Indexing weighted sequences: Neat and efficient

In a weighted sequence, for every position of the sequence and every letter of the alphabet a probability of occurrence of this letter at this position is specified. Weighted sequences are commonly used to represent imprecise or uncertain data, for example in molecular biology, where they are known under the name of Position Weight Matrices. Given a probability threshold 1/z , we say that a string P of length m occurs in a weighted sequence X at position i if the product of probabilities of the letters of P at positions i, . . . , i+m−1 in X is at least 1/z . In this article, we consider an indexing variant of the problem, in which we are to pre-process a weighted sequence to answer multiple pattern matching queries. We present an O(nz)-time construction of an O(nz)-sized index for a weighted sequence of length n that answers pattern matching queries in the optimal O(m+Occ) time, where Occ is the number of occurrences reported. The cornerstone of our data structure is a novel construction of a family of [z] strings that carries the information about all the strings that occur in the weighted sequence with a sufficient probability. We thus improve the most efficient previously known index by Amir et al. (Theor. Comput. Sci., 2008) with size and construction time O(nz2 log z), preserving optimal query time. On the way we develop a new, more straightforward index for the so-called property matching problem. We provide an open-source implementation of our data structure and present experimental results using both synthetic and real data. Our construction allows us also to obtain a significant improvement over the complexities of the approximate variant of the weighted index presented by Biswas et al. at EDBT 2016 and an improvement of the space complexity of their general index. We also present applications of our index

Outcomes of a research project to identify the enablers and barriers to effective preceptorship for newly qualified nurses

Poster presentationFunded by Chesterfield Royal Hospital NHS Trus

Ghost Busting: PT-Symmetric Interpretation of the Lee Model

The Lee model was introduced in the 1950s as an elementary quantum field theory in which mass, wave function, and charge renormalization could be carried out exactly. In early studies of this model it was found that there is a critical value of g^2, the square of the renormalized coupling constant, above which g_0^2, the square of the unrenormalized coupling constant, is negative. Thus, for g^2 larger than this critical value, the Hamiltonian of the Lee model becomes non-Hermitian. It was also discovered that in this non-Hermitian regime a new state appears whose norm is negative. This state is called a ghost state. It has always been assumed that in this ghost regime the Lee model is an unacceptable quantum theory because unitarity appears to be violated. However, in this regime while the Hamiltonian is not Hermitian, it does possess PT symmetry. It has recently been discovered that a non-Hermitian Hamiltonian having PT symmetry may define a quantum theory that is unitary. The proof of unitarity requires the construction of a new time-independent operator called C. In terms of C one can define a new inner product with respect to which the norms of the states in the Hilbert space are positive. Furthermore, it has been shown that time evolution in such a theory is unitary. In this paper the C operator for the Lee model in the ghost regime is constructed exactly in the V/N-theta sector. It is then shown that the ghost state has a positive norm and that the Lee model is an acceptable unitary quantum field theory for all values of g^2.Comment: 20 pages, 9 figure

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-Regulated Pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFb1 reduces production of proinflammatory cytokines, including TNFa, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses

1958: Abilene Christian College Bible Lectures - Full Text

“GOD” Being the Abilene Christian College Annual Bible Lectures 1958 Price: $3.00 Published by FIRM FOUNDATION PUBLISHING HOUSE Box 77 Austin, Texa

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. PAPERCLIP

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa

Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.</jats:p

Calculating Evolutionary Dynamics in Structured Populations

Evolution is shaping the world around us. At the core of every evolutionary process is a population of reproducing individuals. The outcome of an evolutionary process depends on population structure. Here we provide a general formula for calculating evolutionary dynamics in a wide class of structured populations. This class includes the recently introduced “games in phenotype space” and “evolutionary set theory.” There can be local interactions for determining the relative fitness of individuals, but we require global updating, which means all individuals compete uniformly for reproduction. We study the competition of two strategies in the context of an evolutionary game and determine which strategy is favored in the limit of weak selection. We derive an intuitive formula for the structure coefficient, σ, and provide a method for efficient numerical calculation

Genomic variations and epigenomic landscape of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel

The teleost medaka (Oryzias latipes) is a well-established vertebrate model system, with a long history of genetic research, and multiple high-quality reference genomes available for several inbred strains (HdrR, HNI and HSOK). Medaka has a high tolerance to inbreeding from the wild, thus allowing one to establish inbred lines from wild founder individuals. We have exploited this feature to create an inbred panel resource: the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. This panel of 80 near-isogenic inbred lines contains a large amount of genetic variation inherited from the original wild population. We used Oxford Nanopore Technologies (ONT) long read data to further investigate the genomic and epigenomic landscapes of a subset of the MIKK panel. Nanopore sequencing allowed us to identify a much greater variety of high-quality structural variants compared with Illumina sequencing. We also present results and methods using a pan-genome graph representation of 12 individual medaka lines from the MIKK panel. This graph-based reference MIKK panel genome revealed novel differences between the MIKK panel lines compared to standard linear reference genomes. We found additional MIKK panel-specific genomic content that would be missing from linear reference alignment approaches. We were also able to identify and quantify the presence of repeat elements in each of the lines. Finally, we investigated line-specific CpG methylation and performed differential DNA methylation analysis across the 12 lines. We thus present a detailed analysis of the MIKK panel genomes using long and short read sequence technologies, creating a MIKK panel specific pan genome reference dataset allowing for the investigation of novel variation types that would be elusive using standard approaches