Publications

Abstract

Infants learn the meaning of words from accumulated experiences of real-time interactions with their caregivers. To study the effects of visual sensory input on word learning, we recorded infant's view of the world using head-mounted eye trackers during free-flowing play with a caregiver. While playing, infants were exposed to novel label-object mappings and later learning outcomes for these items were tested after the play session. In this study we use a classification based approach to link properties of infants' visual scenes during naturalistic labeling moments to their word learning outcomes. We find that a model which integrates both highly informative and ambiguous sensory evidence is a better fit to infants' individual learning outcomes than models where either type of evidence is taken alone, and that raw labeling frequency is unable to account for the word learning differences we observe. Here we demonstrate how a computational model, using only raw pixels taken from the egocentric scene image, can derive insights on human language learning.

Abstract

The Romance languages have a rich numeral system that includes cardinals—providing the bases on which the other types of numeral series are built—ordinals, fractions, collectives, approximatives, distributives, and multiplicatives. Latin plays a decisive and continued role in their formation, both as the language to which many numerals go back directly and as an ongoing source for lexemes and formatives. While the Latin numeral system was synthetic, with a distinct ending for each type of numeral, the Romance numerals often feature more than one (unevenly distributed) marker or structure per series, which feature varying degrees of inherited, borrowed, or innovative elements. Formal consistency is strongest in cardinals, followed by ordinals and then the other types of numeral, which also tend to be more analytic or periphrastic. From a morphological perspective, Romance numerals overall have moved away from the inherited syntheticity, but several series continue to be synthetic formations—at least in part—with morphological markers drawn from Latin that may have undergone functional change (e.g. distributive > ordinal > collective). The underlying syntax of Romance numerals is in line with the overall grammatical patterns of Romance languages, as reflected in the prevalence of word order (with arithmetical correlates), connectors, (partial) loss of agreement, and analyticity. Innovation is prominent in the formation of higher numerals with bases beyond ‘thousand’, of teens and decads in Romanian, and of vigesimals in numerous Romance varieties.

Abstract

Studies have shown that cross-linguistically, consonants at the left edge of higher-level prosodic boundaries tend to be more forcefully articulated than those at lower-level boundaries, a phenomenon known as domain-initial strengthening. This study tests whether similar effects occur in Turkish, using the Autosegmental-Metrical model proposed by Ipek & Jun [1, 2] as the basis for assessing boundary strength. Productions of /t/ and /d/ were elicited in four domain-initial prosodic positions corresponding to progressively higher-level boundaries: syllable, word, intermediate phrase, and Intonational Phrase. A fifth position, nuclear word, was included in order to better situate it within the prosodic hierarchy. Acoustic correlates of articulatory strength were measured, including closure duration for /d/ and /t/, as well as voice onset time and burst energy for /t/. Our results show that closure duration increases cumulatively from syllable to intermediate phrase, while voice onset time and burst energy are not influenced by boundary strength. These findings provide corroborating evidence for Ipek & Jun’s model, particularly for the distinction between word and intermediate phrase boundaries. Additionally, articulatory strength at the left edge of the nuclear word patterned closely with word-initial position, supporting the view that the nuclear word is not associated with a distinct phrasing domain

Abstract

Speech contains pronounced amplitude modulations in the 1–9 Hz range, correlating with the syllabic rate of speech. Recent models of speech perception propose that this rhythmic nature of speech is central to speech recognition and has beneficial effects on language processing. Here, we investigated the contribution of amplitude modulations to the subjective impression listeners have of public speakers. The speech from US presidential candidates Hillary Clinton and Donald Trump in the three TV debates of 2016 was acoustically analyzed by means of modulation spectra. These indicated that Clinton’s speech had more pronounced amplitude modulations than Trump’s speech, particularly in the 1–9 Hz range. A subsequent perception experiment, with listeners rating the perceived charisma of (low-pass filtered versions of) Clinton’s and Trump’s speech, showed that more pronounced amplitude modulations (i.e., more ‘rhythmic’ speech) increased perceived charisma ratings. These outcomes highlight the important contribution of speech rhythm to charisma perception.

