1,359 research outputs found

    Ultraviolet radiation sensitivity and reduction of telomeric silencing in Saccharomyces cerevisiae cells lacking chromatin assembly factor-I

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    In vivo, nucleosomes are formed rapidly on newly synthesized DNA after polymerase passage. Previously, a protein complex from human cells, termed chromatin assembly factor-I (CAF-I), was isolated that assembles nucleosomes preferentially onto SV40 DNA templates that undergo replication in vitro. Using a similar assay, we now report the purification of CAF-I from the budding yeast Saccharomyces cerevisiae. Amino acid sequence data from purified yeast CAF-I led to identification of the genes encoding each subunit in the yeast genome data base. The CAC1 and CAC2 (chromatin assembly complex) genes encode proteins similar to the p150 and p60 subunits of human CAF-I, respectively. The gene encoding the p50 subunit of yeast CAF-I (CAC3) is similar to the human p48 CAF-I subunit and was identified previously as MSI1, a member of a highly conserved subfamily of WD repeat proteins implicated in histone function in several organisms. Thus, CAF-I has been conserved functionally and structurally from yeast to human cells. Genes encoding the CAF-I subunits (collectively referred to as CAC genes) are not essential for cell viability. However, deletion of any CAC gene causes an increase in sensitivity to ultraviolet radiation, without significantly increasing sensitivity to gamma rays. This is consistent with previous biochemical data demonstrating the ability of CAF-I to assemble nucleosomes on templates undergoing nucleotide excision repair. Deletion of CAC genes also strongly reduces silencing of genes adjacent to telomeric DNA; the CAC1 gene is identical to RLF2 (Rap1p localization factor-2), a gene required for the normal distribution of the telomere-binding Rap1p protein within the nucleus. Together, these data suggest that CAF-I plays a role in generating chromatin structures in vivo

    Knowledge Transfer and Teaching Public Administration: the Academy Model

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    Since the beginnings of Public Administration in the US and its accompanying education in other parts of the world, government and policy have become more complex. The education in Public Administration created a professional pathway to public service. The addition of education to Public Administration came out of the Progressive Movement in the United States to make knowledge in Public Administration more important in the face of corruption brought on by patronage appointments. When nonprofits became part the US public sector as elsewhere along with nonprofit healthcare, the complexity expanded enormously, requiring professionals to know more in what has become a multidisciplinary field of study. Given the diversity and complexity of the public sector and the need for Public Administration to embrace more knowledge from many disciplines, it stands to reason that an earlier start on the education portion of Public Administration or a pathway would be beneficial. A model of early Public Administration knowledge transfer is described and illustrated below. The Academy described is based on the US career pathways and high school academies as part of the school to work educational movement. The success of the combination of these two areas will also be pointed out in the academy described. Translation of lessons learned from the Acdemy to Europe and Asia are also considered

    Excess noise in GaAs and AlGaAs avalanche photodiodes with GaSb absorption regions—composite structures grown using interfacial misfit arrays

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    Interfacial misfit arrays were embedded within two avalanche photodiode (APD) structures. This allowed GaSb absorption layers to be combined with wide-bandgap multiplication regions, consisting of GaAs and Al0.8Ga0.2As, respectively. The GaAs APD represents the simplest case. The Al0.8Ga0.2As APD shows reduced dark currents of 5.07 μAcm−2 at 90% of the breakdown voltage, and values for effective below 0.2. Random-path-length modeled excess noise is compared with experimental data, for both samples. The designs could be developed further, allowing operation to be extended to longer wavelengths, using other established absorber materials which are lattice matched to GaSb

    Clinical Blood Flow Quantification with Segmented k-Space Magnetic Resonance Phase Velocity Mapping

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    To evaluate the accuracy of segmented k-space magnetic resonance phase velocity mapping (PVM) in quantifying aortic blood flow from through-plane velocity measurements. Two segmented PVM schemes were evaluated, one with seven lines per segment (seg-7) and one with nine lines per segment (seg-9), in twenty patients with cardiovascular disease. A non-segmented (non-seg) PVM acquisition was also performed to provide the reference data. There was agreement between the aortic flow curves acquired with segmented and non-segmented PVM. The calculated systolic and total flow volume per cycle from the seg-7 and the seg-9 scans correlated and agreed with the flow volumes from the non-seg scans (differences \u3c 5%). Sign tests showed that there were no statistically significant differences (P-values \u3c 0.05) between the segmented and the non-segmented PVM measurements. Seg-9, which was the fastest among the three sequences, provided adequate spatial and temporal resolution (\u3e 10 phases per cycle)

    An epidemiologic study of early biologic effects of benzene in Chinese workers.

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    Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans

    Curricular orientations to real-world contexts in mathematics

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    A common claim about mathematics education is that it should equip students to use mathematics in the ‘real world’. In this paper, we examine how relationships between mathematics education and the real world are materialised in the curriculum across a sample of eleven jurisdictions. In particular, we address the orientation of the curriculum towards application of mathematics, the ways that real-world contexts are positioned within the curriculum content, the ways in which different groups of students are expected to engage with real-world contexts, and the extent to which high-stakes assessments include real-world problem solving. The analysis reveals variation across jurisdictions and some lack of coherence between official orientations towards use of mathematics in the real world and the ways that this is materialised in the organisation of the content for students

    Reference points for predators will progress ecosystem-based management of fisheries.

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    Ecosystem-based management of fisheries aims to allow sustainable use of fished stocks while keeping impacts upon ecosystems within safe ecological limits. Both the FAO Code of Conduct for Responsible Fisheries and the Aichi Biodiversity Targets promote these aims. We evaluate implementation of ecosystem-based management in six case study fisheries in which potential indirect impacts upon bird or mammal predators of fished stocks are well publicized and well studied. In particular we consider the components needed to enable management strategies to respond to information from predator monitoring. Although such information is available in all case studies, only one has a reference point defining safe ecological limits for predators and none has a method to adjust fishing activities in response to estimates of the state of the predator population. Reference points for predators have been developed outside the fisheries management context but adoption by fisheries managers is hindered a lack of clarity about management objectives and uncertainty about how fishing affects predator dynamics. This also hinders the development of adjustment methods because these generally require information on the state of ecosystem variables relative to reference points. Nonetheless, most of the case studies 58 include precautionary measures to limit impacts on predators. These measures are not used tactically and therefore risk excessive restrictions on sustainable use. Adoption of predator reference points to inform tactical adjustment of precautionary measures would be an appropriate next step towards ecosystem-based management
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