A PRINCIPAL COMPONENTS ANALYSIS OF THE PROCESS OF ATTENTION.

A review of the literature reveals that several models of selective attention have been proposed. Traditionally, these models have been distinguished on the basis of two dimensions: their formulations regarding (1) locus of attentional operations and (2) the nature of capacity limitations. In regard to the former, early theorists have indicated that attention is a prerequisite for in depth perceptual processing whereas late theorists have suggested that attentional activity is confined to postperceptual operations. In regard to the latter, a distinction has been made between structural theorists who have implied that attention, which exerts its influence in isolated processing systems, results from the inability of cognitive structures to simultaneously process competitive stimulus inputs and functional theorists who have described attention as a diffuse cognitive resource that is limited in a general fashion, however, variable in terms of its restrictions and functions. At the empirical level it is noted that although diverse paradigms have been employed to define and measure attention, researchers from varying theoretical positions have for the most part relied upon a particular means of data collection. On the basis of these observations, it was hypothesized that current controversy may stem from the commonly held assumption that attention is a unitary concept/process. An attempt was made to test this premise. Specifically, eight experimental tasks, two supporting each of the four theoretical positions that result from the aforementioned categorization scheme, were administered to 60 subjects. A number of predictions specific to the eight paradigms were tested. Subsequently, the entire data set was submitted to a principal components analysis. The majority of predictions were confirmed suggesting that the diverse methods of assessing attention which currently exist are equally accurate and appropriate. The results of the principal components analysis suggest that attention is a variable process. More specifically, attention appears to operate differently in the visual and the auditory modalities; it appears to manifest both structural and functional limitations; and it appears to intervene at multiple loci in the perceptual cycle.Dept. of Psychology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1984 .P358. Source: Dissertation Abstracts International, Volume: 45-04, Section: B, page: 1309. Thesis (Ph.D.)--University of Windsor (Canada), 1984

Distribution of roots of random real generalized polynomials

The average density of zeros for monic generalized polynomials, $P_n(z)=\phi(z)+\sum_{k=1}^nc_kf_k(z)$, with real holomorphic $\phi ,f_k$ and real Gaussian coefficients is expressed in terms of correlation functions of the values of the polynomial and its derivative. We obtain compact expressions for both the regular component (generated by the complex roots) and the singular one (real roots) of the average density of roots. The density of the regular component goes to zero in the vicinity of the real axis like $|\hbox{\rm Im}\,z|$. We present the low and high disorder asymptotic behaviors. Then we particularize to the large $n$ limit of the average density of complex roots of monic algebraic polynomials of the form $P_n(z) = z^n +\sum_{k=1}^{n}c_kz^{n-k}$ with real independent, identically distributed Gaussian coefficients having zero mean and dispersion $\delta = \frac 1{\sqrt{n\lambda}}$. The average density tends to a simple, {\em universal} function of $\xi={2n}{\log |z|}$ and $\lambda$ in the domain $\xi\coth \frac{\xi}{2}\ll n|\sin \arg (z)|$ where nearly all the roots are located for large $n$.Comment: 17 pages, Revtex. To appear in J. Stat. Phys. Uuencoded gz-compresed tarfile (.66MB) containing 8 Postscript figures is available by e-mail from [email protected]

On a Generalization of Zaslavsky's Theorem for Hyperplane Arrangements

We define arrangements of codimension-1 submanifolds in a smooth manifold which generalize arrangements of hyperplanes. When these submanifolds are removed the manifold breaks up into regions, each of which is homeomorphic to an open disc. The aim of this paper is to derive formulas that count the number of regions formed by such an arrangement. We achieve this aim by generalizing Zaslavsky's theorem to this setting. We show that this number is determined by the combinatorics of the intersections of these submanifolds.Comment: version 3: The title had a typo in v2 which is now fixed. Will appear in Annals of Combinatorics. Version. 2: 19 pages, major revision in terms of style and language, some results improved, contact information updated, final versio

Chiral Cilia orientation in the left-right organizer

Chirality is a property of asymmetry between an object and its mirror image. Most biomolecules and many cell types are chiral. In the left-right organizer (LRO), cilia-driven flows transfer such chirality to the body scale. However, the existence of cellular chirality within tissues remains unknown. Here, we investigate this question in Kupffer’s vesicle (KV), the zebrafish LRO. Quantitative live imaging reveals that cilia populating the KV display asymmetric orientation between the right and left sides, resulting in a chiral structure, which is different from the chiral cilia rotation. This KV chirality establishment is dynamic and depends on planar cell polarity. While its impact on left-right (LR) symmetry breaking remains unclear, we show that this asymmetry does not depend on the LR signaling pathway or flow. This work identifies a different type of tissue asymmetry and sheds light on chirality genesis in developing tissues

A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

Language, Sexuality and Inclusive Pedagogy

This paper examines linguistic practices of inclusion and exclusion relating to sexual orientation and sexual identity as they surface in the context of language education and multilingual contexts. I argue that queer linguistics can provide a helpful theoretical framework for examining how normative and non‐normative constructions of sexual identity are enacted inscribed in language practices in classrooms, and how these language practices may effect particular discourses of sexuality. I examine extracts of interview data with young people analysed using APPRAISAL analysis. The analysis focuses on how language works as a form of social practice which can include and exclude sexual identities in classroom settings

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Correlation of gene expression and protein production rate - a system wide study

<p>Abstract</p> <p>Background</p> <p>Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on <it>Saccharomyces cerevisiae </it>chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus <it>Trichoderma reesei </it>(<it>Hypocrea jecorina</it>) that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype.</p> <p>Results</p> <p>We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of <it>T. reesei</it>. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR). We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response.</p> <p>Conclusions</p> <p>Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR).</p