Multi-scale modelling of macromolecular conformational changes

Modelling protein flexibility and plasticity is computationally challenging but important for understanding the function of biological systems. Furthermore, it has great implications for the prediction of (macro) molecular complex formation. Recently, coarse-grained normal mode approaches have emerged as efficient alternatives for investigating large-scale conformational changes for which more accurate methods like MD simulation are limited due to their computational burden. We have developed a Normal Mode based Simulation (NMSim) approach for efficient conformation generation of macromolecules. Combinations of low energy normal modes are used to guide a simulation pathway, whereas an efficient constraints correction approach is applied to generate stereochemically allowed conformations. Non-covalent bonds like hydrogen bonds and hydrophobic tethers and phi-psi favourable regions are also modelled as constraints. Conformations from our approach were compared with a 10 ns MD trajectory of lysozyme. A 2-D RMSD plot shows a good overlap of conformational space, and rms fluctuations of residues show a correlation coefficient of 0.78 between the two sets of conformations. Furthermore, a comparison of NMSim simulations starting from apo structures of different proteins show that ligand-bound conformations can be sampled for those cases where conformational changes are mainly correlated, e.g., domain-like motion in adenylate kinase. Efforts are currently being made to also model localized but functionally important motions for protein binding pockets and protein-protein interfaces using relevant normal mode selection criteria and implicit rotamer basin creation

Adult Female Spruce Bedworm, \u3ci\u3eChoristoneura Fumiferana\u3c/i\u3e (Lepidoptera: Tortricidae), Dry Weight in Relationship to Pupal Fresh Weight and Case Diameter

(excerpt) The weights of adult insects are often measured in production and population studies in order to estimate such variables as growth rates, food conversion efficiencies, fecundity, and others. For the eastern spruce budworm, Choristoneura fumiferana (Clemens), both pupal fresh weights and pupal case diameters have been measured as indicators of adult fecundity and adult dry weights (Miller 1957). However, there are no reports explicitly showing the relationship between these metric pupal variables and adult dry weights. This is the goal of this note

Bald Eagles at the Savanna Army Depot

Eagle Valley Environmentalists Technical Report #SADE-81, Research Report conducted December 1980 - March 1981, under a contract with the United States Arm

Subclinical Depression, Anxiety, and Alexithymia: Implications for Implicit and Explicit Emotion Regulation

Alexithymia is defined as an inability to identify or experience emotions, and has been connected to both major depressive disorder (MDD) and generalized anxiety disorder (GAD). Both MDD and GAD are associated with a tendency to select maladaptive emotion regulation (ER) techniques. The present studies explored the relationship between alexithymia and subclinical depression/anxiety by proposing that alexithymia is a mediator of the relationship between depressive/anxious symptoms and ER difficulty. Study 1 examined this relationship in the context of implicit, or automatic, ER, as assessed by an emotional conflict task. While the task failed to index implicit ER ability, this study fostered an understanding of the role of response windows in implicit ER paradigms. Study 2 explored this relationship in the context of explicit, or effortful, ER, as assessed by heart rate variability (HRV) and subjectively reported affect associated with an anxiety-inducing task prior to which participants were instructed to implement reappraisal. This study did not find alexithymia to be a mediator of the relationship between symptoms of depression/anxiety and ER, suggesting that alexithymia does not negatively impact individuals’ ability to engage in instructed reappraisal. However, based on the general failure of reappraisal on a physiological level, this study also suggested that the relative success of reappraisal is contextually determined. Finally, this study found depression and anxiety to be associated with heightened subjective distress, and pointed to a decoupling between physiological and subjective emotional experience in subclinical depression and anxiety

Modernisierung der kantonalen Verwaltungen 1990-2008 : Wandel von Administrativstrukturen und Einführung von Verwaltungsreformen = Modernisation des administrations cantonales 1990-2008 : transformations structurelles et gouvernance administrative

