Search

Recently, shape analysis of human organs has achieved much attention, owing to its potential to localize structural abnormalities. For a group-wise shape analysis, it is important to accurately restore the shape of a target structure in each subject and to build the inter-subject shape correspondences. To accomplish this, we propose a shape modeling method based on the Laplacian deformation framework. We deform a template model of a target structure in the segmented images while restoring subject-specific shape features by using Laplacian surface representation. In order to build the inter-subject shape correspondences, we implemented the progressive weighting scheme for adaptively controlling the rigidity parameter of the deformable model. This weighting scheme helps to preserve the relative distance between each point in the template model as much as possible during model deformation. This area-preserving deformation allows each point of the template model to be located at an anatomically consistent position in the target structure. Another advantage of our method is its application to human organs of non-spherical topology. We present the experiments for evaluating the robustness of shape modeling against large variations in shape and size with the synthetic sets of the second cervical vertebrae (C2), which has a complex shape with holes.

N-linked glycosylation is a critical determinant of protein structure and function, regulating processes such as protein folding, stability and localization, ligand–receptor binding and intracellular signalling. TβRII [type II TGF-β (transforming growth factor β) receptor] plays a crucial role in the TGF-β signalling pathway. Although N-linked glycosylation of TβRII was first demonstrated over a decade ago, it was unclear how this modification influenced TβRII biology. In the present study, we show that inhibiting the N-linked glycosylation process successfully hinders binding of TGF-β1 to TβRII and subsequently renders cells resistant to TGF-β signalling. The lung cancer cell line A549, the gastric carcinoma cell line MKN1 and the immortal cell line HEK (human embryonic kidney)-293 exhibit reduced TGF-β signalling when either treated with two inhibitors, including tunicamycin (a potent N-linked glycosylation inhibitor) and kifunensine [an inhibitor of ER (endoplasmic reticulum) and Golgi mannosidase I family members], or introduced with a non-glycosylated mutant version of TβRII. We demonstrate that defective N-linked glycosylation prevents TβRII proteins from being transported to the cell surface. Moreover, we clearly show that not only the complex type, but also a high-mannose type, of TβRII can be localized on the cell surface. Collectively, these findings demonstrate that N-linked glycosylation is essentially required for the successful cell surface transportation of TβRII, suggesting a novel mechanism by which the TGF-β sensitivity can be regulated by N-linked glycosylation levels of TβRII.

Docetaxel-loaded composite nanoparticles were prepared by temperature-induced phase transition of a mixture composed of Pluronic F-68 and liquid Tween 80/soybean oil containing docetaxel. Liquid soybean oil/Tween 80 was used as a solubilizer for docetaxel and Pluronic F-68 to stabilize the liquid soybean oil/Tween 80 containing docetaxel. The phase transition was performed at low temperature to avoid degradation. The docetaxel composite nanoparticles were injected into the tail veins of tumor-bearing mice to evaluate the composite delivery system for the release pattern and the tumor growth. The tumor-targeting capability of composite nanoparticles was verified by noninvasive live animal imaging for the time-dependent excretion profile, the in vivo biodistribution, and the circulation time.

Epiregulin (EREG) induces cell growth by binding to the epidermal growth factor receptor (EGFR). Expression of EREG affects sensitivity to cetuximab a chimeric monoclonal antibody that inhibits the EGFR signaling pathway. The mechanism through which EREG is regulated is largely unknown, but a methyl-array study previously performed by our group revealed that EREG is methylated in gastric cancer cells. In this study, we found that EREG gene expression was low in 7 out of 11 gastric cancer cells and this downregulation was mediated by aberrant CpG methylation of the EREG promoter. Treatment with 5-aza-CdR restored EREG expression and demethylated CpG sites in the EREG promoter. Compared with DNA methyltransferase 1 (DNMT1), knock-down of DNA methyltransferase 3b (DNMT3b) significantly increased the expression of EREG and led to the demethylation of specific CpG sites in the EREG promoter, suggesting that DNMT3b primarily regulates CpG methylation and silencing of the EREG gene. EREG methylation was observed in 30% (4/13) of human primary gastric tumor tissues we evaluated. In addition to DNA methylation, results from a chromatin immunoprecipitation assay demonstrated that transcriptional levels of EREG were associated with the enrichment of active histone marks (H3K4me3 and AcH3) and of a repressive mark (H3K27me2). Treatment with 5-aza-CdR dynamically increased the low occupancy of H3K4me3 and AcH3, while decreasing the high enrichment of H3K27me2, indicating that dynamic histone modifications contribute to EREG regulation in addition to DNA methylation. Finally, the combination of 5-aza-CdR and cetuximab exerted a synergistic anti-proliferative effect on gastric cancer cells. Taken together, the results of our study showed for the first time that EREG is epigenetically silenced in gastric cancer cells by aberrant DNA methylation and histone modification.

