bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10)
Authors: Wang Lili , Ogawa Seishi , Hangaishi Akira , Qiao Ying , Hosoya Noriko , Nanya Yasuhito , Ohyashiki Kazuma , Mizoguchi Hideaki , Hirai Hisamaru
Published: June 2003

An unbalanced translocation der(1;7)(q10; p10) is a nonrandom chromosomal aberration commonly observed in myelodysplastic syndrome and acute myeloid leukemia. We molecularly analyzed the breakpoints of der(1;7)(q10;p10) by quantitative fluorescent in situ hybridization (FISH) analyses using centromeric satellite DNAs mapped to chromosomes 1 and 7 as probes. We found that the signal intensities of 2 centromere alphoid probes, D1Z7 on chromosome 1 and D7Z1 on chromosome 7, were almost invariably reduced on the derivative chromosome compared with those on their normal counterparts. These results suggest that this translocation results from the recombination between the 2 alphoids, which was further confirmed by fiber FISH experiments. Because the relative reduction in the intensities of D1Z7 and D7Z1 signals on the derivative chromosomes was highly variable among patients, it was estimated that the breakpoints in these patients were randomly distributed over several megabase pairs within each alphoid cluster except for its extreme end to the short arm. Our results provide a novel insight into the structural basis for generation of this translocation as well as its leukemogenic roles. (Blood. 2003;102:2597-2604)
Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice compared with nonhuman primates
Authors: Horn Peter A. , Thomasson Bobbie M. , Wood Brent L. , Andrews Robert G. , Morris Julia C. , Kiem Hans-Peter
Published: June 2003

The nonobese diabetic/severe combined immune-deficient (NOD/SCID) mouse xenotransplantation assay is the most commonly used surrogate assay for the study of human candidate stem cells. In contrast to large animal and human studies, however, it is limited by the short life span of the recipients, the limited proliferative demand placed on the transplanted cells, and the inability to support differentiation into all hematopoietic lineages. In the present study, we directly compared hematopoietic repopulation in NOD/SCID mice with autologous reconstitution in the baboon, a well-established preclinical large animal model for stem cell transplantation. Baboon CD34-enriched marrow cells were retrovirally marked and infused into the irradiated baboon and the NOD/SCID mice. Although the percentage of gene-marked cells was high and remained stable in NOD/SCID mice up to 12 weeks and in those that underwent secondary transplantation, we observed a considerable decline and overall a significantly (10-fold) lower percentage of gene-marked cells in the baboons. In addition, clonal integration site analysis revealed common proviral vector integrants in NOD/SCID repopulating cells and in the baboon at 6 weeks but not at 6 months after transplantation. These results suggest that distinct hematopoietic stem/progenitor cells are responsible for hematopoietic reconstitution in NOD/SCID mice compared with nonhuman primates. (Blood. 2003;102:4329-4335)
NF-κB activation in premalignant mouse tal-1/scl thymocytes and tumors
Authors: O'Neil Jennifer , Ventura Juan-Jose , Cusson Nicole , Kelliher Michelle
Published: June 2003

TAL-1/SCL activation is a common genetic event in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Expression of tal-1/scl or a DNA binding mutant of tal-1/scl induces arrest of thymocyte development, resulting in decreases in double-positive and single-positive CD4 thymocytes. Moreover, nuclear p65/p50 heterodimers are detected in premalignant tal-1/scl and mut tal-1/scl thymocytes, suggesting that E2A depletion may induce developmental arrest and stimulate NF-κB activation. Increased NF-κB activity is also observed in tal-1/scl tumors and bcl-2 is overexpressed. To examine the contribution of NF-κB to tal-1/scl tumor growth in vivo, we expressed a mutant form of IκBα in tal-1/scl tumor cells. Although expression of mutant IκBα inhibited the tumor necrosis factor alpha (TNF-α)-induced NF-κB response, it had no effect on tumor growth in mice. These data suggest that NF-κB activation is an early event in tal-1/scl-induced leukemogenesis, associated with arrest of thymocyte development, and does not appear to contribute to tal-1/scl-induced tumor growth. (Blood. 2003;102:2593-2596)
Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax
Authors: Cao Xuefang , Deng Xingming , May W. Stratford
Published: June 2003

