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In convolutional neural networks (CNNs), the filter grouping in convolution layers is known to be useful to reduce the network parameter size. In this paper, we propose a new logarithmic filter grouping which can capture the nonlinearity of filter distribution in CNNs. The proposed logarithmic filter grouping is installed in shallow CNNs applicable in a mobile application. Experiments were performed with the shallow CNNs for classification tasks. Our classification results on Multi-PIE dataset for facial expression recognition and CIFAR-10 dataset for object classification reveal that the compact CNN with the proposed logarithmic filter grouping scheme outperforms the same network with the uniform filter grouping in terms of accuracy and parameter efficiency. Our results indicate that the efficiency of shallow CNNs can be improved by the proposed logarithmic filter grouping.

Compact neural networks with limited memory and computation are demanding in recently popularized mobile applications. The reduction of network parameters is an important priority. In this paper, we address a compact neural network for facial landmark detection. The facial landmark detection is a frontal module that is mandatorily required for face analysis applications. We propose a new teacher and student joint learning method applicable to a compact facial landmark detection network. In the proposed learning scheme, the compact architecture of student regression network is learned jointly with the fully connected layer of the teacher regression network so that they are mimicked each other. To demonstrate the effectiveness of the proposed learning method, experiments were performed on a public database. The experimental results showed that the proposed method could reduce network parameters while maintaining comparable performance to state-of-the-art methods.

In this study, a novel computer aided diagnosis (CADx) framework is devised to investigate interpretability for classifying breast masses. Recently, a deep learning technology has been successfully applied to medical image analysis including CADx. Existing deep learning based CADx approaches, however, have a limitation in explaining the diagnostic decision. In real clinical practice, clinical decisions could be made with reasonable explanation. So current deep learning approaches in CADx are limited in real world deployment. In this paper, we investigate interpretability in CADx with the proposed interpretable CADx (ICADx) framework. The proposed framework is devised with a generative adversarial network, which consists of interpretable diagnosis network and synthetic lesion generative network to learn the relationship between malignancy and a standardized description (BI-RADS). The lesion generative network and the interpretable diagnosis network compete in an adversarial learning so that the two networks are improved. The effectiveness of the proposed method was validated on public mammogram database. Experimental results showed that the proposed ICADx framework could provide the interpretability of mass as well as mass classification. It was mainly attributed to the fact that the proposed method was effectively trained to find the relationship between malignancy and interpretations via the adversarial learning. These results imply that the proposed ICADx framework could be a promising approach to develop the CADx system., Comment: This paper was presented at SPIE Medical Imaging 2018, Houston, TX, USA

Human face analysis is an important task in computer vision. According to cognitive-psychological studies, facial dynamics could provide crucial cues for face analysis. The motion of a facial local region in facial expression is related to the motion of other facial local regions. In this paper, a novel deep learning approach, named facial dynamics interpreter network, has been proposed to interpret the important relations between local dynamics for estimating facial traits from expression sequence. The facial dynamics interpreter network is designed to be able to encode a relational importance, which is used for interpreting the relation between facial local dynamics and estimating facial traits. By comparative experiments, the effectiveness of the proposed method has been verified. The important relations between facial local dynamics are investigated by the proposed facial dynamics interpreter network in gender classification and age estimation. Moreover, experimental results show that the proposed method outperforms the state-of-the-art methods in gender classification and age estimation.

Pancreatic β-cells are critical in the regulation of glucose homeostasis by controlled secretion of insulin in mammals. Activation of protein kinase A by cAMP is shown to be responsible for enhancing this pathway, which is countered by phosphodiesterase (PDE) that converts cAMP to AMP and turns off the signal. Salt-inducible kinases (SIKs) were also known to inhibit cAMP signaling, mostly by promoting inhibitory phosphorylation on CREB-regulated transcription coactivators. Here, we showed that SIK1 regulates insulin secretion in β-cells by modulating PDE4D and cAMP concentrations. Haploinsufficiency of SIK1 led to the improved glucose tolerance due to the increased glucose-stimulated insulin secretion. Depletion of SIK1 promoted higher cAMP concentration and increased insulin secretion from primary islets, suggesting that SIK1 controls insulin secretion through the regulation of cAMP signaling. By using a consensus phosphorylation site of SIK1, we identified PDE4D as a new substrate for this kinase family. In vitro kinase assay as well as mass spectrometry analysis revealed that the predicted Ser136 and the adjacent Ser141 of PDE4D are critical in SIK1-mediated phosphorylation. We found that overexpression of either SIK1 or PDE4D in β-cells reduced insulin secretion, while inhibition of PDE4 activity by rolipram or knockdown of PDE4D restored it, showing indeed that SIK1-dependent phosphorylation of PDE4D is critical in reducing cAMP concentration and insulin secretion from β-cells. Taken together, we propose that SIK1 serves as a part of a self-regulatory circuit to modulate insulin secretion from pancreatic β-cells by controlling cAMP concentration through modulation of PDE4D activity.

This study analyzed the MMPI (Minnesota Multiphashic Personality Inventory), VAS (Visual Analogue Scale), cervical and lumbar curvature (Cervical angle, Ishihara Index, Lumbar angle, Ferguson angle) and satisfaction score of patient of traffic accident. About 59 cases of patients admitted to the Korean Medicine hospital, MMPI and pain levels (VAS) cervical and lumbar curvature (Cervical angle, Ishihara Index, lumbar angle, Ferguson angle) and satisfaction score were measured and statistically analyzed. Depending on the type of accident divided into two groups of In car TA and Out car TA. After hospitalization, patient`s pain index was improved as a whole. Pain index and evaluation of the cervical and lumbar curvature, according to the accident types, the difference was not statistically significant. In the analysis of the MMPI validity scales, In car TA group was analyzed by `V-shaped`, Out car TA group was analyzed by umbrella- shaped, `inverted V-shaped`. Clinical scales of out car TA group were analyzed by 3-1 profile compared to the In car TA group. Results of multiple regression analysis showed no association between factors and MMPI scales. In the case of a traffic accident patients, damage to the body, as well as emotional and psychological factors are thought to affect the condition or prognosis of patients. In the future, for the management and treatment of these parts will be needed to complement the academic or institutional.

