Predicting definite and indefinite referents during discourse comprehension: Evidence from event‐related potentials

Linguistic predictions may be generated from and evaluated against a representation of events and referents described in the discourse. Compatible with this idea, recent work shows that predictions about novel noun phrases include their definiteness. In the current follow-up study, we ask whether people engage similar prediction-related processes for definite and indefinite referents. This question is relevant for linguistic theories that imply a processing difference between definite and indefinite noun phrases, typically because definiteness is thought to require a uniquely identifiable referent in the discourse. We addressed this question in an event-related potential (ERP) study (N = 48) with preregistration of data acquisition, preprocessing, and Bayesian analysis. Participants read Dutch mini-stories with a definite or indefinite novel noun phrase (e.g., “het/een huis,” the/a house), wherein (in)definiteness of the article was either expected or unexpected and the noun was always strongly expected. Unexpected articles elicited enhanced N400s, but unexpectedly indefinite articles also elicited a positive ERP effect at frontal channels compared to expectedly indefinite articles. We tentatively link this effect to an antiuniqueness violation, which may force people to introduce a new referent over and above the already anticipated one. Interestingly, expectedly definite nouns elicited larger N400s than unexpectedly definite nouns (replicating a previous surprising finding) and indefinite nouns. Although the exact nature of these noun effects remains unknown, expectedly definite nouns may have triggered the strongest semantic activation because they alone refer to specific and concrete referents. In sum, results from both the articles and nouns clearly demonstrate that definiteness marking has a rapid effect on processing, counter to recent claims regarding definiteness processing

quantitative trait loci associated with the humoral innate immune response in chickens were confirmed in a cross between green legged partridgelike and white leghorn

Natural antibodies (NA) create a crucial barrier at the initial steps of the innate humoral immune response. The main role of NA in the defense system is to bind the pathogens at early stages of infection. Different pathogens are recognized by the presence of highly conserved antigen determinant [e. g., lipopolysaccharide (LPS) in gram-negative bacteria or lipoteichoic acid (LTA) in gram-positive bacteria]. In chickens, a different genetic background of NA binds LPS and LTA antigens, encoded by different QTL. The main objective of this work was to confirm known QTL associated with LPS and LTA NA. For this purpose a chicken reference population was created by crossing 2 breeds: a commercial layer, White Leghorn, and a Polish indigenous chicken, Green-Legged Partridgelike. The chromosomal regions analyzed harbored to GGA3, GGA5, GGA6, GGA8, GGA9, GGA10, GGA14, GGA15, GGA18, and GGAZ. The data collected consisted of the NA titers binding LPS and LTA (determined by ELISA at 12 wk of age) as well as the genotypes (30 short tandem repeat markers; average of 3 markers/chromosome, collected for generations F(0), F(1), and F(2)). The analyses were performed with 3 statistical models (paternal and maternal half-sib, line cross, and linkage analysis and linkage disequilibrium) implemented in GridQTL software (http://www.gridqtl.org.uk/). The QTL study of humoral innate immune response traits resulted in the confirmation of 3 QTL associated with NA titers binding LPS (located on GGA9, GGA18, and GGAZ) and 2 QTL associated with NA titers binding LTA (located on GGA5 and GGA14). A set of candidate genes within the regions of the validated QTL has been proposed

a quantitative trait locus for a primary antibody response to keyhole limpet hemocyanin on chicken chromosome 14 confirmation and candidate gene approach

A QTL involved in the primary antibody response toward keyhole limpet hemocyanin (KLH) was detected on chicken chromosome 14 in the experimental population, which was created by crossing commercial White Leghorn and a Polish native chicken breed (green-legged partridgelike). The current QTL location is a validation of previous experiments pointing to the same genomic location for the QTL linked to a primary antibody response to KLH. An experimental population was typed with microsatellite markers distributed over the chicken chromosome 14. Titers of antibodies binding KLH were measured for all individuals by ELISA. Statistical models applied in the Grid QTL Web-based software were used to analyze the data: a half-sib model, a line-cross model, and combined analysis in a linkage disequilibrium and linkage analysis model. Candidate genes that have been proposed were genotyped with SNP located in genes exons. Statistical analyses of single SNP associations were performed pointing out 2 SNP of an axis inhibitor protein (AXIN1) gene as significantly associated with the trait of an interest

Objective Function and Constraints for Robust Transonic Aerofoil Optimization

Construction of the aerodynamic optimization problem is considered within the context of robustness. The most common aerodynamic optimization problem considered is a lift-constrained drag minimization problem (also subject to geometric constraints), however, point-design at transonic flow conditions can produce shock-free solutions and therefore the result is highly localised, where the gains obtained at the design point are outweighed by the losses at off-design conditions. As such, a range optimization problem subject to a constraint on fixed non-dimensional lift with a varying design point is considered to mitigate this issue. It is shown, first from an analytical treatment of the problem, and second from inviscid optimizations, that more robust solutions are obtainable when considering range optimization against drag minimization. Furthermore, to effectively capture the trade-offs that exist in three-dimensional aircraft design between range, lift, drag and speed, it is shown that an induced drag factor is required and this is suffcient to produce optimal solutions exhibiting shocks

Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in theJAK3gene

High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene wasTP53(97% mutation frequency) followed byBRCA1(10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, afterBRCA1,JAK3was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-basedin vitrofunctional assay and identified a novel gain-of-function mutation in the kinase domain ofJAK3(p.T1022I). Importantly, p.T1022IJAK3mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entireJAK3coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening ofCDK12in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency ofJAK3andCDK12mutations in a large well characterized cohort. Although p.T1022IJAK3mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation ofCDK12mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency.ISSN:1932-620