333 research outputs found

    The Good and Bad of Ambidexterity: In Which Domains Should Firms Be Ambidextrous or Not to Foster Innovativeness?

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    Because it is difficult and costly for firms to practice exploration and exploitation simultaneously in their new product development, managers need to know when investing in ambidexterity is beneficial for their firm’s innovativeness and when it is not. To date, research has remained undecided about the performance implications of striving for the joint implementation of exploration and exploitation. To address this persistent debate, the current study develops a new conceptualization that distinguishes two forms of ambidexterity, with contrasting effects on innovativeness. Drawing on dynamic capabilities theory, this study proposes that market-based ambidexterity benefits companies’ innovativeness, whereas product-based ambidexterity harms it. The empirical results, obtained from longitudinal data gathered from 229 executives in multiple industries, confirm these theorized effects of the two forms of ambidexterity on product program innovativeness, which in turn increases firm performance. These findings help explain the varying effects of ambidexterity in prior research and offer important managerial and decision-making implications

    Frontline employees’ innovative service behavior as key to customer loyalty:insights into FLEs’ resource gain spiral

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    Many service firms require frontline service employees (FLEs) to follow routines and standardized operating procedures during the service encounter, to deliver consistently high service standards. However, to create superior, pleasurable experiences for customers, featuring both helpful services and novel approaches to meeting their needs, firms in various sectors also have begun to encourage FLEs to engage in more innovative service behaviors. This study therefore investigates a new and complementary route to customer loyalty, beyond the conventional service-profit chain, that moves through FLEs' innovative service behavior. Drawing on conservation of resources (COR) theory, this study introduces a resource gain spiral at the service encounter, which runs from FLEs' emotional job engagement to innovative service behavior, and then leads to customer delight and finally customer loyalty. In accordance with COR theory, the proposed model also includes factors that might hinder (customer aggression, underemployment) or foster (colleague support, supervisor support) FLEs' resource gain spiral. A multilevel analysis of a large-scale, dyadic data set that contains responses from both FLEs and customers in multiple industries strongly supports the proposed resource gain spiral as a complementary route to customer loyalty. The positive emotional job engagement-innovative service behavior relationship is undermined by customer aggression and underemployment, as hypothesized. Surprisingly though, and contrary to the hypotheses, colleague and supervisor support do not seem to foster FLEs' resource gain spiral. Instead, colleague support weakens the engagement-innovative service behavior relationship, and supervisor support does not affect it. These results indicate that if FLEs can solicit resources from other sources, they may not need to invest as many of their individual resources. In particular, colleague support even appears to serve as a substitute for FLEs' individual resource investments in the resource gain spiral

    A Deep Photometric Look at Two of Andromeda's Dwarf Spheroidals: X and XVII

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    We use deep wide-field photometry from the Large Binocular Camera to study the stellar and structural properties of the recently discovered Andromeda X and Andromeda XVII (And X and And XVII) dwarf galaxies. Using the mean apparent magnitude of the horizontal branch (HB), we derive distances of 621 +- 20 kpc to And X and 734+- 23 kpc to And XVII, closer by >60 kpc than the previous estimates which were based on red giant branch (RGB) observations. Thus our results warrant against the use of the RGB tip method for determining distances to systems with sparsely populated RGBs, and show how crucial HB observations are in obtaining accurate distances in systems such as these. We find that And X is a relatively faint (MV = -7.36), highly elongated (e = 0.48) system at a distance of 174 +- 62 kpc from Andromeda. And XVII is brighter (MV = -8.61) with an M31-centric distance of 73 kpc which makes it one of the closest satellites to Andromeda. Both galaxies are metal-poor: we derive =-2.2 for And X, while And XVII shows = -2.0, consistent with the relation of higher luminosity dwarfs being more metal- rich. Additionally, both galaxies show considerable intrinsic spreads in metallicity (0.2 and 0.3 dex for And X and And XVII respectively), consistent with multiple stellar populations.Comment: 8 pages, 6 figure

    Network asynchrony underlying increased broadband gamma power

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    Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression of cortical γ rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband γ power in the local field potential. Increased baseline broadband γ is also a prominent characteristic in schizophrenia and a hallmark of network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced broadband γ is a true rhythm, and if so, whether rhythmic PV inhibition is involved or not, is debated. Asynchronous and increased firing activities are thought to contribute to broadband power increases spanning the γ band. Using male and female mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that neuronal activity with decreased synchronicity is associated with increased prefrontal broadband γ power. Specifically, reduced spike time precision and spectral leakage of spiking activity because of higher firing rates (spike “contamination”) affect the broadband γ band. Desynchronization was evident at multiple time scales, with reduced spike entrainment to the local field potential, reduced cross-frequency coupling, and frag- mentation of brain states. Local application of S(1)-ketamine in (control) mice with intact NMDAR activity in PV neurons triggered network desynchronization and enhanced broadband γ power. However, our investigations suggest that disparate mechanisms underlie increased broadband γ power caused by genetic alteration of PV interneurons and ketamine-induced power increases in broadband c. Our study confirms that enhanced broadband γ power can arise from asynchronous activ- ities and demonstrates that long-term deficiency of PV inhibition can be a contributor.ERCSTINT Program Joint Brazilian-Swedish Research Collaboration GrantCAPES-STINT Program GrantKnut and Alice Wallenberg FoundationSwedish Research CouncilKarolinska InstitutetAccepte