Cyclic AMP promotes chronic expression of target genes mainly by protein kinase A–dependent activation of CREB transcription factor machineries in the metabolic tissues. Here, we wanted to elaborate whether CREB-regulated transcription factor (CRTC)2 and its negative regulator salt-inducible kinase (SIK)2 are involved in the transcriptional control of the metabolic pathway in adipocytes. SIK2 knockout (SIK2 KO) mice exhibited higher blood glucose levels that were associated with impaired glucose and insulin tolerance. Hypertriglyceridemia was apparent in SIK2 KO mice, mainly due to the increased lipolysis from white adipocytes and the decreased fatty acid uptake in the peripheral tissues. Investigation of white adipocytes revealed the increases in fat cell size and macrophage infiltration, which could be linked to the metabolic anomaly that is associated in these mice. Interestingly, SIK2 KO promoted the enhancement in the CRTC2-CREB transcriptional pathway in white adipocytes. SIK2 KO mice displayed increased expression of activating transcription factor (ATF)3 and subsequent downregulation of GLUT4 expression and reduction in high–molecular weight adiponectin levels in the plasma, leading to the reduced glucose uptake in the muscle and white adipocytes. The effect of SIK2-dependent regulation of adipocyte metabolism was further confirmed by in vitro cell cultures of 3T3 L1 adipocytes and the differentiated preadipocytes from the SIK2 or CRTC2 KO mice. Collectively, these data suggest that SIK2 is critical in regulating whole-body glucose metabolism primarily by controlling the CRTC2-CREB function of the white adipocytes.

In the past few decades, automatic face recognition has been an important vision task. In this paper, we exploit the spatial relationships of facial local regions by using a novel deep network. In the proposed method, face is spatially scanned with spatial long short-term memory (LSTM) to encode the spatial correlation of facial regions. Moreover, with facial regions of various scales, the complementary information of the multi-scale facial features is encoded. Experimental results on public database showed that the proposed method outperformed the conventional methods by improving the face recognition accuracy under illumination variation.

Characterization of masses in computer-aided detection systems for digital breast tomosynthesis (DBT) is an important step to reduce false positive (FP) rates. To effectively differentiate masses from FPs in DBT, discriminative mass feature representation is required. In this paper, we propose a new latent feature representation boosted by depth directional long-term recurrent learning for characterizing malignant masses. The proposed network is designed to encode mass characteristics in two parts. First, 2D spatial image characteristics of DBT slices are encoded as a slice feature representation by convolutional neural network (CNN). Then, depth directional characteristics of masses among the slice feature representations are encoded by the proposed depth directional long-term recurrent learning. In addition, to further improve the class discriminability of latent feature representation, we have devised three objective functions aiming to (a) minimize classification error, (b) minimize intra-class variation within the same class, and (c) preserve feature representation consistency in a central slice. Experimental results have demonstrated that the proposed latent feature representation achieves a higher level of classification performance in terms of receiver operating characteristic (ROC) curves and the area under the ROC curve values compared to performance with feature representation learned by conventional CNN and hand-crafted features.

In digital breast tomosynthesis, the three dimensional (3D) reconstructed volumes only provide quasi-3D structure information with limited resolution along the depth direction due to insufficient sampling in depth direction and the limited angular range. The limitation could seriously hamper the conventional 3D image analysis techniques for detecting masses because the limited number of projection views causes blurring in the out-of-focus planes. In this paper, we propose a novel mass detection approach using slice conspicuity in the 3D reconstructed digital breast volumes to overcome the above limitation. First, to overcome the limited resolution along the depth direction, we detect regions of interest (ROIs) on each reconstructed slice and separately utilize the depth directional information to combine the ROIs effectively. Furthermore, we measure the blurriness of each slice for resolving the degradation of performance caused by the blur in the out-of-focus plane. Finally, mass features are extracted from the selected in focus slices and analyzed by a support vector machine classifier to reduce the false positives. Comparative experiments have been conducted on a clinical data set. Experimental results demonstrate that the proposed approach outperforms the conventional 3D approach by achieving a high sensitivity with a small number of false positives.

In current business management, knowledge is considered to be a strategic resource that can strengthen an organization’s competitiveness. Today, under the process of continuous globalization, almost all companies are rapidly exposed to global competition regardless of their scale or type of business. However, multinational management is very complicated and uncertain and it is hard for multinationals to effectively coordinate and manage their global value chains. In light of this, the utility of multinational management based on knowledge is increased. The present study examines multinational firms’ knowledge management systems, knowledge creation processes and global supply chain performance and attempts to reveal any significant linkages between these latent variables. For this research interest, we proposed 18 items to measure four types of knowledge creation processes (SECI) designed by Nonaka (1994) and revised by authors considering the global business environment, in particular involving the global supply chain management concept. Utilizing the confirmed SECI model, 128 sample companies were classified into four groups according to the levels of their knowledge creation processes. The empirical results of this study reveal important linkages between a multinational firm’s knowledge management system and knowledge creation process, as well as between its knowledge creation process and global supply chain management performance. In particular, the current work suggests that the creation and conversion of tacit knowledge as well as explicit knowledge can be effectively supported by information and communication technology.

