Structure of Graphene Grown on Cu(111): X-Ray Standing Wave Measurement and Density Functional Theory Prediction.

We report the quantitative adsorption structure of pristine graphene on Cu(111) determined using the normal incidence x-ray standing wave technique. The experiments constitute an important benchmark reference for the development of density functional theory approximations able to capture long-range dispersion interactions. Electronic structure calculations based on many-body dispersion-inclusive density functional theory are able to accurately predict the absolute measure and variation of adsorption height when the coexistence of multiple moiré superstructures is considered. This provides a structural model consistent with scanning probe microscopy results.

Probing the role of surface termination in the adsorption of azupyrene on copper.

The role of the inorganic substrate termination, within the organic-inorganic interface, has been well studied for systems that contain strong localised bonding. However, how varying the substrate termination affects coordination to delocalised electronic states, like that found in aromatic molecules, is an open question. Azupyrene, a non-alternant polycyclic aromatic hydrocarbon, is known to bind strongly to metal surfaces through its delocalised π orbitals, thus yielding an ideal probe into delocalised surface-adsorbate interactions. Normal incidence X-ray standing wave (NIXSW) measurements and density functional theory calculations are reported for the adsorption of azupyrene on the (111), (110) and (100) surface facets of copper to investigate the dependence of the adsorption structure on the substrate termination. Structural models based on hybrid density functional theory calculations with non-local many-body dispersion yield excellent agreement with the experimental NIXSW results. No statistically significant difference in the azupyrene adsorption height was observed between the (111) and (100) surfaces. On the Cu(110) surface, the molecule was found to adsorb 0.06 ± 0.04 Å closer to the substrate than on the other surface facets. The most energetically favoured adsorption site on each surface, as determined by DFT, is subtly different, but in each case involved a configuration where the aromatic rings were centred above a hollow site, consistent with previous reports for the adsorption of small aromatic molecules on metal surfaces.

Group A Streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation.

Group A Streptococcus (GAS) infection is associated with multiple clinical sequelae, including different subtypes of psoriasis. Such post-streptococcal disorders have been long known but are largely unexplained. CD1a is expressed at constitutively high levels by Langerhans cells and presents lipid antigens to T cells, but the potential relevance to GAS infection has not been studied. Here, we investigated whether GAS-responsive CD1a-restricted T cells contribute to the pathogenesis of psoriasis. Healthy individuals had high frequencies of circulating and cutaneous GAS-responsive CD4+ and CD8+ T cells with rapid effector functions, including the production of interleukin-22 (IL-22). Human skin and blood single-cell CITE-seq analyses of IL-22-producing T cells showed a type 17 signature with proliferative potential, whereas IFN-γ-producing T cells displayed cytotoxic T lymphocyte characteristics. Furthermore, individuals with psoriasis had significantly higher frequencies of circulating GAS-reactive T cells, enriched for markers of activation, cytolytic potential, and tissue association. In addition to responding to GAS, subsets of expanded GAS-reactive T cell clones/lines were found to be autoreactive, which included the recognition of the self-lipid antigen lysophosphatidylcholine. CD8+ T cell clones/lines produced cytolytic mediators and lysed infected CD1a-expressing cells. Furthermore, we established cutaneous models of GAS infection in a humanized CD1a transgenic mouse model and identified enhanced and prolonged local and systemic inflammation, with resolution through a psoriasis-like phenotype. Together, these findings link GAS infection to the CD1a pathway and show that GAS infection promotes the proliferation and activation of CD1a-autoreactive T cells, with relevance to post-streptococcal disease, including the pathogenesis and treatment of psoriasis.

Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial.

BACKGROUND: Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS: After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, -0.07%; 95% CI, -3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS: Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).

N-Heterocyclic Carbenes: Molecular Porters of Surface Mounted Ru-Porphyrins.

