Publications

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 mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies specific for different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed 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 yrosine 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 at tyrosine 845 could be stimulated in vitro by the addition of specific components of the ECM via an integrindependent mechanism. These observations may partially explain why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment

Abstract

In early Dutch learner varieties, there is no evidence of finiteness being a functional category. There is no V2nd: no correlation between inflectional morphology and movement. Initially, learners express the illocutive function of finiteness through the use of illocutive markers, with the non-use of an illocutive marker expressing the default illocutive function of assertion. Illocutive markers are functioning as adjuncts with scope over the predicate. Illocutive markers become re-analysed as functional elements.The driving force is the acquisition of the auxiliary verbs that occur with past participles. It leads to a reanalysis of illocutive markers as two separate elements: an auxiliary verb and a scope adverb. The (modal) auxiliary carries illocutive function. Lexical verb-argument structure (including the external argument) occurs within the domain of the auxiliary verb. The predicate as the focus constituent occurs within the domain of a scope adverb. This reanalysis establishes a position for the external argument within the domain of AUX. The acquisition of AUX causes the acquisition of a (hierarchical) structure with a complement as a constituent which represents an underlying verb-argument structure, a predicate as the domain of elements that are in focus, and an external (specifier) position as a landing site for elements with topic function.

Abstract

One critical aspect of language acquisition is the development of a lexicon that associates sounds and meanings; but developing a lexicon first requires that the infant segment utterances into individual words. How might the infant begin this process? The present study was designed to examine the potential role that sensitivity to predominant stress patterns of words might play in lexical development. In English, by far the majority of words have stressed (strong) initial syllables. Experiment 1 of our study demonstrated that by 9 months of age American infants listen significantly longer to words with strong/weak stress patterns than to words with weak/strong stress patterns. However, Experiment 2 showed that no significant preferences for the predominant stress pattern appear with 6-month-old infants, which suggests that the preference develops as a result of increasing familiarity with the prosodic features of the native language. In a third experiment, 9-month-olds showed a preference for strong/weak patterns even when the speech input was low-pass filtered, which suggests that their preference is specifically for the prosodic structure of the words. Together the results suggest that attention to predominant stress patterns in the native language may form an important part of the infant's process of developing a lexicon.

Abstract

It is an important feature of the human sentence production system that semantic and syntactic processes may overlap in time and do not proceed strictly serially. That is, the process of building the syntactic form of an utterance does not always wait until the complete semantic content for that utterance has been decided upon. On the contrary, speakers will often start pronouncing the first words of a sentence while still working on further details of its semantic content. An important advantage is memory economy. Semantic and syntactic fragments do not have to occupy working memory until complete semantic and syntactic structures for an utterance have been computed. Instead, each semantic and syntactic fragment is processed as soon as possible and is kept in working memory for a minimum period of time. This raises the question of how the sentence production system can maintain syntactic coherence across syntactic fragments. Presumably there are processes of "syntactic bookkeeping" which (1) store in working memory those syntactic properties of a fragmentary sentence which are needed to eliminate ungrammatical continuations, and (2) check whether a prospective continuation is indeed compatible with the sentence constructed so far. In reaction time experiments where subjects described, under time pressure, simple static pictures of an action performed by an actor, the second aspect of syntactic bookkeeping could be demonstrated. This evidence is used for modelling bookkeeping processes as part of a computational sentence generator which aims at simulating the syntactic operations people carry out during spontaneous speech.

Abstract

We outline an algorithm capable of generating varied but natural sounding sequences of argument NPs in subordinate clauses of German, a semi-free word order language. In order to attain the right level of output flexibility, the algorithm considers (1) the relevant lexical properties of the head verb (not only transitivity type but also reflexivity, thematic relations expressed by the NPs, etc.), and (2) the animacy and definiteness values of the arguments, and their length. The relevant statistical data were extracted from the NEGRA–II treebank and from hand-coded features for animacy and definiteness. The algorithm maps the relevant properties onto “primary” versus “secondary” placement options in the generator. The algorithm is restricted in that it does not take into account linear order determinants related to the sentence’s information structure and its discourse context (e.g. contrastiveness). These factors may modulate the above preferences or license “tertiary” linear orders beyond the primary and secondary options considered here.