Beneficial Effect of Hyangsayangwi-tang on the Cisplatin-Induced Gastrointestinal Dysfunctions in Rats Eun-Hee Seo, Seong-Tae Kim, Na-Young Bae, Ae-Ryun Choi Dept. of Sasang Constitutional Medicine, College of Oriental Medicine, Daegu Haany Univ. Dept. of Sasang Constitutional Medicine, Div. of clinical medicine, School of Korean Medicine, Pusan National University Objectives This study aimed to observe the effect of Hyangsayangwi-tang on the cisplatin-induced gastrointestinal dysfunctions in rats. Methods Four groups(each of 8 rats per group) were used in this study. Saline and distilled water treated control rats are Intact vehicle control group. Delayed gatrointestinal mortility was induced by intraperitoneal treatment of cisplatin 2mg/kg, once a week for 5 weeks(Cisplatin control group). Hyangsayangwi-tang aqueous extracts(HY) were orally administered in a volume of 5ml/kg, once a day for 14 days from 4th ciplatin treatmernt(HY group). Ondansetron 1mg/kg was subcutaneously treated, in a volume of 1ml/kg, as same as HY(ondansetron group). We measured the body weights, intestinal charcoal transit ratio, fecal parameters, fundus MDA, GSH contents and SOD, CAT activities, TPH and MAO activities, pyloric gastrin and serotonin contents with their immunoraective cells, colonic serotonin-immunoreactive cells, the histopathology of pylorus, fundus mucosa and colon. Results and Conclusions (1) The body weight gains, the small intestinal charcoal transfer rates, the fecal parameters(numbers, weights and water contents) were increased in HY, ondansetron group. (2) The inhibit of fundus antioxidant defense systems by cisplatin were decreased in HY, ondansetron group. (3) The pyloric TPH activities were increased and the pyloric MAO activities were decreased in HY group. (4) The pyloric gastric contents and the gastrin-immunoreactive cells were increased in HY group. And the pyloric serotonin contents and the pyloric and colonic serotonin-immunoreactive cells were decreased in HY group. (5) The pyloru atrophic changes and the gastric surface erosive damage regions by cisplatin were favorably inhibited by treatment of HY. HY, a representative Soeumin prescription improve GI dysfunctions and constipation retarded by cisplatin through modulations of GI enterochromaffin cells, serotonin and gastrin-producing cells and antioxidative systems. Especially HY showed the highest favorable effects more than those of ondansetron.

Myocyte enhancer factor 2 (MEF2) is a family of transcription factors that regulates many processes, including muscle differentiation. Due to its many target genes, MEF2D requires tight regulation of transcription activity over time and by location. Epigenetic modifiers have been suggested to regulate MEF2-dependent transcription via modifications to histones and MEF2. However, the modulation of MEF2 activity by lysine methylation, an important posttranslational modification that alters the activities of transcription factors, has not been studied. We report the reversible lysine methylation of MEF2D by G9a and LSD1 as a regulatory mechanism of MEF2D activity and skeletal muscle differentiation. G9a methylates lysine-267 of MEF2D and represses its transcriptional activity, but LSD1 counteracts it. This residue is highly conserved between MEF2 members in mammals. During myogenic differentiation of C2C12 mouse skeletal muscle cells, the methylation of MEF2D by G9a decreased, on which MEF2D-dependent myogenic genes were upregulated. We have also identified lysine-267 as a methylation/demethylation site and demonstrate that the lysine methylation state of MEF2D regulates its transcriptional activity and skeletal muscle cell differentiation.

Background Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population. Methods A two-stage GWAS was conducted in a total of 3495 healthy Chinese men (1999 subjects in the GWAS discovery stage and 1496 in the confirmation stage). Results We identified a novel genetic region at 15q21.2 (rs2414095 in CYP19A1 ), which was significantly associated with oestradiol and FSH in the Chinese population at a genome-wide significant level (p=6.54×10−31 and 1.59×10−16, respectively). Another single nucleotide polymorphism in CYP19A1 gene was significantly associated with oestradiol level (rs2445762, p=7.75×10−28). In addition, we confirmed the previous GWAS-identified locus at 17p13.1 for testosterone (rs2075230, p=1.13×10−8) and SHBG level (rs2075230, p=4.75×10−19) in the Chinese population. Conclusions This study is the first GWAS investigation of genetic determinants of FSH and LH. The identification of novel susceptibility loci may provide more biological implications for the synthesis and metabolism of these hormones. More importantly, the confirmation of the genetic loci for testosterone and SHBG suggests common genetic components shared among different ethnicities.

A Case Report of Soeumin Adult Atopic Dermatitis Improved with Sipyimigwanjung-tang. Seong-Tae Kim, Ae-Ryun Choi, Deok-Mo KooDept. of Sasang Constitutional Medicine, college of Korean Medicine, Daegu Haany Univ.ObjectivesThe purpose of this case study is to report that a Soeumin patient diagnosed as adult atopic dermatitis was treatedwith Sipyimigwanjung-tang and then his symptoms improved.MethodsWe diagnosed the patient as Soeumin Greater Yin Pattern based on his nature & emotion, physical characteristics,symptoms. So we treated him with Sipyimigwanjung-tang and used Visual Analogue Scale(VAS), SCORAD(Scoring of Atopic Dermatitis) index and pictures of the affected part for the assessment.Results & ConclusionsAfter treatment, his SCORAD index results significantly decreased from 76.3 to 41.8, VAS of itching decreased from 10 to 4 and the patient's subjective symptom and general condition considerably improved. This case studydescribe the effectiveness of Sipyimigwanjung-tang on Soeumin adult atopic dermatitis symptoms.Key Words: Adult Atopic Dermatitis, Sipyimigwanjung-tang, Soeumin, Sasang Constitutional Medicine

