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      • Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis

        Hwang, Seong-Hye,Jung, Seung-Hyun,Lee, Saseong,Choi, Susanna,Yoo, Seung-Ah,Park, Ji-Hwan,Hwang, Daehee,Shim, Seung Cheol,Sabbagh, Laurent,Kim, Ki-Jo,Park, Sung Hwan,Cho, Chul-Soo,Kim, Bong-Sung,Leng, National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.47

        <P><B>Significance</B></P><P>We screened rheumatoid arthritis (RA)-associated copy number variations (CNVs) across the whole genome and identified significant deletion variants encompassing leukocyte-specific protein 1 (LSP1) gene. Functional assays revealed that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration. Loss of <I>Lsp1</I> promotes T-cell migration into antigen-instilled tissues and draining lymph nodes in mice with T-cell–dependent chronic inflammation. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype, highlighting the importance of <I>LSP1</I> CNVs and LSP1 insufficiency in the pathogenesis of RA.</P><P>Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (<I>LSP1</I>) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in <I>Lsp1-</I>deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell–dependent chronic inflammation, loss of <I>Lsp1</I> promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of <I>LSP1</I> CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA.</P>

      • Rheumatoid arthritis: Modelling cytokine signalling networks

        Hwang, Daehee,Kim, Wan-Uk Nature Publishing Group, a division of Macmillan P 2017 Nature reviews. Rheumatology Vol.13 No.1

        <P>Although an imbalance between proinflammatory and anti-inflammatory cytokines has been implicated in rheumatoid arthritis (RA), the identification of specific cytokines regulating RA pathophysiotogy is still challenging. Modelling cytokine signalling networks and evaluating associated pathway activities might facilitate the effective identification of cytokines for treatment and prevention of RA.</P>

      • SCISCIESCOPUS

        Annual Average Changes in Adult Obesity as a Risk Factor for Papillary Thyroid Cancer : A Large-Scale Case-Control Study

        Hwang, Yunji,Lee, Kyu Eun,Park, Young Joo,Kim, Su-Jin,Kwon, Hyungju,Park, Do Joon,Cho, Belong,Choi, Ho-Chun,Kang, Daehee,Park, Sue K. Wolters Kluwer Health 2016 Medicine Vol.95 No.9

        <▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>We evaluated the association between weight change in middle-aged adults and papillary thyroid cancer (PTC) based on a large-scale case-control study.</P><P>Our study included data from 1551 PTC patients (19.3% men and 80.7% women) who underwent thyroidectomy at the 3 general hospitals in Korea and 15,510 individually matched control subjects. The subjects’ weight history, epidemiologic information, and tumor characteristics confirmed after thyroidectomy were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined for the annual average changes in weight and obesity indicators (body mass index (BMI), body surface area, and body fat percentage (BF%) in subjects since the age of 35 years.</P><P>Subjects with a total weight gain ≥10 kg after age 35 years were more likely to have PTC (men, OR, 5.39, 95% CI, 3.88–7.49; women, OR, 3.36, 95% CI, 2.87–3.93) compared with subjects with a stable weight (loss or gain <5 kg). A marked increase in BMI since age 35 years (annual average change of BMI ≥0.3 kg/m<SUP>2</SUP>/yr) was related to an elevated PTC risk, and the association was more pronounced for large-sized PTC risks (<1 cm, OR, 2.34, 95% CI, 1.92–2.85; ≥1 cm, OR, 4.00, 95% CI, 2.91–5.49, <I>P</I> heterogeneity = 0.005) compared with low PTC risks.</P><P>Weight gain and annual increases in obesity indicators in middle-aged adults may increase the risk of developing PTC.</P></▼2>

      • KCI등재

        Fus3 and Tpk2 protein kinases regulate the phosphorylation-dependent functions of RNA helicase Dhh1 in yeast mating and Ste12 protein expression

        Hwang Jaehee,Jung Daehee,Kim Jinmi 한국미생물학회 2022 The journal of microbiology Vol.60 No.8

        Decapping of mRNA is a key regulatory step for mRNA decay and translation. The RNA helicase, Dhh1, is known as a decapping activator and translation repressor in yeast Saccharomyces cerevisiae. Dhh1 also functions as a gene-specific positive regulator in the expression of Ste12, a mating-specific transcription factor. A previous study showed that the Nerminal phosphorylation of Dhh1 regulates its association with the mRNA-binding protein, Puf6, to affect the protein translation of Ste12. Here, we investigated the roles of the phosphorylated residues of Dhh1 in yeast mating process and Ste12 expression. The phospho-deficient mutation, DHH1- T10A, was associated with decreased diploid formation during mating and decreased level of the Ste12 protein in response to α-mating pheromone. A kinase overexpression analysis revealed that Ste12 protein expression was affected by overexpression of Fus3 MAP kinase or Tpk2 kinase. Tpk2 was shown to be responsible for phosphorylation of Dhh1 at Thr10. Our study shows that overexpression of Fus3 or Tpk2 alters the Dhh1-Puf6 protein interaction and thereby affects Ste12 protein expression.

      • Strong anisotropy of ferroelectricity in lead-free bismuth silicate.

