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Knowledge-Based Reconstruction of mRNA Transcripts with Short Sequencing Reads for Transcriptome Research
Junhee Seok, Weihong Xu, Hui Jiang, Ronald W. Davis, Wenzhong Xiao
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031440
Abstract: While most transcriptome analyses in high-throughput clinical studies focus on gene level expression, the existence of alternative isoforms of gene transcripts is a major source of the diversity in the biological functionalities of the human genome. It is, therefore, essential to annotate isoforms of gene transcripts for genome-wide transcriptome studies. Recently developed mRNA sequencing technology presents an unprecedented opportunity to discover new forms of transcripts, and at the same time brings bioinformatic challenges due to its short read length and incomplete coverage for the transcripts. In this work, we proposed a computational approach to reconstruct new mRNA transcripts from short sequencing reads with reference information of known transcripts in existing databases. The prior knowledge helped to define exon boundaries and fill in the transcript regions not covered by sequencing data. This approach was demonstrated using a deep sequencing data set of human muscle tissue with transcript annotations in RefSeq as prior knowledge. We identified 2,973 junctions, 7,471 exons, and 7,571 transcripts not previously annotated in RefSeq. 73% of these new transcripts found supports from UCSC Known Genes, Ensembl or EST transcript annotations. In addition, the reconstructed transcripts were much longer than those from de novo approaches that assume no prior knowledge. These previously un-annotated transcripts can be integrated with known transcript annotations to improve both the design of microarrays and the follow-up analyses of isoform expression. The overall results demonstrated that incorporating transcript annotations from genomic databases significantly helps the reconstruction of novel transcripts from short sequencing reads for transcriptome research.
A dynamic network of transcription in LPS-treated human subjects
Junhee Seok, Wenzhong Xiao, Lyle L Moldawer, Ronald W Davis, Markus W Covert
BMC Systems Biology , 2009, DOI: 10.1186/1752-0509-3-78
Abstract: In this study, we analyzed a gene expression data set in blood leukocytes from human subjects administered with lipopolysaccharide (LPS), a prototypical inflammatory challenge, in the context of a reconstructed regulatory network including 10 transcription factors, 99 target genes and 149 regulatory interactions. We found that the computationally estimated activities were well correlated to their coordinated action. Furthermore, we found that clustering the genes in the context of regulatory influences greatly facilitated interpretation of the expression data, as clusters of gene expression corresponded to the activity of specific factors or more interestingly, factor combinations which suggest coordinated regulation of gene expression. The resulting clusters were therefore more biologically meaningful, and also led to identification of additional genes under the same regulation.Using NCA, we were able to build a network that accounted for between 8–11% genes in the known transcriptional response to LPS in humans. The dynamic network illustrated changes of transcription factor activities and gene expressions as well as interactions of signaling proteins, transcription factors and target genes.An achievement that would have a major impact on our understanding of transcriptional regulatory networks would be to map out the coordinated dynamic responses of signaling proteins, transcription factors and target genes over time. The primary challenges to such an effort are development of high-throughput technologies to measure transcription factor activities at the genome-scale, and computational tools to interpret the data and predict the structure and dynamics of the underlying networks.Recent development of high-throughput technologies has enabled large-scale measurements of biological signals related to transcription, such as the expression of target genes and the activities of transcription factors. For target gene expression, microarrays measure the expression levels
Distinctive Responsiveness to Stromal Signaling Accompanies Histologic Grade Programming of Cancer Cells
Maria Gloria Luciani,Junhee Seok,Aejaz Sayeed,Stacey Champion,William H. Goodson,Stefanie S. Jeffrey,Wenzhong Xiao,Michael Mindrinos,Ronald W. Davis,Shanaz H. Dairkee
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020016