Mammography, the process of using X-ray to examine the woman breast, is the one of the effective tools for detecting breast cancer at an early state. In screening mammogram, Computer-Aided Detection(CAD) system helps radiologist to diagnose cases by detecting malignant masses. A mass is an important lesion in the breast that can indicate a cancer. Due to various shapes and unclear boundaries of the masses, detecting breast masses is considered a challenging task. To this end, CAD system detects a lot of regions of interest including normal tissues. Thus it is important to develop the well-organized classifier. In this paper, we propose an enhanced sparse representation (SR) based classifier using Fisher discrimination dictionary learning. Experimental results show that the proposed method outperforms the existing support vector machine (SVM) classifier.

BACKGROUND This study sought to identify novel effectors and markers of localized but potentially life-threatening prostate cancer (PCa), by evaluating chromosomal copy number alterations (CNAs) in tumors from patients who underwent prostatectomy and correlating these with clinicopathologic features and outcome. METHODS CNAs in tumor DNA samples from 125 patients in the discovery cohort who underwent prostatectomy were assayed with high-resolution Affymetrix 6.0 single-nucleotide polymorphism microarrays and then analyzed using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm. RESULTS The assays revealed 20 significant regions of CNAs, 4 of them novel, and identified the target genes of 4 of the alterations. By univariate analysis, 7 CNAs were significantly associated with early PCa-specific mortality. These included gains of chromosomal regions that contain the genes MYC, ADAR, or TPD52 and losses of sequences that incorporate SERPINB5, USP10, PTEN, or TP53. On multivariate analysis, only the CNAs of PTEN (phosphatase and tensin homolog) and MYC (v-myc myelocytomatosis viral oncogene homolog) contributed additional prognostic information independent of that provided by pathologic stage, Gleason score, and initial prostate-specific antigen level. Patients whose tumors had alterations of both genes had a markedly elevated risk of PCa-specific mortality (odds ratio = 53; 95% CI = 6.92-405, P = 1 × 10−4). Analyses of 333 tumors from 3 additional distinct patient cohorts confirmed the relationship between CNAs of PTEN and MYC and lethal PCa. CONCLUSIONS This study identified new CNAs and genes that likely contribute to the pathogenesis of localized PCa and suggests that patients whose tumors have acquired CNAs of PTEN, MYC, or both have an increased risk of early PCa-specific mortality. Cancer 2013;119:2405-2412. © 2013 American Cancer Society.

CABIN1 acts as a negative regulator of p53 by keeping p53 in an inactive state on chromatin. Genotoxic stress causes rapid dissociation of CABIN1 and activation of p53. However, its molecular mechanism is still unknown. Here, we reveal the phosphorylation- and ubiquitination-dependent degradation of CABIN1 upon DNA damage, releasing p53 for transcriptional activation. The DNA-damage-signaling kinases, ATM and CHK2, phosphorylate CABIN1 and increase the degradation of CABIN1 protein. Knockdown or overexpression of these kinases influences the stability of CABIN1 protein showing that their activity is critical for degradation of CABIN1. Additionally, CABIN1 was found to undergo ubiquitin-dependent proteasomal degradation mediated by the CRL4DDB2 ubiquitin ligase complex. Both phosphorylation and ubiquitination of CABIN1 appear to be relevant for controlling the level of CABIN1 protein upon genotoxic stress.

Several germline single nucleotide polymorphisms (SNPs) have been consistently associated with prostate cancer (PCa) risk.To determine whether there is an improvement in PCa risk prediction by adding these SNPs to existing predictors of PCa.Subjects included men in the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial in whom germline DNA was available. All men had an initial negative prostate biopsy and underwent study-mandated biopsies at 2 yr and 4 yr. Predictive performance of baseline clinical parameters and/or a genetic score based on 33 established PCa risk-associated SNPs was evaluated.Area under the receiver operating characteristic curves (AUC) were used to compare different models with different predictors. Net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess changes in risk prediction by adding genetic markers.Among 1654 men, genetic score was a significant predictor of positive biopsy, even after adjusting for known clinical variables and family history (p = 3.41 × 10(-8)). The AUC for the genetic score exceeded that of any other PCa predictor at 0.59. Adding the genetic score to the best clinical model improved the AUC from 0.62 to 0.66 (p0.001), reclassified PCa risk in 33% of men (NRI: 0.10; p=0.002), resulted in higher net benefit from DCA, and decreased the number of biopsies needed to detect the same number of PCa instances. The benefit of adding the genetic score was greatest among men at intermediate risk (25th percentile to 75th percentile). Similar results were found for high-grade (Gleason score ≥ 7) PCa. A major limitation of this study was its focus on white patients only.Adding genetic markers to current clinical parameters may improve PCa risk prediction. The improvement is modest but may be helpful for better determining the need for repeat prostate biopsy. The clinical impact of these results requires further study.

