Modeling RNA, protein, and synthetic molecules using coarse-grained and all-atom representations

The aim of computational chemistry is to depict and understand the dynamics and interactions of molecular systems. In addition to increased comprehension in the physical and life sciences, this insight yields important applications to therapeutic design and materials science. In computational chemistry, molecules can be modeled in a number of representations depending on the molecular system and phenomena of interest. In this work, both simplified, coarse-grained representations and all-atom representations are used to model the interactions of RNA, cucurbituril host-guest chemistry, and cadmium selenide quantum dot binding to the Src homology 3 domain. For RNA, a coarse-grained model was developed termed RACER (RnA CoarsE-gRained) to accurately predict RNA structure and folding free energy. After optimization to statistical potentials, RACER accurately predicted the structures of 14 RNAs with an average 4.15Å root mean square deviation (RMSD) to the experimental structure. Further, RACER captured the sequence-specific variation in folding free energy for a set of 6 RNA hairpins and 5 RNA duplexes, with a R² correlation of 0.96 to experiment. The binding free energies of a cucurbituril host with 14 guests were computed using a polarizable force field and the free energy techniques of Bennett acceptance ratio and the orthogonal space random walk. The polarizable force field captured binding accurately, yet unexpectedly, the orthogonal space random walk method converged slowly, albeit at still reduced computational expense to the Bennett acceptance ratio. Lastly, the nanotoxicity effects of trioctylphosphine oxide coated cadmium selenide quantum dots are investigated with the model Src homology 3 protein domain in complex with its native proline rich motif ligand. With increasing quantum dot concentration, there is an increasing preference for the quantum dots to bind to the proline rich motif active site, inhibiting Src homology 3 function.Biomedical Engineerin

Differences in cyst(e)ine content between vegetative cells and spores of clostridium botulinum

M.S.Nancy W. Wall

Beyond Human, Beyond Words: Anthropocentrism, Critical Pedagogy, and the Poststructuralist Turn

Critical pedagogy, even as inflected by certain poststructuralisms, tends to reinforce rather than subvert deep-seated humanist assumptions about humans and nature by taking for granted the borders that define nature as the devalued Other. These assumptions are called into question by discussion of how relationships between language, communication, and meaningful experience are conceptualized outside the field of critical pedagogy. We deal constructively with some anthropocentric blind spots within critical pedagogy generally and within poststructuralist ap- proaches to critical pedagogy in particular. We hope to illuminate places where these streams of thought and practice move in directions compatible with critical environmental education. La pédagogie critique, même celle de quelques poststructuralismes, a tendance à renforcer plutôt que de mettre en doute certains postulats humanistes selon lesquels la nature est, pour les êtres humains, l’Autre dévalué. Ces postulats sont remis en question dans les analyses portant sur le mode de conceptualisation, en dehors du champ de la pédagogie critique, des relations entre le langage, la communication et l’expérience signifiante. Les auteures traitent de quelques présupposés anthro- pocentriques de la pédagogie critique, en particulier dans ses approches post- structuralistes. Elles espèrent ainsi éclairer des courants théoriques et pratiques compatibles entre la pédagogie critique et le respect de l’environnement.