—This paper presents a dual modeling method that simulates the graphic and haptic behavior of a volumetric deformable object and conveys the behavior to a human operator. Although conventional modeling methods (a mass-spring model and a finite element method) are suitable for the real-time computation of an object’s deformation, it is not easy to compute the haptic behavior of a volumetric deformable object with the conventional modeling method in real-time (within a 1kHz) due to a computational burden. Previously, we proposed a fast volume haptic rendering method based on the S-chain model that can compute the deformation of a volumetric non-rigid object and its haptic feedback in real-time. When the S-chain model represents the object, the haptic feeling is realistic, whereas the graphical results of the deformed shape look linear. In order to improve the graphic and haptic behavior at the same time, we propose a dual modeling framework in which a volumetric haptic model and a surface graphical model coexist. In order to inspect the graphic and haptic behavior of objects represented by the proposed dual model, experiments are conducted with volumetric objects consisting of about 20,000 nodes at a haptic update rate of 1000Hz and a graphic update rate of 30Hz. We also conduct human factor studies to show that the haptic and graphic behavior from our model is realistic. Our experiments verify that our model provides a realistic haptic and graphic feeling to users in real-time.

To monitor and predict the change of coastal environment according to the construction of Saemangeum sea dyke and the development of land reclamation, we 2011년 10월 7일 접수 Received on October 7, 2011 / 2011년 11월 11일 수정 Revised on November 11, 2011 / 2011년 12월 5일 심사완료 Accepted on December 5, 2011 1 한국해양연구원 기후연안재해연구부 Climate Change & Coastal Disaster Research Department, Korea Ocean R&D 2 한국해양연구원 해양환경방제연구부 Marine Environments & Conservation Research Department, Korea Ocean R&D 3 한국과학기술원 전산학과 Department of Computer Science, KAIST ※ 연락저자 E-mail : jakim@kordi.re.kr 지리정보시스템을 이용한 새만금 해양환경정보시스템 구축/김진아.김창식.박진아 129 have done real-time and periodic ocean observation and numerical simulation since 2002. Saemangeum coastal environmental data can be largely classified to marine meteorology, ocean physics and circulation, water quality, marine geology and marine ecosystem and each part of data has been generated continuously and accumulated over about 10 years. The collected coastal environmental data are huge amounts of heterogeneous dataset and have some characteristics of multi-dimension, multivariate and spatio-temporal distribution. Thus the implementation of information system possible to data collection, processing, management and service is necessary. In this study, through the implementation of Saemangeum coastal environmental information system using geographic information system, it enables the integral data collection and management and the data querying and analysis of enormous and high-complexity data through the design of intuitive and effective web user interface and scientific data visualization using statistical graphs and thematic cartography. Furthermore, through the quantitative analysis of trend changed over long-term by the geo-spatial analysis with geoprocessing, it's being used as a tool for provide a scientific basis for sustainable development and decision support in Saemangeum coast. Moreover, for the effective web-based information service, multi-level map cache, multi-layer architecture and geospatial database were implemented together.

One of the biggest challenges in the study of biological regulatory networks is the systematic organization and integration of complex interactions taking place within various biological pathways. Currently, the information of the biological pathways is dispersed in multiple databases in various formats. hiPathDB is an integrated pathway database that combines the curated human pathway data of NCI-Nature PID, Reactome, BioCarta and KEGG. In total, it includes 1661 pathways consisting of 8976 distinct physical entities. hiPathDB provides two different types of integration. The pathway-level integration, conceptually a simple collection of individual pathways, was achieved by devising an elaborate model that takes distinct features of four databases into account and subsequently reformatting all pathways in accordance with our model. The entity-level integration creates a single unified pathway that encompasses all pathways by merging common components. Even though the detailed molecular-level information such as complex formation or post-translational modifications tends to be lost, such integration makes it possible to investigate signaling network over the entire pathways and allows identification of pathway cross-talks. Another strong merit of hiPathDB is the built-in pathway visualization module that supports explorative studies of complex networks in an interactive fashion. The layout algorithm is optimized for virtually automatic visualization of the pathways. hiPathDB is available at http://hiPathDB.kobic.re.kr.

