Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

On Formal Consistency between Value and Coordination Models

In information systems (IS) engineering dierent techniques for modeling inter-organizational collaborations are applied. In particular, value models estimate the profitability for involved stakeholders, whereas coordination models are used to agree upon the inter-organizational processes before implementing them. During the execution of inter-organizational collaboration, in addition, event logs are collected by the individual organizations representing another view of the IS. The combination of the two models and the event log represent the IS and they should therefore be consistent, i.e., not contradict each other. Since these models are provided by dierent user groups during design time and the event log is collected during run-time consistency is not straight forward. Inconsistency occurs when models contain a conflicting description of the same information, i.e., there exists a conflicting overlap between the models. In this paper we introduce an abstraction of value models, coordination models and event logs which allows ensuring and maintaining alignment between models and event log. We demonstrate its use by outlining a proof of an inconsistency resolution result based on this abstraction. Thus, the introduction of abstractions allows to explore formal inter-model relations based on consistency

Humanoid Motion Description Language

In this paper we propose a description language for specifying motions for humanoid robots and for allowing humanoid robots to acquire motor skills. Locomotion greatly increases our ability to interact with our environments, which in turn increases our mental abilities. This principle also applies to humanoid robots. However, there are great difficulties to specify humanoid motions and to represent motor skills, which in most cases require four-dimensional space representations. We propose a representation framework that includes the following attributes: motion description layers, egocentric reference system, progressive quantized refinement, and automatic constraint satisfaction. We also outline strategies for acquiring new motor skills by learning from trial and error, macro approach, and programming. Then, we outline the development of a new humanoid motion description language called Cybele

Nematic superconductivity in doped Bi2Se3 topological superconductors

Nematic superconductivity is a novel class of superconductivity characterized by spontaneous rotational-symmetry breaking in the superconducting gap amplitude and/or Cooper-pair spins with respect to the underlying lattice symmetry. Doped Bi2Se3 superconductors, such as CuxBi2Se3, SrxBi2Se3, and NbxBi2Se3, are considered as candidates for nematic superconductors, in addition to the anticipated topological superconductivity. Recently, various bulk probes, such as nuclear magnetic resonance, specific heat, magnetotransport, magnetic torque, and magnetization, have consistently revealed two-fold symmetric behavior in their in-plane magnetic-field-direction dependence, although the underlying crystal lattice possesses three-fold rotational symmetry. More recently, nematic superconductivity is directly visualized using scanning tunneling microscopy and spectroscopy. In this short review, we summarize the current researches on the nematic behavior in superconducting doped Bi2Se3 systems, and discuss issues and perspectives.Comment: 20 pages (incl. 5 pages of reference list), 4 figures; Submitted for the proceedings of Erice Workshop 2018 "Majorana Fermions and Topological Materials Science". Small revisions are made on 14th Dec. Comments are welcom

Stoichiometry determination of chalcogenide superlattices by means of X-ray diffraction and its limits

In this paper we explore the potential of stoichiometry determination for chalcogenide superlattices, promising candidates for next-generation phase-change memory, via X-ray diffraction. To this end, a set of epitaxial GeTe/Sb2Te3 superlattice samples with varying layer thicknesses is sputter-deposited. Kinematical scattering theory is employed to link the average composition with the diffraction features. The observed lattice constants of the superlattice reference unit cell follow Vegard's law, enabling a straight-forward and non-destructive stoichiometry determination.Comment: physica status solidi (RRL) - Rapid Research Letters (2019

Quintuple Helix Innovation Model for the European Union Defense Industry An Empirical Research

: The European defense industry is undergoing profound upheavals, and traditional innovation models may no longer be adequate. For this reason, further investigation is needed to know if the triple helix (TH) is suitable for one of the most influential industries in the world. If not suitable, it is necessary to identify which type of n-helices are appropriate. This article follows an embedded case study research strategy that uses several sources of data collection such as interviews with active-duty military personnel, scholars, the defense industry, and interagency professionals. Field notes and official documentation were also collected for corroboration and triangulation purposes. The results showed that the defense industry is increasingly globalized, leaving the national sphere and weakening the action and participation of European Union governments. This research resulted in the design of a quintuple helix innovation model for the defense industry, which was based on a TH combined with technology and the natural environment. We concluded that the traditional TH may not be adequate for the entry of new supranational players and that political contributions are subject to a further response by the European states. Scientific research is also needed, especially in Asian and American countries, which have national defense policies different from those of Europe.info:eu-repo/semantics/publishedVersio