Wage and Price Guidelines and Incomes Policies

Dans les dernières années, de nombreuses personnes en sont venues à la conclusion qu'une certaine forme de politique de revenus était requise pour permettre au Canada, à la fois un haut niveau d'emploi et une stabilité raisonnable des prix.APPROCHE GÉNÉRALE DU CONSEIL ENVERS L'ÉCONOMIEIl est important de noter, à cet égard ,que les buts ou objectifs du Conseil sont multiples. Ces objectifs économiques et sociaux, établis lors de la fondation du Conseil en 1963 sont les suivants : Plein emploi, haut niveau de croissance économique, une raisonnable stabilité des prix, une balance des paiements viable et une juste distribution des revenus croissants. En poursuivant des politiques particulières, le Conseil doit garder à l'esprit les effets possibles de telles politiques sur l'ensemble de ses objectifs. Ceux-ci ne sont pas toujours compatibles les uns avec les autres. Par exemple, des politiques en vue d'atteindre le plein emploi ou un taux rapide de croissance peuvent venir en conflit avec d'autres politiques nécessaires pour éviter l'inflation et maintenir une balance des paiements viable.LE SENS D'UNE POLITIQUE DE REVENUSLa définition qu'en donne l'O.C.D.E. semble généralement acceptée. Cette définition va beaucoup plus loin que les simples communiqués gouvernementaux sur ce que le comportement général des salaires et des prix devrait être sous certaines conditions économiques. En même temps, elle va moins loin que les contrôles obligatoires des salaires et des prix imposés en temps de guerre.Même s'il est possible d'avancer de nombreux arguments en faveur d'une politique de revenus, les problèmes soulevés quand des essais ont été faits, apparaissent comme formidables.La difficulté fondamentale semble être le passage du général au particulier, c'est-à-dire, comment amener les décisions individuelles de salaires et de prix à tenir compte de l'intérêt national. Comment amener l'adhésion à de telles politiques, de corps intermédiaires comme les organisations de salariés ou la direction des entreprises. Par exemple, même la relation fixe entre les taux d'augmentation dans la productivité du travail et les taux d'augmentations des salaires, est rejetée par le Congrès du Travail du Canada qui désire augmenter la part relative du travail par rapport aux autres groupes de l'économie.AUTRES DIFFICULTÉSSur la base d'études d'expériences étrangères, le Conseil a conclu que la situation canadienne est loin d'être favorable à une politique de revenus. Non seulement notre économie est-elle caractérisée par de fortes différences régionales, mais il y a aussi des divisions de juridiction entre le gouvernement fédéral et les provinces dans des domaines fondamentaux relatifs à une politique de revenus, particulièrement dans le domaine des relations industrielles.CONCLUSIONLe Conseil a donc choisi de s'opposer à toute politique formelle de revenus en tant que moyen d'amener une meilleure relation entre un haut niveau d'emploi et une stabilité raisonnable des prix, sauf dans de rares cas d'urgence et alors, seulement sur une base temporaire.John L. FryerLes difficultés d'une politique de revenus au Canada (structure fédérale — état relatif de non-organisation du travail et de la direction (Management) — difficulté de faire appliquer des décisions de cet ordre) demeurent, selon le Conseil Economique du Canada, des difficultés insurmontables dans l'avenir prévisible. En considérant les politiques à suivre pour maintenir la stabilité des prix, le Conseil rejette donc toute politique formelle de revenus, sauf dans de rares cas d'urgence et alors, seulement sur une base temporaire.La distinction entre les diverses formes de politiques de revenus faite par le Conseil est extrêmement importante surtout lorsque les attitudes des divers secteurs de l'économie envers de telles politiques sont considérées comme des hypothèses.Si le travail ne s'est pas montré particulièrement enthousiaste pour de telles politiques par le passé, c'est que, trop souvent, la conception d'une politique de revenus s'est avérée un euphémisme à une politique de salaires qui, elle même, devenait synonyme de restriction des salaires.Il est grand temps, au Canada, d'étudier sérieusement des politiques de revenus ou au moins des politiques de redistribution du revenu. Le Congrès du Travail du Canada a fait des efforts en ce sens et quelques-uns de nos commentaires se retrouvent dans notre Mémoire au Gouvernement. Nous y insistons sur un aspect trop souvent ignoré d'une telle politique, soit une façon plus socialement juste de redistribuer le revenu dans l’économie.The two following papers discuss the views of the Economic Council of Canada and were presented at the Ottawa CIRRI Conference June 1967. Russell Bell is from the Economic Council of Canada and John L. Fryer is from the Canadian Labour Congress

Systematic review of topical treatments for fungal infections of the skin and nails of the feet

