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This study aims to provide the initial validity of the Autism Diagnostic Observation Schedule-2 (ADOS-2) Toddler Module and Module 1-2 for South Korean toddlers and preschoolers. Based on 143 children, the ASD group (n = 68) showed significantly higher ADOS-2 item and algorithm total scores as well as social affect and repetitive and restricted behaviors domain scores compared with children with nonspectrum (NS; n = 42) disorders and typically developing (TD; n = 33) children. Using lower algorithm cutoffs, sensitivities were excellent for the ASD versus NS/TD comparisons, ranging from 94% to 100% across different Modules. Specificities varied more, ranging from 82% to 100%. Internal consistency was strong with high item-total correlations (r of 0.6-0.9) and Cronbach's Alphas (all above 0.7). Results demonstrated promising, initial evidence for the validity of the ADOS-2 for South Korean toddlers and preschoolers from 1 to 4 years of age. The ADOS-2 could be implemented, with minimal adaptations, in research and clinical settings in South Korea. This study is one of the first steps toward validating the ADOS-2 in other Eastern countries that are in great need for a valid instrument for the detection of ASD. Autism Res 2019, 12: 1356-1366. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Results of this study demonstrated promising, initial evidence for the validity of a gold standard measure for the diagnosis of autism, the Autism Diagnostic Observation Schedule-2 (ADOS-2), for South Korean toddlers and preschoolers. The ADOS-2 could be implemented, with minimal adaptations, in research and clinical settings in South Korea. This study is one of the first steps toward validating the ADOS-2 in other Eastern countries that are in great need of a valid instrument for the detection of ASD.

Navigating a large 3D virtual environment using a generic haptic device can be challenging since the haptic device is usually bounded by its own physical workspace. On the other hand, mouse interaction easily handles the situation with a clutching mechanism—simply lifting the mouse and repositioning its location in the physical space. Since the haptic device is used for both input and output at the same time, in many cases, its freedom needs to be limited in order to accommodate such a situation. In this paper, we propose a new mechanism called Z-Clutching for 3D navigation of a virtual environment by using only the haptic device without any interruption or sacrifice in the given degrees of freedom of the device’s handle. We define the clutching state which is set by pulling the haptic handle back into space. It acts similarly to lifting the mouse off the desk. In this way, the user naturally feels the haptic feedback based on the depth (z-direction), while manipulating the haptic device and moving the view as desired. We conducted a user study to evaluate the proposed interaction technique, and the results are promising in terms of the usefulness of the proposed mechanism.

Highlights • Present a model-based approach to investigate the morphology of the third ventricle. • Assess the regional deformations in relation to the atrophy of surrounding structures. • Use a symmetric template model with the midplane definition for unbiased analysis. • Achieve a robust surface modeling using a progressive surface deformation. • Validate the method on a healthy aging sample with different clinical variables., Background Structural changes of the brain's third ventricle have been acknowledged as an indicative measure of the brain atrophy progression in neurodegenerative and endocrinal diseases. To investigate the ventricular enlargement in relation to the atrophy of the surrounding structures, shape analysis is a promising approach. However, there are hurdles in modeling the third ventricle shape. First, it has topological variations across individuals due to the inter-thalamic adhesion. In addition, as an interhemispheric structure, it needs to be aligned to the midsagittal plane to assess its asymmetric and regional deformation. Method To address these issues, we propose a model-based shape assessment. Our template model of the third ventricle consists of a midplane and a symmetric mesh of generic shape. By mapping the template's midplane to the individuals’ brain midsagittal plane, we align the symmetric mesh on the midline of the brain before quantifying the third ventricle shape. To build the vertex-wise correspondence between the individual third ventricle and the template mesh, we employ a minimal-distortion surface deformation framework. In addition, to account for topological variations, we implement geometric constraints guiding the template mesh to have zero width where the inter-thalamic adhesion passes through, preventing vertices crossing between left and right walls of the third ventricle. The individual shapes are compared using a vertex-wise deformity from the symmetric template. Results Experiments on imaging and demographic data from a study of aging showed that our model was sensitive in assessing morphological differences between individuals in relation to brain volume (i.e. proxy for general brain atrophy), gender and the fluid intelligence at age 72. It also revealed that the proposed method can detect the regional and asymmetrical deformation unlike the conventional measures: volume (median 1.95 ml, IQR 0.96 ml) and width of the third ventricle. Similarity measures between binary masks and the shape model showed that the latter reconstructed shape details with high accuracy (Dice coefficient ≥0.9, mean distance 0.5 mm and Hausdorff distance 2.7 mm). Conclusions We have demonstrated that our approach is suitable to morphometrical analyses of the third ventricle, providing high accuracy and inter-subject consistency in the shape quantification. This shape modeling method with geometric constraints based on anatomical landmarks could be extended to other brain structures which require a consistent measurement basis in the morphometry.

