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To celebrate Prof. Jonathan Sessler's 65th birthday, this Backstory on his life and career follows his path to success. We begin with his early days as an independent researcher and then show how his Texas-sized chemistry has molded over the years with the help of the “Crown and Anchor approach.” We hope this article will inspire readers to pursue their own academic endeavors and remember Jonathan's guiding motto: “people first, science second, money third.”

We report on the search for weakly interacting massive particle (WIMP) dark matter candidates in the galactic halo that interact with sodium and iodine nuclei in the COSINE-100 experiment and produce energetic electrons that accompany recoil nuclei via the the Migdal effect. The WIMP mass sensitivity of previous COSINE-100 searches that relied on the detection of ionization signals produced by target nuclei recoiling from elastic WIMP-nucleus scattering was restricted to WIMP masses above $\sim$5 GeV/$c^2$ by the detectors' 1 keVee energy-electron-equivalent threshold. The search reported here looks for recoil signals enhanced by the Migdal electrons that are ejected during the scattering process. This is particularly effective for the detection of low-mass WIMP scattering from the crystals' sodium nuclei in which a relatively larger fraction of the WIMP's energy is transferred to the nucleus recoil energy and the excitation of its orbital electrons. In this analysis, the low-mass WIMP search window of the COSINE-100 experiment is extended to WIMP mass down to 200 MeV/$c^2$. The low-mass WIMP sensitivity will be further improved by lowering the analysis threshold based on a multivariable analysis technique. We consider the influence of these improvements and recent developments in detector performance to re-evaluate sensitivities for the future COSINE-200 experiment. With a 0.2 keVee analysis threshold and high light-yield NaI(Tl) detectors (22 photoelectrons/keVee), the COSINE-200 experiment can explore low-mass WIMPs down to 20 MeV/$c^2$ and probe previously unexplored regions of parameter space., Comment: 10 pages, 8 figures

Kiyoung Lee,1,2 Ie Byung Park,1,2 Seung Hee Yu,2 Soo-Kyung Kim,3 So Hun Kim,4 Da Hea Seo,4 Seongbin Hong,4 Ja Young Jeon,5 Dae Jung Kim,5 Soo Wan Kim,6 Cheol Soo Choi,1,2Dae Ho Lee1,21Department of Internal Medicine, Gachon University College of Medicine, Incheon, Republic of Korea; 2Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; 4Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea; 5Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea; 6Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaAim: We aimed to evaluate the clinical utility of blood ketone measurement and to test the performance of the diagnostic criteria for diabetic ketoacidosis (DKA) issued by the American Diabetes Association, the Joint British Diabetes Societies, and the American Association of Clinical Endocrinologists and the American College of Endocrinology.Methods: This retrospective analysis included 278 patients with suspected DKA who were hospitalized at 4 university hospitals and aged ≥16years with a blood glucose level of >200mg/dL and a blood ketone level of ≥1.0mmol/L as well as other biochemical data. The patients were categorized into four subgroups (ketosis, typical DKA, atypical DKA, and DKA + lactic acidosis). Atypical DKA in each analysis was defined by our supplementary criteria if the biochemical data did not meet each set of diagnostic criteria from the aforementioned societies.Results: Blood ketone levels in patients with diabetic ketosis and those with DKA varied widely, 1.05–5.13mmol/L and 1.02–15.9mmol/L, respectively. Additionally, there were significant discrepancies between the guidelines in the diagnosis of DKA. Thus, the proportion of patients with atypical DKA ranged from 16.5% to 42.4%. Notably, the in-hospital mortality was comparable between patients with typical and atypical DKA, with a very high mortality in patients with DKA + lactic acidosis (blood lactate >5mmol/L).Conclusions: Our results showed that considering variable presentations of DKA, blood ketone data need to be interpreted cautiously along with other biochemical data and suggested that a new system is required to better characterize DKA.Keywords: Diabetic ketoacidosis, ketone bodies, diagnosis, lactic acidosis, acid base imbalance

Yong Suk Jo,1 Sung Kyoung Kim,2 Seoung Ju Park,3 Soo-Jung Um,4 Yong-Bum Park,5 Ki Suck Jung,6 Deog Kyeom Kim,7 Kwang Ha Yoo8 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Division of Pulmonology, St Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; 4Department of Internal Medicine, Division of Pulmonology, Dong-A University Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 6Department of Internal Medicine, Division of Pulmonary Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 7Department of Internal Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 8Department of Internal Medicine, Division of Pulmonary and Allergy Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: FEV1 is the gold standard for assessment of COPD. We compared efficacy of FEV1, inspiratory capacity (IC), and IC to total lung capacity (TLC) ratio in the evaluation of COPD and their association with exacerbation.Methods: We analyzed the association of dyspnea severity, quality of life status, and lung function with lung function measurements and exacerbation risk in 982 patients enrolled in the Korea COPD Subgroup Registry and Subtype Research study. Exacerbation and longitudinal lung function change were evaluated in 3 years’ follow-up.Results: The FEV1, IC, and IC to TLC ratio showed comparable negative correlations with dyspnea severity and quality of life status, and positive correlation with exercise capacity. In patients with >2 events/year, annual rate of change in FEV1 and IC tended to decline more rapidly in those with FEV150% (-14.46±19.40 mL/year vs 12.29±9.24 mL/year, P=0.213; -4.75±17.28 mL/year vs -78.05±34.16 mL/year, P=0.056 for FEV1 and IC, respectively), without significance.Conclusion: Longitudinal changes in IC and FEV1 were not significantly associated with exacerbation risk. Keywords: COPD, exacerbation, FEV1, inspiratory capacity

