Different platinum crystal surfaces show very distinct protein denaturation capabilities.

Different platinum (Pt) surfaces of nanocrystals usually exhibit significant distinctions with regard to various biological, physical, and chemical characteristics, such as bio-recognition, surface wetting, and catalytic activities. In this study, we report for the first time that two shape-controlled Pt nanocrystals with the most common low-index surfaces, Pt(100) and Pt(111), show very dissimilar protein denaturation capabilities based on all-atom molecular dynamics simulations employing the widely used model protein, villin headpiece (HP35). We demonstrate that HP35 is well preserved on the Pt(100) crystal surface, whereas it is severely disrupted on the Pt(111) crystal surface.

Surface Inhomogeneity of Graphene Oxide Influences Dissociation of Aβ Peptide Assembly.

Abnormal peptide assembly and aggregation is associated with an array of neurodegenerative diseases including Alzheimer's disease (AD). A detailed understanding of how nanostructured materials such as oxidized graphene perturb the peptide assembly and subsequently induce fibril dissociation may open new directions for the development of potential AD treatments. Here, we investigate the impact of surface inhomogeneity of graphene oxide (GO) on the assembly of amyloid-beta Aβ peptides on GO surfaces with different degrees of oxidation using molecular dynamics simulations.

Modeling and Structural Characterization of the Sweet Taste Receptor Heterodimer.

Sweet taste receptor, a heterodimer belonging to the class C G-protein coupled receptor (GPCR) family and composed of the T1R2 and T1R3 subunits, is responsible for the perception of natural sugars, sweet proteins, various d-amino acids, as well as artificial sweeteners. Despite the critical importance of the sweet receptor not only in mediating gustation but also in its role in the food industry, the architecture of the T1R2-T1R3 complex and the mechanism by which extracellular stimuli induce conformational changes that are propagated to the intracellular milieu, i.e.

Seizure initiation in infantile spasms vs. focal seizures: proposed common cellular mechanisms.

Infantile spasms (IS) and seizures with focal onset have different clinical expressions, even when electroencephalography (EEG) associated with IS has some degree of focality. Oddly, identical pathology (with, however, age-dependent expression) can lead to IS in one patient vs. focal seizures in another or even in the same, albeit older, patient.

Parameterization of Molybdenum Disulfide Interacting with Water Using the Free Energy Perturbation Method.

Water contact angles (WCA) are often used to parametrize force field parameters of novel 2D nanomaterials, such as molybdenum disulfide (MoS), which has emerged as a promising nanomaterial in many biomedical applications due to its unique and impressive properties. However, there is a wide range of water-MoS contact angles in the literature depending on the aging process on the surface of a MoS nanosheet and/or substrate material. In this study, we revisit and optimize existing parameters for the basal plane of MoS with two popular water models, TIP3P and SPC/E, using the wide range of WCAs from various experiments.

Lanosterol Disrupts the Aggregation of Amyloid-β Peptides.

Lanosterol, an amphipathic molecule, was discovered only very recently to effectively hinder the aggregation of lens proteins and dissolve the extremely stable fibrillar aggregates in cataracts. Here, we combined computational and experimental approaches to study how lanosterol disrupts the aggregation of another important peptide, amyloid-β (Aβ) peptide, associated with the Alzheimer's Disease (AD). Molecular dynamics simulations using the core amyloidogenic segment (KLVFFA) of Aβ peptide revealed that lanosterol exhibits at least two types of inhibition mechanism on the self-assembly of Aβ peptides.

Parallel entangling operations on a universal ion-trap quantum computer.

The circuit model of a quantum computer consists of sequences of gate operations between quantum bits (qubits), drawn from a universal family of discrete operations. The ability to execute parallel entangling quantum gates offers efficiency gains in numerous quantum circuits, as well as for entire algorithms-such as Shor's factoring algorithm-and quantum simulations. In circuits such as full adders and multiple-control Toffoli gates, parallelism can provide an exponential improvement in overall execution time through the divide-and-conquer technique.

Stability of Ligands on Nanoparticles Regulating the Integrity of Biological Membranes at the Nano-Lipid Interface.

When nanoparticles interact with cellular or organelle membranes, the coating ligands are known to affect the integrity of the membranes, which regulate cell death and inflammation. However, the molecular mechanisms of this modulation remain unresolved. Here, we use synchrotron X-ray liquid surface scattering and molecular dynamics simulations to study interface structures between phospholipids and gold nanorods (AuNRs) coated by surfactant and polyelectrolyte.

Computer algorithms show potential for improving dermatologists' accuracy to diagnose cutaneous melanoma: Results of the International Skin Imaging Collaboration 2017.

Background: Computer vision has promise in image-based cutaneous melanoma diagnosis but clinical utility is uncertain.

Objective: To determine if computer algorithms from an international melanoma detection challenge can improve dermatologists' accuracy in diagnosing melanoma.