The proliferation of accommodation-sharing platforms has changed the ways in which people travel and experience tourist attractions. However, the impact of accommodation sharing on attractions remains under-researched. To fill this gap in the research, we use a mixed methods approach to examine the spillover effect in two key tourism service suppliers. Using difference-in-differences estimations with two-way fixed effects, we find a 15.4% increase in an attraction's online popularity after the entry of accommodation sharing. This positive spillover effect is reduced when the density of commercially operated properties is higher. The qualitative findings speak to the mechanism behind the estimated spillover effect, which involves three dimensions of variation in accommodation sharing and the salient use of mobile technology in modern travel.

This study aimed to analyze the risk factors for secondary new vertebral compression fractures (SNVCFs) after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures.We evaluated the association of SNVCFs (adjacent vertebral compression fractures [AVCFs] and remote vertebral compression fractures) with clinical, radiographic, and PVP procedure-related morphologic parameters based on the data collected from 402 patients over a minimum follow-up of 4 years after PVP. Procedure-related morphologic parameters were assessed using a three-dimensional voxel-based analysis. Univariate and multivariate regression analyses were conducted.On univariate analysis, bone mineral density (BMD), preoperative compression ratio, preoperative sagittal index (SI), and intradiscal bone cement leakage were significantly associated with SNVCF and AVCF (P0.05), whereas only BMD and preoperative SI were significantly associated with remote vertebral compression fracture (P0.05). A large ratio of bone cement volume to vertebral body volume and skewed bone cement distribution along the inferior-to-superior axis were especially significant risk factors for AVCF (P = 0.027 and P = 0.029, respectively). On multivariate analysis, BMD was significantly associated with SNVCF (P = 0.041), whereas upper adjacent intradiscal bone cement leakage was significantly associated with AVCF (P = 0.003).Low BMD, high preoperative compression ratio, and high preoperative SI may be predictive factors for SNVCFs. In particular, to prevent AVCF, the injected bone cement should be distributed both evenly and symmetrically along the inferior-to-superior axis and the relative bone cement volume should not be excessive. Bone cement should be injected carefully to avoid upper adjacent intradiscal leakage. Prompt BMD correction is important to prevent SNVCF.

Haptic feedback takes on an important role in providing spatial cues, which are difficult to convey solely by sight, as well as in increasing the immersion of contents. However, although a number of techniques and applications for haptic media have been proposed in this regard, live streaming of touchable video has yet to be actively deployed due to computational complexity and equipment limitations. In order to mitigate these issues, we introduce an approach to render haptic feedback directly from RGB-D video streams without surface reconstruction, and also describe how to superimpose virtual objects or haptic effects onto real-world scenes. Furthermore, we discuss possible improvements in software and appropriate device setups to extend the proposed system to support a practical solution for multi-sensory and multi-point interaction in streaming touchable media.

This study examined research focus countries and regions in 4,654 articles published in 32 tourism, hospitality, and leisure academic journals from 2002 to 2011 inclusive. Applying a variety of analysis methods, the research showed the spatial distribution, co-occurrence relationships among countries, and the most popular topics of research focus and types of tourism by countries. There was a broad geographic focus of the research in tourism, hospitality, and leisure journals in the decade from 2002 to 2011 spanning 126 countries. It was found that a significant number (70) of countries were not covered in this 10-year snapshot of the academic journal research and require more attention from scholars in the future. Some major countries were underrepresented including France, Germany, and Russia. However, the predominance of the research focus on the Asia-Pacific region and particularly on China was a major finding in this analysis, as was the sparse coverage of South and Central America.

Optical diffraction tomography (ODT) constitutes a novel approach for acquiring cell images since it is capable of capturing morphology of a living cell without chemical treatment. ODT is an interferometric technique that measures the 3D refractive index (RI) distribution of optically transparent samples such as biological cells. Unlike other cell imaging modalities, naive ODT data do not contain encoded information about the cellular properties such as labeled protein in fluorescent microscopic data or the fixed border of a cell wall in scanning electron microscopic data. Therefore, specifying the region of interest in the raw image is an important and challenging task for a quantitative analysis of ODT cell data. We propose an interactive interface for reconstructing 3D shape of cells from ODT image data based on intervening visualization results of the cell data to guide the investigator observing the overall blueprint of cell morphology. The cell organelles are segmented based on the lookup table referring corresponding transfer function items adopted from volume rendering technique. The final shape of the cell is then constructed as mesh models from the segmentation results for further quantitative analyses. In this paper, we also demonstrate the various modeling options accounting characteristics of target cell.

