Conditions for the Quantum to Classical Transition: Trajectories vs. Phase Space Distributions

We contrast two sets of conditions that govern the transition in which classical dynamics emerges from the evolution of a quantum system. The first was derived by considering the trajectories seen by an observer (dubbed the ``strong'' transition) [Bhattacharya, et al., Phys. Rev. Lett. 85: 4852 (2000)], and the second by considering phase-space densities (the ``weak'' transition) [Greenbaum, et al., Chaos 15, 033302 (2005)]. On the face of it these conditions appear rather different. We show, however, that in the semiclassical regime, in which the action of the system is large compared to $\hbar$, and the measurement noise is small, they both offer an essentially equivalent local picture. Within this regime, the weak conditions dominate while in the opposite regime where the action is not much larger than Planck's constant, the strong conditions dominate.Comment: 8 pages, 2 eps figure

Parameter scaling in the decoherent quantum-classical transition for chaotic systems

The quantum to classical transition has been shown to depend on a number of parameters. Key among these are a scale length for the action, $\hbar$, a measure of the coupling between a system and its environment, $D$, and, for chaotic systems, the classical Lyapunov exponent, $\lambda$. We propose computing a measure, reflecting the proximity of quantum and classical evolutions, as a multivariate function of $(\hbar,\lambda,D)$ and searching for transformations that collapse this hyper-surface into a function of a composite parameter $\zeta = \hbar^{\alpha}\lambda^{\beta}D^{\gamma}$. We report results for the quantum Cat Map, showing extremely accurate scaling behavior over a wide range of parameters and suggest that, in general, the technique may be effective in constructing universality classes in this transition.Comment: Submitte

Detecting Exoplanets Closer to Stars with Moderate Spectral Resolution Integral-Field Spectroscopy

While radial velocity surveys have demonstrated that the population of gas giants peaks around $3~\text{au}$, the most recent high-contrast imaging surveys have only been sensitive to planets beyond $\sim~10~\text{au}$. Sensitivity at small angular separations from stars is currently limited by the variability of the point spread function. We demonstrate how moderate-resolution integral field spectrographs can detect planets at smaller separations ($\lesssim~0.3$ arcseconds) by detecting the distinct spectral signature of planets compared to the host star. Using OSIRIS ($R$ $\approx$ 4000) at the W. M. Keck Observatory, we present the results of a planet search via this methodology around 20 young targets in the Ophiuchus and Taurus star-forming regions. We show that OSIRIS can outperform high-contrast coronagraphic instruments equipped with extreme adaptive optics and non-redundant masking in the $0.05-0.3$ arcsecond regime. As a proof of concept, we present the $34\sigma$ detection of a high-contrast M dwarf companion at $\approx0.1$" with a flux ratio of $\approx0.92\%$ around the field F2 star HD 148352. We developed an open-source Python package, breads, for the analysis of moderate-resolution integral field spectroscopy data in which the planet and the host star signal are jointly modeled. The diffracted starlight continuum is forward-modeled using a spline model, which removes the need for prior high-pass filtering or continuum normalization. The code allows for analytic marginalization of linear hyperparameters, simplifying posterior sampling of other parameters (e.g., radial velocity, effective temperature). This technique could prove very powerful when applied to integral field spectrographs like NIRSpec on the JWST and other upcoming first-light instruments on the future Extremely Large Telescopes.Comment: Accepted for publication in the Astronomical Journal on May 12, 202

Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials

SummaryPlasmodium falciparum pathogenesis is affected by various cell types in the blood, including platelets, which can kill intraerythrocytic malaria parasites. Platelets could mediate these antimalarial effects through human defense peptides (HDPs), which exert antimicrobial effects by permeabilizing membranes. Therefore, we screened a panel of HDPs and determined that human platelet factor 4 (hPF4) kills malaria parasites inside erythrocytes by selectively lysing the parasite digestive vacuole (DV). PF4 rapidly accumulates only within infected erythrocytes and is required for parasite killing in infected erythrocyte-platelet cocultures. To exploit this antimalarial mechanism, we tested a library of small, nonpeptidic mimics of HDPs (smHDPs) and identified compounds that kill P. falciparum by rapidly lysing the parasite DV while sparing the erythrocyte plasma membrane. Lead smHDPs also reduced parasitemia in a murine malaria model. Thus, identifying host molecules that control parasite growth can further the development of related molecules with therapeutic potential

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

Conformation-dependent GAD65 autoantibodies in diabetes

Aims/hypothesis. Conformation-dependent autoantibodies directed against GAD65 are markers of Type 1 diabetes. In this study we aimed to determine whether the substitution of GAD65 with GAD67 amino acids would affect the binding of conformation-dependent GAD65 autoantibodies. Methods. We used PCR-based site-directed mutagenesis to generate a series of mutated GAD65 cDNA constructs in which specific GAD65 coding sequences for regions of the protein critical for autoantibody binding were replaced with GAD67 coding sequences. Results. The introduction of a point mutation at position 517, substituting glutamic acid with proline, markedly reduced the binding of disease-associated GAD65 antibodies. The binding of GAD65 antibodies to the E517P mutant was reduced in the sera of all newly diagnosed Type 1 diabetes patients (n=85) by a mean of 72% (p<0.0001) compared with binding to wild-type GAD65. Patients with latent autoimmune diabetes in adults (n=24) showed a similar reduction in binding (79% reduction, p<0.0001). First-degree relatives who subsequently progressed to Type 1 diabetes (n=12) showed a reduction in binding of 80% compared with a reduction of only 65% among relatives who had not progressed to disease (n=38; p=0.025). In healthy GAD65Ab-positive individuals who did not progress to diabetes during a 9-year follow-up period (n=51), binding to GAD65-E517P was reduced by only 28% compared with binding to wild-type GAD65. Conclusions/interpretation. Differences in autoantibody binding to wild-type GAD65 versus GAD65-E517P may provide predictive information about Type 1 diabetes risk beyond that provided by the presence or absence of GAD65 autoantibodies. Lack of binding to mutant GAD65-E517P defines GAD65-positive individuals who are at higher risk of developing diabetes

Dynamic nuclear polarization and spin-diffusion in non-conducting solids

There has been much renewed interest in dynamic nuclear polarization (DNP), particularly in the context of solid state biomolecular NMR and more recently dissolution DNP techniques for liquids. This paper reviews the role of spin diffusion in polarizing nuclear spins and discusses the role of the spin diffusion barrier, before going on to discuss some recent results.Comment: submitted to Applied Magnetic Resonance. The article should appear in a special issue that is being published in connection with the DNP Symposium help in Nottingham in August 200

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease