Representing Polymers as Periodic Graphs with Learned Descriptors for Accurate Polymer Property Predictions.

Accurately predicting new polymers' properties with machine learning models apriori to synthesis has potential to significantly accelerate new polymers' discovery and development. However, accurately and efficiently capturing polymers' complex, periodic structures in machine learning models remains a grand challenge for the polymer cheminformatics community. Specifically, there has yet to be an ideal solution for the problems of how to capture the periodicity of polymers, as well as how to optimally develop polymer descriptors without requiring human-based feature design. In this work, we tackle these problems by utilizing a periodic polymer graph representation that accounts for polymers' periodicity and coupling it with a message-passing neural network that leverages the power of graph deep learning to automatically learn chemically relevant polymer descriptors. Remarkably, this approach achieves state-of-the-art performance on 8 out of 10 distinct polymer property prediction tasks. These results highlight the advancement in predictive capability that is possible through learning descriptors that are specifically optimized for capturing the unique chemical structure of polymers.

Unraveling the contribution of left-right language on spatial perspective taking.

We examine whether acquiring left/right language affects children's ability to take a non-egocentric left-right perspective. In Experiment 1, we tested 10-13 year-old Tseltal (Mayan) and Spanish-speaking children from the same community on a task that required they retrieve a coin they previously seen hidden in one of four boxes to the left/right/front/back of a toy sheep after the entire array was rotated out of view. Their performance on the left/right boxes correlated positively with their comprehension and use of left-right language. In Experiment 2, we found that training Tseltal-speaking children to apply left-right lexical labels to represent the location of the coin improved performance, but improvement was more robust among a second group of children trained to use gestures instead.

Nanomaterial Synthesis Insights from Machine Learning of Scientific Articles by Extracting, Structuring, and Visualizing Knowledge.

Nanomaterials of varying compositions and morphologies are of interest for many applications from catalysis to optics, but the synthesis of nanomaterials and their scale-up are most often time-consuming and Edisonian processes. Information gleaned from the scientific literature can help inform and accelerate nanomaterials development, but again, searching the literature and digesting the information are time-consuming manual processes for researchers. To help address these challenges, we developed scientific article-processing tools that extract and structure information from the text and figures of nanomaterials articles, thereby enabling the creation of a personalized knowledgebase for nanomaterials synthesis that can be mined to help inform further nanomaterials development. Starting with a corpus of ∼35k nanomaterials-related articles, we developed models to classify articles according to the nanomaterial composition and morphology, extract synthesis protocols from within the articles' text, and extract, normalize, and categorize chemical terms within synthesis protocols. We demonstrate the efficiency of the proposed pipeline on an expert-labeled set of nanomaterials synthesis articles, achieving 100% accuracy on composition prediction, 95% accuracy on morphology prediction, 0.99 AUC on protocol identification, and up to a 0.87 F1-score on chemical entity recognition. In addition to processing articles' text, microscopy images of nanomaterials within the articles are also automatically identified and analyzed to determine the nanomaterials' morphologies and size distributions. To enable users to easily explore the database, we developed a complementary browser-based visualization tool that provides flexibility in comparing across subsets of articles of interest. We use these tools and information to identify trends in nanomaterials synthesis, such as the correlation of certain reagents with various nanomaterial morphologies, which is useful in guiding hypotheses and reducing the potential parameter space during experimental design.

Alternative spin on phylogenetically inherited spatial reference frames.

People make use of different frames of reference (north-south; left-right) to talk about space. To explore the cognitive capacity that children bring to learning spatial language, Haun, Rapold, Call, Janzen, and Levinson (2006) examined children's ability to notice and abstract invariant frames of references across instances. They found that 4-year-olds and non-human great apes often noticed environment-defined allocentric relations and not body-defined egocentric ones, leading them to conclude that preschoolers are ready to learn environment-defined terms (e.g. "uphill"), but not body-defined ones (e.g., "left"). However, such a conclusion may be premature. In four new experiments we demonstrate that the previous findings could be an artifact of specific task constraints. With minor experiment modifications, similar-aged children readily noticed egocentric relations. Reviewing additional research, we provide an account of what makes acquiring frames of reference easy or difficult, and why full mastery of terms like "left" and "right" may take many years under normal circumstances.

