2,015 research outputs found

    Launching Literacy in After-School Programs: Early Lessons from the CORAL Initiative

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    The James Irvine Foundation launched the Communities Organizing Resources to Advance Learning (CORAL) initiative in 1999 with the goal of improving the academic achievement of children in the lowest-performing schools in five California cities. In 2004, CORAL adopted a more targeted approach toward reaching this goal by integrating a regular schedule of literacy instruction into its after-school programs. This interim report, based on research conducted between Fall 2004 and Summer 2005, documents CORALs progress toward implementing high-quality and consistent literacy programming. The report presents early results in terms of youths positive reading gains and describes the program components that appear to have contributed to these gains. It also identifies challenges CORAL sites faced and successful strategies for addressing those challenges

    Advancing Achievement: Findings from an Independent Evaluation of a Major After-School Initiative

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    This report presents outcomes from Public/Private Ventures research on CORAL, an eight-year, $58 million after-school initiative of The James Irvine Foundation. Findings described in the report demonstrate the relationship between high-quality literacy programming and academic gains and underscore the potential role that quality programs may play in the ongoing drive to improve academic achievement. The report includes a 12-page executive summary

    HHV-8 encoded LANA-1 alters the higher organization of the cell nucleus

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    The latency-associated nuclear antigen (LANA-1) of Human Herpes Virus 8 (HHV-8), alternatively called Kaposi Sarcoma Herpes Virus (KSHV) is constitutively expressed in all HHV-8 infected cells. LANA-1 accumulates in well-defined foci that co-localize with the viral episomes. We have previously shown that these foci are tightly associated with the borders of heterochromatin [1]. We have also shown that exogenously expressed LANA-1 causes an extensive re-organization of Hoechst 33248 DNA staining patterns of the nuclei in non-HHV-8 infected cells [2]. Here we show that this effect includes the release of the bulk of DNA from heterochromatic areas, in both human and mouse cells, without affecting the overall levels of heterochromatin associated histone H3 lysine 9 tri-methylation (3MK9H3). The release of DNA from the heterochromatic chromocenters in LANA-1 transfected mouse cells co-incides with the dispersion of the chromocenter associated methylcytosin binding protein 2 (MECP2). The localization of 3MK9H3 to the remnants of the chromocenters remains unaltered. Moreover, exogeneously expressed LANA-1 leads to the relocation of the chromocenters to the nuclear periphery, indicating extensive changes in the positioning of the chromosomal domains in the LANA-1 harboring interphase nucleus. Using a series of deletion mutants we have shown that the chromatin rearranging effects of LANA-1 require the presence of a short (57 amino acid) region that is located immediately upstream of the internal acidic repeats. This sequence lies within the previously mapped binding site to histone methyltransferase SUV39H1. We suggest that the highly concentrated LANA-1, anchored to the host genome in the nuclear foci of latently infected cells and replicated through each cell generation, may function as "epigenetic modifier". The induction of histone modification in adjacent host genes may lead to altered gene expression, thereby contributing to the viral oncogenesis

    Diagnostic Performance of Clinicopathological Analytes in Otostrongylus circumlitis-Infected Rehabilitating Juvenile Northern Elephant Seals (Mirounga angustirostris)

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    The nematode lungworm, Otostrongylus circumlitis (OC), is a significant cause of northern elephant seal (NES; Mirounga angustirostris) mortality at The Marine Mammal Center (TMMC, Sausalito, CA). The current lack of specific antemortem diagnostic tests for pre-patent OC infection in NES makes diagnosis, proper treatment, and assessment of efficacy of medications challenging. Severe inflammation and disseminated intravascular coagulation (DIC) develop rapidly and are difficult to treat once clinical signs develop. Certain blood inflammatory and hemostasis biomarkers for early diagnosis have recently been investigated. The objective of this study was to investigate the diagnostic performance of complete blood count, serum chemistry, acute phase proteins, protein electrophoresis, and coagulation parameters for diagnosis of OC clinical infection in NES. Samples from NES with OC infection confirmed by gross pathology with blood collected antemortem during clinical disease (n = 9) and NES initially admitted for malnutrition and sampled shortly before release after successful rehabilitation (n = 20) were included in the study. Using Receiver operator characteristic (ROC) curve analysis, the diagnostic performances (area under the curve [AUC]) of albumin (0.994), albumin:globulin ratio (0.983), serum amyloid A (0.972), activated partial thromboplastin time (0.936), total bilirubin (0.975), and gamma-glutamyl transferase (0.939) were high (AUC > 0.9). These results confirm systemic inflammation and DIC, and support previously reported clinical and gross pathological findings in NES infected with OC. In addition to AUC values, this study produced cut-off points, sensitivity, specificity, confidence intervals, and predictive values for analytes with high diagnostic performance. This data will be useful in the diagnosis and clinical management of OC-infected NES and will aid in assessment of treatment efficacy

    Educational development between faculty and administration

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    This essay employs Identity Theory to explore the professional identities of educational developers, arguing that it is important to pay attention to the different saliences, or weights, that developers attach to the faculty and administrative sides of their identities

