Phenotype-Based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset^TM library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4–10 μM in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT_1–2) at micromolar IC₅₀ values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents.

Design and Qualitative/Quantitative Analysis of Multi-Agent Spatial Simulation Library

Thesis (Master's)--University of Washington, 2012

Occupational exposure to environmental tobacco smoke in hospitality venues: are genetic- or proteomics-based biomarkers predictive of respiratory diseases?

Environmental tobacco smoke (ETS) is recognized as an occupational hazard in the hospitality industry. Although Portuguese legislation banned smoking in most indoor public spaces, it is still allowed in some restaurants/bars, representing a potential risk to the workers’ health, particularly for chronic respiratory diseases. The aims of this work were to characterize biomarkers of early genetic effects and to disclose proteomic signatures associated to occupational exposure to ETS and with potential to predict respiratory diseases development. A detailed lifestyle survey and clinical evaluation (including spirometry) were performed in 81 workers from Lisbon restaurants. ETS exposure was assessed through the level of PM 2.5 in indoor air and the urinary level of cotinine. The plasma samples were immunodepleted and analysed by 2D-SDSPAGE followed by in-gel digestion and LC-MS/MS. DNA lesions and chromosome damage were analysed innlymphocytes and in exfoliated buccal cells from 19 cigarette smokers, 29 involuntary smokers, and 33 non-smokers not exposed to tobacco smoke. Also, the DNA repair capacity was evaluated using an ex vivo challenge comet assay with an alkylating agent (EMS). All workers were considered healthy and recorded normal lung function. Interestingly, following 2D-DIGE-MS (MALDI-TOF/TOF), 61 plasma proteins were found differentially expressed in ETS-exposed subjects, including 38 involved in metabolism, acute-phase respiratory inflammation, and immune or vascular functions. On the other hand, the involuntary smokers showed neither an increased level of DNA/chromosome damage on lymphocytes nor an increased number of micronuclei in buccal cells, when compared to non-exposed non-smokers. Noteworthy, lymphocytes challenge with EMS resulted in a significantly lower level of DNA breaks in ETS-exposed as compared to non-exposed workers (P<0.0001) suggestive of an adaptive response elicited by the previous exposure to low levels of ETS. Overall, changes in proteome may be promising early biomarkers of exposure to ETS. Likewise, alterations of the DNA repair competence observed upon ETS exposure deserves to be further understood. Work supported by Fundação Calouste Gulbenkian, ACSS and FCT/Polyannual Funding Program.

Multi-agent simulation of continental, regional, and micro electricity markets

Renewable based power generation has significantly increased over the last years. However, this process has evolved separately from electricity markets, leading to an inadequacy of the present market models to cope with huge quantities of renewable energy resources, and to take full advantage of the presently existing and the increasing envisaged renewable based and distributed energy resources. This paper proposes the modelling of electricity markets at several levels (continental, regional and micro), taking into account the specific characteristics of the players and resources involved in each level and ensuring that the proposed models accommodate adequate business models able to support the contribution of all the resources in the system, from the largest to the smaller ones. The proposed market models are integrated in MASCEM (Multi- Agent Simulator of Competitive Electricity Markets), using the multi agent approach advantages for overcoming the current inadequacy and significant limitations of the presently existing electricity market simulators to deal with the complex electricity market models that must be adopted.

Self-optimization module for scheduling using case-based reasoning

Metaheuristics performance is highly dependent of the respective parameters which need to be tuned. Parameter tuning may allow a larger flexibility and robustness but requires a careful initialization. The process of defining which parameters setting should be used is not obvious. The values for parameters depend mainly on the problem, the instance to be solved, the search time available to spend in solving the problem, and the required quality of solution. This paper presents a learning module proposal for an autonomous parameterization of Metaheuristics, integrated on a Multi-Agent System for the resolution of Dynamic Scheduling problems. The proposed learning module is inspired on Autonomic Computing Self-Optimization concept, defining that systems must continuously and proactively improve their performance. For the learning implementation it is used Case-based Reasoning, which uses previous similar data to solve new cases. In the use of Case-based Reasoning it is assumed that similar cases have similar solutions. After a literature review on topics used, both AutoDynAgents system and Self-Optimization module are described. Finally, a computational study is presented where the proposed module is evaluated, obtained results are compared with previous ones, some conclusions are reached, and some future work is referred. It is expected that this proposal can be a great contribution for the self-parameterization of Metaheuristics and for the resolution of scheduling problems on dynamic environments.