Background: The molecular adsorbent recirculating system (MARS) is an artificial liver support system that supports excretory liver function in patients with liver failure and is used as bridge therapy for patients waiting for liver transplantation. However, MARS may increase the tendency for bleeding. The objective of this study was to determine how MARS affects coagulopathy and identify specific factors associated with bleeding complications. Methods: We retrospectively analyzed data from 15 patients undergoing a total of 36 MARS sessions. Complete blood count, coagulation profiles, and blood chemistry values were compared before and after MARS. To identify pre-MARS factors associated with increased bleeding after MARS, we divided patients into bleeder and non-bleeder groups and compared their pre-MARS laboratory values. Results: MARS significantly reduced bilirubin and creatinine levels. MARS also increased prothrombin time and activated partial thromboplastin time and reduced fibrinogen, thus negatively impacting coagulation. Seven patients had bleeding complications and were classified into the bleeder group. Pre MARS hemoglobin was significantly lower in the bleeder group (8.3 mg/dl) than in the non bleeder group (10.0 mg/dl, P=0.014). When comparing the upper and lower 25 % of MARS sessions based on the hemoglobin reduction rate, hemoglobin reduction was significantly greater in MARS sessions involving patients with low pre MARS hemoglobin and factor V (P=0.008 and P=0.032, respectively). Conclusions: MARS appears to alter coagulation related factors and increase the risk of bleeding complications. However, individual differences among patients were large, and various factors, such as low hemoglobin and factor V levels, appear to be involved.

Madhusmita Dhupal,1,2 Jae-Min Oh,3 Dipti Ranjan Tripathy,4 Soo-Ki Kim,2 Sang Baek Koh,5 Kyu-Sang Park6 1Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea; 2Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea; 3Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Republic of Korea; 4Department of Neurology, Gauhati Medical College and Hospital, Gauhati, India; 5Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea; 6Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea Background: Titanium dioxide nanoparticles (TiO2 NPs) represent a scientific breakthrough in the areas of biological and medicinal applications. Interaction of TiO2 NPs with components of innate immune system remains elusive. Aim: This study explored in vitro immunotoxicity of murine macrophage RAW 264.7 to TiO2 NPs (20 nm, negative charge) and its underlying molecular mechanism by way of immunoredox profiling. Materials and methods: In this study, chemically synthesized BSA-functionalized TiO2 NPs (20 nm, negative charge) were characterized and immunotoxicity was investigated on RAW 264.7 cells. Results: We found that reactive oxygen species levels significantly increased with increasing nitric oxide production, whereas depleting endogenous antioxidant super oxide dismutase as well as nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels. Furthermore, NPs exposure increased the expression of apoptotic factors such as BAX, BIM, and PUMA with disruption of mitochondrial membrane potential (ΔΨm) that lead to decrease in immunocytes. Molecular immune profiling revealed the activation of multiple toll-like receptors (TLRs) 4/9/12/13 simultaneously with the phosphorylation of p-p38MAPK and p-SAPK/c-Jun N-terminal kinase (JNK) compared to untreated control. Conclusion: Collectively, this study shows that the molecular nature of TiO2SA20(-) NP-induced immunotoxicity in RAW 264.7 macrophage is simultaneous induction of immunocyte apoptosis and multiple TLRs signaling through oxidative stress-dependent SAPK/JNK and p38 mitogen-associated protein kinase activation. This is the first study to address newer molecular mechanism of TiO2SA20(-) NP-induced immunotoxicity. Keywords: titanium dioxide, toll-like receptors, MAPK pathways, apoptosis, nanoparticles, oxidative stress

Kyung Hoon Kim,1 Hye Seon Kang,2 Ju Sang Kim,3 Hyoung Kyu Yoon,4 Sung Kyoung Kim,5 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 3Division of Pulmonary Medicine, Department of Internal Medicine, Incheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 5Division of Pulmonary Medicine, Department of Internal Medicine, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea Introduction: Roflumilast is a phosphodiesterase-4 inhibitor, which can decrease exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, adverse effects are a major barrier to medication use, and little is known regarding the risk factors for discontinuation of roflumilast in COPD patients.Method: A search of the clinical databases identified all patients who were prescribed roflumilast between December 2012 and April 2015 in the four hospitals of The Catholic University of Korea, Korea. The study subjects were limited to patients who had taken 500 µg of roflumilast. We studied the factors associated with drug discontinuation and drug adverse events by univariate and multivariate analyses.Results: Among 154 eligible patients, 54 (35.1%) discontinued their roflumilast prescription. Most patients were elderly, male, current or former smokers, and had moderate-to-severe airflow limitation. Low–body mass index (BMI) patients were more likely to undergo drug discontinuation (1-unit decrease in BMI: odds ratio [OR] =1.165, p=0.006; BMI

Myoung Jin Oh,1 Young Hoon Cho,1 So Yoon Cha,1 Eun Ok Lee,2 Jin Wook Kim,2 Sun Ki Kim,2 Chang Seo Park1 1Department of Chemical and Biochemical Engineering, Dongguk University, Chung-gu, Seoul, 2LCS Biotech, Gwonseon-gu, Suwon-si, Gyeonggi-do, Republic of Korea Abstract: Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer. Keywords: fatty acid, chain length, phytoceramide, skin barrier, natural oil

