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Background Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions.

Background: Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods: For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings: We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation: Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding: Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions.

Evidence of strong photoelectron-valence electron (PEVE) interactions has been observed in the anion photoelectron (PE) spectra of several lanthanide suboxide clusters, which are exceptionally complex from an electronic structure standpoint and are strongly correlated systems. The PE spectrum of Gd2O-, which should have relatively simple electronic structure because of its half-filled 4f subshell, exhibits numerous electronic transitions. The electron affinity determined from the spectrum is 0.26 eV. The intensities of transitions to excited states increase relative to the lower-energy states with lower photon energy, which is consistent with shakeup transitions driven by time-dependent electron-neutral interactions. A group of intense spectral features that lie between electron binding energies of 0.7 and 2.3 eV are assigned to transitions involving detachment of an electron from outer-valence σu and σg orbitals that have large Gd 6s contributions. The spectra show parallel transition manifolds in general, which is consistent with detachment from these orbitals. However, several distinct perpendicular transitions are observed adjacent to several of the vertical transitions. A possible explanation invoking interaction between the ejected electron and the high-spin neutral is proposed. Specifically, the angular momentum of electrons ejected from σu or σg orbitals, which is l = 1, can switch to l = 0, 2 with an associated change in the Ms of the remnant neutral, which is spin-orbit coupling between a free electron and the spin of a neutral.

Photoelectron spectra of Gd2O2– obtained with photon energies ranging from 2.033 to 3.495 eV exhibit numerous close-lying neutral states with photon-energy-dependent relative intensities. Transitio...

Gamma-ray burst (GRB) data suggest that the jets from GRBs in the high redshift universe are more narrowly collimated than those at lower redshifts. This implies that we detect relatively fewer long GRB progenitor systems (i.e. massive stars) at high redshifts, because a greater fraction of GRBs have their jets pointed away from us. As a result, estimates of the star formation rate (from the GRB rate) at high redshifts may be diminished if this effect is not taken into account. In this paper, we estimate the star formation rate (SFR) using the observed GRB rate, accounting for an evolving jet opening angle. We find that the SFR in the early universe (z > 3) can be up to an order of magnitude higher than the canonical estimates, depending on the severity of beaming angle evolution and the fraction of stars that make long gamma-ray bursts. Additionally, we find an excess in the SFR at low redshifts, although this lessens when accounting for evolution of the beaming angle. Finally, under the assumption that GRBs do in fact trace canonical forms of the cosmic SFR, we constrain the resulting fraction of stars that must produce GRBs, again accounting for jet beaming-angle evolution. We find this assumption suggests a high fraction of stars in the early universe producing GRBs - a result that may, in fact, support our initial assertion that GRBs do not trace canonical estimates of the SFR., Final version accepted to MNRAS

IBM quantum computers are used to simulate the dynamics of small systems of interacting quantum spins. For time-independent systems with $N\leq 2$ spins, we construct circuits which compute the exact time evolution at arbitrary times and allow measurement of spin expectation values. Larger systems with spins require a the Lie-Trotter decomposition of the time evolution operator, and we investigate the case of $N=3$ explicitly. Basic readout-error mitigation is introduced to improve the quality of results run on these noisy devices. The simulations provide an interesting experimental component to the standard treatment of quantum spin in an undergraduate quantum mechanics course., Comment: 9 pages, 7 figures

IBM quantum computers are used to perform a recently-proposed experiment testing the necessity of complex numbers in the standard formulation of quantum mechanics. While the noisier devices are incapable of delivering definitive results, it is shown that certain devices possess sufficiently small error rates to yield convincing evidence that a faithful description of quantum phenomena must involve complex numbers. The results are consistent with previous experiments and robust against daily calibration for several freely-available devices. This work demonstrates the feasibility of using cloud-based, noisy, intermediate-scale quantum devices to test certain foundational features of quantum mechanics., Comment: 8 pages, 5 figures + supplementary information

Evidence of strong photoelectron-valence electron (PEVE) interactions has been observed in the anion photoelectron (PE) spectra of several lanthanide suboxide clusters, which are exceptionally complex from an electronic structure standpoint and are strongly correlated systems. The PE spectrum of Gd