Abstract

This study explores how adults and children describe placement events (e.g., putting a book on a table) in a range of different languages (Finnish, English, German, Russian, Hindi, Tzeltal Maya, Spanish, and Turkish). Results show that the eight languages grammatically encode placement events in two main ways (Talmy, 1985, 1991), but further investigation reveals fine-grained crosslinguistic variation within each of the two groups. Children are sensitive to these finer-grained characteristics of the input language at an early age, but only when such features are perceptually salient. Our study demonstrates that a unitary notion of 'event' does not suffice to characterize complex but systematic patterns of event encoding crosslinguistically, and that children are sensitive to multiple influences, including the distributional properties of the target language, in constructing these patterns in their own speech.

Abstract

Reprinted from: Bowerman, M. (1990). Mapping thematic roles onto syntactic functions: Are children helped by innate linking rules? Linguistics, 28, 1253-1289.

Abstract

Narrow focus refers to accent placement that forces one interpretation of a sentence, which is then often perceived contrastively. Narrow focus is formalised in terms of alternative sets, i.e. contextually or situationally salient alternatives. In this paper, we investigate whether this model is valid also in human utterance processing. We present an eye-tracking experiment to study listeners’ expectations (i.e. eye-movements) with respect to upcoming referents. Some of the objects contrast in colour with objects that were previously referred to, others do not; the objects are referred to with either a narrow focus on the colour adjective or with broad focus on the noun. Results show that narrow focus on the adjective increases early fixations to contrastive referents. Narrow focus hence activates alternative referents in human utterance processing

Abstract

Within the ISLE Metadata Initiative (IMDI) project a user-friendly editor to enter metadata descriptions and a browser operating on the linked metadata descriptions were developed. Both tools support the usage of Controlled Vocabulary (CV) repositories by means of the specification of an URL where the formal CV definition data is available.

Abstract

The recent increase in the number and complexity of the language resources available on the Internet is followed by a similar increase of available tools for linguistic analysis. Ideally the user does not need to be confronted with the question in how to match tools with resources. If resource repositories and tool repositories offer adequate metadata information and a suitable exchange protocol is developed this matching process could be performed (semi-) automatically.

Abstract

Native speakers of Dutch with English as a second language and native speakers of English participated in an English lexical decision experiment. Phonemes in real words were replaced by others from which they are hard to distinguish for Dutch listeners. Non-native listeners judged the resulting near-words more often as a word than native listeners. This not only happened when the phonemes that were exchanged did not exist as separate phonemes in the native language Dutch, but also when phoneme pairs that do exist in Dutch were used in word-final position, where they are not distinctive in Dutch. In an English bimodal priming experiment with similar groups of participants, word pairs were used which differed in one phoneme. These phonemes were hard to distinguish for the non-native listeners. Whereas in native listening both words inhibited each other, in non-native listening presentation of one word led to unresolved competition between both words. The results suggest that inaccurate phoneme processing by non-native listeners leads to the activation of spurious lexical competitors.

