An X-ray and Radio Study of the Varying Expansion Velocities in Tycho's Supernova Remnant

We present newly obtained X-ray and radio observations of Tycho's supernova remnant using {\it Chandra} and the Karl G. Jansky Very Large Array in 2015 and 2013/14, respectively. When combined with earlier epoch observations by these instruments, we now have time baselines for expansion measurements of the remnant of 12-15 year in the X-rays and 30 year in the radio. The remnant's large angular size allows for proper motion measurements at many locations around the periphery of the blast wave. We find, consistent with earlier measurements, a clear gradient in the expansion velocity of the remnant, despite its round shape. The proper motions on the western and southwestern sides of the remnant are about a factor of two higher than those in the east and northeast. We showed in an earlier work that this is related to an offset of the explosion site from the geometric center of the remnant due to a density gradient in the ISM, and using our refined measurements reported here, we find that this offset is $\sim 23"$ towards the northeast. An explosion center offset in such a circular remnant has implications for searches for progenitor companions in other remnants.Comment: Accepted for publication in ApJ Letter

Using a novel small molecule inhibitor to investigate the role of Mps1 kinase activity

During mitosis, accurate chromosome segregation is essential: gain or loss of genetic information can be detrimental to cell viability, or promote tumourigenesis. The mitotic checkpoint (also known as the spindle assembly checkpoint or SAC) ensures accurate chromosome segregation by delaying cell cycle progression until accuracy can be guaranteed. Mps1 is a protein kinase that is crucial for mitotic checkpoint signalling and also for proper chromosome alignment at metaphase. However, the precise role of Mps1’s catalytic activity is still unclear. Here, I present AZ3146, a novel small molecule inhibitor of Mps1. AZ3146 inhibits recombinant Mps1 in vitro with an IC50 of ~35 nM, and has low activity against a panel of 50 kinases, suggesting a reasonable degree of selectivity. As predicted for an Mps1 inhibitor, AZ1346 treatment led to spindle checkpoint malfunction in cells, accelerated mitotic timing, and perturbed the kinetochore localisation of the checkpoint effector Mad2. AZ3146 has a negative effect on cell viability, suggesting it leads to detrimental missegregations. Thus, the cellular effects of AZ3146 are consistent with Mps1 inhibition, and I was able to use the compound confidently as a tool to further probe the role of Mps1 activity in cells.Strikingly, levels of Mps1 increased at unattached kinetochores following inhibition of its kinase activity, suggesting Mps1’s kinetochore localisation is regulated by its own activity. A kinase-dead GFP-Mps1 fusion protein only accumulated at kinetochores in the absence of endogenous, active Mps1, implicating intra-molecular interactions in regulation of Mps1’s kinetochore localisation. I confirm a role for Mps1 in the mechanism of chromosome alignment, but in contrast to previous reports I did not detect a decrease in Aurora B activity following Mps1 inhibition. On the contrary, both Mps1’s phosphorylation status and its kinetochore localisation were affected by treatment with the Aurora B inhibitor ZM447439, placing Mps1 downstream of Aurora B. As an alternative explanation for the alignment defect in cells with reduced Mps1 activity, I found that levels of the plus-end directed kinesin Cenp-E were markedly decreased at unaligned kinetochores. I propose a model in which catalytically active Mps1’s auto-release from kinetochores simultaneously promotes both mitotic checkpoint signalling and chromosome alignment by facilitating Mad2 dimerisation and Cenp-E binding at unattached kinetochores.EThOS - Electronic Theses Online ServiceBBSRC : University of Manchester alumni fundGBUnited Kingdo

Species and functional trait turnover in response to broad-scale change and an invasive species

While beta diversity has been implicated as a key factor in controlling resilience of communities to stressors, lack of long-term data sets has limited the study of temporal dynamics of beta diversity. With a time series at two sites in excess of 40yr, we investigated turnover of both species and functional traits in a system stressed by eutrophication and overfishing and undergoing climate change and invasion. The two sites, although located near to each other, differ in water depth (20 cf. 35m), but both sites have displayed increased abundances of an invasive polychaete since 1990. We tested two hypotheses related to the effect of an invasive species; that taxa richness and turnover would decrease, and trait richness would increase post invasion and that trait turnover would increase between arrival and establishment of the invasive. Generally, we observed different dynamics at the two sites and responses not consistent with our hypotheses. We detected an increase in taxa richness at both sites and an increase in taxa turnover and number of traits at one site only. Trait turnover was higher prior to the invasion, although again only at one site. Disjunctive responses between species and trait turnover occurred, with the invader contributing in a nonrandom fashion to trait turnover. The lack of strong, consistent responses to the arrival and establishment of the invasive, and the decrease in trait turnover, suggests that effects of invasives are not only system- and species-dependent, but also depend on community dynamics of the invaded site, in particular the assembly processes, and historical context.Peer reviewe

Relationship between Greenland Ice Sheet surface speed and modeled effective pressure