Drug susceptibility testing ofM. tuberculosisis rooted in a binary susceptible/resistant paradigm. While there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate, it is necessary to measure the epidemiological cut-off values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-tuberculosis compounds, including bedaquiline and delamanid, derived from 20 637 clinical isolates collected by 14 laboratories based in 11 countries on five continents. Each isolate was incubated for 14 days on a dry 96-well broth microdilution plate and then read. Resistance to most of the drugs due to prior exposure is expected and the MIC distributions for many of the compounds are complex, and therefore aphenotypicallywild-type population could not be defined. Since a majority of samples also underwent genetic sequencing, we defined agenotypicallywild-type population and measured the MIC of the 99th percentile by direct measurement andviafitting a Gaussian using interval regression. The proposed ECOFF/ECVs were then validated by comparing with the MIC distributions of high-confidence genetic variants that confer resistance and with qualitative drug susceptibility tests obtainedviathe Mycobacterial Growth Indicator Tube (MGIT) system or Microscopic-Observation Drug Susceptibility (MODS) assay. These ECOFF/ECVs will inform and encourage the more widespread adoption of broth microdilution: this is a cheap culture-based method that tests the susceptibility of 12–14 antibiotics on a single 96-well plate and so could help personalise the treatment of tuberculosis.

We examine the relationship between a number of long gamma-ray burst (lGRB) properties (isotropic emitted energy, luminosity, intrinsic duration, jet opening angle) and redshift. We find that even when accounting for conservative detector flux limits, there appears to be a significant correlation between isotropic equivalent energy and redshift, suggesting cosmological evolution of the lGRB progenitor. Analyzing a sub-sample of lGRBs with jet opening angle estimates, we find the beaming-corrected lGRB emitted energy does not correlate with redshift, but jet opening angle does. Additionally, we find a statistically significant anti-correlation between the intrinsic prompt duration and redshift, even when accounting for potential selection effects. We also find that - for a given redshift - isotropic energy is positively correlated with intrinsic prompt duration. None of these GRB properties appear to be correlated with galactic offset. From our selection-effect-corrected redshift distribution, we estimate a co-moving rate density for lGRBs, and compare this to the global cosmic star formation rate (SFR). We find the lGRB rate mildly exceeds the global star formation rate between a redshift of 3 and 5, and declines rapidly at redshifts above this (although we cannot constrain the lGRB rate above a redshift of about 6 due to sample incompleteness). We find the lGRB rate diverges significantly from the SFR at lower redshifts. We discuss both the correlations and lGRB rate density in terms of various lGRB progenitor models and their apparent preference for low-metallicity environments., Comment: Accepted to MNRAS

The electronic and molecular structure of the CeB6 molecular unit has been probed by anion PE spectroscopy and DFT calculations to gain insight into structural and electronic relaxation on edge and corner sites of this ionic material. While boron in bulk lanthanide hexaboride materials assumes octahedral B63- units, the monomer assumes a less compact structure to delocalize the charge. Two competitive molecular structures were identified for the anion and neutral species, which include a boat-like structure and a planar or near-planar teardrop structure. Ce adopts different orbital occupancies in the two isomers; the boat-like structure has a 4f superconfiguration while the teardrop favors a 4f 6s occupancy. The B6 ligand in these structures carries a charge of -4 and -3, respectively. The teardrop structure, which was calculated to be isoenergetic with the boat structure, was most consistent with the experimental spectrum. B6-local orbitals crowd the energy window between the Ce 4f and 6s (HOMO) orbitals. A low-lying transition from the B-based orbitals is observed slightly less than 1 eV above the ground state. The results suggest that edge and corner conductivity involves stabilized, highly diffuse 6s orbitals or bands rather than the bulk-favored 5d band. High-spin and open-shell low-spin states were calculated to be very close in energy for both the anion and neutral, a characteristic that reflects how decoupled the 4f electron is from the B6 2p- and Ce 6s-based molecular orbitals.