Sun Kyung Kim, Myonghwa Park Education and Research Center for Evidence Based Nursing Knowledge, College of Nursing, Chungnam National University, Daejeon, Republicof Korea Background: Person-centered care is a holistic and integrative approach designed to maintain well-being and quality of life for people with dementia, and it includes the elements of care, the individual, the carers, and the family.Aim: A systematic literature review and meta-analysis were undertaken to investigate the effectiveness of person-centered care for people with dementia.Methods: Literature searches were undertaken using six databases including Medline, EMBASE, CINAHL, PsycINFO, Cochrane Database, and KoreaMed using the following keywords: cognition disorder, dementia, person-centered care, patient-centered care, client-centered care, relationship-centered care, and dementia care. The searches were limited to interventional studies written in English and Korean and included randomized controlled studies and noncontrolled studies for people with dementia living in any setting.Results: Nineteen interventional studies, including 3,985 participants, were identified. Of these, 17 studies were from long-term care facilities and two studies were from homecare settings. The pooled data from randomized controlled studies favored person-centered care in reducing agitation, neuropsychiatric symptoms, and depression and improving the quality of life. Subgroup analysis identified greater effectiveness of person-centered care when implemented for people with less severe dementia. For agitation, short-term interventions had a greater effect (standardized mean difference [SMD]: -0.434; 95% conference interval [CI]: -0.701 to -0.166) than long-term interventions (SMD: -0.098; 95% CI: -0.190 to 0.007). Individualized activities resulted in a significantly greater beneficial effect than standard care (SMD: 0.513; 95% CI: -0.994 to -0.032). However, long-term, staff education, and cultural change interventions had a greater effect on improving the quality of life for people with dementia (SMD: 0.191; 95% CI: 0.079 to 0.302).Conclusion: This systematic review and meta-analysis provided evidence for person-centered care in clinical practice for people with dementia. Person-centered care interventions were shown to reduce agitation, neuropsychiatric symptoms, and depression and to improve the quality of life. Person-centered care interventions can effectively reduce agitation for a short term using intensive and activity-based intervention. However, an educational strategy that promotes learning and skill development of internal care staff is needed to enhance patient’s quality of life and to ensure the sustainability of the effects of behavioral problems. The feasibility and effectiveness of the intervention, the severity of patient disease, and intervention type and duration should be considered as part of an intervention design. Keywords: dementia, meta-analysis, patient-centered care, person-centered care, neuropsychiatric symptoms, systematic review

Chan Ho Lee, Eun Kyung Goag, Su Hwan Lee, Kyung Soo Chung, Ji Ye Jung, Moo Suk Park, Young Sam Kim, Se Kyu Kim, Joon Chang, Joo Han Song Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. Materials and methods: Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40years with serum ferritin levels and spirometric data were selected for this study. Results: The mean age was 56.5years for men (43%) and 56.9years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1second and forced expiratory volume in 1second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. Conclusion: Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher levels of serum ferritin were associated with enhanced spirometric results in a representative sample of the general Korean adult population. Future prospective studies will be needed to clarify the causality between serum ferritin and lung functions and their role in COPD morbidity. Keywords: airway obstruction, ferritin, smoking

Kyung Soo Chung,1,2 Ji Ye Jung,1,2 Moo Suk Park,1,2 Young Sam Kim,1,2 Se Kyu Kim,1,2 Joon Chang,1,2 Joo Han Song1,2 1Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6seconds (FEV6) has been proposed as an alternative to FEV1/forced vital capacity (FVC) for detecting airway obstruction. A fixed cut-off value for FEV1/FEV6 in a Korean population is lacking. We investigated a fixed cut-off for FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction.Materials and methods: We used data obtained in the 5 years of the Fifth and Sixth Korean National Health and Nutrition Examination Survey. A total of 14,978 participants aged ≥40years who underwent spirometry adequately were the study cohort. “Airway obstruction” was a fixed cut-off FEV1/FVC

Joo Kyung Kim,1 Soo Haeng Lee,1 Bho Hyeon Lee,1 Chang Youl Lee,2 Do Jin Kim,3 Kyung Hoon Min,4 Sung Kyoung Kim,5 Kwang Ha Yoo,6 Ki-Suck Jung,1 Yong Il Hwang1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St Vincent’s Hospital, The Catholic University of Korea, Suwon, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea Introduction: COPD exacerbation negatively impacts the patient’s quality of life and lung function, increases mortality, and increases socioeconomic costs. In a real-world setting, the majority of patients with COPD have mild-to-moderate airflow limitation. Therefore, it is important to evaluate COPD exacerbation in patients with mild-to-moderate airflow limitation, although most studies have focused on the patients with moderate or severe COPD. The objective of this study was to evaluate factors associated with COPD exacerbation in patients with mild-to-moderate airflow limitation. Methods: Patients registered in the Korean COPD Subtype Study cohort were recruited from 37 tertiary referral hospitals in Korea. We obtained their clinical data including demographic characteristics, past medical history, and comorbidities from medical records. Patients were required to visit the hospital to document their COPD status using self-administered questionnaires every 6 months. Results: A total of 570 patients with mild-to-moderate airflow limitation were enrolled. During the first year of follow-up, 30.5% patients experienced acute exacerbation, with exacerbations being more common in patients with poor lung function. Assessed factors associated with COPD exacerbation included COPD assessment test scores, modified Medical Research Council dyspnea assessment test scores, St George’s Respiratory Questionnaire for COPD scores, a previous history of exacerbation, and histories of pneumonia and allergic rhinitis. Logistic regression tests revealed St George’s Respiratory Questionnaire for COPD scores (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00–1.04; P=0.034), a previous history of exacerbation (OR, 3.12; 95% CI, 1.35–7.23; P=0.008), and a history of pneumonia (OR, 1.85; 95% CI, 1.06–3.25; P=0.032) as risk factors for COPD exacerbation. Conclusion: Our results suggest that COPD exacerbation in patients with mild-to-moderate airflow limitation is associated with the patient’s quality of life, previous history of exacerbation, and history of pneumonia. Keywords: COPD, exacerbation, risk factors