P-cadherin is frequently up-regulated in solid tumors such as gastric, colon, lung, pancreatic and breast cancers. Although P-cadherin promotes cadherin-mediated cell adhesion, the gastric cancer-linked regulation of P-cadherin has not been extensively investigated. In this study, we found epigenetic regulation of P-cadherin in human gastric cancer cells that was induced by treatment with DNA demethylating drug and histone deacetylase inhibitor. Silencing P-cadherin by using siRNA induces apoptosis in gastric cells and blocks expression of Tie-2, an angiogenic receptor tyrosine kinase. In contrast, ectopically expressed P-cadherin by generating P-cadherin stable cell line enhances Tie-2 expression and cell mobility. We also demonstrated that inhibition of P-cadherin by PF-03732010, a fully humanized anti-P-cadherin IgG1 monoclonal antibody, suppressed cell migration in vitro and tumor growth in BALB/c nude mice bearing SNU620 gastric cancer xenograft. The data reported here are the first to reveal that the inhibition of P-cadherin decreases tumor cell migration and blocks a tumorigenesis by down-regulation of Tie-2 in gastric cancer. This demonstrates the potential for P-cadherin to be used as a target for treatment of gastric cancer.

Fuzzy set refers to the data set which does not have separate, distinct clusters, and they contain data elements whose membership degrees are between 0.0 and 1.0. Many fuzzy sets exist in the real world, and one of the important issues is to make a decision from the fuzzy sets using visual analytics tools by extracting information in the data set intuitively. To analyze the element data in fuzzy sets, the visualization of fuzzy sets needs to show an overview of the data with membership degree and the relationship among the sets. In this article, we suggest an interactive visualization technique of fuzzy set operations, called Disk Diagram, which offers distribution of fuzzy data and two scenarios to allow users to interpret inter-dependency among fuzzy sets. A Disk Diagram enables to depict complexity of fuzzy sets by showing the degree of resemblance between the sets with the layout of star coordinates. This article describes the use of a Disk Diagram with two different data sets such as fuzzy disease set and terror related words set. Lastly, we report the results of heuristic evaluation to show that our technique supports visual perception, usability, and knowledge discovery process in the areas of visual representation and interaction.

For virtual education, the multimodal learning environment with haptic feedback, termed `immersive textbook`, is necessary to enhance the learning effectiveness. However, the learning contents for immersive textbook are not widely available due to the constraints in creation and playback environments. To address this problem, we propose a framework for producing and displaying the multimodal contents for immersive textbook. Our framework provides an XML-based meta-language to produce the multimodal learning contents in the form of intuitive script. Thus it can help the user, without any prior knowledge of multimodal interactions, produce his or her own learning contents. The contents are then interpreted by script engine and delivered to the user by visual and haptic rendering loops. Also we implemented a prototype based on the aforementioned proposals and performed user evaluation to verify the validity of our framework.

Histone deacetylase (HDAC)10, a novel class IIb histone deacetylase, is the most similar to HDAC6, since both contain a unique second catalytic domain. Unlike HDAC6, which is located in the cytoplasm, HDAC10 resides in both the nucleus and cytoplasm. The transcriptional targets of HDAC10 that are associated with HDAC10 gene regulation have not been identified. In the present study, we found that knockdown of HDAC10 significantly increased the mRNA expression levels of thioredoxin-interacting protein (TXNIP) in SNU-620 human gastric cancer cells; whereas inhibition of HDAC1, HDAC2, and HDAC6 did not affect TXNIP expression. TXNIP is the endogenous inhibitor of thioredoxin (TRX), which acts as a cellular antioxidant. Real-time PCR and immunoblot analysis confirmed that inhibition of HDAC10 induced TXNIP expression. Compared to class I only HDAC inhibitors, inhibitors targeting both class I and II upregulated TXNIP, indicating that TXNIP is regulated by class II HDACs such as HDAC10. We further verified that inhibition of HDAC10 induced release of cytochrome c and activated apoptotic signaling molecules through accumulation of reactive oxygen species (ROS). Taken together, our results demonstrate that HDAC10 is involved in transcriptional downregulation of TXNIP, leading to altered ROS signaling in human gastric cancer cells. How TXNIP is preferentially regulated by HDAC10 needs further investigation.

Background Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. Methods We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. Results In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. Conclusions These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes in various cancers.

Tourism is a critical, cross-cultural social behavior in contemporary society and provides diverse experiences based on different regional resources in destinations. This research identified the attributes associated with Korean golf tourists’ images of seven destination regions in Mainland China. A content analysis of 328 golf tourists’ blogs indicated that each region had different combinations of destination attributes, but these were partially hidden in vivid descriptions of playing experiences. The narratives were coded with 15 golf destination attributes with 136 headwords and they reflected both place-centred images and interactions through perceptual experiences with different social groups. The golfers greatly appreciated congestion control at courses and social interaction during their tours, including the services of local human resources and play partners. The seven Chinese golf destinations had different perceived characteristics and relationships with South Korean society. Thus, they had dissimilar destination images for Korean golf tourists. Historical ties and geographical proximity played important roles, including, for example, the significant presence of ethnic Koreans in northeast China.

