38 research outputs found

    The direction of technical change in AI and the trajectory effects of government funding

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    Government funding of innovation can have a significant impact not only on the rate of technical change, but also on its direction. In this paper, we examine the role that government grants and government departments played in the development of artificial intelligence (AI), an emergent general purpose technology with the potential to revolutionize many aspects of the economy and society. We analyze all AI patents filed at the US Patent and Trademark Office and develop network measures that capture each patent’s influence on all possible sequences of follow-on innovation. By identifying the effect of patents on technological trajectories, we are able to account for the long-term cumulative impact of new knowledge that is not captured by standard patent citation measures. We show that patents funded by government grants, but above all patents filed by federal agencies and state departments, profoundly influenced the development of AI. These long-term effects were especially significant in early phases, and weakened over time as private incentives took over. These results are robust to alternative specifications and controlling for endogeneity

    Contaminants from dredged sediments alter the transcriptome of Manila clam and induce shifts in microbiota composition

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    Background The reuse of dredged sediments in ports and lagoons is a big issue as it should not affect the quality and the equilibrium of ecosystems. In the lagoon of Venice, sediment management is of crucial importance as sediments are often utilized to built-up structures necessary to limit erosion. However, the impact of sediment reuse on organisms inhabiting this delicate area is poorly known. The Manila clam is a filter-feeding species of high economic and ecological value for the Venice lagoon experiencing a drastic decline in the last decades. In order to define the molecular mechanisms behind sediment toxicity, we exposed clams to sediments sampled from different sites within one of the Venice lagoon navigable canals close to the industrial area. Moreover, we investigated the impacts of dredged sediments on clam’s microbial communities. Results Concentrations of the trace elements and organic chemicals showed increasing concentrations from the city of Venice to sites close to the industrial area of Porto Marghera, where PCDD/Fs and PCBs concentrations were up to 120 times higher than the southern lagoon. While bioaccumulation of organic contaminants of industrial origin reflected sediments’ chemical concentrations, metal bioaccumulation was not consistent with metal concentrations measured in sediments probably due to the activation of ABC transporters. At the transcriptional level, we found a persistent activation of the mTORC1 signalling pathway, which is central in the coordination of cellular responses to chemical stress. Microbiota characterization showed the over-representation of potential opportunistic pathogens following exposure to the most contaminated sediments, leading to host immune response activation. Despite the limited acquisition of new microbial species from sediments, the latter play an important role in shaping Manila clam microbial communities. Conclusions Sediment management in the Venice lagoon will increase in the next years to maintain and create new canals as well as to allow the operation of the new mobile gates at the three Venice lagoon inlets. Our data reveal important transcriptional and microbial changes of Manila clams after exposure to sediments, therefore reuse of dredged sediments represents a potential risk for the conservation of this species and possibly for other organisms inhabiting the Venice lagoon

    New and atypical combinations: An assessment of novelty and interdisciplinarity

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    Novelty indicators are increasingly important for science policy. This paper challenges the indicators of novelty as an atypical combination of knowledge (Uzzi et al., 2013) and as the first appearance of a knowledge combination (Wang et al., 2017). We exploit a sample of 230,854 articles (1985 - 2005), published on 8 journals of the American Physical Society (APS) and 2.4 million citations to test the indicators using (i) a Configuration Null Model, (ii) an external validation set of articles related to Nobel Prize winning researches and APS Milestones, (iii) a set of established interdisciplinarity indicators, and (iv) the relationship with the articles\u2019 impact. We find that novelty as the first appearance of a knowledge combination captures the key structural properties of the citation network and finds it difficult to tell novel and non-novel articles apart, while novelty as an atypical combination of knowledge overlaps with interdisciplinarity. We suggest that the policy evidence derived from these measures should be reassessed

    Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations

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    Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic spine formation and synaptic stability. Using a Renilla-based sensor, we provide formal proof that inflammatory EVs transfer their miR-146a-5p cargo to neuron. By western blot and immunofluorescence analysis we show that vesicular miR-146a-5p suppresses Syt1 and Nlg1 expression in receiving neurons. Microglia-to-neuron miR-146a-5p transfer and Syt1 and Nlg1 downregulation do not occur when EV\ue2\u80\u93neuron contact is inhibited by cloaking vesicular phosphatidylserine residues and when neurons are exposed to EVs either depleted of miR-146a-5p, produced by pro-regenerative microglia, or storing inactive miR-146a-5p, produced by cells transfected with an anti-miR-146a-5p. Morphological analysis reveals that prolonged exposure to inflammatory EVs leads to significant decrease in dendritic spine density in hippocampal neurons in vivo and in primary culture, which is rescued in vitro by transfection of a miR-insensitive Nlg1 form. Dendritic spine loss is accompanied by a decrease in the density and strength of excitatory synapses, as indicated by reduced mEPSC frequency and amplitude. These findings link inflammatory microglia and enhanced EV production to loss of excitatory synapses, uncovering a previously unrecognized role for microglia-enriched miRNAs, released in association to EVs, in silencing of key synaptic genes

    A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

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    The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control

    The Fragmentation of the Mainstream and Communication in Economics: A View from the Top

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    The decline of Neoclassical dominance has paved the way to a more fragmented Mainstream. In this article, we empirically explore the Mainstream’s thematic structure and its fragmentation’s effects on within-discipline communication. For this purpose, we exploit a dataset containing 10,064 articles published in economics in seven Blue Ribbon Eight journals between 1985 and 2006 and their citations. Articles are assigned to 18 topics created via Latent Dirichlet Allocation to represent specialities within economics. Results show that the economic Mainstream has yet to experience a dramatic increase in fragmentation in the observed period, and the prevailing topics are related to market equilibrium and econometrics. Moreover, the Mainstream’s thematic structure does not include any heterodox approach. Regarding communication, economists increasingly tap into diverse sources of information, and such diversity positively impacts the citational patterns of articles. The same result holds for the articles written by Nobel Prize winners and the most cited articles in the discipline, which exhibit a higher diversity than the whole sample

    Switching behavior in the Italian electricity retail market: Logistic and mixed effect Bayesian estimations of consumer choice

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    The paper highlights the importance of both local effects and market structure in determining the switching decision in retail electricity markets, and also introduces a new definition of household as the bundle of features of its members. We apply a Bayesian mixed Logit model to analyze the switching behavior in the Italian electricity retail market. The data set includes social, demographic, geographic and economic information regarding 18,448 households and 37,217 individuals together with their opinions, expectations and choices regarding national services. Results show that heterogeneity in the geographic and social context of choice and in the household composition has a major impact on the significance and on the identification of switching determinants implying that there is no one-size-fits-all policy to encourage switching and that further efforts should be dedicated to the definition of an optimal scale of analysis

    The interdisciplinarity dilemma. Public versus private interests

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    Researchers often receive contrasting incentives when conducting their work. On the one hand, an interdisciplinary approach is required to produce scientific advances and access to funding. On the other, academic scholarships and evaluation mechanisms are still organized following the criteria of traditional disciplinary fields. If pursuing interdisciplinary research results in contrasting outcomes, science may face an interdisciplinarity dilemma: should researchers pursue their own private interest to build a reputation? Or should they endeavor towards public interest? How costly in terms of reputation is to choose interdisciplinarity research (IDR) over (more) specialized research? We answer these questions by exploiting data on 23,926 articles published by 6,105 researchers affiliated with the University of Florida in the period 2008–2013. Through individual fixed-effect, we compare articles of the same scholar to roll out the influence of individual characteristics on the scientific impact of their research. We find that the diverse dimensions of IDR (Variety, Balance, and Disparity) have a different effect on the reputation of a scholar and on her contribution to societal research. We confirm the existence of trade-off between private and public interest. We also point out that the increase of IDR aiming at connecting distant disciplines reduces the usefulness of the resulting knowledge. Results are robust to various specifications and apply to all scholars, regardless of their gender, collaboration behavior, discipline, and performance. These findings pose challenging questions to policymakers

    64Cu and fluorescein labeled anti-miRNA peptide nucleic acids for the detection of miRNA expression in living cells

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    Abstract MiRNAs are single stranded RNAs of 18–22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (64Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases
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