Detecting sequence dependent transcriptional pauses from RNA and protein number time series

Background: Evidence suggests that in prokaryotes sequence-dependent transcriptional pauses a?ect the dynamics of transcription and translation, as well as of small genetic circuits. So far, a few pause-prone sequences have been identi?ed from in vitro measurements of transcription elongation kinetics.

Results: Using a stochastic model of gene expression at the nucleotide and codon levels with realistic parameter values, we investigate three di?erent but related questions and present statistical methods for their analysis. First, we show that information from in vivo RNA and protein temporal numbers is su?cient to discriminate between models with and without a pause site in their coding sequence. Second, we demonstrate that it is possible to separate a large variety of models from each other with pauses of various durations and locations in the template by means of a hierarchical clustering and a random forest classi?er. Third, we introduce an approximate likelihood function that allows to estimate the location of a pause site.

Conclusions: This method can aid in detecting unknown pause-prone sequences from temporal measurements of RNA and protein numbers at a genome-wide scale and thus elucidate possible roles that these sequences play in the dynamics of genetic networks and phenotype.

"The End" for piano and computer. Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC. General information State: Published Organisations: School of Creative Arts, Sonic Arts, UOA35 - Music, Drama, Dance and Performing Arts Authors: Lyon, E.

Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC.

Minimal Hilbert series for quadratic algebras and the Anick conjecture

We study the question on whether the famous Golod–Shafarevich estimate, which gives a lower bound for the Hilbert series of a (noncommutative) algebra, is attained. This question was considered by Anick in his 1983 paper ‘Generic algebras and CW-complexes’, Princeton Univ. Press, where he proved that the estimate is attained for the number of quadratic relations $d\leq n^2/4$
and $d\geq n^2/2$, and conjectured that it is the case for any number of quadratic relations. The particular point where the number of relations is equal to $n(n-1)/2$ was addressed by Vershik. He conjectured that a generic algebra with this number of relations is finite dimensional. We announce here the result that over any infinite field, the Anick conjecture holds for $d \geq 4(n2+n)/9$ and an arbitrary number of generators. We also discuss the result that confirms the Vershik conjecture over any field of characteristic 0, and a series of related
asymptotic results.

Optimization of an ether series of mGluR5 positive allosteric modulators: Molecular determinants of MPEP site interaction crossover

We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) pos. allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topol. similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site.

Discovery and SAR of a novel series of non-MPEP site mGlu(5) PAMs based on an aryl glycine sulfonammide scaffold

Herein we report the discovery and SAR of a novel series of non-MPEP site metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) based on an aryl glycine sulfonamide scaffold. This series represents a rare non-MPEP site mGlu(5) PAM chemotype.

Fluoroscopic and electrical assessment of a series of defibrillation leads:prevalence of externalized conductors

Introduction : Insulation defects with externalized conductors have been reported in the St. Jude Riata(®) family of defibrillation leads (St. Jude Medical, Sylmar, CA, USA). The objective of the Northern Ireland Riata(®) lead screening program was to identify insulation defects and externalized conductors by systematic fluoroscopic and electrical assessment in a prospectively defined cohort of patients. We sought to estimate the prevalence, identify risk factors, and determine the natural history of this abnormality. Methods : All patients with a Riata(®) lead under follow-up at the Royal Victoria Hospital were invited for fluoroscopic imaging and implantable cardioverter-defibrillator lead parameter checks. Fluoroscopic images were read independently by two cardiologists and the presence of externalized conductors was classified as positive, negative, or borderline. Results: One hundred and sixty-five of 212 patients with a Riata lead were evaluated by fluoroscopy and lead parameter measurements. The mean duration after implantation was 3.98+/-1.43 years. After screening 25 (15%) patients were classified as positive, 137 (83%) negative, and three (1.8%) borderline. Time since implantation (P = 0.001), presence of a single coil lead (P = 0.042), and patient age (P = 0.034) were significantly associated with externalized conductors. The observed rate of externalized conductors was 26.9% for 8-French and 4.7% for 7-French leads. No leads that were identified prospectively with externalized conductors had electrical abnormalities. Seven of 25 (28%) patients had a defective lead extracted by the end of this screening period. Conclusion: A significant proportion (15%) of patients with a Riata lead had an insulation breach 4 years after implantation. High-resolution fluoroscopic imaging in at least two orthogonal views is required to identify this abnormality. (PACE 2012;35:1498-1504).

