Cyanobacteria are photosynthetic bacteria that are currently being developed as biological production platforms. They derive energy from light and carbon from atmospheric carbon dioxide, and some ...species can fix atmospheric nitrogen. One advantage of developing cyanobacteria for renewable production of biofuels and other biological products is that they are amenable to genetic manipulation, facilitating bioengineering and synthetic biology. To expand the currently available genetic toolkit, we have demonstrated the utility of synthetic theophylline-responsive riboswitches for effective regulation of gene expression in four diverse species of cyanobacteria, including two recent isolates. We evaluated a set of six riboswitches driving the expression of a yellow fluorescent protein reporter in Synechococcus elongatus PCC 7942, Leptolyngbya sp. strain BL0902, Anabaena sp. strain PCC 7120, and Synechocystis sp. strain WHSyn. We demonstrated that riboswitches can offer regulation of gene expression superior to that of the commonly used isopropyl-β-d-thiogalactopyranoside induction of a lacI(q)-Ptrc promoter system. We also showed that expression of the toxic protein SacB can be effectively regulated, demonstrating utility for riboswitch regulation of proteins that are detrimental to biomass accumulation. Taken together, the results of this work demonstrate the utility and ease of use of riboswitches in the context of genetic engineering and synthetic biology in diverse cyanobacteria, which will facilitate the development of algal biotechnology.
•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.
ABSTRACT
We present the results of a continuum reverberation mapping study of the radio-quiet type 1 Seyfert galaxy IRAS 09149−6206. The analysis was performed using X-ray, ultraviolet (UV), and ...optical observations made with the Swift telescope between 2017 January and December. The time delays between different light curves were measured using three different algorithms: PyI2CCF, PyROA, and JAVELIN. Our results show that the time delays increase with wavelength after τ ∝ λ4/3, as predicted for a geometrically thin and optically thick accretion disc, but only after accounting for significant diffuse continuum emission from the broad-line region. However, the measured size of the accretion disc can be up to five times larger than that predicted by standard theory. To our surprise, the strong increase in soft X-ray fluxes is delayed by about 15 d compared to the optical UV fluctuations, which challenges the prediction of the lamp-post model. Our analysis of the X-ray variability reveals the presence of a non-variable spectral component at 0.3–6.0 keV along with variable excess emission at 2.0–3.0 keV, which could be partly related to relativistic reflection in the inner region of the accretion disc. IRAS 09149−6206 joins the list of objects for which the traditional lamp-post model cannot explain the observed time delays. A scenario that incorporates other geometric considerations into the lamp-post model, e.g. an extended corona along a scattering source, might be better suited to explain the observed long time delays.
Co‐produced: Using Co(en)32+/3+ based‐electrolytes in p‐type dye‐sensitized solar cells (p‐DSCs) gives record energy conversion efficiencies of 1.3 % and open‐circuit voltages up to 709 mV under ...simulated sun light. The increase in photovoltage is due to the more negative redox potential of Co(en)32+/3+ compared to established mediators.
Type VI secretion systems (T6SSs) have recently been recognized as potential virulence determinants of many Gram-negative bacterial pathogens. Although mechanistic studies are lacking, T6SS-dependent ...phenotypes can be observed in various animal models of infection. Presumably translocation of T6SS effectors into target cells is involved in virulence, but few such effectors have been identified. A hallmark of T6SS function is the in vitro secretion of Hcp and VgrG proteins, which are thought to form part of an extracellular secretion apparatus. One well-characterized effector domain is the C-terminal actin cross-linking domain (ACD) of the VgrG-1 protein, constitutively secreted by the T6SS of Vibrio cholerae strain V52. Previous work indicated that translocation of VgrG-1 occurred only after endocytic uptake of bacteria into host cells. VgrG-1-induced actin cross-linking impaired phagocytic activity of host cells, eventually causing cell death. To determine whether V. cholerae T6SS is functional during animal infection, derivatives of V52 were used to infect infant mice. In this infection model a diarrheal response occurred, and actin cross-linking could be detected. These host responses were dependent on a functional T6SS and on the ACD of VgrG-1. Gene expression and histologic studies showed innate immune activation and immune cell infiltration in the intestinal lumen. The T6SS-dependent inflammatory response was also associated with increased recovery of V. cholerae from the intestine. We conclude that the T6SS of V52 induces an inflammatory diarrhea that facilitates replication of V. cholerae within the intestine.
Perturbation of Disrupted-In-Schizophrenia-1 (DISC1) and D-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of schizophrenia and other psychiatric disorders. In the ...present study, we demonstrate that these two pathways intersect with behavioral consequences. DISC1 binds to and stabilizes serine racemase (SR), the enzyme that generates D-serine, an endogenous co-agonist of the NMDA receptor. Mutant DISC1 fails to bind to SR, facilitating ubiquitination and degradation of SR and a decrease in D-serine production. To elucidate DISC1-SR interactions in vivo, we generated a mouse model of selective and inducible expression of mutant DISC1 in astrocytes, the main source of D-serine in the brain. Expression of mutant DISC1 downregulates endogenous DISC1 and decreases protein but not mRNA levels of SR, resulting in diminished production of D-serine. In contrast, mutant DISC1 does not alter levels of ALDH1L1, connexins, GLT-1 or binding partners of DISC1 and SR, LIS1 or PICK1. Adult male and female mice with lifelong expression of mutant DISC1 exhibit behavioral abnormalities consistent with hypofunction of NMDA neurotransmission. Specifically, mutant mice display greater responses to an NMDA antagonist, MK-801, in open field and pre-pulse inhibition of the acoustic startle tests and are significantly more sensitive to the ameliorative effects of D-serine. These findings support a model wherein mutant DISC1 leads to SR degradation via dominant negative effects, resulting in D-serine deficiency that diminishes NMDA neurotransmission thus linking DISC1 and NMDA pathophysiological mechanisms in mental illness.
In megabar shock waves, materials compress and undergo a phase transition to a dense charged-particle system that is dominated by strong correlations and quantum effects. This complex state, known as ...warm dense matter, exists in planetary interiors and many laboratory experiments (for example, during high-power laser interactions with solids or the compression phase of inertial confinement fusion implosions). Here, we apply record peak brightness X-rays at the Linac Coherent Light Source to resolve ionic interactions at atomic (ångström) scale lengths and to determine their physical properties. Our in situ measurements characterize the compressed lattice and resolve the transition to warm dense matter, demonstrating that short-range repulsion between ions must be accounted for to obtain accurate structure factor and equation of state data. In addition, the unique properties of the X-ray laser provide plasmon spectra that yield the temperature and density with unprecedented precision at micrometre-scale resolution in dynamic compression experiments.
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