• 한국진공학회:학술대회논문집
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• 한국진공학회 2011년도 제40회 동계학술대회 초록집
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• pp.431-431
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• 2011

Graphene, two dimensional sheet of sp2-hybridized carbon, has attracted an enormous amount of interest due to excellent electrical, chemical and mechanical properties for the application of transparent conducting films, clean energy devices, field-effect transistors, optoelectronic devices and chemical sensors. Especially, graphene is promising candidate to detect the gas molecules and biomolecules due to the large specific surface area and signal-to-noise ratios. Despite of importance to the disease diagnosis, there are a few reports to demonstrate the graphene- and rGO-FET for biological sensors and the sensing mechanism are not fully understood. Here we describe scalable and facile fabrication of rGO-FET with the capability of label-free, ultrasensitive electrical detection of a cancer biomarker, prostate specific antigen/${\alpha}1$-antichymotrypsin (PSA-ACT) complex, in which the ultrathin rGO sensing channel was simply formed by a uniform self-assembly of two-dimensional rGO nanosheets on aminated pattern generated by inkjet printing. Sensing characteristics of rGO-FET immunosensor showed the highly precise, reliable, and linear shift in the Dirac point with the analyte concentration of PSA-ACT complex and extremely low detection limit as low as 1 fg/ml. We further analyzed the charge doping mechanism, which is the change in the charge carrier in the rGO channel varying by the concentration of biomolecules. Amenability of solution-based scalable fabrication and extremely high performance may enable rGO-FET device as a versatile multiplexed diagnostic biosensor for disease biomarkers.

• Molecules and Cells
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• 제37권6호
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• pp.467-472
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• 2014

Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic- pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and $30kg/m^2$. However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.

• 응용통계연구
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• 제29권4호
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• pp.643-656
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• 2016

고차원 자료(high dimensional data)는 변수의 수가 표본의 수보다 많은 자료로 다양한 분야에서 관측 또는 생성되고 있다. 일반적으로, 고차원 자료에 대한 회귀 모형에서는 모수의 추정과 과적합을 피하기 위하여 변수 선택이 이루어진다. 벌점화 회귀 모형(penalized regression model)은 변수 선택과 회귀 계수의 추정을 동시에 수행하는 장점으로 인하여 고차원 자료에 빈번하게 적용되고 있다. 하지만, 벌점화 회귀 모형에서도 여전히 조율 모수 선택(tuning parameter selection)을 통한 최적의 모형 선택이 요구된다. 본 논문에서는 벌점화 회귀 모형 중에서 대표적인 LASSO 회귀 모형을 기반으로 모형 선택의 기준들에 대한 LASSO 회귀 추정량의 편의가 어떠한 영향을 미치는지 모의실험을 통하여 수치적으로 연구하였고 편의의 보정의 필요성에 대하여 나타내었다. 실제 자료 분석에서의 영향을 나타내기 위하여, 폐암 환자의 유전자 발현량(gene expression) 자료를 기반으로 바이오마커 식별(biomarker identification) 문제에 적용하였다.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.63-69
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• 2014

In this study, we present a new isotope-coded carbamidomethylation (iCCM)-based quantitative proteomics, as a complementary strategy for conventional isotope labeling strategies, with providing the simplicity, ease of use, and robustness. In iCCM-based quantification, two proteome samples can be separately isotope-labeled by means of covalently reaction of all cysteinyl residues in proteins with iodoacetamide (IAA) and its isotope (IAA-$^{13}C_2$, $D_2$), denoted as CM and iCCM, respectively, leading to a mass shift of all cysteinyl residues to be + 4 Da. To evaluate iCCM-based isotope labeling in proteomic quantification, 6 protein standards (i.e., bovine serum albumin, serotransferrin, lysozyme, beta-lactoglobulin, beta-galactosidase, and alpha-lactalbumin) isotopically labeled with IAA and its isotope, mixed equally, and followed by proteolytic digestion. The resulting CM-/iCCM-labeled peptide mixtures were analyzed using a nLC-ESI-FT orbitrap-MS/MS. From our experimental results, we found that the efficiency of iCCM-based quantification is more superior to that of mTRAQ, as a conventional nonisobaric labeling method, in which both of a number of identified peptides from 6 protein standards and the less quantitative variations in the relative abundance ratios of heavy-/light-labeled corresponding peptide pairs. Finally, we applied the developed iCCM-based quantitative method to lung cancer serum proteome in order to evaluate the potential in biomarker discovery study.

• Safety and Health at Work
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• 제11권4호
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• pp.425-430
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• 2020

Background: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM. Methods: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months. Results: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy. Conclusion: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.

• Journal of Veterinary Science
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• 제22권6호
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• pp.79.1-79.14
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• 2021

Background: In contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool. Objectives: This study examined whether survivin could be suitable as a potential canine serum tumor marker. Methods: This study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17). Results: Dogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively). Conclusions: The serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.

• Journal of Periodontal and Implant Science
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• 제51권6호
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• pp.386-397
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• 2021

Purpose: MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators that modulate gene expression and have been identified as biomarkers for several diseases, including cancer. This study aimed to systematically review the relationship between miRNAs and periodontal disease in humans, and to evaluate the potential of miRNAs as diagnostic and prognostic biomarkers of disease. Methods: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42020180683). The MEDLINE, Scopus, Cochrane Library, Embase, Web of Science, and SciELO databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs. Expression levels of miRNAs across the different groups were analysed using the collected data. Results: A total of 1,299 references were identified in the initial literature search, and 23 articles were finally included in the review. The study designs were heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-146a. Most studies reported higher expression levels of miR-146a in patients with periodontitis than in healthy controls. In addition, many studies also focused on identifying target genes of the differentially expressed miRNAs that were significantly related to periodontal inflammation. Conclusions: The results of the studies that we analysed are promising, but diagnostic tests are needed to confirm the use of miRNAs as biomarkers to monitor and aid in the early diagnosis of periodontitis in clinical practice.

• 한국정보통신학회논문지
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• 제25권8호
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• pp.1046-1052
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• 2021

4차 산업의 발전과 고성능의 컴퓨팅 환경 구축으로 다양한 산업분야에서 인공지능이 적용되고 있다. 의료분야에서는 X-Ray, MRI, PET 등의 의료 영상 및 임상 자료를 이용하여 암, COVID-19, 골 연령 측정 등의 딥 러닝 학습이 진행되었다. 또한 스마트 의료기기, IoT 디바이스와 딥 러닝 알고리즘을 적용하여 ICT 의료 융합 기술 등이 연구되고 있다. 이러한 기술 중 의료 영상 기반 딥 러닝 학습은 의료 영상의 바이오마커를 정확히 찾아내고, 최소한의 손실률과 높은 정확도가 필요하다. 따라서 본 논문은 흉부 X-Ray 이미지 기반 딥 러닝 학습 과정에서 손실률을 도출하는 손실 함수 중 영상분류 알고리즘에서 사용되는 Cross-Entropy 함수들의 성능을 비교·분석하고자 한다.

• Molecules and Cells
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• 제45권9호
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• pp.640-648
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• 2022

CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the prominin-like (promL) gene, an orthologue of mammalian CD133 in Drosophila, plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of promL in Drosophila locomotion. Both promL mutants and pan-neuronal promL inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of promL inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in promL mutant and pan-neuronal promL inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, promL mutant and pan-neuronal promL inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of promL in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that promL expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in Drosophila.

• Journal of Korean Neurosurgical Society
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• 제67권3호
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• pp.364-375
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• 2024

Objective : Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. Methods : Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. Results : The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. Conclusion : Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.