Methods: In this cross-sectional study, we used 150 dermoscopy images (50 melanomas, 50 nevi, 50 seborrheic keratoses) from the test dataset of a melanoma detection challenge, along with algorithm results from 23 teams.

Robust Antibacterial Activity of Tungsten Oxide (WO) Nanodots.

Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO), synthesized by a simple one-pot synthetic approach, were found to exhibit strong antibacterial capabilities.

A 3,2-Hydroxypyridinone-based Decorporation Agent that Removes Uranium from Bones In Vivo.

Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands.

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen.

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments.

Field Deployment of a Portable Optical Spectrometer for Methane Fugitive Emissions Monitoring on Oil and Gas Well Pads.

We present field deployment results of a portable optical absorption spectrometer for localization and quantification of fugitive methane (CH) emissions. Our near-infrared sensor targets the 2ν R(4) CH transition at 6057.1 cm (1651 nm) via line-scanned tunable diode-laser absorption spectroscopy (TDLAS), with Allan deviation analysis yielding a normalized 2.

A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.

T and B cells are the two known lineages of adaptive immune cells. Here, we describe a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of both B and T cells. In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site.

Different protonated states at the C-terminal of the amyloid-β peptide modulate the stability of S-shaped protofibril.

Studies have found strong correlations between polymorphism and structural variations in amyloid-β (Aβ) fibrils and the diverse clinical subtypes of Alzheimer's disease (AD). Thus, a detailed understanding of the conformational behavior of Aβ fibrils may be an aid to elucidate the pathological mechanisms involved in AD. However, a key point that has been inadvertently underestimated or dismissed is the role of the protonated state at the C-terminal residue of amyloid-β peptides, which can give rise to intrinsic differences in the morphology and stability of the fibrils.

Molecular Origin of the Stability Difference in Four Shark IgNAR Constant Domains.

Improving the stability of antibodies for manufacture and shelf life is one of the main focuses of antibody engineering. One stabilization strategy is to perform specific mutations in human antibodies based on highly stable antibodies in other species. To identify the key residues for mutagenesis, it is necessary to understand the roles of these residues in stabilizing the antibody.

Deceased Donor-initiated Chains: First Report of a Successful Deliberate Case and Its Ethical Implications.

Background: It has been suggested that deceased donor kidneys could be used to initiate chains of living donor kidney paired donation, but the potential gains of this practice need to be quantified and the ethical implications must be addressed before it can be implemented.

Methods: The gain of implementing deceased donor-initiated chains was measured with an algorithm, using retrospective data on the pool of incompatible donor/recipient pairs, at a single center. The allocation rules for chain-ending kidneys and the characteristics and quality of the chain-initiating kidney are described.

TeraPCA: a fast and scalable software package to study genetic variation in tera-scale genotypes.

Motivation: Principal Component Analysis is a key tool in the study of population structure in human genetics. As modern datasets become increasingly larger in size, traditional approaches based on loading the entire dataset in the system memory (Random Access Memory) become impractical and out-of-core implementations are the only viable alternative.

Results: We present TeraPCA, a C++ implementation of the Randomized Subspace Iteration method to perform Principal Component Analysis of large-scale datasets.

Single-trial classification of awareness state during anesthesia by measuring critical dynamics of global brain activity.

In daily life, in the operating room and in the laboratory, the operational way to assess wakefulness and consciousness is through responsiveness. A number of studies suggest that the awake, conscious state is not the default behavior of an assembly of neurons, but rather a very special state of activity that has to be actively maintained and curated to support its functional properties. Thus responsiveness is a feature that requires active maintenance, such as a homeostatic mechanism to balance excitation and inhibition.

Theta/delta coupling across cortical laminae contributes to semantic cognition.

Rhythmic activity in populations of neurons is associated with cognitive and motor function. Our understanding of the neuronal mechanisms underlying these core brain functions has benefitted from demonstrations of cellular, synaptic, and network phenomena, leading to the generation of discrete rhythms at the local network level. However, discrete frequencies of rhythmic activity rarely occur alone.

Physical and Toxicological Profiles of Human IAPP Amyloids and Plaques.

Although much has been learned about the fibrillization kinetics, structure and toxicity of amyloid proteins, the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert, despite evidence suggesting otherwise. To fill this knowledge gap, we examined the physical and biological characteristics of human islet amyloid polypeptide (IAPP) fibrils that were aged up to two months. Not only did aging decrease the toxicity of IAPP fibrils, but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model.

MSC: a metagenomic sequence classification algorithm.

Motivation: Metagenomics is the study of genetic materials directly sampled from natural habitats. It has the potential to reveal previously hidden diversity of microscopic life largely due to the existence of highly parallel and low-cost next-generation sequencing technology. Conventional approaches align metagenomic reads onto known reference genomes to identify microbes in the sample.