• 약학회지
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• 제49권1호
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• pp.103-108
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• 2005

Tacrine analogues for degenerative brain disease treatments have been designed. A series of diazaanthrine derivatives as novel analogues of tacrine has been prepared through the alkyl substitution and the ring expansion. They were expected to retain anti-inflammatory activity by inhibition of prostaglandin production with reduction of side effect as the selective prostaglandin synthase inhibitor. Prostaglandin synthase expression is associated with the deposition of beta-amyloid protein in neuritic plaques in brain inflammation. Therefore selective prostaglandin synthase blockade is important for the prevention and treatment of alzheimer's disease. To evaluate inhibitory effect of prostaglandin synthase, synthetic tacrine derivatives were screened with accumulation of prostaglandin biosynthesis by lipopolysaccharide in aspirin-treated murine macrophage cell. Most of synthetic compounds have shown significant prostaglandin synthase activities in vitro screening with $84.3{\sim}33.6\%$ inhibition of the prostaglandin $E_2$ production at $10\;{\mu}g/ml$.

• Journal of Yeungnam Medical Science
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• 제35권1호
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• pp.1-6
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• 2018

Alzheimer's disease (AD) is a neurodegenerative disorder associated with extracellular plaques, composed of amyloid-beta ($A{\beta}$), in the brain. Although the precise mechanism underlying the neurotoxicity of $A{\beta}$ has not been established, $A{\beta}$ accumulation is the primary event in a cascade of events that lead to neurofibrillary degeneration and dementia. In particular, the $A{\beta}$ burden, as assessed by neuroimaging, has proved to be an excellent predictive biomarker. Positron emission tomography, using ligands such as $^{11}C$-labeled Pittsburgh Compound B or $^{18}F$-labeled tracers, such as $^{18}F$-florbetaben, $^{18}F$-florbetapir, and $^{18}F$-flutemetamol, which bind to $A{\beta}$ deposits in the brain, has been a valuable technique for visualizing and quantifying the deposition of $A{\beta}$ throughout the brain in living subjects. $A{\beta}$ imaging has very high sensitivity for detecting AD pathology. In addition, it can predict the progression from mild cognitive impairment to AD, and contribute to the development of disease-specific therapies.

• 대한영상의학회지
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• 제83권3호
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• pp.527-537
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• 2022

철은 중추신경계 및 인체에 필수적인 성분으로 노화 및 다양한 퇴행성 뇌질환에서 뇌의 철 침착이 증가된다. 철은 MRI에서 독특한 특성을 가지고 있어 인체의 철 침착과 분포를 비침 습적으로 평가 및 정량화가 가능하다. 이 종설에서는 철 영상을 위한 MRI 기법에 대하여 알아보고, 노화 및 알츠하이머병을 포함한 퇴행성 뇌질환에서 변화를 고찰해 보고자 한다. 또한 현재 접근법의 제한점과 앞으로 기대되는 새로운 접근도 확인해 보고자 한다.

• 동의신경정신과학회지
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• 제9궈1호
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• pp.73-82
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• 1998

Substantial evidence has accumulated that Alzheimer's disease is associated with a local inflammatory reaction in senile plaques which may be immunemediated, and includes extensive Brain Neuroglial invasion, lymphocytic infiltration, cytokine deposition. Tumor necrosis factor a (TNF-a) is a cytokine which plays an important immunoenhancing role in the local acute and chronic inflammatory response in response to a variety of stimuli. The neuropeptide, substance P, can stimulate secretion of TNF-a from Brain Neuroglial cells. Neuroglia have substance P receptors in the central nervous system. WQ investigated whether RADIX ASPARAGI inhibits secretion of TNF-a from primary cultures of Brain Neuroglial cells containing both astrocyte (∼90%) and microglia (∼10%). RADIX ASPARAGI dose-dependently inhibited the TNF-a secretion induced by substance P plus lipopolysaccharide (LPS). In cultures enriched for micoglia (>95% pure). LPS stimulated the secretion of TNF-a but substance P caused no enhancement. Because there was no synergism between substance P and LPS in the microglial cultures it is resonable to substance P madiated enhancement of TNF-a secretion. IL-1 is a modulator of TNF-a secretion in the immune system. Also IL-1 has been shown to elevate TNF- a secretion from LPS-stimulated Brain Neuroglial cells while having no effect on Brain Neuroglial cells in the absence of LPS. We therfore investigated whether IL-1 mediates the RADIX ASPARAGI inhibition of TNF-a secretion form primary Brain Neuroglial cells. Treatment of RADIX ASPARAGI to mixed cultures stimulated with both substance P and LPS decreased TNF-a secretion to the level observed with LPS alone. These results indicate that RADIX ASPARAGI possess strong antiinflammatory activity in the cental nervous system by inhibition of inflammatory cytokines secretion from Brain Neuroglial cells.

