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Craniofacial morphologic alteration induced by bone-targeted mutants of FGFR2 causing Apert and Crouzon syndrome (어퍼트 및 크루즌 증후군을 유발하는 골조직 특이성 FGFR2 돌연변이에 의한 두개안면 형태의 변화)

  • Lee, Kee-Joon;Nah, Hyun-Duck;Tjoa, Stephen T. J.;Park, Young-Chel;Baik, Hyoung-Seon;Yun, Tae-Min;Song, Jin-Wook
    • The korean journal of orthodontics
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    • v.36 no.4
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    • pp.284-294
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    • 2006
  • Objective: Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively. Methods: Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results. Results: Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype. Conclusion: Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.

Analysis of Trading Performance on Intelligent Trading System for Directional Trading (방향성매매를 위한 지능형 매매시스템의 투자성과분석)

  • Choi, Heung-Sik;Kim, Sun-Woong;Park, Sung-Cheol
    • Journal of Intelligence and Information Systems
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    • v.17 no.3
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    • pp.187-201
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    • 2011
  • KOSPI200 index is the Korean stock price index consisting of actively traded 200 stocks in the Korean stock market. Its base value of 100 was set on January 3, 1990. The Korea Exchange (KRX) developed derivatives markets on the KOSPI200 index. KOSPI200 index futures market, introduced in 1996, has become one of the most actively traded indexes markets in the world. Traders can make profit by entering a long position on the KOSPI200 index futures contract if the KOSPI200 index will rise in the future. Likewise, they can make profit by entering a short position if the KOSPI200 index will decline in the future. Basically, KOSPI200 index futures trading is a short-term zero-sum game and therefore most futures traders are using technical indicators. Advanced traders make stable profits by using system trading technique, also known as algorithm trading. Algorithm trading uses computer programs for receiving real-time stock market data, analyzing stock price movements with various technical indicators and automatically entering trading orders such as timing, price or quantity of the order without any human intervention. Recent studies have shown the usefulness of artificial intelligent systems in forecasting stock prices or investment risk. KOSPI200 index data is numerical time-series data which is a sequence of data points measured at successive uniform time intervals such as minute, day, week or month. KOSPI200 index futures traders use technical analysis to find out some patterns on the time-series chart. Although there are many technical indicators, their results indicate the market states among bull, bear and flat. Most strategies based on technical analysis are divided into trend following strategy and non-trend following strategy. Both strategies decide the market states based on the patterns of the KOSPI200 index time-series data. This goes well with Markov model (MM). Everybody knows that the next price is upper or lower than the last price or similar to the last price, and knows that the next price is influenced by the last price. However, nobody knows the exact status of the next price whether it goes up or down or flat. So, hidden Markov model (HMM) is better fitted than MM. HMM is divided into discrete HMM (DHMM) and continuous HMM (CHMM). The only difference between DHMM and CHMM is in their representation of state probabilities. DHMM uses discrete probability density function and CHMM uses continuous probability density function such as Gaussian Mixture Model. KOSPI200 index values are real number and these follow a continuous probability density function, so CHMM is proper than DHMM for the KOSPI200 index. In this paper, we present an artificial intelligent trading system based on CHMM for the KOSPI200 index futures system traders. Traders have experienced on technical trading for the KOSPI200 index futures market ever since the introduction of the KOSPI200 index futures market. They have applied many strategies to make profit in trading the KOSPI200 index futures. Some strategies are based on technical indicators such as moving averages or stochastics, and others are based on candlestick patterns such as three outside up, three outside down, harami or doji star. We show a trading system of moving average cross strategy based on CHMM, and we compare it to a traditional algorithmic trading system. We set the parameter values of moving averages at common values used by market practitioners. Empirical results are presented to compare the simulation performance with the traditional algorithmic trading system using long-term daily KOSPI200 index data of more than 20 years. Our suggested trading system shows higher trading performance than naive system trading.