Abstract

In a famous paper Harvey Sacks (1974) argued that the sequential properties of greeting conventions, as well as those governing the flow of information, mean that 'everyone has to lie'. In this paper I show this dictum to be equally true in the Tzeltal Mayan community of Tenejapa, in southern Mexico, but for somewhat different reasons. The phenomenon of interest is the practice of routine fearsome threats to small children. Based on a longitudinal corpus of videotaped and tape-recorded naturally-occurring interaction between caregivers and children in five Tzeltal families, the study examines sequences of Tzeltal caregivers' speech aimed at controlling the children's behaviour and analyzes the children's developing pragmatic skills in handling such controlling utterances, from prelinguistic infants to age five and over. Infants in this society are considered to be vulnerable, easily scared or shocked into losing their 'souls', and therefore at all costs to be protected and hidden from outsiders and other dangers. Nonetheless, the chief form of control (aside from physically removing a child from danger) is to threaten, saying things like "Don't do that, or I'll take you to the clinic for an injection," These overt scare-threats - rarely actually realized - lead Tzeltal children by the age of 2;6 to 3;0 to the understanding that speech does not necessarily convey true propositions, and to a sensitivity to the underlying motivations for utterances distinct from their literal meaning. By age 4;0 children perform the same role to their younger siblings;they also begin to use more subtle non-true (e.g. ironic) utterances. The caretaker practice described here is related to adult norms of social lying, to the sociocultural context of constraints on information flow, social control through gossip, and the different notion of 'truth' that arises in the context of non-verifiability characteristic of a small-scale nonliterate society.

Abstract

This is an encyclopedia entry surveying research and theoretical approaches to politeness phenomena in language usage.

Abstract

This paper surveys the concept of culture as used in recent work in cognitive science, assessing the very different (and sometimes minimal) role 'culture' plays in different branches and schools of linguistics: generative approaches, descriptive/comparative linguistics, typology, cognitive linguistics, semantics, pragmatics, psycholinguistics, linguistic and cognitive anthropology. The paper then describes research on one specific topic, spatial language and conceptualization, describes a methodology for studying it cross-linguistically and cross-culturally. Finally, it considers the implications of results in this area for how we can fruitfully conceptualize 'culture', arguing for an approach which shifts back and forth between individual mind and collective representations, between universals and particulars, and ties 'culture' to our biological roots.

Abstract

For multimodal annotations an exhaustive encoding system for gestures was developed to facilitate research. The structural requirements of multimodal annotations were analyzed to develop an Abstract Corpus Model which is the basis for a powerful annotation and exploitation tool for multimedia recordings and the definition of the XML-based EUDICO Annotation Format. Finally, a metadata-based data management environment has been setup to facilitate resource discovery and especially corpus management. Bt means of an appropriate digitization policy and their online availability researchers have been able to build up a large corpus covering gesture and sign language data.

Abstract

The present study set out to pin down the role of four pitch accents, fall (H*L), rise-fall (L*HL), rise (L*H), fall-rise (H*LH), as well as deaccentuation, in interpreting new vs. given information in British English by the eyetracking paradigm. The pitch accents in question were claimed to convey information status in theories of English intonational meaning. There is, however, no consensus on the postulated roles of these pitch accents. Results clearly show that pitch accent type can and does matter when interpreting information status. The effects can be reflected in the mean proportions of fixations to the competitor in a selected time window. These patterns are also present in proportions of fixations to the target but to a lesser extent. Interestingly, the effects of pitch accent types are also reflected in how fast the participants could adjust their decision as to which picture to move before the name of the picture was fully revealed. For example, when the competitor was a given entity, the proportion of fixations to the competitor increased initially in most accent conditions in the first as a result of subjects' bias towards a given entity, but started to decrease substantially earlier in the H*L condition than in the L*H and deaccentuation conditions.

Abstract

This study investigates how Mandarin-speaking children interpret state-change verbs. In Mandarin, state-change is typically encoded with resultative verb compounds (RVCs), in which the first verb (V1) specifies an action and the second (V2) a result, for example, zhai-xia 'pick-descend' (= pick, pick off/down). Unlike English state-change verb such as pick, smash, mix and fill, the action verb (V1) may imply a state-change but it does not entail it; the state-change is specified by the additional result verb (V2). Previous studies have shown that children learning English and German tend to neglect the state-change meaning in monomorphemic state-change verbs like mix and fill (Gentner, 1978; Gropen et al, 1991) and verb-particle constructions like abplücken 'pick off' (Wittek, 1999, 2000) - they do not realize that this meaning is entailed. This study examines how Mandarin-speaking children interpret resultative verb compounds and the first verb of an RVC. Four groups of Mandarin-speaking children (mean ages 2;6, 3;6, 4;6, 6;1) and an adult group participated in a judgment task. The results show that Mandarin-speaking children know from a very young age that RVCs entail a state-change; ironically, however, they make a mistake that is just the opposite to that made by the learners of English and German: they often incorrectly interpret the action verb (V1) of an RVC as if it, in itself, also entails a state-change, even though it does not. This result suggests that children do not have a uniform strategy for interpreting verb meaning, but are influenced by the language-specific lexicalization patterns they encounter in their language.

