Effect of Field Direction on Electrowetting in a Nanopore

We manifest a significant influence of field direction and polarity on surface wetting, when the latter is tuned by application of an external electric field. Thermodynamics of field-induced filling of hydrocarbon-like nanopores with water is studied by open ensemble molecular simulation. Increased field strength consistently results in water-filling and electrostriction in hydrophobic nanopores. A threshold field commensurate with surface charge density of about one elementary charge per 10 nm2 suffices to render prototypical paraffin surfaces hydrophilic. When a field is applied in the direction perpendicular to the confining walls, the competition between orientational polarization and angle preferences of interfacial water molecules relative to the walls results in an asymmetric wettability of opposing surfaces (Janus interface). Reduction of surface free energy observed upon alignment of confinement walls with field direction suggests a novel mechanism whereby the applied electric field can operate selectively on water-filled nanotubes while empty ones remain unaffected

Ab Initio Molecular Dynamics Simulations of the Influence of Lithium Bromide on the Structure of the Aqueous Solution-Air Interface

We present the results of ab initio molecular dynamics simulations of the solution-air interface of aqueous lithium bromide (LiBr). We find that, in agreement with the experimental data and previous simulation results with empirical polarizable force field models, Br- anions prefer to accumulate just below the first molecular water layer near the interface, whereas Li+ cations remain deeply buried several molecular layers from the interface, even at very high concentration. The separation of ions has a profound effect on the average orientation of water molecules in the vicinity of the interface. We also find that the hydration number of Li+ cations in the center of the slab Na-c,Na-Li+-H2O approximate to 4.7 +/- 0.3, regardless of the salt concentration. This estimate is consistent with the recent experimental neutron scattering data, confirming that results from nonpolarizable empirical models, which consistently predict tetrahedral coordination of Li+ to four solvent molecules, are incorrect. Consequently, disruption of the hydrogen bond network caused by Li+ may be overestimated in nonpolarizable empirical models. Overall, our results suggest that empirical models, in particular nonpolarizable models, may not capture all of the properties of the solution-air interface necessary to fully understand the interfacial chemistry.Peer reviewe

Thermo-molecular orientation effects in fluids of dipolar dumbbells

Abstract We use molecular dynamics simulations in applied thermal gradients to study thermomolecular orientation (TMO) of size-asymmetric dipolar dumbbells with different molecular dipole moments. We find that the direction of the TMO is the same as in apolar dumbbells of the same size, i.e. the smaller atom in the dumbbell tends to orient towards the colder temperature. The ratio of the electrical polarization to the magnitude of the thermal gradient does not vary much with the magnitude of the molecular dipole moment. We also investigate a novel second order TMO that persists even in size-symmetric dipolar dumbbells where molecules have a slight tendency to orient perpendicular to the gradient except very close to the hot region, where (anti-)parallel orientations are preferred. Finally, we investigate rotational correlation functions and characteristic rotational times in these systems in an attempt to model possible spectroscopic signatures of TMO in experiments. Although we cannot detect any difference in integrated rotational times between equilibrium simulations and simulations in a thermal gradient, more careful modelling of the anisotropic rotational dynamics in the thermal gradient may be more successful

Field exposed water in a nanopore: liquid or vapour?

We study the behavior of ambient temperature water under the combined effects of nanoscale confinement and applied electric field. Using molecular simulations we analyze the thermodynamic causes of field-induced expansion at some, and contraction at other conditions. Repulsion among parallel water dipoles and mild weakening of interactions between partially aligned water molecules prove sufficient to destabilize the aqueous liquid phase in isobaric systems in which all water molecules are permanently exposed to a uniform electric field. At the same time, simulations reveal comparatively weak field-induced perturbations of water structure upheld by flexible hydrogen bonding. In open systems with fixed chemical potential, these perturbations do not suffice to offset attraction of water into the field; additional water is typically driven from unperturbed bulk phase to the field-exposed region. In contrast to recent theoretical predictions in the literature, our analysis and simulations confirm that classical electrostriction characterizes usual electrowetting behavior in nanoscale channels and nanoporous materials.Comment: 20 pages, 6 figures + T.O.C. figure, in press in PCC

