models, the recovery process described by the devised model can describe the human health recovery mechanism.

A Study on the Micro-defects Characteristics and Latch-up Immune Structure by RTA in 1MeV P Ion Implantation (1MeV 인 이온 주입시 RTA에 의한 미세결함 특성과 latch-up 면역에 관한 구조 연구)

  • Roh, Byeong-Gyu;Yoon, Seok-Beom
    • Journal of IKEEE
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    • v.2 no.1 s.2
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    • pp.101-107
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    • 1998
  • This paper is studied micro-defect characteristics by phosphorus 1MeV ion implantation and Rs, SRP, SIMS, XTEM for the RTA process was measured and simulated. As the dose is higher, the Rs is lower. When the dose are $1{\times}10^{13}/cm^2,\;5{\times}10^{13}/cm^2,\;1{\times}10^{14}/cm^2$, the Rp are $1.15{\mu}m,\;1.15{\mu},\;1.10{\mu}m$ respectively. As the RTA time is longer, the maximum concentration position is deeper from the surface and the concentration is lower. Before the RTA was done, we didn't observe any defect. But after the RTA process was done, we could observe the RTA process changed the micro-defects into the secondary defects. The simulation using the buried layer and connecting layer structure was performed. As results, the connecting layer had more effect than the buried layer to latch-up immune. Trigger current was more $0.6mA/{\mu}m$ and trigger voltage was 6V at dose $1{\times}10^{14}/cm^2$ and the energy 500KeV of connecting layer Lower connecting layer dose, latch-up immune characteristics was better.

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Zoning Permanent Basic Farmland Based on Artificial Immune System coupling with spatial constraints

  • Hua, Wang;Mengyu, Wang;Yuxin, Zhu;Jiqiang, Niu;Xueye, Chen;Yang, Zhang
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.15 no.5
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    • pp.1666-1689
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    • 2021
  • The red line of Permanent Basic Farmland is the most important part in the "three-line" demarcation of China's national territorial development plan. The scientific and reasonable delineation of the red line is a major strategic measure being taken by China to improve its ability to safeguard the practical interests of farmers and guarantee national food security. The delineation of Permanent Basic Farmland zoning (DPBFZ) is essentially a multi-objective optimization problem. However, the traditional method of demarcation does not take into account the synergistic development goals of conservation of cultivated land utilization, ecological conservation, or urban expansion. Therefore, this research introduces the idea of artificial immune optimization and proposes a multi-objective model of DPBFZ red line delineation based on a clone selection algorithm. This research proposes an objective functional system consisting of these three sub-objectives: optimal quality of cropland, spatially concentrated distribution, and stability of cropland. It also takes into consideration constraints such as the red line of ecological protection, topography, and space for major development projects. The mathematical formal expressions for the objectives and constraints are given in the paper, and a multi-objective optimal decision model with multiple constraints for the DPBFZ problem is constructed based on the clone selection algorithm. An antibody coding scheme was designed according to the spatial pattern of DPBFZ zoning. In addition, the antibody-antigen affinity function, the clone mechanism, and mutation strategy were constructed and improved to solve the DPBFZ problem with a spatial optimization feature. Finally, Tongxu County in Henan province was selected as the study area, and a controlled experiment was set up according to different target preferences. The results show that the model proposed in this paper is operational in the work of delineating DPBFZ. It not only avoids the adverse effects of subjective factors in the delineation process but also provides multiple scenarios DPBFZ layouts for decision makers by adjusting the weighting of the objective function.

A Subthreshold Slope and Low-frequency Noise Characteristics in Charge Trap Flash Memories with Gate-All-Around and Planar Structure

  • Lee, Myoung-Sun;Joe, Sung-Min;Yun, Jang-Gn;Shin, Hyung-Cheol;Park, Byung-Gook;Park, Sang-Sik;Lee, Jong-Ho
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.12 no.3
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    • pp.360-369
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    • 2012
  • The causes of showing different subthreshold slopes (SS) in programmed and erased states for two different charge trap flash (CTF) memory devices, SONOS type flash memory with gate-all-around (GAA) structure and TANOS type NAND flash memory with planar structure were investigated. To analyze the difference in SSs, TCAD simulation and low-frequency noise (LFN) measurement were fulfilled. The device simulation was performed to compare SSs considering the gate electric field effect to the channel and to check the localized trapped charge distribution effect in nitride layer while the comparison of noise power spectrum was carried out to inspect the generation of interface traps ($N_{IT}$). When each cell in the measured two memory devices is erased, the normalized LFN power is increased by one order of magnitude, which is attributed to the generation of $N_{IT}$ originated by the movement of hydrogen species ($h^*$) from the interface. As a result, the SS is degraded for the GAA SONOS memory device when erased where the $N_{IT}$ generation is a prominent factor. However, the TANOS memory cell is relatively immune to the SS degradation effect induced by the generated $N_{IT}$.