DNA methyltransferase 3B has been demonstrated to mediate gene silencing. The mechanisms how DNA methyltransferase 3B is targeted to specific regions and represses gene transcription, however, are not well understood. Here we show that by using yeast two-hybrid screening, DNA methyltransferase 3B interacts with the human polycomb protein, hPc2. This interaction was verified via co-immunoprecipitation and GST pull-down assay. Sequential deletion analysis showed that the region of DNA methyltransferase 3B responsible for interaction is mapped to the N-terminal regulatory domain. By performing a cDNA microarray analysis in HCT 116 cells, we identified that the expression of fibroblast growth factor receptor 3 is significantly increased upon the small interference RNA-mediated knockdown of hPc2, suggesting fibroblast growth factor receptor 3 as a potential target of hPc2. We further found that DNA methyltransferase 3B enhances hPc2-mediated transcriptional repression of fibroblast growth factor receptor 3, which does not require its de novo methyltransferase activity. Taken together, these results suggest that DNA methyltransferase 3B functions as a co-repressor of polycomb protein in inducing transcriptional repression independent of DNA methylation.

DNA methyltransferases (DNMT) 3B is a de novo DNMT that represses transcription independent of DNMT activity. In order to gain a better insight into DNMT3B-mediated transcriptional repression, we performed a yeast two-hybrid analysis using DNMT3B as a bait. Of the various binding candidates, ZHX1, a member of zinc-finger and homeobox protein, was found to interact with DNMT3B in vivo and in vitro. N-terminal PWWP domain of DNMT3B was required for its interaction with homeobox motifs of ZHX1. ZHX1 contains nuclear localization signal at C-terminal homeobox motif, and both ZHX1 and DNMT3B were co-localized in nucleus. Furthermore, we found that ZHX1 enhanced the transcriptional repression mediated by DNMT3B when DNMT3B is directly targeted to DNA. These results showed for the first the direct linkage between DNMT and zinc-fingers homeoboxes protein, leading to enhanced gene silencing by DNMT3B.

Although people usually contact a surface with some area rather than a point, most haptic devices allow a user to interact with a virtual object at one point at a time and likewise most haptic rendering algorithms deal with such situations only. In a palpation procedure, medical doctors push and rub the organ's surface, and are provided the sensation of distributed pressure and contact force (reflecting force) for discerning doubtable areas of the organ. In this paper, we suggest real-time area-based haptic rendering to describe distributed pressure and contact force simultaneously, and present a haptic interface system to generate surface properties in accordance with the haptic rendering algorithm. We represent the haptic model using the shape-retaining chain link (S-chain) framework for a fast and stable computation of the contact force and distributed pressure from a volumetric virtual object. In addition, we developed a compact pin-array-type tactile display unit and attached it to the PHANToMTM hapt...

Accurately recovering the hippocampal shapes against rough and noisy segmentations is as challenging as achieving good anatomical correspondence between the individual shapes. To address these issues, we propose a mesh-to-volume registration approach, characterized by a progressive model deformation. Our model implements flexible weighting scheme for model rigidity under a multi-level neighborhood for vertex connectivity. This method induces a large-to-small scale deformation of a template surface to build the pairwise correspondence by minimizing geometric distortion while robustly restoring the individuals' shape characteristics. We evaluated the proposed method's (1) accuracy and robustness in smooth surface reconstruction, (2) sensitivity in detecting significant shape differences between healthy control and disease groups (mild cognitive impairment and Alzheimer's disease), (3) robustness in constructing the anatomical correspondence between individual shape models, and (4) applicability in identifying subtle shape changes in relation to cognitive abilities in a healthy population. We compared the performance of the proposed method with other well-known methods--SPHARM-PDM, ShapeWorks and LDDMM volume registration with template injection--using various metrics of shape similarity, surface roughness, volume, and shape deformity. The experimental results showed that the proposed method generated smooth surfaces with less volume differences and better shape similarity to input volumes than others. The statistical analyses with clinical variables also showed that it was sensitive in detecting subtle shape changes of hippocampus.

