• JSTS:Journal of Semiconductor Technology and Science
• /
• 제12권3호
• /
• pp.360-369
• /
• 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 $N_{IT}$.

• 동의신경정신과학회지
• /
• 제19권3호
• /
• pp.55-68
• /
• 2008

Background: Microglia produces a barrage of factors (IL-l, TNF-$\alpha$, NO, superoxide) that are toxic to neurons and playa major role in the cellular immune response associated with the pathology of Alzheimer's disease(AD). OJaJiHwangEumJa(OJJHEJ) has been usually used for the treatment of senile disorders. For enhancing efficacy and convenience, the change of the drug delivery device of oriental herbal medicine is required. Objective: This experiment was designed to investigate the effect of the OJJHEJ hot water extract & ultra-fine powder on proinflammatory cytokine of microglia and memory deficit model. Method: The effects of the OJJHEJ hot water extract on production of IL-1$\beta$, IL-6, TNF-$\alpha$, in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. The effects of the OJJHEJ hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine and AChE in serum of the memory deficit mice induced by scopolamine were investigated. Results: 1. The OJJHEJ hot water extract suppressed the production of IL-1$\beta$, IL-6, TNF-$\alpha$ in BV2 microglial cell line and the production of IL-6 was suppressed significantly. 2. The OJJHEJ hot water extract & ultra-fine powder decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 3. The OJJHEJ hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. Conclusions: This experiment shows that the OJJHEJ hot water extract & ultra-fine powder might be effective for the prevention and treatment of memory impairment diseases. Investigation into the clinical use of the OJJHEJ hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• IMMUNE NETWORK
• /
• 제23권5호
• /
• pp.41.1-41.21
• /
• 2023

CD4 and CD8 T cells are key players in the immune response against both pathogenic infections and cancer. CD4 T cells provide help to CD8 T cells via multiple mechanisms, including licensing dendritic cells (DCs), co-stimulation, and cytokine production. During acute infection and vaccination, CD4 T cell help is important for the development of CD8 T cell memory. However, during chronic viral infection and cancer, CD4 helper T cells are critical for the sustained effector CD8 T cell response, through a variety of mechanisms. In this review, we focus on T cell responses in conditions of chronic Ag stimulation, such as chronic viral infection and cancer. In particular, we address the significant role of CD4 T cell help in promoting effector CD8 T cell responses, emerging techniques that can be utilized to further our understanding of how these interactions may take place in the context of tertiary lymphoid structures, and how this key information can be harnessed for therapeutic utility against cancer.

• IMMUNE NETWORK
• /
• 제16권4호
• /
• pp.219-232
• /
• 2016

Production of high affinity antibodies for antigens is a critical component for the immune system to fight off infectious pathogens. However, it could be detrimental to our body when the antigens that B cells recognize are of self-origin. Follicular helper T, or Tfh, cells are required for the generation of germinal center reactions, where high affinity antibody-producing B cells and memory B cells predominantly develop. As such, Tfh cells are considered as targets to prevent B cells from producing high affinity antibodies against self-antigens, when high affinity autoantibodies are responsible for immunopathologies in autoimmune disorders. This review article provides an overview of current understanding of Tfh cells and discusses it in the context of animal models of autoimmune diseases and allograft rejections for generation of novel therapeutic interventions.

• 한국통신학회논문지
• /
• 제34권3B호
• /
• pp.311-317
• /
• 2009

기존의 망 이상 상태 탐지 시스템들은 주로 정상 상태의 시스템 사용률 등과 같은 통계 값으로 결정된 임계값을 기반으로 탐지하기 때문에 이상 상태임에도 불구하고 정상 상태와 비슷한 시스템 통계 값을 가지면 탐지하지 못하는 문제점이 있다. 이러한 단점들을 해결하기 위하여 본 논문에서는 인간면역체계의 학습, 적응, 기억 능력등의 특성을 이용하는 인공면역체계 기반의 적응적 망 이상 상태 탐지 모델을 제안한다. 이를 위하여 인간면역 시스템의 수지상 세포 (Dendritic Cell)와 T 세포 사이의 상호 작용을 이용한 탐지 모델을 설계하고 각 구성 요소 및 기능을 정의한다. 중앙 집중 제어 노드는 각 라우터 노드로부터 전달받은 정보를 분석하여 대응 방법을 해당 라우터들에게 전달한다. 또한 라우터 노드는 학습을 통해 얻어진 데이터를 기반으로 이상 상태를 탐지할 뿐만 아니라 중앙 집중 제어 노드로부터 전달받은 정보를 이용하여 이상 상태를 처리한다. 최종적으로 제안된 이상 상태탐지 모델의 타당성을 검증하기 위하여 구성 모듈을 설계하고 flooding 공격에 대한 시뮬레이션을 수행한다.

