The genome of the kinetoplastid parasite Trypanosoma brucei encodes four homologs of the Saccharomyces cerevisiae 59/39 exoribonucleases Xrn1p and Xrn2p/Rat1p, XRNA, XRNB, XRNC, and XRND. In S. cerevisiae, Xrn1p is a cytosolic enzyme involved in degradation of mRNA, whereas Xrn2p is involved in RNA processing in the nucleus. Trypanosome XRND was found in the nucleus, XRNB and XRNC were found in the cytoplasm, and XRNA appeared to be in both compartments. XRND and XRNA were essential for parasite growth. Depletion of XRNA increased the abundances of highly unstable developmentally regulated mRNAs, perhaps by delaying a deadenylation-independent decay pathway. Degradation of more stable or unregulated mRNAs was not affected by XRNA depletion although a slight decrease in average poly(A) tail length was observed. We conclude that in trypanosomes 59/39 exonuclease activity is important in degradation of highly unstable, regulated mRNAs, but that for other mRNAs another step is more important in determining the decay rate.
A series of trisubstituted hydroxylactams was identified as potent enzymatic and cellular inhibitors of human lactate dehydrogenase A. Utilizing structure-based design and physical property optimization, multiple inhibitors were discovered with <10 μM lactate IC in a MiaPaca2 cell line. Optimization of the series led to , a potent cell active molecule (MiaPaca2 IC = 0.67 μM) that also possessed good exposure when dosed orally to mice.
Inspired by the incremental TER alignment, we redesigned the Indirect HMM (IHMM) alignment, which is one of the best hypothesis alignment methods for conventional MT system combination, in an incremental manner. One crucial problem of incremental alignment is to align a hypothesis to a confusion network (CN). Our incremental IHMM alignment is implemented in three different ways: 1) treat CN spans as HMM states and define state transition as distortion over covered ngrams between two spans; 2) treat CN spans as HMM states and define state transition as distortion over words in component translations in the CN; and 3) use a consensus decoding algorithm over one hypothesis and multiple IHMMs, each of which corresponds to a component translation in the CN. All these three approaches of incremental alignment based on IHMM are shown to be superior to both incremental TER alignment and conventional IHMM alignment in the setting of the Chinese-to-English track of the 2008 NIST Open MT evaluation.
Query boundaries carry useful information for query segmentation, especially when analyzing queries in a language with no space, e.g., Chinese. This paper presents our research on Chinese query segmentation via averaged perceptron to model query boundaries through an L-R tagging scheme on a large amount of unlabeled queries. Experimental results indicate that query boundaries are very informative and they significantly improve supervised Chinese query segmentation when labeled training data is very limited.
The treatment of 'spurious' words of source language is an important problem but often ignored in the discussion on phrase-based SMT. This paper explains why it is important and why it is not a trivial problem, and proposes three models to handle spurious source words. Experiments show that any source word deletion model can improve a phrase-based system by at least 1.6 BLEU points and the most sophisticated model improves by nearly 2 BLEU points. This paper also explores the impact of training data size and training data domain/genre on source word deletion.
Text generation requires a planning module to select an object of discourse and its properties. This is specially hard in descriptive games, where a computer agent tries to describe some aspects of a game world. We propose to formalize this problem as a Markov Decision Process, in which an optimal message policy can be defined and learned through simulation. Furthermore, we propose back-off policies as a novel and effective technique to fight state dimensionality explosion in this framework.
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