88,289 research outputs found
Systematic reviews with language restrictions and no author contact have lower overall credibility: a methodology study
No full textZhen Wang,1–3 Juan P Brito,4 Apostolos Tsapas,5 Marcio L Griebeler,4 Fares Alahdab,1,3 Mohammad Hassan Murad,1,3,61Robert D and Patricia E Kern Center for the Science of Health Care Delivery, 2Division of Health Care Policy and Research, Department of Health Sciences Research, 3Knowledge and Evaluation Research Unit, 4Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA; 5Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN, USABackground: High-quality systematic reviews (SRs) require rigorous approaches to identify, appraise, select, and synthesize research evidence relevant to a specific question. In this study, we evaluated the association between two steps in the conduct of an SR – restricting the search to English, and author contact for missing data – and the overall credibility of a SR.Methods: All SRs cited by the Endocrine Society's Clinical Practice Guidelines published from October 2006 through January 2012 were included. The main outcome was the overall A Measurement Tool to Assess Systematic Reviews (AMSTAR) score, as a surrogate of SR credibility. Nonparametric Kruskal–Wallis tests and multivariable linear regression models were used to investigate the association between language restriction, author contact for missing data, and the overall AMSTAR score.Results: In all, 69 SRs were included in the analysis. Only 31 SRs (45%) reported searching non-English literature, with an average AMSTAR score of 7.90 (standard deviation [SD] =1.64). SRs that reported language restriction received significantly lower AMSTAR scores (mean =5.25, SD =2.32) (P<0.001). Only 30 SRs (43%) reported contacting authors for missing data, and these received, on average, 2.59 more AMSTAR points (SD =1.95) than those who did not (P<0.001). In multivariable analyses, AMSTAR score was significantly correlated with language restriction (beta =-1.31, 95% confidence interval [CI]: -2.62, -0.01, P=0.05) and author contact for missing data (beta =2.16, 95% CI: 0.91, 3.41, P=0.001). However, after adjusting for compliance with reporting guidelines, language restriction was no longer significantly associated with the AMSTAR score.Conclusion: Fewer than half of the SRs conducted to support the clinical practice guidelines we examined reported contacting study authors or searched non–English literature. SRs that did not conduct these two steps had lower quality scores, suggesting the importance of these two steps for overall SR credibility.Keywords: evidence-based medicine, research design, validity, quality of evidenc
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Der Einfluss molekularer Mechanismen auf die Expression des NO-sensitiven Rezeptors lösliche Guanylatzyklase (sGC)
No full textSoluble guanylyl cyclase (sGC) is a cytosolic enzyme producing the intracellular messenger cyclic guanosine monophosphate (cGMP) on activation with nitric oxide (NO) which leads to the activation of GMP dependent protein kinases and to vasodilation. NO signaling may be affected by altered expression of sGC subunits, as has been shown in different pathological and physiological conditions and developmental stages. The molecular mechanisms underlying altered sGC expression in these and other conditions have not yet been revealed. Gene expression can also be regulated at the level of mRNA through alterations in translational efficiency and in mRNA stability. HuR (Human R) is a ubiquitously expressed member of the embryonic lethal abnormal vision (ELAV) family of RNA-binding proteins. Among other RNAs, there has been recent evidence that the expression of sGC is subject to post-transcriptional regulation by HuR. It has been shown that chronic hypertension induces changes in HuR expression and activity, which account for decreased sGC expression and activity in the aorta of hypertensive rats. This thesis should study was performed in an effort to provide some insight to the transcriptional and post-transcriptional regulation of sGC expression in a mammal, the rat. We investigated rat sGC alpha-1 transcriptional regulation in rat lung fibroblast (RLF-6) cells. The 3000bp 5' upstream region of the alpha-1 sGC gene was isolated and analyzed for promoter activity by using luciferase reporter constructs- Alpha3000 (with -2794 bp), Alpha1100 (-1092 bp), Alpha350 (-346 bp) and Alpha200 (-200 bp). The promoter activity was the highest in the 200bp construct (about 6-fold higher than Alpha3000) suggesting that this fragment contains all the crucial elements necessary to support basal transcription