106 research outputs found

    Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol

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    Cb2 is a novel protooncogene encoding the peripheral cannabinoid receptor. Previous studies demonstrated that 2 distinct noncoding first exons exist: exon-1A and exon-1B, which both splice to protein-coding exon-2. We demonstrate that in retrovirally induced murine myeloid leukemia cells with proviral insertion in Cb2, exon-1B/exon-2 Cb2 messenger RNA levels have been increased, resulting in high receptor numbers. In myeloid leukemia cells without virus insertion in this locus, low levels of only exon-1A/exon-2 Cb2 transcripts were present and receptors could not be detected. To elucidate the function of Cb2 in myeloid leukemia cells, a set of in vitro experiments was carried out using 32D/G-CSF-R (granulocyte colony-stimulating factor receptor) cells transfected with exon-1B/exon-2 Cb2 complementary DNA and a myeloid cell line carrying a virus insertion In Cb2 (ie, NFS 78). We demonstrate that a major function of the Cb2 receptor is stimulation of migration as determined in a trans-well assay. Exposure of Cb2-expressing cells to different cannabinoids showed that the true ligand for Cb2 is 2-arachidonoylglycerol (2-AG), which may act as chemoatractant and as a chemokinetic agent. Furthermore, we observed a significant synergistic activity between 2-AG and interleukin-3 or G-CSF, suggesting cross-talk between the different receptor systems. Radioactive-ligand binding studies revealed significant numbers of Cb2 receptors in normal spleen. Transwell experiments carried out with normal mouse spleen cells showed 2-AG-induced migration of B220-, CD19-, immunoglobulin M-, and immunoglobulin D-expressing B lymphocytes. Our study demonstrates that a major function of Cb2 receptor expressed on myeloid leukemia cells or normal splenocytes is stimulation of migration. (C) 2002 by The American Society of Hematology

    Impact and sensitivity analyses of energy sector emissions: air quality modeling of the PJM region

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    One in eight deaths globally is due to air pollution. Exposure to high concentrations of atmospheric fine particulate matter (PM2.5) has negative health consequences. Air quality models, such as the Community Multiscale Air Quality (CMAQ) model, are employed to evaluate effectiveness of air pollution abatement strategies partly designed to minimize PM2.5 exposure and protect human health. Energy production and consumption is the largest controllable source sector contributing to ambient PM2.5 mass. The highest electricity sector (energy subdivision) emissions occur on hot, stagnant summer days, when energy demand is highest and the atmosphere is most conducive to photochemical production and PM2.5 accumulation. Electricity generation is positively correlated with peak PM2.5 concentrations. CMAQ consistently underpredicts these peak values. Accurate prediction of peak pollutant concentrations is critical to develop strategies that protect human health. This dissertation works to reduce underprediction of peak PM2.5 concentrations from an energy sector and heat wave event perspective in the Northeast U.S., where PJM Interconnection governs the electricity transmission for 61 million people. Temporal representation of electricity sector emissions is improved in CMAQ during a heat wave, and episodic increases in peak PM2.5 at the surface and aloft are predicted. PJM EGU emissions, especially sulfate, impact not only the PJM region, but also outlying areas. Monitored and controlled peaking units, EGUs used during highest electricity demand, contribute up to 87% of maximum hourly PM2.5 concentrations. Urban areas experience the highest potential exposure (calculated as population-weighted concentrations (PWCs)) from peaking unit emissions, regardless of the location of predicted peak ambient concentrations. Peaking units contribute substantially to exposure potential on the worse air quality days, but are historically exempt from Federal air quality rules. Eight sensitivity experiments indicate CMAQ-predicted PM2.5 PWCs are most sensitive to uncertainty in onroad primary organic carbon emissions, while ambient PM2.5 concentrations are most sensitive to planetary boundary layer height. Model development strategies optimized to protect health may look different than traditional evaluation-focused strategies optimized to match annual averages in measured PM2.5 mass. This dissertation provides issues to consider for prioritizing model development to address peak air quality events that drive non-attainment and threaten human health.Ph.D.Includes bibliographical referencesby Caroline M. Farka

    Measuring Wikipedia

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    Wikipedia, an international project that uses Wiki software to collaboratively create an encyclopaedia, is becoming more and more popular. Everyone can directly edit articles and every edit is recorded. The version history of all articles is freely available and allows a multitude of examinations. This paper gives an overview on Wikipedia research. Wikipedia’s fundamental components, i.e. articles, authors, edits, and links, as well as content and quality are analysed. Possibilities of research are explored including examples and first results. Several characteristics that are found in Wikipedia, such as exponential growth and scale-free networks are already known in other context. However the Wiki architecture also possesses some intrinsic specialities. General trends are measured that are typical for all Wikipedias but vary between languages in detail