The Senses of Muriel Rukeyser’s The Book of the Dead

When Muriel Rukeyser travelled to Gauley Bridge in 1936 to report on the industrial disaster that had led to the deaths of over 700 miners, her findings led her to write what is arguably her masterpiece – the 1938 poem series The Book of the Dead. Of all Rukeyser's writings, this hybrid work of documentary techniques and metaphors, of testimony and elegy, has attracted the most critical attention. However, analyses of the series have tended to focus on the ways in which the poet adopted and adapted documentary methods in order to offer a leftist ideological critique on capitalist-born social injustice. The purpose of this article is not to negate such readings, but to offer alongside them insight into a more ethical-philosophical approach that I believe guided Rukeyser's entire career. Via an examination of the ways in which Rukeyser employs the human senses to articulate the complexities of human political, metaphysical and social relations, this article explores the influence of the Zionist Martin Buber on the poet. Rukeyser acknowledged Buber's writings in her later work, but I contend here that they played a large part in the formation of her poetics, especially in connection with her documentary aesthetic. Whilst several critics have noted, albeit often superficially, the Marxist flavour of Rukeyser's poetry in The Book of the Dead, I argue for the influence of Buber over Marx in terms or responsibility, community and dialogue. Both Rukeyser's and Buber's methods of expressing and promoting these ethical necessities rely on a synaesthetic response to the world. Where Buber advances a dialogue between the self and alterity through transcendent personal encounter, Rukeyser locates such encounter in the poem, arguing for an exchange that leads to creation, and to personal and interpersonal growth.

Modified Information Criteria and Selection of Long Memory Time Series Models

The problem of model selection of a univariate long memory time series is investigated once a semi parametric estimator for the long memory parameter has been used. Standard information criteria are not consistent in this case. A Modified Information Criterion (MIC) that overcomes these difficulties is introduced and proofs that show its asymptotic validity are provided. The results are general and cover a wide range of short memory processes. Simulation evidence compares the new and existing methodologies and empirical applications in monthly inflation and daily realized volatility are presented.

Creating a Circus of Words, Music, and Sound: From Roaratorio to Owenvarragh

This article documents the creation of a work by the authors based on a score written by the composer John Cage entitled 'Owenvarragh: A Belfast Circus on The Star Factory.' The article is part of a documentary portfolio in the journal which also includes a volume of the poetry created by Dowling in accordance with the instructions of the Cage score, and a series of documentary videos on the creation of the work and its first performance. Cage's score is based on his work 'Roaratorio: An Irish Circus on Finnegan's Wake' (1979) and it provides a set of detailed instructions for the musical realisation of a literary work. The article documents this first fully realised version of the score since Cage first produced 'Roaratorio' in 1979. The work, which was motivated by the Cage centenary year in 2012, musically realises Carson's book 'The Star Factory' (1998), a novelestic autobiography of Carson's Belfast childhood. The score required the creation of a fixed media piece based on over 300 field recordings of the sounds and places mentioned in the book, a volume of poetry created from the book which is recited to form the rhythmic spine of the work, and the arrangement of a performance including these two components along with live musical performance by the authors in collaboration with three other musicians under their direction, and a video installation created for the work. The piece has been performed three times: in association with the Sonorities 2012 Festival at Queen's University of Belfast (March 2012), at The Belfast Festival at Queen's (October 2012), and in the Rymer Auditoium of the University of York (June 2013).

Additional information:

The work which the article documents was conceived by Monaghan and Dowling, and the project was initiated by Monaghan after a she received a student prize to support its development and first performance. Elements of the project will be included in her PhD dissertation for which Dowling is a supervisor. Monaghan created the fixed media piece based on over 300 field recordings, the largest single aspect of realising Cage's score. Dowling was responsible for initiating the collaboration with Ciaran Carson, and for two other components: the creation of a volume of poetry derived from the literary work which is recited in the performance, and the creation of and supervision of the technical work on a video which accompanies the piece. The co-authors consulted closely during the work on these large components from May 2011 until March 2012 when the first performance took place. The co-authors also shared in numerous other artistic and organisational aspects of the production, including the arrangement and performnance of the music, musical direction to other performers, and marketing.