ResearchFlow: Understanding the Knowledge Flow between Academia and Industry

Understanding, monitoring, and predicting the flow of knowledge between academia and industry is of critical importance for a variety of stakeholders, including governments, funding bodies, researchers, investors, and companies. To this purpose, we introduce ResearchFlow, an approach that integrates semantic technologies and machine learning to quantifying the diachronic behaviour of research topics across academia and industry. ResearchFlow exploits the novel Academia/Industry DynAmics (AIDA) Knowledge Graph in order to characterize each topic according to the frequency in time of the related i) publications from academia, ii) publications from industry, iii) patents from academia, and iv) patents from industry. This representation is then used to produce several analytics regarding the academia/industry knowledge flow and to forecast the impact of research topics on industry. We applied ResearchFlow to a dataset of 3.5M papers and 2M patents in Computer Science and highlighted several interesting patterns. We found that 89.8% of the topics first emerge in academic publications, which typically precede industrial publications by about 5.6 years and industrial patents by about 6.6 years. However this does not mean that academia always dictates the research agenda. In fact, our analysis also shows that industrial trends tend to influence academia more than academic trends affect industry. We evaluated ResearchFlow on the task of forecasting the impact of research topics on the industrial sector and found that its granular characterization of topics improves significantly the performance with respect to alternative solutions

Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron-haem enzyme

C–H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C–H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor

Modeling vascular inflammation and atherogenicity after inhalation of ambient levels of ozone: exploratory lessons from transcriptomics

BackgroundEpidemiologic studies have linked inhalation of air pollutants such as ozone to cardiovascular mortality. Human exposure studies have shown that inhalation of ambient levels of ozone causes airway and systemic inflammation and an imbalance in sympathetic/parasympathetic tone.MethodsTo explore molecular mechanisms through which ozone inhalation contributes to cardiovascular mortality, we compared transcriptomics data previously obtained from bronchoalveolar lavage (BAL) cells obtained from healthy subjects after inhalational exposure to ozone (200 ppb for 4 h) to those of various cell samples from 11 published studies of patients with atherosclerotic disease using the Nextbio genomic data platform. Overlapping gene ontologies that may be involved in the transition from pulmonary to systemic vascular inflammation after ozone inhalation were explored. Local and systemic enzymatic activity of an overlapping upregulated gene, matrix metalloproteinase-9 (MMP-9), was measured by zymography after ozone exposure.ResultsA set of differentially expressed genes involved in response to stimulus, stress, and wounding were in common between the ozone and most of the atherosclerosis studies. Many of these genes contribute to biological processes such as cholesterol metabolism dysfunction, increased monocyte adherence, endothelial cell lesions, and matrix remodeling, and to diseases such as heart failure, ischemia, and atherosclerotic occlusive disease. Inhalation of ozone increased MMP-9 enzymatic activity in both BAL fluid and serum.ConclusionsComparison of transcriptomics between BAL cells after ozone exposure and various cell types from patients with atherosclerotic disease reveals commonly regulated processes and potential mechanisms by which ozone inhalation may contribute to progression of pre-existent atherosclerotic lesions

Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway.

Reactive oxygen species (ROS) are generated by virus-infected cells; however, the physiological importance of ROS generated under these conditions is unclear. Here we found that the inflammation and cell death induced by exposure of mice or cells to sources of ROS were not altered in the absence of canonical ROS-sensing pathways or known cell-death pathways. ROS-induced cell-death signaling involved interactions among the cellular ROS sensor and antioxidant factor KEAP1, the phosphatase PGAM5 and the proapoptotic factor AIFM1. Pgam5(-/-) mice showed exacerbated lung inflammation and proinflammatory cytokines in an ozone-exposure model. Similarly, challenge with influenza A virus led to increased infiltration of the virus, lymphocytic bronchiolitis and reduced survival of Pgam5(-/-) mice. This pathway, which we have called 'oxeiptosis', was a ROS-sensitive, caspase independent, non-inflammatory cell-death pathway and was important for protection against inflammation induced by ROS or ROS-generating agents such as viral pathogens

Biochemical Establishment and Characterization of EncM’s Flavin-N5-oxide Cofactor

The ubiquitous flavin-dependent monooxygenases commonly catalyze oxygenation reactions by means of a transient C4a–peroxyflavin. A recent study, however, suggested an unprecedented flavin-oxygenating species, proposed as the flavin-N5-oxide (Fl_N5[O]), as key to an oxidative Favorskii-type rearrangement in the biosynthesis of the bacterial polyketide antibiotic enterocin. This stable superoxidized flavin is covalently tethered to the enzyme EncM and converted into FADH₂ (Fl_red) during substrate turnover. Subsequent reaction of Fl_red with molecular oxygen restores the postulated Fl_N5[O] via an unknown pathway. Here, we provide direct evidence for the Fl_N5[O] species via isotope labeling, proteolytic digestion, and high-resolution tandem mass spectrometry of EncM. We propose that formation of this species occurs by hydrogen-transfer from Fl_red to molecular oxygen, allowing radical coupling of the formed protonated superoxide and anionic flavin semiquinone at N5, before elimination of water affords the Fl_N5[O] cofactor. Further biochemical and spectroscopic investigations reveal important features of the Fl_N5[O] species and the EncM catalytic mechanism. We speculate that flavin-N5-oxides may be intermediates or catalytically active species in other flavoproteins that form the anionic semiquinone and promote access of oxygen to N5