Trapped O2 and the origin of voltage fade in layered Li-rich cathodes.

Oxygen redox cathodes, such as Li1.2Ni0.13Co0.13Mn0.54O2, deliver higher energy densities than those based on transition metal redox alone. However, they commonly exhibit voltage fade, a gradually diminishing discharge voltage on extended cycling. Recent research has shown that, on the first charge, oxidation of O2- ions forms O2 molecules trapped in nano-sized voids within the structure, which can be fully reduced to O2- on the subsequent discharge. Here we show that the loss of O-redox capacity on cycling and therefore voltage fade arises from a combination of a reduction in the reversibility of the O2-/O2 redox process and O2 loss. The closed voids that trap O2 grow on cycling, rendering more of the trapped O2 electrochemically inactive. The size and density of voids leads to cracking of the particles and open voids at the surfaces, releasing O2. Our findings implicate the thermodynamic driving force to form O2 as the root cause of transition metal migration, void formation and consequently voltage fade in Li-rich cathodes.

Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation.

BACKGROUND: Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology. METHODS: Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min). RESULTS: A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity. CONCLUSIONS: Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies.

RNA Bind-n-Seq: quantitative assessment of the sequence and structural binding specificity of RNA binding proteins.

Specific protein-RNA interactions guide posttranscriptional gene regulation. Here, we describe RNA Bind-n-Seq (RBNS), a method that comprehensively characterizes sequence and structural specificity of RNA binding proteins (RBPs), and its application to the developmental alternative splicing factors RBFOX2, CELF1/CUGBP1, and MBNL1. For each factor, we recovered both canonical motifs and additional near-optimal binding motifs. RNA secondary structure inhibits binding of RBFOX2 and CELF1, while MBNL1 favors unpaired Us but tolerates C/G pairing in motifs containing UGC and/or GCU. Dissociation constants calculated from RBNS data using a novel algorithm correlated highly with values measured by surface plasmon resonance. Motifs identified by RBNS were conserved, were bound and active in vivo, and distinguished the subset of motifs enriched by CLIP-Seq that had regulatory activity. Together, our data demonstrate that RBNS complements crosslinking-based methods and show that in vivo binding and activity of these splicing factors is driven largely by intrinsic RNA affinity.

A cardiopulmonary bypass strategy to support a patient with vein of Galen malformation.

We present a dissection of the patent ductus arteriosus and pulmonary artery for surgical repair utilising cardiopulmonary bypass in the setting of vein of Galen malformation. Several strategies were employed to attenuate the cerebral shunt including pH-stat, high cardiac index, restrictive venous drainage, continuous ventilation and deep hypothermic circulatory arrest. The patient recovered from surgery with no apparent neurological sequelae.

Understanding the conversion mechanism and performance of monodisperse FeF2 nanocrystal cathodes.

The application of transition metal fluorides as energy-dense cathode materials for lithium ion batteries has been hindered by inadequate understanding of their electrochemical capabilities and limitations. Here, we present an ideal system for mechanistic study through the colloidal synthesis of single-crystalline, monodisperse iron(II) fluoride nanorods. Near theoretical capacity (570 mA h g-1) and extraordinary cycling stability (>90% capacity retention after 50 cycles at C/20) is achieved solely through the use of an ionic liquid electrolyte (1 m LiFSI/Pyr1,3FSI), which forms a stable solid electrolyte interphase and prevents the fusing of particles. This stability extends over 200 cycles at much higher rates (C/2) and temperatures (50 °C). High-resolution analytical transmission electron microscopy reveals intricate morphological features, lattice orientation relationships and oxidation state changes that comprehensively describe the conversion mechanism. Phase evolution, diffusion kinetics and cell failure are critically influenced by surface-specific reactions. The reversibility of the conversion reaction is governed by topotactic cation diffusion through an invariant lattice of fluoride anions and the nucleation of metallic particles on semicoherent interfaces. This new understanding is used to showcase the inherently high discharge rate capability of FeF2.

The Great Ormond Street Hospital immunoadsorption method for ABO-incompatible heart transplantation: a practical technique.

Traditionally, ABO-incompatible heart transplantation was accomplished using a plasma exchange technique to remove recipient plasma containing donor-incompatible anti-A/B isohaemagglutinins. However, this technique exposed patients to large volumes of allogeneic blood and blood products (up to three times the patient's circulating volume). In 2018, we published the first reported case of an ABO-incompatible heart transplant using an intraoperative immunoadsorption technique which minimises the exposure to blood products by specifically targeting anti-A/B isohaemagglutinins. We have subsequently used this technique in all children undergoing ABO-incompatible heart transplantation and become convinced of its efficacy in this population while observing no adverse effects. This article outlines the practical details required to perform the technique in order to avoid hyperacute rejection.