The novel SCR-based ESD Protection Device with High Holding Voltage (높은 홀딩전압을 갖는 사이리스터 기반 새로운 구조의 ESD 보호소자)

  • Won, Jong-Il;Koo, Yong-Seo
    • Journal of IKEEE
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    • v.13 no.1
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    • pp.87-93
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    • 2009
  • The paper introduces a silicon controlled rectifier (SCR)-based device with high holding voltage for ESD power clamp. The holding voltage can be increased by extending a p+ cathode to the first n-well and adding second n-well wrapping around n+ cathode. The increase of the holding voltage above the supply voltage enables latch-up immune normal operation. In this study, the proposed device has been simulated using synopsys TCAD simulator for electrical characteristic, temperature characteristic, and ESD robustness. In the simulation result, the proposed device has holding voltage of 3.6V and trigger voltage of 10.5V. And it is confirmed that the device could have holding voltage of above 4V with the size variation of extended p+ cathode and additional n-well.

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Gradual Reduction of Drug Dosage on an HIV Infection Model with Helper-independent CTL (보조세포 비의존형 CTL 반응이 고려된 HIV 감염 모형에 대한 점진적 약물 감소 기법의 적용)

  • Chang Hyeygjeon;Jo Nam Hoon;Shim Hyungbo
    • Journal of Institute of Control, Robotics and Systems
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    • v.10 no.12
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    • pp.1148-1154
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    • 2004
  • The goal of this paper is to verity that the gradual reduction of drug dose (GRDD), which has already been shown by authors to be effective for a simplified HIV infection model, still works for a more realistic model. While the simplified HIV infection model does not take into account an helper-independent CTL, the five state nonlinear model proposed by Wodarz describes the dynamics of both helper-dependent and helper-independent CTL in HIV infection. In this paper, it is shown that, by applying GRDD to Wodarz's five state HIV infection model, the state of HIV infected patient converges to that of non-progressor whose immune response is excited so that his symptom would not be developed into AIDS. Roughly speaking, GRDD is 'slow reduction of dose after the maximum dose for a certain period.' It turns out that an equilibrium representing non-progressor is locally asymptotically stable for the most values of drug dosage, which is required to hold in order to apply GRDD. Simulation results establish that GRDD is still considerably effective both for an AIDS patient and a patient who has been on HAART for a long time.

Metabolic Pathways Associated with Kimchi, a Traditional Korean Food, Based on In Silico Modeling of Published Data

  • Shin, Ga Hee;Kang, Byeong-Chul;Jang, Dai Ja
    • Genomics & Informatics
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    • v.14 no.4
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    • pp.222-229
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    • 2016
  • Kimchi is a traditional Korean food prepared by fermenting vegetables, such as Chinese cabbage and radishes, which are seasoned with various ingredients, including red pepper powder, garlic, ginger, green onion, fermented seafood (Jeotgal), and salt. The various unique microorganisms and bioactive components in kimchi show antioxidant activity and have been associated with an enhanced immune response, as well as anti-cancer and anti-diabetic effects. Red pepper inhibits decay due to microorganisms and prevents food from spoiling. The vast amount of biological information generated by academic and industrial research groups is reflected in a rapidly growing body of scientific literature and expanding data resources. However, the genome, biological pathway, and related disease data are insufficient to explain the health benefits of kimchi because of the varied and heterogeneous data types. Therefore, we have constructed an appropriate semantic data model based on an integrated food knowledge database and analyzed the functional and biological processes associated with kimchi in silico. This complex semantic network of several entities and connections was generalized to answer complex questions, and we demonstrated how specific disease pathways are related to kimchi consumption.

A Novel DC Bus Voltage Balancing of Cascaded H-Bridge Converters in D-SSSC Application

  • Saradarzadeh, Mehdi;Farhangi, Shahrokh;Schanen, Jean-Luc;Frey, David;Jeannin, Pierre-Olivier
    • Journal of Power Electronics
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    • v.12 no.4
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    • pp.567-577
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    • 2012
  • This paper introduces a new scheme to balance the DC bus voltages of a cascaded H-bridge converter which is used as a Distribution Static Synchronous Series Compensator (D-SSSC) in electrical distribution network. The aim of D-SSSC is to control the power flow between two feeders from different substations. As a result of different cell losses and capacitors tolerance the cells DC bus voltage can deviate from their reference values. In the proposed scheme, by individually modifying the reference PWM signal for each cell, an effective balancing procedure is derived. The new balancing procedure needs only the line current sign and is independent of the main control strategy, which controls the total DC bus voltages of cascaded H-bridge. The effect of modulation index variation on the capacitor voltage is analytically derived for the proposed strategy. The proposed method takes advantages of phase shift carrier based modulation and can be applied for a cascaded H-bridge with any number of cells. Also the system is immune to loss of one cell and the presented procedure can keep balancing between the remaining cells. Simulation studies and experimental results validate the effectiveness of the proposed method in the balancing of DC bus voltages.

Weighted Voting Game and Stochastic Learning Based Certificate Revocation for the Mobile Ad-hoc Network (이동 애드 혹 네트워크 환경에서 가중투표게임과 확률러닝을 이용한 악의적인 노드의 인증서 폐지 기법)

  • Kim, Min Jung;Kim, Sung Wook
    • KIPS Transactions on Computer and Communication Systems
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    • v.6 no.7
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    • pp.315-320
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    • 2017
  • In this paper, I design a new scheme that is immune to malicious attack based on the weighted voting game. By using stochastic learning, the proposed scheme can revoke the certification of malicious node. Through the revocation process, the proposed scheme can effectively adapt the dynamic Mobile Ad hoc network situation. Simulation results clearly indicate that the developed scheme has better performance than other existing schemes under widely diverse network environments.