Rational fragment-based design of compounds targeting the PWWP domain of the HRP family.

Lens epithelium-derived growth factor p75 (LEDGF/p75), member of the hepatoma-derived growth-factor-related protein (HRP) family, is a transcriptional co-activator and involved in several pathologies including HIV infection and malignancies such as MLL-rearranged leukemia. LEDGF/p75 acts by tethering proteins to the chromatin through its integrase binding domain. This chromatin interaction occurs between the PWWP domain of LEDGF/p75 and nucleosomes carrying a di- or trimethylation mark on histone H3 Lys36 (H3K36me2/3).

A Two-Layer Self-Organizing Map with Vector Symbolic Architecture for Spatiotemporal Sequence Learning and Prediction.

We propose a new nature- and neuro-science-inspired algorithm for spatiotemporal learning and prediction based on sequential recall and vector symbolic architecture. A key novelty is the learning of spatial and temporal patterns as decoupled concepts where the temporal pattern sequences are constructed using the learned spatial patterns as an alphabet of elements. The decoupling, motivated by cognitive neuroscience research, provides the flexibility for fast and adaptive learning with dynamic changes to data and concept drift and as such is better suited for real-time learning and prediction.

Hardware Efficient Direct Policy Imitation Learning for Robotic Navigation in Resource-Constrained Settings.

Direct policy learning (DPL) is a widely used approach in imitation learning for time-efficient and effective convergence when training mobile robots. However, using DPL in real-world applications is not sufficiently explored due to the inherent challenges of mobilizing direct human expertise and the difficulty of measuring comparative performance. Furthermore, autonomous systems are often resource-constrained, thereby limiting the potential application and implementation of highly effective deep learning models.

Vector Symbolic Architectures as a Computing Framework for Emerging Hardware.

This article reviews recent progress in the development of the computing framework (also known as Hyperdimensional Computing). This framework is well suited for implementation in stochastic, emerging hardware and it naturally expresses the types of cognitive operations required for Artificial Intelligence (AI). We demonstrate in this article that the field-like algebraic structure of Vector Symbolic Architectures offers simple but powerful operations on high-dimensional vectors that can support all data structures and manipulations relevant to modern computing.

Extracellular Fe(III) reductase structure reveals a modular organization enabling S-layer insertion and electron transfer to insoluble substrates.

The thermophilic anaerobic Gram-positive bacterium Carboxydothermus ferrireducens utilizes insoluble Fe(III) oxides as electron acceptors in respiratory processes using an extracellular 11-heme cytochrome c OmhA as a terminal reductase. OmhA is able to transfer electrons to soluble and insoluble Fe(III) compounds, substrates of multiheme oxidoreductases, and soluble electron shuttles. The crystal structure of OmhA at 2.

5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro.

Amphipathic nucleoside and non-nucleoside derivatives of pentacyclic aromatic hydrocarbon perylene are known as potent non-cytotoxic broad-spectrum antivirals. Here we report 3-methyl-5-(perylen-3-ylethynyl)-uracil-1-acetic acid and its amides, a new series of compounds based on a 5-(perylen-3-ylethynyl)-uracil scaffold. The compounds demonstrate pronounced in vitro activity against arthropod-borne viruses, namely tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV), in plaque reduction assays with EC values below 1.

Structural Basis of Cysteine Ligase MshC Inhibition by Cysteinyl-Sulfonamides.

Mycothiol (MSH), the major cellular thiol in (Mtb), plays an essential role in the resistance of Mtb to various antibiotics and oxidative stresses. MshC catalyzes the ATP-dependent ligation of 1--(2-amino-2-deoxy-α-d-glucopyranosyl)-d--inositol (GlcN-Ins) with l-cysteine (l-Cys) to form l-Cys-GlcN-Ins, the penultimate step in MSH biosynthesis. The inhibition of MshC is lethal to Mtb.

Hyperseed: Unsupervised Learning With Vector Symbolic Architectures.

Motivated by recent innovations in biologically inspired neuromorphic hardware, this article presents a novel unsupervised machine learning algorithm named Hyperseed that draws on the principles of vector symbolic architectures (VSAs) for fast learning of a topology preserving feature map of unlabeled data. It relies on two major operations of VSA, binding and bundling. The algorithmic part of Hyperseed is expressed within the Fourier holographic reduced representations (FHRR) model, which is specifically suited for implementation on spiking neuromorphic hardware.

The role of the local environment on the structural heterogeneity of carotenoid β-ionone rings.

Our analysis of the X-ray crystal structure of canthaxanthin (CAN) showed that its ketolated β-ionone rings can adopt two energetically equal, but structurally distinct puckers. Quantum chemistry calculations revealed that the potential energy surface of the β-ionone ring rotation over the plane of the conjugated π-system in carotenoids depends on the pucker state of the β-ring. Considering different pucker states and β-ionone ring rotation, we found six separate local minima on the potential energy surface defining the geometry of the keto-β-ionone ring-two cis and one trans orientation for each of two pucker states.

Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors.