Chronic Ethanol Feeding in Mice Decreases Expression of Genes for Major Structural Bone Proteins in a Nox4-Independent Manner.

Bone loss in response to alcohol intake has previously been hypothesized to be mediated by excessive production of reactive oxygen species via NADPH oxidase (Nox) enzymes. Nox4 is one of several Nox enzymes expressed in bone. We investigated the role of Nox4 in the chondro-osteoblastic lineage of the long bones in mice during normal chow feeding and during chronic ethanol feeding for 90 days. We generated mice with a genotype (PrxCre +/- Nox4 fl/fl) allowing conditional knockout of Nox4 in the limb bud mesenchyme. Adult mice had 95% knockdown of Nox4 expression in the femoral shafts. For mice on regular chow, only whole-body Nox4 knockout mice had clearly increased cortical thickness and bone mineral density in the tibiae. When chronically fed a liquid diet with and without ethanol, conditional Nox4 knockout mice had slightly reduced dimensions of the cortical and trabecular regions of the tibiae (P < 0.1). The ethanol diet caused a significant reduction in cortical bone area and cortical thickness relative to a control diet without ethanol (P < 0.05). The ethanol diet further reduced gene expression of Frizzled related protein (Frzb), myosin heavy chain 3, and several genes encoding collagen and other major structural bone proteins (P < 0.05), whereas the Nox4 genotype had no effects on these genes. In conclusion, Nox4 expression from both mesenchymal and nonmesenchymal cell lineages appears to exert subtle effects on bone. However, chronic ethanol feeding reduces cortical bone mass and cortical gene expression of major structural bone proteins in a Nox4-independent manner. SIGNIFICANCE STATEMENT: Excessive alcohol intake contributes to osteopenia and osteoporosis, with oxidative stress caused by the activity of NADPH oxidases hypothesized to be a mediator. We tested the role of NADPH oxidase (Nox) 4 in osteoblast precursors in the long bones of mice with a conditional Nox4 knockout model. We found that Nox4 exerted effects independent of alcohol intake, and ethanol effects on bone were Nox4-independent.

Addressing the isomer cataloguing problem for nanopores in two-dimensional materials.

The presence of extended defects or nanopores in two-dimensional (2D) materials can change the electronic, magnetic and barrier membrane properties of the materials. However, the large number of possible lattice isomers of nanopores makes their quantitative study a seemingly intractable problem, confounding the interpretation of experimental and simulated data. Here we formulate a solution to this isomer cataloguing problem (ICP), combining electronic-structure calculations, kinetic Monte Carlo simulations, and chemical graph theory, to generate a catalogue of unique, most-probable isomers of 2D lattice nanopores. The results demonstrate remarkable agreement with precise nanopore shapes observed experimentally in graphene and show that the thermodynamic stability of a nanopore is distinct from its kinetic stability. Triangular nanopores prevalent in hexagonal boron nitride are also predicted, extending this approach to other 2D lattices. The proposed method should accelerate the application of nanoporous 2D materials by establishing specific links between experiment and theory/simulations, and by providing a much-needed connection between molecular design and fabrication.

Deep hypothermic extracorporeal membrane oxygenation cannula exchange in a child with necrotic pneumonia.

Necrotizing pneumonia can lead to respiratory insufficiency in previously healthy children. Extracorporeal membrane oxygenation can be used for hemodynamic salvage and subsequent lung rest awaiting recovery. We present a case of a child initially placed on veno-arterial extracorporeal membrane oxygenation and converted to veno-venous extracorporeal membrane oxygenation. This was done under deep hypothermia in the operating theater.

Atomic structure of defects and dopants in 2D layered transition metal dichalcogenides.

Layered transition metal dichalcogenides (TMDs) offer monolayer 2D systems with diverse properties that extend beyond what graphene alone can achieve. The properties of TMDs are heavily influenced by the atomic structure and in particular imperfects in the crystallinity in the form of vacancy defects, grain boundaries, cracks, impurity dopants, ripples and edge terminations. This review will cover the current knowledge of the detailed structural forms of some of the most intensively studied 2D TMDs, such as MoS2, WSe2, MoTe2, WTe2, NbSe2, PtSe2, and also covers MXenes. The review will utilize results achieved using state-of-the-art aberration corrected transmission electron microscopy, including annular dark-field scanning transmission electron microscopy (ADF-STEM) and electron energy loss spectroscopy (EELS), showing how elemental discrimination can be achieved to understand structure at a deep level. The review will also cover the impact of single atom substitutional dopants, such as Cr, V and Mn, and electron energy loss spectroscopy used to understand the local bonding configuration. It is expected that this review will provide an atomic level understanding of 2D TMDs with a connection to imperfections that can arise from chemical vapour deposition synthesis, intentional doping, rips and tears, dislocations, strain, polycrystallinity and confinement to nanoribbons.

