bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal Grammar and critical periods: A most amusing paradox
Authors: Lieberman Philip
Published: February 2010

Epstein et al. take as given that, (1) a hypothetical Universal Grammar (UG) exists that allows children effortlessly to acquire their first language; they then argue (2) that critical or sensitive periods do not block the UG from second language acquisition. Therefore, why can't we all effortlessly “acquire” Tibetan in six months or so? Data concerning the neural bases of language are also noted.
On gradience and optionality in non-native grammars
Authors: Sorace Antonella
Published: February 2010

Epstein et al.'s “full access to Universal Grammar” position is conceptually and empirically problematic. Its shortcomings are illustrated through a brief discussion of the following issues: (1) initial versus final states of grammatical knowledge in a second language, (2) knowledge of gradience of grainmaticality, (3) optionality and retention in non-native grammars, and (4) the empirical measurement of syntactic knowledge.
Appreciating the poverty of the stimulus in second language acquisition
Authors: Sprouse Rex A.
Published: February 2010

The most compelling evidence for Epstein et al.'s central thesis that adult second language acquisition is constrained by the innate cognitive structures that constrain native language acquisition would be evidence of poverty of the stimulus. Although there are studies that point to such evidence, Epstein et al.'s primary form of argumentation, targetlike performance by second-language acquiring adults, is much less convincing.
Universal Grammar and second language acquisition: The null hypothesis
Authors: Epstein Samuel David , Flynn Suzanne , Martohardjono Gita
Published: February 2010

The target article advanced the null, unified and widely misinterpreted generative hypothesis regarding second language (L2) acquisition. Postulating that UG (Universal Grammar) constrains L2 knowledge growth does not entail identical developmental trajectories for L2 and first language (LI) acquisition; nor does it preclude a role for the L1. In embracing this hypothesis, we maintain a distinction between competence and performance. Those who conflate the two repeat fundamental and by no means unprecedented misconstruals of the generative enterprise, and more specifically, of the empirical content of the null hypothesis regarding L2 linguistic knowledge growth. We hope to have identified certain common goals, the adoption of which might constitute a firm foundation for continued productive interdisciplinary development of contemporary theoretical and experimental L2 acquisition research.
In search of nonvisual motor images
Authors: Rossetti Yves , Rode Gilles
Published: February 2010

Jeannerod's target article and a number of commentators stressed the necessity of distinguishing between motor representation and perceptual images. A patient with a lesion of the central somatosensory pathways allowed us to test for this distinction. The outcome suggests that motor images may not be visual and that the “pragmatic” framework proposed by Jeannerod for vision can apply to other sensory modalities.
Motor representations: One or many?
Authors: Jeannerod M.
Published: February 2010

Two issues have been raised. The first concerns whether consciousness is attached to a given type of action. It is argued that purposive actions are represented before being executed and that motor representations can either remain implicit or become explicit according to the task. The second issue concerns whether or not mental imagery of action is independent from action. Recent evidence showing the commonality of neural mechanisms for motor imagery and action, respectively, goes against the idea of independent processes.
Hippocampus, delay neurons, and sensory heterogeneity
Authors: Colombo Michael , Gross Charles G.
Published: February 2010

We raise three issues concerning the Eichenbaum, Otto & Cohen (1994) model. (1) We argue against the strict division of labor that Eichenbaum et al. attribute to neocortical and limbic regions. (2) We raise the possibility that the anterior and posterior portions of the hippocampus may be important for different types of information processing. (3) We argue that, rather than reflecting relational processing, different neural responses to “match” and “nonmatch” trials may relate to different required spatial responses.
The hunting of the hippocampal function
Authors: Crusio Wim E.
Published: February 2010

Eichenbaum et al.'s (1994a) theory suffers from a lack of ecological validation. It is not at all clear why the hypothesized faculties would have evolved and what their adaptive value would be. I argue that hippocampal function can only be understood if the animal is seen in its natural context.
Sequential processing of “items” and “relations”
Authors: Mumby Dave G.
Published: February 2010

Eichenbaum et al. (1994a) hypothesized that perceptually distinct items and the relations among them are processed sequentially by the parahippocampal region and the hippocampal formation, respectively. Predictions based solely on their model's sequential-processing feature might prove easier to disconfirm than those based on its representational features. Two such predictions are discussed: (1) double dissociations should be impossible following hippocampal vs. parahippocampal lesions, and (2) hippocampal lesions should not exacerbate impairments that follow complete parahippocampal lesions.
The hippocampus seen in the context of declarative and procedural control
Authors: Toates Frederick
Published: February 2010

Various apparently incompatible theories of hippocampal function have been proposed but integration is now needed. It is argued that the involvement of the hippocampus is most clearly seen when the animal needs to extrapolate beyond current sensory information. Such control can involve both the initiation of behaviour in the absence of appropriate sensory input and the inhibition of behaviour that might otherwise be triggered by current sensory input.
Group selection and “the pious gene”
Authors: Barresi John
Published: February 2010