THE EFFECT OF ALTERED FUNCTIONAL FORCE ON THE EXPRESSION OF SPECIFIC MRNAS IN THE DEVELOPING MOUSE MANDIBLE (하악골의 발육중인 생쥐에서 기능력의 변화가 특이-유전자 발현에 미치는 영향)

  • Kim, Hyung-Tae;Park, Joo-Cheol;Lee, Chang-Seop;Park, Heon-Dong
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.2
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    • pp.308-319
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    • 2003
  • Mechanical forces are known to have an effect on bone formation, maintenance and remodeling, and there is evidence that the development of the mandibular condyle in the rat or mouse is influenced by altered functional force. However, studies are lacking in molecular-biologic mechanism such as the identification of differentiation factor induced from functional force. Here a mouse model was used to investigate the functional stress-responsive gene or factors which is related to the altered force by comparing the expression genes of functional state and hypo-functional state of the mouse mandible. ICR mice were provisioned with either a soft, mushy diet (soft-diet group) or hard rat pellets (hard-diet group) beginning at weaning for the alteration of functional force and subsequently sacrificed at 89 days of age. Incisor of mice in group 1 were trimmed twice a week to reduce occlusal forces. After killing the animals, mandibular bone including condyle were collected for RNA extraction, subtractive hybridization, northern blot analysis and mRNA in-situ hybridization. The results as follows; 1. A total of 39 clones were sequenced, and 11 individual sequence types were subsequently identified by subtractive hybridization, as 28 clones were represented twice in the analyzed sets. 2. Consequently four candidate clones, FS-s (functional stress-specific)2, -5, -18, and -22 were identified and characterized by homolgy search and northern analysis. Four of these clones, FS-s2, -5, -18, and -22, were shown to be expressed differentially in the hard-diet group. 3. Histologic sections showed that osteoblastic activity along the bone trabeculae and active bone remodeling were significantly lower in soft than in hard diet animals. A soft diet seems to enable a longer period of endochondral ossification in the mandibular condyle. 4. Although the mRNAs of FS-s2, -5, -18, and -22 were expressed rarely by cells of the soft-diet group, highest expression was detected in the cells of the hard-diet group. Together with the above results, it is suggested that FS-s2, -5, -18, and -22 could act as an important factors controlling the tissue changes in response to functional stress. The exact functional significance of these findings remains to be established.

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Cis-acting Replication Element Variation of the Foot-and-mouth Disease Virus is Associated with the Determination of Host Susceptibility (구제역바이러스의 숙주 특이성 결정에 연관되어있는 구제역바이러스 cis-acting replication element 변이 분석 연구)

  • Kang, Hyo Rin;Seong, Mi So;Ku, Bok Kyung;Cheong, JaeHun
    • Journal of Life Science
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    • v.30 no.11
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    • pp.947-955
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    • 2020
  • The foot-and-mouth disease virus (FMDV), a member of the Aphthovirus genus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. During replication of the FMDV RNA (ribonucleic acid) genome, FMDV-encoding RNA polymerase 3D acts in a highly location-specific manner. This suggests that specific RNA structures recognized by 3D polymerase within non-coding regions of the FMDV genome assist with binding during replication. One such region is the cis-acting replication element (CRE), which functions as a template for RNA replication. The FMDV CRE adopts a stem-loop conformation with an extended duplex stem, supporting a novel 15-17 nucleotide loop that derives stability from base-stacking interactions, with the exact RNA nucleotide sequence of the CRE producing different RNA secondary structures. Here, we show that CRE sequences of FMDVs isolated in Korea from 2010 to 2017 exhibit A and O genotypes. Interestingly, variations in the RNA secondary structure of the Korean FMDVs are consistent with the phylogenetic relationships between these viruses and reveal the specificity of FMDV infections for particular host species. Therefore, we conclude that each genetic clade of Korean FMDV is characterized by a unique functional CRE and that the evolutionary success of new genetic lineages may be associated with the invention of a novel CRE motif. Therefore, we propose that the specific RNA structure of a CRE is an additional criterion for FMDV classification dependent on the host species. These findings will help correctly analyze CRE sequences and indicate the specificity of host species for future FMDV epidemics.

