University American Sign Language (ASL) Second Language Learners: Receptive and Expressive ASL Performance

American Sign Language (ASL) is used by estimates of up to 500,000 people (deaf and hearing) in the United States (Mitchell et al., 2006); however, the majority of users are typically hearing university students, frequently within university interpreting or deaf education preparation programs, who learn ASL as a second language (L2). It is unclear how these learners develop their skills as they progress through university training programs. The present study documents university learners’ receptive and expressive ASL skills, factors related to performance, and self-evaluation and strategy use at the end of their ASL IV course. Both assessments are readily available, efficient to administer and score, and provide immediate feedback to learners. Self-reported years of ASL experience, hours of academic ASL use, fluency, and university major related to scores on an expressive handshape phonological fluency task as measured by correlations and ANOVAs. Based on student performance, implications for university instructors of L2 ASL learners are discussed

Goodnight Gorilla: How Do Second Language Learners’ American Sign Language Narrative Renditions Change after Viewing an ASL Model?

We investigated the effects of a single viewing of an American Sign Language (ASL) model on university second language learners’ ASL narrative renditions. Spoken English was the first language of all participants and they had varied lengths of signing experience, ranging from 1 to 26 years. Participants completed a receptive measure of ASL. Then they rendered a wordless picture book in ASL. Afterwards, they watched a native-signing adult model of the story in ASL, and then told the story again. We investigated their inclusion of specific details and how they expressed them, including their use of constructed action (CA), depicting constructions (DCs), blended CA+DC, and lexical signs. After one viewing of the model, participants significantly increased their inclusion of details and use of all constructs except lexical signs, although not to the level of the model. Their receptive ASL scores correlated with their use of CA within their narrative renditions at both time points. We present an analysis of their strengths and areas of need, as well as future research implications

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer

International audienceBACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg(-1). Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody

TDP-43 Identified from a Genome Wide RNAi Screen for SOD1 Regulators

Amyotrophic Lateral Sclerosis (ALS) is a late-onset, progressive neurodegenerative disease affecting motor neurons in the brain stem and spinal cord leading to loss of voluntary muscular function and ultimately, death due to respiratory failure. A subset of ALS cases are familial and associated with mutations in superoxide dismutase 1 (SOD1) that destabilize the protein and predispose it to aggregation. In spite of the fact that sporadic and familial forms of ALS share many common patho-physiological features, the mechanistic relationship between SOD1-associated and sporadic forms of the disease if any, is not well understood. To better understand any molecular connections, a cell-based protein folding assay was employed to screen a whole genome RNAi library for genes that regulate levels of soluble SOD1. Statistically significant hits that modulate SOD1 levels, when analyzed by pathway analysis revealed a highly ranked network containing TAR DNA binging protein (TDP-43), a major component of aggregates characteristic of sporadic ALS. Biochemical experiments confirmed the action of TDP-43 on SOD1. These results highlight an unexpected relationship between TDP-43 and SOD1 which may have implications in disease pathogenesis

Oxidative stress and immunologic responses following a dietary exposure to PAHs in Mya arenaria

<p>Abstract</p> <p>Background</p> <p>The aim of this research was to investigate oxidative stress and immune responses following a dietary polycyclic aromatic hydrocarbon (PAH) exposure in a marine bioindicator organism, the soft shell clam, <it>Mya arenaria</it>. Immune parameters in hemolymph (haemocyte number, efficiency of phagocytosis and haemocyte activity) and assessment of oxidative stress using catalase (CAT) activity and levels of malondialdehyde (MDA) performed on the digestive gland were estimated as biomarkers in clams fed in mesocosm with PAH contaminated phytoplankton. MDA levels and CAT activities were also measured <it>in situ </it>in organisms sampled in a control site (Metis Beach, Québec, Canada) as well as organisms sampled in a site receiving domestic effluents (Pointe-au-Père, Québec, Canada), to assess effects of abiotic variables related to seasonal variations and mixed contamination on the selected parameters.</p> <p>Results</p> <p>Results on immune parameters suggest that the PAHs may interfere with the maturation and/or differentiation processes of haemocytes. MDA results showed that lipid peroxidation did not occur following the exposure. The levels of CAT activity corresponded to weak antioxidant activity (no significant differences). Recovery was noted for all the immune endpoints at the end of the experiment.</p> <p>Conclusion</p> <p>Results suggest that immune parameters are early biomarkers that can efficiently detect a physiological change during a short term exposure to low concentrations of PAHs. The <it>in situ </it>survey (in the natural environment) suggested that clams from the Pointe-au-Père site did not show any oxidative stress as well as the clams contaminated in mesocosm, probably due to the low concentrations of PAHs used for this study. MDA levels increased however in organisms from Metis Beach, a response probably related to domestic effluents or parasitism.</p

The Role of the Substantia Nigra Pars Compacta in Regulating Sleep Patterns in Rats

Background. As of late, dopaminergic neurotransmission has been recognized to be involved in the generation of sleep disturbances. Increasing evidence shows that sleep disturbances in Parkinson's disease (PD) patients are mostly related to the disease itself, rather than being a secondary phenomenon. Evidence contained in the literature lends support to the hypothesis that the dopaminergic nigrostriatal pathway is closely involved in the regulation of sleep patterns. Methodology/Principal Findings. To test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We demonstrated that a 50% lesion of the substantia nigra pars compacta (SNpc) suffices to produce disruptions of several parameters in the sleep-wake pattern of rats. A robust and constant decrease in the latency to the onset of slow wave sleep (SWS) was detected throughout the five days of recording in both light [F((22.16)) = 72.46, p<0.0001] and dark [F((22.16)) = 75.0, p<0.0001] periods. Also found was a pronounced increase in the percentage of sleep efficiency during the first four days of recording [F((21.15)) = 21.48, p<0.0001], in comparison to the sham group. Additionally, the reduction in the SNpc dopaminergic neurons provoked an ablation in the percentage of rapid eye movement sleep (REM) during three days of the sleep-wake recording period with a strong correlation (r = 0.91; p<0.0001) between the number of dopaminergic neurons lost and the percentage decrease of REM sleep on the first day of recording. On day 4, the percentage of REM sleep during the light and dark periods was increased, [F((22.16)) = 2.46, p<0.0007], a phenomenon consistent with REM rebound. Conclusions/Significance. We propose that dopaminergic neurons present in the SNpc possess a fundamental function in the regulation of sleep processes, particularly in promoting REM sleep.AFIPCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniv Fed Parana, Dept Farmacol, BR-80060000 Curitiba, Parana, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilFAPESP: 98/14.303-3Web of Scienc

Ensembl 2014

Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate genomic analysis in chordate species with an emphasis on human, major vertebrate model organisms and farm animals. Over the past year we have increased the number of species that we support to 77 and expanded our genome browser with a new scrollable overview and improved variation and phenotype views. We also report updates to our core datasets and improvements to our gene homology relationships from the addition of new species. Our REST service has been extended with additional support for comparative genomics and ontology information. Finally, we provide updated information about our methods for data access and resources for user training