L2 Domain Research Articles

Meta-analysis of second language research with complex research designs

AbstractMeta-analyses play an instrumental role in informing second language (L2) theory and practice. However, current (i.e., classic) approaches to meta-analysis are limited in their ability to do so because they often fail to capture the complexity inherent in primary studies’ research designs. As we argue in this article, when complex L2 studies are represented by simplistic meta-analyses, the latter cannot reach its potential to contribute to the development of cumulative knowledge. To mitigate this issue, we first discuss the fundamental problems of the classic approaches to meta-analysis of complex L2 research. Second, we introduce an alternative meta-analytic framework that will address those problems. Third, we apply the meta-analytic framework discussed to a complex L2 domain. Fourth, we offer free software to facilitate the conduct of the alternative meta-analytic approach described. Finally, we discuss the implications of this alternative framework for making evidence-based recommendations to the relevant stakeholders.

Listening Errors at Chunk Level in The Case of Vietnamese University Learners of English as a Foreign Language

Research has shown that error analysis (EA) can be a valuable tool for linguistic scholars to collect useful information on second language (L2) acquisition. In the domain of L2 listening development, identifying patterns of learners’ erroneous output allows both teachers and students to have an overview of learners’ listening problems. On this premise, remedial actions can be taken for the achievement of effective listening comprehension. Having said that, the goal of this study is to investigate the common types of listening errors made by 12 EFL university students at a private university in Vietnam. Specifically, the study attempts to seek an understanding of how listeners process speech at chunk level and how their listening transcriptions reflect their listening processes. Sixty chunks extracted as a separate clip from 15 dialogues with basic features of the oral language were embedded in listening tasks on a self-access online platform. Error analysis of a total of 720 transcriptions reveals that chunks containing errors occupied 44 percent, suggesting that at the chunk level, students still struggled to construct the meanings of the aural input. Major listening errors identified are related to sound misperception, including confusion, omission, addition, and misformation. The findings of this study stress the significance of respecting learners’ meaning-making mechanisms in the listening process by giving listeners more control in accessing listening materials. On top of that, it highlights the priority of listening at the chunk level without contextual clues at the earlier stages of listening, which can be a head start for their listening development. More implications for language teachers and researchers in listening are also discussed. Keywords: Listening; listening errors; error analysis; chunks; Vietnamese EFL learners

The significance of Q-methodology as an innovative method for the investigation of affective variables in second language acquisition.

Q methodology has been used in a variety of fields to employ a scientific approach to dealing with subjectivity; yet, its use has just gained momentum in the second language acquisition (SLA) domain recently (Damio, 2016). The present paper argues that Q methodology is remarkably efficient in representing the dynamic quality of complex systems involved in the language learning process, which is, thus, compatible with the complexity and dynamic systems theory (CDST). As Q methodology enjoys advantages of both qualitative and quantitative lines of research (Irie, 2014), it helps to explore and reflect L2 learners' subjective views and perceptions about their emotions in an L2 class in a comprehensive manner. With the current growing attention to individuals' emotional experiences in recent years, SLA research domain is ripe for many scientific inquiries about L2 learners' affective variables benefiting from this method. The few existing studies in the L2 domain have had interesting findings, which show the Q methodology should be more extensively used in the field to reveal facts about how learners feel in class from a within-individual point of view. Q methodology can hopefully be capable of representing the dynamicity and complexity of the affective variables language learners experience in the interactive network of classroom learning. Thus, it is expected that innovative research methods such as the Q methodology be employed significantly more than before in the dynamic phase of SLA research in the upcoming years.

Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection.

Intracellular trafficking of human papillomavirus (HPV) during virus entry requires γ-secretase, a cellular protease consisting of a complex of four cellular transmembrane (TM) proteins. γ-secretase typically cleaves substrate proteins but it plays a non-canonical role during HPV entry. γ-secretase binds to the HPV minor capsid protein L2 and facilitates its insertion into the endosomal membrane. After insertion, L2 protrudes into the cytoplasm, which allows HPV to bind other cellular factors required for proper virus trafficking into the retrograde transport pathway. Here, we further characterize the interaction between γ-secretase and HPV L2. We show that γ-secretase is required for cytoplasmic protrusion of L2 and that L2 associates strongly with the PS1 catalytic subunit of γ-secretase and stabilizes the γ-secretase complex. Mutational studies revealed that a putative TM domain in HPV16 L2 cannot be replaced by a foreign TM domain, that infectivity of HPV TM mutants is tightly correlated with γ-secretase binding and stabilization, and that the L2 TM domain is required for protrusion of the L2 protein into the cytoplasm. These results provide new insight into the interaction between γ-secretase and L2 and highlight the importance of the native HPV L2 TM domain for proper virus trafficking during entry.