This analysis produced a tourism system research categorization framework comprising mutually exclusive subject areas to classify the keywords in academic journal articles. The primary research goals were to develop this framework and then assess the frequency levels of specific tourism research subject areas in the 10-year period of 2002–2011. A database of 37,918 author-selected keywords from 9,588 research articles in 31 tourism, hospitality, and leisure journals was created. Using the proposed framework, the database was divided into six main categories (destination; demand; travel; marketing; geographical areas; and generic terms) and 61 sub-categories. The destination category captured the most keywords, followed by demand and then marketing.

Gene amplification is a hallmark of cancer with chromosomal instability although the underlying mechanism by which altered copy numbers are maintained is largely unclear. Cohesin, involved in sister chromatid cohesion, DNA repair, cell cycle progression and transcriptional regulation of key developmental genes, is frequently overexpressed in human cancer. Here we show that cohesin-dependent change in DNA replication controls the copy numbers of amplified genes in cancer cells with chromosomal instability. We found that the down-regulation of elevated cohesin leads to copy number-associated gene expression changes without disturbing chromosomal segregation. Highly amplified genes form typical long-range chromatin interactions, which are stabilized by enriched cohesin. The spatial proximities among cohesin binding sites within amplified genes are decreased by RAD21-knockdown, resulting in the rapid decline of amplified gene expression. After several passages, cohesin depletion inhibits DNA replication initiation by reducing the recruitment of pre-replication complexes such as minichromosome maintenance subunits 7 (MCM7), DNA polymerase alpha, and CDC45 at replication origins near the amplified regions, and as a result, decreases the DNA copy numbers of highly amplified genes. Collectively, our data demonstrate that cohesin-mediated chromatin organization and DNA replication are important for stabilizing gene amplification in cancer cells with chromosomal instability.

Recent advances in genome and transcriptome analysis have contributed to the identification of many potential cancer-related genes. Furthermore, biological and clinical investigations of the candidate genes provide us with a better understanding of carcinogenesis and development of cancer treatment. Here, we report a novel role of KIAA1324 as a tumor suppressor in gastric cancer. We observed that KIAA1324 was downregulated in most gastric cancers from transcriptome sequencing data and found that histone deacetylase was involved in the suppression of KIAA1324. Low KIAA1324 levels were associated with poor prognosis in gastric cancer patients. In the xenograft model, KIAA1324 significantly reduced tumor formation of gastric cancer cells and decreased development of preformed tumors. KIAA1324 also suppressed proliferation, invasion, and drug resistance and induced apoptosis in gastric cancer cells. Through protein interaction analysis, we identified GRP78 (glucose-regulated protein 78 kDa) as a KIAA1324-binding partner. KIAA1324 blocked oncogenic activities of GRP78 by inhibiting GRP78–caspase-7 interaction and suppressing GRP78-mediated AKT activation, thereby inducing apoptosis. In conclusion, our study reveals a tumor suppressive role of KIAA1324 via inhibition of GRP78 oncoprotein activities and provides new insight into the diagnosis and treatment of gastric cancer. Cancer Res; 75(15); 3087–97. ©2015 AACR.

Seas and swells are basic wave types in ocean surface simulation and are very important elements in the simulation of ocean background. In this paper, we propose a real-time simulation method, for reproducing realistic seas and swells, to be used in real-time simulators such as ship maneuvering simulators. Seas and swells have different visual properties. Swells have relatively longer wavelengths and round crests compared with seas, therefore they are visualized globally with large meshes and procedural methods. Parameters to illustrate swells are extracted from ocean wave spectra. Conversely, seas have shorter wavelengths and their characteristics are only clearly apparent near to the observation point. Here, we present visualization of seas based on a statistical wave model using ocean wave spectra, which provides realistic results in a reactively small area.

To improve the ocean waves of the ship maneuvering simulator, we study and summarize the visualization elements of the ocean waves and the overall direction of their implementation in detail. We categorize the visualization elements of the ocean waves into five groups, including wave surface, wave breaking, interaction, lighting effects, and underwater. We also analyze the design and implementation issues of the visualization of the ocean waves for ship maneuvering simulator with respect to realistic and real-time ocean visualization, ship dynamics, and application purposes. Through the analysis, we have found that the realistic visualization of ocean waves plays an important role in the generation of immersiveness, more accurate ship motion, and the various and controllable simulation scenarios for the ship maneuvering simulator. Additionally, we have confirmed that there are many visualization elements, methods, and limitations to be considered for the visualization of the ocean waves for ship maneuvering simulator, and we have concluded that the systematic design is required before implementation.

