On-line processing of wh-questions in children with G-SLI and typically developing children

Background: The computational grammatical complexity ( CGC) hypothesis claims that children with G(rammatical)-specific language impairment ( SLI) have a domain-specific deficit in the computational system affecting syntactic dependencies involving 'movement'. One type of such syntactic dependencies is filler-gap dependencies. In contrast, the Generalized Slowing Hypothesis claims that SLI children have a domain-general deficit affecting processing speed and capacity. Aims: To test contrasting accounts of SLI we investigate processing of syntactic (filler-gap) dependencies in wh-questions. Methods & Procedures: Fourteen 10; 2 - 17; 2 G-SLI children, 14 age- matched and 17 vocabulary-matched controls were studied using the cross- modal picturepriming paradigm. Outcomes & Results: G-SLI children's processing speed was significantly slower than the age controls, but not younger vocabulary controls. The G- SLI children and vocabulary controls did not differ on memory span. However, the typically developing and G-SLI children showed a qualitatively different processing pattern. The age and vocabulary controls showed priming at the gap, indicating that they process wh-questions through syntactic filler-gap dependencies. In contrast, G-SLI children showed priming only at the verb. Conclusions: The findings indicate that G-SLI children fail to establish reliably a syntactic filler- gap dependency and instead interpret wh-questions via lexical thematic information. These data challenge the Generalized Slowing Hypothesis account, but support the CGC hypothesis, according to which G-SLI children have a particular deficit in the computational system affecting syntactic dependencies involving 'movement'. As effective remediation often depends on aetiological insight, the discovery of the nature of the syntactic deficit, along side a possible compensatory use of semantics to facilitate sentence processing, can be used to direct therapy. However, the therapeutic strategy to be used, and whether such similar strengths and weaknesses within the language system are found in other SLI subgroups are empirical issues that warrant further research.

Criteria for validation and selection of cognitive tests for investigating the effects of foods and nutrients.

This review is an output of the International Life Sciences Institute (ILSI) Europe Marker Initiative, which aims to identify evidence-based criteria for selecting adequate measures of nutrient effects on health through comprehensive literature review. Experts in cognitive and nutrition sciences examined the applicability of these proposed criteria to the field of cognition with respect to the various cognitive domains usually assessed to reflect brain or neurological function. This review covers cognitive domains important in the assessment of neuronal integrity and function, commonly used tests and their state of validation, and the application of the measures to studies of nutrition and nutritional intervention trials. The aim is to identify domain-specific cognitive tests that are sensitive to nutrient interventions and from which guidance can be provided to aid the application of selection criteria for choosing the most suitable tests for proposed nutritional intervention studies using cognitive outcomes. The material in this review serves as a background and guidance document for nutritionists, neuropsychologists, psychiatrists, and neurologists interested in assessing mental health in terms of cognitive test performance and for scientists intending to test the effects of food or food components on cognitive function.

Parenting difficulties and postnatal depression: implications for primary healthcare assessment and intervention

Postnatal depression (PND) is associated with impairments in the mother–child relationship, and these impairments are themselves associated with adverse child outcomes. Thus, compared to the children of non-depressed mothers, children of mothers with PND are more likely to be insecurely attached, and to have externalising behaviour problems and poor cognitive development. Each of these three child outcomes is predicted by a particular pattern of difficulty in parenting: insecure attachment is related to maternal insensitivity, particularly in relation to infant distress and emotional vulnerability; externalising problems are particularly common in the context of hostile parenting; and poor cognitive development is related to parental difficulties in noticing infant signs of interest and supporting their engagement with the environment. This article sets out procedures for how parenting could be assessed in ways that are sensitive to the domain-specific associations between parenting and child outcome, while remaining sensitive to the child's developmental stage. This set of assessments requires field testing.

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain

Background: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. Method: 2 7 children who had a sibling with AS were administered the children's version of the 'Eyes Test'(Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. Results: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. Discussion: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.

The application of Prony’s method to time-domain waveform data modeling in the presence of noise

In this paper,the Prony's method is applied to the time-domain waveform data modelling in the presence of noise.The following three problems encountered in this work are studied:(1)determination of the order of waveform;(2)de-termination of numbers of multiple roots;(3)determination of the residues.The methods of solving these problems are given and simulated on the computer.Finally,an output pulse of model PG-10N signal generator and the distorted waveform obtained by transmitting the pulse above mentioned through a piece of coaxial cable are modelled,and satisfactory results are obtained.So the effectiveness of Prony's method in waveform data modelling in the presence of noise is confirmed.