Abstract

Remarques sur les facteurs intervenant dans le processus de formulation des énoncés.

Abstract

The psychology of language as developed by Wilhelm Wundt in his fundamental work Die Sprache (1900) has a strongly mentalistic character. The dominating positions held by behaviorism in psychology and structuralism in linguistics have overruled Wundt’s language theory to the effect that it has remained relatively unknown. This situation has changed recently under the influence of transformational linguistics and cognitive psychology. The paper discusses how Wundt applied the basic psychological concepts of apperception and association to language behavior, in particular to the construction and production of sentences during unprepared speech. The final part of the paper is devoted to the work, published in 1917, of the Dutch linguistic scholar Jacques van Ginneken, who elaborated Wundt’s ideas towards an explanation of some syntactic phenomena during the language acquisition of children.

Abstract

Four probe latency experiments show that the ‘constituent boundary effect’ (transitions between constituents are more difficult than within constituents) is a retrieval and not a storage phenomenon. The experimental logic used is called paraphrastic reproduction: after verbatim memorization of some sentences, subjects were instructed to reproduce them both in their original wording and in the form of sentences that, whilst preserving the original meaning, embodied different syntactic constructions. Syntactic constructions are defined as pairs which consist of a pattern of conceptual information and a syntactic scheme, i.e. a sequence of syntactic word categories and function words. For example, the sequence noun + finite intransitive main verb (‘John runs’) expresses a conceptual actor-action relationship. It is proposed that for each overlearned and simple syntactic construction there exists a retrieval plan which does the following. It searches through the long-term memory information that has been designated as the conceptual content of the utterance(s) to be produced, looking for a token of its conceptual pattern. The retrieved information is then cast into the format of its syntactic scheme. The organization of such plans is held responsible for the constituent boundary effect.

Abstract

A series of experiments is reported in which subjects describe simple visual scenes by means of both sentential and non-sentential responses. The data support the following statements about the lexicalization (word finding) process. (1) Words used by speakers in overt naming or sentence production responses are selected by a sequence of two lexical retrieval processes, the first yielding abstract pre-phonological items (Ll -items), the second one adding their phonological shapes (L2-items). (2) The selection of several Ll-items for a multi-word utterance can take place simultaneously. (3) A monitoring process is watching the output of Ll-lexicalization to check if it is in keeping with prevailing constraints upon utterance format. (4) Retrieval of the L2-item which corresponds with a given LI-item waits until the Ld-item has been checked by the monitor, and all other Ll-items needed for the utterance under construction have become available. A coherent picture of the lexicalization process begins to emerge when these characteristics are brought together with other empirical results in the area of naming and sentence production, e.g., picture naming reaction times (Seymour, 1979), speech errors (Garrett, 1980), and word order preferences (Bock, 1982).

Abstract

Listeners cannot recognize highly reduced word forms in isolation, but they can do so when these forms are presented in context (Ernestus, Baayen, & Schreuder, 2002). This suggests that not all possible surface forms of words have equal status in the mental lexicon. The present study shows that the reduced forms are linked to the canonical representations in the mental lexicon, and that these latter representations induce reconstruction processes. Listeners restore suffixes that are partly or completely missing in reduced word forms. A series of phoneme-monitoring experiments reveals the nature of this restoration: the basis for suffix restoration is mainly phonological in nature, but orthography has an influence as well.