This study outlines measures related to fiscal policies aimed at responding to the financial crisis according to the timing of commencement and then examines impacts of expansionary fiscal policies on macro variables so as to extract policy implications. The size of expansionary fiscal policy to respond to the financial crisis is found to total 59.8 trillion won (6.1% of GDP in 2007), among which a total of 30.5 trillion won was the increased fiscal expenditure made by the 2008 supplementary budget, the 2009 revised budget and the 2009 supplementary budget. In addition, tax reductions are found to be a total of 29.3 trillion won, mainly driven by the tax reforms in 2008 and 2009. Examining dynamic changes in macro variables caused by the temporary increase in fiscal expenditure and the tax reductions reveals that the increase effect of the real GDP growth rate brought by a temporary rise in fiscal expenditure excluding tax reduction effects turned out to be 1.1%p in 2009 and 0.3%p in 2010, compared to the period without the increase in fiscal expenditure. Meanwhile, when taking into account the effect of expansionary fiscal policies including tax reduction effects, the increase effect of real GDP turns out to be much higher. In the case of 2009, the real GDP rose additionally by 1.9%p, in which 1.1%p by the increase in fiscal expenditure and 0.8%p by tax reduction. Based on these results, the expansionary fiscal policy conducted during the financial crisis since the second half of 2008 can be seen to have played a significant role in helping the Korean economy post a higher-than-anticipated recovery pace from the economic slowdown triggered by the crisis.

Postprandial insulin plays a critical role in suppressing hepatic glucose production to maintain euglycemia in mammals. Insulin-dependent activation of protein kinase B (Akt) regulates this process, in part, by inhibiting FoxO1-dependent hepatic gluconeogenesis by direct phosphorylation and subsequent cytoplasmic exclusion. Previously, it was demonstrated that protein arginine methyltransferase 1 (PRMT1)-dependent arginine modification of FoxO1 interferes with Akt-dependent phosphorylation, both in cancer cells and in the Caenorhabditis elegans model, suggesting that this additional modification of FoxO1 might be critical in its transcriptional activity. In this study, we attempted to directly test the effect of arginine methylation of FoxO1 on hepatic glucose metabolism. The ectopic expression of PRMT1 enhanced messenger RNA levels of FoxO1 target genes in gluconeogenesis, resulting in increased glucose production from primary hepatocytes. Phosphorylation of FoxO1 at serine 253 was reduced with PRMT1 expression, without affecting the serine 473 phosphorylation of Akt. Conversely, knockdown of PRMT1 promoted an inhibition of FoxO1 activity and hepatic gluconeogenesis by enhancing the phosphorylation of FoxO1. In addition, genetic haploinsufficiency of Prmt1 reduced hepatic gluconeogenesis and blood-glucose levels in mouse models, underscoring the importance of this factor in hepatic glucose metabolism in vivo. Finally, we were able to observe an amelioration of the hyperglycemic phenotype of db/db mice with PRMT1 knockdown, showing a potential importance of this protein as a therapeutic target for the treatment of diabetes. Conclusion: Our data strongly suggest that the PRMT1-dependent regulation of FoxO1 is critical in hepatic glucose metabolism in vivo. (HEPATOLOGY 2012)

In this paper, we propose a new facial landmarks detection method based on deep learning with facial contour and facial components constraints. The proposed deep convolutional neural networks (DCNNs) for facial landmark detection consists of two deep networks: one DCNN is to detect landmarks constrained on the facial contour and the other is to detect landmarks constrained on facial components. A novel DCNN structure for the landmarks detection with facial component constraints is proposed, which branches the network at higher layers in order to capture the intricate local facial components features. Moreover, a novel learning strategy is proposed to learn the DCNN for detecting the landmarks on the facial contour by exploiting the relationship between facial contour landmarks and those on facial components. Experimental results have shown that the proposed method outperforms the state-of-the-art FLD methods.

For human identification, facial motion is useful in representing specific dynamic signature. In this paper, we present an effective spatio-temporal representation from facial motion as well as appearance by devising a 3D convolutional neural network (CNN). To maintain the intra-class invariance with limited number of training samples, a multi-task learning approach with human attributes, which are high-level semantic descriptions for identity, has been proposed. Identity-related human attributes can be leveraged to learn the 3D CNN. Comparative experiment has showed that the proposed method improves the performance of the face-based authentication system compared to conventional methods by effectively encoding facial appearance and motions with identity-related human attributes.

According to the supplementary information hypothesis in psychology, facial motion benefits the perception of identity for human. In this study, we propose a face authentication framework which exploits facial dynamics with appearance to effectively improve the authentication performance. In our face authentication scenario, users are guided to make smile expression and the identity behind smile dynamics has been utilized. In order to model the facial dynamics, the recurrent neural network with long short-term memory cells is adopted and the facial dynamics from onset to offset duration is encoded. Comparative experiment has showed that the combination of facial dynamic features with appearance features improves the accuracy of the face authentication system compared to conventional appearance features and spatio-temporal features by effectively capturing facial dynamic and appearance features.