An Adverse Event Analysis: Inadvertent Exsanguination Following Left Ventricular Assist Device Implantation in a Child.

Neurologic deficit subsequent to cardiac surgery remains a cause of postoperative morbidity and mortality. Although myriad risk factors for postoperative cognitive decline have been identified, their individual influence remains undefined. Although less emphasis is now placed on the heart lung machine as the major source of postoperative cognitive decline, the conduct of cardiopulmonary bypass and, in particular, the management of the bypass circuit remain key to patient safety. We present a case of inadvertent intraoperative exsanguination of a patient following open heart surgery for implantation of a left ventricular assist device. The patient suffered significant neurologic damage. However, the nature of the patient's cerebral injury indicated thromboembolism as the likely cause, rather than hypoxic-ischemic injury caused by hypoperfusion. Subsequent investigation of the incident identified several possible sources and potential causes of embolization to the brain that could not rule out the exsanguination event as a contributing factor.

Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay.

UPF1 is a DNA/RNA helicase with essential roles in nonsense-mediated mRNA decay (NMD) and embryonic development. How UPF1 regulates target abundance and the relationship between NMD and embryogenesis are not well understood. To explore how NMD shapes the embryonic transcriptome, we integrated genome-wide analyses of UPF1 binding locations, NMD-regulated gene expression, and translation in murine embryonic stem cells (mESCs). We identified over 200 direct UPF1 binding targets using crosslinking/immunoprecipitation-sequencing (CLIP-seq) and revealed a repression pathway that involves 3' UTR binding by UPF1 and translation but is independent of canonical targeting features involving 3' UTR length and stop codon placement. Interestingly, NMD targeting of this set of mRNAs occurs in other mouse tissues and is conserved in human. We also show, using ribosome footprint profiling, that actively translated upstream open reading frames (uORFs) are enriched in transcription factor mRNAs and predict mRNA repression by NMD, while poorly translated mRNAs escape repression. Together, our results identify novel NMD determinants and targets and provide context for understanding the impact of UPF1 and NMD on the mESC transcriptome.

Partial Dislocations in Graphene and Their Atomic Level Migration Dynamics.

We demonstrate the formation of partial dislocations in graphene at elevated temperatures of ≥500 °C with single atom resolution aberration corrected transmission electron microscopy. The partial dislocations spatially redistribute strain in the lattice, providing an energetically more favorable configuration to the perfect dislocation. Low-energy migration paths mediated by partial dislocation formation have been observed, providing insights into the atomistic dynamics of graphene during annealing. These results are important for understanding the high temperature plasticity of graphene and partial dislocation behavior in related crystal systems, such as diamond cubic materials.

Inflating graphene with atomic scale blisters.

Using 80 kV electron beam irradiation we have created graphene blister defects of additional carbon atoms incorporated into a graphene lattice. These structures are the antithesis of the vacancy defect with blister defects observed to contain up to six additional carbon atoms. We present aberration-corrected transmission electron microscopy data demonstrating the formation of a blister from an existing divacancy, together with further examples that undergo reconfiguration and annihilation under the electron beam. The relative stability of the observed variations of blister are discussed and considered in the context of previous calculations. It is shown that the blister defect is seldom found in isolation and is more commonly coupled with dislocations where it can act as an intermediate state, permitting dislocation core climb without the atom ejection from the graphene lattice required for nonconservative motion.

Stability and dynamics of the tetravacancy in graphene.

The relative prevalence of various configurations of the tetravacancy defect in monolayer graphene has been examined using aberration corrected transmission electron microscopy (TEM). It was found that the two most common structures are extended linear defect structures, with the 3-fold symmetric Y-tetravacancy seldom imaged, in spite of this being a low energy state. Using density functional theory and tight-binding molecular dynamics calculations, we have determined that our TEM observations support a dynamic model of the tetravacancy under electron irradiation, with Stone-Wales bond rotations providing a mechanism for defect relaxation into lowest energy configurations. The most prevalent tetravacancy structures, while not necessarily having the lowest formation energy, are found to have a local energy minimum in the overall energy landscape for tetravacancies, explaining their relatively high occurrence.