Abstract

This dissertation investigates two seemingly contradictory properties of the speech perception system. On the one hand, listeners are extremely sensitive to the fine phonetic details in the speech signal. These subtle acoustic cues can reduce the temporal ambiguity between words that show initial segmental overlap, and can guide lexical activation. On the other hand, comprehension does not seem to be hampered at all by the drastic reductions that typically occur in casual speech. Complete segments, and sometimes even complete syllables, may be missing, but comprehension is seemingly unaffected. This thesis aims at elucidating how words are represented and accessed in the mental lexicon, by investigating these contradictory phenomena for the domain of morphology

Abstract

Drozd's critique of Crain & Thornton's (C&T) (1998) book Investigations in Universal Grammar (IUG) raises many issues concerning theory and experimental design within generative approaches to language acquisition. I focus here on one of the strongest theoretical claims of the Modularity Matching Model (MMM): continuity of processing. For reasons different to Drozd, I argue that the assumption is tenuous. Furthermore, I argue that the focus of the MMM and the methodological prescriptions contained in IUG are too narrow to capture language acquisition.

Abstract

Pauses during continuous speech, particularly those that occur within clauses, are thought to reflect the planning of forthcoming verbal output. We used functional Magnetic Resonance Imaging (fMRI) to examine their neural correlates. Six volunteers were scanned while describing seven Rorschach inkblots, producing 3 min of speech per inkblot. In an event-related design, the level of blood oxygenation level dependent (BOLD) contrast during brief speech pauses (mean duration 1.3 s, SD 0.3 s) during overt speech was contrasted with that during intervening periods of articulation. We then examined activity associated with pauses that occurred within clauses and pauses that occurred between grammatical junctions. Relative to articulation during speech, pauses were associated with activation in the banks of the left superior temporal sulcus (BA 39/22), at the temporoparietal junction. Continuous speech was associated with greater activation bilaterally in the inferior frontal (BA 44/45), middle frontal (BA 8) and anterior cingulate (BA 24) gyri, the middle temporal sulcus (BA 21/22), the occipital cortex and the cerebellum. Left temporal activation was evident during pauses that occurred within clauses but not during pauses at grammatical junctions. In summary, articulation during continuous speech involved frontal, temporal and cerebellar areas, while pausing was associated with activity in the left temporal cortex, especially when this occurred within a clause. The latter finding is consistent with evidence that within-clause pauses are a correlate of speech planning and in particular lexical retrieval.

Abstract

Recently, the Max Planck Society founded a new Project group for Psycholinguistics. This article reviews some of the kernel issues of the group's research program. The central concern is with the context dependency of the speaker's linguistic behavior. The process of linguistically formulating depends not only on what the speaker wants to express, but also on what has been said previously (linguistic context), and on the physical and social situation (nonlinguistic context). Special attention is paid to two context-dependent phenomena.

Abstract

This study addresses the supralexical inferential processes underlying wellformedness judgements and latencies for a specic sublexical unit that appears in Dutch compounds, the interfix. Production studies have shown that the selection of interfixes in novel Dutch compounds and the speed of
this selection is primarily determined by the distribution of interfixes in existing compounds that share the left constituent with the target compound, i.e. the ‘‘left constituent family’’. In this paper, we consider the question whether constituent families also affect wellformedness decisions of novel as well as existing Dutch compounds in comprehension. We visually presented compounds containing interfixes that were either in line with the bias of the left constituent family or not. In the case of existing compounds, we also presented variants with replaced interfixes. As in production, the bias of the left constituent family emerged as a crucial predictor for both acceptance rates and response latencies. This result supports the hypothesis that, as in production, constituent families are (co-)activated in comprehension. We argue that this co-activation is part of a supralexical inferential process, and we discuss how our data might be interpreted within sublexical and supralexical theories of morphological processing.

Abstract

This study addresses the possibility that interfixes in multiconstituent nominal compounds in German and Dutch are functional as markers of immediate constituent structure.We report a lexical statistical survey of interfixation in the lexicons of German and Dutch which shows that all interfixes of German and one interfix of Dutch are significantly more likely to appear at the major constituent boundary than expected under chance conditions. A series of experiments provides evidence that speakers of German and Dutch are sensitive to the probabilistic cues to constituent structure provided by the interfixes. Thus, our data provide evidence that probability is part and parcel of grammatical competence.

Abstract

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS. We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups. Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error. Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.