of the alpha-1 sGC gene. Analysis of the 200 bp of the 5’ UTR of the alpha-1 gene was performed using the MATINSPECTOR V2.2 software for putative transcription factors. The constructs containing the deleted sites for NFY and Sp1 showed a significant decrease in constitutive promoter activity by almost 80% and 60% respectively, implying that these transcription factors are crucial elements in the basal expression of the of sGC alpha-1 subunit. Treatment of RLF-6 cells with genistein 50 microM and mithramycinA 100 nM, known to inhibit the NFY and Sp1 binding to DNA respectively, reflected the same effects. Furthermore the cGMP content of the cells was significantly reduced by both inhibitors, almost completely by genistein, and by about 40 % by mithramycinA. Electrophoretic mobility-shift assay (EMSA) clearly showed the formation of multiple complexes with the biotinylated ODN (decoy oligodeoxynucleotide) probes for NFY and Sp1 when incubated with RLF-6 nuclear extract. A “supershift” observed in the presence of antibodies to the individual transcription factors confirmed that these factors were present in the shifted band, indeed. NFY and Sp1 are instrumental in several physiological and pathophysiological effects mediated by several growth factors in smooth muscle cells. Thus the regulation of the promoter, in response to serum, was also analysed. 10% foetal calf serum led to decreased alpha-1 sGC level as shown by western blots performed with rat aorta. Decreased sGC alpha-1 mRNA expression was observed in RLF-6 cells and cultured rat aortic smooth muscle cells incubated with FCS for 24 hours. This decrease was reflected in the promoter activity in RLF-6 cells using both Alpha3000 and Alpha200 constructs confirming that the regulation took place at promoter level. EMSA performed with nuclear extracts from FCS treated RLF-6 cells led to diminished binding to NFY, but to an enhanced binding to Sp1 site. We concluded that the factors Sp1 and NFY (the sites overlapping) compete for binding, and in the presence of FCS, it is Sp1 that binds stronger, and hence results in diminishing promoter activity. In order to delineate the post-transcriptional regulation of sGC alpha-1 subunit, studies were performed to demonstrate the regulation of expression of the mRNA stabilizing protein HuR. It has been observed that exposure of isolated rat aortic segments to the activator of adenylyl cyclase, forskolin, strongly reduced sGC alpha-1/beta-1 and HuR protein and mRNA expression in a time-dependent and actinomycin D-sensitive fashion. Transcription factor decoy approach proved that the cAMP-induced down-regulation of HuR is mediated by the activation of AP-1. It has been established that HuR stabilises the sGC alpha-1 and beta-1 mRNA. However the pathway underlying this regulation remains unknown. In order to identify the mechanism of this regulation, we looked for HuR interacting proteins employing the yeast two hybrid assay. The enzyme of the polyamine catabolic pathway spermidine/spermine N1-acetyltransferase (SSAT) was found to interact with the hinge region of HuR. This interaction was confirmed by performing immunoprecipitation and GST-pulldown experiments. A direct effect of these proteins on each other’s biological activity was not visible as tested through the SSAT activity assay and HuR gel shift. It might be possible that SSAT-mediated modulation of local polyamine concentrations enhances/reduces HuR activity and sGC expression to affect cell proliferation. In summary, this study represents an analysis of the rat sGC alpha-1 promoter regulation in rat fibroblast cells and identifies NFY and Sp1 as important factors in sGC alpha-1 expression. It also gives first evidence of sGC regulation at the transcriptional level in response to an external stimulus, and proposes the possible mechanism. It also identifies SSAT as a HuR interacting protein. These might have implications in the various pathophysiological conditions where sGC plays an important role.Die lösliche Guanylatzyklase (soluble guanylyl cyclase, sGC) ist ein Schlüsselenzym der NO/cGMP Signaltransduktion im kardiovaskulären System. Nach Aktivierung der sGC durch Stickstoffmonoxid (NO) kommt es in glatten Muskelzellen zur Produktion von zyklischem 3’,5’-Guanosinmonophosphat (cGMP), das als intrazelluläres Signaltransduktionsmolekül die Aktivierung von cGMP-abhängigen Proteinkinasen vermittelt und zur Vasodilatation führt. Die NO/cGMP-Signaltransduktion kann auch auf der Ebene der Gen-Expression beeinflusst werden. So konnte in verschiedenen physiologischen bzw. pathophysiologischen Modellen gezeigt werden, dass die unterschiedliche Expression von sGC-Untereinheiten