•We show deep learning to extract features from structured tabular data.•We apply information-fusion-based sensitivity analysis to feature importance.•Deep learning-based features enable more ...accurate classification of trader risk.•Deep learning-based risk management increases profits in our case study.
The paper examines the potential of deep learning to support decisions in financial risk management. We develop a deep learning model for predicting whether individual spread traders secure profits from future trades. This task embodies typical modeling challenges faced in risk and behavior forecasting. Conventional machine learning requires data that is representative of the feature-target relationship and relies on the often costly development, maintenance, and revision of handcrafted features. Consequently, modeling highly variable, heterogeneous patterns such as trader behavior is challenging. Deep learning promises a remedy. Learning hierarchical distributed representations of the data in an automatic manner (e.g. risk taking behavior), it uncovers generative features that determine the target (e.g., trader’s profitability), avoids manual feature engineering, and is more robust toward change (e.g. dynamic market conditions). The results of employing a deep network for operational risk forecasting confirm the feature learning capability of deep learning, provide guidance on designing a suitable network architecture and demonstrate the superiority of deep learning over machine learning and rule-based benchmarks.
Aim
Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely ...insufficient. The aim of this study was to elucidate the microbiota‐driven mechanisms involved in the development of nonalcoholic hepatic steatosis.
Methods and Results
Ob/ob mice and their wild‐type lean control mice were fed an AIN‐93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine‐conjugated BAs compared to their lean controls. The proportions of butyrate‐producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol‐7α‐hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice.
Conclusion
Microbiota‐associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR‐SHP pathway, thereby accelerating fat synthesis.
Significance and Impact of the Study
We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.
Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity ...of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (4-week-old) GCs can efficiently drive distal CA3 targets but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition toward maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus.
1 Centre for Infection, Department of Cellular & Molecular Medicine, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
2 Department of Veterinary Clinical Sciences, Royal ...Veterinary College, University of London, Hawkshead Campus, North Mymms AL9 7TA, UK
Correspondence Jodi A. Lindsay jlindsay{at}sgul.ac.uk
Staphylococcus aureus is a commensal and pathogen of several mammalian species, particularly humans and cattle. We aimed to (i) identify S. aureus genes associated with host specificity, (ii) determine the relatedness of human and animal isolates, and (iii) identify whether human and animal isolates typically exchanged mobile genetic elements encoding virulence and resistance genes. Using a well-validated seven-strain S. aureus microarray, we compared 56 UK S. aureus isolates that caused infection in cows, horses, goats, sheep and a camel with 161 human S. aureus isolates from healthy carriers and community acquired infections in the UK. We had previously shown that human isolates are clustered into ten dominant and a few minor lineages, each with unique combinations of surface proteins predicted to bind to human proteins. We found that the animal-associated S. aureus clustered into ten lineages, with 61 % assigned to four lineages, ST151, ST771, ST130 and ST873, that were unique to animals. The majority of bovine mastitis was caused by isolates of lineage ST151, ST771 and ST97, but a few human lineages also caused mastitis. S. aureus isolated from horses were more likely to cluster into human-associated lineages, with 54 % of horse-associated S. aureus assigned to the human clusters CC1, CC8 and CC22; along with the presence of some multi-drug resistant strains, this suggests a human origin. This is the most comprehensive genetic comparison of human versus animal S. aureus isolates conducted, and because we used a whole-genome approach we could estimate the key genes with the greatest variability that are associated with host specificity. Several genes conserved in all human isolates were variable or missing in one or more animal lineages, including the well-characterized lineage specific genes fnbA, fnbB and coa . Interestingly, genes carried on mobile genetic elements (MGEs) such as chp , scn and sak were less common in animal S. aureus isolates, and bap was not found. There was a lot of MGE variation within lineages, and some evidence that exchange of MGEs such as bacteriophage and pathogenicity islands between animal and human lineages is feasible, but there was less evidence of antibiotic resistance gene transfer on the staphylococcal cassette chromosomes (SCC) or plasmids. Surprisingly, animal lineages are closely related to human lineages and only a handful of genes or gene combinations may be responsible for host specificity.
Abbreviations: CA-MRSA, community-acquired MRSA; CC, clonal complex; CV, core variable; MLST, multi-locus sequence typing; MRSA, meticillin-resistant Staphylococcus aureus ; RVC, Royal Veterinary College; SaPI, S. aureus pathogenicity islands; SCC, staphylococcal cassette chromosome; ST, sequence type; VLA, Veterinary Laboratories Agency; VRE, vancomycin-resistant enterococci; VRSA, vancomycin-resistant S. aureus
Present address: Division of Cell Biology and Imaging, National Institute for Biological Standards and Control, South Mimms EN6 3QG, UK.
Microarray data from this study can be found in µG@Sbase and ArrayExpress, with accession numbers A-BUGS-17 and E-BUGS-62.
A supplementary table with details of the Staphylococcus aureus isolates studied is available with the online version of this paper.
