Applying the UFO Ontology to Design an Agent-Oriented Engineering Language

Abstract. The problem of designing suitable conceptual modeling languages for system engineering is far from being solved. In the past years, some works have proposed the use of foundational ontologies as analysis tools to enable semantic coherence when (re)designing such languages. In this paper, we exemplify this approach by applying a foundational ontology named UFO in the design of an agent-oriented modeling language for the ARKnowD methodology. Instead of proposing new concepts and constructs, ARKnowD relies on existing work, combining two different approaches, namely Tropos and AORML. Each work is applied in a different development activity, according to their natural propensity: Tropos in Requirements Analysis and AORML in System Design. Besides the ontological approach, we propose some mapping rules between the notations, inspired in the Model Driven Architecture (MDA) metamodel transformation method. This approach helps to guarantee a smooth transition from one activity to the other

STIM Proteins and Orai Ca2+ Channels Are Involved in the Intracellular Pathways Activated by TLQP-21 in RAW264.7 Macrophages

TLQP-21 is a neuropeptide which has been implicated in regulation of nociception and other relevant physiologic functions. Although recent studies identified C3a and gC1q receptors as targets for TLQP-21, its intracellular molecular mechanisms of action remain largely unidentified. Our aim was (i) to explore the intracellular signaling pathway(s) activated by JMV5656, a novel derivative of TLQP-21, in RAW264.7 macrophages, and (ii) to assess linkages of these pathways with its purported receptors. JMV5656 stimulated, in a dose-dependent fashion, a rapid and transient increase in intracellular Ca2+ concentrations in RAW264.7 cells; repeated exposure to the peptide resulted in a lower response, suggesting a possible desensitization mechanism of the receptor. In particular, JMV5656 increased cytoplasmic Ca2+ levels by a PLC-dependent release of Ca2+ from the endoplasmic reticulum. STIM proteins and Orai Ca2+ channels were activated and played a crucial role. In fact, treatment of the cells with U73122 and thapsigargin modulated the increase of intracellular Ca2+ levels stimulated by JMV5656. Moreover, in RAW264.7 cells intracellular Ca2+ increases did not occur through the binding of JMV5656 to the C3a receptor, since the increase of intracellular Ca2+ levels induced by JMV5656 was not affected by specific siRNA against C3aR. In summary, our study provides new indications for the downstream effects of JMV5656 in macrophages, suggesting that it could activate receptors different from the C3aR

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa-Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study

Scope: The present study assesses the absorption, pharmacokinetics, and urinary excretion of coffee pyridines and their metabolites after daily regular exposure to specific dosages of coffee or cocoa-based products containing coffee (CBPCC), considering different patterns of consumption. Methods and results: In a three-arm, crossover, randomized trial, 21 volunteers are requested to randomly consume for 1 month: one cup of espresso coffee per day, three cups of espresso coffee per day, or one cup of espresso coffee plus two CBPCC twice per day. The last day of the one-month treatment, blood and urine samples are collected for 24 h. Trigonelline, N-methylpyridinium, N-methylnicotinamide, and N-methyl-4-pyridone-5-carboxamide are quantified. Trigonelline and N-methylpyridinium absorption curves and 24-h urinary excretion reflect the daily consumption of different servings of coffee or CBPCC, showing also significant differences in main pharmacokinetic parameters. Moreover, inter-subject variability due to sex and smoking is assessed, showing sex-related differences in the metabolism of trigonelline and smoking-related ones for N-methylpyridinium. Conclusion: The daily exposure to coffee pyridines after consumption of different coffee dosages in a real-life setting is established. This data will be useful for future studies aiming at evaluating the bioactivity of coffee-derived circulating metabolites in cell experiments, mimicking more realistic experimental conditions

Preliminary archaeoentomological analyses of permafrost-preserved cultural layers from the pre-contact Yup’ik Eskimo site of Nunalleq, Alaska : implications, potential and methodological considerations

Acknowledgements Site excavation and samples collection were conducted by archaeologists from the University of Aberdeen, with the help of archaeologists and student excavators from the University of Aberdeen University of Alaska Fairbanks and Bryn Mawr College, Kuskokwim Campus, College of Rural Alaska and residents of Quinhagak and Mekoryuk. This study is funded through AHRC grant to the project ‘Understanding Cultural Resilience and Climate Change on the Bering Sea through Yup’ik Ecological Knowledge, Lifeways, Learning and Archaeology’ to Rick Knecht, Kate Britton and Charlotta Hillderal (University of Aberdeen; AH/K006029/1). Thanks are due to Qanirtuuq Inc. and Quinhagak, Alaska for sampling permissions and to entomologists working at the CNC in Ottawa for allowing access to reference collections of beetles, lice and fleas. Yves Bousquet, Ales Smetana and Anthony E. Davies are specially acknowledged for their help with the identification of coleopteran specimens. Finally, we would also like to thank Scott Elias for useful comments on the original manuscript.Peer reviewedPublisher PD

A rule driven approach for developing adaptive service oriented business collaboration