In recent years, increased HPC resources and performance has enabled significant advances in the quality and reliability of non-linear MHD simulations of tokamak instabilities. In the domain of Edge-Localised-Modes, validation of the JOREK code has been achieved by addressing various characteristics of this instability. The necessity to control ELMs, in order to reduce divertor heat-fluxes in ITER, while maximising the flushing of high-Z impurities, motivates a thorough validation of the numerical and physical model, so that reliable predictions can be provided for future devices. With increasing concordance between simulation results and experimental observations, non-linear MHD is starting to provide insight into several open questions about ELM physics and ELM-control techniques, in time for the development and exploitation of ITER operation., 27th IAEA Fusion Energy Conference

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

This study was performed to identify the sexual orientation in association with brain activation pattern in response to visual erotic stimuli in female-to-male (FtM) transsexuals by using functional magnetic resonance imaging (fMRI). Eleven FtM transsexuals who have had sex-reassignment surgery to alter their natal bodies with the gender-identity disorder were participated. Brain activation for sexual orientation was induced by visual stimuli with female and male erotic nude pictures compared with emotionally-neutral pictures. During viewing the erotic female pictures, the brain areas dominantly activated consist of the superior frontal gyrus, supplementary motor area, anterior/median cingulate gyri and hypothalamus, whereas during viewing male pictures, the brain areas with predominant activities were the middle frontal gyrus, precentral gyrus, middle temporal gyrus, fusiform gyrus, angular gyrus, precuneus, superior/middle occipital gyri, cerebellar cortex and vermis. These findings demonstrate that the brain activation patterns induced by viewing male or female erotic pictures show some correlation to the sexual orientation opposite to the genetic sex in FtM transsexuals. This study would be helpful to understand the neural mechanism associated with visual sexual arousal in patients with gender disorder.

Hee Jin Park, Ah Young Leem, Sang Hoon Lee, Ju Han Song, Moo Suk Park, Young Sam Kim, Se Kyu Kim, Joon Chang, Kyung Soo Chung Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Institute of Chest Disease, Yonsei University College of Medicine, Seoul, South Korea Background: Comorbidities can occur frequently in patients with chronic obstructive pulmonary disease (COPD) and can influence mortality and morbidity independently. It is increasingly recognized that many patients with COPD have comorbidities that have a major impact on their quality of life and survival. Therefore, we investigated the prevalence of comorbidities in Korean COPD populations. Methods: We used data obtained in the 6 years of the fourth and fifth Korean National Health and Nutrition Examination Survey (KNHANES) IV and V. Among 50,405 subjects, 16,151 subjects aged ≥40 years who performed spirometry adequately were included in this study. Airway obstruction was defined as forced expiratory volume in 1 second/forced vital capacity

Ah Young Leem, Se Kyu Kim, Joon Chang, Young Ae Kang, Young Sam Kim, Moo Suk Park, Song Yee Kim, Eun Young Kim, Kyung Soo Chung, Ji Ye Jung Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Heavy metal exposure may contribute to inflammation in the lungs via increased oxidative stress, resulting in tissue destruction and obstructive lung function (OLF). In this study, we evaluated the relationship between lead and cadmium levels in blood, and lung function in the Korean population.Methods: Pooled cross-sectional data from 5,972 subjects who participated in the Korean National Health and Nutrition Examination Survey 2008–2012 were used for this study. OLF was defined as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)

Moo-Yong Rhee,1 Sang Hong Baek,2 Weon Kim,3 Chang Gyu Park,4 Seung Woo Park,5 Byung-Hee Oh,6 Sang-Hyun Kim,7 Jae-Joong Kim,8 Joon-Han Shin,9 Byung-Su Yoo,10 Se-Joong Rim,11 Jong-Won Ha,12 Joon Hyung Doh,13Youngkeun Ahn,14 Jei Keon Chae,15 Jeong Bae Park,16 Soon-Kil Kim,17 Cheol Ho Kim18 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, 2Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 3Cardiovascular Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 4Division of Cardiology, Guro Hospital, Korea University College of Medicine, Seoul, 5Division of Cardiology, Samsung Medical Center, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, 8Division of Cardiology, Asan Medical Center, Seoul, 9Division of Cardiology, Ajou University Hospital, Suwon, 10Division of Cardiology, Wonju Severance Christian Hospital, Wonju, 11Division of Cardiology, GangNam Severance Hospital, Seoul, 12Division of Cardiology, Severance Hospital, Seoul, 13Division of Cardiology, Inje University Ilsan Hospital, Goyang, 14Department of Cardiology, Chonnam National University Hospital, Gwangju, 15Chonbuk National University Hospital, Jeonju, 16Department of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, 17Department of Cardiology, Hanyang University Guri Hospital, Guri, 18Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60mg.Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90mmHg with 4 weeks of once-daily fimasartan 60mg were randomly assigned to receive either once-daily fimasartan 60mg/HCTZ 12.5mg or fimasartan 60mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60mg/HCTZ 12.5mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60mg to fimasartan 120 mg if siDBP was ≥90mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week4 (6.88±8.10mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week8 (8.67±9.39mmHg vs 5.02±8.27mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week4, 10.50±13.76mmHg vs 5.75±12.18mmHg, P=0.0069 and, at Week8, 13.45±15.15mmHg vs 6.84±13.57mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10mmHg from baseline and/or a mean siDBP&nbsp