    Product Journey Mapping: a design method to shift towards the circular economy

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    The Product Journey Map was developed through an iterative process, preceded by research on design methodologies and existing mapping methodologies such as the Customer Journey Map and Service Blueprint. By synthesising the research on design- and existing mapping methodologies, a vision of the Product Journey Map was developed and explored through four concepts. The concepts took inspiration from sustainable value mapping, the synergy between strategic disciplines, product obsolescence and end-of-life scenarios, and circular design methodologies. The concepts were prototyped with Castor Ventures and Gorenje. Castor Ventures is a Dutch company specialising in manufacturing industrial pushcarts used by supermarket chains like Albert Heijn. Gorenje is a Slovenian major appliance manufacturer and is the fourth largest manufacturer of household appliances in Europe. The synthesis of the prototype sessions and the PJM concepts resulted in a final PJM concept presented in the Product Journey Map playbook.Strategic Product Desig

    BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia

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    MECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony-forming cells by 34% and moderately reduces BCR-ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in K562 cells. We also show that both E and ME are expressed in CD34<sup>+</sup> selected cells of both CML chronic phase (CML-CP), and non-CML (normal) origin. Furthermore, MECOM mRNA and protein expression were repressed by imatinib mesylate treatment of CML-CP CD34<sup>+</sup> cells, K562 and KY01 cell lines whereas imatinib had no effect in non-CML BCR-ABL1 −ve CD34<sup>+</sup> cells. Together these results suggest that BCR-ABL1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML-CP progenitor cells and that the BCR-ABL1 oncoprotein partially mediates its biological activity through MECOM. MECOM gene expression in CML-CP progenitor cells would provide an in vivo selective advantage, contributing to CML pathogenesis

    expert panel

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    : With the availability of effective targeted agents, significant changes have occurred in the management of patients with acute myeloid leukemia (AML) over the past several years, particularly for those considered unfit for intensive chemotherapy. While testing for measurable residual disease (MRD) is now routinely performed in patients treated with intensive chemotherapy to refine prognosis and, possibly, inform treatment decision-making, its value in the context of lower-intensity regimens is unclear. As such regimens have gained in popularity and can be associated with higher response rates, the need to better define the role of MRD assessment and the appropriate time points and assays used for this purpose has increased. This report outlines a roadmap for MRD testing in patients with AML treated with lower-intensity regimens. Experts from the European LeukemiaNet (ELN)-DAVID AML MRD working group reviewed all available data to propose a framework for MRD testing in future trials and clinical practice. A Delphi poll served to optimize consensus. Establishment of uniform standards for MRD assessments in lower-intensity regimens used in treating patients with AML is clinically relevant and important for optimizing testing and, ultimately, improving treatment outcomes of these patients

    uczniów z uszkodzeniem narządu słuchu Levels of Students with a Hearing Impairment

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    This paper discusses the problem of the psychological assessment of hearing-impaired children in Poland. Its aim is to provide a guide to reliable and accurate instruments for IQ assessment of the Deaf. The author adopts a position that people who are deaf and for whom the PJM (Polish Sign Language) is the mother tongue, should be regarded as a cultural minority. The paper reviews all of the psychological tools used in Poland like WAIS-R and WISC-R scale to evaluate the level of cognitive functioning of the hard of hearing. Given the lack of appropriate assessment tools for measuring deaf children’s intelligence, many psychologists in Poland use testing methods that are not welladapted, e.g. they only account for the Polish culture and disregard the characteristics of the PJM. The article reveals the consequences of using such ill-adapted tests as well as assessing child’s learning difficulties based on them.3022924313Studia Edukacyjn

    Review of wind generation within adequacy calculations and capacity markets for different power systems

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    The integration of renewable energy sources, including wind power, in the adequacy assessment of electricity generation capacity becomes increasingly important as renewable energy generation increases in volume and replaces conventional power plants. The contribution of wind power to cover the electricity demand is less certain than conventional power sources; therefore, the capacity value of wind power is smaller than that of conventional plants. This article presents an overview of the adequacy challenge, how wind power is handled in the regulation of capacity adequacy, and how wind power is treated in a selection of jurisdictions. The jurisdictions included in the overview are Sweden, Great Britain, France, Ireland, United States (PJM and ERCOT), Finland, Portugal, Spain, Norway, Denmark, Belgium, Germany, Italy and the Netherlands.Energie and Industri
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