Judging the animacy of words: The influence of typicality and age of acquisition in a semantic decision task.

The age at which members of a semantic category are learned (age of acquisition), the typicality they demonstrate within their corresponding category, and the semantic domain to which they belong (living, non-living) are known to influence the speed and accuracy of lexical/semantic processing. So far, only a few studies have looked at the origin of age of acquisition and its interdependence with typicality and semantic domain within the same experimental design. Twenty adult participants performed an animacy decision task in which nouns were classified according to their semantic domain as being living or non-living. Response times were influenced by the independent main effects of each parameter: typicality, age of acquisition, semantic domain, and frequency. However, there were no interactions. The results are discussed with respect to recent models concerning the origin of age of acquisition effects.

The origins of age of acquisition and typicality effects: Semantic processing in aphasia and the ageing brain.

Age of acquisition (AOA) has frequently been shown to influence response times and accuracy rates in word processing and constitutes a meaningful variable in aphasic language processing, while its origin in the language processing system is still under debate. To find out where AOA originates and whether and how it is related to another important psycholinguistic variable, namely semantic typicality (TYP), we studied healthy, elderly controls and semantically impaired individuals using semantic priming. For this purpose, we collected reaction times and accuracy rates as well as event-related potential data in an auditory category-member-verification task. The present results confirm a semantic origin of TYP, but question the same for AOA while favouring its origin at the phonology-semantics interface. The data are further interpreted in consideration of recent theories of ageing.

On the influence of typicality and age of acquisition on semantic processing: Diverging evidence from behavioural and ERP responses.

Various behavioural studies show that semantic typicality (TYP) and age of acquisition (AOA) of a specific word influence processing time and accuracy during the performance of lexical-semantic tasks. This study examines the influence of TYP and AOA on semantic processing at behavioural (response times and accuracy data) and electrophysiological levels using an auditory category-member-verification task. Reaction time data reveal independent TYP and AOA effects, while in the accuracy data and the event-related potentials predominantly effects of TYP can be found. The present study thus confirms previous findings and extends evidence found in the visual modality to the auditory modality. A modality-independent influence on semantic word processing is manifested. However, with regard to the influence of AOA, the diverging results raise questions on the origin of AOA effects as well as on the interpretation of offline and online data. Hence, results will be discussed against the background of recent theories on N400 correlates in semantic processing. In addition, an argument in favour of a complementary use of research techniques will be made.

Training-induced improvement of noncanonical sentence production does not generalize to comprehension: evidence for modality-specific processes.

The presence or absence of generalization after treatment can provide important insights into the functional relationship between cognitive processes. The aim of the present study was to investigate the relationship between the cognitive processes that underlie sentence comprehension and production in aphasia. Using data from seven participants who took part in a case-series intervention study that focused on noncanonical sentence production [Stadie et al. (2008). Unambiguous generalization effects after treatment of noncanonical sentence production in German agrammatism. Brain and Language, 104, 211-229], we identified patterns of impairments and generalization effects for the two modalities. Results showed (a) dissociations between sentence structures and modalities before treatment, (b) an absence of cross-modal generalization from production to comprehension after treatment, and (c), a co-occurrence of spared comprehension before treatment and generalization across sentence structures within production after treatment. These findings are in line with the assumption of modality-specific, but interacting, cognitive processes in sentence comprehension and production. More specifically, this interaction is assumed to be unidirectional, allowing treatment-induced improvements in production to be supported by preserved comprehension.

German norms for semantic typicality, age of acquisition, and concept familiarity.

The present study introduces the first substantial German database with norms for semantic typicality, age of acquisition, and concept familiarity for 824 exemplars of 11 semantic categories, including four natural (ANIMALS, BIRDS, FRUITS,: and VEGETABLES: ) and five man-made (CLOTHING, FURNITURE, VEHICLES, TOOLS: , and MUSICAL INSTRUMENTS: ) categories, as well as PROFESSIONS: and SPORTS: . Each category exemplar in the database was collected empirically in an exemplar generation study. For each category exemplar, norms for semantic typicality, estimated age of acquisition, and concept familiarity were gathered in three different rating studies. Reliability data and additional analyses on effects of semantic category and intercorrelations between age of acquisition, semantic typicality, concept familiarity, word length, and word frequency are provided. Overall, the data show high inter- and intrastudy reliabilities, providing a new resource tool for designing experiments with German word materials. The full database is available in the supplementary material of this file and also at www.psychonomic.org/archive .

Analytical characterization of the APTIMA HPV Assay.