Competing perspectives on frames of reference in language and thought.

A study found that Dutch-speaking children who prefer an egocentric (left/right) reference frame when describing spatial relationships, and Hai||om-speaking children who use a geocentric (north/south) frame had difficulty recreating small-scale spatial arrays using their language-incongruent system (Haun, Rapold, Janzen, & Levinson, 2011). In five experiments, we reconciled these results with another study showing that English (egocentric) and Tseltal Mayan (geocentric) speakers can flexibly use both systems (Abarbanell, 2010; Li, Abarbanell, Gleitman, & Papafragou, 2011). In replicating and extending Haun et al. (Experiment 1), English- but not Tseltal-speaking children could use their language-incongruent system when the instructions used their non-preferred frame of reference. Perseveration due to task order may explain the discrepancies between present English- and previous Dutch-speaking children, while not understanding task instructions using left/right language may explain why present Tseltal- and previous Hai||om-speaking children had difficulty with their language-incongruent systems. In support, Tseltal-speaking children could use an egocentric system when the instructions were conveyed without left/right language (Experiments 2-4), and many did not know left/right language (Experiment 5). These findings help reconcile seemingly conflicting sets of results and suggest that task constraints, rather than language, determine which system is easier to use (Experiment 2 vs. 3).

Frames of reference in spatial language acquisition.

Languages differ in how they encode spatial frames of reference. It is unknown how children acquire the particular frame-of-reference terms in their language (e.g., left/right, north/south). The present paper uses a word-learning paradigm to investigate 4-year-old English-speaking children's acquisition of such terms. In Part I, with five experiments, we contrasted children's acquisition of novel word pairs meaning left-right and north-south to examine their initial hypotheses and the relative ease of learning the meanings of these terms. Children interpreted ambiguous spatial terms as having environment-based meanings akin to north and south, and they readily learned and generalized north-south meanings. These studies provide the first direct evidence that children invoke geocentric representations in spatial language acquisition. However, the studies leave unanswered how children ultimately acquire "left" and "right." In Part II, with three more experiments, we investigated why children struggle to master body-based frame-of-reference words. Children successfully learned "left" and "right" when the novel words were systematically introduced on their own bodies and extended these words to novel (intrinsic and relative) uses; however, they had difficulty learning to talk about the left and right sides of a doll. This difficulty was paralleled in identifying the left and right sides of the doll in a non-linguistic memory task. In contrast, children had no difficulties learning to label the front and back sides of a doll. These studies begin to paint a detailed account of the acquisition of spatial terms in English, and provide insights into the origins of diverse spatial reference frames in the world's languages.

Numerical morphology supports early number word learning: Evidence from a comparison of young Mandarin and English learners.

Previous studies showed that children learning a language with an obligatory singular/plural distinction (Russian and English) learn the meaning of the number word for one earlier than children learning Japanese, a language without obligatory number morphology (Barner, Libenson, Cheung, & Takasaki, 2009; Sarnecka, Kamenskaya, Yamana, Ogura, & Yudovina, 2007). This can be explained by differences in number morphology, but it can also be explained by many other differences between the languages and the environments of the children who were compared. The present study tests the hypothesis that the morphological singular/plural distinction supports the early acquisition of the meaning of the number word for one by comparing young English learners to age and SES matched young Mandarin Chinese learners. Mandarin does not have obligatory number morphology but is more similar to English than Japanese in many crucial respects. Corpus analyses show that, compared to English learners, Mandarin learners hear number words more frequently, are more likely to hear number words followed by a noun, and are more likely to hear number words in contexts where they denote a cardinal value. Two tasks show that, despite these advantages, Mandarin learners learn the meaning of the number word for one three to six months later than do English learners. These results provide the strongest evidence to date that prior knowledge of the numerical meaning of the distinction between singular and plural supports the acquisition of the meaning of the number word for one.

Sortal concepts and pragmatic inference in children's early quantification of objects.