Photoelectron spectra of Gd

The immense power of gamma-ray bursts (GRBs) makes them ideal probes of the early universe. By using absorption lines in the afterglows of high-redshift GRBs, astronomers can study the evolution of metals in the early universe. With an understanding of the nature of GRB progenitors, the rate and properties of GRBs observed at high redshift can probe the star formation history and the initial mass function of stars at high redshift. This paper presents a detailed study of the dependence on metallicity and mass of the properties of long-duration GRBs under the black hole accretion disk paradigm to predict the evolution of these properties with redshift. These models are calibrated on the current GRB observations and then used to make predictions for new observations and new missions (e.g., the proposed Gamow mission) studying high-redshift GRBs.

Photoelectron spectra of Gd2O2− obtained with photon energies from 2.033 eV to 3.495 eV exhibit numerous close-lying neutral states with photon-energy-dependent relative intensities. Transitions to states falling within the electron binding energy window of 0.9 and 1.6 eV are attributed to one- or two-electron transitions to the ground and low-lying excited neutral states. An additional, manifold of electronic states observed in the 2.1 to 2.8 eV window cannot be assigned to any simple one-electron transitions. Because of the relatively simple electronic structure from the half-filled 4f7 subshell occupancy in Gd2O2–, the numerous transitions observed in the spectra are fairly well-resolved, allowing a detailed view of the changes in relative intensities of individual transitions with photon energy. With supporting calculations on the numerous close-lying electronic states, we suggest a description of strong photoelectron-valence electron interactions that result in the photon-energy dependent shake-up transitions and switching between ferro- and antiferromagnetic coupling.

Tidal marsh and estuarine marine microbial sediment metagenomes from the Great Bay Estuary of New Hampshire were sequenced and found to be dominated by Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Both types of sediment contained many unclassified bacterial sequences, including the mollusk pathogen Perkinsus marinus, and detectable xenobiotic degradation and nitrogen transformation genes.

We report on design, fabrication, and characterization of superconducting nanostripe single-photon detectors integrated with dielectric optical waveguides, whereby part of the upper cladding is removed to enhance absorption of photons by the superconducting nanostripes.

Boronyl (B≡O) ligands have garnered much attention as isoelectronic and isolobal analogues of CO and CN-, yet successful efforts in synthesizing metal boronyl complexes remain scarce. Anion photoelectron (PE) spectroscopy and density functional theory calculations were employed to investigate two small CeO2B x- ( x = 2, 3) complexes generated from laser ablation of a mixed Ce/B pressed powder target. The spectra reveal markedly different bonding upon incorporation of an additional B atom. Most interestingly, CeO2B2- was found to have a Ce(I) center coordinated to two monoanionic boronyl ligands in a bent geometry. This result was unexpected as previous studies suggest electron-rich metals are most suitable for stabilizing such ligands; furthermore, it is one of the first examples of an experimental metal-polyboronyl complex. Introducing another boron atom, however, favors a much different geometry in which Ce(II) coordinates an O2B33- unit through both the O and B atoms, which was evident in the markedly different PE spectra.

Determination of the vibrational frequency of the ZnBr radical has been elusive, having previously been reported as 220 cm−1 and 318 cm−1 by different investigators. Recently, Burton and Ziurys reported a rotational spectrum of ZnBr from which they were able to estimate a harmonic frequency of 284 cm−1 and an anharmonicity of 1.0 cm−1. In this communication, we report a direct measurement of the vibrational spacing of ZnBr by anion photoelectron spectroscopy of ZnBr−. We determine the neutral vibrational frequency to be 280 ± 5 cm−1 (ωexe = 1.5 ± 0.5 cm−1) and the anion vibrational frequency to be 120 ± 10 cm−1. In addition, we measure the electron affinity of the neutral radical to be 2.45 ± 0.06 eV, and determine that the bond dissociation energy of the anion is lower than that of the neutral by 0.91 ± 0.06 eV.

