134 research outputs found

    Observation of near-inertial wave reflections within the thermostad layer of an anticyclonic mesoscale eddy

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    Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 37 (2010): L01606, doi:10.1029/2009GL041601.Moored current observations in the southwestern East/Japan Sea of 16.5 months duration clearly captured two episodes of downward phase propagation (upward energy propagation) of near-inertial waves (NIWs). Time series of temperature and velocity from the mooring and ancillary information indicate that the mooring was located near the center of an anticyclonic eddy during these events. Considering the typical vertical structure of quasi-permanent eddy features in the region, the observed downward phase propagation appeared to occur within the seasonal thermocline and upper thermostad of the anticyclonic mesoscale eddy. Ray tracing simulation of NIW using the observed subinertial currents suggests that the upward energy propagation is caused by the reflection of the NIWs within the thermostad of the anticyclonic eddy, where the effect of the vertical shear of subinertial horizontal currents is larger than the buoyancy effect in controlling the propagation of NIWs.This work was supported by grants from the Ministry of Land, Transport, and Maritime Affairs (Ocean Climate Variability Program), and the US NSF, grant OCE-0647949 to RWS

    Coculture of Marine Streptomyces sp. With Bacillus sp. Produces a New Piperazic Acid-Bearing Cyclic Peptide

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    Microbial culture conditions in the laboratory, which conventionally involve the cultivation of one strain in one culture vessel, are vastly different from natural microbial environments. Even though perfectly mimicking natural microbial interactions is virtually impossible, the cocultivation of multiple microbial strains is a reasonable strategy to induce the production of secondary metabolites, which enables the discovery of new bioactive natural products. Our coculture of marine Streptomyces and Bacillus strains isolated together from an intertidal mudflat led to discover a new metabolite, dentigerumycin E (1). Dentigerumycin E was determined to be a new cyclic hexapeptide incorporating three piperazic acids, N-OH-Thr, N-OH-Gly, β-OH-Leu, and a pyran-bearing polyketide acyl chain mainly by analysis of its NMR and MS spectroscopic data. The putative PKS-NRPS biosynthetic gene cluster for dentigerumycin E was found in the Streptomyces strain, providing clear evidence that this cyclic peptide is produced by the Streptomyces strain. The absolute configuration of dentigerumycin E was established based on the advanced Marfey's method, ROESY NMR correlations, and analysis of the amino acid sequence of the ketoreductase domain in the biosynthetic gene cluster. In biological evaluation of dentigerumycin E (1) and its chemical derivatives [2-N,16-N-deoxydenteigerumycin E (2) and dentigerumycin methyl ester (3)], only dentigerumycin E exhibited antiproliferative and antimetastatic activities against human cancer cells, indicating that N-OH and carboxylic acid functional groups are essential for the biological activity

    Real-Life Efficacy and Tolerability of Lacosamide in Pediatric Patients Aged 4 Years or Older with Drug-Resistant Epilepsy

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    Purpose The aim of this study was to evaluate the efficacy and safety of adjunctive lacosamide therapy in pediatric patients aged ≥4 years with drug-resistant epilepsy (DRE). Methods Medical records of children aged 4 to 19 years treated with lacosamide as adjunctive therapy for DRE were retrospectively reviewed. The patients were divided into two groups according to their age at the start of lacosamide treatment: group A (aged 4–15 years) and group B (aged 16–19 years). Changes in seizure frequency from baseline, adverse events, and the retention rate were evaluated at each follow-up visit. Results Sixty-two patients (33 males and 29 females) with a mean age of 11.4 years (range, 4 to 19) were included. The mean duration of follow-up was 20.1±12.9 months. The mean maintenance dose of lacosamide was 6.7±4.8 mg/kg/day. Forty-two patients (67.7%) were responders (≥50% reduction in seizures) with 19.4% (12/62) achieving freedom from seizures. The response rate did not differ significantly between groups A and B (67.6% vs. 68.0%, P=0.795) and was not affected by the concomitant use of sodium channel blockers. Significant independent factors associated with a good response to lacosamide treatment were a shorter duration of epilepsy (P=0.035) and fewer concomitant anti-seizure medications (P=0.002). Mild transient adverse events were observed in 20 patients (32.3%). Conclusion Lacosamide adjunctive therapy was efficacious and tolerated in children aged ≥4 years with DRE. Early use of lacosamide may be helpful for a good response to drug-resistant seizures

    A Case of Congenital Central Hypoventilation Syndrome with PHOX2B Gene Mutation in a Korean Neonate

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    Congenital central hypoventilation syndrome (CCHS) is a life-threatening disorder with apnea and cyanosis during sleep requiring immediate endotracheal intubation during the first day of life. The PHOX2B gene has been identified as the major gene involved in CCHS. This is the first report of a Korean neonate with CCHS confirmed to have a PHOX2B mutation with expanded alleles containing 20 polyalanine repeats that is a relatively small number compared to previous cases. The patient required intermittent ventilator support during sleep only and did not suffer from any other disorders of the autonomic nerve system. He consistently needs ventilator support during sleep and remains alive. Analysis of PHOX2B gene is useful for diagnosis and appropriate therapeutic intervention of CCHS patients

    Diagnostic performance of ultrasonography-guided core-needle biopsy according to MRI LI-RADS diagnostic categories

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    Purpose According to the American Association for the Study of Liver Diseases (AASLD) guidelines, biopsy is a diagnostic option for focal hepatic lesions depending on the Liver Imaging Reporting and Data System (LI-RADS) category. We evaluated the diagnostic performance of ultrasonography-guided core-needle biopsy (CNB) according to LI-RADS categories. Methods A total of 145 High-risk patients for hepatocellular carcinoma (HCC) who underwent magnetic resonance imaging (MRI) followed by CNB for a focal hepatic lesion preoperatively were retrospectively enrolled. Focal hepatic lesions on MRI were evaluated according to LI-RADS version 2018. Pathologic results were categorized into HCC, non-HCC malignancies, and benignity. The categorization was defined as correct when the CNB pathology and surgical pathology reports were identical. Nondiagnostic results were defined as inadequate CNB pathology findings for a specific diagnosis. The proportion of correct categorizations was calculated for each LI-RADS category, excluding nondiagnostic results. Results After excluding 16 nondiagnostic results, 131 lesions were analyzed (45 LR-5, 24 LR-4, 4 LR-3, and 58 LR-M). All LR-5 lesions were HCC, and CNB correctly categorized 97.8% (44/45) of LR-5 lesions. CNB correctly categorized all 24 LR-4 lesions, 16.7% (4/24) of which were non-HCC malignancies. All LR-M lesions were malignant, and 62.1% (36/58) were non-HCC malignancies. CNB correctly categorized 93.1% (54/58) of LR-M lesions, and 12.5% (3/24) of lesions with CNB results of HCC were confirmed as non-HCC malignancies. Conclusion In agreement with AASLD guidelines, CNB could be helpful for LR-4 lesions, but is unnecessary for LR-5 lesions. In LR-M lesions, CNB results of HCC did not exclude non-HCC malignancy

    Synthetic lethality by targeting the RUVBL1/2-TTT complex in mTORC1-hyperactive cancer cells

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    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.Despite considerable efforts, mTOR inhibitors have produced limited success in the clinic. To define the vulnerabilities of mTORC1-addicted cancer cells and to find previously unknown therapeutic targets, we investigated the mechanism of piperlongumine, a small molecule identified in a chemical library screen to specifically target cancer cells with a hyperactive mTORC1 phenotype. Sensitivity to piperlongumine was dependent on its ability to suppress RUVBL1/2-TTT, a complex involved in chromatin remodeling and DNA repair. Cancer cells with high mTORC1 activity are subjected to higher levels of DNA damage stress via c-Myc and displayed an increased dependency on RUVBL1/2 for survival and counteracting genotoxic stress. Examination of clinical cancer tissues also demonstrated that high mTORC1 activity was accompanied by high RUVBL2 expression. Our findings reveal a previously unknown role for RUVBL1/2 in cell survival, where it acts as a functional chaperone to mitigate stress levels induced in the mTORC1-Myc-DNA damage axis.NIH 1RO1CA142805National Research Foundation of Korea (NRF) grant (NRF-2017R1C1B1006072

    Sex differences in coronary angiographic findings in patients with stable chest pain: analysis of data from the KoRean wOmenS chest pain rEgistry (KoROSE)

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    Abstract Background Focused evaluations on potential sex differences in the angiographic findings of the coronary arteries are scarce. This study was performed to compare the angiographic extent and localization of coronary stenosis between men and women. Methods A total of 2348 patients (mean age 62.5 years and 60% women) with stable chest pain undergoing invasive coronary angiography (CAG) were recruited from the database of the nation-wide chest pain registry. Obstructive coronary artery disease (CAD) was defined as ≥ 50% stenosis of the left main coronary artery and/or ≥ 70% stenosis of any other epicardial coronary arteries. Results Although women were older than men (64.4 ± 10.3 vs. 59.5 ± 11.4 years, P < 0.001), men had worse risk profiles including high blood pressure, more frequent smoking and elevated triglyceride and C-reactive protein. The prevalence of obstructive CAD was significantly higher in men than in women (37.0% vs. 28.4%, P < 0.001). Men had a higher prevalence of LM disease (10.3% vs. 3.5%, P < 0.001) and three-vessel disease (16.1% vs. 9.5%, P = 0.007) compared to women. In multiple binary logistic regression analysis, the risk of men having LM disease or three-vessel disease was 7.4 (95% confidence interval 3.48–15.97; P < 0.001) and 2.7 (95% confidence interval 1.57–4.64; P < 0.001) times that of women, respectively, even after controlling for potential confounders. Conclusions In patients with chest pain undergoing invasive CAG, men had higher obstructive CAD prevalence and more high-risk angiographic findings such as LM disease or three-vessel disease.Highlights Focused evaluation on sex differences in the angiographic findings of the coronary arteries is limited. We evaluated sex differences in the angiographic extent and localization of coronary stenosis in 2348 patients. Men had higher prevalence of obstructive coronary artery disease and more high-risk angiographic findings such as left main disease or three-vessel disease. This sex difference could be applied in the clinical evaluation and management of patients with suspected coronary artery disease

    Clinical Features of Re-Emerging Hepatitis A: An Analysis of Patients Hospitalized during an Urban Epidemic in Korea

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    From April 2008 to November 2008, many cases of hepatitis A were reported in Seoul and Gyeonggi Province in Korea. Furthermore, the rate of severe or fulminant hepatitis have significantly increased during the latest epidemic (13.4% vs. 5.2%, p=0.044). Therefore, widespread use of vaccine is warranted to reduce the burden of hepatitis A in Korea
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