Data-Driven Forecasting of High-Dimensional Chaotic Systems with Long Short-Term Memory Networks

We introduce a data-driven forecasting method for high-dimensional chaotic systems using long short-term memory (LSTM) recurrent neural networks. The proposed LSTM neural networks perform inference of high-dimensional dynamical systems in their reduced order space and are shown to be an effective set of nonlinear approximators of their attractor. We demonstrate the forecasting performance of the LSTM and compare it with Gaussian processes (GPs) in time series obtained from the Lorenz 96 system, the Kuramoto-Sivashinsky equation and a prototype climate model. The LSTM networks outperform the GPs in short-term forecasting accuracy in all applications considered. A hybrid architecture, extending the LSTM with a mean stochastic model (MSM-LSTM), is proposed to ensure convergence to the invariant measure. This novel hybrid method is fully data-driven and extends the forecasting capabilities of LSTM networks.Comment: 31 page

The orbitofrontal cortex functionally links obesity and white matter hyperintensities

© 2020, The Author(s).Many studies have linked dysfunction in cognitive control-related brain regions with obesity and the burden of white matter hyperintensities (WMHs). This study aimed to explore how functional connectivity differences in the brain are associated with WMH burden and degree of obesity using resting-state functional magnetic resonance imaging (fMRI) in 182 participants. Functional connectivity measures were compared among four different groups: (1) low WMH burden, non-obese; (2) low WMH burden, obese; (3) high WMH burden, non-obese; and (4) high WMH burden, obese. At a large-scale network-level, no networks showed significant interaction effects, but the frontoparietal network showed a main effect of degree of obesity. At a finer node level, the orbitofrontal cortex showed interaction effects between periventricular WMH burden and degree of obesity. Higher functional connectivity was observed when the periventricular WMH burden and degree of obesity were both high. These results indicate that the functional connectivity of the orbitofrontal cortex is affected by the mutual interaction between the periventricular WMHs and degree of obesity. Our results suggest that this region links obesity with WMHs in terms of functional connectivity11sciescopu

Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection

Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide-receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized

The Non-Destructive and Nano-Microstructural Characterization of Thermal-Barrier Coatings

The durability of thermal barrier coatings (TBCs) plays an important role in the service reliability and maintainability of hot-section components in advanced turbine engines for aerospace and utility applications. Photostimulated luminescence spectroscopy (PSLS) and electrochemical impedance spectroscopy (EIS) are being concurrently developed as complimentary nondestructive evaluation (NDE) techniques for quality control and liferemain assessment of TBCs. This paper discusses recent achievements in understanding the residual stress, phase constituents, and electrochemical resistance (or capacitance) of TBC constituents—with an emphasis on the thermally grown oxide. Results from NDE by PSLS and EIS are correlated to the nano- and microstructural development of TBCs

The Non-Destructive and Nano-Microstructural Characterization of Thermal-Barrier Coatings

The durability of thermal barrier coatings (TBCs) plays an important role in the service reliability and maintainability of hot-section components in advanced turbine engines for aerospace and utility applications. Photostimulated luminescence spectroscopy (PSLS) and electrochemical impedance spectroscopy (EIS) are being concurrently developed as complimentary nondestructive evaluation (NDE) techniques for quality control and liferemain assessment of TBCs. This paper discusses recent achievements in understanding the residual stress, phase constituents, and electrochemical resistance (or capacitance) of TBC constituents—with an emphasis on the thermally grown oxide. Results from NDE by PSLS and EIS are correlated to the nano- and microstructural development of TBCs

Chemical Accident Hazard Assessment by Spatial Analysis of Chemical Factories and Accident Records in South Korea

