43 research outputs found
Planning for Institutional Development and Developing Budgets and Financial Management Systems
This section lays out issues related to strategic planning by the Foundation for Community Development (FDC) and illustrates the development of budgets and financial management systems by the Philippine Business for Social Progress (PBSP). Also explored here is the financial reporting system set up by the Esquel Ecuador Foundation (FEE) for their grantees
CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus
Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.United States. National Institutes of Health (DK085713)National Cancer Institute (U.S.) (P30-CA14051)National Institute of Environmental Health Sciences (P30-ES002109)United States. National Institutes of Health (1K08DK101754
China whispers : the symbolic, economic, and political presence of China in contemporary American science fiction film
China has long been present in Western science fiction, but largely through notions of Orientalism
and depictions as the 'Yellow Peril'. However, with China's new ascendancy and modernization over the
last 15 years, along with its investment and collaboration with Hollywood in particular, contemporary film
in general, and contemporary science fiction in particular, has embraced this new China in ways hitherto
unseen before. This essay examines three contemporary western/American science fiction films which
each represent and construct China in slightly different ways, and in ways which reveal the West, and
Hollywood's reappraisal of the relationship with China and its emerging 'Soft Power'
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Frequentist and Bayesian Meta-Analyses with Dynamic Variance
When researchers conduct a meta-analysis, the sampling variances of individual study effects are important for estimating the meta-analytic model. However, for some effect size measures such as correlations and standardized mean differences, the variance is dependent on the true effect size in the population, which is not normally known. This study uses a new âdynamic methodâ for mixed-effects meta-analysis for correlations and standardized mean differences that takes this dependence into account. Comparing results using the dynamic method with other commonly used meta-analysis methods in the frequentist and bayesian framework shows that the dynamic approach has improved estimation, particularly with correlation effect-size. Another finding of note is that incorporating Hedges bias correction (1981) standardized mean differences is shown to increase bias in conventional meta-analytic results
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Frequentist and Bayesian Meta-Analyses with Dynamic Variance
When researchers conduct a meta-analysis, the sampling variances of individual study effects are important for estimating the meta-analytic model. However, for some effect size measures such as correlations and standardized mean differences, the variance is dependent on the true effect size in the population, which is not normally known. This study uses a new âdynamic methodâ for mixed-effects meta-analysis for correlations and standardized mean differences that takes this dependence into account. Comparing results using the dynamic method with other commonly used meta-analysis methods in the frequentist and bayesian framework shows that the dynamic approach has improved estimation, particularly with correlation effect-size. Another finding of note is that incorporating Hedges bias correction (1981) standardized mean differences is shown to increase bias in conventional meta-analytic results
Sambandet mellan nedsatt lungfunktion och upplevd fysisk hÀlsorelaterad livskvalité relaterat till BMI och fysisk aktivitet
Bakgrund: I Sverige Ă€r det omkring var Ă„ttonde person som lever med nedsatt lungfunktion. Antalet mĂ€nniskor som lider av nedsatt lungfunktion förvĂ€ntas öka pĂ„ grund av den kraftiga ökningen av fetma och lĂ„g fysisk aktivitet. Ăndrade levnadsvanor har visat sig kunna bidra till förbĂ€ttrad lungfunktion som i sin tur ökar den fysiskt upplevda HRQoL. Sjuksköterskan ska arbeta evidensbaserat och kan genom motiverande samtal hjĂ€lpa patienten till positiv beteendeförĂ€ndring. Syfte: Att beskriva relationen mellan fysisk hĂ€lsorelaterad livskvalitet, BMI och fysisk aktivitet hos Ă€ldre med nedsatt lungfunktion. Metod: Studien var en kvantitativ tvĂ€rsnittsstudie baserad pĂ„ data inhĂ€mtad frĂ„n Swedish National study on Aging and Care - Blekinge (SNAC-B). Datan analyserades med deskriptiv statistik i frekvenstabell och korstabeller för att tydliggöra relationen mellan variablerna. Resultat: Störst andel inom gruppen med BMI â€24,9 upplevde hög fysisk HRQoL nĂ€r de utövade lĂ„gintensiv fysisk aktivitet 2â3 gĂ„nger per mĂ„nad, respektive nĂ€r de utövade högintensiv fysisk aktivitet 1 gĂ„ng per mĂ„nad. Störst andel inom gruppen med BMI >24,9 upplevde hög fysisk HRQoL nĂ€r de utövade lĂ„gintensiv fysisk aktivitet flera gĂ„nger per vecka, respektive nĂ€r de utövade högintensiv fysisk aktivitet 2â3 gĂ„nger per mĂ„nad. Slutsats: Den upplevda fysiska HRQoL ökade i alla grupper vid utövandet av fysisk aktivitet. Störst andel inom gruppen med BMI â€24,9 upplevde hög HRQoL vid utövandet av lĂ„gintensiv fysisk aktivitet 2â3 gĂ„nger per mĂ„nad. Vid utövande av lĂ„gintensiv fysisk aktivitet oftare Ă€n 2â3 gĂ„nger per mĂ„nad upplevde en reducerad andel inom gruppen med BMI â€24,9 hög upplevd fysisk HRQoL, vilket var motsĂ€gande WHO:s rekommendationer om fysisk aktivitet för personer Ă€ldre Ă€n 65 Ă„r
Characterization and application of type VI-B RNA-targeting CRISPR systems
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018.Cataloged from PDF version of thesis.Includes bibliographical references.The ability to modify nucleic acids is critical for establishing the role of genetic and transcribed elements in mediating biological phenotypes. Manipulating endogenous DNA sequences in eukaryotic genomes has been greatly aided by the advent of genome editing technologies that utilize programmable nucleases. DNA nucleases derived from class 2 CRISPR systems, which provide adaptive immunity in prokaryotes through cleavage of nucleic acids using a single, multi-domain, RNA-guided endonuclease, have been particularly useful in this regard because they enable targeting of new sites through simple Watson-Crick base pairing rules. Recent computational studies have uncovered the existence of predicted RNA-targeting class 2 CRISPR systems, suggesting that the power of genome editing techniques might be extended to the level of transcripts. In this thesis, I present work describing the discovery and characterization of a new RNA-targeting class 2 CRISPR system: type VI-B. Using a combination of biochemistry and bacterial genetics, we demonstrated that the predicted nuclease of the VI-B system, Casl3b, is an RNA-guided RNase, whose activity can be modulated by the csx genes that often appear in genetic proximity to casl3b. Next, we characterized the behavior of Casl3b and the related enzymes Casl3a and Casl3c in mammalian cells, identifying orthologs of Casl3a and Casl3b with specific RNA interference activity in mammalian cells. Finally, we showed that catalytically inactive versions of a Casl3b ortholog can direct adenosine-to-inosine deaminase activity to transcripts in human cells when fused to the catalytic domain of ADAR2. Using structure-guided mutagenesis, we created a high-specificity version of this system that can be utilized in research or potentially therapeutic contexts. The description of a Casl3b ortholog that can be used to knockdown or recruit RNA-modifying domains to transcripts in mammalian cells suggests the utility of this technology to interrogate and modify transcript function in diverse contexts.by David Benjamin Turitz Cox.Ph. D