If selection at the group level is to be considered more than a mere possibility, it is important to find phenomena that are best explained at this level of selection. I argue that human religious phenomena provide evidence for the selection of a “pious gene” at the group level, which results in a human tendency to believe in a transcendental reality that encourages behavioral conformity to collective as opposed to individual interest.
What is selected in group selection?
Authors: Lamb Michael E.
Published: February 2010

Misunderstandings often develop when scientists from different backgrounds use the same words (e.g., “selection”) when they mean different things by them. Theorists must therefore choose and define their terms carefully. In addition, proponents of “new” theories need to demonstrate empirically that theirs are more powerful than the existing theories they wish to supplant. Wilson & Sober have not yet done this.
More on group selection and human behavior
Authors: Wilson David Sloan , Sober Elliott
Published: February 2010

The six commentaries raise five issues about multi-level selection theory that we attempt to address: (1) replicators without vehicles, (2) group selection and movement between groups, (3) absolute versus relative fitness, (4) group-level psychological adaptions, and (5) multi-level selection as a predictive theory.
Strategies for the control of voluntary movements with one mechanical degree of freedom
Authors: Gottlieb Gerald L. , Corcos Daniel M. , Agarwal Gyan C.
Published: February 2010

A theory is presented to explain how accurate, single-joint movements are controlled. The theory applies to movements across different distances, with different inertial loads, toward targets of different widths over a wide range of experimentally manipulated velocities. The theory is based on three propositions. (1) Movements are planned according to “strategies” of which there are at least two: a speed-insensitive (SI) and a speed-sensitive (SS) one. (2) These strategies can be equated with sets of rules for performing diverse movement tasks. The choice between SI and SS depends on whether movement speed and/or movement time (and hence appropriate muscle forces) must be constrained to meet task requirements. (3) The electromyogram can be interpreted as a low-pass filtered version of the controlling signal to the motoneuron pools. This controlling signal can be modelled as a rectangular excitation pulse in which modulation occurs in either pulse amplitude or pulse width. Movements to different distances and with loads are controlled by the SI strategy, which modulates pulse width. Movements in which speed must be explicitly regulated are controlled by the SS strategy, which modulates pulse amplitude. The distinction between the two movement strategies reconciles many apparent conflicts in the motor control literature.
Reconciling Fechner and Stevens: Toward a unified psychophysical law
Authors: Krueger Lester E.
Published: February 2010

How does subjective magnitude,S. increase as physical magnitude or intensity,I, increases? Direct ratings (magnitude scales; partition or category scales) can be fitted by the power function,S = aIb, in which SequalsIraised to a power or exponent,b, and multiplied by a measure constant,a. The exponent is typically about twice as large for the magnitude scale (Stevens) as for the corresponding partition or category scale, but the higher exponent may be explained by the overly expansive way people use numbers in making magnitude estimations. The partition or category scale and the adjusted (for the use of number) magnitude scale for a given modality or condition generally agree with the neurelectric scale and the summated just noticeable difference (jnd) scale. A unified psychophysical law is proposed in which each jnd has the same subjective magnitude for a given modality or condition, subjective magnitude increases as approximately a power function of physical magnitude with the exponent ranging from near 0 to 1 (compressive function), and subjective magnitude depends primarily on peripheral sensory processes, that is, no nonlinear central transformations occur. An undue reliance on Weber's law blinded Fechner to the fact that the true psychophysical scale is approximately a power function. Rejecting Weber's law, which is not valid, means that we no longer have to choose between letting the summated jnd scale be a logarithmic function (Fechner's law) and introducing a nonlinear central transformation to make it into a power function (Brentano–Ekman-Teghtsoonian's law). Fechner and Stevens erred equally about the true psychophysical power function, whose exponent lies halfway between that of Fechner (an exponent approaching zero) and that of Stevens. To be reconciled, Fechnerians must give up the assumptions that Webers law is valid and that the jnd has the same subjective magnitude across modalities and conditions; Stevensians must give up the assumption that the unadjusted (for the use of number) magnitude scale is a direct measure of subjective magnitude.
A solution to the tag-assignment problem for neural networks
Authors: Strong Gary W. , Whitehead Bruce A.
Published: February 2010