Abstract

Two groups of listeners with Dutch and British English language backgrounds judged Dutch and British English utterances, respectively, which varied in the intonation contour on the scales EMPHATIC vs. NOT EMPHATIC and SURPRISED vs. NOT SURPRISED, two meanings derived from the Effort Code. The stimuli, which differed in sentence mode but were otherwise lexically equivalent, were varied in peak height, peak alignment, end pitch, and overall register. In both languages, there are positive correlations between peak height and degree of emphasis, between peak height and degree of surprise, between peak alignment and degree of surprise, and between pitch register and degree of surprise. However, in all these cases, Dutch stimuli lead to larger perceived meaning differences than the British English stimuli. This difference in the extent to which increased pitch height triggers increases in perceived emphasis and surprise is argued to be due to the difference in the standard pitch ranges between Dutch and British English. In addition, we found a positive correlation between pitch register and the degree of emphasis in Dutch, but a negative correlation in British English. This is an unexpected difference, which illustrates a case of ambiguity in the meaning of pitch.

Abstract

In this study, we compared the performance of a long short-term memory (LSTM) neural network to the behavior of human participants on a language task that requires hierarchically structured knowledge. We show that humans interpret ambiguous noun phrases, such as second blue ball, in line with their hierarchical constituent structure. LSTMs, instead, only do
so after unambiguous training, and they do not systematically generalize to novel items. Overall, the results of our simulations indicate that a model can behave hierarchically without relying on hierarchical constituent structure.

Abstract

Speech segmentation procedures may differ in speakers of different languages. Earlier work based on French speakers listening to French words suggested that the syllable functions as a segmentation unit in speech processing. However, while French has relatively regular and clearly bounded syllables, other languages, such as English, do not. No trace of syllabifying segmentation was found in English listeners listening to English words, French words, or nonsense words. French listeners, however, showed evidence of syllabification even when they were listening to English words. We conclude that alternative segmentation routines are available to the human language processor. In some cases speech segmentation may involve the operation of more than one procedure.

Abstract

The Possible Word Constraint is a proposed mechanism whereby listeners avoid recognising words spuriously embedded in other words. It applies to words leaving a vowelless residue between their edge and the nearest known word or syllable boundary. The present study tests the usefulness of this constraint via lexical statistics of both English and Dutch. The analyses demonstrate that the constraint removes a clear majority of embedded words in speech, and thus can contribute significantly to the efficiency of human speech recognition

Abstract

Bisyllabic sequences which could be interpreted as one word or two were produced in sentence contexts by a trained speaker, and syllabic durations measured. Listeners judged whether the bisyllables, excised from context, were one word or two. The proportion of two-word choices correlated positively with measured duration, but only for bisyllables stressed on the second syllable. The results may suggest a limit for listener sensitivity to syllabic lengthening as a word boundary cue.

Abstract

Phoneme detection is a psycholinguistic task in which listeners' response time to detect the presence of a pre-specified phoneme target is measured. Typically, detection tasks have used consonant targets. This paper reports two experiments in which subjects responded to vowels as phoneme detection targets. In the first experiment, targets occurred in real words, in the second in nonsense words. Response times were long by comparison with consonantal targets. Targets in initial syllables were responded to much more slowly than targets in second syllables. Strong vowels were responded to faster than reduced vowels in real words but not in nonwords. These results suggest that the process of phoneme detection produces different results for vowels and for consonants. We discuss possible explanations for this difference, in particular the possibility of language-specificity.