        Seol, Daehee,Taniguchi, Hiroki,Hwang, Jae-Yeol,Itoh, Mitsuru,Shin, Hyunjung,Kim, Sung Wng,Kim, Yunseok RSC Pub 2015 Nanoscale Vol.7 No.27

        <P>Bismuth silicate (Bi2SiO5) was recently suggested as a potential silicate based lead-free ferroelectric material. Here, we show the existence of ferroelectricity and explore the strong anisotropy of local ferroelectricity using piezoresponse force microscopy (PFM). Domain structures are reconstructed using angle-resolved PFM. Furthermore, piezoresponse hysteresis loops and piezoelectric coefficients are spatially investigated at the nanoscale. The obtained results confirm the existence of ferroelectricity with strong c-axis polarization. These results could provide basic information on the anisotropic ferroelectricity in Bi2SiO5 and furthermore suggest its considerable potential for lead-free ferroelectric applications with silicon technologies.</P>

      • SCISCIESCOPUS

        Dynamic mechanical control of local vacancies in NiO thin films

        Seol, Daehee,Yang, Sang Mo,Jesse, Stephen,Choi, Minseok,Hwang, Inrok,Choi, Taekjib,Park, Bae Ho,Kalinin, Sergei V,Kim, Yunseok IOP 2018 Nanotechnology Vol.29 No.27

        <P>The manipulation of local ionic behavior via external stimuli in oxide systems is of great interest because it can help in directly tuning material properties. Among external stimuli, mechanical force has attracted intriguing attention as novel stimulus for ionic modulation. Even though effectiveness of mechanical force on local ionic modulation has been validated in terms of static effect, its real-time i.e., dynamic, behavior under an application of the force is barely investigated in spite of its crucial impact on device performance such as force or pressure sensors. In this study, we explore dynamic ionic behavior modulated by mechanical force in NiO thin films using electrochemical strain microscopy (ESM). Ionically mediated ESM hysteresis loops were significantly varied under an application of mechanical force. Based on these results, we were able to investigate relative relationship between the force and voltage effects on ionic motion and, further, control effectively ionic behavior through combination of mechanical and electrical stimuli. Our results can provide comprehensive information on the effect of mechanical forces on ionic dynamics in ionic systems.</P>

      • KCI등재

        A Study on Data Sharing Scheme using ECP-ABSC that Provides Data User Traceability in the Cloud

        YongWoon Hwang,Taehoon Kim,Daehee Seo,Im-Yeong Lee 한국인터넷정보학회 2022 KSII Transactions on Internet and Information Syst Vol.16 No.12

        Recently, various security threats such as data leakage and data forgery have been possible in the communication and storage of data shared in the cloud environment. This paper conducted a study on the CP-ABSC scheme to solve these security threats. In the existing CP-ABSC scheme, if the data is obtained by the unsigncryption of the data user incorrectly, the identity of the data owner who uploaded the ciphertext cannot be known. Also, when verifying the leaked secret key, the identity information of the data user who leaked the secret key cannot be known. In terms of efficiency, the number of attributes can affect the ciphertext. In addition, a large amount of computation is required for the user to unsigncrypt the ciphertext. In this paper, we propose ECP-ABSC that provides data user traceability, and use it in a cloud environment to provide an efficient and secure data sharing scheme. The proposed ECP-ABSC scheme can trace and verify the identity of the data owner who uploaded the ciphertext incorrectly and the data user who leaked the secret key for the first time. In addition, the ciphertext of a constant size is output and the efficiency of the user's unsigncryption computation were improved.

      • KCI우수등재

        API 정보와 기계학습을 통한 윈도우 실행파일 분류

        조대희(DaeHee Cho),임경환(Kyeonghwan Lim),조성제(Seong-je Cho),한상철(Sangchul Han),황영섭(Young-sup Hwang) 한국정보과학회 2016 정보과학회논문지 Vol.43 No.12

        소프트웨어 분류 기법은 저작권 침해 탐지, 악성코드의 분류, 소프트웨어 보관소의 소프트웨어 자동분류 등에 활용할 수 있으며, 불법 소프트웨어의 전송을 차단하기 위한 소프트웨어 필터링 시스템에도 활용할 수 있다. 소프트웨어 필터링 시스템에서 유사도 측정을 통해 불법 소프트웨어를 식별할 경우, 소프트웨어 분류를 활용하여 탐색 범위를 축소하면 평균 비교 횟수를 줄일 수 있다. 본 논문은 API 호출 정보와 기계학습을 통한 윈도우즈 실행파일 분류를 연구한다. 다양한 API 호출 정보 정제 방식과 기계학습 알고리즘을 적용하여 실행파일 분류 성능을 평가한다. 실험 결과, PolyKernel을 사용한 SVM (Support Vector Machine)이 가장 높은 성공률을 보였다. API 호출 정보는 바이너리 실행파일에서 추출할 수 있는 정보이며, 기계학습을 적용하여 변조 프로그램을 식별하고 실행파일의 빠른 분류가 가능하다. 그러므로 API 호출 정보와 기계학습에 기반한 소프트웨어 분류는 소프트웨어 필터링 시스템에 활용하기에 적당하다. Software classification has several applications such as copyright infringement detection, malware classification, and software automatic categorization in software repositories. It can be also employed by software filtering systems to prevent the transmission of illegal software. If illegal software is identified by measuring software similarity in software filtering systems, the average number of comparisons can be reduced by shrinking the search space. In this study, we focused on the classification of Windows executables using API call information and machine learning. We evaluated the classification performance of machine learning-based classifier according to the refinement method for API information and machine learning algorithm. The results showed that the classification success rate of SVM (Support Vector Machine) with PolyKernel was higher than other algorithms. Since the API call information can be extracted from binary executables and machine learning-based classifier can identify tampered executables, API call information and machine learning-based software classifiers are suitable for software filtering systems.

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