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We start by summarizing noise and vibration problematics.Then available modeling tools are presented: materials and sub-structures, absorption, isolation, damping and encapsulation.Concerning vibrations, emphasis is put on structural damping: decoupling pads, viscous damping, Tuned mass dampers and Non-linear energy sinks. These solutions are compared in terms of pro and cons.

[ES] KMT2D es una metiltransferasa que se encarga de transferir un grupo metilo a la histona H3, lo que está relacionado con la activación génica. Esta proteína es esencial en el desarrollo embrionario temprano y, además, se expresa también en numerosos tejidos adultos. Las mutaciones en el gen que codifica para la síntesis de KMT2D en la línea germinal están relacionadas con el síndrome de Kabuki, una enfermedad congénita rara. También se ha visto que las mutaciones somáticas están relacionadas con la formación de tumores, siendo KMT2D una de las proteínas más frecuentemente mutadas en el cáncer. Por su actividad metiltransferasa de histonas, se sabe que KMT2D desarrolla su función en el núcleo. Partiendo de la hipótesis inicial de que KMT2D puede tener señales de transporte nucleocitoplásmico funcionales, se realizaron análisis bioinformáticos para predecir tanto posibles señales de localización nuclear (NLS) como señales de exportación nuclear (NES) en su secuencia. Los ensayos experimentales revelaron que KMT2D tiene una NLS funcional y una NES débil. De este modo, si se identifican mutaciones relacionadas con patologías en las regiones en las que se encuentran estas señales, se podría investigar la relación del transporte alterado de KMT2D con las diferentes patologías.

As a transcription factor, localization to the nucleus and the recruitment of co-factors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc finger transcription factor CASZ1 to function as neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized. Through alanine scanning, immunofluorescence cell staining and co-immunoprecipitation we define a critical region at the CASZ1 N-terminus (AA23-40) that mediates the CASZ1b nuclear localization and NuRD interaction. Furthermore, we identify a nuclear export signal (NES) at the N-terminus (AA176-192) that contributes to CASZ1 nuclear-cytoplasmic shuttling in a chromosomal maintenance 1 (CRM1)-dependent manner. An analysis of CASZ1 protein expression in a primary neuroblastoma tissue microarray shows that high nuclear CASZ1 staining is detected in tumors from NB patients with good prognoses. In contrast, cytoplasmic-restricted CASZ1 staining or low nuclear CASZ1 staining is found in tumors from patients with poor prognoses. These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as neuroblastoma tumorigenesis.

The Perusahaan Inti Rakyat (PIR) scheme, a smallholder support scheme in collaboration with plantation companies, was developed in the late 1970s in Indonesia. The idea of the PIR scheme is to improve the socioeconomic condition of smallholders. One of the ways of doing so is by providing technical and economic support and capacity building to help them develop as modern self-owned farmers. The PIR scheme also aims to change the relationship between companies' large-scale modern plantations and smallholders' traditional estates from an antagonistic one to a mutually interdependent one, while recognizing the existence of a dualism between the two, as indicated by Boeke (1884–1956) in his theory on dual societies. This article shows the transition of the PIR scheme within the historical context of socioeconomic and political changes in Indonesia. The development of PIR-Bun, PIR-Trans, and PIR-KKPA during the authoritarian Suharto era (1966–98), the stagnation of the PIR scheme during the Reformation era (1999– 2003), and the development of PIR-Revitalisasi in the democratic era (2004–) are reported and analyzed. Over time, the main companies participating in the programs of the PIR scheme changed from state-owned companies to private ones. The gap in productivity between companies' large-scale plantations and smallholders' estates was not resolved during the Reformation era. As a result, PIR-Revitalisasi has applied a united management system in which a company manages the whole process of smallholders' estates, including planting, growing, harvesting, and marketing in order to enhance the latter's productivity, effectiveness, and profitability. Smallholders are excluded from the management of their estates, while they receive benefits shared by the contracted company. It seems that the PIR scheme has given up the idea of developing smallholders as modern self-owned farmers. However, we may evaluate the result of the PIR scheme before the adoption of the united manage

