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      • The human AQP4 gene : Definition of the locus encoding two water channel polypeptides in brain

        LU, MINGOI,LEE, M.DOUGLAS,SMITH, BARBARA L.,JUNG, JIN SUP,AGRE, PETER,VERDUK, MARIAN A.J.,MERKX, GERARD,RUSS, JOHAN P.L.,DEEN, PETER M.T. 부산대학교 유전공학연구소 1996 분자생물학 연구보 Vol.12 No.-

        The aquaporin family of membrane water transport proteins are expressed in diverse tissues, and in brain the predominant water channel protein is AQP4. Here we report the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Two cDNAs were isolated corresponding to the two initiating methionines (M1 in a 323-aa polypeptide and M23 in a 301-aa polypeptide) previously indentified in rat [Jung, J. S., Bhat, R. V., Preston, G. M., Guggino, W. B. & Agre, P. (1994) Proc. Natl. Acad. Sci. USA 91, 13052-13056]. Similar to other aquaporins, the AQP4 gene is composed of four exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. Transcription initiation sites have been mapped in the proximal promoters of exons 0 and 1. RNase protection revealed distinct transcripts corresponding to M1 and M23 mRNAs, and AQP4 immunoblots of cerebellum demonstrated reactive polypeptides of 31 and 34 kDa. Using a P1 and a λEMBL subclone, the chromosomal site of the human AQP4 gene was mapped to chromosome 18 at the junction of q11.2 and q12.1 by fluorescence in situ hybridization. These studies may now permit molecular characterization of AQP4 during human development and in clinical disorders.

      • KCI등재

        Sphingolipids and the Orchestration of Endothelium-Derived Vasoactive Factors: When Endothelial Function Demands Greasing

        Léon J.A. Spijkers,Astrid E. Alewijnse,L.M. Peters 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.2

        Vasomotor tone is regulated by a complex interplay of a variety of extrinsic neurohumoral and intrinsic factors. It is the endothelium that has a major influence on smooth mu-scle cell tone via the release of intrinsic vasoactive factors and is therefore an important regulator of vasomotor tone. Sphingolipids are an emerging class of lipid mediators with important physiological properties. In the last two decades it has not only become increasingly clear that sphingolipid signaling plays a pivotal role in immune function, but also its role in the vascular system is now becoming more re-cognized. In this mini-review we will highlight the possible cross-talk between sphingolipids and intrinsic vasoactive factors released by the endothelium. Via this cross-talk sphingolipids can orchestrate vasomotor tone and may therefore also be involved in the pathophysiology of disease states associated with endothelial dysfunction.

      • SCISCIESCOPUS
      • THE RR LYRAE VARIABLES AND HORIZONTAL BRANCH OF NGC 6656 (M22)<sup>,</sup>

        Kunder, Andrea,Stetson, Peter B.,Cassisi, Santi,Layden, Andrew,Bono, Giuseppe,Catelan, Má,rcio,Walker, Alistair R.,Paredes Alvarez, Leonardo,Clem, James L.,Matsunaga, Noriyuki,Salaris, Maurizio American Institute of Physics 2013 The Astronomical journal Vol.146 No.5

        <P>The first calibrated broadband UBVI time-series photometry is presented for the RR Lyrae variable stars in NGC 6656 (M22), with observations spanning a range of 22 years. We have also redetermined the variability types and periods for the RR Lyrae stars identified previously by photographic observations, revising the number of fundamental-mode RR Lyrae variables (RR0) to 10 and the number of first-overtone variables (RR1) to 16. The mean periods of the RR0 and RR1 variables are ⟨P⟩<SUB>RR0</SUB> = 0.66 ± 0.02 days and ⟨P⟩<SUB>RR1</SUB> = 0.33 ± 0.01 days, respectively, supporting an Oosterhoff II classification for the cluster. The number ratio of RR1-type to all RR-type variables is N<SUB>1</SUB>/N<SUB>RR</SUB> = 0.61, also consistent with an Oosterhoff II designation. Both the RR Lyrae stars' minimum light colors and the blue edge of the RR Lyrae instability strip suggest E( B – – V) = 0.36 ± 0.02 mag toward M22. Regarding the HB morphology of M22, we find (B-R)/(B+V+R) = +0.97 ± 0.1 and at least one 'gap' located in an unusual part of the blue HB, in the middle of the so-called hot HB stars.</P>

