Unraveling sources of emission heterogeneity in Silicon Vacancy color centers with cryo-cathodoluminescence microscopy.

Diamond color centers have proven to be versatile quantum emitters and exquisite sensors of stress, temperature, electric and magnetic fields, and biochemical processes. Among color centers, the silicon-vacancy (SiV[Formula: see text]) defect exhibits high brightness, minimal phonon coupling, narrow optical linewidths, and high degrees of photon indistinguishability. Yet the creation of reliable and scalable SiV[Formula: see text]-based color centers has been hampered by heterogeneous emission, theorized to originate from surface imperfections, crystal lattice strain, defect symmetry, or other lattice impurities. Here, we advance high-resolution cryo-electron microscopy combined with cathodoluminescence spectroscopy and 4D scanning transmission electron microscopy (STEM) to elucidate the structural sources of heterogeneity in SiV[Formula: see text] emission from nanodiamond with sub-nanometer-scale resolution. Our diamond nanoparticles are grown directly on TEM membranes from molecular-level seedings, representing the natural formation conditions of color centers in diamond. We show that individual subcrystallites within a single nanodiamond exhibit distinct zero-phonon line (ZPL) energies and differences in brightness that can vary by 0.1 meV in energy and over 70% in brightness. These changes are correlated with the atomic-scale lattice structure. We find that ZPL blue-shifts result from tensile strain, while ZPL red shifts are due to compressive strain. We also find that distinct crystallites host distinct densities of SiV[Formula: see text] emitters and that grain boundaries impact SiV[Formula: see text] emission significantly. Finally, we interrogate nanodiamonds as small as 40 nm in diameter and show that these diamonds exhibit no spatial change to their ZPL energy. Our work provides a foundation for atomic-scale structure-emission correlation, e.g., of single atomic defects in a range of quantum and two-dimensional materials.

The role of micrometastasis in high-risk skin cancers.

The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.

Resolving Current-Dependent Regimes of Electroplating Mechanisms for Fast Charging Lithium Metal Anodes.

Poor fast-charge capabilities limit the usage of rechargeable Li metal anodes. Understanding the connection between charging rate, electroplating mechanism, and Li morphology could enable fast-charging solutions. Here, we develop a combined electroanalytical and nanoscale characterization approach to resolve the current-dependent regimes of Li plating mechanisms and morphology. Measurement of Li+ transport through the solid electrolyte interphase (SEI) shows that low currents induce plating at buried Li||SEI interfaces, but high currents initiate SEI-breakdown and plating at fresh Li||electrolyte interfaces. The latter pathway can induce uniform growth of {110}-faceted Li at extremely high currents, suggesting ion-transport limitations alone are insufficient to predict Li morphology. At battery relevant fast-charging rates, SEI-breakdown above a critical current density produces detrimental morphology and poor cyclability. Thus, prevention of both SEI-breakdown and slow ion-transport in the electrolyte is essential. This mechanistic insight can inform further electrolyte engineering and customization of fast-charging protocols for Li metal batteries.

Method of Assessing Skin Cancerization and KeratosesTM (MASCK™): development and photographic validation in multiple anatomical sites of a novel assessment tool intended for clinical evaluation of patients with extensive skin field cancerization.

BACKGROUND: A range of 'field-directed' treatments is available for the management of extensive skin field cancerization (ESFC), but to date, the only validated objective quantitative tools are limited to assessment of actinic keratoses (AKs) affecting the head. AIMS: To develop a versatile quantitative instrument for objective clinical assessment of ESFC and perform initial internal validation across multiple anatomical zones. METHODS: The study comprised instrument development, pilot testing and instrument refinement and two rounds of reliability and inter-rater validation testing. The study was noninterventional and used a convenience sample of de-identified patient photographs selected based on preset criteria. An expert panel developed the instrument and scoring system via a modified Delphi voting process. A sample of 16 healthcare professionals from multiple specialties undertook the pilot testing, and a panel of seven dermatologists were involved in validation testing. Validation was determined by assessment of overall inter-rater agreement using Gwet chance-corrected agreement coefficients (ACs). RESULTS: The instrument produced, called the Method for Assessing Skin Cancer and Keratoses™ (MASCK™), comprises the Skin Field Cancerization Index (SFCIndex), derived from area of skin involvement and AKs (number and thickness), a global assessment score and a cancer-in-zone score, and uses Likert scales for quantitative scoring. The SFCIndex is a composite score comprising the number and thickness of AKs multiplied by area of skin involvement. ACs for the SFCIndex components, the overall SFCIndex score and the global assessment score were > 0.80 (rated 'almost perfect') while the AC for the cancer-in-zone metric was lower (0.33, rated 'fair'). Internal consistency was demonstrated via positive correlation between the overall SFCIndex score and the global assessment score. CONCLUSIONS: Our study found near-perfect agreement in inter-rater reliability when using MASCK to assess the severity of ESFC in multiple anatomical sites. Further validation of this novel instrument is planned to specifically assess its reliability, utility and feasibility in clinical practice.