Modeling the user knowledge by belief networks

This paper describes the user modeling component of EPIAIM, a consultation system for data analysis in epidemiology. The component is aimed at representing knowledge of concepts in the domain, so that their explanations can be adapted to user needs. The first part of the paper describes two studies aimed at analysing user requirements. The first one is a questionnaire study which examines the respondents' familiarity with concepts. The second one is an analysis of concept descriptions in textbooks and from expert epidemiologists, which examines how discourse strategies are tailored to the level of experience of the expected audience. The second part of the paper describes how the results of these studies have been used to design the user modeling component of EPIAIM. This module works in a two-step approach. In the first step, a few trigger questions allow the activation of a stereotype that includes a "body" and an "inference component". The body is the representation of the body of knowledge that a class of users is expected to know, along with the probability that the knowledge is known. In the inference component, the learning process of concepts is represented as a belief network. Hence, in the second step the belief network is used to refine the initial default information in the stereotype's body. This is done by asking a few questions on those concepts where it is uncertain whether or not they are known to the user, and propagating this new evidence to revise the whole situation. The system has been implemented on a workstation under UNIX. An example of functioning is presented, and advantages and limitations of the approach are discussed.

Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional kinase-phosphatase

Understanding how multiple signals are integrated in living cells to produce a balanced response is a major challenge in biology. Two-component signal transduction pathways, such as bacterial chemotaxis, comprise histidine protein kinases (HPKs) and response regulators (RRs). These are used to sense and respond to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory network with two signaling clusters, each containing a HPK, CheA. Here we demonstrate, using a mathematical model, how the outputs of the two signaling clusters may be integrated. We use our mathematical model supported by experimental data to predict that: (1) the main RR controlling flagellar rotation, CheY6, aided by its specific phosphatase, the bifunctional kinase CheA3, acts as a phosphate sink for the other RRs; and (2) a phosphorelay pathway involving CheB2 connects the cytoplasmic cluster kinase CheA3 with the polar localised kinase CheA2, and allows CheA3-P to phosphorylate non-cognate chemotaxis RRs. These two mechanisms enable the bifunctional kinase/phosphatase activity of CheA3 to integrate and tune the sensory output of each signaling cluster to produce a balanced response. The signal integration mechanisms identified here may be widely used by other bacteria, since like R. sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and need to integrate signals from different sources.

Molecule modeling of human pentameric alpha(7) neuronal nicotinic acetylcholine receptor and its interaction with its agonist and competitive antagonist

The nicotinic Acetylcholine Receptor (nAChR) is the major class of neurotransmitter receptors that is involved in many neurodegenerative conditions such as schizophrenia, Alzheimer's and Parkinson's diseases. The N-terminal region or Ligand Binding Domain (LBD) of nAChR is located at pre- and post-synaptic nervous system, which mediates synaptic transmission. nAChR acts as the drug target for agonist and competitive antagonist molecules that modulate signal transmission at the nerve terminals. Based on Acetylcholine Binding Protein (AChBP) from Lymnea stagnalis as the structural template, the homology modeling approach was carried out to build three dimensional model of the N-terminal region of human alpha(7)nAChR. This theoretical model is an assembly of five alpha(7) subunits with 5 fold axis symmetry, constituting a channel, with the binding picket present at the interface region of the subunits. alpha-netlrotoxin is a potent nAChR competitive antagonist that readily blocks the channel resulting in paralysis. The molecular interaction of alpha-Bungarotoxin, a long chain alpha-neurotoxin from (Bungarus multicinctus) and human alpha(7)nAChR seas studied. Agonists such as acetylcholine, nicotine, which are used in it diverse array of biological activities, such as enhancements of cognitive performances, were also docked with the theoretical model of human alpha(7)nAChR. These docked complexes were analyzed further for identifying the crucial residues involved in interaction. These results provide the details of interaction of agonists and competitive antagonists with three dimensional model of the N-terminal region of human alpha(7)nAChR and thereby point to the design of novel lead compounds.

Mapping the immune response to the outer domain of a human immunodeficiency virus-1 clade C gp120

The outer domain (OD) of human immunodeficiency virus (HIV)-1 gp120 represents an attractive, if difficult, target for a beneficial immune response to HIV infection. Unlike the entire gp120, the OD is structurally stable and contains the surfaces that interact with both the primary and secondary cellular receptors. The primary strain-specific neutralizing target, the V3 loop, lies within the OD, as do epitopes for two cross-reactive neutralizing monoclonal antibodies (mAbs), b12 and 2G12, and the contact sites for a number of inhibitory lectins. The OD is poorly immunogenic, at least in the context of complete gp120, but purposeful OD immunization can lead to a substantial antibody response. Here, we map the antibody generated following immunization with a clade C OD. In contrast to published data for the clade B OD, the majority of the polyclonal response to the complete clade C OD is to the V3 loop; deletion of the loop substantially reduces immunogenicity. When the loop sequence was substituted for the epitope for 2F5, a well-characterized human cross-neutralizing mAb, a polyclonal response to the epitope was generated. A panel of mAbs against the clade C OD identified two mAbs that reacted with the loop and were neutralizing for clade C but not B isolates. Other mAbs recognized both linear and conformational epitopes in the OD. We conclude that, as for complete gp120, V3 immunodominance is a property of OD immunogens, that the responses can be neutralizing and that it could be exploited for the presentation of other epitopes.