      • A Randomized, Controlled Trial of Sofosbuvir/Velpatasvir/Voxilaprevir or Sofosbuvir/Velpatasvir for 12 Weeks in DAA-Experienced Patients with GT1-6 HCV Infection: The POLARIS-4 Study

        ( Paul Kwo ),( Stefan Zeuzem ),( Steven L. Flamm ),( Myron Tong ),( John M Vierling ),( Stephen Pianko ),( Peter Buggisch ),( Victor de Lédinghen ),( Robert H. Hyland ),( Xiaoru Wu ),( Evguenia S. Sva 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: DAAs provide safe and highly efficacious therapies for HCV infection. However, the small proportion of patients who do not achieve a sustained virologic response with DAA-based regimens represent a population with an unmet medical need. Sofosbuvir(SOF) and velpatasvir(VEL) are pangenotypic inhibitors of the HCV NS5B and NS5A proteins, respectively, and voxilaprevir(VOX) is a pangenotypic HCV NS3/4A protease inhibitor. This study evaluates treatment with a SOF/VEL/VOX for 12weeks and a SOF/VEL for 12weeks as salvage regimens in DAA-experienced patients who had not previously received an NS5A inhibitor. Methods: Patients with genotypes 1-3 were randomized 1:1 to receive open-label SOF/VEL/VOX or SOF/VEL for 12weeks, stratified according to genotype and cirrhosis status. Patients of all other genotypes were assigned to receive SOF/VEL/VOX for 12weeks. DAA-experienced patients who previously were treated with an NS5A inhibitor or with only an NS3/4A protease inhibitor in combination with ribavirin and Peg-IFN were excluded. The primary endpoint evaluates the superiority of the SVR12 of each treatment to a prespecified goal of 85%. Results: Of the 333 patients who were randomized and treated, 77% were male, 19% had the IL28B CC genotype, 46% had compensated cirrhosis and 43% had genotype 1 infection. Most patients had prior DAA experience with either an NS5B inhibitor alone(73%) or an N5SB inhibitor and an NS3/4A protease inhibitor(25%); the most common prior treatment regimens were SOF with ribavirin ±Peg-IFN and SOF combined with simeprevir. Treatment was well tolerated.No SAE was assessed to be attributable to study drug. Overall, SVR12 was achieved in 97%(177/182) of patients treated with SOF/VEL/VOX and 90%(136/151) patients treated with SOF/VEL. SOF/VEL/VOX met the prespecified 85% SVR12 performance goal(p<0.001); SOF/VEL did not. Conclusions: SOF/VEL/VOX for 12 weeks provides a safe, well tolerated and effective retreatment options for patients who did not previously achieve SVR following treatment with non-NS5A inhibitor-containing DAA regimens.

      • SCISCIESCOPUS

        CARMA LARGE AREA STAR FORMATION SURVEY: DENSE GAS IN THE YOUNG L1451 REGION OF PERSEUS

        Storm, Shaye,Mundy, Lee G.,Lee, Katherine I.,Ferná,ndez-Ló,pez, Manuel,Looney, Leslie W.,Teuben, Peter,Arce, Hé,ctor G.,Rosolowsky, Erik W.,Meisner, Aaron M.,Isella, Andrea,Kauffmann American Astronomical Society 2016 The Astrophysical journal Vol.830 No.2