Abstract: Whether stromal components facilitate growth, invasion, and dissemination of cancer cells or suppress neoplastic lesions from further malignant progression is a continuing conundrum in tumor biology. Conceptualizing a dynamic picture of tumorigenesis is complicated by inter-individual heterogeneity. In the post genomic era, unraveling such complexity remains a challenge for the cancer biologist. Towards establishing a functional association between cellular crosstalk and differential cancer aggressiveness, we identified a signature of malignant breast epithelial response to stromal signaling. Proximity to fibroblasts resulted in gene transcript alterations of >2-fold for 107 probes, collectively designated as Fibroblast Triggered Gene Expression in Tumor (FTExT). The hazard ratio predicted by the FTExT classifier for distant relapse in patients with intermediate and high grade breast tumors was significant compared to routine clinical variables (dataset 1, n = 258, HR – 2.11, 95% CI 1.17–3.80, p-value 0.01; dataset 2, n = 171, HR - 3.07, 95% CI 1.21–7.83, p-value 0.01). Biofunctions represented by FTExT included inflammatory signaling, free radical scavenging, cell death, and cell proliferation. Unlike genes of the ‘proliferation cluster’, which are overexpressed in aggressive primary tumors, FTExT genes were uniquely repressed in such cases. As proof of concept for our correlative findings, which link stromal-epithelial crosstalk and tumor behavior, we show a distinctive differential in stromal impact on prognosis-defining functional endpoints of cell cycle progression, and resistance to therapy-induced growth arrest and apoptosis in low vs. high grade cancer cells. Our experimental data thus reveal aspects of ‘paracrine cooperativity’ that are exclusively contingent upon the histopathologically defined grade of interacting tumor epithelium, and demonstrate that epithelial responsiveness to the tumor microenvironment is a deterministic factor underlying clinical outcome. In this light, early attenuation of epithelial-stromal crosstalk could improve the management of cases prone to be clinically challenging.
Finite Element Analysis with Paraxial & Viscous Boundary Conditions for Elastic Wave Propagation  [PDF]
Hee Seok Kim
Engineering (ENG) , 2012, DOI: 10.4236/eng.2012.412107
Abstract: In this study, two studies are performed. One is to apply paraxial boundary conditions which are local boundary conditions based on paraxial approximations of the one-way wave equations to finite element analysis. To do this, a penalty functional is proposed and the existence and uniqueness of the extremum of the proposed functional is demonstrated. The other is to improve the capacity of viscous boundary conditions using dashpots. To do this, customary viscous boundary conditions are modified to maximize the efficiency according to angles of incidence and materials. For the numerical analysis of elasticity with paraxial boundary conditions and the modified viscous boundary conditions, the coding of the finite element models is implemented, and the efficiency of those boundary conditions is investigated.
Crime Prevention in Ethnic Areas Focusing on Crime Prevention through Environmental Design  [PDF]
Seok-Jin Kang
Journal of Building Construction and Planning Research (JBCPR) , 2013, DOI: 10.4236/jbcpr.2013.11003
Abstract: The purpose of this study is to consider crime prevention measures in ethnic areas focusing on Crime Prevention through Environmental Design (CPTED) by an analysis of crime data and field survey. In this study, it was found that the main type of foreign crime that occurred in the research area was violence, and crimes committed by Koreans, which were mainly violence and crimes such as burglary, theft, robbery, and sexual offences, occurred steadily. Because it was found that crimes were related to the urban planning elements comprised of land use such as traditional market, inn, pub, and complicated space structure and the architectural design for natural surveillance and security facilities such as CCTV, lighting, alarm, and target hardening device, a new strategy for crime prevention design should include street environmental management, improvement of commercial facilities, and reinforcement security device of each buildings has to be spread through support of policy. In conclusion it was thought that CPTED would be a valuable measure to prevention crime and support community activities in ethnic area as expecting an improvement of physical environment and resident participatory for safer community.
A Study on the Characteristics for the Ground Vibration Due to the Travelling Tilting Train  [PDF]
Hee Seok Kim
Engineering (ENG) , 2013, DOI: 10.4236/eng.2013.59087