Cheol-Su Kim,1,* Hai-Duong Nguyen,1,* Rosa Mistica Ignacio,2 Jae-Hyun Kim,1Hyeon-Cheol Cho,1Eun Ho Maeng,3 Yu-Ri Kim,4 Meyoung-Kon Kim,4 Bae-Keun Park,5 Soo-Ki Kim1,5 1Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 2Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 3Healthcare Laboratory, Medical Device Evaluation Team, Korea Testing and Research Institute, Gimpo-si, Gyeonggi-do, Republic of Korea; 4Department of Biochemistry and Molecular Biology, Medical School and College, Korea University, Seoul, Republic of Korea; 5Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea *These authors contributed equally to this work Abstract: While zinc oxide (ZnO) nanoparticles (NPs) have been recognized to have promising applications in biomedicine, their immunotoxicity has been inconsistent and even contradictory. To address this issue, we investigated whether ZnO NPs with different size (20 or 100 nm) and electrostatic charge (positive or negative) would cause immunotoxicity in vitro and in vivo, and explored their underlying molecular mechanism. Using Raw 264.7 cell line, we examined the immunotoxicity mechanism of ZnO NPs as cell viability. We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells. Specifically, the positively charged ZnO NPs exerted higher cytotoxicity than the negatively charged ones. Next, to gauge systemic immunotoxicity, we assessed immune responses of C57BL/6 mice after oral administration of 750 mg/kg/day dose of ZnO NPs for 2 weeks. In parallel, ZnO NPs did not alter the cell-mediated immune response in mice but suppressed innate immunity such as natural killer cell activity. The CD4+/CD8+ ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs. Accordingly, nitric oxide production from splenocyte culture supernatant in ZnO NP-fed mice was lower than control. Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1Β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed. Collectively, our results indicate that different sized and charged ZnO NPs would cause in vitro and in vivo immunotoxicity, of which nature is an immunosuppression. Keywords: immunosuppression, cytokine, ZnO, immune response, cytotoxicity, innate immunity

Yu-Ri Kim,1,* Seung-Young Lee,3,* Eun Jeong Lee,1 Sung Ha Park,4 Nak-won Seong,3 Heung-Sik Seo,3 Sung-Sup Shin,3 Seon-Ju Kim,3 Eun-Ho Meang,3 Myeong-Kyu Park,3 Min-Seok Kim,3 Cheol-Su Kim,5 Soo-Ki Kim,5 Sang Wook Son,2 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo AAn,9 Beom-Jun Lee,10 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, 2Department of Dermatology, Korea University Medical School and College, 3General Toxicology Team, Korea Testing and Research Institute, Seoul, Republic of Korea; 4Department of Biochemistry, University of Bath, Bath, UK; 5Department of Microbiology, Wonju College of Medicine, Yonsei University, Gangwon, 6Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, 7Nonclinical Research Institute, Chemon Inc, Gyeonggi, 8Toxicological Research Center, Hoseo University, Chungnam, 9Department of Bionanotechnology, Gachon University, Gyeonggi, 10College of Veterinary Medicine, Chungbuk National University, Chungbuk, Republic of Korea *These authors contributed equally to this work Abstract: This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2EN,20(-) (20nm) or SiO2EN,100(-) (100nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000mg/kg, and middle and low doses were set at 1,000and 500mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN,20(-) (20nm) or SiO2EN,100(-) (100nm) was observed. The results of this study indicate that the NOAEL for SiO2EN,20(-) and SiO2EN,100(-) would most likely be 2,000mg/kg, and no target organ was identified in rats of either sex. Keywords: silica nanoparticles, particle size, 90-day oral dose toxicity, no observed adverse effect level