This paper presents a new model which computes the deformation and the feedback force of high-resolution biomedical volumetric objects consisting of hundreds of thousands of volume elements. The main difficulty in the simulation of these high-resolution volumetric objects is to compute and generate stable feedback force from the objects within a haptic update time (1 msec). In our model, springs are used in order to represent material properties of volume elements and cylinders are used to activate corresponding springs according to the amount of deformation. Unlike in a mass-spring model, springs in our model have constraint conditions. In our model, the deformation is calculated locally and then is propagated outward through object's volume as if a chain is pulled or pushed. The deformed configuration is then used to compute the object's internal potential energy that is reflected to the user. The simple nature of our model allows the much faster calculation of the deformation and the feedback force from the volumetric deformable object than the conventional model (an FEM or a mass-spring model). Experiments are conducted with homogenous and non-homogenous volumetric cubic objects and a volumetric human liver model obtained from CT data at a haptic update rate of 1000 Hz and a graphic update rate of 100 Hz to show that our model can be utilized in the real-time volume haptic rendering. We verify that our model provides a realistic haptic feeling for the user in real time through comparative study.

A collaborative virtual environment (CVE) is a shared environment that allows geographically separated users to watch and manipulate the same object at the same time. This paper presents a fast haptic rendering method when users interact with a virtual object at multiple points or multiple areas in a CVE. Previously, we proposed a new model (Shape-retaining Chain Linked Model) for real-time volume haptic rendering. The haptic rendering of an object represented by our model guarantees real-time performance because the deformation of the object is computed locally and is then propagated outward through its volume. However, this local computation approach presented us with a new issue for handling virtual deformable objects in a CVE, where interactions occur at multiple points or multiple areas. In order to overcome the limitation of the local computation, we construct a modeling framework that allows colliding interactions among geographically separated users. For the modeling framework, we vectorially sum ...

An abundant amount of information is produced in the digital domain, and an effective information extraction (IE) system is required to surf through this sea of information. In this paper, we show that an interactive visualization system works effectively to complement an IE system. In particular, three-dimensional (3D) visualization can turn a data-centric system into a user-centric one by facilitating the human visual system as a powerful pattern recognizer to become a part of the IE cycle. Because information as data is multidimensional in nature, 2D visualization has been the preferred mode. However, we argue that the extra dimension available for us in a 3D mode provides a valuable space where we can pack an orthogonal aspect of the available information. As for candidates of this orthogonal information, we have considered the following two aspects: 1) abstraction of the unstructured source data, and 2) the history line of the discovery process. We have applied our proposal to text data mining in bioinformatics. Through case studies of data mining for molecular interaction in the yeast and mitogen-activated protein kinase pathways, we demonstrate the possibility of interpreting the extracted results with a 3D visualization system.

Chromosomal rearrangements that facilitate tumor formation and progression through activation of oncogenic tyrosine kinase are frequently observed in cancer. The ETV6-NTRK3 (EN) fusion has been implicated in various cancers, including infantile fibrosarcoma, secretory breast carcinoma and acute myeloblastic leukemia, and has exhibited in vivo and in vitro transforming ability. In the present study, we analyzed transcriptome alterations using RNA-Seq in EN-transduced NIH3T3 fibroblasts to identify the mechanisms that are involved in EN-mediated tumorigenesis. Through functional profile assessment of EN-regulated transcriptome alterations, we found that EN up-regulated genes mainly associated with cell motion, membrane invagination, and cell proliferation, while down-regulated genes are involved in cell adhesion, which described the transforming potential and increased proliferation in EN-transduced cells. Notably, KEGG pathway analysis identified the JAK-STAT signaling pathway with the highest statistical significance. Moreover, Ingenuity Pathway Analysis and gene regulatory network analysis identified the Stat1 transcription factor and its target genes as top EN-regulated molecules. We further demonstrated that EN enhanced STAT1 phosphorylation but attenuated STAT1 acetylation, thereby inhibiting the interaction between NF-κB p65 and acetylated STAT1. Consequently, nuclear translocation of NF-κB p65 and subsequent anti-apoptotic NF-κB activity were increased by EN. Taken together, here we report, for the first time, STAT1 as a significantly EN-regulated transcription factor and a crucial mediator of EN-induced tumorigenesis. [This work was supported by a National Research Foundation grant of Korea (NRF-2014M3A9B5073918) funded by the Korea government.] Citation Format: Jinah Park, Junil Kim, Poul H. Sorensen, Seong-Jin Kim. Novel identification of STAT1 as a crucial mediator of ETV6-NTRK3-induced tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 536. doi:10.1158/1538-7445.AM2017-536

In this paper, we present a haptic plug-in system that operates on already-developed existing interactive 3D graphics applications. There are various high-quality graphics applications developed without taking into consideration the haptic features. Our system augments haptic interaction in a simple manner to enhance the experience. The proposed system consists of two separate modules. While one module captures the depth map from a graphics pipeline of the target application, the other module calculates the haptic feedback force based on the captured depth map. We address efficient and effective ways of capturing and transferring depth map data for haptic rendering and present a working solution.