The development of the tilting train can contribute to solve the economic burden and enhance the transportation means of areas that did not share the benefits of the high speed railway. But the dynamic behavior caused by the interaction between the train and the track as well as the environmental vibrations along the railway should be evaluated to secure the safety of the train and riding comfort. In this paper a study on the characteristics for ground vibration due to the tilting train travelling in the conventional line are carried out. The transmitted load into the ground is computed through a study on the interrelation between the tilting car and the line. This load is applied into the numerical model which is one for the analysis of ground vibration due to the travelling tilting car. The far fields on the numerical model are formed by the absorbing boundary using dashpot, one of the most widely used absorbing boundary in finite element analysis. Using this numerical model, the analysis of the ground vibration characteristics caused by travelling tilting car is performed. From the analysis, it is shown that the transferred load due to the tilting train is larger than that of the conventional train.

A Study on the Performance of Absorbing Boundaries Using Dashpot  [PDF]
Hee Seok Kim
Engineering (ENG) , 2014, DOI: 10.4236/eng.2014.610060
Abstract: In this paper an analytical study is carried out to examine the effectiveness of absorbing boundaries using dashpot. Validity of the absorbing boundary conditions suggested by Lysmer-Kuhle- meyer and White et al. is investigated by adopting the solution of Miller and Pursey. The Miller and Pursey’s problem is then numerically simulated using the finite element method. The absorption ratios are calculated by comparing the displacements at the absorbing boundary to those at the free field without the absorbing boundary. The numerical verification is carried out through comparison of displacement at the boundary.
A Study on the Characteristics and the Effective Reduction Methods for the Ground Vibration Due to the Travelling Tilting Train  [PDF]
Hee Seok Kim
Engineering (ENG) , 2014, DOI: 10.4236/eng.2014.64024

In this paper, a study on the characteristics and the reduction methods of ground vibration due to the tilting train travelling in the conventional line is carried out. The load transmitted into the ground is computed considering the interaction between the tilting car and the line. This load is then applied in the numerical model for the analysis of ground vibration due to the travelling tilting car. The far-fields of the numerical model are modeled using the dashpot, as one of the most widely used absorbing boundaries in finite element analysis. Using this numerical model, the analysis of the ground vibration characteristics caused by the travelling tilting car and the analysis of the blocking effect of the ground vibration by wave barriers are performed. From the numerical analysis, it is shown that the blocking effect of the trench and the barrier filled with soft material is more effective than that of the barrier filled with hard material.

An Investigation into the Questionable Practice of Using Excessive Massively Multiplayer Online Game Play as a Marker of Pathological Video Game Dependence among Adolescent and Young Adult Male Players  [PDF]
Soonhwa Seok, Boaventura DaCosta
Psychology (PSYCH) , 2014, DOI: 10.4236/psych.2014.54039

The present study explored pathological online video game dependence among adolescent and young adult males in the context of excessive massively multiplayer online game (MMOG) play. Psychological criteria distinguishing high engagement from addiction were used, as a means of examining MMOG play in the context of an excessive and addictive activity. This is a distinction that has been lost in the previous research, setting this study apart from other studies investigating frequency of play in the context of video game addiction. A total of 1121 male students in grades 7 through 12 across 12 schools in and around Seoul, South Korea, participated. The study used a 65-item questionnaire developed to examine constructs related to online video game play. Findings revealed no statistically significant differences between those classified as addicted and those classified as highly engaged with regard to items designed to measure frequency of MMOG play. Furthermore, in comparison to those classified as addicted, those classified as highly engaged reported a higher average number of hours per week they felt was an acceptable amount of time dedicated to game play. All in all, the findings revealed that those classified as highly engaged spent a significant portion of their time playing in massively multiplayer online worlds alongside those classified as addicted. These findings help illustrate the difficulties in using frequency of online video game play, even if viewed as excessive, as a criterion for identifying pathological dependence.

Sasang Constitutional Medicine and Traditional Chinese Medicine: A Comparative Overview
Junghee Yoo,Euiju Lee,Chungmi Kim,Junhee Lee,Lao Lixing
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/980807
Abstract: Sasang constitutional medicine (SCM) is a holistic typological constitution medicine which balances psychological, social, and physical aspects of an individual to achieve wellness and increase longevity. SCM has the qualities of preventative medicine, as it emphasizes daily health management based on constitutionally differentiated regimens and self-cultivation of the mind and body. This review's goal is to establish a fundamental understanding of SCM and to provide a foundation for further study. It compares the similarities and differences of philosophical origins, perspectives on the mind (heart), typological systems, pathology, and therapeutics between SCM and traditional Chinese medicine (TCM). TCM is based on the Taoist view of the universe and humanity. The health and longevity of an individual depends on a harmonious relationship with the universe. On the other hand, SCM is based on the Confucian view of the universe and humanity. SCM focuses on the influence of human affairs on the psyche, physiology, and pathology.
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