Period-Color and Amplitude-Color Relations in Classical Cepheid Variables - VI. New Challenges for Pulsation Models

We present multiphase Period-Color/Amplitude-Color/Period-Luminosity relations using OGLE III and Galactic Cepheid data and compare with state of the art theoretical pulsation models. Using this new way to compare models and observations, we find convincing evidence that both Period-Color and Period-Luminosity Relations as a function of phase are dynamic and highly nonlinear at certain pulsation phases. We extend this to a multiphase Wesenheit function and find the same result. Hence our results cannot be due to reddening errors. We present statistical tests and the urls of movies depicting the Period-Color/Period Luminosity and Wesenheit relations as a function of phase for the LMC OGLE III Cepheid data: these tests and movies clearly demonstrate nonlinearity as a function of phase and offer a new window toward a deeper understanding of stellar pulsation. When comparing with models, we find that the models also predict this nonlinearity in both Period-Color and Period-Luminosity planes. The models with (Z=0.004, Y=0.25) fare better in mimicking the LMC Cepheid relations, particularly at longer periods, though the models predict systematically higher amplitudes than the observations

Transduction by Phi Bb-1, a Bacteriophage of Borrelia Burgdorferi

We previously described a bacteriophage of the Lyme disease agent Borrelia burgdorferi designated phi BB-1. This phage packages the host complement of the 32-kb circular plasmids (cp32s), a group of homologous molecules found throughout the genus Borrelia. To demonstrate the ability of phi BB-1 to package and transduce DNA, a kanamycin resistance cassette was inserted into a cloned fragment of phage DNA, and the resulting construct was transformed into B. burgdorferi CA-11.2A cells. The kan cassette recombined into a resident cp32 and was stably maintained. The cp32 containing the kan cassette was packaged by phi BB-1 released from this B. burgdorferi strain. phi BB-1 has been used to transduce this antibiotic resistance marker into naive CA-11.2A cells, as well as two other strains of B. burgdorferi. This is the first direct evidence of a mechanism for lateral gene transfer in B. burgdorferi

Evolution of a zoonotic pathogen:investigating prophage diversity in enterohaemorrhagic Escherichia coli O157 by long-read sequencing

Enterohaemorrhagic Escherichia coli (EHEC) O157 is a zoonotic pathogen for which colonization of cattle and virulence in humans is associated with multiple horizontally acquired genes, the majority present in active or cryptic prophages. Our understanding of the evolution and phylogeny of EHEC O157 continues to develop primarily based on core genome analyses; however, such short-read sequences have limited value for the analysis of prophage content and its chromosomal location. In this study, we applied Single Molecule Real Time (SMRT) sequencing, using the Pacific Biosciences long-read sequencing platform, to isolates selected from the main sub-clusters of this clonal group. Prophage regions were extracted from these sequences and from published reference strains. Genome position and prophage diversity were analysed along with genetic content. Prophages could be assigned to clusters, with smaller prophages generally exhibiting less diversity and preferential loss of structural genes. Prophages encoding Shiga toxin (Stx) 2a and Stx1a were the most diverse, and more variable compared to prophages encoding Stx2c, further supporting the hypothesis that Stx2c-prophage integration was ancestral to acquisition of other Stx types. The concept that phage type (PT) 21/28 (Stx2a+, Stx2c+) strains evolved from PT32 (Stx2c+) was supported by analysis of strains with excised Stx-encoding prophages. Insertion sequence elements were over-represented in prophage sequences compared to the rest of the genome, showing integration in key genes such as stx and an excisionase, the latter potentially acting to capture the bacteriophage into the genome. Prophage profiling should allow more accurate prediction of the pathogenic potential of isolates

Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial

There are compelling reasons to study the addition of both enzalutamide and abiraterone, in combination, to standard-of-care for hormone-naïve prostate cancer. Through a protocol amendment, this will be assessed in the STAMPEDE trial, with overall survival as primary outcome measure. © 2014 European Association of Urology