    Re-visioning ultrasound through women's accounts of pre-abortion care in England

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    Feminist scholarship has demonstrated the importance of sustained critical engagement with ultrasound visualizations of pregnant women’s bodies. In response to portrayals of these images as “objective” forms of knowledge about the fetus, it has drawn attention to the social practices through which the meanings of ultrasound are produced. This article makes a novel contribution to this project by addressing an empirical context that has been neglected in the existing feminist literature concerning ultrasound, namely, its use during pregnancies that women decide to terminate. Drawing on semi-structured interviews with women concerning their experiences of abortion in England, I explore how the meanings of having an ultrasound prior to terminating a pregnancy are discursively constructed. I argue that women’s accounts complicate dominant representations of ultrasound and that in so doing, they multiply the subject positions available to pregnant women

    Factors Influencing Engagement, Perceived Usefulness and Behavioral Mechanisms Associated with a Text Message Support Program

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    Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours. We aimed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement, perceived usefulness, behavior change and program delivery preferences. Methods Mixed methods qualitative design combining four data sources; (i) analytic data extracted directly from the software system, (ii) participant survey, (iii) focus groups to identify barriers and enablers to implementation and mechanisms of effect and (iv) recruitment screening logs and text message responses to examine engagement. This evaluation was conducted within the TEXT ME trial—a parallel design, single-blind randomized controlled trial (RCT) of 710 patients with coronary heart disease (CHD). Qualitative data were interpreted using inductive thematic analysis. Results 307/352 (87% response rate) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group. Factors increasing engagement included (i) ability to save and share messages, (ii) having the support of providers and family, (iii) a feeling of support through participation in the program, (iv) the program being initiated close to the time of a cardiovascular event, (v) personalization of the messages, (vi) opportunity for initial face-to-face contact with a provider and (vii) that program and content was perceived to be from a credible source. Clear themes relating to program delivery were that diet and physical activity messages were most valued, four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer. Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aimed at improving health-related behavior. The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling

    Chemical Synthesis of Staphyloferrin B Affords Insight into the Molecular Structure, Iron Chelation, and Biological Activity of a Polycarboxylate Siderophore Deployed by the Human Pathogen

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    Staphyloferrin B (SB) is a citrate-based polycarboxylate siderophore produced and utilized by the human pathogen Staphylococcus aureus for acquiring iron when colonizing the vertebrate host. The first chemical synthesis of SB is reported, which enables further molecular and biological characterization and provides access to structural analogues of the siderophore. Under conditions of iron limitation, addition of synthetic SB to bacterial growth medium recovered the growth of the antibiotic resistant community isolate S. aureus USA300 JE2. Two structural analogues of SB, epiSB and SBimide, were also synthesized and employed to investigate how epimerization of the citric acid moiety or imide formation influence its function as a siderophore. Epimerization of the citric acid stereocenter perturbed the iron-binding properties and siderophore function of SB as evidenced by experimental and computational modeling studies. Although epiSB provided growth recovery to S. aureus USA300 JE2 cultured in iron-deficient medium, the effect was attenuated relative to that of SB. Moreover, SB more effectively sequestered the Fe(III) bound to human holo-transferrin, an iron source of S. aureus, than epiSB. SBimide is an imide analogous to the imide forms of other citric acid siderophores that are often observed when these molecules are isolated from natural sources. Here, SBimide is shown to be unstable, converting to native SB at physiological pH. SB is considered to be a virulence factor of S. aureus, a pathogen that poses a particular threat to public health because of the number of drug-resistant strains emerging in hospital and community settings. Iron acquisition by S. aureus is important for its ability to colonize the human host and cause disease, and new chemical insights into the structure and function of SB will inform the search for new therapeutic strategies for combating S. aureus infections.Alfred Benzon Foundation (Postdoctoral fellowship)Pacific Southwest Regional Center of ExcellenceAlfred P. Sloan Foundatio

    Identification by Automated Screening of a Small Molecule that Selectively Eliminates Neural Stem Cells Derived from hESCs but Not Dopamine Neurons

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    BACKGROUND:We have previously described fundamental differences in the biology of stem cells as compared to other dividing cell populations. We reasoned therefore that a differential screen using US Food and Drug Administration (FDA)-approved compounds may identify either selective survival factors or specific toxins and may be useful for the therapeutically-driven manufacturing of cells in vitro and possibly in vivo. METHODOLOGY/PRINCIPAL FINDINGS:In this study we report on optimized methods for feeder-free culture of hESCs and hESC-derived neural stem cells (NSCs) to facilitate automated screening. We show that we are able to measure ATP as an indicator of metabolic activity in an automated screening assay. With this optimized platform we screened a collection of FDA-approved drugs to identify compounds that have differential toxicity to hESCs and their neural derivatives. Nine compounds were identified to be specifically toxic for NSCs to a greater extent than for hESCs. Six of these initial hits were retested and verified by large-scale cell culture to determine dose-responsive NSC toxicity. One of the compounds retested, amiodarone HCL, was further tested for possible effects on postmitotic neurons, a likely target for transplant therapy. Amiodarone HCL was found to be selectively toxic to NSCs but not to differentiated neurons or glial cells. Treated and untreated NSCs and neurons were then interrogated with global gene expression analysis to explore the mechanisms of action of amiodarone HCl. The gene expression analysis suggests that activation of cell-type specific cationic channels may underlie the toxicity of the drug. CONCLUSIONS/SIGNIFICANCE:In conclusion, we have developed a screening strategy that allows us to rapidly identify clinically approved drugs for use in a Chemistry, Manufacture and Control protocol that can be safely used to deplete unwanted contaminating precursor cells from a differentiated cell product. Our results also suggest that such a strategy is rich in the potential of identifying lineage specific reagents and provides additional evidence for the utility of stem cells in screening and discovery paradigms
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