Background The shape morphology using 3D surface models has been recently emerged for biomechanics research, such as the quantitative assessment of bone deformity with clinical factors [1] and the correlation analysis between bone shape and joint motion [2]. In the bone shape morphology, the morphological difference of the bones across subjects is quantified by the geometric measures, such as the curvature of the articular surface and the relative bone orientation in joints, defined with the anatomical landmarks and regions on the bone surface. However, the landmark and region determination on individual cases is a difficult and time-consuming task, because of the various size and shape of the bones and operator’s errors. In this paper, we propose an automated landmark and region mapping method based on a non-rigid template-toimage registration. The template model is a triangular mesh including the generic shape of the target. It also encodes the landmarks and regions as a subset of the points in the triangular mesh. For the landmark and region mapping to individual bones, the template model is nonrigidly deformed by a Laplacian deformation framework [3]. This framework derives the point transformation into the image boundary while minimizing the distortion of the point distribution in the template model. This behavior of the deformation framework helps to trace the positions of the anatomical landmarks and regions across subjects.

Morphological changes of the brain lateral ventricles are known to be a marker of brain atrophy. Anatomically, each lateral ventricle has three horns, which extend into the different parts (i.e. frontal, occipital and temporal lobes) of the brain; their deformations can be associated with morphological alterations of the surrounding structures and they are revealed as complex patterns of their shape variations across subjects. In this paper, we propose a novel approach for the ventricular morphometry using structural feature descriptors, defined on the 3D shape model of the lateral ventricles, to characterize its shape, namely width, length and bending of individual horns and relative orientations between horns. We also demonstrate the descriptive ability of our feature-based morphometry through statistical analyses on a clinical dataset from a study of aging.

Background Exposure to perinatal anxiety affects disease susceptibility in offspring but studies on the association between perinatal anxiety and gene polymorphisms are lacking. This study aimed to elucidate the interaction between perinatal anxiety and polymorphisms in antioxidant defense and innate immunity genes on the development of respiratory tract infections (RTIs) during early infancy. Methods Trait anxiety levels in 440 women were assessed by the State-Trait Anxiety Inventory during late gestation. The occurrence of RTIs, including bronchiolitis, during the first year of life was assessed by parent-reported doctor diagnosis. Polymorphisms in glutathione S-transferase P-1 (GSTP1, rs1695) and CD14 (rs2569190) were genotyped using the TaqMan assay. Copy number variations of GSTT1 were measured by real-time polymerase chain reaction. Results Exposure to high levels of perinatal anxiety increased the risk of bronchiolitis in the first year of life (adjusted odds ratio [aOR], 1.30; 95% confidence interval [CI]: 1.00–1.80), in particular among children with the AG + GG genotype of GSTP1 or the GSTT1 null genotype (aOR 3.36 and 2.79). In infants with the TC + CC genotype of CD14, high levels of perinatal anxiety were associated with an increased risk of upper RTI, lower RTI, and bronchiolitis (aOR 2.51, 4.60, and 4.31, respectively). Conclusions Perinatal maternal anxiety levels affect the occurrence of bronchiolitis in offspring. The effect of perinatal anxiety on the occurrence of bronchiolitis during infancy was influenced by genetic polymorphisms in antioxidant defense and innate immunity genes. Electronic supplementary material The online version of this article (doi:10.1186/1471-2466-14-154) contains supplementary material, which is available to authorized users.

In this letter, we present a new approximation for the two-dimensional (2-D) Gaussian Q-function. The result is represented by only the one-dimensional (1-D) Gaussian Q-function. Unlike the previous 1-D Gaussian-type approximation, the presented approximation can be applied to compute the 2-D Gaussian Q-function with large correlations. Keywords: Gaussian distribution, probability, Q-function.

Clinical utility of computational models is crucial in the applications of medical data visualization. Previously we have developed a new class of volumetric models whose parameters are functions in conjunction with physically based deformable modeling framework, and have applied the technique to estimate the left ventricular (LV) wall motion. We have successfully showed that the model parameter functions characterize the LV motion of normal and abnormal states and that no further non-trivial post-processing is required for anatomically meaningful interpretation. In an effort to evaluate the LV model, this paper presents a method and results from a strain analysis based on the nodal displacements of the deformable LV model. Furthermore, in order to visualize the local quantities on the volumetric model for an effective analysis, we also developed a methodology to assist in assessing the cardiac function utilizing principal strains, Von-Mises’ yield criteria, and a smoothing filter. Each strain tensor component was in the range of values observed in other reported studies. The application of a smoothing filter on the model improved in visualizing the overall trend of each strain variation. With our platform for a comprehensive strain analysis, we have augmented a clinical utility to the deformable models with parameter functions.