KCNQ channels are critical determinants of neuronal excitability, thus emerging as a novel target of anti-epileptic drugs. To date, the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors, Ca2+/CaM, and protein kinase C. Here we demonstrate that methylation of KCNQ by protein arginine methyltransferase 1 (Prmt1) positively regulates KCNQ channel activity, thereby preventing neuronal hyperexcitability. Prmt1+/- mice exhibit epileptic seizures. Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP2 binding, and Prmt1 depletion lowers PIP2 affinity of KCNQ2 channels and thereby the channel activities. Consistently, exogenous PIP2 addition to Prmt1+/- neurons restores KCNQ currents and neuronal excitability to the WT level. Collectively, we propose that Prmt1-dependent facilitation of KCNQ-PIP2 interaction underlies the positive regulation of KCNQ activity by arginine methylation, which may serve as a key target for prevention of neuronal hyperexcitability and seizures. DOI: http://dx.doi.org/10.7554/eLife.17159.001, eLife digest In the brain, cells called neurons transmit information along their length in the form of electrical signals. To generate electrical signals, ions move into and out of neurons through ion channel proteins – such as the KCNQ channel – in the surface of these cells, which open and close to control the electrical response of the neuron. Abnormally intense bursts of electrical activity from many neurons at once can cause seizures such as those experienced by people with epilepsy. A significant proportion of patients do not respond to current anti-seizure medications. Openers of KCNQ channels have emerged as a potential new class of anti-epileptic drugs. A better understanding of how KCNQ channels work, and how their opening by PIP2lipid signals is regulated, could help to develop more effective therapies for epilepsy. A process called methylation controls many biological tasks by changing the structure of key proteins inside cells. Although methylation occurs throughout the brain, its role in controlling how easily neurons are activated (a property known as “excitability”) remains unclear. Kim, Jeong, Kim, Jung et al. now show that a protein called Prmt1 methylates the KCNQ channels in mice, and that this methylation is essential for suppressing seizures. Mice born without the Prmt1 protein developed epileptic seizures and the KCNQ channels in their neurons featured a reduced level of methylation. However, increasing the amount of PIP2 in these neurons restored their excitability back to normal levels. The methylation of KCNQ channel proteins increases their affinity for PIP2, which is critical to open KCNQ channels. Kim et al. propose that these “opening” controllers balance the action of known “closers” of KCNQ channels to maintain neurons in a healthy condition. In future, Kim et al. plan to investigate whether methylation affects the activity of other ion channels controlled by PIP2. Such experiments will complement a more widespread investigation into other ways in which the Prtmt1 protein may control the activity of neurons. DOI: http://dx.doi.org/10.7554/eLife.17159.002

CA) have been increasing obliteration rate of AVMs after embolization (24, 25). Pre-radiosurgery embolization allows better dose planning by decreasing the size of AVMs (24, 25). In our study, we assessed angiographic results and clinical outcomes in 11 giant AVM patients treated with Gamma knife radiosurgery (GKS) and embolization between 1994 and 2012. AIM: Giant arteriovenous malformations (i.e., those greater than 6 cm maximum diameter or volume > 33 cc) are difficult to treat and often carry higher treatment morbidity and mortality rates. In our study, we reviewed the angiographic results and clinical outcomes for 11 patients with giant arteriovenous malformations who were treated between 1994 and 2012. MATERIAL and METHODS: The patients selected included 9 males (82%) and 2 females (18%). Their presenting symptoms were hemorrhage (n=2; 18%), seizure (n=7; 64%), and headache (n=2; 12%). Nine patients were Spetzler-Martin Grade III, 2 were Spetzler-Martin Grade IV. The mean arteriovenous malformation volume was 41 cc (33-52 cc). The mean age of the patients was 45.1 years (24-57 years) and the mean radiation dose delivered to the margin of the nidus was 14.2 Gy. RESULTS: Ten patients received pre-Gamma Knife radiosurgery embolization and Gamma Knife radiosurgery, 1 patient received pre-Gamma Knife radiosurgery embolization and Gamma Knife radiosurgery twice and the interval between Gamma Knife radiosurgeries was 3 months. The complete obliteration rate following Gamma Knife radiosurgery was 36%, subtotal obliteration (> 70% decreased size of nidus) was 36%, and partial obliteration was 28%. One patient experienced a small hemorrhage after embolization. CONCLUSION: Combined embolization and Gamma Knife radiosurgery showed successful obliteration of the arteriovenous malformation nidus. The use of embolization to initially reduce nidus size followed by Gamma Knife radiosurgery improves the treatment results. Repeated Gamma Knife radiosurgery should be a treatment option when there is a small nidus remnant.

In clinical studies of breast cancer, masses appear as asymmetric densities between the left and the right breasts, which show different breast tissue structures. For classifying breast masses, most researchers have developed hand-crafted bilateral features by extracting the asymmetric information in 2-D mammograms. In digital breast tomosynthesis (DBT), which has 3D volume data, effective bilateral features are needed to detect masses. In this paper, we propose latent bilateral feature representation with 3-D multi-view deep convolutional neural network (DCNN) in the DBT reconstructed volume. The proposed DCNN is designed to discover hidden or latent bilateral feature representation of masses in self-taught learning. Experimental results show that the proposed latent bilateral feature representation outperforms conventional hand-crafted features by achieving a high area under the receiver operating characteristic curve.

PurposeThe purpose of this study is to investigate the role of eco‐oriented culture (EOC) in the relationship between stakeholder pressure (SP) and the adoption of environmental logistics practices (ELPs). It is proposed that the adoption of ELPs is influenced by SP perceived by a firm, and in turn this relationship is mediated by EOC.Design/methodology/approachMultiple theoretical perspectives are considered to explain why a firm adopts environmental strategies and how the firm overcomes environmental barriers. A structural equation modelling was utilized to empirically test the effect of SP on the adoption of ELPs, and the mediating role of EOC in its relationship, based on the survey data from Korean logistics and manufacturing companies.FindingsEmpirical analysis shows significant relationships between SP and ELPs, and the mediating role of EOC in the SP‐ELPs path. The results indicate that corporate EOC fully mediates the relationship between perceived SP and the adoption of ELPs.Research limitations/implicationsSP is able to influence the adoption of ELPs only through its efforts to build a unique environmental culture. This implies that a firm with well‐developed EOC may more effectively correspond to an environmental paradigm shift and gain an edge over its competitors.Originality/valueThis study focused on the logistics area, where the environmental concerns have increased but little research interest has been exhibited. This research attempts to empirically test the mediating role of EOC that may explain the equivocal relationship between SP and ELPs while the previous studies have focused on the direct connections between ELPs and their antecedents.

