Fixed parameter tractability of crossing minimization of almost-trees

We investigate exact crossing minimization for graphs that differ from trees by a small number of additional edges, for several variants of the crossing minimization problem. In particular, we provide fixed parameter tractable algorithms for the 1-page book crossing number, the 2-page book crossing number, and the minimum number of crossed edges in 1-page and 2-page book drawings.Comment: Graph Drawing 201

A pulsed NMR relaxation and diffusion study of water in treated and untreated waterlogged wood

Freezing curve, NMR relaxation data, and steady field gradient and pulsed field gradient experiments were conducted on samples of water-logged woods excavated from the Tudor warship, the Mary Rose and on similar samples impregnated with Polyethylene-Glycol solutions: the polymer used as a bulking agent to prevent decay. At least two distinguishable populations of water molecules are found in wood. Freezing curves indicate the presence of approximately 0.38 g/g of hydration water, close to that observed in fresh timbers. Relaxation measurements on pre-treated samples provides evidence of a very tightly bound fraction, present at water contents of below 0.14 g/g 0i hydration water, with a second population of hydration water being present up to 0.1.8 9/9. Above this value a third ‘free' population is observed. The relaxation decays in longitudinal and transverse direction have been analysed in terms of a sum of exponentials. These indicate the presence of two populations of water which do not correspond to populations observed in freezing curve analysis. Exchange mechanisms dominate the temperature dependency of the relaxation behaviour in pre-treated samples, which is similar to that observed in other fibrous materials such as meat. However, t he different components do not appear to correspond to the physical characteristics of the wood and the spin populations cannot be associated with a distribution between identifiable compartments within the system. In PEG impregnated samples the contribution to the signal from the polymer is not resolvable on the equipment used. Samples treated with PEGs for which the degree of polymerisation is greater than 1540 show a dependency of relaxation characteristics on the water content of the sample. At low water contents PEGs of low molecular weight impart a mobility to the "bound" water molecules which is not seen in untreated samples. . Belt diffusion coefficients for water molecules in wood are anisotropic, and are reduced from those observed in distilled water. This reduction is brought about because water molecules are both held in a hydration layer, and bounded by the cellular structure of the wood. In impregnated samples the diffusion rates are lowered by a factor of 10, though this is not reflected in the relaxation behaviour. The anisotropy is reduced, and proton exchange mechanisms are blocked

A pulsed NMR relaxation and diffusion study of water in treated and untreated waterlogged wood

Freezing curve, NMR relaxation data, and steady field gradient and pulsed field gradient experiments were conducted on samples of water-logged woods excavated from the Tudor warship, the Mary Rose and on similar samples impregnated with Polyethylene-Glycol solutions: the polymer used as a bulking agent to prevent decay. At least two distinguishable populations of water molecules are found in wood. Freezing curves indicate the presence of approximately 0.38 g/g of hydration water, close to that observed in fresh timbers. Relaxation measurements on pre-treated samples provides evidence of a very tightly bound fraction, present at water contents of below 0.14 g/g 0i hydration water, with a second population of hydration water being present up to 0.1.8 9/9. Above this value a third ‘free' population is observed. The relaxation decays in longitudinal and transverse direction have been analysed in terms of a sum of exponentials. These indicate the presence of two populations of water which do not correspond to populations observed in freezing curve analysis. Exchange mechanisms dominate the temperature dependency of the relaxation behaviour in pre-treated samples, which is similar to that observed in other fibrous materials such as meat. However, t he different components do not appear to correspond to the physical characteristics of the wood and the spin populations cannot be associated with a distribution between identifiable compartments within the system. In PEG impregnated samples the contribution to the signal from the polymer is not resolvable on the equipment used. Samples treated with PEGs for which the degree of polymerisation is greater than 1540 show a dependency of relaxation characteristics on the water content of the sample. At low water contents PEGs of low molecular weight impart a mobility to the "bound" water molecules which is not seen in untreated samples. . Belt diffusion coefficients for water molecules in wood are anisotropic, and are reduced from those observed in distilled water. This reduction is brought about because water molecules are both held in a hydration layer, and bounded by the cellular structure of the wood. In impregnated samples the diffusion rates are lowered by a factor of 10, though this is not reflected in the relaxation behaviour. The anisotropy is reduced, and proton exchange mechanisms are blocked

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals

This article is made available through the Brunel Open Access Publishing Fund. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and bisphenol A, respectively) would do otherwise.BBSR

Detection of fast radio transients with multiple stations: a case study using the Very Long Baseline Array

Recent investigations reveal an important new class of transient radio phenomena that occur on sub-millisecond timescales. Often transient surveys' data volumes are too large to archive exhaustively. Instead, an on-line automatic system must excise impulsive interference and detect candidate events in real-time. This work presents a case study using data from multiple geographically distributed stations to perform simultaneous interference excision and transient detection. We present several algorithms that incorporate dedispersed data from multiple sites, and report experiments with a commensal real-time transient detection system on the Very Long Baseline Array (VLBA). We test the system using observations of pulsar B0329+54. The multiple-station algorithms enhanced sensitivity for detection of individual pulses. These strategies could improve detection performance for a future generation of geographically distributed arrays such as the Australian Square Kilometre Array Pathfinder and the Square Kilometre Array.Comment: 12 pages, 14 figures. Accepted for Ap