The PRQ instrument is parental perspectives of the parent-child relationship. It measured parent-child dimensions that include attachment and involvement. Also, it provides additional information on parenting style, parenting stress and satisfaction with the child’s school. This study tested reliability and validity of the Korean version of Parenting Relationship Questionnaire-Child (K-PRQ-C). The K-PRQ-C was administered to parents of 713 elementary school children including 362 boys and 351 girls. They were from 1st to 6th grade children who were recruited form 4 elementary schools in Korea. Reliability was tested through internal consistency. We conducted confirmatory factor analysis. Moreover, scale inter-correlation was conducted for validity test. Discriminant validity conducted through administration to the parents of clinical children with emotional and behavior disorders. Construct validity was also examined through Korean version of the Parenting Sense of Competence. The results of confirmatory factor analysis indicated that the similar factor structures exist for PRQ-C and K-PRQ-C. The results showed a high level of internal consistency as well as construct and discriminant validity. These results showed valid psychometric properties for the K-PRQ-C. The K-PRQ-C provides a reliable and valid means of gathering information about the parent-child relationship. We discussed Implications for the use of the K-PRQ-C as a clinical tool and as a research instrument.

Smad3 linker phosphorylation is a candidate target for several kinases that play important roles in cancer cell initiation, proliferation and progression. Also, Smad3 is an essential intracellular mediator of TGF-β1-induced transcriptional responses during carcinogenesis. Therefore, it is highly advantageous to identify and develop inhibitors targeting Smad3 linker phosphorylation for the treatment of cancers. Galangin (3,5,7-trihydroxyflavone) has been known to be an active flavonoid showing a cytotoxic effect on several cancer cells. However, the mechanism of action of galangin in various cancers remains unclear, and there has been no report concerning regulation of Smad3 phosphorylation by galangin. In the present study, we show that galangin significantly induced apoptosis and inhibited cell proliferation in the presence of TGF-β1 in both human prostate and pancreatic cancer cell lines. Particularly, galangin effectively inhibits phosphorylation of the Thr-179 site at Smad3 linker region through suppression of CDK4 phosphorylation. Thus, galangin can be a promising candidate as a selective inhibitor to suppress phosphorylation of Smad3 linker region.

The development of haptic display devices has brought a new level of immersion and realistic fidelity to virtual environments, allowing users to ‘feel’ the virtual world. In this paper, a virtual environment with bimanual haptic feedback for users will be demonstrated, both engaging the user with weight feedback of lifted objects and maintaining the stability of the interaction and simulation when passing objects between hands. Users can then complete a simple speed-training task in a virtual kitchen environment.

The sense of touch plays an important role in reinforcing presence of distant physical targets for telepresence applications. Among various data representations for defining haptic cues, a point cloud is considered to be suitable for dynamically changing environments in virtue of its simplicity. However, ambiguous and noisy data caused by the lack of geometrical structure and the characteristics of sensors often lead to unreliable haptic feedback during interaction. To address this issue, we propose a robust point-cloud-based haptic rendering method for palpable exploration of remote environments without reconstruction of surface meshes. Surface information, which is a key element of haptic rendering, is directly estimated from the raw point cloud data by principal component analysis. This method is then applied to a prototype server-client system on real network for proof of concept and evaluation of performance. The experimental results confirm the accuracy and stability of the proposed method in estimating surface information as well as in handling contact situations.

This research focused on meeting planners’ perceptions about selecting Beijing as an international convention destination. Twenty-three convention destination site selection criteria organized into five categories were identified. It was found that, with respect to Beijing, the importance of site selection criteria has changed since the late 1990s, with meeting planners now attaching more weight to the quality of convention services, quality of convention planning assistance, and city image. The meeting planners who had previously held international conventions in Beijing attached greater importance to research and development cooperation opportunities and choice of accommodations than those who had not. They rated Beijing's performance lower on the convenience of the application process (required by Chinese governments) and government support. It was concluded that Beijing needs to improve most on the quality of convention services and convention planning assistance, and by relaxing government policies r...

Owing to the popularity of various hand tracking interfaces, there have been numerous applications developed to provide intuitive hand interaction with the virtual world. As users start with great anticipation, they end up with dissatisfaction due to difficulties of manipulation or physical tiredness coming very short. Although the task itself is rather trivial in a real life situation, it requires much effort in the virtual environment. We address this awkwardness as 'VR interaction-induced fatigue symptom' and hypothesize its causes based on our observations. We argue that the source of the fatigue comes from the restricted sensory information of the VR interfaces, and that users try to accommodate the missing sensory feedback by excessive motion leading to wrong posture or bad timing. We demonstrate our hypothesis by conducting experiments of two types of virtual interaction scenarios: object transport and 3D selection. Furthermore, by analyzing the behaviors of users' action collected from our experiment, we derive essential factors to be considered in designing VR applications, and propose a conceptual interaction model for orchestrating virtual grasping.