Ru-porphyrins act as convenient pedestals for the assembly of N-heterocyclic carbenes (NHCs) on solid surfaces. Upon deposition of a simple NHC ligand on a close packed Ru-porphyrin monolayer, an extraordinary phenomenon can be observed: Ru-porphyrin molecules are transferred from the silver surface to the next molecular layer. We have investigated the structural features and dynamics of this portering process and analysed the associated binding strengths and work function changes. A rearrangement of the molecular layer is induced by the NHC uptake: the NHC selective binding to the Ru causes the ejection of whole porphyrin molecules from the molecular layer on silver to the layer on top. This reorganisation can be reversed by thermally induced desorption of the NHC ligand. We anticipate that the understanding of such mass transport processes will have crucial implications for the functionalisation of surfaces with carbenes.

Selective hydrogenation of graphene on Ir(111): an X-ray standing wave study.

A combined high resolution X-ray photoelectron spectroscopy and X-ray standing wave study into the adsorption structure of hydrogenated graphene on Ir(111) is presented. By exploiting the unique absorption profiles and significant modulations in signal intensity found within the X-ray standing wave results, we refine the fitting of the C 1s X-ray photoelectron spectra, allowing us to disentangle the contributions from hydrogenation of graphene in different high-symmetry regions of the moiré supercell. We clearly demonstrate that hydrogenation in the FCC regions results in the formation of a graphane-like structure, giving a standalone component that is separated from the component assigned to the similar structure in the HCP regions. The contribution from dimer structures in the ATOP regions is found to be minor or negligible. This is in contrast to the previous findings where a dimer structure was assumed to contribute significantly to the sp3 part of the C 1s spectra. The corrugation of the remaining pristine parts of the H-graphene is shown to increase with the H coverage, reflecting an increasing number and size of pinning centers of the graphene to the Ir(111) substrate with increasing H exposure.

Direct Experimental Evidence for Substrate Adatom Incorporation into a Molecular Overlayer.

While the phenomenon of metal substrate adatom incorporation into molecular overlayers is generally believed to occur in several systems, the experimental evidence for this relies on the interpretation of scanning tunneling microscopy (STM) images, which can be ambiguous and provides no quantitative structural information. We show that surface X-ray diffraction (SXRD) uniquely provides unambiguous identification of these metal adatoms. We present the results of a detailed structural study of the Au(111)-F4TCNQ system, combining surface characterization by STM, low-energy electron diffraction, and soft X-ray photoelectron spectroscopy with quantitative experimental structural information from normal incidence X-ray standing wave (NIXSW) and SXRD, together with dispersion-corrected density functional theory (DFT) calculations. Excellent agreement is found between the NIXSW data and the DFT calculations regarding the height and conformation of the adsorbed molecule, which has a twisted geometry rather than the previously supposed inverted bowl shape. SXRD measurements provide unequivocal evidence for the presence and location of Au adatoms, while the DFT calculations show this reconstruction to be strongly energetically favored.

Thermodynamic Driving Forces for Substrate Atom Extraction by Adsorption of Strong Electron Acceptor Molecules.

A quantitative structural investigation is reported, aimed at resolving the issue of whether substrate adatoms are incorporated into the monolayers formed by strong molecular electron acceptors deposited onto metallic electrodes. A combination of normal-incidence X-ray standing waves, low-energy electron diffraction, scanning tunnelling microscopy, and X-ray photoelectron spectroscopy measurements demonstrate that the systems TCNQ and F4TCNQ on Ag(100) lie at the boundary between these two possibilities and thus represent ideal model systems with which to study this effect. A room-temperature commensurate phase of adsorbed TCNQ is found not to involve Ag adatoms, but to adopt an inverted bowl configuration, long predicted but not previously identified experimentally. By contrast, a similar phase of adsorbed F4TCNQ does lead to Ag adatom incorporation in the overlayer, the cyano end groups of the molecule being twisted relative to the planar quinoid ring. Density functional theory (DFT) calculations show that this behavior is consistent with the adsorption energetics. Annealing of the commensurate TCNQ overlayer phase leads to an incommensurate phase that does appear to incorporate Ag adatoms. Our results indicate that the inclusion (or exclusion) of metal atoms into the organic monolayers is the result of both thermodynamic and kinetic factors.

WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial.

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Quantitative Insights into the Adsorption Structure of Diindeno[1,2-a;1',2'-c]fluorene-5,10,15-trione (Truxenone) on a Cu(111) Surface Using X-ray Standing Waves.

The adsorption structure of truxenone on Cu(111) was determined quantitatively using normal-incidence X-ray standing waves. The truxenone molecule was found to chemisorb on the surface, with all adsorption heights of the dominant species on the surface less than ∼2.5 Å. The phenyl backbone of the molecule adsorbs mostly parallel to the underlying surface, with an adsorption height of 2.32 ± 0.08 Å. The C atoms bound to the carbonyl groups are located closer to the surface at 2.15 ± 0.10 Å, a similar adsorption height to that of the chemisorbed O species; however, these O species were found to adsorb at two different adsorption heights, 1.96 ± 0.08 and 2.15 ± 0.06 Å, at a ratio of 1:2, suggesting that on average, one O atom per adsorbed truxenone molecule interacts more strongly with the surface. The adsorption geometry determined herein is an important benchmark for future theoretical calculations concerning both the interaction with solid surfaces and the electronic properties of a molecule with electron-accepting properties for applications in organic electronic devices.

Evolution of adsorption heights in the on-surface synthesis and decoupling of covalent organic networks on Ag(111) by normal-incidence X-ray standing wave.

Structural characterization in on-surface synthesis is primarily carried out by Scanning Probe Microscopy (SPM) which provides high lateral resolution. Yet, important fresh perspectives on surface interactions and molecular conformations are gained from adsorption heights that remain largely inaccessible to SPM, but can be precisely measured with both elemental and chemical sensitivity by Normal-Incidence X-ray Standing Wave (NIXSW) analysis. Here, we study the evolution of adsorption heights in the on-surface synthesis and post-synthetic decoupling of porous covalent triazine-phenylene networks obtained from 2,4,6-tris(4-bromophenyl)-1,3,5-triazine (TBPT) precursors on Ag(111). Room temperature deposition of TBPT and mild annealing to ∼150 °C result in full debromination and formation of organometallic intermediates, where the monomers are linked into reticulated networks by C-Ag-C bonds. Topologically identical covalent networks comprised of triazine vertices that are interconnected by biphenyl units are obtained by a thermally activated chemical transformation of the organometallic intermediates. Exposure to iodine vapor facilitates decoupling by intercalation of an iodine monolayer between the covalent networks and the Ag(111) surface. Accordingly, Scanning Tunneling Microscopy (STM), X-ray Photoelectron Spectroscopy (XPS) and NIXSW experiments are carried out for three successive sample stages: organometallic intermediates, covalent networks directly on Ag(111) and after decoupling. NIXSW analysis facilitates the determination of adsorption heights of chemically distinct carbon species, i.e. in the phenyl and triazine rings, and also for the organometallic carbon atoms. Thereby, molecular conformations are assessed for each sample stage. The interpretation of experimental results is informed by Density Functional Theory (DFT) calculations, providing a consistent picture of adsorption heights and molecular deformations in the networks that result from the interplay between steric hindrance and surface interactions. Quantitative adsorption heights, i.e. vertical distances between adsorbates and surface, provide detailed insight into surface interactions, but are underexplored in on-surface synthesis. In particular, the direct comparison with an in situ prepared decoupled state unveils the surface influence on the network structure, and shows that iodine intercalation is a powerful decoupling strategy.

Experimental measurement and prediction of ionic liquid ionisation energies.