Multi-agent electricity market simulation with dynamic strategies & virtual power producers

Distributed energy resources will provide a significant amount of the electricity generation and will be a normal profitable business. In the new decentralized grid, customers will be among the many decentralized players and may even help to co-produce the required energy services such as demand-side management and load shedding. So, they will gain the opportunity to be more active market players. The aggregation of DG plants gives place to a new concept: the Virtual Power Producer (VPP). VPPs can reinforce the importance of these generation technologies making them valuable in electricity markets. In this paper we propose the improvement of MASCEM, a multi-agent simulation tool to study negotiations in electricity spot markets based on different market mechanisms and behavior strategies, in order to take account of decentralized players such as VPP.

Cost dependent strategy for electricity markets bidding based on adaptive reinforcement learning

Electricity markets are complex environments, involving a large number of different entities, playing in a dynamic scene to obtain the best advantages and profits. MASCEM is a multi-agent electricity market simulator to model market players and simulate their operation in the market. Market players are entities with specific characteristics and objectives, making their decisions and interacting with other players. MASCEM provides several dynamic strategies for agents’ behavior. This paper presents a method that aims to provide market players with strategic bidding capabilities, allowing them to obtain the higher possible gains out of the market. This method uses a reinforcement learning algorithm to learn from experience how to choose the best from a set of possible bids. These bids are defined accordingly to the cost function that each producer presents.

Multi-apprentice learning for meta-heuristics parameter tuning in a multi agent scheduling system

The scheduling problem is considered in complexity theory as a NP-hard combinatorial optimization problem. Meta-heuristics proved to be very useful in the resolution of this class of problems. However, these techniques require parameter tuning which is a very hard task to perform. A Case-based Reasoning module is proposed in order to solve the parameter tuning problem in a Multi-Agent Scheduling System. A computational study is performed in order to evaluate the proposed CBR module performance.

Case-based reasoning for self-optimizing behavior

In this paper we present a Self-Optimizing module, inspired on Autonomic Computing, acquiring a scheduling system with the ability to automatically select a Meta-heuristic to use in the optimization process, so as its parameterization. Case-based Reasoning was used so the system may be able of learning from the acquired experience, in the resolution of similar problems. From the obtained results we conclude about the benefit of its use.

New recycling approaches for thermoset polymeric composite wastes – an experimental study on polyester based concrete materials filled with fibre reinforced plastic recyclates

In this study, a new waste management solution for thermoset glass fibre reinforced polymer (GFRP) based products was assessed. Mechanical recycling approach, with reduction of GFRP waste to powdered and fibrous materials was applied, and the prospective added-value of obtained recyclates was experimentally investigated as raw material for polyester based mortars. Different GFRP waste admixed mortar formulations were analyzed varying the content, between 4% up to 12% in weight, of GFRP powder and fibre mix waste. The effect of incorporation of a silane coupling agent was also assessed. Design of experiments and data treatment was accomplished through implementation of full factorial design and analysis of variance ANOVA. Added value of potential recycling solution was assessed by means of flexural and compressive loading capacity of GFRP waste admixed mortars with regard to unmodified polymer mortars. The key findings of this study showed a viable technological option for improving the quality of polyester based mortars and highlight a potential cost-effective waste management solution for thermoset composite materials in the production of sustainable concrete-polymer based products.

