Formal Linguistic Approaches to Adult Second Language (L2) Acquisition and Processing

The relative conformity with which (typically developing) children attain adult grammatical competence—ultimate attainment—and the similarity in developmental paths along which they progress is remarkable (e.g., Ambridge & Lieven, 2011; Clark, 2003; Guasti, 2002; Synder, 2007). This achievement is, however, so ubiquitous and mundane that we seldom marvel at it. Of course, monolingual adult grammars may also differ from one another, especially for some domains of grammar (e.g., Dąbrowska, 1997, 2012), but such variability pales in comparison to the variation in adult non-native second language (L2) grammars. Indeed, the path and outcomes of L2 acquisition can be highly variable from one individual to another, even under seemingly comparable contexts. Individual and group-level factors in adulthood that either do not apply or apply with much less consequence in young childhood conspire to explain at least some of the gamut of L2 variability

Metal worker’s lung: spatial association with Mycobacterium avium

Background Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak. Objectives After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone. Methods Custom-quantitative PCR assays, microscopy and phylogenetic analyses were performed on blinded MWF samples to quantify microbial burden and identify potential aetiological agents of HP in metal workers. Measurements and main results MWF from machines fed by a central sump, but not those with an isolated supply, was contaminated by mycobacteria. The factory sump and a single linked machine at the centre of the outbreak zone, known to be the workstation of the index cases, had very high levels of detectable organisms. Phylogenetic placement of mycobacterial taxonomic marker genes generated from these samples indicated that the contaminating organisms were closely related to Mycobacterium avium. Conclusions We describe, for the first time, a close spatial relationship between the abundance of a mycobacterium-like organism, most probably M. avium, and a localised outbreak of MWF-associated HP. The further development of sequence-based analytic techniques should assist in the prevention of this important occupational disease

Improving Salmonella vector with rec mutation to stabilize the DNA cargoes

<p>Abstract</p> <p>Background</p> <p><it>Salmonella </it>has been employed to deliver therapeutic molecules against cancer and infectious diseases. As the carrier for target gene(s), the cargo plasmid should be stable in the bacterial vector. Plasmid recombination has been reduced in <it>E. coli </it>by mutating several genes including the <it>recA</it>, <it>recE</it>, <it>recF </it>and <it>recJ</it>. However, to our knowledge, there have been no published studies of the effect of these or any other genes that play a role in plasmid recombination in <it>Salmonella enterica</it>.</p> <p>Results</p> <p>The effect of <it>recA</it>, <it>recF </it>and <it>recJ </it>deletions on DNA recombination was examined in three serotypes of <it>Salmonella enterica</it>. We found that (1) intraplasmid recombination between direct duplications was RecF-independent in Typhimurium and Paratyphi A, but could be significantly reduced in Typhi by a Δ<it>recA </it>or Δ<it>recF </it>mutation; (2) in all three <it>Salmonella </it>serotypes, both Δ<it>recA </it>and Δ<it>recF </it>mutations reduced intraplasmid recombination when a 1041 bp intervening sequence was present between the duplications; (3) Δ<it>recA </it>and Δ<it>recF </it>mutations resulted in lower frequencies of interplasmid recombination in Typhimurium and Paratyphi A, but not in Typhi; (4) in some cases, a Δ<it>recJ </it>mutation could reduce plasmid recombination but was less effective than Δ<it>recA </it>and Δ<it>recF </it>mutations. We also examined chromosome-related recombination. The frequencies of intrachromosomal recombination and plasmid integration into the chromosome were 2 and 3 logs lower than plasmid recombination frequencies in Rec⁺strains. A Δ<it>recA </it>mutation reduced both intrachromosomal recombination and plasmid integration frequencies.</p> <p>Conclusions</p> <p>The Δ<it>recA </it>and Δ<it>recF </it>mutations can reduce plasmid recombination frequencies in <it>Salmonella enterica</it>, but the effect can vary between serovars. This information will be useful for developing <it>Salmonella </it>delivery vectors able to stably maintain plasmid cargoes for vaccine development and gene therapy.</p

A Flavin-dependent Monooxygenase from Mycobacterium tuberculosis Involved in Cholesterol Catabolism

