Evaluation of live human-computer music-making: Quantitative and qualitative approaches

NOTICE: this is the author’s version of a work that was accepted for publication in International Journal of Human-Computer Studies. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Human-Computer Studies, [VOL 67,ISS 11(2009)] DOI: 10.1016/j.ijhcs.2009.05.00

Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.

*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. 

*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

An evaluation of the psychometric properties of the Indicator of Relative Need (IoRN) instrument

BACKGROUND: The Indicator of Relative Need (IoRN) instrument is designed for both health and social care services to measure function and dependency in older people. To date, the tool has not undergone assessment of validity. We report two studies aimed to evaluate psychometric properties of the IoRN. METHODS: The first study recruited patients receiving social care at discharge from hospital, those rehabilitating in intermediate care, and those in a rehabilitation at home service. Participants were assessed using the IoRN by a single researcher and by the clinical team at baseline and 8 weeks. Comparator instruments (Barthel ADL, Nottingham Extended ADL and Townsend Disability Scale) were also administered. Overall change in ability was assessed with a 7 point Likert scale at 8 weeks. The second study analysed linked routinely collected, health and social care data (including IoRN scores) to assess the relationship between IoRN category and death, hospitalisation and care home admission as a test of external validity. RESULTS: Ninety participants were included in the first study, mean age 77.9 (SD 12.0). Cronbach’s alpha for IoRN subscales was high (0.87 to 0.93); subscales showed moderate correlation with comparator tools (r = 0.43 to 0.63). Cohen’s weighted kappa showed moderate agreement between researcher and clinician IoRN category (0.49 to 0.53). Two-way intraclass correlation coefficients for IoRN subscales in participants reporting no change in ability were high (0.88 to 0.98) suggesting good stability; responsiveness coefficients in participants reporting overall change were equal to or better than comparator tools. 1712 patients were included in the second study, mean age 81.0 years (SD 7.7). Adjusted hazard ratios for death, care home admission and hospitalisation in the most dependent category compared to the least dependent IoRN category were 5.9 (95 % CI 2.0–17.0); 7.2 (95 % CI 4.4–12.0); 1.1 (95 % CI 0.5–2.6) respectively. The mean number of allocated hours of care 6 months after assessment was higher in the most dependent group compared to the least dependent group (5.6 vs 1.4 h, p = 0.005). CONCLUSIONS: Findings from these analyses support the use of the IoRN across a range of clinical environments although some limitations are highlighted

Adoption of Integrated Pest Management Practices by South Carolina Cotton Growers

The project reported here assessed the level of adoption of integrated pest management (IPM) by South Carolina cotton growers. A mail survey of growers was used to provide data on specific IPM practices utilized. Growers were categorized as low, medium, or high IPM adopters based on the frequency with which they implemented specific practices. The majority of growers fell into the medium or high IPM rankings. However, only 7% of respondents attained a high IPM ranking in the Cultural Pest Management section. This suggests that future cotton IPM Extension efforts should be directed towards increasing grower adoption of cultural IPM practices

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Adoption of Integrated Pest Management Practices by South Carolina Cotton Growers

The project reported here assessed the level of adoption of integrated pest management (IPM) by South Carolina cotton growers. A mail survey of growers was used to provide data on specific IPM practices utilized. Growers were categorized as low, medium, or high IPM adopters based on the frequency with which they implemented specific practices. The majority of growers fell into the medium or high IPM rankings. However, only 7% of respondents attained a high IPM ranking in the Cultural Pest Management section. This suggests that future cotton IPM Extension efforts should be directed towards increasing grower adoption of cultural IPM practices