        <P>We present a 3 mm spectral line and continuum survey of L1451 in the Perseus Molecular Cloud. These observations are from the CARMA Large Area Star Formation Survey (CLASSy), which also imaged Barnard. 1, NGC 1333, Serpens Main, and Serpens South. L1451 is the survey region with the lowest level of star formation activity-it contains no confirmed protostars. HCO+, HCN, and N2H+ (J = 1 -> 0). are all detected throughout the region, with HCO+ being the most spatially widespread, and molecular emission seen toward 90% of the area above N(H-2) column densities of 1.9 x 10(21) cm(-2). HCO+ has the broadest velocity dispersion, near 0.3 km s(-1) on average, compared with similar to 0.15 km s(-1) for the other molecules, thus representing a range of subsonic to supersonic gas motions. Our non-binary dendrogram analysis reveals that the dense gas traced by each molecule has a similar hierarchical structure, and that gas surrounding the candidate first hydrostatic core (FHSC), L1451-mm, and other previously detected single-dish continuum clumps has similar hierarchical structure; this suggests that different subregions of L1451 are fragmenting on the pathway to forming young stars. We determined that the three-dimensional morphology of the largest detectable dense-gas structures was relatively ellipsoidal compared with other CLASSy regions, which appeared more flattened at the largest scales. A virial analysis shows that the most centrally condensed dust structures are likely unstable against collapse. Additionally, we identify a new spherical, centrally condensed N2H+ feature that could be a new FHSC candidate. The overall results suggest that L1451 is a young region starting to form its generation of stars within turbulent, hierarchical structures.</P>

      • SCISCIESCOPUS

        <i>SPITZER</i>AND HEINRICH HERTZ TELESCOPE OBSERVATIONS OF STARLESS CORES: MASSES AND ENVIRONMENTS

        Stutz, Amelia M.,Rieke, George H.,Bieging, John H.,Balog, Zoltan,Heitsch, Fabian,Kang, Miju,Peters, William L.,Shirley, Yancy L.,Werner, Michael W. IOP Publishing 2009 The Astrophysical journal Vol.707 No.1

        <P>We present Spitzer observations of a sample of 12 starless cores selected to have prominent 24 mu m shadows. The Spitzer images show 8 mu m and 24 mu m shadows and in some cases 70 mu m shadows; these spatially resolved absorption features trace the densest regions of the cores. We have carried out a (CO)-C-12 (2-1) and (CO)-C-13 (2-1) mapping survey of these cores with the Heinrich Hertz Telescope (HHT). We use the shadow features to derive optical depth maps. We derive molecular masses for the cores and the surrounding environment; we find that the 24 mu m shadow masses are always greater than or equal to the molecular masses derived in the same region, a discrepancy likely caused by CO freezeout onto dust grains. We combine this sample with two additional cores that we studied previously to bring the total sample to 14 cores. Using a simple Jeans mass criterion, we find that similar to 2/3 of the cores selected to have prominent 24 mu m shadows are collapsing or near collapse, a result that is supported by millimeter line observations. Of this subset at least half have indications of 70 mu m shadows. All cores observed to produce absorption features at 70 mu m are close to collapse. We conclude that 24 mu m shadows, and even more so the 70 mu m ones, are useful markers of cloud cores that are approaching collapse.</P>

      • New Hypotheses To Explain the Development and Subsequent Loss of Pigmentation in Humans

