Publications by authors named "David Nicholson"

As multiple UN fora develop parallel rules for sharing benefits from digital sequence information, we urge better coordination. International policymakers should focus on harmonizing new benefit-sharing rules to ensure open access to data, database interoperability, and better benefit sharing outcomes.

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Background: Biogeochemical-Argo floats are collecting an unprecedented number of profiles of optical backscattering measurements in the global ocean. Backscattering (BBP) data are crucial to understanding ocean particle dynamics and the biological carbon pump. Yet, so far, no procedures have been agreed upon to quality control BBP data in real time.

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G-Quadruplexes (G4s) are ubiquitous nucleic acid folding motifs that exhibit structural diversity that is dependent on cationic conditions. In this work, we exploit temperature-controlled single-molecule fluorescence resonance energy transfer (smFRET) to elucidate the kinetic and thermodynamic mechanisms by which monovalent cations (K and Na) impact folding topologies for a simple G-quadruplex sequence (5'-GGG-(TAAGGG)-3') with a three-state folding equilibrium. Kinetic measurements indicate that Na and K influence G4 formation in two distinctly different ways: the presence of Na modestly enhances an antiparallel G4 topology through an induced fit (IF) mechanism with a low affinity ( = 228 ± 26 mM), while K drives G4 into a parallel/hybrid topology via a conformational selection (CS) mechanism with much higher affinity ( = 1.

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Background: Hetnets, short for "heterogeneous networks," contain multiple node and relationship types and offer a way to encode biomedical knowledge. One such example, Hetionet, connects 11 types of nodes-including genes, diseases, drugs, pathways, and anatomical structures-with over 2 million edges of 24 types. Previous work has demonstrated that supervised machine learning methods applied to such networks can identify drug repurposing opportunities.

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While we often think of words as having a fixed meaning that we use to describe a changing world, words are also dynamic and changing. Scientific research can also be remarkably fast-moving, with new concepts or approaches rapidly gaining mind share. We examined scientific writing, both preprint and pre-publication peer-reviewed text, to identify terms that have changed and examine their use.

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Gas exchange between the atmosphere and ocean interior profoundly impacts global climate and biogeochemistry. However, our understanding of the relevant physical processes remains limited by a scarcity of direct observations. Dissolved noble gases in the deep ocean are powerful tracers of physical air-sea interaction due to their chemical and biological inertness, yet their isotope ratios have remained underexplored.

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Hetnets, short for "heterogeneous networks", contain multiple node and relationship types and offer a way to encode biomedical knowledge. One such example, Hetionet connects 11 types of nodes - including genes, diseases, drugs, pathways, and anatomical structures - with over 2 million edges of 24 types. Previous work has demonstrated that supervised machine learning methods applied to such networks can identify drug repurposing opportunities.

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Past responses to environmental change provide vital baseline data for estimating the potential resilience of extant taxa to future change. Here, we investigate the latitudinal range contraction that terrestrial and freshwater turtles (Testudinata) experienced from the Late Cretaceous to the Paleogene (100.5-23.

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Background: Knowledge graphs support biomedical research efforts by providing contextual information for biomedical entities, constructing networks, and supporting the interpretation of high-throughput analyses. These databases are populated via manual curation, which is challenging to scale with an exponentially rising publication rate. Data programming is a paradigm that circumvents this arduous manual process by combining databases with simple rules and heuristics written as label functions, which are programs designed to annotate textual data automatically.

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A computational and experimental framework for quantifying flow-enhanced nucleation (FEN) in polymers is presented and demonstrated for an industrial-grade linear low-density polyethylene (LLDPE). Experimentally, kinetic measurements of isothermal crystallization were performed by using fast-scanning calorimetry (FSC) for melts that were presheared at various strain rates. The effect of shear on the average conformation tensor of the melt was modeled with the discrete slip-link model (DSM).

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Visual search is a complex behavior influenced by many factors. To control for these factors, many studies use highly simplified stimuli. However, the statistics of these stimuli are very different from the statistics of the natural images that the human visual system is optimized by evolution and experience to perceive.

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Natural silks crafted by spiders comprise some of the most versatile materials known. Artificial silks-based on the sequences of their natural brethren-replicate some desirable biophysical properties and are increasingly utilized in commercial and medical applications today. To characterize the repertoire of protein sequences giving silks their biophysical properties and to determine the set of expressed genes across each unique silk gland contributing to the formation of natural silks, we report here draft genomic and transcriptomic assemblies of Darwin's bark spider, Caerostris darwini, an orb-weaving spider whose dragline is one of the toughest known biomaterials on Earth.