Bax is cleaved by calpain at aspartate 33 (Asp33) to yield p18 Bax during stress-induced apoptosis. To assess the role of p18 Bax in apoptosis, an ecdysone-inducible expression system was generated. Similar levels of wild-type (WT) and noncleavable Asp33Ala (Asp→Ala) Bax are induced in 293 cells while expression of N-terminal-deleted p18 (Δ1-33) Bax remains low (20% of full-length p21 Bax) due to a reduced half-life (2 hours versus 12 hours for p21 Bax) resulting from increased sensitivity to cathepsin-like proteolytic degradation. Expression of p18 Bax is enhanced to levels comparable to p21 Bax when induction is carried out in the presence of cathepsin inhibitors, Z-Phe-Gly-NHO-Bz or N-Acetyl-Leu-Leu-Met-CHO. Compared with WT Bax, expression of similar levels of p18 Bax and, surprisingly, Asp33Ala Bax more potently induces apoptosis as indicated by increased cytochrome c release, caspase-9/-3 activation, and DNA fragmentation, potentially due to their increased homo-oligomerization in mitochondrial membranes. Studies in A-549, U-937, K-562, and HL-60 cells confirm that inhibition of Bax cleavage results in 25% to 35% reduction of drug-induced apoptosis, while inhibition of p18 Bax degradation enhances apoptosis by 25% to 40%. Results indicate that although cleavage to p18 Bax is not required for Bax to initiate apoptosis, p18 Bax potently accelerates the apoptotic process. (Blood. 2003;102:2605-2614)
Disruption of the β3 663-687 disulfide bridge confers constitutive activity to β3 integrins
Authors: Butta Nora , Arias-Salgado Elena G. , González-Manchón Consuelo , Ferrer Milagros , Larrucea Susana , Ayuso Matilde S. , Parrilla Roberto
Published: June 2003

The platelet fibrinogen receptor, integrin αIIbβ3, is a noncovalent heterodimer of glycoproteins IIb and IIIa. This work was aimed at elucidating the role played by the carboxy-terminal extracellular, trans-membrane, and cytoplasmic regions of the glycoprotein β3 in the formation of functional complexes with α subunits. Progressive carboxy-terminal deletions of β3 revealed that surface exposure of αIIbβ3 or αvβ3 could not occur in the absence of the transmembrane domain of β3. In contrast, internal deletions 616 to 690 of the carboxy-terminal regions of the β3 ectodomain led to surface exposure of constitu tive active receptors in CHO cells, as indicated by the enhanced rate of cell adhesion to immobilized ligands and spontaneous binding to soluble fibrinogen or activation-dependent antibody PAC-1. The functional analysis of cysteine mutations within the 616 to 690 region of β3 or chimeric β3-β7 subunits revealed that disruption of the C663-C687 disulfide bridge endows constitutive activity to the αIIbβ3 receptor. It is concluded that the carboxy-terminal tail of the β3 ectodomain, so-called β tail domain (βTD), is not essential for cell surface expression of β3 receptors. However, a basal, nonactivated, low ligand-affinity state of the β3 integrins demands a normal conformation of this domain. (Blood. 2003;102:2491-2497)
NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma
Authors: Catley Laurence , Weisberg Ellen , Tai Yu-Tzu , Atadja Peter , Remiszewski Stacy , Hideshima Teru , Mitsiades Nicholas , Shringarpure Reshma , LeBlanc Richard , Chauhan Dharminder , Munshi Nikhil C. , Schlossman Robert , Richardson Paul , Griffin James , Anderson Kenneth C.
Published: June 2003

Histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in hematologic malignancies. Here we show that NVP-LAQ824, a novel hydroxamic acid derivative, induces apoptosis at physiologically achievable concentrations (median inhibitory concentration [IC50] of 100 nM at 24 hours) in multiple myeloma (MM) cell lines resistant to conventional therapies. MM.1S myeloma cell proliferation was also inhibited when cocultured with bone marrow stromal cells, demonstrating ability to overcome the stimulatory effects of the bone marrow microenvironment. Importantly, NVP-LAQ824 also inhibited patient MM cell growth in a dose- and time-dependent manner. NVP-LAQ824-induced apoptotic signaling includes up-regulation of p21, caspase cascade activation, and poly (adenosine diphosphate [ADP]) ribose (PARP) cleavage. Apoptosis was confirmed with cell cycle analysis and annexin-propidium iodide staining. Interestingly, treatment of MM cells with NVPLAQ824 also led to proteasome inhibition, as determined by reduced proteasome chymotrypsin-like activity and increased levels of cellular polyubiquitin conjugates. Finally, a study using NVP-LAQ824 in a preclinical murine myeloma model provides in vivo relevance to our in vitro studies. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in MM. (Blood. 2003;102:2615-2622)
CD94 transcripts imply a better prognosis in nasal-type extranodal NK/T-cell lymphoma
Authors: Lin Chung-Wu , Chen Yu-Hua , Chuang Yi-Chun , Liu Ting-Yun , Hsu Su-Ming
Published: June 2003