        ( Peter M Eliasa ),( Mary L Williamsc ) 한국피부장벽학회 2013 한국피부장벽학회지 Vol.15 No.2

        Humans with darkly-pigmented skin (DS) (Fitzpatrick Type IV/V) display superior permeability barrier function and stratum corneum (SC) integrity/cohesion in comparison to humans with lightly-pigmented (Type I/II) skin (LS), independent of race, and barrier function is inferior in involved vs. uninvolved vitiligo skin. The reduced pH of the SC of DS skin (. ½ pH unit) could contribute to enhanced function, because reducing the pH of SC in LS individuals resets barrier function to DS levels. We evaluated here how pigmentation enhances epidermal barrier function in Skh1 (hairless albino) mice, which contain residual (non-melanized) melanocytes that lack pigment, and Skh2 (hairless pigmented) mice, where melanocytes generate abundant melanin restricted to the interfollicular epidermis. Barrier function was enhanced in Skh2 vs. Skh1 mice, which correlated with a more acidic pH that localized to the lower SC. The lower pH correlated further with persistence and extrusion of melanin granules into the extracellular spaces in the outer epidermis. Archived samples of DS human epidermis also showed melanin extrusion at and above the stratum granulosum (SG)-SC interface. Both acute barrier disruption and topical basic pH challenges accelerated melanin extrusion in Skh2, but not Skh1 mice, which correlated with a further decline in pH, enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, b-glucocerebrosidase and acidic sphingomyelinase, and accelerated maturation of SC extracellular lamellar bilayers. Yet, pigmented melanocytes also could enhance barrier function by paracrine mechanisms, because Skh2 epidermis displays enhanced mRNA and/or protein levels for: a) epidermal differentiation proteins; b) lipid synthetic proteins; c) lipid transporters; and d) lipid-processing enzymes, changes that likely cannot be attributed to reduced acidity alone. Together, these studies demonstrate that superior barrier function in pigmented epidermis can be attributed to both pH-lowering juxtacrine and as-yet-undefined paracrine mechanisms.

      • KCI등재

        Induced Systemic Resistance and the Rhizosphere Microbiome

        Peter A.H.M. Bakker,Rogier F. Doornbos,Christos Zamioudis,Roeland L. Berendsen,Corné M.J. Pieterse 한국식물병리학회 2013 Plant Pathology Journal Vol.29 No.2

        Microbial communities that are associated with plant roots are highly diverse and harbor tens of thousands of species. This so-called microbiome controls plant health through several mechanisms including the suppression of infectious diseases, which is especially prominent in disease suppressive soils. The mechanisms implicated in disease suppression include competition for nutrients,antibiosis, and induced systemic resistance (ISR). For many biological control agents ISR has been recognized as the mechanism that at least partly explains disease suppression. Implications of ISR on recruitment and functioning of the rhizosphere microbiome are discussed.

      • KCI등재

        Electrocardiogram and cardiac testing among patients in the emergency department with seizure versus syncope

        Jennifer L. White,Judd E. Hollander,Jesse M. Pines,Peter M. Mullins,Anna Marie Chang 대한응급의학회 2019 Clinical and Experimental Emergency Medicine Vol.6 No.2

        Objective Cardiogenic syncope can present as a seizure. The distinction between seizure disorder and cardiogenic syncope can only be made if one considers the diagnosis. Our main objective was to identify whether patients presenting with a chief complaint (reason for visit) as seizure or syncope received an electrocardiogram in the emergency department across all age groups. Methods We conducted a secondary analysis of data collected in the 2010 to 2014 National Hospital Ambulatory Medical Care Survey comparing patients presenting with a chief complaint of syncope versus seizure to determine likelihood of getting an evaluation for possible life threatening cardiovascular disease. The primary endpoint was receiving an electrocardiogram in the emergency department; secondary endpoint was receiving cardiac biomarkers. Results There was a total of 144,094 patient encounters. Of these visits, 1,553 had syncope and 1,470 had seizure (60.3% vs. 44.2% female, 19.9% vs. 29.0% non-white). After adjusting for age, sex, mode of arrival and insurance, patients with syncope were more likely to receive an electrocardiogram compared to patients with seizure (odds ratio, 10.86; 95% confidence interval [CI], 8.52 to 13.84). This was true across all age groups (0 to 18 years, 56% vs. 7.5%; 18 to 44 years, 60% vs. 27%; 45 to 64 years, 82% vs. 41%; ≥65 years, 85% vs. 68%; P<0.01 for all). Car- diac biomarkers were also obtained more frequently in adult patients with syncope patients (18 to 44 years, 17.5% vs. 10.5%; 45 to 64 years, 33.8% vs. 21.4%; ≥65 years, 47.1% vs. 32.3%; P<0.01 for all). Conclusion Patients evaluated in the emergency department for syncope received an electrocar- diogram and cardiac biomarkers more frequently than those that had seizure.

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