Detta examensarbete skapades med målet att undersöka skillnader i preferensen gällande arpeggios i NES- och Famicom-musik baserat på kultur. Bakgrundskapitlet tar upp tidigare forskning inom tangentiella ämnen, samt beskriver arpeggios och hur NES- och Famicom-konsolerna är uppbyggda. En kvantitativ metod utvecklas sedan, och problematiseras. Detta följs av en beskrivning av det förarbete som gjordes, och skapandet av de två artefakter som användes. En enkät genomfördes efter förarbetet, och resultatet av denna analyseras därefter i rapporten. Resultatet visar på att det finns vissa skillnader i preferens mellan svenska och japanska lyssnare. Denna slutsats, samt resterande delar av rapporten diskuteras sedan och till sist skrivs det om framtida arbete, så som att en plug-in möjligtvis skulle kunna skapas efter detta arbete har gjorts. Denna plugin skulle göra det lättare att få musik att låta mer europeisk eller japansk.

We start by summarizing noise and vibration problematics.Then available modeling tools are presented: materials and sub-structures, absorption, isolation, damping and encapsulation.Concerning vibrations, emphasis is put on structural damping: decoupling pads, viscous damping, Tuned mass dampers and Non-linear energy sinks. These solutions are compared in terms of pro and cons.

Recent studies have demonstrated the interference of nucleocytoplasmic trafficking with the establishment and maintenance of various cancers. Nucleocytoplasmic transport is highly regulated and coordinated, involving different nuclear transport factors or receptors, importins and exportins, that mediate cargo transport from the cytoplasm into the nucleus or the other way round, respectively. The exportin CRM1 (Chromosome region maintenance 1) exports a plethora of different protein cargoes and ribonucleoprotein complexes. Structural and biochemical analyses have enabled the deduction of individual steps of the CRM1 transport cycle. In addition, CRM1 turned out to be a valid target for anticancer drugs as it exports numerous proto-oncoproteins and tumor suppressors. Clearly, detailed understanding of the flexibility, regulatory features and cooperative binding properties of CRM1 for Ran and cargo is a prerequisite for the design of highly effective drugs. The first compound found to inhibit CRM1-dependent nuclear export was the natural drug Leptomycin B (LMB), which blocks export by competitively interacting with a highly conserved cleft on CRM1 required for nuclear export signal recognition. Clinical studies revealed serious side effects of LMB, leading to a search for alternative natural and synthetic drugs and hence a multitude of novel therapeutics. The present review examines recent progress in understanding the binding mode of natural and synthetic compounds and their inhibitory effects.

L’objectif de cette thèse est de contrôler passivement une instabilité dynamique appliquée au flottement d’un profil aéroélastique à l’aide de différents types d’Amortisseurs à Masse Accordés (AMA). Un profil 2D appelé Section Typique est utilisé tout au long de l’étude. En première partie, une étude comparative de trois modèles mathématiques d’interaction fluide/structure appliqués à la Section Typique (Theodorsen, LUVLM et UVLM) met en valeur les forces et faiblesses de chacun. Le banc d’essai aéroélastique en soufflerie, utilisé par la suite, est présenté puis identifié avec et sans vent (GVT). En deuxième partie, les calculs des vitesses critiques de Divergence, d’Inversion des Gouvernes et de Flottement sont automatisés avec le modèle Theodorsen afin de réaliser une étude paramétrique du banc d’essai et mettre en lumière les variables de conception les plus influentes. L’analyse modale présente différentes bifurcations liées au changement soudain du mode instable. Ensuite, le même algorithme est utilisé afin d’analyser la suppression du flottement à l’aide de trois géométries d’AMAs linéaires. La dernière partie présente l’étude expérimentale et numérique d’un AMA non linéaire de type Nonlinear Energy Sink (NES). La singularité de cette configuration est d’utiliser le volet en tant qu’amortisseur et ainsi, ne pas ajouter de masse (FSI-VA). En soufflerie, six comportements non linéaires sous-critiques (en deçà de la vitesse de flottement dans la configuration linéaire) sont observés, identifiés et analysés : cinq Cycles Limites d’Oscillations (LCO) et un battement non linéaire chaotique. The aim of this thesis is to passively control a dynamic instability applied to an aeroelastic profile’s flutter using different types of Tuned Mass Dampers (TMD). A 2D profile called Typical Section is used throughout the study. In the first part, a comparative study of three mathematical models of fluid-structure interaction applied to the Typical Section (Theodorsen, LUVLM and UVLM) highlights the strengths and weaknesses of each code. The aeroelastic test bench, used subsequently, is presented and identified with and without wind (Ground Vibration Test, GVT). In the second part, critical velocities computations (Divergence, Control Surface Reversal and flutter) are automated while using the Theodorsen model in order to carry out the test bench parametrical study to highlight most influential variables. The modal analysis presents different bifurcations linked to the sudden change of the unstable mode. The last part presents the experimental and numerical studies of a nonlinear TMD called Nonlinear Energy Sink (NES). The uniqueness of this configuration consists in recycling flap’s vibrations as a flutter damper and thus, get a zero added mass. A nonlinear restoring force can be achieved by a highly nonlinear mechanism. The nonlinear structural behavior is derived analyticaly and is in good agreement with experimental torsion tests. In the wind tunnel, six subcritical nonlinear behaviors (below the flutter velocity in the linear configuration case) are observed, identified and then analyzed : five Limit Cycle Oscillations (LCO) and a chaotic nonlinear beating.