A Case Report of Herpes Zoster in Tae-eumin Improved with Yeold ahanso-tang. Seong-Tae Kim, Ae-Ryun Choi, Deok-Mo Koo Dept. of Sasang Constitutional Medicine, collage of Oriental Medicine, Daegu Haany Univ. 1. Objectives The Purpose of this case is to report that a Tae-eumin patient diagnosed as Herpes Zoster was treated with Yeoldahanso-tang and then his symptoms improved. 2. Methods We diagnosed the patient as Tae-eumin-Kanyeol-byung(太陰人肝熱病). So we treated him With Yeoldahanso-tang, and used Visual Analogue Scale(VAS) and pictures of the affected part for the assessment. 3. Results After we treated the patient with Yeoldahanso-tang, the vesicles were cleared and his symptoms improved. 4. Conclusions This case study show an efficient result of using Yeoldahanso-tang in Tae-eumin diagnosed to Herpes Zoster. Key Words : Yeoldahanso-tang, Tae-eumin, Herpes Zoster 16)∙접수일 2012년 05월 08일; 심사일 2012년 05월 22일; 승인일 2012년 06월 07일∙교신저자 : 최애련대구광역시 수성구 신천동로 136 대구한의대학교 부속 대구한방병원 사상체질의학과 교실Tel : +82-53-770-2079 Fax : +82-53-770-2189E-mail : nadia2144@naver.com∙The Society of Sasang Constitutional Medicine. All rights reser ved. This is an open acess article distributed under the terms of th e Creative Commons attribution Non-commercial License(http://creativecommons.org/licenses/by-nc/3.0/)

Recently, genome-wide association studies (GWAS) have identified over 12 single-nucleotide polymorphisms (SNPs) associated with bladder cancer risk in populations of European descent. However, effects of these SNPs in bladder cancer have not been systemically evaluated in the Chinese population. We conducted association studies of 12 SNPs in a Chinese population of 184 cases and 962 controls. These SNPs were previously identified in European GWAS and a fine mapping study. The reported risk alleles of rs798766 on TACC3 at 4p16 and rs9624880 on MYC at 8q24 were significantly associated with increased bladder cancer risk with P-values of 0.003 and 0.03, respectively. Next, we performed a meta-analysis, by combining our study with previous association studies performed in Chinese. In the meta-analysis, the reported risk allele for four SNPs were significantly associated with increased bladder cancer risk, including rs798766 on TACC3 at 4p16, rs9624880 on MYC at 8q24, rs2294008 on PSCA at 8q24, and rs2736100 on TERT at 5p15. The meta-analysis P-values for the four SNPs ranged from 0.017 to 5.52E� 05. The results from our study suggest that a sub-set of bladder cancer risk-associated SNPs identified from the European population are also associated with bladder cancer risk in the Chinese population. Additional studies with larger sample sizes are needed to further confirm our results. 2012 Wiley Periodicals, Inc.

This paper considers the potential role of organisational learning (OL) in the relationship between stakeholder pressure and the adoption of environmental logistics practices. It is believed that, as a strategic resource, OL explains how logistics firms address environmental challenges and thus attain their environmental aims. Accordingly, we employed a hierarchical moderated regression analysis using a data set of 127 Korean logistics firms. The findings suggest that high learning-oriented logistics firms are more capable of adopting specific environmental practices, which may be associated with creating sustainable competitive advantages.

A functional link is identified between Cdo and Stim1 that leads to NFATc3 activation. Stim1 is required for muscle differentiation via activation of the calcineurin/NFAT pathway. The netrin-2–mediated activation of NFATc3 is coincident with an interaction between Cdo and Stim1 via ERK-mediated phosphorylation of Stim1 at Ser-575., The promyogenic cell surface molecule Cdo is required for activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells c3 (NFATc3) induced by netrin-2 in myogenic differentiation. However, the molecular mechanism leading to NFATc3 activation is unknown. Stromal interaction molecule 1 (Stim1), an internal calcium sensor of the endoplasmic reticulum store, promotes myogenesis via activation of NFATc3. In this study we investigated the functional interaction between Cdo and Stim1 in myogenic differentiation. Overexpression and depletion of Stim1 enhanced or decreased myotube formation, respectively. Of interest, Stim1 protein levels were decreased in Cdo-deficient perinatal hindlimb muscles or primary myoblasts; this correlates with defective NFATc3 activation in Cdo−/− myoblasts upon differentiation. Forced activation of NFATc3 by overexpression of calcineurin restored differentiation of Cdo-depleted C2C12 myoblasts. Furthermore, Cdo and Stim1 formed a complex in 293T cells or in differentiating C2C12 myoblasts. The netrin-2–mediated NFATc3 activation was coincident with robust interactions between Cdo and Stim1 in myoblasts and the ERK-mediated Stim1 phosphorylation at serine 575. The serine 575 phosphorylation was enhanced in C2C12 cells upon differentiation, and the alanine substitution of serine 575 failed to restore differentiation of Stim1-depleted myoblasts. Taken together, the results indicate that cell adhesion signaling triggered by netrin-2/Cdo induces Stim1 phosphorylation at serine 575 by ERK, which promotes myoblast differentiation.

Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 3 10 28 . These four loci were MS4A3 (11q12.1; rs2298585; P 5 2.64 3 10 215 ), CLYBL (13q32; rs41281112; P 5 9.23 3 10 210 ), FUT6 (19p13.3; rs3760776; P 5 3.68 3 10 213 ) and 5q32 region (rs10515552; P 5 3.94 3 10 28 ). In addition, we also confirmed the association with the serum level o fV itB12 for the previously reportedFUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P 5 3.62 3 10 236 ). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease.