Uncertainty quantification in classical molecular dynamics.

Molecular dynamics simulation is now a widespread approach for understanding complex systems on the atomistic scale. It finds applications from physics and chemistry to engineering, life and medical science. In the last decade, the approach has begun to advance from being a computer-based means of rationalizing experimental observations to producing apparently credible predictions for a number of real-world applications within industrial sectors such as advanced materials and drug discovery. However, key aspects concerning the reproducibility of the method have not kept pace with the speed of its uptake in the scientific community. Here, we present a discussion of uncertainty quantification for molecular dynamics simulation designed to endow the method with better error estimates that will enable it to be used to report actionable results. The approach adopted is a standard one in the field of uncertainty quantification, namely using ensemble methods, in which a sufficiently large number of replicas are run concurrently, from which reliable statistics can be extracted. Indeed, because molecular dynamics is intrinsically chaotic, the need to use ensemble methods is fundamental and holds regardless of the duration of the simulations performed. We discuss the approach and illustrate it in a range of applications from materials science to ligand-protein binding free energy estimation. This article is part of the theme issue 'Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantification in silico'.

A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies.

While a wide range of treatments exist for actinic keratosis and skin field cancerisation, the long-term benefits of the most common topical therapies are poorly defined. This report reviews the efficacy of the most commonly used topical therapies to treat regional or field lesions. Limited clinical and histopathological data are available on clearance rates at 12 months post-treatment for the most commonly used agents, with varied outcome measures making any comparison difficult. In general, total field clearance rates at 12 months are suboptimal for the most commonly employed agents. Given the increasing incidence of actinic keratosis and skin field cancerisation due to an ageing population, further research into the efficacy of therapies is critical to guide treatment choice.

Caught between Scylla and Charybdis: How Economic Stressors and Occupational Risk Factors Influence Workers' Occupational Health Reactions to COVID-19.

Workers and their families bear much of the economic burden of COVID-19. Even though they have declined somewhat, unemployment rates are considerably higher than before the start of the pandemic. Many workers also face uncertainty about their future employment prospects and increasing financial strain. At the same time, the workplace is a common source of transmission of COVID-19 and many jobs previously seen as relatively safe are now viewed as potentially hazardous. Thus, many workers face dual threats of economic stress and COVID-19 exposure. This paper develops a model of workers' responses to these dual threats, including risk perception and resource depletion as mediating factors that influence the relationship of economic stress and occupational risk factors with COVID-19 compliance-related attitudes, safe behavior at work, and physical and mental health outcomes. The paper also describes contextual moderators of these relationships at the individual, unit, and regional level. Directions for future research are discussed.

Modeling Nanostructure in Graphene Oxide: Inhomogeneity and the Percolation Threshold.

Graphene oxide (GO) is an amorphous 2D material, which has found widespread use in the fields of chemistry, physics, and materials science due to its similarity to graphene with the benefit of being far easier to synthesize and process. However, the standard of GO characterization is very poor because its structure is irregular, being sensitive to the preparation method, and it has a propensity to transform due to its reactive nature. Atomistic simulations of GO are common, but the nanostructure in these simulations is often based on little evidence or thought. We have written a computer program to generate graphene oxide nanostructures for general purpose atomistic simulation based on theoretical and experimental evidence. The structures generated offer a significant improvement to the current standard of randomly placed oxidized functional groups and successfully recreate the two-phase nature of oxidized and unoxidized graphene domains observed in microscopy experiments. Using this model, we reveal new features of GO structure and predict that a critical point in the oxidation reaction exists as the oxidized region reaches a percolation threshold. Even by a conservative estimate, we show that, if the carbon to oxygen ratio is kept above 6, a continuous aromatic network will remain, preserving many of graphene's desirable properties, irrespective of the oxidation method or the size distribution of graphene sheets. This is an experimentally achievable degree of oxidation and should aid better GO synthesis for many applications.