Transcription of natural killer (NK) cell antigen receptors (NKRs), such as CD94, NKG2, and killer immunoglobulin-like receptors (KIRs), is developmentally regulated and clonally distributed. We have shown a restricted KIR repertoire (rKIR-R) without monoclonal T-cell receptor rearrangement (mTCR-R) supports a NK lineage in nasal-type extranodal NK/T-cell lymphoma (NTENL) but does not correlate with clinical outcomes. Developing NK cells express first CD94, then NKG2A, NKG2E, and finally NKG2C. This sequence suggests an immature CD94- and a mature CD94+ subtype of NTENL. Using a rKIR-R without a mTCR-R as a criterion in 25 cases of NTENL, we confirmed a true NK lineage in 19 cases, including 10 CD94+ and 9 CD94- patients by reverse transcriptase-polymerase chain reaction (RT-PCR). Eight of the 10 CD94+ patients but only 2 of the 9 CD94- patients survived beyond 1 year (median survival, 60 months versus 10 months by Meier-Kaplan survival analysis, P = .026 by Cox F test). The remaining 6 patients had a rKIR-R plus a mTCR-R, suggesting mixed NK/T differentiation. They were CD94- by RT-PCR, found predominantly in young women, and had a median survival of 35 months. Thus, on the basis of the transcripts of NKRs, a division of NTENLs into CD94+, CD94-, and mixed NK/T types reflects a true biologic divergence with different clinical behaviors. (Blood. 2003;102:2623-2631)
Rituximab in relapsed or refractory hairy cell leukemia
Authors: Thomas Deborah A. , O'Brien Susan , Bueso-Ramos Carlos , Faderl Stefan , Keating Michael J. , Giles Francis J. , Cortes Jorge , Kantarjian Hagop M.
Published: June 2003

The purpose of this study was to investigate the efficacy and safety of the monoclonal antibody, rituximab, in relapsed or refractory hairy cell leukemia (HCL). Fifteen patients with relapsed or primary refractory HCL after nucleoside analogs received rituximab 375 mg/m2 weekly for a total of 8 planned doses. An additional 4 doses could be administered to responders who had not achieved complete response (CR). The overall response rate was 80%. Eight patients (53%) achieved CR, 2 (13%) attained CR by hematologic parameters with residual marrow disease (1% to 5% marrow hairy cells), and 2 (13%) had a partial response. Of the 12 responders followed for a median of 32 months (range, 8 to 45+ months), 5 patients (42%) had progression of disease 8, 12, 18, 23, and 39 months from the start of therapy. Three patients failed to respond (after 4, 6, or 8 doses). Reductions in serum interleukin-2 receptor (sIL-2R) levels correlated with response. Toxicity was minimal, and no infectious episodes were observed. Rituximab has significant activity and minimal toxicity in HCL and warrants further study. Rituximab should be explored further in HCL with regard to eradication of minimal residual disease and in combination with nucleoside analogs.
Tie-2–dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1
Authors: Cascone Ilaria , Audero Enrica , Giraudo Enrico , Napione Lucia , Maniero Fabrizio , Philips Mark R. , Collard John G. , Serini Guido , Bussolino Federico
Published: June 2003

Angiopoietin-1 is implicated in the maturation and remodeling of the vascular network during embryo development and in adult life. Through its tyrosine kinase receptor Tie-2 it stimulates endothelial cells to migrate and change shape. Here we show that angiopoietin-1 elicits chemokinesis of endothelial cells by a phosphoinositide 3-OH kinase/son of sevenless-dependent modulation of Rac1 and RhoA. The resulting temporal events are associated with cytoskeletal rearrangements and occur in discrete zones of the cell. Endothelial cells carrying dominant-negative mutants of RhoA and Rac1 or treated with LY294002, an inhibitor of phosphoinositide 3-OH kinase, dramatically decrease their chemokinetic velocity. Taken together, these results further expand our understanding of angiopoietin-1-mediated endothelial cell motility during vascular network assembly and angiogenesis. (Blood. 2003;102:2482-2490)
Clinical and molecular characterization of 6 patients affected by severe deficiency of coagulation factor V: broadening of the mutational spectrum of factor V gene and in vitro analysis of the newly identified missense mutations
Authors: Montefusco Maria Claudia , Duga Stefano , Asselta Rosanna , Malcovati Massimo , Peyvandi Flora , Santagostino Elena , Mannucci Pier Mannuccio , Tenchini Maria Luisa
Published: June 2003

Severe factor V (FV) deficiency is a rare bleeding disorder, whose genetic bases have been characterized only in a limited number of cases. We investigated 6 unrelated patients with extremely reduced plasma FV levels, associated with a bleeding tendency ranging from moderately severe to severe. Clinical manifestations were substantially concordant with the previously established spectrum of hemorrhagic symptoms of the disease. Molecular analysis of FV gene identified 9 different mutations, 7 hitherto unknown, and 2 previously reported (Arg712ter and Tyr1702Cys). Four of 6 analyzed patients were compound heterozygotes, indicating the high allelic heterogeneity of this disease. Among novel mutations, 5 led to premature termination codons, because of nonsense (Arg1002ter, Arg1606ter, and Trp1854ter), or frameshift mutations (5127-5128insA and 6122-6123insAACAG). The remaining 2 were missense mutations (Cys472Gly and Val1813Met), located in FV A2 and A3 domains. Their effect on FV expression was studied by transient transfection experiments, demonstrating that the presence of each mutation impaired FV secretion. These data increase the number of severe FV deficiency–causing mutations by about 50%. The high number of “private” mutations identified in FV-deficient families indicates that full mutational screening of FV gene is still required for molecular diagnosis.
Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group
Authors: Gringeri Alessandro , Mantovani Lorenzo G. , Scalone Luciana , Mannucci Pier Mannuccio ,   the COCIS Study Group
Published: June 2003