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)-replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta-analysed external SNP effect estimates - one via a weighted PCa 'risk' score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver-operating-characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.

The growth rate of piglets will be decreased and the mortality of piglets will be increased in the postpartum sow with mastitis. The aim of this study was to isolate microorganisms from milk samples found in postpartum sows with suckling piglets and to further investigate antimicrobial susceptibility against isolated bacteria. Milk samples were collected from 567 udders of 42 lactating sows and the isolated bacteria was then identified. Isolated bacteria were tested with 12 antimicrobial agents. Bacteria were isolated from 260 milk samples (64.5%). Staphylococcus spp. were the most common microorganisms (74.5%) isolated from sow milk, followed by Streptococcus hyicus (53.9%), Staphylococcus epidermis (11.8%), Staphylococcus aureus (9.8%), and Staphylococcus haemolyticus (53.9%). In the Staphylococcus spp., Streptococcus pneumoniae (5.1%) was isolated as was Streptococcus sanguinis (3.8%) and Streptococcus ovis (2.9%). Results indicated that bacteria isolated from healthy sow milk were mostly susceptible to cephalothin (88.0%), amikacin (85.3%) and cefoxitin (82.4%), but were resistant to streptomycin (10.0%), kanamycin (33.1%) and tetracycline (19.6%).

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

A clearer definition of the molecular determinants that drive the development and progression of prostate cancer (PCa) is urgently needed. Efforts to map recurrent somatic deletions in the tumor genome, especially homozygous deletions (HODs), have provided important positional information in the search for cancer-causing genes. Analyzing HODs in the tumors of 244 patients from two independent cohorts and 22 PCa xenografts using high-resolution single-nucleotide polymorphism arrays, herein we report the identification of CHD1, a chromatin remodeler, as one of the most frequently homozygously deleted genes in PCa, second only to PTEN in this regard. The HODs observed in CHD1, including deletions affecting only internal exons of CHD1, were found to completely extinguish the expression of mRNA of this gene in PCa xenografts. Loss of this chromatin remodeler in clinical specimens is significantly associated with an increased number of additional chromosomal deletions, both hemi- and homozygous, especially on 2q, 5q and 6q. Together with the deletions observed in HEK293 cells stably transfected with CHD1 small hairpin RNA, these data suggest a causal relationship. Downregulation of Chd1 in mouse prostate epithelial cells caused dramatic morphological changes indicative of increased invasiveness, but did not result in transformation. Indicating a new role of CHD1, these findings collectively suggest that distinct CHD1-associated alterations of genomic structure evolve during and are required for the development of PCa.

von-Hippel Lindau protein (pVHL) suppresses tumorigenesis in the kidney, in part through regulation of hypoxia-inducible factor alpha (HIF alpha). However, HIF has been proposed to be necessary but insufficient for renal tumorigenesis. p53 was implicated as a transcription factor that is regulated by pVHL, but the molecular mechanism by which pVHL regulates p53 on DNA damage is unknown. We demonstrated that checkpoint kinase-2 (Chk2) binds to the beta-domain of pVHL and phosphorylates Ser 111 on DNA damage. Notably, this modification enhances pVHL-mediated transactivation of p53 by recruiting p300 and Tip60 to the chromatin of p53 target gene. Further, the naturally occurring pVHL mutants pVHL-S111R and pVHL-S111C showed diminished binding to coactivators, ultimately retarding p53-mediated growth arrest and apoptosis. In this study, we determined the molecular mechanism by which pVHL transactivates p53 on DNA damage and demonstrated that p53-related pVHL subtype mutants regulate tumorigenecity in VHL diseases.

The prediction method of future events using the time histories of velocity or pressure, etc., is a useful way for controlling various air vehicles. For example, the sensors of velocity or pressure can be used to extract the time mode coefficients of eigenmode of flow field, and then the result is applied to suppress wake or drag. The velocity information is mapped to the entire flow field, so this mapping function can be used to predict the future events based on the current information. The mapping function is composed of the huge amount of weight parameters, so the efficient way of finding these parameters is needed. Here, the neural network algorithm is studied to draw a mapping function using the number and location of velocity sensors.

The fin of high speed air vehicle is composed of skins and stro ng skeletons. In the flutter analysis, the eigenmodes of a fin are used for evaluati ng the unsteady aerodynamic force and the modal approach is applied for solving the flutter equation in both time and frequency domain. Therefore, the proper eigenmodes used for a modal flutter analysis should be chosen. For the appropriate choice of eigenmodes, whe n there exist local modes of a skin in the high modes, the effects of those modes on the unsteady aerodynamic force and flutter characteristics are anlalyzed. 초 록 고속 비행체의 날개 구조물은 스킨과 튼튼한 골격으로 구성되어 있다. 플러터 해석시 날개 구조물의 고유진동모드를 이용하여 비정상공기력을 계산하고 모달접근법을 이용하여 시간영역이나 주파수 영역에서 구조물의 진동안정성을 분석하게 되므로, 사용되는 고유 진동모드는 신중하게 선정되어야 한다. 이를 위해 날개 구조물과 같이 고차에서 스킨의 국부 진동모드가 있는 경우 이러한 모드가 비정상공기력 및 플러터 특성에 미치는 영향을 분석하였다.Key Words : Eigenmode(고유모드), Local skin mode(국부스킨모드), Unsteady aerodynamic force(비정상공기력), Flutter(플러터) †2011년 7월 12일 접수 ～ 2011년 9월 27일 심사완료* 정회원, 국방과학연구소교신저자, E-mail : youngsug_shin@yahoo.com대전시 유성우체국 사서함 35-1, 1-3