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs. DOI: http://dx.doi.org/10.7554/eLife.23961.001

To reduce the vibrations seen by a product, three main families of solutions (physics) exist: to realize a decoupling (decoupling pads), to thermally dissipate energy (viscous damping) or to mechanically capture energy (Tuned mass dampers; Non-linear energy sinks).We will briefly present these different possibilities, their drawbacks and advantages, their scope of use, and the main points entering their dimensioning.Emphasis will be put on viscous damping and NES since experimental results will be presented and compared to simulation.

International audience; We try to enlighten the time multi-scale energy exchange between a main oscillator of Bouc-Wen type and a nonlinear energy sink. A general methodology is presented to detect the invariant manifold of the system at fast time scale and then to search equilibrium points and fold singularities at the slow time scale. A numerical example is enclosed to show the application of the coupled nonlinear energy sink in passive control of Bouc-Wen type main structures.

ZO-2 is a cytoplasmic protein of tight junctions (TJs). Here, we describe ZO-2 involvement in the formation of the apical junctional complex during early development and in TJ biogenesis in epithelial cultured cells. ZO-2 acts as a scaffold for the polymerization of claudins at TJs and plays a unique role in the blood–testis barrier, as well as at TJs of the human liver and the inner ear. ZO-2 movement between the cytoplasm and nucleus is regulated by nuclear localization and exportation signals and post-translation modifications, while ZO-2 arrival at the cell border is triggered by activation of calcium sensing receptors and corresponding downstream signaling. Depending on its location, ZO-2 associates with junctional proteins and the actomyosin cytoskeleton or a variety of nuclear proteins, playing a role as a transcriptional repressor that leads to inhibition of cell proliferation and transformation. ZO-2 regulates cell architecture through modulation of Rho proteins and its absence induces hypertrophy due to inactivation of the Hippo pathway and activation of mTOR and S6K. The interaction of ZO-2 with viral oncoproteins and kinases and its silencing in diverse carcinomas reinforce the view of ZO-2 as a tumor regulator protein.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:29:49Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:29:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-01 The objective was to evaluate reproductive tract development (ovary and uterus) and onset of puberty in two lines of Nellore heifers (Bos indicus) selected for postweaning weight. A total of 123 heifers, including 46 from the control Nellore line (NeC) and 77 from the selection Nellore line (NeS) were used. Every 18 to 21 days from 12 to 24 months of age, average ovarian area (OVA), endometrial thickness (ETh), and diameter of the largest follicle in each ovary were evaluated (using transrectal ultrasonography), and body weight, hip height, and body condition score were measured. There were no differences between NeS and NeC heifers for ETh or OVA (P < 0.05). Genetic selection for higher postweaning weight had no negative influence on the onset of puberty, with 52% and 48% of NeC and NeS heifers, respectively, pubertal at 24 months of age (P = 0.49). Heifers that reached puberty at the end of the study were heavier (NeC, 296.9 vs. 276.7 kg; NeS, 343.5 vs. 327.9 kg; P < 0.01) and younger (NeC, 23.4 vs. 24.2 mo; NeS, 22.7 vs. 24.0 months; P < 0.01) than those that did not. Furthermore, heifers that were heavier at weaning reached puberty earlier. Pubertal heifers had a greater OVA (4.15 vs. 3.14 cm2; P < 0.01) and ETh (12.15 vs. 9.93 mm; P < 0.01) than nonpubertal heifers. Taken together, OVA and ETh had positive effects (P < 0.01) on the onset of puberty and were suitable indicator traits of heifer sexual precocity in pasture management systems. However, selection for weight did not alter ovarian or endometrial development, or manifestation of puberty at 24 months of age. Among the growth traits studied, weaning weight and weight at puberty had significant positive effects on manifestation of first estrus. © 2013 Elsevier Inc. Centro APTA Bovinos de Corte IZ-APTA, Sertãozinho, São Paulo Department of Animal Reproduction FCAV-UNESP, Jaboticabal, São Paulo Department of Pharmacology IBB-UNESP, Botucatu, Sao Paulo Department of Animal Breeding and Nutrition FMVZ-UNESP, Botucatu, São Paulo Department of Animal Reproduction FCAV-UNESP, Jaboticabal, São Paulo Department of Pharmacology IBB-UNESP, Botucatu, Sao Paulo Department of Animal Breeding and Nutrition FMVZ-UNESP, Botucatu, São Paulo