    Adult trkB signaling in parvalbumin interneurons is essential to prefrontal network dynamics

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    Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of c oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.ERCSwedish Research CouncilCAPES-STINT Program GrantKarolinska InstitutetKnut and Alice Wallenberg FoundationSTINT Program Joint Brazilian-Swedish Research Collaboration GrantPublishe

    Modeling the early stage of DNA sequence recognition within RecA nucleoprotein filaments

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    Homologous recombination is a fundamental process enabling the repair of double-strand breaks with a high degree of fidelity. In prokaryotes, it is carried out by RecA nucleofilaments formed on single-stranded DNA (ssDNA). These filaments incorporate genomic sequences that are homologous to the ssDNA and exchange the homologous strands. Due to the highly dynamic character of this process and its rapid propagation along the filament, the sequence recognition and strand exchange mechanism remains unknown at the structural level. The recently published structure of the RecA/DNA filament active for recombination (Chen et al., Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structure, Nature 2008, 453, 489) provides a starting point for new exploration of the system. Here, we investigate the possible geometries of association of the early encounter complex between RecA/ssDNA filament and double-stranded DNA (dsDNA). Due to the huge size of the system and its dense packing, we use a reduced representation for protein and DNA together with state-of-the-art molecular modeling methods, including systematic docking and virtual reality simulations. The results indicate that it is possible for the double-stranded DNA to access the RecA-bound ssDNA while initially retaining its Watson–Crick pairing. They emphasize the importance of RecA L2 loop mobility for both recognition and strand exchange

    Discovery of new companions to high proper motion stars from the VVV Survey

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    Accepted for publication in A&A; 14 pages, 3 figures, 6 tablesWe acknowledge support by the FONDAP Center for Astrophysics 15010003; BASAL CATA Center for Astrophysics and Associated Technologies PFB-06; the Ministry for the Economy, Development, and Tourism’s Programa Iniciativa Científica Milenio through grant P07-021- F, awarded to The Milky Way Millennium Nucleus; FONDECYT grants No. 1090213 and 1110326 from CONICYT, and the European Southern Observatory. J.C.B. acknowledge support from a Ph.D. Fellowship from CONICYT. M.G. is financed by the GEMINI-CONICYT Fund, allocated to the project 32110014. R.K. acknowledges partial support from FONDECYT through grant 1130140. E.L.M. acknowledges support from grant AyA2011- 30147-C03-03; J.B. acknowledge support from FONDECYT No. 1120601; A.N.C. acknowledges support from GEMINI-CONICYT No. 32110005 and from Comitee Mixto ESO-GOBIERNO DE CHILE. J.A.G. acknowledges support from Proyecto Fondecyt Postdoctoral 3130552, Fondecyt Regular 1110326, and Anillos ACT-86

    The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

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    The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

    Understanding the Sequence-Dependence of DNA Groove Dimensions: Implications for DNA Interactions

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    BACKGROUND: The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves. METHODOLOGY/PRINCIPAL FINDINGS: The present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR (31)P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The (31)P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties. CONCLUSIONS/SIGNIFICANCE: The study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions

    Dynamics of Co-Transcriptional Pre-mRNA Folding Influences the Induction of Dystrophin Exon Skipping by Antisense Oligonucleotides

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    Antisense oligonucleotides (AONs) mediated exon skipping offers potential therapy for Duchenne muscular dystrophy. However, the identification of effective AON target sites remains unsatisfactory for lack of a precise method to predict their binding accessibility. This study demonstrates the importance of co-transcriptional pre-mRNA folding in determining the accessibility of AON target sites for AON induction of selective exon skipping in DMD. Because transcription and splicing occur in tandem, AONs must bind to their target sites before splicing factors. Furthermore, co-transcriptional pre-mRNA folding forms transient secondary structures, which redistributes accessible binding sites. In our analysis, to approximate transcription elongation, a “window of analysis” that included the entire targeted exon was shifted one nucleotide at a time along the pre-mRNA. Possible co-transcriptional secondary structures were predicted using the sequence in each step of transcriptional analysis. A nucleotide was considered “engaged” if it formed a complementary base pairing in all predicted secondary structures of a particular step. Correlation of frequency and localisation of engaged nucleotides in AON target sites accounted for the performance (efficacy and efficiency) of 94% of 176 previously reported AONs. Four novel insights are inferred: (1) the lowest frequencies of engaged nucleotides are associated with the most efficient AONs; (2) engaged nucleotides at 3′ or 5′ ends of the target site attenuate AON performance more than at other sites; (3) the performance of longer AONs is less attenuated by engaged nucleotides at 3′ or 5′ ends of the target site compared to shorter AONs; (4) engaged nucleotides at 3′ end of a short target site attenuates AON efficiency more than at 5′ end
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