SNPAnalyzer: a web-based integrated workbench for single-nucleotide polymorphism analysis

SNPAnalyzer is a software that performs four essential statistical analyses of SNPs in a common computational environment. It is composed of three main modules: (i) data manipulation, (ii) analysis and (iii) visualization. The data manipulation module is responsible for data input and output, and handles genotype, phenotype and genetic distance data. To ensure user convenience, the data format is simple. The analysis module performs statistical calculations and consists of four subcomponents: (i) Hardy–Weinberg equilibrium, (ii) Haplotype Estimation, (iii) linkage disequilibrium (LD) and (iv) quantitative trait locus analysis. The main feature of the analysis module is multiple implementations of different algorithms and indices for haplotype estimation and for LD analysis. This enables users to compare separate results generated by different algorithms, which help to avoid biased results acquired by applying a single statistical algorithm. The performance of all implemented algorithms has been validated using experimentally proven datasets. The visualization module presents most of the analyzed results as figures, rather than as simple text, which aids in the intuitive understanding of complex data. The SNPAnalyzer has been developed using C and C++ and is available at

Hysteresis and Averaging the Forecasts of Exchange Rates

Real exchange rates evolve independently of money supply shocks in accordance with long-run monetary neutrality. However, the prolonged disequilibrium errors of the Korean won―US dollar real exchange rates in the 1990s prior to the Asian financial crisis and the hike subsequent to the crisis indicate hysteresis of the real exchange rates. The hysteresis may originate from two sources, namely, the instability of the equilibrium relationship and the regime-dependent persistence of real exchange rates. The current paper provides a statistical evaluation of the hysteresis in the won―dollar real exchange rates using forecast combination. The behavior of asymmetric mean reversion and regime-dependent persistence dominates the parameter instability in real exchange rates. A substantial improvement in predictive accuracy is observed as the forecasting model incorporates the hysteresis effect.This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF- 2010-330-B00060)

Vacancy driven surface disorder catalyzes anisotropic evaporation of ZnO (0001) polar surface

The evaporation and crystal growth rates of ZnO are highly anisotropic and are fastest on the Zn-terminated ZnO (0001) polar surface. Herein, we study this behavior by direct atomic-scale observations and simulations of the dynamic processes of the ZnO (0001) polar surface during evaporation. The evaporation of the (0001) polar surface is accelerated dramatically at around 300 °C with the spontaneous formation of a few nanometer-thick quasi-liquid layer. This structurally disordered and chemically Zn-deficient quasi-liquid is derived from the formation and inward diffusion of Zn vacancies that stabilize the (0001) polar surface. The quasi-liquid controls the dissociative evaporation of ZnO with establishing steady state reactions with Zn and O$_{2}$ vapors and the underlying ZnO crystal; while the quasi-liquid catalyzes the disordering of ZnO lattice by injecting Zn vacancies, it facilitates the desorption of O$_{2}$ molecules. This study reveals that the polarity-driven surface disorder is the key structural feature driving the fast anisotropic evaporation and crystal growth of ZnO nanostructures along the [0001] direction

Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma

Purpose4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model.MethodsBALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, IgG1, and IgG2a levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated.ResultsIn mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific IgG1 levels and increased serum IgG2a level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue.ConclusionAdministration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma

Beclin 1 functions as a negative modulator of MLKL oligomerisation by integrating into the necrosome complex

Necroptosis is a form of regulated cell death caused by formation of the necrosome complex. However, the factors modulating this process and the systemic pathophysiological effects of necroptosis are yet to be understood. Here, we identified that Beclin 1 functions as an anti-necroptosis factor by being recruited into the necrosome complex upon treatment with TNF alpha, Smac mimetic, and pan-caspase inhibitor and by repressing MLKL oligomerisation, thus preventing the disruption of the plasma membrane. Cells ablated or knocked-out for Beclin 1 become sensitised to necroptosis in an autophagy-independent manner without affecting the necrosome formation itself. Interestingly, the recruitment of Beclin 1 into the necrosome complex is dependent on the activation and phosphorylation of MLKL. Biochemically, the coiled-coil domain (CCD) of Beclin 1 binds to the CCD of MLKL, which restrains the oligomerisation of phosphorylated MLKL. Finally, Beclin 1 depletion was found to promote necroptosis in leukaemia cells and enhance regression of xenografted-tumour upon treatment with Smac mimetics and caspase inhibitors. These results suggest that Beclin 1 functions as a negative regulator in the execution of necroptosis by suppressing MLKL oligomerisation

