Minimal decoherence from inflation

We compute the rate with which super-Hubble cosmological fluctuations are decohered during inflation, by their gravitational interactions with unobserved shorter-wavelength scalar and tensor modes. We do so using Open Effective Field Theory methods, that remain under control at the late times of observational interest, contrary to perturbative calculations. Our result is minimal in the sense that it only incorporates the self-interactions predicted by General Relativity in single-clock models (additional interaction channels should only speed up decoherence). We find that decoherence is both suppressed by the first slow-roll parameter and by the energy density during inflation in Planckian units, but that it is enhanced by the volume comprised within the scale of interest, in Hubble units. This implies that, for the scales probed in the Cosmic Microwave Background, decoherence is effective as soon as inflation proceeds above $\sim 5\times 10^{9}$ GeV. Alternatively, if inflation proceeds at GUT scale decoherence is incomplete only for the scales crossing out the Hubble radius in the last ~ 13 e-folds, of inflation. We also compute how short-wavelength scalar modes decohere primordial tensor perturbations, finding a faster rate unsuppressed by slow-roll parameters. Identifying the parametric dependence of decoherence, and the rate at which it proceeds, helps suggest ways to look for quantum effects.Comment: 31 pages + appendices, 7 figure

The Structure of a Complex of Bovine &-Thrombin and Recombinant Hirudin at 2.8-A Resolution

Crystals of the complex of bovine alpha-thrombin with recombinant hirudin variant 1 have space group C222(1) with cell constants a = 59.11, b = 102.62, and c = 143.26 A. The orientation and position of the thrombin component was determined by molecular replacement and the hirudin molecule was fit in 2 magnitude of Fo - magnitude of Fc electron density maps. The structure was refined by restrained least squares and simulated annealing to R = 0.161 at 2.8-A resolution. The binding of hirudin to thrombin is generally similar to that observed in the crystals of human thrombin-hirudin. Several differences in the interactions of the COOH-terminal polypeptide of hirudin, specifically of residues Asp-55h, Phe-56h, Glu-57h, and Glu-58h, and a few differences in the interactions of the hirudin core, specifically of residues Asp-5h, Ser-19h, and Asn-20h, with thrombin from human thrombin-hirudin suggest that there is some flexibility in the binding of these 2 molecules. Most of the residues in the 9 subsites that bind fibrinopeptide A7-16 to thrombin also interact with the NH2-terminal domain of hirudin. The S1 subsite is a notable exception in that only 1 of its 6 residues, namely Ser-214, interacts with hirudin. The only difference between human and bovine thrombins that appears to influence the binding of hirudin is the replacement of Lys-149E by an acidic glutamate in the bovine enzyme

The Structure of a Complex of Bovine &-Thrombin and Recombinant Hirudin at 2.8-A Resolution

Crystals of the complex of bovine alpha-thrombin with recombinant hirudin variant 1 have space group C222(1) with cell constants a = 59.11, b = 102.62, and c = 143.26 A. The orientation and position of the thrombin component was determined by molecular replacement and the hirudin molecule was fit in 2 magnitude of Fo - magnitude of Fc electron density maps. The structure was refined by restrained least squares and simulated annealing to R = 0.161 at 2.8-A resolution. The binding of hirudin to thrombin is generally similar to that observed in the crystals of human thrombin-hirudin. Several differences in the interactions of the COOH-terminal polypeptide of hirudin, specifically of residues Asp-55h, Phe-56h, Glu-57h, and Glu-58h, and a few differences in the interactions of the hirudin core, specifically of residues Asp-5h, Ser-19h, and Asn-20h, with thrombin from human thrombin-hirudin suggest that there is some flexibility in the binding of these 2 molecules. Most of the residues in the 9 subsites that bind fibrinopeptide A7-16 to thrombin also interact with the NH2-terminal domain of hirudin. The S1 subsite is a notable exception in that only 1 of its 6 residues, namely Ser-214, interacts with hirudin. The only difference between human and bovine thrombins that appears to influence the binding of hirudin is the replacement of Lys-149E by an acidic glutamate in the bovine enzyme