De nombreuses études ont été consacrées en Suisse à la promotion de la nouvelle gestion publique (NGP) au niveau des cantons, puis à son évaluation. Or, les chercheurs se sont peu intéressés jusqu'ici aux effets de son introduction sur les structures administratives et les effectifs de la fonction publique. Ils n'ont pas non plus expliqué suffisamment les facteurs ayant favorisé ou freiné la modernisation de l'Etat au-delà de la NGP. Les réformes de l'Etat menées au sein des administrations cantonales dans le cadre de la revitalisation du fédéralisme ont des causes multiples. Cette étude exploratoire tente de décrire les transformations au niveau des structures et de l'organisation de l'Etat depuis le début des années 1990 en analysant le niveau et l'impact des principes NGP ou d'autres facteurs ayant pu jouer un rôle dans la modernisation des administrations: force des partis, degré de professionnalisation des législatifs, taille de la population et des administrations, RPT et revitalisation de la collaboration intercantonale. Il ressort de l'étude qu'un groupe de cantons essentiellement alémaniques, plutôt de taille moyenne à grande (AG, BE, LU, SO, TG, VS, ZH) ont réussi à davantage réformer les administrations selon les principes de la NGP alors que d'autres ont choisi des voies différentes ou médianes (tels que BS, GE, JU, SG, TI, VD). Ces réformes se sont traduites pratiquement partout par un resserrement des structures décisionnelles (modèle ministériel 5/7), par une variation du nombre de services (hausse dans une première phase puis réduction) mais aussi du personnel (plutôt hausse à l'exception de BS et ZH) allant dans le sens d'une convergence des modèles institutionnels déterminée autant par des facteurs externes qu'internes aux cantons. Notre étude montre que la professionnalisation des parlements, davantage développée dans les cantons où le système représentatif est étendu (cantons latins, Bâle-Ville), retarde ou empêche l'essor des principes NGP alors que les cantons alémaniques à démocratie directe plus prononcée favorisent l'autonomisation des processus de réformes administratives avec une capacité de blocage moins grande des parlements

Effects of scopolamine on matching to sample paradigm and related tests in human subjects

This was a double-blind placebo-controlled study with a cross-over design to examine the effects of scopolamine on cognitive functions in young healthy subjects. Scopolamine hydrobromide was administered subcutaneously to 12 subjects (mean +/- SD age 23.8 +/- 2.2 years) at doses of 0.3 and 0.6 mg in comparison with two placebo conditions. Scopolamine at both doses produced marked sedation as rated by subjects and an observer. In the continuous performance test, vigilance was impaired by both doses of scopolamine. The span of apprehension test showed differing results (only the high dose of scopolamine showed a performance decrement only in the three-character version of the span of apprehension test). Significant impairment by both doses of scopolamine was seen in immediate and delayed free recall, continuous visual recognition, running word recognition and running picture recognition. While scopolamine caused a significant slowing in average reaction times for simultaneous matching as well as for delayed matching, subjects made more errors under scopolamine compared to placebo only in delayed matching, not in simultaneous matching. Also, the main outcome of matching to sample showed significant effects only in delayed matching, not in simultaneous matching. Notable in this study is the incongruity between the simultaneous matching test and the span of apprehension test on the one hand and the other cognitive tests used on the other. These results demonstrated that scopolamine has a greater effect on memory than on attention. Thus, the scopolamine-induced effects in the present study seem to be more relevant to Alzheimer's disease in an advanced phase than to normal aging. Copyright (C) 2003 S. Karger AG, Basel

Using NLP technology in CALL

This paper outlines the research and guiding research principles of the (I)CALL group at Dublin City University, Ireland. Our research activities include the development of (I)CALL systems targeted at a variety of user groups including advanced Romance language learners, intermediate to advanced German learners, primary and secondary school students as well as students with L1 learning disabilities requiring a variety of system types which cater to individual user needs and abilities. Suitable CL/NLP technology is incorporated where appropriate for the learner

Polaron cross-overs and d-wave superconductivity in Hubbard-Holstein model

We present a theoretical study of superconductivity of polarons in the Hubbard-Holstein model. A residual kinematic interaction proportional to the square of the polaron hopping energy between polarons and phonons provides a pairing field for the polarons. We find that superconducting instability in the d-wave channel is possible with small transition temperatures which is maximum in the large to small polaron cross-over region. An s-wave instability is found to be not possible when the effective on-site interaction between polarons is repulsive