It is typically assumed that count nouns like fork act as logical sortals, specifying whether objects are countable units of a kind (e.g., that a whole fork counts as "one fork") or not (e.g., that a piece of a fork does not count as "one fork"). In four experiments, we provide evidence from linguistic and conceptual development that nouns do not specify units of quantification, but include both whole objects and their arbitrary parts in their denotations. We argue that, to restrict quantification to whole objects, nominal concepts are enriched pragmatically, via contrast with concepts denoted by alternative descriptions: a piece of a fork is not counted as "one fork" because it is "one piece of fork." Experiment 1 replicated previous findings that children count pieces of broken objects as whole objects (e.g., two pieces of fork as "two forks"), and showed that children also accept whole object labels as descriptions of object pieces (e.g., "two forks" to describe two pieces of fork). Experiment 2 showed that although children accept such descriptions in isolation, they prefer measure phrases (e.g., "two pieces of fork") when they are explicitly presented as alternatives. Experiment 3 found that children were better at excluding pieces from their counts of whole objects when measure phrases were primed prior to counting, making them accessible as alternatives to whole object labels. Finally, Experiment 4 taught children names for novel objects, and found that they do not count parts that are given unique labels or that have non-linguistic properties that suggest they are members of distinct object kinds (e.g., unique functions or physical affordances). Together, our results suggest that for children and adults alike, nominal concepts do not provide necessary and sufficient criteria for excluding parts from object kinds. To specify units of quantification--and do the work of sortals--concepts are contrasted with one another and enriched pragmatically.

Caveosomal oxidative stress causes Src-p21ras activation and lysine 63 TRAF6 protein polyubiquitination in iron-induced M1 hepatic macrophage activation.

Proinflammatory M1 activation of hepatic macrophages (HM) is critical in pathogenesis of hepatitis, but its mechanisms are still elusive. Our earlier work demonstrates the role of ferrous iron (Fe(2+)) as a pathogen-associated molecular pattern-independent agonist for activation of IκB kinase (IKK) and NF-κB in HM via activation and interaction of p21(ras), transforming growth factor ß-activated kinase-1 (TAK1), and phosphatidylinositol 3-kinase (PI3K) in caveosomes. However, iron-induced signaling upstream of these kinases is not known. Here we show that Fe(2+) induces generation of superoxide anion (O(2)()) in endosomes, reduces protein-tyrosine phosphatase (PTP) activity, and activates Src at 2∼10 min of Fe(2+) addition to rat primary HM culture. Superoxide dismutase (SOD) blocks O(2)() generation, PTP inhibition, and Src activation. Fe(2+)-induced p21(ras) activity is abrogated with the Src inhibitor PP2 and SOD. Fe(2+) stimulates Lys(63)-linked polyubiquitination (polyUb) of TRAF6 in caveosomes, and a dominant negative K63R mutant of ubiquitin or SOD prevents iron-induced TRAF6 polyUb and TAK1 activation. These results demonstrate that Fe(2+)-generated O(2)() mediates p21(ras) and TAK1 activation via PTP inhibition and Lys(63)-polyUb of TRAF6 in caveosomes for proinflammatory M1 activation in HM.

Spatial reasoning in Tenejapan Mayans.

Language communities differ in their stock of reference frames (coordinate systems for specifying locations and directions). English typically uses egocentrically-defined axes (e.g., "left-right"), especially when describing small-scale relationships. Other languages such as Tseltal Mayan prefer to use geocentrically-defined axes (e.g., "north-south") and do not use any type of projective body-defined axes. It has been argued that the availability of specific frames of reference in language determines the availability or salience of the corresponding spatial concepts. In four experiments, we explored this hypothesis by testing Tseltal speakers' spatial reasoning skills. Whereas most prior tasks in this domain were open-ended (allowing several correct solutions), the present tasks required a unique solution that favored adopting a frame-of-reference that was either congruent or incongruent with what is habitually lexicalized in the participants' language. In these tasks, Tseltal speakers easily solved the language-incongruent problems, and performance was generally more robust for these than for the language-congruent problems that favored geocentrically-defined coordinates. We suggest that listeners' probabilistic inferences when instruction is open to more than one interpretation account for why there are greater cross-linguistic differences in the solutions to open-ended spatial problems than to less ambiguous ones.

Words as windows to thought: The case of object representation.

Languages differ in how they express thought, leading some researchers to conclude that speakers of different languages perceive objects differently. Others, in contrast, argue that words are windows to thought - reflecting its structure without modifying it. Here, we explore the case study of object representation. Studies of Japanese, Chinese, and English indicate that speakers of these languages do not perceive objects differently, despite their grammatical differences. Syntax provides frames for words that can select among meanings without affecting underlying object perception.