Inhibitors in patients with hemophilia are a rare complication of a rare disease causing pain and disability in patients and impairment to the quality of their lives. Recent advances in treatment have brought improvements, but they have done so by absorbing larger amounts of financial resources. This study involved 52 Italian patients with hemophilia with high-responding inhibitors who were longitudinally observed for 18 months to evaluate concomitantly cost of care and quality of life. Overall, 0.6 bleeding episodes per patient per month were recorded. This frequency of events was lower than that reported in other cohorts of patients with hemophilia who were not taking inhibitors. The average monthly cost of care was, in euros, €18 000 (US $18 000) per patient, mainly because of treatment products. Recombinant activated factor VII, mostly used for orthopedic surgery, represented 50% of the expenses. Quality of life, measured through validated questionnaires, was similar to that of patients with severe hemophilia without inhibitors. In particular, physical quality of life was similar to that in patients with diabetes and on dialysis, whereas mental quality of life was comparable to that in the general population. This study shows that hemophilia complicated by inhibitors, a prototype of rare disease, requires high amounts of resources for management that provides a satisfactory quality of life. (Blood. 2003;102:2358-2363)
ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases
Authors: Onciu Mihaela , Behm Frederick G. , Downing James R. , Shurtleff Sheila A. , Raimondi Susana C. , Ma Zhigui , Morris Stephan W. , Kennedy Wren , Jones Sandra C. , Sandlund John T.
Published: June 2003

While most anaplastic lymphoma kinase (ALK)-positive non-Hodgkin lymphomas (NHLs) are of T-cell lineage, a small number of B-lineage tumors with plasmablastic morphology and expression of the full-length ALK protein have been described in the literature. All of these reported tumors lacked the NPM-ALK fusion transcript. There is controversy regarding the existence of ALK fusion-positive B-cell NHL, with many investigators contending that ALK fusions are expressed uniquely in T- or null-cell lymphomas. Here we describe 2 well-characterized cases of ALK-positive B-cell lymphoma expressing the NPM-ALK fusion. Both tumors occurred in pediatric patients and showed poor response to chemotherapy. Each had plasmablastic morphology, showed immunoglobulin A restriction, and was ALK positive and CD30- by immunohistochemistry. One tumor showed the t(2;5)(p23;q35) chromosomal translocation by conventional cytogenetics. Both were positive for NPM-ALK by reverse transcriptase-polymerase chain reaction. Thus, ALK-positive plasmablastic B-cell lymphomas are more heterogeneous at the molecular level than previously recognized. (Blood. 2003;102:2642-2644)
Where are the minimal trees? Evidence from early Zulu L2 subordination
Authors: Dube Busi
Published: June 2003

The Minimal Trees Hypothesis (Vainikka and Young-Scholten 1994; 1996a; 1996b) proposes that second language (L2) initial state grammars lack functional categories because functional categories are not subject to transfer effects. The aim of this article is to argue that, to some extent, functional categories instantiated in the learner's first language (L1) transfer to the initial state of L2 syntactic development. On the basis of Zulu interlanguage (IL) data on the acquisition of the obligatory declarative complementizer ukuthi(‘that’) by English native speakers, it is argued that Comp contains a null complementizer system which has sufficient syntactic content to generate subordination in the learners' initial Zulu IL grammar. Regarding transfer of functional categories, it is suggested that null Comp evident at the Zulu L2 initial state is transferred from English, the subjects' L1.
When-questions in second language acquisition
Authors: Park Hyeson
Published: June 2003

It has been observed that when-questions are one of the last wh-questions produced by children learning English either as a first language (L1) or as a second language (L2). Explanations proposed for the late appearance of when-questions in L1 acquisition have been mostly based on cognitive factors. However, the cognition-based approach to when-questions faces problems in explaining L2 acquisition data, which show that L2 children who are cognitively more mature than L1 children follow the same developmental sequence. In this paper, I propose a possible explanation based on internal linguistic factors. According to Enç (1987), tense is a referential expression and temporal adverbials are antecedents of tense. I develop Enç's theory further and propose that in a when-question, tense is a bound variable, which is bound by the quantificational interrogative when. Thus, in order to produce when-questions, children must be at a stage where they understand bound variable readings. According to Roeper and de Villiers (1991), English-speaking children learn a bound variable reading approximately after 36 months, and the learning continues through the kindergarten years. The age at which a bound variable reading first appears corresponds to the point at which when-questions begin to occur. I propose that the complexity of the interaction between the quantificational when and tense, a bound variable, causes the delayed production of when-questions in developing grammars.
Stable and developmental optionality in native and non-native Hungarian grammars
Authors: Papp Szilvia
Published: June 2003

The existence of optionality is well attested in natural languages. It can be defined as the coexistence of two variants of a given construction with identical Logical Form (LF) representations within the same grammatical system. The existence of optionality within both stable (native and non-native) and developing grammars seems to contradict the fundamental claim of the Minimalist Program (MP). In the MP, syntactic optionality is excluded within the computational system because of economy principles which require an ‘optimal realization of interface conditions' (Chomsky, 1995: 171).As a result, movement is possible only if it is necessary. Movement which is possible but not necessary (i.e., truly optional) is not permitted. Thus, at the level of competence, optionality may occur precisely because neither alternative qualifies as a unique optimal realization of interface conditions.