Current composite web service development and management solutions, e.g. BPEL, do not cater for flexible and adaptive business collaborations due to their pre-defined and inflexible nature that precludes them accommodating business dynamics. In this paper we propose a rule driven approach for adaptive business collaboration development in which rules drive and govern the development process. We introduce the Business Collaboration Development Framework (BCDF), which provides enterprizes with the context to define their capabilities and business collaboration agreements. Subsequently, we explain how rules can drive and control the business collaboration development process to develop complete, correct and consistent business collaboration agreements that are conform the conditions under which parties wish to cooperate.12 page(s

Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia

Purpose: This study aimed at investigating the mechanisms underlying the oxygenation response to proning and recruitment maneuvers in coronavirus disease 2019 (COVID-19) pneumonia. Methods: Twenty-five patients with COVID-19 pneumonia, at variable times since admission (from 1 to 3 weeks), underwent computed tomography (CT) lung scans, gas-exchange and lung-mechanics measurement in supine and prone positions at 5 cmH2O and during recruiting maneuver (supine, 35 cmH2O). Within the non-aerated tissue, we differentiated the atelectatic and consolidated tissue (recruitable and non-recruitable at 35 cmH2O of airway pressure). Positive/negative response to proning/recruitment was defined as increase/decrease of PaO2/FiO2. Apparent perfusion ratio was computed as venous admixture/non aerated tissue fraction. Results: The average values of venous admixture and PaO2/FiO2 ratio were similar in supine-5 and prone-5. However, the PaO2/FiO2 changes (increasing in 65% of the patients and decreasing in 35%, from supine to prone) correlated with the balance between resolution of dorsal atelectasis and formation of ventral atelectasis (p = 0.002). Dorsal consolidated tissue determined this balance, being inversely related with dorsal recruitment (p = 0.012). From supine-5 to supine-35, the apparent perfusion ratio increased from 1.38 ± 0.71 to 2.15 ± 1.15 (p = 0.004) while PaO2/FiO2 ratio increased in 52% and decreased in 48% of patients. Non-responders had consolidated tissue fraction of 0.27 ± 0.1 vs. 0.18 ± 0.1 in the responding cohort (p = 0.04). Consolidated tissue, PaCO2 and respiratory system elastance were higher in patients assessed late (all p < 0.05), suggesting, all together, “fibrotic-like” changes of the lung over time. Conclusion: The amount of consolidated tissue was higher in patients assessed during the third week and determined the oxygenation responses following pronation and recruitment maneuvers

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible

Catabolism of raw and cooked green pepper (Capsicum annuum) (poly)phenolic compounds after simulated gastrointestinal digestion and fecal fermentation.

A total of 21 (poly)phenolic compounds (free and bound) were quantified in raw, olive oil fried, sunflower oil fried and griddled green pepper before and after a simulated gastrointestinal digestion. Flavonoids, particularly quercetin rhamnoside, were the main compounds. The bioaccessibility of (poly)phenolic compounds after gastrointestinal digestion was higher in cooked (>82%) than in raw (48%) samples, showing a positive effect of heat treatment on the release of (poly)phenols from the vegetal matrix. Additionally, a faecal fermentation was carried out for 24h. A time-dependent microbial metabolic activity was observed, which resulted firstly (<5h) in the hydrolysis of flavonoid glycosides and then in the formation of 3 catabolites, namely 3,4-dihydroxybenzoic acid, dihydrocaffeic acid and 3-(3′-hydroxyphenyl)propionic acid, this being by far the most abundant. Catabolic pathways for colonic microbial degradation of flavonoids and hydroxycinnamic acids have been proposed. Griddled pepper showed the highest amount of (poly)phenols both after gastrointestinal digestion and colonic fermentation

Enhancing secure Tropos to effectively deal with security requirements in the development of multiagent systems

The consideration of security requirements in the development of multi-agent systems is a very difficult task. However, only few approaches have been proposed that try to integrate security issues as internal part of the development process. Amongst them, secure Tropos has been proposed as a structured approach towards the consideration of security issues in the development of multiagent systems. In this paper we enhance secure Tropos by integrating to its stages: (i) a process for selecting amongst alternative architectural styles using as criteria the security requirements of the system; (ii) a pattern-based approach to transform security requirements to design, and (iii) a security attack scenarios approach to test the developed solution. The electronic single assessment process (eSAP) case study is used to illustrate our approach

A novel integrated platform for the identification of surgical margins in oral squamous cell carcinoma: results from a prospective single-institution series

BackgroundThe optimal surgical margins assessment is capital in oral squamous cell carcinoma (OSCC) management. We evaluated the clinical benefits of integrating intraoperative macroscopic margin (MM) assessment and narrow band imaging (NBI).MethodsSixteen OSCC patients eligible for surgery were prospectively enrolled. For each patient, 2 to 6 bioptic samples of MM and NBI margins were obtained and histologically analyzed for the presence of dysplasia and lymphocytes. Microvessel density was investigated by CD34 immunohistochemistry.ResultsTaken together, 104 specimens were analyzed, including 15% tumors, 33% MM, 33% NBI margins, and 19% MM-NBI overlapping margins. The NBI margins were closer to the lesion in 50% cases, while the same number of MM were more conservative than NBI, irrespective of the tumor site. The rate of histologically positive margins was similar among the two methods, akin to the microvessel density.ConclusionsMM assessment should be integrated but not replaced with the NBI technology to allow for more conservative surgery