The existence of quasi-long range order is demonstrated in nonequilibrium steady states in isotropic $XY$ spin chains including of two types of additional terms that each generate a gap in the energy spectrum. The system is driven out of equilibrium by initializing a domain-wall magnetization profile through application of an external magnetic field and switching off the magnetic field at the same time the energy gap is activated. An energy gap is produced by either applying a staggered magnetic field in the $z$ direction or introducing a modulation to the $XY$ coupling. The magnetization, spin current, and spin-spin correlation functions are computed analytically in the thermodynamic limit at long times after the quench. For both types of systems, we find the persistence of power-law correlations despite the ground-state correlation functions exhibiting exponential decay., Comment: 19 pages, 9 figures, published version

ConspectusLanthanide (Ln) oxide clusters and molecular systems provide a bottom-up look at the electronic structures of the bulk materials because of close parallels in the patterns of Ln 4fN subshell occupancy between the molecular and bulk Ln2O3 size limits. At the same time, these clusters and molecules offer a challenge to the theory community to find appropriate and robust treatments for the 4fN patterns across the Ln series. Anion photoelectron (PE) spectroscopy provides a powerful experimental tool for studying these systems, mapping the energies of the ground and low-lying excited states of the neutral relative to the initial anion state, providing spectroscopic patterns that reflect the Ln 4fN occupancy. In this Account, we review our anion PE spectroscopic and computational studies on a range of small lanthanide molecules and cluster species. The PE spectra of LnO– (Ln = Ce, Pr, Sm, Eu) diatomic molecules show spectroscopic signatures associated with detachment of an electron from what can be de...

The electronic and molecular structure of the CeB

11 págs, 4 figuras y fórmulas matemáticas. Material suplementario en: http://dx.doi.org/10.1093/molbev/msaa069, The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap's simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species., D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre

Jet opening angles of long gamma-ray bursts (lGRBs) appear to evolve in cosmic time, with lGRBs at higher redshifts being on average more narrowly beamed than those at lower redshifts. We examine the nature of this anticorrelation in the context of collimation by the progenitor stellar envelope. First, we show that the data indicate a strong correlation between gamma-ray luminosity and jet opening angle, and suggest this is a natural selection effect – only the most luminous GRBs are able to successfully launch jets with large opening angles. Then, by considering progenitor properties expected to evolve through cosmic time, we show that denser stars lead to more collimated jets; we argue that the apparent anticorrelation between opening angle and redshift can be accounted for if lGRB massive star progenitors at high redshifts have higher average density compared to those at lower redshifts. This may be viable for an evolving initial mass function (IMF) – under the assumption that average density scales directly with mass, this relationship is consistent with the form of the IMF mass evolution suggested in the literature. The jet angle–redshift anticorrelation may also be explained if the lGRB progenitor population is dominated by massive stars at high redshift, while lower redshift lGRBs allow for a greater diversity of progenitor systems (that may fail to collimate the jet as acutely). Overall, however, we find both the jet angle–redshift anticorrelation and jet angle–luminosity correlation are consistent with the conditions of jet launch through, and collimation by, the envelope of a massive star progenitor.

Small clusters have captured the imaginations of experimentalists and theorists alike for decades. In addition to providing insight into the evolution of properties between the atomic or molecular limits and the bulk, small clusters have revealed a myriad of fascinating properties that make them interesting in their own right. This perspective reviews how the application of anion photoelectron (PE) spectroscopy, typically coupled with supporting calculations, is particularly well-suited to probing the molecular and electronic structure of small clusters. Clusters provide a powerful platform for the study of the properties of local phenomena (e.g., dopants or defect sites in heterogeneous catalysts), the evolution of the band structure and the transition from semiconductor to metallic behavior in metal clusters, control of electronic structures of clusters through electron donating or withdrawing ligands, and the control of magnetic properties by interactions between the photoelectron and remnant neutral states, among other important topics of fundamental interest. This perspective revisits historical, groundbreaking anion PE spectroscopic finding and details more recent advances and insight gleaned from the PE spectra of small covalently or ionically bound clusters. The properties of the broad range of systems studied are uniquely small-cluster like in that incremental size differences are associated with striking changes in stability, electronic structures, and symmetry, but they can also be readily related to larger or bulk species in a broader range of materials and applications.