This article presents evidence from the grammaticality intuitions of native speakers and English-speaking second language (L2) learners of Hungarian about optional and categorical constructions. It is argued that while often observed, stable native optionality is highly restricted and difficult to capture. This might be due to the fact that developmental L1 optionality disappears when the input that children receive is sufficient and/or sufficiently robust. Where the input is not sufficient, optionality lingers on, creating fuzzy grammars and borderline cases in grammaticality. However, such stable native optionality may eventually be resolved by categorization (one alternative is expunged from the grammar) or by semantic differentiation (leading to quasi-optionality).

While stable native optionality is unpredictable, developmental optionality is relatively predictable in both early and end-state non-native grammars. The nature of early L2 optionality depends on the characteristics of the initial state. Advanced and end-state non-native optionality persists only if the target language input is non-robust or parametrically ambiguous. Therefore the resolution of optionality at ultimate attainment depends not only on the L2 initial state but also on the intrinsic nature of the primary linguistic data that the learners are exposed to. It is well known that the evidence L2 learners receive is qualitatively different from that obtained by first language (L1) acquirers, and quantitatively limited compared to it. This, in conjunction with the hypotheses created initially, may lead to non-native-like representations that are nonoptimal realizations of the interface conditions. In the face of non-robust and parametrically ambiguous data, L2 learners are either found to fall back on L1 values or resort to general learning strategies, thus ultimately exhibiting divergent representations in end-state grammars.
Optimality in second language phonology: codas in Thai ESL
Authors: Hancin-Bhatt Barbara
Published: June 2003

This study presents an Optimality Theoretic account of syllable codas in Thai ESL. To date, there is little research in the literature on the study of codas, and Thai ESL presents an interesting test case since Thai has a more restrictive set of constraints on what can occur syllable-finally than does English. Thai ESL learners thus need to resolve the conflict between what they know (their first language or L1) and what they are learning (their second language or L2 grammar). Optimality Theory provides the mechanisms to understand how this phonological conflict is resolved,and in what ways. The main findings of this study are that the native language constraint rankings interact with target constraint rankings in a specific way, allowing a restricted and predictable range of production types by intermediate Thai learners of ESL. The study argues that constraint rerankings occur in an ordered fashion:the constraints on which segments can appear in codas (CODA-AC) re-rank before the constraint disallowing complex codas (*COMPLEX), thereby correctly defining the observed stages in ESL coda development.
Second language acquisition: from theory to data
Authors: Jansen Louise M.
Published: June 2003

Clahsen's (1988) and Clahsen and Muysken's (1989) claim that subject–verb agreement and verb-second are unrelated in the acquisition of German second language acquisition (SLA) has met a number of counterpositions; for example: Pienemann and Johnston (1987) and Pienemann (1988; 1998), Jordens (1988), Eubank (1992; 1994) and Vainikka and Young-Scholten (1994; 1996). The conflicting claims source essentially the same data. The presentation and analysis of these data is scrutinized and a number of inconsistencies and methodological questions are identified. The paper argues that, when it comes to underpinning theoretical claims, more rigour in data description should be exercised.
Variability in the use of the English article system by Chinese learners of English
Authors: Robertson Daniel
Published: June 2003

It is well known that the Chinese language does not have functional equivalents of the English definite and indefinite article. Correspondingly, there is plenty of observational evidence that Chinese learners have difficulty with the article system in English. In particular, these learners have a marked tendency to omit the article where native speakers of English would use one. In this article we report the results of an experimental investigation of the variable use of the definite and indefinite articles by 18 Chinese learners of English. A referential communication task was used to elicit samples of the speech of these learners which was rich in referring noun phrases. From the resulting corpus 1884 noun phrases were coded, using a taxonomy based on Hawkins' (1978) description of the definite and indefinite articles and demonstratives in English. The analysis shows an overall rate of 78% suppliance of articles in contexts where a native speaker would use the definite or indefinite article. Of the remaining 22% of contexts where articles are not used, we found that many of the instances of nonsuppliance of articles could be explained by three principles:

1) a syntactic principle of ‘determiner drop’, whereby an NP with definite or indefinite reference need not be overtly marked for [± definiteness] if it is included in the scope of the determiner of a preceding NP;

2) a ‘recoverability’ principle, whereby an NP need not be marked for [± definiteness] if the information encoded in this feature is recoverable from the context; and

3) a ‘lexical transfer principle’, whereby some of these learners are using demonstratives (particularly this) and the numeral one as markers of definiteness and indefiniteness respectively.

