The AF-1 Domain of the Orphan Nuclear Receptor NOR-1 Mediates Trans-activation, Coactivator Recruitment, and Activation by the Purine Anti-metabolite 6-Mercaptopurine

NOR-1/NR4A3 is an orphan member of the nuclear hormone receptor superfamily. NOR-1 and its close relatives Nurr1 and Nur77 are members of the NR4A subgroup of nuclear receptors. Members of the NR4A subgroup are induced through multiple signal transduction pathways. They have been implicated in cell proliferation, differentiation, T-cell apoptosis, chondrosarcomas, neurological disorders, inflammation, and atherogenesis. However, the mechanism of transcriptional activation, coactivator recruitment, and agonist-mediated activation remain obscure. Hence, we examined the molecular basis of NOR-1-mediated activation. We observed that NOR-1 trans-activates gene expression in a cell- and target-specific manner; moreover, it operates in an activation function (AF)-1-dependent manner. The N-terminal AF-1 domain delimited to between amino acids 1 and 112, preferentially recruits the steroid receptor coactivator (SRC). Furthermore, SRC-2 modulates the activity of the AF-1 domain but not the C-terminal ligand binding domain (LBD). Homology modeling indicated that the NOR-1 LBD was substantially different from that of hRORbeta, a closely related AF-2-dependent receptor. In particular, the hydrophobic cleft characteristic of nuclear receptors was replaced with a very hydrophilic surface with a distinct topology. This observation may account for the inability of this nuclear receptor LBD to efficiently mediate cofactor recruitment and transcriptional activation. In contrast, the N-terminal AF-1 is necessary for cofactor recruitment and can independently conscript coactivators. Finally, we demonstrate that the purine anti-metabolite 6-mercaptopurine, a widely used antineoplastic and anti-inflammatory drug, activates NOR-1 in an AF-1-dependent manner. Additional 6-mercaptopurine analogs all efficiently activated NOR-1, suggesting that the signaling pathways that modulate proliferation via inhibition of de novo purine and/or nucleic acid biosynthesis are involved in the regulation NR4A activity. We hypothesize that the NR4A subgroup mediates the genotoxic stress response and suggest that this subgroup may function as sensors that respond to genotoxicity.

Designing competitive international compensation programs

Over the past 25 years, expatriate managers have voiced increased disenchantment with their compensation packages whíle abroad. This paper takes a prescriptive approach, outlíning severa I elements of a successful human resources strategy and stressing key ingredients of effective international compensation programs. Particular ettention is given to the adherence of cultural values and distrlbutive justice when working across nations and cultures.

Unit Commitment in a Competitive and Emission Constrained Environment

This paper is on the unit commitment problem, considering not only the economic perspective, but also the environmental perspective. We propose a bi-objective approach to handle the problem with conflicting profit and emission objectives. Numerical results based on the standard IEEE 30-bus test system illustrate the proficiency of the proposed approach.

Short-term electricity prices forecasting in a competitive market by a hybrid PSO-ANFIS approach

In this paper, a novel hybrid approach is proposed for electricity prices forecasting in a competitive market, considering a time horizon of 1 week. The proposed approach is based on the combination of particle swarm optimization and adaptive-network based fuzzy inference system. Results from a case study based on the electricity market of mainland Spain are presented. A thorough comparison is carried out, taking into account the results of previous publications, to demonstrate its effectiveness regarding forecasting accuracy and computation time. Finally, conclusions are duly drawn. (C) 2012 Elsevier Ltd. All rights reserved.

Learning business strategies for competitive electronic marketplaces

This paper presents a Multi-Agent Market simulator designed for developing new agent market strategies based on a complete understanding of buyer and seller behaviors, preference models and pricing algorithms, considering user risk preferences and game theory for scenario analysis. This tool studies negotiations based on different market mechanisms and, time and behavior dependent strategies. The results of the negotiations between agents are analyzed by data mining algorithms in order to extract rules that give agents feedback to improve their strategies. The system also includes agents that are capable of improving their performance with their own experience, by adapting to the market conditions, and capable of considering other agent reactions.

A congestion management and transmission price simulator for competitive electricity markets

In a liberalized electricity market, the Transmission System Operator (TSO) plays a crucial role in power system operation. Among many other tasks, TSO detects congestion situations and allocates the payments of electricity transmission. This paper presents a software tool for congestion management and transmission price determination in electricity markets. The congestion management is based on a reformulated Optimal Power Flow (OPF), whose main goal is to obtain a feasible solution for the re-dispatch minimizing the changes in the dispatch proposed by the market operator. The transmission price computation considers the physical impact caused by the market agents in the transmission network. The final tariff includes existing system costs and also costs due to the initial congestion situation and losses costs. The paper includes a case study for the IEEE 30 bus power system.

VPPs information needs for effective operation in competitive electricity markets

The large increase of renewable energy sources and Distributed Generation (DG) of electricity gives place to the Virtual Power Producer (VPP) concept. VPPs may turn electricity generation by renewable sources valuable in electricity markets. Information availability and adequate decision-support tools are crucial for achieving VPPs’ goals. This involves information concerning associated producers and market operation. This paper presents ViProd, a simulation tool that allows simulating VPPs operation, focusing mainly in the information requirements for adequate decision making.

Short-term electricity prices forecasting in a competitive market by a hybrid intelligent approach

In this paper, a hybrid intelligent approach is proposed for short-term electricity prices forecasting in a competitive market. The proposed approach is based on the wavelet transform and a hybrid of neural networks and fuzzy logic. Results from a case study based on the electricity market of mainland Spain are presented. A thorough comparison is carried out, taking into account the results of previous publications. Conclusions are duly drawn. (C) 2010 Elsevier Ltd. All rights reserved.

Energy resources scheduling in competitive environment

The increasing use of distributed generation units based on renewable energy sources, the consideration of demand-side management as a distributed resource, and the operation in the scope of competitive electricity markets have caused important changes in the way that power systems are operated. The new distributed resources require an entity (player) capable to make them able to participate in electricity markets. This entity has been known as Virtual Power Player (VPP). VPPs need to consider all the business opportunities available to their resources, considering all the relevant players, the market and/or other VPPs to accomplish their goals. This paper presents a methodology that considers all these opportunities to minimize the operation costs of a VPP. The method is applied to a distribution network managed by four independent VPPs with intensive use of distributed resources.