Eigenvalue problems for a class of infinite complex symmetric tridiagonal matrices with related three-term recurrence relation

We consider the eigenvalue problem of a class of infinite complex symmetric tridiagonal matrices whose diagonal and off-diagonal elements diverge in modulus, and which have a compact inverse. We regard the matrix as a linear operator mapping a maximal domain in Hilbert space ℓ2 into ℓ2. This paper aims to extend the work of Ikebe et al. on a class of eigenvalue problems and for which asymptotic error estimates have been obtained. In this paper we focus on the following points: (1) considering what class of zero-finding problems of three-term recurrence relations can be reformulated as eigenvalue problems of the class of infinite tridiagonal matrices stated above; (2) determining a class of matrices for which obtaining good approximate eigenvalues is guaranteed by using those of truncated principal sub-matrices; and (3) determining a class of matrices that permits us the asymptotic error estimates computed as in (2).

Grit and motivation for learning English among Japanese university students

This study contributes to the limited research assessing how constructs (e.g., grit) from Positive Psychology (PosPsy) can contribute to better understanding motivation for learning a second language (L2). A total number of 441 Japanese female university students enrolled in English language classes participated in this study. Results showed that a positive global self-construct (i.e., grit), positive L2 domain self-constructs (i.e., grit for L2 learning and interested L2 self) and positive L2 motivational constructs (i.e., L2 reading and listening self-efficacy) and negative L2 motivational variables (i.e., L2 reading and listening anxiety) can be reliably measured with self-report scales with female Japanese students and how the relationship strength among variables followed the predicted order. This paper contributes by introducing new concepts from PosPsy to motivation in L2 learning and offers validation evidence that scales can be created to measure selected constructs from PosPsy that augment L2 motivation studies.

Self-Views and Positive Psychology Constructs Among Second Language Learners in Japan, Taiwan, and the United States.

The present study is the first to empirically test a hierarchical, positive-oriented model of the self and its relationship to second language (L2) achievement motivation, and compare it in three different cultural contexts of Japan, the United States, and Taiwan. Based on the L2 self-model (Lake, 2016), three levels of constructs were developed: Global Self (i.e., Flourishing, Curiosity, and Hope); Positive L2 domain self (i.e., interested-in-L2 self, harmonious passion for L2 learning, and mastery L2 goal orientation); and L2 Motivational Variables (i.e., reading, speaking and listening self-efficacy). A total of 667 students participated in this study, including 181 first-year college students in Japan, 159 high school students in Taiwan, and 327 community college students in the United States. All the participants were learning L2 in school. Results showed that the measures of positive global self, L2 domain self, and L2 motivational self all had a stronger relationship within their respective levels, and progressively weaker relationships as level of generality/specificity became more distal. Furthermore, the relationships among measures varied in the differing cultural contexts with the Japan-based student participants relatively lower on all measures. Implications for teacher educators in the L2 context have been discussed.

A trace theorem for Sobolev spaces on the Sierpinski gasket

We give a discrete characterization of the trace of a class of Sobolev spaces on the Sierpinski gasket to the bottom line. This includes the L2 domain of the Laplacian as a special case. In addition, for Sobolev spaces of low orders, including the domain of the Dirichlet form, the trace spaces are Besov spaces on the line.

Structural basis of the activation of type 1 insulin-like growth factor receptor

Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the cryo-EM structure of full-length IGF1R–IGF1 complex in the active state. This structure reveals that only one IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like structure with the unliganded α-CT, which hinders the conformational change of the unliganded α-CT required for binding of a second IGF1 molecule. We further identify an L1–FnIII-2 interaction that mediates the dimerization of membrane-proximal domains of IGF1R. This interaction is required for optimal receptor activation. Our study identifies a source of the negative cooperativity in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation.

Discovery of novel helix binding sites at protein-protein interfaces

Protein-protein interactions (PPIs) play a key role in numerous biological processes. Many efforts have been undertaken to develop PPI modulators for therapeutic applications; however, to date, most of the peptide binders designed to target PPIs are derived from native binding helices or using the native helix binding site, which has limited the applications of protein-protein interface binding peptide design. Here, we developed a general computational algorithm, HPer (Helix Positioner), that locates single-helix binding sites at protein-protein interfaces based on the structure of protein targets. HPer performed well on known single-helix-mediated PPIs and recaptured the key interactions and hot-spot residues of native helical binders. We also screened non-helical-mediated PPIs in the PDBbind database and identified 17 PPIs that were suitable for helical peptide binding, and the helical binding sites in these PPIs were also predicted for designing novel peptide ligands. The L2 domain of EGFR, which was the top ranked, was selected as an example to show the protocol and results of designing novel helical peptide ligands on the searched binding site. The binding stability of the designed sequences were further investigated using molecular dynamics simulations.