The Age, Extinction and Distance of the Old, Metal-Rich Open Cluster NGC 6791

An extensive grid of metal-rich isochrones utilizing the latest available input physics has been calculated for comparison with the old, metal-rich open cluster NGC 6791. The isochrones have been simultaneously fit to BV and VI color magnitude diagrams, with the same composition, reddening and distance modulus required for both colors. Our best fitting isochrone assumes [Fe/H] = +0.4, scaled solar abundance ratios, and dY/dZ = 2 (Y = 0.31), yielding an excellent fit to the data at all points along the major sequences. The resulting age is 8 Gyr, with E(B-V) = 0.10 and (m-M)_v = 13.42. The derived cluster parameters are fairly robust to variations in the isochrone [Fe/H] and helium abundances. All of the acceptable fits indicate that 0.07 < E(B-V) < 0.14$, 13.29 < (m-M)_v < 13.46, and that NGC 6791 has an age of 8.0+/- 0.5 Gyr. The fits also suggest that dY/dZ lies between 1 and 3. A metallicity as low as solar is clearly ruled out, as is dY/dZ = 0. Comparison with previous isochrone studies indicates that the derived reddening is primarily due to our use of the most recent color transformations, whereas the age depends upon both the colors and the input physics. Our isochrones provide an excellent fit to the Hyades zero-age main sequence as determined by Hipparcos, providing evidence that our derived reddening and distance modulus are reliable.Comment: 37 pages, 13 figures, to appear in A

Young children's research: children aged 4-8 years finding solutions at home and at school

Children's research capacities have become increasingly recognised by adults, yet children remain excluded from the academy, with reports of their research participation generally located in adults' agenda. Such practice restricts children's freedom to make choices in matters affecting them, underestimates children’s capabilities and denies children particular rights. The present paper reports on one aspect of a small-scale critical ethnographic study adopting a constructivist grounded approach to conceptualise ways in which children's naturalistic behaviours may be perceived as research. The study builds on multi-disciplinary theoretical perspectives, embracing 'new' sociology, psychology, economics, philosophy and early childhood education and care (ECEC). Research questions include: 'What is the nature of ECEC research?' and 'Do children’s enquiries count as research?' Initially, data were collected from the academy: professional researchers (n=14) confirmed 'finding solutions' as a research behaviour and indicated children aged 4-8 years, their practitioners and primary carers as 'theoretical sampling'. Consequently, multi-modal case studies were constructed with children (n=138) and their practitioners (n=17) in three ‘good’ schools, with selected children and their primary carers also participating at home. This paper reports on data emerging from children aged 4-8 years at school (n=17) and at home (n=5). Outcomes indicate that participating children found diverse solutions to diverse problems, some of which they set themselves. Some solutions engaged children in high order thinking, whilst others did not; selecting resources and trialing activities engaged children in 'finding solutions'. Conversely, when children's time, provocations and activities were directed by adults, the quality of their solutions was limited, they focused on pleasing adults and their motivation to propose solutions decreased. In this study, professional researchers recognised 'finding solutions' as research behaviour and children aged 4-8 years naturalistically presented with capacities for finding solutions; however, the children's encounters with adults affected the solutions they found

Genome structural variation in Escherichia coli O157:H7

The human zoonotic pathogen Escherichia coli O157:H7 is defined by its extensive prophage repertoire including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage can enable the generation of large-chromosomal rearrangements (LCRs) by homologous recombination. This work examines the types and frequencies of LCRs across the major lineages of the O157:H7 serotype. We demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157:H7 and by using both optical mapping and Oxford Nanopore long-read sequencing prove that LCRs are generated in laboratory cultures started from a single colony and that these variants can be recovered from colonized cattle. LCRs are biased towards the terminus region of the genome and are bounded by specific prophages that share large regions of sequence homology associated with the recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants indicated that important virulence phenotypes such as Shiga-toxin production, type-3 secretion and motility can be affected by LCRs. In summary, E. coli O157:H7 has acquired multiple prophage regions over time that act to continually produce structural variants of the genome. These findings raise important questions about the significance of this prophage-mediated genome contingency to enhance adaptability between environments

Support Vector Machine applied to predict the zoonotic potential of E. coli O157 cattle isolates

Sequence analyses of pathogen genomes facilitate the tracking of disease outbreaks and allow relationships between strains to be reconstructed and virulence factors to be identified. However, these methods are generally used after an outbreak has happened. Here, we show that support vector machine analysis of bovine E. coli O157 isolate sequences can be applied to predict their zoonotic potential, identifying cattle strains more likely to be a serious threat to human health. Notably, only a minor subset (less than 10%) of bovine E. coli O157 isolates analyzed in our datasets were predicted to have the potential to cause human disease; this is despite the fact that the majority are within previously defined pathogenic lineages I or I/II and encode key virulence factors. The predictive capacity was retained when tested across datasets. The major differences between human and bovine E. coli O157 isolates were due to the relative abundances of hundreds of predicted prophage proteins. This finding has profound implications for public health management of disease because interventions in cattle, such a vaccination, can be targeted at herds carrying strains of high zoonotic potential. Machine-learning approaches should be applied broadly to further our understanding of pathogen biology