Renal fibrosis is a common consequence of unilateral ureteral obstruction, which provides a useful model to investigate the pathogenesis of obstructive nephropathy and progressive renal fibrosis. Transforming growth factor (TGF-β1) has been recognized as a key mediator in renal fibrosis by stimulating matrix-producing fibrogenic cells and promoting extracellular matrix deposition. Therefore, considerable efforts have been made to regulate TGF-β signaling for antifibrotic therapy. Here, we investigated the mode of action of glucosamine hydrochloride (GS-HCl) on TGF-β1-induced renal fibrosis. In the obstructed kidneys and TGF-β1-treated renal cells, GS-HCl significantly decreased renal expression of α-smooth muscle actin, collagen I, and fibronectin. By investigating the inhibitory mechanism of GS-HCl on renal fibrosis, we found that GS-HCl suppressed TGF-β signaling by inhibiting N-linked glycosylation of the type II TGF-β receptor (TβRII), leading to an inefficient trafficking of TβRII to the membrane surface. Defective N-glycosylation of TβRII further suppressed the TGF-β1-binding to TβRII, thereby decreasing TGF-β signaling. Notably, GS-HCl treatment significantly reduced TGF-β1-induced up-regulation of Smad2/3 phosphorylation and transcriptional activity in vivo and in vitro. Taken together, GS-HCl-mediated regulation of TGF-β signaling exerted an antifibrotic effect, thereby ameliorating renal fibrosis. Our study suggests that GS-HCl would be a promising agent for therapeutic intervention for preventing TGF-β1-induced renal fibrosis in kidney diseases. Key message Glucosamine-mediated attenuation of TGF-β signaling ameliorates renal fibrosis in vivo TGF-β1-induced fibrogenic action is reduced by glucosamine in vitro N-glycosylation of the type II TGF-β receptor is suppressed by glucosamine Glucosamine-induced defective N-glycosylation of TβRII decreases TGF-β signaling. Electronic supplementary material The online version of this article (doi:10.1007/s00109-013-1086-1) contains supplementary material, which is available to authorized users.

Purpose: This study was performed to understand the relationship between ego-resilience and the clinical competence of nursing students. Methods: The subjects were 291 juniors and seniors who received clinical training from nursing universities in Gyeongsang, Jeolla, and Chungcheong. General characteristics, main study variables were analyzed using descriptive statistics such as frequency, percentage, mean, standard deviation; ego-resilience and clinical competence by general characteristics were analyzed using t-test, ANOVA; correlations between ego-resilience and clinical competence were analyzed using Pearson correlation coefficients. Results: The mean score for ego-resilience was 3.44; and the mean score for clinical competence was 3.71. The data showed a positive correlation between ego-resilience and clinical competence. Conclusion: According to the results, there is a correlation between clinical competence and the ego-resilience of nursing students. Therefore, to enhance clinical competence, a follow-up study on the development of a program for advanced ego-resilience is needed.

Kim, J. and Park, J., 2013. A statistical model for computing causal relationships to assess changes in a marine environment In order to manage sustainable coastal development, it is essential to identify the causal relationships among observation parameters that reveal the changes in the marine environment in a quantitative manner. On the Saemangeum coast, a land reclamation project by constructing sea dike has been underway since 1991. To monitor and assess the changes in the marine environment due to the project, the states of the ocean's physics and circulation, water quality, marine geology, and the marine ecosystem have been measured through the integrated ocean observation networks. In this paper, the observed data are statistically investigated with regard to observed and latent variables, in order to identify their causal relationships and compute the degrees of their influence. We performed a multivariate statistical analysis using a structural equation model based on oceanographic theo...

Haptic virtual fixtures have a key role in telepresence systems to enhance spatial perception as well as to improve task efficiency. However, there are some difficulties in bringing real and virtual constraints together due to the extremely different characteristics of their representations. This paper proposes a unified virtual fixture model for the telepresence systems to combine the autonomously obtained real-world obstacles with the manually defined virtual surfaces for preventing unpreferred motions. The real environment is scanned by an RGB-D camera in the form of a point cloud, and the implicit virtual surfaces are added to the task environment by an augmented reality technique. When the user interacts with the task environment through a haptic device, our method detects a collision between the proxy and the environmental constraints and estimates the local information of the contact point without reconstruction of surface topologies. Once collisions are detected, the optimal proxy position for resolving the collisions is computed by an integrated constraint solver in a convergent manner. The proposed model provides stable and faithful haptic feedback from the heterogeneous and unstructured geometric representations. We verified that our method is fast enough for real-time haptic rendering and renders the target geometries properly.