Purely parallel neural networks can model object recognition in brief displays – the same conditions under which illusory conjunctions (the incorrect combination of features into perceived objects in a stimulus array) have been demonstrated empirically (Treisman 1986; Treisman & Gelade 1980). Correcting errors of illusory conjunction is the “tag-assignment” problem for a purely parallel processor: the problem of assigning a spatial tag to nonspatial features, feature combinations, and objects. This problem must be solved to model human object recognition over a longer time scale. Our model simulates both the parallel processes that may underlie illusory conjunctions and the serial processes that may solve the tag-assignment problem in normal perception. One component of the model extracts pooled features and another provides attentional tags that correct illusory conjunctions. Our approach addresses two questions: (i) How can objects be identified from simultaneously attended features in a parallel, distributed representation? (ii) How can the spatial selectional requirements of such an attentional process be met by a separation of pathways for spatial and nonspatial processing? Our analysis of these questions yields a neurally plausible simulation of tag assignment based on synchronizing feature processing activity in a spatial focus of attention.
Addiction is not as puzzling as it seems
Authors: Orford Jim
Published: February 2010

Heyman's target article seeks to resolve the apparent paradox surrounding the issue of control in relation to addictive behaviour. The present commentary argues that addiction is in fact less paradoxical and more easily understandable than Heyman supposes. A fully satisfactory model of addiction, however, requires a more multifaceted approach than that provided by the type of behavioural choice theory favoured by Heyman.
The stage question in cognitive-developmental theory
Authors: Brainerd Charles J.
Published: February 2010

The term “stage” appears to be used in three general senses in theories of behavioral development: (a) as a metaphor: (b) as a description of behaviors that undergo age change; (c) as an explanation of age-related changes in behavior. Although most existing stage models are purely descriptive, a few of them purport to have explanatory power. One such model, Piaget's stages of cognitive development, is considered in this paper.

To be viewed as potentially explanatory, a stage model must describe some behaviors that undergo age change, posit antecedent variables believed to cause the changes, and provide procedures whereby the behavioral changes and the antecedent variables can be independently measured. Piaget's stages seem to satisfy some but not all of these requirements. Piaget's stages describe many agerelated changes in behavior, and some antecedent variables have been proposed. However, procedures do not exist for measuring the two factors independently. In lieu of such procedures, Piaget has outlined a “program” of five empirical criteria whereby the reality of his stages can ostensibly be verified. Some objections to these criteria are considered.

The five criteria in Piaget's program are invariant sequence, cognitive structure, integration, consolidation, and equilibration. Three of the criteria (invariant sequence, integration, and consolidation) lead to the same sorts of empirical predictions (culturally universal sequences in the acquisition of certain behaviors). Such predictions are subject to the objection that Piagetian invariant sequences are often measurement sequences. A measurement sequence is said to occur when some late-appearing behavior consists of some earlier-appearing behavior plus additional things. The cognitive structure criterion is subject to at least three criticisms: First, it yields, at most, descriptions of behavior; second, these are often nothing more than descriptions of task structure; third, they cannot be regarded as unique to the given stages for which they are posited. The fifth criterion, equilibration, generates some predictions that might be considered as prima facie evidence for the existence of stages. However, these predictions conflict with the current data base on Piaget's stages.

It is concluded that there is no compelling support for Piaget's hypothesis that his cognitive stages do more than describe age-related changes in behavior. Since explanatory statements involving stages appear with some regularity in Piagetian and neo-Piagetian writings, there are grounds for supposing this conclusion to be nontrivial.
The combined semi-classical and relaxation limit in a quantum hydrodynamic semiconductor model
Authors: Li Yeping
Published: February 2010

We discuss the combined semi-classical and relaxation limit of a one-dimensional isentropic quantum hydrodynamical model for semiconductors. The quantum hydrodynamic equations consist of the isentropic Euler equations for the particle density and current density, including the quantum potential and a momentum relaxation term. The momentum equation is highly nonlinear and contains a dispersive term with third-order derivatives. The equations are self-consistently coupled to the Poisson equation for the electrostatic potential. With the help of the Maxwell-type iteration, we prove that, as the relaxation time and Planck constant tend to zero, periodic initial-value problems of a scaled one-dimensional isentropic quantum hydrodynamic model have unique smooth solutions existing in the time interval where the classical drift-diffusion model has smooth solutions. Meanwhile, we justify a formal derivation of the classical drift-diffusion model from the quantum hydrodynamic model.
Boundary blow-up of a logistic-type porous media equation in a multiply connected domain
Authors: Li Huiling , Pang Peter Y. H. , Wang Mingxin
Published: February 2010

We study positive solutions to the porous media equation of degenerate logistic type −Δu = a(x)u1/m – b(x)f(u), m > 1, which blow up at the inner boundary and satisfy a homogeneous boundary condition at the outer boundary of a multiply connected domain. In particular, we investigate uniqueness and blow-up rate near the inner boundary for such solutions. We also look at the limiting behaviour as m ↘ 1 for the special case where b(x) > 0 and f(u) = up/m with p > m.
Asymptotic behaviour, uniqueness and stability of coexistence states of a non-cooperative reaction–diffusion model of nuclear reactors
Authors: Peng Rui , Wei Dong , Yang Guoying
Published: February 2010