Learning that classifiers count: Mandarin-speaking children's acquisition of sortal and mensural classifiers.

Two experiments explored two-to five-year-old Mandarin-speaking children's acquisition of classifiers, mandatory morphemes for expressing quantities in many Asian languages. Classifiers are similar to measure words in English (e.g., a piece of apple; a cup of apples), with the main difference being that classifiers are also required when counting sortals (e.g., yi ge pinguo or "one unit apple" in Mandarin means "one apple"). The current study extended prior studies (e.g., Chien et al., J East Asian Linguist 12:91-120, 2003) to examine Mandarin-speaking children's understanding of classifiers as indicating units of quantification. Children were also tested on their knowledge of numerals to assess the relationship between children's acquisition of numerals and classifiers. The findings suggest that children first notice that sortal classifiers specify properties such as shape. Only after learning some numerals do they begin to work out how classifiers indicate units of quantification. By age four, children scored above chance on most classifiers tested.

Does the conceptual distinction between singular and plural sets depend on language?

Previous studies indicate that English-learning children acquire the distinction between singular and plural nouns between 22 and 24 months of age. Also, their use of the distinction is correlated with the capacity to distinguish nonlinguistically between singular and plural sets in a manual search paradigm (D. Barner, D. Thalwitz, J. Wood, S. Yang, & S. Carey, 2007). The authors used 3 experiments to explore the causal relation between these 2 capacities. Relative to English, Japanese and Mandarin had impoverished singular-plural marking. Using the manual search task, in Experiment 1 the authors found that by around 22 months of age, Japanese children also distinguished between singular and plural sets. Experiments 2 and 3 extended this finding to Mandarin-learning toddlers. Mandarin learners who were 20-24 months of age did not yet comprehend Mandarin singular-plural marking (i.e., yige vs. yixie, or -men), yet they did distinguish between singular and plural sets in manual search. These experiments suggest that knowledge of singular-plural morphology is not necessary for deploying the nonlinguistic distinction between singular and plural sets.

Language, thought, and real nouns.

We test the claim that acquiring a mass-count language, like English, causes speakers to think differently about entities in the world, relative to speakers of classifier languages like Japanese. We use three tasks to assess this claim: object-substance rating, quantity judgment, and word extension. Using the first two tasks, we present evidence that learning mass-count syntax has little effect on the interpretation of familiar nouns between Japanese and English, and that speakers of these languages do not divide up referents differently along an individuation continuum, as claimed in some previous reports [Gentner, D., & Boroditsky, L. (2001). Individuation, relativity, and early word learning. In M. Bowerman, & S. Levinson (Eds.), Language acquisition and conceptual development (pp. 215-256). Cambridge University Press]. Instead, we argue that previous cross-linguistic differences [Imai, M., & Gentner, D. (1997). A cross-linguistic study of early word meaning: Universal ontology and linguistic influence. Cognition, 62, 169-200] are attributable to "lexical statistics" [Gleitman, L., & Papafragou, A. (2005). Language and thought. In K. Holyoak, & R. Morrison (Eds.), Cambridge handbook of thinking and reasoning (pp. 633-661). Cambridge University Press]. Speakers of English are more likely to think that a novel ambiguous expression like "the blicket" refers to a kind of object (relative to speakers of Japanese) because speakers of English are likely to assume that "blicket" is a count noun rather than a mass noun, based on the relative frequency of each kind of word in English. This is confirmed by testing Mandarin-English bilinguals with a word extension task. We find that bilinguals tested in English with mass-count ambiguous syntax extend novel words like English monolinguals (and assume that a word like "blicket" refers to a kind of object). In contrast, bilinguals tested in Mandarin are significantly more likely to extend novel words by material. Thus, online lexical statistics, rather than non-linguistic thought, mediate cross-linguistic differences in word extension. We suggest that speakers of Mandarin, English, and Japanese draw on a universal set of lexical meanings, and that mass-count syntax allows speakers of English to select among these meanings.

Of substance: the nature of language effects on entity construal.