• 한국정보디스플레이학회:학술대회논문집
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• 한국정보디스플레이학회 2003년도 International Meeting on Information Display
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• pp.889-892
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• 2003

Effects of $N_{2}$ plasma treatment of the Al bottom cathode on the characteristics of top emission inverted organic light emitting diodes (TEIOLEDs) were studied. TEIOLEDs were fabricated by depositing an Al bottom cathode, a tris-(8-hydroxyquinoline) aluminum $(Alq_{3})$ emitting layer, an N,N'-diphenyl-N,N'-bis(3-methylphenyl)-1,1'-diphenyl-4,4'diamine (TPD) hole transport layer, and an indium tin oxide (ITO) top anode sequentially. The Al bottom cathode layer was subjected to $N_{2}$ plasma treatment before deposition of the $Alq_{3}$ layer. X-ray photoelectron spectroscopy suggested that the existence of and the amount of $AIN_x$ between the $Alq_{3}$ emitting layer and the Al bottom cathode significantly affect the characteristics of TEIOLEDs. The maximum external quantum efficiency of the TEIOLED with an Ai bottom cathode subjected to $N_{2}$ plasma treatment for 30 s was about twice as high as that of the TEIOLED with an untreated Al bottom cathode.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.245-255
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• 2012

Amyloid-${\beta}$ peptide ($A{\beta}$) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduction of $A{\beta}$ in the brain. Since accumulation of $A{\beta}$ depends on the rate of its synthesis and clearance, the metabolic pathway of $A{\beta}$ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of $A{\beta}$ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of $A{\beta}$ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple $A{\beta}$-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on $A{\beta}$ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.

• 대한의생명과학회지
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• 제24권4호
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• pp.418-425
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• 2018

Amyloid brain positron emission tomography (PET) images are visually and subjectively analyzed by the physician with a lot of time and effort to determine the ${\beta}$-Amyloid ($A{\beta}$) deposition. We designed a convolutional neural network (CNN) model that predicts the $A{\beta}$-positive and $A{\beta}$-negative status. We performed 18F-florbetaben (FBB) brain PET on controls and patients (n=176) with mild cognitive impairment and Alzheimer's Disease (AD). We classified brain PET images visually as per the on the brain amyloid plaque load score. We designed the visual geometry group (VGG16) model for the visual assessment of slice-based samples. To evaluate only the gray matter and not the white matter, gray matter masking (GMM) was applied to the slice-based standard samples. All the performance metrics were higher with GMM than without GMM (accuracy 92.39 vs. 89.60, sensitivity 87.93 vs. 85.76, and specificity 98.94 vs. 95.32). For the patient-based standard, all the performance metrics were almost the same (accuracy 89.78 vs. 89.21), lower (sensitivity 93.97 vs. 99.14), and higher (specificity 81.67 vs. 70.00). The area under curve with the VGG16 model that observed the gray matter region only was slightly higher than the model that observed the whole brain for both slice-based and patient-based decision processes. Amyloid brain PET images can be appropriately analyzed using the CNN model for predicting the $A{\beta}$-positive and $A{\beta}$-negative status.

• Korean Journal of Radiology
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• 제24권11호
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• pp.1131-1141
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• 2023

Objective: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. Materials and Methods: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). Results: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (β = -216.21, P = 0.019) and insular cortex (β = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. Conclusion: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2013년도 제44회 동계 정기학술대회 초록집
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• pp.344-344
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• 2013

칩의 크기가 감소함에 따라 RC (Resistance, Capacitance) 지연, 전력소비증가 및 신호잡음 등이 문제가 되어왔다. RC지연 문제는 배선에 알루미늄 보다 비저항이 낮은 구리를 사용하고 절연막으로 유전상수가 낮은 물질을 사용하여 개선될 수 있다. 이와 같은 맥락에서 점차 저유전상수 박막의 필요성은 증가하고 있다. 그러므로 이를 개선하기 위해 저 유전상수 값을 가지는 물질을 개발 혹은, UV나 플라즈마 그리고 열을 이용하여 처리하는 연구가 절실히 요구되고 있으며, 현재 많은 연구가 진행되고 있다. 이 논문에서 저유전박막은 HDP-CVD (High Density Plasma Chemical Vapor Deposition) 시스템에서 (CyOz)-SiHx와 O2의 비율을 각각 변화시키면서 증착 되었다. (CyOz)-SiHx와 O2의 비율은 60/150, 60/180, 60/210, 60/240로 증가하면서 증착하였다. 그리고 surface profilometer을 이용하여 박막의 증착율을 측정하고 LCR meter를 이용하여 정전용량을 측정하여 유전상수 값을 얻었다. 박막의 화학적 조성과 구조는 FTIR (Fourier Transform Infrared Spectroscopy)로 측정하였다. 박막의 유동 특성은 SEM (Scanning electron microscope) 이미지로 살펴보았다.

• Molecules and Cells
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• 제37권5호
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• pp.406-411
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• 2014

The initial step of atrioventricular (AV) valve development involves the deposition of extracellular matrix (ECM) components of the endocardial cushion and the endocardialmesenchymal transition. While the appropriately regulated expression of the major ECM components, Versican and Hyaluronan, that form the endocardial cushion is important for heart valve development, the underlying mechanism that regulates ECM gene expression remains unclear. We found that zebrafish crip2 expression is restricted to a subset of cells in the AV canal (AVC) endocardium at 55 hours post-fertilization (hpf). Knockdown of crip2 induced a heart-looping defect in zebrafish embryos, although the development of cardiac chambers appeared to be normal. In the AVC of Crip2-deficient embryos, the expression of both versican a and hyaluronan synthase 2 (has2) was highly upregulated, but the expression of bone morphogenetic protein 4 (bmp4) and T-box 2b (tbx2b) in the myocardium and of notch1b in the endocardium in the AVC did not change. Taken together, these results indicate that crip2 plays an important role in AV valve development by downregulating the expression of ECM components in the endocardial cushion.