Erratum: Dirichlet Forms and Dirichlet Operators for Infinite Particle Systems: Essential Self-adjointness

We reprove the essential self-adjointness of the Dirichlet operators of Dirchlet forms for infinite particle systems with superstable and sub-exponentially decreasing interactions.Comment: This is an erratum to the work appeared in J. Math. Phys. 39(12), 6509-6536 (1998

Minimum mass of galaxies from BEC or scalar field dark matter

Many problems of cold dark matter models such as the cusp problem and the missing satellite problem can be alleviated, if galactic halo dark matter particles are ultra-light scalar particles and in Bose-Einstein condensate (BEC), thanks to a characteristic length scale of the particles. We show that this finite length scale of the dark matter can also explain the recently observed common central mass of the Milky Way satellites ($\sim 10^7 M_\odot$) independent of their luminosity, if the mass of the dark matter particle is about $10^{-22} eV$.Comment: 10 pages, 1 figure, accepted in JCA

Ethanol-activated CaMKII signaling induces neuronal apoptosis through Drp1-mediated excessive mitochondrial fission and JNK1-dependent NLRP3 inflammasome activation

Abstract Background Neurodegeneration is a representative phenotype of patients with chronic alcoholism. Ethanol-induced calcium overload causes NOD-like receptor protein 3 (NLRP3) inflammasome formation and an imbalance in mitochondrial dynamics, closely associated with the pathogenesis of neurodegeneration. However, how calcium regulates this process in neuronal cells is poorly understood. Therefore, the present study investigated the detailed mechanism of calcium-regulated mitochondrial dynamics and NLRP3 inflammasome formation in neuronal cells by ethanol. Methods In this study, we used the SK-N-MC human neuroblastoma cell line. To confirm the expression level of the mRNA and protein, real time quantitative PCR and western blot were performed. Co-immunoprecipitation and Immunofluorescence staining were conducted to confirm the complex formation or interaction of the proteins. Flow cytometry was used to analyze intracellular calcium, mitochondrial dysfunction and neuronal apoptosis. Results Ethanol increased cleaved caspase-3 levels and mitochondrial reactive oxygen species (ROS) generation associated with neuronal apoptosis. In addition, ethanol increased protein kinase A (PKA) activation and cAMP-response-element-binding protein (CREB) phosphorylation, which increased N-methyl-D-aspartate receptor (NMDAR) expression. Ethanol-increased NMDAR induced intracellular calcium overload and calmodulin-dependent protein kinase II (CaMKII) activation leading to phosphorylation of dynamin-related protein 1 (Drp1) and c-Jun N-terminal protein kinase 1 (JNK1). Drp1 phosphorylation promoted Drp1 translocation to the mitochondria, resulting in excessive mitochondrial fission, mitochondrial ROS accumulation, and loss of mitochondrial membrane potential, which was recovered by Drp1 inhibitor pretreatment. Ethanol-induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death. Suppressing caspase-1 induced mitophagy and reversed the ethanol-induced apoptosis in neuronal cells. Conclusions Our results demonstrated that ethanol upregulated NMDAR-dependent CaMKII phosphorylation which is essential for Drp1-mediated excessive mitochondrial fission and the JNK1-induced NLRP3 inflammasome activation resulting in neuronal apoptosis. Video abstract Graphical abstrac

Multi-factor service design: identification and consideration of multiple factors of the service in its design process

Service design is a multidisciplinary area that helps innovate services by bringing new ideas to customers through a design-thinking approach. Services are affected by multiple factors, which should be considered in designing services. In this paper, we propose the multi-factor service design (MFSD) method, which helps consider the multi-factor nature of service in the service design process. The MFSD method has been developed through and used in five service design studies with industry and government. The method addresses the multi-factor nature of service for systematic service design by providing the following guidelines: (1) identify key factors that affect the customer value creation of the service in question (in short, value creation factors), (2) define the design space of the service based on the value creation factors, and (3) design services and represent them based on the factors. We provide real stories and examples from the five service design studies to illustrate the MFSD method and demonstrate its utility. This study will contribute to the design of modern complex services that are affected by varied factors

Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the most common tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, nicotinamide N-methyltransferase (NNMT), a key enzyme in drug metabolism, was investigated as a potential prognostic factor.</p> <p>Methods</p> <p>Frozen tumors and non-cancerous surrounding tissues from 120 patients with primary HCC were studied. Expressions of NNMT and internal control genes were measured by real-time reverse-transcription PCR (RT-PCR). The relationship of NNMT mRNA level with clinicopathologic parameters and clinical outcome was evaluated.</p> <p>Results</p> <p>NNMT mRNA level is markedly reduced in HCCs compared to non-cancerous surrounding tissues (P < 0.0001), and NNMT expression in tumors was significantly correlated with tumor stage (P = 0.010). Moreover, stratification of patients based on tumor NNMT mRNA levels revealed that the patients who expressed higher NNMT mRNA levels tended to have a shorter overall survival (OS) time (P = 0.053) and a significantly shorter disease-free survival (DFS) time (P = 0.016). Both NNMT expression (P = 0.0096) and tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis.</p> <p>Conclusion</p> <p>The results of this study indicated that NNMT gene expression is associated with tumor stage and DFS time in HCC cases. Because of the broad substrate specificity of NNMT, which could alter the efficacy and adverse effects of chemotherapy, NNMT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.</p

Estrogen Receptor-1 Genetic Polymorphisms for the Risk of Premature Ovarian Failure and Early Menopause

Background: The aim of this study was to investigate the role of the estrogen receptor 1 (ESR1) genetic polymorphisms for early menopause that was classified as premature ovarian failure (POF) and early menopause (EM) and to examine whether the associations of ESR1 genetic variants are different for POF and EM. Methods: We selected 100 POF cases and matched 100 EM cases and 200 normal menopause (NM) controls from the Korean Multi-Center Cohort. Among them, we restricted idiopathic POF and EM cases vs NM controls by excluding POF/EM cases with medical/surgical causes. The XbaI (rs9340799) and PvuII (rs2234693) in the ESR1 gene were genotyped. The single-nucleotide polymorphism (SNP) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis. Also nominal polytomous logistic regression was used to find whether ESR1 genetic variants are differently associated with POF and EM. Results: The global p values for idiopathic POF and EM were 0.08 and 0.39 (SNP-based), and <0.001 and 0.12 (haplotype-based), respectively. The XbaI genetic variant containing the X allele was marginally significantly associated with a reduced risk of idiopathic POF (OR=0.6, 95% CI 0.3-1.0). The P-x haplotype and diplotypes significantly decreased the risk of idiopathic POF (OR=0.5, 95% CI 0.2-0.9; OR 0.4, 95% CI 0.2-0.9, respectively). In contrast from POF, the P-x haplotypes and diplotypes insignificantly increased the risk for both idiopathic EM (p(polytomous)=0.009 for P-x haplotype; p(polytomous)=0.02 for P-x diplotypes). Conclusion: Our results suggest that the ESR1 gene including PvuII and XbaI polymorphisms may modify the risk of idiopathic premature ovarian failure (POF) but not idiopathic early menopause (EM) risk.Bretherick KL, 2008, FERTIL STERIL, V89, P318, DOI 10.1016/j.fertnstert.2007.03.008Chang SH, 2007, MATURITAS, V58, P19, DOI 10.1016/j.maturitas.2007.04.001Kitamura I, 2007, BONE, V40, P1623, DOI 10.1016/j.bone.2007.02.016Molvarec A, 2007, HYPERTENS RES, V30, P205Hsieh YY, 2007, MOL HUM REPROD, V13, P117, DOI 10.1093/molehr/gal099Dvornyk V, 2006, MATURITAS, V54, P19, DOI 10.1016/j.maturitas.2005.08.005Onland-Moret NC, 2005, CANCER CAUSE CONTROL, V16, P1195, DOI 10.1007/s10552-005-0307-5Popat RA, 2005, NEUROLOGY, V65, P383Schuit SCE, 2005, EUR J ENDOCRINOL, V153, P327, DOI 10.1530/eje.1.01973Kok HS, 2005, HUM REPROD, V20, P536, DOI 10.1093/humrep/deh600Ioannidis JPA, 2004, JAMA-J AM MED ASSOC, V292, P2105van der Klift M, 2004, J BONE MINER RES, V19, P1172, DOI 10.1359/JBMR.040215Schuit SCE, 2004, JAMA-J AM MED ASSOC, V291, P2969Wasserman L, 2004, INT J OBESITY, V28, P49, DOI 10.1038/sj.ijo.0802481van Meurs JBJ, 2003, HUM MOL GENET, V12, P1745, DOI 10.1093/hmg/ddg176Gorai I, 2003, J CLIN ENDOCR METAB, V88, P799, DOI 10.1210/jc.2002-020353Laml T, 2002, HUM REPROD UPDATE, V8, P483Herrington DM, 2002, CIRCULATION, V105, P1879, DOI 10.1161/01.CIR.0000016173.98826.88Kobayashi N, 2002, MATURITAS, V41, P193YOO KY, 2002, ASIAN PAC J CANCER P, V3, P85de Bruin JP, 2001, HUM REPROD, V16, P2014Pelletier G, 2000, J CLIN ENDOCR METAB, V85, P4835Weiderpass E, 2000, CARCINOGENESIS, V21, P623Yan G, 2000, J WOMEN HEALTH GEN-B, V9, P275Lorentzon M, 1999, J CLIN ENDOCR METAB, V84, P4597Weel AEAM, 1999, J CLIN ENDOCR METAB, V84, P3146Drummond AE, 1999, MOL CELL ENDOCRINOL, V151, P57, DOI 10.1016/S0303-7207(99)00038-6Christin-Maitre S, 1998, MOL CELL ENDOCRINOL, V145, P75Torgerson DJ, 1997, EUR J OBSTET GYN R B, V74, P63vanderSchouw YT, 1996, LANCET, V347, P714Kobayashi S, 1996, J BONE MINER RES, V11, P306NELSON LM, 1996, REPROD ENDOCRINOLOGY, P1394KAPRIO J, 1995, HUM BIOL, V67, P739CRAMER DW, 1995, FERTIL STERIL, V64, P740EXCOFFIER L, 1995, MOL BIOL EVOL, V12, P921NELSON LM, 1994, J CLIN ENDOCR METAB, V79, P1470CAPLAN GA, 1994, J ROY SOC MED, V87, P200PALMER JR, 1992, AM J EPIDEMIOL, V136, P408BAGUR AC, 1992, CALCIFIED TISSUE INT, V51, P4FRANCESCHI S, 1991, INT J CANCER, V49, P57MEYER JM, 1991, AM J MED GENET, V39, P148TRELOAR SA, 1990, AM J HUM GENET, V47, P137SNOWDON DA, 1989, AM J PUBLIC HEALTH, V79, P709

Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery

10.1371/journal.pone.0090133PLoS ONE93-POLN

Protective Effect of Ginseng Polysaccharides on Influenza Viral Infection

Ginseng polysaccharide has been known to have multiple immunomodulatory effects. In this study, we investigated whether Panax ginseng polysaccharide (GP) would have a preventive effect on influenza infection. Administration of mice with GP prior to infection was found to confer a survival benefit against infection with H1N1 (A/PR/8/34) and H3N2 (A/Philippines/82) influenza viruses. Mice infected with the 2009 H1N1 virus suspended in GP solution showed moderately enhanced survival rates and lower levels of lung viral titers and the inflammatory cytokine (IL-6). Daily treatment of vaccinated mice with GP improved their survival against heterosubtypic lethal challenge. This study demonstrates the first evidence that GP can be used as a remedy against influenza viral infection

Digital Signal Processing

Contains summary of research and reports on sixteen research projects.U.S. Navy - Office of Naval Research (Contract N00014-75-C-0852)National Science Foundation FellowshipNATO FellowshipU.S. Navy - Office of Naval Research (Contract N00014-75-C-0951)National Science Foundation (Grant ECS79-15226)U.S. Navy - Office of Naval Research (Contract N00014-77-C-0257)Bell LaboratoriesNational Science Foundation (Grant ECS80-07102)Schlumberger-Doll Research Center FellowshipHertz Foundation FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196)U.S. Air Force (Contract F19628-81-C-0002)Hughes Aircraft Company Fellowshi