Abstract

Under what circumstances do languages die? Why has their “mortality rate” increased dramatically in the recent past? What “causes of death” can be identified for historical cases, to what extent are these generalizable, and how can they be captured in an explanatory theory? In pursuing these questions, it becomes apparent that in typical cases of language death various causes tend to interact in multiple ways. Speakers’ attitudes towards their language play a critical role in all of this. Existing categorial taxonomies do not succeed in modeling the complex relationships between these factors. Therefore, an alternative, dimensional approach is called for to more adequately address (and counter) the causes of language death in a given scenario.

Abstract

Anaphora, a ubiquitous feature of natural language, poses a particular challenge to young children as they first learn language due to its referential ambiguity. In spite of this, parents and caregivers use anaphora frequently in child-directed speech, potentially presenting a risk to effective communication if children do not yet have the linguistic capabilities of resolving anaphora successfully. Through an eye-tracking study in a naturalistic free-play context, we examine the strategies that parents employ to calibrate their use of anaphora to their child's linguistic development level. We show that, in this way, parents are able to intuitively scaffold the complexity of their speech such that greater referential ambiguity does not hurt overall communication success.

Abstract

This chapter highlights the research in isolating genetic factors underlying specific language impairment (SLI), or developmental dysphasia, which exploits newly developed genotyping technology, novel statistical methodology, and DNA sequence data generated by the Human Genome Project. The author begins with an overview of results from family, twin, and adoption studies supporting genetic involvement and then goes on to outline progress in a number of genetic mapping efforts that have been recently completed or are currently under way. It has been possible for genetic researchers to pinpoint the specific mutation responsible for some speech and language disorders, providing an example of how the availability of human genomic sequence data can greatly accelerate the pace of disease gene discovery. Finally, the author discusses future prospects on how molecular genetics may offer new insight into the etiology underlying speech and language disorders, leading to improvements in diagnosis and treatment.

Abstract

In this paper we investigate the neural correlates of syntactic classification of an acquired grammatical sequence structure in an event-related FMRI study. During acquisition, participants were engaged in an implicit short-term memory task without performance feedback. We manipulated the statistical frequency-based and rule-based characteristics of the classification stimuli independently in order to investigate their role in artificial grammar acquisition. The participants performed reliably above chance on the classification task. We observed a partly overlapping corticostriatal processing network activated by both manipulations including inferior prefrontal, cingulate, inferior parietal regions, and the caudate nucleus. More specifically, the left inferior frontal BA 45 and the caudate nucleus were sensitive to syntactic violations and endorsement, respectively. In contrast, these structures were insensitive to the frequency-based manipulation.

Abstract

Language acquisition is complex. However, one thing that has been suggested to help learning is the way that information is distributed throughout language; co-occurrences among particular items (e.g., syllables and words) have been shown to help learners discover the words that a language contains and figure out how those words are used. Humans’ ability to draw on this information—“statistical learning”—has been demonstrated across a broad range of studies. However, evidence from non-WEIRD (Western, Educated, Industrialized, Rich, and Democratic) societies is critically lacking, which limits theorizing on the universality of this skill. We extended work on statistical language learning to a new, non-WEIRD linguistic population: speakers of Yélî Dnye, who live on a remote island off mainland Papua New Guinea (Rossel Island). We performed a replication of an existing statistical learning study, training adults on an artificial language with statistically defined words, then examining what they had learnt using a two-alternative forced-choice test. Crucially, we implemented several key amendments to the original study to ensure the replication was suitable for remote field-site testing with speakers of Yélî Dnye. We made critical changes to the stimuli and materials (to test speakers of Yélî Dnye, rather than English), the instructions (we re-worked these significantly, and added practice tasks to optimize participants’ understanding), and the study format (shifting from a lab-based to a portable tablet-based setup). We discuss the requirement for acute sensitivity to linguistic, cultural, and environmental factors when adapting studies to test new populations.