The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. DOI: http://dx.doi.org/10.7554/eLife.15460.001

Methoprene-tolerant protein (MET) is a key mediator of antimetamorphic signaling in insects. MET belongs to the family of bHLH-PAS transcription factors which regulate gene expression and determine essential physiological and developmental processes. The ability of many bHLH-PAS proteins to carry out their functions is related to the patterns of intracellular trafficking, which are determined by specific sequences and indicate that a nuclear localization signal (NLS) or a nuclear export signal (NES) is present and active. Therefore, the identification of NLS and NES signals is fundamental in order to understand the intracellular signaling role of MET. Nevertheless, data on the intracellular trafficking of MET are inconsistent, and until now there hasn’t been any data on potential NLS and NES sequences. To analyze the trafficking of MET we designed a number of expression vectors encoding full-length MET, as well as various derivatives, that were fused to yellow fluorescent protein (YFP). Confocal microscopy analysis of the subcellular distribution of YFP–MET indicated that while this protein was localized mainly in the nucleus, it was also observed in the cytoplasm. This suggested the presence of both an NLS and NES in MET. Our work has shown that each of the two PAS domains of MET (PAS-A and PAS-B, respectively) contain one NLS and one NES sequence. Additional NES activity was present in the C-terminal fragment. The NLS activity located in PAS-B was dependent on the presence of juvenile hormone (JH), the potential ligand for MET. In contrast to this, JH didn’t seem to be required for the NLS in PAS-A to be active. However, on the basis of current knowledge about the function of PAS-A in other bHLH-PAS proteins, we suggest there might be other proteins that control the activity of the NLS and possibly the NES located in the PAS-A of MET. Thus, the intracellular trafficking of MET seems to be regulated by a rather complicated network of different factors.

Homeodomain proteins are crucial transcription factors for cell differentiation, cell proliferation and organ development. Interestingly, their homeodomain signature structure is important for both their DNA-binding and their nucleocytoplasmic trafficking. The accurate nucleocytoplasmic distribution of these proteins is essential for their functions. We summarize information on (a) the roles of karyopherins for import and export of homeoproteins, (b) the regulation of their nuclear transport during development, and (c) the corresponding complexity of homeoprotein nucleocytoplasmic transport signals. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import.

The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38MAPK, extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38MAPK, ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phosphomimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38MAPK, ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser-115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5. Electronic supplementary material The online version of this article (doi:10.1007/s00018-010-0496-2) contains supplementary material, which is available to authorized users.

P68 RNA helicase is a prototypical DEAD box RNA helicase. The protein plays a very important role in early organ development and maturation. In consistence with the function of the protein in transcriptional regulation and pre-mRNA splicing, p68 was found to predominately localize in the cell nucleus. However, recent experiments demonstrate a transient cytoplasmic localization of the protein. We report here that p68 shuttles between the nucleus and the cytoplasm. The nucleocytoplasmic shuttling of p68 is mediated by two nuclear localization signal (NLS) and two nuclear exporting signal (NES) sequence elements. Our experiments reveal that p68 shuttles via a classical RanGTPase dependent pathway.