Polyomaviruses are a family of ubiquitous double-stranded DNA viruses many of which are human pathogens. These include BK polyomavirus which causes severe urinary tract infection in immunocompromised patients and Merkel cell polyomavirus associated with aggressive cancers. The small genome of polyomaviruses lacks conventional drug targets, and no specific drugs are available at present.

Surface energy balance of the Sygyktinsky Glacier, south Eastern Siberia, during the ablation period and its sensitivity to meteorological fluctuations.

The physically based melt of the low elevation Eastern Siberian glaciers is poorly understood due to the lack of direct micrometeorological studies. We used an automatic meteorological station to record the meteorological and energy characteristics of the Sygyktinsky Glacier, south Eastern Siberia (56.8° N, 117.

Catalytic Properties of Flavocytochrome c Sulfide Dehydrogenase from Haloalkaliphilic Bacterium Thioalkalivibrio paradoxus.

Flavocytochrome c sulfide dehydrogenase (FCC) is one of the central enzymes of the respiratory chain in sulfur-oxidizing bacteria. FCC catalyzes oxidation of sulfide and polysulfide ions to elemental sulfur accompanied by electron transfer to cytochrome c. The catalytically active form of the enzyme is a non-covalently linked heterodimer composed of flavin- and heme-binding subunits.

A Comprehensive Study of Complexity and Performance of Automatic Detection of Atrial Fibrillation: Classification of Long ECG Recordings Based on the PhysioNet Computing in Cardiology Challenge 2017.

Objective: The 2017 PhysioNet/CinC Challenge focused on automatic classification of atrial fibrillation (AF) in short ECGs. This study aimed to evaluate the use of the data and results from the challenge for detection of AF in longer ECGs, taken from three other PhysioNet datasets.

Approach: The used data-driven models were based on features extracted from ECG recordings, calculated according to three solutions from the challenge.

Integer Echo State Networks: Efficient Reservoir Computing for Digital Hardware.

We propose an approximation of echo state networks (ESNs) that can be efficiently implemented on digital hardware based on the mathematics of hyperdimensional computing. The reservoir of the proposed integer ESN (intESN) is a vector containing only n -bits integers (where is normally sufficient for a satisfactory performance). The recurrent matrix multiplication is replaced with an efficient cyclic shift operation.

Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group.

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group.

Automatic Recognition of Sucker-Rod Pumping System Working Conditions Using Dynamometer Cards with Transfer Learning and SVM.

Sucker-rod pumping systems are the most widely applied artificial lift equipment in the oil and gas industry. Accurate and intelligent working condition recognition of pumping systems imposes major impacts on oilfield production benefits and efficiency. The shape of dynamometer card reflects the working conditions of sucker-rod pumping systems, and different conditions can be indicated by their typical card characteristics.

Density Encoding Enables Resource-Efficient Randomly Connected Neural Networks.

The deployment of machine learning algorithms on resource-constrained edge devices is an important challenge from both theoretical and applied points of view. In this brief, we focus on resource-efficient randomly connected neural networks known as random vector functional link (RVFL) networks since their simple design and extremely fast training time make them very attractive for solving many applied classification tasks. We propose to represent input features via the density-based encoding known in the area of stochastic computing and use the operations of binding and bundling from the area of hyperdimensional computing for obtaining the activations of the hidden neurons.

Enhancement of spontaneous emission of semiconductor quantum dots inside one-dimensional porous silicon photonic crystals.

Controlling spontaneous emission by modifying the local electromagnetic environment is of great interest for applications in optoelectronics, biosensing and energy harvesting. Although the development of devices based on one-dimensional porous silicon photonic crystals with embedded luminophores is a promising approach for applications, the efficiency of the embedded luminophores remains a key challenge because of the strong quenching of the emission due to the contact of the luminophores with the surface of porous silicon preventing the observation of interesting light-matter coupling effects. Here, we experimentally demonstrate an increase in the quantum dot (QD) spontaneous emission rate inside a porous silicon microcavity and almost an order of magnitude enhancement of QD photoluminescence intensity in the weak light-matter coupling regime.

Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group.

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis.

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide.

Crystal structure of Arabidopsis thaliana neutral invertase 2.

The metabolism of sucrose is of crucial importance for life on Earth. In plants, enzymes called invertases split sucrose into glucose and fructose, contributing to the regulation of metabolic fluxes. Invertases differ in their localization and pH optimum.

White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group.

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium.

No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis.

Objective: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected.

Structure of the Anti-C60 Fullerene Antibody Fab Fragment: Structural Determinants of Fullerene Binding.

The structure of the anti-C fullerene antibody Fab fragment (FabC) was solved by X-ray crystallography. The computer-aided docking of C into the antigen-binding pocket of FabC showed that binding of C to FabC is governed by the enthalpy and entropy; namely, by π-π stacking interactions with aromatic residues of the antigen-binding site and reduction of the solvent-accessible area of the hydrophobic surface of C. A fragment of the mobile CDR H3 loop located on the surface of FabC interferes with C binding in the antigen-binding site, thereby resulting in low antibody affinity for C.