However, these principles do not account for all the instances of non-native-like usage in the corpus. There remains a residue of 206 noun phrases without articles in contexts where native speakers would use an article.There are identical contexts, moreover, where these learners use the articles. We suggest that this evidence of unsystematic variation in the use of the articles by these learners lends support to the hypothesis that the optionality in the use of articles is due to difficulty acquiring the correct mapping from the surface features of definiteness and referentiality ( the, a, and the zero article Ø) onto the abstract features of the DP.
Case and the ECP revisited: reply to Kellerman and Yoshioka (1999)
Authors: Kanno Kazue
Published: June 2003

Kellerman and Yoshioka (1999) report the results of three studies on case drop in Japanese involving Dutch-speaking L2 learners. They claim that contra Kanno (1996 and 1998), there was no evidence that their subjects have access to the Empty Category Principle (ECP), which is claimed to regulate the omission of case particles in Japanese. In its place, they propose an alternative functional account: the one-noun hypothesis. Kellerman and Yoshioka point to the availability of Japanese in Hawaii (where Kanno's studies took place) as the source for the ‘inter-population intra-principle’ inconsistency between their study and hers. This paper re-examines their results and argues that they do not undermine the ECP hypothesis. In support of Kanno (1996 and 1998), this paper also presents the results of a new experiment and a reanalysis of Hirakawa's (1998) study.
Relevance: communication and cognition
Authors: Foster-Cohen Susan H.
Published: June 2003

This review article outlines the major tenets of Relevance Theory as presented in the original book (1986) and in the second edition (1995). Each chapter summary is followed by a brief exploration of the points of contact between Sperber and Wilson's ideas and second language research. In some cases this leads to new predictions, in other cases it suffices to point out parallel discussions, which might profit from a Relevance Theory vantage point. It is concluded that Relevance Theory can be usefully exploited to understand second language comprehension and, perhaps, to understand second language acquisition.
The acquisition of multiple wh-questions by high-proficiency non-native speakers of English
Authors: roman Robert Bley-V , Yoshinaga Naoko
Published: June 2003

This paper investigates the knowledge of multiple wh-questions such as Who ate what? by high-proficiency non-native speakers of English whose first language is Japanese. Japanese grammar is known to license a wider range of such questions than English – who came why, for example – although the precise theoretical account is not yet clear. Acceptability judgements were obtained on 6 different types of such questions. Acceptability of English examples was rated by native speakers of English, Japanese examples were judged by native speakers of Japanese, and the English examples were judged by high-proficiency Japanese speakers of English. The results for native speakers judging their own language were generally in accord with expectations. The high-level non-native speakers of English were significantly different from native speakers in their ratings of these sentences. However, the ratings were clearly not simply the result of transfer. The consequences of this finding for theories of Universal Grammar (UG) in second language acquisition (SLA) are discussed.
Missing Surface Inflection or Impairment in second language acquisition? Evidence from tense and agreement
Authors: Prévost Philippe , White Lydia
Published: June 2003

In this article, two accounts of the variable use of inflection in adult second language (L2) acquisition are examined. The Missing Surface Inflection Hypothesis (MSIH) proposes that L2 learners have unconscious knowledge of the functional projections and features underlying tense and agreement. However, learners sometimes have a problem with realization of surface morphology, such that they resort to non-finite forms (e.g. Haznedar and Schwartz, 1997; Prévost and White, 1999). The Impaired Representation Hypothesis (IRH) claims that L2 inflection is essentially impaired, due to lack of functional categories, features or feature strength (e.g. Eubank, 1993/94; Meisel, 1997). These views make different predictions for adult L2 acquisition. Spontaneous production data from two adult learners of French and two adult learners of German are examined. The data show that finite forms do not occur in non-finite contexts, that learners exhibit syntactic reflexes of finiteness and that inflected forms largely show accurate agreement. These results suggest that adult L2 learners represent finiteness and agreement at an abstract level, rather than being impaired in this domain, supporting the MSIH.
The acquisition of the syntax of negation in French and German: contrasting first and second language development
Authors: Meisel Jürgen M.
Published: June 2003

The acquisition of negation is perhaps the best-studied syntactic phenomenon in early interlanguage research,and many of these publications concluded that first (L1) and second language (L2) development had much more in common than had previously been assumed. In the present paper, the problem of whether the same underlying principles and mechanisms guide L1 and L2 acquisition will be re-examined from the perspective of more recent grammatical theory. The empirical basis consists of longitudinal case-studies of the acquisition of French and German as first and second languages. The L2 learners' first language is Spanish.

In L1 data one finds a rapid, uniform and almost error-free course of development across languages exhibiting quite different morphosyntactic means of expressing negation. This is explained in terms of Parameter Theory, primarily referring to functional categories determining the placement of finite verbal elements. L2 acquisition, on the other hand, is characterized by considerable variability, not only crosslinguistically, but also across learners and even within individuals. This can be accounted for by assuming different strategies of language use. More importantly, different kinds of linguistic knowledge are drawn upon in L1 as opposed to L2. It is claimed that adult L2 learners, rather than using structure-dependent operations constrained by Universal Grammar (UG), rely primarily on linear sequencing strategies which apply to surface strings.
Why is this happened? Passive morphology and unaccusativity
Authors: Balcom Patricia
Published: June 2003

Zobl discussed inappropriate passive morphology (‘be’ and the past participle) in the English writing of L2 learners, linking its occurrence to the class of unaccusative verbs and proposing that learners subsume unaccusatives under the syntactic rule for passive formation.