RAMP: response-aware multi-task learning with contrastive regularization for cancer drug response prediction

The accurate prediction of cancer drug sensitivity according to the multiomics profiles of individual patients is crucial for precision cancer medicine. However, the development of prediction models has been challenged by the complex crosstalk of input features and the resistance-dominant drug response information contained in public databases. In this study, we propose a novel multidrug response prediction framework, response-aware multitask prediction (RAMP), via a Bayesian neural network and restrict it by soft-supervised contrastive regularization. To utilize network embedding vectors as representation learning features for heterogeneous networks, we harness response-aware negative sampling, which applies cell line???drug response information to the training of network embeddings. RAMP overcomes the prediction accuracy limitation induced by the imbalance of trained response data based on the comprehensive selection and utilization of drug response features. When trained on the Genomics of Drug Sensitivity in Cancer dataset, RAMP achieved an area under the receiver operating characteristic curve > 89%, an area under the precision-recall curve > 59% and an F1 score > 52% and outperformed previously developed methods on both balanced and imbalanced datasets. Furthermore, RAMP predicted many missing drug responses that were not included in the public databases. Our results showed that RAMP will be suitable for the high-throughput prediction of cancer drug sensitivity and will be useful for guiding cancer drug selection processes. The Python implementation for RAMP is available at https://github.com/hvcl/RAMP

Changes in the Prevalence of Childhood Asthma in Seoul from 1995 to 2008 and Its Risk Factors

PURPOSE: To investigate the prevalence of asthma and determine its risk factors in elementary school students in Seoul. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 4,731 elementary school students from five areas in Seoul between April and October, 2008. RESULTS: In elementary school children, the lifetime and recent 12-month prevalence of wheezing were 11.7% and 5.6%, respectively. The lifetime prevalence of asthma diagnosis was 7.9%, and the recent 12-month prevalence of asthma treatment was 2.7%. Male sex (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.36-2.66), history of atopic dermatitis (AD) (aOR, 2.76; 95% CI, 1.98-3.84), history of allergic rhinitis (AR) (aOR, 3.71; 95% CI, 2.61-5.26), history of bronchiolitis before 2 years of age (aOR, 2.06; 95% CI, 1.39-3.07), use of antibiotics during infancy for >3 days (aOR, 1.88; 95% CI, 1.35-2.62), parental history of asthma (aOR, 2.83; 95% CI, 1.52-5.27), exposure to household molds during infancy (aOR, 1.84; 95% CI, 1.18-2.89), and the development or aggravation of asthma symptoms within 6 months after moving to a new house (aOR, 11.76; 95% CI, 5.35-25.86) were the independent risk factors for wheezing within 12 months. CONCLUSIONS: The prevalence of wheezing and asthma in elementary school students in 2008 was similar to that in the past decade. Male sex, history of AD, history of AR, history of bronchiolitis before 2 years of age, parental asthma, use of antibiotics during infancy, exposure to molds in the house during infancy, and development or aggravation of asthma symptoms within 6 months after moving to a new house, could be risk factors for wheezing within 12 months.ope

Vacancy driven surface disorder catalyzes anisotropic evaporation of ZnO (0001) polar surface

Evaporation and crystal growth occur at different rates on different surfaces. Here authors show dissociative evaporation from ZnO (0001) polar surfaces is accelerated by the formation of a Zn-deficient quasi-liquid layer derived from the formation and inward diffusion of Zn vacancies that stabilize the polar surface. The evaporation and crystal growth rates of ZnO are highly anisotropic and are fastest on the Zn-terminated ZnO (0001) polar surface. Herein, we study this behavior by direct atomic-scale observations and simulations of the dynamic processes of the ZnO (0001) polar surface during evaporation. The evaporation of the (0001) polar surface is accelerated dramatically at around 300 degrees C with the spontaneous formation of a few nanometer-thick quasi-liquid layer. This structurally disordered and chemically Zn-deficient quasi-liquid is derived from the formation and inward diffusion of Zn vacancies that stabilize the (0001) polar surface. The quasi-liquid controls the dissociative evaporation of ZnO with establishing steady state reactions with Zn and O-2 vapors and the underlying ZnO crystal; while the quasi-liquid catalyzes the disordering of ZnO lattice by injecting Zn vacancies, it facilitates the desorption of O-2 molecules. This study reveals that the polarity-driven surface disorder is the key structural feature driving the fast anisotropic evaporation and crystal growth of ZnO nanostructures along the [0001] direction