The matrix protein M1, the organizer of assembly of influenza virus, interacts with other virus components and with cellular membranes. It has been proposed that M1 binding to lipids is mediated by its polybasic region, but this could hitherto not been investigated in vivo since M1 accumulates in the nucleus of transfected cells. We have equipped M1 with nuclear export signals and showed that the constructs are bound to cellular membranes. Exchange of the complete polybasic region and of further hydrophobic amino acids in its vicinity did not prevent association of M1 with membranes. We therefore suppose that M1 probably interacts with membranes via multiple binding sites.

Recent studies have demonstrated nuclear export by papillomavirus E1 proteins, but the requisite export sequence(s) for bovine papillomavirus (BPV) E1 were not defined. In this report we identify three functional nuclear export sequences (NES) present in BPV E1, with NES2 being the strongest in reporter assays. Nuclear localization of BPV1 E1 was modulated by over- or under-expression of CRM1, the major cellular exportin, and export was strongly reduced by the CRM1 inhibitor, Leptomycin B, indicating that E1 export occurs primarily through a CRM1-dependent process. Consistent with the in vivo functional results, E1 bound CRM1 in an in vitro pull-down assay. In addition, sumoylated E1 bound CRM1 more effectively than unmodified E1, suggesting that E1 export may be regulated by SUMO modification. Lastly, an E1 NES2 mutant accumulated in the nucleus to a greater extent than wild-type E1, yet was defective for viral origin replication in vivo. However, NES2 exhibited no intrinsic replication defect in an in vitro replication assay, implying that nucleocytoplasmic shuttling may be required to maintain E1 in a replication competent state.

International audience; beta-arrestins (beta-arrs), two ubiquitous proteins involved in serpentine heptahelical receptor regulation and signaling, form constitutive homo- and heterooligomers stabilized by inositol 1,2,3,4,5,6-hexakisphosphate (IP6). Monomeric beta-arrs are believed to interact with receptors after agonist activation, and therefore, beta-arr oligomers have been proposed to represent a resting biologically inactive state. In contrast to this, we report here that the interaction with and subsequent titration out of the nucleus of the protooncogene Mdm2 specifically require beta-arr2 oligomers together with the previously characterized nucleocytoplasmic shuttling of beta-arr2. Mutation of the IP6-binding sites impair oligomerization, reduce interaction with Mdm2, and inhibit p53-dependent antiproliferative effects of beta-arr2, whereas the competence for receptor regulation and signaling is maintained. These observations suggest that the intracellular concentration of beta-arr2 oligomers might control cell survival and proliferation.

El diseño curricular de la Nueva Escuela Secundaria (NES) de Buenos Aires (Argentina) sugiere la difícil tarea de que los docentes integren el discurso con la gramática. La dificultad radica en que los enfoques predominantes siempre fueron los modelos estructuralistas, que consideran la lengua como un conjunto inmanente de reglas invariables. En contraste, el Enfoque Cognitivo Prototípico (ECP) sostiene que la Gramática emerge del discurso como un conjunto de rutinas constantemente renegociadas en el habla. El objetivo del presente trabajo es demostrar que el ECP permite la conciliación de gramática y discurso. Para ello, tomamos una prueba sobre el concepto de "sustantivo" a dos cursos de primer año (nivel secundario): un curso resolvió consignas confeccionadas desde la Gramática estructuralista, mientras que el otro resolvió consignas hechas desde el ECP. Los resultados demuestran que los alumnos que aprendieron el tema mediante el ECP lograron una mejor comprensión que el otro grupo. Fil: Funes, María Soledad. Universidad de Buenos Aires. Facultad de Filosofía y Letras; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Poggio, Anabella Laura. Universidad de Buenos Aires. Facultad de Filosofía y Letras; Argentina

International audience; Targeted energy transfer between a main oscillator with a set of parallel Saint-Venant elements and a nonlinear energy sink with a general nonlinear and odd potential function around 1:1 resonance is studied. The complexified system has been investigated at fast and slow time scales by detecting its invariant manifold, equilibrium and singular points, which can explain bifurcation(s) and different regimes of the system. Then, we introduce an example which treats vibratory energy exchanges between a main oscillator with two parallel Saint-Venant elements and a coupled cubic nonlinear energy sink. Finally, analytical predictions are compared with results obtained by numerical integrations of system equations.

