614 research outputs found

    Domain-specific reasoning for method engineering based on Toulmin's argumentation theory

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    Methods describe and embody a broad range of relevant knowledge of enterprises. Usually they have to account for requirements stated by a multitude of various stakeholders. These are typically those that are in charge of business related actions and those that are in charge to support such actions with an IT-Infrastructure. The statement of requirements as well as the validation of methods and in particular process models with respect to those requirements relies drastically on natural language. Natural language seems to be a substantial component to explain and to give an understanding about process models or certain aspects of it. This fact requires closing the gap between the natural language and the respective modelling language. This paper proposes argumentative method engineering for purposefully depicting design decisions and convictions for method engineering through arguments. The approach is derived from Toulmin’s Argumentation Model and explicates the process of negotiating with various stakeholders. So, a model, depicting a method, specified by means of argumentative method engineering, not just includes the claims about a certain domain, it further justifies these claims by referring to already established knowledge. While it can’t be ensured that certain requirements are considered in future project, if the reasons for design decisions of method engineering are transcribed in natural language text, but the semi- formalising of arguments regarding these methods allows such an assurance. So the argumentative approach enables the sophisticated management and reuse of knowledge during the development and extension of methods. The approach is evaluated using a case study, in which a software development method was outsourced to contractors

    The effect of forage management on carbon storage in pastureland and rotation

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    Non-Peer ReviewedDegraded land with less than 1.5% organic carbon (class 4 and 5 land) in the Parkland of Western Canada has significant potential, from 5 to 15 Mg C ha-1 depending on management, for carbon storage with forages in the Parkland. The potential ranges from 5 to 15 Mg C ha-1, over a period from 15 to 20 years, depending on fertility management of forages in pasture and initial levels of soil organic carbon. Nitrogen fertilizer increased organic carbon stored in reseeded pastures at Pathlow and Brandon relative to paddocks without fertilizer. Over a period of 12 years (1978-1989) in the Pathlow study, 21.9 Mg C ha- 1 (0-15 cm) was stored when N fertilizer was applied at an annual rate of 45 kg ha-1 compared to the control treatment, which was attributed to accumulation of plant debris and roots at the surface. Increases in organic carbon did not persist 10 years after N fertilizer was discontinued at the study at Pathlow, Saskatchewan. At Brandon, Manitoba, fertilized grass pasture stored 16.2 Mg C ha-1 (0-50 cm) compared to unfertilized bromegrass from 1994 to 1999. Long-term forage rotations at Melfort showed no significant difference in the wheat phase of a F-W-W-H-H-W rotation due to nitrogen fertilizer (147.3 Mg C ha-1 150.7 Mg C ha-1) over a period from 1957 to 1994. This was attributed to the high levels of soil carbon in soils at Melfort. Forages in rotation had no significant effect on organic carbon in a study at Glenlea MB conducted from 1992 to 1999, though a range from 110.8 to 145.7 Mg C ha-1 was observed. Significant differences may occur in the long term as organic carbon accumulates in the treatments at Glenlea

    Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation

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    Oxidation of low-density lipoprotein (LDL) generates proinflammatory and prothrombotic mediators that may play a crucial role in cardiovascular and inflammatory diseases. In order to study platelet-activating components of oxidized LDL 1-stearoyl-2-arachidonoyl-sn-glycero-3- phosphocholine, a representative of the major phospholipid species in LDL, the 1-acyl-phosphatidylcholines (PC), was oxidized by CuCl2 and H2O2. After separation by high-performance liquid chromatography, three compounds were detected which induced platelet shape change at low micromolar concentrations. Platelet activation by these compounds was distinct from the pathways stimulated by platelet-activating factor, lysophosphatidic acid, lyso-PC and thromboxane A(2), as evidenced by the use of specific receptor antagonists. Further analyses of the oxidized phospholipids by electrospray ionization mass spectrometry structurally identified them as 1-stearoyl-2-azelaoyl-sn-glycero-3-phosphocholine (m/z 694; SAzPC), 1-stearoyl-2-glutaroyl-snglycero-3- phosphocholine (m/z 638; SGPC), and 1-stearoyl-2-( 5-oxovaleroyl)-sn-glycero-3-phosphocholine (m/z 622; SOVPC). These observations demonstrate that novel 1-acyl-PC which had previously been found to stimulate interaction of monocytes with endothelial cells also induce platelet activation, a central step in acute thrombogenic and atherogenic processes. Copyright (C) 2005 S. Karger AG, Basel