Jae-Hyun Kim,1,* Cheol-Su Kim,1,* Rosa Mistica Coles Ignacio,2,* Dong-Heui Kim,2 Ma Easter Joy Sajo,2 Eun Ho Maeng,3 Xu-Feng Qi,4 Seong-Eun Park,5 Yu-Ri Kim,7 Meyoung-Kon Kim,7 Kyu-Jae Lee,2 Soo-Ki Kim1,5,6 1Department of Microbiology, 2Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 3Healthcare Laboratory, Medical Device Evaluation, Korea Testing and Research Institute, Wonju-si, Gangwon-do, Republic of Korea; 4Key Laboratory for Regenerative Medicine of Ministry of Education and Department of Developmental and Regenerative Biology, School of Life Science and Technology, Ji Nan University, Guangzhou, People’s Republic of China; 5Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea; 6Institute of Biomaterials, Yonsei University, Wonju Campus, Wonju-si, Gangwon-do, Republic of Korea; 7Department of Biochemistry and Molecular Biology, Medical School and College, Korea University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Silicon dioxide (SiO2) nanoparticles (NPs) have been widely used in the biomedical field, such as in drug delivery and gene therapy. However, little is known about the biological effects and potential hazards of SiO2. Herein, the colloidal SiO2 NPs with two different sizes (20 nm and 100 nm) and different charges (L-arginine modified: SiO2EN20[R], SiO2EN100[R]; and negative: SiO2EN20[-], SiO2EN100[-]) were orally administered (750 mg/kg/day) in female C57BL/6 mice for 14 days. Assessments of immunotoxicity include hematology profiling, reactive oxygen species generation and their antioxidant effect, stimulation assays for B- and T-lymphocytes, the activity of natural killer (NK) cells, and cytokine profiling. In vitro toxicity was also investigated in the RAW 264.7 cell line. When the cellularity of mouse spleen was evaluated, there was an overall decrease in the proliferation of B- and T-cells for all the groups fed with SiO2 NPs. Specifically, the SiO2EN20(-) NPs showed the most pronounced reduction. In addition, the nitric oxide production and NK cell activity in SiO2 NP-fed mice were significantly suppressed. Moreover, there was a decrease in the serum concentration of inflammatory cytokines such as interleukin (IL)-1Β, IL-12 (p70), IL-6, tumor necrosis factor-α, and interferon-γ. To elucidate the cytotoxicity mechanism of SiO2 in vivo, an in vitro study using the RAW 264.7 cell line was performed. Both the size and charge of SiO2 using murine macrophage RAW 264.7 cells decreased cell viability dose-dependently. Collectively, our data indicate that different sized and charged SiO2 NPs would cause differential immunotoxicity. Interestingly, the small-sized and negatively charged SiO2 NPs showed the most potent in vivo immunotoxicity by way of suppressing the proliferation of lymphocytes, depressing the killing activity of NK cells, and decreasing proinflammatory cytokine production, thus leading to immunosuppression. Keywords: silicon dioxide, nanoparticle, immunotoxicity, oxidative stress, cytokines, immunosuppression

Jung-Hoon Kim, Sa Kang Kim, Sang Beom Han, Seung-Jun Lee, Moosang KimDepartment of Ophthalmology, School of Medicine, Kangwon National University, Chuncheon, KoreaAbstract: A 31-year-old man presented to our clinic for an ocular trauma to his left eye. His best-corrected visual acuity was 20/200 OS (left eye). Anterior segment examination showed an epithelial defect, which implies a direct injury to the cornea. A marked focal stromal edema accompanied by Descemet’s membrane folds were located at 10 o’clock in the paraxial area, about 4 mm apart from the corneal center. Anterior segment optical coherence tomography (AS-OCT) revealed marked corneal swelling of the lesion. Five days later, the patient’s best-corrected visual acuity improved to 20/50 OS. The stromal edema resolved showing no signs of epithelial defect, although small opacity remained. AS-OCT revealed complete resolution of corneal swelling. Despite the resolution of corneal edema, however, specular microscopy showed substantially decreased endothelial cell density in the lesion compared to the fellow eye. Here we report a case of traumatic corneal stromal edema discovered by AS-OCT.Keywords: AS-OCT, stromal edema, trauma

Thin ZrO2/Al2O3 films that consisted of alternating monoclinic ZrO2 nanolayers and amorphous Al2O3 nanolayers were deposited on a tool steel substrate using Zr and Al cathodes in a cathodic arc plasma deposition system, and then oxidized at 600-900 degrees C in air for up to 50 h. The ZrO2/Al2O3 films effectively suppressed the oxidation of the substrate up to 800 degrees C by acting as a barrier layer against the outward diffusion of the substrate elements and inward diffusion of oxygen. However, rapid oxidation occurred at 900 degrees C due mainly to the increased diffusion and subsequent oxidation of steel as well as the crystallization of amorphous Al2O3.

The present study was conducted to evaluate the effects of feeding broilers with garlic fermented by Leuconostoc citreum SK2556. A total of 250 male broiler chicks was randomly housed into 25 floor pens. Five dietary treatments with five replicates of 10 chicks each (n=50 chicks/treatment). A corn and soybean meal based diet was used as the control diet (NC). The experimental diets were formulated by mixing the basal diet either with antibiotics (10 ppm; PC) or fermented garlic (FG) at the concentrations of 0.1% (FG1), 0.3% (FG3) or 0.5% (FG5) in diets. Daily weight gain, feed intake, and feed:gain ratio were not affected by any of the dietary treatments. Average daily gain on day 21 linearly increased (p= 0.024) with increasing FG levels. The relative weight of the bursa of Fabricius showed a progressive decline with increasing the FG levels. Jejunal villus height was not influenced by dietary treatments. Villus width linearly decreased as FG levels increased (p= 0.17). Jejunal crypt depth was significantly lower (p< 0.05) in the FG1 and FG3 groups compared with the NC group. Villus height:crypt depth ratio linearly increased (p= 0.018) with increasing FG levels. The population of cecal microflora was not altered by dietary treatments. Broiler chickens fed the FG5 diet exhibited (p< 0.05) higher blood levels of total protein and cholesterol compared with those fed the NC diet. Collectively, the results show that dietary FG marginally affected growth performance, especially during the first days rearing, improved intestinal morphology, and altered blood characteristics of broiler chickens.

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("SLEUTH") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e muX collected in 108 pb(-1) of p(p) over bar collisions at roots=1.8 TeV at the DO experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p(T) physics in this sample.