Fragmentation inside proton-transfer-reaction-based mass spectrometers limits the detection of ROOR and ROOH peroxides

Proton transfer reaction (PTR) is a commonly applied ionization technique for mass spectrometers, in which hydronium ions (H3O+) transfer a proton to analytes with higher proton affinities than the water molecule. This method has most commonly been used to quantify volatile hydrocarbons, but later-generation PTR instruments have been designed for better throughput of less volatile species, allowing detection of more functionalized molecules as well. For example, the recently developed Vocus PTR time-of-flight mass spectrometer (PTR-TOF) has been shown to agree well with an iodide-adduct-based chemical ionization mass spectrometer (CIMS) for products with 3-5 O atoms from oxidation of monoterpenes (C10H16). However, while several different types of CIMS instruments (including those using iodide) detect abundant signals also at "dimeric" species, believed to be primarily ROOR peroxides, no such signals have been observed in the Vocus PTR even though these compounds fulfil the condition of having higher proton affinity than water. More traditional PTR instruments have been limited to volatile molecules as the inlets have not been designed for transmission of easily condensable species. Some newer instruments, like the Vocus PTR, have overcome this limitation but are still not able to detect the full range of functionalized products, suggesting that other limitations need to be considered. One such limitation, well-documented in PTR literature, is the tendency of protonation to lead to fragmentation of some analytes. In this work, we evaluate the potential for PTR to detect dimers and the most oxygenated compounds as these have been shown to be crucial for forming atmospheric aerosol particles. We studied the detection of dimers using a Vocus PTR-TOF in laboratory experiments, as well as through quantum chemical calculations. Only noisy signals of potential dimers were observed during experiments on the ozonolysis of the monoterpene alpha-pinene, while a few small signals of dimeric compounds were detected during the ozonolysis of cyclohexene. During the latter experiments, we also tested varying the pressures and electric fields in the ionization region of the Vocus PTR-TOF, finding that only small improvements were possible in the relative dimer contributions. Calculations for model ROOR and ROOH systems showed that most of these peroxides should fragment partially following protonation. With the inclusion of additional energy from the ion-molecule collisions driven by the electric fields in the ionization source, computational results suggest substantial or nearly complete fragmentation of dimers. Our study thus suggests that while the improved versions of PTR-based mass spectrometers are very powerful tools for measuring hydrocarbons and their moderately oxidized products, other types of CIMS are likely more suitable for the detection of ROOR and ROOH species.Peer reviewe

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

<div><p>Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.</p></div

Gateways to the FANTOM5 promoter level mammalian expression atlas

The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). This resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0560-6) contains supplementary material, which is available to authorized users

An integrated expression atlas of miRNAs and their promoters in human and mouse

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Ab Initio Molecular Dynamics Simulations of the Influence of Lithium Bromide Salt on the Deprotonation of Formic Acid in Aqueous Solution

The deprotonation of formic acid is investigated using metadynamics in tandem with Born-Oppenheimer molecular dynamics simulations. We compare our findings for formic acid in pure water with previous studies before examining formic acid in aqueous solutions of lithium bromide. We carefully consider different definitions for the collective variable(s) used to drive the metadynamics, emphasizing that the variables used must include all of the possible reactive atoms in the system, in this case carboxylate oxygens and water hydrogens. This ensures that all the various possible proton exchange events can be accommodated and the collective variable(s) can distinguish the protonated and deprotonated states, even over rather long ab initio simulation runs (ca. 200-300 ps). Our findings show that the formic acid deprotonation barrier and the free energy of the deprotonated state are higher in concentrated lithium bromide, in agreement with the available experimental data for acids in salt solution. We show that the presence of Br- in proximity to the formic acid hydroxyl group effectively inhibits deprotonation. Our study extends previous work on acid deprotonation in pure water and at air-water interfaces to more complex multicomponent systems of importance in atmospheric and marine chemistry.Peer reviewe