Improved Original Entry Point Detection Method Based on PinDemonium (PinDemonium 기반 Original Entry Point 탐지 방법 개선)

  • Kim, Gyeong Min;Park, Yong Su
    • KIPS Transactions on Computer and Communication Systems
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    • v.7 no.6
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    • pp.155-164
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    • 2018
  • Many malicious programs have been compressed or encrypted using various commercial packers to prevent reverse engineering, So malicious code analysts must decompress or decrypt them first. The OEP (Original Entry Point) is the address of the first instruction executed after returning the encrypted or compressed executable file back to the original binary state. Several unpackers, including PinDemonium, execute the packed file and keep tracks of the addresses until the OEP appears and find the OEP among the addresses. However, instead of finding exact one OEP, unpackers provide a relatively large set of OEP candidates and sometimes OEP is missing among candidates. In other words, existing unpackers have difficulty in finding the correct OEP. We have developed new tool which provides fewer OEP candidate sets by adding two methods based on the property of the OEP. In this paper, we propose two methods to provide fewer OEP candidate sets by using the property that the function call sequence and parameters are same between packed program and original program. First way is based on a function call. Programs written in the C/C++ language are compiled to translate languages into binary code. Compiler-specific system functions are added to the compiled program. After examining these functions, we have added a method that we suggest to PinDemonium to detect the unpacking work by matching the patterns of system functions that are called in packed programs and unpacked programs. Second way is based on parameters. The parameters include not only the user-entered inputs, but also the system inputs. We have added a method that we suggest to PinDemonium to find the OEP using the system parameters of a particular function in stack memory. OEP detection experiments were performed on sample programs packed by 16 commercial packers. We can reduce the OEP candidate by more than 40% on average compared to PinDemonium except 2 commercial packers which are can not be executed due to the anti-debugging technique.

An Examination on Dongbeomwas if Convex Roofing Tiles (수막새의 동범와(同范瓦)에 대한 검토 - 월성해자 출토 단판연화문 수막새를 중심으로 -)

  • Lee, Seonhui
    • Korean Journal of Heritage: History & Science
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    • v.39
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    • pp.59-93
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    • 2006
  • Wolseong in Gyeongju is a historic fortress site of Silla constructed under the reign of Pasanisageum that played politically and militarily important roles. The moat surrounding Wolseong had a function of protecting the fortress in wartimes but became a part of gardening in the unified Silla era. Lots of relics have been excavated from Wolseong moat since 1985. Among them a great number and kinds of convex roofing tiles are regarded as invaluable sources to show different aspects of Silla, from its earlier time through to the unified and on. Roofing tiles were widely used for national buildings such as royal palaces, temples and fortresses and even for other popular architecture and have been dug out a lot more than any other relics. Research on them, however, has been done poorly. Vigorous study is in progress with increasing number of roofing tiles coming from many recent excavations, though it has been limited to the studies on general genealogy of patterns and manufacture processes. Thus this essay seeks to find which are dongbeomwas, roofing tiles of a same mold, out of convex tiles with the pattern of a unilobed lotus flower dug out of Wolseong moat. It also attempts to identify dongbeomwas by examining detail characteristics of roofing tiles which have been confusingly termed as yusawa, similar roofing tiles, or donghyeongwa, roofing tiles of the same shape. The significance of identifying dongbeomwas could be emphasized by various facts resulting from researches on dongbeomwas; the ways to identify them correctly, their time sequence and their excavated sites. In conclusion, dongbeomwas were identified out of many kinds of convex tiles. If they were excavated from the same site, they share some common features. The sites where they were dug out also tell what changes were made with passage of time and what relations they had with neighboring Anapji. Since roofing tile molds haven't been found yet, the only way to identify dongbeomwas is to examine details of roofing tiles. Dongbeomwas excavated in Wolseong moat help to discuss the time of each district of it. Meanwhile it should be noted that the term 'dongbeomwa' be used only after exact examining.

Development of Quantification Methods for the Myocardial Blood Flow Using Ensemble Independent Component Analysis for Dynamic $H_2^{15}O$ PET (동적 $H_2^{15}O$ PET에서 앙상블 독립성분분석법을 이용한 심근 혈류 정량화 방법 개발)

  • Lee, Byeong-Il;Lee, Jae-Sung;Lee, Dong-Soo;Kang, Won-Jun;Lee, Jong-Jin;Kim, Soo-Jin;Choi, Seung-Jin;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.6
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    • pp.486-491
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    • 2004
  • Purpose: factor analysis and independent component analysis (ICA) has been used for handling dynamic image sequences. Theoretical advantages of a newly suggested ICA method, ensemble ICA, leaded us to consider applying this method to the analysis of dynamic myocardial $H_2^{15}O$ PET data. In this study, we quantified patients' blood flow using the ensemble ICA method. Materials and Methods: Twenty subjects underwent $H_2^{15}O$ PET scans using ECAT EXACT 47 scanner and myocardial perfusion SPECT using Vertex scanner. After transmission scanning, dynamic emission scans were initiated simultaneously with the injection of $555{\sim}740$ MBq $H_2^{15}O$. Hidden independent components can be extracted from the observed mixed data (PET image) by means of ICA algorithms. Ensemble learning is a variational Bayesian method that provides an analytical approximation to the parameter posterior using a tractable distribution. Variational approximation forms a lower bound on the ensemble likelihood and the maximization of the lower bound is achieved through minimizing the Kullback-Leibler divergence between the true posterior and the variational posterior. In this study, posterior pdf was approximated by a rectified Gaussian distribution to incorporate non-negativity constraint, which is suitable to dynamic images in nuclear medicine. Blood flow was measured in 9 regions - apex, four areas in mid wall, and four areas in base wall. Myocardial perfusion SPECT score and angiography results were compared with the regional blood flow. Results: Major cardiac components were separated successfully by the ensemble ICA method and blood flow could be estimated in 15 among 20 patients. Mean myocardial blood flow was $1.2{\pm}0.40$ ml/min/g in rest, $1.85{\pm}1.12$ ml/min/g in stress state. Blood flow values obtained by an operator in two different occasion were highly correlated (r=0.99). In myocardium component image, the image contrast between left ventricle and myocardium was 1:2.7 in average. Perfusion reserve was significantly different between the regions with and without stenosis detected by the coronary angiography (P<0.01). In 66 segment with stenosis confirmed by angiography, the segments with reversible perfusion decrease in perfusion SPECT showed lower perfusion reserve values in $H_2^{15}O$ PET. Conclusions: Myocardial blood flow could be estimated using an ICA method with ensemble learning. We suggest that the ensemble ICA incorporating non-negative constraint is a feasible method to handle dynamic image sequence obtained by the nuclear medicine techniques.

Time Course Change of Phagocytes and Proinflammatory Activities in BALF in Endotoxin-induced Acute Lung Injury (시간별 내독소 정맥주입으로 유발된 급성폐손상의 변화양상에 대한 고찰)

  • Moon, Seung-Hyug;Oh, Je-Ho;Park, Sung-Woo;NamGung, Eun-Kyung;Ki, Shin-Young;Im, Gun-Il;Jung, Sung-Whan;Kim, Hyeon-Tae;Uh, Soo-Tack;Kim, Yong-Hoon;Park, Choon-Sik;Jin, Byeng-Weon
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.360-378
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    • 1997
  • Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.

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