BACKGROUND: Human papillomavirus (HPV) testing has improved the sensitivity for the detection of cervical pre-cancer and cancer as compared to Pap testing. Several HPV tests are commercially available and most target the DNA from 13 or 14 high-risk HPV types. The APTIMA HPV Assay however, detects HPV E6/E7 mRNA from 14 high-risk types of HPV: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. OBJECTIVE: To determine the analytical performance characteristics of the APTIMA HPV Assay. STUDY DESIGN: Analytical sensitivity, analytical specificity, reproducibility, and the effect of potentially interfering substances was determined for the APTIMA HPV Assay on both the DTS (semi-automated) and TIGRIS DTS (fully automated) systems. RESULTS: The 95% detection limit for both systems was between 17 and 488 copies/reaction, depending on the HPV type. The assay did not cross-react with normal flora and opportunistic organisms that may be found in cervical samples, or low-risk HPV types. Spermicides, anti-fungal and anti-itch medications, whole blood, glacial acetic acid, and most lubricants did not interfere with assay performance. Those lubricants containing polyquaternium 15 did interfere with assay performance. Inter-instrument, inter-operator, inter-lot, and inter-run signal variability were <10% for >99% of the data. Intra-run variability was <15%, except for those samples with concentrations at or below the 95% detection limit of the assay. CONCLUSIONS: Based upon the analytical sensitivity, analytical specificity, and low variability, the APTIMA HPV Assay showed excellent performance and robustness.

Clinical performance of the APTIMA HPV Assay for the detection of high-risk HPV and high-grade cervical lesions.

BACKGROUND: Human papillomavirus (HPV) DNA testing is widely used in conjunction with Papanicolaou (Pap) testing in cervical cancer screening programs to improve the detection of high-grade lesions. While HPV DNA test sensitivity is good, an improvement in specificity is desired. Detection of HPV mRNA may improve specificity. The APTIMA HPV Assay detects the mRNA of 14 high-risk HPV types in liquid-based cytology specimens. OBJECTIVE: To evaluate APTIMA HPV Assay performance for detection of high-risk HPV and high-grade cervical intraepithelial neoplasia (CIN) compared to Qiagen's Hybrid Capture 2 HPV DNA (HC2) test. STUDY DESIGN: Liquid Pap specimens were collected from 800 women referred to colposcopy and tested with the APTIMA HPV Assay and the HC2 test. Complete results were available for 753 subjects. A subset of samples (n = 393) were typed using Roche's Linear Array HPV Genotyping Test. RESULTS: Sensitivity and specificity for detection of high-risk HPV were >92% and 99% for the APTIMA HPV Assay and 93% and 82% for the HC2 test. Clinical sensitivity and specificity were 91% and >55% for detection of CIN 2+, and 98% and 53% for detection of CIN 3+ for the APTIMA HPV Assay; values for the HC2 test were 95% and 47% for CIN 2+, and 99% and 44% for CIN 3+. CONCLUSIONS: The APTIMA HPV Assay is sensitive and very specific for detection of high-risk HPV. The APTIMA HPV Assay had similar clinical sensitivity for disease detection but higher clinical specificity than the HC2 test, which may improve patient management and reduce the cost of care.

Unambiguous generalization effects after treatment of non-canonical sentence production in German agrammatism.

Agrammatism is-among others, characterized by a deficit in producing grammatical structures. Of specific difficulty is the utilization of complex, non-canonical sentence structures (e.g. object-questions, passives, object-clefts). Several studies have documented positive effects when applying a specific treatment protocol in terms of increasingly correct production of target complex sentence structures with some variance in generalization patterns noted across individuals. The objective of this intervention study was to evaluate an intervention program focussing on the production of non-canonical sentences. Hypotheses about the occurrence of treatment effects were formulated on the basis of syntactic complexity, referring to the amount of syntactic phrase structures necessary to generate specific German sentence structures. A multiple single case study with seven agrammatic participants was applied, each participant receiving training in the production of object-relative-clauses and who-questions. The investigation was designed to unambiguously evaluate for each individual, structure specific and generalized learning effects with respect to the production of object-relative-clauses, who-questions and passive sentences. Results showed significant improvements for all sentences types. This outcome is considered within methodological issues of treatment studies. Theoretical and clinical implications are discussed.

Mobilization of vacuolar iron by AtNRAMP3 and AtNRAMP4 is essential for seed germination on low iron.

Iron (Fe) is necessary for all living cells, but its bioavailability is often limited. Fe deficiency limits agriculture in many areas and affects over a billion human beings worldwide. In mammals, NRAMP2/DMT1/DCT1 was identified as a major pathway for Fe acquisition and recycling. In plants, AtNRAMP3 and AtNRAMP4 are induced under Fe deficiency. The similitude of AtNRAMP3 and AtNRAMP4 expression patterns and their common targeting to the vacuole, together with the lack of obvious phenotype in nramp3-1 and nramp4-1 single knockout mutants, suggested a functional redundancy. Indeed, the germination of nramp3 nramp4 double mutants is arrested under low Fe nutrition and fully rescued by high Fe supply. Mutant seeds have wild type Fe content, but fail to retrieve Fe from the vacuolar globoids. Our work thus identifies for the first time the vacuole as an essential compartment for Fe storage in seeds. Our data indicate that mobilization of vacuolar Fe stores by AtNRAMP3 and AtNRAMP4 is crucial to support Arabidopsis early development until efficient systems for Fe acquisition from the soil take over.