We investigate a non-cooperative reaction-diffusion model arising in the theory of nuclear reactors and are concerned with the associated steady-state problem. We determine the asymptotic behaviour of the coexistence states near the point of bifurcation from infinity, which exhibits the following very interesting spatial blow-up pattern: when the fuel temperature reaches a certain value, the free fast neutrons undergoing nuclear reaction will blow up in each spatial point of the interior of the reactor. Without any restriction on spatial dimensions, we also discuss the uniqueness and stability of the coexistence states. Our results complement and sharpen those derived in two recent works by Arioli and Lóopez-Gómez.
On the operating unit size of load/store architectures
Authors: BERGSTRA J. A. , MIDDELBURG C. A.
Published: February 2010

We introduce a strict version of the concept of a load/store instruction set architecture in the setting of Maurer machines. We take the view that transformations on the states of a Maurer machine are achieved by applying threads as considered in thread algebra to the Maurer machine. We study how the transformations on the states of the main memory of a strict load/store instruction set architecture that can be achieved by applying threads depend on the operating unit size, the cardinality of the instruction set and the maximal number of states of the threads.
Definition und epidemiologische Übersicht des Delirs bei älteren Patienten
Authors: Hafner Martina , Singler Katrin
Published: February 2010

Ein Delir ist beim hospitalisierten älteren Patienten eine häufige Komplikation. Das Delir führt zu einer verlängerten Hospitalisation, einer Einbuße der Funktionalität bis zum Verlust der Selbständigkeit und ist assoziert mit einer erhöhten Sterblichkeit. Daten bezüglich Inzidenz und Prävalenz gibt es vor allem bei hospitalisierten Patienten. Zudem hat das Delir eine wesentliche Auswirkung auf die Gesundheitskosten, die mit steigender Lebenserwartung höher werden. Das Delir ist ein Syndrom, das nicht exklusiv in psychiatrischen und geriatrischen Abteilungen auftritt und deshalb das Interesse aller Fachdisziplinen mit älteren Patienten wecken sollte.
Demenz und Delirium
Authors: Ehrensperger Michael M. , Monsch Andreas U.
Published: February 2010

Demenz und Delirium sind nosologische Entitäten, deren klinische Unterscheidbarkeit durch ähnliche Präsentation von Symptomen oftmals erschwert ist. Die diagnostischen Kriterien einer Demenz sowie des als Übergangsstadium konzeptualisierten Mild Cognitive Impairment werden dargestellt und dabei die Bedeutung der Frühdiagnostik und der Fremdanamnese betont. Anhand wichtiger Unterscheidungsmerkmale wird dann die differentialdiagnostische Abgrenzung des Deliriums speziell von der vaskulär bedingten Demenz sowie der Demenz mit Lewy-Körperchen aufgezeigt.
Increased Food Intake and Energy Expenditure Following Administration of Olanzapine to Healthy Men
Authors: Fountaine Robert J. , Taylor Ann E. , Mancuso James P. , Greenway Frank L. , Byerley Lauri O. , Smith Steven R. , Most Marlene M. , Fryburg David A.
Published: February 2010

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ‐induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double‐blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12‐day washout. Twenty‐four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18–49 years) and 22.6 ± 2.2 kg/m2, respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor‐I (PAI‐I), leptin, and tumor necrosis factor‐α (TNF‐α) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short‐term perturbations in IS.
Adipocytes IGFBP‐2 Expression in Prepubertal Obese Children
Authors: Claudio Maffeis , Benjamim Ficial , Riccardo Bonadonna , Massimiliano Corradi , Francesco Bertoldo , Luciano Cominacini
Published: February 2010

Aims of the study were to measure insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP‐2 expression, circulating IGFBP‐2, obesity, and insulin sensitivity in obese children. Thirty‐eight obese children were recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test and body composition by total‐body dual‐energy X‐ray absorptiometry. Serum free and total IGF‐I, IGFBP‐2, adiponectin, and leptin were measured. Relative quantification of IGFBP‐2 mRNA by subcutaneous adipose tissue biopsies was obtained using real‐time PCR. Circulating IGFBP‐2 was positively associated with insulin sensitivity, in agreement with previous studies. IGFBP‐2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = −0.604; P < 0.05), free IGF‐I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP‐2 (r = 0.003, P = ns). The association between IGFBP‐2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate). In conclusion, circulating IGFBP‐2 was positively associated with insulin sensitivity. IGFBP‐2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity. IGFBP‐2 expression may potentially be one of the local mechanisms used by adipocytes to limit further fat gain.
Attribution of climate forcing to economic sectors
Authors: Unger Nadine , Bond Tami C. , Wang James S. , Koch Dorothy M. , Menon Surabi , Shindell Drew T. , Bauer Susanne
Published: February 2010