die NO/cGMP-Signaltransduktion beeinflusst. Die molekularen Mechanismen, die auf der unterschiedlichen Expression der sGC-Untereinheiten basieren, wurden bisher noch nicht ausreichend aufgeklärt. Die Gen-Expression kann auf mRNA-Ebene durch Veränderung der Translation und der mRNA- (messenger ribonucleic acid, Boten-Ribonnukleinsäure) Stabilität reguliert werden. HuR (Human R) ist ist ein ubiquitär vorkommendes Mitglied der embryonic lethal abnormal vision (ELAV-) Familie der RNA-bindenden Proteine. Neben der Regulierung anderer Gene gibt es Hinweise darauf, dass auch die Expression der sGC einer post-translationalen Regulation durch HuR unterliegt. So wurde gezeigt, dass chronischer Bluthochdruck Veränderungen in der HuR-Expression und -Aktivität verursacht, was zu einer verminderten sGC-Expression und -Aktivität in der Aorta von hypertensiven Ratten führt. Diese Arbeit soll einen Einblick in die transkriptionale und post-transkriptionale Regulation der sGC-Expression im Rattenmodell liefern. Im Rahmen dieser Arbeit wurde die translationale Regulation der alpha-1 sGC-Untereinheit der Ratte in Rattenlungen-Fibroblastenzellen (rat lung fibroblast cells, RLA-6) untersucht. Es wurden die 3000 bp der 5´ upstream Region des Gens der alpha-1 sGC-Untereinheit isoliert und mit Hilfe von Luziferase-Reporter-Konstrukten - Alpha3000 (mit -2794 bp), Alpha1100 (-1092 bp), Alpha350 (-346 bp) und Alpha200 (-200 bp) - auf Promotor-Aktivität untersucht. Dabei war die Promotor-Aktivität des 200 bp Konstrukts am höchsten (ca. 6-fach im Vergleich zu Alpha3000). Dies deutete daraufhin, dass dieses Fragment entscheidende Elemente enthält, die für die basale Transkription des alpha-1 sGC Gens nötig sind. Um nach vermeintlichen Transkriptionsfaktoren zu suchen, wurde die Analyse der 200 bp am 5´ UTR des alpha-1 Gens mit der MATINSPECTOR V2.2 Software durchgeführt. Die Konstrukte mit den entfernten Stellen für NFY und Sp1 zeigten eine signifikante Verminderung in der konstitutiven Promotor-Aktivität zu fast 80 und 60%. Dies deutete daraufhin, dass diese Transkriptionsfaktoren entscheidend sind für die basale Expression der alpha-1 sGC-Untereinheit. Die Behandlung der RLF-6 Zellen mit Genistein (50 mikroM) und Mithramycin A (100 nM), die die Anbindung von NFY und Sp1 an die DNA inhibieren, führte ebenfalls zu einer Reduktion der Promotor-Aktivität. Außerdem war der Gehalt von cGMP in den Zellen durch die beiden Inhibitoren signifikant reduziert - mit Genistein wurde eine fast komplette Inhibition erreicht und mit Mithramycin A eine Reduktion um ca. 40%. Der EMSA (electrophoretic mobility-shift assay) zeigte deutlich die Bildung von multiplen Komplexen mit biotinylierten ODN (decoy oligodeoxynucleotide) Proben für NFY und Sp1, wenn diese mit RLF-6 Zellkern-Extrakt inkubiert wurden. In einem „supershift“ konnten die einzelnen Transkriptionsfaktoren mit Antikörpern nachgewiesen werden. NFY und Sp1 sind an zahlreichen physiologischen und pathophysiologischen Prozessen in glatten Muskelzellen beteiligt, die durch Wachstumsfaktoren gesteuert werden. Aus diesem Grund wurde die Regulation des Promotors in Gegenwart von Serum analysiert. Mit Western-Blot Analysen konnte gezeigt werden, dass 10 % fötales Kälber-Serum (foetal calf serum, FCS) zu einer verminderten Expression von alpha-1 sGC in Rattenaortenringen führte. Eine verminderte sGC alpha-1 mRNA-Expression wurde in RLF-6 Zellen und in kultivierten glatten Muskelzellen der Rattenaorta, die mit FCS über 24 Stunden inkubiert wurden, demonstriert. Diese Verminderung ging einher mit einer verminderten Promotor-Aktivität der Konstrukte Alpha3000 und Alpha200 in RLF-6 Zellen, was eine Regulation auf Promotor-Ebene aufzeigte. EMSA Studien mit Zellkern-Extrakt aus FCS-vorbehandelten RLF-6 Zellen zeigten eine verminderte NFY-, aber eine gesteigerte Sp1-Bindung. Daraus wurde gefolgert, dass die Faktoren Sp1 und NFY um eine Bindungsstelle am Promotor konkurrieren und dass die Gegenwart von FCS zu einer verstärkten Sp1-Bindung und damit zu einer verminderten Promotor-Aktivität führt. Um die post-transkriptionale Regulation der alpha-1 sGC-Untereinheit zu demonstrieren, wurden Versuche zur Regulation der Expression des mRNA-stablisierenden Proteins HuR durchgeführt. Es konnte gezeigt werden, dass die Inkubation von isolierten Rattengefäßringen mit Forskolin, einem Aktivator der Adenylatzyklase, die sGC alpha-1/beta-1 und die HuR Protein- und mRNA-Expression zeitabhängig und Actinomycin D-sensitiv reduziert. Der Transkriptionsfaktor-Abbau bewies, dass die cAMP-induzierte Runterregulation von HuR durch die Aktivierung von AP-1 vermittelt wird. Es konnte festgestellt werden, dass HuR die alpha-1 und beta-1 