This report summarizes the objectives and evaluation of the SemEval 2015 task on the sentiment analysis of figurative language on Twitter (Task 11). This is the first sentiment analysis task wholly dedicated to analyzing figurative language on Twitter. Specifically, three broad classes of figurative language are considered: irony, sarcasm and metaphor. Gold standard sets of 8000 training tweets and 4000 test tweets were annotated using workers on the crowdsourcing platform CrowdFlower. Participating systems were required to provide a fine-grained sentiment score on an 11-point scale (-5 to +5, including 0 for neutral intent) for each tweet, and systems were evaluated against the gold standard using both a Cosinesimilarity and a Mean-Squared-Error measure.

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Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor approved for the treatment of attention-deficit/ hyperactivity disorder (ADHD) in children ( ‡6 years of age), adolescents, and adults. Its metabolism and disposition are fairly complex, and primarily governed by cytochrome P450 (CYP) 2D6 (CYP2D6), whose protein expression varies substantially from person to person, and by race and ethnicity because of genetic polymorphism. These differences can be substantial, resulting in 8-10-fold differences in atomoxetine exposure between CYP2D6 poor metabolizers and extensive metabolizers. In this review, we have attempted to revisit and analyze all published clinical pharmacokinetic data on atomoxetine inclusive of public access documents from the new drug application submitted to the United States Food and Drug Administration (FDA). The present review focuses on atomoxetine metabolism, disposition, and genetic polymorphisms of CYP2D6 as they specifically relate to atomoxetine, and provides an in-depth discussion of the fundamental pharmacokinetics of the drug including its absorption, distribution, metabolism, and excretion in pediatric and adult populations. Further, a summary of relationships between genetic variants of CYP2D6 and to some degree, CYP2C19, are provided with respect to atomoxetine plasma concentrations, central nervous system (CNS) pharmacokinetics, and associated clinical implications for pharmacotherapy. Lastly, dosage adjustments based on pharmacokinetic principles are discussed.

Extensive studies of the ␤-phaseolin (phas) gene in transgenic tobacco have shown that it is highly active during seed embryogenesis but is completely silent in leaf and other vegetative tissues. In vivo footprinting revealed that the lack of even basal transcriptional activity in vegetative tissues is associated with the presence of a nucleosome that is rotationally positioned with base pair precision over three phased TATA boxes present in the phas promoter. Positioning is sequence-dependent because an identical rotational setting is obtained upon nucleosome reconstitution in vitro. A comparison of DNase I and dimethyl sulfate footprints in vivo and in vitro strongly suggests that this repressive chromatin architecture is remodeled concomitant with gene activation in the developing seed. This leads to the disruption of histonemediated DNA wrapping and the assembly of the TATA boxes into a transcriptionally competent nucleoprotein complex.Chromatin structure is known to regulate expression from several animal and yeast genes, and evidence that precisely positioned nucleosomes serve as general repressors of transcription has been obtained in vivo and in vitro (1-4). Precise positioning of nucleosomes on DNA is a complex process that can be governed by the primary sequence (5, 6). Whereas most positioned nucleosomes are remodeled before, or concurrent with, transcriptional activation, the nucleosome over the TATA region must be displaced to permit formation of an initiation complex, possibly through exchange with TFIID (7,8). Evidence supporting this exchange includes recent biochemical and crystallographic evidence for a histone octamer-like substructure in TFIID (9-11). Additionally, the 10-bp repeat pattern of DNase I cleavage and protection in the adenovirus major late promoter region, which is protected by TFIID (12, 13), is similar to that obtained for nucleosomes (14) and is indicative of DNA lying on the surface of a protein complex.In plants, the rapid accumulation of storage proteins during embryogenesis and seed development requires high transcriptional and translational activity. In contrast, promoters for seed storage protein genes are inactive in vegetative tissues. The spatial regulation of the promoter for ␤-phaseolin (phas), one of eight related genes encoding the major storage protein of bean (Phaseolus vulgaris) seed, is exceptionally tight both in bean and in transgenic tobacco (15)(16)(17). This is exemplified by the contrasting results for nuclear run-on transcription and ␤-glucuronidase (GUS) product accumulation shown in Fig. 1 for developing seeds and leaf tissues of tobacco transgenic for a Ϫ1470phas͞uidA chimeric construct (17). The absolute constraint on expression from phas in vegetative tissues was demonstrated previously in tobacco transformed with phas͞DT-A (diphtheria toxin A-chain) constructs. Although a single molecule per cell of DT-A is lethal, phenotypically normal plants were obtained (reflecting the complete absence of DT-A expression) (18). Initial zygotic developm...

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We have shown previously that a rotationally and translationally positioned nucleosome is responsible for the absence of transcriptional expression from the phaseolin (phas) gene promoter in leaf tissue and that the repressive chromatin structure is disrupted on transcriptional activation during embryogenesis. To investigate how the chromatin structure is modified, we ectopically expressed PvALF, a putative seed-specific phas activator, in leaf tissue of a tobacco line transgenic for a chimeric phas/uidA construct. DNase I footprinting in vivo revealed that the ectopic expression of PvALF resulted in remodeling of the chromatin architecture over the TATA region of the phas promoter but did not lead to transcriptional activation in the absence of abscisic acid (ABA). Treatment of the transgenic tobacco leaves with ABA in the absence of PvALF neither alleviated the repressive chromatin architecture nor activated transcription. However, in the presence of PvALF, high levels of ␤-glucuronidase expression were obtained on exposure of leaves to ABA. These results reveal that expression from the phas promoter involves at least two discrete steps: chromatin potentiation by PvALF followed by ABA-mediated transcriptional activation.

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