The research reported here supports and amplifies Zobl' proposal, based on a grammaticality judgement task and a controlled production task containing verbs from a variety of subclasses of unaccusatives. The tasks were administered to Chinese L1 learners of English and a control group of English native speakers. Results show that subjects both used and judged as grammatical inappropriate passive morphology with all verbs falling under the rubric of unaccusativity. The article concludes with linguistic representations which maintain Zobl’s insights but are consistent with current theories of argument structure.
The partial availability of Universal Grammar in second language acquisition: the ‘failed functional features hypothesis’
Authors: Hawkins Roger , Chan Cecilia Yuet-hung
Published: June 2003

A number of studies in the research literature have proposed that Universal Grammar (UG) is partially available to adult second language learners. Attempts to provide a syntactic characterization of that partial availability have only recently begun to appear, however. In this article we will argue that speakers of Chinese (a language without wh-operator movement in overt syntax) learning second language English (a language with wh-operator movement in overt syntax) establish mental representations for English which involve pronominal binding rather than operator movement. It will be suggested that this divergence from native-speaker representations is an effect of the inaccessibility of features of functional categories in second language acquisition, what we will refer to as the ‘failed functional features hypothesis’. Implications are drawn from the findings for the syntactic characterization of accessibility to UG more generally in second language acquisition.
The effect of modality on a grammaticality judgement task
Authors: Murphy Victoria A.
Published: June 2003

Typical experiments investigating the accessibility and/or role of principles of Universal Grammar (UG) in adult second language acquisition (SLA) use a written grammaticality judgement (GJ) task to infer knowledge of principles of UG. This investigation examined whether subjects would judge sentences differently in the aural modality from the visual. It was hypothesized that subjects in the aural condition would be less accurate and slower at judging sentences than subjects in the visual condition. Four language groups were tested: ESL (English second language), FSL (French second language), L1.E (English first language) and L1.F (French first language). Subjects were assigned to either an aural or a visual condition. The target sentences presented to the subjects were declarative sentences involving embedded questions, as well as ungrammatical wh-questions which violated Subjacency. The presentation times for all sentences were matched across conditions. Accuracy and reaction time to grammaticality judgement were measured. The hypothesis that subjects would be slower and less accurate in the aural condition than the visual one was supported. Furthermore, subjects were less accurate and slower to judge violations of Subjacency than other sentences, in both modalities. The detrimental effects of the auditory task on judgements were most pronounced for the L2 learners. These results are discussed in the context of the informativeness and validity of outcomes derived from GJ tasks, and the ways in which they are presented.
The effects of semantic and thematic clustering on the learning of second language vocabulary
Authors: Tinkham Thomas
Published: June 2003

ESL students are often presented much of their new English vocabulary preorganized for them in ‘semantic clusters’, sets of semantically and syntactically similar words, e.g., eye, nose, ear, mouth, chin. Although clustering of this sort facilitates the activities which serve current approaches to language teaching and would seem,at first glance, to facilitate vocabulary learning as well, little or no empirical justification is offered by researchers in support of its employment. In fact, research that might apply, psychological research generated by interference theory, would predict that such clustering of similar items impedes rather than enhances learning.

On a more positive note, a more ‘thematic’ manner of organizing new L2 vocabulary is suggested by more recent psychological research which would predict that clusters like frog, green,hop, pond,slippery, croak would be more easily learnt than groups of unassociated words.

With these predictions in mind,the reported research explored the effects upon L2 vocabulary learning of both ‘semantic’ and ‘thematic’ clustering. The results provide a wide range of evidence that suggests that semantic clustering does indeed serve as a hindrance while thematic clustering serves as a facilitator of new language vocabulary learning.
The acquisition of null and overt pronominals in Japanese by English speakers
Authors: Kanno Kazue
Published: June 2003

This article reports on an experimental study that examines the role of UG in the L2 acquisition of Japanese by English speakers. The study focuses on the acquisition of the principle that prevents overt pronouns from having quantified NPs as antecedents in languages (such as Japanese) that have null pronouns. A group of 28 English speakers taking a fourth semester course in Japanese were asked to interpret the null and overt pronominal in the Japanese equivalent of patterns such as Everyone i thinks he/Øi is smart.Not only did the L2 learners exhibit a statistically significant difference in their interpretation of null and overt pronominals with respect to binding by a quantified NP, consistent with the UG principle, but their performance was not significantly different from that of a native-speaker control group.
Markedness, operator movement and discourse effects in the acquisition of purpose clause constructions in a second language
Authors: Finney Malcolm A.
Published: June 2003

This article appraises the effects of gap position and discourse information in the acquisition of purpose clause constructions (PCs) by adult Francophones learning English as L2. L1 acquisition studies reveal children having little difficulty interpreting a PC with a subject gap only (SPC) while a PC with an object gap (OPC) has been problematic to interpret. This may be the result of the number of syntactic operations–including operator movement–involved in its derivation plus lexically specified restrictions on the matrix verb. There are grounds for hypothesizing a late emergence of OPCs in English for French speakers. They are not allowed in French and, in addition to lexical restrictions associated with the choice of matrix verb, are marked semantically and typologically; an OPC with a prepositional object gap is additionally syntactically marked. This may thus result in the late acquisition of OPCs relative to SPCs. An additional hypothesis addresses whether L2 learners are adept at using discourse clues to interpret syntactic structure.

