We studied the similarity search performance of differently designed molecular fingerprints using multiple reference structures and different search strategies. For this purpose, nine compound activity classes were assembled that exclusively consisted of molecules with different core structures and that represented different levels of intra-class structural diversity. Thus, there was a strict one-to-one correspondence between test compounds and core structures. Analysis of unique core structures was found to be a better measure of class diversity than distributions of simplified scaffolds. On increasingly diverse classes, a trainable fingerprint using a unique search strategy performed better than others tested herein. Overall, clear preferences were detected for nearest-neighbor search strategies over fingerprint-averaging techniques. Nearest-neighbor searching that relied on selecting database compounds most similar to one of the reference structures often improved compound recovery over other averaging methods, but at the cost of decreasing the ability to detect hits that were structurally distinct from reference molecules.

One of the defining characteristics of autism spectrum disorder (ASD) is difficulty with language and communication.1 Children with ASD's onset of speaking is usually delayed, and many children with ASD consistently produce language less frequently and of lower lexical and grammatical complexity than their typically developing (TD) peers. 6,8,12,23 However, children with ASD also exhibit a significant social deficit, and researchers and clinicians continue to debate the extent to which the deficits in social interaction account for or contribute to the deficits in language production. 5,14,19,25 Standardized assessments of language in children with ASD usually do include a comprehension component; however, many such comprehension tasks assess just one aspect of language (e.g., vocabulary), 5 or include a significant motor component (e.g., pointing, act-out), and/or require children to deliberately choose between a number of alternatives. These last two behaviors are known to also be challenging to children with ASD. 7,12,13,16 We present a method which can assess the language comprehension of young typically developing children (9-36 months) and children with autism. 2,4,9,11,22 This method, Portable Intermodal Preferential Looking (P-IPL), projects side-by-side video images from a laptop onto a portable screen. The video images are paired first with a 'baseline' (nondirecting) audio, and then presented again paired with a 'test' linguistic audio that matches only one of the video images. Children's eye movements while watching the video are filmed and later coded. Children who understand the linguistic audio will look more quickly to, and longer at, the video that matches the linguistic audio. 2,4,11,18,22,26 This paradigm includes a number of components that have recently been miniaturized (projector, camcorder, digitizer) to enable portability and easy setup in children's homes. This is a crucial point for assessing young children with ASD, who are frequently uncomfortable in new (e.g., laboratory) settings. Videos can be created to assess a wide range of specific components of linguistic knowledge, such as Subject-Verb-Object word order, wh-questions, and tense/aspect suffixes on verbs; videos can also assess principles of word learning such as a noun bias, a shape bias, and syntactic bootstrapping. 10,14,17,21,24 Videos include characters and speech that are visually and acoustically salient and well tolerated by children with ASD. Video LinkThe video component of this article can be found at http://www.jove.com/video/4331/ Protocol IPL Video CreationWe design the videos to be interesting and attractive, but also non-aversive to young children with autism, in a number of ways: When animate characters are needed, we use animals rather than humans to make the scenes less socially/emotionally challenging for children with ASD. We use dynamic scenes with brightly colored objects to capture and hold attention. A red blinking light during the intertrial intervals (ITIs) holds the children's attention when...

Purpose The comprehension of tense/aspect morphology by children with ASD was assessed via Intermodal Preferential Looking (IPL) to determine whether this population's difficulties with producing these morphemes extended to their comprehension. Method Four-year-old participants were assessed twice, four months apart. They viewed a video which presented side-by-side ongoing and completed events paired with familiar verbs with past tense and progressive morphology. Their eye movements were recorded and coded offline; the IPL measures included percentage of looking time at, and latency of first look to, the matching scene. Spontaneous speech samples were also obtained, and coded for number of words, past tense, and progressive inflections. Results Relative to their baseline preferences, these four-year-old children with ASD looked more quickly to and longer at the matching scene for both morphemes. Children who produced more words, progressive, and past morphemes, as well as who performed better on standardized language assessments, demonstrated better comprehension of –ing. Conclusion Overall these children with ASD demonstrated consistent comprehension of grammatical aspect morphology; moreover, their degree of comprehension was found to correlate with spontaneous production and standardized test scores.

No abstract