Structural Plasticity of Neurexin 1α: Implications for its Role as Synaptic Organizer

α-Neurexins are synaptic organizing molecules implicated in neuropsychiatric disorders. They bind and arrange an array of different partners in the synaptic cleft. The extracellular region of neurexin 1α (n1α) contains six LNS domains (L1–L6) interspersed by three Egf-like repeats. N1α must encode highly evolved structure–function relationships in order to fit into the narrow confines of the synaptic cleft, and also recruit its large, membrane-bound partners. Internal molecular flexibility could provide a solution; however, it is challenging to delineate because currently no structural methods permit high-resolution structure determination of large, flexible, multi-domain protein molecules. To investigate the structural plasticity of n1α, in particular the conformation of domains that carry validated binding sites for different protein partners, we used a panel of structural techniques. Individual particle electron tomography revealed that the N-terminally and C-terminally tethered domains, L1 and L6, have a surprisingly limited range of conformational freedom with respect to the linear central core containing L2 through L5. A 2.8-Å crystal structure revealed an unexpected arrangement of the L2 and L3 domains. Small-angle X-ray scattering and electron tomography indicated that incorporation of the alternative splice insert SS6 relieves the restricted conformational freedom between L5 and L6, suggesting that SS6 may work as a molecular toggle. The architecture of n1α thus encodes a combination of rigid and flexibly tethered domains that are uniquely poised to work together to promote its organizing function in the synaptic cleft, and may permit allosterically regulated and/or concerted protein partner binding.

Elliptic complexes of first-order cone operators: ideal boundary conditions

The purpose of this paper is to provide a detailed description of the spaces that can be specified as L2 domains for the operators of a first order elliptic complex on a compact manifold with conical singularities. This entails an analysis of the nature of the minimal domain and of a complementary space in the maximal domain of each of the operators. The key technical result is the nondegeneracy of a certain pairing of cohomology classes associated with the indicial complex. It is further proved that the set of choices of domains leading to Hilbert complexes in the sense of Bruning and Lesch form a variety, as well as a theorem establishing a necessary and sufficient condition for the operator in a given degree to map its maximal domain into the minimal domain of the next operator.

The SH3-binding domain of Cx43 participates in loop/tail interactions critical for Cx43-hemichannel activity.

Connexin 43 (Cx43) hemichannels establish local signaling networks via the release of ATP and other molecules, but their excessive opening may result in cell death. Hence, the activity of Cx43-hemichannels ought to be critically controlled. This involves interactions between the C-terminal tail (CT) and the cytoplasmic loop (CL), more particularly the L2 domain within CL. Previous work revealed an important role for the last nine amino acids of the Cx43 CT by targeting the L2 domain, as these nine amino acids were sufficient to restore the activity of CT-truncated Cx43-hemichannels. However, we discovered that deletion of the last 19 amino acids of the CT only partially lowered the binding to the L2 domain, indicating that a second L2-binding region is present in the CT. We here provide evidence that the SH3-binding domain is another CT region that targets the L2 domain. At the functional level, the SH3-binding domain was able to restore the activity of CT-truncated Cx43-hemichannels and alleviate the inhibition of full-length Cx43-hemichannels by high intracellular Ca2+ concentration ([Ca2+]i) as demonstrated by various approaches including patch clamp studies of unitary Cx43-hemichannel activity. Finally, we show that in full-length Cx43-hemichannels, deletion of either the SH3-binding domain or the CT9 region suppresses the hemichannel activity, while deletion of both domains completely annihilates the hemichannel activity. These results demonstrate that the Cx43 SH3-binding domain, in addition to the CT9 region, critically controls hemichannel activity at high [Ca2+]i, which may be involved in pathological hemichannel opening.

Trotter’s limit formula for the Schrödinger equation with singular potential

We discuss the Schrödinger equation with singular potentials. Our focus is non-relativistic Schrödinger operators H with scalar potentials V defined on Rd, hence covering such quantum systems as atoms, molecules, and subatomic particles whether free, bound, or localized. By a “singular potential” V, we refer to the case when the corresponding Schrödinger operators H, with their natural minimal domain in L2(Rd), are not essentially self-adjoint. Since V is assumed real valued, the corresponding Hermitian symmetric operator H commutes with the conjugation in L2(Rd), and so (by von Neumann’s theorem), H has deficiency indices (n, n). The case of singular potentials V refers to when n > 0. Hence, by von Neumann’s theory, we know the full variety of all the self-adjoint extensions. Since the Trotter formula is restricted to the case when n = 0, and here n > 0, two questions arise: (i) existence of the Trotter limit and (ii) the nature of this limit. We answer (i) affirmatively. Our answer to (ii) is that when n > 0, the Trotter limit is a strongly continuous contraction semigroup; so it is not time-reversible.