Arabidopsis thaliana MTP1 is a Zn transporter in the vacuolar membrane which mediates Zn detoxification and drives leaf Zn accumulation.

The Arabidopsis thaliana metal tolerance protein 1 (MTP1) of the cation diffusion facilitator family of membrane transport proteins can mediate the detoxification of Zn in Arabidopsis and yeast. Xenopus laevis oocytes expressing AtMTP1 accumulate more Zn than oocytes expressing the AtMTP1(D94A) mutant or water-injected oocytes. An AtMTP1-GFP fusion protein localizes to the vacuolar membrane in root and leaf cells. The analysis of Arabidopsis transformed with a promoter-GUS construct suggests that AtMTP1 is not produced throughout the plant, but primarily in the subpopulation of dividing, differentiating and expanding cells. RNA interference-mediated silencing of AtMTP1 causes Zn hypersensitivity and a reduction in Zn concentrations in vegetative plant tissues.

Multiple sample amplification and genotyping integrated on a single electronic microarray.

We report a novel method that allows simultaneous in situ amplification and then genotyping of single nucleotide polymorphism (SNP) for multiple samples on a single electronic microarray. The locus coding for one of the common inherited thrombosis risk factors, Factor V Leiden (FVL), was chosen as a model system for SNP analysis. This method combines strand displacement amplification (SDA) with electrophoretic movement and concentration of DNA on electronic microarrays to provide a single platform for DNA amplification and analysis. The method includes: electronic anchoring of allele-specific SDA amplifiable primers (APs) and a nonamplifiable primer (NAP) to different electrodes, electronic hybridization of genomic DNA from different samples to those primers, in situ amplification of target DNA, and genotyping of FVL. Compared to previous anchored SDA methods, the addition of a NAP improves detection signals by at least 20-fold. The sensitivity of this method is dependent on the amplification time. Using this method, nine different genomic DNA samples with known FVL genotypes were amplified and correctly genotyped on a single electronic microarray without any contamination between samples. The present method could streamline development of nucleic acid-based assays in applications of molecular diagnostic, point-of-care testing, and forensic detection, which often require the capability to analyze multiple samples efficiently.

Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.

The completion of the human genome sequence has made possible genome-wide studies of retroviral DNA integration. Here we report an analysis of 3,127 integration site sequences from human cells. We compared retroviral vectors derived from human immunodeficiency virus (HIV), avian sarcoma-leukosis virus (ASLV), and murine leukemia virus (MLV). Effects of gene activity on integration targeting were assessed by transcriptional profiling of infected cells. Integration by HIV vectors, analyzed in two primary cell types and several cell lines, strongly favored active genes. An analysis of the effects of tissue-specific transcription showed that it resulted in tissue-specific integration targeting by HIV, though the effect was quantitatively modest. Chromosomal regions rich in expressed genes were favored for HIV integration, but these regions were found to be interleaved with unfavorable regions at CpG islands. MLV vectors showed a strong bias in favor of integration near transcription start sites, as reported previously. ASLV vectors showed only a weak preference for active genes and no preference for transcription start regions. Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection.

HIV-1 integration in the human genome favors active genes and local hotspots.

A defining feature of HIV replication is integration of the proviral cDNA into human DNA. The selection of chromosomal targets for integration is crucial for efficient viral replication, but the mechanism is poorly understood. Here we describe mapping of 524 sites of HIV cDNA integration on the human genome sequence. Genes were found to be strongly favored as integration acceptor sites. Global analysis of cellular transcription indicated that active genes were preferential integration targets, particularly genes that were activated in cells after infection by HIV-1. Regional hotspots for integration were also found, including a 2.4 kb region containing 1% of sites. These data document unexpectedly strong biases in integration site selection and suggest how selective targeting promotes aggressive HIV replication.

Detection and analysis of hairpin II, an essential metastable structural element in viroid replication intermediates.

In (-)-stranded replication intermediates of the potato spindle tuber viroid (PSTVd) a thermodynamically metastable structure containing a specific hairpin structure (HP II) has been proposed to be essential for viroid replication. In the present work a method was devised allowing the direct detection of the HP II structure in vitro and in vivo using a biophysical approach. An RNA oligonucleotide was constructed which specifically binds to the HP II loop region in transient (-)-strand intermediates. Analysis of the resulting oligonucleotide/HP II complexes on temperature-gradient gels enabled us to follow the formation of HP II during in vitro transcription by T7 RNA polymerase. Moreover, we were able to demonstrate the formation of HP II during viroid replication in potato (Solanum tuberosum) cells.