Micromechanical exfoliation of graphene on the atomistic scale.

Mechanical exfoliation techniques are widely used to create high quality graphene samples for analytical use. Increasingly, mechanical methods are used to create large quantities of graphene, yet there is surprisingly little molecular insight into the mechanisms involved. We study the exfoliation of graphene with sticky tape using molecular dynamics. This is made possible by using a recently developed molecular dynamics forcefield, GraFF, to represent graphene's dispersion interactions. For nano-sized flakes we observe two different mechanisms depending on the polymer-adhesive used. A peeling mechanism which mixes shearing and normal mode exfoliation promotes synthesis of graphene rather than many-layered graphite. Armed with this new chemical insight we discuss the experimental methods that could preferentially produce graphene by mechanical exfoliation. We also introduce a mathematical model describing the repeated exfoliation of graphite.

Visualizing Facet-Dependent Hydrogenation Dynamics in Individual Palladium Nanoparticles.

Surface faceting in nanoparticles can profoundly impact the rate and selectivity of chemical transformations. However, the precise role of surface termination can be challenging to elucidate because many measurements are performed on ensembles of particles and do not have sufficient spatial resolution to observe reactions at the single and subparticle level. Here, we investigate solute intercalation in individual palladium hydride nanoparticles with distinct surface terminations. Using a combination of diffraction, electron energy loss spectroscopy, and dark-field contrast in an environmental transmission electron microscope (TEM), we compare the thermodynamics and directly visualize the kinetics of 40-70 nm {100}-terminated cubes and {111}-terminated octahedra with approximately 2 nm spatial resolution. Despite their distinct surface terminations, both particle morphologies nucleate the new phase at the tips of the particle. However, whereas the hydrogenated phase-front must rotate from [111] to [100] to propagate in cubes, the phase-front can propagate along the [100], [11̅0], and [111] directions in octahedra. Once the phase-front is established, the interface propagates linearly with time and is rate-limited by surface-to-subsurface diffusion and/or the atomic rearrangements needed to accommodate lattice strain. Following nucleation, both particle morphologies take approximately the same time to reach equilibrium, hydrogenating at similar pressures and without equilibrium phase coexistence. Our results highlight the importance of low-coordination number sites and strain, more so than surface faceting, in governing solute-driven reactions.

Designing Boron Nitride Islands in Carbon Materials for Efficient Electrochemical Synthesis of Hydrogen Peroxide.

Heteroatom-doped carbons have drawn increasing research interest as catalysts for various electrochemical reactions due to their unique electronic and surface structures. In particular, co-doping of carbon with boron and nitrogen has been shown to provide significant catalytic activity for oxygen reduction reaction (ORR). However, limited experimental work has been done to systematically study these materials, and much remains to be understood about the nature of the active site(s), particularly with regards to the factors underlying the activity enhancements of these boron-carbon-nitrogen (BCN) materials. Herein, we prepare several BCN materials experimentally with a facile and controlled synthesis method, and systematically study their electrochemical performance. We demonstrate the existence of h-BN domains embedded in the graphitic structures of these materials using X-ray spectroscopy. These synthesized structures yield higher activity and selectivity toward the 2e- ORR to H2O2 than structures with individual B or N doping. We further employ density functional theory calculations to understand the role of a variety of h-BN domains within the carbon lattice for the ORR and find that the interface between h-BN domains and graphene exhibits unique catalytic behavior that can preferentially drive the production of H2O2. To the best of our knowledge, this is the first example of h-BN domains in carbon identified as a novel system for the electrochemical production of H2O2.

Nucleic and Amino Acid Sequences Support Structure-Based Viral Classification.

Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome and capsid and between individual capsid proteins (i.e., capsid architecture) are intimate and are expected to be characterized by strong evolutionary conservation. For this reason, a capsid structure-based viral classification has been proposed as a way to bring order to the viral universe. The seeming lack of sufficient sequence similarity to reproduce this classification has made it difficult to reject structural convergence as the basis for the classification. We reinvestigate whether the structure-based classification for viral coat proteins making icosahedral virus capsids is in fact supported by previously undetected sequence similarity. Since codon choices can influence nascent protein folding cotranslationally, we searched for both amino acid and nucleotide sequence similarity. To demonstrate the sensitivity of the approach, we identify a candidate gene for the pandoravirus capsid protein. We show that the structure-based classification is strongly supported by amino acid and also nucleotide sequence similarities, suggesting that the similarities are due to common descent. The correspondence between structure-based and sequence-based analyses of the same proteins shown here allow them to be used in future analyses of the relationship between linear sequence information and macromolecular function, as well as between linear sequence and protein folds.IMPORTANCE Viral capsids protect nucleic acid genomes, which in turn encode capsid proteins. This tight coupling of protein shell and nucleic acids, together with strong functional constraints on capsid protein folding and architecture, leads to the hypothesis that capsid protein-coding nucleotide sequences may retain signatures of ancient viral evolution. We have been able to show that this is indeed the case, using the major capsid proteins of viruses forming icosahedral capsids. Importantly, we detected similarity at the nucleotide level between capsid protein-coding regions from viruses infecting cells belonging to all three domains of life, reproducing a previously established structure-based classification of icosahedral viral capsids.

Rapid genome reshaping by multiple-gene loss after whole-genome duplication in teleost fish suggested by mathematical modeling.

Whole-genome duplication (WGD) is believed to be a significant source of major evolutionary innovation. Redundant genes resulting from WGD are thought to be lost or acquire new functions. However, the rates of gene loss and thus temporal process of genome reshaping after WGD remain unclear. The WGD shared by all teleost fish, one-half of all jawed vertebrates, was more recent than the two ancient WGDs that occurred before the origin of jawed vertebrates, and thus lends itself to analysis of gene loss and genome reshaping. Using a newly developed orthology identification pipeline, we inferred the post-teleost-specific WGD evolutionary histories of 6,892 protein-coding genes from nine phylogenetically representative teleost genomes on a time-calibrated tree. We found that rapid gene loss did occur in the first 60 My, with a loss of more than 70-80% of duplicated genes, and produced similar genomic gene arrangements within teleosts in that relatively short time. Mathematical modeling suggests that rapid gene loss occurred mainly by events involving simultaneous loss of multiple genes. We found that the subsequent 250 My were characterized by slow and steady loss of individual genes. Our pipeline also identified about 1,100 shared single-copy genes that are inferred to have become singletons before the divergence of clupeocephalan teleosts. Therefore, our comparative genome analysis suggests that rapid gene loss just after the WGD reshaped teleost genomes before the major divergence, and provides a useful set of marker genes for future phylogenetic analysis.

Reconstructing solute-induced phase transformations within individual nanocrystals.

Strain and defects can significantly impact the performance of functional nanomaterials. This effect is well exemplified by energy storage systems, in which structural changes such as volume expansion and defect generation govern the phase transformations associated with charging and discharging. The rational design of next-generation storage materials therefore depends crucially on understanding the correlation between the structure of individual nanoparticles and their solute uptake and release. Here, we experimentally reconstruct the spatial distribution of hydride phases within individual palladium nanocrystals during hydrogen absorption, using a combination of electron spectroscopy, dark-field imaging, and electron diffraction in an environmental transmission electron microscope. We show that single-crystalline cubes and pyramids exhibit a uniform hydrogen distribution at equilibrium, whereas multiply twinned icosahedra exclude hydrogen from regions of high compressive strains. Our technique offers unprecedented insight into nanoscale phase transformations in reactive environments and can be extended to a variety of functional nanomaterials.

Synthesis and Characterization of Graphite-Encapsulated Iron Nanoparticles from Ball Milling-Assisted Low-Pressure Chemical Vapor Deposition.

Graphite-encapsulated Fe nanoparticles were synthesized using a combined method of high-energy ball milling and low-pressure chemical vapor deposition (LPCVD). Fe2O3 and graphite powders were milled to increase their surface areas and obtain a more homogeneous distribution. LPCVD was performed at a pressure of ~0.57 Torr in a tube furnace under a CH4/H2 atmosphere at 1050°C for 1 and 3 h. As-synthesized samples were purified in a 2 M HF solution. Characterization was performed using X-ray diffractometry (XRD), scanning and transmission electron microscopy (SEM and TEM) and alternating gradient magnetometry (AGM). XRD revealed the presence of body centered cubic (BCC) and face centered cubic (FCC) Fe phases without residual iron oxides. SEM confirmed the powders were better mixed and smaller after ball milling compared to mortar and pestle milled powders. High resolution TEM showed all nanoparticles had at least four and on average 16 graphitic layers, around an Fe core ranging from 20-300 nm. Magnetic measurements indicated that nanoparticles exhibit soft ferromagnetic behavior with low saturation magnetization (17-21 emu/g) and coercivity (110 Oe). A chemical stability test performed in a 2 M HCl solution showed that graphitic shells did not degrade, nor was there evidence of core dissolution or shell discontinuity.

