Exactly Marginal Deformations and Their Supergravity Duals.

We study the space of supersymmetric AdS_{5} solutions of type IIB supergravity corresponding to the conformal manifold of the dual N=1 conformal field theory. We show that the background geometry naturally encodes a generalized holomorphic structure, dual to the superpotential of the field theory, with the existence of the full solution following from a continuity argument. In particular, this work allows us to address the long-standing problem of finding the gravity dual of the generic N=1 deformations of N=4 conformal field theory: even if we are not able to give it in a fully explicit form, we provide a proof-of-existence of the supergravity solution. Using this formalism, we derive a new result for the Hilbert series of the deformed field theories.

A Community-Based, Bionic Leg Rehabilitation Program for Patients with Chronic Stroke: Clinical Trial Protocol.

Stroke is a major global health problem whereby many survivors have unmet needs concerning mobility during recovery. As such, the use of robotic-assisted devices (i.e., a bionic leg) within a community setting may be an important adjunct to normal physiotherapy in chronic stroke survivors. This study will be a dual-center, randomized, parallel group clinical trial to investigate the impact of a community-based training program using a bionic leg on biomechanical, cardiovascular, and functional outcomes in stroke survivors. Following a baseline assessment that will assess gait, postural sway, vascular health (blood pressure, arterial stiffness), and functional outcomes (6-minute walk), participants will be randomized to a 10-week program group, incorporating (1) a physiotherapy plus community-based bionic leg training program; (2) physiotherapy only; or (3) usual care control. The training program will involve participants engaging in a minimum of 1 hour per day of bionic leg activities at home. Follow-up assessments, identical to baseline, will occur after 10 weeks, and 3 and 12 months postintervention. Given the practical implications of the study, the clinical significance of using the bionic leg will be assessed for each outcome variable. The potential improvements in gait, balance, vascular health, and functional status may have a meaningful impact on patients' quality of life. The integration of robotic devices within home-based rehabilitation programs may prove to be a cost-effective, practical, and beneficial resource for stroke survivors.

Genome-wide identification of conserved intronic non-coding sequences using a Bayesian segmentation approach.

BACKGROUND: Computational identification of non-coding RNAs (ncRNAs) is a challenging problem. We describe a genome-wide analysis using Bayesian segmentation to identify intronic elements highly conserved between three evolutionarily distant vertebrate species: human, mouse and zebrafish. We investigate the extent to which these elements include ncRNAs (or conserved domains of ncRNAs) and regulatory sequences. RESULTS: We identified 655 deeply conserved intronic sequences in a genome-wide analysis. We also performed a pathway-focussed analysis on genes involved in muscle development, detecting 27 intronic elements, of which 22 were not detected in the genome-wide analysis. At least 87% of the genome-wide and 70% of the pathway-focussed elements have existing annotations indicative of conserved RNA secondary structure. The expression of 26 of the pathway-focused elements was examined using RT-PCR, providing confirmation that they include expressed ncRNAs. Consistent with previous studies, these elements are significantly over-represented in the introns of transcription factors. CONCLUSIONS: This study demonstrates a novel, highly effective, Bayesian approach to identifying conserved non-coding sequences. Our results complement previous findings that these sequences are enriched in transcription factors. However, in contrast to previous studies which suggest the majority of conserved sequences are regulatory factor binding sites, the majority of conserved sequences identified using our approach contain evidence of conserved RNA secondary structures, and our laboratory results suggest most are expressed. Functional roles at DNA and RNA levels are not mutually exclusive, and many of our elements possess evidence of both. Moreover, ncRNAs play roles in transcriptional and post-transcriptional regulation, and this may contribute to the over-representation of these elements in introns of transcription factors. We attribute the higher sensitivity of the pathway-focussed analysis compared to the genome-wide analysis to improved alignment quality, suggesting that enhanced genomic alignments may reveal many more conserved intronic sequences.

Inferring short tandem repeat variation from paired-end short reads.

The advances of high-throughput sequencing offer an unprecedented opportunity to study genetic variation. This is challenged by the difficulty of resolving variant calls in repetitive DNA regions. We present a Bayesian method to estimate repeat-length variation from paired-end sequence read data. The method makes variant calls based on deviations in sequence fragment sizes, allowing the analysis of repeats at lengths of relevance to a range of phenotypes. We demonstrate the method's ability to detect and quantify changes in repeat lengths from short read genomic sequence data across genotypes. We use the method to estimate repeat variation among 12 strains of Arabidopsis thaliana and demonstrate experimentally that our method compares favourably against existing methods. Using this method, we have identified all repeats across the genome, which are likely to be polymorphic. In addition, our predicted polymorphic repeats also included the only known repeat expansion in A. thaliana, suggesting an ability to discover potential unstable repeats.

Sequence Segmentation with changeptGUI.

Many biological sequences have a segmental structure that can provide valuable clues to their content, structure, and function. The program changept is a tool for investigating the segmental structure of a sequence, and can also be applied to multiple sequences in parallel to identify a common segmental structure, thus providing a method for integrating multiple data types to identify functional elements in genomes. In the previous edition of this book, a command line interface for changept is described. Here we present a graphical user interface for this package, called changeptGUI. This interface also includes tools for pre- and post-processing of data and results to facilitate investigation of the number and characteristics of segment classes.

Drosophila 3' UTRs are more complex than protein-coding sequences.

The 3' UTRs of eukaryotic genes participate in a variety of post-transcriptional (and some transcriptional) regulatory interactions. Some of these interactions are well characterised, but an undetermined number remain to be discovered. While some regulatory sequences in 3' UTRs may be conserved over long evolutionary time scales, others may have only ephemeral functional significance as regulatory profiles respond to changing selective pressures. Here we propose a sensitive segmentation methodology for investigating patterns of composition and conservation in 3' UTRs based on comparison of closely related species. We describe encodings of pairwise and three-way alignments integrating information about conservation, GC content and transition/transversion ratios and apply the method to three closely related Drosophila species: D. melanogaster, D. simulans and D. yakuba. Incorporating multiple data types greatly increased the number of segment classes identified compared to similar methods based on conservation or GC content alone. We propose that the number of segments and number of types of segment identified by the method can be used as proxies for functional complexity. Our main finding is that the number of segments and segment classes identified in 3' UTRs is greater than in the same length of protein-coding sequence, suggesting greater functional complexity in 3' UTRs. There is thus a need for sustained and extensive efforts by bioinformaticians to delineate functional elements in this important genomic fraction. C code, data and results are available upon request.