A much-cited bar chart provided by the Intergovernmental Panel on Climate Change displays the climate impact, as expressed by radiative forcing in watts per meter squared, of individual chemical species. The organization of the chart reflects the history of atmospheric chemistry, in which investigators typically focused on a single species of interest. However, changes in pollutant emissions and concentrations are a symptom, not a
cause
, of the primary driver of anthropogenic climate change: human activity. In this paper, we suggest organizing the bar chart according to drivers of change—that is, by economic sector. Climate impacts of tropospheric ozone, fine aerosols, aerosol-cloud interactions, methane, and long-lived greenhouse gases are considered. We quantify the future evolution of the total radiative forcing due to perpetual constant year 2000 emissions by sector, most relevant for the development of climate policy now, and focus on two specific time points, near-term at 2020 and long-term at 2100. Because sector profiles differ greatly, this approach fosters the development of smart climate policy and is useful to identify effective opportunities for rapid mitigation of anthropogenic radiative forcing.
Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast
Authors: Fukunaga Masaki , Li Tie-Qiang , van Gelderen Peter , de Zwart Jacco A. , Shmueli Karin , Yao Bing , Lee Jongho , Maric Dragan , Aronova Maria A. , Zhang Guofeng , Leapman Richard D. , Schenck John F. , Merkle Hellmut , Duyn Jeff H.
Published: February 2010

Recent advances in high-field MRI have dramatically improved the visualization of human brain anatomy in vivo. Most notably, in cortical gray matter, strong contrast variations have been observed that appear to reflect the local laminar architecture. This contrast has been attributed to subtle variations in the magnetic properties of brain tissue, possibly reflecting varying iron and myelin content. To establish the origin of this contrast, MRI data from postmortem brain samples were compared with electron microscopy and histological staining for iron and myelin. The results show that iron is distributed over laminae in a pattern that is suggestive of each region’s myeloarchitecture and forms the dominant source of the observed MRI contrast.
ATP-independent CFTR channel gating and allosteric modulation by phosphorylation
Authors: Wang Wei , Wu Jianping , Bernard Karen , Li Ge , Wang Guangyu , Bevensee Mark O. , Kirk Kevin L.
Published: February 2010

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel, an ATP binding cassette (ABC) transporter. CFTR gating is linked to ATP binding and dimerization of its two nucleotide binding domains (NBDs). Channel activation also requires phosphorylation of the R domain by poorly understood mechanisms. Unlike conventional ligand-gated channels, CFTR is an ATPase for which ligand (ATP) release typically involves nucleotide hydrolysis. The extent to which CFTR gating conforms to classic allosteric schemes of ligand activation is unclear. Here, we describe point mutations in the CFTR cytosolic loops that markedly increase ATP-independent (constitutive) channel activity. This finding is consistent with an allosteric gating mechanism in which ligand shifts the equilibrium between inactive and active states but is not essential for channel opening. Constitutive mutations mapped to the putative symmetry axis of CFTR based on the crystal structures of related ABC transporters, a common theme for activating mutations in ligand-gated channels. Furthermore, the ATP sensitivity of channel activation was strongly enhanced by these constitutive mutations, as predicted for an allosteric mechanism (reciprocity between protein activation and ligand occupancy). Introducing constitutive mutations into CFTR channels that cannot open in response to ATP (i.e., the G551D CF mutant and an NBD2-deletion mutant) substantially rescued their activities. Importantly, constitutive mutants that opened without ATP or NBD2 still required R domain phosphorylation for optimal activity. Our results confirm that (
i
) CFTR gating exhibits features of protein allostery that are shared with conventional ligand-gated channels and (
ii
) the R domain modulates CFTR activity independent of ATP-induced NBD dimerization.
Noninvasive diagnosis of seed viability using infrared thermography
Authors: Kranner Ilse , Kastberger Gerald , Hartbauer Manfred , Pritchard Hugh W.
Published: February 2010

Recent advances in the noninvasive analyses of plant metabolism include stress imaging techniques, mainly developed for vegetative tissues. We explored if infrared thermography can be used to predict whether a quiescent seed will germinate or die upon water uptake. Thermal profiles of viable, aged, and dead
Pisum sativum
seeds were recorded, and image analysis of 22,000 images per individual seed showed that infrared thermography can detect imbibition- and germination-associated biophysical and biochemical changes. These “thermal fingerprints” vary with viability in this species and in
Triticum aestivum
and
Brassica napus
seeds. Thermogenesis of the small individual
B. napus
seeds was at the limit of the technology. We developed a computer model of “virtual pea seeds,” that uses Monte Carlo simulation, based on the heat production of major seed storage compounds to unravel physico-chemical processes of thermogenesis. The simulation suggests that the cooling that dominates the early thermal profiles results from the dissolution of low molecular-weight carbohydrates. Moreover, the kinetics of the production of such “cooling” compounds over the following 100 h is dependent on seed viability. We also developed a deterministic tool that predicts in the first 3 hours of water uptake, when seeds can be redried and stored again, whether or not a pea seed will germinate. We believe that the early separation of individual, ungerminated seeds (live, aged, or dead) before destructive germination assessment creates unique opportunities for integrative studies on cell death, differentiation, and development.
The role of SAP97 in synaptic glutamate receptor dynamics
Authors: Howard MacKenzie A. , Elias Guillermo M. , Elias Laura A. B. , Swat Wojciech , Nicoll Roger A.
Published: February 2010

