5,213 research outputs found
Mashing up Visual Languages and Web Mash-ups
Research on web mashups and visual languages
share an interest in human-centered computing. Both
research communities are concerned with supporting
programming by everyday, technically inexpert users.
Visual programming environments have been a focus for
both communities, and we believe that there is much to
be gained by further discussion between these research
communities. In this paper we explore some connections
between web mashups and visual languages, and try to
identify what each might be able to learn from the other.
Our goal is to establish a framework for a dialog
between the communities, and to promote the exchange
of ideas and our respective understandings of humancentered
computing.published or submitted for publicationis peer reviewe
Advertising effects of FSIs
Thesis (M.S.)--Massachusetts Institute of Technology, Sloan School of Management, 1992.Includes bibliographical references (leaves 42-43).by Elizabeth B. Jones.M.S
Can the microbiome drive the suppression of grapevine trunk diseases?
Grapevine trunk diseases (GTDs), caused by several fungal species, are among the most destructive grapevine diseases in New Zealand and other grape-growing countries. The control of the diseases is problematic, and there is currently no approved fungicide for their eradication. This has necessitated seeking alternative strategies, including a sustainable
biological control approach, to manage the diseases. Therefore, this study aimed to identify taxa in the grapevine microbiome that contribute to plant health. In some New Zealand vineyards, observations have revealed vines that remain healthy within a background of trunk diseases. These grapevines were termed ‘disease-escape’ to represent their apparent health under heavy disease pressure. Recent research on the grapevine microbiome has shown that microorganisms from these ‘disease-escape’ plants could contribute to disease suppression. Putative disease escape vines were identified in vineyards in two grape-growing regions in New Zealand: Hawke’s Bay and Canterbury. The vines were selected based on their presence in a diseased area, maturity, and absence of trunk disease symptoms. Trunk core samples were taken from the disease-escape vines and neighbouring symptomatic vines. Subsequently, the samples’ total fungal and bacterial communities were identified and compared using culture-independent DNA metabarcoding and culture-dependent approaches. After analysing the metabarcoding and culturing results, microbial taxa that were differentially more abundant in disease-escape grapevines and the ones that correlated negatively with GTD pathogens were identified. The next stage of the study is to design a synthetic community using members of the taxa of interest from the disease-escape grapevines. This SynCom will be introduced into young grapevines and monitored for their ability to suppress the development and severity of GTDs. The research results will provide information on the roles (if any) that the grapevine trunk’s microbiome plays in suppressing GTDs
Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children
BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence
Telomerase Inhibition by Everolimus Suppresses Smooth Muscle Cell Proliferation and Neointima Formation Through Epigenetic Gene Silencing
Proliferation of smooth muscle cells (SMCs) during neointima formation is prevented by drug-eluting stents. The replicative capacity of mammalian cells is enhanced by telomerase expression; however, the contribution of telomerase to the proliferative response underlying neointima formation and its potential role as a pharmacological target are unknown. The present study investigated the mechanisms underlying the mitogenic function of telomerase, and tested the hypothesis that everolimus, which is commonly used on drug-eluting stents, suppresses SMC proliferation by targeting telomerase. Inhibition of neointima formation by everolimus was lost in mice overexpressing telomerase reverse transcriptase (TERT), indicating that repression of telomerase confers the anti-proliferative efficacy of everolimus. Everolimus reduced TERT expression in SMC through an Ets-1-dependent inhibition of promoter activation. The inhibition of TERT-dependent SMC proliferation by everolimus occurred in the absence of telomere shortening but rather as a result of a G1→S-phase arrest. Although everolimus failed to inhibit phosphorylation of the retinoblastoma protein as the gatekeeper of S-phase entry, it potently repressed downstream target genes. Chromatin immunoprecipitation assays demonstrated that TERT induced E2F binding to S-phase gene promoters and supported histone acetylation. These effects were sensitive to inhibition by everolimus. These results characterize telomerase as a previously unrecognized target for the antiproliferative activity of everolimus, and further identify a novel mitogenic pathway in SMC that depends on the epigenetic activation of S-phase gene promoters by TERT
Modeling the Near-Infrared Luminosity Functions of Young Stellar Clusters
We present the results of numerical experiments designed to evaluate the
usefulness of near-infrared luminosity functions for constraining the Initial
Mass Function (IMF) of young stellar populations. From this numerical modeling,
we find that the luminosity function of a young stellar population is
considerably more sensitive to variations in the underlying initial mass
function than to either variations in the star forming history or assumed
pre-main-sequence (PMS) mass-to-luminosity relation. To illustrate the
potential effectiveness of using the KLF of a young cluster to constrain its
IMF, we model the observed K band luminosity function of the nearby Trapezium
cluster. Our derived mass function for the Trapezium spans two orders of
magnitude in stellar mass (5 Msun to 0.02 Msun), has a peak near the hydrogen
burning limit, and has an IMF for Brown Dwarfs which steadily decreases with
decreasing mass.Comment: To appear in ApJ (1 April 2000). 37 pages including 11 figures, AAS:
ver 5.
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Associations of Blood Pressure and Cholesterol Levels During Young Adulthood With Later Cardiovascular Events.
BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk.ConclusionsCumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures
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