Abstract

Graph neural networks (GNNs) have emerged as the standard method for numerous tasks on graph-structured data such as node classification. However, real-world graphs are often evolving over time and even new classes may arise. We model these challenges as an instance of lifelong learning, in which a learner faces a sequence of tasks and may take over knowledge acquired in past tasks. Such knowledge may be stored explicitly as historic data or implicitly within model parameters. In this work, we systematically analyze the influence of implicit and explicit knowledge. Therefore, we present an incremental training method for lifelong learning on graphs and introduce a new measure based on k-neighborhood time differences to address variances in the historic data. We apply our training method to five representative GNN architectures and evaluate them on three new lifelong node classification datasets. Our results show that no more than 50% of the GNN's receptive field is necessary to retain at least 95% accuracy compared to training over the complete history of the graph data. Furthermore, our experiments confirm that implicit knowledge becomes more important when fewer explicit knowledge is available.

Abstract

COVID-19 research datasets are crucial for analyzing research dynamics. Most collections of COVID-19 research items do not to include cited works and do not have annotations
from a controlled vocabulary. Starting with ZB MED KE data on COVID-19, which comprises CORD-19, we assemble a new dataset that includes cited work and MeSH annotations for all records. Furthermore, we conduct experiments on the analysis of research dynamics, in which we investigate predicting links in a co-annotation graph created on the basis of the new dataset. Surprisingly, we find that simple heuristic methods are better at
predicting future links than more sophisticated approaches such as graph neural networks.

Abstract

Trumai, a genetically isolated language spoken in Brazil (Xingu reserve), is an example of an endangered language. Although the Trumai population consists of more than 100 individuals, only 51 people speak the language. The oral traditions are progressively dying. Given the current scenario, the documentation of this language and its cultural aspects is of great importance. In the framework of the DoBeS program (Documentation of Endangered Languages), the project "Documentation of Trumai" has selected and organized a collection of Trumai texts, with a multi-media representation of the corpus. Several kinds of information and data types are being included in the archive of the language: texts with audio and video recordings; written texts from educational materials; drawings; photos; songs; annotations in different formats; lexicon; field notes; results from scientific studies of the language (sound system, sketch grammar, comparative studies with other Xinguan languages), etc. All materials are integrated into the IMDI-Browser, a specialized tool for presenting and searching for linguistic data. This paper explores the processing phases and the results of the Trumai project taking into consideration the issue of how to combine the needs and wishes of field linguistics (content and research aspects) and the needs of archiving (structure and workflow aspects) in a well-organized corpus.

Abstract

A prototypical lexicon tool was implemented which was intended to allow researchers to collaboratively create lexicons of endangered languages. Increasingly often researchers documenting or analyzing a language work at different locations. Lexicons that evolve through continuous interaction between the collaborators can only be efficiently produced when it can be accessed and manipulated via the Internet. The SHAWEL tool was developed to address these needs; it makes use of a thin Java client and a central database solution.

Abstract

We present a quantitative model of word order and movement constraints that enables a simple and uniform treatment of a seemingly heterogeneous collection of linear order phenomena in English, Dutch and German complement constructions (Wh-extraction, clause union, extraposition, verb clustering, particle movement, etc.). Underlying the scheme are central assumptions of the psycholinguistically motivated Performance Grammar (PG). Here we describe this formalism in declarative terms based on typed feature unification. PG allows a homogenous treatment of both the within- and between-language variations of the ordering phenomena under discussion, which reduce to different settings of a small number of quantitative parameters.