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Open access to sequence data is a cornerstone of biology and biodiversity research, but has created tension under the United Nations Convention on Biological Diversity (CBD). Policy decisions could compromise research and development, unless a practical multilateral solution is implemented.

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The first member of the pleuromutilin (PLM) class suitable for systemic antibacterial chemotherapy in humans recently entered clinical use, underscoring the need to better understand mechanisms of PLM resistance in disease-causing bacterial genera. Of the proteins reported to mediate PLM resistance in staphylococci, the least-well studied to date is Sal(A), a putative ABC-F NTPase that-by analogy to other proteins of this type-may act to protect the ribosome from PLMs. Here, we establish the importance of Sal proteins as a common source of PLM resistance across multiple species of staphylococci.

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The evolution of microbial parasites involves the counterplay between natural selection forcing parasites to improve and genetic drifts forcing parasites to lose genes and accumulate deleterious mutations. Here, to understand how this counterplay occurs at the scale of individual macromolecules, we describe cryo-EM structure of ribosomes from Encephalitozoon cuniculi, a eukaryote with one of the smallest genomes in nature. The extreme rRNA reduction in E.

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Preprints allow researchers to make their findings available to the scientific community before they have undergone peer review. Studies on preprints within bioRxiv have been largely focused on article metadata and how often these preprints are downloaded, cited, published, and discussed online. A missing element that has yet to be examined is the language contained within the bioRxiv preprint repository.

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Songbirds provide a powerful model system for studying sensory-motor learning. However, many analyses of birdsong require time-consuming, manual annotation of its elements, called syllables. Automated methods for annotation have been proposed, but these methods assume that audio can be cleanly segmented into syllables, or they require carefully tuning multiple statistical models.

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Measurements of the thermodynamic properties of biomolecular folding (Δ°, Δ°, Δ°, etc.) provide a wealth of information on the folding process and have long played a central role in biophysical investigation. In particular, the excess heat capacity of folding (Δ) is crucial, as typically measured in bulk ensemble studies by differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC).

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Single-molecule fluorescence resonance energy transfer (smFRET) experiments permit detailed examination of microscopic dynamics. However, kinetic rate constants determined by smFRET are susceptible to systematic underestimation when the rate constants are comparable to the data acquisition rate. We demonstrate how such systematic errors in camera-based total internal reflection fluorescence microscopy experiments can be greatly reduced by using stroboscopic illumination/detection, allowing accurate rate constant determination up to the data sampling rate and yielding an order of magnitude increase in the dynamic range.

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The Wiener-Khinchin theorem for the Fourier-Laplace transformation (WKT-FLT) provides a robust method to obtain the single-side Fourier transforms of arbitrary time-domain relaxation functions (or autocorrelation functions). Moreover, by combining an on-the-fly algorithm with the WKT-FLT, the numerical calculations of various complex spectroscopic data in a wide frequency range become significantly more efficient. However, the discretized WKT-FLT equation, obtained simply by replacing the integrations with the discrete summations, always produces two artifacts in the frequency-domain relaxation function.

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The preponderance of a specific d- or l-chirality in fats, sugars, amino acids, nucleic acids, and so on is ubiquitous in nature, yet the biological origin of such chiral dominance (i.e., with one enantiomer overwhelmingly present) remains an open question.

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Acinetobacter baumannii is a Gram-negative bacterium primarily associated with hospital-acquired, often multidrug-resistant (MDR) infections. The ribosome-targeting antibiotics amikacin and tigecycline are among the limited arsenal of drugs available for treatment of such infections. We present high-resolution structures of the 70S ribosome from A.

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Knowledge graphs can support many biomedical applications. These graphs represent biomedical concepts and relationships in the form of nodes and edges. In this review, we discuss how these graphs are constructed and applied with a particular focus on how machine learning approaches are changing these processes.

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Polymer crystallization occurs in many plastic manufacturing processes, from injection molding to film blowing. Linear low-density polyethylene (LLDPE) is one of the most commonly processed polymers, wherein the type and extent of short-chain branching (SCB) may be varied to influence crystallization. In this work, we report simultaneous measurements of the rheology and Raman spectra, using a Rheo-Raman microscope, for two industrial-grade LLDPEs undergoing crystallization.

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