Ionic liquid (IL) valence electronic structure provides key descriptors for understanding and predicting IL properties. The ionisation energies of 60 ILs are measured and the most readily ionised valence state of each IL (the highest occupied molecular orbital, HOMO) is identified using a combination of X-ray photoelectron spectroscopy (XPS) and synchrotron resonant XPS. A structurally diverse range of cations and anions were studied. The cation gave rise to the HOMO for nine of the 60 ILs presented here, meaning it is energetically more favourable to remove an electron from the cation than the anion. The influence of the cation on the anion electronic structure (and vice versa) were established; the electrostatic effects are well understood and demonstrated to be consistently predictable. We used this knowledge to make predictions of both ionisation energy and HOMO identity for a further 516 ILs, providing a very valuable dataset for benchmarking electronic structure calculations and enabling the development of models linking experimental valence electronic structure descriptors to other IL properties, e.g. electrochemical stability. Furthermore, we provide design rules for the prediction of the electronic structure of ILs.

Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.

Pre-existing asthma as a comorbidity does not modify cytokine responses and severity of COVID-19.

BACKGROUND: A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma. METHODS: Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups. RESULTS: Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8. CONCLUSIONS: Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality.

Conformational Control of Chemical Reactivity for Surface-Confined Ru-Porphyrins.

We assess the crucial role of tetrapyrrole flexibility in the CO ligation to distinct Ru-porphyrins supported on an atomistically well-defined Ag(111) substrate. Our systematic real-space visualisation and manipulation experiments with scanning tunnelling microscopy directly probe the ligation, while bond-resolving atomic force microscopy and X-ray standing-wave measurements characterise the geometry, X-ray and ultraviolet photoelectron spectroscopy the electronic structure, and temperature-programmed desorption the binding strength. Density-functional-theory calculations provide additional insight into the functional interface. We unambiguously demonstrate that the substituents regulate the interfacial conformational adaptability, either promoting or obstructing the uptake of axial CO adducts.

Assembly and Manipulation of a Prototypical N-Heterocyclic Carbene with a Metalloporphyrin Pedestal on a Solid Surface.

The controlled arrangement of N-heterocyclic carbenes (NHCs) on solid surfaces is a current challenge of surface functionalization. We introduce a strategy of using Ru porphyrins in order to control both the orientation and lateral arrangement of NHCs on a planar surface. The coupling of the NHC to the Ru porphyrin is a facile process which takes place on the interface: we apply NHCs as functional, robust pillars on well-defined, preassembled Ru porphyrin monolayers on silver and characterize these interfaces with atomic precision via a battery of experimental techniques and theoretical considerations. The NHCs assemble at room temperature modularly and reversibly on the Ru porphyrin arrays. We demonstrate a selective and complete functionalization of the Ru centers. With its binding, the NHC modifies the interaction of the Ru porphyrin with the Ag surface, displacing the Ru atom by 1 Å away from the surface. This arrangement of NHCs allows us to address individual ligands by controlled manipulation with the tip of a scanning tunneling microscope, creating patterned structures on the nanometer scale.

Determination of the preferred reaction pathway of acetophenone on Si(001) using photoelectron diffraction.

The adsorption configurations of a technologically relevant model organic adsorbate on the silicon (001) surface were studied using energy scanned x-ray photoelectron diffraction (PhD). Previous work has established the existence of an interesting vertically-aligned ('flagpole') configuration, where the acetophenone attaches to Si(001) via the acetyl group carbon and oxygen atoms. Density functional theory calculations have predicted two energetically similar variants of this structure, where the phenyl ring is orientated parallel or perpendicular to the rows of silicon dimers on this reconstructed surface. However, previously published experimental measurements, including scanning tunnelling microscopy, x-ray photoelectron spectroscopy, and near-edge x-ray absorption fine structure investigations were unable to distinguish between these two configurations. Here, we apply the unique experimental capabilities of the PhD technique to this system and demonstrate that the dominant adsorption configuration has the phenyl ring parallel to the dimer rows (the end-bridge structure). This information in turn facilitates the determination of the dominant reaction pathway for acetophenone on Si(001), which has remained elusive until now. Information about subtle preferences in reaction pathways that affect the alignment and orientation of organic adsorbates such as acetophenone on technologically-relevant semiconductor surfaces such as Si(001) is critical for the fabrication of future atomically-precise atomic and molecular-scale electronic devices utilising the organic-silicon interface, and this work demonstrates the unique and complementary capabilities of PhD for providing this information.

