904 research outputs found

    Actor-Critic Sequence Training for Image Captioning.

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    Generating natural language descriptions of images is an important capability for a robot or other visual-intelligence driven AI agent that may need to communicate with human users about what it is seeing. Such image captioning methods are typically trained by maximising the likelihood of ground-truth annotated caption given the image. While simple and easy to implement, this approach does not directly maximise the language quality metrics we care about such as CIDEr. In this paper we investigate training image captioning methods based on actor-critic reinforcement learning in order to directly optimise non-differentiable quality metrics of interest. By formulating a per-token advantage and value computation strategy in this novel reinforcement learning based captioning model, we show that it is possible to achieve the state of the art performance on the widely used MSCOCO benchmark

    Turnover During a Corporate Merger: How Workplace Network Change Influences Staying

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    This is the author accepted manuscript. The final version is available from the American Psychological Association via the DOI in this recordThe upheaval created by a merger can precipitate voluntary employee turnover, causing merging organizations to lose valuable knowledge-based resources and competencies precisely when they are needed most to achieve the merger’s integration goals. While prior research has shown that employees' connections to coworkers reduces their likelihood of leaving, we know little about how personal social networks should change to increase the likelihood of staying through the disruptive post-merger integration period. In a pre-post study of social network change, we investigate over fifteen million email communications between employees within two large merging consumer goods firms over two years. We use insights from network activation theory to posit and find that employees with high formal power (rank) and high informal status (indegree centrality) react to the merger's general uncertainty and threat by developing new social connections in a manner indicative of a network widening response: reaching out and connecting with those in the counterpart legacy organization. We also investigate whether increased personally-felt threat in the form of merger-related job insecurity strengthens these relationships, finding it does in the case of high formal power. We also find that employees increasing their cross-legacy social connections is key in reducing those employees' turnover after a merger. Our study suggests that network activation theory can be extended to explain network changes and not simply network cognition

    The highly rearranged mitochondrial genomes of the crabs Maja crispata and Maja squinado (Majidae) and gene order evolution in Brachyura

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    Abstract We sequenced the mitochondrial genomes of the spider crabs Maja crispata and Maja squinado (Majidae, Brachyura). Both genomes contain the whole set of 37 genes characteristic of Bilaterian genomes, encoded on both \u3b1- and \u3b2-strands. Both species exhibit the same gene order, which is unique among known animal genomes. In particular, all the genes located on the \u3b2-strand form a single block. This gene order was analysed together with the other nine gene orders known for the Brachyura. Our study confirms that the most widespread gene order (BraGO) represents the plesiomorphic condition for Brachyura and was established at the onset of this clade. All other gene orders are the result of transformational pathways originating from BraGO. The different gene orders exhibit variable levels of genes rearrangements, which involve only tRNAs or all types of genes. Local homoplastic arrangements were identified, while complete gene orders remain unique and represent signatures that can have a diagnostic value. Brachyura appear to be a hot-spot of gene order diversity within the phylum Arthropoda. Our analysis, allowed to track, for the first time, the fully evolutionary pathways producing the Brachyuran gene orders. This goal was achieved by coupling sophisticated bioinformatic tools with phylogenetic analysis

    The Characteristics of Seebeck Coefficient in Silicon Nanowires Manufactured by CMOS Compatible Process

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    Silicon nanowires are patterned down to 30 nm using complementary metal-oxide-semiconductor (CMOS) compatible process. The electrical conductivities of n-/p-leg nanowires are extracted with the variation of width. Using this structure, Seebeck coefficients are measured. The obtained maximum Seebeck coefficient values are 122 ΞΌV/K for p-leg and βˆ’94 ΞΌV/K for n-leg. The maximum attainable power factor is 0.74 mW/m K2 at room temperature

    Intertwined Ξ±Ξ² Spectrin Meeting Helical Actin Protofilament in the Erythrocyte Membrane Skeleton: Wrap-Around vs. Point-Attachment

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    Our 3-D model for a junctional complex (JC) in the erythrocyte membrane skeleton proposed that the helical actin protofilament functions as a mechanical axis for three pairs of Ξ±Ξ² spectrin (Sp), and each pair wraps around the protofilament in a back-to-back fashion. The distal end of each Sp is further associated with the lipid bilayer by a suspension complex (SC). Here, we detail how splitting and rejoining of Ξ±Ξ² Sp around a protofilament may form a loop that sustains and equilibrates tension. Sequential association of Ξ² and Ξ± Sp solves the challenge of constructing multiple loops along the protofilament, and topological connection facilitates their re-association. The wrap-around model minimizes the strain of the actin binding site on Ξ² Sp due to tension, redirection, or sliding of intertwined Sp. Pairing Sp balances the opposing forces and provides a mechanism for elastic recovery. The wrap-around junction thus provides mechanical advantages over a point-attachment junction in maintaining the integrity and functionality of the network. Severing Ξ± or Ξ² Sp may convert a wrapping-around junction to a point-attachment junction. In that case, a β€œbow up” motion of JC during deformation may disturb or flip the overlaid lipid bilayer, and mark stressed erythrocytes for phagocytosis

    Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

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    Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies

    LEDGF1-326 Decreases P23H and Wild Type Rhodopsin Aggregates and P23H Rhodopsin Mediated Cell Damage in Human Retinal Pigment Epithelial Cells

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    P23H rhodopsin, a mutant rhodopsin, is known to aggregate and cause retinal degeneration. However, its effects on retinal pigment epithelial (RPE) cells are unknown. The purpose of this study was to determine the effect of P23H rhodopsin in RPE cells and further assess whether LEDGF(1-326), a protein devoid of heat shock elements of LEDGF, a cell survival factor, reduces P23H rhodopsin aggregates and any associated cellular damage.ARPE-19 cells were transiently transfected/cotransfected with pLEDGF(1-326) and/or pWT-Rho (wild type)/pP23H-Rho. Rhodopsin mediated cellular damage and rescue by LEDGF(1-326) was assessed using cell viability, cell proliferation, and confocal microscopy assays. Rhodopsin monomers, oligomers, and their reduction in the presence of LEDGF(1-326) were quantified by western blot analysis. P23H rhodopsin mRNA levels in the presence and absence of LEDGF(1-326) was determined by real time quantitative PCR.P23H rhodopsin reduced RPE cell viability and cell proliferation in a dose dependent manner, and disrupted the nuclear material. LEDGF(1-326) did not alter P23H rhodopsin mRNA levels, reduced its oligomers, and significantly increased RPE cell viability as well as proliferation, while reducing nuclear damage. WT rhodopsin formed oligomers, although to a smaller extent than P23H rhodopsin. Further, LEDGF(1-326) decreased WT rhodopsin aggregates.P23H rhodopsin as well as WT rhodopsin form aggregates in RPE cells and LEDGF(1-326) decreases these aggregates. Further, LEDGF(1-326) reduces the RPE cell damage caused by P23H rhodopsin. LEDGF(1-326) might be useful in treating cellular damage associated with protein aggregation diseases such as retinitis pigmentosa

    Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniae

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    Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniaeThe contribution of specific factors to bacterial virulence is generally investigated through creation of genetic "knockouts" that are then compared to wild-type strains or complemented mutants. This paradigm is useful to understand the effect of presence vs. absence of a specific gene product but cannot account for concentration-dependent effects, such as may occur with some bacterial toxins. In order to assess threshold and dose-response effects of virulence factors, robust systems for tunable expression are required. Recent evidence suggests that the folding free energy (?G) of the 5' end of mRNA transcripts can have a significant effect on translation efficiency and overall protein abundance. Here we demonstrate that rational alteration of 5' mRNA folding free energy by introduction of synonymous mutations allows for predictable changes in pneumolysin (PLY) expression by Streptococcus pneumoniae without the need for chemical inducers or heterologous promoters. We created a panel of isogenic S. pneumoniae strains, differing only in synonymous (silent) mutations at the 5' end of the PLY mRNA that are predicted to alter ?G. Such manipulation allows rheostat-like control of PLY production and alters the cytotoxicity of whole S. pneumoniae on primary and immortalized human cells. These studies provide proof-of-principle for further investigation of mRNA ?G manipulation as a tool in studies of bacterial pathogenesis.National Institutes of Health (www.nih.gov) (R01 AI092743 and R21 AI111020 to A.J.R.). F.E.A. was supported by the Portuguese Foundation for Science and Technology (www.fct.pt) SFRH/BD/33901/2009 and the Luso-American Development Foundation (www.flad.pt). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    F-Actin-Dependent Regulation of NESH Dynamics in Rat Hippocampal Neurons

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    Synaptic plasticity is an important feature of neurons essential for learning and memory. Postsynaptic organization and composition are dynamically remodeled in response to diverse synaptic inputs during synaptic plasticity. During this process, the dynamics and localization of postsynaptic proteins are also precisely regulated. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family. Overexpression of NESH is associated with reduced cell motility and tumor metastasis. Strong evidence of a close relationship between NESH and the actin cytoskeleton has been documented. Although earlier studies have shown that NESH is prominently expressed in the brain, its function and characteristics are yet to be established. Data from the present investigation suggest that synaptic localization of NESH in hippocampal neurons is regulated in an F-actin-dependent manner. The dynamic fraction of NESH in the dendritic spine was analyzed using FRAP (fluorescence recovery after photobleaching). Interestingly, F-actin stabilization and disruption significantly affected the mobile fraction of NESH, possibly through altered interactions of NESH with the F-actin. In addition, NESH was synaptically targeted from the dendritic shaft to spine after induction of chemical LTP (long-term potentiation) and the translocation was dependent on F-actin. Our data collectively support the significance of the F-actin cytoskeleton in synaptic targeting of NESH as well as its dynamics
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