Spatiotemporal patterns of action potentials are considered to be closely related to information processing in the brain. Auto-generating neurons contributing to these processing tasks are known to cause multifractal behavior in the inter-spike intervals of the output action potentials. In this paper we define a novel relationship between this multifractality and the adaptive Nernst equilibrium in hippocampal neurons. Using this relationship we are able to differentiate between various drugs at varying dosages. Conventional methods limit their ability to account for cellular charge depletion by not including these adaptive Nernst equilibria. Our results provide a new theoretical approach for measuring the effects which drugs have on single-cell dynamics.

BACKGROUND –: Short-term exposure to air pollution, particularly from vehicular sources, increases the risk of acute clinical cardiovascular events. However, cardiotoxicity is not always clearly discernible under ambient conditions; therefore, more subtle measures of cardiac dysfunction are necessary to elucidate the latent effects of exposure. OBJECTIVE –: Determine the effect of whole diesel exhaust (DE) exposure on reserve of refractoriness (RoR), an intrinsic electrophysiological measure of the heart’s minimum level of refractoriness relative to development of electrical conduction instability, in rats undergoing exercise-like stress. METHODS –: Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters to continuously collect electrocardiogram (ECG) and heart rate (HR) were exposed to 150 μg/m(3) of DE and challenged with dobutamine twenty-four hours later to mimic exercise-induced increases of the heart rate. The Chernyak-Starobin-Cohen (CSC) model was then applied to the ECG-derived QT and RR intervals collected during progressive increases in heart rate to calculate RoR for each rat. RESULTS –: Filtered air (FA)-exposed WKY and SH rats did not have any decrease in RoR, which indicates increased risk of cardiac conduction instability; however, DE caused a significant decrease in both strains. Yet, the decrease in RoR in SH rats was eight times steeper when compared to WKY rats indicating greater cardiac conduction instability in the hypertensive strain. CONCLUSION –: These data indicate that after exposure to DE, risk of cardiac instability increases during increasing stress, particularly in the presence of underlying cardiovascular disease. Furthermore, the CSC model, which was previously shown to reveal cardiac risk in humans, can be applied to rodent toxicology studies.

We present results obtained from electrocardiogram (ECG) measurements performed on mice exposed to single-walled carbon nanotubes and ceria nanoparticles through instillation. From these non-invasive ECG measurements, QT and RR intervals were obtained at various times after exposure and used to compute a novel metric for evaluating cardiac signal propagation stability, the reserve of refractoriness (RoR). It is demonstrated that while the isolated QT and RR intervals are essentially uncorrelated with histological data from hematoxylin and eosin stains of control and exposed tissue samples, the RoR is sensitive to cardiovascular effects from the exposure to nanoparticles.

Mixed-metal oxides have proven to be effective catalysts for the hydrogen evolution reaction, often outperforming either of the binary metal oxides. The reactivity of MnxMoOy− (x = 1, 2; y = 3, 4) clusters toward H2O was investigated via time-of-flight mass spectrometry with clear evidence of cluster oxidation and corresponding H2 production, specifically for MnxMoO3− (x = 1, 2) clusters. Unlike previously studied MoxOy− clusters, which assumed a broad distribution of stoichiometries (typically x ≤ y ≤ 3x), both MnMoOy− and Mn2MoOy− preferentially formed y = 3 and 4 compositions in significant quantities under our source conditions. The electronic and molecular structures of the MnxMoOy (x = 1, 2; y = 3, 4) anion and neutral clusters were probed with anion photoelectron spectroscopy and analyzed with supporting density functional theory calculations. Our studies suggest that both metal centers are involved in initial cluster–water complex formation, while Mo is the center that undergoes oxidation; hence, reactivity terminates when Mo is saturated in its highest oxidation state of +6. Across these four clusters, Mn remains relatively reduced and is stable in a high-spin electronic configuration. The preferential reactivity of water molecules toward the Mo center rather than Mn is rationalized by the much lower relative oxophilicity of Mn.

