17,453 research outputs found
An introduction to crowdsourcing for language and multimedia technology research
Language and multimedia technology research often relies on
large manually constructed datasets for training or evaluation of algorithms and systems. Constructing these datasets is often expensive with significant challenges in terms of recruitment of personnel to carry out the work. Crowdsourcing methods using scalable pools of workers available on-demand offers a flexible means of rapid low-cost construction of many of these datasets to support existing research requirements and potentially promote new research initiatives that would otherwise not be possible
Word searches: on the use of verbal and non-verbal resources during classroom talk
Word finding difficulties in children are typically characterised by search behaviours such as silence, circumlocution, repetition and empty words. Yet, how childrenās word searches are constructed (including gesture, gaze and prosody) and the actions accomplished during interaction have not yet been researched. In this study, eightyear- old Ciara is interacting with her teacher in the classroom. 37 segments containing word searches were analysed according to the procedures used by conversation analysts. Ciaraās interactional resources include co-ordinated deployment of syntax, pitch height and downward gaze during solitary searching that assist the enterprise of self-repair. Gaze shift towards the teacher signals a transition relevance place, thus constituting a direct invitation for her to participate in the search. Ciaraās interactional resources include semantic category labelling, phonological self-cuing and pronominal substitution that supply valuable linguistic information to the teacher and trigger production of the searched-for item. Recommendations for language teaching and therapy are presented
Statistical-mechanical lattice models for protein-DNA binding in chromatin
Statistical-mechanical lattice models for protein-DNA binding are well
established as a method to describe complex ligand binding equilibriums
measured in vitro with purified DNA and protein components. Recently, a new
field of applications has opened up for this approach since it has become
possible to experimentally quantify genome-wide protein occupancies in relation
to the DNA sequence. In particular, the organization of the eukaryotic genome
by histone proteins into a nucleoprotein complex termed chromatin has been
recognized as a key parameter that controls the access of transcription factors
to the DNA sequence. New approaches have to be developed to derive statistical
mechanical lattice descriptions of chromatin-associated protein-DNA
interactions. Here, we present the theoretical framework for lattice models of
histone-DNA interactions in chromatin and investigate the (competitive) DNA
binding of other chromosomal proteins and transcription factors. The results
have a number of applications for quantitative models for the regulation of
gene expression.Comment: 19 pages, 7 figures, accepted author manuscript, to appear in J.
Phys.: Cond. Mat
Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain.
Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). Recently, it was shown that an increase in SNCA copy numbers leads to elevated levels of wild-type SNCA-mRNA and protein and is sufficient to cause early-onset, familial PD. A critical question concerning the molecular pathogenesis of PD is what contributory role, if any, is played by the SNCA gene in sporadic PD. The expansion of SNCA-Rep1, an upstream, polymorphic microsatellite of the SNCA gene, is associated with elevated risk for sporadic PD. However, whether SNCA-Rep1 is the causal variant and the underlying mechanism with which its effect is mediated by remained elusive. We report here the effects of three distinct SNCA-Rep1 variants in the brains of 72 mice transgenic for the entire human SNCA locus. Human SNCA-mRNA and protein levels were increased 1.7- and 1.25-fold, respectively, in homozygotes for the expanded, PD risk-conferring allele compared with homozygotes for the shorter, protective allele. When adjusting for the total SNCA-protein concentration (endogenous mouse and transgenic human) expressed in each brain, the expanded risk allele contributed 2.6-fold more to the SNCA steady-state than the shorter allele. Furthermore, targeted deletion of Rep1 resulted in the lowest human SNCA-mRNA and protein concentrations in murine brain. In contrast, the Rep1 effect was not observed in blood lysates from the same mice. These results demonstrate that Rep1 regulates human SNCA expression by enhancing its transcription in the adult nervous system and suggest that homozygosity for the expanded Rep1 allele may mimic locus multiplication, thereby elevating PD risk
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