Results indicate initial difficulty interpreting only PCs with prepositional object gaps, providing support for the hypothesis that syntactically (structurally) marked constructions may create initial learning difficulty in L2 acquisition.
The structure of age: in search of barriers to second language acquisition
Authors: Bialystok Ellen
Published: June 2003

The article examines recent evidence that has been offered to support the notion of a sensitive period for second language acquisition. An analysis of that research leaves several questions unresolved. Two small-scale studies are described which attempt to explore some of these issues. In both cases, it is found that the correspondence between language structures in the first and second language is the most important factor affecting acquisition. The age at which second language acquisitions begins is not a significant factor in either study, but the length of residence, indicating the amount of time spent speaking the second language, is significant in the second study. The conclusion is that there is insufficient evidence to accept the claim that mastery of a second language is determined wholly, or even primarily, by maturational factors. Some suggestions are made for an alternative interpretation based on processing differences between older and younger language learners.
Consistency and variation in second language acquisition
Authors: Kanno Kazue
Published: June 2003

This article proposes that L2 learners differ from native speakers with respect to two benchmarks–the extent to which native-like success on one principle of UG predicts comparable success on other principles (lateral consistency), and the extent to which this level of success is stable over time (longitudinal). Results of two experimental studies on the acquisition of Japanese as a second language show that L2 learners exhibit neither lateral nor longitudinal consistency with respect to UG, at least in the early stages of the acquisition process.
Some effects of first language argument structure and morphosyntax on second language sentence processing
Authors: Juffs Alan
Published: June 2003

This article explores some effects of first language verb-argument structure on second language processing of English as a second language. Speakers of Chinese, Japanese or Korean, three Romance languages and native English speakers provided word-by-word reading times and grammaticality judgement data in a self-paced reading task. Results suggest that reliable differences in parsing are not restricted to cases where verb-argument structure differs crosslinguistically.
The L2 acquisition of dative experiencer subjects
Authors: Montrul Silvina A.
Published: June 2003

This longitudinal experimental study is concerned with the L2 acquisition of argument structure and its relationship with Case Theory. French ( n = 17) and English ( n = 19) intermediate learners of Spanish as a Second Language were tested three times over a period of eight months on their knowledge of dative experiencers. Eighteen Spanish native speakers acted as a control group. Dative experiencers in Spanish are common with a subset of psych verbs and unaccusative predicates. These experiencers look like indirect objects on the surface, and indeed can appear in the position of indirect objects. Most of the time, however, they appear in canonical subject position and behave like subjects for some modules of the grammar, such as Control PRO in adjunct clauses. It was hypothesized that if a thematic hierarchy is operative in SLA,both English and French learners would have no difficulty interpreting experiencers as subjects, but that English learners would experience greater difficulty with dative case because there is no dative case in English.An Interpretation Task and a Preference Task were designed to test these hypotheses. Results indicate that,whereas both groups of subjects have access to the thematic hierarchy (a UG component),L1 influence plays an important role with case assignment and checking.
The role of the L1 grammar in the L2 acquisition of segmental structure
Authors: Brown Cynthia A.
Published: June 2003

Acquisition of segmental structure in first language acquisition is accomplished through the interaction of Universal Grammar and the learner's detection of phonemic contrasts in the input (Rice and Avery, 1995; Brown and Matthews, 1993,1997). This article investigates the acquisition of the English /l–r/,/b–v/ and /f–v/ contrasts by second language learners whose L1s do not contrast these segments. Based on L1 phonological acquisition and infant speech perception research,a model of phonological interference is developed which explains how the influence of the L1 phonology originates and identifies the level of phonological knowledge that impinges upon L2 acquisition. It is proposed that if a learner's L1 grammar lacks the phonological feature that differentiates a particular non-native contrast, he or she will be unable to perceive the contrast and therefore unable to acquire the novel segmental representations. In order to evaluate this hypothesis, two experimental studies were conducted. Experiment 1 investigates the acquisition of /l/ and /r/ by Chinese and Japanese speakers; the acquisition of the /l–r/, /b–v/ and /f–v/ contrasts by Japanese speakers is compared in experiment 2. The results from an AX discrimination task and a picture selection task indicate that successful acquisition of a non-native contrast is constrained by the learner's L1 grammar. Differences between Chinese and Japanese speakers (experiment 1) and differences in the acquisition of several different contrasts among Japanese speakers (experiment 2) are argued to reflect subtle phonological properties of the learners' respective L1s. These findings demonstrate that a speaker's L1 grammar may actually impede the operation of UG, preventing the L2 learner from acquiring a non-native phonemic contrast.