Display omitted
•La2O3-supported Ni, Ni–Fe or Ni–Co catalysts were obtained from perovskite precursors.•Ni–Co was more active and less prone to coke formation than mono-metallic Ni.•Ni–Fe was ...inactive for the dry reforming of methane.•In-situ XRD confirmed that the addition of Co increased the rate of La2O2CO3 formation.•In-situ XRD and electron microscopy confirmed the de-alloying of Ni–Fe and the encapsulation of Ni particles by LaFeO3.
Previous reports, albeit being partially contradictory, have indicated that the alloying of Ni with inexpensive transition metals, e.g. Co or Fe can affect the activity and stability of Ni-based catalysts under dry reforming conditions. In this work we critically assess the catalytic performance of Ni-based bi-metallic catalysts derived via the reduction of perovskite precursors, i.e. LaNi0.8M0.2O3 (M=Ni, Co and Fe). In-situ XRD and energy dispersive X-ray spectroscopy techniques were employed to probe metal–metal and metal–support interactions and phase transformations under reactive conditions. Ni–Co was found to be the most active catalyst, whereas Ni–Fe showed no activity. We observed that the addition of Co increases the rate of La2O2CO3 formation, which in turn enhances the removal of carbonaceous deposits from neighbouring active sites, thus, leading to a catalyst with an increased stability and activity. The poor activity of Ni–Fe was explained by the encapsulation of active Ni particle by LaFeO3.
Infections caused by the Middle East respiratory syndrome coronavirus (MERS‐CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the ...virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS‐CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi‐agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long‐range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi‐agent modeling framework. Least‐squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super‐spreader, our model simulations suggested that MERS‐CoV probably spread via the long‐range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long‐range airborne and close contact route.
Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit ...long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.
We report a facile roll-printing method, geometrically confined lateral crystal growth, for the fabrication of large-scale, single-crystal CH
NH
PbI
perovskite thin films. Geometrically confined ...lateral crystal growth is based on transfer of a perovskite ink solution via a patterned rolling mould to a heated substrate, where the solution crystallizes instantly with the immediate evaporation of the solvent. The striking feature of this method is that the instant crystallization of the feeding solution under geometrical confinement leads to the unidirectional lateral growth of single-crystal perovskites. Here, we fabricated single-crystal perovskites in the form of a patterned thin film (3 × 3 inch) with a high carrier mobility of 45.64 cm
V
s
. We also used these single-crystal perovskite thin films to construct solar cells with a lateral configuration. Their active-area power conversion efficiency shows a highest value of 4.83%, which exceeds the literature efficiency values of lateral perovskite solar cells.
Nitric oxide, the classic endothelium-derived relaxing factor (EDRF), acts through cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from ...hyperpolarization and is termed endothelium-derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H(2)S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine γ-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine.
The purpose of this study was to determine if H(2)S is a major physiological EDHF.
We now show that H(2)S is a major EDHF because in blood vessels of CSE-deleted mice, hyperpolarization is virtually abolished. H(2)S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H(2)S-elicited hyperpolarization. The endothelial intermediate conductance (IK(Ca)) and small conductance (SK(Ca)) potassium channels mediate in part the effects of H(2)S, as selective IK(Ca) and SK(Ca) channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide-insensitive, H(2)S-induced vasorelaxation.
H(2)S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. Because EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H(2)S biosynthesis offer therapeutic potential.
Background
Ischemic stroke and intracranial hemorrhage (ICH) following left ventricular assist device (LVAD) placement are major causes of morbidity. The incidence and mortality associated with these ...events stratified by device type have not been systematically explored.
Methods
A systematic review of PubMed was conducted from January 2007 through June 2016 for all English-language articles involving HeartMate II (HMII) and HeartWare LVAD patients. Ischemic stroke and/or ICH incidence (events per patient-year) and associated mortality rates were abstracted for each device type.
Results
Of 735 articles reviewed, 48 (11,310 patients) met inclusion criteria (33 HMII, six HeartWare, eight both devices, and one unspecified). The median duration of device support was 112 days (total 13,723 patient-years). Overall, ischemic stroke or ICH occurred in 9.8% (1110 persons and 0.08 events per patient year EPPY). Ischemic stroke occurred in a median of 6.0% or 0.06 EPPY (range 0–16% or 0–0.21 EPPY) of HMII patients versus 7.5% or 0.09 EPPY (range 4–17.1% or 0.01–0.94 EPPY) of HeartWare patients. ICH occurred in a median of 3.0% or 0.04 EPPY (range 0–13.5% or 0–0.13 EPPY) of HMII and 8.0% or 0.08 EPPY (range 3–23% or 0.01–0.56 EPPY) of HeartWare patients. The median mortality rate for LVAD-associated ischemic stroke was 31% (HMII: 33%, range 2.4–75% and HeartWare: 11.5% range 3.9–40%), and the median mortality rate following ICH was 71% (HMII: 75%, range 3.9–100% and HeartWare: 44%, range 3.1–88%).
Conclusions
Ischemic stroke and ICH are common after LVAD placement, but heterogeneous event rates are reported in the literature. Given the high associated mortality, further prospective study is warranted.
PDF