Chemical shielding of H2O and HF encapsulated inside a C60 cage.

Molecular surgery provides the opportunity to study relatively large molecules encapsulated within a fullerene cage. Here we determine the location of an H2O molecule isolated within an adsorbed buckminsterfullerene cage, and compare this to the intrafullerene position of HF. Using normal incidence X-ray standing wave (NIXSW) analysis, coupled with density functional theory and molecular dynamics simulations, we show that both H2O and HF are located at an off-centre position within the fullerene cage, caused by substantial intra-cage electrostatic fields generated by surface adsorption of the fullerene. The atomistic and electronic structure simulations also reveal significant internal rotational motion consistent with the NIXSW data. Despite this substantial intra-cage interaction, we find that neither HF or H2O contribute to the endofullerene frontier orbitals, confirming the chemical isolation of the encapsulated molecules. We also show that our experimental NIXSW measurements and theoretical data are best described by a mixed adsorption site model.

Growth and electronic properties of bi- and trilayer graphene on Ir(111).

Interesting electronic properties arise in vertically stacked graphene sheets, some of which can be controlled by mutual orientation of the adjacent layers. In this study, we investigate the MBE grown multilayer graphene on Ir(111) by means of STM, LEED and XPS and we examine the influence of the substrate on the geometric and electronic properties of bilayer graphene by employing XSW and ARPES measurements. We find that the MBE method does not limit the growth to two graphene layers and that the wrinkles, which arise through extended carbon deposition, play a crucial role in the multilayer growth. We also find that the bilayer and trilayer graphene sheets have graphitic-like properties in terms of the separation between the two layers and their stacking. The presence of the iridium substrate imposes a periodic potential induced by the moiré pattern that was found to lead to the formation of replica bands and minigaps in bilayer graphene. From tight-binding fits to our ARPES data we find that band renormalization takes place in multilayer graphene due to a weaker coupling of the upper-most graphene layer to the iridium substrate.

Alkali Doping Leads to Charge-Transfer Salt Formation in a Two-Dimensional Metal-Organic Framework.

Efficient charge transfer across metal-organic interfaces is a key physical process in modern organic electronics devices, and characterization of the energy level alignment at the interface is crucial to enable a rational device design. We show that the insertion of alkali atoms can significantly change the structure and electronic properties of a metal-organic interface. Coadsorption of tetracyanoquinodimethane (TCNQ) and potassium on a Ag(111) surface leads to the formation of a two-dimensional charge transfer salt, with properties quite different from those of the two-dimensional Ag adatom TCNQ metal-organic framework formed in the absence of K doping. We establish a highly accurate structural model by combination of quantitative X-ray standing wave measurements, scanning tunnelling microscopy, and density-functional theory (DFT) calculations. Full agreement between the experimental data and the computational prediction of the structure is only achieved by inclusion of a charge-transfer-scaled dispersion correction in the DFT, which correctly accounts for the effects of strong charge transfer on the atomic polarizability of potassium. The commensurate surface layer formed by TCNQ and K is dominated by strong charge transfer and ionic bonding and is accompanied by a structural and electronic decoupling from the underlying metal substrate. The consequence is a significant change in energy level alignment and work function compared to TCNQ on Ag(111). Possible implications of charge-transfer salt formation at metal-organic interfaces for organic thin-film devices are discussed.