We apply a quasi-model-independent strategy ("Sleuth") to search for new high p_T physics in approximately 100 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV collected by the DZero experiment during 1992-1996 at the Fermilab Tevatron. Over thirty-two e mu X, W+jets-like, Z+jets-like, and 3(lepton/photon)X exclusive final states are systematically analyzed for hints of physics beyond the standard model. Simultaneous sensitivity to a variety of models predicting new phenomena at the electroweak scale is demonstrated by testing the method on a particular signature in each set of final states. No evidence of new high p_T physics is observed in the course of this search, and we find that 89% of an ensemble of hypothetical similar experimental runs would have produced a final state with a candidate signal more interesting than the most interesting observed in these data., Comment: 28 pages, 17 figures. Submitted to Physical Review D

© 2016 Elsevier Ltd Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07–1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87–1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71–1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75–1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67–1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22–3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00–4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93–2·99, p=0·084). Interpretation The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. Funding Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Kang HS, Rhee CK, Kim SK, Kim JW, Lee SH, Yoon HK, Ahn JH, Kim YH. Int J Chron Obstruct Pulmon Dis. 2016;11:2467–2473.Page 2467, Abstract, Results section, line 1, the text “COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included” should read “COPD exacerbations (177 eosinophilic, 380 neutrophilic and 48 paucigranulocytic) were included. Of these, we compared patients with eosinophilic and neutrophilic COPD exacerbations”.Read the original article

Oral Diseases (2011) 17, 320–327 Objective: Periodontal ligament has been reported to have adult stem cells (PDLSCs) which are responsible to regenerate the alveolar bone tissue after tooth is removed from its socket. Also PDLSCs may be the stem cells responsible for the osseointegration of titanium implants after installing the implant immediately in the fresh extracted socket. Here we tested cellular responses of PDLSCs on the various titanium surfaces to verify this notion. Materials and methods: Titanium disc were prepared for the different surface textures; smooth machined, blasted with 75 and 125 μm Al2O3 particles, and anodized. PDLSCs were cultured on these titanium discs and tested their proliferation and gene expressions of osteocalcin, osteopontin, type I collagen, and GAPDH. Results: Proliferation of PDLSCs was higher on the rough surface blasted with 75 μm Al2O3 particles. Osteocalcin expression was increased on the Al2O3 particle treated-surface regardless of its particle size. Type I collagen expression was generally decreased with time in 6 days culture. Conclusions: In this experiment, it was shown that cultured PDLSCs proliferate in higher rate on the rough surface especially at the 75 μm Al2O3 particle treated surface than other surfaces. Also, osteocalcin was highly expressed on the rough surfaces treated with 75 μm and 125 μm Al2O3 particles.

© 2015. Aims: Type 2 diabetes mellitus (T2DM) and visceral obesity are associated with each other and with cardiovascular diseases. We determined whether increased visceral adiposity without weight gain was associated with sex-specific accelerated carotid atherosclerosis in South Koreans with T2DM. Methods: From 2003 to 2012, we recruited 280 participants with T2DM for the Seoul Metabolic Syndrome cohort who had body weight, visceral fat thickness (VFT), and carotid intima-media thickness (CIMT) measured at intervals of 2. years. According to VFT change, sex-specific quartiles of clinical characteristics and changes of CIMT were determined. Logistic regression models predicted the odds of the progression of CIMTs in each quartile. Results: During 2. years of observation, VFTs fell by 5.2. ±. 13.5. mm in men (P

Summary Background Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern countries for the treatment of atopic dermatitis (AD). It has been shown to have an antioxidative effect in human skin disease. Objectives To examine whether RJH extract (RJH-E) suppresses the development of AD-like skin lesions in NC/Nga mice, which are induced by the repeated application of picryl chloride (PC). Methods The efficacy of RJH-E in NC/Nga mice was assessed by measuring symptom severity, scratching behaviour, Staphylococcus aureus numbers on an ear, and serum levels of IgE, interleukin (IL)-4 and interferon (IFN)-γ. Results Oral administration of RJH-E to NC/Nga mice treated with PC inhibited the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores, and a decrease in hypertrophy, hyperkeratosis and infiltration of inflammatory cells in the skin. The scratching behaviour and numbers of S. aureus, which are known to be exacerbated in AD, were also significantly reduced by RJH-E. No significant change was observed in the serum levels of IFN-γ, whereas IgE and IL-4 levels were significantly reduced by RJH-E. Conclusions These results suggest that RJH-E inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response. Our results indicate that RJH treatment could provide an effective alternative therapy for the management of AD.

Purpose: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. © 2014 by American Society of Clinical Oncology.

Thorough resistivity measurements on single crystals of CeZn11 under pressure p and magnetic field H are presented. At ambient pressure, CeZn11 orders antiferromagnetically at TN=2 K. The pressure dependence of the resistivity reveals an increase of the Kondo effect. We determine the pressure evolution of the magnetic exchange interaction between conduction and localized 4f electrons. It qualitatively reproduces the pressure evolution of the magnetic ordering temperature TO1 (with T O1=TN at ambient pressure). In addition to TO1, a new anomaly TO2 appears under pressure. Both anomalies are found to increase with applied pressure up to 4.9 GPa, indicating that CeZn 11 is far from a pressure induced quantum critical point. Complex T-H phase diagrams are obtained under pressure which reveal the instability of the ground state in this compound. © 2013 American Physical Society.

