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      • What Is Hermeneutics and How Is It Critical?

        Le Gottesman 대한사고개발학회 1996 The International Journal of Creativity & Problem Vol.6 No.2

        Hermeneutics tries to answer the question, what does it mean to "understand"? Once an arcane sub-specialty of Biblical studies and philology, hermeneutics in the last 30 years has quietly influenced theories and practice~ in history, sociology, anthropology, literary studies, science, politics, and even business. Hermeneutics has both descriptive and prescriptive dimensions. For teachers, hermeneutics usefully · describes processes of learning. As a prescriptive model, hermeneutics can be used to guide students' encounters with texts and other objects of study, and to orchestrate a critical dialogue which exposes and tests prejudices, ideology, and misunderstanding. Out of these encounters, students come to greater self knowledge and realize possibilities for choice and change. The paper illustrates hermeneutic concepts and processes with classroom examples and student testimony.

      • Nonalcoholic fatty liver disease is associated with cognitive function in adults

        Seo, Sang Won,Gottesman, Rebecca F.,Clark, Jeanne M.,Hernaez, Ruben,Chang, Yoosoo,Kim, Changsoo,Ha, Kyoung Hwa,Guallar, Eliseo,Lazo, Mariana Ovid Technologies (Wolters Kluwer) - American Acad 2016 Clinical Neurophysiology Vol.86 No.12

        <P>Objective: We hypothesized that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment in a representative sample of the general US population regardless of the presence of cardiovascular disease (CVD) or its risk factors. Methods: This was a cross-sectional study of 4,472 adults aged 20-59 years who participated in the Third National Health and Nutritional Examination Survey. The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound, and underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT). We defined NAFLD as moderate/severe steatosis as determined by ultrasound in the absence of hepatitis B or C or excessive alcohol consumption. We used multiple linear regression models to examine the association between NAFLD and cognitive function while controlling for potential confounders. Results: Participants with NAFLD showed lower overall performance on the SDLT (beta = 0.726, 95% confidence interval [CI] 0.105-1.347), while associations with SRTT and SDST did not reach significance. Increased activity of the liver enzymes alanine aminotransferase (beta = 0.018, 95% CI 0.006-0.030) and aspartate aminotransferase (beta = 0.021, 95% CI 0.005-0.037) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST (beta = 0.002, 95% CI 0.0001-0.004). Conclusions: NAFLD was independently associated with lower cognitive performance independent of CVD and its risk factors. Given the scarcity of risk factors associated with age-related cognitive decline, these findings may have significant implications.</P>

      • KCI등재

        Liver Enzymes and Risk of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

        Angela Ruban,Natalie Daya,Andrea L.C. Schneider,Rebecca Gottesman,Elizabeth Selvin,Josef Coresh,Mariana Lazo,Silvia Koton 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.3

        Background and Purpose Liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [GGT]) are glutamate-regulatory enzymes, and higher glutamate levels correlated with worse prognosis of patients with neurotrauma. However, less is known about the association between liver enzymes and incidence of stroke. We evaluated the association between serum levels of AST, ALT, and GGT and incidence of stroke in the Atherosclerosis Risk in Communities (ARIC) study cohort from 1990 to 1992 through December 31, 2016. Methods We included 12,588 ARIC participants without prevalent stroke and with data on liver enzymes ALT, AST, and GGT at baseline. We used multivariable Cox regression models to examine the associations between liver enzymes levels at baseline and stroke risk (overall, ischemic stroke, and intracerebral hemorrhage [ICH]) through December 31, 2016, adjusting for potential confounders. Results During a median follow-up time of 24.2 years, we observed 1,012 incident strokes (922 ischemic strokes and 90 ICH). In age, sex, and race-center adjusted models, the hazard ratios (HRs; 95% confidence intervals [CIs]) for the highest compared to lowest GGT quartile were 1.94 (95% CI, 1.64 to 2.30) for all incident stroke and 2.01 (95% CI, 1.68 to 2.41) for ischemic stroke, with the results supporting a dose-response association (P for linear trend <0.001). Levels of AST were associated with increased risk of ICH, but the association was significant only when comparing the third quartile with the lowest quartile (adjusted HR, 1.82; 95% CI, 1.06 to 3.13). Conclusions Elevated levels of GGT (within normal levels), independent of liver disease, are associated with higher risk of incident stroke overall and ischemic stroke, but not ICH.

      • SCISCIESCOPUS

        A “Silent” Polymorphism in the <i>MDR</i>1 Gene Changes Substrate Specificity

        Kimchi-Sarfaty, Chava,Oh, Jung Mi,Kim, In-Wha,Sauna, Zuben E.,Calcagno, Anna Maria,Ambudkar, Suresh V.,Gottesman, Michael M. American Association for the Advancement of Scienc 2007 Science Vol.315 No.5811

        <P>Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the function of the protein in which they occur. We report that a synonymous SNP in the <I>Multidrug Resistance</I> 1 (<I>MDR</I>1) gene, part of a haplotype previously linked to altered function of the <I>MDR</I>1 gene product P-glycoprotein (P-gp), nonetheless results in P-gp with altered drug and inhibitor interactions. Similar mRNA and protein levels, but altered conformations, were found for wild-type and polymorphic P-gp. We hypothesize that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.</P>

      • Decreased Catalytic Subunit mRNA Levels and Altered Catalytic Subunit mRNA Structure in a cAMP-resistant Chinese Hamster Ovary Cell line

        Howard, Paul,Day, Kathleen H.,Kim, Kyoon E.,Richardson, Jeanne,Thomas, James,Abraham,Irene,Fleischmann, Robert D.,Gottesman, Michael M.,Maurer, Richard A. 충남대학교부설 생명공학연구소 1992 생물공학연구지 Vol.2 No.-

        The mechansims responsible for decreased levels of cAMP-dependent protein kinase activity in a mutant Chinese hamster ovary cell line have been examined. The cAMP-resistant Chinese hamster ovary 10260 cell line was found to possess only 20% of the cAMP-dependent protein kinase activity found in wild-type cells. The pressence of decreased concentrations of the catalytic subunit in these cells was confirmed through binding studies using a radiolabeled, heat-stable inhibitor of the kinase. Cloned Chinese hamster ovary catalytic subunit cDNAs were isolated, characterized, and used as hybridization probes to examine the relative concentrations of catalytic subunit mRNAs in the wild-type and 10260 cell lines. A 40-50% decrease in the concentration of the mRNA for the Cα isozyme of the catalytic subunit was observed in 10260 cells, as compared with wild-type. This decrease in catalytic subunit mRNA concentration probably accounts for a portion of the decreased kinase activity in the mutant cell. Further analysis of Cα mRNA by polymerase chain reaction confirmed the decreased expression of Cα mRNA in 10260 cells and further demonstrated the presence of two different species of Cα cDNAs was indistinguishable from the wild-type cDNA, but the other species was shorter. Nucleotide sequence analysis of the amplified cDNAs led to the identification of a 191-base pair deletion in the shorter cDNA. Gene transfer studies using wild-type and 10260 Cα cDNAs demonstrated wild-type activity, but the shorter cDNA was inactive. These studies suggest that at least two alternations in gene expression are responsible for decreased cAMP-dependent protein kinase activity in the 10260 cell line. One alteration results in an approximately 2-fold decrease in the concentrations of Cα mRNA in the cells.

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