• IMMUNE NETWORK
• /
• 제21권4호
• /
• pp.28.1-28.14
• /
• 2021

Lung-resident memory T cells (T_RM) play an essential role in protecting against pulmonary virus infection. Parenteral administration of DNA vaccine is generally not sufficient to induce lung CD8 T_RM cells. This study investigates whether intramuscularly administered DNA vaccine expressing the nucleoprotein (NP) induces lung T_RM cells and protects against the influenza B virus. The results show that DNA vaccination poorly generates lung T_RM cells and massive secondary effector CD8 T cells entering the lungs after challenge infection do not offer sufficient protection. Nonetheless, intranasal administration of non-replicating adenovirus vector expressing no Ag following priming DNA vaccination deploys NP-specific CD8 T_RM cells in the lungs, which subsequently offers complete protection. This novel 'prime and deploy' strategy could be a promising regimen for a universal influenza vaccine targeting the conserved NP Ag.

• IMMUNE NETWORK
• /
• 제23권4호
• /
• pp.32.1-32.15
• /
• 2023

Most influenza vaccines currently in use target the highly variable hemagglutinin protein to induce neutralizing antibodies and therefore require yearly reformulation. T cell-based universal influenza vaccines focus on eliciting broadly cross-reactive T-cell responses, especially the tissue-resident memory T cell (T_RM) population in the respiratory tract, providing superior protection to circulating memory T cells. This study demonstrated that intramuscular (i.m.) administration of the adenovirus-based vaccine expressing influenza virus nucleoprotein (rAd/NP) elicited weak CD8 T_RM responses in the lungs and airways, and yielded poor protection against lethal influenza virus challenge. However, a novel "prime-and-deploy" strategy that combines i.m. vaccination of rAd/NP with subsequent intranasal administration of an empty adenovector induced strong NP-specific CD8⁺ T_RM cells and provided complete protection against influenza virus challenge. Overall, our results demonstrate that this "prime-and-deploy" vaccination strategy is potentially applicable to the development of universal influenza vaccines.

• IMMUNE NETWORK
• /
• 제5권4호
• /
• pp.252-257
• /
• 2005

Background: This study was designed to investigate the effect of exercise training on defense mechanism of chronic degenerative disease, aging, and memory impairments of senescence-accelerated mouse (SAM)P8 under the hypothesis that "Senile dementia may be prevented by regular exercises". Methods: To evaluate the effects of exercise training on the defense mechanism of aging and memory impairment, SAMP8 were divided into two groups, the control group and exercise training groups. the exercise training group were performed with low $(\dot{V}O_2max\;25{\sim}33%)$, middle ($\dot{V}O_2max$ 50%) and high $(\dot{V}O_2max\;66{\sim}75%)$ intensity exercise. All SAMP8 mice were fed experimental diet ad libitum until 4, 8 months, and dead period. Results: Median lifespan in middle exercise group resulted in a significantly increased (23.5% and 18.7%, respectively), whereas these lifespan in high exercise group resulted in an unexpectedly decreased (13.5% and 12.1%, respectively) compared with control group. Body fat levels in 4 and 8 months of age were significantly decreased 43% to 51% in middle exercise group, whereas were remarkably deceased to 57% in high exercise group compared with control group. It is believed that extended median and maximum lifespan may be effected by calory restriction through the exercise training. Acetylcholine (ACh) levels were significantly increased 6.7% and 8.5% in middle and high exercise groups, and also choline acetyltransfease (ChAT) activities were significantly increased 10.3% and 11.9% in middle and high exercise groups. Conclusion: These results suggest that proper and regular exercises such as middle group ($\dot{V}O_2max$ 50%) may play an effective role in attenuating an oxygen radicals and may play an important role in improving a learning and memory impairments of senile dementia.

• IMMUNE NETWORK
• /
• 제24권1호
• /
• pp.9.1-9.21
• /
• 2024

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

• Biomolecules & Therapeutics
• /
• 제30권5호
• /
• pp.418-426
• /
• 2022

Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1⁺ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8⁺ T cells having CD8⁺CD44⁺CD62L^low phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.