Proteins of the PSD-95–like membrane-associated guanylate kinase (PSD-MAGUK) family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process necessary for both basal synaptic transmission and forms of synaptic plasticity. Synapse-associated protein 97 (SAP97) exhibits protein interactions, such as direct interaction with the GluA1 AMPAR subunit, and subcellular localization (synaptic, perisynaptic, and dendritic) unique within this protein family. Due in part to the lethality of the germline knockout of SAP97, this protein’s role in synaptic transmission and plasticity is poorly understood. We found that overexpression of SAP97 during early development traffics AMPARs and NMDA receptors (NMDARs) to synapses, and that SAP97 rescues the deficits in AMPAR currents normally seen in PSD-93/-95 double-knockout neurons. Mature neurons that have experienced the overexpression of SAP97 throughout development exhibit enhanced AMPAR and NMDAR currents, as well as faster NMDAR current decay kinetics. In loss-of-function experiments using conditional SAP97 gene deletion, we recorded no deficits in glutamatergic transmission or long-term potentiation. These results support the hypothesis that SAP97 is part of the machinery that traffics glutamate receptors and compensates for other PSD-MAGUKs in knockout mouse models. However, due to functional redundancy, other PSD-MAGUKs can presumably compensate when SAP97 is conditionally deleted during development.
Identifying the amylome, proteins capable of forming amyloid-like fibrils
Authors: Goldschmidt Lukasz , Teng Poh K. , Riek Roland , Eisenberg David
Published: February 2010

The amylome is the universe of proteins that are capable of forming amyloid-like fibrils. Here we investigate the factors that enable a protein to belong to the amylome. A major factor is the presence in the protein of a segment that can form a tightly complementary interface with an identical segment, which permits the formation of a steric zipper—two self-complementary beta sheets that form the spine of an amyloid fibril. Another factor is sufficient conformational freedom of the self-complementary segment to interact with other molecules. Using RNase A as a model system, we validate our fibrillogenic predictions by the 3D profile method based on the crystal structure of NNQQNY and demonstrate that a specific residue order is required for fiber formation. Our genome-wide analysis revealed that self-complementary segments are found in almost all proteins, yet not all proteins form amyloids. The implication is that chaperoning effects have evolved to constrain self-complementary segments from interaction with each other.
Syntaxin 6 and CAL Mediate the Degradation of the Cystic Fibrosis Transmembrane Conductance Regulator
Authors: Cheng Jie , Cebotaru Valeriu , Cebotaru Liudmila , Guggino William B.
Published: February 2010

The PDZ domain–containing protein CAL mediates lysosomal trafficking and degradation of CFTR. Here we demonstrate the involvement of a CAL-binding SNARE protein syntaxin 6 (STX6) in this process. Overexpression of STX6, which colocalizes and coimmunoprecipitates with CAL, dramatically reduces the steady-state level and stability of CFTR. Conversely, overexpression of a STX6 dominant-negative mutant increases CFTR. Silencing endogenous STX6 increases CFTR but has no effect on ΔTRL-CFTR, which cannot bind to CAL. Silencing CAL eliminates the effect of STX6 on CFTR. Both results suggest a dependence of CAL on STX6 function. Consistent with its Golgi localization, STX6 does not bind to ER-localized ΔF508-CFTR. Silencing STX6 has no effect on ΔF508-CFTR expression. However, overexpression of STX6 coimmunoprecipitates with and reduces temperature-rescued ΔF508-CFTR that escapes ER degradation. Conversely, silencing STX6 enhances the effect of low temperature in rescuing ΔF508-CFTR. Finally, in human bronchial epithelial cells, silencing endogenous STX6 leads to increases in protein levels and Cl− currents of both wild-type and temperature-rescued CFTR. We have identified STX6 as a new component of the CAL complex that regulates the abundance and function of CFTR at the post-ER level. Our results suggest a therapeutic role of STX6 in enhancing rescued ΔF508-CFTR.
Improving protein secondary structure prediction using a simplek-mer model
Authors: Madera Martin , Calmus Ryan , Thiltgen Grant , Karplus Kevin , Gough Julian
Published: February 2010

Motivation: Some first order methods for protein sequence analysis inherently treat each position as independent. We develop a general framework for introducing longer range interactions. We then demonstrate the power of our approach by applying it to secondary structure prediction; under the independence assumption, sequences produced by existing methods can produce features that are not protein like, an extreme example being a helix of length 1. Our goal was to make the predictions from state of the art methods more realistic, without loss of performance by other measures.