The photoelectron spectra of Sm2O– obtained over a range of photon energies exhibit anomalous changes in relative excited-state band intensities. Specifically, the excited-state transition intensities increase relative to the transition to the neutral ground state with decreasing photon energy, the opposite of what is expected from threshold effects. This phenomenon was previously observed in studies on several Sm-rich homo- and heterolanthanide oxides collected with two different harmonic outputs of a Nd:YAG (2.330 and 3.495 eV) [J. Chem. Phys. 2017, 146, 194310]. We relate these anomalous intensities to populations of ground and excited anionic and neutrals states through the inspection of time-dependent perturbation theory within the adiabatic and sudden limits and for the first time show that transition intensities in photoelectron spectroscopy have a deep significance in gauging participation from excited states. We believe our results will have significance in the study of other electron-rich system...

Boronyl (B≡O) ligands have garnered much attention as isoelectronic and isolobal analogues of CO and CN

We investigate the environment in which direct-collapse black holes may form by analysing a cosmological, hydrodynamical simulation that is part of the First Billion Years project. This simulation includes the most relevant physical processes leading to direct collapse of haloes, most importantly, molecular hydrogen depletion by dissociation of $H_2$ and $H^-$ from the evolving Lyman-Werner radiation field. We selected a sample of pristine atomic cooling haloes that have never formed stars in their past, have not been polluted with heavy elements and are cooling predominantly via atomic hydrogen lines. Amongst them we identified six haloes that could potentially harbour massive seed black holes formed via direct collapse (with masses in the range of $10^{4-6} M_{sun}$). These potential hosts of direct-collapse black holes form as satellites and are found within 15 physical kpc of proto-galaxies, with stellar masses in the range $10^{5-7} M_{sun}$ and maximal star formation rates of 0.1 Msun/yr over the past 5 Myr, and are exposed to the highest flux of Lyman-Werner radiation emitted from the neighbouring galaxies. It is the proximity to these proto-galaxies that differentiates these haloes from rest of the sample., 10 pages, 8 figures, accepted MNRAS

The Seebeck coefficient S is a temperature- and material-dependent property, which linearly and causally relates the temperature difference △T between the “hot” and “cold” junctions of a thermoelectric power generator (TEC-PG) to the voltage difference △V. This phenomenon is the Seebeck effect (SE), and can be used to convert waste heat into usable energy. This work investigates the trends of the effective voltage output △V(t) and effective Seebeck coefficient S'(t) versus several hours of activity of a solid state TEC-PG device. The effective Seebeck coefficient S'(t) here is related to a device, not just to a material’s performance. The observations are pursued in an insulated compartment in various geometrical and environmental configurations. The results indicate that the SE does not substantially depend on the geometrical and environmental configurations. However, the effective Seebeck coefficient S'(t) and the produced effective △V(t) are affected by the environmental configuration, once the temperature is fixed. Heat transfer calculations do not completely explain this finding. Alternative explanations are hypothesized.

The mechanism that activates a bi-junction power generator under the effects of heat is the Seebeck effect, that is, the production of voltage difference ΔVt is directly proportional to the temperature difference ΔTt between the "hot" and "cold" junctions of the device. This phenomenon is well established and is known as thermoelectric power generation. Here, it is shown that, instead, the causal and linear relationship between ΔVt and ΔTt is lost when continuous broadband infrared CB-IR radiation illuminates a bi-junction power generator in an insulated compartment. The observed phenomenon is IR power generation. Heat transfer calculations fail in explaining the experimental trends. The interaction between CB-IR radiation and the charge carriers in the bi-junction power generator might play a role in the ΔVt production, depending upon the geometry of the experimental setup. The longitudinal propagation of collective oscillations, for example, polaritons, in the plates protecting the "hot" and "cold" junctions of the bi-junction power generator could explain the ΔVt production and the characteristic time constants. The findings should be considered in the design, fabrication, and improvement of thermopiles, power meters, and IR energy-harvesting devices. © 2013 Wiley Periodicals, Inc. Complexity 19: 44-55, 2014

