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Institution

Case Western Reserve University

EducationCleveland, Ohio, United States
About: Case Western Reserve University is a education organization based out in Cleveland, Ohio, United States. It is known for research contribution in the topics: Population & Health care. The organization has 54617 authors who have published 106568 publications receiving 5071613 citations. The organization is also known as: Case & Case Western.


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Journal ArticleDOI
TL;DR: The results demonstrate that tumours can acquire somatic mutations that presumably do not directly affect cell growth but result only in genetic instability and suggest that many sporadic tumours with microsatellite instability have alterations in genes other than the four now known to participate in MMR.
Abstract: Microsatellite instability has been observed in both sporadic and hereditary forms of colorectal cancer. In the hereditary form, this instability is generally due to germline mutations in mismatch repair (MMR) genes. However, only one in ten patients with sporadic tumours exhibiting microsatellite instability had a detectable germline mutation. Moreover, only three of seven sporadic tumour cell lines with microsatellite instability had mutations in a MMR gene, and these mutations could occur somatically. These results demonstrate that tumours can acquire somatic mutations that presumably do not directly affect cell growth but result only in genetic instability. They also suggest that many sporadic tumours with microsatellite instability have alterations in genes other than the four now known to participate in MMR.

811 citations

Journal ArticleDOI
TL;DR: Rhodopsins found in Eukaryotes, Bacteria, and Archaea consist of opsin apoproteins and a covalently linked retinal which is employed to absorb photons for energy conversion or the initiation of intra- or intercellular signaling.
Abstract: Organisms of all domains of life use photoreceptor proteins to sense and respond to light. The light-sensitivity of photoreceptor proteins arises from bound chromophores such as retinal in retinylidene proteins, bilin in biliproteins, and flavin in flavoproteins. Rhodopsins found in Eukaryotes, Bacteria, and Archaea consist of opsin apoproteins and a covalently linked retinal which is employed to absorb photons for energy conversion or the initiation of intra- or intercellular signaling.1 Both functions are important for organisms to survive and to adapt to the environment. While lower organisms utilize the family of microbial rhodopsins for both purposes, animals solely use a different family of rhodopsins, a specialized subset of G-protein-coupled receptors (GPCRs).1,2 Animal rhodopsins, for example, are employed in visual and nonvisual phototransduction, in the maintenance of the circadian clock and as photoisomerases.3,4 While sharing practically no sequence similarity, microbial and animal rhodopsins, also termed type-I and type-II rhodopsins, respectively, share a common architecture of seven transmembrane α-helices (TM) with the N- and C-terminus facing out- and inside of the cell, respectively (Figure ​(Figure11).1,5 Retinal is attached by a Schiff base linkage to the e-amino group of a lysine side chain in the middle of TM7 (Figures ​(Figures11 and ​and2).2). The retinal Schiff base (RSB) is protonated (RSBH+) in most cases, and changes in protonation state are integral to the signaling or transport activity of rhodopsins. Figure 1 Topology of the retinal proteins. (A) These membrane proteins contain seven α-helices (typically denoted helix A to G in microbial opsins and TM1 to 7 in the animal opsins) spanning the lipid bilayer. The N-terminus faces the outside of the cell ...

811 citations

Journal ArticleDOI
Jennifer K. Adelman-McCarthy1, Marcel A. Agüeros2, S. Allam3, S. Allam1  +163 moreInstitutions (54)
TL;DR: The Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS) was released in 2005 June and represents the completion of the SDSS-I project as mentioned in this paper, which includes five-band photometric data for 217 million objects selected over 8000 deg 2 and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 deg 2 of imaging data.
Abstract: This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through 2005 June and represents the completion of the SDSS-I project (whose successor, SDSS-II, will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 deg^2 and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 deg^2 of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus Cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.

811 citations

Journal ArticleDOI
01 Dec 2001-Diabetes
TL;DR: Data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-KappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF- kappaB activation observed in hyperglycemia and possibly other chronic diseases.
Abstract: Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.

809 citations

Journal ArticleDOI
TL;DR: Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine isMore effective than olanZapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.
Abstract: Background Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression. Objective To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Design Double-blind, 8-week, randomized controlled trial. Setting Eighty-four sites (inpatient and outpatient) in 13 countries. Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86). Main Outcome Measure Changes in MADRS total scores using mixed-effects model repeated-measures analyses. Results During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group ( P Conclusions Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.

807 citations


Authors

Showing all 54953 results

NameH-indexPapersCitations
Robert Langer2812324326306
Bert Vogelstein247757332094
Zhong Lin Wang2452529259003
John Q. Trojanowski2261467213948
Kenneth W. Kinzler215640243944
Peter Libby211932182724
David Baltimore203876162955
Carlo M. Croce1981135189007
Ronald Klein1941305149140
Eric J. Topol1931373151025
Paul M. Thompson1832271146736
Yusuke Nakamura1792076160313
Dennis J. Selkoe177607145825
David L. Kaplan1771944146082
Evan E. Eichler170567150409
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023142
2022411
20214,337
20204,141
20193,978
20183,663