International audience; Recently, it has been demonstrated that a vibro-impact type nonlinear energy sink (VI-NES) can be used efficiently to mitigate vibration of a linear oscillator (LO) under transient loading. The objective of this paper is to investigate theoretically and experimentally the potential of a VI-NES to mitigate vibrations of a LO subjected to a harmonic excitation (nevertheless, the presentation of an optimal VI-NES is beyond the scope of this paper). Due to the small mass ratio between the LO and the flying mass of the NES, the obtained equation of motion are analyzed using the method of multiple scales in the case of 1 : 1 resonance. It is shown that in addition to periodic response, system with VI-NES can exhibit strongly modulated response (SMR). Experimentally, the whole system is embedded on an electrodynamic shaker. The VI-NES is realized with a ball which is free to move in a cavity with a predesigned gap. The mass of the ball is less than 1% of the mass of the LO. The experiment confirms the existence of periodic and SMR response regimes. A good agreement between theoretical and experimental results is observed.

Colloque avec actes et comité de lecture. Internationale.; International audience; Ce travail s'intéresse à la problématique du contrôle des oscillations libres horizontales d'un câble par un amortisseur à non linéarité cubique. Il retrace une démarche complète : l'analyse du comportement du système réel initial à contrôler, le dimensionnement théorique de l'amortisseur, les essais de mise en évidence du bon fonctionnement du prototype et de ses différents comportements. Il s'agit également de tester la robustesse du dispositif en faisant varier la rigidité du couplage.

CRM1 is a highly conserved, RanGTPase-driven exportin that carries proteins and RNPs from the nucleus to the cytoplasm. We now explored the cargo-spectrum of CRM1 in depth and identified surprisingly large numbers, namely >700 export substrates from the yeast S. cerevisiae, ≈1000 from Xenopus oocytes and >1050 from human cells. In addition, we quantified the partitioning of ≈5000 unique proteins between nucleus and cytoplasm of Xenopus oocytes. The data suggest new CRM1 functions in spatial control of vesicle coat-assembly, centrosomes, autophagy, peroxisome biogenesis, cytoskeleton, ribosome maturation, translation, mRNA degradation, and more generally in precluding a potentially detrimental action of cytoplasmic pathways within the nuclear interior. There are also numerous new instances where CRM1 appears to act in regulatory circuits. Altogether, our dataset allows unprecedented insights into the nucleocytoplasmic organisation of eukaryotic cells, into the contributions of an exceedingly promiscuous exportin and it provides a new basis for NES prediction. DOI: http://dx.doi.org/10.7554/eLife.11466.001, eLife digest Animals, plants and other eukaryotic organisms subdivide their cells into compartments that carry out specific tasks. For example, the cell nucleus hosts the genome and handles the genetic information, whereas the surrounding cytoplasm is specialized in making proteins. These proteins are then either used in the cytoplasm or transported to the nucleus and other cell compartments. Since proteins are not made in the nucleus, all proteins in this compartment must be imported from the cytoplasm. Two layers of membrane separate the nucleus and cytoplasm from each other. Any exchange of material must therefore proceed through channels called nuclear pore complexes, or NPCs for short. The NPCs have filters that allow only small molecules a free transit, while larger ones are typically rejected. However, larger proteins may also rapidly pass through the nuclear pore complexes if loaded onto dedicated shuttle molecules; for example, “exportins” transport proteins out of the nucleus. Kırlı, Karaca et al. used an approach called proteomics to measure the levels of 5,000 different proteins within the nucleus and the cytoplasm. Such a census helps to predict where a given protein works and where it might cause problems. Further experiments also used proteomics to identify which proteins are carried by an exportin called CRM1. This revealed that a remarkably large number of different proteins (around 1,000) are exported by CRM1 from either yeast, human or frog cell nuclei. Most of these “cargo” proteins were previously thought to never leave the cytoplasm. It now seems, however, that these proteins can leak into the nucleus, but CRM1 recognizes them as cytoplasmic proteins and expels them from the nucleus. These findings suggest that the border control at NPCs is less perfect than was previously believed. If not remedied, this would pose a serious problem for the cell, because the accumulation of "wrong" proteins inside the nucleus would disturb the processes that occur there and could destabilize the genome. Kırlı, Karaca et al. propose that the export of such accidentally displaced proteins by CRM1 is a crucial measure to protect the nucleus. DOI: http://dx.doi.org/10.7554/eLife.11466.002