We estimate the maximum temperature at which planets can form via gravitational instability (GI) in the outskirts of early circumstellar disks. We show that due to the temperature floor set by the cosmic microwave background, there is a maximum distance from their host stars beyond which gas giants cannot form via GI, which decreases with their present-day age. Furthermore, we show that planet formation via GI is not possible at metallicities < 10^-4 Z_Sun, due to the reduced cooling efficiency of low-metallicity gas. This critical metallicity for planet formation via GI implies a minimum distance from their host stars of ~ 6 AU within which planets cannot form via GI; at higher metallicity, this minimum distance can be significantly greater, out to several tens of AU. We show that these maximum and minimum distances significantly constrain the number of observed planets to date that are likely to have formed via GI at their present locations. That said, the critical metallicity we find for GI is well below that for core accretion to operate; thus, the first planets may have formed via GI, although only within a narrow region of their host circumstellar disks., 6 pages, 3 figures; version accepted for publication in MNRAS

We present the first ab initio cosmological simulations of a CR7-like object which approximately reproduce the observed line widths and strengths. In our model, CR7 is powered by a massive ($3.23 \times 10^7$ $M_\odot$) black hole (BH) the accretion rate of which varies between $\simeq$ 0.25 and $\simeq$ 0.9 times the Eddington rate on timescales as short as 10$^3$ yr. Our model takes into account multi-dimensional effects, X-ray feedback, secondary ionizations and primordial chemistry. We estimate Ly-$\alpha$ line widths by post-processing simulation output with Monte Carlo radiative transfer and calculate emissivity contributions from radiative recombination and collisional excitation. We find the luminosities in the Lyman-$\alpha$ and He II 1640 angstrom lines to be $5.0\times10^{44}$ and $2.4\times10^{43}$ erg s$^{-1}$, respectively, in agreement with the observed values of $>$ $8.3\times10^{43}$ and $2.0\times10^{43}$ erg s$^{-1}$. We also find that the black hole heats the halo and renders it unable to produce stars as required to keep the halo metal free. These results demonstrate the viability of the BH hypothesis for CR7 in a cosmological context. Assuming the BH mass and accretion rate that we find, we estimate the synchrotron luminosity of CR7 to be $P \simeq 10^{40} - 10^{41}$ erg s$^{-1}$, which is sufficiently luminous to be observed in $\mu$Jy observations and would discriminate this scenario from one where the luminosity is driven by Population III stars., Comment: 5 pages, 4 figures, Accepted by ApJ Letters

Out-of-equilibrium behavior is explored in the one-dimensional anisotropic $XY$ model. Initially preparing the system in the isotropic $XX$ model with a linearly varying magnetic field to create a domain-wall magnetization profile, dynamics is generated by rapidly changing the exchange interaction anisotropy and external magnetic field. Relaxation to a nonequilibrium steady state is studied analytically at the critical transverse Ising point, where correlation functions may be computed in closed form. For arbitrary values of anisotropy and external field, an effective generalized Gibbs' ensemble is shown to accurately describe observables in the long-time limit. Additionally, we find spatial oscillations in the exponentially decaying, transverse spin-spin correlation functions with wavelength set by the magnetization jump across the initial domain wall. This wavelength depends only weakly on anisotropy and magnetic field in contrast to the current, which is highly dependent on these parameters., Comment: typos corrected, references added

The critical Lyman--Werner flux required for direct collapse blackholes (DCBH) formation, or J$_{crit}$, depends on the shape of the irradiating spectral energy distribution (SED). The SEDs employed thus far have been representative of {realistic} single stellar populations. We study the effect of binary stellar populations on the formation of DCBH, as a result of their contribution to the Lyman--Werner radiation field. Although binary populations with ages $>$ 10 Myr yield a larger LW photon output, we find that the corresponding values of J$_{crit}$ can be up to 100 times higher than single stellar populations. We attribute this to the shape of the binary SEDs as they produce a sub--critical rate of H$^-$ photodetaching 0.76 eV photons as compared to single stellar populations, reaffirming the role that H$^-$ plays in DCBH formation. This further corroborates the idea that DCBH formation is better understood in terms of a critical region in the H$_2$--H$^-$ photo--destruction rate parameter space, rather than a single value of LW flux., 5 pages, 4 figures. accepted MNRAS