    Red Clover Improves the Energy to Protein Balance of Lucerne-Grass Herbage

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    Low ratio of readily fermentable carbohydrate to soluble protein concentrations in lucerne (Medicago sativa L.) leads to inefficient use of herbage N by ruminants. To improve the energy to protein balance in lucerne-grass herbage, four proportions of lucerne:red clover (Trifolium pratense L.) were compared in mixtures with and without grasses: timothy (Phleum pratense L.) and tall fescue (Schedonorus arundinaceus Schreb. Dumort.) in Quebec (QC, Canada). In the first post-seeding year, red clover proportion averaged (across grasses and four harvests) 0, 37, 59, and 74% in herbage mixtures. Increasing the proportion of red clover caused a slight but significant decrease in herbage total nitrogen (TN) concentration (32 to 31 g kg-1 DM) but substantial decreases in non-protein N (PA), rapidly (PB1) and moderately (PB2) degraded protein fractions, and a significant increase in the slowly degraded protein fractions (PB3+PC) (157 to 308 g kg-1 TN). With the inclusion of 74% of red clover, the ratio of soluble sugar to crude protein (CP) in herbage increased from 0.25 to 0.36 because of the increase in the soluble sugar concentration (48 to 66 g kg-1 DM). The inclusion of red clover in mixture with lucerne improved the energy to CP balance compared to lucerne alone, and caused a linear increase in the herbage in vitro neutral detergent fiber digestibility from 568 to 639 g kg-1 aNDF with similar herbage dry matter yield (10.3 Mg ha-1)

    Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue

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    Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81 % for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42 % to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue

    Residual N effects from livestock manure inputs to soils

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    Organic inputs including livestock manures provide nitrogen (N) to crops beyond the year of their application. This so-called residual N effect should be taken into account when making decisions on N rates for individual fields, but also when interpreting N response trials in preparation of recommendations. This paper addresses general principles of residual N effects, gives literature-based estimates of them, and reviews to which extent residual N effects are included in recommendations and regulations in selected countries

    Alkaline air: changing perspectives on nitrogen and air pollution in an ammonia-rich world

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    Ammonia and ammonium have received less attention than other forms of air pollution, with limited progress in controlling emissions at UK, European and global scales. By contrast, these compounds have been of significant past interest to science and society, the recollection of which can inform future strategies. Sal ammoniac (nūshādir, nao sha) is found to have been extremely valuable in long-distance trade (ca AD 600–1150) from Egypt and China, where 6–8 kg N could purchase a human life, while air pollution associated with nūshādir collection was attributed to this nitrogen form. Ammonia was one of the keys to alchemy—seen as an early experimental mesocosm to understand the world—and later became of interest as ‘alkaline air’ within the eighteenth century development of pneumatic chemistry. The same economic, chemical and environmental properties are found to make ammonia and ammonium of huge relevance today. Successful control of acidifying SO2 and NOx emissions leaves atmospheric NH3 in excess in many areas, contributing to particulate matter (PM2.5) formation, while leading to a new significance of alkaline air, with adverse impacts on natural ecosystems. Investigations of epiphytic lichens and bog ecosystems show how the alkalinity effect of NH3 may explain its having three to five times the adverse effect of ammonium and nitrate, respectively. It is concluded that future air pollution policy should no longer neglect ammonia. Progress is likely to be mobilized by emphasizing the lost economic value of global N emissions ($200 billion yr−1), as part of developing the circular economy for sustainable nitrogen management

    Destabilisation of dimeric 14-3-3 proteins as a novel approach to anti-cancer therapeutics

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    14-3-3 proteins play a pivotal role in controlling cell proliferation and survival, two commonly dysregulated hallmarks of cancers. 14-3-3 protein expression is enhanced in many human cancers and correlates with more aggressive tumors and poor prognosis, suggesting a role for 14-3-3 proteins in tumorigenesis and/or progression. We showed previously that the dimeric state of 14-3-3 proteins is regulated by the lipid sphingosine, a physiological inducer of apoptosis. As the functions of 14-3-3 proteins are dependent on their dimeric state, this sphingosine-mediated 14-3-3 regulation provides a possible means to target dimeric 14-3-3 for therapeutic effect. However, sphingosine mimics are needed that are not susceptible to sphingolipid metabolism. We show here the identification and optimization of sphingosine mimetics that render dimeric 14-3-3 susceptible to phosphorylation at a site buried in the dimer interface and induce mitochondrial-mediated apoptosis. Two such compounds, RB-011 and RB-012, disrupt 14-3-3 dimers at low micromolar concentrations and induce rapid down-regulation of Raf-MAPK and PI3K-Akt signaling in Jurkat cells. Importantly, both RB-011 and RB-012 induce apoptosis of human A549 lung cancer cells and RB-012, through disruption of MAPK signaling, reduces xenograft growth in mice. Thus, these compounds provide proof-of-principle for this novel 14-3-3-targeting approach for anti-cancer drug discovery
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