This study identified the potential chemical accident occurrence in Korea by analyzing the spatial distribution of chemical factories and accidents. The number of chemical factories and accidents in 25-km2 grids were used as the attribute value for spatial analysis. First, semi-variograms were conducted to examine spatial distribution patterns and to identify spatial autocorrelation of chemical factories and accidents. Semi-variograms explained that the spatial distribution of chemical factories and accidents were spatially autocorrelated. Second, the results of the semi-variograms were used in Ordinary Kriging to estimate chemical hazard levels. The level values were extracted from the Ordinary Kriging result and their spatial similarity was examined by juxtaposing the two values with respect to their location. Six peaks were identified in both the factory hazard and accident hazard estimation result, and the peaks correlated with major cities in Korea. Third, the estimated two hazard levels were classified with geometrical interval and could be classified into four quadrants: Low Factory and Low Accident (LFLA), High Factory and Low Accident (HFLA), Low Factory and High Accident(LFHA), and High Factory and High Accident (HFHA). The 4 groups identified different chemical safety management issues in Korea; safe LFLA group, many chemical reseller factories were found in HFLA group, chemical transportation accidents were in the LFHA group, and an abundance of factories and accidents were in the HFHA group. Each quadrant represented different safety management obstacles in Korea, and studying spatial differences can support the establishment of an efficient risk management plan

Semiclassical stationary states for nonlinear Schroedinger equations with fast decaying potentials

We study the existence of stationnary positive solutions for a class of nonlinear Schroedinger equations with a nonnegative continuous potential V. Amongst other results, we prove that if V has a positive local minimum, and if the exponent of the nonlinearity satisfies N/(N-2)<p<(N+2)/(N-2), then for small epsilon the problem admits positive solutions which concentrate as epsilon goes to 0 around the local minimum point of V. The novelty is that no restriction is imposed on the rate of decay of V. In particular, we cover the case where V is compactly supported.Comment: 22 page

Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities

Background: Human APOBEC3H (A3H) belongs to the A3 family of host restriction factors, which are cytidine deaminases that catalyze conversion of deoxycytidine to deoxyuridine in single-stranded DNA. A3 proteins contain either one (A3A, A3C, A3H) or two (A3B, A3D, A3F, A3G) Zn-binding domains. A3H has seven haplotypes (I-VII) that exhibit diverse biological phenotypes and geographical distribution in the human population. Its single Zn-coordinating deaminase domain belongs to a phylogenetic cluster (Z3) that is different from the Z1- and Z2-type domains in other human A3 proteins. A3H HapII, unlike A3A or A3C, has potent activity against HIV-1. Here, we sought to identify the determinants of A3H HapII deaminase and antiviral activities, using site-directed sequence- and structure-guided mutagenesis together with cell-based, biochemical, and HIV-1 infectivity assays. Results: We have constructed a homology model of A3H HapII, which is similar to the known structures of other A3 proteins. The model revealed a large cluster of basic residues (not present in A3A or A3C) that are likely to be involved in nucleic acid binding. Indeed, RNase A pretreatment of 293T cell lysates expressing A3H was shown to be required for detection of deaminase activity, indicating that interaction with cellular RNAs inhibits A3H catalytic function. Similar observations have been made with A3G. Analysis of A3H deaminase substrate specificity demonstrated that a 5" T adjacent to the catalytic C is preferred. Changing the putative nucleic acid binding residues identified by the model resulted in reduction or abrogation of enzymatic activity, while substituting Z3-specific residues in A3H to the corresponding residues in other A3 proteins did not affect enzyme function. As shown for A3G and A3F, some A3H mutants were defective in catalysis, but retained antiviral activity against HIV-1vif (-) virions. Furthermore, endogenous reverse transcription assays demonstrated that the E56A catalytic mutant inhibits HIV-1 DNA synthesis, although not as efficiently as wild type. Conclusions: The molecular and biological activities of A3H are more similar to those of the double-domain A3 proteins than to those of A3A or A3C. Importantly, A3H appears to use both deaminase-dependent and -independent mechanisms to target reverse transcription and restrict HIV-1 replication

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al