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Earth Surface 123 (2018): 2258-2278, doi:10.1029/2017JF004581.We use a numerical subglacial hydrology model and remotely sensed observations of Greenland Ice Sheet surface motion to test whether the inverse relationship between effective pressure and regional melt season surface speeds observed at individual sites holds on a regional scale. The model is forced with daily surface runoff estimates for 2009 and 2010 across an ~8,000‐km2 region on the western margin. The overall subglacial drainage system morphology develops similarly in both years, with subglacial channel networks growing inland from the ice sheet margin and robust subglacial pathways forming over bedrock ridges. Modeled effective pressures are compared to contemporaneous regional surface speeds derived from TerraSAR‐X imagery to investigate spatial relationships. Our results show an inverse spatial relationship between effective pressure and ice speed in the mid‐melt season, when surface speeds are elevated, indicating that effective pressure is the dominant control on surface velocities in the mid‐melt season. By contrast, in the early and late melt seasons, when surface speeds are slower, effective pressure and surface speed have a positive relationship. Our results suggest that outside of the mid‐melt season, the influence of effective pressures on sliding speeds may be secondary to the influence of driving stress and spatially variable bed roughness.National Aeronautics and Space Administration (NASA). Grant Number: NXX10AI30G National Science Foundation (NSF) American Geophysical Union Horton Research Grant; National Science Foundation Graduate Research Fellowship; National Science Foundation's Office of Polar Programs (NSF‐OPP) Grant Numbers: PLR‐1418256, ARC‐1023364, ARC‐0520077; Woods Hole Oceanographic Institution's Ocean and Climate Change Institute (OCCI)2019-03-2

The Etiology of Observed Negative Emotionality from 14 to 24 Months

We examined the magnitude of genetic and environmental influences on observed negative emotionality at age 14, 20, and 24 months. Participants were 403 same-sex twin pairs recruited from the Longitudinal Twin Study whose emotional responses to four different situations were coded by independent raters. Negative emotionality showed significant consistency across settings, and there was evidence of a latent underlying negative emotionality construct. Heritability decreased, and the magnitude of shared environmental influences increased, for the latent negative emotionality construct from age 14 to 24 months. There were significant correlations between negative emotionality assessed at age 14, 20, and 24 months, and results suggested common genetic and shared environmental influences affecting negative emotionality across age, and that age-specific influences are limited to non-shared environmental influences, which include measurement error

NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

D.K.M., L.K.K., D.W.S., J.R., and D.A.O. are employees of NovaBiotics Ltd. D.A.O. is a director and shareholder of NovaBiotics Ltd. D.K.M., L.K.K., F.H., D.W.S., and J.R. carried out the experiments described in the manuscript. D.K.M., L.K.K., and D.A.O. came up with the ideas and designed the experiments conducted in the manuscript. D.K.M., D.A.O., and L.K.K. wrote and edited the manuscript. Samples for electron microscopy were prepared by the microscopy and histology facility at the University of Aberdeen. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1). AUTHOR CORRECTION Volume 61, no. 9, e00502-17, 2017, https://doi.org/10.1128/AAC.00502-17. Page 1: Carol A. Munro should be added to the list of authors. The updated byline and affiliations are shown above. Page 11: the last paragraph of Acknowledgments should be replaced with the following sentences. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1). Copyright © 2018 American Society for Microbiology.Peer reviewedPublisher PD

Pragmatic cluster randomised controlled trial of contextualised grammar teaching and small group teaching to improve the writing skills of 11 year old children

Introduction: We evaluated two interventions: a contextualised grammar teaching intervention – Grammar for Writing - to assess whether it improved 11 year old children’s writing skills; and a small group literacy intervention to assess whether or not this was effective. Design and method: We used a pragmatic cluster randomised trial with partial split plot design. Independent concealed randomisation was undertaken at the class level, and, within the intervention group, children were also individually randomised to receive the whole class intervention plus a small group intervention or to receive the intervention in a whole class setting only. The main outcomes were writing and reading assessed by the Progress in English 11 (Long Form) test (GL Assessment). Results: In 2013, 55 schools in England, each with two classes, were recruited and randomised. Within each school, the two classes were randomly allocated to receive either the intervention or the control condition. After randomisation, 2 schools withdrew, leaving 53 schools, 106 classes and 2510 pupils. We observed an effect size (ES) of 0.10 favouring the Grammar for Writing classes; however, this was not statistically significant (95% confidence interval (CI) -0.10 to 0.31). Pupils randomised to the small groups had an increased literacy score when compared with the control classes (ES = 0.24, 95% CI 0.00 to 0.49) and when compared with the intervention children taught in the whole class (ES = 0.21, 95% CI 0.04 to 0.38). Conclusion: There is little evidence that this form of contextualised grammar teaching had an effect on 11 year old children’s writing skills. There was some evidence of an effect for small group teaching

Multidimensional sexual perfectionism and female sexual function: A longitudinal investigation

Research on multidimensional sexual perfectionism differentiates four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people’s beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people’s beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and female sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual perfectionism contributes to women’s negative sexual self-concept and female sexual dysfunction