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

Modern word processors begin to offer a range of facilities for spelling, grammar and style checking in English. For the Dutch language hardly anything is available as yet. Many commercial word processing packages do include a hyphenation routine and a lexicon-based spelling checker but the practical usefulness of these tools is limited due to certain properties of Dutch orthography, as we will explain below. In this chapter we describe a text editor which incorporates a great deal of lexical, morphological and syntactic knowledge of Dutch and monitors the orthographical quality of Dutch texts. Section 1 deals with those aspects of Dutch orthography which pose problems to human authors as well as to computational language sensitive text editing tools. In section 2 we describe the design and the implementation of the text editor we have built. Section 3 is mainly devoted to a provisional evaluation of the system.

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

A new cognitive architecture is proposed for the syntactic aspects of human sentence processing. The architecture, called Unification Space, is biologically inspired but not based on neural nets. Instead it relies on biosynthesis as a basic metaphor. We use simulated annealing as an optimization technique which searches for the best configuration of isolated syntactic segments or subtrees in the final parse tree. The gradually decaying activation of individual syntactic nodes determines the ‘global excitation level’ of the system. This parameter serves the function of ‘computational temperature’ in simulated annealing. We have built a computer implementation of the architecture which simulates well-known sentence understanding phenomena. We report successful simulations of the psycholinguistic effects of clause embedding, minimal attachment, right association and lexical ambiguity. In addition, we simulated impaired sentence understanding as observable in agrammatic patients. Since the Unification Space allows for contextual (semantic and pragmatic) influences on the syntactic tree formation process, it belongs to the class of interactive sentence processing models.

Abstract

[Seven one-page psycholinguistic sketches]

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

Nobel's legacy, or the metamorphosis of what is idealistic Ever since the first Nobel prize in literature was awarded to Prudhomme in 1901, the decisions of the Swedish Academy have been subject to criticism. What is surprising in the changing decision policy as well as in its criticism is the fact that Alfred Nobel's original intentions are hardly ever taken into account: the Nobel prize is a philanthropic prize, it is not meant to select and honour the most eminent literary work but the work with maximal benefit to human beings. What is even more surprising is the fact that no one seems to care that the donator's Last Will is regularly broken.

Abstract

In this article, we discuss the implications of the fact that adult second language learners (outside the classroom) universally develop a well-structured, efficient and simple form of language–the Basic Variety (BV). Three questions are asked as to (1) the structural properties of the BV, (2) the status of these properties and (3) why some structural properties of ‘fully fledged’ languages are more complex. First, we characterize the BV in four respects: its lexical repertoire, the principles according to which utterances are structured, and temporality and spatiality expressed. The organizational principles proposed are small in number, and interact. We analyse this interaction, describing how the BV is put to use in various complex verbal tasks, in order to establish both what its communicative potentialities are, and also those discourse contexts where the constraints come into conflict and where the variety breaks down. This latter phenomenon provides a partial answer to the third question,concerning the relative complexity of ‘fully fledged’ languages–they have devices to deal with such cases. As for the second question, it is argued firstly that the empirically established continuity of the adult acquisition process precludes any assignment of the BV to a mode of linguistic expression (e.g., ‘protolanguage’) distinct from that of ‘fully fledged’ languages and, moreover, that the organizational constraints of the BV belong to the core attributes of the human language capacity, whereas a number of complexifications not attested in the BV are less central properties of this capacity. Finally, it is shown that the notion of feature strength, as used in recent versions of Generative Grammar, allows a straightforward characterization of the BV as a special case of an I-language, in the sense of this theory. Under this perspective, the acquisition of an Ilanguage beyond the BV can essentially be described as a change in feature strength.

Abstract

In John has left London, it is clear that the event in question, John's leaving London, has occurred in the past, for example yesterday at ten. Why is it impossible, then, to make this the event time more explicit by such an adverbial, as in Yesterday at ten, John has left London? Any solution of this puzzle crucially hinges on the meaning assigned to the perfect, and the present perfect in particular. Two such solutions, a scope solution and the 'current relevance'-solution, are discussed and shown to be inadequate. A new, strictly compositional analysis of the English perfect is suggested, and it is argued that the imcompatibility of the present perfect and most past tense adverbials has neither syntactic nor semantic reasons but follows from a simple pragmatical constraint, called here the 'position-definiteness constraint'. It is the very same constraint, which also makes an utterance such as At ten, John had left at nine pragmatically odd, even if John indeed had left at nine, and hence the utterance is true.

Abstract

Words can be distinguished by segmental differences or by suprasegmental differences or both. Studies from English suggest that suprasegmentals play little role in human spoken-word recognition; English stress, however, is nearly always unambiguously coded in segmental structure (vowel quality); this relationship is less close in Dutch. The present study directly compared the effects of segmental and suprasegmental mispronunciation on word recognition in Dutch. There was a strong effect of suprasegmental mispronunciation, suggesting that Dutch listeners do exploit suprasegmental information in word recognition. Previous findings indicating the effects of mis-stressing for Dutch differ with stress position were replicated only when segmental change was involved, suggesting that this is an effect of segmental rather than suprasegmental processing.

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.

Abstract

How can one conceive of the neuronal implementation of the processing model we proposed in our target article? In his commentary (Pulvermüller 1999, reprinted here in this issue), Pulvermüller makes various proposals concerning the underlying neural mechanisms and their potential localizations in the brain. These proposals demonstrate the compatibility of our processing model and current neuroscience. We add further evidence on details of localization based on a recent meta-analysis of neuroimaging studies of word production (Indefrey & Levelt 2000). We also express some minor disagreements with respect to Pulvermüller’s interpretation of the “lemma” notion, and concerning his neural modeling of phonological code retrieval. Branigan & Pickering discuss important aspects of syntactic encoding, which was not the topic of the target article. We discuss their well-taken proposal that multiple syntactic frames for a single verb lemma are represented as independent nodes, which can be shared with other verbs, such as accounting for syntactic priming in speech production. We also discuss how, in principle, the alternative multiple-frame-multiplelemma account can be tested empirically. The available evidence does not seem to support that account.

Abstract

During the second half of the 19th century, the psychology of language was invented as a discipline for the sole purpose of explaining the evolution of spoken language. These efforts culminated in Wilhelm Wundt’s monumental Die Sprache of 1900, which outlined the psychological mechanisms involved in producing utterances and considered how these mechanisms could have evolved. Wundt assumes that articulatory movements were originally rather arbitrary concomitants of larger, meaningful expressive bodily gestures. The sounds such articulations happened to produce slowly acquired the meaning of the gesture as a whole, ultimately making the gesture superfluous. Over a century later, gestural theories of language origins still abound. I argue that such theories are unlikely and wasteful, given the biological, neurological and genetic evidence.