Oxidation of Carbon Nanotubes in an Ionizing Environment.

In this work, we present systematic studies on how an illuminating electron beam which ionizes molecular gas species can influence the mechanism of carbon nanotube oxidation in an environmental transmission electron microscope (ETEM). We found that preferential attack of the nanotube tips is much more prevalent than for oxidation in a molecular gas environment. We establish the cumulative electron doses required to damage carbon nanotubes from 80 keV electron beam irradiation in gas versus in high vacuum. Our results provide guidelines for the electron doses required to study carbon nanotubes within or without a gas environment, to determine or ameliorate the influence of the imaging electron beam. This work has important implications for in situ studies as well as for the oxidation of carbon nanotubes in an ionizing environment such as that occurring during field emission.

Torsional Deformations in Subnanometer MoS Interconnecting Wires.

We use aberration-corrected transmission electron microscopy to track the real time atomic level torsional dynamics of subnanometer wires of MoS interconnecting monolayer regions of MoS2. An in situ heating holder is used inside the transmission electron microscope to raise the temperature of the sample to 400 °C to increase crystallization rates of the wires and reduce contamination effects. Frequent rotational twisting of the MoS wire is captured, demonstrating elastic torsional deformation of the MoS wires. We show that torsional rotations of the crystal structure of the MoS wires depend upon the specific atomic structure of the anchored sections of the suspended wire and the number of unit cells that make up the wire length. Elastic torsional flexibility of the MoS wires is revealed to help their self-adapting connectivity during the structural changes. Plastic torsional deformation is also seen for MoS wires that contain defects in their crystal structure, which produce small scale rotational disorder within the wires. Upon removal of the defects, the wire returns back to pristine form. These results provide detailed insights into how the atomic structure of the anchoring site significantly influences the nanowire configurations relative to the monolayered MoS2.

Necessary relations for nucleotide frequencies.

Genome composition analysis of di-, tri- and tetra-nucleotide frequencies is known to be evolutionarily informative, and useful in metagenomic studies, where binning of raw sequence data is often an important first step. Patterns appearing in genome composition analysis may be due to evolutionary processes or purely mathematical relations. For example, the total number of dinucleotides in a sequence is equal to the sum of the individual totals of the sixteen types of dinucleotide, and this is entirely independent of any assumptions made regarding mutation or selection, or indeed any physical or chemical process. Before any statistical analysis can be attempted, a knowledge of all necessary mathematical relations is required. I show that 25% of di-, tri- and tetra-nucleotide frequencies can be written as simple sums and differences of the remainder. The vast majority of organisms have circular genomes, for which these relations are exact and necessary. In the case of linear molecules, the absolute error is very nearly zero, and does not grow with contiguous sequence length. As a result of the new, necessary relations presented here, the foundations of the statistical analysis of di-, tri- and tetra-nucleotide frequencies, and k-mer analysis in general, need to be revisited.

Bad Versus Good, What Matters More on the Treatment Floor? Relationships of Positive and Negative Events With Nurses' Burnout and Engagement.

Many investigators have reported the stressful aspects of nursing; fewer have focused on nurses' positive work experiences. For this study, we developed a 2 × 2 typology of positive and negative events related to the tasks of nursing work and the social and organizational context of that work: successes, supports, constraints, and conflicts. We hypothesized that positive events would predict engagement, negative events would predict burnout, and negative events would be more strongly related to both burnout and engagement. In secondary analyses of data from 310 acute care nurses who completed survey measures of workplace events at one time point and burnout and engagement measures approximately eight months later, regression results indicated that both positive and negative work events contributed to engagement, whereas only negative events were related to burnout. The results of dominance analyses established that constraints and conflicts more strongly predicted burnout than did supports and successes. Additionally, consistent with a "bad is stronger than good" perspective, the strongest predictor of engagement was lower constraints, although successes, supports, and conflicts also predicted engagement.