Site-Directed Mutagenesis of the Fibronectin Domains in Insulin Receptor-Related Receptor.

The orphan insulin receptor-related receptor (IRR), in contrast to its close homologs, the insulin receptor (IR) and insulin-like growth factor receptor (IGF-IR) can be activated by mildly alkaline extracellular medium. We have previously demonstrated that IRR activation is defined by its extracellular region, involves multiple domains, and shows positive cooperativity with two synergistic sites. By the analyses of point mutants and chimeras of IRR with IR in, we now address the role of the fibronectin type III (FnIII) repeats in the IRR pH-sensing. The first activation site includes the intrinsically disordered subdomain ID (646–716) within the FnIII-2 domain at the C-terminus of IRR alpha subunit together with closely located residues L135, G188, R244, H318, and K319 of L1 and C domains of the second subunit. The second site involves residue T582 of FnIII-1 domain at the top of IRR lambda-shape pyramid together with M406, V407, and D408 from L2 domain within the second subunit. A possible importance of the IRR carbohydrate moiety for its activation was also assessed. IRR is normally less glycosylated than IR and IGF-IR. Swapping both FnIII-2 and FnIII-3 IRR domains with those of IR shifted beta-subunit mass from 68 kDa for IRR to about 100 kDa due to increased glycosylation and abolished the IRR pH response. However, mutations of four asparagine residues, potential glycosylation sites in chimera IRR with swapped FnIII-2/3 domains of IR, decreased the chimera glycosylation and resulted in a partial restoration of IRR pH-sensing activity, suggesting that the extensive glycosylation of FnIII-2/3 provides steric hindrance for the alkali-induced rearrangement of the IRR ectodomain.

A novel recombinant anti-epidermal growth factor receptor peptide vaccine capable of active immunization and reduction of tumor volume in a mouse model.

Over-expression of epidermal growth factor receptor (EGFR) has been reported in a number of human malignancies. Strong expression of this receptor has been associated with poor survival in many such patients. Active immunizations that elicit antibodies of the desired type could be an appealing alternative to conventional passive immunization. In this regard, a novel recombinant peptide vaccine capable of prophylactic and therapeutic effects was constructed. A novel fusion recombinant peptide base vaccine consisting of L2 domain of murine extra-cellular domain-EGFR and EGFR mimotope (EM-L2) was constructed and its prophylactic and therapeutic effects in a Lewis lung carcinoma mouse (C57/BL6) model evaluated. Constructed recombinant peptide vaccine is capable of reacting with anti-EGFR antibodies. Immunization of mice with EM-L2 peptide resulted in antibody production against EM-L2. The constructed recombinant peptide vaccine reduced tumor growth and increased the survival rate. Designing effective peptide vaccines could be an encouraging strategy in contemporary cancer immunotherapy. Investigating the efficacy of such cancer immunotherapy approaches may open exciting possibilities concerning hyperimmunization, leading to more promising effects on tumor regression and proliferation.

New findings on phosphodiesterases, MoPdeH and MoPdeL, in Magnaporthe oryzae revealed by structural analysis.

The cyclic adenosine monophosphate (cAMP) signalling pathway mediates signal communication and sensing during infection-related morphogenesis in eukaryotes. Many studies have implicated cAMP as a critical mediator of appressorium development in the rice blast fungus, Magnaporthe oryzae. The cAMP phosphodiesterases, MoPdeH and MoPdeL, as key regulators of intracellular cAMP levels, play pleiotropic roles in cell wall integrity, cellular morphology, appressorium formation and infectious growth in M. oryzae. Here, we analysed the roles of domains of MoPdeH and MoPdeL separately or in chimeras. The results indicated that the HD and EAL domains of MoPdeH are indispensable for its phosphodiesterase activity and function. Replacement of the MoPdeH HD domain with the L1 and L2 domains of MoPdeL, either singly or together, resulted in decreased cAMP hydrolysis activity of MoPdeH. All of the transformants exhibited phenotypes similar to that of the ΔMopdeH mutant, but also revealed that EAL and L1 play additional roles in conidiation, and that L1 is involved in infectious growth. We further found that the intracellular cAMP level is important for surface signal recognition and hyphal autolysis. The intracellular cAMP level negatively regulates Mps1-MAPK and positively regulates Pmk1-MAPK in the rice blast fungus. Our results provide new information to better understand the cAMP signalling pathway in the development, differentiation and plant infection of the fungus.