Adapting Meeting Tools to Agent Decision

Electricity markets are complex environments comprising several negotiation mechanisms. MASCEM (Multi- Agent System for Competitive Electricity Markets) is a simulator developed to allow deep studies of the interactions between the players that take part in the electricity market negotiations. ALBidS (Adaptive Learning Strategic Bidding System) is a multiagent system created to provide decision support to market negotiating players. Fully integrated with MASCEM it considers several different methodologies based on very distinct approaches. The Six Thinking Hats is a powerful technique used to look at decisions from different perspectives. This paper aims to complement ALBidS strategies usage by MASCEM players, providing, through the Six Thinking Hats group decision technique, a means to combine them and take advantages from their different perspectives. The combination of the different proposals resulting from ALBidS’ strategies is performed through the application of a Genetic Algorithm, resulting in an evolutionary learning approach.

Intelligent Micro Grid Management using a Multi-Agent approach

Recent changes in electricity markets (EMs) have been potentiating the globalization of distributed generation. With distributed generation the number of players acting in the EMs and connected to the main grid has grown, increasing the market complexity. Multi-agent simulation arises as an interesting way of analysing players’ behaviour and interactions, namely coalitions of players, as well as their effects on the market. MASCEM was developed to allow studying the market operation of several different players and MASGriP is being developed to allow the simulation of the micro and smart grid concepts in very different scenarios This paper presents a methodology based on artificial intelligence techniques (AI) for the management of a micro grid. The use of fuzzy logic is proposed for the analysis of the agent consumption elasticity, while a case based reasoning, used to predict agents’ reaction to price changes, is an interesting tool for the micro grid operator.

Metalearner based on Dynamic Neural Network for Strategic Bidding in electricity Markets

The restructuring of electricity markets, conducted to increase the competition in this sector, and decrease the electricity prices, brought with it an enormous increase in the complexity of the considered mechanisms. The electricity market became a complex and unpredictable environment, involving a large number of different entities, playing in a dynamic scene to obtain the best advantages and profits. Software tools became, therefore, essential to provide simulation and decision support capabilities, in order to potentiate the involved players’ actions. This paper presents the development of a metalearner, applied to the decision support of electricity markets’ negotiation entities. The proposed metalearner executes a dynamic artificial neural network to create its own output, taking advantage on several learning algorithms implemented in ALBidS, an adaptive learning system that provides decision support to electricity markets’ players. The proposed metalearner considers different weights for each strategy, depending on its individual quality of performance. The results of the proposed method are studied and analyzed in scenarios based on real electricity markets’ data, using MASCEM - a multi-agent electricity market simulator that simulates market players’ operation in the market.

Realistic Multi-Agent Simulation of Competitive Electricity Markets

The dynamism and ongoing changes that the electricity markets sector is constantly suffering, enhanced by the huge increase in competitiveness, create the need of using simulation platforms to support operators, regulators, and the involved players in understanding and dealing with this complex environment. This paper presents an enhanced electricity market simulator, based on multi-agent technology, which provides an advanced simulation framework for the study of real electricity markets operation, and the interactions between the involved players. MASCEM (Multi-Agent Simulator of Competitive Electricity Markets) uses real data for the creation of realistic simulation scenarios, which allow the study of the impacts and implications that electricity markets transformations bring to different countries. Also, the development of an upper-ontology to support the communication between participating agents, provides the means for the integration of this simulator with other frameworks, such as MAN-REM (Multi-Agent Negotiation and Risk Management in Electricity Markets). A case study using the enhanced simulation platform that results from the integration of several systems and different tools is presented, with a scenario based on real data, simulating the MIBEL electricity market environment, and comparing the simulation performance with the real electricity market results.

Data Mining Approach to support the Generation of Realistic Scenarios for Multi-Agent simulation of Electricity Markets

This paper presents the Realistic Scenarios Generator (RealScen), a tool that processes data from real electricity markets to generate realistic scenarios that enable the modeling of electricity market players’ characteristics and strategic behavior. The proposed tool provides significant advantages to the decision making process in an electricity market environment, especially when coupled with a multi-agent electricity markets simulator. The generation of realistic scenarios is performed using mechanisms for intelligent data analysis, which are based on artificial intelligence and data mining algorithms. These techniques allow the study of realistic scenarios, adapted to the existing markets, and improve the representation of market entities as software agents, enabling a detailed modeling of their profiles and strategies. This work contributes significantly to the understanding of the interactions between the entities acting in electricity markets by increasing the capability and realism of market simulations.