En la línea de investigación que relaciona la actividad emprendedora con el desarrollo económico, este trabajo tiene como objetivo analizar la relación entre las condiciones del entorno emprendedor con las distintas etapas de desarrollo económico de los países. Para su realización se han utilizado los datos procedentes de la encuesta a los expertos (NES) del proyecto GEM de los 67 países que han participado en la edición de 2013. Los resultados obtenidos confirman la existencia de relación entre las condiciones del entorno emprendedor y distintas etapas de desarrollo económico de los países. La principal aportación del trabajo es la caracterización de un patrón de condiciones del entorno emprendedor de cada grupo de países, según su etapa de desarrollo. In the line of research linking entrepreneurship to economic development, this paper aims to analyze the relationship between entrepreneurial framework conditions with different stages of economic development of countries. To do it data from the national experts survey (NES) of the GEM project of the 67 countries participating in the edition of 2013 has been used. The results confirm the existence of relationship between entrepreneurial framework conditions and different stages of economic development of countries. The main contribution of this paper is the creation of a pattern entrepreneurial framework conditions for each group of countries according to their stage of development.

This article analyzes the relationship between exports and output using econometric multivariate time series techniques (the Johansen cointegration test and Granger causality analysis). Using an error-correction model estimate, the authors show the long-term relationship between Mexico s exports and gdp as well as the causality between these variables. This makes it possible to elucidate the kind of trade the country carries out, one of the causes of its low growth over the last three decades. En el presente artículo se analiza la relación entre las exportaciones y el producto, mediante técnicas econométricas de series de tiempo multivariadas (prueba de cointegración de Johansen y análisis de causalidad de Granger). A través de la estimación de un modelo de corrección de error, se muestra la relación de largo plazo que existe entre las exportaciones y el pib de México, así como la causalidad entre dichas variables. De esta forma, es posible dilucidar el tipo de comercio que el país ejerce, una de las causas de su bajo crecimiento durante las últimas tres décadas.

The 1998 reauthorization of the Higher Education Act requires states to report annually to the U.S. Department of Education the number of prospective teachers at each of their teacher training institutions who pass the state’s tests for licensure. However, the law left decisions on what licensure tests to require, what to assess on them, and their passing scores up to each state. This paper provides an analysis of the descriptions of the subject tests assessing reading instructional knowledge that prospective elementary teachers in this country take for licensure: those offered by Educational Testing Service, a variety of those provided by National Evaluation Systems, and the one offered by American Board for Certification of Teacher Excellence. I examined these descriptions to determine whether the tests appear to address three major components of a research-based approach to reading pedagogy (instruction in phonemic awareness, phonics, and vocabulary knowledge), the weights attached to knowledge of these three components, and the quality of the sample questions they provide. In order to estimate the percentage of test items addressing these three components on each test, I drew on information on the websites of the three major organizations that develop teacher tests as well as of the states that have contracts with NES. To judge by the topics mentioned in the profile for the tests that states require for elementary licensure and the weights attached to the sections of the test containing these topics, most of ETS’s tests devote a tiny proportion of their content to these three components. These tests are used by over 35 states for licensure. The profiles of the tests developed by NES for its client states for elementary licensure range from some that are similar to the ETS tests to some that substantially address these three components. I also analyzed the profiles of the tests required for licensure as a reading teacher, reading specialist, early childhood teacher, or special education teacher. This extended analysis was undertaken to determine the extent to which professional preparation programs may be accountable for teaching these four other groups of educators what they need to know to support or supplement the reading pedagogy provided by elementary classroom teachers. To judge by the online information provided by the testing companies, tests for licensing reading teachers and reading specialists range from a few NES tests that seem to assess these components fully to other NES and ETS tests that seem to address them quite meagerly. Alarmingly, the tests most states require for licensing special education and early childhood teachers do not address these components at all. In addition, ETS offers a set of pedagogical tests of “principles of teaching and learning,” required by many states for the initial license of all teachers in addition to a subject test, that, to judge from its sample questions, seems to denigrate non-constructivist approaches to pedagogy. The findings of this study suggest that even a drastic revision of currently deficient licensure tests for prospective elementary teachers to ensure they are taught a research-based approach to reading pedagogy will not be sufficient to guarantee the use of such an approach. What is needed is systematic revision of all licensure tests for those who teach children or who supervise or supplement the work of those who do to make sure that they all promote a research-based approach to reading pedagogy.