With detections of quasars powered by increasingly massive black holes (BHs) at increasingly early times in cosmic history over the past decade, there has been correspondingly rapid progress made on the theory of early BH formation and growth. Here we review the emerging picture of how the first massive BHs formed from the primordial gas and then grew to supermassive scales. We discuss the initial conditions for the formation of the progenitors of these seed BHs, the factors dictating the initial masses with which they form, and their initial stages of growth via accretion, which may occur at super-Eddington rates. Finally, we briefly discuss how these results connect to large-scale simulations of the growth of supermassive BHs over the course of the first billion years following the Big Bang., Comment: 13 pages, 9 figures, invited review accepted for publication in PASA

With the first metal enrichment by Population (Pop) III supernovae (SNe), the formation of the first metal-enriched, Pop II stars becomes possible. In turn, Pop III star formation and early metal enrichment are slowed by the high energy radiation emitted by Pop II stars. Thus, through the SNe and radiation they produce, Populations II and III coevolve in the early Universe, one regulated by the other. We present large (4 Mpc)^3, high resolution cosmological simulations in which we self-consistently model early metal enrichment and the stellar radiation responsible for the destruction of the coolants (H2 and HD) required for Pop III star formation. We find that the molecule-dissociating stellar radiation produced both locally and over cosmological distances reduces the Pop III star formation rate at z > 10 by up to an order of magnitude compared to the case in which this radiation is not included. However, we find that the effect of LW feedback is to enhance the amount of Pop II star formation. We attribute this to the reduced rate at which gas is blown out of dark matter haloes by SNe in the simulation with LW feedback, which results in larger reservoirs for metal-enriched star formation. Even accounting for metal enrichment, molecule-dissociating radiation and the strong suppression of low-mass galaxy formation due to reionization at z < 10, we find that Pop III stars are still formed at a rate of ~ 10^-5 M_sun yr^-1 Mpc^-3 down to z ~ 6. This suggests that the majority of primordial pair-instability SNe that may be uncovered in future surveys will be found at z < 10. We also find that the molecule-dissociating radiation emitted from Pop II stars may destroy H2 molecules at a high enough rate to suppress gas cooling and allow for the formation of supermassive primordial stars which collapse to form ~ 100,000 solar mass black holes., 17 pages, 11 figures; accepted for publication in MNRAS; some figures downgraded, high resolution version available at http://www.as.utexas.edu/~jljohnson/FiBY_III.pdf

We study for the first time the environment of massive black hole (BH) seeds (~10^4-5 Msun) formed via the direct collapse of pristine gas clouds in massive haloes (>10^7 Msun) at z>6. Our model is based on the evolution of dark matter haloes within a cosmological N-body simulation, combined with prescriptions for the formation of BH along with both Pop III and Pop II stars. We calculate the spatially-varying intensity of Lyman Werner (LW) radiation from stars and identify the massive pristine haloes in which it is high enough to shut down molecular hydrogen cooling. In contrast to previous BH seeding models with a spatially constant LW background, we find that the intensity of LW radiation due to local sources, J_local, can be up to 10^6 times the spatially averaged background in the simulated volume and exceeds the critical value, J_crit, for the complete suppression of molecular cooling, in some cases by 4 orders of magnitude. Even after accounting for possible metal pollution in a halo from previous episodes of star formation, we find a steady rise in the formation rate of direct collapse (DC) BHs with decreasing redshift from 10^{-3}/Mpc^3/z at z=12 to 10^{-2}/Mpc^3/z at z=6. The onset of Pop II star formation at z~16 simultaneously marks the onset of the epoch of DCBH formation, as the increased level of LW radiation from Pop II stars is able to elevate the local levels of the LW intensity to J_local > J_crit while Pop III stars fail to do so at any time. The number density of DCBHs is sensitive to the number of LW photons and can vary by an order of magnitude at z=6 after accounting for reionisation feedback. Haloes hosting DCBHs are more clustered than similar massive counterparts that do not host DCBHs, especially at redshifts z>10. We also show that planned surveys with JWST should be able to detect the supermassive stellar precursors of DCBHs.