OBJECTIVE: To identify and synthesise the evidence for efficacy and cost effectiveness of topical treatments for superficial fungal infections of the skin and nails of the feet. DESIGN: Systematic review. INTERVENTIONS: Topical treatments for superficial fungal infections. MAIN OUTCOME MEASURES: Cure confirmed by culture and microscopy for skin and by culture for nails in patients with clinically diagnosed fungal infections. RESULTS: Of 126 trials identified in 121 papers, 72 (57.1%) met the inclusion criteria. Placebo controlled trials yielded pooled relative risks of failure to cure skin infections: allylamines (0.30, 95% confidence interval 0.24 to 0.38); azoles (0.54, 0.42 to 0.68); undecenoic acid (0.28, 0.11 to 0.74); and tolnaftate (0.46, 0.17 to 1.22). Although meta-analysis of 11 trials comparing allylamines and azoles showed a relative risk of failure to cure of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidence of language bias. Seven reports in English favoured allylamines (0.79, 0.69 to 0.91), but four reports in foreign languages showed no difference between the two drugs (1.01, 0.90 to 1.13). Neither trial of nail infections showed significant differences between alternative topical treatments. CONCLUSIONS: Allylamines, azoles, and undecenoic acid were efficacious in placebo controlled trials. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive than azoles. The most cost effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails

Near Their Thresholds for Detection, Shapes Are Discriminated by the Angular Separation of Their Corners

Observers make sense of scenes by parsing images on the retina into meaningful objects. This ability is retained for line drawings, demonstrating that critical information is concentrated at object boundaries. Information theoretic studies argue for further concentration at points of maximum curvature, or corners, on such boundaries [1]-[3] suggesting that the relative positions of such corners might be important in defining shape. In this study we use patterns subtly deformed from circular, by a sinusoidal modulation of radius, in order to measure threshold sensitivity to shape change. By examining the ability of observers to discriminate between patterns of different frequency and/or number of cycles of modulation in a 2x2 forced choice task we were able to show, psychophysically, that difference in a single cue, the periodicity of the corners (specifically the polar angle between two points of maximum curvature) was sufficient to allow discrimination of two patterns near their thresholds for detection. We conclude that patterns could be considered as labelled for this measure. These results suggest that a small number of such labels might be sufficient to identify an object.Funding came from Australian reserch council grants DP0666206, DP1097003 and DP110104553 to DRB and DP110101511 to JB, www.arc.gov.au. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Persistent isolated hypocortisolism following brief treatment with trilostane

A 12-year-old male neutered Miniature Poodle with confirmed pituitary-dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism ('atypical hypoadrenocorticism'), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life-threatening situation

Completeness II: A signal-to-noise approach for completeness estimators applied to galaxy magnitude-redshift surveys

This is the second paper in our completeness series which addresses some of the issues raised in the previous article by Johnston, Teodoro & Hendry (2007) in which we developed statistical tests for assessing the completeness in apparent magnitude of magnitude-redshift surveys defined by two flux limits. The statistics, Tc and Tv, associated with these tests are non-parametric and defined in terms of the observed cumulative distribution function of sources; they represent powerful tools for identifying the true flux limit and/or characterising systematic errors in magnitude-redshift data. In this paper we present a new approach to constructing these estimators that resembles an "adaptive smoothing" procedure - i.e. by seeking to maintain the same amount the information, as measured by the signal-to-noise ratio, allocated to each galaxy. For consistency with our previous work, we apply our improved estimators to the Millennium Galaxy Catalogue (MGC) and the Two Degree Field Galaxy Redshift Survey (2dFGRS) data, and demonstrate that one needs to use a signal-to-noise appropriately tailored for each individual catalogue to optimise the performance of the completeness estimators. Furthermore, unless such an adaptive procedure is employed, the assessment of completeness may result in a spurious outcome if one uses other estimators present in the literature which have not been designed taking into account "shot noise" due to sampling.Comment: 9 pages, 6 figures, MNRAS accepte