In this letter, we derive an analytical expression for computing the symbol error probability (SEP) of the M-ary quadrature amplitude modulation (M-QAM) in the joint presence of phase/quadrature error and VQ gain imbalance over an additive white Gaussian noise (AWGN) channel. The derived expression containing only the two-dimensional Gaussian Q-function can be used to compute the SEP of M-QAM in various fading channels by making use of the moment-generating function (MGF) approach.

Two rotational transformations are used to derive a new expression for the symbol error probability (SEP) of an M-ary phase shift keying (MPSK) with an I-Q unbalance over additive white Gaussian noise (AWGN) and Rician fading channels. We used the new expression to investigate the effect of the I-Q unbalance on the MPSK SEP performance. Our investigation confirms that this approach is a convenient way to evaluate the average SEP of an MPSK for various cases of the Riciaa factor.

OBJECTIVES This paper proposes a measurement method to quantify the abnormal characteristics of the broken parts of ribs using local texture and shape features in chest radiographs. METHODS OUR MEASUREMENT METHOD COMPRISES TWO STEPS: a measurement area assignment and sampling step using a spline curve and sampling lines orthogonal to the spline curve, and a fracture-ness measurement step with three measures, asymmetry and gray-level co-occurrence matrix based measures (contrast and homogeneity). They were designed to quantify the regional shape and texture features of ribs along the centerline. The discriminating ability of our method was evaluated through region of interest (ROI) analysis and rib fracture classification test using support vector machine. RESULTS The statistically significant difference was found between the measured values from fracture and normal ROIs; asymmetry (p < 0.0001), contrast (p < 0.001), and homogeneity (p = 0.022). The rib fracture classifier, trained with the measured values in ROI analysis, detected every rib fracture from chest radiographs used for ROI analysis, but it also classified some unbroken parts of ribs as abnormal parts (8 to 17 line sets; length of each line set, 2.998 ± 2.652 mm; length of centerlines, 131.067 ± 29.460 mm). CONCLUSIONS Our measurement method, which includes a flexible measurement technique for the curved shape of ribs and the proposed shape and texture measures, could discriminate the suspicious regions of ribs for possible rib fractures in chest radiographs.

The authors present a new method for analyzing the motion of the heart's left ventricle (LV) from tagged magnetic resonance imaging (MRI) data. Their technique is based on the development of a new class of physics-based deformable models whose parameters are functions. They allow the definition of new parameterized primitives and parameterized deformations which can capture the local shape variation of a complex object. Furthermore, these parameters are intuitive and require no complex post-processing in order to be used by a physician. Using a physics-based approach, the authors convert the geometric models into dynamic models that deform due to forces exerted from the datapoints and conform to the given dataset. The authors present experiments involving the extraction of the shape and motion of the LV's mid-wall during systole from tagged MRI data based on a few parameter functions. Furthermore, by plotting the variations over time of the extracted LV model parameters from normal and abnormal heart data along the long axis, the authors are able to quantitatively characterize their differences.

We present a new approach for the analysis of the left ventricular shape and motion based on the development of a new class of volumetric deformable models. We estimate the deformation and complex motion of the left ventricle (LV) in terms of a few parameters that are functions and whose values vary locally across the LV. These parameters capture the radial and longitudinal contraction, the axial twisting, and the long-axis deformation. Using Lagrangian dynamics and finite-element theory, we convert these volumetric primitives into dynamic models that deform due to forces exerted by the datapoints. We present experiments where we used magnetic tagging (MRI-SPAMM) to acquire datapoints from the LV during systole. By applying our method to MRI-SPAMM datapoints, we were able to characterize the 3-D shape and motion of the LV both locally and globally, in a clinically useful way. In addition, based on the model parameters we were able to extract quantitative differences between normal and abnormal hearts and visualize them in a way that is useful to physicians.

Virtual hand is one of the most intuitive metaphors for object selection in the virtual environment because of its natural mapping between the user action input and the cursor. However, it has a limitation of lengthy cursor manipulation for object selection task which is directly related to the level of workload of the user in performing object selection. In this paper, we propose 'Select Ahead' as a new object selection technique that improves efficiency by reducing the physical workload. Select Ahead guides the user to select the distant object along the estimated tendency of the recent cursor movements. We evaluate the relative performance of Select Ahead through the experiments in the 3D virtual environment with various object densities. The results show that Select Ahead significantly reduces the length of the cursor movements compared to those of the 3D point cursor and the 3D bubble cursor regardless of the object density. In the aspect of the total duration time for selection, Select Ahead outperforms the 3D point cursor and has no significant difference compared to that of the 3D bubble cursor.