The Structure of a Complex of Bovine ɑ-Thrombin and Recombinant Hirudin at 2.8-Å Resolution

Crystals of the complex of bovine alpha-thrombin with recombinant hirudin variant 1 have space group C222(1) with cell constants a = 59.11, b = 102.62, and c = 143.26 A. The orientation and position of the thrombin component was determined by molecular replacement and the hirudin molecule was fit in 2 magnitude of Fo - magnitude of Fc electron density maps. The structure was refined by restrained least squares and simulated annealing to R = 0.161 at 2.8-A resolution. The binding of hirudin to thrombin is generally similar to that observed in the crystals of human thrombin-hirudin. Several differences in the interactions of the COOH-terminal polypeptide of hirudin, specifically of residues Asp-55h, Phe-56h, Glu-57h, and Glu-58h, and a few differences in the interactions of the hirudin core, specifically of residues Asp-5h, Ser-19h, and Asn-20h, with thrombin from human thrombin-hirudin suggest that there is some flexibility in the binding of these 2 molecules. Most of the residues in the 9 subsites that bind fibrinopeptide A7-16 to thrombin also interact with the NH2-terminal domain of hirudin. The S1 subsite is a notable exception in that only 1 of its 6 residues, namely Ser-214, interacts with hirudin. The only difference between human and bovine thrombins that appears to influence the binding of hirudin is the replacement of Lys-149E by an acidic glutamate in the bovine enzyme

Controlling the {111}/{110} Surface Ratio of Cuboidal Ceria Nanoparticles

The ability to control size and morphology is crucial in optimizing nanoceria catalytic activity as this is governed by the atomistic arrangement of species and structural features at the surfaces. Here, we show that cuboidal cerium oxide nanoparticles can be obtained via microwave-assisted hydrothermal synthesis in highly alkaline media. HRTEM revealed that the cube edges were truncated by CeO2{110} surfaces and the cube corners by CeO2{111} surfaces. When adjusting synthesis conditions by increasing NaOH concentration, the average particle size increased. Although this was accompanied by an increase of the cube faces, CeO2{100}, the cube edges, CeO2{110}, and cube corners, CeO2{111} remained of constant size. Molecular Dynamics (MD) was used to rationalise this behaviour and revealed that energetically, the corners and edges cannot be atomically sharp, rather they are truncated by {111} and {110} surfaces respectively to stabilise the nanocube; both experiment and simulation agreed a minimum size of ~1.6 nm associated with this truncation. Moreover, HRTEM and MD revealed {111}/{110} faceting of the {110} edges, which balances the surface energy associated with the exposed surfaces, which follows {111}>{110}>{100}, although only the {110} surface facets because of the ease of extracting oxygen from its surface, which follows {111}>{100}>{110}. Finally, MD revealed that the {100} surfaces are ‘liquid-like’ with a surface oxygen mobility 5 orders of magnitude higher than that on the {111} surfaces; this arises from the flexibility of the surface species network that can access many different surface arrangements due to very small energy differences. This finding has implications for understanding the surface chemistry of nanoceria and provides avenues to rationalize the design of catalytically active materials at the nanoscale

Novel Changes in Discoidal High Density Lipoprotein Morphology: A Molecular Dynamics Study

AbstractApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating phospholipids into stable particles. Here we report molecular dynamics simulations on a series of progressively smaller discoidal high density lipoprotein particles produced by incremental removal of palmitoyloleoylphosphatidylcholine via four different pathways. The starting model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two antiparallel amphipathic helical lipid-associating domains of apolipoprotein (apo) A-I. The results are particularly compelling. After a few nanoseconds of molecular dynamics simulation, independent of the starting particle and method of size reduction, all simulated double belts of the four lipidated apoA-I particles have helical domains that impressively approximate the x-ray crystal structure of lipid-free apoA-I, particularly between residues 88 and 186. These results provide atomic resolution models for two of the particles produced by in vitro reconstitution of nascent high density lipoprotein particles. These particles, measuring 95Å and 78Å by nondenaturing gradient gel electrophoresis, correspond in composition and in size/shape (by negative stain electron microscopy) to the simulated particles with molar ratios of 100:2 and 50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces at their monolayer-monolayer interface, whereas the 50:2 particle family displays a lipid pocket capable of binding a dynamic range of phospholipid molecules

Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression

BACKGROUND: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR. However, the statistical method does not weigh the relative clinical importance of the end point components. A HCE accounts for the clinical importance of the end point components and enables combining dichotomous outcomes with continuous measures. METHODS: We developed and validated a new HCE for kidney disease progression, performing post hoc analyses of seven major Phase 3 placebo-controlled trials that assessed the effects of canagliflozin, dapagliflozin, finerenone, atrasentan, losartan, irbesartan, and aliskiren in patients with CKD. We calculated the win odds (WOs) for treatment effects on a kidney HCE, defined as a hierarchical composite of all-cause mortality; kidney failure; sustained 57%, 50%, and 40% GFR declines from baseline; and GFR slope. The WO describes the odds of a more favorable outcome for receiving the active compared with the control. We compared the WO with the hazard ratio (HR) of the primary kidney outcome of the original trials. RESULTS: In all trials, treatment effects calculated with the WO reflected a similar direction and magnitude of the treatment effect compared with the HR. Clinical trials incorporating the HCE would achieve increased statistical power compared with the established composite end point at equivalent sample sizes. CONCLUSIONS: In seven major kidney clinical trials, the WO and HR provided similar direction of treatment effect estimates with smaller HRs associated with larger WOs. The prioritization of clinical outcomes and inclusion of broader composite end points makes the HCE an attractive alternative to the established kidney end point

Pedestrian Approach to the Two-Channel Kondo Model

We reformulate the two-channel Kondo model to explicitly remove the unscattered charge degrees of freedom. This procedure permits us to move the non-Fermi liquid fixed point to infinite coupling where we can apply a perturbative strong-coupling expansion. The fixed point Hamiltonian involves a three-body Majorana zero mode whose scattering effects give rise to marginal self-energies. The compactified model is the N=3 member of a family of "O(N)" Kondo models that can be solved by semiclassical methods in the large $N$ limit. For odd $N$, {\em fermionic} "Kink" fluctuations about the $N=\infty$ mean-field theory generate a fermionic $N$-body bound-state which asymptotically decouples at low energies. For N=3, our semi-classical methods fully recover the non-Fermi liquid physics of the original two channel model. Using the same methods, we find that the corresponding O(3) Kondo lattice model develops a spin-gap and a gapless band of coherently propagating three-body bound-states. Its strong-coupling limit offers a rather interesting realization of marginal Fermi liquid behavior.Comment: 17 pages, Revtex 3.0. Replaced with fully compiled postscript file

Multiple Transits during a Single Conjunction: Identifying Transiting Circumbinary Planetary Candidates from TESS

We present results of a study on identifying circumbinary planet candidates that produce multiple transits during one conjunction with eclipsing binary systems. The occurrence of these transits enables us to estimate the candidates' orbital periods, which is crucial as the periods of the currently known transiting circumbinary planets are significantly longer than the typical observational baseline of TESS. Combined with the derived radii, it also provides valuable information needed for follow-up observations and subsequent confirmation of a large number of circumbinary planet candidates from TESS. Motivated by the discovery of the 1108-day circumbinary planet Kepler-1647, we show the application of this technique to four of Kepler's circumbinary planets that produce such transits. Our results indicate that in systems where the circumbinary planet is on a low-eccentricity orbit, the estimated planetary orbital period is within <10-20% of the true value. This estimate is derived from photometric observations spanning less than 5% of the planet's period, demonstrating the strong capability of the technique. Capitalizing on the current and future eclipsing binaries monitored by NASA's TESS mission, we estimate that hundreds of circumbinary planets candidates producing multiple transits during one conjunction will be detected in the TESS data. Such a large sample will enable statistical understanding of the population of planets orbiting binary stars and shed new light on their formation and evolution.Comment: 16 pages, 6 figures, 2 tables, AJ accepte

Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health