Results: Our framework for longer range interactions is described as a k-mer order model. We succeeded in applying our model to the specific problem of secondary structure prediction, to be used as an additional layer on top of existing methods. We achieved our goal of making the predictions more realistic and protein like, and remarkably this also improved the overall performance. We improve the Segment OVerlap (SOV) score by 1.8%, but more importantly we radically improve the probability of the real sequence given a prediction from an average of 0.271 per residue to 0.385. Crucially, this improvement is obtained using no additional information.

Availability:  http://supfam.cs.bris.ac.uk/kmer

Contact:  gough@cs.bris.ac.uk
Small-sample precision of ROC-related estimates
Authors: Hanczar Blaise , Hua Jianping , Sima Chao , Weinstein John , Bittner Michael , Dougherty Edward R.
Published: February 2010

Motivation: The receiver operator characteristic (ROC) curves are commonly used in biomedical applications to judge the performance of a discriminant across varying decision thresholds. The estimated ROC curve depends on the true positive rate (TPR) and false positive rate (FPR), with the key metric being the area under the curve (AUC). With small samples these rates need to be estimated from the training data, so a natural question arises: How well do the estimates of the AUC, TPR and FPR compare with the true metrics?

Results: Through a simulation study using data models and analysis of real microarray data, we show that (i) for small samples the root mean square differences of the estimated and true metrics are considerable; (ii) even for large samples, there is only weak correlation between the true and estimated metrics; and (iii) generally, there is weak regression of the true metric on the estimated metric. For classification rules, we consider linear discriminant analysis, linear support vector machine (SVM) and radial basis function SVM. For error estimation, we consider resubstitution, three kinds of cross-validation and bootstrap. Using resampling, we show the unreliability of some published ROC results.

Availability: Companion web site at http://compbio.tgen.org/paper_supp/ROC/roc.html

Contact:  edward@mail.ece.tamu.edu
Maximal conditional chi-square importance in random forests
Authors: Wang Minghui , Chen Xiang , Zhang Heping
Published: February 2010

Motivation: High-dimensional data are frequently generated in genome-wide association studies (GWAS) and other studies. It is important to identify features such as single nucleotide polymorphisms (SNPs) in GWAS that are associated with a disease. Random forests represent a very useful approach for this purpose, using a variable importance score. This importance score has several shortcomings. We propose an alternative importance measure to overcome those shortcomings.

Results: We characterized the effect of multiple SNPs under various models using our proposed importance measure in random forests, which uses maximal conditional chi-square (MCC) as a measure of association between a SNP and the trait conditional on other SNPs. Based on this importance measure, we employed a permutation test to estimate empirical P-values of SNPs. Our method was compared to a univariate test and the permutation test using the Gini and permutation importance. In simulation, the proposed method performed consistently superior to the other methods in identifying of risk SNPs. In a GWAS of age-related macular degeneration, the proposed method confirmed two significant SNPs (at the genome-wide adjusted level of 0.05). Further analysis showed that these two SNPs conformed with a heterogeneity model. Compared with the existing importance measures, the MCC importance measure is more sensitive to complex effects of risk SNPs by utilizing conditional information on different SNPs. The permutation test with the MCC importance measure provides an efficient way to identify candidate SNPs in GWAS and facilitates the understanding of the etiology between genetic variants and complex diseases.

Contact:  heping.zhang@yale.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cassia auriculata: Aspects of Safety Pharmacology and Drug Interaction
Authors: Puranik Amrutesh S. , Halade Ganesh , Kumar Sandeep , Mogre Ranjan , Apte Kishori , Vaidya Ashok D. B. , Patwardhan Bhushan
Published: February 2010

Safety pharmacology studies help in identifying preclinical adverse drug reactions. We carried out routine safety pharmacology with focus on cardiovascular variables and pharmacokinetic herb‐drug interaction studies on rats fed with standardized traditional hydro‐alcoholic extract and technology‐based supercritical extract of Cassia auriculata for 12 weeks. Our studies indicate that both these extracts are pharmacologically safe and did not show any significant adverse reactions at the tested doses. The traditional hydro‐alcoholic extract did not show any significant effect on pharmacokinetics; however, the technology‐based supercritical extract caused a significant reduction in absorption of metformin. Our results indicate the need to include pharmacokinetic herb‐drug interaction studies as evidence for safety especially for technology‐based extracts.
Vortex interactions with flapping wings and fins can be unpredictable
Authors: Lentink David , Van Heijst GertJan F. , Muijres Florian T. , Van Leeuwen Johan L.
Published: February 2010