Abstract

Children with developmental language disorder (DLD) regularly use the base form of verbs (e.g., dance) instead of inflected forms (e.g., danced). We propose an account of this behavior in which children with DLD have difficulty processing novel inflected verbs in their input. This leads the inflected form to face stronger competition from alternatives. Competition is resolved by the production of a more accessible alternative with high semantic overlap with the inflected form: in English, the bare form. We test our account computationally by training a nonparametric Bayesian model that infers the productivity of the inflectional suffix (-ed). We systematically vary the number of novel types of inflected verbs in the input to simulate the input as processed by children with and without DLD. Modeling results are consistent with our hypothesis, suggesting that children’s inconsistent use of inflectional morphemes could stem from inferences they make on the basis of impoverished data.

Abstract

This paper reports on an on-going project designed to collect comparable corpus data on child language and child-directed language in under-researched languages. Despite a long history of cross-linguistic research, there is a severe empirical bias within language acquisition research: Data is available for less than 2% of the world's languages, heavily skewed towards the larger and better-described languages. As a result, theories of language development tend to be grounded in a non-representative sample, and we know little about the acquisition of typologically-diverse languages from different families, regions, or sociocultural contexts. It is very likely that the reasons are to be found in the forbidding methodological challenges of constructing child language corpora under fieldwork conditions with their strict requirements on participant selection, sampling intervals, and amounts of data. There is thus an urgent need for proposals that facilitate and encourage language acquisition research across a wide variety of languages. Adopting a language documentation perspective, we illustrate an approach that combines the construction of manageable corpora of natural interaction with and between children with a sketch description of the corpus data – resulting in a set of comparable corpora and comparable sketches that form the basis for cross-linguistic comparisons.

Abstract

Using the visual-word paradigm, the present study investigated the effects of word onset and offset masking on the time course of non-native spoken-word recognition in the presence of background noise. In two experiments, Dutch non-native listeners heard English target words, preceded by carrier sentences that were noise-free (Experiment 1) or contained intermittent noise (Experiment 2). Target words were either onset- or offset-masked or not masked at all. Results showed that onset masking delayed target word recognition more than offset masking did, suggesting that – similar to natives – non-native listeners strongly rely on word onset information during word recognition in noise.

Abstract

This study investigates the time-course of information processing in both visual as well as in the auditory speech as used for word identification in face-to-face communication. It extends the limited previous research on this topic and provides a valuable database for future research in audiovisual speech perception. An evaluation of models of speech perception by ear and eye in their ability to account for the audiovisual gating data shows a superior role of the fuzzy logical model of perception (FLMP) [1] over additive models of perception. A new dynamic version of the FLMP seems to be a promising model to account for the complex interplay of perceptual and cognitive information in audiovisual spoken word recognition.

Abstract

Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2–7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active at a low level. Transfection of human glioma cells with the de2-7 EGFR has little effect in vitro, but when grown as tumor xenografts this mutated receptor imparts a dramatic growth advantage. We have now mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies unique to the different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed both in vitro and in vivo, including tyrosine 845, a known target in the wild-type EGFR for src kinase. There was a substantial upregulation of phosphorylation at every tyrosine residue of the de2-7 EGFR when cells were grown in vivo compared to the receptor isolated from cells cultured in vitro. Upregulation of phosphorylation could be mimicked in vitro by the addition of specifi c components of the ECM such as collagen via an integrin-dependent mechanism. Since this increase in in vivo phosphorylation enhances de2-7 EGFR signaling, this observation explains why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment. In a second set of experiments we analyzed the interaction between EGFRvIII and ErbB2. Co-expression of these proteins in NR6 cells, a mouse fi broblast line devoid of ErbB family members, dramatically enhanced in vivo tumorigenicity of these cells compared to cells expressing either protein alone. Detailed analysis of these xenografts demonstrated that EGFRvIII could heterodimerize and transphosphorylate the ErbB2. Since both EGFRvIII and ErbB2 are commonly expressed at gliomas, this data suggests that the co-expression of these two proteins may enhance glioma tumorigenicity.