Structure and RNA recognition of ribosome assembly factor Utp30.

The 90S preribosomes are gigantic early assembly intermediates of small ribosomal subunits. Cryo-EM structures of 90S were recently determined, but many of its components have not been accurately modeled. Here we determine the crystal structure of yeast Utp30, a ribosomal L1 domain-containing protein in 90S, at 2.65 Å resolution, revealing a classic two-domain fold. The structure of Utp30 fits well into the cryo-EM density of 90S, confirming its previously assigned location. Utp30 binds to the rearranged helix 41 of 18S rRNA and helix 4 of 5′ external transcribed spacer in 90S. Comparison of RNA-binding modes of different L1 domains illustrates that they consistently recognize a short RNA duplex with the concaved surface of domain I, but are versatile in RNA recognition outside the core interface. Cic1 is a paralog of Utp30 associating with large subunit preribosomes. Utp30 and Cic1 share similar RNA-binding modes, suggesting that their distinct functions may be executed by a single protein in other organisms. Deletion of Utp30 does not affect the composition of 90S. The nonessential role of Utp30 could be ascribed to its peripheral localization and redundant interactions in 90S.

Development of a Novel Human scFv Against EGFR L2 Domain by Phage Display Technology.

Epidermal growth factor receptor (EGFR) as a transmembrane tyrosine kinase receptor frequently overexpresses in tumors with epithelial origin. The L2 domain from extracellular part of EGFR is involved in ligand binding and the blockage of this domain prevents activation of related signaling pathways. This study was aimed to develop a novel human scFv against EGFR L2 domain as a promising target for cancer therapy. The L2 recombinant protein was purified and used for panning a human scFv phage library (Tomlinson I). In this study, a novel screening strategy was applied to select clones with high binding and enrichment of rare specific phage clones of the L2 protein. After five biopanning rounds several specific clones were isolated which among them one phage clone with high binding was purified for further analysis. The specific interaction of selected clone against target antigen was confirmed by ELISA and western blotting. Immunofluorescence staining showed that purified scFv binds to A431 cells surface, displaying EGFR surface receptor. In the present study, we isolated for the first time a novel human scFv against EGFR L2 domain. This study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFR overexpressing cancers using this novel human anti-L2 ScFv.

The Long-Term English Language and Literacy Outcomes of First-Generation Former Child Immigrants in the United States

Background/Context Children from Asian ethnic backgrounds currently constitute the second largest group of child immigrants in the United States. Although stereotyped as model minority students due to their academic and economic success, studies have revealed that many Asian immigrant students struggle in school. Research has also shown that, compared to child immigrants from an Indo-European language background such as Spanish and French, Asian child immigrants experience more challenges in learning English as a second language (L2) due to greater cross-linguistic differences. However, little is known about the long-term English language outcomes of first-generation Asian child immigrants. Purpose/Objective The present study examines the effects of learner-level and input-level factors on first-generation Asian child immigrants’ long-term English outcomes. Research Design Data for the current study are selected from a larger correlational and cross-sectional study that examined the effect of the age of arrival variable on Chinese immigrants’ English L2 outcomes. We used two criteria to select participants from the larger study: (1) those who had arrived in the United States between the ages of 5 to 18 (to qualify as a “child immigrant”), and (2) those who had resided in the United States for at least 10 years (to examine long-term outcomes). These criteria resulted in the current sample of 69 participants. The English language proficiency data include participants’ phonological production ratings, performances on a grammaticality judgment task, and their self-ratings of English proficiency in listening, speaking, reading, and writing. Conclusions/Recommendations The current study showed a complex interplay of factors affecting former child immigrants’ English L2 acquisition. Although age of arrival played a critical role in their L2 learning outcomes, it exerted varying degrees of influence by L2 domain. Age of arrival was a strong predictor of L2 phonological production, grammar knowledge, and oral language proficiency, but not literacy skills. L2 input, language learning aptitude, and child immigrants’ affective status also contributed to their L2 outcomes, and carried more weight than age of arrival. We interpreted the results to be in line with the multiple sensitive period hypothesis in developmental psycholinguistics research. The results also suggested that literacy is not susceptible to age-related effects in the same way in which oral language and more specifically the phonological and syntactic systems are. Literacy as a cultural construct rather than a biologically unique human system is intensively taught throughout the school years and curriculum. Malleable factors, such as instruction and reading strategies, are thus perhaps more important in determining child immigrants’ long-term literacy outcomes.