The p53 and NF-kappa B pathways play important roles in diverse cellular functions, including cell growth, apoptosis, and tumorigenesis. Mutations that inactivate the p53 gene and constitutive NF-kappa B pathway activation are common occurrences in human cancers. Although many drugs are being developed that selectively activate p53 or inhibit NF-kappa B, there are few drug candidates that can do both. Simultaneous activation of p53 and inhibition of the NF-kappa B pathway is therefore a prime target for new cancer drug development. This study is the first report of a high-throughput approach with mass compounds that concurrently target both pathways. Using a cell-based screening assay and a library of 200,000 synthetic compounds, we identified 9 small molecules that simultaneously inhibit NF-kappa B and activate p53. One of these compounds, N-2, increased the expression of p53 target genes, including p21 and GADD45a. In addition, N-2 inhibited the transcriptional activity of NF-kappa B, concomitantly repressing interleukin-6 and monocyte chemotactic protein-1 (MCP-1) expression. When cell lines derived from a diverse range of cancers were treated in vitro with N-2, we observed increased cell death. N-2 also significantly inhibited allograft growth in murine models of melanoma and lung carcinoma. Our findings suggest that N-2 may act as a bivalent anti-cancer agent through simultaneous modulation of NF-kappa B and p53 activities.

This paper presents a haptic-based dental simulator for training of two prevalent interventions: tooth restoration and ultrasonic scaling. The voxel-based collision model is applied to deal with various interactions between the sharp instrument and the tooth. In addition, the spray effect based on a particle system and the adhesion attenuation model for a calculus simulation are introduced. Our training program provides the removal ratio of tooth, caries, and cavity, and also the excessive removal ratio of a tooth for the skills assessment. To develop both manual dexterity and surgical judgment, the haptic training program is associated with 3D animation and put into a scenario of procedural steps of each intervention.

The mixture of poly(lactide-co-glycolide) (PLGA) and poly(ethylene vinyl acetate) (PEVA) forms a homogeneous liquid in an organic solvent such as tetrahydrofuran, and a phase-separated PLGA/PEVA composite can be prepared from it by evaporating the organic solvent. Exploiting this phenomenon, we designed a novel method of preparing a drug-loaded PLGA/PEVA composite and used it for coating drug-eluting stents (DESs). Paclitaxel (PTX), an anticancer drug, was chosen as a model drug. PLGA acts as a microdepot for PTX, and PEVA provides mechanical strength to the coating material. The presence of PLGA in the PLGA/PEVA composite suppressed PTX crystallization in the coating material, and PTX showed a sustained release rate over more than 30 days. The mechanical strength of the PLGA/PEVA composite was better than that of PEVA used as a control. After coating the stent with a PLGA/PEVA composite using ultrasonic atomizing spray, the morphology of the coated material was observed by scanning electron microscopy, and the release pattern of PTX was measured by high-performance liquid chromatography.

Aberrations of Phosphoinositide 3-kinase (PI3K)/AKT signaling are frequently observed in many types of cancer, promoting its emergence as a promising target for cancer treatment. PI3K can become activated by various pathways, one of which includes RAS. RAS can not only directly activate the PI3K/AKT pathway via binding to p110 of PI3K, but also regulates mTOR via ERK or RSK independently of the PI3K/AKT pathway. Thus, actively mutated RAS can constitutively activate PI3K signaling. Additionally, in RAS tumorigenic transformation, signal transducer and activator of transcription 3 (STAT3) has been known also to be required. In this study, we examined the efficacy of NVP-BKM120, a pan-class I PI3K inhibitor in human gastric cancer cells and hypothesized that the combined inhibition of PI3K and STAT3 would be synergistic in KRAS mutant gastric cancer cells. NVP-BKM120 demonstrated anti-proliferative activity in 11 human gastric cancer cell lines by decreasing mTOR downstream signaling. But NVP-BKM120 treatment increased p-AKT by subsequent abrogation of feedback inhibition by stabilizing insulin receptor substrate-1. In KRAS mutant gastric cancer cells, either p-ERK or p-STAT3 was also increased upon treatment of NVP-BKM120. The synergistic efficacy study demonstrated that dual PI3K and STAT3 blockade showed a synergism in cells harboring mutated KRAS by inducing apoptosis. The synergistic effect was not seen in KRAS wild-type cells. Together, these findings suggest for the first time that the dual inhibition of PI3K and STAT3 signaling may be an effective therapeutic strategy for KRAS mutant gastric cancer patients.

Background Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult. Methods We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm. Results We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (MDM2, DYRK2, and LYZ) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue. Conclusions Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.