mRNA der sGC stabilisiert. Aber die Regulation dieser Signalwege war bisher unbekannt. Um den Mechanismus der Regulation zu identifizieren, haben wir nach HuR-interagierenden Proteinen durch Anwendung des Yeast-two-hybrid assays gesucht. Die Enzyme des Polyamin-katabolischen Signalwegs Spermidin/ Spermin N1-Acetyltransferase (SSAT) wurden als eine hinge Region von HuR entdeckt. Diese Interaktion wurde bestätigt durch Immunopräzipitation und GST-pulldown Experimente. Einen direkten gegenseitigen Effekt auf die Aktivität dieser Proteine war nicht sichtbar, was durch SSAT activity assays und HuR gel shifts getested wurde. Es könnte möglich sein, dass die SSAT-vermittelte Modulation der lokalen Polyamin-Konzentration die HuR-Aktivität und die sGC-Expression fördert bzw. vermindert bei der Zellproliferation. Diese Arbeit zeigt eine Analyse der Promotor-Regulation der alpha-1 sGC-Untereinheit der Ratte in Fibroblastenzellen der Ratte und identifiziert NFY und Sp1 als wichtige Faktoren in der alpha-1 sGC-Expression. Die sGC-Regulation auf transkriptionaler Ebene unter Beteiligung der Transkriptionsfaktoren NFY und Sp1, ausgelöst durch Serum als externen Stimulus, weist auf einen möglichen Mechanismus hin. Außerdem wurde SSAT als HuR-Interaktionsprotein identifiziert. Die in dieser Arbeit dargestellte Regulation der sGC-Expression könnte Einfluss haben auf verschiedene pathophysiologische Zustände
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
John F. Kennedy telegram to Roosevelt
No full textJersey Homesteads (later the Borough of Roosevelt) was established in the 1930s as an agro-industrial cooperative community. It was established specifically for urban Jewish garment workers, many of whom had emigrated from Europe. President John F. Kennedy sent a telegram to the citizens of Roosevelt, New Jersey, apologizing for not being able to attend the memorial dedication in honor of former President Franklin Delano Roosevelt. (Jersey Homesteads became Roosevelt in 1945 in honor of the president.) President Kennedy expressed his gratitude to the people of Roosevelt for constructing the memorial, and commented that it will serve as a constant reminder of Roosevelt's good works
Logarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection
No full textWe report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either
Maine author Franklin F. Gould recalls his first glimpse of the outside world
No full textMaine author Franklin F. Gould recalls his first glimpse of the outside world as he relates how, as a young farm boy in the late 1800\u27s, he drove his father\u27s horses on an errand to an icebound river
Asymptotic normality of wavelet estimators of the memory parameter for linear processes
No full textWe consider linear processes, not necessarily Gaussian, with long, short or negative memory. The memory parameter is estimated semi‐parametrically using wavelets from a sample X1,…, Xn of the process. We treat both the log‐regression wavelet estimator and the wavelet Whittle estimator. We show that these estimators are asymptotically normal as the sample size n → ∞ and we obtain an explicit expression for the limit variance. These results are derived from a general result on the asymptotic normality of the scalogram for linear processes, conveniently centred and normalized. The scalogram is an array of quadratic forms of the observed sample, computed from the wavelet coefficients of this sample. In contrast to quadratic forms computed on the basis of Fourier coefficients such as the periodogram, the scalogram involves correlations which do not vanish as the sample size n → ∞.We thank the referee for his comments. Murad S. Taqqu thanks Telecom ParisTech for their hospitality. This research was partially supported by the NSF Grants DMS-0505747 and DMS-0706786 at Boston University. (DMS-0505747 - NSF; DMS-0706786 - NSF)First author draf
Mapping the Discipline of the Olympic Games An Author-Cocitation Analysis
No full textThe authors conducted an author cocitation analysis on prominent authors writing about the Olympics during the 1990s. Author cocitation is an established bibliometric technique that can be used to measure the relative similarities of topics written about by the cited authors. This enables a visual representation of the “intellectual space” of the discipline, in this case the Olympics, to be created for the period under review. So core and peripheral research areas are identified, along with their major contributors. The representation appears as a two-dimensional cluster-enhanced map. Subject expertise was then applied to the results to place labels on the generated clusters of authors and their topics
- …