Shown an entity (e.g., a plastic whisk) labeled by a novel noun in neutral syntax, speakers of Japanese, a classifier language, are more likely to assume the noun refers to the substance (plastic) than are speakers of English, a count/mass language, who are instead more likely to assume it refers to the object kind [whisk; Imai, M., & Gentner, D. (1997). A cross-linguistic study of early word meaning: Universal ontology and linguistic influence. Cognition, 62, 169-200]. Five experiments replicated this language type effect on entity construal, extended it to quite different stimuli from those studied before, and extended it to a comparison between Mandarin speakers and English speakers. A sixth experiment, which did not involve interpreting the meaning of a noun or a pronoun that stands for a noun, failed to find any effect of language type on entity construal. Thus, the overall pattern of findings supports a non-Whorfian, language on language account, according to which sensitivity to lexical statistics in a count/mass language leads adults to assign a novel noun in neutral syntax the status of a count noun, influencing construal of ambiguous entities. The experiments also document and explore cross-linguistically universal factors that influence entity construal, and favor Prasada's [Prasada, S. (1999). Names for things and stuff: An Aristotelian perspective. In R. Jackendoff, P. Bloom, & K. Wynn (Eds.), Language, logic, and concepts (pp. 119-146). Cambridge, MA: MIT Press] hypothesis that features indicating non-accidentalness of an entity's form lead participants to a construal of object kind rather than substance kind. Finally, the experiments document the age at which the language type effect emerges in lexical projection. The details of the developmental pattern are consistent with the lexical statistics hypothesis, along with a universal increase in sensitivity to material kind.

Association of simian virus 40 vp1 with 70-kilodalton heat shock proteins and viral tumor antigens.

Proper folding of newly synthesized viral proteins in the cytoplasm is a prerequisite for the formation of infectious virions. The major capsid protein Vp1 of simian virus 40 forms a series of disulfide-linked intermediates during folding and capsid formation. In addition, we report here that Vp1 is associated with cellular chaperones (HSP70) and a cochaperone (Hsp40) which can be coimmunoprecipitated with Vp1. Studies in vitro demonstrated the ATP-dependent interaction of Vp1 and cellular chaperones. Interestingly, viral cochaperones LT and ST were essential for stable interaction of HSP70 with the core Vp1 pentamer Vp1 (22-303). LT and ST also coimmunoprecipitated with Vp1 in vivo. In addition to these identified (co)chaperones, stable, covalently modified forms of Vp1 were identified for a folding-defective double mutant, C49A-C87A, and may represent a "trapped" assembly intermediate. By a truncation of the carboxyl arm of Vp1 to prevent the Vp1 folding from proceeding beyond pentamers, we detected several apparently modified Vp1 species, some of which were absent in cells transfected with the folding-defective mutant DNA. These results suggest that transient covalent interactions with known or unknown cellular and viral proteins are important in the assembly process.

Syntactic Cues to Individuation in Mandarin Chinese.

When presented with an entity (e.g., a wooden honey-dipper) labeled with a novel noun, how does a listener know that the noun refers to an instance of an object kind (honey-dipper) rather than to a substance kind (wood)? While English speakers draw upon count-mass syntax for clues to the noun's meaning, linguists have proposed that classifier languages, which lack count-mass syntax, provide other syntactic cues. Three experiments tested Mandarin-speakers' sensitivity to the diminutive suffix -zi and the general classifier ge when interpreting novel nouns. Experiment 1 found that -zi occurs more frequently with nouns that denote object kinds. Experiment 2 demonstrated Mandarin-speaking adults' sensitivity to ge and -zi when inferring novel word meanings. Experiment 3 tested Mandarin three- to six-year-olds' sensitivity to ge. We discuss differences in the developmental course of these cues relative to cues in English, and the impact of this difference to children's understanding of individuation.

Classifiers as Count Syntax: Individuation and Measurement in the Acquisition of Mandarin Chinese.

