445 research outputs found

    The Loss in Efficiency from Using Grouped Data

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    We derive the efficiency loss from using grouped data to estimate coefficients of variables that vary across groups but not individuals within a group (e.g., state unemployment rates) when micro data are unavailable on the dependent variable. We present an empirical example of our theoretical results, and show that the efficiency loss in this application is small.grouped data, relative efficiency

    The Hours of Jean d\u27Evreux : an analysis of size

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    Dualisms : what women say about working in ICT

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    This paper revisits the reported dualism associated with the perceptions of the ICT industry and the actual work experiences of women with this career. Eighteen female ICT professionals participated in a series of interviews in which their journeys towards their current employment roles were traced. Given the low numbers of women attracted to the ICT profession, we sought to explore what had attracted these women to pursue careers in ICT and what could be learnt about improving perceptions of ICT careers. Reported here are the women’ s responses about their initial career trajectories and their views of their current workplaces. A small number of the respondents were in the careers they had always aspired towards; the others, the vast majority, had stumbled serendipitously into the ICT industry. In general, the women enjoyed their jobs. While several were unaware of gender issues in their workplaces, others did perceive a male-dominated culture and felt that technically skilled females still encountered challenges in some work contexts. It would appear that the traditional stereotypes associated with computing careers have not yet been overcome. The implications of these findings are discussed

    Observation as a formal assessment tool in early childhood classrooms: A professional development module

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    The purpose of this professional development module to is to explore various purposes and methods of implementing observational techniques in assessment tools in early childhood classrooms. The research reviewed focused on early childhood assessment types, including a brief review of six specific instruments, and implementation methods available to infant and toddler through preschool-aged teachers. This professional development module\u27s base is a resource support system to help advance the observational skills of current and future teachers in the early childhood field

    Massive Stars in the Field and Associations of the Magellanic Clouds: the Upper Mass Limit, the Initial Mass Function, and a Critical Test of Main-Sequence Stellar Evolutionary Theory

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    We investigate the massive star population of the Magellanic Clouds with an emphasis on the field population, which we define as stars located further from any OB association than massive stars are likely to travel during their short lifetimes. The field stars must have been born as part of more modest star-forming events than those that have populated the large OB associations found throughout the Clouds. We use new and existing data to answer the following questions: Does the field produce stars as massive as those found in associations? Is the initial mass function (IMF) of these field massive stars the same as those of large OB complexes? How well do the Geneva low-metallicity evolutionary models reproduce what is seen in the field population, with its mixed ages? To address these issues we begin by updating existing catalogs of LMC and SMC members with our own new spectral types and derive H-R diagrams (HRDs) of 1584 LMC and 512 SMC stars. We use new photometry and spectroscopy of selected regions in order to determine the incompleteness corrections of the catalogs as a function of mass and find that we can reliably correct the number of stars in our HRDs down to 25 M.. Using these data, we derive distance moduli for the Clouds via spectroscopic parallax, finding values of 18.4 +/- 0.1 and 19.1 +/- 0.3 for the LMC and SMC. The average reddening of the field stars is small: E(B - V) = 0.13 (LMC) and 0.09 (SMC), with little spread. We find that the field does produce stars as massive as any found in associations, with stars as massive as 85 M. present in the HRD even when safeguards against the inclusion of runaway stars are included. However, such massive stars are much less likely to be produced in the field (relative to lower mass stars) than in large OB complexes: the slope of the IMF of the field stars is very steep, GAMMA = -4.1 +/- 0.2 (LMC) and GAMMA = -3.7 +/- 0.5 (SMC). These may be compared with GAMMA = -1.3 +/- 0.3, which we rederive for the Magellanic Cloud associations. (We compare our association IMFs with the somewhat different results recently derived by Hill et al. and demonstrate that the latter suffer from systematic effects due to the lack of spectroscopy.) Our reanalysis of the Garmany et al. data reveals that the Galactic field population has a similarly steep slope, with GAMMA = -3.4 +/- 1.3, compared to GAMMA = -1.5 +/- 0.2 for the entire Galactic sample. We do not see any difference in the IMFs of associations in the Milky Way, LMC, and SMC. We find that the low metallicity evolutionary tracks and isochrones do an excellent job of reproducing the distribution of stars in the HRD at higher masses, and in particular match the width of the main-sequence well. There may or may not be an absence of massive stars with ages less than 2 Myr in the Magellanic Clouds, as others have found for Galactic stars; our reddening data renders unlikely the suggestion that such an absence (if real) would be due to the length of time it takes for a massive star to emerge. There is an increasing discrepancy between the theoretical ZAMS and the blue edge of the main-sequence at lower luminosities; this may reflect a metallicity dependence for the intrinsic colors of stars of early B and later beyond that predicted by model atmospheres, or it may be that the low metallicity ZAMS is misplaced to higher temperatures. Finally, we use the relative number of field main-sequence and Wolf-Rayet stars to provide a selection-free determination of what mass progenitors become WR stars in the Magellanic Clouds. Our data suggest that stars with initial masses > 30 M. evolve to a WR phase in the LMC; while the statistics are considerably less certain for the SMC, they are consistent with this limit being modestly higher there, possibly 50 M., in qualitative agreement with modern evolutionary calculations

    Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction

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    Inflammation promotes endothelial dysfunction, but the underlying mechanisms remain poorly defined in vivo. Using translational vascular function testing in myocardial infarction patients, a situation where inflammation is prevalent, and knock-out (KO) mouse models we demonstrate a role for mitogen-activated-protein-kinases (MAPKs) in endothelial dysfunction. Myocardial infarction significantly lowers mitogen and stress kinase 1/2 (MSK1/2) expression in peripheral blood mononuclear cells and diminished endothelial function. To further understand the role of MSK1/2 in vascular function we developed in vivo animal models to assess vascular responses to vasoactive drugs using laser Doppler imaging. Genetic deficiency of MSK1/2 in mice increased plasma levels of pro-inflammatory cytokines and promoted endothelial dysfunction, through attenuated production of nitric oxide (NO), which were further exacerbated by cholesterol feeding. MSK1/2 are activated by toll-like receptors through MyD88. MyD88 KO mice showed preserved endothelial function and reduced plasma cytokine expression, despite significant hypercholesterolemia. MSK1/2 kinases interact with MAPK-activated proteins 2/3 (MAPKAP2/3), which limit cytokine synthesis. Cholesterol-fed MAPKAP2/3 KO mice showed reduced plasma cytokine expression and preservation of endothelial function. MSK1/2 plays a significant role in the development of endothelial dysfunction and may provide a novel target for intervention to reduce vascular inflammation. Activation of MSK1/2 could reduce pro-inflammatory responses and preserve endothelial vasodilator function before development of significant vascular disease

    GASZ Is Essential for Male Meiosis and Suppression of Retrotransposon Expression in the Male Germline

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    Nuage are amorphous ultrastructural granules in the cytoplasm of male germ cells as divergent as Drosophila, Xenopus, and Homo sapiens. Most nuage are cytoplasmic ribonucleoprotein structures implicated in diverse RNA metabolism including the regulation of PIWI-interacting RNA (piRNA) synthesis by the PIWI family (i.e., MILI, MIWI2, and MIWI). MILI is prominent in embryonic and early post-natal germ cells in nuage also called germinal granules that are often associated with mitochondria and called intermitochondrial cement. We find that GASZ (Germ cell protein with Ankyrin repeats, Sterile alpha motif, and leucine Zipper) co-localizes with MILI in intermitochondrial cement. Knockout of Gasz in mice results in a dramatic downregulation of MILI, and phenocopies the zygotene–pachytene spermatocyte block and male sterility defect observed in MILI null mice. In Gasz null testes, we observe increased hypomethylation and expression of retrotransposons similar to MILI null testes. We also find global shifts in the small RNAome, including down-regulation of repeat-associated, known, and novel piRNAs. These studies provide the first evidence for an essential structural role for GASZ in male fertility and epigenetic and post-transcriptional silencing of retrotransposons by stabilizing MILI in nuage

    Effect of PSI-697, a novel P-selectin inhibitor, on platelet-monocyte aggregate formation in humans

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    Background: Platelet activation is central to the pathogenesis of acute coronary syndromes. Surface expression of P‐selectin on activated platelets induces formation of platelet–monocyte aggregates and promotes vascular inflammation and thrombosis. P‐selectin antagonism may represent a novel therapeutic strategy in vascular disease. We aimed to investigate the effects of the novel P‐selectin antagonist PSI‐697 on platelet–monocyte aggregate formation in humans. Methods and Results: In a double‐blind, randomized, placebo‐controlled crossover study, healthy smokers were randomized to receive either oral PSI‐697 600 mg or matched placebo. The sequence of treatment was also randomized, with all subjects receiving both PSI‐697 and placebo. Platelet–monocyte aggregates were measured by flow cytometry at 4 and 24 hours in the presence and absence of thrombin receptor‐activating peptide (TRAP; 0.1 to 1.0 μm/L). The ex vivo addition of TRAP caused a concentration‐dependent increase in platelet–monocyte aggregates from 8.2% to 94.8% (P<0.001). At 4 and 24 hours, plasma concentrations of PSI‐697 increased to 1906 and 83 ng/mL, respectively (P<0.001). PSI‐697 had no demonstrable effect on either stimulated or unstimulated platelet–monocyte aggregates at 4 or 24 hours (P>0.05). P‐selectin‐blocking antibody (CLB‐Thromb6), but not PSI‐697, inhibited both stimulated and unstimulated platelet–monocyte aggregate formation in vitro (P<0.001). Conclusions: The novel small‐molecule P‐selectin antagonist PSI‐697 did not inhibit basal or stimulated platelet–monocyte aggregate formation in humans at the dose tested. Its clinical efficacy remains to be established

    Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

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    Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC
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