The role of the bridging atom in stabilizing odd numbered graphene vacancies.

Vacancy defects in graphene with an odd number of missing atoms, such as the trivacancy, have been imaged at atomic resolution using aberration corrected transmission electron microscopy. These defects are not just stabilized by simple bond reconstructions between under-coordinated carbon atoms, as exhibited by even vacancies such as the divacancy. Instead we have observed reconstructions consisting of under-coordinated bridging carbon atoms spanning the vacancy to saturate edge atoms. We report detailed studies of the effect of this bridging atom on the configuration of the trivacancy and higher order odd number vacancies, as well as its role in defect stabilization in amorphous systems. Theoretical analysis using density functional theory and tight-binding molecular dynamics calculations demonstrate that the bridging atom enables the low energy reconfiguration of these defect structures.

Atomic structure and dynamics of metal dopant pairs in graphene.

We present an atomic resolution structural study of covalently bonded dopant pairs in the lattice of monolayer graphene. Two iron (Fe) metal atoms that are covalently bonded within the graphene lattice are observed and their interaction with each other is investigated. The two metal atom dopants can form small paired clusters of varied geometry within graphene vacancy defects. The two Fe atoms are created within a 10 nm diameter predefined location in graphene by manipulating a focused electron beam (80 kV) on the surface of graphene containing an intentionally deposited Fe precursor reservoir. Aberration-corrected transmission electron microscopy at 80 kV has been used to investigate the atomic structure and real time dynamics of Fe dimers embedded in graphene vacancies. Four different stable structures have been observed; two variants of an Fe dimer in a graphene trivacancy, an Fe dimer embedded in two adjacent monovacancies and an Fe dimer trapped by a quadvacancy. According to spin-sensitive DFT calculations, these dimer structures all possess magnetic moments of either 2.00 or 4.00 µB. The dimer structures were found to evolve from an initial single Fe atom dopant trapped in a graphene vacancy.

Sensitivity of graphene edge states to surface adatom interactions.

Electron beam irradiation at 60 kV is used to open holes in graphene and expose fresh clean edges for further examination by electron energy loss spectroscopy (EELS) at the single atom level combined with scanning transmission electron microscopy (STEM). We show that light element surface adatoms attached on top of the edges of graphene influence the carbon K-edge EELS. A single nitrogen adatom on graphene was imaged by STEM and chemically identified by EELS. We also extend this study to small graphene nanoribbons, termed nanoconstrictions. The arrival of surface adatoms disrupt the detection of unique carbon edge states present in both single edges and in the nanoconstrictions. The spatial distribution of the EELS signals is also examined. These results show that edge states in graphene are highly sensitive to single atom functionalization and sheds light on their long-term stability.

Rippling graphene at the nanoscale through dislocation addition.

Ripples in graphene are an out-of-plane distortion that help stabilize suspended monolayer graphene. The introduction of disclinations and dislocations into the lattice of graphene is predicted to extensively ripple graphene to form "hillocks" to accommodate the strain in the system. Here, we confirm this theoretical prediction by intentionally introducing large numbers of dislocations into a predefined area of pristine monolayer graphene by scanning focused electron beam irradiation and imaging the rippled atomic lattice structure with aberration-corrected transmission electron microscopy. Hillocks are observed and analyzed using geometric phase analysis to determine heights of ~0.5 nm. Time-dependent imaging shows the rippling is dynamic under the electron beam and can fluctuate between different structural configurations. This demonstrates a means of perturbing the structure of graphene in all three spatial dimensions with nanoscale precision.

Dynamics of single Fe atoms in graphene vacancies.

Focused electron beam irradiation has been used to create mono and divacancies in graphene within a defined area, which then act as trap sites for mobile Fe atoms initially resident on the graphene surface. Aberration-corrected transmission electron microscopy at 80 kV has been used to study the real time dynamics of Fe atoms filling the vacancy sites in graphene with atomic resolution. We find that the incorporation of a dopant atom results in pronounced displacements of the surrounding carbon atoms of up to 0.5 Å, which is in good agreement with density functional theory calculations. Once incorporated into the graphene lattice, Fe atoms can transition to adjacent lattice positions and reversibly switch their bonding between four and three nearest neighbors. The C atoms adjacent to the Fe atoms are found to be more susceptible to Stone-Wales type bond rotations with these bond rotations associated with changes in the dopant bonding configuration. These results demonstrate the use of controlled electron beam irradiation to incorporate dopants into the graphene lattice with nanoscale spatial control.