InterAKTions with FKBPs - mutational and pharmacological exploration

The FK506-binding protein 51 (FKBP51) is an Hsp90-associated co-chaperone which regulates steroid receptors and kinases. In pancreatic cancer cell lines, FKBP51 was shown to recruit the phosphatase PHLPP to facilitate dephosphorylation of the kinase Akt, which was associated with reduced chemoresistance. Here we show that in addition to FKBP51 several other members of the FKBP family bind directly to Akt. FKBP51 can also form complexes with other AGC kinases and mapping studies revealed that FKBP51 interacts with Akt via multiple domains independent of their activation or phosphorylation status. The FKBP51-Akt1 interaction was not affected by FK506 analogs or Akt active site inhibitors, but was abolished by the allosteric Akt inhibitor VIII. None of the FKBP51 inhibitors affected AktS473 phosphorylation or downstream targets of Akt. In summary, we show that FKBP51 binds to Akt directly as well as via Hsp90. The FKBP51-Akt interaction is sensitive to the conformation of Akt1, but does not depend on the FK506-binding pocket of FKBP51. Therefore, FKBP inhibitors are unlikely to inhibit the Akt-FKBP-PHLPP network

Environmental Licensing Challenges of Xingu Rio Transmission System Route Definition

Based on the Brazilian electric sector planning, by 2026 the transmission grid will be increased by 64 thousand km, so that the analysis of how to incorporate the environmental criteria in the discussions of route optimization are important for the decision-making of the various actors (government, environmental agencies and entrepreneurs). Therefore, this article aims to identify the challenges of the incorporation of the socio-environmental criteria for the route optimization as well as the deadlines and costs of the Xingu-Rio Transmission System known to be the largest transmission system in Brazil

Os obstáculos do licenciamento ambiental municipal - Análise das principais dificuldades e dos entraves existentes nos procedimentos de licenciamentos ambiental de competência dos municípios

Environmental licensing is one of the main instruments of the National Environmental Policy, mainly due to its nature of prevention of the significance of environmental damages. After the enactment of complementary law no. 140/11, municipalities were given the explicit competence to license enterprises and activities whose environmental impact is classified as local, provided they have a qualified technical body and a municipal environmental council. After almost six years of enforcement of the aforementioned complementary law, it is verified that most municipalities have not yet been able to implement an efficient and effective environmental licensing system, configuring themselves as mere emitters of environmental licenses. The main problems encountered in municipal environmental licensing are addressed in this paper, such as inconsistencies in the definition of competence of the licensing body, deficiencies in the normative framework, mainly regarding legislation on land use and occupation (zoning), low technical capacity and Lack of independence of municipal environmental agencies, excessive bureaucracy and high processing time, as well as lack of transparency and social control. The analysis of these obstacles points to the need for improvements and effective changes in municipal environmental systems, making environmental licensing play the role of collective protection.O licenciamento ambiental constitui um dos principais instrumentos da Política Nacional de Meio Ambiente, principalmente pelo seu caráter de prevenção da significância dos danos ambientais. Após a edição da lei complementar nº 140/11, os municípios passaram a ter a competência explícita para licenciar os empreendimentos e atividades cujo impacto ambiental seja classificado como de âmbito local, desde que possuam órgão técnico capacitado e conselho municipal de meio ambiente. Após quase seis anos de vigência da referida lei complementar, verifica-se que grande parte dos municípios ainda não consegui implementar um sistema de licenciamento ambiental eficiente e eficaz, configurando-se como meros emissores de licenças ambientais. Os principais problemas encontrados no licenciamento ambiental municipal são tratados no presente trabalho, a saber: incongruências na definição de competência do órgão licenciador, as deficiências no arcabouço normativo, principalmente quanto às legislações de uso e ocupação do solo (zoneamentos), a baixa capacidade técnica e falta de independência dos órgãos ambientais municipais, a excessiva burocracia e o elevado tempo de tramitação dos processos, além da falta de transparência e de controle social. A análise desses obstáculos aponta para a necessidade de melhorias e mudanças efetivas nos sistemas municipais de meio ambiente, fazendo com que o licenciamento ambiental cumpra o papel de proteção da coletividade

Commutative homotopical algebra embeds into non-commutative homotopical algebra

Over a field of characteristic zero, we show that the forgetful functor from the homotopy category of commutative dg algebras to the homotopy category of dg associative algebras is faithful. In fact, the induced map of derived mapping spaces gives an injection on all homotopy groups at any basepoint. We prove similar results both for unital and non-unital algebras, and also Koszul dually for the universal enveloping algebra functor from dg Lie algebras to dg associative algebras. An important ingredient is a natural model for these derived mapping spaces as Maurer-Cartan spaces of complete filtered dg Lie algebras (or curved Lie algebras, in the unital case).Comment: 14 page

The Implementation of Scenarios using DSGE Models

The new generation of dynamic stochastic general equilibrium (DSGE) models seems particularly suited for conducting scenario analysis. These models formalise the behaviour of economic agents on the basis of explicit micro-foundations. As a result, they appear less prone to the Lucas critique than traditional macroeconometric models. DSGE models provide researchers with powerful tools, which allow for the design of a broad range of scenarios and can tackle a large range of issues, while at the same time offering an appealing structural interpretation of the scenario specification and simulation results. This paper provides illustrations of some of the modelling issues that often arise when implementing scenarios using DSGE models in the context of projection exercises or policy analysis. These issues reflect the sensitivity of DSGE model-based analysis to scenario assumptions, which in more traditional models are apparently less critical, such as, for example, scenario event anticipation and duration, as well as treatment of monetary and fiscal policy rules.Business fluctuations, monetary policy, fiscal policy, forecasting and simulation