2,269 research outputs found

    Problems Affecting Labor

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    Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by ℙ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G A (a 3-α helix fold) and G B (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G A domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G Bs, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed

    Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7Îł

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    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 Fbw7Îł, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7Îł 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 Fbw7Îł, 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

    Coherent amplitudon generation in K_0.3MoO_3 through ultrafast inter-band quasi particle decay

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    The charge density wave system K_0.3MoO_3 has been studied using variable energy pump-probe spectroscopy, ellipsometry, and inelastic light scattering. The observed transient reflectivity response exhibits quite a complex behavior, containing contributions due to quasi particle excitations, coherent amplitudons and phonons, and heating effects. The generation of coherent amplitudons is discussed in terms of relaxation of photo-excited quasi particles, and is found to be resonant with the interband plasmon frequency. Two additional coherent excitations observed in the transients are assigned to zone-folding modes of the charge density wave state

    Instanton Calculus and Nonperturbative Relations in N=2 Supersymmetric Gauge Theories

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    Using instanton calculus we check, in the weak coupling region, the nonperturbative relation =i\pi\left(\cf-{a\over 2} {\partial\cf\over\partial a}\right) obtained for a N=2 globally supersymmetric gauge theory. Our computations are performed for instantons of winding number k, up to k=2 and turn out to agree with previous nonperturbative results.Comment: 18 pages, latex file, no figure

    CUGC for hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome

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    From 1999 to date, 50 affecting function variants have been identified and associated to HHH syndrome [1–5]. As it is not available in the literature a complete up-to-date list of disease-causing variants for SLC25A15 gene, we included this information as a Supplementary Excel sheet (See Supplementary Material File #1): this list was created by using LOVD and ClinVar databases and liked to the relevant literature reference. Reported variants consist of: 29 missense variants, 4 frameshift, 11 nonsense, 2 splicing, 2 small deletion, 1 in frame insertion, 1 gross deletion

    BMN operators with vector impurities, Z_2 symmetry and pp-waves

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    We calculate the coefficients of three-point functions of BMN operators with two vector impurities. We find that these coefficients can be obtained from those of the three-point functions of scalar BMN operators by interchanging the coefficient for the symmetric-traceless representation with the coefficient for the singlet. We conclude that the Z_2 symmetry of the pp-wave string theory is not manifest at the level of field theory three-point correlators.Comment: 25 pages, 7 figures. v1: A reference and a footnote added; v2: New contributions found, Z_2 symmetry lost in 3-point function

    Non-fermi-liquid single particle lineshape of the quasi-one-dimensional non-CDW metal Li_{0.9}Mo_{6}O_{17} : comparison to the Luttinger liquid

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    We report the detailed non-Fermi liquid (NFL) lineshape of the dispersing excitation which defines the Fermi surface (FS) for quasi-one-dimensional Li_{0.9}Mo_{6}O_{17}. The properties of Li_{0.9}Mo_{6}O_{17} strongly suggest that the NFL behavior has a purely electronic origin. Relative to the theoretical Luttinger liquid lineshape, we identify significant similarities, but also important differences.Comment: 5 pages, 3 eps figure

    A multi-channel trigger and acquisition board for TDC-based readout: Application to the cosmic rays detector of the PolarQuEEEst 2018 project

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    In the summer of 2018, the PolarQuEEEst experiment accomplished a measurement of cosmic rays flux in the Arctic. The detector, installed on a sailboat, was based on scintillation tiles read by a total of 16 SiPM. A multi-channel board (called TRB) has been designed to process the discriminated SiPM signals providing both self-trigger capability and time-to-digital conversion; it was based on a Cyclone-V Intel FPGA. Time-to-digital conversion has been implemented both into FPGA and with the HPTDC chip (as a backup). In this document the board will be described, enlightening the main features and the achieved performance. Lastly, the PolarQuEEEst measurement campaigns will be briefly described, showing how the TRB board has proved to be effective for experiments which require low power consumption, integration with position and environmental sensors and great portability as well. Final thoughts on future improvements will be also discussed

    Plantation de chênes méditerranéens avec accompagnement ligneux : amélioration de la forme mais réduction de la croissance

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    Une plantation expérimentale de chênes (Q. ilex, Q. pubescens) avec un accompagnement ligneux de pin d’Alep et de coronille a été réalisée afin d’analyser l’influence des espèces ligneuses accompagnatrices sur la survie, la croissance et la morphologie des chênes sur une période de sept années. La végétation au sol a été, soit enlevée, soit laissée en place, pour détecter une éventuelle facilitation indirecte. Les résultats montrent que ce sont les relations de compétition qui dominent. La survie est fortement réduite pour le chêne blanc sous coronille en raison d’une interception forte de la lumière. Pour les deux chênes, la croissance est toujours plus forte dans les témoins que dans les traitements avec accompagnement, même dans le système enherbé. L’accompagnement avec pin d’Alep est cependant plus favorable que le traitement avec coronille pour le développement initial des chênes. En revanche, la forme des chênes est améliorée par l’accompagnement : les plants sont plus élancés, présentent un houppier moins large et un port moins buissonnant. Sur la base de ces résultats, nous soulignons l’importance de bien identifier les objectifs poursuivis avant d’installer une plantation mixte (par exemple maximiser la croissance des espèces cibles, ou celle du mélange, améliorer la morphologie, etc.) et la nécessité d’une gestion active pour contrôler les effets potentiels indésirables de la végétation accompagnatrice sur les espèces cibles
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