Thorough resistivity measurements on single crystals of CeZn11under pressure p and magnetic field H are presented. At ambient pressure, CeZn11orders antiferromagnetically at TN=2 K. The pressure dependence of the resistivity reveals an increase of the Kondo effect. We determine the pressure evolution of the magnetic exchange interaction between conduction and localized 4f electrons. It qualitatively reproduces the pressure evolution of the magnetic ordering temperature TO1(with TO1=TNat ambient pressure). In addition to TO1, a new anomaly TO2appears under pressure. Both anomalies are found to increase with applied pressure up to 4.9 GPa, indicating that CeZn11is far from a pressure induced quantum critical point. Complex T-H phase diagrams are obtained under pressure which reveal the instability of the ground state in this compound. © 2013 American Physical Society.

We sequenced reduced representation libraries by means of Illumina technology to generate over 1.5 Mb of orthologous sequence from a representative of each of the four extant gibbon genera (Nomascus, Hylobates, Symphalangus, and Hoolock). We used these dat

The population genetic structure of Native Hawaiians has yet to be comprehensively studied, and the ancestral origins of Polynesians remain in question. In this study, we utilized high-resolution genome-wide SNP data and mitochondrial genomes of 148 and 16

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. All rights reserved.

Purpose: Peroxisome proliferator-activated receptor (PPAR)-γ ligand is known to repress the expression of pro-inflammatory mediators. However, it is unclear how it affects PPAR-γ expression and the inflammatory response in the human lung. We investigated the effects of rosiglitazone (synthetic PPAR-γ ligand) on the PPAR-γ expression and on the IL-6 and IL-8 production in acute lung injury model using human lung epithelial cells.Methods: A549 and Beas-2B cells were pre-treated with rosiglitazone and/or BADGE (selective PPAR-γ antagonist) and then treated with media control or cytokine mixture including TNF-α, IL-1β, and IFN-γ. PPAR-γ expression was analyzed in cell lysates by Western blot. IL-6 and IL-8 production was measured in the culture supernatants by ELISA.Results: PPAR-γ expression was identified in all experimental groups except for the control. The cytokine mixture-induced IL-6 and IL-8 production was significantly inhibited by pre-treatment with rosiglitazone (P

We report on the vertical-structure light emitting diodes (VLEDs) fabricated with wafer bonding method using Al-alloyed graphite and Si supporter. VLEDs with Al-alloyed graphite produced no crack during/after laser lift-off (LLO) techniques while the wafer crack took place using Si supporter because of the difference of thermal expansion coefficients between Si and sapphire. The performance of VLEDs with wafer bonding method using Al-alloyed graphite supporter was compared to those fabricated by Cu plating methods. The output power of the chips with wafer bonding method was nearly same as the one with Cu-plating method. However, the forward voltage of VLEDs with wafer bonding method was higher than those with Cu-plating method. In the terms of reliabilities the wafer bonding process is more preferable to Cu-plating and our report proposes that Al-alloyed graphite could be one of promising candidates for the supporters in wafer bonding process.

To evaluate systems for barrier immunoisolation of transplanted hepatocytes, we used transgenic mouse hepatocytes that secrete HBsAg. Hepatocytes were rapidly encapsulated in chitosan, a cationic polymer derived by deacetylation of chitin. Chitosan was allowed to electrostatically bond with anionic sodium alginate for creating an outer bipolymer membrane of the capsules. After encapsulation, hepatocyte viability remained unchanged for seven days in vitro with secretion of HBsAg into the culture medium throughout this period. Following intraperitoneal transplantation of encapsulated hepatocytes, HBsAg promptly appeared in blood of recipients. In congeneic recipients, serum HBsAg peaked at two weeks. Hepatocytes were present in recovered chitosan capsules and expressed HBsAg mRNA. In allogeneic recipients, however, serum HBsAg disappeared within one week and recovered chitosan capsules showed lymphomononuclear cells but not hepatocytes. Transplantation of chitosan encapsulatd HbsAg secreting hepatocytes failed to induce an anti-HBs response, suggesting modulation of the host immune response. These results indicate that transplantation systems using genetically modified hepatocytes which secrete gene products in the blood of recipients should facilitate evaluation of hepatocyte encapsulation.

Cross-cultural and cross-discipline teams are commonplace in ICT global work projects, an area where students in an IT program may head. This paper presents preliminary research that is concerned with outcomes from an intervention strategy designed to help students identify and address cross-cultural and crossdisciplinary team issues while undertaking a series of team-based assessment tasks in a web design course. Students were asked to complete an online questionnaire three times over the semester to rate attributes for communication, task management, relationships, and cultural dimensions as a means of self-assessing their approach to teamwork. Using the data collected from the three surveys, a quantitative evaluation was conducted. This paper presents a preliminary result from this analysis and also discusses future research directions. © 2010, Australian Computer Society, Inc.

We present measurements of B+→D̄ *0τ+ντ and B+→D̄0τ+ντ decays in a data sample of 657×106 BB̄ pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We find 446-56+58 B+→D̄*0τ+ντ events with a significance of 8.1 standard deviations, and 146-41+42 B+→D̄0τ+ν τ events with a significance of 3.5 standard deviations. The latter signal provides the first evidence for this decay mode. The measured branching fractions are B(B+→D̄*0τ+ντ)=(2. 12-0.27+0.28(stat)±0.29(syst))% and B(B+→D̄0τ+ν τ)=(0.77±0.22(stat)±0.12(syst))%. © 2010 The American Physical Society.