19 research outputs found

    Anglo-Dutch Premium Auctions in Eighteenth-Century Amsterdam

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    Précision de l’estimation de l’équivalent en eau de la neige obtenue avec la sonde SNOWPOWER au Québec (Canada)

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    Cet article présente la précision obtenue pour l’estimation de l’Équivalent en Eau de la Neige (ÉEN) et de sa Teneur en Eau Liquide (TEL) avec une nouvelle sonde surnommée la sonde ‘SNOWPOWER’. Cette dernière mesure la constante diélectrique de la neige le long d’un câble coaxial plat de 10 à 20 m dans deux fréquences, soit une haute fréquence à l’aide d’un réflectomètre dans le domaine temporel (‘Time Domain Reflectometry’ TDR) et une basse fréquence au moyen d’un analyseur d’impédance. Ces deux mesures permettent de déterminer simultanément la densité de la neige et sa TEL. La méthodologie originale proposée permet, en plus, d’extraire la hauteur de la neige des données haute fréquence et par conséquent fait aussi de la sonde un outil d’estimation de ÉEN. Cet article présente les résultats d’une année d’expérimentation, l’hiver 2003-2004, dans une parcelle agricole localisée au sud de la ville de Québec au Canada (48°28'12" N, 71˚10'48"W). Les valeurs estimées dérivées de la sonde sont comparées à des mesures manuelles des propriétés de la neige. Les résultats montrent une bonne estimation de la TEL (0.40% volumique) et de l’ÉEN (14.07 mm). Cependant, nous soulignons dans cette étude l’importance du choix adéquat de la basse fréquence ainsi que du choix de l’algorithme d’extrapolation des températures dans la précision de l’estimation. Enfin, nous discutons de l’apport potentiel des données de densité de la sonde pour la cartographie de l’ÉEN à partir des données radar satellite et du modèle EQeau

    Journal of Environmental Quality TECHNICAL REPORTS ECOLOGICAL RISK ASSESSMENT Risk of Phosphorus Desorption from Canadian Agricultural Land: 25-Year Temporal Trend

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    Phosphorus (P) use in excess of crop needs may impact surface water quality and contribute to eutrophication. However, P loss from agricultural land to water has never been estimated at the Canadian national scale. In this paper, the risk of P desorption from Canadian agricultural land is assessed by the source component of the indicator of risk of water contamination by P (IROWC-P). The IROWC-P source component (P_source) characterized the mobilization potential of soluble P and integrated four models of P desorption by water for dominant agricultural soil series of Canada on the soil landscape of Canada polygon scale (1:1,000,000). The objective of our study was to describe and evaluate a standardized method for deriving the P_source component. The P_source was assessed over 5-yr intervals from 1981 to 2006 for scientifically based knowledge by relating annual P balance values, soil test P (STP) analyses, soil P saturation index, and Self-Davis water extractable P extractio

    Variation of an indicator of

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    Escherichia coli is an indicator of fecal pollution used to mandate recreational and drinking water quality. Concentrations of culturable E. coli following contamination of surface water are determined by three factors: dilution; cell attachment to particulate material and settling or resuspension in the water column; and the net rate of change in viability. This study evaluated the variability in the latter parameter, and how predictive variation in death rate was of culturable population densities at the time of sampling. Water samples (N=232) with varying levels of E. coli contamination were collected from 46 discrete locations in four watersheds across Canada over a three-month period and enumerated for culturable E. coli by membrane filtration plate counting (T0EC). Water samples were again enumerated following a laboratory 24 h holding period at 30°C in the dark, and the difference considered the death rate (ΔEC). Relationships of T0EC and ΔEC with environmental and water chemistry factors were explored using step-wise multiple regression. The model predicting T0EC indicated that stream order, total rainfall seven days in advance of sampling day, total phosphorus, and ΔEC were the most significant contributors. The model predicting ΔEC indicated that turbidity and NH3+NH4 were the most important contributors. A model suggests that the persistence factor is less important than dilution (i.e. stream order) in describing E. coli densities, followed by factors that influence the loading of E. coli into watersheds