Mycobacterium tuberculosis (Mtb) and Rhodococcus jostii RHA1 have similar cholesterol catabolic pathways. This pathway contributes to the pathogenicity of Mtb. The hsaAB cholesterol catabolic genes have been predicted to encode the oxygenase and reductase, respectively, of a flavin-dependent mono-oxygenase that hydroxylates 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione (3-HSA) to a catechol. An hsaA deletion mutant of RHA1 did not grow on cholesterol but transformed the latter to 3-HSA and related metabolites in which each of the two keto groups was reduced: 3,9-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-17-one (3,9-DHSA) and 3,17-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9-one (3,17-DHSA). Purified 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione 4-hydroxylase (HsaAB) from Mtb had higher specificity for 3-HSA than for 3,17-DHSA (apparent k_(cat)/K_m = 1000 ± 100 M^(−1) s^(−1) versus 700 ± 100 M^(−1) s^(−1)). However, 3,9-DHSA was a poorer substrate than 3-hydroxybiphenyl (apparent k_(cat)/K_m = 80 ± 40 M^(−1) s^(−1)). In the presence of 3-HSA the K_(mapp) for O_2 was 100 ± 10 μM. The crystal structure of HsaA to 2.5-Å resolution revealed that the enzyme has the same fold, flavin-binding site, and catalytic residues as p-hydroxyphenyl acetate hydroxylase. However, HsaA has a much larger phenol-binding site, consistent with the enzyme's substrate specificity. In addition, a second crystal form of HsaA revealed that a C-terminal flap (Val^(367)–Val^(394)) could adopt two conformations differing by a rigid body rotation of 25° around Arg^(366). This rotation appears to gate the likely flavin entrance to the active site. In docking studies with 3-HSA and flavin, the closed conformation provided a rationale for the enzyme's substrate specificity. Overall, the structural and functional data establish the physiological role of HsaAB and provide a basis to further investigate an important class of monooxygenases as well as the bacterial catabolism of steroids

Ab initio van der Waals interactions in simulations of water alter structure from mainly tetrahedral to high-density-like

The structure of liquid water at ambient conditions is studied in ab initio molecular dynamics simulations using van der Waals (vdW) density-functional theory, i.e. using the new exchange-correlation functionals optPBE-vdW and vdW-DF2. Inclusion of the more isotropic vdW interactions counteracts highly directional hydrogen-bonds, which are enhanced by standard functionals. This brings about a softening of the microscopic structure of water, as seen from the broadening of angular distribution functions and, in particular, from the much lower and broader first peak in the oxygen-oxygen pair-correlation function (PCF), indicating loss of structure in the outer solvation shells. In combination with softer non-local correlation terms, as in the new parameterization of vdW-DF, inclusion of vdW interactions is shown to shift the balance of resulting structures from open tetrahedral to more close-packed. The resulting O-O PCF shows some resemblance with experiment for high-density water (A. K. Soper and M. A. Ricci, Phys. Rev. Lett., 84:2881, 2000), but not directly with experiment for ambient water. However, an O-O PCF consisting of a linear combination of 70% from vdW-DF2 and 30% from experiment on low-density liquid water reproduces near-quantitatively the experimental O-O PCF for ambient water, indicating consistency with a two-liquid model with fluctuations between high- and low-density regions

Grammar Is a System That Characterizes Talk in Interaction

Much of contemporary mainstream formal grammar theory is unable to provide analyses for language as it occurs in actual spoken interaction. Its analyses are developed for a cleaned up version of language which omits the disfluencies, non-sentential utterances, gestures, and many other phenomena that are ubiquitous in spoken language. Using evidence from linguistics, conversation analysis, multimodal communication, psychology, language acquisition, and neuroscience, we show these aspects of language use are rule governed in much the same way as phenomena captured by conventional grammars. Furthermore, we argue that over the past few years some of the tools required to provide a precise characterizations of such phenomena have begun to emerge in theoretical and computational linguistics; hence, there is no reason for treating them as "second class citizens" other than pre-theoretical assumptions about what should fall under the purview of grammar. Finally, we suggest that grammar formalisms covering such phenomena would provide a better foundation not just for linguistic analysis of face-to-face interaction, but also for sister disciplines, such as research on spoken dialogue systems and/or psychological work on language acquisition

Input and age-dependent variation in second language learning: A connectionist account

Language learning requires linguistic input, but several studies have found that knowledge of second language (L2) rules does not seem to improve with more language exposure (e.g., Johnson & Newport, 1989). One reason for this is that previous studies did not factor out variation due to the different rules tested. To examine this issue, we reanalyzed grammaticality judgment scores in Flege, Yeni‐Komshian, and Liu's (1999) study of L2 learners using rule‐related predictors and found that, in addition to the overall drop in performance due to a sensitive period, L2 knowledge increased with years of input. Knowledge of different grammar rules was negatively associated with input frequency of those rules. To better understand these effects, we modeled the results using a connectionist model that was trained using Korean as a first language (L1) and then English as an L2. To explain the sensitive period in L2 learning, the model's learning rate was reduced in an age‐related manner. By assigning different learning rates for syntax and lexical learning, we were able to model the difference between early and late L2 learners in input sensitivity. The model's learning mechanism allowed transfer between the L1 and L2, and this helped to explain the differences between different rules in the grammaticality judgment task. This work demonstrates that an L1 model of learning and processing can be adapted to provide an explicit account of how the input and the sensitive period interact in L2 learning