The distinction between mass nouns (e.g., butter) and count nouns (e.g., table) offers a test case for asking how the syntax and semantics of natural language are related, and how children exploit syntax-semantics mappings when acquiring language. Virtually no studies have examined this distinction in classifier languages (e.g., Mandarin Chinese) due to the widespread assumption that such languages lack mass-count syntax. However, Cheng and Sybesma (1998) argue that Mandarin encodes the mass-count at the classifier level: classifiers can be categorized as "mass-classifiers" or "count-classifiers." Mass and count classifiers differ in semantic interpretation and occur in different syntactic constructions. The current study is first an empirical test of Cheng and Sybesma's hypothesis, and second, a test of the acquisition of putative mass and count classifiers by children learning Mandarin. Experiments 1 and 2 asked whether count-classifiers select individuals and mass classifiers select nonindividuals and sets of individuals. Adult Mandarin-speakers indeed showed this pattern of interpretation, while 4- to 6-year-olds had not fully mastered the distinction. Experiment 3 tested participants' syntactic sensitivity by asking them to match two syntactic constructions (one that supported the mass or portion reading and one that did not) to two contrasting choices (a portion of an object and a whole object). A developmental trend was observed for the syntactic knowledge from 4-year-old children into adulthood: adults were near perfect and the older children were more likely than the younger children to correctly match the contrasting phrases to the objects. Thus, in three experiments we find support for Cheng and Sybesma's analysis, but also find that children master the syntax and semantics of Mandarin classifiers much later than English-speaking children acquire knowledge of the English mass-count distinction.

Importance of calcium-binding site 2 in simian virus 40 infection.

The exposure of molecular signals for simian virus 40 (SV40) cell entry and nuclear entry has been postulated to involve calcium coordination at two sites on the capsid made of Vp1. The role of calcium-binding site 2 in SV40 infection was examined by analyzing four single mutants of site 2, the Glu160Lys, Glu160Arg, Glu157Lys (E157K), and Glu157Arg mutants, and an E157K-E330K combination mutant. The last three mutants were nonviable. All mutants replicated viral DNA normally, and all except the last two produced particles containing all three capsid proteins and viral DNA. The defect of the site 1-site 2 E157K-E330K double mutant implies that at least one of the sites is required for particle assembly in vivo. The nonviable E157K particles, about 10% larger in diameter than the wild type, were able to enter cells but did not lead to T-antigen expression. Cell-internalized E157K DNA effectively coimmunoprecipitated with anti-Vp1 antibody, but little of the DNA did so with anti-Vp3 antibody, and none was detected in anti-importin immunoprecipitate. Yet, a substantial amount of Vp3 was present in anti-Vp1 immune complexes, suggesting that internalized E157K particles are ineffective at exposing Vp3. Our data show that E157K mutant infection is blocked at a stage prior to the interaction of the Vp3 nuclear localization signal with importins, consistent with a role for calcium-binding site 2 in postentry steps leading to the nuclear import of the infecting SV40.

Minor capsid proteins of simian virus 40 are dispensable for nucleocapsid assembly and cell entry but are required for nuclear entry of the viral genome.

We investigated the roles of simian virus 40 capsid proteins in the viral life cycle by analyzing point mutants in Vp1 and Vp2/3, as well as a deletion mutant lacking the Vp2/3 coding sequence. The Vp1 mutants (V243E and L245E) and the Vp2/3 mutants (F157E-I158E and P164R-G165E-G166R) were previously shown to be defective in Vp1-Vp2/3 interaction and to be noninfectious or poorly infectious, respectively. Here, we show that all these point mutants form stable particles following DNA transfection into cells. The Vp2/3-mutant particles contained very low levels of Vp2/3, whereas the Vp1 mutant particles contained no detectable Vp2/3. As expected, the deletion mutant also formed particles that were noninfectious. We further characterized the two Vp1 point mutants and the deletion mutant. All three mutant particles comprised Vp1 and histone-associated viral DNA, and all were able to enter cells. However, the mutant complexes failed to associate with host importins (owing to the loss of the Vp2/3 nuclear localization signal), and the mutant viral DNAs prematurely dissociated from the Vp1s, suggesting that the nucleocapsids did not enter the nucleus. Consistently, all three mutant particles failed to express large T antigen. Together, our results demonstrate unequivocally that Vp2/3 is dispensable for the formation of nucleocapsids. Further, the nucleocapsids' ability to enter cells implies that Vp1 contains the major determinants for cell attachment and entry. We propose that the major role of Vp2/3 in infectivity is to mediate the nuclear entry of viral DNA.