High fidelity simulations of ion trajectories in miniature ion traps using the boundary-element method

In this paper we present numerical modeling results for endcap and linear ion traps, used for experiments at the National Physical Laboratory in the UK and Innsbruck University respectively. The secular frequencies for Strontium-88 and Calcium-40 ions were calculated from ion trajectories, simulated using boundary-element and finite-difference numerical methods. The results were compared against experimental measurements. Both numerical methods showed high accuracy with boundary-element method being more accurate. Such simulations can be useful tools for designing new traps and trap arrays. They can also be used for obtaining precise trapping parameters for desired ion control when no analytical approach is possible as well as for investigating the ion heating rates due to thermal electronic noise.Comment: 6 pages, 5 figures, changes made to the text according to the editor's and referee's comment

Ecophysiological traits of grasses: resolving the effects of photosynthetic pathway and phylogeny

C4 photosynthesis is an important example of convergent evolution in plants, having arisen in eudicots, monocots and diatoms. Comparisons between such diverse groups are confounded by phylogenetic and ecological differences, so that only broad generalisations can be made about the role of C4 photosynthesis in
determining ecophysiological traits. However, 60% of C4 species occur in the grasses (Poaceae) and molecular phylogenetic techniques confirm that there are between 8 and 17 independent origins of C4 photosynthesis in the Poaceae. In a screening experiment, we compared leaf physiology and growth traits across several major
independent C3 & C4 groups within the Poaceae, asking 1) which traits differ consistently between photosynthetic
types and 2) which traits differ consistently between clades within each photosynthetic type

A microfluidic processor for gene expression profiling of single human embryonic stem cells

The gene expression of human embryonic stem cells (hESC) is a critical aspect for understanding the normal and pathological development of human cells and tissues. Current bulk gene expression assays rely on RNA extracted from cell and tissue samples with various degree of cellular heterogeneity. These cell population averaging data are difficult to interpret, especially for the purpose of understanding the regulatory relationship of genes in the earliest phases of development and differentiation of individual cells. Here, we report a microfluidic approach that can extract total mRNA from individual single-cells and synthesize cDNA on the same device with high mRNA-to-cDNA efficiency. This feature makes large-scale single-cell gene expression profiling possible. Using this microfluidic device, we measured the absolute numbers of mRNA molecules of three genes (B2M, Nodal and Fzd4) in a single hESC. Our results indicate that gene expression data measured from cDNA of a cell population is not a good representation of the expression levels in individual single cells. Within the G0/G1 phase pluripotent hESC population, some individual cells did not express all of the 3 interrogated genes in detectable levels. Consequently, the relative expression levels, which are broadly used in gene expression studies, are very different between measurements from population cDNA and single-cell cDNA. The results underscore the importance of discrete single-cell analysis, and the advantages of a microfluidic approach in stem cell gene expression studies

Mapping gravitational-wave backgrounds using methods from CMB analysis: Application to pulsar timing arrays

We describe an alternative approach to the analysis of gravitational-wave backgrounds, based on the formalism used to characterize the polarization of the cosmic microwave background. In contrast to standard analyses, this approach makes no assumptions about the nature of the background and so has the potential to reveal much more about the physical processes that generated it. An arbitrary background can be decomposed into modes whose angular dependence on the sky is given by gradients and curls of spherical harmonics. We derive the pulsar timing overlap reduction functions for the individual modes, which are given by simple combinations of spherical harmonics evaluated at the pulsar locations. We show how these can be used to recover the components of an arbitrary background, giving explicit results for both isotropic and anisotropic uncorrelated backgrounds. We also find that the response of a pulsar timing array to curl modes is identically zero, so half of the gravitational-wave sky will never be observed using pulsar timing, no matter how many pulsars are included in the array. An isotropic, unpolarized and uncorrelated background can be accurately represented using only three modes, and so a search of this type will be only slightly more complicated than the standard cross-correlation search using the Hellings and Downs overlap reduction function. However, by measuring the components of individual modes of the background and checking for consistency with isotropy, this approach has the potential to reveal much more information. Each individual mode on its own describes a background that is correlated between different points on the sky. A measurement of the components that indicates the presence of correlations in the background on large angular scales would suggest startling new physics

The Local Nanohertz Gravitational-Wave Landscape From Supermassive Black Hole Binaries

Supermassive black hole binaries (SMBHBs) in the 10 million to 10 billion $M_\odot$ range form in galaxy mergers, and live in galactic nuclei with large and poorly constrained concentrations of gas and stars. There are currently no observations of merging SMBHBs--- it is in fact possible that they stall at their final parsec of separation and never merge. While LIGO has detected high frequency GWs, SMBHBs emit GWs in the nanohertz to millihertz band. This is inaccessible to ground-based interferometers, but possible with Pulsar Timing Arrays (PTAs). Using data from local galaxies in the 2 Micron All-Sky Survey, together with galaxy merger rates from Illustris, we find that there are on average $91\pm7$ sources emitting GWs in the PTA band, and $7\pm2$ binaries which will never merge. Local unresolved SMBHBs can contribute to GW background anisotropy at a level of $\sim20\%$, and if the GW background can be successfully isolated, GWs from at least one local SMBHB can be detected in 10 years.Comment: submitted to Nature Astronomy (reformatted for arXiv

Pharmacology of Dextromethorphan: Relevance to Dextromethorphan/Quinidine (Nuedexta®) Clinical Use

Dextromethorphan (DM) has been used for more than 50 years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-D-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors

Isothiourea-catalysed acylative kinetic resolution of aryl-alkenyl (sp2 vs. sp2) substituted secondary alcohols

We would like to thank the Engineering and Physical Sciences Research Council and CRITICAT Centre for Doctoral Training [Ph.D. studentship to S.F.M.; Grant code: EP/L016419/1 and EP/J018139/1] and The Leverhulme Trust [Early Career Fellowship to J.E.T.; ECF-2014-005] for financial support. A.D.S. thanks the Royal Society for a Wolfson Merit Award.The non-enzymatic acylative kinetic resolution of challenging aryl–alkenyl (sp2 vs. sp2) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol %) and isobutyric anhydride. The kinetic resolution of a wide range of aryl–alkenyl substituted alcohols has been evaluated, with either electron-rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity (S=2–1980). The use of this protocol for the gram-scale (2.5 g) kinetic resolution of a model aryl–vinyl (sp2 vs. sp2) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 e.r.Publisher PDFPeer reviewe