Highlights • Elevated cortisol does not appear to be associated with regional variations in hippocampal shape. • Novel shape morphology analysis applied to study possible effect of cortisol on hippocampus. • Mean diffusivity in hippocampus is associated with reactive cortisol slope in older men., High, unabated glucocorticoid (GC) levels are thought to selectively damage certain tissue types. The hippocampus is thought to be particularly susceptible to such effects, and though findings from animal models and human patients provide some support for this hypothesis, evidence for associations between elevated GCs and lower hippocampal volumes in older age (when GC levels are at greater risk of dysregulation) is inconclusive. To address the possibility that the effects of GCs in non-pathological ageing may be too subtle for gross volumetry to reliably detect, we analyse associations between salivary cortisol (diurnal and reactive measures), hippocampal morphology and diffusion characteristics in 88 males, aged ∼73 years. However, our results provide only weak support for this hypothesis. Though nominally significant peaks in morphology were found in both hippocampi across all salivary cortisol measures (standardised β magnitudes 0.0000003), associations were both positive and negative, and none survived false discovery rate correction. We found one single significant association (out of 12 comparisons) between a general measure of hippocampal diffusion and reactive cortisol slope (β = 0.290, p = 0.008) which appeared to be driven predominantly by mean diffusivity but did not survive correction for multiple testing. The current data therefore do not clearly support the hypothesis that elevated cortisol levels are associated with subtle variations in hippocampal shape or microstructure in non-pathological older age.

Structural measures of the hippocampus have been linked to a variety of memory processes and also to broader cognitive abilities. Gross volumetry has been widely used, yet the hippocampus has a complex formation, comprising distinct subfields which may be differentially sensitive to the deleterious effects of age, and to different aspects of cognitive performance. However, a comprehensive analysis of multidomain cognitive associations with hippocampal deformations among a large group of cognitively normal older adults is currently lacking. In 654 participants of the Lothian Birth Cohort 1936 (mean age = 72.5, SD = 0.71 years), we examined associations between the morphology of the hippocampus and a variety of memory tests (spatial span, letter-number sequencing, verbal recall, and digit backwards), as well as broader cognitive domains (latent measures of speed, fluid intelligence, and memory). Following correction for age, sex, and vascular risk factors, analysis of memory subtests revealed that only right hippocampal associations in relation to spatial memory survived type 1 error correction in subiculum and in CA1 at the head (β = 0.201, p = 5.843 × 10−4, outward), and in the ventral tail section of CA1 (β = −0.272, p = 1.347 × 10−5, inward). With respect to latent measures of cognitive domains, only deformations associated with processing speed survived type 1 error correction in bilateral subiculum (βabsolute ≤ 0.247, p < 1.369 × 10−4, outward), bilaterally in the ventral tail section of CA1 (βabsolute ≤ 0.242, p < 3.451 × 10−6, inward), and a cluster at the left anterior-to-dorsal region of the head (β = 0.199, p = 5.220 × 10−6, outward). Overall, our results indicate that a complex pattern of both inward and outward hippocampal deformations are associated with better processing speed and spatial memory in older age, suggesting that complex shape-based hippocampal analyses may provide valuable information beyond gross volumetry.

Circadian typology and sleep quality may be essential factors associated with the promotion of resilience. However, previous studies investigating the association between circadian typology and resilience did not analyze the effects of sleep quality on resilience. Thus, the present study evaluated the association between circadian typology and resilience in Korean college students after controlling for sleep quality. Additionally, this study investigated several sleep-related variables, including sleep duration, social jetlag and sunlight exposure during the daytime, to examine the modifiable behavioral features of morningness and also investigated whether the findings regarding morningness-related modifiable habits were associated with resilience. This study included 1094 participants (947 males and 147 females) between 19 and 29 years of age (22.8 ± 1.9 years) who completed the 10-item Korean version of the Connor-Davidson Resilience Scale (CD-RISC-10), the Korean version of the Morningness-Eveningness Questionnaire (MEQ), the Pittsburgh Sleep Quality Index (PSQI), the Korean version of the Hospital Anxiety and Depression Scale (HADS) and a survey about social jetlag that determined misalignments between weekday and weekend times of awakening and activity duration under conditions of sunlight between 10:00 and 15:00. A multiple linear regression analysis revealed that sleep duration, mean daily sunlight exposure between 10:00 and 15:00 and age were positive predictors of morningness, whereas social jetlag was a negative predictor of morningness. Of these morningness-related modifiable behavioral features, mean daily sunlight exposure between 10:00 and 15:00 significantly predicted greater resilience. An additional multiple linear regression analysis revealed that morningness was a positive predictor of resilience after controlling for age, sex, depression, anxiety and sleep quality. These results support the idea that morningness and better sleep quality are associated with greater resilience. Morningness was also associated with longer sleep duration, longer sunlight exposure during the daytime and less social jetlag, whereas longer daily sunlight exposure between 10:00 and 15:00 was associated with greater resilience. Future longitudinal studies are needed to examine whether manipulations of morningness-related modifiable behavioral features can rearrange chronotype and promote resilience.

Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.

Category: Basic Sciences/Biologics Introduction/Purpose: Although weight-bearing CT of the foot and ankle definitely reflect the morphology of joint and foot deformity, it is hard to obtain the standing CT due to difficulty of availability. The purpose of this study is to introduce a semi- automatic method based on a deformable surface fitting for achieving the weight-bearing 3D model reconstruction from standing radiographs for foot and ankle. Methods: Our method is based on a Laplacian surface deformation framework using a template model of foot bones. As pre- processing step, we obtained template surface meshes having the average shapes of foot bones from standing CT images (Planmed Verity® CT scanner) in 10 normal volunteers. First, 3D standing CT was obtained by Planmed Verity® CT scanner and used as gold standard of reconstruction for one patient with flatfoot. Second, in the reconstruction step, the surface meshes are deformed following guided user inputs (talus 6, calcaneus 8 in lateral, talus 6, calcaneus 6 in anteroposterior standing radiograph) with geometric constraints to recover the target shapes of patients while preserving average bone shape and smoothness as much as possible. Finally, we compared reconstructed 3D model to original standing CT images. Results: In this study, the comparison results indicate that the obtained reconstruction is close to the actual standing foot and ankle geometry. We present the accuracy and robustness of our method via comparison between the reconstructed 3D models and the original bone surfaces Conclusion: Weight-bearing 3D foot model reconstruction from standing radiographs is concise and the effective method for analysis of foot joint alignment and deformity.

BACKGROUND AND PURPOSE With the aim of facilitating the early detection of Alzheimer's disease, the Alzheimer's Disease Neuroimaging Initiative proposed two stages based on the memory performance: early mild cognitive impairment (EMCI) and late mild cognitive impairment (LMCI). The current study was designed to investigate structural differences in terms of surface atrophy and microstructural changes of the hippocampus in EMCI and LMCI. METHODS Hippocampal shape modeling based on progressive template surface deformation was performed on T1-weighted MRI images obtained from 20 cognitive normal (CN) subjects, 17 EMCI patients, and 20 LMCI patients. A template surface in CN was used as a region of interest for diffusion-tensor imaging (DTI) voxel-based morphometry (VBM) analysis. Cluster-wise group comparison was performed based on DTI indices within the hippocampus. Linear regression was performed to identify correlations between DTI metrics and clinical scores. RESULTS The hippocampal surface analysis showed significant atrophies in bilateral CA1 regions and the right ventral subiculum in EMCI, in contrast to widespread atrophy in LMCI. DTI VBM analysis showed increased diffusivity in the CA2-CA4 regions in EMCI and additionally in the subiculum region in LMCI. Hippocampal diffusivity was significantly correlated with scores both for the Mini Mental State Examination and on the Modified Alzheimer Disease Assessment Scale cognitive subscale. However, the hippocampal diffusivity did not vary significantly with the fractional anisotropy. CONCLUSIONS EMCI showed hippocampal surface changes mainly in the CA1 region and ventral subiculum. Diffusivity increased mainly in the CA2-CA4 regions in EMCI, while it decreased throughout the hippocampus in LMCI. Although axial diffusivity showed prominent changes in the right hippocampus in EMCI, future studies need to confirm the presence of this laterality difference. In addition, diffusivity is strongly correlated with the cognitive performance, indicating the possibility of using diffusivity as a biomarker for disease progression.

Clinical management of foot pathology requires accurate and robust measurement of the anatomical angles. In order to measure a 3D angle, recent approaches have adopted a landmark-based local coordinate system to establish bone angles used in orthopedics. These measurement methods mainly assess the relative angle between bones using a representative axis derived from the morphological feature of the bone and therefore, the results can be affected by bone deformities. In this study, we propose a method of deriving a global frame-of-reference to acquire consistent direction of the foot by extracting the undersurface of the foot from the CT image data. The two lowest positions of the foot skin are identified from the surface to define the base plane, and the direction from the hallux to the fourth toe is defined together to construct the global coordinate system. We performed the experiment on 10 volumes of foot CT images of healthy subjects to verify that the proposed method provides reliable measurements. We measured 3D angles for talus-calcaneus and talus-navicular using facing articular surfaces of paired bones. The angle was reported in 3 projection angles based on both coordinate systems defined by proposed global frame-of-reference and by CT image planes (saggital, frontal, and transverse). The result shows that the quantified angle using the proposed method considerably reduced the standard deviation (SD) against the angle using the conventional projection planes, and it was also comparable with the measured angles obtained from local coordinate systems of the bones. Since our method is independent from any individual local shape of a bone, unlike the measurement method using the local coordinate system, it is suitable for inter-subject comparison studies.

Clean bone segmentation is critical in studying the joint anatomy for measuring the spacing between the bones. However, separation of the coupled bones in CT images is sometimes difficult due to ambiguous gray values coming from the noise and the heterogeneity of bone materials as well as narrowing of the joint space. For fine reconstruction of the individual local boundaries, manual operation is a common practice where the segmentation remains to be a bottleneck. In this paper, we present an automatic method for extracting the joint space by applying graph cut on Markov random field model to the region of interest (ROI) which is identified by a template of 3D bone structures. The template includes encoded articular surface which identifies the tight region of the high-intensity bone boundaries together with the fuzzy joint area of interest. The localized shape information from the template model within the ROI effectively separates the bones nearby. By narrowing the ROI down to the region including two types of tissue, the object extraction problem was reduced to binary segmentation and solved via graph cut. Based on the shape of a joint space marked by the template, the hard constraint was set by the initial seeds which were automatically generated from thresholding and morphological operations. The performance and the robustness of the proposed method are evaluated on 12 volumes of ankle CT data, where each volume includes a set of 4 tarsal bones (calcaneus, talus, navicular and cuboid).

OD (origin-destination) data represent the movement of people or goods between geographical points, and play important roles in establishing policies for migration and transportation. However, since most of raw OD data are very massive and written in unintuitive form, it is difficult to grasp meaningful information from the data themselves especially without visual aids. We propose an effective visualization method for the OD data by combining the key features of Radial Table and Parallel Sets. Radial Table is an intuitive and aesthetically attractive data visualization technique based on a circular layout, but it is unfit to visualize the OD data due to its single-layered structure. To overcome its limitation, we refer to the visual structure of Parallel Sets and divide the original Radial Table into multiple concentric layers which contain origins and destinations separately. Each pair of the origin and destination is connected by a B-spline curve, and it indicates a direction and a scale of the flow. Also we validate the proposed method by implementing and applying to real-world datasets. In this way, our method will help an analyst understand the pattern and volume of traffic at a glance, and support a decision making process.

Objectives Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. Materials and methods Clinical evaluation, comprehensive neuropsychological test, and 18F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. Results All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: −0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (β = 0.43, P = 0.02). Conclusions Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time.

Optical diffraction tomography (ODT) is an interferometric microscopy technique capable of measuring 3-D refractive index (RI) distribution of transparent samples. Multiple 2-D holograms of a sample illuminated with various angles are measured, from which 3-D RI map of the sample is reconstructed via the diffraction theory. ODT has been proved as a powerful tool for the study of biological cells, due to its non-invasiveness, label-free and quantitative imaging capability. Recently, our group has demonstrated that a digital micromirror device (DMD) can be exploited for fast and precise control of illumination beams for ODT. In this work, we systematically study the precision and stability of the ODT system equipped with a DMD and present measurements of 3-D and 4-D RI maps of various types of live cells including human red blood cells, white blood cells, hepatocytes, and HeLa cells. Furthermore, we also demonstrate the effective visualization of 3-D RI maps of live cells utilizing the measured information about the values and gradient of RI tomograms., Comment: 8 pages, submitted for publication in SPIE Proceeding 9718-39

The Saemangeum Coast, located on the west side of the Korean peninsula, is undergoing a 30-year land reclamation project involving approximately 40 kilohectares. Because this project will drastically change the marine environment, monitoring and analyzing the water quality and marine life forms are necessary. However, the observation data are accumulating past the terabyte level, and the simulation data based on that data are also growing. Moreover, the gathered data are heterogeneous, and combining the datasets is often critical for gaining a better understanding of the environmental situation and for making predictions and decisions. A new visual-analytics tool for analyzing this situation fuses geographic-information-system data with ocean environmental data. It has three main components: data collection, geoprocessing, and data visualization. Researchers have used it to monitor and analyze changes in water quality, zooplankton distribution, and seabed topography.