The extrapolation problem and how population modeling can help

We argue that population modeling can add value to ecological risk assessment by reducing uncertainty when extrapolating from ecotoxicological observations to relevant ecological effects. We review other methods of extrapolation, ranging from application factors to species sensitivity distributions to suborganismal (biomarker and "-omics'') responses to quantitative structure activity relationships and model ecosystems, drawing attention to the limitations of each. We suggest a simple classification of population models and critically examine each model in an extrapolation context. We conclude that population models have the potential for adding value to ecological risk assessment by incorporating better understanding of the links between individual responses and population size and structure and by incorporating greater levels of ecological complexity. A number of issues, however, need to be addressed before such models are likely to become more widely used. In a science context, these involve challenges in parameterization, questions about appropriate levels of complexity, issues concerning how specific or general the models need to be, and the extent to which interactions through competition and trophic relationships can be easily incorporated.

Modeling cumulative evidence for freedom from disease with applications to BSE surveillance trials

This investigation deals with the question of when a particular population can be considered to be disease-free. The motivation is the case of BSE where specific birth cohorts may present distinct disease-free subpopulations. The specific objective is to develop a statistical approach suitable for documenting freedom of disease, in particular, freedom from BSE in birth cohorts. The approach is based upon a geometric waiting time distribution for the occurrence of positive surveillance results and formalizes the relationship between design prevalence, cumulative sample size and statistical power. The simple geometric waiting time model is further modified to account for the diagnostic sensitivity and specificity associated with the detection of disease. This is exemplified for BSE using two different models for the diagnostic sensitivity. The model is furthermore modified in such a way that a set of different values for the design prevalence in the surveillance streams can be accommodated (prevalence heterogeneity) and a general expression for the power function is developed. For illustration, numerical results for BSE suggest that currently (data status September 2004) a birth cohort of Danish cattle born after March 1999 is free from BSE with probability (power) of 0.8746 or 0.8509, depending on the choice of a model for the diagnostic sensitivity.

Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n = 8), lean (fal-, n = 8) and lean (-/-, n = 8)) were characterized via high-resolution H-1 NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fal- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

New mathematical modeling approach for predicting microbial inactivation by high hydrostatic pressure

A new primary model based on a thermodynamically consistent first-order kinetic approach was constructed to describe non-log-linear inactivation kinetics of pressure-treated bacteria. The model assumes a first-order process in which the specific inactivation rate changes inversely with the square root of time. The model gave reasonable fits to experimental data over six to seven orders of magnitude. It was also tested on 138 published data sets and provided good fits in about 70% of cases in which the shape of the curve followed the typical convex upward form. In the remainder of published examples, curves contained additional shoulder regions or extended tail regions. Curves with shoulders could be accommodated by including an additional time delay parameter and curves with tails shoulders could be accommodated by omitting points in the tail beyond the point at which survival levels remained more or less constant. The model parameters varied regularly with pressure, which may reflect a genuine mechanistic basis for the model. This property also allowed the calculation of (a) parameters analogous to the decimal reduction time D and z, the temperature increase needed to change the D value by a factor of 10, in thermal processing, and hence the processing conditions needed to attain a desired level of inactivation; and (b) the apparent thermodynamic volumes of activation associated with the lethal events. The hypothesis that inactivation rates changed as a function of the square root of time would be consistent with a diffusion-limited process.

Efficient modeling and inference for event-related fMRI data

Event-related functional magnetic resonance imaging (efMRI) has emerged as a powerful technique for detecting brains' responses to presented stimuli. A primary goal in efMRI data analysis is to estimate the Hemodynamic Response Function (HRF) and to locate activated regions in human brains when specific tasks are performed. This paper develops new methodologies that are important improvements not only to parametric but also to nonparametric estimation and hypothesis testing of the HRF. First, an effective and computationally fast scheme for estimating the error covariance matrix for efMRI is proposed. Second, methodologies for estimation and hypothesis testing of the HRF are developed. Simulations support the effectiveness of our proposed methods. When applied to an efMRI dataset from an emotional control study, our method reveals more meaningful findings than the popular methods offered by AFNI and FSL. (C) 2008 Elsevier B.V. All rights reserved.

Orientation coding: a specific deficit in Williams syndrome?

Williams syndrome (WS) is a rare genetic disorder with a unique cognitive profile in which verbal abilities are markedly stronger than visuospatial abilities. This study investigated the claim that orientation coding is a specific deficit within the visuospatial domain in WS. Experiment I employed a simplified version of the Benton Judgement of Line Orientation task and a control, length-matching task. Results demonstrated comparable levels of orientation matching performance in the group with WS and a group of typically developing (TD) controls matched by nonverbal ability, although it is possible that floor effects masked group differences. A group difference was observed in the length-matching task due to stronger performance from the control group. Experiment 2 employed an orientation-discrimination task and a length-discrimination task. Contrary to previous reports, the results showed that individuals with WS were able to code by orientation to a comparable level as that of their matched controls. This demonstrates that, although some impairment is apparent, orientation coding does not represent a specific deficit in WS. Comparison between Experiments I and 2 suggests that orientation coding is vulnerable to task complexity. However, once again, this vulnerability does not appear to be specific to the population with WS, as it was also apparent in the TD controls.