Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.

Transcription factors of the nuclear factor κB (NF-κB) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-κB activation also contributes to the pathogenesis of some of the most common current threats to global human health, including chronic inflammatory diseases, autoimmune disorders, diabetes, vascular diseases and the majority of cancers. Accordingly, the NF-κB pathway is widely considered an attractive therapeutic target in a broad range of malignant and non-malignant diseases. Yet, despite the aggressive efforts by the pharmaceutical industry to develop a specific NF-κB inhibitor, none has been clinically approved, due to the dose-limiting toxicities associated with the global suppression of NF-κB. In this review, we summarise the main strategies historically adopted to therapeutically target the NF-κB pathway with an emphasis on oncology, and some of the emerging strategies and newer agents being developed to pharmacologically inhibit this pathway

Estimating preferences for controlling beach erosion in Sicily

This study applied discrete-choice experiments to estimate preferences for a program aimed at reducing the retreatment of the sandy beach at "Lido di Noto", a renowned Sicilian bathing resort close to Noto (Italy). Econometric analysis of data was based on Multinomial Logit (MNL), Latent Class (LC) and Mixed Logit (MXL) models. Findings shown that users appreciated the advancement of the current coastline through nourishment, and negatively perceived the construction of emerged sea barriers. MXL and LC models revealed that preferences were heterogeneous

The alignment of European Law in pre-candidate countries: the case of Bosnia and Herzegovina wine law

The purpose of this paper is to examine mechanism of Europeanisation trough the creation process example of a new wine law in Bosnia and Herzegovina (BiH), combining domestic wine regulations and EU legislative frameworks. We will analyze criteria and implications of Europeanization process, focusing on mechanism of assistance to candidate and pre-candidate countries. The aim is to understand the genesis of the conflict that hinders the development process and represents a barrier to trade liberalization. Adoption of law in BiH, as well as ordinances and regulations for its implementation and enforcement, is a precondition for a harmonized legal framework and competitive rules for the agriculture sector. For the analysis, we used dimensions of integrations and institutionalism theories as lenses to explore this processes. This approach is the one of the theoretical perspectives that has won converts and provided in many cases a useful tool for analyzing EU integration

Research in Geant4 electromagnetic physics design, and its effects on computational performance and quality assurance

The Geant4 toolkit offers a rich variety of electromagnetic physics models; so far the evaluation of this Geant4 domain has been mostly focused on its physics functionality, while the features of its design and their impact on simulation accuracy, computational performance and facilities for verification and validation have not been the object of comparable attention yet, despite the critical role they play in many experimental applications. A new project is in progress to study the application of new design concepts and software techniques in Geant4 electromagnetic physics, and to evaluate how they can improve on the current simulation capabilities. The application of a policy-based class design is investigated as a means to achieve the objective of granular decomposition of processes; this design technique offers various advantages in terms of flexibility of configuration and computational performance. The current Geant4 physics models have been re-implemented according to the new design as a pilot project. The main features of the new design and first results of performance improvement and testing simplification are presented; they are relevant to many Geant4 applications, where computational speed and the containment of resources invested in simulation production and quality assurance play a critical role.Comment: 4 pages, 4 figures and images, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

Geant4-related R&D for new particle transport methods

A R&D project has been launched in 2009 to address fundamental methods in radiation transport simulation and revisit Geant4 kernel design to cope with new experimental requirements. The project focuses on simulation at different scales in the same experimental environment: this set of problems requires new methods across the current boundaries of condensed-random-walk and discrete transport schemes. An exploration is also foreseen about exploiting and extending already existing Geant4 features to apply Monte Carlo and deterministic transport methods in the same simulation environment. An overview of this new R&D associated with Geant4 is presented, together with the first developments in progress.Comment: 4 pages, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

The Public Choice theory as a tool for CMO wine analysis

The objective of this work is to reconstruct the role of agricultural lobbyist and the national alliances, in determining the outcome of the process of the latest wine common market (CMO) regulations entered into force on 1st August 2009 (Reg. 479/2008), and how these have changed the Commission\u2019s initial proposals. Four example of public decisions have been discussed: grubbing up vineyards and liberalization of replanting rights; the abolition of market measures (the case of distillation measures); quality policies (designations of origin) and new rules of wine labels. The approach to the models of Public Choice, included for the first time in a specific context such as the wine sector, has served to focus attention on the processes and the interactions between the politicians and the agricultural associations.The most important innovation in this work is the inclusion of different organizational forms of political interests and wine business representation. It covers not only traditional collective action but also individual action and third party representation. This is fundamentally different from the usual focus on collective action in isolation from other organizational form (Coen, 1997)

Public Choice theory as a tool for CMO wine reform analysis

The purpose of this paper is a partial reconstruction the role of agricultural lobbyist and national alliances, determining the effort of re-opening the common market organization of wine (CMO) Reg. 479/2008. The case considered is the liberalization of replanting rights chosen as a tool of Public Choice (P.C) analysis. The paper is divided into three parts. The first is a brief summary of P.C literature and methodological applications. The second a study of the structure, behavior and the relationship of the main actors involved in the policy genesis of the CMO. Third analyzes the effects that lobbyist actions have generated in the case of vineyard liberalization.The methodological approach is the P.C. model derived from Pokrivcak et.al.(2006).This is partially used in this discussion, to explain the general idea and concept of bargaining and trade-offs in wine policy by the mayor actors in a simplified scenario

Inter-Comparison and Validation of Geant4 Photon Interaction Models

A R&D project, named Nano5, has been recently launched to study an architectural design in view of addressing new experimental issues related to particle transport in high energy physics and other related physics disciplines with Geant4. In this frame, the first step has involved the redesign of the photon interaction models currently available in Geant4; this task has motivated a thorough investigation of the physics and computational features of these models, whose first results are presented here.Comment: 4 pages, 7 figures and images, 2 tables, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

R&D on co-working transport schemes in Geant4

A research and development (R&D) project related to the extension of the Geant4 toolkit has been recently launched to address fundamental methods in radiation transport simulation. The project focuses on simulation at different scales in the same experimental environment; this problem requires new methods across the current boundaries of condensed-random-walk and discrete transport schemes. The new developments have been motivated by experimental requirements in various domains, including nanodosimetry, astronomy and detector developments for high energy physics applications.Comment: To be published in the Proceedings of the CHEP (Computing in High Energy Physics) 2009 conferenc

The Z-Z' Mass Hierarchy in a Supersymmetric Model with a Secluded U(1)'-Breaking Sector

We consider the Z'/Z mass hierarchy in a supersymmetric model in which the U(1)' is broken in a secluded sector coupled to the ordinary sector only by gauge and possibly soft terms. A large mass hierarchy can be achieved while maintaining the normal sparticle spectra if there is a direction in which the tree level potential becomes flat when a particular Yukawa coupling vanishes. We describe the conditions needed for the desired breaking pattern, to avoid unwanted global symmetries, and for an acceptable effective mu parameter. The electroweak breaking is dominated by A terms rather than scalar masses, leading to tan beta ~ 1. The spectrum of the symmetry breaking sector is displayed. There is significant mixing between the MSSM particles and new standard model singlets, for both the Higgs scalars and the neutralinos. A larger Yukawa coupling for the effective mu parameter is allowed than in the NMSSM because of the U(1)' contribution to the running from a high scale. The upper bound on the tree-level mass of the lightest CP even Higgs doublet mass is about c x 174 GeV, where c is of order unity, but the actual mass eigenvalues are generally smaller because of singlet mixing.Comment: Latex, 12 Tables, 22 page