Detailed quantification of glacier elevation and mass changes in South Georgia

Most glaciers in South America and on the Antarctic Peninsula are retreating and thinning. They are considered strong contributors to global sea level rise. However, there is a lack of glacier mass balance studies in other areas of the Southern Hemisphere, such as the surrounding Antarctic Islands. Here, we present a detailed quantification of the 21st century glacier elevation and mass changes for the entire South Georgia Island using bi-static synthetic aperture radar interferometry between 2000 and 2013. The results suggest a significant mass loss since the beginning of the present century. We calculate an average glacier mass balance of -1.04 0.09 m w.e.a(-1) and a mass loss rate of 2.28 0.19 Gt a(-1) (2000-2013), contributing 0.006 0.001 mm a(-1) to sea-level rise. Additionally, we calculate a subaqueous mass loss of 0.77 0.04 Gt a(-1) (2003-2016), with an area change at the marine and lake-terminating glacier fronts of -6.58 0.33 km(2) a(-1), corresponding to similar to 4% of the total glacier area. Overall, we observe negative mass balance rates in South Georgia, with the highest thinning and retreat rates at the large outlet glaciers located at the north-east coast. Although the spaceborne remote sensing dataset analysed in this research is a key contribution to better understanding of the glacier changes in South Georgia, more detailed field measurements, glacier dynamics studies or further long-term analysis with high-resolution regional climate models are required to precisely identify the forcing factors

Utilization of the propensity score method: an exploratory comparison of proxy-completed to self-completed responses in the Medicare Health Outcomes Survey

BACKGROUND: This research examined the use of the propensity score method to compare proxy-completed responses to self-completed responses in the first three baseline cohorts of the Medicare Health Outcomes Survey, administered in 1998, 1999, and 2000, respectively. A proxy is someone other than the respondent who completes the survey for the respondent. METHODS: The propensity score method of matched sampling was used to compare proxy and self-completed responses. A propensity score is a value that equals the estimated probability of a given individual belonging to a treatment group given the observed background characteristics of that individual. Proxy and self-completed responses were compared on demographics, the SF-36, chronic conditions, activities of daily living, and depression-screening questions. For each individual survey respondent, logistic regression was used to calculate the probability that this individual belonged to the proxy respondent group (propensity score). Pre and post adjustment comparisons were tested by calculating effect sizes. RESULTS: Differences between self and proxy-completed responses were substantially reduced with the use of the propensity score method. However, differences were still found in the SF-36, several demographics, several impaired activities of daily living, several chronic conditions, and one depression-screening question. CONCLUSION: The propensity score method helped to reduce differences between proxy-completed and self-completed survey responses, thereby providing an approximation to a randomized controlled experiment of proxy-completed versus self-completed survey responses

Citrullination of HP1γ chromodomain affects association with chromatin.

BACKGROUND: Stem cell differentiation involves major chromatin reorganisation, heterochromatin formation and genomic relocalisation of structural proteins, including heterochromatin protein 1 gamma (HP1γ). As the principal reader of the repressive histone marks H3K9me2/3, HP1 plays a key role in numerous processes including heterochromatin formation and maintenance. RESULTS: We find that HP1γ is citrullinated in mouse embryonic stem cells (mESCs) and this diminishes when cells differentiate, indicating that it is a dynamically regulated post-translational modification during stem cell differentiation. Peptidylarginine deiminase 4, a known regulator of pluripotency, citrullinates HP1γ in vitro. This requires R38 and R39 within the HP1γ chromodomain, and the catalytic activity is enhanced by trimethylated H3K9 (H3K9me3) peptides. Mutation of R38 and R39, designed to mimic citrullination, affects HP1γ binding to H3K9me3-containing peptides. Using live-cell single-particle tracking, we demonstrate that R38 and R39 are important for HP1γ binding to chromatin in vivo. Furthermore, their mutation reduces the residence time of HP1γ on chromatin in differentiating mESCs. CONCLUSION: Citrullination is a novel post-translational modification of the structural heterochromatin protein HP1γ in mESCs that is dynamically regulated during mESC differentiation. The citrullinated residues lie within the HP1γ chromodomain and are important for H3K9me3 binding in vitro and chromatin association in vivo.Cancer Research UK (grant reference RG17001) Wellcome Trust (Core Grant reference WT203144) Cancer Research UK (grant reference C6946/A24843). Wellcome Trust (206291/Z/17/Z) Medical Research Council (MR/P019471/1 and MR/M010082/1). Royal Society Professorship (RP150066) Medical Research Council (MR/K015850/1

Molecular Identification of a Malaria Merozoite Surface Sheddase

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface “sheddase,” but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor

Background and Purpose Flecainide is a use-dependent blocker of cardiac Na+ channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na+ channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca2+-release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na+ and/or RyR2 channels. Experimental Approach We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca2+ sparks in intact adult rat cardiac myocytes. Key Results Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca2+ spark frequency. Conclusions and Implications Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca2+ sparks is likely, by analogy with flecainide, to result from Na+ channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na+ and RyR2 channels