    Development of a Ravelling test for asphalt

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    7ICONFBMP, Proceedings of the 7th International Conference : Bituminous Mixtures and Pavements, Thessalonique, GRECE, 12-/06/2019 - 14/06/2019The test methods for four scuffing devices had been written up as technical specification PR CEN/TS 12697-50, Resistance to scuffing, which was reviewed by the DRaT project, under CEDR Call 2014: Asset Management and Maintenance. Existing knowledge on scuffing was reviewed and a round robin testing programme was undertaken with four replicate samples of three variations each of three mixture types. A statistical analysis found that results from the different devices could not be accurately correlated, either for specific asphalt mixture types or overall, nor could specific designs of scuffing equipment be identified as be-ing best for identifying the scuffing-resistance of asphalt mixtures. Nevertheless, enhancements to PR CEN/TS 2697-50:2016 were identified that can be made to make a better and more unified document without rejecting any of the designs of scuffing apparatus. A copy of the revised version of the standard was given in the final report

    IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells

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    Chronic lymphocytic leukemia (CLL) cells multiply in secondary lymphoid tissue, but the mechanisms leading to their proliferation are still uncertain. In addition to B-cell receptor (BCR)-triggered signals, other microenvironmental factors might well be involved. In proliferation centers, leukemic B cells are in close contact with CD4(+)CD40L(+) T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an interleukin (IL)-21-induced gene signature in CLL, containing components of Janus kinase/signal transducer and activator of transcription and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 production ex vivo by LN CD4(+)CXCR5(+) follicular helper T cells. These results indicate that in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CL

    Implementation and Relevance of FAIR Data Principles in Biopharmaceutical Research and Development

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    Biopharmaceutical industry R&D, and indeed other Life Sciences R&D such as agri-food, is data-driven and can significantly improve its efficiency and effectiveness by implementing the FAIR (Findable, Accessible, Interoperable, Reusable) Guiding Principles for scientific data management and stewardship. By so doing, the plethora of new and powerful analytical tools such as artificial intelligence and machine learning will be able automatically and at scale to access the data from which they learn, and on which they thrive. FAIR is a fundamental enabler for digital transformation

    Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia

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    Inhibition of B-cell receptor (BCR) signaling pathways in chronic lymphocytic leukemia (CLL) provides significant clinical benefit to patients, mainly by blocking adhesion of CLL cells in the lymph node microenvironment. The currently applied inhibitors ibrutinib and idelalisib have limited capacity however to induce cell death as monotherapy and are unlikely to eradicate the disease. Acquired resistance to therapy in CLL is often caused by mutations in the response network being targeted, both for DNA damage or BCR signaling pathways. Thus, drugswith dual targeting capacity could offer improved therapeutic value. Here, the potency of CC-115, a novel inhibitor of mammalian target of rapamycin kinase (TORK) and DNA-dependent proteinkinase (DNA-PK), was evaluated in primary CLL cells in vitro and in CLL patients. Combined TORK and DNA-PK inhibition in vitro resulted in caspase-dependent cell killing irrespective of p53, ATM, NOTCH1, or SF3B1 status. Proliferation induced by CD40(+) interleukin-21 stimulation was completely blocked by CC-115, and CD40-mediated resistance to fludarabine and venetoclax could be reverted by CC-115. BCR-mediated signaling was inhibited by CC-115 and also in CLL samples obtained from patients with acquired resistance to idelalisib treatment. Clinical efficacy of CC-115 was demonstrated in 8 patients with relapsed/refractory CLL/small lymphocytic lymphoma harboring ATM deletions/mutations; all but 1 patient had a decrease in lymphadenopathy, resulting in 1 IWCLL partial response (PR) and 3 PRs with lymphocytosis. In conclusion, these preclinical results, along with early promising clinical activity, suggest that CC-115 may be developed further for treatment of CLL
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