As they fly or swim, many animals generate a wake of vortices with their flapping fins and wings that reveals the dynamics of their locomotion. Previous studies have shown that the dynamic interaction of vortices in the wake with fins and wings can increase propulsive force. Here, we explore whether the dynamics of the vortex interactions could affect the predictability of propulsive forces. We studied the dynamics of the interactions between a symmetrically and periodically pitching and heaving foil and the vortices in its wake, in a soap-film tunnel. The phase-locked movie sequences reveal that abundant chaotic vortex-wake interactions occur at high Strouhal numbers. These high numbers are representative for the fins and wings of near-hovering animals. The chaotic wake limits the forecast horizon of the corresponding force and moment integrals. By contrast, we find periodic vortex wakes with an unlimited forecast horizon for the lower Strouhal numbers (0.2–0.4) at which many animals cruise. These findings suggest that swimming and flying animals could control the predictability of vortex-wake interactions, and the corresponding propulsive forces with their fins and wings.
Taqman real-time quantitative PCR for identification of western flower thrip (
Frankliniella occidentalis
) for plant quarantine
Authors: Huang K. S. , Lee S. E. , Yeh Y. , Shen G. S. , Mei E. , Chang C. M.
Published: February 2010

Western flower thrip (
Frankliniella occidentalis
) is a major global pest of agricultural products. It directly damages crops through feeding, oviposition activity or transmission of several plant viruses. We describe a Taqman real-time quantitative PCR detection system, which can rapidly identify
F. occidentalis
from thrips larvae to complement the traditional morphological identification. The data showed that our detection system targeted on the ribosomal RNA gene regions of
F. occidentalis
has high sensitivity and specificity. The rapid method can be used for on-site testing of samples at ports-of-entry in the future.
On reconstruction of three-dimensional harmonic functions from discrete data
Authors: Galybin A. N. , Irša J.
Published: February 2010

This study presents an approach for reconstruction of harmonic functions in three dimensions from the finite number of field and surface measurements. The approach, based on the Trefftz method, performs reconstruction as the best fit to the data and provides smoothness of the reconstructed function. Two particular algorithms are proposed; the first one uses specific radial basis functions and the second one is of finite element type. Either of them can be applied to analyse different data types but the latter can handle larger problems. The data types considered in this study also cover direct and inverse boundary value problems. Therefore, the proposed approach is universal and capable of dealing with both well-posed and ill-posed formulations. Examples from steady heat conduction and elastostatics are examined in order to investigate the efficiency of the approach.
Dispersal and ejaculatory strategies associated with exaggeration of weapon in an armed beetle
Authors: Yamane Takashi , Okada Kensuke , Nakayama Satoshi , Miyatake Takahisa
Published: February 2010

Weapons used in male fighting can be costly to males and are often reported to trade off with other characters such as wings or spermatogenic investment. This study investigated whether increased investment into weapons can generate evolutionary changes in mating strategy for armed males. Male flour beetles,
Gnatocerus cornutus
, have enlarged mandibles that are used in male–male competition. We subjected these weapons to 12 generations of bidirectional selection and found trade-offs between weapons and two other male characters: wing and testis size. In addition, probably as a consequence of the observed changes in investment, dispersal ability and ejaculatory volume differ significantly between the lines. This indicates that the exaggeration of a weapon can be associated with dispersal and ejaculatory strategies. Thus, altered investment into weapons can lead to correlated changes in life-history traits.
An unexpected advantage of whiteness in horses: the most horsefly-proof horse has a depolarizing white coat
Authors: Horváth Gábor , Blahó Miklós , Kriska György , Hegedüs Ramón , Gerics Balázs , Farkas Róbert , Åkesson Susanne
Published: February 2010

White horses frequently suffer from malign skin cancer and visual deficiencies owing to their high sensitivity to the ultraviolet solar radiation. Furthermore, in the wild, white horses suffer a larger predation risk than dark individuals because they can more easily be detected. In spite of their greater vulnerability, white horses have been highly appreciated for centuries owing to their natural rarity. Here, we show that blood-sucking tabanid flies, known to transmit disease agents to mammals, are less attracted to white than dark horses. We also demonstrate that tabanids use reflected polarized light from the coat as a signal to find a host. The attraction of tabanids to mainly black and brown fur coats is explained by positive polarotaxis. As the host's colour determines its attractiveness to tabanids, this parameter has a strong influence on the parasite load of the host. Although we have studied only the tabanid–horse interaction, our results can probably be extrapolated to other host animals of polarotactic tabanids, as the reflection–polarization characteristics of the host's body surface are physically the same, and thus not species-dependent.